2018 Book MechanicalVentilationInTheCrit PDF

Mechanical Ventilation
in the Critically Ill Obese

Patient
Antonio M. Esquinas
Malcolm Lemyze
Editors
123
in the Critically Ill Obese Patient
Antonio M. Esquinas • Malcolm Lemyze
Editors
in the Critically Ill Obese
Patient
Editors
Antonio M. Esquinas Malcolm Lemyze
Intensive Care and Non Invasive Department Respiratory and CC Medicine
Ventilatory Unit Schaffner Hospital
Hospital Morales Meseguer Lens
Murcia France
Spain
ISBN 978-3-319-49252-0 ISBN 978-3-319-49253-7 (eBook)

https://doi.org/10.1007/978-3-319-49253-7
Library of Congress Control Number: 2017955688
© Springer International Publishing AG 2018

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Preface
There is no doubt that obesity has become one of the leading public health threats
worldwide. The number of obese subjects has doubled during the last 25 years to
reach more than 600 million subjects in 2015. Considering the 100 million obese
children in the world, obesity’s future is assured at least for the next generation. Of
course, the continuously increasing incidence of the disease is problematic, but the
new alarming phenomenon is the explosion of the cases of massively obese indi-
viduals. Indeed, the higher the severity of obesity according to body mass index, the
higher the incidence of obesity-associated cardio-respiratory disorders and meta-
bolic diseases. Obesity-induced chronic respiratory failure—commonly referred to
as obesity hypoventilation syndrome—is encountered in more than half of the
superobese patients with a BMI exceeding 50 kg·m−2. The management of these
patients in the emergency setting is often challenging and raises specific problems
that must be addressed and overcome at the bedside in a short time. At the interface
between multiple health specialties, the obese patient usually requires a time-
consuming multidisciplinary approach involving different stakeholders in respira-
tory care, cardiovascular diseases, endocrinology, surgery, anesthesiology, and also
a necessary implication of the nursing staff. This book is intended to highlight the
critically ill obese patient’s specificities that must be taken into account when
mechanical ventilation is part of the therapeutic management of such a patient.
Given the singularity of the massively obese critically ill patient, it can be assumed
that an individualizing care approach is particularly adapted for this topic. Good
knowledge of the respiratory physiology and cardio-respiratory interactions appears
to be an essential prerequisite to the management of a critically ill obese patient,
especially when oxygenation and mechanical ventilation are needed. The first part
of the book is devoted to delivering insight into the basic understanding of the phys-
iological characteristics of the respiratory system of the obese patient and their
implications for mechanical ventilation. The second part deals with the comorbidi-
ties of the obese patient and the causes of acute respiratory failure that can impact
on the outcome. The third part of the book includes chapters about preoxygenation,
positioning, recruitment strategy, sedation and analgesia during invasive mechani-
cal ventilation, and its associated complications. Another part is about noninvasive
ventilation and the promising technique of high-flow oxygen via nasal cannula,
which both have the potential to avoid the resort to invasive mechanical ventilation
in many situations. Finally, nutritional support and outcome after mechanical
v
vi Preface
ventilation are two main issues that are developed in the last part. We are convinced
that this book provides a useful didactic tool for an everyday practice of critical care
medicine in obese patients with respiratory failure.
Both editors are very grateful to all authors for their valuable contribution to the
book. We are deeply aware of the time they spent in writing the chapters, making it
possible to share their knowledge and expertise with the readers. We greatly appre-
ciate having so many internationally recognized experts in the field of obesity and
mechanical ventilation who accepted to participate in the writing of this book.
Lens, France Malcolm Lemyze, M.D.

Murcia, Spain Antonio M. Esquinas, M.D., Ph.D.
Contents
Part I Effects of Obesity on Respiratory Physiology
1 Control of Ventilation in Obesity�� 3

Nikolaos Markou, Heleni Stefanatou, and Maria Kanakaki
2 Obesity, Respiratory Mechanics and Its Impact on the Work
of Breathing, Neural Respiratory Drive, Gas Exchange
and the Development of Sleep-Disordered Breathing�� 15
Culadeeban Ratneswaran, Patrick Murphy, Nicholas Hart,
and Joerg Steier
3 Implications of Obesity for Mechanical Ventilation �� 27
Paolo Formenti and John J. Marini
Part II Causes of Acute Respiratory Failure in the Obese Patient
4 Obesity and Comorbidities�� 43

Cintia Zappe Fiori, Denis Martinez, and Alicia Carissimi
5 Atelectasis �� 51
Sevinc Sarinc Ulasli
6 Obesity and Congestive Heart Failure �� 57
Stephan Steiner
7 Intra-abdominal Hypertension and Abdominal Compartment
Syndrome: Consequences for Mechanical Ventilation �� 65
Peter D. Liebling and Behrouz Jafari
8 Impact of Sleep Breathing Disorders in Obese Critically
Ill Patients �� 77
Moh’d Al-Halawani and Christine Won
9 Drugs and Medications�� 87
Clement Lee, Kate Millington, and Ari Manuel
vii
viii Contents
Part III Invasive Mechanical Ventilation in the Critically

Ill Obese Patient
10 Preoxygenation Before Intubation in the Critically

Ill Obese Patient �� 99
Francesco Zarantonello, Carlo Ori, and Michele Carron
11 Analgesia in the Obese Patient�� 109
Preet Mohinder Singh and Adrian Alvarez
12 Sedation of the Obese Patient: Indications, Management,
and Complications �� 123
Krysta Wolfe and John Kress
13 Positioning of the Critically Ill Obese Patient for Mechanical
Ventilation�� 139
Malcolm Lemyze
14 Obesity and Positive End-Expiratory Pressure (PEEP)-Obesity
and Recruitment Maneuvers During the Intraoperative Period�� 145
Seniyye Ulgen Zengin and Güniz Köksal
15 Complications Associated with Invasive Mechanical Ventilation
in Obese Patients�� 151
Nishant Chauhan
16 Management of Ventilator-Induced Lung Injury �� 157
Sven Stieglitz
17 Ventilation Modes for Obese Patients Under Mechanical
Ventilation�� 163
Rachel Jones, Jason Gittens, and Ari Manuel
18 Obesity and Tracheostomy: Indications, Timing, and Techniques �� 179
Bahman Saatian and Julie H. Lyou
19 Decannulation Process in the Tracheostomised Obese Patients�� 187
Pia Lebiedz, Martin Bachmann, and Stephan Braune
Part IV Noninvasive Ventilation and Oxygen Delivery in the Critically

Ill Obese Patient
20 The Choice of Interface �� 193

Ahmed S. BaHammam, Tripat Singh, and Antonio M. Esquinas
21 The Choice of Ventilator and Ventilator Setting �� 199
Ebru Ortaç Ersoy
22 Obesity and Bi-level Positive Airway Pressure�� 205
Ayelet B. Hilewitz, Andrew L. Miller, and Bushra Mina
Contents ix
23 High-Flow Nasal Cannula Therapy: Principles and Potential Use

in Obese Patients�� 215
Emmanuel Besnier, Jean-Pierre Frat, and Christophe Girault
24 NIV in Type 2 (Hypercapnic) Acute Respiratory Failure�� 229
Shaden O. Qasrawi and Ahmed S. BaHammam
25 Prevention of Post-extubation Failure in Critically
Ill Obese Patient �� 239
Ali A. El Solh
26 NIV in the Obese Patient After Surgery�� 251
Giuseppe Fiorentino, Antonio M. Esquinas, and Anna Annunziata
27 Determinants of NIV Success or Failure�� 259
Antonello Nicolini, Ines Maria Grazia Piroddi, Cornelius Barlascini,
Gianluca Ferraioli, and Paolo Banfi
28 Chronic Ventilation in Obese Patients�� 265
Jean Christian Borel, Jean-Paul Janssens, Renaud Tamisier, Olivier
Contal, Dan Adler, and Jean-Louis Pépin
Part V How to Support Nutritionally the Critically Ill Obese Patient
29 Nutritional Support in the Critically Ill Obese Ventilated Patient�� 281

Kasuen Mauldin and Janine W. Berta
30 Long-Term Outcomes After Mechanical Ventilation�� 287
Rose Franco and Rahul Nanchal
Index�� 307
Abbreviations
ABG Arterial blood gas

AECOPD Acute exacerbation of chronic obstructive pulmonary disease
AHI Apnea-hypopnea index
AHRF Acute hypercapnic respiratory failure
APACHE II Acute physiology and chronic health evaluation II
ARF Acute respiratory failure
ASPEN American Society for Parenteral and Enteral Nutrition
ASV Adaptive servoventilation
AVAPS Average volume-assured pressure support
BMI Body mass index
BNP Brain natriuretic peptide
BPAP Bi-level positive airway pressure
bpm Breath per minute
CF Cystic fibrosis
CHF Congestive heart failure
CI Confidence interval
CKD Chronic kidney disease
CO2 Carbon dioxide
COPD Chronic obstructive pulmonary disease
CPAP Continuous positive airway pressure
CRF Chronic respiratory failure
CSA Central sleep apnea
CVEs Cardiovascular events
DLCO Carbon monoxide diffusion capacity
ECG Electrocardiogram
EN Enteral nutrition
EPAP Expiratory positive airway pressure
ERV Expiratory reserve volume
ETO2 End-tidal oxygen concentration
FAO2 Fraction of alveolar oxygen
FEO2 Fraction of expired oxygen
FEV1 Forced expiratory volume in 1 s
FFM Full face mask
FiO2 Fraction of inspired oxygen
xi
xii Abbreviations
FRC Functional residual capacity

FVC Forced vital capacity
HDU High dependency unit
HF Heart failure
HFNC High-flow nasal cannulae
HFpEF Heart failure with preserved ejection fraction
HFrEF Heart failure with reduced ejection fraction
hsCRP High-sensitivity C-reactive protein
IC Indirect calorimetry
ICU Intensive care unit
IMV Invasive mechanical ventilation
IPAP Inspiratory positive airway pressure
LVEF Left ventricular ejection fraction
LVH Left ventricular hypertrophy
MV Mechanical ventilation
NIPPV Noninvasive positive pressure ventilation
NIV Noninvasive ventilation
NMD Neuromuscular diseases
NPPV Noninvasive positive pressure ventilation
OHS Obesity hypoventilation syndrome
OR Operating room
OSA Obstructive sleep apnea
PaCO2 Arterial partial pressure of carbon dioxide
PACU Postanesthesia care unit
PAD Peripheral artery disease
PaO2 Arterial partial pressure of oxygen
PAP Positive airway pressure
PE Pulmonary embolism
PEEP Positive end-expiratory pressure
PN Parenteral nutrition
PSV Pressure support ventilation
RCT Randomized controlled trials
RM Recruitment maneuver
RMs Recruitment maneuvers
RR Risk ratio
RV Residual volume
SAP Safe apnea period
SCCM Society of Critical Care Medicine
SpO2 Peripheral oxygen saturation
SRBD Sleep-related breathing disorders
TLC Total lung capacity
TVB Tidal volume breathing
VC Vital capacity
VO2max Maximal oxygen consumption
Vt Tidal volume
VtPS Volume-targeted pressure support
Part I
Effects of Obesity on Respiratory Physiology
Control of Ventilation in Obesity
1
Nikolaos Markou, Heleni Stefanatou, and Maria Kanakaki
1.1 Introduction
The literature on the control of ventilation in obesity suggests a fundamental dichot-

omy: eucapnic subjects tend to maintain normal or augmented chemosensitivity,
whereas hypercapnic subjects have a blunted chemosensitivity [1, 2]. Yet existing
studies often pose methodological problems. Thus, they do not always take into
account other factors which may also affect chemical control of breathing like gen-
der or the coexistence of sleep-disordered breathing (SDB), which is very common
in obese subjects. Furthermore, although most of these studies utilize rebreathing
assessments of chemoreflex sensitivity, they do not always use the same rebreathing
protocols. Additionally the output of the ventilatory center is not uniformly evalu-
ated: some investigators measure minute ventilation (VE) alterations, while others
evaluate neural drive more directly, in terms of alterations in mouth occlusion pres-
sure (P0,1) or in diaphragmatic electromyogram activity (EMGdi). Finally, practi-
cally all studies deal with chemical control of breathing only at the awake state, with
very few data on chemosensitivity during sleep.
In the rest of the chapter, we shall initially present data on the neural control of
breathing at rest. Then we shall discuss data on the hypercapnic ventilatory response
(HCVR) and the hypoxic ventilatory response (HOVR) in eucapnic and in hyper-
capnic obesity (obesity hypoventilation syndrome—OHS), with emphasis on stud-
ies accounting for the coexistence of obstructive sleep apnea (OSA). Finally we
shall discuss the cause of alterations in the chemical control of breathing in OHS
and the possible consequences of these alterations.
N. Markou, M.D. (*) • H. Stefanatou, M.D.

ICU at Latseion Burn Center, General Hospital of Eleusis “Thriasion”, Athens, Greece
e-mail: nikolaos_markou@hotmail.com
M. Kanakaki, M.D.
1st University Clinic of Pulmonary Medicine, General Hospital of Diseases of the Chest
“Sotiria”, Athens, Greece
© Springer International Publishing AG 2018 3

A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill
Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_1
4 N. Markou et al.
1.2 Respiratory Neural Drive at Rest in Obesity
In otherwise healthy eucapnic obese adults, measurements of P0,1 and EMGdi

suggest that respiratory neural drive at rest is increased compared to nonobese
controls or to reference values [3–8]. Even in hypercapnic obesity, some limited
data suggest that P0,1 at rest is not reduced and may even be increased relative to
normal reference values [9, 10]. In eucapnic obesity, respiratory drive at rest
seems to be closely related to indices of body weight [4, 7]. In a large cohort of
245 obese subjects with no obstructive or restrictive syndrome or neuromuscular
impairment, P0,1 at rest was independently associated with severity of obesity
(defined as percentage of body fat) and inversely associated with minimum oxy-
gen saturation during sleep, total lung capacity, partial pressure of end-tidal CO2,
and leptin levels [6].
In normal subjects, external elastic loading is known to augment neural drive by
activating neural load-compensating mechanisms [11–13]. The increase of neural
drive at rest in obesity seems to represent a similar compensatory mechanism in
order to maintain an adequate minute ventilation in the face of increased mechanical
loading due to weight gain [1, 2, 14]. From another viewpoint, an increased EMGdi
in obesity might also indicate a reduced ventilatory reserve, that is, an inability in
obese subjects to adequately augment their neural drive when needed, which might
predispose to hypoventilation and hypercapnia in situations of increased work of
breathing [7].
1.3 Chemical Control of Breathing in Eucapnic Obesity
In normal volunteers, the application of external elastic loading results in compen-

satory increases of neural drive responses to CO2 rebreathing and to exercise. The
range of these neural adjustments may vary with load size and type of load—e.g.,
loading of the rib cage compartment might elicit more intense responses, than load-
ing of the abdominal compartment [11–13, 15]. Similar compensatory mechanisms
have been reported to be operative in eucapnic obesity as well [2, 16], and they
probably contribute to the increased sensation of dyspnea often encountered in
these subjects [17]. In spite of this neural adjustment, in obesity the final output in
terms of minute ventilation response may remain unaffected or even decreased.
Thus, Lopata et al. report that obese eucapnic subjects without OSA had an increased
response of respiratory neural drive (evaluated as EMGdi) to CO2 rebreathing com-
pared with normal controls, whereas the VE response was decreased. They con-
clude that compensatory adjustments in respiratory neural drive are not always
adequate to completely overcome the increased mechanical load in obesity [3].
Eucapnic subjects with less preserved HCVR may be more prone to ventilatory
compromise: Sampson et al. have observed an impairment of the VE response to
CO2 rebreathing in eucapnic massively obese patients who had previously suffered
an episode of transient hypercapnia at the time of a respiratory insult, compared
with carefully matched controls who had never been hypercapnic [4].
1 Control of Ventilation in Obesity 5
Yet, perhaps because of methodological differences, not all studies on chemo-

sensitivity in eucapnic obesity come to the same conclusions. A shortcoming of
many of these studies is that they do not account for the frequent coexistence of
obstructive sleep apnea (OSA) in obesity. Yet, OSA has also been associated with
increased chemosensitivity [18–22]—although the literature again is not unanimous
[23–27], with an increased gain of the central controller of breathing implicated in
OSA pathogenesis [28–30].
In studies addressing the question of chemosensitivity in eucapnic obesity with-
out taking into account the possible presence of sleep-disordered breathing (SDB),
the HCVR has been reported to be normal [5, 31] or increased [4, 32, 33] or even
gender-depended, with normal responses for males and increased responses for
females [34].
An association has also been suggested between an increased HCVR in obesity
and the percentage and distribution of body fat [32]. The HOVR has similarly been
reported as normal [31] or increased [5, 32–34]. Before and after studies with
weight loss after surgical treatment of obesity conclude that eucapnic obesity is
associated with an augmented HCVR [17, 35].
Methodological problems are encountered in some of these studies, like a great
imbalance as regards age and gender between obese subjects and normal controls
[5] or the measurement of HCVR without a hyperoxic background mixture, which
may have contributed to the finding of an augmented HCVR in another study [33].
1.4 hemical Control of Breathing in Eucapnic Obesity

C
Without OSA
Studies of eucapnic obese subjects in whom OSA had been rigorously excluded
with polysomnography also provide somewhat conflicting data.
Thus, Lopata et al. [3] report a lower VE response to CO2 rebreathing compared
with normal controls in spite of a normal or increased response in terms of mouth
occlusion pressure and EMGdi. According to Narkiewicz et al., eucapnic obese sub-
jects without OSA had a higher HCVR compared to normal controls matched for
age and sex but a similar HOVR [36]. Buyse et al. on the other hand, compared the
chemosensitivity of 138 healthy obese subjects without OSA (21 men and 117
women) of whom more than half had morbid obesity (BMI > 40), with reference
values from their laboratory, and concluded that in obesity, chemosensitivity is
affected by gender differences [37]. Obese women had an increased response of VE
normalized for vital capacity and of P0,1 to hyperoxic hypercapnia and an even
more increased response to hypoxia. HCVR and HOVR slopes correlated with
BMI. On the contrary, obese men did not have an altered chemosensitivity. Women
deemed to be menopausal in this study had lower HCVR and HOVR than women
deemed to be premenopausal. Estrogen and progestin are known to augment respi-
ratory drive [38], and an augmented chemosensitivity in obese women may be asso-
ciated with increased estrogen production from fat tissue in the premenopausal
period [37].
6 N. Markou et al.
An interplay between weight increase and sex on chemosensitivity is further cor-

roborated by the findings of Sin DD et al. in a large cohort of 219 patients (many of
them obese) who underwent polysomnography under suspicion for OSA and in whom
HCVR independently correlated with BMI in women and with age in men [39].
Finally, in a study of obese adolescents, it was found that after exclusion of OSA,
obese subjects in the awake state had a higher VE response to CO2 than age-matched
lean subjects but that this difference did not persist during sleep [40].
1.5 hemical Control of Breathing in Eucapnic Obesity

C
with OSA
Coexistence of OSA seems to blunt neural drive responses and to diminish the VE
response to CO2 in the study of Lopata et al. [3]. A blunting effect of coexisting
OSA on HCVR has also been confirmed by Gold et al. in eucapnic obese males,
while HOVR was not affected by the coexistence of OSA [41].
On the other hand, in a case-control comparison of 21 men and 34 women with
obesity and OSA matched 1:1 with obese subjects without OSA, on the basis of age,
height, and BMI, coexistence of OSA resulted in a higher VE/VC and P0,1 response
to hypoxia (but not hypercapnia) in women, while it did not affect chemosensitivity
in obese men [37].
Finally, in obese adolescents, coexistence of OSA did not affect the HCVR in the
awake state. Nevertheless, during sleep, obese subjects with OSA had blunted ventila-
tory responses to CO2 administration compared both to normal controls and to obese
subjects without OSA, although the neural drive response was not evaluated [40]. The
blunted response during sleep might conceivably result in prolonged respiratory
events in these subjects (promoting nocturnal hypercapnia), while the enhanced
response during wakefulness might lead to an inappropriately high ventilatory
response upon arousal from apnea with concomitant ventilatory instability because of
fluctuations in PaCO2 [40].
1.6 hemical Control of Breathing in Hypercapnic Obesity

C
(Obesity Hypoventilation Syndrome)
The simplest evidence for a defective central respiratory drive in OHS is that
most of these patients are able to voluntarily hyperventilate to eucapnia, implying
that impairments in respiratory system mechanics alone do not explain the
hypoventilation [42].
This impression is further confirmed by several small studies that report a blunted
HCVR in OHS compared to normal weight subjects [3, 43] or subjects with eucap-
nic obesity [44], at least in the absence of OSA [3]. Interestingly, Lopata et al. report
that in eucapnic obesity coexisting with OSA, the HCVR is similarly blunted [3],
but this finding has not been confirmed by Garay et al., who report a substantially
higher HCVR in eucapnic obesity compared with OHS [23].
Data on HOVR in OHS are fewer, but it seems that HOVR is also decreased
compared with lean controls [43]. A trend for lower HOVR has also been observed
in hypercapnic compared with eucapnic obese subjects with OSA [21], while in
another study of OSA patients not necessarily obese, this difference in HOVR
between hypercapnic and eucapnic subjects was significant [45].
This blunted chemosensitivity in OHS is not likely to be associated with genetic
influences: HCVR and HOVR were similar between first-degree relatives of patients
with OHS and controls matched for age and weight [46]. It should be noted that
neither the decreased drive observed in hypercapnic OSA can be attributed to
genetic influences [45].
The demonstration of increases in HCVR and HOVR as early as 2 weeks from
initiation of treatment of OHS with continuous positive airway pressure (CPAP) or
noninvasive positive pressure ventilation (NIPPV) [10, 46–48] constitutes addi-
tional evidence that blunting of chemosensitivity does not preexist but is a second-
ary effect of the syndrome, probably mediated by hypercapnia, which is similarly
reversed with CPAP or NIPPV treatment. This improvement in HCVR is probably
confined to subjects with substantially blunted chemosensitivity, in whom an
increase of 47% has been reported after NIPPV [49].
Blunted HCVR has also been observed in patients with hypercapnic OSA (many
of whom are obese and suffering in fact from OHS) compared with normal controls
[19, 23] or with eucapnic OSA patients [45, 47, 48] and is similarly reversed—
together with hypercapnia—by effective OSA treatment.
A weak but significant inverse association between HCVR and PaCO2 has been
demonstrated in a large cohort of 219 patients who underwent polysomnography
under suspicion of OSA, although only a few of them had severe obesity or hyper-
capnia [40].
Development of nocturnal hypercapnia is believed to be a critical factor toward
the establishment of a blunted HCVR in obesity as well as in isolated OSA. Notably,
the study of Chouri-Pontarollo N et al. confirms that in patients with OHS, the
HCVR correlates moderately with the amount of nocturnal hypoventilation during
REM sleep [49].
Obesity may promote nighttime hypercapnia by increasing metabolic rate and
CO2 production [50] while at the same time imposing increases in elastance and
resistance of the respiratory system and perhaps impairing respiratory muscle func-
tion [1, 2]. During sleep these effects may promote nocturnal alveolar hypoventila-
tion, more pronounced during REM sleep. Additionally, obesity often compromises
upper airway patency causing OSA, which is in fact present in 90% of patients with
OHS [1]. Most individuals with OSA can sufficiently hyperventilate after apneas to
eliminate the accumulated CO2 and therefore can maintain overall eucapnia during
sleep [51–53]. Yet in obesity, this interapnea elimination of CO2 can be impaired
due to mass loading and reduced FRC, or because the ventilatory response to accu-
mulated CO2 during sleep may be blunted [41, 52].
Once nocturnal hypercapnia develops, kidneys retain at night small amounts of
bicarbonate to buffer the decrease in pH. This increase in serum bicarbonate is not
always corrected before the next sleep period as the time constant of bicarbonate
8 N. Markou et al.
excretion is longer than that of CO2. The result will be a net gain of bicarbonate
which will cause a secondary depression of central respiratory drive [53–55] and
will promote further CO2 accumulation at night [51].
Thus a vicious circle begins, with more severe exposure to hypoxemia and
hypercapnia and further attenuation of central drive, with a decreased HCVR
during daytime and maintenance of the state of hypoventilation during the day as
well [1, 2, 56].
A blunted HOVR may also contribute to daytime hypercapnia in obesity. Blunted
HOVR may be caused by sleep desaturation in the settings of OSA or of alveolar
hypoventilation during sleep: this nocturnal hypoxemia may lead to depression of
HOVR, in way similar to that seen in high-altitude hypoxia [57]. Sustained hypoxia
may also impair the arousal response to external resistive loading, and this may
worsen sleep-associated airway occlusion [58]. Nocturnal hypoxemia in obese
patients may thus further impair the compensatory hyperventilation between apneic
events, contributing to nocturnal rise in CO2 [1].
There are some indirect indications of a poor correlation of central drive at the
awake state with central drive during sleep [40, 51]. This might explain why some
patients with OHS may still have normal HCVR. Regrettably data on respiratory
drive during sleep are scarce in obesity [40] and nonexistent in OHS, and it remains
unclear if what matters more is respiratory drive during wakefulness or during sleep.
In addition to its contribution to the establishment and maintenance of OHS, an
impaired chemosensitivity may be responsible for the worsening of hypercapnic
acidosis observed in a randomized crossover study of patients with OHS after
breathing an oxygen mixture with an FiO2 0,5 [59]. It has also been found that OHS
patients with the lowest HCVR responses had a greater propensity for increased
objective sleepiness, while they also demonstrated significant improvement in
objective daytime sleepiness with NIPPV [49].
Respiratory stimulants (medroxyprogesterone, acetazolamide) have occasion-
ally been used in the past in OHS in order to reverse CO2 retention [60–63]. Yet
experience remains limited, and such drugs do not currently constitute a part of the
mainstream approach in OHS, which remains based on application of CPAP or
NIPPV during sleep.
1.7 he Role of Leptin in Alterations of Chemosensitivity

T
in Obesity
Neurohormonal changes may also be implicated in alterations of chemosensitivity

in obesity. In this context, the interplay between obesity, leptin, and ventilatory
drive seems to play an important although not fully clarified role.
Leptin is a satiety hormone produced by adipocytes that, in addition to reducing
appetite and weight via receptors in the hypothalamus, increases ventilation in ani-
mal models by stimulating central respiratory centers after penetrating the blood-
brain barrier [64].
Leptin levels rise in proportion to body fat and obese subjects usually have high
leptin levels, while hypoxia (in the context of OSA and OHS) also seems to exert an
influence on leptin production [1, 2].
The association of leptin with chemosensitivity in humans is not absolutely
clear. In mostly nonobese eucapnic OSA patients, both HCVR and leptin levels
were higher than in matched healthy controls, and a significant correlation existed
between HCVR and leptin levels [20]. Yet hypercapnic OSA patients, in spite of a
significantly lower HCVR, had leptin levels similar to those found in eucapnic
OSA [20].
High serum leptin concentrations have been associated with the presence of
hypercapnia in obesity [65] and OSA [66]. In obese subjects leptin was a better
predictor of hypercapnia than the degree of adiposity [65], while in OSA leptin
was the only independent predictor of hypercapnia [66]. Furthermore, serum
leptin levels are inversely associated with respiratory drive (P0,1) at rest in obese
subjects [6].
In order to explain the paradox of a depressed ventilatory drive and hypercapnia
in the presence of high leptin levels, it has been suggested that in some obese sub-
jects, central resistance to ventilatory stimulatory effects of leptin may develop [2].
Leptin has to penetrate the blood-brain barrier in order to affect the respiratory
center. The finding that obese individuals have leptin levels three times higher com-
pared to lean controls while their leptin CSF/serum ratio is fourfold lower [67] sug-
gests that such resistance may be the result of reduced leptin CSF penetration [1].
The observation that NIPPV use significantly reduces leptin levels [68] has led to
the hypothesis that the improvement noted with positive pressure treatment in the
central chemosensitivity of OHS patients [10, 47, 48] may be mediated through a
reduced leptin resistance.
Yet the hypothesis of leptin resistance is not uniformly supported by all
studies. Redolfi et al. [69] found that leptin levels were considerably elevated
in OHS patients compared with reference values but remained much lower
than those observed in matched obese eucapnic controls. Several months after
initiation of NIPPV, PaCO2 was normalized in these patients, HCVR was
increased by 100%, and leptin levels were increased by 50%, although they
still remained significantly lower than in eucapnic obesity. More study is
therefore needed in order to clarify the exact role of leptin in the control of
ventilation in obesity.
Conclusion
Eucapnic obesity may be associated with an augmented chemosensitivity which
represents a compensatory response to mass loading of the respiratory system.
Yet, a small subset of obese subjects who develop daytime hypercapnia demon-
strates a blunted respiratory drive. Although secondary to nocturnal hypoventila-
tion and the subsequent development of daytime hypercapnia, this blunted
chemosensitivity contributes to the establishment and maintenance of daytime
hypercapnia.
10 N. Markou et al.
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Obesity, Respiratory Mechanics and Its
Impact on the Work of Breathing, 2
Neural Respiratory Drive, Gas
Exchange and the Development
of Sleep-Disordered Breathing
Culadeeban Ratneswaran, Patrick Murphy, Nicholas Hart,

and Joerg Steier
2.1 Respiratory Mechanics and Obesity
2.1.1 Background
Obesity reduces life expectancy and increases morbidity and mortality [1, 2]. It
causes serious health risks including diabetes, cardiovascular disease and cancer
[3]. Despite this, the worldwide prevalence of obesity has doubled since the 1980s
[4]. Although there is extensive knowledge about the cardiovascular and metabolic
risks of obesity, respiratory comorbidities of obesity are less well understood.
The degree of obesity can be measured using the body mass index (BMI), often
used due to its ease of use and correlation with adverse health outcomes. BMI, how-
ever, is not a good measure of body fat distribution. There is ongoing discussion
whether indices of fat distribution may be better predictors of morbidity [5] and
whether they are of greater relevance to the development of sleep-disordered breath-
ing, but this has not been born out by prospective studies [6, 7].
2.1.2 Non-communicable Disease
According to the World Health Organization (WHO), non-communicable disease

(NCD) contributes to the majority of mortality worldwide. NCD is commonly
C. Ratneswaran
Lane Fox Unit, Guy’s & St Thomas’ NHS Foundation Trust, London, UK
P. Murphy • N. Hart • J. Steier (*)
Lane Fox Unit, Guy’s & St Thomas’ NHS Foundation Trust, London, UK
King’s College London, Faculty of Life Sciences and Medicine, London, UK
e-mail: joerg.steier@kcl.ac.uk

16 C. Ratneswaran et al.
attributable to one of the following four factors: alcohol, tobacco, unhealthy diet
and physical inactivity [8]. The trend to lead a more sedentary lifestyle with reduced
metabolic needs, while energy intake increases, results in a general rise in body
weight with age [9, 10]. The population most at risk of obesity-related ill health
therefore tends to be middle-aged.
2.1.3 The Respiratory Muscle Pump
Effects of obesity can impact on the respiratory mechanics, as well as on neural

respiratory drive. The respiratory muscle pump sums up all muscle groups that con-
tribute to ventilation; it contains the diaphragm, chest wall muscles, neck and shoul-
der muscles and the abdominal muscles. Different parts of the respiratory muscle
pump are active during inspiration, expiration, awake at rest, during exercise or
while asleep. The most important muscle for inspiration is the diaphragm, which
separates the thoracic from the abdominal cavity. It delivers the majority of the work
of breathing in healthy individuals [11]. Due to its contribution to intrathoracic and
intra-abdominal pressure swings while breathing, it impacts on various effects asso-
ciated with ventilation. The diaphragm is made of three parts, the costal part, the
crural part and a central tendon (Fig. 2.1).
Fig. 2.1 The human diaphragm (reproduced from Gray’s Anatomy, 20th US edition, originally
published in 1918)
2 Obesity, Respiratory Physiology and Sleep-Disordered Breathing 17
Contraction of the diaphragm results in caudal movement of the dome-like struc-

ture in addition to expansion of the ribcage which is supported by other inspiratory
muscle groups like the parasternal intercostal muscles, the scalenes and accessory
muscle groups. The resulting negative intrathoracic pressure results in inspiratory
airflow. In expiration, the diaphragm is largely relaxed and positive intra-abdominal
pressures will push it back up into the thoracic cavity. Elevated intra-abdominal
pressures in obesity significantly impact on the function of the diaphragm by
increasing the load during inspiration and expiration (Fig. 2.2).
2.1.4 Gas Exchange in Obesity
Gas exchange is typically measured using the diffusing capacity of the lungs for
carbon monoxide (DLCO). The DLCO is relatively well preserved in mild obesity
[12–16], but the pattern in severe obesity is less well understood [16, 17]. However,
intra-abdominal pressures in obesity impact on the diaphragm and the intrathoracic
Brain
Neural Obesity
Sleep Respiratory OSA
Drive OHS
EMG
Capacity Respiratory Load
Muscles
Respiratory
Failure
↓02, ↑CO2
Fig. 2.2 The load-capacity ratio of the respiratory muscle pump, simplified scheme. Multiple fac-
tors in obesity contribute to an increased load that leads to an elevated neural respiratory drive to
recruit from the capacity of the respiratory muscle pump. If the elevated level of neural drive can-
not be sustained (e.g., fatigue) or is influenced by other factors (e.g., sleep, drugs), an imbalance
between load and capacity will develop and cause symptoms and respiratory failure when awake
and sleep-disordered breathing when asleep
cavity, particularly in supine posture, and contribute to a ventilation-perfusion mis-

match in the posterobasal compartments of the lung, and this mismatch contributes
to the effect of alveolar hypoventilation.
2.1.5 Lung Volumes in Obesity
Lung volumes in obesity are either relatively normal or slightly reduced, indicating
a restrictive ventilatory defect (Fig. 2.3). The forced expiratory volume in 1 s
(FEV1) is lower in obesity compared to nonobese subjects [19, 20], suggesting that
in addition to an increased elastic load, obese subjects must overcome an increased
airway resistance which is a consequence of the reduction in operational lung vol-
umes (Figs. 2.4 and 2.5). The expiratory reserve volume (ERV) is low in morbidly
obese subjects, and the functional residual capacity (FRC) is close to the residual
volume (Fig. 2.3).
2.1.6 Respiratory Mechanics and Changes in Obesity
During normal inspiration, the diaphragm descends and the decrease in intratho-
racic pressures initiates inspiratory airflow; in parallel, the diaphragm descent draws
blood into the vena cava and the right side of the heart. During expiration, an
increase in intrathoracic pressures leads to air being expelled from the lungs. While
inspiration is generally an active process, expiration follows passively due to the
elastic recoil of the chest compartment and positive intra-abdominal pressures, and,
unless enforced, expiration does not require significant muscle activity in the nor-
mal subject at rest.
In obesity, many factors related to the respiratory system change. Intra-abdominal
pressures are high, particularly with visceral obesity, and this causes an increased
preload on the diaphragm movement, specifically in supine posture. The abdominal
pressures are transmitted to the thoracic cavity where they result in reduced trans-
pulmonary pressures [18]. Due to the reduced pressure gradient, it is more likely
that obese subjects breathe close to the residual volume (RV) with the functional
residual capacity (Fig. 2.2) which leads to increased airway resistance due to the
closing volume of the small airways [21]. This effect increases the work of breath-
ing due to a low compliance [22] (Figs. 2.4 and 2.5). In supine posture, the work of
breathing increases further [18, 23, 24], the intra-abdominal pressure impacts
directly on the diaphragm, and an intrinsic positive end-expiratory pressure (PEEPi)
develops [24, 25]. Neural respiratory drive increases to recruit force, but it can be
offset by inflating the chest with continuous positive airway pressure (CPAP;
Fig. 2.6) [24]. However, without noninvasive support, patients with obesity are
prone to develop a restrictive spirometry. With sleep onset, neural respiratory drive
falls and the required minute ventilation is no longer maintained, which results in
hypoventilation and the development of hypercapnia.
a
TLC
6 Non-obese 6
Obese
IRV TLC
Lung Volume (L)
Lung Volume (L)

IRV
3 V1 3
ERV V1
ERV
RV
RV
0 0
seated supine seated supine
100 TLC 100
TLC
80 80
Non-obese IRV Obese
Lung Volume (%predTLC)
Lung Volume (%predTLC)
60 60 IRV
V1
40 40 V1
ERV ERV
20 20
RV RV
0 0
seated supine seated supine
Fig. 2.3 Simplified schematic illustration of lung volumes seated and supine in normal and obese
subjects, expressed as litres (upper panel) and per cent predicted TLC (lower panel). TLC total
lung capacity, IRV inspiratory reserve volume, Vt tidal volume, ERV expiratory reserve volume,
RV residual volume. With friendly permission from Thorax [18]
PV seated, N9 + O1
140
120
Volume (%predTLC)
100
80
60
20
-40 -30 -20 -10 0 10 20 30 40 50

Transpulmonary Pressure (cmH20)
Fig. 2.4 Pressure–volume (PV) curves seated of a normal (N9, male, 66 years, 1.72 m, body mass
index (BMI) 23.3 kg/m2; filled circles) and matched obese (01, male, 60 years, 1.73 m, BMI
34.4 kg/m2; open circles) subject. Functional residual capacity (FRC) levels and dynamic compli-
ance are indicated by bold grey bars. The PV curve in the obese is restricted in lung volume and
diminished in slope, the FRC is low. Despite the differences in the slope of the static PV curves,
the dynamic compliance, illustrated by the diagonal grey bars, is not substantially different
between the obese and normal subject. With friendly permission from Thorax [18]
PV supine, N9 + O1
140
120
Volume (%predTLC)
100
80
60
20
0
-40 -30 -20 -10 0 10 20 30 40 50
Transpulmonary Pressure (cmH20)
Fig. 2.5 Pressure–volume curves supine of a normal (N9, filled circles) and matched obese (01,
open circles) subject. Compared with the seated posture, the slope of the curves is diminished, in
the obese functional residual capacity approximates residual volume. Dynamic compliance is
lower than when seated and more different between obese and normal subject. With friendly per-
mission from Thorax [18]
Sitting Supine Supine+CPAP

EMGdi channel 5 EMGdi channel 5 EMGdi channel 5
20 cm H2O 20 cm H2O 20 cm H2O 400 µV
Poes 3
Poes 2
Poes
1
Pgas Pgas Pgas
Pdi
Pdi
Pdi
2 cm H2O
Pmask
40 I/min
Flow
Flow
10 s 10 s 10 s
Fig. 2.6 Resting breathing in an obese subject (body mass index 42 kg/m2, neck circumference
43 cm) when seated (left), supine without CPAP (middle) and with CPAP (right). The change in
end-expiratory oesophageal baseline pressure is reflected by the horizontal dotted lines (nos 1–3).
There is PEEPi of approximately 6 cm H2O (vertical lines indicate the start of inspiratory flow,
difference between horizontal dotted lines 2 and 4 = PEEPi). Zero flow is indicated by the horizon-
tal line. The right panel shows the same patient supine breathing with CPAP of 6 cm H2O (full
facemask). Neural respiratory drive to the diaphragm increases when changing posture from sitting
to supine and decreases with CPAP; PEEPi is offset with CPAP and pressure swings of Poes and
Pdi are smaller. Note that on the lower right trace we do not measure flow but mask pressure
because flow is predominantly inspiratory when receiving CPAP. The inspiratory deflection in
mask pressure was chosen instead of flow to mark the beginning of inspiration (vertical line).
CPAP continuous positive airway pressure, EMGdi electromyogram of the diagram (channel 5
records the biggest EMG signal; Poes oesophageal pressure, Pgas gastric pressure; Pdi transdia-
phragmatic pressure (Pdi = Pgas − Poes); PEEPi, intrinsic positive end-expiratory pressure;
EMGdi in μV, all pressures in cm H2O, flow in l/min. With friendly permission from Thorax [24]
2.2 Sleep-Disordered Breathing
2.2.1 Fat Distribution
Sleep-disordered breathing relates to abnormal breathing when asleep; the most

common types of abnormal breathing during sleep in obesity are obstructive sleep
apnoea (OSA), obesity hypoventilation syndrome (OHS) and an overlap syndrome
(OSA/OHS). Neck circumference is a predictor of OSA which suggests that upper
body or central obesity contributes more to its pathogenesis than general weight
gain [26]. Upper body obesity is thought to have a greater cardiovascular and meta-
bolic risk than lower body obesity, and central obesity has a greater impact on spi-
rometric results compared to the subcutaneous deposition of adipose tissue [27].
2.2.2 T
he Relationship of Weight Gain and Obesity
with Poor Sleep
Obesity is directly related to poor sleep quality, through the development of diseases
including obstructive sleep apnoea (OSA) and obesity hypoventilation syndrome
(OHS). Weight gain is also known to cause poor sleep independent of other underly-
ing conditions [28, 29]. Furthermore, poor sleep quality and reduced sleep quantity
have been found to lead to weight gain, hence perpetuating a vicious cycle of poor
sleep and obesity.
Chronic sleep deprivation and the associated daytime sleepiness lead to reduced
levels of exercise, and sleep deprivation is known to increase appetite and produce
hyperphagia [30, 31]. These changes occur due to complex hormonal regulation
including cortisol, an increased level of ghrelin and altered levels of leptin [30, 32].
Poor sleep quality and quantity have also been suggested to reduce energy expendi-
ture due to abnormal thermoregulation and energy expenditure [33].
Adipose tissue is the largest endocrine organ, and it secretes leptin. Leptin par-
ticipates in a number of metabolic pathways. It directly affects neuroendocrine
functioning, and energy intake, via specific receptors in the hypothalamus, with one
of its main roles being the reduction of appetite. Leptin levels increase exponen-
tially with increasing levels of fat mass. However, obese individuals are thought to
develop a ‘leptin resistance’ due to permanently increased levels of leptin [34], and
obese patients with OSA have significantly higher levels of leptin than those with-
out, independent of body fat [35]. These hormonal changes, in addition to changing
the societal sleep pattern, perpetuate a cycle whereby poor sleep and weight gain are
intrinsically related. The weight gain can lead to altered respiratory mechanics and,
eventually, the development of sleep-disordered breathing.
2.2.3 Obstructive Sleep Apnoea
Obesity is a significant risk factor in the pathogenesis of OSA [26, 36]. OSA is a
syndrome in which recurrent collapse of the upper airway leads to apnoeas and
hypopnoeas during sleep [37]. Besides upper airway collapsibility, mechanical
changes related to the respiratory muscle pump during obstructive respiratory events
include increasing pleural pressure swings [38], decreased transpulmonary pres-
sures [18], reductions in expiratory reserve volumes [18] and functional residual
capacity [39] and decreased compliance [24, 40] compared to healthy individuals
[25, 41]. Additionally, expiratory flow limitation and an intrinsic PEEP have been
described [24, 25]. Most of these limitations are successfully counterbalanced by
continuous positive airway pressure (CPAP; Fig. 2.6).
2.2.4 Obesity Hypoventilation Syndrome
Obesity hypoventilation syndrome (OHS) [42] was historically known as the

‘Pickwickian’ syndrome after Charles Dicken’s stories that described the features in
the character of fat boy ‘Joe’. These patients have a propensity towards a blunted
neural respiratory drive which results in hypercapnia and hypoxia, whilst awake and
more markedly during sleep. Obese patients tend to develop this condition as a con-
sequence of the imposed mechanical limitations on their respiratory requirements
secondary to the high intra-abdominal pressures caused by adipose tissue deposi-
tion. Problems caused by OHS are directly related to an increased body habitus, and
weight loss can potentially reverse this condition. To improve the hypercapnic respi-
ratory failure, patients benefit from noninvasive ventilatory support, typically
offered at night. OHS has some clinical features of OSA, and many of these patients
tend to have an overlap syndrome (OSA/OHS).
With increasing prevalence of obesity, particularly morbid obesity, screening for
sleep-disordered breathing becomes important. The majority of patients with mor-
bid obesity have at least a mild degree of sleep-disordered breathing [43], while
around a quarter of pre-bariatric patients who score >4 points on the STOP-BANG
questionnaire [44] require CPAP therapy [45]. A restrictive spirometry (FVC <3.5 L
in men and <2.3 L in women) and reduced daytime oxygenation (SpO2 <95% in
men and <93% in women) can also be useful markers to indicate patients with fea-
tures of nocturnal hypercapnia [46].
2.3 Summary
The load on the respiratory muscles in obesity is high, and this leads to an increased
work of breathing and elevated levels of neural respiratory drive. High intra-
abdominal pressures become more relevant with supine posture; they cause an
intrinsic PEEP in morbidly obese subjects and impose an inspiratory preload on the
diaphragm. Increased airway resistance due to the low operational volumes increases
the work of breathing further and impacts on the compliance of the respiratory sys-
tem. Lastly, the reduced transpulmonary pressures lead to a more restrictive lung
function in obesity.
Sleep-disordered breathing in obesity develops due to upper airway collapse
(OSA) or hypoventilation (OHS) which is more likely with the increased load in
obesity. With increasing neck circumference, the upper airway is more likely to
collapse when asleep, and this explains the high prevalence of OSA in obesity.
The impact of obesity on the intrathoracic compartment requires elevated levels
of neural respiratory drive which are not maintained when falling asleep; the sub-
sequent loss of the neuromuscular tone of the respiratory muscles leads to
hypoventilation. The blood gas analysis and restrictive lung function parameters
indicate the imbalance between load and capacity of the respiratory system and
determine the likelihood of sleep-disordered breathing. Acknowledging patho-
physiological changes is important in the context of screening for sleep-disor-
dered breathing in this cohort.
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Implications of Obesity
for Mechanical Ventilation 3
Paolo Formenti and John J. Marini
3.1 Introduction
Recent data from the United States and Europe indicate that approximately one
third of adult men and women are overweight, with body mass index (BMI) values
exceeding 25. Results from studies that focused attention on the risks associated
with overweight have reported conflicting results [1–4]. Improved medical man-
agement of obesity-related chronic diseases or differences between the US general
population and populations in other studies may account for the findings of some
reports that overweight was not associated with an excess risk of death [5].
However, a large prospective study reported that obesity was strongly associated
with mortality risk and suggested that even moderate elevations in BMI portend an
increased mortality risk [6]. Despite these conflicts, it is clear that obesity has
potential to directly affect respiratory mechanics, since it increases oxygen con-
sumption and carbon dioxide production while at the same time stiffens the chest
wall, compresses the lungs, and increases the work of breathing. Adipose tissue
around the rib cage and abdomen inhibits chest wall expansion and reduces func-
tional residual capacity (FRC). For this and other reasons that we examine in the
present chapter, ventilator settings should be adjusted to minimize potentially
adverse consequences of obesity.
P. Formenti
SC Anestesia e Terapia Intensiva, Università degli studi di Milano, Milan, Italy
J.J. Marini (*)
University of Minnesota, Minneapolis, MN, USA
e-mail: marin002@umn.edu

28 P. Formenti and J.J. Marini
3.2 natomic and Physiologic Considerations

A
in Obesity (Fig. 3.1)
3.2.1 Non-pulmonary-Associated Alterations
Both excess adipose tissue and its distribution are considered obesity-associated
risk factors for cardiovascular respiratory disease [7]. Centralized deposits of adi-
pose tissue are metabolically more active than fat distributed in the periphery and
are more highly associated with metabolic complications such as dyslipidemia, glu-
cose intolerance, and diabetes mellitus [8]. Morbidly obese patients with a high
proportion of visceral fat are also at greater risk from cardiovascular disease, left
ventricular dysfunction, and stroke [9]. The exact mechanism for this increased
attributable risk is not known, but recent studies focused on hormonal changes,
inflammation, and circulatory impairment may help explain the correlation [10].
Elevated body mass index seems to be associated with a deregulation of leptin and
adiponectin secretion, two hormones that influence inflammation and oxidative
stress regulation [11]. In fact, some experimental and clinical studies showed how
these hormones are involved in the activation of macrophages, leukotriene synthe-
sis, and inflammatory cytokine expression that increase airway responsiveness and
smooth muscle activation of the vessels [12, 13], affecting both the right heart mass
and volume and the pulmonary arteries [14]. Other obesity-related physiological
Small mouth opening Low FRC

Short thyromental distance Increased intrapulmonary shunt
Increased neck Decreased chest wall and lung
circumference compliances
Decreased neck motility Increased airway resistance
Large breasts and tongue
Increased mechanical
pressure
increased metabolic
demands
simultaneously
increase the work of
breathing
Increased intrabdominal
pressure
Reduced diaphragmatic
excursion
Reduced chest wall compliance
Normal subject Obese subject
Fig. 3.1 (a) Anatomic challenges of obesity for ventilatory support. (b) Consequences of obesity
for lung mechanics during passive ventilation
3 Implications of Obesity for Mechanical Ventilation 29
disturbances include menstrual disorders, irregular bleeding, and amenorrhea. Some

studies demonstrate that obesity is associated with osteoarthritis, even if the central
role of excess body weight in causing of this condition remains unconfirmed [15].
Increased triglyceride stores are associated with a linear increase in the production
of cholesterol. In turn, greater cholesterol production is associated with increased
cholesterol secretion in bile and the development of gall bladder disease. Increased
levels of circulating triacylglycerides in obesity are associated with decreased con-
centrations of high-density lipoprotein (HDL) cholesterol with the attendant predis-
position to cardiovascular disease. Enhanced insulin resistance and increased insulin
demand may promote diabetes mellitus, sodium retention, and hypertension [16].
3.2.2 Pulmonary Consequences of Obesity
Increased abdominal volume, intrathoracic fat, and obesity-associated chronic heart

disease affect both lung volumes and gas exchange.
3.2.2.1 Upper Airway Anatomy

Deposition of adipose tissue in the pharyngeal walls narrows the air passage,
encourages upper airway collapse during spontaneous ventilation [17], and imposes
difficulty in accomplishing mask ventilation and/or endotracheal intubation.
Physical signs portending difficult mask ventilation or intubation include small
mouth opening, short thyromental distance, increased neck circumference,
decreased neck motility, and large breasts and tongue. For such patients optimal
positioning is important, and advanced airway devices (such as fiberoptic broncho-
scope, glidescope, and laryngeal mask) should be available to facilitate securing the
airway. Availability of bronchial blockers and tube exchangers may help in cases of
difficult single-lumen tube placement [18].
3.2.2.2 Lung Volume

Morbid obesity is associated with reduced end-expiratory lung volumes (EELV) in
mechanically ventilated patients, as FRC declines exponentially with increasing
BMI. A low FRC, paired with increased intrapulmonary shunt, decreased chest wall
and lung compliances, increased airway resistance, and atelectasis, predisposes the
obese patient to rapid desaturation upon induction of anesthesia [19]. Abnormal
upper airway anatomy aggravates the difficulty of effective mask ventilation and
safe intubation, especially in the presence of OSA [20]. The supine position further
decreases FRC, due to cephalad displacement of the diaphragm, airway closure in
recumbency, and positional increase of pulmonary blood volume. Lung as well as
chest wall compliances are decreased when supine, encouraging ventilation/perfu-
sion mismatching [8].
3.2.2.3 Gas Exchange

Oxygen consumption and carbon dioxide production tend to increase in the obese
as a result of the metabolic activity of the excess fat and the increased energy
consumption of weight supporting skeletal muscle [21]. Moreover, normocapnia is

usually maintained by increasing minute ventilation, a breathing burden that adds to
the increased oxygen demand. Some patients, however, develop obesity hypoventi-
lation syndrome (OHS), defined as chronic hypoventilation in the absence of lung,
chest wall, and neurological disease [22]. In these, hypoventilation and apnea origi-
nate centrally due to progressive desensitization to hypercapnia, which leads to an
increased dependence on the hypoxic drive to maintain respiration [23]. Even when
impairment of oxygen exchange due to CO2 buildup is modest, relatively low perfu-
sion of tissues due to inadequate blood flow per cell alters the oxidative response
[24], perhaps contributing to the propensity of such patients to develop infection
and atelectasis during their hospital stays [25].
3.2.2.4 Lung Elastance and Resistance

Increased fat in the thorax and abdomen is associated with an exponential decline in
respiratory compliance, which in some cases can fall to around 35% of predicted
normal [26], especially when small tidal breaths are taken in the supine position
[27]. Although accumulation of fat tissue in and around the chest wall leads to a
modest increment in chest wall elastance, recent work suggests that the increment
in total elastance is principally a consequence of an increased lung elastance [28].
Obesity is also associated with an increase in total respiratory resistance [29] indi-
cating that the number and/or caliber of functioning airways is reduced throughout
the tidal breathing cycle. However, although asthma and aspiration occur more
commonly in the very obese, specific airway resistance (calculated by adjusting for
the lung volume at which the measurements are made) generally remains within the
normal range [30]. Thus, the apparent reduction in airway caliber in the obese might
be attributable to the reduction in lung volumes rather than to airway obstruction
[26]. It is also possible that airway structures could be remodeled by exposure to
pro-inflammatory adipokines, or damaged by the continual opening and closing of
small airways during the breathing cycle [31]. For the same minute ventilation,
these derangements of lung elastance and resistance result in a relatively shallow
and rapid breathing pattern, an increase in the work of breathing and a limitation of
the maximum ventilatory capacity. In severe cases, breathing at low lung volume
places the tidal flow volume loop into a region where it may encroach on the maxi-
mal flow-volume envelope, increasing the possibility of expiratory flow limitation
during tidal breathing.
3.2.2.5 Respiratory Efficiency and Work of Breathing

Increased mechanical pressure from the abdomen, increments in pulmonary elas-
tance and resistance, and increased metabolic demands simultaneously burden the
respiratory pump and increase the work of breathing. In normocapnic obese indi-
viduals at rest, this may be reflected in a modest 30% increase in the workload, but
respiratory muscle inefficiency may limit the maximum ventilatory capacity and
lead to relative hypoventilation at times of high metabolic activity [32]. In the obese
individual with established daytime hypoventilation syndrome, work of breathing
may approach four times than predicted.
Because an obese individual’s respiratory muscles must work constantly

against a less compliant chest wall and higher airway resistance, it would be
expected that they could generate normal or even increased pressures. An early
study [33] examined the maximum inspiratory and expiratory pressures at differ-
ent lung volumes in morbidly obese compared with nonobese patients. At all
lung volumes, the pressures generated by obese patients were lower than those of
the nonobese patients, despite chronically heightened demands for diaphrag-
matic work. This deficiency may result from diaphragm dysfunction due to
increased abdominal and visceral deposits of adipose tissue. It has been sug-
gested that the additional load causes a length-tension disadvantage for the dia-
phragm due to muscle fiber overstretching, which is accentuated while the
individual is supine [34].
3.3 Mechanical Ventilation of the Obese Patient
The respiratory and non-respiratory changes described above require special atten-
tion during the management of obese individuals receiving ventilatory support,
especially during deep sedation or anesthesia (Table 3.1). A key objective is to keep
the lung open during the entire respiratory cycle.
Table 3.1 Special aspects of Body position

ventilating the obese patient • Avoid the customary <30 ° recumbent posture
• Upright
• Beach Chair
• Prone
• Lateral
• Reverse Trendelenburg
During ventilation
• Higher PEEP
• Recruiting maneuvers
• Minimize sedation
• Maintain patient’s baseline PaCO2 and pH
Monitor
• Mental alertness
• PECO2
• Oxygenation
• Cautiously interpret
–– Plateau pressure
–– Driving pressure
–– Stress index
• Selected patients
–– Transpulmonary pressure
–– Bladder pressure
Liberal post-extubation use of BiPAP
3.3.1 Airway Management
Obesity significantly increases the complexity of airway management procedures.

Patients with obesity present high risk for aspiration due to elevated intra-abdominal
pressure and large gastric volume. A large neck with limited mobility, decreased
mouth opening, big tongue, and short sternomental distance can pose serious chal-
lenges during endotracheal intubation attempts [35]. Any factor that contributes to
difficult viewing of the airway opening increases the possibility of complications.
Positioning the obese patient for intubation also presents unique challenges when
compared to those of lower body weight. In patients of normal weight, intubation
typically is performed while the patient is horizontal. However, in obese patients
decreased functional residual capacity, increased airway resistance, and propensity for
compressive airway closure often lead rapidly to hypoxemia in the supine, fully
recumbent position. Various compensatory techniques, including CPAP and high-
flow oxygen, may be employed to avoid desaturation during intubation attempts [36].
Equipment selection must be carefully considered prior to airway procedures. Other
than routine laryngoscope blades and endotracheal tubes, rapidly accessible equip-
ment should include laryngeal mask airways, flexible bronchoscopes, and an emer-
gency cricoidotomy kit. In addition, considerable operator strength may be required to
open, maintain, and properly secure the airway of an extremely obese patient.
3.3.2 Ventilatory Support
Selected special aspects of ventilating the massively obese patient are highlighted in
Table 3.1. Even more than in other patients in need of assistance for respiratory
insufficiency or failure, care should be taken in these vulnerable patients to avoid
injury to the lung parenchyma during ventilation. Advances in the understanding of
the mechanisms of ventilator-induced lung injury from animal studies and random-
ized controlled trials in patients with uninjured lungs in intensive care unit and
operation room have pushed anesthesiologists to consider lung-protective strategies
during intraoperative ventilation [37]. Doing so has been linked to better outcomes
in the postoperative period. There is general agreement that such approaches to lung
protection should include the use of relatively low tidal volume. Whereas higher
PEEP may not be universally helpful in patients of normal body mass, moderate
PEEP may prevent intra- and perioperative atelectasis and attendant pulmonary
complications in the obese. Protective effects, however, are currently ascribed more
to low VT than to PEEP. In fact, the use of relatively high PEEP does not seem to
protect against postoperative pulmonary complications in nonobese patients under-
going open abdominal surgery [38]. Furthermore, the role of driving pressure for
titrating ventilation settings in patients with uninjured lungs remains to be carefully
investigated, and virtually no data are available regarding driving pressures in the
massively obese.
A lung-protective strategy designed to minimize alveolar overdistention has
been reported to decrease mortality by 20% compared with a traditional ventilator
strategy [39]. However, the commonly applied plateau pressure (Pplat) limit of
30 cmH2O may prove inadequate to accomplish adequate gas exchange in morbidly
obese patients because of the increased elastance of the chest wall and altered lung
volumes. Numeric guidelines for safe airway pressure in such patients may be mis-
leading with regard to safe and effective ventilation, as the effects of obesity on the
chest wall must be separated from those attributable to increased lung elastance.
When selecting mechanical ventilator settings for obese patients, important physi-
ological factors are critical to consider. Thus, under conditions of no flow that char-
acterize the extremes of the tidal cycle, the pressure difference between airway
opening and pleural space (transpulmonary pressure, Ptp) is the distending pressure
across the lung. The Ptp is measurement useful in assessing the risk of ventilator-
induced lung injury [40]. Impressive increases in airway pressure may be observed
despite acceptable lung stresses and low injury potential because the excursions of
pleural pressure are unusually high [41]. Pleural pressure approximated by the use
of an esophageal balloon may help in PEEP selection and in determining the actual
peak and driving pressures applied to the lung, especially during spontaneous
breathing efforts [42]. A challenge at the bedside is that pleural pressure is not rou-
tinely measured, and therefore transpulmonary pressure is not known in most cases.
Clinicians who rely on airway pressures alone must estimate what pleural pressures
are in any given patient, and this limitation may lead to suboptimal ventilator
management.
In sample populations of patients with ALI/ARDS, one landmark randomized
controlled trial has shown a net reduction in mortality risk across the studied
population with the use of 6 mL/kg tidal volume compared with 12 mL/kg [43].
In supporting patients with obesity, it is especially important that tidal volume be
calculated on the predicted body weight, rather than on the measured value so as
to avoid the application of hazardous tidal volumes and resulting plateau and
driving pressures. (Predicted body weight is based on height and gender, and the
rationale for using it is that when a patient gains weight, the lung does not change
in size.) Even when selection of tidal volume is appropriately based on predicted
weight, regional over distension may occur. With changes in the impedance to
ventilation, pressure-targeted modes may result unpredictably in inappropriately
low tidal volumes in the massively obese. Conversely, pressure-targeted modes
allow marked increases in tidal volume and transpulmonary driving pressures
during vigorous spontaneous efforts. Such patients can generate large and poten-
tially damaging Ptp that may not be obvious to the clinician focused on airway
pressure alone.
3.3.2.1 Importance of Monitoring Respiratory Mechanics

and Gas Exchange
High baseline values of PaCO2, a tendency to develop dependent atelectasis,
and stiffness of the chest wall require that the clinician monitor gas exchange
and mechanics carefully. Alterations in respiratory impedance caused by
changes of body position or retention of airway secretions, for example, may
have pronounced effects on the adequacy of ventilation. Apart from pulse
oximetry, capnography of the exhaled airstream may give early clues to devel-
oping hypercapnia and end-expiratory airway closure [44]. Close monitoring
of mental status is also advisable during noninvasive ventilation and through-
out the immediate pre- and post- extubation periods to forewarn against
progressive CO2 retention.
Whether using a volume- or pressure-based approach to invasive mechanical
ventilation, estimated lung stress should be considered and attempts made to moder-
ate it in all patients with ALI/ARDS so as to avoid worsening of lung injury or
retarding of healing. This mandate is particularly important to observe in obese
patients who require elevated mechanical ventilation pressure settings. Interestingly,
prone positioning tends to improve FRC and oxygenation in obese patients, just as
it does in those with normal body habitus [45]. On the other hand, allowing PaCO2
to increase (“permissive hypercapnia”), a consequence of reduced driving pressures
[46], may not be tolerated well by obese patients, many of whom already have ele-
vated levels of arterial CO2 at baseline.
3.3.2.2 PEEP Setting

PEEP functions to increase lung recruitment and prevent unstable lung units from
collapsing in patients who are mechanically ventilated for ARDS. The level of
PEEP required to achieve these benefits, however, is influenced by the properties
both of the lung and of the chest wall 46[47]. Because chest wall elastance may be
profoundly increased in morbid obesity, such characteristics increase the intrapleu-
ral pressure and decrease the Ptp resulting from any given airway pressure. Thus,
the level of PEEP needed to support equivalent oxygenation may be higher in mor-
bidly obese patients than in patients with normal BMI. A study finding that conven-
tional levels of PEEP superimposed on high tidal volumes did not improve
intraoperative arterial oxygenation of morbidly obese patients might support this
concept [48]. Ineffectiveness of PEEP, however, may also be secondary to redistri-
bution of blood flow to poorly or non-ventilated regions, resulting in increased
venous admixture and intrapulmonary shunt, even in patients who have no intrinsic
lung disease. Higher levels of PEEP may be more beneficial in obese patients with
ALI/ARDS who receive lung-protective, low tidal volume ventilation [49].
Respiratory system mechanics have been studied in spontaneously breathing
obese patients and in those who were paralyzed and/or deeply sedated during the
postoperative period. Obese patients exhibit reduced EELV, increased lung elas-
tance, and increased chest wall impedance [50]. FRC values in morbidly obese
patients are often below closing volume, especially while in the supine position.
This can result in sustained lung unit closure and/or expiratory gas trapping in the
dependent lung zones, worsening hypoxemia [51]. Wang and colleagues [48]
recently conducted a network meta-analysis with the intention to identify the opti-
mal mechanical ventilation strategy for obese patients. The results of this meta-
analysis show that using VCV associated with higher PEEP and single RM was
superior to other strategies in improving oxygenation, intraoperative pulmonary
compliance, and atelectasis in obese patients under anesthesia, whereas an alterna-
tive strategy (i.e., pressure-controlled ventilation with lower PEEP) was less
effective.
3.3.2.3 Effects of Body Positioning

In the supine obese patient, the cranial displacement of the diaphragm and the gravi-
tational effect of the abdominal contents upon the diaphragm and the thoracic cavity
reduce lung volumes [52, 53]. The use of paralytic agents and the subsequent decrease
in diaphragmatic muscle tone further enhance the atelectasis induced by the abdomi-
nal contents. Morbidly obese patients (BMI 42 ± 5 kg/m2) undergoing laparoscopic
gastric banding have a lower lung elastance and a greater end-expiratory lung volume
(EELV) when in the beach chair position compared to supine position [54]. Lemyze
and colleagues observed in critically ill mechanically ventilated obese patients (BMI
48.4 (95% confidence interval, 45–51.2) kg/m2) that the sitting position significantly
diminishes expiratory flow limitation and leads to a significant drop in auto-PEEP
compared to supine positioning [52]. In a study, prone positioning compared to supine
positioning leads to an increase in FRC, an increase in lung compliance, and improved
oxygenation in mechanically ventilated obese patients undergoing elective surgery in
the prone position [45]. This increase in lung volume observed in the prone position
might be most indicative of the influence upon the lungs of the mediastinal contents
during supine positioning. The improvement of oxygenation is also a result of a more
uniform distribution of pulmonary perfusion in the prone position that has been seen
in studies with healthy nonobese volunteers [55, 56].
3.3.3 Extubation and Weaning Period
Certain postoperative complications (specifically, surgical site infection and atelec-

tasis) occur more frequently among the obese population. Increased intra-abdominal
pressure and venous stasis help explain the link between perioperative deep venous
thrombosis, pulmonary embolism, and obesity. As expected, surgical procedures
that involve prolonged immobility are associated with greater risk. Abdominal and
thoracic operations pose significant risks to obese patients; atelectasis has been
found in up to 45% of obese patients following upper abdominal surgery [57]. Early
mobilization should be prioritized in obese patients to reduce the risk of pulmonary
dysfunction as well as veno-thrombosis [58].
The relatively prolonged duration of mechanical ventilation and higher oxygen
requirements of obese patients reflect their numerous physiologic alterations of pul-
monary function [8]. Studies of respiratory function have uniformly shown reduced
functional residual capacity due primarily to the cephalad intrusion of abdominal
contents in the peri-diaphragmatic lung zones, particularly in the recumbent pos-
tures [32]. Liberation from mechanical ventilation also tends to be delayed in mor-
bidly obese patients, due to increased work of breathing resulting from increased
airway resistance, abnormal chest elasticity, and inefficiency of the respiratory
muscles. It has been suggested that the reverse Trendelenburg positions at > = 45°
can facilitate the weaning process by facilitating larger tidal volumes and lower
respiratory rates. The beach chair position—a positioning angle of >60 ° from hori-
zontal—has been demonstrated to improve gas exchange as it minimizes the gas
trapping during tidal closure of dependent airways that otherwise is in evidence in
other recumbent postures [51, 52, 58].
3.3.4 Indications for Tracheotomy
Critically ill morbidly obese patients are more likely to be intubated, to remain
intubated, to stay in the ICU longer, and to encounter higher risk for in-hospital
death when compared with their nonobese counterparts [59, 60]. Patients with
obesity tend to require more sedation and store sedative medications that impede
recovery of alertness once the full support period has ended. Strong consider-
ation should be given to noninvasive ventilation in the period immediately fol-
lowing airway extubation so as to counter their heightened tendencies for OSA
and CO2 retention. For reasons already given, maintaining an upright position is
also helpful. As with patients with normal body habitus, the obese often require
tracheotomy for prolonged mechanical ventilation. Some morbidly obese patients
require tracheotomy to counter OHS and OSA, as well. The optimal timing of
tracheotomy and its impact on weaning from mechanical ventilation in critically
ill, morbidly obese patients remain controversial. Results from a retrospective
study suggest that tracheotomy performed in morbidly obese subjects within the
first 9 days may reduce the duration of MV but may not affect hospital mortality
[59]. Although it can be safely performed when appropriate precautions are
taken, obesity is a relative contraindication to percutaneous dilational tracheos-
tomy (PDT) because precise identification of neck anatomy is frequently difficult
[61]. The most common serious complication of tracheostomy is tube obstruc-
tion. Some procedures started percutaneously need to be converted to open tra-
cheostomy procedures due to bleeding, inability to pass the guidewire, and loss
of airway control. PDT was complicated by the inability to identify anatomic
landmarks, by non-life-threatening hemorrhage, and by malpositioning of the
tracheostomy tube that result in hypoxemia and bradycardia. Tube obstruction
within the first 24 hours after surgery usually results from tube impingement on
the posterior wall of the trachea, partial displacement into the mediastinum,
occlusive blood clot, or mucus plug. In a study of 89 obese patients with trache-
ostomy [62], the incidence of complications due to the procedure was 25%, with
an estimated mortality of 2%.
Conclusion
Obesity presents numerous challenges to the safe and effective implementation
of mechanical ventilation. Difficult access to the upper airway, chest wall restric-
tion, positional gas trapping, atelectasis, impaired ventilatory drive, compro-
mised gas exchange, and increased work of breathing are routinely encountered.
Evaluation of underlying lung mechanics is often challenging when attempting
to choose safe and effective machine settings, and the obese are at elevated risk
for complications during and after invasive ventilatory support. Careful consid-
eration of the patho-pathophysiology of this common condition serves to guide
the selection of treatment approaches best suited to optimize ventilation through-
out all stages of ventilatory support.
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Part II
Causes of Acute Respiratory Failure in the
Obese Patient
Obesity and Comorbidities
4
Cintia Zappe Fiori, Denis Martinez, and Alicia Carissimi
4.1 Introduction
In 2014, worldwide, 13% of the adults aged 18 years and over were classified as
obese [1, 2]. The relationship between obesity and the development of comorbidi-
ties is well established in the literature. The main comorbidities of obesity, accord-
ing to the American Heart Association/American College of Cardiology Foundation
guidelines for the Management of Overweight and Obesity in Adults, include
hypertension, dyslipidemia, type 2 diabetes mellitus, coronary heart disease, stroke,
obstructive sleep apnea (OSA), and respiratory problems.
C.Z. Fiori, Ph.D. (*)

Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio
Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil
Cardiology Division, Hospital de Clínicas de Porto Alegre (HCPA),
Porto Alegre, Rio Grande do Sul, Brazil
e-mail: cintiazfiori@gmail.com
D. Martinez, M.D., Ph.D.
Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio
Cardiology Division, Hospital de Clínicas de Porto Alegre (HCPA),
Porto Alegre, Rio Grande do Sul, Brazil
Graduate Program in Medicine, Medical Sciences, Universidade Federal do Rio Grande do
Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil
A. Carissimi, Ph.D.
Graduate Program in Psychiatry and Behavioral Science, Universidade Federal do Rio

44 C.Z. Fiori et al.
4.1.1 Obesity and Comorbidities
The primary aim of this chapter is to perform a systematic literature review of the
Medline and Cochrane databases. The search was based on a PICO (population,
intervention, comparator, and outcome) strategy. From 75,900 articles retrieved, the
filters listed in Table 4.1 allowed to identify 97 articles, further selected to our inclu-
sion criteria. Eleven studies met inclusion criteria (Table 4.2).
Table 4.1 Search strategy

Population Obese subjects
Intervention Not applied
Comparator Comorbidities (hypertension, dyslipidemia, type 2 diabetes mellitus, coronary
heart disease, stroke, sleep apnea, and respiratory problems)
Outcome Obesity associated with adverse comorbidities
Design Meta-analysis
Excluded Age <18 years or ≥65 years; animal species; publication dates older than 5 years
Table 4.2 Summary of studies

Author Number of Number of
(year) studies patients Comorbidities Conclusion
Zhang et al. 28 2403 Left ventricular Obesity is an independent
(2014) [5] randomized hypertensive hypertrophy risk factor for left
clinical trial patients (LVH) ventricular hypertrophy in
(mean age hypertensive patients
43.8–66.7 years)
Chen et al. 21 cohorts 1,124,897 (mean Cardiovascular Obesity is a risk factor for
(2013) [11] age 53.4 years) disease, coronary mortality from overall
heart disease, cardiovascular disease and
stroke for specific diseases,
including coronary heart
disease, ischemic stroke,
and hemorrhagic stroke
Lytsy et al. 2 cohorts 6069 Hypertension Obesity has a strong
(2014) [9] positive association with
development of
hypertension even in
absence of insulin
resistance
Cuspidi et al. 22 cohorts 5486 (mean age Left ventricular LVH occurs in a high
(2014) [4] range hypertrophy fraction of the obese
31–76 years population, as obesity-
related LVH is a powerful
risk factor for systolic/
diastolic dysfunction
4 Obesity and Comorbidities 45
Table 4.2 (continued)
Author Number of Number of
(year) studies patients Comorbidities Conclusion
Padwal et al. 14 cohorts 23,967 (mean Heart failure (HF) In patients with chronic
(2014) [6] age 66.8 years) HF, the obesity was
present in both those with
reduced and preserved
ventricular systolic
function. Mortality in both
HF subtypes was
U-shaped, with a nadir
at BMI levels of
30–34.9 kg m2
Kivimäki 7 cohorts 102,128 (mean Coronary artery Obesity was associated
et al. (2013) age disease (defined with an increased risk of
[13] 44.3 ± 9 years) as first nonfatal coronary artery disease
myocardial
infarction or
cardiac-related
death)
Cronin et al. 7 prospective 9319 patients Major Obesity is an independent
(2013) [7] studies with peripheral cardiovascular risk factor for CVEs
artery disease events (CVEs) (nonfatal myocardial
(PAD) (mean infarction, nonfatal stroke,
age 67–74) cardiovascular death) in
patients with PAD
Park et al. 11 23,181 patients Cardiovascular Low BMI was associated
(2013) [10] prospective (mean age causes, nonfatal with increased risks of
percutaneous 62 ± 10 years) myocardial major CVEs and death
coronary infarction, stent
intervention thrombosis, or
studies stroke
Juonala et al. 4 prospective 6328 patients Type 2 diabetes, Overweight or obese
(2011 [3] cohort (mean age of hypertension, children who were obese
studies 11.4 ± 4.0 years dyslipidemia, and as adults had increased
at baseline. The carotid artery risks of type 2 diabetes,
mean length of atherosclerosis hypertension,
follow-up was dyslipidemia, and carotid
23.1 ± 3.3 years) artery atherosclerosis
Thomas 11 30,146 adult Microalbuminuria Metabolic syndrome and
et al. (2011) prospective participants with or proteinuria and its components are
[12] cohort metabolic chronic kidney associated with the
studies syndrome disease (CKD) development of CKD
The 58 221,934 people Cardiovascular BMI, waist circumference,
Emerging prospective in 17 countries disease and waist-to-hip ratio do
Risk Factors cohort (age ≥40) not importantly improve
Collaboration studies cardiovascular disease risk
Wormser prediction in people in
et al. (2011) developed countries when
[8] additional information is
available for systolic
blood pressure, history of
diabetes, and lipids
BMI body mass index, CKD chronic kidney disease, CVEs cardiovascular events, HF heart failure,
LVH left ventricular hypertrophy, OSA obstructive sleep apnea, PAD peripheral artery disease
4.2 Discussion and Analysis
The risks for complications of obesity start in childhood. One meta-analysis

included four prospective cohort studies with mean length of 23 years at follow-up
of body mass index (BMI) from childhood to adult age. The mean prevalence of
obesity observed among adults was 20.7%. The individuals classified as overweight
or obese in childhood and obese as adults had increased risks of type 2 diabetes,
hypertension, dyslipidemia, and carotid artery atherosclerosis [3].
Left ventricular hypertrophy is a common consequence of obesity, indepen-
dently of hypertension. In 22 echocardiographic studies, with overall 5486 obese
individuals of both sexes, in the pooled obese population, the prevalence of left
ventricular hypertrophy was 56%. The likelihood of having left ventricular hyper-
trophy was 4.2-fold greater in obese than in their nonobese counterparts. A meta-
regression analysis of 14 studies with 2214 persons showed a significantly direct
correlation between BMI and left ventricular mass [4]. Zhang et al. [5] evaluated
28 randomized controlled trials comprising 2403 hypertensive patients. The over-
weight and obesity status were associated with left ventricular mass independently
of hypertension. There was statistical heterogeneity among studies due to differ-
ent blood pressure levels and left ventricular mass measurement methods at
baseline.
Heart failure is another major comorbidity, associated with elevated disability
and mortality rates. A meta-analysis of 14 studies of individuals with heart failure
with preserved versus reduced ejection fraction explored a relationship between
BMI and survival of these patients. Interestingly, mortality in both heart failure
subtypes was U-shaped, with a nadir at BMI levels of 30–34.9 kg m2, i.e., degree of
obesity I [6]. The shape is present in most studies of the meta-analysis.
Major cardiovascular events (CVEs) are often seen in obese individual, particu-
larly when atherosclerotic phenomena are already present. Cronin et al. [7] reviewed
seven prospective studies in patients with peripheral artery disease searching for an
association between markers of obesity and major CVEs, defined as nonfatal myo-
cardial infarction, nonfatal stroke, and cardiovascular death. The markers of obesity
were BMI, waist circumference, or waist-to-hip ratio. In 1872 patients with periph-
eral artery disease, a mild positive association between combined measures of obe-
sity and CVEs was found.
Adiposity is the major modifiable determinant of cardiovascular disease, but sev-
eral confounders need to be accounted. The Emerging Risk Factors Collaboration
evaluated the risk of first-onset cardiovascular disease in 58 prospective studies.
BMI, waist circumference, and waist-to-hip ratio did not importantly change the
prediction of cardiovascular disease risk in developed countries when compared
with systolic blood pressure, history of diabetes, and lipids [8].
The risk of incident hypertension is another example of the etiologic role of obe-
sity on cardiovascular disease. In two prospective cohorts with a median of 10 years
of follow-up, 884 (48%) persons developed hypertension and 1639 (39%) pro-
gressed to a higher blood pressure stage. Patients who are overweight or obese,
without insulin resistance, had 46% higher odds to develop high blood pressure and
32% higher odds of hypertension progression than those with normal weight and no
insulin resistance [9].
Eleven prospective percutaneous coronary intervention studies evaluated the
association between BMI and the risk of major CVEs, defined as death from cardio-
vascular causes, nonfatal myocardial infarction, stent thrombosis, or stroke, and
death after percutaneous coronary intervention. The risk of major CVEs and mortal-
ity declined among patients with higher BMI [10]. As this analysis supports an
inverse relationship of BMI with major CVEs and all-cause mortality, it is possible
that more obese people are selected for resistance to coronary complications, having
adapted and survived immense overloads. Less obese subjects, on the other hand,
were not challenged to survive cardiac overworks, being exposed to early coronary
problems and mortality.
Chen et al. [11] analyzed 20 cohorts and identified 49,184 cardiovascular deaths
after a mean follow-up of 9.7 years. East Asians with a BMI of 25 or above had a
9% higher risk of death from overall cardiovascular disease, compared with the
reference range of 22.5–24.9 BMI. Compared to BMI ranges of 30–32.4, 32.5–34.9,
and 35–50, the risk was increased by 59%, 74%, and 97%, respectively.
Thomas et al. [12] included eleven studies in a meta-analysis that evaluated the
development of microalbuminuria or proteinuria and/or chronic kidney disease in
participants with metabolic syndrome. Nine studies evaluating 28,897 patients dem-
onstrated that the obesity component was associated with an odds ratio increase to
19% for development of estimated glomerular filtration rate <60 ml/min per 1.73 m2.
Kivimäki et al. [13] assessed the association of job strain and lifestyle risk fac-
tors with the risk of coronary artery disease in 14 prospective cohort studies with a
mean follow-up time of 7.3 years. Obesity was one of four lifestyle risk factors.
Compared to healthy controls, the risk of incident for coronary artery disease was
66% greater for participants with obesity and 113% for obese people reporting job
strain.
Our search strategy did not retrieve meta-analysis evidence evaluating obesity
and respiratory system-related comorbidities. Obstructive and central sleep apnea,
obesity hypoventilation syndrome, asthma, and chronic obstructive pulmonary dis-
ease are seriously impacted by obesity, but the evidence is mostly of low level.
Irrespective of the search, it is important to highlight the epidemiological studies
corroborating the OSA-obesity association [14–16].
Peppard et al. [14] evaluated the longitudinal association between weight change
and OSA, in a sample from the Wisconsin Sleep Cohort Study of the natural history
of OSA in 690 middle-aged adults. A 10% weight gain predicted an increase of
approximately 32% in the apnea-hypopnea index (AHI). This weight gain increased
sixfold the odds for AHI >15.
A population-based investigation of more than one thousand people, from the
Sao Paulo Epidemiologic Sleep Study, showed that one in three (32.8%) subjects
investigated had an AHI >5. The risk for OSA was 2.6-fold higher among over-
weight subjects and 10.5-fold higher for obese subjects [15].
Brown et al. [16] investigated 3040 subjects of the Sleep Heart Health Study, in
search of association between baseline OSA severity and increase in BMI after
5 years. While people with normal AHI had an increase of 0.34 kg/m2 in BMI,
people with AHI 5–30 had a BMI increase of 0.55 kg/m2 and with AHI >30 of
0.85 kg/m2. This data represents an explanation for the difficulty of weight loss in
people with comorbid OSA.
Conclusion
Cardiovascular diseases were the comorbidities more often associated with obe-
sity in meta-analysis studies. However, larger and more homogeneous studies
and meta-analyses including respiratory comorbidities, such as OSA, are needed
to improve evidence level.
4.3 Key Major Recommendations
• Meta-analyses of epidemiological studies and randomized trials are necessary to

improve the evidence level of the literature on obesity and its consequences.
• Obesity should not be regarded as a homogeneous state of increased body mass
since differential effects of fat accumulation were seen in the reviewed
literature.
• Respiratory, including OSA, metabolic, osteoarticular, neoplastic, and even
social consequences of obesity are seldom investigated and lack high level
evidence.
References
1. WHO (World Health Organization) Obesity and overweight, Fact Sheet n 311, 2015. Available:
http://www.Who.Int/Mediacentre/Factsheets/fs311/en/# Accessed on: 06 Jan. 2016.
2. WHO Physical status. The use and interpretation of anthropometry. Report of a WHO expert
committee. WHO technical report series, vol. 854. Geneva: World Health Organization;
1995.
3. Juonala M, Magnussen CG, Berenson GS, Venn A, Burns TL, Sabin MA, Srinivasan SR, Daniels
SR, Davis PH, Chen W, Sun C, Cheung M, Viikari JS, Dwyer T, Raitakari OT. Childhood adi-
posity, adult adiposity, and cardiovascular risk factors. N Engl J Med. 2011;365(20):1876–85.
4. Cuspidi C, Rescaldani M, Sala C, Grassi G. Left-ventricular hypertrophy and obesity: a system-
atic review and meta-analysis of echocardiographic studies. J Hypertens. 2014;32(1):16–25.
5. Zhang K, Huang F, Chen J, Cai Q, Wang T, Zou R, Zuo Z, Wang J, Huang H. Independent
influence of overweight and obesity on the regression of left ventricular hypertrophy in hyper-
tensive patients: a meta-analysis. Medicine (Baltimore). 2014;93(25):e130.
6. Padwal R, McAlister FA, McMurray JJ, Cowie MR, Rich M, Pocock S, Swedberg K, Maggioni
A, Gamble G, Ariti C, Earle N, Whalley G, Poppe KK, Doughty RN, Bayes-Genis A, Meta-
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patient data. Int J Obes (Lond). 2014;38(8):1110–4.
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events in patients with peripheral artery disease. Atherosclerosis. 2013;228(2):316–23.
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AM, Pennells L, Thompson A, Sarwar N, Kizer JR, Lawlor DA, Nordestgaard BG, Ridker
P, Salomaa V, Stevens J, Woodward M, Sattar N, Collins R, Thompson SG, Whitlock G,
Danesh J. Separate and combined associations of body-mass index and abdominal adipos-
ity with cardiovascular disease: collaborative analysis of 58 prospective studies. Lancet.
2011;377(9771):1085–95.
9. Lytsy P, Ingelsson E, Lind L, Arnlöv J, Sundström J. Interplay of overweight and insulin resis-
tance on hypertension development. J Hypertens. 2014;32(4):834–9.
10. Park DW, Kim YH, Yun SC, Ahn JM, Lee JY, Kim WJ, Kang SJ, Lee SW, Lee CW, Park SW,
Park SJ. Association of body mass index with major cardiovascular events and with mortality
after percutaneous coronary intervention. Circ Cardiovasc Interv. 2013;6(2):146–53.
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M, Tsugane S, Tamakoshi A, Gao YT, Yuan JM, Shu XO, Ozasa K, Tsuji I, Kakizaki M,
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Pednekar MS, Sauvaget C, Sasazuki S, Yang G, Koh WP, Xiang YB, Ohishi W, Watanabe
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B, McLerran D, Sinha R, Thornquist M, Kang D, Feng Z, Boffetta P, Zheng W, He J, Potter
JD. Association between body mass index and cardiovascular disease mortality in East Asians
and South Asians: pooled analysis of prospective data from the Asia cohort consortium. BMJ.
2013;347:f5446.
12. Thomas G, Sehgal AR, Kashyap SR, Srinivas TR, Kirwan JP, Navaneethan SD. Metabolic
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D, Dragano N, Ferrie JE, Goldberg M, Hamer M, Jokela M, Karasek R, Kittel F, Knutsson A,
Koskenvuo M, Nordin M, Oksanen T, Pentti J, Rugulies R, Salo P, Siegrist J, Suominen SB,
Theorell T, Vahtera J, Virtanen M, Westerholm PJ, Westerlund H, Zins M, Steptoe A, Singh-
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tors with risk of coronary artery disease: a meta-analysis of individual participant data. CMAJ.
2013;185(9):763–9.
14. Peppard PE, Young T, Palta M, Dempsey J, Skatrud J. Longitudinal study of moderate weight
change and sleep-disordered breathing. JAMA. 2000;284(23):3015–21.
15. Tufik S, Santos-Silva R, Taddei JA, Bittencourt LR. Obstructive sleep apnea syndrome in the
Sao Paulo epidemiologic sleep study. Sleep Med. 2010;11(5):441–6.
16. Brown MA, Goodwin JL, Silva GE, Behari A, Newman AB, Punjabi NM, Resnick HE,
Robbins JA, Quan SF. The impact of sleep-disordered breathing on body mass index (BMI):
the sleep heart health study (SHHS). Southwest J Pulm Crit Care. 2011;3:159–68.
Atelectasis
5
Sevinc Sarinc Ulasli
5.1 Introduction
Atelectasis is defined as the collapse of lung. Atelectasis can be classified according

to the pathophysiologic mechanisms (obstructive, nonobstructive), the amount of
collapsed lung (lobar, segmental, total), or the location (lobe or segment). Surgery,
pain, mechanical ventilation, blockage in airway due to foreign object, mucus plug,
lung cancer, a poorly placed endotracheal tube, smoking history, and obesity are the
conditions of increasing atelectasis risk [1].
It has been well defined that obesity alters respiratory mechanics [2]. Restrictive
pattern with decreased compliance of respiratory system involving chest wall and
lungs in obese patients favors atelectasis [3].
In this chapter acute respiratory failure due to atelectasis in obese patients will be
discussed mainly focusing on the outcomes and prevention of atelectasis in obese
critically ill patients.
5.2.1 Causes of Atelectasis in Critically Ill Obese Patients
Functional residual capacity is reduced in obese patients [4]. Supine position and
longer bedbound periods also aggravate the reduction of functional residual capac-
ity in critically ill obese patients. Reduced traction of airway passage due to
decreased lung volumes causes airway collapse and atelectasis. Collapse of
S.S. Ulasli, M.D.

Department of Pulmonary Diseases, Hacettepe University,
School of Medicine, Sihhiye, 06100 Ankara, Turkey
e-mail: sevincsarinc@hacettepe.edu.tr

52 S.S. Ulasli
posterior and basal segments of lungs is frequently seen when anesthesia reduces
diaphragmatic tonus [5]. Moreover decreased residual capacity and increased clos-
ing volume during anesthesia, analgesia, and sedation also cause alveolar collapse.
Alveolar collapse alters the distribution and synthesis of surfactant which accelerate
atelectasis. Obese patients have also larger amount of atelectatic area when com-
pared with lean patients [6].
In obese patients, suppression of cough and deep breathing due to pain or
decreased mucociliary clearance as a result of intubation, anesthesia, and analgesia
leads to the accumulation of secretions and atelectasis. Moreover obese patients
frequently have respiratory comorbidities such as chronic obstructive pulmonary
disease (COPD), obstructive sleep apnea, or obesity hypoventilation syndrome
which prolong hospital and intensive care unit stays [3].
5.2.2 Outcomes of Atelectasis in Critically Ill Obese Patients
Atelectasis reduces compliance and increases work of breath. Ventilation perfusion

mismatch and intrapulmonary shunt due to atelectasis cause respiratory failure.
The amount of atelectasis is related with pulmonary shunt and respiratory failure
[2]. Atelectasis is often used as an explanation for otherwise unexplained postop-
erative fever. However their occurrence seems as a coincidence rather than causal.
Lack of association between atelectasis and fever has been demonstrated [7]. Thus
attribution of a postoperative fever to atelectasis leads to the misdiagnosis of fever
origin.
5.2.3 P
revention and Treatment of Atelectasis in Critically Ill
Obese Patients
It has been demonstrated that perioperative atelectasis is more frequent and atelec-
tasis persists for longer (for up to 24 h after surgery) postoperatively in obese
patients in comparison with full resolution in lean patients in a few hours [6]. In the
study by Baltieri et al., prevalence of atelectasis in obese patients without respira-
tory comorbidities was found to be 37.8% at 48 h after bariatric surgery indicating
the importance of interventions to prevent atelectasis formation [8].
In obese patients different approaches have been stated to prevent atelectasis dur-
ing perioperative period and follow-up period in intensive cares [9].
From the beginning of mechanical ventilation and during the follow-up period
under mechanical ventilation, optimal tidal volume and adequate level of end-
expiratory pressure (PEEP) should be applied to prevent atelectasis. Optimal tidal
volume should be between 6 mL/kg and 8 mL/kg of predicted body weight. The
tidal volume setting must be guided by the patient’s height and not by their mea-
sured weight [3].
5 Atelectasis 53
The easiest predicted body weight formula can be used as
Predicted bodyweight (kg) = height (cm)–100 for male.

Predicted bodyweight (kg) = height (cm)–110 for female.
Higher PEEP decreases venous return and causes arterial hypotension with
decreasing oxygenation [10]. Two thirds of intrinsic PEEP should be applied to
subjects with auto-PEEP.
Proper levels of PEEP and recruitment maneuvers (RMs) can be used to reopen
collapsed lung area and to maintain the lungs fully aerated [11], whereas PEEP
alone does not reduce atelectasis in morbid obesity after anesthesia induction, and
recruitment maneuvers up to 55 cmH2O show only transient effects, a combination
of recruitment maneuvers and PEEP improves oxygenation with reducing atelecta-
sis for at least 20 min [12].
Recruitment maneuvers (RMs) improve gas exchange and increase transpulmo-
nary pressure and intrathoracic blood volume. Optimal frequency of RMs is not
estimated but can be applied with hemodynamic monitorization [13]. Moreover
stepwise RMs, instead of abrupt RMs, should be used in obese patients.
Treatment of atelectasis depends on the cause. Subjects with abundant secretions
will benefit from chest physiotherapy (i.e., coughing, postural drainage, deep
breathing exercises (incentive spirometry), and percussion), suctioning, and bron-
choscopy. Noninvasive ventilation (NIV) is an option for patients with few secre-
tions as demonstrated by a randomized controlled trial in which 60 obese patients
undergoing minor peripheral surgery were randomly assigned to receive short-term
NIV or supplemental oxygen via venturi mask during their postanesthesia care unit
(PACU) stay [14]. NIV promoted more rapid recovery of postoperative lung func-
tion and oxygenation in the obese with 24 h lasting effect. Important limitations to
this evidence are that the trial was unblinded and could not draw any conclusion
regarding clinical outcome [14].
A recent meta-analysis described the benefits in oxygenation, clearance of car-
bon dioxide, and pulmonary function testing after general anesthesia with NIV
compared with standard care in obese patients [15]. Postoperatively, NIV was found
to be associated with a decreased risk of respiratory complications but not of rein-
tubation after tracheal extubation and unplanned intensive care unit admission.
NIV-related anastomotic leakage was not reported. NIV-related complications in
obese patients were mainly due to intolerance and ranged from 7% to 28% of cases
suggesting well tolerance and effectiveness of NIV in obese patients [15].
Fiberoptic bronchoscopy is frequently used in the treatment of atelectasis, but
evidence suggests that it may be no more effective than standard chest physiother-
apy. The role of flexible bronchoscopy for the treatment of atelectasis is also unclear
in obese patients. In a recent prospective study by Khan et al., flexible bronchos-
copy was found to be safe without increased needs for sedation in obese patients
[16]. Moreover no difference in complications during fiberoptic bronchoscopy or
54 S.S. Ulasli
procedural success based on obesity criteria was detected [16]. However there has
been no study regarding the efficacy and safety of fiberoptic bronchoscopy for the
treatment of atelectasis in critically ill obese patients.
Mucolytics are commonly used to assist clearance of tenacious secretions; how-
ever, their efficacy in this setting has not been well documented. Nasotracheal suc-
tioning of the nonintubated patient with a weak and ineffective cough is
uncomfortable and transient in the meaning of clearing secretions from the tracheo-
bronchial tree.
Conclusion
Obese patients are more likely to develop atelectasis during the follow-up in
intensive care. Interventions to prevent and treat atelectasis are very important to
reduce mortality and morbidity in critically ill obese patients.
References
1. Kotlo RM. Chapter 104. Acute respiratory failure in the surgical patient. In: Fishman's pulmo-
nary diseases and disorders. 5th ed. New York: McGraw-Hill Education; 2015. p. 1592–606.
2. Harris AT, Morell D, Bajaj Y, Martin-Hirsch DP. A discussion of airway and respiratory compli-
cations along with general considerations in obese patients. Int J Clin Pract. 2010;64(6):802–6.
doi:10.1111/j.17421241.2010.02350.x.
3. Pépin JL, Timsit JF, Tamisier R, et al. Prevention and care of respiratory failure in obese
patients. Lancet Respir Med. 2016;4(5):407–18. doi:10.1016/S2213-2600(16)00054-0.
4. Pelosi P, Croci M, Ravagnan I, et al. Respiratory system mechanics in sedated, paralyzed,
morbidly obese patients. J Appl Physiol. 1997;82:811–8.
5. Magnusson L, Spahn DR. New concepts of atelectasis during general anaesthesia. Br J
Anaesth. 2003;91(1):61–72.
6. Eichenberger A-S, Proietti S, Wicky S, et al. Morbid obesity and postoperative pulmonary
atelectasis: an underestimated problem. Anesth Analg. 2002;95:1788–92.
7. Engoren M. Lack of association between atelectasis and fever. Chest. 1995;107:81–4.
8. Baltieri L, Peixoto-Souza FS, Rasera-Junior I, Montebelo MI, Costa D, Pazzianotto-Forti
EM. Analysis of the prevalence of atelectasis in patients undergoing bariatric surgery. Braz J
Anesthesiol. 2016;66(6):577–82. doi:10.1016/j.bjane.2014.11.016.
9. Fernandez-Bustamante A, Hashimoto S, Serpa Neto A, Moine P, Vidal Melo MF, Repine
JE. Perioperative lung protective ventilation in obese patients. BMC Anesthesiol. 2015;15:56.
10. Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in
patients with acute lung injury and acute respiratory distress syndrome: systematic review and
meta-analysis. JAMA. 2010;303:865–73.
11. Pelosi P, Ravagnan I, Giurati G, et al. Positive end-expiratory pressure improves respiratory
function in obese but not in normal subjects during anesthesia and paralysis. Anesthesiology.
1999;91:1221–31.
12. Reinius H, Jonsson L, Gustafsson S, et al. Prevention of atelectasis in morbidly obese patients
during general anesthesia and paralysis: a computerized tomography study. Anesthesiology.
2009;111:979–87.
13. Futier E, Constantin JM, Pelosi P, et al. Noninvasive ventilation and alveolar recruitment
maneuver improve respiratory function during and after intubation of morbidly obese patients:
a randomized controlled study. Anesthesiology. 2011;114:1354–63.
5 Atelectasis 55
14. Zoremba M, Kalmus G, Begemann D, et al. Short term non-invasive ventilation post-surgery
improves arterial blood-gases in obese subjects compared to supplemental oxygen delivery - a
randomized controlled trial. BMC Anesthesiol. 2011;11:10.
15. Carron M, Zarantonello F, Tellaroli P, Ori C. Perioperative noninvasive ventilation in obese
patients: a qualitative review and meta-analysis. Surg Obes Relat Dis. 2016;12(3):681–91.
doi:10.1016/j.soard.2015.12.013. Epub 2015 Dec 10
16. Khan I, Chatterjee AB, Bellinger CR, Haponik E. Sedation for bronchoscopy and complica-
tions in obese patients. Respiration. 2016;92(3):158–65.
Obesity and Congestive Heart Failure
6
Stephan Steiner
6.1 Introduction
Obesity is known to be a main health problem in the industrial countries. Only one
third of men and less than half of women have normal weight based on BMI mea-
surements [1], and up to 40% of the ICU patients are obese [2]. Obesity is associ-
ated with an increased risk of cardiovascular disease [3–5], especially heart failure
[3, 6, 7]. Some researches hypothesize that the steady increase of life expectancy
might be stopped by the “obesity endemic” [4]. Consequently, intervention in obe-
sity seems to be an advisable goal in the primary prevention of cardiovascular
disease [4].
6.2 Definition and Diagnosis of Left Heart Failure
Heart failure is defined as a “complex clinical syndrome that results from any struc-
tural or functional impairment of ventricular filling or ejection of blood [8].” The
AHA Guideline for the management of heart failure differentiates between heart
failure with reduced (EF <40%, HFrEF) and those with preserved ejection fraction
(HFpEF, EF >50%). Keeping in mind that there might be bias with respect to differ-
ent methods of imaging (echocardiography, magnetic resonance imaging, ventricu-
lography), patients between the above mentioned range are considered to have
borderline HFpEF [8] (Table 6.1).
S. Steiner, Prof.
Department of Cardiology, Pneumology and Intensive Care Medicine, St. Vincenz Hospital,
Auf dem Schafsberg, 65549 Limburg/Lahn, Germany
e-mail: s.steiner@st-vincenz.de

58 S. Steiner
Table 6.1 Definition of Heart failure with preserved ejection fraction (HFpEF) (EF >50%)
heart failure [8] Borderline HFpEF (EF 40–50%)
Heart failure with reduced ejection fraction (HFrEF) (EF <40%)
Diagnosis of heart failure might be complicated in obese patients. Obesity as well

as heart failure can cause dyspnea, exercise intolerance, and edema [9, 10]. It seems
that cardiorespiratory fitness is severely reduced in morbidly obese individuals—
similar to those with HFrEF [11]. Nevertheless, as in non-obese patients, diagnosis is
based on clinical examination, noninvasive methods (e.g., echocardiography, mag-
netic resonance tomography, cardiopulmonary exercise testing), and, in some cases,
heart catheterization and myocardial biopsy, the latter allowing histological study of
a myocardial specimen. With respect to obesity, it should be kept in mind that even
the detection of brain natriuretic peptides, which are surrogate markers of myocar-
dial wall stress, might be misleading. There is an inverse relationship between BMI
and BNP, even in healthy people. Therefore it is not surprising that BNP levels are
lower in obese patients with heart failure and that at least slight elevations in BNP
might have implications for heart failure risk [12]. On the other hand, natriuretic
peptides increase after weight loss [13].
Compared with HFrEF, diagnosis of HFpEF is even more complex. HFpEF
has been diagnosed traditionally by Swan Ganz catheterization (pulmonary cap-
illary wedge pressure as a marker of left ventricular filling pressure), E/A ratio
quantified by Doppler echocardiography, or measuring left ventricular end-dia-
stolic pressure during left heart catheterization. The European Society of
Cardiology has added some challenging methods to improve categorization of
HFpEF, for example, biomarkers and modern echocardiographic methods like
speckle tracking [9].
6.3 athophysiology of Heart Failure with

P
Respect to Obesity
Echocardiography has shown subclinical alterations of left ventricular myocardial

characteristics related to the degree of obesity [14]. Using longitudinal strain analy-
sis, Wang et al. noted longer longitudinal strain, greater dyssynchrony, and signs of
early diastolic dysfunction in asymptomatic obese patients [15]. Even after adjust-
ing for age, mean arterial pressure, left ventricular hypertrophy, or insulin levels,
BMI was shown to be independently associated with left ventricular dysfunction
[14], mild myocyte hypertrophy [16], increased myocardial triglyceride levels and
epicardial fat [17], and the burden of atrial fibrillation [18]. Mahajan et al. [19]
found that obesity results in global biatrial endocardial remodeling in an animal
model. Remodeling has been characterized by left atrial enlargement and conduc-
tion abnormalities. Furthermore, left atrial muscle has been infiltrated by epicardial
fat and fibrosis. These findings were thought to represent a unique substrate for
atrial fibrillation [19]. In a small sample of healthy monozygotic twin pairs, who
6 Obesity and Congestive Heart Failure 59
Coronary artery disease

“Framingham RF” Myocardial infarction
– HTN, DM, DLP
Sleep apnea (SRBD)
Small vessel disease
Obesity HFpEF HFrEF
Hyperdynamic
circulation
(↑SV, ↑HR)
Heart metabolism
– Fatty degeneration,
– Inflammation
Fig. 6.1 Pathophysiology of heart failure in obese patients. There is a high prevalence of tradi-
tional cardiovascular risk factors (e.g., hyperlipidemia, arterial hypertension, coronary artery dis-
ease, and myocardial infarction). However, there are specific mechanisms associated with obesity
which might lead to HFpEF and HFrEF. For detailed information, see [10, 14, 17]. HTN:
Hypertension, DM: Diabetes mellitus, DLP: Dyslipidemia, SV: Stroke volume, HF: Heart rate
were discordant for obesity, there was increased epicardial fat independent of
genetic factors. Additionally, there was a close relationship between obesity and
low-grade inflammation as a potential pathophysiological link to the development
of cardiovascular disease [20]. Next to these pathomechanisms, comorbidities such
as arterial hypertension, hypercholesterinemia, or coronary artery disease might
raise or worsen heart failure. Sleep apnea is often associated with obesity and heart
failure. Ongoing registry data on 6876 patients with clinically stable heart failure
had demonstrated a prevalence of sleep-related breathing disorders (SRBD) of 36%
in women and 49% in men [21]. Predictors for SRBD were age, BMI, and severity
of heart failure. Therefore, nocturnal breathing disorders might play an additional
role in the development of left heart failure [22] in obese patients because of arterial
hypertension [23] and left ventricular hypertrophy [24]. The complex interaction
between obesity and heart failure is summarized in Fig. 6.1 without a claim to be
complete.
6.4 Association of Obesity and Right Ventricular Function
There is a complex pathophysiologic relationship between sleep-related breathing

disorders, right ventricular dysfunction, and pulmonary hypertension [16, 25–27].
Chahal et al. [27] hypothesized that right ventricular functional and morphologic
alterations are explained by an obesity-associated increase of right ventricular after-
load, increased blood volume, hormonal effects, or specific obesity-related effects.
Wong et al. used tissue Doppler imaging techniques to identify determinants of
60 S. Steiner
right ventricular function in overweight and obese patients compared to a control

group [28]. They conclude that BMI was associated with right ventricular dysfunc-
tion which interestingly has been independent of coexisting sleep apnea. Therefore,
obesity itself seems to affect right ventricular geometry and worsens RV function
which also might be negatively impacted by the occurrence of sleep-related breath-
ing disorders (as a result of, e.g., hypoxemia, intrathoracal pressure changes).
6.5 Obesity Paradox
For decades it has been recognized that obese patients with heart failure and a very
high BMI have shown a decreased mortality compared to those with normal weight,
whereas patients with low BMI and CHF have a lower life expectancy [3]. These
findings were confirmed even after heart transplantation where overweight patients
were found to have an improved survival rate. These observations have been termed
“obesity paradox” [29]. Shah [30] et al. studied 6142 heart failure patients with
acute decompensation in a worldwide observational study. Without regional differ-
ences a higher BMI was protective. Aging, heart failure severity, and metabolism
explained, at least in part, the obesity paradox in this study. With respect to acute
decompensated heart failure, the authors summarized that a lower BMI might iden-
tify patients at particularly high risk.
6.6 Therapy of Heart Failure in Obese Patients
Therapy of heart failure does not differ between normal weight and obese patients,
neither with respect to medication nor respective device therapy [9, 31]. Medication
should be initiated with a starting dose on purpose to titrate the target dose which is
defined in different controlled studies. Apart from some anticoagulants, e.g., dabi-
gatran which is indicated in case of atrial fibrillation in order to prevent thromboem-
bolism, dose adjustments are not recommended.
Concerning body weight there is no consistent recommendation. In obese
patients without manifest heart failure, weight loss is recommended [9] with a view
to prevent heart failure [31] and symptom benefit. With respect to left and right
ventricular geometry and performance, Alpert et al. summarized the positive effects
of excessive weight in a detailed review of the literature [32].
Kitzman et al. studied the effect of a caloric restriction on peak oxygen consump-
tion and the quality of life in 100 patients with preserved left ventricular ejection
fraction and a BMI greater than 30 kg/m2 [33]. Further inclusion criteria were signs
or symptoms of heart failure (HFpEF). After a study period of 20 weeks of diet,
exercise, or both, they found an increase in VO2max. Nevertheless, the intervention
was not associated to a better quality of life.
Farrell et al. [34] examined the association among cardiovascular fitness, body mass
index, and heart failure mortality. Between 1971 and 2010, a total of 44,674 individuals
were included in the study. BMI was significantly associated with heart failure mortal-
ity, but mortality rates were lower in fit than in unfit men within each BMI stratum.
Obesity
Heart failure (HF)?
No Yes
Weight loss beneficial < 35 kg/m2 BMI > 35 kg/m2

(Prevention of HF)
Weight loss not Weight loss might

recommended be considered
(Worse prognosis) (Managing symptoms/
exercise capacity)
Fig. 6.2 Recommendation on weight loss in heart failure patients. There is no doubt that weight
loss is beneficial in obese patients without manifest heart failure as a primary prevention. If heart
failure is still present, weight loss is not recommended because of the “obesity paradox” and there-
fore worse prognosis. Except in severely symptomatic patients, weight loss might be considered in
order to attenuate symptoms
Bariatric surgery can achieve marked weight loss and seems to be safe and effec-
tive in obese patients with heart failure. In a retrospective study, weight loss (−22.6%
body weight) by bariatric surgery was associated with an increase of left ventricular
ejection fraction (+5.1 ± 8.3%) [35]. Unfortunately the authors could not give infor-
mation on quality of life and clinical course/prognosis of these patients because of
the retrospective character of the study.
In patients with overt heart failure, weight loss could not be recommended con-
cerning prognosis. However, in some patients with advanced obesity, weight loss
might help to manage symptoms and increase exercise capacity [9]. In obese indi-
viduals without heart failure, weight reduction should be pursued as soon as possi-
ble, even in adolescence as a primary prevention of heart failure. These
recommendations are supported by a current Swedish study reporting a nearly ten-
fold higher risk of early heart failure in those individuals with a BMI >35 kg/m2
compared with non-obese individuals [36]. Recommendations on weight loss in
heart failure patients are illustrated in Fig. 6.2.
6.7 eaning of Obesity in Cardiogenic Shock

M
and Myocardial Infarction
Critically ill obese patients are at increased risk of mortality [37] due to pro-
longed mechanical ventilation and extended weaning. With reference to myocar-
dial infarction, obese patients did not show worse outcomes compared with
62 S. Steiner
non-obese patients [38]. Until now there is no evidence that obesity is associated
with worse—or even better—outcomes in cardiogenic shock; nevertheless, clini-
cal trials on mechanical support have excluded massive obese patients [10].
Concerning the efficacy of mechanical support, registry data on 1638 patients
(INTERMACS, Interagency Registry for Mechanical Circulatory Support [39])
show that patients with a higher BMI more often have poor outcomes (death or
poor quality of life).
Conclusion
Obesity is associated with multiple negative effects on right and left ventricular
geometry and poses function and an immense risk for the development of heart
failure. Therefore, weight reduction should be recommended to prevent heart
failure. If heart failure or even heart decompensation is present, weight reduction
might be aimed with respect to physical capacity and improvement of symptoms
(e.g., dyspnea). Nevertheless, because of the obesity paradox, there is no recom-
mendation to lose weight in these patients.
• Obesity has negative impact on left/right heart geometry as well as myocardial

function due to multiple mechanisms.
• Be aware of obesity even in adolescents in order to recommend weight loss as a
tool to prevent heart failure.
• Weight loss might be beneficial in clinically stable obese patients with heart
failure with respect to symptomatic benefit.
• There is a partially explained “obesity paradox” which describes a better out-
come in obese patients with severe heart failure compared with lean patients.
Therefore, there is no recommendation for weight loss in these patients.
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Intra-abdominal Hypertension
and Abdominal Compartment 7
Syndrome: Consequences
for Mechanical Ventilation
Peter D. Liebling and Behrouz Jafari
7.1 Introduction
There is growing evidence showing that intra-abdominal hypertension (IAH) is

extremely important in the care of critically ill patients. This phenomenon can
evolve to the end-stage abdominal compartment syndrome (ACS) with a serious
impact on the function of respiratory system and other vital organs. ACS can esca-
late lung injury and increase intrathoracic pressures, leading to atelectasis, airway
closure, and deterioration of respiratory mechanics and gas exchange. Abdominal
compartment syndrome is a particular challenge for mechanical ventilation. It is the
only extrathoracic entity that can significantly decrease the compliance of the respi-
ratory system and is increasingly recognized in critically ill patients. In this chapter
we will review in detail the consequences of raised intra-abdominal pressure as a
cause of respiratory failure and comment on what is known about mechanical ven-
tilation in these patients.
7.2 Definitions
The latest consensus definitions on IAH and ACS have been published by the World
Society of Abdominal Compartment Syndrome (WSACS) in 2013.
Table 7.1 summarizes these consensus definitions: a sustained increase in intra-
abdominal pressure (IAP) equal to or above 12 mmHg defines IAH where ACS is
defined by a sustained IAP above 20 mmHg with new-onset organ dysfunction [1]
(Table 7.1).
P.D. Liebling, M.D. • B. Jafari, M.D. (*)

Section of Pulmonary, Critical Care and Sleep Medicine, University of California-Irvine,
School of Medicine, Irvine, CA, USA
VA Long Beach Healthcare System, 5901 East 7th Street, Long Beach, CA 90822, USA
e-mail: jafarib@uci.edu

66 P.D. Liebling and B. Jafari
Table 7.1 2013 consensus definitions of the World Society of the Abdominal Compartment
Syndrome
Definition
Retained definitions from the original 2006 consensus statements
1. IAP is the steady-state pressure concealed within the abdominal cavity
2. The reference standard for intermittent IAP measurements is via the bladder with a
maximal instillation volume of 25 mL of sterile saline
3. IAP should be expressed in mmHg and measured at end expiration in the supine position
after ensuring that abdominal muscle contractions are absent and with the transducer
zeroed at the level of the midaxillary line
4. IAP is approximately 5–7 mmHg in critically ill adults
5. IAH is defined by a sustained or repeated pathological elevation in IAP ≥12 mmHg
6. ACS is defined as a sustained IAP ˃20 mmHg (with or without an APP ˂60 mmHg) that is
associated with new organ dysfunction/failure
7. IAH is graded as follows:
Grade I, IAP 12–15 mmHg
Grade II, IAP 16–20 mmHg
Grade III, IAP 21–25 mmHg
Grade IV, IAP ˃25 mmHg
8. Primary IAH or ACS is a condition associated with injury or disease in the
abdominopelvic region that frequently requires early surgical or interventional
radiological intervention
9. Secondary IAH or ACS refers to conditions that do not originate from the
abdominopelvic region
10. Recurrent IAH or ACS refers to the condition in which IAH or ACS redevelops
following previous surgical or medical treatment of primary or secondary IAH or ACS
11. APP = MAP − IAP
New definitions accepted by the 2013 consensus panel
12. A polycompartment syndrome is a condition where two or more anatomical
compartments have elevated compartmental pressures
13. Abdominal compliance is a measure of the ease of abdominal expansion, which is
determined by the elasticity of the abdominal wall and diaphragm. It should be expressed
as the change in intra-abdominal volume per change in IAP
14. The open abdomen is one that requires a temporary abdominal closure due to the skin
and fascia not being closed after laparotomy
15. Lateralization of the abdominal wall is the phenomenon where the musculature and
fascia of the abdominal wall, most exemplified by the rectus abdominis muscles and their
enveloping fascia, move laterally away from the midline with time
Abbreviations: ACS abdominal compartment syndrome, APP abdominal perfusion pressure, FG
filtration gradient, GFP glomerular filtration pressure, IAH intra-abdominal hypertension, IAP
intra-abdominal pressure, MAP mean arterial pressure, PTP proximal tubular pressure
Adapted from Kirkpatrick A, et al. Intra-abdominal hypertension and the abdominal compartment
syndrome: Updated consensus definitions and clinical practice guidelines from the World Society
of the Abdominal Compartment Syndrome. Intensive Care Med 2013;39(2):1190–1206 (with
permission)
7 Intra-abdominal Hypertension and Abdominal Compartment Syndrome 67
7.3 Etiologies
There are several etiologies which can cause or contribute to IAH/ACS, including
massive fluid resuscitation, ileus, abdominal infection, pancreatitis, pneumoperito-
neum, and hemoperitoneum. WSACS categorized the causes of IAH/ACS into pri-
mary and secondary conditions [3]. Primary IAH or ACS is a condition associated
with injury or disease in the abdominopelvic region that frequently requires early
surgical or interventional radiological intervention. These include trauma, liver
transplantation, ruptured abdominal aortic aneurysm, postoperative bleeding, retro-
peritoneal hemorrhage, intestinal obstruction, and bleeding pelvic fracture. By the
other hand, the secondary causes refer to conditions that do not originate from the
abdominopelvic region and do not require any surgical intervention, like sepsis,
major burns, peritoneal dialysis, pregnancy, morbid obesity, large-volume fluid
replacement, and intra-abdominal infection [3, 4].
7.4 Clinical Features
7.4.1 Symptoms
Patients may describe dyspnea, abdominal fullness or pain, nausea, and low urine
output. However, most patients with ACS require mechanical ventilation and are
unable to voice their symptoms.
7.4.2 Physical Examination
Vital sign abnormalities may include tachypnea, tachycardia, and hypoxemia. If

intra-abdominal infection is present, fever can be present. The chest examination
may include decreased breath sounds at the bases owing to bilateral elevated hemi-
diaphragms. Abdominal examination may reveal a distended abdomen, tense to pal-
pation, with or without bowel sounds. Incision sites may be a clue to recent
abdominal surgery which is the most frequent etiology of IAH. Unfortunately, the
above findings are all very nonspecific, as the physical exam has both low sensitiv-
ity (61%) and specificity (81%) for elevations in IAP [5].
7.4.3 Hemodynamics
I ncreased IAP has been shown to decrease cardiac output, raise central venous pres-
sure, and raise pulmonary artery pressure and pulmonary capillary wedge pressure
[6]. Surprisingly, arterial blood pressure is usually preserved.
7.4.4 Laboratory
Chemistries in ACS will often demonstrate a lactic acidosis, elevated blood urea
nitrogen, creatinine, and decreased bicarbonate. In cases of hemoperitoneum caus-
ing ACS, anemia can be found. Leukocytosis is common, and in the presence of
pancreatitis, elevated lipase and amylase levels are often seen.
Blood gasses often show concurrent metabolic acidosis and respiratory acidosis
with hypoxemia and decreased PaO2/FiO2 ratio. The metabolic component is likely
from abdominal hypoperfusion or global hypoperfusion from low cardiac output.
The respiratory acidosis arises as the patient hypoventilates in the setting of elevated
hemidiaphragms and decreased ability to maintain tidal volumes.
Renin and aldosterone levels are also elevated in ACS but generally are not used
for the diagnosis [7].
7.4.5 Imaging
The most common imaging abnormality in patients with IAH and ACS is elevated
hemidiaphragms and low lung volumes on chest X-ray. Abdominal CT may show a
“round abdomen sign” where the usual roughly oval-shaped abdomen becomes cir-
cular, with an anteroposterior/transverse abdominal diameter ratio greater than 0.8
[8]. Other disease-specific imaging findings can be present, including air under the
diaphragms in pneumoperitoneum, blood in the peritoneal or retroperitoneal space
in the setting of intra-abdominal hemorrhage, evidence of acute pancreatitis, or
dilated loops of bowel in the case of ileus.
7.5 Diagnosis
The diagnosis of IAH or ACS begins with clinical suspicion. If the history or physi-
cal examination includes risk factors for IAH, it is prudent to transduce a bladder
pressure. Given the shortcomings of physical examination, diagnosis requires an
elevation of transduced IAP.
Historically there have been multiple modalities of transducing the intra-
abdominal pressure. These have included gastric pressure transduced from a naso-
gastric or orogastric tube, inferior vena cava pressure transduced from a femoral
venous line placed in the vena cava, transduction of the insufflation pressure during
laparoscopy, and direct transduction of peritoneal pressure via intraperitoneal cath-
eters. The most clinically useful and easiest method however is transduction of a
bladder pressure. This is done by inserting a Foley catheter, instilling 25 cm3 of
sterile saline, clamping the drainage tube, and connecting the transducer to the flush
port on the catheter. IAP should be expressed in mmHg and measured at end expira-
tion in the supine position after ensuring that abdominal muscle contractions are
absent and with the transducer zeroed at the level of the midaxillary line [9].
If elevated IAP is found, a comprehensive search for organ dysfunction should

be undertaken. This should include assessment of respiratory insufficiency, record-
ing of hourly urine output, close monitoring of vital signs, and serial measurements
of the IAP. A laboratory evaluation should be completed including blood gas, chem-
istries, lactic acid, and blood counts.
7.6 Consequences
ICU patients with IAH on ICU day 1 have significantly higher mortality (38.8%)
than those without IAH (22.2%). Predictors of mortality for patients with IAH
include age, APACHE II score, medical compared to surgical ICU admission, and
the presence of liver dysfunction [2].
7.7 besity and Intra-abdominal Hypertension/Abdominal

O
Compartment Syndrome
7.7.1 IAH
IAP is significantly higher in obese patients compared to controls and is most closely
correlated with sagittal abdominal diameter [10, 11]. Increases in IAP correlate with
increasing number of obesity-related comorbidities. Interestingly, the increased IAP
seen in morbidly obese patients is not alleviated by laparotomy incision, the usual
method of decompressing the abdominal compartment. This suggests the elevated
IAP in morbidly obese patients does not truly represent an ACS [12]. There is a sig-
nificant elevation in plasma renin and aldosterone with elevation in IAP and in obe-
sity [7]. This elevation is alleviated with weight loss in parallel with reduction in
blood pressure, suggesting a possible underlying mechanism of systemic hyperten-
sion in morbidly obese patients [13, 14]. The correlation between elevated IAP and
elevated renin and aldosterone specifically in obese patients has not been well
studied.
7.7.2 ACS
There is no evidence that obesity is a risk factor for ACS or that prognosis is worse
in obese patients with ACS. In a large epidemiologic study, there was no difference
in BMI between survivors and non-survivors of ACS [2]. However, intraoperatively
during laparoscopic Roux-en-Y gastric bypass surgery, anuria is sometimes seen
during abdominal insufflation. This should be managed like any other ACS, and the
abdomen should desufflated until urine output resumes [15].
7.8 ulmonary Physiology in Intra-abdominal

P
Hypertension/Abdominal Compartment Syndrome
As far back as the 1970s, animal studies of intra-abdominal hypertension demon-

strated increased peak pressures at fixed tidal volume and decreased partial pres-
sure of oxygen in dogs with artificially elevated intra-abdominal pressure [16]. In
a case series of patients with massively elevated IAP, who had very low dynamic
compliance, elevated diaphragms, low lung volumes, and high positive end-expira-
tory pressure (PEEP), patients were required to maintain oxygenation [17]. In
another animal study, the application of 10 cm H2O of positive end-expiratory pres-
sure was associated with an exaggerated response to increasing intra-abdominal
pressure on central venous pressure, pulmonary capillary wedge pressure, pulmo-
nary artery pressure, pulmonary vascular resistance, and blood lactate levels [18].
However, in a case series of 15 patients with intra-abdominal hypertension, incre-
mental increase in PEEP had no effect on intra-abdominal pressure. This is postu-
lated to be due to the bulk of the PEEP being dissipated at the pulmonary transmural
pressure gradient and not actually increasing the pleural pressure [19]. In mechani-
cally ventilated patients without IAH, increases in PEEP do however demonstrate
a mild but statistically significant increase in IAP [20]. Conversely, in a swine
model, incremental increases in IAH increased peak inspiratory pressure markedly.
This study also demonstrated that elevations in intra-abdominal pressure correlated
with an increase in PaCO2 and a decrease in PaO2 [21]. In a study of 26 adult
patients undergoing laparoscopic cholecystectomy, increased insufflation pres-
sures markedly affected pulmonary compliance. With intra-abdominal pressure
increases of 12 mmHg, the pulmonary compliance was halved [22]. These studies
show an interesting relationship between the chest and the abdominal compart-
ments (Table 7.2). Increases in pulmonary pressures are not communicated to the
abdomen meaningfully, but increases in abdominal pressures are rapidly commu-
nicated to the chest.
ACS not only affects the pulmonary and cardiovascular system but also results in
other abnormalities such as renal dysfunction, hepatic impairment, and even
immune dysfunction [23].
7.9 anagement of Mechanical Ventilation in

M
Intra-abdominal Hypertension/Abdominal
Compartment Syndrome
7.9.1 Management of ACS
The first task when a diagnosis of abdominal compartment syndrome is made is to

address the underlying cause and obtain surgical consultation for decompressive
options. Surgical decompression reverses the deleterious effects of ACS on the
respiratory, cardiovascular, and renal systems [24].
Table 7.2 Pulmonary System Parameter Effect

physiologic parameters Cardiovascular Cardiac output ↓
affected by IAH
Venous return ↓
Peripheral vascular resistance ↑
Intrathoracic pressure ↑
Heart rate ↑
Mean blood pressure –
Pulmonary Pulmonary compliance ↓
Peak inspiratory pressure ↑
Pulmonary vascular ↑
resistance
Total lung capacity ↓
Functional residual capacity ↓
Residual volume ↓
Renal Renal vascular resistance ↑
Renal arterial flow ↓
Glomerular filtration rate ↓
Abdominal viscera Splanchnic blood flow ↓
Abdominal wall Abdominal wall blood flow ↓
Abdominal wall compliance ↓
Intracranial Intracranial pressure ↑
Cerebral perfusion pressure ↓
Adapted from K.-M. Sieh, et al. Intra-abdominal hypertension
and the abdominal compartment syndrome. Langenbeck’s Arch
Surg 2001:386;53–61 (with permission)
7.9.2 Noninvasive Ventilation in ACS
There have been no formal trials of noninvasive ventilation in ACS. The use of non-
invasive ventilator modes is probably ill-advised, as there is a significant risk of
aerophagia-induced gastric distension which may further increase IAP. There is a
case report of this exact phenomenon inducing ACS [25].
7.9.3 Invasive Mechanical Ventilation in ACS
7.9.3.1 Ventilator Mode

There are no firm guidelines establishing the best ventilator mode in ACS. As such,
conventional volume control or pressure control modes are acceptable, as long as
the settings conform to the below recommended parameters. Even though eleva-
tions in PEEP are not communicated to the abdominal compartment in a meaningful
way, transitioning from conventional ventilation to airway pressure release ventila-
tion can significantly elevate IAP [26].
7.9.3.2 Tidal Volume

It is common that patients who have abdominal compartment syndrome have con-
current acute respiratory distress syndrome (ARDS). There has only been one trial
evaluating tidal volume goals in IAH. This was a rat model in which 6 cm3/kg vs.
10 cm3/kg tidal volumes were compared with and without IAH. In the IAH group,
10 cm3/kg tidal volume resulted in less inflammation in lung tissue samples com-
pared to 6 cm3/kg. This has not been evaluated in human trials, and this is counter to
current ARDS Network recommendations. Given the lack of human data to support
this finding, these patients should be managed with a low tidal volume strategy as
recommended by the ARDS Network guidelines [27]. This is certainly an area in
which further research is needed.
7.9.3.3 Recruitment Maneuvers

In the presence of ACS and increased chest wall elastance, the inspiratory pressure
applied during recruitment maneuver should be higher, in order to achieve an inspi-
ratory transpulmonary pressure that is large enough to reopen collapsed alveoli.
7.9.3.4 PEEP
High PEEP is usually required in patients with IAH. Theoretically PEEP should be
titrated to normalize the position of the diaphragm, which is shifted upward by
increases in IAP [27]. This recommendation is supported by a swine study where
IAP-matched PEEP decreased shunt, dead space ventilation, increased lung vol-
umes, and improved oxygenation.
Application of PEEP did however decrease cardiac output and chest wall elas-
tance. However, independent of IAH, studies found that the “optimal” PEEP should
be selected according to the “best” elastance of the respiratory system [28, 29]. The
authors found that a reasonable compromise between the deleterious and beneficial
effects of PEEP would be to use a strategy of setting it at 0.5 × IAP [28]. There are
however multiple mentions in the literature of the best PEEP being equal to the IAP,
but this should be considered expert opinion, as there have been no trials in humans
to evaluate this recommendation.
7.9.3.5 Plateau Pressure

Outside of the ARDS Network guidelines recommending a plateau pressure goal of
≤30 cmH2O, only expert opinion is available on the safe plateau pressure in IAH/
ACS. Several articles suggest that it is safe to allow plateau pressure to elevate to
30 cmH2O + IAP/2. Again, this has not been evaluated by trial data.
7.9.4 Positioning During Mechanical Ventilation
There is a growing body of evidence that shows a mortality benefit in patients placed
in the prone position with ARDS. In a swine study, it was demonstrated that prone
positioning improved PaO2/FiO2 ratio in pigs with increased intra-abdominal pres-
sure more than those with normal abdominal pressures, suggesting an added
therapeutic benefit to prone positioning in patients with concomitant ARDS and IAH
[30]. There is a very reasonable concern however that placing a patient prone may in
fact increase IAP and therefore worsen or precipitate ACS. This is reassuringly not
the case, as demonstrated by a human study in which IAP did not significantly
change from supine to prone positioning in ARDS patients [31]. However, a follow-
up study did demonstrate a statistically significant increase in IAP from supine to
prone. This study did not demonstrate any ill effects of this small 2 mmHg increase
[32]. The support surface that patients are placed on when they are placed in the
prone position does affect IAP. Foam mattresses increase IAP and specialty air sup-
port mattresses do not. However, the increase noted in the foam support surface did
not result in a meaningful change in oxygenation, hemodynamic parameters, nor
splanchnic circulation. Therefore there is not enough evidence to recommend an air
support surface to prevent ACS when utilizing prone positioning in ARDS [33].
Positioning of the head of the bed (HOB) has also shown to change IAP. There is
a linear relationship between IAH and increasing the HOB [34]. Whether this sim-
ply represents the column of abdominal contents being loaded above, the trans-
duced location of the abdominal pressure in the bladder or a clinically significant
increase related to compression of the abdomen by induction of kyphoscoliosis or
the rib cage compressing the abdomen downward is unknown.
7.10 Summary
Mechanical ventilation is certainly a challenge in patients with IAH/ACS. However,

several key factors need to be considered. ARDS protocol gives a good direction to
ventilate these patients while considering IAP into account. This means use of pro-
tective tidal volume, recruitment maneuvers, and PEEP level is set according to the
“best” compliance of the respiratory system while at the same time avoiding over-
inflation of already well-aerated lung regions. Also the reverse Trendelenburg posi-
tion as well as deep sedation with or without neuromuscular paralysis in severe
ARDS cases may improve respiratory mechanics.
There is still a general lack of clinical awareness in many ICUs, and no consen-
sus exists on optimal timing of measurement or decompression. Given the effect of
this syndrome on any aspect of vital organs, clinicians should measure IAP when
any known risk factor for IAH/ACS is present in a critically ill or injured.
References
1. Kirkpatrick AW, Roberts DJ, De Waele J, Jaeschke R, Malbrain ML, et al. Intra-abdominal
hypertension and the abdominal compartment syndrome: updated consensus definitions and
clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome.
Intensive Care Med. 2013;39(7):1190–206.
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Impact of Sleep Breathing Disorders
in Obese Critically Ill Patients 8
Moh’d Al-Halawani and Christine Won
8.1 Introduction
Sleep breathing disorders are a common but under-recognized cause of acute on

chronic hypercapnic respiratory failure in the intensive care unit. Sleep disorders in
the intensive care unit may present in the form of obesity hypoventilation syndrome
(OHS), obstructive or central sleep apnea, or a combination of the former. Patients
may present to the hospital with shortness of breath or acute on chronic hypercapnic
respiratory failure and are likely to require monitoring in the intensive care unit [1].
In this section, we will discuss sleep-related breathing disorders that are com-
monly encountered by clinicians and affect obese patients in the intensive care
setting.
8.2 besity Hypoventilation Syndrome and Obstructive

O
Sleep Apnea Syndrome
8.2.1 Definitions
Obesity hypoventilation syndrome is a common ailment defined by a triad of obe-

sity—characterized by a body mass index (BMI) more than 30 kg/m2, daytime
hypoventilation, and sleep-disordered breathing. Daytime hypoventilation is defined
by an arterial partial pressure of carbon dioxide (PaCO2) greater than 45 mmHg
during wakefulness and an arterial partial pressure of oxygen (PaO2) lower than
M. Al-Halawani, M.D. • C. Won, M.D., M.S. (*)

Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine,
New Haven, CT 06520-8057, USA
e-mail: mohd.al-halawani@yale.edu; christine.won@yale.edu

78 M. Al-Halawani and C. Won
70 mmHg. Sleep-disordered breathing occurs in two forms in OHS, one form being
obstructive sleep apnea (OSA), which occurs in 70–90% of cases, and the other as
nocturnal hypoventilation, occurring in 10–30% [2, 3]. Other causes that could
account for daytime hypoventilation, such as neuromuscular disease, obstructive
lung disease, and metabolic or central etiologies, must be ruled out [2, 4].
Obstructive sleep apnea syndrome is defined by recurrent episodes of upper air-
way narrowing or obstruction during sleep, leading to marked reduction or cessa-
tion of airflow, hypopneas, and apneas, respectively, associated with recurrent
arousals and oxygen desaturation, which leads to sleep fragmentation and daytime
symptoms. It is characterized by an Apnea-Hypopnea Index (a measure of the num-
ber of events per hour measured on a sleep study) of greater than five per hour of
sleep in a symptomatic patient. Daytime symptoms may present as excessive day-
time sleepiness, excessive fatigue, mood changes, and concentration difficulties [5,
6]. Patients with OHS and OSA usually suffer from severe OSA with AHI > 30
events per hour, with breathing events often associated with significant arterial oxy-
gen desaturation [2, 3]. OSA is also a growing health concern with a prevalence
estimate ranging between 3 and 24% in the general population and 10 and 50% in
obese men and women. OHS is more prevalent in males, and most patients are diag-
nosed in their fifth or sixth decade of life. It has a reported prevalence of 10–20% in
outpatients presenting to sleep clinics, with the prevalence increasing with BMI,
and 30% in hospitalized obese patients [1, 4]. The prevalence of OSA in the inten-
sive care unit population is unknown [2, 5, 6].
As the prevalence of obesity increases, so does the incidence of OHS. However,
only a minority of obese individuals develop OHS, suggesting that other factors
may be playing a role in its pathogenesis. The respiratory muscles’ response to mass
loading due to obesity differs from one patient to another. Studies comparing
patients with OHS with matched controls show that OHS patients had lower lung
compliance, functional residual capacity, chest wall compliance, and higher lung
resistance. This suggests that patient’s BMI and the mechanical load due to obesity
may play an important but partial role and is only one factor among many others in
the pathogenesis of OHS [3].
8.2.2 Pathophysiology
The pathophysiology of obesity hypoventilation syndrome is complex and not fully

understood. Several mechanisms have been proposed in its pathogenesis, including
abnormal respiratory system mechanics and restrictive lung disease due to obesity
which leads to decreased lung compliance, functional residual capacity, chest wall
compliance, and increased lung resistance; impaired central responsiveness to
hypercapnia and hypoxemia and ventilatory drive; sleep-disordered breathing; and
neurohormonal abnormalities (e.g., leptin resistance). During normal sleep, there is
mild hypoventilation and PaCO2 levels increase by 3–5 mmHg. In patients with
obesity hypoventilation syndrome, PaCO2 is often increased by greater than
10 mmHg [2, 3].
8 Impact of Sleep Breathing Disorders in Obese Critically Ill Patients 79
8.2.3 Presentation and Diagnosis
Obesity hypoventilation syndrome and obstructive sleep apnea were first observed
in patients with severe obesity. Patients present with nonspecific symptoms but may
present with snoring, nocturnal gasping or choking, episodes of apnea, and exces-
sive daytime sleepiness. Facial plethora, large neck circumference, rapid shallow
respirations, a loud P2 on cardiac examination, and elevated jugular venous disten-
sion are findings on physical examination. The clinician who evaluates severely
obese patients should always suspect OHS in individuals presenting with a serum
bicarbonate level > 27 mEq/L and consider sleep-disordered breathing in patients
with secondary erythrocytosis who present with the symptoms and signs mentioned
earlier [2, 7, 8].
OHS patients may present for symptoms of shortness of breath or acute on
chronic hypercapnic respiratory failure necessitating admission to the ICU; this
diagnosis is usually missed and requires an intensivist with a high index of suspi-
cion. It may be argued that obese patients are more susceptible to hypercapnic respi-
ratory failure due to their tremendous baseline work of breathing and lack of
respiratory reserve. These patients may be more susceptible to ventilatory failure
when challenged by common hospital events such as atelectasis, aspiration, pneu-
monia, sepsis, and pulmonary edema. Likewise, patients may decompensate during
the course of hospital treatment. For example, when given large amounts of narcotic
pain medications or sedatives, metabolic alkalosis induced by diuretics or hyperoxic
supplementation may predispose to acute hypercapnic respiratory failure in OHS
patients [2].
The definitive test for hypoventilation is an arterial blood gas performed on
room air done during wakefulness. The arterial blood gas in OHS demonstrates
hypercapnia with PaCO2 > 45 mmHg, hypoxemia with PaO2 < 70 mmHg, and a
relatively normal Alveolar-arterial (A-a) gradient. However, due to the ventilation
and perfusion mismatch in the lung bases of obese patients (mainly due to atelec-
tasis), there might be a slight increase in A-a gradient [2]. The diagnosis also
becomes complicated in the acute setting, when underlying pulmonary injury or
the use of sedatives or narcotics may affect arterial blood gas measurements. An
astute clinician is able to interpret acute and chronic changes in blood gases and
explore a stable-state medical history, to help make a diagnosis of sleep-disordered
breathing.
Pulmonary function testing reveals a mild-to-moderate restrictive ventilatory
defect and a severely reduced expiratory reserve volume [8]. Obese individuals
require more work for their ventilation as their breathing lies on a less compliant
portion of the pressure-volume curve. They may also experience expiratory flow
limitation with increased alveolar end-expiratory pressure due to incomplete expira-
tion. Lung hyperinflation in severely obese individuals overstretches the diaphragm
leading to inefficient respiration, as the oxygen consumption dedicated to the work
of breathing increases by fivefold [3].
Nocturnal polysomnography is the gold standard for the diagnosis of sleep-
disordered breathing (e.g., OSA) that may accompany or occur independent of
OHS. Home sleep testing is also an option for selected patients, especially those
with high probability of straightforward OSA [9]. Some studies have shown the
feasibility of performing overnight polysomnography in the ICU setting or in
patients who had acute respiratory failure immediately after recovery for the diag-
nosis of sleep-related breathing disorders. Although it is challenging to diagnose
OHS or OSA in the acute setting, evaluation and the initiation of treatment during
hospitalization allow the patient to be discharged from the hospital with appropriate
care and follow-up [2].
8.2.4 Clinical Implications
Untreated OSA or OHS may lead to significant morbidity to the patients and carry
risks independent of obesity alone. Compared with obese controls, OHS patients are
at greater risk for developing congestive heart failure, angina, and cor pulmonale.
Patients with OHS also have higher rates of hospitalization, increased healthcare
costs, intensive care unit admission, need for mechanical ventilation during hospi-
talization, and an overall worse quality of life [1, 2]. OHS is a systemic illness
involving many organ systems with complicated interactions between these sys-
tems. Patients admitted to the ICU with OHS also have a high risk of severe obesity-
related multisystem organ dysfunction. The organ system derangements include
hypercapnic respiratory failure, systemic hypertension, left ventricular hypertrophy
with diastolic dysfunction, right ventricular volume overload, pulmonary hyperten-
sion, chronic renal failure, and nonalcoholic steatohepatitis [4].
OSA has been identified as an important independent risk factor for cardiovascu-
lar disease. It also carries a high incidence of comorbid conditions that commonly
present in patients admitted to the ICU, including diabetes mellitus, hypertension,
ischemic heart disease, heart failure, and cerebrovascular disease. OSA-induced
nocturnal hypoxemia has been shown to be a major contributor in the pathogenesis
of pulmonary hypertension and is a risk factor for the development of arrhythmias
including idiopathic atrial fibrillation, atrial flutter, ventricular tachycardia, and
bradyarrhythmias in obese patients. Sleep-disordered breathing was also identified
as a common contributing cause of hypercapnic respiratory failure in obese patients
in the ICU setting with these patients being more likely to require intubation or
noninvasive positive pressure ventilation. Patients with untreated OSA, given the
association with the comorbidities listed above, may have a higher risk of morbidity
and mortality in the ICU [5, 7].
Furthermore, obese patients with OHS or OSA have a higher rate of preoperative
and postoperative cardiopulmonary complications compared to lean patients, and
this risk increases with the number of associated comorbidities.
This may be related in part to the effects of medications (e.g., anesthetics,
sedatives, opiates) that affect the central nervous system, suppressing the breath-
ing center and upper airway muscle tone and precipitating sleep-disordered
breathing. This effect is seen mostly in the immediate postoperative period. In
addition, on the first postoperative night, patients will have decreased to absent
rapid eye movement (REM) sleep; this is usually followed by REM rebound on
subsequent nights. It is known that OSA may worsen in REM sleep, which leads
to an increase in hypoxemic episodes about threefold on the second and third
postoperative nights, increasing the risk of complications. Therefore, it is impor-
tant to identify patients that have a high risk of having OSA in the preoperative
period. One method is by using the STOP-BANG questionnaire, an easy-to-
administer questionnaire that has been approved to identify patients with high risk
of OSA. It consists of 8 yes or no questions related to the signs and symptoms of
OSA including snoring, tiredness during the day, observed apneas, high blood
pressure, body mass index > 35 Kg/m2, age > 50, neck circumference > 40 cm,
and male gender. A STOP-BANG score higher than or equal to three suggests that
the patient has a high risk of having OSA [9].
8.2.5 Management
Treatment of OHS in the critically ill patient should include acute management of
respiratory failure as well as the planning of a long-term care strategy to deal with
obesity, chronic respiratory failure, and other comorbidities. Continuous positive
airway pressure (CPAP), bi-level positive airway pressure (BPAP), and average
volume-assured pressure support (AVAPS) are all modes of noninvasive positive
pressure ventilation (NIPPV) that are currently used to manage patients with
OHS. NIPPV reduces the work of breathing and decreases respiratory muscle exer-
tion during sleep. It provides positive end-expiratory pressure, which promotes
alveolar recruitment and oxygenation, while eliminating obstructive apneas and
hypopneas by maintaining airway patency, leading to improvements in oxygen-
ation, arousals and sympathetic hyperactivity, and daytime function [3].
Bi-level positive airway pressure therapy may be a more attractive option for
OHS treatment as BPAP augments ventilation during sleep in addition to treatment
of sleep-disordered breathing [8]. Tracheostomy is often considered definitive ther-
apy for OSA as it bypasses the upper airway. However, in patients with OHS, tra-
cheostomy may improve but does not reliably eliminate hypoventilation, and
positive airway pressure support may still be required [2].
The treatment of OHS and the accompanying sleep-disordered breathing using
positive airway pressure (PAP) or tracheostomy can have significant improve-
ments in daytime PaCO2 and PaO2 even in the absence of weight loss, with an
effect that is more pronounced with greater hours of usage at night, although the
effect reaches a plateau beyond 4.5 h of PAP usage. Every hour of PAP use
improves the daytime PaCO2 by 2 mmHg and PaO2 by 3 mmHg, approximately.
Moreover, the need for daytime oxygen supplementation decreases from 30 to 6%
in patients treated with PAP. Improvement in the hypercapnic and hypoxemic
ventilator responses is also noted after only 2 weeks of PAP therapy. Treatment of
OHS is also associated with improved quality of life, sleep-related symptoms,
pulmonary arterial pressures, erythrocytosis, and mortality. Nonetheless, the ten-
dency to develop sleep-disordered breathing and chronic hypoventilation does not
reverse despite PAP therapy, and the negative effects will recur if OHS patients
stop using PAP [3, 8].
Acute respiratory failure in patients with OHS may be managed with invasive
and noninvasive ventilatory strategies. NIPPV (CPAP, BPAP, or AVAPS), oxygen,
or both will possibly be needed at home to manage chronic respiratory failure.
Critically ill OHS patients may have contraindications to the use of NIPPV via a
nasal or oronasal interface and may require endotracheal intubation and receive
mechanical ventilation. Reasons for invasive mechanical ventilation would include
altered mental status, hemodynamic instability, multi-organ failure, and severe aci-
dosis. Clinicians must be aware of the challenges that they may face when attempt-
ing invasive airway management of a critically ill obese patient. Endotracheal
intubation may be difficult in this population owing to the limited neck mobility and
mouth opening and rapid oxygen desaturation when obese patients assume the
supine position, which occurs due to an additional decrease in the functional resid-
ual capacity and expiratory reserve volume. Therefore, intubation in obese critically
ill patients requires technical skill and familiarity with advanced techniques [8].
Upon clinical stabilization, OHS patients may require a PAP titration (with
CPAP, BPAP, or AVAPS) during overnight polysomnography to determine optimal
PAP settings for treatment of their sleep-disordered breathing and hypoventilation.
During the titration study, expiratory pressures are adjusted to eliminate OSA, and
inspiratory pressures are adjusted to ensure adequate tidal volumes, CO2 levels, and
oxygenation [2].
Other important aspects that should be considered in the chronic management
of OHS patients include weight loss strategies and pharmacologic respiratory
stimulation [8]. Weight loss is the most important element in the management of
OHS, and treating OHS without achieving significant weight loss is unlikely to
reduce the significant morbidity and mortality associated with this syndrome.
Weight loss in morbidly obese persons has been shown to improve lung volumes,
lung function, gas exchange, and pulmonary artery pressures. Respiratory muscle
strength and performance are also improved by weight loss. It is difficult to
achieve and maintain weight loss by dieting and medical management alone.
Bariatric surgery is the most effective weight loss remedy, where patients lose
weight quickly and maintain this weight loss over a long period of time. Bariatric
surgery has thus been the focus of studies on OSA and obesity. Around 70% of
bariatric surgery patients have OSA. Weight loss surgery leads to an average BMI
reduction of 15 kg/m2, and this has been associated with improvements in AHI of
>30 events per hour. In addition, bariatric surgery has been shown to improve
pulmonary function, pulmonary hypertension, and reverse left ventricular hyper-
trophy [2, 4].
Tracheostomy may be an option for patients with refractory OHS who are intol-
erant or non-compliant to NIPPV, have severe cor pulmonale, or fail weaning off
mechanical ventilation. Tracheostomy bypasses the upper airway, significantly
decreasing the apneas and hypopneas related to airway obstruction. OSA and day-
time hypercarbia improve but may not be reliably eliminated due to several factors
including anatomic (e.g., partial obstruction of the tracheostomy tube by redundant

chin and neck skin), the emergence of central apneas, work of breathing through the
tracheostomy, or persistent central hypoventilation [1, 2, 8].
Respiratory stimulants have been the most explored pharmacological treatment
for OHS and are used as an adjunct to PAP therapy. Acetazolamide is a carbonic
anhydrase inhibitor that decreases serum bicarbonate levels by 5 mEq/L within
24 h, decreasing the serum pH up to 0.1, thereby promoting increased minute ven-
tilation by up to 15% and reducing PaCO2 by 5–6 mmHg. Medroxyprogesterone
can also be used in some patients in conjunction with PAP therapy to promote ven-
tilation [1, 2].
As mentioned earlier, there is a higher risk of perioperative complications in
patients with sleep-disordered breathing and OHS. Several studies addressed the
management of severely obese patients immediately after surgery. The primary
issue in postoperative period is the interaction between the untreated sleep apnea,
the recovery from anesthesia and sedation, and the need for postoperative pain man-
agement. In obese patients, there is evidence that NIPPV prevents respiratory fail-
ure immediately postextubation. Many patients with OSA use CPAP at home to
maintain arterial oxygenation; therefore, the use of CPAP postoperatively in these
patients is critical to maintain oxygenation [2, 7].
8.3 Central Sleep Apnea
Central sleep apnea (CSA) is characterized by apneas and hypopneas in the setting
of a markedly decreased or absent breathing effort.
Normally, the ventilatory drive during sleep is regulated by chemoreceptors in
the brainstem and carotid bodies. The respiratory drive increases in response to
elevated levels of PaCO2 maintaining its range within the normal limits. Patients
with CSA have an abnormal regulation of breathing in the respiratory centers of the
brainstem.
Patients with heart failure (HF) are at high risk of developing CSA as they are
inclined to have an exaggerated response to hypercapnia. This results in an inappro-
priate hyperventilation during sleep, which in turn results in hypocapnia and sup-
pression of the central respiratory drive causing a central apnea. This tends to occur
in cyclical waxing and waning pattern and is termed Cheyne-Stokes breathing.
CSA and Cheyne-Stokes breathing were identified as a marker of poor prognosis in
HF; studies have shown that patients with HF and CSA may have decreased survival
compared to patients with HF alone and were at higher risk of recurrent hospital admis-
sions. CSA is also associated with an increased sympathetic tone during sleep, periph-
eral vasoconstriction, tachycardia, and activation of the renin-angiotensin-aldosterone
system which may have detrimental effects on patients with HF [10].
Treatment of CSA can be achieved by supplemental oxygen, CPAP, or adaptive
servoventilation (ASV). Supplemental oxygen therapy has been shown to improve
the nocturnal oxygen saturation and lessen the sympathetic activity associated with
CSA. Similarly, treatment with CPAP has been associated with improvement in AHI,
sympathetic tone, as well as improvement in the left ventricular ejection fraction
(LVEF) in patients with HF and CSA. A more recent technology, ASV, is an advanced
mode of NIPPV in which the device provides inspiratory support and additional
breaths to overcome apneas and hypopneas and withdraws support during hyperven-
tilation, while delivering a baseline positive airway pressure. ASV has been shown to
be a more effective treatment modality for CSA and Cheyne-Stokes breathing than
CPAP or oxygen therapy and is usually better tolerated by patients than CPAP.
A recently published large randomized controlled trial, SERVE-HF, evaluated
the effects of ASV on hospitalization, lifesaving cardiovascular intervention, or
death in patients with symptomatic New York Heart Association class II–III systolic
HF (with LVEF ≤ 45%) and CSA. ASV appeared to be highly efficacious in reduc-
ing AHI but was associated with an increased all-cause and cardiovascular mortality
in this patient population. As a result of this study, ASV is no longer a recommended
treatment for CSA in patients with symptomatic systolic HF with reduced LVEF
(≤45%) [10]. The optimal treatment, and whether therapy is even required for this
patient population, is currently unknown and requires further investigation.
Conclusion
Sleep disorders in the critical care setting are often underdiagnosed and under-
treated, leading to increased morbidity and mortality in the critically ill, obese
population. Prompt diagnosis and treatment and long-term follow-up are essen-
tial for improved clinical outcomes.
8.4 Key Points
1. Sleep breathing disorders commonly affect obese patients in the critical care set-
ting but are usually under-recognized or undertreated by clinicians. The most
common forms are obesity hypoventilation syndrome, obstructive sleep apnea,
or a combination of these.
2. Patients may present with acute on chronic hypercapnic respiratory failure that
usually requires admission to the intensive care unit.
3. Diagnosis of OHS is made by arterial blood gases and pulmonary function test.
Patients also require polysomnography to evaluate for sleep-disordered
breathing.
4. Positive airway pressure using CPAP, BPAP, or AVAPS with or without supple-
mental oxygen is the treatment of choice in the acute setting. Weight loss is also
important to consider as part of chronic management.
5. Central sleep apnea is usually seen in patients with heart failure. Treatment with
supplemental oxygen, CPAP, or ASV may be considered in the appropriate
patient.
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Drugs and Medications
9
Clement Lee, Kate Millington, and Ari Manuel
9.1 Introduction
Obesity is becoming one of the major health problems across the world [1]. The
risks involved with being overweight or obese are related to the deposition of
adipose tissue (adiposity) that is associated with increased risk of adverse health
problems. Dosing medications in obese subjects is a challenge as these patients
are often excluded from many premarketing clinical drug trials. Current dosage
recommendations for most drugs for obese patients are most often inferred from
normal-weight persons. As the pharmacokinetics (PK) and pharmacodynamics
(PD) of many drugs are altered by the disproportional increase of adiposity rela-
tive to lean body mass in morbid obesity, dosing based on total body weight
could lead to the risk of overdose and serious clinical complications. An individu-
alised dosing scalar that takes into account the changed body composition
should be used in MO patient, particularly in anaesthesia and intensive care.
9.1.1 Methods for Measuring Adiposity
Body mass index (BMI) is a very simple formula and still commonly used as a
screening tool in assessing the total body adiposity. However, the calculation
takes absolute body weight into account and cannot differentiate between fat
and muscle mass. The simple formula has a pooled specificity of 90% and a
C. Lee (*) • K. Millington

Department of Anaesthesia and Perioperative Medicine, Westmead Hospital,
Westmead, NSW, Australia
e-mail: workpecker@aol.com; kjmilly44@doctors.org.uk
A. Manuel
Oxford Sleep Unit, Respiratory Department, Churchil Hospital, Oxford OX3 7LE, UK
e-mail: arimanuel1979@yahoo.co.uk

88 C. Lee et al.
pooled sensitivity of 50% to identify excess adiposity [2]. The poor sensitivity of the
BMI criteria is because it is unable to take the variations of adiposity with different
age groups, gender and ethnicity into account [3].
Body fat distribution can be estimated by waist circumference. It has excellent
correlation with imaging techniques and is a good predictor of all-cause mortal-
ity. However, it does have some practical limitations including location of mea-
surement and cut-off values. Various ratios such as waist-to-height and
waist-to-thigh ratios have been introduced to predict the risk of metabolic disor-
ders in obesity, but they have sparked debate and controversy. Gelber et al. and
Taylor et al. could not identify enough clinical evidence to show these ratios were
more accurate to predict adverse health events compared to BMI, and the rou-
tine use of ratios to assess adiposity is hence not recommended [4, 5].
Assessment of adipose tissue with CT and MRI is mainly restricted to research
and limited by costs as well as the body size of severely obese patients.
9.1.2 Methods of Measuring Body Composition
Apart from measuring body fat, interest has been developing to measure other body
composition like fat distribution, muscle mass, fat-free mass and bone mass. Several
techniques can be used including anthropometry, skinfold thickness, near-infrared
interactance, dual-energy X-ray absorptiometry, bioelectric impedance analysis (BIA)
and CT/MRI. None of the methods stand out without error as most are extrapolated
from normal-weight persons. Anthropometry and BIA are the most routinely used
clinically. The other methods are expensive and require more expertise and training.
9.2 hich Weight Approaches Should Be Used

W
for Calculating Drug Dosage?
9.2.1 Total Body Weight
Total body weight (TBW) is valid for dosing medications in normal-weight patients.
However, blind use of TBW for dosing any drugs could lead to an overdose in obese
patients. Generally, fat tissue increased proportionally with TBW, but the percent-
age of lean body tissue per kilogramme of TBW decreases. Highly lipophilic drugs
tend to have an increased volume of distribution (Vd), but this relationship is not
linear with TBW due to changes in other factors such as drug clearance and plasma
protein binding in obesity. Less lipophilic or water-soluble agents show less signifi-
cant or no change in Vd.
9.2.2 Ideal Body Weight
The term ideal body weight (IBW) was originally developed by the insurance
industry to correlate maximum life expectancy with the ideal body weight, for
9 Drugs and Medications 89
each gender and height. IBW as a dosing scalar is irrational as all obese indi-
viduals with the same sex and height would receive the same dose, regardless
of their body composition. IBW could be useful in patients up to a BMI of
40 kg/m2, but there is a risk of underdosing. Some practitioners correct this
shortcoming by adding 40% of TBW to IBW in the dosage (adjusted body
weight).
9.2.3 Lean Body Weight
Lean body weight (LBW), sometimes known as fat-free mass (FFM), describes
weight without the adipose tissue. The formula is sex specific and included mea-
sures of TBW and BMI. The calculations have accurate predictive properties when
compared to dual-energy X-ray absorptiometry, a gold standard for measure-
ment of LBW. In obese patients, LBW is significantly correlated with cardiac out-
put, an important factor for early drug distribution kinetics. Researchers suggest
that drug dosage based on LBW is more appropriate since almost all metabolic
activity in the body occurs in the LBW compartment, and drug clearance increases
linearly with LBW.
9.2.4 Predicted Normal Weight
This formula is to predict the normal weight of an overweight or obese person. It

works out the sum of an individual’s LBW and their predicted normal fat mass [6].
This has been specifically developed to characterise the pharmacokinetics of drugs.
Weight terms Formula
Total body weight Actual body weight of the person
Ideal body weight Female: Height (cm) –105

Male: Height (cm) –100
Adjusted body weight IBW (kg) + 0.4 (TBW (kg) – IBW (kg)
Lean body weight Female: 9270 x TBW/ (8780 +244x BMI)

(Janmahasatian 2005) Male: 9270 x TBW/(6680 +216 x BMI)
Predicted body weight Female: 1.75 x TBW – 0.0242 x BMI x TBW –12.6
Male: 1.57 x TBW – 0.0183 x BMI x TBW –10.5
Fig. 9.1 The five most useful terms for describing patients’ weight
90 C. Lee et al.
Total body 190 cm male

weight (kg) (With 15% body fat,
IBW 82 kg)
300
Excess fat
200
Fat mass
100
‘Normal’ fat
Learn body mass
20 40 60 80 100
BMI (kg.m-2)
Fig. 9.2 Relationship between total body weight and body mass index (BMI) and lean body mass
(Source: CE Nightingale Distributed under CC BY-NC-ND 3.0)
9.3 Pharmacokinetic Changes in Obesity
Oral absorption of drugs does not appear to change in obesity as suggested previ-
ously. Intramuscular administration should be avoided due to unpredictable
pharmacokinetics.
Obesity increases both adipose and lean tissue masses compared with nonobese
subjects of the same age, height and sex. These changes in body composition alter
the volume of distribution of many drugs. The volume of the central compartment
is largely unchanged, but dosages of lipophilic and polar drugs need to be adjusted
due to the increased volume of distribution. An increased in Vd could prolong the
elimination half-life despite increased clearance. Metabolic changes are caused by
high concentrations of the drug accumulating into adipose tissue that is relatively
metabolically inactive. For the less fat-soluble drugs, the LBW should be used.
MO patients have an increased cardiac output, and this alters the early pharma-
cokinetics of drug distribution. Obesity-induced cardiomyopathy may lead to heart
failure which can affect tissue perfusion and drug distribution [7].
Drug metabolism and clearance may be affected by obesity-induced changes in
hepatic and renal function. Hepatic clearance is usually unchanged or even
increased in obese patients. Non-alcoholic steatohepatitis causes hepatocyte dys-

function [8] and affects drug elimination. Creatinine clearance increases in other-
wise healthy obese subjects in proportion to their estimated LBW. Dosage of
drugs dependent on renal excretion needs to be adjusted in individuals with
chronic renal impairment.
The effects of obesity on the binding of drugs to plasma proteins are still unclear.
It has been reported increased concentrations of plasma protein and fatty acid mol-
ecules may interfere with protein binding of some drugs, increasing their free
plasma concentrations [9]. On the other hand, the increase in concentrations of
acute phase proteins, including α1-acid glycoprotein, may reduce the free plasma
concentrations of certain drugs.
Volume of distribution
Decreased fraction of total body water
Increased adipose tissue
Increased lean body mass
Altered tissue protein binding
Increased blood volume and cardiac output
Plasma protein binding
Increased 1 -acid glycoprotein and free fatty acids
Drug clearance
Increased renal blood flow
Increased GFR and tubular secretion
Abnormal liver function
Fig. 9.3 Factors affecting drug pharmacokinetics in obesity

92 C. Lee et al.
9.4 I mpact of Obesity on Pharmacokinetics of Common

Anaesthetic Drugs
9.4.1 Intravenous Induction Agents
9.4.1.1 Thiopental
Thiopental is rapidly distributed from the blood to highly perfused tissues, followed
by less inactive tissue depots such as muscles and fat. The induction dose for obese
patients should be calculated based on LBW and not on TBW [10]. Limited infor-
mation is available on the most appropriate weight scalar to use for continuous infu-
sion as thiopental is very rarely used for maintenance of general anaesthesia because
of its long context-sensitive half-life and prolonged recovery period.
9.4.1.2 Propofol
Like thiopental, it is a highly lipophilic drug which distributes rapidly from the
blood to tissues. The speed of onset and duration of effect are determined by the
cardiac output. LBW is a more appropriate weight-based scalar than TBW for
induction of general anaesthesia in MO patients. Propofol is ideally suited for
maintenance infusions in MO patients due to its favourable pharmacokinetic
profile [11]. In a study done in obese patients, Servin et al. demonstrated minimum
propofol accumulation or delayed emergence when obese patients received continu-
ous infusion based on their TBW [12].
9.4.1.3 Etomidate
Induction with this induction agent may be preferable over thiopental and propofol
in haemodynamically unstable MO patients. The standard induction dose is 0.3 mg/
kg (range 0.2–0.6 mg/kg). The PK and PD of etomidate in obese patient are lacking.
Induction dose is justifiable to be based on LBW given that the drug has similar
pharmacokinetics to propofol and thiopental.
9.4.1.4 Benzodiazepines
Benzodiazepines are highly fat-soluble drugs, and the excess fat tissue in obese
patients significantly influences their volume of distribution and elimination
half-life. A single intravenous dose should be increased at least in proportion to
TBW in MO patients because of the large volume of distribution. On the con-
trary, the dose should be adjusted to IBW rather than TBW if a continuous infu-
sion is used as clearance is not significantly different compared to nonobese
subjects [13]. Due to longer half-lives in obese critically ill patients, the time to
awaken can be prolonged after 48 h of continuous infusion even when IBW is
used as the dosing scalar.
9.4.1.5 Inhalational Anaesthetics

The pharmacokinetics of modern volatile agents does not seem to be significantly
influenced by obesity [14]. All halogenated agents have been used safely in obese
patients. Desflurane and sevoflurane are both characterised by a more rapid cerebral
wash-in and wash-out than other halogenated agents resulting in a more rapid recov-
ery from anaesthesia. These agents have been marketed as the ‘anaesthetic of
choice’ for obese patients.
Desflurane has the lowest fat-to-blood solubility among all the commonly
used inhalational agents. Its smaller blood/gas coefficient (0.42) suggests a
more rapid kinetic profile [15]. These properties make desflurane as a favour-
able agent to be used in MO patients especially for long procedures. One clini-
cal study, however, demonstrated the low-fat solubility property of desflurane
contributed to only a 2-min difference in time to awakening when compared to
sevoflurane [16].
9.4.1.6 Muscle Relaxants

Muscle relaxants are polar and hydrophilic drugs. Succinylcholine is a rapid onset
depolarising muscle relaxant with short duration of action. Due to increased
plasma cholinesterase in MO patients, succinylcholine administration should be
based on TBW as it has been shown to provide better intubating conditions
when compared to dosing on LBW or IBW [17].
Non-depolarising muscle relaxants such as rocuronium and vecuronium are
hydrophilic. They are primarily distributed in the central component, and dosing
should be based on LBW to avoid a prolonged duration of action, particularly in
MO patients [18].
Since cisatracurium is eliminated by Hoffman degradation, it had been suggested
to be the neuromuscular-blocking drug of choice in obese patients [19] until sugam-
madex became widely available in recent years. Like other agents, dosing for cisa-
tracurium should be based on IBW.
Reported recovery times for rocuronium and all other muscle relaxants are
highly variable in obese patients. Intraoperative neuromuscular monitoring is
strongly recommended in all MO patients. Recovery from neuromuscular block-
ade is defined as a train-of-four (TOF) ratio > 0.9. Postoperative residual paraly-
sis is one of the major causes for increased risk of these critical respiratory
events. Even minimal degrees of neuromuscular blockade can result in func-
tional impairment of the pharyngeal and oesophageal muscles resulting in
aspiration.
9.4.1.7 Neuromuscular Block Reversal Agents

The recommended dose of neostigmine is 0.04–0.8 mg/kg, not to exceed a total
dose of 5.0 mg. The reversal effect appears within 1–2 min, and the maximum
effect occurs within 6–10 min. Some studies demonstrated the maximum effect
was more delayed in obese patients than in the normal-weight patients. The dose-
response relationship of neostigmine in obese patient is not studied. Neostigmine/
glycopyrrolate combinations are not effective in reversing profound neuromus-
cular block.
Sugammadex is a selective agent that encapsulates rocuronium and
vecuronium. Although sugammadex has a lower affinity for vecuronium than for
rocuronium, reversal of vecuronium is still effective because fewer vecuronium
94 C. Lee et al.
molecules are present in vivo for equivalent blockade (vecuronium is approxi-

mately seven times more potent than rocuronium). The bound complex is excreted
via kidneys. Since sugammadex only distributes in the extracellular fluid vol-
ume, a dose of 2–4 mg/kg based on IBW is recommended for an incomplete
block [20].
9.4.1.8 Opioids
New synthetic opioids (fentanyl/sufentanil/remifentanil) are widely used for pain
treatment, but MO patients may be particularly susceptible to the side effects of this
class of drugs due to altered pharmacokinetics of these drugs in these subjects. The
high cardiac output in obese patients will result in lower fentanyl concentration in
the initial phase of distribution. Both loading and maintenance dose of these drugs
should be based on LBW because the drug clearance does not increase linearly with
TBW in obese patients [21]. Using the TBW to calculate the dose of opioids may
increase the risk of overdose and respiratory depression.
Morphine is a hydrophilic opioid which is mainly distributed in the LBW com-
partment only [21]. The dosage for hydrophilic drug should be on IBW rather than
on LBW. Patient age [22] and comorbidities such as the presence of obstructive
sleep apnoea (OSA) and obesity hypoventilation syndrome (OHS) and chronic
renal impairment must be considered when used in MO patients. There are case
reports describing respiratory distress after initiation of morphine PCA postopera-
tively in MO patients [23].
For postoperative analgesia after major operations, patient-controlled analge-
sia (PCA) without background infusion is advised. PCA dosage and lockout time
period should be individualised to each patient. All patients with known signifi-
cant OSA and OHS will warrant continuous pulse oximetry monitoring in a level
2 unit [24]. In some cases, arterial lines will allow repeated blood gas sampling
to detect rising carbon dioxide level. Percutaneous CO2 monitoring is a potential
alternative.
A multimodal approach to pain therapy that involves opioid-sparing adjuncts
will be beneficial in MO patients. Epidural or regional nerve blocks (both intermit-
tent and continuous) are effective techniques resulting in reduced postoperative opi-
oid requirements [25, 26]. Given the range of comorbidities in MO patients, the
potential benefits of multimodal approaches must weigh against the individual
patient’s risk factors.
Conclusions
Obesity is a rapidly growing global health problem. As the pharmacokinetics of
many intravenous drugs are affected by obesity, the adaptation of drug dosages
to obese patients is a subject of concern for many health practitioners. Future
dose exposure-response studies are needed to provide evidence-based dosing
instructions in drug labels for all classes of obese patients.
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15. Strum DP, Eger EI. Partition coefficients of desflurane in human blood saline and olive oil.
Anesth Analg. 1987;66:971–3.
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patient: sevoflurane or desflurane. J Clin Anesth. 2005;17:413–9.
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Part III
Invasive Mechanical Ventilation in the
Critically Ill Obese Patient
Preoxygenation Before Intubation
in the Critically Ill Obese Patient 10
Francesco Zarantonello, Carlo Ori, and Michele Carron
10.1 Introduction
10.1.1 The Impact of Obesity on the Respiratory System
Obese patients exhibit alterations both in lung volumes and respiratory mechanical
properties that are inversely correlated with body mass index (BMI) [1]. With
regard to lung volume, expiratory reserve volume (ERV) and functional residual
capacity (FRC) are significantly decreased, and the supine position further
decreases ERV and FRC in both awake and anesthetized obese patients [2]. This
results in ventilation–perfusion mismatch and increased intrapulmonary shunting,
which eventually leads to arterial hypoxemia and hypercapnia [1–3]. Both forced
vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) may be reduced,
particularly among morbidly obese patients [1], even if the FEV1/FVC ratio often
remains unchanged [1–3]. Breathing effort, basal metabolic rate, and oxygen con-
sumption are also increased in obese patients [1], contributing to a further decrease
in respiratory reserve [4]. Obesity decreases the compliance and increases the
resistance of the respiratory system. These alterations may be explained, at least in
part, by the reduction in lung volume due to atelectasis formation and/or airway
closure [1–3].
F. Zarantonello, M.D. (*) • C. Ori, M.D. • M. Carron, M.D.

Department of Medicine, Anesthesiology and Intensive Care, University of Padova,
Via C. Battisti, 267, 35121 Padova, Italy
e-mail: fzarantonello@gmail.com; carloori@unipd.it; michele.carron@unipd.it

100 F. Zarantonello et al.
10.1.2 The Impact of Obesity on Airway Management

in Obese Patients in Acute Care Settings
Obesity is associated with various clinical features including fat deposition in tis-
sues surrounding the upper airway, at the occipitus and in the neck, as well as
pharyngeal tissue inflammation. In patients with obstructive sleep apnea (OSA), all
the aforementioned characteristics may lead to difficulty with face mask ventila-
tion, endotracheal intubation, or both [1–3]. OSA, neck circumference > 42 cm,
and BMI > 50 kg/m2 are independent predictors of difficult airway management in
obese patients [5–7], and anatomic as well as physiopathologic alterations in respi-
ratory function [8, 9] adversely affect the ability to maintain adequate oxygenation
after loss of consciousness during intubation attempts [10]. Increased oxygen con-
sumption and alterations of gas exchange due to lung disease, pulmonary edema,
atelectasis, or acute respiratory distress syndrome in critically ill patients might
make intubation even more difficult, especially in emergency situations [11]. A
recent prospective observational study reported that the incidence of difficult intu-
bation of obese patients was doubled in an intensive care unit (ICU) setting com-
pared to the operating room (OR) (16.2% vs. 8.2%, risk ratio [RR] 1.9, 95%
confidence interval [CI] 1.5–2.6, p < 0.0001). Severe life-threatening complica-
tions associated with intubation were also more frequent in the ICU than in the OR
(41% vs. 2%, RR 21.6, 95% CI 15.4–30.3, p < 0.01) [11]. Intubation may expose
critically ill patients to severe hypoxemia, especially when the procedure takes a
long time or requires multiple attempts. Indeed, hypoxemia has been reported to
occur in up to 20% of ICU patients during intubation, and multiple attempts at
laryngoscopy were required in 10% of cases [12].
10.2.1 Preoxygenation
Preoxygenation aims to increase the oxygen reserve to extend the “safe apnea
period” (SAP). The SAP is the time available before hypoxemia develops between
anesthesia induction and the moment in which the airway is secured, and it repre-
sents the most critical period during intubation, particularly in critically ill obese
patients [13, 14].
The main determinants of SAP length are the patient’s own oxygen reserve,
which is contained mainly in the blood and lungs, and its consumption rate. Oxygen
in the blood is either freely dissolved in plasma or bound to hemoglobin, but these
reserves are barely enhanced by breathing pure oxygen as the hemoglobin is already
fully saturated when the healthy individual breaths room air, while the content of
oxygen dissolved in plasma is almost negligible [15]. The FRC is the most relevant
oxygen store available in the lung, and in the normal patient it has a volume of about
2500–3000 mL. Breathing ambient air and having a fraction of alveolar oxygen
(FAO2) of 16%, a person is theoretically able to store up to 0.16 × 3000 = 480 mL
10 Preoxygenation Before Intubation in the Critically Ill Obese Patient 101
of oxygen. Breathing pure oxygen can hypothetically bring the FAO2 up to 95%,
increasing the oxygen reserve stored in the FRC to 0.95 × 3000 = 2850 mL [16] and
almost doubling SAP length in the lean patient [15]. Optimizing intubation condi-
tions by improving oxygenation before tracheal intubation is therefore of crucial
importance in critically ill obese patients.
10.2.2 Preoxygenation Strategies
10.2.2.1 Oxygen Supplementation During Spontaneous Breathing

This strategy consists of supplying oxygen-rich gas while the patient continues to
breathe spontaneously and can be either “slow” or “fast.” The “slow” method allows
most of the patients to reach a good level of preoxygenation after 3 min of tidal
volume breathing (TVB) at 100% fraction of inspired oxygen [17], while “fast”
preoxygenation, which is based on four to eight deep vital capacity breaths, theo-
retically achieves the same result in 30–60 s [17]. A randomized clinical trial com-
pared 3 min of TVB versus eight deep breaths in 1 min as preoxygenation methods
in morbidly obese patients: no differences were found in end-tidal oxygen concen-
tration or SAP length [18].
The fraction of expired oxygen (FEO2) is a good indicator to ensure adequate
preoxygenation, which can be considered satisfactory when FEO2 is >90% [19]. In
the ICU, the analysis of expired oxygen concentration is seldom available, and fre-
quently clinicians only rely on peripheral oxygen saturation (SpO2). It is important
to note that SpO2 does not reflect preoxygenation adequacy, because even if the lung
reserve is not filled with oxygen, the SpO2 might already be 100% [16].
Whatever the technique, the key step for obtaining adequate preoxygenation
depends on ensuring a tight seal between the mask and the patient’s face. In fact,
failure in obtaining a tight seal results in 20% dilution of oxygen with air, and keep-
ing the face mask just 1 cm from the patient’s face results in 40% dilution [20]. This
can have detrimental consequences on the primary aim of preoxygenation, which is
filling the FRC with oxygen-rich gas. When conventional preoxygenation is judged
inadequate, further methods can be employed before proceeding with intubation, if
time permits.
10.2.2.2 Noninvasive Positive Pressure Ventilation

Severe ventilation–perfusion mismatch and significant intrapulmonary shunting
may limit the increase in SpO2 during standard preoxygenation. Lung atelectasis,
one cause of these alterations, may be managed by applying positive pressure to
reduce the proportion of collapsed lung, improve the ventilation–perfusion ratio,
and increase the FRC and oxygen reserve [19].
In a recent meta-analysis, noninvasive positive pressure ventilation (NPPV)
compared with conventional preoxygenation in obese patients was associated with
a significant improvement in partial arterial oxygen pressure (PaO2) (p < 0.0001)
before tracheal intubation and in end-tidal oxygen concentration (ETO2) after tra-
cheal intubation (p < 0.0001) [21].
Harbut et al. found a significantly higher post-intubation PaO2 (p < 0.001) and

fewer episodes of desaturation with pressure support ventilation (PSV) 5 cmH2O
over continuous positive airway pressure (CPAP) 5 cmH2O for 2 min compared to
conventional preoxygenation in morbidly obese patients [22].
Cressey et al. compared CPAP 7.5 cmH2O with a standard technique using the
Mapleson A breathing system for 3 min in morbidly obese females. No statistically
significant difference in mean time to desaturate to 90% after succinylcholine
administration was observed in the CPAP group compared to the Mapleson A group
(240 ± 64 vs. 203 ± 31 s), and the mean lowest SpO2 values were similar in the two
groups (SpO2 85%) [23].
Futier et al. compared 5 min of PSV and PSV plus recruitment maneuver (RM)
to conventional preoxygenation. PSV was adjusted to attain an expiratory tidal vol-
ume of 8 mL/kg predicted body weight, a positive end-expiratory pressure (PEEP)
level of 6–8 cmH2O, and an airway pressure (pressure support level + PEEP) of no
more than 18 cmH2O [24]. A higher PaO2 was observed in PSV group and PSV plus
RM group compared to TVB group (382 ± 87 mmHg and 375 ± 82 mmHg com-
pared to 306 ± 51 mmHg, p < 0.001). A higher ETO2 was also found (95.6 ± 1.1%
and 96 ± 1% compared to 92.3 ± 2.3%, p < 0.01) [25]. After intubation, PaO2
remained higher, and, compared to preanesthesia values, end-expiratory lung vol-
ume was greater in the PSV and PSV plus RM groups compared to the TVB group
(88% and 87% compared to 58%, p = 0.002) [24].
Gander et al. compared PEEP 10 cmH2O applied 5 min before and 5 min after anes-
thesia induction with conventional preoxygenation without PEEP in morbidly obese
patients. Patients in PEEP group had significantly higher PaO2 before apnea
(376 ± 145 mmHg vs. 243 ± 136 mmHg, p = 0.038) and longer SAP (from intubation to
an SpO2 of 92%, 188 ± 46 s vs. 127 ± 43 s, p = 0.002) compared with TVB group [26].
Comparing conventional preoxygenation to CPAP 4 cmH2O plus PSV 4 cmH2O
for 3 min, Georgescu and colleagues showed that an FEO2 ≥ 90% was reached more
frequently with NPPV (80%) than with TVB (60%) (p = 0.008) [27].
Coussa et al. compared the application of CPAP 10 cmH2O before intubation and
mechanical ventilation (MV) with PEEP 10 cmH2O thereafter, versus TVB and MV
without PEEP in morbidly obese patients. PaO2 after anesthesia induction was signifi-
cantly higher in the PEEP group compared with the control group (457 ± 130 mmHg
vs. 315 ± 100 mmHg, p = 0.035). In addition, control group patients had a signifi-
cantly higher amount of lung atelectasis determined by computed tomography, com-
pared to the PEEP group (10.4 ± 4.8% vs. 1.7 ± 1.3%, p < 0.001) [9].
Data on this topic are limited in the acute care setting. Baillard and colleagues
randomized nonobese patients with acute respiratory failure who required intuba-
tion to be preoxygenated for 3 min with a nonrebreather bag-valve mask or PSV
before a rapid sequence intubation in the ICU [25]. At the end of preoxygenation,
SpO2 was higher in the PSV group compared with the control group (98 ± 2% vs.
93 ± 6%, p < 0.001). During the intubation procedure, lower SpO2 values were
observed in the control group (81 ± 15% vs. 93 ± 8%, p < 0.001), and fewer epi-
sodes of SpO2 < 80% were reported in the PSV group (2/27 vs. 12/26, p < 0.01).
Five minutes after intubation, SpO2 values were still higher in the PSV group com-
pared with the control group (98 ± 2% vs. 94 ± 6%, p < 0.01) [25].
10.2.2.3 Apneic Oxygenation

Apneic oxygenation is used to extend the SAP beyond that which can be achieved
by preoxygenation alone. When the patient is apneic, oxygen constantly flows from
the alveoli to the bloodstream at a rate of about 250 mL/min, while carbon dioxide
is eliminated from the blood at a rate of 8–20 mL/min. This difference between
oxygen and carbon dioxide generates a negative pressure that promotes the move-
ment of air from the upper airway to the alveoli [28]. Theoretically, filling the pha-
ryngeal space with oxygen in the presence of a patent airway might allow
maintenance of adequate arterial oxygen saturation during the apnea period, as oxy-
gen is gradually moved to the alveoli and thereafter to the bloodstream.
Baraka et al. demonstrated that in morbidly obese patients placed in a 25° sit-
ting position, preoxygenation alone is followed by a more rapid desaturation dur-
ing the subsequent apnea, compared to preoxygenation with additional
nasopharyngeal oxygen supplementation at 5 L/min [3]. The authors also found a
significant negative correlation between the time to desaturation and BMI
(r2 = 0.66, p < 0.05) [3].
Ramachandran et al. showed that apneic oxygenation with 5 L/min oxygen via
nasal prongs compared to preoxygenation alone in patients in a 25° head-up posi-
tion significantly prolonged the SAP (5.29 ± 1.02 vs. 3.49 ± 1.33 min, p < 0.05),
and more patients in apneic oxygenation group had SpO2 > 95% at 6 min (8/15 vs.
1/15, p = 0.001) [29]. The lowest SpO2 reached after intubation was also signifi-
cantly higher in the apneic oxygenation group (94.3 ± 4.4% vs. 87.7 ± 9.3%,
p < 0.05) [30].
Cardiopulmonary alterations are nearly always present in the critical care setting,
so the benefit gained with apneic oxygenation might be lower than that previously
reported. In nonobese critical care patients, Miguel-Montanes et al. showed that
oxygen administered via high-flow nasal cannulae (HFNC) significantly improved
preoxygenation and reduced the prevalence of severe hypoxemia (2% vs. 14%,
p = 0.03) compared with a nonrebreathing reservoir face mask during tracheal intu-
bation of ICU patients with mild-to-moderate hypoxemia [31]. However, this ben-
efit has not been always confirmed.
In 119 critical care patients, Vourc’h and colleagues compared preoxygenation
before intubation by means of HFNC with that by means of facial mask and found
no difference in the rise of SpO2 (p = 0.98), the lowest SpO2 during the intubation
(p = 0.44), or the incidence of severe desaturations (p = 0.70) [32]. Similarly, Semler
et al. showed that apneic oxygenation with HFNC did not seem to increase the low-
est arterial oxygen saturation during the endotracheal intubation of 150 critically ill
patients compared with usual care [33]. The authors found no difference between
apneic oxygenation with nasal high-flow oxygen (15 L/min) and usual care in inci-
dence of SpO2 less than 90% (p = 0.87), SpO2 < 80% (p = 0.22), or decrease in SpO2
of more than 3% (p = 0.87) [33].
Due to the urgency with which intubation is usually performed in the intensive
care setting, SAP was not an outcome of these studies; furthermore, results in the
nonobese population are conflicting. At this time, no definite conclusion can be
drawn regarding the use of apneic oxygenation during prolonged intubation attempts
in the critically ill obese patient.
10.2.2.4 Patient Positioning

The position of the obese patient has a relevant effect both on lung volumes, particu-
larly the FRC, and on the work of breathing [2, 4]. This happens at least in part due
to the upward displacement of abdominal contents that might decrease the effective-
ness of preoxygenation and tolerance to apnea [34].
Altermatt et al. compared sitting and supine positions for preoxygenation. In the
predetermined body position, preoxygenation was achieved with eight deep breaths
within 60 s and an oxygen flow of 10 L/min. All patients were intubated after rapid
sequence induction of anesthesia in the supine position and then left apneic and
disconnected from the anesthesia circuit until SpO2 decreased to 90%. The SAP was
almost 1 min longer in the sitting group (216 ± 35 s vs. 164 ± 38 s, p < 0.05) [34].
Dixon et al. explored preoxygenation with a 25° head-up position compared to a
supine position in obese patients. After induction, ventilation was delayed until
blood oxygen saturation reached 92%, and this desaturation safety period was
recorded. The authors found that SAP was significantly longer in the 25° head-up
position group (201 ± 56 s vs. 155 ± 70 s, p = 0.02) [29]. The authors reported that
this “intermediate” position between sitting and supine was also more comfortable
in terms of ease of intubation, as it allowed optimal head positioning during laryn-
goscopy [29].
Boyce et al. previously investigated a 30° reverse Trendelenburg, a supine-
horizontal, and a 30° back-up Fowler position in obese patients. After intubation,
subjects were ventilated for 5 min in a mixture of 50% oxygen/50% air and then
disconnected from the ventilation circuit. The time required for SpO2 to decline
from 100% to 92% was noted and identified as the SAP [35]. The authors found that
higher BMI was associated with a reduced SAP and that a 30° reverse Trendelenburg
was associated with the longest SAP compared to a supine-horizontal position and
30° back-up Fowler position (178 ± 55 s, 153 ± 63 s, 123 ± 24 s, p < 0.05) [35].
Pirrone et al. recently confirmed the benefit of elevating the head of the bed for
increasing end-expiratory lung volumes and gas exchange after recruitment maneu-
vers followed by titrated positive end-expiratory pressure [36]. Using the beach
chair or reverse Trendelenburg position may further improve lung volumes, respira-
tory system elastance, and oxygenation in critically ill, mechanically ventilated,
morbidly obese patients [37].
Conclusion
According to the most recent difficult airway management guidelines, all
patients should receive preoxygenation before tracheal intubation [38] to
increase the body’s oxygen reserve and prolong the SAP. Preoxygenation is
even more important when there is an increased risk of hypoxemia due to diffi-
cult airway management or pulmonary alterations, such as in obese patient, par-
ticularly in the acute care setting. Due to concomitant problems and diseases,
critically ill patients are at increased risk of severe hypoxemia during intubation
[19]. Most of the evidence has been obtained in nonobese or otherwise healthy
obese patients undergoing general anesthesia (Table 10.1); however, preoxy-
genation techniques should be carefully considered. Conventional preoxygen-
ation might not be sufficient in the obese critically ill patient, while NPPV
Table 10.1 Summary of cited studies
Patients
Intervention Author (year) Setting Number BMI Position Preoxygenation Techniques Main results
Cressey (2001) OR 20 > 35 NR 3 min TVB/CPAP No difference
Coussa (2004) OR 18 > 35 NR 5 min TVB + no PEEP/ Higher PaO2 and less lung atelectasis
CPAP + PEEP with CPAP
Gander (2005) OR 30 > 35 Ramped 5 min TVB + no PEEP/PSV + PEEP Higher PaO2 and longer SAP with PSV
Baillard (2006) ICU 52 Nonobese NR 3 min TVB/PSV Higher SpO2 and fewer desaturations
with PSV
Futier (2011) OR 66 > 40 Beach chair 5 min TVB/PSV/PSV + RM Higher PaO2, ETO2, and EELV with
PSV
Positive pressure (PP)

Georgescu (2012) OR 30 > 30 Supine 3 min TVB/PSV FEO2 of 90% more frequently with PSV
Harbut (2014) OR 44 > 35 25–30° head up 2 min TVB/CPAP Higher PaO2 and fewer desaturations
with CPAP
Boyce (2003) OR 26 26 ± 3 Supine/ 5 min Supine/back-up/reverse Longest SAP with reverse
back-up/reverse Trendelenburg Trendelenburg
Trendelenburg
Altermatt (2005) OR 40 > 35 Sitting/supine 1 min Supine/sitting (90°) Longer SAP with sitting position
Dixon (2005) OR 42 > 40 Supine/25° 3 min Supine/25° head up Longer SAP with head-up position
Position (POS)
head up
Baraka (2007) OR 34 > 35 25° head up 3 min No oxygen/nasopharyngeal Longer SAP with apneic oxygenation
catheter
Ramachandran OR 30 30–35 25° head up Variable according No oxygen/nasal oxygen Longer SAP with apneic oxygenation
(2010)
10 Preoxygenation Before Intubation in the Critically Ill Obese Patient
to ETO2
Miguel-Montanes ICU 101 Nonobese NR 3 min Facial mask + nasal oxygen/ Fewer episodes of severe hypoxemia
(2015) HFNC with HNFC
Vourc’h (2015) ICU 119 Nonobese NR 4 min Facial mask/HFNC No difference
Semler (2016) ICU 150 Nonobese Variable Variable No oxygen during intubation/ No difference
Apneic oxygenation (AO)

HFNC during intubation
CPAP continuous positive airway pressure, EELV end-expiratory lung volume, ETO2 end-tidal oxygen concentration, FEO2 fraction of expired oxygen, HFNC high-flow
nasal cannulae, NA not applicable, NIV noninvasive ventilation, NR not reported, PaO2 partial arterial oxygen pressure, PEEP positive end-expiratory pressure, PSV pres-
105
sure support ventilation, RM recruitment maneuver, SAP safe apnea period, SpO2 peripheral oxygen saturation, TVB tidal volume breathing
might grant some additional benefit. Regarding apneic oxygenation, results

from critical care settings are conflicting at this time, and a specific evaluation
of this technique in the obese population is missing. Optimization of the patient’s
position, with a slight elevation of the thorax or the reverse Trendelenburg posi-
tion, should be considered due to the advantages in terms of oxygenation, lung
volumes, and SAP [11].
• Preoxygenation is recommended before intubating obese patients.

• Noninvasive positive pressure ventilation increases oxygenation and lung vol-
umes. It should be considered whenever possible for critically ill nonobese
patients.
• The benefit of apneic oxygenation needs to be confirmed in the critically ill
obese population.
• A slight back-up position provides a longer safe apnea period in obese patients.
Conflict of Interest The authors have no interests to disclose.
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Analgesia in the Obese Patient
11
Preet Mohinder Singh and Adrian Alvarez
11.1 Introduction
Obese patients pose unique challenges to the anesthesiologist for optimal

perioperative management. The perioperative universal goal of comfortable yet safe
surgery is no less than a double-edged sword in the morbidly obese. In order to
achieve high patient satisfaction (directly related to quality of recovery and analge-
sia), the anesthesiologist has to strike a delicate balance between the life-threatening
adverse events and analgesic potential of opioids. Further to compound the issue,
the interindividual pharmacokinetic variations in opioid effects make this job almost
next to impossible. Despite these safety hurdles and pharmacological barriers, a
postsurgical obese patient in pain cannot be ethically or morally justified! Over the
years, gradual progress has been made in analgesic management of the morbidly
obese that not only resorts to alternative analgesic regimens but also strikes a safety
balance for the use of “dangerous” opioids. The “danger” here is not by any stan-
dards a misrepresentation as it can be adjudged by the fact that as per the American
Society of Anesthesiologists (ASA) closed claim data, highest perioperative com-
plications/mortality in obese occurs due to opioid-related airway complications [1].
Postoperative complications in morbidly obese have been repeatedly linked to
increasing the body mass index (BMI). Evidence suggests that most of airway-
related complications in fact possess a near-linear relationship with the increasing
BMI. This can be attributed to the proportionate increase in obstructive sleep apnea
P.M. Singh
Department of Anesthesia, All India Institute of Medical Sciences,
New Delhi 110029, India
e-mail: preetrajpal@gmail.com
A. Alvarez (*)
Hospital Italiano de Buenos Aires,
Avenida Medrano 364, First Floor, CABA, Buenos Aires 1179, Argentina
e-mail: tatotatun@gmail.com

110 P.M. Singh and A. Alvarez
(OSA) incidence with increasing BMI values [2]. Thus, in real context, the actual
problem is to address the interaction of these high ceiling frontline perioperative
analgesics (opioids) on OSA (or patients susceptible to OSA).
11.2 Opioids and Obese: What’s Wrong?
Opioid-related breathing problems are more strongly related to OSA; however,

obese patients without OSA are also predisposed to the same. Ahmad et al. showed
that in morbidly obese patients (with or without OSA), the perioperative desatura-
tion rates were significantly higher than nonobese with the use of morphine-based
patient–controlled analgesia [3]. Studies have also demonstrated that even the use of
epidural or intrathecal opioids also depresses the respiratory frequency and depth to
alarming limits and thus limiting the utility of this route as well [4]. Compared to
nonobese patients, various physiological alterations account for the clinical predis-
positions for complications.
11.2.1 Peripheral Mechanisms
Recent studies have proved the existence of mechanoreceptors on the laryngeal

adductor motor neurons. After an opioid agonist binds to these receptors, the laryn-
geal adductors are activated and abductors are inhibited [5]. The density of these
receptors increases with the increasing BMI, and clinically evident opioid-related
obstruction could be attributed to this. Most induction agents actually enhance this
obstructive potential of opioids, and the chances of airway collapse increase. Ehsan
et al. also showed that dexmedetomidine is least likely to have effect on these
peripheral receptors and complication rates would not actually rise. In view of these
findings and in coherence with many other clinical trials, dexmedetomidine has
emerged as an attractive opioid-sparing drug in morbidly obese patients.
Both anatomical and physiological alterations in pharynx predispose to airway
collapse in patients with morbid obesity. Opioids are well known to lower the pha-
ryngeal tone as well, and this predisposes to airway collapse. In an interesting study
by Wang et al., it was shown that nearly 30% of patients who received methadone
for deaddiction eventually developed OSA-like symptoms [6]. It is expected that
these opioid-related effects would be further magnified in patients actually suffering
from OSA. Needless to say that opioids thus have potential to cause airway obstruc-
tion in obese with or even without OSA.
11.2.2 Central Effects
The evidence base for opioid-related central adverse effects in obese is much stron-
ger. The direct effect of opioids when used as analgesics causes sedation, and pre-
cipitate OSA is already well established. These effects are compounded by further
11 Analgesia in the Obese Patient 111
decrease in sensitivity of respiratory centers to both hypoxic and hypercapnic stimu-

lus. In OSA these reflexes are already dampened and thus on sedation further makes
it worse. Studies have shown that the clinical effects actually persist beyond the
pharmacological half-lives of the opioids. Opioids have shown to promote delayed
sedation when used during the first 3 postoperative days (by direct central action).
The pathophysiology of this is based on the fact that opioids alter the natural sleep
architecture by promoting non-rapid eye movement (NREM) and suppression of
rapid eye movement (REM) phase of sleep. During the phase of highest pain (initial
3 days after surgery), patients often receive highest amount of opioids. Subsequently
following these days, patients tend to compensate for the REM sleep and the REM
sleep rebounds. Thus in postoperative phase of recovery, the danger of life-threaten-
ing natural deep sleep-induced apnea again increases. As a result of the opioid use
in obese with OSA, the incidence of airway obstruction not only increases during
opioid therapy but also after cessation of opioids [7].
Obese patients have wide variations in weight and alterations in volume of distribu-
tion of drugs. This is even more variable for lipid-soluble drugs like opioids. Arguments
can be made that with available technologies, estimates of the body fat percentage and
subsequently the volume of distribution can be made. This would be something similar
to the use of target-controlled infusions (TCIs) technology in the population. However,
the actual problem extends beyond these pharmacokinetic issues. The crux of this trou-
ble originates from the completely unpredictable yet highly variable pharmacodynamic
effects of the opioids in the obese. There is strong evidence both in humans and animals
that suggest that central nervous system has increased sensitivity toward opioid seda-
tive propensity and eventually respiratory depression. Evaluating this pharmacological
aspect of obesity, Colleen et al. demonstrated that obese patients undergoing abdomi-
nal surgeries require much less opioids for comparable levels of analgesia in contrast to
the nonobese patients undergoing similar surgeries [8].
Thus, with all this said, the unwanted effects of opioid-based analgesia in obese
patients may often outweigh the expected benefits. Not only it is likely to compro-
mise the safety but also in long term adds to healthcare financial burden (more
monitoring and staffing to prevent/monitor for complications). Keeping in mind that
the frontline analgesics (opioids) are of limited use in obese, analgesic plans often
need individualization. Targets should aim at use minimal to almost no opioids in
these patients during the perioperative period.
11.3 The Ideal Strategy: A Multimodal Approach
Defining an ideal analgesic regimen eventually relies upon the use of combination
of analgesics. The multimodal analgesia targets to prevent/treat pain at different
levels in the pain pathway. Thus, drugs other than opioids should be targeted to
prevent generation of pain, transmission, and eventual perception of pain. When
drug combinations are used to target these aspects of pain, multimodal regimen is
achieved. The present ASA task force guidelines for the perioperative management
of OSA patients clearly advocate preferential use of regional analgesic techniques
Morbidly obese
The multimodal approach
Madulation
Sensory CNS Descending
affronts perception inhibitory
pathways
Peripheral Spinal Spinal Adjuvants

Narcotics
action cord cord
• PCA/PCEA
Regional Adjuvants • Tramadol
• NSAIDS • IV
• Spinal/ Limited for MO • Paracetamol • NMDA
• Narcotics
Epidural Antagonists • Alpha–2 agonists
• NMDA
• Nerve blocks Antagonists
• Infiltration • 5HT3 antagonists
• Gabapentinoids
NASIDS
Fig. 11.1 Analgesic regimens in obese patients
over systemic opioid analgesics. The guidelines also recommend exclusion of opi-
oids even from neuraxial techniques favoring NSAIDs (nonsteroidal anti-
inflammatory drugs) [9]. Local anesthetic-based regional blocks can certainly aid in
achieving these targets. Evidence suggests that wherever opioids cannot be com-
pletely avoided in obese patients, extreme vigilance and monitoring can safeguard
against complications [10]. A framework of useful drugs that form the basis of mul-
timodal analgesia in obese is depicted in Fig. 11.1.
11.4 No Opioids: What’s the Alternative
Most perioperative care teams often develop a notion that the quality of opioid-
based analgesia remains unmatched by that of non-opioid techniques. Literature
however is replete with evidence contrary to this instinctive thinking. Mansour et al.
demonstrated that non-opioid-based general anesthesia for bariatric surgery is as
effective as opioid one. They resorted to multimodal analgesic regimens (without
opioids) in one of the group, and pain scores were comparable to opioid-based anal-
gesic group [11]. Similarly, Feld et al. compared intraoperative non-opioid analge-
sic regimen to fentanyl-based analgesia surgeries in morbidly obese patients
undergoing gastric bypass. They concluded that well-titrated non-opioids (ketoro-
lac, clonidine, and regional techniques) produced equivalent analgesia to opioid
group. They also reported that non-opioid-based group showed lower sedation
scores postoperatively that was further associated with better hemodynamic stabil-
ity. Additionally, multimodal group patients required lower total postoperative anal-
gesic supplementation [12].
11.5 What Drugs for Analgesia?
A number of systemic alternatives exist for providing analgesia. These drugs can be
either primary analgesics themselves or adjuvants that decrease the analgesic dose
requirements. The frontline drugs that are used in perioperative period in obese are.
11.5.1 NSAIDs
NSAIDs inhibit the cyclooxygenase (COX), thus preventing conversion of arachi-

donic acid to prostaglandins. These prostaglandins act as inflammatory mediators
and sensitize the peripheral nerves to painful stimulus. With the advent of COX-2-
specific inhibitors, the safety profile of these drugs has improved. The renal and
gastric effects that complicated NSAID use are diminished. Patients undergoing
bariatric surgery in particular have shown marked opioid-sparing effect with appro-
priate use of NSAIDs. Govindarajan et al. in morbidly obese undergoing laparo-
scopic surgery demonstrated significant reduction of narcotic requirements and
further continued administration of ketorolac during the first 24 h postoperatively
that led to improved patient satisfaction as well. This allowed active patient partici-
pation in respiratory physical therapy and thus enhanced the recovery as well [13].
The limitation of most NSAIDs is that they are low ceiling analgesics and dose-
response curve flattens after particular dose increments. Among the available
NSADs, ketorolac has shown promising results. The pharmacological profile of this
drug makes it a preferable analgesic in the perioperative period where opioids need
to be avoided. It is one of the highest efficacy NSAID with potency equivalent to
one-third to one-fifth of that of morphine. However, unlike morphine it has no respi-
ratory effects that limit the use of morphine in bariatric patients. Yet another advan-
tage that NSAIDs offer over opioids in obese is early return of bowel motility after
surgery. As a result, most of the enhanced recovery after surgery (ERAS) protocols
for bariatric surgery incorporate the use of NSAID analgesics as the frontline pain
medications [14–16]. To attain optimal pain relief with NSAIDs, they must be used
in combination with adjuvants (discussed subsequently) or regional techniques.
This can allow cutting down opioid requirement to almost nil [17].
11.5.2 Paracetamol
Over the last decade, paracetamol has gained a lot of popularity as a potent analge-
sic with minimal adverse effects. It has unique mechanism of action that extends
beyond inhibition of cyclooxygenase at the peripheral level alone. Pharmacological
studies have demonstrated a unique ability to inhibit hypothalamic cyclooxygenase

(called COX-3). In addition, it also alters the central serotonergic transmission as
well that adds to its analgesic potency. It is free of bleeding, gastric, and renal side
effects that limit the use of NSAIDs. Trials consistently have shown it to possess
significant opioid-sparing effects [18, 19]. As per the conventional ideology, the
paracetamol dose in obese needs to be based upon ideal body weight. However,
recent study by van Rongen et al. demonstrated that obesity leads to lower acet-
aminophen concentration due to increased CYP2E1-mediated oxidation of acet-
aminophen in obese [20]. Paracetamol often needs to be supplemented with
additional analgesics for the first few days after surgery to attain optimal pain relief.
11.5.3 Flupirtine
Flupirtine is an aminopyridine that is a non-opioid, non-NSAID analgesic. It is also

an N-methyl-d-aspartate (NMDA) receptor antagonistic activity that adds to its
analgesic potential. However, it has central analgesic action (like opioids), but it
does not cause sedation, which is a desirable property in obese patients [21]. The
present perioperative role of this drug is limited due to the lack of clinical experi-
ence/evidence. Preliminary trials have shown significant morphine-sparing effect in
the perioperative period in non-bariatric surgeries [22].
11.6 Adjuvants
Most of the analgesic adjuvants work by lowering sensitivity of the central nervous
system to the perception of pain. An ideal adjuvant is likely to have minimal seda-
tive effect, and further on, its mechanism of action should preferably be different
from the primary analgesic. For the purpose of opioid sparing, clinical evidence
exists for the following pharmacological agents in the obese patients.
11.6.1 Ketamine
Ketamine is a NMDA receptor antagonist that has a well-established role in man-

agement of patients with chronic pain [23, 24]. Low-dose ketamine infusions lead
to decrease in pain sensitivity without significant sedation or airway-related compli-
cations (which is a desired property in obese). Perioperatively, its use lowers the
incidence of acute pain turning into a chronic pain syndrome [25]. Pharmacological
studies have suggested that ketamine may have an additional anti-inflammatory
property, which could be of great clinical relevance in the postoperative period [26].
Recently, Feld et al. reported significantly low patient-controlled analgesia (PCA)
morphine requirements in morbidly obese patients receiving ketamine adjuvant
[12]. Many randomized controlled trials evaluating the impact of ketamine infusion
on opioid consumption after major abdominothoracic surgeries have reported a
notable reduction in morphine requirements postoperatively [27, 28]. The doses

evaluated and found safe (free of hallucination, impairment of cognition) in various
trials ranges from a 0.5 mg/kg bolus followed by a continuous infusion of 2.0–
2.5 mcg/kg/min for the first 48 h postoperatively [24].
11.6.2 Alpha-Agonist
Most clinical experience exists for this class of drugs in terms of efficacy of analge-
sic potential. Antinociceptive action for this class is explained on the basis of antag-
onism of alpha-2A receptors present on the substantia gelatinosa in the spinal cord.
Available drugs in this subset include clonidine and dexmedetomidine. Among
these, dexmedetomidine is much more selective in its action at alpha-2A receptors
and thus has better analgesic potential. Bakhamees et al. recently concluded that an
intraoperative infusion of dexmedetomidine decreases the total amount of propofol
and fentanyl required to maintain anesthesia; it offers better control of intraopera-
tive and postoperative hemodynamics. Further it decreases postoperative pain level,
decreases the total amount of morphine consumed, and eventually leads to better
recovery profile compared to placebo [29]. Dexmedetomidine possesses additional
desirable properties like it does not lead to loss of airway tone despite higher degree
of sedation [30]. Another recent finding that makes it a preferred drug in obese is
that it does not apparently suppress the REM sleep [31]. Such a property prevents
the delayed REM rebound in obese patients and lowers airway-related complica-
tions in the postoperative phase. Presently, alternative routes (epidural, subarach-
noid block) of dexmedetomidine are being explored, and the preliminary results are
promising in terms of opioid-sparing action [32]. Both clonidine and dexmedetomi-
dine can safely lower rescue analgesic requirements by 25 and 30%, respectively, in
postoperative phase in morbidly obese [33].
11.6.3 Gabapentinoids
Gabapentinoids (gabapentin and pregabalin) were originally introduced as antiepi-

leptics but have additional analgesic, anticonvulsant, and anxiolytic effects as well.
Over the years, these drugs have shown very good patient acceptance and tolerance
without significant side effects [34]. In a recent study, Cabrera and colleagues con-
cluded that a single preoperative oral dose of 150 mg pregabalin is useful for reduc-
ing morphine consumption after sleeve gastrectomy. It promotes effective and safe
analgesia with a low incidence of sedation or airway-related side effects.
11.6.4 Magnesium
Much has been already written about analgesic potential of magnesium. A strong
evidence base exists for nonobese patients for its perioperative opioid-sparing effect.
Although direct trials evaluating magnesium in obese could not be found at the time
of writing, results from nonobese population are fairly encouraging. Magnesium by
blocking NMDA receptors (at site different from ketamine) is known to suppress
both intraoperative and postoperative analgesic/anesthetic requirements [35].
Steinlechner et al. demonstrated that magnesium gluconate moderately reduced the
remifentanil consumption without serious side effects in patients undergoing cardiac
surgery. Interestingly the opioid-sparing effect of magnesium was greater at higher
pain intensities and further increased with dose escalation [36]. Studies recommend
that magnesium at a dose of 50 mg/kg given at the time of induction is highly effica-
cious in improving quality of postoperative analgesia [37]. Being non-sedating along
with capability to lower intraoperative anesthetic requirements (possibly translating
into lesser residual effects of anesthesia in obese), magnesium is a promising agent
for further clinical utility in obese patients. Being a water-soluble drug, it is advisable
to dose it as per the ideal body weight rather than actual body weight.
11.7 Place of Regional Anesthesia in the Obese
Blocking the sensory affronts can certainly lower the pain or even sensation percep-
tion. As a result, it is understandable that analgesic requirements would drop expo-
nentially in absence of sensory/pain stimulation. An optimally performed block can
in fact cut down the opioid requirements to nearly zero. However, there are few
ground realities that limit this idealistic outcome. Regional blocks rely on the local-
ization of the nerves (by ultrasound or by stimulation) which would be a challenge
in case of obese. Although ultrasound has almost revolutionized the field of regional
anesthesia, yet it does require a learning curve. The deeper the nerves, the harder
they may be to locate and in plane techniques would further require additional skills
and expertise. The conventional central neuraxial blocks are also not as easy in
obese. Location of the interspinous spaces may not be easy, and even ultrasound is
not very helpful in these patients. Also, one needs to consider that most of the sur-
geries these days are preferably performed laparoscopically in the obese and no
ideal block for this exists. The laparoscopic port sites (where highest somatic pain
occurs) lie in widely varying dermatomal distribution, and a single block would fail
to cover these effectively.
The rationale of above discussion is not to discourage the use of regional anes-
thesia in obese but to prepare the anesthesiologist for possible limitations.
Nevertheless, there is ample evidence that clearly demonstrates that clinically rele-
vant opioid-sparing effect can be achieved with the use of regional techniques.
Various blocks/regional techniques for which evidence presently exists are.
11.8 Peripheral Blocks
Patient satisfaction scores studied retrospectively in morbid obese have shown to be

high with the use of regional anesthesia [38]. Regional anesthetic techniques in
numerous studies have demonstrated to be highly efficient in reducing opioid
requirements and airway- or OSA-related complications [39, 40]. Franco et al. dem-
onstrated once the learning curve is attained the actual success rates of blocks in
morbidly obese (94.3%) may not be very different from nonobese (97.3%). They
also suggested that the success rate improves with experience of the anesthesiolo-
gist [41]. One important aspect that should be kept in mind is that anesthesiologists
must evaluate these patients preoperatively for nerve injuries/palsies or vitamin
deficiencies that would have postoperative medicolegal significance.
Blocks that have been evaluated in obese include brachial plexus, lumber plexus,
truncal blocks, and abdominal wall blocks. Cotter et al. in their retrospective analy-
sis of 9342 regional blocks used in patients with BMI > 25 kg/m2 found obesity as
independent risk factor for block failure [42]. Ultrasound-guided transversus
abdominis plane (TAP) block is particularly effective in blocking T10 to L1 seg-
ments and seems to be an attractive option for laparoscopic/open surgery. Bilateral
TAP block in nonobese has shown efficacy for midline incisions [43] and can be a
valid option in situations of failed/difficult epidurals in obese. Trials show much
higher efficacy of thoracic epidurals when compared to TAP block [44]; thus, we
recommend thoracic epidurals to take priority over TAP block unless specific con-
traindications exist.
11.9 Surgical Site Infusions
Multi-orifice catheters have been used for infusion of local anesthetics at the surgi-
cal site for providing prolonged analgesia. Initial concerns existed for possible
delay in wound healing; however, recent trials have concluded contrarily to the
older thinking. Continuous bupivacaine infusion has been used to reduce the use of
opioids in morbid obese undergoing laparoscopic bariatric surgery [45].
11.10 Intraperitoneal Infusions
Sherwinter et al. evaluated continuous infusion of intraperitoneal 0.375% bupiva-

caine in morbidly obese patients undergoing laparoscopic gastric banding. They
reported a clinically relevant pain reduction that was not associated with any
increase in adverse effects [46]. Studies have shown in nonobese patients that when
small dose of opioid is added to the infusion analgesic efficacy significantly
increases [47].
11.11 Central Neuraxial Block
It goes without saying that neuraxial blocks (epidural and subarachnoid) from the
densest and most reliable of all the regional techniques. This would be true in both
obese and nonobese population. In obese patients, there are multiple trials that illus-
trate beneficial effects of epidural analgesia on respiratory functions by lowering
postoperative pulmonary complications following abdominal surgeries [48–50].
A congruent epidural (one put at the dermatomal distribution of surgical incision)

achieves high-efficacy analgesic potential with local anesthetic (completely opioid-
free) infusion. Many centers practice the use of thoracic epidurals in obese patients
and recommend their use for enhanced patient recovery. Another, indirect benefit
that exists with the use of neuraxial techniques is that the anesthesiologist can evade
the difficult airway in these patients and thus improve overall safety. Literature has
repeatedly documented that technical difficulties offset the common use of epidur-
als in obese. We however believe that these concerns are only opinion based.
Supporting this Ellinas et al. found that technical difficulties of placing epidurals in
obese pregnant patients are overrated and stressed upon use of optimal positioning
prior to placement [51].
11.12 Future Strategies
Interesting trials by Nguyen et al. and Farley et al. have suggested that the use of
warm humidified carbon dioxide for insufflation may be associated with analgesic
properties. Exploring this further Savel et al. conducted a randomized controlled
trial in morbidly obese patients addressing the same issue and eventually could not
demonstrate an analgesic advantage [52–54].
Multimodal and combination techniques are the ideal and most appropriate anal-
gesic regimens for obese patients. One may be very tempted to use opioids to
achieve high analgesic levels but in doing so can subject the patient to catastrophic
complications. We support the view that patient must be pain-free; however, there
are other avenues that must be explored in obese for better recovery and safety
profile.
Conflicts of Interest None.
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Sedation of the Obese Patient:
Indications, Management, 12
and Complications
Krysta Wolfe and John Kress
12.1 Introduction
As the prevalence of obesity increases, so too does the number of obese patients
being cared for in the critical care setting. Many patients will require the admin-
istration of analgesics and sedative medications during the course of their critical
illness. Therefore, it is important for clinicians to recognize not only the effect of
critical illness on the pharmacokinetics and pharmacodynamics of these medica-
tions but also how obesity further alters these effects. A lack of knowledge in
these areas may lead to excessive or inadequate sedation.
12.2 Drug Dosing in Obese Patients
In general, dosing of medications for any patient in the intensive care unit may be
erratic due to changes in organ function, volume of distribution, and other effects of
critical illness. Obesity further adds to this variability. A major challenge in caring
for critically ill obese patients is the lack of evidence guiding administration of
common drugs. It remains unclear in many cases how obesity impacts drug han-
dling. The physiologic changes associated with obesity may alter the distribution,
metabolism, protein binding, and clearance of many drugs [1, 2].
12.2.1 Absorption
The oral absorption of drugs is unchanged in obese patients [3].
K. Wolfe • J. Kress (*)

Medical ICU, Department of Medicine, Section of Pulmonary and Critical Care,
University of Chicago, 5841 S. Maryland Ave. MC 6026, Chicago, IL 60637, USA
e-mail: jkress@medicine.bsd.uchicago.edu

124 K. Wolfe and J. Kress
12.2.2 Protein Binding
Protein binding can be altered in the obese patient due to elevated levels of circulat-
ing lipoproteins, triglycerides, cholesterol, and free fatty acids that can bind serum
proteins thus inhibiting protein binding of drugs. The clinical significance of this is
unclear [4, 5].
12.2.3 Volume of Distribution
The volume of distribution of a drug depends on the amount of adipose tissue, lean
body mass, blood volume, cardiac output, total body water, and lipophilicity of the
drug [3, 6]. For lipophilic drugs such as benzodiazepines, the volume of distribution
is very large in an obese patient.
12.2.4 Elimination
Obesity can impact drug clearance as well. Hepatic clearance of drugs is typically
unchanged. More specifically, phase I reactions (oxidation, reduction, hydrolysis)
may be unchanged or increased in obesity, and phase II reactions are consis-
tently increased [7, 8].
Renal clearance is typically increased in the obese patient due to increased blood
flow and glomerular filtration rate [9]. When renal dysfunction is present, it is
important to base dosing of renally excreted drugs on the measured creatinine clear-
ance as the calculated clearance correlates poorly with the measured creatinine
clearance in obese patients [10].
The alterations described are not uniform and in combination with the wide vari-
ation in the pharmacodynamics of drugs commonly given in the ICU make a single
dosing strategy impossible to implement. Therefore, all patients, and in particular
obese patients with critical illness, should receive close monitoring of dosing based
on clinical end points.
12.3 Analgesia: Indications and Monitoring
The experience of pain is common in the critical care setting, with approximately
80% of patients experiencing moderate to severe pain while in the ICU [11–13].
Common sources of pain include routine ICU care (such as turning), presence of
an endotracheal tube, tissue injury (such as surgical or pressure wounds), vascu-
lar access, and prolonged immobility [14, 15]. Agitation is a common conse-
quence of unrecognized pain, often leading to the use of non-analgesic sedatives
instead of pain medications. Additional adverse effects of pain include increased
endogenous catecholamine activity, myocardial ischemia, hypercoagulability,
12 Sedation of the Obese Patient: Indications, Management, and Complications 125
hypermetabolic states, hyperglycemia, sleep deprivation, anxiety, and delirium

[16]. Non-pharmacologic interventions, such as optimal bed positioning, are useful
and should be the first step in management but alone are often inadequate in reliev-
ing pain. Therefore, an aggressive approach to pain management is advocated by
several published consensus opinions regarding sedation in the ICU [12, 17, 18].
Despite recommendations for aggressive pain management, treatment of pain in
the ICU is often inadequate in practice [19]. Ineffective communication, due to phys-
ical barriers or an altered level of consciousness, is the main impediment to both
recognition and treatment of pain in patients with critical illness. Other possible bar-
riers include concerns over addiction to opiates, adverse cardiopulmonary effects of
analgesics, and arbitrary limits on drug dosing [20]. Routine pain assessment aids in
achieving optimal patient comfort by prompting increased recognition of pain and
evaluation of response to interventions aimed at pain reduction. The use of routine
assessment has been associated with decreased need for sedative medications and
improved outcomes [21].
The best tool for assessment of pain is patient self-report, but due to a variety of
reasons, this is often not possible in the ICU. Physiologic parameters, such as hyper-
tension and tachycardia, correlate poorly with pain levels [22]. Therefore, tools such
as the Visual Analog Scale (VAS), which has been shown to have very good reli-
ability and validity, are utilized for routine and frequent pain assessment [23, 24].
The VAS consists of a horizontal line with the extremes of “no pain” and “severe
pain” on the ends. The Numeric Rating Scale is also commonly used and utilizes a
similar horizontal line with numeric markings from 1 to 10 indicating pain severity
[25]. In patients that cannot self-report, tools that utilize behavioral or physiologic
responses such as facial expression, body movements, muscle tension, and ventila-
tor compliance have been validated. Examples of these tools include the behavioral
pain score (BPS) and critical care pain observation tool (CPOT) [26, 27].
12.4 Analgesia: Management
Intravenous administration of analgesic medications is generally the preferred route

in patients with acute pain in the ICU. Both continuous infusion and intermittent dos-
ing strategies can be employed and tailored in a patient-specific manner. Patients
alert enough to respond may benefit from patient-controlled analgesia. PCA provides
effective analgesia in the obese, although close monitoring for respiratory depression
is prudent [28]. Intramuscular injection is not preferred due to pain from the injection
itself and inconsistent absorption in critically ill patients. Similarly, transdermal opi-
ates may have altered absorption in the setting of critical illness. Oral administration
can be limited by unpredictable absorption due to gastrointestinal dysfunction.
There are limited studies guiding opiate choice and dosing requirements in
obese patients. Widespread variability in morphine requirements has been reported
in postoperative patients with obesity [29]. Therefore, regular pain assessments
are necessary in managing analgesia in critically ill obese patients.
12.5 Analgesia: Medication Choice
An ideal analgesic medication has a rapid onset, rapid offset, lack of drug accumu-
lation, and lack of side effects. Unfortunately, none of the available analgesic medi-
cations have all these attributes (Table 12.1); therefore, the properties of each drug
must be considered in the context of each individual patient.
12.5.1 Opiates
Opiate receptors are found throughout the central nervous system and peripheral
tissues. The primary effect of opioids is analgesia, which is predominantly mediated
through the μ and к receptors. They also provide mild to moderate anxiolysis, but
have no amnestic properties.
Table 12.1 Analgesics
Fentanyl Morphine Hydromorphone Remifentanil
Mechanism of μ-opioid μ-opioid agonist μ-opioid agonist μ-opioid
action agonist agonist
Onset 1–2 min 5–10 min 5–10 min 1–3 min
Elimination 2–4 h 3–4 h 2–3 h 3–10 min
half-life
Metabolic pathway N-dealkylation Hepatic, Hepatic, Hydrolysis by
CYP3A4/5 glucuronidation glucuronidation plasma
substrate esterases
Active metabolite None 6- and 3- None None
glucuronide
metabolite
(renally
excreted)
Intermittent dosing 0.35–0.5 μg/ 2–4 mg IV 0.2–0.6 mg IV None
kg IV q0.5–1 h q1–2 h q1–2 h
Continuous 25–200 μg/h 2–30 mg/h 0.5–3 mg/h 1.5 μg/kg IV
infusion loading dose;
then
0.5–15 μg/
kg/h
Side effects Less Accumulation Accumulation No
hypotension; with hepatic/ with hepatic/ accumulation
accumulation renal renal with organ
with hepatic impairment, impairment dysfunction
impairment histamine
release
Pharmacokinetics No significant No significant No significant No significant
in obese patients change change change change
Dosage in obese Based on Based on IBW Based on IBW Based on LBW
patients LBW
LBW lean body weight, IBW ideal body weight
Opiates have a number of side effects, most notably dose-dependent centrally

mediated respiratory depression. This is mediated by the μ2 receptors in the brain-
stem (medulla), leading to a decreased respiratory rate. Other side effects of opiates
include CNS depression, hallucinations, hypotension, pruritus, peripheral vasodila-
tion, nausea and vomiting, ileus, urinary retention, and in rare cases increased intra-
cranial pressure.
Patients receiving prolonged high daily opioid doses typically develop tolerance
leading to a diminishing effect over time. Another consideration when using opiates
for prolonged periods or in high doses is the risk of precipitating withdrawal when
rapidly tapering or abruptly stopping these medications. In one study of mechanically
ventilated trauma and surgical ICU patients receiving large doses of analgesic and
sedative medications for over 7 days, symptoms of withdrawal were experienced by
32% [30]. Signs and symptoms of withdrawal are extensive and nonspecific. They
include pupillary dilation, sweating, lacrimation, rhinorrhea, piloerection, tachycar-
dia, vomiting, diarrhea, hypertension, yawning, fever, tachypnea, restlessness, irrita-
bility, increased sensitivity to pain, nausea, cramps, muscle aches, dysphoria,
insomnia, and anxiety [30]. It is not known if regular interruption of opiate adminis-
tration or downward titration of doses is effective in preventing withdrawal. The use
of longer-acting opiates, such as transdermal fentanyl or methadone, can be consid-
ered in patients in whom withdrawal is a concern. Because of the stigma around meth-
adone and heroin addiction, transdermal fentanyl is currently used more frequently.
Morphine: Intravenous morphine has an onset of action ranging from 5 to 10 min
due to its low lipid solubility, which delays its movement across the blood-brain
barrier. Its duration of action is approximately 2–4 h. If given repeatedly, morphine
accumulates in peripheral tissues which may prolong its effect. This may be particu-
larly relevant in obese patients. Importantly, morphine undergoes glucuronide con-
jugation in the liver, and its active metabolite, morphine-6-glucuronide, is eliminated
by the kidney. Therefore, its effects may be prolonged in patients with renal
failure.
Hydromorphone: Intravenous hydromorphone has a similar onset of action as
morphine with a shorter duration of action (2–3 h). Hydromorphone does not have
active metabolites, which contributes to its relatively shorter duration of action.
Fentanyl: Due to its high lipid solubility, fentanyl rapidly crosses the blood-brain
barrier leading to a quick onset of action (1–2 min). Its duration of action is short
(30–60 min) due to tissue redistribution. As with all opiates, tissue redistribution
can lead to accumulation and prolongation of effect with repeated or prolonged
exposure, particularly in obese patients.
Remifentanil: Remifentanil is a highly lipid-soluble drug with a rapid onset of
action (1–3 min). Its elimination half-life is very short leading to rapid recovery
within minutes of cessation. This is due to metabolism through hydrolysis by
plasma esterases. Therefore, its action is not affected by hepatic or renal function.
The pharmacokinetics of remifentanil appears to be similar between obese and
lean patients. It is recommended that dosing be based on ideal body weight instead
of total body weight [31].
12.6 Sedation: Indications and Monitoring
Once appropriate analgesia is obtained, some patients in the ICU will still experi-
ence varying degrees of agitation or unpleasant awareness. Common causes of this
include anxiety; frustration; lack of homeostasis due to thirst, hunger, or dyspnea;
ventilator dyssynchrony; inability to communicate; or need for physical restraints.
Once the need for sedation has been established, it is important to then determine
the desired level of sedation for an individual patient.
The level of desired sedation is dependent on a patient’s underlying condition.
Indications for continuous deep sedation include treatment of intracranial hyperten-
sion, severe respiratory failure, refractory status epilepticus, and prevention of
awareness in all patients treated with neuromuscular blockade. The majority of
patients treated in the ICU do not have one of these indications, and for these
patients, the goal is to minimize the use of sedatives. Ideally a patient is kept in a
pain-free state where he/she is lucid and able to interact and cooperate with care
providers. Reaching this goal may be difficult and requires close monitoring of the
sedation level. In many instances the level of sedation reached is suboptimal, with a
tendency toward providing oversedation [32, 33].
Several tools have been developed to help standardize sedation monitoring. The
most commonly used scales are the Riker Sedation-Agitation Scale (SAS) (Table
12.2) and Richmond Agitation-Sedation Scale (RASS) (Table 12.3) [34, 35]. Both
the SAS and RASS have been evaluated extensively for validity and reliability and
performed similarly in a direct comparison [36]. They can be used to detect changes
in level of sedation over repeated assessments and correlate well to dosage of seda-
tive and analgesic medication administered. For most patients, a goal level of seda-
tion (calm and interactive) is represented by a RASS score of 0 or −1 and a SAS
score of 3 or 4 (Table 12.2 and 12.3).
Table 12.2 Riker Sedation-Agitation Scale (SAS)

Score Term Description
7 Dangerous Pulling at endotracheal tube, trying to remove catheters,
agitation climbing over bed rail, striking at staff, thrashing from side to
side
6 Very agitated Requiring restraint and frequent verbal reminding of limits,
biting endotracheal tube
5 Agitated Anxious or physically agitated, calming at verbal instruction
4 Calm and Calm, easily arousable, follows commands
cooperative
3 Sedated Difficult to arouse but awakens to verbal stimuli or gentle
shaking, follows simple commands but drifts off again
2 Very sedated Arouses to physical stimuli but does not communicate or follow
commands, may move spontaneously
1 Cannot be Minimal or no response to noxious stimuli, does not
aroused communicate or follow commands
Table 12.3 Richmond Agitation-Sedation Scale (RASS)

Score Term Description
+4 Combative Overtly combative, violent, immediate danger to staff
+3 Very agitated Pulls or removes tubes or catheters; aggressive
+2 Agitated Frequent non-purposeful movement, fights ventilator
+1 Restless Anxious but movements not aggressive or vigorous
0 Alert and calm
−1 Drowsy but has sustained (>10 s) awakening, with eye opening
in response to verbal command
−2 Light sedation Awakens briefly (<10 s) with eye contact to verbal command
−3 Moderate Any movement, except eye contact, in response to command
sedation
−4 Deep sedation No response to voice, but any movement to physical
stimulation
−5 Unarousable No response
An additional property of many sedative medications is amnesia. The importance

of amnesia in ICU patients is less well established than the anxiolytic property of
sedative medications. It is clearly indicated and considered mandatory during the
administration of neuromuscular blockade. In short periods, such as during an
unpleasant intervention, amnesia appears to be desirable, but prolonged periods of
amnesia may be detrimental. [37, 38].
12.7 Sedation: Management
The choice and dosage of sedative medication needed to maintain an optimal seda-
tion level may vary widely between patients and even for the same patient at differ-
ent points in his or her care. Dosing of sedative medications in the ICU is highly
variable due to altered pharmacokinetics and pharmacodynamics of drugs during
critical illness, particularly in the setting of obesity [39]. Important considerations
in dosing include volume of distribution, clearance, altered protein binding, and
organ function. The alterations in pharmacology due to critical illness are often
unpredictable; therefore, there cannot be a uniform dosing strategy for critically ill
patients, but rather dosing and titration must be against discernible clinical end
points.
In order to reach the optimal sedation level for a patient, either an intermittent or
continuous method of administration can be utilized. While a continuous infusion
may result in fewer fluctuations in medication levels and be less demanding on nurs-
ing, it can also lead to increased drug accumulation. The 2013 Clinical Practice
Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients
in the Intensive Care Unit recommend the practice of analgosedation, which pro-
motes the use of lighter sedation whenever possible [12]. This recommendation is
based on a substantial body of evidence that lower cumulative sedative doses are
associated with decreased risk of negative short- and long-term outcomes.
A landmark study that compared routine daily interruption of sedation with dis-
cretionary interruption by the treating physician found that patients randomized to
daily interruption received less total sedation and had a shorter duration of mechani-
cal ventilation and ICU length of stay [40]. A large, multicenter trial of daily inter-
ruption of sedation paired with daily spontaneous breathing trials showed that
interruption of sedation was associated with decreased administration of benzodiaz-
epines, reduced duration of mechanical ventilation, reduced ICU length of stay, and
significantly increased survival [41].
A 2012 study that evaluated the addition of daily interruption of sedation to
a protocol that minimized the level of sedation found no clinical benefit to the
addition of a daily interruption [42]. In a trial of mechanically ventilated
patients receiving analgesia with morphine, a comparison of no sedation versus
sedation with daily interruption found that no sedation was associated with
shorter ICU and hospital length of stay and decreased duration of mechanical
ventilation [43]. Depth of sedation has been independently associated with the
duration of mechanical ventilation, in-hospital mortality, and rates of death
within 180 days [44].
A clear and consistent message from the evidence available is that minimization
of sedation in the ICU results in clinical benefit. Reaching this goal requires careful
monitoring of the level of sedation provided. Protocol-driven sedation strategies aid
in the careful monitoring required by incorporating continuous reassessment of
sedation level and response to sedative medications [45].
In addition to the evidence supporting the use of light sedation when possible,
it is important to consider the limits deep sedation places on the ability to perform
a neurologic exam. Brain injury can be a devastating consequence of critical ill-
ness, and the ability to do a mental status examination to assess brain function is
critical. Early detection of acute cerebral dysfunction may allow for the ability to
correct the underlying process if possible before permanent injury takes place
(Table 12.3).
12.8 Choice of Medication: Sedation
The most commonly used sedative medications in the ICU are propofol and dexme-
detomidine. Benzodiazepines have largely fallen out of favor. Knowledge of the
pharmacokinetics and associated effects of sedative medications is imperative in
choosing a sedation strategy that provides an optimal level of patient comfort while
simultaneously minimizing the depth and duration of sedation (Table 12.4). While
there have been numerous studies comparing sedative regimens, there is a paucity
of evidence guiding this choice in obese patients.
Clearly, an important consideration when formulating a sedation strategy for all
patients is the impact of medication choice on critical care outcomes. In a meta-
analysis of randomized trials, the use of either a dexmedetomidine- or propofol-
based sedation regimen compared to a benzodiazepine-based sedation regimen was
Table 12.4 Sedatives
Dexmedetomidine Propofol Midazolam Lorazepam
Mechanism of action α2-agonist GABAA agonist (with other GABAA agonist GABAA agonist
effects)
Onset 5–10 min 1–2 min 3–5 min 15–20 min
Half-life Up to 3 h, duration 26–32 h 2–6 h, duration < 2 h (dose 8–15 h
60–120 min dependent)
Metabolism Hepatic, N-glucuronidation Hepatic, CYP2B6 Hepatic CYP3A4 Hepatic, glucuronidation
and N-methylation, CYP2A6
Active metabolite None None Yes, 1-hydroxymidazolam None
(accumulates with
prolonged infusion, renally
excreted)
Adverse effects Bradycardia, hypotension, Hypotension, respiratory Respiratory depression Respiratory depression,
xerostomia depression, hypertriglyceridemia, propylene glycol-related
pain on injection, pancreatitis, acidosis, renal failure
PRIS
Dose 0.2–1.5 μg/kg/h 5–50 μg/kg/min (doses greater 0.5–2 mg 0.5–2 mg
than 80 μg/kg/min increase risk
of HTG and PRIS)
Pharmacokinetics in obese No studies No significant change Increased volume of Increased volume of
patients distribution, increased distribution, increased
terminal elimination half-life, terminal elimination
prolonged duration of half-life, prolonged
action with infusion duration of action with
infusion
12 Sedation of the Obese Patient: Indications, Management, and Complications
Dosage in obese patients No specific dosing Based on TBW Loading dose based on TBW, Loading dose based on
recommendations. maintenance dosing based TBW, maintenance
Typically based on TBW on IBW dosing based on IBW
HTG hypertriglyceridemia, PRIS propofol infusion syndrome, TBW total body weight, IBW ideal body weight
131
associated with a shorter ICU length of stay and duration of mechanical ventilation
[46]. When comparing long-acting benzodiazepines with propofol, there was no
difference in mortality, but there was a reduction in the length of stay in the ICU
[47]. In a randomized trial of ICU patients receiving prolonged mechanical ventila-
tion, dexmedetomidine was associated with reduced duration of mechanical ventila-
tion compared to midazolam. Its use was also associated with an improved ability to
communicate pain level when compared to midazolam or propofol [48].
Delirium in mechanically ventilated patients in the ICU is common. Sedative use
is consistently linked to the development of delirium [49–51]. Delirium, defined as
a disturbance of consciousness characterized by acute onset and fluctuating course
of impaired cognitive functioning, is associated with increased mortality, prolonged
duration of mechanical ventilation, increased hospital length of stay, and higher risk
of cognitive impairment [52–54]. Therefore, minimizing the risk of delirium is
imperative to improving patient outcomes. In a randomized trial of sedation with
dexmedetomidine versus midazolam, the group receiving dexmedetomidine had a
reduced risk of delirium and shorter duration of mechanical ventilation despite
comparable sedation levels [55]. In a study of dexmedetomidine compared with
lorazepam infusion, the use of dexmedetomidine was associated with longer sur-
vival without delirium or coma [56].
Propofol: Propofol is a short-acting intravenous anesthetic agent. Its exact mech-
anism of action is unknown but is thought to act through the GABA receptor. It is
highly lipid soluble and rapidly crosses the blood-brain barrier, leading to an onset
of action of 1–5 min. The duration of action is short due to rapid distribution to
peripheral tissues [57, 58]. Its duration of action may increase with higher doses
used but typically remains short. Once propofol is stopped, it is redistributed back
into the plasma from fat tissue, but usually not in clinically significant levels. It
appears to have similar pharmacokinetics in obese and nonobese patients [59].
Propofol is a hypnotic agent that leads to dose-dependent suppression of aware-
ness. It also has potent anxiolytic and amnestic properties [60]. It does not provide
analgesia. In addition to its CNS effects, propofol causes respiratory depression and
significant hemodynamic changes. Hypotension is caused by dilation of venous
capacitance vessels leading to a reduction in preload. It is also associated with mild
myocardial depression.
Propofol is delivered by an intralipid carrier; therefore, continuous infusions can
lead to hypertriglyceridemia [61]. It is recommended that triglyceride levels are
checked every 48–72 h while receiving propofol, and it should be stopped if hyper-
triglyceridemia (> 500 mg/dL) occurs.
A rare adverse effect is propofol infusion syndrome. This typically occurs with
infusions over 48 h and high doses (> 80 μg/kg/min) and is characterized by meta-
bolic acidosis, rhabdomyolysis, hyperkalemia, dysrhythmias, and renal and heart
failure [62, 63].
Dexmedetomidine: Dexmedetomidine is a highly selective α2 agonist that has
sedative, anxiolytic, and analgesic properties [64–66]. Its distribution half-life is
6 min with a terminal half-life of 2 h. It undergoes hepatic metabolism; therefore,

hepatic impairment significantly reduces its clearance [67].
Dexmedetomidine provides light sedation allowing the patient to be more inter-
active and communicative resulting in improved ability to participate in routine care
and, importantly, the neurologic exam. Additionally, it does not cause respiratory
depression, allowing its use in non-intubated patients. Due to its analgesic effects,
the use of dexmedetomidine is associated with decreased requirements for opiate
analgesia [68]. Adverse effects of dexmedetomidine include xerostomia, bradycar-
dia, and hypotension [48, 55].
Benzodiazepines: Benzodiazepines act through the γ-aminobutyric acid (GABA)
receptor leading to inhibition of the central nervous system and dose-dependent
suppression of awareness. They are potent anxiolytic and amnestic agents [69, 70].
Additionally, all benzodiazepines have anticonvulsant properties [71].
They cause a dose-dependent, centrally mediated respiratory depression that is
less potent than opiates. This manifests as smaller tidal volumes and an increased
respiratory rate with a decreased ventilator response to hypoxia. Benzodiazepines
have minimal hemodynamic effects but may cause hypotension in hypovolemic
patients. All benzodiazepines are lipid soluble with a large volume of distribution.
The duration of action of various benzodiazepines depends on the rate of redistribu-
tion to peripheral tissues, especially adipose tissue. Maintenance dosing of benzodi-
azepines in obese patients should be based on ideal body weight [72].
Midazolam: Intravenous midazolam has a rapid onset of action (0.5–5 min) and
duration of action of approximately 2 h. It undergoes hepatic metabolism and renal
excretion. In the presence of renal failure, the active metabolite alpha-hydroxymidazolam
can accumulate leading to prolonged effects. When given as a continuous infusion, it
accumulates in peripheral tissues, leading to prolonged duration of clinical effect after
discontinuation [73]. Midazolam has an increased volume of distribution in obese
patients, and its terminal elimination half-life is prolonged [74, 75].
Lorazepam: Intravenous lorazepam has lower lipid solubility than midazolam
leading to a slower onset of action (5–20 min). Its lower lipid solubility leads to
decreased peripheral tissue redistribution and a longer duration of action (6–10 h).
High doses of lorazepam (> 6 mg/h for more than 48 h) increases the risk of propyl-
ene glycol toxicity, which presents as metabolic acidosis (increased lactate) and
renal failure.
Conclusion
Appropriate use of sedation and analgesia is an important component in the man-
agement of mechanically ventilated critically ill patients. There is significant
variation in medication requirements based on a patient’s underlying disease,
physiology, and the drug’s pharmacology. In obese patients this variation is fur-
ther increased. Directing treatment to individualized goals and implementation
of a strategy (Figure 12.1) that includes frequent and standardized assessment of
pain and sedation level will ensure that patient needs are met.
Pain Assessment
- Numeric Pain Rating Scale

- Begavioral Pain Scale
- Critical Care Pain Observation Tool
- Nonverbal Pain Scale
Treat Pain if Present
- Hydromorphone
- Morphine
- Fentanyl
- Remifenantil
Choose Sedation Strategy

- Daily Interruption of Sedation
- Sedation Scale-based Protocol
(Target to a RASS score -2 to 0)
- No sedation
Choose Sedative
- Dexmedetomidine
- Propofol
- Midazolam
Fig. 12.1 Analgesia and sedation algorithm

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Positioning of the Critically Ill Obese
Patient for Mechanical Ventilation 13
Malcolm Lemyze
13.1 Introduction
Positioning of the critically ill obese patient is often considered by the attending
clinician after the other therapeutic targets have been reached, while actually obese
patients’ position drastically impacts on mechanical ventilation success or failure
and may be a main determinant of the obese patients’ outcome.
13.2 Supine Position and Trendelenburg Position
When massively obese patients are allowed to lie completely flat, the abdomen
pushes the diaphragm upward, which leads to both an increase in intrathoracic pres-
sures and an extending airway collapse of the dependent parts of the lungs [1],
promoting expiratory flow limitation, gas trapping, auto-positive end-expiratory
pressure (auto-PEEP) [2–4], and severe hypoxemia [5, 6]. As demonstrated in
supine pregnant women [7], extrinsic compression of the inferior vena cava by the
abdominal weight may dangerously impair cardiac preload especially in hypovole-
mic patients with massive abdominal obesity. The combination of all these deleteri-
ous hemodynamic effects—the increased cardiac afterload, the decreased cardiac
preload, and an insufficient oxygen supply to the heart—is the winning recipe to
culminate in cardiac arrest. This scenario has been called “obesity supine death
syndrome” to describe the fulminant cardiorespiratory failure that results from the
supine positioning of a massively obese patient [8, 9]. Although rarely reported, it is
certainly underrecognized and misdiagnosed in clinical practice. Morbidly obese
patients in acute respiratory failure should therefore be assisted by noninvasive
M. Lemyze, M.D.
Department of Respiratory and Critical Care Medicine, Schaffner Hospital,
99 Route de la Bassée, Lens, France
e-mail: malcolmlemyze@yahoo.fr

140 M. Lemyze
Fig. 13.1 Panel (a): The classic “sniff position” offers poor conditions for intubation of the mas-
sively obese patient. Panel (b): The HELP or ramped position improves oxygenation and facilitates
laryngoscopy by placing the obese patient in 30 degrees reverse Trendelenburg in order to obtain a
horizontal alignment between the external auditory meatus and the sternal notch
mechanical ventilation each time they need to be kept supine (Fig. 13.1, Panel a),
and this should be limited in time to prevent the catastrophic syndrome described
above.
13.3 The Ramped Position or “HELP” Position for Intubation
Several anatomical characteristics of the morbidly obese patient increase the risk of
difficult intubation especially in the commonly used “sniff position” (Fig. 13.1,
Panel a). It cannot be emphasized enough that massively obese patients can become
13 Positioning of the Critically Ill Obese Patient for Mechanical Ventilation 141
severely hypoxemic immediately after they are placed in the supine position [5, 6].
The HELP (head-elevated laryngoscopy position) facilitates bag mask ventilation
and enhances the rate of successful intubation [10]. This position also called
“ramped position” is achieved by placing the patient in 30° reverse Trendelenburg
in order to obtain a horizontal alignment between the external auditory meatus and
the sternal notch, which significantly improves direct laryngoscopy (Fig. 13.1,
Panel b). Furthermore, it prolongs the “safe apnea time”—the delay between anes-
thetic induction and hemoglobin desaturation below 90%—which gives the clini-
cian some more time to intubate the patient safely [11].
13.4 Prone Position
In the obese patient, impaired pulmonary gas exchange mainly results from
ventilation-perfusion mismatch. The cephalad displacement of the diaphragm and
the extrinsic compression exerted by the thoracoabdominal wall reduce ventilation
of the lower posterior parts of the lungs. These dependent parts of the lungs are well
perfused especially in the supine position which results in a drop of ventilation-
perfusion ratio (shunt effect) that generates severe hypoxemia [12]. Proning the
obese patient may facilitate alveolar recruitment of the dependent parts of the lungs,
improves perfusion of the most aerated lung area, and thus may substantially
improves pulmonary gas exchange. Pelosi et al. demonstrated that prone position
significantly increases functional residual capacity, lung compliance, and oxygen-
ation during general anesthesia [12]. This is especially interesting for the most
hypoxemic obese patients—those exhibiting ARDS or extensive atelectasis—under
invasive mechanical ventilation. One special hurdle that needs to be overcome in
order to get the most benefit from this strategy is to alleviate thoracoabdominal wall
compression. Pillows may be placed under the patient’s upper chest and pelvis in
order to maintain an abdomen-free position [12]. When executed by a well-trained
team with at least 5–6 individuals per obese patient during the procedure, prone
positioning does not result in more complication than in non-obese patients with a
greater benefit in terms of increase in PaO2/FiO2 ratio and a better survival [13].
13.5 Lateral Decubitus Position
Lateral decubitus position probably relieves the diaphragm and the large intra-
abdominal vessels from the weight of the panniculus. Objectively, it diminishes
auto-PEEP and reverses expiratory flow limitation phenomenon that is commonly
encountered in supine obese patients [2]. However, during mechanical ventilation,
this position exposes the most obese patients to the risk of developing extensive
atelectasis of the dependent lung which then promotes severe hypoxemia and super-
infection. A more appealing strategy would be based on a periodical rotation alter-
nating right lateral with left lateral decubitus position in case of absolute
contraindication to the sitting position.
142 M. Lemyze
13.6 Sitting Position or “Cardiac Chair Position”
Sitting position (Fig. 13.2) reverses expiratory flow limitation of the obese patient
and relieves the respiratory system from the additional elastic load induced by
auto-PEEP in the supine position [3, 4]. It could therefore avoid the unnecessary
use of inefficient but potentially dangerous drugs (high doses of corticosteroids or
bronchodilators, for instance) or useless risky interventions (high increase in
PEEP level, fiber optic bronchoscopy) in the morbidly obese patient in acute
respiratory failure [4, 14]. The excursion course of the diaphragm is also facili-
tated by the gravitational forces in the sitting or upright position, while the abdo-
men crushes the diaphragm in supine morbidly obese patients (Fig. 13.1, Panel a).
A change in posture from sitting to supine causes an increase in neural drive with
higher esophageal pressure swings and electromyogram activity of the diaphragm
[15]. On the opposite, all intrathoracic pressures—including plateau pressure and
intrinsic PEEP—are reduced when the obese patient is seated [4]. Sitting position
offers better conditions for the application of noninvasive ventilation and for the
weaning process from mechanical ventilation and may be part of the protective
a b
Fig. 13.2 Panel (a): Sitting position during the weaning process from mechanical ventilation in a
critically ill morbidly obese woman. Panel (b): The successful combination of noninvasive ventila-
tion and cardiac chair position is applied immediately after extubation
13 Positioning of the Critically Ill Obese Patient for Mechanical Ventilation 143
ventilation strategy that is currently recommended in acute lung injuries. By lim-

iting auto-PEEP and reducing inspiratory efforts, it can be assumed that sitting
position decreases pleural pressure swings and thus transpulmonary pressure dur-
ing insufflation [4, 15]. Combining sitting position and high external PEEP may
keep transpulmonary pressure positive at expiration and thus may prevent airway
collapse.
Of course, critically ill obese patients should be regularly repositioned to ensure
that they tolerate the sitting position for a few hours straight and to prevent them
from slipping off the bed. One solution is to place the critically ill obese patient in a
chair as soon as possible (Fig. 13.2, Panel b). Attention should be paid on not com-
pressing the patient’s abdomen by maintaining slightly open legs in the sitting pos-
ture. An early rehabilitation program can be safely implemented in the most
critically ill patients, although nearly 90% of them exhibit a situation that is com-
monly regarded as a major barrier to physical therapy and mobilization during
mechanical ventilation [16]. Obesity is usually considered as one of these potential
barriers that hinder early mobilization [16]. However, providing that bariatric equip-
ment and a high caregivers-to-patients ratio are available—two conditions that are
generally fulfilled in the ICU—sitting position should be easily achieved in most of
the massively obese patients in acute respiratory failure.
Conclusion
Based on physiological considerations, good positioning of the morbidly obese
patient in acute respiratory failure should be regarded as a main therapeutic tar-
get as important as the settings of the ventilator, the choice of antibiotics, the
volume of fluids, or any other treatment that can impact obese patients’ outcome
in the emergency setting. When this will be figured out, physicians will do every-
thing in their power to convince their staff to implement sitting position and early
rehabilitation in critically ill obese patients.
13.7 Key Messages
1. More than for any other critically ill patients, obese patients’ positioning is a key
determinant of mechanical ventilation success or failure and drastically impacts
on obese patients’ outcome.
2. Everything should be done to avoid supine position and Trendelenburg position
in critically ill patients with massive android obesity.
3. The ramped position or “HELP” (head-elevated laryngoscopy position) facili-
tates obese patients’ intubation.
4. For the more severely hypoxemic obese patients, prone position has proved safe
and effective in recruiting the atelectatic dependent parts of the lungs during
mechanical ventilation.
5. Sitting position is the optimal position to provide noninvasive ventilation, to
facilitate the weaning process from mechanical ventilation, and to prevent atel-
ectasis and acute respiratory failure episodes in massively obese patients.
144 M. Lemyze
References
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atelectasis: an underestimated problem. Anesth Analg. 2002;95:1788–92.
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expiratory pressure on respiratory mechanics of critically ill obese patients receiving mechani-
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5. Yamane T, Date T, Tokuda M, et al. Hypoxemia in inferior pulmonary veins in supine position
is dependent on obesity. Am J Respir Crit Care Med. 2008;178:295–9.
6. Pelosi P, Croci M, Ravagnan I, et al. Respiratory system mechanics in sedated, paralyzed,
morbidly obese patients. J Appl Physiol. 1997;82:811–8.
7. Wright L. Postural hypotension in late pregnancy. “The supine hypotensive syndrome”. Br
Med J. 1962;1:760–2.
8. Tsueda K, Debrand M, Zeok SS, et al. Obesity supine death syndrome: reports of two mor-
bidly obese patients. Anesth Analg. 1979;58:345–7.
9. Lemyze M, Guerry MJ, Mallat J, Thevenin D. Obesity supine death syndrome revisited. Eur
Respir J. 2012;40:1568–9.
10. Collins JS, Lemmens HJ, Brodsky JB, et al. Laryngoscopy and morbid obesity: a comparison
of the “sniff” and “ramped” positions. Obes Surg. 2004;14:1171–5.
11. Boyce JR, Ness T, Castroman P, et al. A preliminary study of the optimal anesthesia position-
ing for the morbidly obese patient. Obes Surg. 2003;13:4–9.
12. Pelosi P, Croci M, Calappi E, et al. Prone positioning improves pulmonary function in obese
patients during general anesthesia. Anesth Analg. 1996;83:578–83.
13. De Jong A, Molinari N, Sebbane M, Prades A, Futier E, Jung B, Chanques G, Jaber

S. Feasibility and effectiveness of prone position in morbidly obese patients with ARDS: a
case-control clinical study. Chest. 2013;143:1554–61.
14. Fortis S, Kittah J, De Aguirre M, et al. Perseverant, nonindicated treatment of obese patients
for obstructive lung disease. BMC Pulm Med. 2013;13:68.
15. Steier J, Jolley CJ, Seymour J, et al. Neural respiratory drive in obesity. Thorax. 2009;64:719–25.
16. Pohlman MC, Schweickert WD, Pohlman AS, Nigos C, et al. Feasibility of physical and
occupational therapy beginning from initiation of mechanical ventilation. Crit Care Med.
2010;38:2089–94.
Obesity and Positive End-Expiratory
Pressure (PEEP)-Obesity 14
and Recruitment Maneuvers During
the Intraoperative Period
Seniyye Ulgen Zengin and Güniz Köksal
14.1 Introduction
Obesity is a global and growing public health problem. Worldwide obesity has more
than doubled since the 1980s with around 600 million people being obese [1]. There
has been a steady increase in the number of obese patients undergoing both bariatric
and non-bariatric surgeries, and it seems likely that there will be more obese patients
undergoing surgery in the future. Obesity is a risk factor for the onset of intra- and
postoperative respiratory complications when compared to non-obese individuals [2].
Due to excessive weight load on the chest wall and intra-abdominal and intratho-
racic compartments, there is a decrease in lung volumes and pulmonary compliance
that causes restrictive pulmonary physiology. Every unit of BMI increase can be
expected to reduce residual volume, total lung capacity, and vital capacity by 0.5%.
Even at a BMI of 30 kg/m2, the EVR and functional residual capacity (FRC) can be
reduced by 53 and 25%, respectively. It is possible that with reduced FRC and EVR,
tidal volume is closer to RV. In the upright position, the lower part of the lungs of
the obese is overperfused and underventilated. So with these findings, obese patients
more easily lead to airway closure during tidal breathing, atelectasis, and
ventilation—perfusion mismatch and shunt formation lending impairment of gas
exchange [2]. In anesthetic patient, a 20% reduction in FRC in non-obese subjects
compared with a 50% FRC reduction in the obese was demonstrated [3].
S.U. Zengin, M.D. (*)

Department of Anesthesiology and Reanimation, Bezmialem Vakif University Faculty of
Medicine, Istanbul, Turkey
e-mail: ulgen_t@yahoo.com
G. Köksal, M.D.
Department of Anesthesiology and Reanimation, Istanbul University, Cerrahpasa Medical
School, Istanbul, Turkey
e-mail: gunizkoksal@hotmail.com

146 S.U. Zengin and G. Köksal
Respiratory complications occur within minutes after the induction of anesthesia

in 85–90% of patients, and the adverse effects persist during the postoperative period,
affecting the patient’s recovery. Furthermore, it has been demonstrated that obesity is
a risk factor for postoperative tracheal re-intubation, morbidity, and mortality.
Several strategies have reported about the benefits of respiratory physiotherapy
in the pre- and postoperative periods of these patients, thus preventing the pulmo-
nary complications related to surgeries [4]. These ventilation strategies would be
expected to optimize gas exchange and pulmonary mechanics and to minimize the
risk of postoperative respiratory complications.
14.2 Intraoperative Techniques
Different ventilation strategies including PEEP (positive end-expiratory pressure),

RM (recruitment maneuver), ventilation modes, and high tidal volume are used to
reduce pulmonary complications. However, the ideal ventilation strategy in obese
patients undergoing surgery under general anesthesia has not yet been established.
Positive end-expiratory pressure (PEEP) is an easily implemented intervention
that can be used in ventilating a patient with positive pressure ventilation. It is a
mechanical maneuver that positive pressure is exerted in the lungs at the end of each
exhalation [4]. This end-expiratory pressure increases the functional residual capac-
ity (FRC) and prevents collapse of the small airways, thereby reducing atelectasis.
In patients with healthy lungs, PEEP leads to improved lung compliance, decreased
shunting, and higher arterial oxygen pressure (PaO2). Coussa et al. ventilated the
patients with PEEP at 10 cm H2O during surgery and observed the prevention of
intraoperative atelectasis [5]. However, there was no follow-up of these patients in
the postoperative period. In a study Baltieri et al. confirmed that high levels of PEEP
during surgery can maintain lung expansion for up to 48 h after extubation, as con-
firmed by the decreased prevalence of atelectasis shown on the chest radiographies
on the second day after surgery [6].
Timing of the PEEP is another controversial aspect. In a recent study, PEEP
decreased the prevalence of postoperative atelectasis, but the most effective treat-
ment for this purpose was observed with the use of positive pressure immediately
after surgery, in which case the incidence of atelectasis was null [6].
Using PEEP like two-edged sword, in damaged lungs, PEEP may cause overdis-
tension of normal lung areas without improvement in abnormal areas [7]. So it is
possible that PEEP may actually impair respiratory function. The risk of barotrauma
may increase because of increased intrapleural pressure caused by PEEP and may
induce negative cardiovascular effects. Cardiovascular effects can change the intra-
operative management of a patient’s condition, sometimes causing an increase in the
need for cardiovascular support. Pelosi et al. found that 10 cm H2O PEEP improved
oxygenation in obese but not in normal subjects [8]. The application of PEEP resulted
in greater alveolar recruitment in obese patients. The unchanged oxygenation in nor-
mal patients is attributed to decreased cardiac output associated with PEEP.
14 Recruitment Maneuver 147
The RM most commonly described in the literature is sustained inflation, with

a rapid increase in pressure to 40 cm H2O that is applied for a period of 40–60 s.
Different types of recruitment maneuvers are described in the literature [9]: pro-
longed recruitment maneuvers with low pressure and increased positive end-
expiratory pressure (PEEP) to 15 cm H2O, associated with expiratory pauses of 7 s
twice per minute for 15 min; [2] incremental increases in PEEP, limiting the maxi-
mum inspiratory pressure; and [3] ventilation with constant controlled pressure
with PEEP staggering. There is no clear consensus about the optimal duration or
time of application of recruitment maneuver. Recent studies have been summited
where a single recruitment maneuver was applied either after induction of anesthe-
sia, after abdominal opening, after pneumoperitoneum, or after suture of abdomi-
nal aponeurosis [9–11]. Rothen et al. represent that reopening of the alveoli occurs
within first 7–8 s of vital capacity maneuver in healthy anesthetized subjects with
no previous lung disease [12]. More studies are needed to determine the optimal
timing of application of recruitment maneuver and its duration. Repetition is also
another factor that influences the effectiveness of RM, so increasing the frequency
of the maneuver is important. Ahmed et al. aimed to represent the effect of RM
repetition with respect to oxygenation and the reduction of atelectasis [13]. To do
so, 60 patients were randomly divided into 3 groups: conventional ventilation,
single RM (40 cm H2O for 7 s), and ARM repeated every 30 min. All groups were
treated with PEEP set at 10 cm H2O. In addition to improving gas exchange and
respiratory mechanics, repeated RM maintained its beneficial effects during the
postoperative period [13].
RM in the presence of PEEP, and compared with PEEP alone, has a beneficial
effect on oxygenation and compliance in obese patients undergoing surgery. The
mechanism is how the combination of RM and PEEP works, and the positive
effect could be that RM opens the collapsed alveoli and PEEP keeps them open.
When a recruitment maneuver was applied without PEEP, the effect was short
lasting. 20 min after the recruitment maneuver, no beneficial effects remained.
This is in contrast to what has been observed in normal-weight patients in whom
a recruitment maneuver followed by ZEEP (zero PEEP) reduced atelectasis sig-
nificantly for at least 20 min if FIO2 was kept at 0.4. This observation suggests
that the application of PEEP in morbidly obese patients is necessary to keep the
lung open and improve respiratory function after an effective recruitment maneu-
ver. It was observed that repeated inspiratory pressure maneuver combined with
10 cm H2O of PEEP increased respiratory system compliance and PaO2 and
decreased PaCO2 in obese patients undergoing laparoscopic gastric banding with-
out adverse effects and the positive effects on oxygenation continued into the
early recovery period [6]. In a study Reinus et al. reported lung recruitment using
inspiratory pressure of 40 cm H2O for 15 s repeated every 10 min and combined
with PEEP of 10 cm H2O was associated with the best respiratory system compli-
ance and best PaO2 in obese patients undergoing laparoscopic bariatric surgery,
when compared with PEEP of 10 cm H2O alone, inspiratory pressure of 40 cm
H2O applied once for 15 s, or both.
148 S.U. Zengin and G. Köksal
Although barotrauma is a major problem in patients treated with RM, only two
randomized trials reported on this complication, and both analyzed the effect of RM
plus PEEP. In those trials, patients (n = 92) were ventilated with different RM regi-
mens and none was reported to suffer from barotrauma [2, 14]. This does not
exclude the risk of barotrauma in obese surgical patients who are ventilated with
RM. But, there were similar data from critical care patients with ALI. One of the
important problems is in hypovolemic patients’ recruitment maneuver with exces-
sive pressure may cause hemodynamic instability [10]. In addition RM can decrease
the venous return by increasing intrathoracic pressure, which can cause venous sta-
sis, especially in the low the lower extremities, increasing the risk of deep vein
thrombosis [6].
In conclusion, studies indicate that anesthesia in morbidly obese patients induces
atelectasis formation and impairment in oxygenation. An effective recruitment
maneuver followed by PEEP was the good choice to reduce the amount of atelecta-
sis and improve oxygenation for a prolonged period of time. However, PEEP or
recruitment maneuver alone was not effective to reach a sustained improvement of
respiratory function.
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14 Recruitment Maneuver 149
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Anesth Analg. 2009;109:1511–6.
Complications Associated with Invasive
Mechanical Ventilation in Obese Patients 15
Nishant Chauhan
15.1 Introduction
Obesity is not a problem of any particular geographic area. With rising living stan-
dards, changing lifestyles and dietary habits, the prevalence of obesity has increased
world over. Obesity has more than doubled since 1980, and most of the world’s
population live in countries where overweight and obesity leads to more mortality
than underweight [1]. Not only does obesity pose a problem in managing a particu-
lar critical illness but also in areas related to invasive mechanical ventilation (IMV),
hemodynamic monitoring, etc. Obesity-related respiratory morbidity arises mainly
from derangements in control of breathing and chest wall mechanics. It is associ-
ated with reduction in respiratory drive, decreased lung volumes, reduced respira-
tory muscle strength and increased work of breathing [2, 3]. Respiratory system
compliance is usually reduced in obese patients and is primarily attributed to
decrease in lung compliance. This leads to risk of developing atelectasis. Some of
the morbidly obese patients show increased airway resistance, causing airflow limi-
tation and development of intrinsic positive end-expiratory pressure (iPEEP).
Respiratory muscle strength and endurance are generally well preserved in simple
obesity but reduced in morbidly obese patients. This leads to decrease in total lung
capacity (TLC) in these patients. Upper airway collapsibility seen during sleep
causes episodic apnoeas and desaturations in patients of obstructive sleep apnoea
(OSA).Ventilatory response to hypoxia and hypercapnia is reduced to some extent
in simple obesity but more so in obesity hypoventilation syndrome (OHS)
patients [4]. This fact has to be kept in mind while mechanically ventilating as well
as weaning obese patients from ventilation.
N. Chauhan
Pulmonary Medicine, All India Institute of Medical Sciences (AIIMS),
Jodhpur, Rajasthan 342005, India
e-mail: nishant97@gmail.com

152 N. Chauhan
15.2 Discussion
Before we dwell into the complications associated with IMV in obese patients, we
should know about the effects of obesity on lung volumes and lung functions. Two
medical conditions causing sleep-disordered breathing, OSA and OHS, are highly
prevalent in obese and morbidly obese patients, respectively. Unless we are able to
recognise these conditions prior to or during mechanical ventilation, there are higher
chances of complications related to the disease itself in addition to inefficient venti-
lator settings.
15.2.1 Lung Volumes and Functions
It has been found that the greatest impact of obesity is on functional residual capac-
ity (FRC) and the expiratory reserve volume (ERV), affecting total lung capacity
(TLC) and vital capacity (VC) to a lesser extent. TLC is reduced in morbidly obese
patients who have reduced muscle strength and endurance. Obesity also affects air-
way resistance. According to the Poiseuille equation, the pressure-flow characteris-
tics of laminar flow depend on the length and the radius of the tube and viscosity of
the gas [5]. This signifies the importance of airway in determining the driving pres-
sure for a given flow, so that if the radius of the tube (airway in this case) is halved,
the pressure that is required to maintain a given flow rate must be increased 16-fold.
Since airway size is a function of lung volume, lower lung volumes are related with
reduced airway size leading to increase in airway resistance. This is clinically
important in choosing ventilator settings in obese patients and not simply or solely
relating this increased airway resistance to asthma or any other obstructive lung
disorder. Since obesity itself is a systemic inflammatory disorder, this inflammation
may act on distal airways causing increased airway responsiveness. Respiratory
system compliance is also reduced in obese patients which is mainly attributed to
reduction in lung compliance.
15.2.2 Sleep-Disordered Breathing
Obesity is a major risk factor for the development of sleep-disordered breathing

which primarily includes OSA and OHS. A proper evaluation of relevant clinical
symptoms and signs along with sleep history is essential to suspect these entities in
an obese patient who is being mechanically ventilated. Since a detailed description
of these two disorders is beyond the scope of this chapter, a brief mention is being
made. OSA is characterised by repeated episodes of apnoea or hypopnoeas during
sleep, leading to intermittent hypoxemia and sleep fragmentation. Apnoeas and
hypopnoeas are due to episodes of airway collapsibility seen in these patients which
occur only during sleep. Another spectrum of obese patients with higher BMI is
those which may be suffering from what is known as OHS which consists of day-
time and nocturnal hypoventilation after excluding other causes of alveolar
15 Complications Associated with Invasive Mechanical Ventilation in Obese Patients 153
hypoventilation, such as chronic obstructive pulmonary disease (COPD) and paren-

chymal and extraparenchymal restrictive respiratory disorders. In arterial blood gas
(ABG), we find that OHS patients have daytime and nocturnal PCO2 >45 mm Hg
with more elevation of PCO2 during sleep. These patients are at risk to present in the
ICU or emergency room with acute or chronic respiratory failure.
Once the patient has been intubated and connected to the ventilator all the above
facts should be borne in mind while ventilating an obese patient. The following
parameters need special consideration: [1] optimum tidal volume delivery (VT), [2]
optimum PEEP and [3] application of recruitment manoeuvres.
Many studies have shown that lung protection strategies used for ventilating
adult respiratory distress syndrome (ARDS) patients suit well for obese patients as
well. Due to increased mechanical load on the chest wall and reduced compliance
of the respiratory system in obese patients, the dependent posterior segments of the
lungs of obese patients are prone to hypoventilation and atelectasis [6]. Due to low
lung volumes, the distal most airways have a tendency to remain collapsed with
sudden and repeated opening and collapse with each ventilator breaths leading to
“recruitment-derecruitment phenomenon” causing atelectrauma. This will not only
trigger but also enhance the ongoing lung inflammation, known as biotrauma, histo-
logically seen as diffuse alveolar damage. Experimental laboratory study has shown
histological evidences of lung injury due to repeated derecruitments during mechan-
ical ventilation [7]. As of now, there are no clear guidelines for setting VT in patients
without ARDS. Most of the studies show the association of higher VT and ARDS,
suggesting that low tidal volume lung protection strategies, VT of 6–8 mL/Kg pre-
dicted body weight (PBW), are useful for obese patients as well. The use of PBW
instead of actual body weight is preferred because lung volumes are proportional to
height but independent of body weight.
Ventilating obese patients and limiting airway plateau pressure (Pplat) ≤30 cm
H2O are difficult due to reduced chest wall and lung compliance. Transpulmonary
pressure (TPP) defined as the difference between airway and pleural pressures is
important in gauging the risk of barotrauma. Use of pleural pressure which is mea-
sured by oesophageal manometry can be used in advanced ICU settings. Alveolar
overdistension can be prevented during inspiration by keeping the TPP below 25 cm
H2O. There is a tendency for the gravity-dependent segments of the lung to undergo
atelectasis during the expiratory phase of respiratory cycle. There are some lung
units which are open, and some are collapsed leading to heterogeneity in ventilated
areas of the lungs. Alveolar overdistension and cyclical opening and collapse of the
alveoli lead to atelectrauma. One of the ways to counteract this lung damaging phe-
nomenon is to apply appropriate PEEP to keep the alveoli open throughout the
phase of respiratory cycle. This also leads to homogeneity in lung ventilation and
reduction in the number of atelectatic lung units. As explained above, obese patients
have higher pleural pressure on end expiration so higher levels of PEEP are required
in such patients. Optimum PEEP calculation can be done by setting the PEEP to
maintain TPP of 0–10 cm H2O at end expiration. There are other methods like best
lung compliance, gas exchange method, etc. The aim is to keep the alveoli distended
at end expiration with minimal positive pressure that will not allow derecruitment to
154 N. Chauhan
occur and maintain adequate oxygenation. It has been shown in various studies that
recruitment manoeuvres reduce atelectasis and lung compliance, thereby improving
oxygenation in the mechanically ventilated obese patients. Application of PEEP
after a recruitment manoeuvre would prevent alveolar collapse in obese patients.
The adverse effects associated with these manoeuvres are transient desaturation,
hypotension, arrhythmias and barotrauma. Close monitoring for anticipation and
occurrence of these complications is required.
Obese patients with underlying OSA have a tendency of going into repetitive
episodes of apnoeas and desaturations when they are being ventilated on assist con-
trol or pressure support modes while they are sedated. This is due to upper airway
collapsibility during sleep or under general anaesthesia. Application of
PEEP/continuous positive airway pressure (CPAP) adequate enough to provide
splinting action on the upper airway will abort these apnoeic events, thus easing the
process of liberating them from mechanical ventilation. Inability to diagnose or
suspect OSA would lead to inadvertent increase in fractional inhalation of oxygen
(FiO2) delivery which would further deteriorate the condition by increasing the
length of apnoeas duration and risk of causing hypercarbia. On the other hand, OHS
patients additionally hypoventilate as evidenced by raised PCO2 levels. A simple
way to treat this is to provide pressure support or bilevel positive airway pressure
(BiPAP) support to such patients which would deliver them adequate tidal volume,
thereby preventing hypoventilation. A high index of suspicion should be kept for the
possibility of these sleep disorders in obese patients. This would lead to reduction
of duration of mechanical ventilation once the primary illness has been treated. Any
prolongation due to these conditions will put the patient at risk for both ventilator-
and non-ventilator-associated complications during the ICU stay.
Various changes described in the respiratory physiology along with the related
problem are mentioned in Table 15.1. The pharmacokinetics of sedatives and
Table 15.1 Changes in the respiratory physiology along with the related problem
Changes in respiratory physiology Problem
Excessive oropharyngeal fat Upper airway obstruction leading to difficult
intubation and ventilation
Reduced chest wall and lung compliance Inadequate tidal volume delivery in pressure
control mode
Reduced FRC and ERV Risk of atelectasis and hypoxemia
Alveolar collapse Hypoxemia
Increased airway resistance Increased airway pressures
Increased body weight Difficulty in changing positions, including
prone positioning
Airway collapsibility Recurrent episodes of apnoea during weaning
seen in OSA patients
Reduced respiratory drive and airway Episodes of hypercapnia seen in OHS patients
collapsibility
Auto PEEP due to airway closure during Increased work of breathing
expiration
15 Complications Associated with Invasive Mechanical Ventilation in Obese Patients 155
neuromuscular blockers (NMBs) is affected by the mass of adipose tissue which is

more in an obese patient, producing a prolonged and less predictable effect causing
difficulty in arousal assessment [8] while the patient is on mechanical ventilation
and at the time of liberation from mechanical ventilation.
15.2.3 Weaning from Mechanical Ventilation
Due to excess fat deposition and deranged physiology, obese patients are at risk
of prolonged ventilation and difficult weaning. Use of non-invasive positive pres-
sure ventilation (NIPPV) early after extubation has shown to significantly reduce
the duration of mechanical ventilation and prevent reintubation. Reversal to
spontaneous breathing and arousal state may be delayed after stopping the infu-
sion of sedative and NMBs in obese patients due to altered pharmacokinetics as
mentioned earlier. Recognition of sleep disorders such as OSA and OHS is
important especially more so when planning to liberate these patient from the
ventilator.
Conclusion
The increase in the proportion of obese patients requiring mechanical ventila-
tion for different medical conditions is a challenge for the anaesthesiologists,
pulmonologists and critical care physicians. Mechanical ventilation of criti-
cally ill obese patients requires detailed knowledge of the altered respiratory
physiology and related complications seen in these patients. Two important
sleep disorders to suspect in obese patients are OSA and OHS. Appropriate
tidal volume delivery and optimal PEEP to avoid ventilator-induced lung
injury, including barotrauma and atelectrauma, are the primary objectives.
Consideration must be given to combine recruitment manoeuvres in the venti-
lator management rather than reserving it as a last resort. Weaning with the use
of CPAP/NIPPV/BiPAP has shown good results in multiple studies and must
be tried when indicated.
• Knowledge of the impact of obesity on respiratory physiology is the key compo-

nent in providing better ventilatory support to critically ill obese patients.
• Optimised tidal volume delivery along with application of PEEP and recruitment
manoeuvres would minimise volutrauma, atelectrauma and nonhomogeneous
ventilation in different parts of the lungs.
• Early recognition of sleep disorders like OSA and OHS would help in choosing
better modes of mechanical ventilation.
• Use of CPAP/NIPPV in select group of obese patients during weaning process is
likely to avoid prolonged ventilation and ICU stay.
156 N. Chauhan
References
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Pharmacol. 2012;4:53–63.
Management of Ventilator-Induced
Lung Injury 16
Sven Stieglitz
The study from Dreyfuss in 1985 demonstrated impressively that ventilation alone
may harm and destroy even healthy lungs [1]. The reason is that ventilation itself
may damage the lung by developing a ventilator-induced lung injury (VILI).
16.1 What Is the Characterization of VILI?
Initially, the development of VILI was explained by two different mechanisms:

firstly baro- and volutrauma due to overdistension and rupture of alveolar walls in
non-dependent lung regions by high inspiratory pressure and/or high volume and
secondly cyclical reopening (tidal recruitment) of the alveoli during inspiration fol-
lowed by the next expiration leading to shear stress and atelectrauma, a phenome-
non occurring in dependent lung regions due to insufficient PEEP. The volutrauma
rather leads to pulmonary edema with persistent inflammation followed by fibrosis
and atelectrauma to alveolar capillary damage with surfactant dysfunction leading
to alveolar collapse. The relation between PEEP and inspiratory pressure is
described by the driving pressure ΔP = VT/C (VT = tidal volume, C = compliance)
or plateau pressure minus PEEP (in controlled ventilation only) [2]. These
pathomechanisms are not integrating dynamic aspects of stress and strain. In fact,
dynamic strain (ratio between tidal volume and functional residual capacity) seems
to be worse than static strain [3]. A high strain (amplitude) rate (velocity) is a risk
factor for ventilator-induced pulmonary edema, possibly because it amplifies lung
viscoelastic behavior [4]. Recently, the dynamic predictors of VILI risk were
assessed by the key values of ventilator settings [5]: the mechanical power mea-
sured by the pressure–volume loops and its components tidal volume (TV)/driving
S. Stieglitz
Clinic for Pneumology, Allergology, Sleep und Intensive Care Medicine at Petrus Hospital
Wuppertal, Wuppertal, Germany
e-mail: sven.stieglitz@cellitinnen.de

158 S. Stieglitz
pressure (ΔPaw), flow, positive end-expiratory pressure (PEEP), and respiratory

rate (RR) [6]. Since ventilation and perfusion are distributed heterogeneously
already in the healthy lung, the ventilation-perfusion mismatch is even marked in
obesity. The inhomogeneity of the lung in ARDS dictates an inhomogeneous distri-
bution not only of alveolar gases but also of forces and mechanical power, which is
likely the main lung-dependent cause of VILI [6]. The initial local inflammation of
the lung may finally damage the whole lung and even can lead to multi-organ failure
(MOV) and sepsis [7]. In rats an increase of white blood cell count, H2O2, interleu-
kin-1, tumor necrosis factor alpha, and macrophage inflammatory protein-2 in bron-
choalveolar lavage may be observed [8]. The damage-associated molecular pattern
linked to VILI is characterized by activation of recognition receptors, releasing pro-
inflammatory cytokines and chemokines [9], and may trigger MOV.
16.2 W
hich Kind of Respiratory Mechanics Are Altered
in Obese Patients and Is Obesity a Risk Factor
for Developing VILI During Invasive Ventilation?
Since there are no data about the prevalence of VILI in obese patients, we first shall
have a look at the respiratory mechanics in obesity. Surprisingly, lung function in
obesity is hardly changed both at rest and during exercise. The most common find-
ing is a decrease in functional residual capacity (FRC) and a decrease of the expira-
tory reserve volume (ERV). This leads to a more common expiratory flow limitation
with development of intrinsic positive end-expiratory pressure (iPEEP). All
changes of lung function are marked in supine position which is important for
understanding ventilation strategies in obese patients [10]. Ventilation-perfusion
mismatch is a leading finding in obesity which reduces gas exchange and contrib-
utes to hypoxemia, which is also marked in the supine patient. Breathing with a
reduced FRC means breathing on the flat part of the pressure-volume curve (with
low compliance), which requires a higher work of breathing to overcome the tho-
rax wall that is thickened anyway (reducing the compliance furthermore). These
factors increase the work of breathing which seemed to be doubled in the supine
compared with the upper position [11]. All these factors impair the function or
respiratory muscles [12]. The typical breathing pattern in obese patients is charac-
terized by a low tidal volume and a higher breathing rate. Moreover, fatty deposits
increase the pharyngeal collapsibility which together with a blunted ventilatory
drive, an increase of bicarbonate and leptin [13] concentration and other neurohu-
moral influences lead to the development of sleep apnea and obesity hypoventila-
tion syndrome (OHS).
Summarizing the pathophysiology of respiratory mechanics in obesity, theoreti-
cally there is an increased risk for VILI by cyclical reopening (tidal recruitment) of
alveoli during inspiration (shear stress) due to the lower FRC in combination of
higher necessary IPAP due to an elevated abdominal pressure which counteracts the
motion of the diaphragm.
Hypoxemia may either be caused by hypoventilation or due to ventilation-
perfusion mismatch. Treating the hypoxemia with high inspiratory oxygen
16 Management of Ventilator-Induced Lung Injury 159
concentration may also harm [14] since it triggers inflammation and edema of the
lung (Lorrain-Smith effect) and aggravates atelectasis by absorption.
16.3 VILI: Which Treatment?
There are some animal studies on medical treatment of VILI. N-acetylcysteine [15] and
apocynin [16] in a rat lung model, inhaled interleukin-10 [17], as well as airway instal-
lation of budesonide in rats [15] ameliorate VILI and/or even improve outcome. Since
there is no established medical treatment against VILI in man, ventilator strategies to
avoid the development of VILI are the most important measures. Ventilating the lung
with low volume but high positive end-expiratory pressure (PEEP) has been proven to
be less harmful (“lung protective” is a critical term since ventilation itself never can be
protective but remains always a risk for the lung) in several outcome studies since the
milestone set by the first ARDS network trial [18]. The effect of ventilation with low
volume and higher PEEP is attributed to a reduction in volutrauma. The major consid-
eration in ventilating obese patients is a higher PEEP than usual (≥7 cmH2O) to antag-
onize the iPEEP, to increase the FRC, to recruit the lung, and to keep the lung open.
The oxygenation is optimized by PEEP titration and supporting the ventilation
rather than increasing the oxygen supply. There are numerous ways to achieve alve-
olar recruitment, and still there is no gold standard to set PEEP [19], an issue which
is not discussed in this chapter. A bedside test to estimate the contribution of
hypoventilation to hypoxemia is the alveolar gas equation: it answers the question if
the hypoxemia is explained by the hypercapnia. The alveolar PAO2 is calculated by
PIO2–PaCO2/R. Breathing room air, PIO2 may be estimated being 149 mmHg.
Otherwise PIO2 has to be calculated by Patm–PH2O × FiO2 ≈ 713 × FiO2. R is the
respiratory exchange ratio which usually is 0.8. The PaCO2 and the PaO2 can be
obtained by blood gas analysis. For example, if the PaCO2 is 65 mmHg, then the
alveolar PAO2 is 149–65/0.8 = 67.75 (breathing room air). The normal alveolar-
arterial PO2 difference is no more than <10 mmHg. In our example a
PaO2 ≥57.75 mmHg would be explained by hypercapnia alone. This consideration
is important as hypoxemia is a common finding in obesity but not always the treat-
ment when oxygen is appropriate: ventilation-perfusion inhomogeneity usually
needs no treatment, and hypoxemia due to hypercapnic failure rather requires ven-
tilation. The situation is entirely different when a hypoxemic respiratory failure
develops in an obese patient (e.g., pneumonia).
Prone positioning is recommended in severe (PaO2:FiO2 ratio <150 mmHg)
ARDS since early prone positioning reduces mortality when performed for at least
16 h by homogenizing the distribution of stress and strain within the lungs [20].
Nevertheless, this is difficult to perform in obesity, and prone positioning in obese
patients with ARDS increases the risk of sclerosing cholangitis which is an unfavor-
able complication of ICU therapy [21].
Additionally, there is experience with obese patients with BMI even greater than 40
and 50 kg/m2 and ARDS who were treated by extracorporeal membrane oxygenation
(ECMO) support with the same outcome as other patients [22]. Therefore, ECMO
seems also to be a treatment option in obesity allowing defensive ventilator settings.
160 S. Stieglitz
16.4 W
hat Are the Clinical Data of Obese Patients with ARDS
or VILI?
A large prospective study analyzed the outcome of more than four million morbidly
obese patients with invasive ventilation (patients with NIV were excluded). Those
patients with solely a respiratory failure had a normal prognosis compared to
patients with normal weight. Even the rate of prolonged mechanical ventilation was
unchanged. Nevertheless, if more organs failed, morbidly obese people showed an
increased risk for mortality [23]. Taking these facts into account, one may have the
impression that regarding the outcome ventilation of obese patients is not more
sophisticated than ventilating other patients. Concerning ARDS, obesity is a risk
factor for the occurrence of ARDS. Nevertheless, the outcome is improved com-
pared to patients with normal body weight [24] whereas obstructive sleep apnea, a
common feature of obesity, itself is not an independent risk factor for the develop-
ment of ARDS [25]. Therefore it is unlikely that obesity is a risk factor for VILI
when the outcome is even better. There are no epidemiological data regarding the
prevalence of VILI in obesity.
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jcsm.3794.
Ventilation Modes for Obese Patients
Under Mechanical Ventilation 17
Rachel Jones, Jason Gittens, and Ari Manuel
17.1 Introduction
Obesity puts stresses on all body systems, including the respiratory system. There
have been a number of studies to look at obese patients’ outcomes in the ICU. There
is no conclusive evidence to show that they have poorer outcomes [1].
17.2 Obesity Applied Pathophysiology
Obesity is associated with low-grade chronic inflammation and airway inflamma-

tion. “The majority of the forty cross-sectional studies published to date report a
modest positive association between obesity and asthma, with odds ratios of 1.5–
3.5” [3]. This can have an effect on airway pressure and physiology and affect ven-
tilation mode choices.
Morbid obesity is known to severely reduce functional residual capacity (FRC)
and expiratory reserve volume (ERV). It has minimal impact on TLC or VC. Jones
et al. have shown that this effect can happen even at BMI less than 30 kg/m2 [24].
Intra-abdominal pressure is increased by the fat deposition resulting in upward shift
of the diaphragm, which, in combination with increased chest wall elastance, leads
R. Jones
Intesive Care Unit, Papworth Hospital, Cambridge, UK
e-mail: rachel.jones3@uhbristol.nhs.uk
J. Gittens
Respiratory Department, Aintree Hospital, Liverpool, UK
e-mail: jason.gittens@nhs.net
A. Manuel (*)
Respiratory Department, Bristol Royal Infirmary, Bristol, UK
e-mail: ari.manuel@oriel.ox.ac.uk; arimanuel1979@yahoo.co.uk

164 R. Jones et al.
to higher resting pleural pressure. The combined effects of a low FRC and high pleu-
ral pressure will cause early closure of smaller airways, contributing to pulmonary
atelectasis and reducing lung compliance. This will inevitably lead to a worsening
perfusion and ventilation mismatch due to the dependent areas being poorly venti-
lated with no change in the distribution of pulmonary perfusion placing the patient at
risk of hypoxaemia. The patient placed in the supine position will compound these
effects.
Obesity causes a well-recognised restrictive deficit manifesting in decreased
FVC and forced expiratory volume 1 (FEV1). This is multifactorial due in part to
increased chest wall mass from adipose tissue [3] as well as increased pulmonary
blood flow leading to low pulmonary compliance.
In addition, morbidly obese patients have been found to require a greater propor-
tion of the total oxygen consumption (VO2) for respiratory work [4]. The VO2 for
respiratory work in non-obese patients at rest is small and is thought to be less than
3% of the total body O2 consumption. Kres et al. found that the VO2 was reduced in
obese patients requiring mechanical ventilation, which was not reciprocated in non-
obese patients [5]. There have been a number of estimations in literature on the
estimated VO2 for the work of breathing on obese patients ranging from 60 to 70%
compared to non-obese patients [6].
This concludes the high risk of respiratory failure in obese patients arising from
the greater baseline requirement of a high oxygen consumption for breathing in
combination with reduced respiratory reserve.
17.3 Ventilation
The need for mechanical ventilation will be the result of respiratory pathophysio-
logical changes that occur in obese patients in combination with the increased risks
of underlying obesity hypoventilation syndrome, obstructive sleep apnoea, pulmo-
nary hypertension and pre-existing comorbidities. Post-operatively obese patients
may require ongoing support due to the prolonged effects of sedation, development
of pulmonary atelectasis and hypoxaemia during anaesthesia.
Overall there is a general view that morbidly obese patients may be protective
during mechanical ventilation and have a mortality benefit. Nevertheless there is a
recognition of past studies that was pointed out recently that highlights the prob-
lems with the study designs.
The general recommendation for ventilating in obese patients with a BMI greater
than 40 would be between 15 and 21 breaths [7]. This is also mirrored by the British
Thoracic Society (BTS) recent guidelines published in 2016 on hypercapnia respi-
ratory failure recommended PCV with an initial set rate of 20 [8]. Further adjust-
ments to the ventilatory settings should be guided by dynamic compliance plateau
pressures and patient comfort. Similar to patients on NIV, it was noted that high
inspiratory pressures and PEEP may be required in OHS [8].
17 Ventilation Modes for Obese Patients Under Mechanical Ventilation 165
17.4 Modes of Ventilation
There is a scarcity of research on the modes of ventilation for obese patients in the criti-
cal care setting. Extrapolation is therefore made from the intraoperative research in
bariatric and non-bariatric surgery. This information limits its interpretation in the criti-
cal care setting as tidal volume targets are commonly different with 8–10 mL ideal
body weight (IBW) in anaesthetics compared to 4–6 mL IBW in critical care.
Furthermore, the duration of ventilation in many of the studies is short and not reflec-
tive of the critical care population. Pressure-controlled ventilation (PCV) and volume-
controlled ventilation (VCV) are commonly referred to in many of the research papers.
17.4.1 Pressure-Controlled Ventilation (PCV)
PCV selects a target pressure and cycled by time mode with an inspiratory flow pattern
decreasing exponentially with reducing peak pressures [9]. This mode of ventilation
may be preferred in critical care because of the heterogeneity of the time constants of
alveoli optimising gas exchange, particularly in ARDS. Therefore, the theoretical advan-
tage will be recruitment of additional lung units and improved ventilation among alveoli
with prolonged time constants. It is believed that this leads to laminar airflow at the end
of inspiration, with a more even distribution of ventilation [10]. However, the target tidal
volume may not be achieved, which in obese patients with poor lung compliance and
increased airway resistance will result in a reduction in the minute volume.
17.4.2 Volume-Controlled Ventilation (VCV)
Volume-controlled ventilation (VCV) selects a target volume which is delivered

regardless of the pressure. This can lead to difficulties with barotrauma but can
ensure that constant minute ventilation is achieved. Nevertheless, there is a risk of
alveolar overdistension.
17.4.3 Comparing VCV and PCV
A review article comparing data on ventilation strategies in obese patients undergo-

ing operations showed no difference between VCV and PCV modes. It looked at
four randomised controlled trials when comparing intraoperative PaO2/FIO2 ratio,
intraoperative tidal volume or mean airway pressure [11]. There was also no evi-
dence of any difference in mean arterial pressure or mean heart rate. There was not
enough data on other outcomes to comment on any other aspects [11]. This echoes
other work on patients with ARDS or on non-obese patients undergoing thoracic
surgery which also showed no difference between the two modes.
166 R. Jones et al.
In studies looking at morbidly obese patients undergoing laparoscopic gastric

banding, De Baerdemaeker et al. [12] and Hans et al. [13] showed that volume-
controlled ventilation (VCV) as compared to pressure-controlled ventilation (PCV)
showed no difference in outcomes and gas exchange.
Recently there was a large systematic review and network meta-analysis suggest-
ing that a combination of VCV, high PEEP and a single recruitment manoeuvre may
be the superior option [14]. This was compared with 12 ventilation options compar-
ing the PaO2/FiO2 ratio, optimal intraoperative pulmonary compliance and decreased
intraoperative atelectasis as measure of success.
17.4.4 Pressure-Controlled Ventilation Volume Guaranteed

(PCV-VG)
Pressure-controlled ventilation volume guaranteed (PCV-VG) is a hybrid mode of

ventilation in anaesthesia, using time mode, a preset tidal volume but pressure-
regulated with variable inspiratory flow. PCV-VG will deliver the preset tidal vol-
ume for each breath cycle using the lowest pressure possible and thus in theory
minimising the peak inspiratory pressure (PIP). Dion et al. [15] looked at 20
severely obese young patients during laparoscopic-assisted bariatric surgery who
received 20 min of ventilation with VCV, PCV or PCV-VG. The main finding
from the study was a lower PIP with PCV and PCV-VG modes as compared with
VCV. There was no advantage with oxygenation or ventilation between the modes.
This was also concluded in a study comparing VCV with PCV-VG where 30
patients undergoing abdominal surgery received PCV for 45 min and then alter-
nating to PCV-VG modes [16]. No difference was found with plateau pressure,
mean airway pressure or oxygenation [16]. This went against the authors’ initial
hypothesis that the dual mode ventilation may alter the flow pattern improving
oxygenation. There was no conclusive reason for this finding. Overall it remains
difficult to interpret with small numbers included and the crossover format of the
study design.
17.4.5 Pressure-Regulated Controlled Volume (PRCV)
There are no large randomised controlled trials assessing PRCV in general anaes-
thesia or intensive care evaluating its efficacy. In 2014 [17] there was an article
published which looked at 79 patients receiving PRCV for a range of aetiologies
both in type I and type II respiratory failure. Thirteen of these patients in this
study who presented with acute on chronic respiratory failure were labelled as
having obesity hypoventilation syndrome and obstructive sleep apnoea syndrome
(OHS-OSAS). The study did not compare other ventilation modes. The main
conclusion from this study was early improvement in oxygenation [17]. This
result was also found in a small paediatric critical care study of 28 patients com-
paring VCV and PRCV, which demonstrated improved oxygenation through
changes in PaO2 and PaO2/FiO2 in initial stages of ventilation [18]. It is recog-

nised that randomised clinical trials are required to determine PRCV mode in
critical care for respiratory failure as well as for obese patients requiring mechan-
ical ventilation [17, 18].
17.4.6 Pressure Support Mode in Invasive Mechanical Ventilation
Pressure support ventilation (PSV) is essentially a spontaneous breathing mode

supported by a set inspiratory pressure and cycled by a change in the inspiratory
flow. The benefit of PSV is the reduction of atelectasis, which is thought to be
due to the optimal diaphragmatic contraction of the posterior portion of the dia-
phragm [4, 6]. This concept of diaphragmatic activity has been looked at by
Hedenstierna et al. [19], who demonstrated that phrenic nerve stimulation
resulted in reduced atelectasis particularly after PEEP application. Another
advantage is the avoidance of the need for neuromuscular blocking agents. PSV
may theoretically offer an advantage when the patient is in the supine position
through better ventilation in dependent lung regions when compared with con-
trolled mode ventilation. A German study looked into 68 moderately obese (BMI
25–35) patients [20] intraoperatively and showed that PSV was superior to PCV
in terms of oxygenating patients but had a trade-off of raised pCO2. The author
concluded that the improved oxygenation was a result of better ventilation and
perfusion matching through better diaphragmatic contraction and reduced alveo-
lar compression [20]. With the advent of new ventilation modes, Pepin et al. [7]
in the review article suggest studies comparing them with PSV. In obese patients,
there have been concerns that spontaneous breathing leads to increased intra-
abdominal pressure from the increased thoracic activity [20]. The long-term out-
comes and potential adverse effects of using PSV in patients who have undergone
major abdominal surgery remain unknown. The BMI of the patient has been
found to be linked to the degree of intra-abdominal pressure (IAP) [21]. The IAP
transmitted to the thoracic cavity and the ultimate pleural pressure cannot be
predicted and thus has no role as a surrogate marker. Fluid accumulation has also
been found to complicate things [22]. Using PSV for ventilation brings the risk
of a variable minute volume, and therefore it should not be used when near-total
ventilation support is required.
17.4.7 Open Lung Ventilation
Open lung ventilation involves combining PEEP with low tidal volumes to create a
protective ventilation strategy. It should maximise alveolar recruitment and reduce
atelectasis. Lower tidal volumes should protect from trauma. There is no formally
agreed open lung strategy, but a meta-analysis [23] of several approaches showed a
mortality benefit in patients with ARDS. This is a standard of care in ARDS, but its
role outside of this category is not yet clarified.
168 R. Jones et al.
17.4.8 Airway Pressure Release Ventilation (APRV)
This method of ventilation was first described by Stock in the 1980s with currently
its main application within critical care as an advanced mode of ventilation for
patients with ARDS.
APRV is a type of pressure control ventilation using time mode providing high
and low PEEP at inverse ratio so that the majority of time is at a high pressure with
set timed interval releases to a lower pressure. APRV is considered to be a mode of
ventilation to achieve open lung ventilation. There remains no standard strategy for
setting the APRV parameters, and its explanation goes beyond the remit of this
chapter. On APRV patients are able to spontaneously breathe with optimal ventila-
tor synchrony by the presence of a dynamic expiratory valve. This provides the
means of reducing the sedation requirements and promoting protective lung
ventilation.The advantages of this technique include alveolar recruitment and
improved oxygenation. The spontaneous breathing will also offer physiological
benefit to include better ventilation and perfusion matching and improved central
venous return and transmural pressure. The explanation is thought to improve arte-
rial oxygenation and reduce pulmonary vascular resistance (PVR). In a case study
[25] of a patient with pulmonary hypertension and abdominal compartment syn-
drome, it was demonstrated that APRV improved the oxygenation, increased mean
airway pressure, reduced transmural pressure and improved lung compliance,
though at the time the patient had received nitrous oxide which would also improve
ventilation perfusion matching [25]. It is also recognised that PVR may be increased
in APRV as a result of prolonged time spent with lung volumes that are greater than
the patient’s FRC [25].
The disadvantages include the risk of volume trauma. If the patient is allowed
spontaneous breaths, then there is also the potential issue of increased work of
breathing and energy expenditure. In addition, achieving the 6 mL/kg IBW target
will become challenging in the spontaneous mode. Other considerations include
increased right ventricular afterload exacerbating pulmonary hypertension. It can
also cause a reduction of right ventricular venous return which can exacerbate the
intracranial hypertension and reduces cardiac output in circumstances with hypovo-
laemia and the risk of dynamic hyperinflation. Dynamic hyperinflation could be an
issue in patients with chronic obstructive pulmonary disease (COPD) [26]. There
was a case report published by Arshad et al. [50] who demonstrated success in using
APRV in a COPD patient. In their patient, the inverse ratio was not used, but Arshad
et al. concluded the physiological benefits of APRV with the mean airway pressure
kept at the lower infection point, reducing overdistension in addition to maintaining
the FRC optimised ventilation and gas exchange [50].
There are no randomised trials that determine the role of APRV in obese critical
care patients, but there are single and case series reports concluding its efficacy.
Hirani et al. [27] show the successful use of APRV in treating a morbidly obese
patient with ARDS. Transthoracic echo performed on the patient showed normal
cardiac function. APRV increased lung recruitment but prevented over distention.
There is no data to indicate the APRV mortality. Testerman et al. [28], in their
case series of 12 general surgical and trauma patients, demonstrated no deaths from
hypoxaemic respiratory failure without the need for additional rescue therapies,
including muscle paralysis. A recently published review [29] on APRV highlights
the challenges over the last three decades in regard to this mode of ventilation and
the optimal settings. The first problem is there is no one criterion or setting in defin-
ing APRV [29]. Currently, they can be broadly divided into fixed modes and person-
alised modes (adjusting settings depending on lung mechanics) with variation in the
settings used in experimental studies and in clinical practice, making comparisons
difficult. The timing of applying APRV for critical care patients has also been ques-
tioned. Authors from an animal model which compared early APRV application
with low tidal ventilation strategy demonstrated clinically and histologically that
systemically inflammatory reaction syndrome (SIRS)-induced ARDS was pre-
vented with APRV [30]. There remains further work to be done to determine the
optimal APRV parameters and timing with this mode of ventilation, before its appli-
cation in critical care obese patient can be fully determined.
17.4.9 Noninvasive Positive Pressure Ventilation (NIPPV)
NIPPV in critical care may be used as a type of ventilation in obese patients present-
ing with acute hypercapnia failure, to allow early liberation from invasive mechani-
cal ventilation and post extubation failure. The role of NIPPV in hypoxaemic
respiratory failure is yet to be defined in the general critical care population and has
a significant failure rate. In the subgroup of critically ill obese patients, there remain
no randomised controlled trials with regard to NIV in critical care for respiratory
failure. There are numerous NIPPV ventilation strategies available; the most com-
monly used is the pressure support ventilation. The difference between the inspira-
tory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP)
provides the pressure support.
Pressure support is usually delivered through a spontaneous/time (S/T) ventila-
tory mode where the patients’ breath triggers the ventilator and a set pressure is
delivered. This mode allows patients to take spontaneous breaths with a backup rate
ensuring that if the respiratory rate falls below this set rate, then an automatic breath
is delivered by the ventilator. Having this S/T ventilatory mode feature is recom-
mended as the obese patient may be at risk of having underlying breathing-related
sleep disorders causing central sleep apnoea. Having this additional option can
theoretically allow the operator to adjust the minute ventilation [31]. Nevertheless,
this may be at the risk of increasing the possibility of ventilation and patient
dyssynchrony.
Time-mode options of ventilation in NIPPV may include either pressure control
(difference between the IPAP and EPAP) or volume control. Average volume-
assured pressure support (AVAPS) is a hybrid mode of NIPPV. In a dynamic real-
life setting, the respiratory compliance will change and this model reflects this. In
170 R. Jones et al.
this mode, the IPAP varies in order to achieve a present tidal volume, which is usu-
ally set at 7–10 mL per kg of ideal body weight. This mode was compared in a
randomised controlled trial [32] to standard pressure support in patients with super
obesity (average BMI = 50). This mode theoretically has the advantage of more
consistent ventilation as shown by stable nocturnal transcutaneous CO2 monitoring,
but this can also disrupt sleep [32], therefore negating this improvement. In the trial
no difference in outcome was demonstrated between automated AVAPS mode and
fixed-level PS.
Currently there remains no study which demonstrates superiority with regard to
the choice of ventilation mode for acute NIV for obese patients presenting in critical
care with acute hypercapnia failure. There is no agreed optimal ventilation setting
though a review article in 2016 [31] that recognised that an IPAP of 18 ± 3 cm H2O
and EPAP of 7 ± 3 cm H2O were commonly used in numerous studies in this popu-
lation group. The BTS guidelines 2016 on hypercapnia respiratory failure [8]
recognises the lack of randomised controlled trials. The guidelines on NIV set-
tings recommend a prolonged inspiratory time (I:E ratio of 1:1) to optimise tidal
volume, positioning the patient upright and using a high EPAP ranging between 10
and 15 cm H2O [8]. The document also acknowledges that an IPAP in excess of
30 cm H2O and an EPAP greater than 8 cm H2O may be required for optimal
ventilation [8].
One author performed a retrospective study of 73 obese patients receiving NIV
for hypercapnic failure in ICU for various medical causes [33]. The main conclu-
sion is that using a higher PEEP and a longer duration receiving ventilation was
found to successfully reverse hypercapnia in obese patients [33]. The obesity arm of
the study was mixed and included patients with OSA and overlap syndrome, which
may also reflect the need for a higher PEEP. It is important to note in this study that
the medical condition for admission when comparing the obese patients with the
non-obese patients is that pulmonary oedema was more common (p = 0.003) and
pulmonary infection less common (p = 0.043) in the former group. It was noted that
the duration to achieve a pCO2 below 6.6 was 4 days longer in the obese patients
compared to those with a BMI of less than 35. There was a direct link between the
BMI and the duration of NIV for normalising CO2 [33]. In contrast to Lemyze
et al.’s study, Gursel and the team used APACHE II score for assessing the severity
of the patient which had no correlation to the outcome [33]. There was a small ret-
rospective study of 20 patients which also identified a similar conclusion that higher
PEEP and prolonged ventilation may be required [34].
An important consideration is that the patients who normally sit upright are at
risk of developing a respiratory decompensation or difficulty in becoming liberated
from the NIPPV as patients in critical care are placed in the supine position.
El-Solh et al. [35] conducted a prospective study measuring respiratory failure at
48 h post extubation as the primary endpoint comparing NIV with conventional
therapy and found a 16% absolute risk reduction in the rate of respiratory failure
with the former. The author identified that on subgroup analysis there was a reduced
hospital mortality in the NIV group [35]. This suggests that NIV may be of benefit,
though the actual patient criteria are still not fully recognised.
17.4.10 Obesity Hypoventilation Syndrome (OHS)
There is no conclusion in the current literature on the optimal delivery of respiratory

support when comparing NIV with CPAP for the management of OHS. Though
there is greater literature referencing NIV, CPAP is thought to be the preferred mode
when OSA is the predominant feature. However, an explanation for the lack of dif-
ference in CPAP and NIV may be that the trials used very conservative ventilatory
strategies—with low IPAP and EPAP such as the Piper study [36].
Carrillo et al. [37] in 2012 demonstrated through a prospective study the efficacy
of NIV in managing patients with OHS. The study compared COPD and OHS
patients in acute type II respiratory failure. The number of patients in the COPD arm
of the study was 543 vs 173 in the OHS group. The OHS patients had a 1-year sur-
vival rate of an odds ratio of 1.83, 95% CI 1.24–2.69, P = 0.002 [37], though when
adjusted for cofounders both COPD and OHS group had a similar outcome.
Furthermore, the subgroup of patients with COPD with OHS had fewer late NIV
failure. The author went on to conclude from this that overall OHS had a better
outcome with NIV compared to COPD [37]. The BTS guidelines refer the manage-
ment of patients with OHS to include not only the acute respiratory failure but also
the need for domiciliary NIV [8]. The long-term management of OHS also includes
lifestyle changes in combination with domiciliary NIV [38].
The aim of Pickwick study [39] (2015) was to compare NIV with CPAP in
patients with OHS using daytime partial pressure of carbon dioxide as the main
outcome measure. The consensus is that NIV is likely to be better than CPAP in
restoring physiological parameters, though the information is difficult to extrapo-
late as the study population was outside of critical care. This trial remains ongoing
and will delineate cardiovascular mortality which is the leading cause of death in
OHS.
The duration at which patients with OHS improve from their type II respiratory
failure has been found to differ from the non-obese patient. A longer duration on
NIV was required which may be explained by an altered response to hypoxia and
hypercapnia in obese patients that was demonstrated in a small study by Zwillich
et al. in 1975 [40]. Obese patients without OHS have shown in numerous studies to
have an increased central ventilatory drive which is in contrast to OHS.
Lemyze et al. [41] conducted a study that showed a good outcome from using
NIV in hypercapnia respiratory failure. Out of the total of 76 obese patients, only 7
failed to reverse their respiratory failure. The main taking points from the study
were that patients’ success in reversing the respiratory failure was likely with
decompensated OHS and hypercapnia on admission. A better outcome was also
noted in patients with idiopathic decompensated hypercapnia failure [41]. NIV fail-
ure was defined as the need for intubation and was found to occur in patients with
pneumonia (n = 12/13, 92% vs n = 9/63, 14%; p < 0.0001), high SOFA (10 vs 5;
p < 0.0001) and SAPS2 score (63 vs 39; p < 0.0001) on admission [41]. This would
support the view that when OHS patients present in respiratory failure, with addi-
tional pulmonary pathology, or another organ dysfunction, the potential outcome
with NIV is less clear.
172 R. Jones et al.
17.4.11 Oesophageal Pressure-Guided Mechanical Ventilation
Oesophageal pressure (Pes)-guided mechanical ventilation in respiratory failure can

be used to set the optimal level of PEEP throughout the respiratory cycle. Currently,
its use in critical care has mainly been applied as a research tool. The respiratory
changes in Pes are representative of change in plateau pressure applied to the lung
surface. The resting pleural pressure in obese patients in the supine position is
raised; therefore, there is the risk of the operator applying suboptimal PEEP settings
resulting in lower tidal volumes and the development of atelectasis. One recent
study [42] looked at morbidly obese patients in critical care setting and used oesoph-
ageal pressure via NG tube to act as a surrogate for pleural pressure. In order to have
a positive pressure throughout the respiratory cycle, PEEP should at least equal the
end-expiratory oesophageal pressure. This showed the optimum PEEP was around
21 cm H2O [42]. This in turn improved end-expiratory lung volumes and oxygen-
ation. Using this monitoring to generate Pes values could be applied in the clinical
setting. One immediate benefit would allow for an alteration in the target plateau
pressure, and as the paper demonstrated, higher pressures could be applied [42, 43].
Doubt remains as to whether oesophageal pressure is a reliable surrogate measure
of the pleural pressure. This may be because the Pes is influenced by many factors,
and our understanding of how this impacts on the value remains limited [43].
Nevertheless, it has been recognised that the pleural pressure may not be uniform
throughout the space because of variable gravitational gradients and regional differ-
ences of the pleural architecture [43]. Measuring the Pes may overcome these fac-
tors. In determining whether higher plateau pressures could be applied, there
remains no study which endorses this concept in the obese population requiring
mechanical ventilation. Therefore, safe ventilation settings as evidenced by the
ARDS trials are recommended [43]. There continues to be work led by the pleural
pressure working group into better defining the role of oesophageal pressure moni-
toring in clinical practice.
17.4.11.1 Recruitment Manoeuvres

Recruitment manoeuvres are used as an adjunct to achieving open lung for mechan-
ical ventilation. The objective is to reopen alveoli which are collapsed in conjunc-
tion with PEEP to ensure the alveoli are not subjected to further collapse on each
ventilatory cycle. Decruitment remains an ongoing risk for specifically obese
patients but also as a result of a change in respiratory mechanics during anaesthesia
which includes the use of high fraction of oxygen, low tidal volumes and inadequate
PEEP. There are various recruitment strategies, but all leading to an increase in the
transpulmonary pressure, commonly using a high inspiratory pressure of up to
40 cm H2O for at least 15 s. This can be as an isolated episode or as part of ramped
increased pressure ventilation leading to sustained high pressure. There are some
concerns that the increased intrathoracic pressure may reduce cardiac output as
shown in animal models [44].
In an anaesthetic review article [11], recruitment manoeuvres and PEEP were
shown to be superior to PEEP alone in intraoperative PaO2/FIO2 ratio and
respiratory compliance. There was no effect on mean arterial pressure [11]. They
were not sufficiently homogeneous to comment on barotrauma. Most of this data is
gathered preoperatively or intraoperatively.
The IMPROVE study by Futier et al. [45] was a large randomised controlled
study of 400 patients that looked at protected lung ventilation with PEEP and
recruitment manoeuvre versus nonprotected lung ventilation in patients receiving
major abdominal surgery. The mode of ventilation was volume controlled. The pri-
mary outcome was to compare pulmonary and extrapulmonary complications
within the first 7 days. The main finding from the protected lung group with higher
PEEP and recruitment manoeuvres had a relative risk of 0.40; 95% confidence inter-
val [CI], 0.24–0.68; p = 0.001. In the secondary outcomes, the protected lung patient
group had a reduced length of stay in hospital. The study is difficult to conclude for
the critical care population as the PEEP used in the IMPROVE study 6–8 cm H2O is
low in comparison to usual practice, and nonprotective lung ventilation does not
apply. Other studies that have looked at ventilation strategies in the intraoperative
period include Jaber et al. [47], which was a large observational multicentre trial of
2900 patients. It demonstrated that higher tidal volumes were administered greater
than 10 mL/kg of IBW in patients [47]. This study demonstrates the operator’s ten-
dency for higher tidal volumes during mechanical ventilation with patients present-
ing higher BMIs. The author went on to recognise that the previous practice from
work published in the 1960s which had advocated using high tidal volumes as a
strategy for improving oxygenation was a recognised strategy. Their study did find
that recruitment manoeuvres were more common in patients with a high BMI, but
overall this intervention was not commonly used [46].
As mentioned in the previous section on oesophageal pressure, the study pub-
lished in February 2016 [46] remains the one study which specifically looked at
recruitment manoeuvres of the critical care population. The author suggests that cur-
rent practice in targeting PEEP in the obese population is inadequate [46]. There
remains the need for large randomised controlled studies on outcome in the obese
critical care group with respect to mortality, number of days requiring mechanical
ventilation, number of ventilation free days and the risk of pulmonary and extrapul-
monary complications. Furthermore, to conclude, there remains no guidance on the
frequency in performing the recruitment manoeuvre during mechanical ventilation.
17.5 Patients Positioning
17.5.1 Reverse Trendelenburg
Reverse Trendelenburg is achieved by tilting the bed enabling the head to be higher
than the feet. This helps relieve the effect of the intra-abdominal pressure on the
diaphragm reducing intrathoracic pressure and improving lung compliance.
Preliminary studies in positioning in bariatric surgery [48] showed that it was a safer
position compared to the 30° backup Fowler and horizontal-supine positions (length
of apnoea and time to recover to Sat greater than 97%).
174 R. Jones et al.
There is also evidence that ventilator-associated pneumonia (VAP) is lower. This

may relate to gravity and intra-abdominal pressure. VAP is a well-recognised major
complication of invasive mechanical ventilation.
17.5.1.1 Proning
Proning is changing the patient position from the usual supine position onto their
front, lying face down. This strategy traditionally used in ARDS can help with oxy-
genation. Morbid obesity carries increased risk with position change.
Positioning patients in a prone position, while being IMV, reduces atelectasis and
improves oxygenation. It has proven outcomes in ARDS with a review article in
2010 [49] showing an absolute mortality reduction of around 10%.
In obesity, there is also some evidence that proning can be effective as seen in the
French Montpellier Study where it was associated with survival benefit and no
increased complication rate [49]. The physiology in obesity (decreased FRC and
increased atelectasis) may have even a better outcome in proning patients than in
those patients who are non-obese.
There are risks associated with proning ventilation. Some are generic to all
patients, such as endotracheal tube displacement. Others, such as intra-abdominal
hypertension (IAH), are linked to morbid obesity. In a review article looking at the
subject, there is mixed evidence regarding proning which appears to have the poten-
tial to either exacerbate or ameliorate IAH, depending on the technique.
Conclusion
Obesity has a number of effects on respiratory physiology which can be a chal-
lenge to ventilation techniques. Overall goals should be to maximise airway
recruitment and minimise atelectasis while avoiding barotrauma and ventilation-
induced lung injury.
VCV and PCV have advantages and disadvantages but have similar outcomes
in studies. The hybrid modes of ventilation are increasingly being used in anaes-
thetics. The limiting factor is that very few trials have been performed in the criti-
cal care setting. Patients’ physiology should help guide an individualised
approach when formulating a ventilation strategy. Tidal volumes delivered
should be 6–8 mL/kg with the aim of reducing barotrauma. The objective should
be to provide adequate oxygenation and ventilation which may not immediately
normalise their respiratory physiology.
In ARDS APRV can be considered to increase lung recruitment while pro-
tecting the airway from barotrauma. The role APRV has still needs to be defined
and better standardised through conducting randomised controlled trials. PEEP
should be used to increase lung recruitment and avoid atelectasis. NIV is
increasingly being used in critical care with good outcomes with hypercapnia
respiratory failure in OHS. Patients with OHS have a clearer benefit with NIV
for hypercapnia failure when there is no other organ failure. There continues to
be a need for randomised controlled trials to determine the superiority of the
traditional and hybrid modes of NIV. Recruitment manoeuvres also have shown
additional benefits and may be used alongside if effective. The use of oesopha-
geal guide to aid mechanical ventilation may have a role in obese patients
requiring IMV, aiding the operator in using higher pressures without the risk of
inducing barotrauma. Nevertheless caution remains about using liberal plateau
pressures without the support of a randomised controlled study.
The use of patient position should be optimised ideally in a reverse
Trendelenburg initially, and if not successful, one should consider proning the
patient. The clinician should be aware of the risks associated with this position in
certain patient groups.
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Obesity and Tracheostomy: Indications,
Timing, and Techniques 18
Bahman Saatian and Julie H. Lyou
18.1 Introduction
Obesity has become a major health issue in the United States and Europe [1]. It is esti-
mated that more than one-third of the population in the United States is obese [2].
Obesity and morbid obesity are defined as body mass index (BMI) ≥30—<40 kg·m−2
and ≥40 kg·m−2, respectively. A broad range of health issues such as cardiac disease,
hypertension, stroke, type 2 diabetes mellitus, obstructive sleep apnea, and obesity
hypoventilation syndrome are associated with obesity. All of the latter consequently
increase the risk of hospitalization and a need for higher level of care. A recent study
showed obesity was associated with significantly higher all-cause mortality relative to
normal weight population [3]. From a pulmonary standpoint, lung physiology is sig-
nificantly altered in the obese patient, including respiratory muscle insufficiency,
reduced functional residual capacity (FRC), expiratory reserve volume (ERV), and
lung compliance [4]. Ventilation and perfusion (V/Q) matching is altered due to a small
airway closure caused by a lower ERV. When compared with nonobese controls,
reduced chest wall compliance due to adipose tissue in the chest wall and abdomen
leads to an increase in airway resistance. Furthermore, these changes in pulmonary
physiology lead to a prolonged need for mechanical ventilation which increases the
length of intensive care unit (ICU) stay [4]. During any airway intervention such as
endotracheal intubation, excess soft tissue in the hypopharynx and altered respiratory
physiology may also result in the rapid onset of hypoxemia and slow recovery in obese
patients. It has been shown that higher BMI leads to higher likelihood of ICU admis-
sion, mechanical ventilation, and tracheostomy in hospitalized obese patients [5].
B. Saatian, M.D. (*)

UC Irvine, School of Medicine, Irvine, CA, USA
Veterans Affair Long Beach Healthcare System, Long Beach, CA, USA
e-mail: bsaatian@uci.edu
J.H. Lyou, M.D.
UC Irvine, School of Medicine, Irvine, CA, USA

180 B. Saatian and J.H. Lyou
Tracheostomy is one of the oldest surgical procedures dating back 3500 BC [6].
Tracheostomy is a commonly performed procedure that establishes a long-term
secure airway for patients who require extended mechanical ventilation from a vari-
ety of disease processes. More than 100,000 tracheostomies are performed in the
United States annually [7]. The procedure can be performed either in the operating
room or at the bedside. Although newer techniques and instruments have evolved
over the years, some studies suggest morbid obesity is a risk factor for tracheostomy
regardless of utilized technique (percutaneous versus surgical) [6, 8]. Technique and
optimal timing of tracheostomy in obese patients remain a subject of debate. The
current recommendations suggest an individualized approach taking in consider-
ation the reason for prolonged mechanical ventilation, the underlying comorbidi-
ties, and the potential risk factors that increase the incidence of complications [9].
18.2 Indications
Obese and morbidly obese patients are at higher risk for medical comorbidities, hospi-
talization, and admission to critical care units when compared to nonobese counter-
parts. The likelihood of intubation and the persistence of mechanical ventilation are
higher in this patient population due to altered lung physiology and variety of medical
comorbidities. The potential benefits and outcomes of tracheostomy should be assessed
with a patient-centered approach. Tracheostomy should be considered if it is consistent
with the patient’s wishes and preferences. Patients who have good prognosis with
meaningful recovery from underlying illness are more likely to benefit from tracheos-
tomy. It is proposed that tracheostomy decreases the length of ICU and hospital stay,
improves patient comfort, and reduces mortality. However there is no consistent data to
support the aforementioned benefits. Similar to the general population, the main reason
for tracheostomy in critically ill and obese patients is the need for prolonged mechani-
cal ventilation and failure to wean from mechanical ventilation. Other indications for
tracheostomy include chronic respiratory failure, upper airway obstruction, obstructive
sleep apnea, copious secretion [10, 11], chronic neurologic disorders resulting in respi-
ratory muscle weakness such as amyotrophic lateral sclerosis (ALS) and cerebral palsy
(CP), spinal cord injury, and traumatic and non-traumatic brain injuries (Table 18.1).
Table 18.1 Indications and contraindications of tracheostomy

Indications Relative contraindications Absolute contraindications
Prolonged mechanical High ventilatory demand Inexperienced practitioner
ventilation Hemodynamic instability Unstable cervical spine
Chronic respiratory failure Radiation therapy to neck Prior major neck surgery
Obstructive sleep apnea Enlarged thyroid gland Pediatric age <8 years
Upper airway stenosis Coagulopathy
Trauma Inability to extend neck
Excessive secretion Elevated intracranial pressure
Neurologic disease High-riding innominate artery
Local skin infection
Gross distortion of the neck
anatomy
18 Obesity and Tracheostomy: Indications, Timing, and Techniques 181
Tracheostomy (surgical or percutaneous) should be performed by an experienced

physician, especially for those patients with relative contraindications. De Leyn
et al. specified skin infection and prior major neck surgery which completely
obscures the anatomy as relative contraindications to tracheostomy [10].
18.3 Timing
The optimal timing for elective tracheostomy is still a subject of debate. In the1980s,
tracheostomy was considered “early” if it was performed within 21 days of endotra-
cheal intubation. Otorhinolaryngology literatures recommended performance of
tracheostomy within 3 days of intubation to prevent vocal cord damage from endo-
tracheal intubation [12]. Several studies have shown early tracheostomy (within
7 days) reduced the duration of mechanical ventilation and the length of ICU stay as
well as overall hospital length of stay in trauma patients [13]. The early tracheos-
tomy group had a statistically significant lower incidence of pneumonia (78% vs.
96%, p < 0.05) compared to late tracheostomy (greater than 7 days) [13–15]. It is
believed that the reduced rate of pneumonia is attributed to the normal closure of
vocal cords following removal of the endotracheal tube. A multicenter randomized
clinical trial comparing early (within 4 days) versus late (after 10 days) tracheos-
tomy showed no improvement in 30 day all-cause mortality, mortality at critical
care unit and hospital discharge at 1 and 2 years [16]. Two other multicenter ran-
domized studies on early versus late tracheostomy also demonstrated no difference
in 28 day mortality and pneumonia [17, 18]. A single center study by Rumbac and
colleagues found mortality benefit in the medical ICU patients with early tracheos-
tomy (within 48 h) as compared to delayed tracheostomy (14–16 days) patients
[19]. Majority of the studies has not found a survival benefit from early tracheos-
tomy [14, 20]. Lack of strong evidence for early versus late tracheostomy hindered
an expert consensus on a standardized timeframe for tracheostomy placement.
Liberation from mechanical ventilation in critically ill morbidly obese patients is
more challenging due to increased work of breathing secondary to altered respira-
tory mechanics, impaired ventilatory drive, and higher prevalence of obstructive
sleep apnea. Potential procedural complications are also higher in the obese patients.
Therefore, the decision for timing of tracheostomy placement should be made on
case by case basis.
18.4 Techniques
The technique by which tracheostomy is performed in obese patient remains contro-

versial. The technical difficulty in performing tracheostomy in obese patients has
been examined in several studies in the past decade. Selection of proper tracheos-
tomy technique depends on several factors, necessitating a thorough pre-procedural
assessment of the patient’s anatomy and relevant comorbidities. Anatomic varia-
tions, including excessive submental and upper thoracic tissue obstructing the surgi-
cal field, difficulty palpating the landmarks due to excess adipose tissue overlying
the trachea, short neck displacing the airway structures inferiorly into the chest,
limited neck extension, and prior tracheostomy, are important procedural factors
that must be considered prior to the procedure [21]. These anatomic concerns are
added to medical comorbidities, severity of acute illness, and anesthetic risks.
There are two major techniques, percutaneous dilational tracheostomy (PDT)
and traditional open surgical tracheostomy (ST). Multiple studies and reviews have
compared the percutaneous and open tracheostomy techniques.
A meta-analysis by Higgins identified 15 prospective, randomized controlled stud-
ies involving nearly 1000 patients [22]. This study demonstrated significantly fewer
complications in percutaneous tracheostomy group with respect to wound infection
and unfavorable scaring. The rate of decannulation and obstruction was higher in the
percutaneous tracheostomy group [22]. False passage, minor and major bleeding, and
subglottic stenosis were not significantly different between the two groups [22]. The
complication rates in high-risk patients including the obese were not reported in this
meta-analysis, and bronchoscopy was only used in seven of the studies. A large study
by Dennis et al. reported a complication rate of 1% with percutaneous tracheostomy
without bronchoscopy guidance in obese patients [23]. In 2008, Aldawood and col-
leagues showed a higher rate of major complications in obese patients who underwent
PDT compared to nonobese patients [24]. Byhahn reported increased life-threatening
complications (9.6% vs. 0.7%, P < 0.001) in obese patients who underwent bronchos-
copy-assisted PDT compared to nonobese patients [25]. Obese patients had a 2.7-fold
increased risk for operative complications and a 4.9-fold increased risk for serious
complications [25]. In contrast, Blankenship showed there were no significant differ-
ences in procedure time, estimated blood loss, and postoperative complications
between morbidly obese and nonobese patients [26]. In 2007, El Solh et al. found that
conventional open surgical tracheostomy was associated with an increased risk of
perioperative complications in the critically ill morbidly obese patients compared to
non-morbidly obese patients [27]. The reported outcomes were in favor of PDT com-
pared to surgical tracheostomy and those included wound infections, smaller incision
scars, shorter operation time, and reduction in cost with PDT [28]. Despite this, open
tracheostomy is still being performed in cases where PDT is thought to be difficult or
where there is insufficient expertise of those who can perform PDT.
18.5 Percutaneous Tracheostomy
Percutaneous dilational tracheostomy (PDT) has become the widely accepted pro-
cedure of choice for tracheostomy in intensive care units [29]. Percutaneous trache-
ostomy was initially described by Shelden in 1955, and subsequently Ciaglia
introduced his technique of serial dilation in 1985. The six major types of PDT that
are currently being performed are the following:
Slight modification of the dilational technique with a single tapered dilator
(Ciaglia Blue Rhino)
Forceps dilation referred to as the Griggs’ technique
Translaryngeal tracheotomy (also known as the Fantoni technique)
Variation of the dilational technique with a screw-in dilator

T-shaped dilator (Ambesh)
Balloon-facilitated dilational tracheostomy (Ciaglia Blue Dolphin) [12, 28]
In a systematic review of 13 randomized trials looking at the six different tech-
niques, the single-step dilation technique had fewer failures than the rotational dila-
tion and fewer complications compared to the balloon dilation and guidewire
dilating forceps method [28].
Based on expert opinion and case reports, recommendations for anesthesia for
PDT include intravenous general anesthesia, neuromuscular blockade, or local anal-
gesia [30]. Inhalation anesthesia is not suggested since there is gas leakage during the
procedure. Appropriate positioning in obese patients, while difficult, is a sentinel step
in the success of this technique. The patient should be positioned with the upper back
elevated and the neck hyperextended, which may make direct laryngoscopy difficult.
The endotracheal tube is then retracted until the cuff is below the vocal cords, and then
the trachea is punctured with the introducing needle. An alternative method is to
remove the endotracheal tube and place a laryngeal mask airway, which carries the
risks of pulmonary aspiration, air leakage, and compromised ventilation [30].
Typically, two physicians are needed to allow for bronchoscopy guidance and man-
agement of airway complications. The operator begins by palpating the cricoid and
tracheal rings. The optimal site is between the second and third tracheal ring under the
cricoid cartilage. Locations that are more proximal increase the risk of tracheal stenosis
while distal locations increase the risk of erosion of the great vessels in the mediasti-
num [30]. Ultrasound can be used to identify the intended level of puncture site. An
8–12 mm skin incision is made at the chosen level. The cuff of the endotracheal tube is
deflated, and the trachea is punctured with the introducing needle. The guidewire is
introduced, and the stoma is dilated with one or more dilators and possible use of dilat-
ing forceps. The cannula is then placed and guidewire is removed. Minor bleeding is
managed with manual compression, subcutaneous infiltration with adrenaline-contain-
ing local analgesic, and compression with gauze soaked in adrenaline solution (1 mg
adrenaline, 4 ml sterile water). Major bleeding requiring transfusion requires an emer-
gent surgery consult for exploration, suture, and cautery. Notably, four of the nine prior
nonrandomized studies on tracheostomy in obese patients which bronchoscopy guid-
ance was not consistently used demonstrated no significant increase in periprocedural
complications [24, 27, 31]. Although there are no randomized controlled trials compar-
ing PDT with and without bronchoscopy guidance, a literature review of published
mortality related to PDT identified the lack of use of bronchoscopy guidance to be a
major risk factor [30, 32]. Randomized controlled studies are warranted to assess safety
of tracheostomy without bronchoscopy guidance.
18.6 Rigid Bronchoscopy-Guided Tracheostomy
Although flexible bronchoscopy-guided PDT is an acceptable and commonly used

technique, it has inherent limitations such as loss of airway, inadequate ventilation
due to occlusion of endotracheal tube, inadequate ability to provide suction in case
of major bleed, and inadvertent puncture of cuff and posterior tracheal membrane.
Suspension laryngoscopy-assisted PDT and rigid bronchoscopy-guided PDT have
been advocated to avoid these potential complications in high-risk patients [6, 33].
Rigid bronchoscopy-guided PDT can be utilized in patients who have relative con-
traindications to having standard PDT performed, including morbid obesity, prior
neck surgery, distorted airway anatomy, and uncorrected coagulopathy [33]. In a
retrospective case series of 35 patients who underwent rigid bronchoscopy-guided
PDT, there were no periprocedural complications or mortality associated with the
procedure [33]. The advantage of utilizing the rigid bronchoscope over the flexible
bronchoscope is airway security and protection of posterior tracheal membrane.
The rigid bronchoscope also allows for adequate ventilation and suctioning
throughout the entire procedure. In comparison to PDT with flexible bronchos-
copy, rigid bronchoscopy allows for full visibility of the subglottic space and dis-
placement of the trachea anteriorly for ease of accessibility. The procedure is
performed in the operating room with the patient in the supine position. The upper
back is elevated with a towel roll placed between the scapulae, extending the neck.
The rigid bronchoscope is advanced to the posterior pharynx and glottis and then
positioned just distal to the true vocal cords. At this point the endotracheal tube is
removed from the airway and the rigid bronchoscope is advanced into the subglot-
tic area. After establishing a sterile field, the thyroid and cricoid cartilages are
palpated to mark the site of incision. The skin and subcutaneous tissue are anesthe-
tized with lidocaine and epinephrine. A small vertical incision (1 cm) is made, and
a Kelly clamp is used to dissect the tissue. The finder needle is then introduced
through the trachea under the guidance of the bronchoscope. The guiding angio-
cath is then inserted and the needle is removed. The guidewire is introduced
through the angiocath, which is then withdrawn. Sequential dilation is performed
with a punch dilator followed by the Blue Rhino tapered dilator into the stoma.
Finally, the tracheostomy tube is introduced onto a dilator and advanced into the
trachea, with the dilator and guidewire being withdrawn. The tube is then secured
in place with sutures on both sides.
18.7 Ultrasound-Guided Tracheostomy
Recently, use of real-time ultrasound guidance (RUSG) was shown to reduce the
complications of PDT in patients with risk factors such as morbid obesity, short
neck, deviated trachea, massive goiter, edema, and subcutaneous emphysema [16,
34]. It has been demonstrated that real-time ultrasound guidance improves the pro-
cedure safety by identifying the intended level of penetration, avoiding the posterior
membrane damage, and improving the rate of first-pass puncture accuracy [17, 34].
Ultrasound can be used as an adjunct to PDT to evaluate the anatomy of the major
vessels and the thyroid gland in relation to the tracheostomy site, especially in obese
patients. A linear array probe is utilized to avoid vascular structures during tracheal
puncture and to confirm guidewire entry. Lung sliding can be assessed after trache-
ostomy placement as well. In morbidly obese patients with increased neck girth,
ultrasound can be used to assess pretracheal tissue thickness while placing the head
in neutral position in order to select the tracheostomy tube length and size.
18.8 Surgical Tracheostomy
Surgical tracheostomy takes place in the operating room, most often by otolaryn-
gologists (ENT), followed by general or thoracic surgeons. Standard technique rec-
ommends a horizontal incision, but this is a matter of debate as a vertical incision
may assist with tracheostomy tube mobility during swallowing [12, 21]. The lower
rates of wound infection in PDT are thought to be due to the smaller incision
(1–1.5 cm), in comparison to the larger (up to 4 cm) incision performed in surgical
tracheostomy.
In conclusion, tracheotomy tube placement can be challenging in obese patients.
Proper tracheostomy technique should be selected after evaluating the patient’s air-
way anatomy, risk factors, and potential complications. Standard tracheostomy
tubes are usually functionally inadequate in the obese patients due to length limita-
tions. The curvature mismatch between the standard size tracheostomy tube and the
increased distance between the skin of anterior neck and tracheal wall can lead to
complications such as accidental decannulation and extratracheal tube misplace-
ment. Therefore, tracheostomy tubes with extra length are commercially available
for this purpose. The utility of flexible bronchoscopy, ultrasound, and rigid bron-
choscopy has made PDT become a safer and more feasible procedure to perform in
high-risk patients who were previously considered to have relative contraindica-
tions for PDT.
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2. Sturm R, Hattori A. Morbid obesity rates continue to rise rapidly in the United States. Int J
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3. Flegal KM, Kit BK, Orpana H, et al. Association of all-cause mortality with overweight and
obesity using standard body mass index categories.A systematic review and meta-analysis.
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tional tracheostomy in high-risk patients. Laryngoscope. 2010;120:2423–9.
7. Yu M. Tracheostomy patients on the ward: multiple benefits from a multidisciplinary team?
Crit Care. 2010;14(1):109.
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with bronchoscopy in the obese patient. Laryngoscope. 2012;122:1031–4.
9. Akinnusi ME, Pineda AL, El Solh AA. Effect of obesity on intensive care morbidity and mor-
tality: a meta-analysis. Crit Care Med. 2008;36(1):151–8.
10. De Leyn P, Bedert L, Delcroix M, et al. Tracheotomy: clinical review and guidelines. Eur J
Cardiothorac Surg. 2007;32(3):412–21.
11. Rana S, Pendem S, Pogodzinski MS, et al. Tracheostomy in critically ill patients. Mayo Clin
Proc. 2005;80(12):1632–8.
12. McWhorter AJ. Tracheotomy: timing and techniques. Curr Opin Otolaryngol Head Neck Surg.
2003;11(6):473–9.
13. Michele H, Dunham M, Brautigan R, et al. Practice management guidelines for timing of trache-
ostomy: the EAST practice management guidelines work group. J Trauma. 2009;67(4):870–4.
14. Rodriguez JL, Steinberg SM, Luchetti FA, et al. Early tracheostomy for primary airway man-
agement in the surgical critical care setting. Surgery. 1990;108:655–9.
15. Jeon YT, Hwang JW, Lim YJ, et al. Effect of tracheostomy timing on clinical outcome in neu-
rosurgical patients: early versus late tracheostomy. J Neurosurg Anesthesiol. 2014;26(1):22–6.
16. Young D, Harrison D, Cuthbertson B, Rowan K. Effect of early versus late tracheostomy
placement on survival in patients receiving mechanical ventilation. The TracMan randomized
trial. JAMA. 2013;309(20):2121–9.
17. Terragni PP, Antonelli M, Fumagalli R, et al. Early versus late tracheostomy for prevention
of pneumonia in mechanically ventilated adult ICU patients. A randomized controlled trial.
JAMA. 2010;303(15):1483–9.
18. Blot F, Similowski T, Trouillet JL, et al. Early tracheostomy versus prolonged endotracheal
intubation in unselected severely ill ICU patients. Intensive Care Med. 2008;34(10):1779–87.
19. Rumbak M, Newton M, Truncale T, et al. A prospective, randomized study comparing early
percutaneous dilational tracheotomy to prolonged translaryngeal intubation (delayed trache-
otomy) in critically ill medical patients. Crit Care Med. 2004;32:1689–94.
20. Saffle JR, Morris SE, Edelman L. Early tracheostomy does not improve outcome in burn
patients. J Burn Care Rehabil. 2002;23:431–8.
21. Walts PA, Murthy SC, DeCamp MM. Techniques of surgical tracheostomy. Clin Chest Med.
2003;24:413–22.
22. Higgins KM, Punthakee X. Meta-analysis comparison of open versus percutaneous tracheos-
tomy. Laryncoscope. 2007;117(3):447–54.
23. Dennis BM, Eckert MJ, Gunter OL, Morris JA Jr. Safety of bedside percutaneous tra-
cheostomy in the critically ill: evaluation of more than 3000 procedures. J Am Coll Surg.
2013;216(4):858–65.
24. Aldawood AS, Arabi YM, Haddad S. Safety of percutaneous tracheostomy in obese critically
ill patients: a prospective cohort study. Anaesth Intensive Care. 2008;36:69–73.
25. Byhahn C, Lischke V, Meininger D, et al. Perioperative complications during percutaneous
tracheostomy in obese patients. Anesthesia. 2005;60:12–5.
26. Blankenship DR, Kullbersh BD, Gourin CG, et al. High-risk tracheostomy: exploring the lim-
its of the percutaneous tracheostomy. Laryngoscope. 2005;115:987–9.
27. El Solh AA, Jaafar W. A comparative study of the complications of surgical tracheostomy in
morbidly obese critically ill patients. Crit Care. 2007;11(1)
28. Cheung NH, Napolitano LM. Tracheostomy: epidemiology, indications, timing, technique,
and outcomes. Respir Care. 2014;59(6):895–919.
29. Freeman BD, Morris PE. Tracheostomy practice in adults with acute respiratory failure. Crit
Care Med. 2012;40:2890–6.
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tomy in the intensive care unit. Dan Med J. 2015:1–8.
31. Mansharamani NG, Koziel H, Garland R, et al. Safety of bedside percutaneous dilatational
tracheostomy in obese patients in the ICU. Chest. 2000;117(5):1426–9.
32. Simon M, Metschke M, Braune SA, et al. Death after percutaneous dilatational tracheostomy:
a systematic review and analysis of risk factors. Crit Care. 2013;17(5):R258.
33. Majid A, Cheng GZ, et al. Evaluation of rigid bronchoscopy-guided percutaneous dilation
tracheostomy: a pilot study. Ann Am Thorac Soc. 2014;11:789–94.
34. Rajajee V, Williamson CA, West BT. Impact of real-time ultrasound guidance on compli-
cations of percutaneous dilatational tracheostomy: a propensity score analysis. Crit Care.
2015;19:198.
Decannulation Process
in the Tracheostomised Obese Patients 19
Pia Lebiedz, Martin Bachmann, and Stephan Braune
The decannulation process of critically ill obese patients can be more difficult than
that of nonobese patients. A recent study showed a high rate of persistent invasive
mechanical ventilation at hospital discharge (49%) in obese tracheostomised patients
[1]. Surgical tracheotomy, African American ethnicity, obstructive sleep apnoea and
pulmonary hypertension were associated with decannulation failure [1]. Therefore,
risk factors for decannulation of obese patients must be identified and optimal condi-
tions established before decannulation in addition to general criteria of clinical and
respiratory stability and exclusion of neurological disorders such as swallowing
problems [2]. Moreover, a careful history taking from patients and/or their next of
kin will have to clarify the existence of any diagnosed or suspected pre-existing
obstructive sleep apnoea (OSA) or obesity hypoventilation syndrome (OHS).
19.1 Spontaneous Breathing Trial
Prior to decannulation, the ability for sufficient spontaneous breathing must be

assessed. Sufficient spontaneous breathing capacity can be assumed, if the patient is
able to breathe without significant mechanical support, such as T-piece, CPAP with-
out pressure support or assisted mechanical ventilation with low pressure support [3].
P. Lebiedz (*)
Department of Cardiovascular Medicine, University Hospital of Münster, Münster, Germany
e-mail: pia.lebiedz@ukmuenster.de
M. Bachmann
Department of Intensive Care and Ventilatory Medicine, Asklepios Klinikum Hamburg-
Harburg, Hamburg, Germany
S. Braune, M.P.H.
Department of Medical Intensive Care and Emergency Medicine, St. Franziskus Hospital
Münster, Münster, Germany

188 P. Lebiedz et al.
Due to high pleural pressures caused by low chest wall compliance and abdomi-
nal hypertension, obesity is associated with pulmonary restriction and reduced
functional residual capacity. These factors lead to a higher risk of hypoxemic and/or
ventilatory failure than in nonobese patients. The ventilatory capacity and the work
of breathing in obese patients can be assessed by a spontaneous breathing trial via
T-piece or on assisted ventilation with or without low pressure support before extu-
bation or decannulation [4].
19.2 Positioning
Optimal positioning of the patient in upright position, sitting or beach chair position
is crucial to facilitate mechanical ventilation of obese patients [5]. Due to the above
mentioned changes in respiratory physiology caused by obesity and due to the often
accompanying obstructive upper airway diseases, we recommend optimal position-
ing as described above before decannulation of obese patients.
19.3 Percutaneous Dilatational Versus Surgical Tracheotomy
Particularly in obese patients, recannulation after failure of decannulation is techni-

cally significantly easier in surgically tracheotomised patients compared to percuta-
neously tracheotomised patients. After decannulation of a percutaneous dilatational
tracheostoma, shifting of multiple subcutaneous tissue layers can lead to closure of
tracheotomy and make recannulation impossible. This is the reason why a difficult
airway for conventional intubation is a contraindication for percutaneous tracheos-
tomy. Thus, physicians must always be aware of the patients’ airway anatomy before
decannulation of percutaneously tracheotomised obese patients in case of decannula-
tion failure and subsequent necessity for conventional (emergency) reintubation. A
tracheal button or a downsizing cannula to maintain tracheal access should be used
in the decannulation process in obese patients [6]. With a well-fitted placeholder
device, NIV can be effectively applied, and at the same time, this leaves an access for
deep tracheal suctioning and facilitates recannulation in case of NIV failure.
Due to the above described risk, surgical tracheotomy may seem more reason-
able for obese patients. However, surgical tracheotomy carries other risks such as
higher tracheostomy infection rates [7]. Furthermore, obesity has been reported to
be a risk factor for development of tracheal stenosis after surgical tracheotomy [8].
19.4 Non-invasive Ventilation After Decannulation
Because of the altered respiratory physiology of obese patients with reduced func-
tional residual capacity caused by atelectasis and higher risk of ventilatory failure due
to functional pulmonary restriction as well as the higher prevalence of OSA, the pre-
emptive application of non-invasive ventilation (NIV) shortly after decannulation
19 Decannulation Process in the Tracheostomised Obese Patients 189
seems reasonable to minimise the risk of decannulation failure as has been shown for
extubation of obese patients [9]. The mechanisms responsible for these positive effects
are adequate positive end-expiratory pressures (PEEP) aiming for a positive end-expi-
ratory transpulmonary pressure to counterbalance atelectasis and to treat OSA as well
as to apply adequate driving pressures to reduce work of breathing.
Conclusions
Decannulation of tracheotomised obese patients requires careful planning and
optimal setting. This includes testing for sufficient unassisted ventilatory capacity,
optimal positioning and the pre-emptive application of NIV post-decannulation.
• Pre-assessment of unassisted ventilatory capacity before decannulation

• Sitting or beach chair positioning on decannulation
• Pre-emptive NIV after decannulation
References
1. Byrd JK, Ranasinghe VJ, Day KE, Wolf BJ, Lentsch EJ. Predictors of clinical outcome after
tracheotomy in critically ill obese patients. Laryngoscope. 2014;124:1118–22.
2 . Ceriana P, Carlucci A, Navalesi P, Rampulla C, Delmastro M, Piaggi G, De Mattia E, Nava
S. Weaning from tracheotomy in long-term mechanically ventilated patients: feasibility
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Respir Crit Care Med. 2013;187:1294–302.
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G, Brochard L, Jaber S. Spontaneous breathing trial and post-extubation work of breathing in
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5. Lemyze M, Mallat J, Duhamel A, Pepy F, Gasan G, Barrailler S, Vangrunderbeeck N, Tronchon
L, Thevenin D. Effects of sitting position and applied positive end-expiratory pressure on respi-
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LaMonica D, Moscatello A, Khosla S, Cauley CE, Maronian NC, Melki S, Wick C, Sinacori
JT, White Z, Younes A, Ekbom DC, Sardesai MG, Merati AL. A multi-institutional analysis of
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2006;28:588–95.
Part IV
Noninvasive Ventilation and Oxygen Delivery
in the Critically Ill Obese Patient
The Choice of Interface
20
Ahmed S. BaHammam, Tripat Singh,
and Antonio M. Esquinas
20.1 Introduction
Noninvasive ventilation (NIV) applied through different interfaces is increasingly

used in the treatment of acute respiratory failure (ARF) and in some chronic respira-
tory disorders such as sleep-disordered breathing (e.g., obstructive sleep apnea
(OSA) and obesity hypoventilation syndrome (OHS)). Despite the great improve-
ment in NIV technology and experience of the medical staff, the failure rate of NIV
in the acute setting remains high ranging between 18 and 40% [1]. The success of
NIV depends on the underlying pathology, patients’ cooperation, and staff experi-
ence. Nevertheless, success of therapy depends to a large extent on the selection of
the proper interface.
20.2 Types of Interfaces for NIV
Choosing the right mask for patients with ARF involves patient preference, finding
the right size, and fit of the mask. There are six available types of masks that can be
used to deliver NIV therapy in the acute setting:
A.S. BaHammam, F.R.C.P., F.C.C.P. (*)

Department of Medicine, The University Sleep Disorders Center, College of Medicine, King
Saud University, Box 225503, Riyadh 11324, Saudi Arabia
Strategic Technologies Program of the National Plan for Sciences and Technology and
Innovation in the Kingdom of Saudi Arabia, Riyadh, Saudi Arabia
e-mail: ashammam2@gmail.com; ashammam@ksu.edu.sa
T. Singh, M.D.
Philips, Respironics, Delhi, India
A.M. Esquinas, M.D., Ph.D.
Intensive Care Unit, Hospital Morales Meseguer, Murcia, Spain

194 A.S. BaHammam et al.
1. Nasal masks. This type of mask covers the nose only while resting on the upper
lip, sides of the nose, and on the nasal bridge.
2. Oronasal masks. It is also referred to as full-face masks. This type of masks
covers the nose and mouth while resting on the chin, sides of the nose and mouth,
and on the nasal bridge.
3. Nasal pillows. This type of mask rests on the rim of the nostrils. They are a good
option for people who find nasal or oronasal mask too obtrusive and who have
skin breakdown on the nasal bridge.
4. Oral masks. This type fits in the mouth between the teeth and lips. It also has a
tongue guide to prevent tongue obstructing the passage of airway. This type is
not common in practice.
5. Total face mask. It covers the entire face and used mainly in patients with ARF [2].
6. Helmet. The helmet is used as an alternative to oronasal mask in patients with
acute hypoxemic respiratory failure or acute cardiogenic pulmonary edema in
certain countries [3]. It is not commonly used in patients with acute hypercapnic
respiratory failure.
Masks are made of a variety of materials but the commonly used material is sili-
cone, and some manufacturers have gel masks as well. The advantage of gel masks
is that they adapt to the contours of the face. The availability of several types of
interfaces makes the choice of the appropriate interface for the patient with ARF a
great challenge.
NIV in the form of continuous positive airway pressure (CPAP), bi-level positive
airway pressure (BPAP), or other pressure- and volume-limited ventilatory modes is
used in patients with ARF. For all modes of NIV, a good fit interface is needed.
20.3 Difference Between Nasal and Oronasal Masks
In ARF, NIV efficacy is more important than patient’s comfort, yet appropriate
mask fitting and care are essential to increase patient tolerance and subsequently
improve NIV outcome [4]. Although there is no ideal NIV interface, choosing an
interface needs thorough evaluation of patient’s features, ventilatory modes, and
respiratory failure type [5, 6]. The choice of the proper interface is influenced by the
patient’s face shape, mouth/nose breathing pattern, patient preference, and experi-
ence of the staff.
Limited number of studies has assessed the impact of different interfaces on the
success of treatment in patients with ARF and the improvements in respiratory
parameters, i.e., respiratory rate, dyspnea, and arterial blood gases. Two randomized
controlled trials that compared oronasal mask with the use of nasal mask in patients
who had ARF showed no evidence that one type of interface is consistently better
than the other in terms of clinical efficiency [7, 8].
Since mouth breathing is predominant in patients with ARF, full-face mask (orona-
sal mask) is considered to be the most suitable and effective interface followed by nasal
mask, helmet, and mouthpiece [5, 7, 8]. Therefore, the most commonly used interface
20 The Choice of Interface 195
in patients with ARF is oronasal mask. This was revealed in a large web-based survey
in North America and Europe, which showed that oronasal mask was used in 70% of
the patients followed by total face masks, nasal masks, and helmets [9].
To accommodate the variability in the human face shape, full-face mask comes
in a different range of shapes and sizes [5].
20.4 Mask Type and Upper Airway Obstruction
As most obese patients with ARF have an element of upper airway obstruction dur-
ing sleep, it is important in this context to discuss the effect of different routes of
interface on the upper airway patency. As oronasal and nasal masks are the most
commonly used masks during ARF [9], we will review the studies that assessed the
effect of each type on upper airway dynamics.
Upper airway dynamics differ when we breathe through the nose than when we
breathe through the mouth [10]. Upper airway resistance and propensity to develop
OSA are higher when breathing occurs through the mouth as compared to breathing
through the nose. Mouth opening is associated with a significant reduction in the ret-
ropalatal and retroglossal cross-sectional areas in awake subjects, as well as a reduc-
tion in the positive pharyngeal critical closing pressure during natural sleep [11].
Oronasal mask violates the Starling resistor model as pressure applied through the
mouth and nose simultaneously may lead to collapse of the airway [12]. In 18 severe
OSA patients treated with nasal CPAP, when the CPAP flow route was shifted from
nasal to oronasal or oral route, there was a significant and progressive reduction in the
distance between the epiglottis and tongue base and the retroglossal area, respectively
[13]. The study demonstrated that patients showed upper airway obstruction during
oronasal CPAP despite being predominantly breathing through the nose preceding the
obstructive event [13]. The authors speculated that positive pressure applied through
the mouth pushed the tongue posteriorly resulting in occlusion of the upper airway
[13]. Moreover, they proposed that oronasal CPAP applies equal positive pressure in
both nasopharyngeal and oropharyngeal compartments, which eliminates pressure
gradient and hence allows gravity to displace the soft palate and tongue backward,
resulting in airway obstruction [13]. Similar results were reported by Smith et al. who
showed that oronasal CPAP was unable to open the upper airway even with CPAP
pressure above the pharyngeal critical closing pressure obtained when nasal mask was
applied [14]. Borel et al. [15] in a large prospective cohort study involving 2311 OSA
patients confirmed the above findings, demonstrating that CPAP pressure is higher
with oronasal mask as compared to nasal mask or nasal pillow.
The above findings of the effect of oronasal masks on upper airway anatomy
have been corroborated with radiological investigations of the upper airway in OSA
patients. In ten OSA patients who were treated with CPAP using nasal and oronasal
masks, upper airway was evaluated by cMRI while using CPAP [16]. In mouth
breathers, applying CPAP at pressure of 15 cm H2O via oronasal mask produced
significantly less airway opening in the retropalatal region of upper airway com-
pared with nasal mask at the same CPAP pressure [16].
The above differences in the efficacy of positive airway pressure applied via
nasal and oronasal masks may influence the effectiveness of NIV therapy particu-
larly in patients with OHS who present with AHRF.
20.4.1 Fitting the Mask
Correct mask fitting is essential for the success of NIV therapy. Therefore, most
masks come with a fitting guage to assure the choice of the correct size mask to
improve acceptance and avoid complications. If a significant leak is detected or
patients could not tolerate the mask, the interface should be changed to avoid NIV
failure. However, when a different mask is used, trigger sensitivity, pressurization
level, and compatibility with the circuitry must be checked [1]. Once the patient is
stable and mouth leak is not present, nasal mask can be tried as it is less claustro-
phobic and has lower risk of skin problems. Straps should not be overtightened to
avoid pressure ulcers. In general, when the headgear is fixed, it should be possible
to permit two fingers beneath it (the two-finger rule) [17].
20.5 Type of Ventilator and Interface Choice
NIV can be applied through a close double-tube circuit or an open single-tube cir-
cuit. A double-tube circuit has one tube for inhalation and another for exhalation
and a built-in exhalation port or filter for CO2 removal. Therefore, a non-vented
mask is used to maintain the closed circuit. On the other hand, the open single-tube
circuit uses one tube only; therefore, it requires a vented mask with a built-in exha-
lation port. If a non-vented mask is used, an additional exhalation valve in the cir-
cuit to allow CO2 removal must be added. Clinicians must be aware of this important
difference between ventilators, because the use of non-vented mask in an open
single-tube system without exhalation port in the system can be disastrous [1].
It is worth mentioning that the interface itself acts as a dead space, which theo-
retically may increase the risk of CO2 rebreathing and retention particularly in acute
hypercapnic respiratory failure. The dead space is related to the internal volume of
the interface [18]. Nevertheless, an in vivo study showed that the internal volume of
the masks had no apparent short-term dead space effect on gas exchange, minute
ventilation, or patient’s effort, suggesting that the interfaces may be interchangeable
in clinical practice with the exception of the helmet [19].
20.5.1 Oxygen (O2) Supply and Interface
When using an ICU ventilator, the fraction of inspired oxygen (FiO2) can be pre-
cisely controlled. However, in some portable ventilators that are used outside the
ICU setting, there is no oxygen control, and thus supplemental oxygen is bled into
the mask or the ventilator circuit. Usually, low flow oxygen is bled into the circuit,
20 The Choice of Interface 197
and this results in variable FiO2. In contrast to ICU ventilators that have an inhala-
tion tube and an exhalation tube, portable devices for NIV operate with one tube
only. Therefore, an additional exhalation port is added to the circuit. The actual
inspired FiO2 when oxygen is bled into the circuit or the mask is variable and is
influenced by several factors such as intentional and unintentional leak through the
mask or the circuit, inspiratory and expiratory pressure settings of the NIV, the
interface, oxygen flow, and the oxygen administration site [20–22]. Frequently, oxy-
gen supply is bled into an oxygen port already built into the frame of the mask. The
site of oxygen delivery into the circuit is the most important factor in determining
inspired FiO2 [20]. Administering oxygen into the mask results in exhaustion of
oxygen out of the exhalation port [22]. Moreover, oxygen may leak unintentionally
between the mask and the face resulting in low inspired oxygen concentration and
hence low arterial partial pressure of oxygen (PaO2) and oxygen saturation.
Consequently, when oxygen is bled directly into a mask with a leak port, patients
may receive very low oxygen concentrations, which may result in low oxygen satu-
ration in the blood [21, 22]. Therefore, during NIV of patients with ARF, it is rec-
ommended to use a ventilator in which FiO2 can be precisely controlled.
20.6 Summary
The best mask is the one that patient will wear. It is important to let the patient try
different types of masks and choose the most comfortable mask. Aside from patient
preference, oronasal masks are preferred in patients with ARF. Experience with
mask fitting and prevention of mask-related problems such as air leak, skin irrita-
tion, and pressure ulcers are essential for NIV therapy success. Once stable, patients
may be shifted to nasal masks.
Acknowledgment This project was partially funded by The Strategic Technologies Program of
the National Plan for Sciences and Technology and Innovation in the Kingdom of Saudi Arabia.
Conflict of Interest AB and AE have no conflict of interest to declare. TS is an employee of

Philips, Respironics.
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13. Andrade RG, Madeiro F, Piccin VS, Moriya HT, Schorr F, Sardinha PS, et al. Impact of acute
changes in CPAP flow route in sleep apnea treatment. Chest. 2016;50(6):1194–201.
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ships in obstructive sleep apnea. J Appl Physiol (1985). 1988;64(2):789–95.
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The Choice of Ventilator and Ventilator
Setting 21
Ebru Ortaç Ersoy
21.1 Introduction
Obesity is highly prevalent throughout the world. There have been multiple studies
about obese critically ill patients, and the prevalence of obesity in intensive care unit
(ICU) is estimated at 25%. Critically ill morbidly obese patients have higher ICU
mortality compared to nonobese patients; morbid obesity is associated with pro-
longed mechanical ventilation and extended “weaning” period. Obesity results in
anatomic and physiologic alterations in the face, neck, larynx, lungs, and chest wall
and also affects pulmonary system function especially in critically ill patients by
increasing work of breathing and by increasing respiratory system compliance and
resistance [1, 2]. Excess facial fat may compromise fit of mask for ventilation, while
pharyngeal fat increases upper airway resistance. Respiratory mechanics are mark-
edly altered in obese patients; functional residual capacity is about one third of
normal, and lung compliance is reduced for about 50%. Total lung resistance is
threefold higher in obese patients. In summary, both elastic and resistive work of
breathing are significantly higher [3].
Effective treatment strategies must relieve upper airway obstruction and increase
alveolar ventilation in obese critical patients affected by respiratory failure. Morbid
obesity is associated with an increase in work of breathing and oxygen cost of
breathing and a decrease in compliance of the respiratory system, lung volumes,
ventilatory drive, and respiratory muscle dysfunction [3].
Therefore, choosing ventilator and managing settings is important in obese
patients in ICU. NIV can be applied with volume-limited or pressure-limited
devices. Both ICU ventilators and portable noninvasive ventilators can be used.
E.O. Ersoy
Medical Intensive Care Unit, Hacettepe University Hospital, Ankara, Turkey
e-mail: ebru.ortac@hacettepe.edu.tr

200 E.O. Ersoy
Positioning of obese patient is also important. In this chapter, the choice of ventila-
tor and ventilator settings will be described in obese ICU patients.
21.2 Ventilator Type
The choice of a ventilator can be important for the success of NIV in the obese
patients for acute settings, because intolerance is especially important for NIV
success.
NIV can be delivered via standard type of ventilators found in the ICU: regular
ICU ventilators with no NIV algorithms, ICU ventilators with NIV algorithms, or
portable ventilators that are used for NIV only. Standard ICU ventilators have some
advantages.
An accurate concentration of oxygen can be delivered by ICU ventilators, sepa-
rate inspiratory and expiratory tubing minimizes the rebreathing of CO2 (it is impor-
tant especially in obesity hypoventilation patients), monitoring of alarms is better,
and certain modes can only be delivered with standard ICU ventilators. But in ICU
ventilators, leak compensation is poor. If leak is great, the ventilator leak alarm may
be activated and leak can abort the breath of patient. Critical care ventilators have
traditionally been designed for invasive ventilation, but newer generations have NIV
modes. For critical care ventilators, dual-limb circuits are used, and these have
inspiratory and expiratory valves and separate hoses for the inspiratory gas and the
expiratory gas. Several recent studies have evaluated the ability of critical care ven-
tilators to compensate for leaks. Vignaux et al. [4] found that leaks interfere with the
function of ICU ventilators and that NIV modes can correct this problem but with
wide variations between ventilators. In a follow-up study, Vignaux et al. [5] reported
that NIV modes on ICU ventilators decreased the incidence of asynchrony typically
associated with leaks. In a laboratory and clinical study, Carteaux et al. [6] sug-
gested that, as a group, bi-level ventilators outperform critical care ventilators for
NIV. However, the NIV modes on some, but not all, critical care ventilators improve
synchrony in the presence of leaks. Some critical care ventilators also allow clini-
cians to make adjustments to improve synchrony. These embellishments include an
adjustable trigger type and sensitivity, an adjustable flow cycle criteria with PSV,
and a maximal inspiratory time during PSV. Due to the differences in the ability to
compensate for leaks among ventilators used for NIV, it is important for clinicians
to appreciate the unique characteristics of the ventilators they use [7]. Either pres-
sure- or volume-cycled ventilators may be used to deliver NIV.
The ventilatory mode used by pressure-cycled ventilators is also known as bi-
level positive airway pressure (BPAP). It delivers both a preset inspiratory positive
airway pressure (IPAP) and expiratory positive airway pressure (EPAP). The assist-
control mode is used for volume-cycled ventilators. Additional “hybrid” modes
such as average volume-assured pressure support (AVAPS) mode or intelligent
volume-assured pressure support (iVPAPS) are available for NIV, and these hybrid
modes can be used even in ICU. In difficult ventilated obese patients, hybrid modes
may be used especially in patients with acute on chronic respiratory failure, e.g.,
OHS, OSA, and scoliosis.
21 The Choice of Ventilator and Ventilator Setting 201
Evidence to guide ventilator selection is lacking, but most practitioners prescribe

pressure-cycled ventilators. Regardless of whether a volume- or pressure-cycled
device is used, though, the initial priority should be to achieve patient comfort and
acceptance rather than any particular level of improvement in gas exchange.
21.3 Ventilator Settings
Before maintaining the settings of ventilators, positioning of obese patient is important.

Obese patients are at risk for severe oxygen desaturation that can occur precipitously
because of lower functional capacity and atelectasis that is exacerbated in the supine
position. Sitting position prevents gravitational atelectasis, unloads the diaphragm, and
reduces work of breathing. In morbidly obese patients, elevated abdominal pressure
can affect pulmonary function in sitting position. NIV should be administered at
ramped position to obese ICU patients. Reverse Trendelenburg position in 30–45° is
important [8, 9]. NIV can be delivered using the same modes with invasive ventilation.
Especially with the ICU ventilators, more frequently used modes are the following:
1. Assist control (AC): The most common mode chosen for guaranteed minute ven-
tilation. In an obese patient, it can be difficult to use AC mode because of high
airway resistance and patient intolerance.
2. Pressure support ventilation (PSV): The most common mode for patient comfort
and synchrony. Obese ICU patients can easily tolerate this mode for NIV. PSV is
used most commonly for NIV applications in patients with acute respiratory
failure. With a critical care ventilator, the level of PSV is applied as a pressure
above the baseline PEEP. However, the approach is different with bi-level venti-
lators, where an inspiratory positive airway pressure and expiratory airway pres-
sure are set. In this configuration, the difference between the inspiratory and
expiratory airway pressure is the level of PSV [10].
3. Continuous positive airway pressure (CPAP): Often used for patients with acute
respiratory failure due to pulmonary edema and with obstructive sleep apnea
(OSA). Especially in postoperative morbidly obese patients, CPAP can prevent
atelectasis.
4. BPAP: The most common mode in patients with hypercapnic respiratory

failure.
5. Proportional assist ventilation (PAV): Delivers an inspiratory pressure that is
proportional to patient effort and may be helpful in patients who do not tolerate
PSV or CPAP.
6. Hybrid modes: Average volume-assured pressure support (AVAPS). In this

mode, the IPAP varies in order to achieve a present tidal volume. This mode can
be used with portable NIV ventilators [11].
In ICU ventilators selected mode determines which parameters need to be set.

The initial settings for NIV are similar to those for invasive ventilation. There is not
any universal approach for initial settings especially for obese ICU patients. NIV
settings have to be patient based. The goal of initial settings is to provide a modest
202 E.O. Ersoy
amount of ventilatory support, while allowing the patient to become acclimated to

NIV. The ventilator setting should be different in obese patients. Theoretically, the
recommended Vt should be calculated according to the predicted body weight based
solely on height and gender and should be adjusted for inflation pressure and gas
exchange [12].
Tolerance of bi-level positive airway pressure devices is facilitated by using low
initial pressures. Pressures should be titrated slowly to allow the patient to accli-
mate the device. Initial inspiratory positive airway pressure (IPAP) is typically
8–10 cm H2O and expiratory positive airway pressure (EPAP) 4–5 cm H2O (thus
providing inspiratory pressure support [IPAP minus EPAP] (pressure boost) of
approximately 4–6 cm H2O). Indeed, the respiratory compliance of obese patients is
decreased. Brochard et al. [13] used a pressure boost between 12 and 20 cm H2O in
patients with acute exacerbation of COPD. In a patient with acute restrictive respira-
tory failure, a 6 cm H2O pressure boost significantly reduced diaphragmatic activity
and allowed recovery of normal thoracoabdominal motion. When the pressure boost
was increased to 11 cm H2O, diaphragmatic activity disappeared [14].
This suggests that pressure boost must reach a threshold to place the diaphragm
at rest. This threshold may differ, depending on the stage and the type of respiratory
disease, as well as the respiratory compliance due to severity of obesity.
The IPAP can be increased until there is an acceptable level of steady oxygen-
ation (SaO2 >92%). To achieve adequate ventilation in BPAP, the IPAP should be at
least 8–10 cm H2O greater than EPAP [15].
Initial tidal volumes of 6–10 mL/kg (ideal body weight) are employed when
using a volume-cycled ventilator, starting at the low end of the range and increasing,
as needed. These volumes may be higher than those commonly used for invasive
ventilation, because of the frequent need to compensate for air leaks during nonin-
vasive ventilation. Positive end-expiratory pressure (PEEP) is usually provided at
4–5 cm H2O; slightly higher PEEP levels may be needed for patients with concomi-
tant chronic obstructive pulmonary disease (COPD). In obese patients, Vt based on
patients’ actual body weight is likely to result in high airway pressure and alveolar
overdistention. In settings usage of ideal body weight is advised.
In clinical practice, obese patients in ARF need high levels of IPAP (12–25 cm
H2O) and PEEP (5–13 cm H2O) [16]. Refractory hypoxemia is the main determi-
nant of NIV failure.
For volume-controlled NIV, the ventilator mode, respiratory rate, tidal volume,
and PEEP must be selected. The largest tidal volume that consistently maintains an
airway pressure less than 3 cm H2O is generally chosen. And respiratory rate is then
set to achieve minute ventilation of 6–10 L/min.
In acute decompensated obese patient with respiratory failure, NIV should be
used as BPAP or volume-controlled NIV instead of CPAP, although BPAP is usually
preferred unless it is insufficient to maintain an open upper airway or to overcome
the decreased respiratory system compliance in obese patients [17]. In postoperative
morbidly obese patients in the ICU, NIV is mostly used for preventing respiratory
failure. CPAP provides ventilatory support to restore and maintain the lung volumes
by recruiting atelectatic lung which, in turn, improves oxygenation and reduces
21 The Choice of Ventilator and Ventilator Setting 203
work of breathing in these patients. Animal studies have shown that minimizing
lung atelectasis decreases bacterial growth and translocation of organisms to the
bloodstream by reducing the permeability of the epithelial-endothelial barrier [18,
19]. A meta-analysis [20] has shown that postoperative CPAP following abdominal
surgery significantly reduced post-pulmonary complications, atelectasis, and pneu-
monia which is in contrast with a more recent Cochrane review concluding that the
evidence to support the use of CPAP to reduce pneumonia and re-intubation is of
low quality [21, 22].
Although humidification necessary during NIV is controversial, humidification
should be considered during NIV [23]. During NIV, unidirectional flow dries the
upper airway and increases nasal airway resistance. Upper airway drying contrib-
utes to discomfort of patient and may affect tolerance to NIV. It can be done either
actively by heated humidifiers (HH) or passively by heat and moisture exchangers
(HME) in ICU settings. A heat and moisture exchanger is not recommended for use
with NIV, because the additional dead space decreases carbon dioxide elimination,
particularly in patients with hypercapnia [24, 25].
Conclusion
The number of obese patients in ICU is increasing. It is important to pay special
attention during mechanical ventilation in these patients because of lung dynam-
ics and comorbidities. The choice of ventilator and setting is especially impor-
tant especially in NIV. There is no any recommended setting. We have to choose
ventilator and setting according to our critical patient and the medical problem of
the patient.
References
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2. Harris RS. Pressure-volume curves of the respiratory system. Respir Care. 2005;50:78–98.
3. Janssens J-P, Pepin J-L, Guo YF. NIV and chronic respiratory failure secondary to obesity. Eur
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lators during pressure support: a bench model study. Intensive Care Med. 2007;33(8):1444–51.
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Respir J. 2012;40:1568–9.
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disease by inspiratory assistance with a face mask. N Engl J Med. 1990;323:1523–30.
14. Carrey Z, Gottfried SB, Levy RD. Ventilatory muscle support in respiratory failure with nasal
positive pressure ventilation. Chest. 1990;97:150–5831.
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intermittent positive pressure ventilation in patients with obesity hypoventilation syndrome.
Chest. 2005;128:587–94.
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failure in morbidly obese patients in acute respiratory failure. PLoS One. 9(5):e97563.
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obesity hypoventilation syndrome without severe nocturnal desaturation. Thorax. 2008;63:395.
18. Duggan M, McCaul CL, McNamara PJ, et al. Atelectasis causes vascular leak and lethal right
ventricular failure in uninjured rat lungs. Am J Respir Crit Care Med. 2003;167:1633–40.
19. van Kaam AH, Lachmann RA, Herting E, et al. Reducing atelectasis attenuates bacterial growth
and translocation in experimental pneumonia. Am J Respir Crit Care Med. 2004;169:1046–53.
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ing the postoperative period for prevention of postoperative morbidity and mortality following
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23. Respeto RD, Walsh BK. AARC Practice Guideline. Humidification during invasive and non
invasive mechanical ventilation. Respir Care. 2012;57(5):782–8.
24. Branson RD, Gentile MA. Is humidification always necessary during noninvasive ventilation
in the hospital? Respir Care. 2010;55(2):209–16.
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2009;35(6):987–95.
Obesity and Bi-level Positive Airway
Pressure 22
Ayelet B. Hilewitz, Andrew L. Miller, and Bushra Mina
22.1 Introduction
Obesity has become an increasingly concerning global epidemic. Obesity, defined

as a body mass index (BMI) more than 30 kg/m2, is classified based on severity with
BMI 30–39.9 kg/m2 classified as obesity and BMI >40 kg/m2 classified as morbid
or severe obesity. Obesity is a major risk factor for many acute and chronic diseases.
It worsens chronic conditions including hypertension, dyslipidemia, type 2 diabetes
mellitus, cholelithiasis, and osteoarthritis and is known to increase all-cause mortal-
ity. Obesity also has significant negative effects on the respiratory system and causes
profound changes to the physiology of breathing, pulmonary mechanics, and gas
exchange. A brief review of some of the changes will be discussed.
One important change is the decrease in total respiratory system compliance.
Compliance can be decreased by as much as two-thirds the normal value. This is
likely due to accumulation of fat in and around the ribs, the diaphragm, and the
abdomen [1]. Recumbency further worsens compliance in obese patients and is
almost entirely due to decreased compliance of the chest wall. Increased work of
breathing in obese patients is caused by this decrease in compliance, but more
importantly is secondary to an increase in nonelastic work of the respiratory mus-
cles [1]. Airway resistance is also significantly increased likely as a result of reduc-
tion in lung volumes due to obesity itself.
A.B. Hilewitz, M.D. (*)

Division of Pulmonary, Hosftra Northwell School of Medicine, Northwell Health, Critical
Care and Sleep Medicine, New Hyde Park, NY, USA
e-mail: ahilew@northwell.edu
A.L. Miller, M.D.
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado,
Denver, CO, USA
B. Mina, M.D.
Northwell Health, Lenox Hill Hospital, New York, NY, USA

206 A.B. Hilewitz et al.
Another important effect is changes in pulmonary function tests. The most com-
mon pulmonary function abnormality is reduction in expiratory reserve volume
(ERV) [1]. ERV is likely the most sensitive indicator of obesity on lung function.
This takes place due to mass loading, causing a decrease in functional reserve
capacity (FRC), and since residual volume (RV) does not change in these patients,
the ERV decreases. ERV decreases the most when the patient is supine, which
causes the diaphragm to ascend and the weight of the lower thorax and abdomen to
be applied to the lungs. When it reaches this stage, the ERV may come close to or
surpass the closing volume, and gas may be trapped in the chest [1]. It has been
shown that the decrease in FRC and ERV is proportionate to the degree of obesity.
Of note, vital capacity (VC), total lung capacity (TLC), and other spirometric mea-
sures tend to be within normal limits in mild obesity. However, as BMI increases
especially to the extreme (i.e., severe obesity), there is a decrease in expiratory flow
and decreases in both forced expiratory volume in 1 second (FEV1) and forced viral
capacity (FVC), as well as decreases in TLC and VC [1].
An additional change is an increased carbon monoxide diffusion capacity (DLCO).
This is thought to be due to increased pulmonary blood flow. However, it should be noted
that DLCO is directly proportional to lung volumes, so any decrease in lung volumes, such
as those seen with high BMIs causing atelectasis, will lead to a low to normal DLCO [1].
A further effect of obesity is the distribution of ventilation and perfusion. In non-
obese patients, ventilation is greatest in the dependent lung zones and decreases in
the nondependent lung zones. In obese patients, however, there seems to be increased
ventilation of the upper nondependent lung zones, leading to hypoxemia. The mech-
anism behind this ventilation perfusion mismatch is thought to be due to airway
closure and atelectasis in the peripheral lung zones and smaller airways [1, 3].
Obesity is also associated with increased dyspnea on exertion and poor perfor-
mance on 6-min walk test. Obesity causes additional stress to ventilation during
exercise directly resulting from increased body mass requiring greater metabolic
expenditure, as well as from functional impairment of the respiratory system [1].
Lastly, dyspnea on exertion, which is a prevalent complaint in obese patients, has
been found to increase with increasing BMI. The cause is multifactorial, including
increased work of breathing, airflow obstruction especially at low lung volumes,
and respiratory muscle fatigue and weakness, among others [1].
There is a subset of obese patients who develop obesity hypoventilation syn-
drome (OHS). These patients tend to be morbidly obese and have the hallmark find-
ing of daytime hypercapnia. It is unclear why certain obese patients develop this
syndrome and others do not. The definition of OHS is obesity defined as BMI
>30 kg/m2 and awake arterial hypercapnia (arterial pressure of carbon dioxide
PACO2 > 45 mmHg) in the absence of other known causes of hypoventilation,
including pulmonary, thoracic, metabolic, or neuromuscular disorders [2]. The
reported prevalence of OHS is 10–20% of the obese population, and more than 50%
of hospitalized patients with a BMI more than 50 meet diagnostic criteria for OHS
[5]. Patients typically present with excessive daytime sleepiness, morning head-
aches, and fatigue. It is important to note that these patients have daytime hypercap-
nia and hypoxemia, which is strongly associated with pulmonary hypertension and
22 Obesity and Bi-level Positive Airway Pressure 207
subsequent cor pulmonale. In addition, many patients develop polycythemia. There

is significant morbidity and mortality associated with this disease. Daytime hyper-
capnia in obesity is significantly associated with higher BMI levels and degree of
restrictive chest wall mechanics, specifically lower VC and TLC [9]. The majority
of patients with OHS have concurrent obstructive sleep apnea (OSA).
The exact pathophysiology of OHS has not been elucidated fully, but it likely
results from intricate interplays among defective respiratory mechanics, neurohor-
monal abnormalities, sleep-disordered breathing, and an abnormal central ventila-
tory control [2]. Abnormal ventilatory drive is probably one of the more important
factors in its development [1]. These patients lack compensatory hyperventilation
mechanisms to overcome the mechanical abnormalities of obesity. It has been pos-
tulated that OSA may be an important contributor to this depressed ventilatory
response and resultant hypoventilation. Chronic exposure to hypoxia and sleep frag-
mentation, as seen in OSA, has been found to lessen central ventilatory drive [2].
Patients with these concurrent syndromes get stuck in a vicious cycle where contin-
ued apnea-induced hypoxemia and hypercapnia cause more sleep fragmentation,
leading to worsening of the ventilatory drive, impeding ventilatory compensation in
post-apneic period, causing more severe hypoxemia further diminishing central
ventilatory drive, and so on [2]. OHS is commonly underrecognized and is fre-
quently diagnosed when a patient presents with an episode of acute respiratory fail-
ure (ARF), and it has been reported that OHS is frequently overlooked as a possible
cause of ARF, thus leading to inappropriate treatment [3]. Studies have found that
more than 75% of OHS exacerbations have been erroneously diagnosed and treated
for asthma or chronic obstructive pulmonary disease (COPD) exacerbation [5].
Therefore, physicians should maintain a low index of suspicion.
Bi-level positive airway pressure (BPAP) improves many aspects of respiratory
mechanics and physiology. The inspiratory positive airway pressure (IPAP) aug-
ments tidal volume, while the expiratory positive airway pressure (EPAP) maintains
airway pressures keeping airways open, as well as recruits collapsed alveolar units,
thereby improving oxygenation. The difference between the IPAP and EPAP is the
pressure support which enhances ventilation, thereby treating hypercapnia. It also
improves work of breathing and improves diaphragmatic function.
Data pertaining to BPAP use in the general obese population is sparse. The dis-
cussion will focus on its use in patients with OHS, as the overwhelming majority of
the literature describes its use in this population. The use of continuous positive
airway pressure (CPAP) has been well described as a treatment modality for patients
with OSA. However, patients with OHS require ventilatory support to help correct
their hypercapnia and will require BPAP. Morbid obesity puts patients at risk for
both acute and chronic respiratory failure. Many OHS patients develop acute respi-
ratory failure secondary to their disease, as well as many other common disease
states, and can be treated with BPAP. Furthermore, many of these patients who
recover from their acute event will continue to require ventilatory support. Most
OHS patients will have chronic respiratory failure (CRF), as demonstrated by their
symptoms and blood gas abnormalities, and will benefit from the BPAP use, as will
be discussed below, preventing the need for tracheostomy.
22.2 Discussion
22.2.1 OHS and Acute Respiratory Failure
The prevalence of obesity in ICU patients ranges from 9 to 26% and morbid obesity
ranges from 1.4 to 7% [3]. Obese patients with all of their associated changes to
respiratory physiology have a diminished respiratory reserve, thus predisposing
them to respiratory failure. Treating acute respiratory failure in obese patients rep-
resents a new challenge for healthcare providers. For many years, noninvasive
positive pressure ventilation (NIPPV) has been a popular mode of ventilator support
in many acute pulmonary disease processes, such as COPD, acute cardiogenic pul-
monary edema, and pneumonia, among others. Only more recently, with the grow-
ing obese population has BPAP been considered in this group. There is strong
evidence to support the use of BPAP, when no contraindications exist, as first-line
therapy for ARF, particularly hypercapnic failure in obese patients, in order to avoid
endotracheal intubations and all of its associated complications. Early recognition
is especially important. Of note, acute hypoxemic respiratory failure is less likely to
respond to supplemental oxygen and NIPPV, such as BPAP, and will frequently
require mechanical ventilation. However, BPAP can be attempted in these patients
particularly if the etiology of ARF is cardiogenic pulmonary edema, as NIPPV has
been shown to be successful in this subset of patients [3]. NIPPV improves upper
airway patency, reduces work of breathing, increases the FRC, unloads respiratory
muscles, improves perfusion ventilation mismatching, and resolves the alveolar
hypoventilation by augmenting tidal volume [3].
A prospective observational study was performed to evaluate if patients with
OHS and acute hypercapnic respiratory failure would respond to NIPPV with the
same efficacy as those with COPD, where BPAP has been shown to be effective in
acute hypercapnic respiratory failure. Overall patients with OHS had lower rates of
late BPAP failure, readmissions to the ICU, and ICU and hospital mortality and
lower PACO2 on discharge as compared to those with COPD. The results showed
that BPAP was highly effective in patients with OHS and acute hypercapnic respira-
tory failure and even had better outcomes, particularly survival, which will be dis-
cussed in more detail in the next section [4].
Another recent prospective observational study was performed to identify the
factors associated with BPAP failure or success in the OHS population with acute
hypercapnic respiratory failure no matter the cause of ARF. It was found that BPAP
failed in only 17% of the population. Additionally, patients who were more likely to
have early BPAP failure were more likely to be male and have a diagnosis of pneu-
monia and multisystem organ failure at admission, hypoxemic respiratory failure,
lower PACO2 and serum bicarbonate levels, and higher severity scores at admission.
Factors associated with successful response to BPAP were high PACO2 and bicar-
bonate levels at admission and idiopathic hypercapnic OHS exacerbation [5]. An
interesting finding of the study concerned a delayed response to BPAP in patients
with hypercapnic ARF. ABGs were improved significantly over the first 48 h. About
half the patients would have been considered poor responders given their
unimproved PACO2 and pH after the initial trial of BPAP, but were continued on
BPAP because they failed to meet criteria for BPAP failure as set by the study. None
of these patients were eventually intubated. These findings advocate for further
NIPPV rather than immediate intubation and should be considered for morbidly
obese patients with persistently severe acute hypercapnic respiratory failure after
the first several hours of NIPPV [5]. The decreased responsiveness of the ventilatory
drive may explain why these patients need more time to correct their acid-base
derangements.
Patients who present with ARF suspicious for OHS should be started on BPAP
before performing a sleep study. Bahammam and Al-Jawder suggested a treatment
algorithm with BPAP as follows: initiate EPAP of 4–6 cm H2O and IPAP of 8–10 cm
H2O. EPAP should be gradually titrated up by 1–2 cm H2O until snoring, witnessed
apneas and dips in oxygen saturation cease; IPAP should be gradually titrated up by
1–2 cm H2O until oxygen saturation is maintained in a range of 90–92% and should
usually be 4–8 cm H2O above EPAP to maintain alveolar ventilation [3]. Most
patients during ARF will require supplemental oxygen.
It should be noted that the vast majority of the studies did not contain a control
group of patients, as it was believed that it is unethical to withhold BPAP, which is
considered the standard of therapy. In addition, most studies were performed on a
small sample size. However, attempting BPAP is safe in these patients and should
be tried first prior to endotracheal intubation. Caution should always be taken that
patients do not meet any of the known contraindications to BPAP use. This nonin-
vasive intervention should be started in the emergency room or general medicine
floors. All these patients require close monitoring of vital signs, mental status, pat-
tern of breathing, and serial blood gas monitoring and should be moved to an ICU.
22.2.2 OHS and Chronic Respiratory Failure
OHS causes many derangements to normal respiratory physiology, as described

above, having many downstream effects causing significant morbidity and mortal-
ity. The resultant hypoxia can cause pulmonary vasoconstriction and eventual pul-
monary hypertension, as well as many other cardiovascular effects, and polycythemia.
Treating this disease is becoming more important as the rates of obesity continue to
rise worldwide. BPAP can help reverse some of these abnormalities and has been
suggested as a long-term treatment for these patients. CPAP alone cannot correct
alveolar hypoventilation that occurs in OHS. There is the need for both inspiratory
and expiratory pressures to help support ventilation.
Several studies have been performed to evaluate the utility of nighttime BPAP in
chronic respiratory failure due to OHS. Masa et al. performed a study in 2001 look-
ing at the effectiveness of BPAP in patients with OHS compared to patients with
kyphoscoliosis, in which BPAP has previously been shown to be successful. Overall
the results showed that BPAP is effective in improving symptoms and reversing
respiratory failure in patients with OHS, similar to the effect seen in patients with
kyphoscoliosis [6].
It is postulated that nighttime BPAP can help reverse daytime hypercapnia by

improving chemoreceptor sensitivity to arterial pressure of oxygen (PAO2) and
PACO2, in addition to increases in lung volume and compliance, as well as improved
efficiency of respiratory muscles [6]. Other studies have shown improvement in
PAO2 and PACO2 levels. In severely obese patients, BPAP has also been shown to
unload the inspiratory muscles [7]. Heinemann et al. showed normalization of
PACO2 during daytime spontaneous breathing without supplemental oxygen,
accompanied by a significant improvement in hypoxemia after both 12 and
24 months of treatment with BPAP [8]. The degree of change was positively corre-
lated with compliance with therapy. Meaning, the daily use of BPAP more than
4 hours per night was correlated with decreases in PACO2 after 12 and 24 months.
This study also looked at changes in pulmonary function tests. After 12 months of
therapy, there was a normalization of the restrictive ventilatory defect with a signifi-
cant increase in TLC and VC. ERV also showed a significant increase [8]. These
findings were present independent of weight changes. Sleep architecture is also
known to improve due to normalization of ventilation with increases in REM sleep
and decreases in stage 1 and 2 sleep [9].
There have been several positive long-term outcomes found in those patients
who use BPAP consistently. Studies have shown decreased emergency room
visits and hospital admissions in OHS patients treated with BPAP compared
with untreated OHS patients [3, 4, 7]. Again, compliance is essential for good
outcomes. Studies have shown that patients discharged from the hospital after
hypercapnic ARF had increased mortality if they refused BPAP with one study
showing 6% mortality in the treated group vs. 46% mortality in those who
refused [3]. In addition, improvements in hemoglobin and subsequent polycy-
themia have been reported. This change is not related to supplemental oxygen
usage [3].
Another positive effect of BPAP is eliminating the use of daytime supplemental
oxygen over time. Most OHS patients will require supplemental oxygen despite
both inspiratory and expiratory pressure provided, as well as during the day. Studies
have demonstrated that after several months of BPAP use, these patients may no
longer require daytime oxygen with decreases in pulmonary artery pressures [3].
Subjective symptoms have also been shown to improve. Dyspnea, daytime somno-
lence, headaches, and general quality of life all improved in this population. In
addition, many patients are able to be titrated from BPAP therapy to CPAP after
several months of therapy [7].
Many of the studies above have compared BPAP use in OHS to BPAP use in
patients with other chest wall or pulmonary diseases. There have been very few true
control trials in CRF, as stated above, due to the BPAP being standard of care in this
population. However, one study was performed evaluating whether nocturnal BPAP
use in OHS vs. a control group, which received lifestyle counseling, could be effec-
tive on sleep structure, daytime somnolence, and inflammatory, metabolic, and car-
diovascular consequences [9]. The OHS patients were characterized as having mild
disease. It was a short-term study following patients for 1 month. As expected, the
BPAP group had improvements in diurnal PACO2, serum bicarbonate, and pH, as
well as nocturnal oxygen measurements. Sleep architecture also improved signifi-

cantly, as did subjective daytime sleepiness, although this was nonsignificant after 1
month. A significant reduction in BMI was seen in the lifestyle modification group.
More importantly, no changes were seen on any metabolic parameters in either
group despite improvement in oxygenation. The markers that were studied included
several anti-inflammatory and inflammatory cytokines, high-sensitivity C-reactive
protein (hsCRP), as well as measures on vascular endothelial function and arterial
wall stiffness, blood pressure, lipid panel, fasting glucose, and hemoglobin A1C [9].
This is an important point as BPAP cannot be the only intervention for these patients
to improve their cardiovascular and metabolic risk factors. OHS patients need inten-
sive physical and pulmonary rehabilitation programs, as well as weight loss reduc-
tion plans, and should be considered for bariatric surgical interventions as well.
Conclusion
Overweight and obesity have become a widespread global disease affecting mil-
lions of people across all age groups. It has significant morbidity and mortality,
causing cardiovascular, metabolic, pulmonary, and musculoskeletal derange-
ments. Some of the effects on the pulmonary system include decreased compli-
ance, ventilation/perfusion mismatching, changes in static lung volumes, as well
as increased work of breathing and dyspnea. A proportion of severely obese
patients develop OHS, where patients characteristically have daytime hypercap-
nia. These patients have worse morbidity and mortality, especially the develop-
ment of pulmonary hypertension and cor pulmonale, as well as secondary
polycythemia, than is observed in the general obese population. OHS is com-
monly underrecognized, misdiagnosed, and undertreated and has a high preva-
lence among hospitalized patients, especially ICU patients. Its recognition and
treatment is becoming more important as the prevalence increases in the general
population.
BPAP is a well-known mode of noninvasive ventilation that has been proven
useful in several acute and chronic disease states, such as COPD, acute cardio-
genic pulmonary edema, kyphoscoliosis, as well as others. It provides both inspi-
ratory and expiratory support, aiding in both ventilation and oxygenation, with
which OHS patients have issues.
Data over the last 20 years suggests that OHS patients with both acute and
chronic hypercapnic respiratory failure will benefit from BPAP use. Patients
with ARF benefit from the more immediate improvements in gas exchange
and decreased work of breathing, and BPAP can safely be used in this popula-
tion to prevent endotracheal intubation. Of note, patients with acute hypox-
emic respiratory failure may not improve with BPAP and many progress to
endotracheal intubation, but BPAP is still a reasonable initial ventilation
modality. In CRF, long-term nighttime use has shown benefits, with decreases
in mortality, hospitalizations, gas exchange abnormalities, as well as subjective
symptoms, such as daytime somnolence and headaches. As stated previously,
there is little data on the use of BPAP in the general obese population, but it is
safe to extrapolate its safety in this group. Presumably, BPAP would be a good
choice for patients with ARF in the non-OHS obese population who are at base-
line less severely ill, just as in the OHS population where patients may be more
severely ill at baseline. The benefits of BPAP use would outweigh the risks.
Avoiding endotracheal intubation in ARF is paramount, as mechanical ventila-
tion in obese patients has a host of challenges and complications. Caution must
always be used that patients are appropriate for this mode of ventilation and
patients must be closely monitored in an ICU setting. In CRF, the use of BPAP
in the non-OHS obese population is not as clear-cut, as many of these patients
do not have the blood gas abnormalities that would necessitate the use of night-
time BPAP.
Compliance with BPAP in both the acute and chronic setting cannot be under-
stated. Poor compliance or patients not being able to tolerate the mask is a well-
known contraindication to its use in the acute setting. In the CRF population,
long-term studies have shown that patients who did not comply with the minimal
amount of nighttime use had poor outcomes and did not reap the benefits that
BPAP provided and were more similar to the group of patients who did not use
BPAP at all. Education of patients and their family members is vital in this popu-
lation so that they understand its importance and its benefits.
Lastly, despite the positive short- and long-term effects of BPAP in the OHS
population, weight loss cannot be ignored. Weight loss is the conclusive cure for
OHS. This must be emphasized in this population. Patients must be referred to
weight loss programs and/or should strongly be considered for bariatric surgical
procedures. BPAP helps improve many of the abnormalities that are caused by
hypoventilation and hypoxemia and will eventually help optimize them for any
surgical procedures. However, the excess adipose tissue with all of its known
negative effects cannot be resolved by BPAP alone.
• Obesity is a growing worldwide epidemic with significant morbidity and mortal-

ity, with a small proportion of patients developing OHS.
• BPAP is a reasonable mode of NIPPV to attempt in obese and OHS patients with
acute respiratory failure, especially hypercapnic failure, to prevent endotracheal
intubation.
• In chronic respiratory failure in OHS patients, the use of nocturnal BPAP has
been shown to decrease mortality and hospitalizations and improve subjective
symptoms and should be used in this population.
• Compliance with BPAP must be emphasized in OHS patients ensuring that they
reap the benefits that BPAP provides.
• Weight loss is an imperative part of treatment in these patients.
References
1. Parameswaran K, Todd DC, Soth M. Altered respiratory physiology in obesity. Can Respir J.
2006;13(4):203–10.
2. Olson AL, Zwillich C. The obesity hypoventilations syndrome. Am J Med. 2005;118(9):948–56.
3. Bahammam AS, Al-Jawder SE. Managing acute respiratory decompensation in the morbidly
obese. Respirology. 2012;17(5):759–71.
4. Carrillo A, Ferrer M, Gonzalez-Diaz G, et al. Noninvasive ventilation in acute hypercapnic
respiratory failure caused by obesity hypoventilation syndrome and chronic obstructive pulmo-
nary disease. Am J Respir Crit Care Med. 2012;186(12):1279–85.
5. Lemyze M, Taufour P, Duhamel A, et al. Determinants of noninvasive ventilation success or
failure in morbidly obese patients in acute respiratory failure. PLoS One. 2014;9(5):e97563.
6. Masa JF, Celli BR, Riesco JA, et al. The obesity hypoventilation syndrome can be treated with
noninvasive mechanical ventilation. Chest. 2001;119(4):1102–7.
7. Perez de Llano LA, Golpe R, Piquer MO, et al. Short-term and long-term effects of nasal inter-
mittent positive pressure ventilation in patients with obesity-hypoventilation syndrome. Chest.
2005;128(2):587–94.
8. Heinemann F, Budweiser S, Dobroschke J, et al. Non-invasive positive pressure ventilation
improves lung volumes in obesity hypoventilation syndrome. Respir Med. 2007;101(6):1229–35.
9. Borel JC, Tamisier R, Gonzalez-Bermejo J, et al. Noninvasive ventilation in mild obesity
hypoventilation syndrome: a randomized controlled trial. Chest. 2012;141(3):692–702.
High-Flow Nasal Cannula Therapy:
Principles and Potential Use in Obese 23
Patients
Emmanuel Besnier, Jean-Pierre Frat,
and Christophe Girault
Oxygen therapy is probably one of the most frequent treatments administrated in

hospital setting. Its main goal is to correct or prevent the occurrence of hypoxemia,
potentially provider of cellular or tissue hypoxia. A large panel of devices is cur-
rently available to administer conventional oxygen therapy (COT) using various
interfaces and/or flows. However, some cases can catch out its use, and some major
disadvantages can limit the expected benefits. Since few years, a new technique of
oxygen therapy has been developed as an alternative to COT, the high-flow nasal
cannula (HFNC) oxygen therapy. The HFNC consists of an air/oxygen blender con-
nected via an active heated humidifier to specific nasal cannula and allows adjust-
ment of the inspired fraction of oxygen (FIO2: 21–100%) independently from the
gas mixture flow rate (up to 70 L/min in adults).
In this chapter, we will discuss on the main limits of COT before focusing on the
principles of HFNC and its potential interest in adult obese patients.
E. Besnier, M.D.
Department of Anesthesia and Critical Care, Charles Nicolle University Hospital,
Rouen University, 76031 Rouen Cedex, France
J.-P. Frat, M.D.
Department of Medical Intensive Care, Poitiers University Hospital,
Poitiers University, 86021 Poitiers, France
INSERM, CIC-1402, 5 ALIVE Team, Poitiers University, 86021 Poitiers, France
C. Girault, M.D. (*)
Department of Medical Intensive Care, Charles Nicolle University Hospital,
Rouen University, 76031 Rouen Cedex, France
UPRES EA 3830-IRIB, Institute for Biomedical Research and Innovation, Rouen University,
76031 Rouen Cedex, France
Service de Réanimation Médicale, Hôpital Charles Nicolle, Centre Hospitalier Universitaire-
Hôpitaux de Rouen, 1, rue de Germont, 76031 Rouen Cedex, France
e-mail: Christophe.Girault@chu-rouen.fr

216 E. Besnier et al.
23.1 Conventional Oxygen Therapy
23.1.1 Rational for Using Oxygen Therapy
Normal composition of room air is approximately 21% of oxygen and 79% of

diazote with an insignificant proportion of CO2. This proportion of oxygen is suffi-
cient in current life situations but may be faulted in some pathological conditions,
leading to a decrease in arterial concentration of oxygen, itself potentially provider
of tissue hypoxia and possible subsequent complications on organ functions and
prognosis. Indeed, Bowton et al. [1] identified that the occurrence of at least one
episode of hypoxemia during hospitalization in medical patients was strongly asso-
ciated with an increased risk of mortality within the 6 following months (RR 3.3
[1.41–8.2]) [1]. Oxygen therapy is consequently indicated in all situations with
potential or existing hypoxemia in order to enhance arterial concentration of oxygen
and therefore to optimize its transport to tissues. Current guidelines recommend a
sufficient flow to obtain a transcutaneous oxygen arterial saturation (SpO2) com-
prised between 94 and 98% in acute respiratory failure (ARF) [2]. In order to
achieve this objective, multiple interfaces are currently available allowing different
flows of oxygen. Usually for COT, we distinguish low flows (<6 L/min) and high
flows (> 6–15 L/min) of oxygen. The low-flow COT can be achieved through simple
nasal prongs, whereas high-flow COT can be obtained thanks to non-rebreathing
face masks with or without reservoir bags or Venturi device enhancing their
efficacy.
23.1.2 Main Limits of Conventional Oxygen Therapy
23.1.2.1 Dilution of FiO2

The aim of oxygen administration is to raise the FiO2 in order to increase the pres-
sure gradient between alveoli and pulmonary capillaries. Nevertheless, the actual
FiO2 delivered to alveoli depends on the patient’s breathing pattern, peak inspira-
tory flow rate (PIFR), delivery system, and mask characteristics [3]. Moreover,
patients with ARF often have high PIFR that substantially exceed the flow rates of
COT delivery devices [3]. Consequently, the inadequacy between needs and oxy-
gen delivery can induce a dilution of FiO2 with COT. For example, a patient pre-
senting with ARF may generate a peak inspiratory flow of 40 L/min or more.
Whether he is treated with 8 L/min of COT through facemask, this flow will not
cover the PIFR, and, consequently, 32 L/min of the remaining gas mixture will be
taken from the entrained room air, leading to a dilution of FiO2 down to approxi-
mately 35% [3]. The decrease in expected alveolar concentration of oxygen can
be therefore highly deleterious in most severe patient, notably during ARF, with
exaggerated work of breathing, increased oxygen consumption, and hypoxemia.
23.1.2.2 Humidification and Heating of Inspired Gases

The important vascularization of upper airways, particularly in the nasopharyngeal
space, increases the temperature and water content of inspired gases [4, 5]. Indeed,
23 High-Flow Nasal Cannula Therapy: Principles and Potential Use in Obese Patients 217
ambient air usually presents a relative humidity of 50%, corresponding to 10 mg H2O/L
at 22 °C. Inspired gases are progressively warmed and water saturated along airways
until the temperature and water gradients become null between the airways and the
blood content. This equilibrium point is called the isothermic saturation boundary and
usually obtained between the third and the fifth bronchial subdivision. Beneath this
point, a 37 °C temperature with a water content of 44 mg H2O/L (absolute humidity) is
observed. Conversely, expired gases cool down all along the airways and thus produce
condensation. The evaporated water is incorporated into the mucosa allowing an opti-
mal fluidity for the mucociliary function. In front of these features, inspiration of a dry
and cold gas mixture can induce a desiccation of mucosa with elevated viscosity and
potentially an alteration of ciliary movement, a perturbed clearance of bronchial secre-
tions and then the formation of bronchial clots and atelectasis. Moreover, the inhalation
of cold and/or dry gases can lead to a rise in airways resistance mediated through ther-
mic or osmoreceptors located in the nasopharyngeal cavity [6].
Because of all these physiological points, humidification and heating of gas mix-
ture appear to be beneficial for oxygen therapy. Most frequently, COT is adminis-
trated directly from oxygen reservoir through piping connected to a wall outlet. The
gas mixture is dry and cold with a 15–20 °C temperature and thus can induce inju-
ries in mucociliary function. Humidification of inspired gases is strongly recom-
mended for flow above 4 L/min to limit the drying of mucosa [3]. A usual device for
COT humidification is the bubble humidifier where oxygen flow bullheads and
becomes saturated with non-heated water. In these conditions, unfortunately,
humidification turns of poor quality with an absolute water content of 13 mg/L at
15 °C, corresponding to a relative humidity of only 29% at 37 °C. In addition, this
low yield worsens with increasing flow. Conversely, heated humidifiers provide a
flow of oxygen warmed in a specific chamber filled of water. Their use has been
demonstrated to improve respiratory comfort in patients treated with COT of at least
5 L/min, reducing mouth and throat dryness [7]. Moreover, a recent animal study
showed that humidification and heating at 40 °C in mechanically ventilated rabbits
could reduce pulmonary inflammation and preserve ciliary integrity [8]. All these
data strongly argue, therefore, for an optimal conditioning of inspired gases by heat-
ing and humidification during oxygen therapy.
23.2 High-Flow Nasal Cannula Oxygen Therapy
23.2.1 Technical Characteristics
HFNC has been developed as an alternative to COT, notably in specific setting such
as ICU or neonatology. Thanks to a high-flow generator, HFNC can deliver an oxy-
gen flow up to 70 L/min (and even more in some recent ICU ventilators) with a
controlled FiO2 ranging from 21 to 100%. It is working in association with a sepa-
rated humidification-heating chamber to provide an optimized conditioning of
inspired gases. The gas mixture is conveyed through a single-branch system to a
simple nasal cannula interface (Fig. 23.1). Because of these high-quality perfor-
mances, several benefits can be expected, therefore, from the HFNC use.
Flowmeter
(Fisher & Paykel©)
Respiratory circuit
(Evaqua™,Fisher & Paykel©)
Humidification device
(MR850™, Fisher & Paykel©)
HFNC : highflow nasal cannula
Fig. 23.1 HFNC device (Optiflow™, Fisher & Paykel©)

23.2.2 Main Advantages of HFNC
23.2.2.1 Reduction in FiO2 Dilution

As stated above, patients with ARF often generate a high PIFR, exceeding, most of
the time, the capacity of COT delivery devices [3]. The high flow generated by
HFNC is most often able to cover this increased PIFR, limiting room air entrain-
ment and mixing of inspired gases, avoiding thus a reduction in delivered FiO2 [9,
10]. In addition, this better performance of HFNC can be maximal with closed-
mouth breathing as compared to open-mouth breathing [9, 10].
23.2.2.2 PEEP and PIP Effects

The use of a sufficient gas flow can generate a low to moderate level of positive end-
expiratory pressure (PEEP) in the pharyngeal space. Indeed, PEEP recorded in pharyn-
geal space has been shown to be comprised between 3 and 7 cm H2O [10–12] and
directly correlated to the magnitude of the flow applied with a 0.6 cmH2O increase every
10 L/min of flow [10]. Best results were observed for nasal closed-mouth breathing as
compared to open-mouth breathing which reduced by twofold the pharyngeal PEEP
effect. These results were first demonstrated on healthy volunteers [11], but also subse-
quently in patients after cardiac surgery [12], with chronic obstructive pulmonary dis-
ease (COPD) or fibrosis [13], suggesting new perspectives in such pathologic conditions.
Moreover, a close relationship has been demonstrated between oropharyngeal pressures
induced by HFNC and the end-expiratory lung volume, suggesting that HFNC can gen-
erate a mild PEEP effect in distal airways, responsible for alveolar recruitment [14].
Nevertheless, the efficiency of HFNC to generate a PEEP effect depends not only on the
mouth closure but also on the leakage around nasal cannula, requiring a special attention
in the choice of cannula size, designed to fit with nostril diameters [15]. In addition, the
PEEP effect may depends, in part, on the gender with higher levels for female, as well
as on the height with a small decrease every 10 cm [11].
Moreover, a small positive inspiratory pressure (PIP) could be observed regard-
less of the mouth opening. This pressure has been shown to be low, less than
3 cm H2O despite a 50 L/min of gas flow but could be somewhat helpful in provid-
ing little inspiratory assistance [11, 12]. However, this PIP effect appears small, and
inspiratory assistance provided is far from being compared with noninvasive
ventilation (NIV).
23.2.2.3 Humidification and Heating of Gas Mixture

The presence within the circuit of a device specifically dedicated to humidification
and warming improves the conditioning of inspired gases, resulting in a 100% of
water saturated mixture at a 37 °C temperature. Because dry gas induces an early
alteration of mucus and bronchial epithelium functions, an optimized humidifica-
tion could protect mucociliary function and fluidity, facilitate clearance of mucus
and therefore local host defense, and limit the bronchial resistance to flow. Indeed,
high-quality humidification at 37 °C has been demonstrated to improve mucosal
clearance of patients with bronchiectasis [16] and to reduce inflammatory stress
during mechanical ventilation [8]. Thus, its use through HFNC could be helpful
during acute pulmonary inflammation, especially during pneumonia, as well as in

patients with altered mucosal secretion such as COPD.
Moreover, heated humidifiers have been demonstrated to reduce the intensity of
throat and mouth dryness and improve global comfort in ICU patients [7, 17].
23.2.2.4 Dead Space Washout

Due to the high-flow use of fresh gases, HFNC has been suggested to decrease the
re-inhalation of exhaled CO2 by flushing the upper airways gases and, thus, a part of
the airway dead space [18, 19]. Consequently, no change or even an improvement in
PaCO2 and/or pH may be expected with the use of HFNC. In an experimental model
of acute lung injury, HFNC reduced PaCO2 in a flow dependent manner with a con-
comitant rise in PaO2 [20]. In a recent report, a COPD patient intolerant to noninvasive
ventilation (NIV) with acute hypercapnic exacerbation exhibited a decrease in respira-
tory symptoms and PaCO2 with HFNC therapy [21]. Also, a retrospective analysis of
46 patients with hypercapnic respiratory failure observed a small (−6 mmHg) but
significant reduction in PaCO2 after 24 h of HFNC therapy [22]. Another study,
including “do-not intubate” patients with ARF and a moderate respiratory acidosis
(pH > 7.28 and PaCO2 < 65 mmHg), reported that the use of HFNC did not result in a
rise of PaCO2 over time and even a trend toward reduction [23]. In an open-labeled
prospective trial, HFNC use for hypoxemia after cardiac surgery was associated with
a better oxygenation and a mild reduction in PaCO2 levels (−3 mmHg) during the first
24 h [24]. All these data represent strong arguments for a CO2 washout effect and sug-
gest a potential benefit of HFNC in cases of hypercapnia, such as in exacerbation of
COPD or obese patient with restrictive or overlap syndrome.
23.2.3 Indications of HFNC
23.2.3.1 Hypoxemic Acute Respiratory Failure

HFNC has now been extensively used in hypoxemic ARF patients because of all its
beneficial features exposed previously. First clinical observational studies dealt
mainly with the efficacy and feasibility of HFNC in hypoxemic ARF. HFNC has
been shown to rapidly improve comfort, tolerance, respiratory rate, symptoms of
distress, and oxygenation in ICU [25] and emergency department [26] patients.
HFNC could also be used sequentially with NIV in ARF to avoid alveolar de-
recruitment and impairment in oxygenation during spontaneous breathing period,
with a better tolerance than NIV [27]. In a multicenter randomized trial, Frat et al.
[28] have compared facemask COT, HFNC alone, and NIV with HFNC in 310
medical patients with hypoxemic ARF. HFNC alone was found a better strategy to
decrease intubation rate and mortality in more hypoxemic patients (PaO2/FiO2
ratio ≤ 200 mmHg). Consequently, NIV was considered as potentially deleterious
by delivering a higher expired tidal volume (>9 mL/kg) than expected, increasing
thus the risk of intubation and mortality. A recent post hoc analysis of immunocom-
promised patients included in the previous trial has confirmed these results [29].
These findings were also suggested in a randomized controlled trial involving only
immunocompromised patients and comparing NIV with oxygen support including

HFNC [30]. Finally, based on the positive results of HFNC in hypoxemic ARF, ICU
clinician should certainly be cautious with the use of NIV in this indication.
23.2.3.2 Postoperative Period

Major surgery exposes to numerous postoperative complications including pain,
diaphragmatic dysfunction, atelectasis, and impaired oxygenation requiring to be
prevented at the best [31]. Thus, the prophylactic and curative use of continuous
positive airway pressure (CPAP) or NIV has been demonstrated to improve oxygen-
ation and outcomes after major thoracic, abdominal, or cardiac surgeries [32–35].
Like CPAP or NIV, HFNC could be a simpler technique in preventing or treating
postoperative ARF. Parke et al. [36] randomized 60 patients with moderate hypox-
emic ARF after cardiac surgery to receive either HFNC or COT with facemask.
HFNC was associated with less need for NIV and fewer desaturations. In another
multicenter randomized controlled trial, Stephan et al. [37] did not show any differ-
ence between NIV and HFNC applied to 810 patients presenting ARF (or at risk of
ARF) after cardiac surgery, suggesting that HFNC may be a valuable alternative to
NIV for postoperative ARF. Skin lesions were also reduced in HFNC group. Few
data concerning the prophylactic use of HFNC are available. Parke et al. have evalu-
ated its use in 340 patients after cardiac surgery in comparison with conventional
therapy. Despite a lack of difference regarding oxygenation, HFNC reduced the
escalation in respiratory support with less requirements for NIV or reintubation and
a small reduction in PaCO2 [38]. Thus, as demonstrated for standard ARF, strong
data support the use of HFNC during postoperative ARF. Its benefit as a prophylac-
tic strategy is suggested, but further trials are required.
Nevertheless, the use of NIV in the postoperative setting cannot be ruled out,
notably in patients at risk of atelectasis. The association of both therapies could be
complementary as the use of HFNC between NIV periods by improving oxygen-
ation could also limit alveolar de-recruitment and enhance NIV tolerance by reduc-
ing its duration.
23.2.3.3 Post-extubation Support

Post-extubation period after prolonged invasive mechanical ventilation is at high risk
of failure in ICU patients. Reasons for this unsuccessful weaning are numerous: air-
way obstruction, excess of respiratory secretions, insufficient cough, pneumonia,
heart failure, or comatose status. NIV has been proposed with success for patients at
high risk of reintubation [39, 40]. Some recent studies explored the use of HFNC in
such situations. Maggiore et al. [41] applied HNFC or Venturi mask to 105 patients
with a 240 mmHg PaO2/FiO2 ratio just before extubation. HFNC was associated with
a better oxygenation and comfort, a reduction in mask displacements and therefore
in desaturation events, and a fewer cases of reintubation. Similarly, Hernandez et al.
[42] showed that HFNC after extubation in ICU patients at low risk of extubation
failure strongly decreases the reintubation rate within 72 h. Nevertheless, no study
has compared yet HFNC and NIV during post-extubation period, and further clinical
trials should be designed to define the respective indication of each device.
23.2.3.4 Preoxygenation Before Endotracheal Intubation

Endotracheal intubation is a potential high-risk situation of desaturation, hypox-
emia, and even mortality, particularly in ICU patients. NIV has been proposed as an
alternative technique to non-rebreathing facemask (NRFM) to prevent the risk of
severe hypoxemia during ETI. As compared to NRFM, NIV has been shown to
optimize preoxygenation and reduce per-procedure desaturation in severe hypox-
emic ARF patients [43], as well as in obese patients [44]. However, to perform
laryngoscopy, NIV needs to be interrupted leading to the absence of oxygenation
during the apneic phase of ETI, and thus, to the potential occurrence of severe desat-
uration. Two recent studies explored the use of HFNC as a preoxygenation tech-
nique with contradictory results. The first one from Miguel-Montanes et al. [45]
compared a before period (NRFM) with an after period (HFNC) with a reduction in
severe hypoxemia per-procedure in a non-selected ICU population. The second one
was a randomized clinical trial and did not identify any difference between the two
groups concerning severe desaturation [46]. Nevertheless, the absence of difference
in this later could be related to a possible technical bias like the absence of mandibu-
lar subluxation during the preoxygenation procedure. More recently, an observa-
tional study has compared the use of HFNC versus NIV for preoxygenation in
non-selected ICU patients [47]. No difference was observed regarding severe desat-
uration or complications during the procedure, suggesting that HFNC could be a
simpler alternative than NIV for preoxygenation. Currently, a French multicenter
randomized clinical trial is ongoing to explore the respective role of these two strat-
egies in this indication.
23.3 HFNC Therapy in Obese Patients
Obese patients exhibit many physiological modifications related to the excess of

adipose tissue. Some of them may impact the respiratory function and deserve com-
ments [48]. First, patients have an increased overall oxygen consumption leading to
a rise in minute ventilation and, therefore, in the work of breathing, with enhanced
production of CO2. Second, a restrictive syndrome is observed with a reduction in
pulmonary volumes, inversely correlated with the body mass index (BMI). Indeed,
a diminution in functional residual capacity, end-expiratory lung volume (EELV),
expiratory reserve volume, and vital capacity is often observed and can be respon-
sible for atelectasis in obesity hypoventilation syndrome. The reduction in lung vol-
umes can even lead to a rise in lower airway resistances with an increased risk of
asthma and/or overlap syndrome. Moreover, adipose infiltration in pharyngeal
structures leads to a rise in upper airway resistances and, at worse, to an obstructive
sleep apnea syndrome, which can negatively affect postoperative outcomes. All
these physiological modifications can worsen prognosis and outcomes in obese
patients admitted to the ICU or during the perioperative period. Due to these obesity-
related comorbidities, the use of CPAP or NIV has been found associated with
improved oxygenation and lung volumes in morbid obese patients after bariatric
surgery [49, 50].
Fig. 23.2 High flow nasal cannula oxygen therapy via an ICU ventilator in an obese patient
Table 23.1 Potential physiological advantages of high-flow nasal cannula oxygen therapy in
obese patients
Dead space
Oxygenation PEEP effect PIP effect Heated humidification washout
Reduced room Prevention of Mild Improved respiratory Limitation of
air oropharyngeal inspiratory comfort respiratory
entrainment collapse support Preserved mucociliary acidosis and
Controlled Alveolar Decrease in functiona PaCO2
FiO2 recruitment with the work of Limitation of dry increase
Improved increased EELV breathing gas-induced
oxygenation Prevention of bronchoconstrictiona
atelectasis
a
Theorical effects with no clinical demonstration as yet
PEEP positive end-expiratory pressure, PIP positive inspiratory pressure, COPD chronic obstruc-
tive pulmonary disease, EELV end-expiratory lung volume
As discussed above, HFNC exhibits physiological effects which could be of ben-

efit in obese patients (Fig. 23.2): the high flow of oxygen can cover the high minute
ventilation and the enhanced oxygen consumption; the moderate PEEP effect may
prevent the occurrence of atelectasis and collapse of upper airways, especially in
patients with underlying obstructive sleep apnea syndrome; the mild PIP may provide
ventilator support; the dead space washout may reduce PaCO2; and the humidification
of inspired gases could prevent reduction in inferior airways caliber as compared to
COT. These potential benefits of HFNC in obese patients are resumed in Table 23.1.
Unfortunately, although numerous studies have included some obese patients,
only few studies have specifically explored the reality of these physiological effects
as well as the clinical use of HFNC in this particular population. A crossover study
has evaluated the effects of COT and HFNC on pulmonary function after cardiac
surgery in obese patients [14]. HFNC increased the EELV and tidal volume in com-
parison with COT. Benefits were particularly marked for higher BMI, with a 13.3%
mean increase of EELV for BMI of 25 kg/m2 and a 24.4% mean increase for BMI
of 40 kg/m2 [14]. The same team recently compared HFNC with COT as a prophy-
lactic strategy after cardiac surgery. One hundred and fifty-five obese patients were
randomized but, surprisingly, no difference in the atelectasis score, PaO2/FiO2 ratio
or respiratory rate was observed between both strategies [51]. Nevertheless, some
study limitations have to be underlined: the small number of patients included as
regard to the frequency of respiratory complications in this population, the duration
of HFNC use limited to 8 h post-extubation, and the small proportion of morbid
obese patients (mean BMI of 35 and 36 kg/m2). Moreover, the choice of HFNC as
compared to NIV as a prophylactic therapy could be questionable. Indeed, NIV has
been demonstrated to be superior to CPAP in preventing atelectasis after major sur-
gery [52]. As HFNC represents, from a physiological point of view, a respiratory
support closer to CPAP than NIV, its use can logically be expected as inferior to
NIV to prevent ARF in obese patients. As yet, no study has specifically explored the
use of HFNC in obese patients with hypoxemic or hypercapnic ARF and in the post-
extubation period. Further studies are warranted therefore in these indications.
Meanwhile, the use of HFNC as an alternative to NIV in case of patient intolerance
or refusal could be considered in these settings. Moreover, alternate HFNC periods
with NIV27 could be considered as a promising strategy in this specific population.
Another field of interest for HFNC could be the preoxygenation for intubation in
obese patients. Indeed, airway management of these patients is frequently difficult
with a higher risk of complications and hypoxemia [53]. A recent randomized study
has evaluated preoxygenation with COT, CPAP, or HFNC in 33 morbidly obese
patients [54]. A higher PaO2 was reported with HFNC, but neither the apnea dura-
tion without desaturation nor the occurrence of atelectasis was evaluated. In addi-
tion, the role of HFNC as a potential alternative to NIV preoxygenation in obese
patients remains to be demonstrated [44].
In conclusion, HFNC oxygen therapy is a recent technique with potential bene-
fits on morbidity and mortality in ICU patients. Its use in obese patients remains
poorly investigated but could theoretically and potentially improve physiological
parameters and patient outcome. Before implementing HFNC in the routine man-
agement of obese patients, further studies are obviously needed. Clinicians should
also keep in mind that NIV remains an efficient respiratory support in these patients
in numerous indications. In addition, like NIV, HFNC should never delay the intu-
bation time whatever its indication since its unreasonable use can dramatically
worsen the patient prognosis [55].
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NIV in Type 2 (Hypercapnic) Acute
Respiratory Failure 24
Shaden O. Qasrawi and Ahmed S. BaHammam
24.1 Introduction
Noninvasive ventilation (NIV) refers to providing ventilatory support using a

mask or a similar device without the use of invasive artificial airway (endotra-
cheal tube or tracheostomy tube). The use of NIV has markedly increased in the
recent years and is currently considered to be essential in the management of
acute respiratory failure and in particular acute hypercapnic respiratory failure
(AHRF) [1, 2].
AHRF results from inadequate alveolar ventilation, which is needed to maintain
normal arterial oxygen and carbon dioxide levels [3]. Conventionally, pH <7.35 and
arterial partial pressure of carbon dioxide (PaCO2) >6.5 kPa (>50 mmHg) define
acute respiratory acidemia and AHRF [3]. In general, if AHRF persists despite ini-
tial medical therapy, those values have been used as a threshold for considering
commencing NIV [3]. AHRF could complicate many respiratory disorders includ-
ing chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis, bron-
chiectasis, and neuromuscular and chest wall diseases, including morbid obesity
and kyphoscoliosis (see Table 24.1) [3]. This section aims to discuss AHRF in obese
patients. However, as obese patients may develop AHRF secondary to several respi-
ratory disorders, we will cover briefly the utility of NIV in different respiratory
disorders that cause AHRF and then will focus on AHRF in patients with obesity
hypoventilation syndrome (OHS).
S.O. Qasrawi, M.B.B.S., M.R.C.P. • A.S. BaHammam, M.D., F.A.C.P. (*)

University Sleep Disorders Center, College of Medicine, King Saud University,
Box 225503, Riyadh 11324, Saudi Arabia
e-mail: ashammam2@gmail.com; ashammam@ksu.edu.sa

230 S.O. Qasrawi and A.S. BaHammam
Table 24.1 Causes of hypercapnic respiratory failure

• Chronic obstructive pulmonary disease (COPD)
• Acute severe asthma
• Bronchiectasis
• Cystic fibrosis
• Obstructive sleep apnea
• Kyphoscoliosis
• Morbid obesity
• Opioid and sedative drugs
• Neuromuscular diseases (e.g., cervical cord lesions, Guillain–Barré syndrome, myasthenia
gravis, muscular dystrophy)
24.2 Indications and Contraindications to NIV in AHRF
The indications for NIV are variable based on the underlying cause, its severity, and
the associated comorbidities. Clinical manifestations that support the early use of
NIV include moderate to severe dyspnea, tachypnea (>24 breaths per min in obstruc-
tive lung diseases, >30 per min in restrictive lung diseases), and signs suggestive of
increased work of breathing including accessory muscle use and thoracoabdominal
paradox [4]. Other indications are usually based on investigations showing impaired
gas exchange reflecting acute or acute on chronic ventilatory failure with raised
PaCO2 and acidemia [5, 6]. Table 24.2 summarizes the indications and contraindica-
tion to NIV. Application of NIV could be difficult in patients with severe facial
deformity, fixed upper airway obstruction, or facial burns [4]. There are a number of
other potential contraindications; however, most of those have been employed as
exclusion criteria in clinical trials rather than being proven to be associated with
worse outcome [3, 7].
24.3 Chronic Obstructive Lung Disease (COPD)
Acute exacerbations of COPD account for a significant number of annual admis-

sions worldwide [8]. Of these, many present with hypercapnia [9], which increases
the risk of mortality [10, 11]. Developing AHRF in COPD is usually multifactorial
with many underlying causes such as infection, mucosal edema, bronchospasm,
sputum retention, sedation, pneumothorax, pulmonary embolism, left ventricular
failure, and excessive oxygen therapy. There is now strong evidence showing that
uncontrolled oxygen therapy increases acidemia and subsequently mortality in
acute exacerbations of COPD (AECOPD) [10]. This oxygen-induced hypercapnia
applies with variable degree, to other causes of AHRF [3]. Hence, in managing all
patients at a risk for AHRF, controlled oxygen therapy with oxygen saturation target
of 88–92% is recommended initially [3].
24 NIV in Type 2 (Hypercapnic) Acute Respiratory Failure 231
Table 24.2 Indications and Indications

contraindications for NIV Clinical manifestations
• Moderate to severe dyspnea
• Tachypnea (>24 bpm in obstructive, >30 bpm in
restrictive)
• Signs of increased work of breathing (e.g., accessory
muscle use and abdominal paradox)
Gas exchange
• Acute or acute on chronic ventilatory failure
(PaCO2 > 6.5, kPa, pH < 7.35)
• Hypoxemia
Contraindicationsa
• Respiratory or cardiac arrest
• Inability to fit the mask (e.g., severe facial deformity
or facial burns)
• Fixed upper airway obstruction
• Hypotensive shock
• Uncontrolled upper gastrointestinal bleeding
• Agitation/confusion
• Inability to protect the upper airway
• Swallowing impairment
• Excessive secretions not managed by secretion
clearance techniques
• Multiple (i.e., two or more) organ failure
• Recent upper airway or upper gastrointestinal surgery
Some are relative contraindications
a
The use of NIV in AECOPD has increased markedly, and its use is currently
viewed as a part of the standard therapy for patients who have persistent respiratory
acidemia despite receiving standard medical therapy [12, 13]. The use of NIV in
AECOPD has reduced the need for IMV, thereby reducing complications and cut-
ting hospital costs associated with IMV, in addition to improving survival [13].
Hence, NIV is currently considered as a major progress in the management of
AECOPD [13].
Severe acidemia alone is not a contraindication for NIV trial in an appropriately
equipped setting where shifting the patient to IMV can be rapidly achieved.
Nevertheless, the use of NIV should not delay commencing IMV when needed [3].
The treating team should keep in mind other possible causes of AHRF that may
coexist with COPD such as obstructive sleep apnea (OSA) and OHS [3, 14]. Obese
patients with COPD may have coexisting sleep-disordered breathing, which is
called overlap syndrome. For patients with overlap syndrome, NIV should aim to
correct both hypoventilation and upper airway obstruction.
An improvement in physiological parameters such as pH and respiratory rate
within 1–2 h of initiating treatment is usually a predictor of success of NIV, whereas
Table 24.3 Predictors for Predictors for NIV success/failure in AHRF in COPD
NIV success/failure in Predictors for treatment success
patients with COPD
pH 7.25–7.35, PaCO2 > 6.5 kPa
exacerbation and AHRF
GCS > 14
Respiratory rate 24–30/min
Response to NIV within 1–2 h
APACHE II < 29
Predictors for treatment failure
pH <7.25
GCS ≤ 11
Respiratory rate > 30/min
Additional pneumonia
Severe mask leakage
Patient-ventilator asynchrony
Agitation or intolerance
Inability to clear secretions
APACHE II >29
worsening of those parameters is predictive of failure of NIV with increased risk for
intubation or mortality [3]. Table 24.3 shows the predictors of NIV success in
patients with COPD exacerbation and AHRF [3, 15–20].
Monitoring of PaCO2 serves as a useful guide in planning the withdrawal of NIV,
and transcutaneous PaCO2 measurement serves as a convenient alternative to arte-
rial or capillary sampling [3].
24.4 Acute Exacerbation of Asthma
Patients with acute attack of asthma present usually with hypoxemic respiratory
failure. However, in advanced cases, patients may present with AHRF. Nevertheless,
the use of NIV in acute exacerbation of asthma remains a controversial topic, and
reports of NIV use in patients with severe acute asthma are limited. A few RCTs
have explored the utility of NIV in hypoxemic respiratory failure in patients with
acute exacerbation of asthma [21]. However, the existing evidence is equivocal
and limited by a small number of published trials with methodological problems
[21]. Moreover, at present, there is no strong evidence to support NIV use in asth-
matics with AHRF. The two studies reporting clear beneficial effect of NIV use in
AHRF asthma were retrospective studies with methodological limitations [22,
23]. One of them included population who seem more likely a COPD than asth-
matic population [24]. At present, there is limited evidence to recommend the use
of NIV in patients with asthma exacerbation and respiratory failure. Larger, pro-
spective RCTs of properly selected patients and a good methodological design are
needed.
24.5 Non-CF Bronchiectasis
Patients who suffer from non-CF bronchiectasis can present with recurrent episodes
of hypercapnic respiratory failure [3]. Despite little data, there is no evidence that
patients with non-CF bronchiectasis presenting with AHRF do worse on NIV com-
pared to those commenced on IMV [25]. Therefore, NIV is indicated in the pres-
ence of respiratory acidemia using the same criteria applicable in AECOPD [3]. It
is not unusual to find sleep-disordered breathing in obese patients with bronchiecta-
sis [26]. Such patients should be managed with NIV to improve ventilation and
eliminate the obstructive events during sleep.
Although managing and clearing excessive sputum while on NIV can be chal-
lenging, NIV could actually assist by improving dyspnea and hence help patients to
participate more effectively in physiotherapy [27].
24.6 Extrapulmonary Restrictive Lung Diseases
Severe chest wall deformity and neuromuscular diseases (NMD) can markedly
impair the respiratory muscles function and hence result in a restrictive lung func-
tion pattern characterized by reduced vital capacity (VC), total lung capacity, and
functional residual capacity, which in turn can lead to AHRF [28]. Such patients
will usually present with chronic hypercapnia and acute respiratory failure that is
commonly precipitated by infection [28]. The risk of hypercapnic respiratory failure
increases when the VC falls below 1–1.5 L [29]. Obese patients with neuromuscular
diseases are at an increased risk for sleep-disordered breathing, and those with bul-
bar dysfunction are at a higher risk for OSA [30].There are no available RCTs
comparing NIV with IMV in the management of AHRF complicating extrapulmo-
nary restrictive lung diseases, and the current recommendations are extended from
the evidence available for AECOPD management [3, 28]. Generally, NIV should be
tried in patients presenting with hypercapnia without waiting for the development of
acidemia, but if NIV fails, intubation should not be delayed unless IMV is not
desired for whatever valid reason. In patients with NMD with bulbar dysfunction
and communication difficulties, NIV is usually difficult. Moreover, patients with
bulbar dysfunction have an increased risk of aspiration. In general, patients with
NMD and chest wall deformities need an overnight sleep study once stable and
might require nocturnal NIV at home [3].
24.7 Obesity Hypoventilation Syndrome (OHS)
Hypercapnia in hospitalized obese patients is associated with increased morbidity

and mortality [31]. OHS is generally underdiagnosed and undertreated [32]. It is
also not uncommon for chronic hypercapnia to be discovered when obese patients
who are otherwise not known to have OHS are assessed for emergency or elective
operations. However, patients with OHS commonly present with acute on top of
chronic hypercapnic respiratory failure [33]. A recent study has shown that approxi-
mately 40% of patients with OHS present for the first time with AHRF [34].
Additionally, OHS patients admitted with AHRF have a high rate of in-hospital
mortality (18%) [35]. Therefore, it is important to keep in mind the possibility of
OHS as a cause of AHRF in the morbidly obese patients.
OHS is the second most frequent indication (after COPD) for NIV treatment
among hospitalized patients with AHRF [36, 37]. It is recommended to initiate NIV
in all patients suspected of having AHRF secondary to OHS, before performing
sleep study, since early initiation of NIV may obviate the need for IMV [2].
Nevertheless, there is no enough evidence to provide a guidance for the use of NIV
in the treatment of both chronic hypercapnia and AHRF in obese patients [2]. The
majority of patients with OHS have coexisting severe OSA [38]. In general, NIV
will be needed as an emergency treatment in all patients with OHS presenting with
AHRF [2]. In addition, NIV can be considered in admitted patients with raised
PaCO2 and excessive daytime sleepiness, sleep-disordered breathing, and/or right
heart failure even when acidemia is absent [39].
Pressure- and volume-limited ventilation have been reported in patients with
AHRF; however, we recommend initiating treatment with bi-level PAP (BPAP)
ventilation as there is no evidence indicating that other ventilatory modes are supe-
rior to BPAP [2]. During NIV therapy, observation and monitoring of the level of
consciousness, vital signs, respiratory pattern, oxygen saturation, and arterial blood
gases are crucial [2, 40]. As most patients with OHS have coexisting OSA, EPAP
should be increased gradually until snoring, witnessed apneas, and dips in oxygen
saturation are eliminated. IPAP should be gradually increased to ensure optimal
ventilation until an acceptable level of steady-state oxygen saturation (≥ 90%) is
attained [33]. Figure 24.1 shows a proposed algorithm for the NIV management of
OHS patients with AHRF [2].
In patients who do not respond to BPAP mode, volume-targeted pressure support
(VtPS) can be attempted [41]. VtPS is a hybrid mode that combines the advantages
of pressure-limited and volume-limited modes of ventilation into one ventilation
mode. Studies concerning the use of volume-targeted pressure support mode to treat
OHS patients did not show clinical benefits over those achieved with a fixed bi-level
mode [41]. Moreover, VtPS mode has not directly been assessed in OHS during
AHRF.
Limited studies have assessed the predictors of NIV failure in OHS patients with
acute respiratory failure. Lemyze et al. demonstrated in a prospective study (n = 76)
that severe pneumonia and multiple organ failure predict early NIV failure in mor-
bidly obese patients with acute respiratory failure [42]. The same study reported
that more than half of the patients experienced a delayed response to NIV, with
persistence of hypercapnic acidemia during the first 6 h [42].
Once the patient is stable, it is recommended to perform a sleep study for patients
with OHS to choose the right ventilatory mode and pressure needed to eliminate the
obstructive respiratory events and hypoventilation. All patients with OHS will
Obese patient with AHRF
No contra-indications to NIV
Start Bi-level PAP
EPAP IPAP
o Start with 4-6 cmH2O o Start with 8-10 cmH2O
o Build-up pressure up by o Build-up pressure up by
1-2 cm H2O to eliminate: 1-2 cm H2O until:
Snoring Steady SpO2>88%
Witnessed apneas To achieve good alveolar
Paradoxical breathing ventilation IPAP is kept
Intermittent hypoxemia 8-10 cm H2O above EPAP
Monitor the following

Vital signs, level of consciousness, respiratory pattern, SpO2, minute
ventilation, blood gases (after 1 hr)
Add oxygen, if the patient continues to desaturate (<88%) despite

delivering high positive airway pressure
Consider intubation if the NIV trail fails
Fig. 24.1 A proposed algorithm for the NIV management of OHS patients with AHRF
eventually need NIV use at home. Studies that followed OHS patients with AHRF
after discharge indicated higher mortality in patients who refused PAP therapy [33,
40]. Several studies have reported that good compliance with domiciliary NIV
results in improvement in gas exchange, daytime sleepiness, quality of life, and
number of hospitalizations in patients with OHS [43].
Conclusion
Obesity represents a global epidemic, and obese patients are at a higher risk for
developing AHRF. Practitioners should recognize that morbidly obese patients
with sleep hypoventilation, daytime hypercapnia, and pulmonary hypertension
have an increased risk of AHRF. NIV is currently an accepted therapeutic
s trategy in several disorders that can be complicated by respiratory failure and

in particular AHRF. The use of NIV in obese patients with AHRF helps to pre-
vent further deterioration and avert the need for IMV. When NIV is imple-
mented, clear treatment goals should be defined, and a plan of care should
document escalation measures in the event of failure of NIV. Although NIV is
considered now as a great progress in managing respiratory failure, it should not
delay intubation and IMV in those patients who fail to respond to NIV or in
whom NIV is not indicated.
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Prevention of Post-extubation Failure
in Critically Ill Obese Patient 25
Ali A. El Solh
25.1 Background
With the rise in prevalence of obesity worldwide, clinical providers are encounter-
ing an increasing number of critically ill obese patients requiring intensive care. The
management of these patients poses significant challenges in the settings of respira-
tory failure or artificial ventilation. Observational studies of this population have
uniformly described prolonged periods of ventilatory support and length of stay in
intensive care units [1–3]. Mechanical ventilation requires specific ventilatory set-
tings due to the mechanical and physiologic alterations dictated by body habitus.
Conventional respiratory function tests have unvaryingly showed a reduction in
functional residual capacity due to the effect of abdominal contents on the dia-
phragm [4]. The buildup of adipose tissue in the anterior abdominal wall and in the
intra-abdominal visceral tissue hinders diaphragmatic movement, diminishes basal
lung expansion during inspiration, and with the closure of peripheral lung units
causes ventilation–perfusion abnormalities. These alterations are further aggravated
in the reclined or Trendelenburg position. Respiratory muscle strength is compro-
mised as the load of the extra adipose tissue poses undue burden on muscle activity
[5]. The combined effect of these changes is a tendency for hypoxemia at rest and
rapid desaturation under condition of apnea. The care of these patients is further
complicated by the observation that up to 30% of patients with morbid obesity have
obesity hypoventilation syndrome manifested by CO2 retention, pulmonary
A.A. El Solh, M.D., M.P.H.

The Veterans Affairs Western New York Healthcare System, 3495 Bailey Avenue,
Medical Research, Bldg. 20 (151) VISN02, Buffalo, NY 14215-1199, USA
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine,
State University of New York at Buffalo School of Medicine and Biomedical Sciences and
School of Public Health and Health Professions, Buffalo, NY, USA
e-mail: solh@buffalo.edu

240 A.A. El Solh
hypertension, and biventricular failure [6]. As a result, morbid obesity is associated

with extended weaning periods and an additional threat in the form of ventilator-
associated events.
Determining readiness for liberation from mechanical ventilation is of consider-
able clinical relevance for obese patients. Commonly used predictors for weaning
and successful liberation from mechanical ventilation have not shown to be reliable
parameters. This may be due to differences in the pathophysiology of weaning and
extubation readiness. While weaning failure underlines the imbalance between respi-
ratory capacity and load [7], extubation failure is impacted by extrinsic factors.
Hence, decisions regarding timing of extubation are based on thorough assessment
of respiratory and non-respiratory parameters. Prior to extubation, the usual criteria
should be met, including hemodynamic stability, satisfactory oxygen-carrying capac-
ity, normothermia, adequate respiratory rate and tidal volume, good oxygen satura-
tion, and a conscious, alert patient who is able to clear secretions, protect the airway,
and maintain airway patency. While there is no definitive evidence that the frequency
of reintubation in severely obese patients mechanical ventilation for >48 h is differ-
ent from non-obese patients, the adverse impact on outcome from failure to be liber-
ated successfully from mechanical ventilation necessitates that accurate prediction of
extubation is potentially important. The outcome for patients who tolerate extubation
is generally favorable, with hospital mortality rates below 10–15% [8, 9]. In contrast,
the mortality rate associated with extubation failure ranges from 2.5 to 10 times that
are experienced by successfully extubated patients [10, 11]. The worse prognosis has
been attributed to complications related to the act of reintubation itself, to the rise of
unfavorable events in the interval between extubation and reintubation, and to the
fact that reintubation is a surrogate for a poor prognosis. With these facts in mind, the
process used to make extubation decisions in obese critically ill needs to be reliable,
especially regarding the identification of patients at high risk for extubation failure.
25.2 Causes of Post-extubation Failure
The causes for post-extubation failure in obese patients are multifactorial in nature
(Table 25.1). The vast majority of patients do so because of an imbalance between
respiratory muscle capacity and the load placed on the respiratory system [12, 13].
High airway resistance (bronchospasm and excessive airway secretions) [14] and
low respiratory system compliance (stiff chest wall, stiff lungs, consolidated alveoli)
[15] contribute to the increased work of breathing and lead to unsuccessful liberation
from mechanical ventilation. This pathophysiologic mechanism is amplified by the
coexistence of obstructive sleep apnea (OSA) in patients with severe obesity. Patients
with OSA have relatively narrow airways and require disproportionate activation of
pharyngeal muscles during wakefulness to maintain patency [16]. Activation is
driven by a combination of influences including the wakeful state itself, ventilatory
drive, and reflex activation initiated by upper airway mechanoreceptors that respond
to intraluminal negative pressure developed during inspiration. If the patient is
obtunded from residual sedatives or anxiolytics or lingering systemic disease, there
is reduced drive to the upper airway muscles from all these sources.
25 Prevention of Post-extubation Failure in Critically Ill Obese Patient 241
Table 25.1 Risk factors for extubation failure in obese patients

Risk factor Pre-extubation test
Increased secretions • A sawtooth pattern on the flow volume curve
• Frequency of suctioning (every 2 h or less)
Poor cough strength • Placing a white card at 1–2 cm from the end of endotracheal tube.
Any wetness on the card is classified as a positive test
• A peak expiratory flow (PEF) rate during a cough of <35 L/min
Upper airway • Cuff-leak test
edema • Visual assessment via indirect laryngoscopy
Vocal cord paralysis • Cuff-leak test
Respiratory failure • Noninvasive positive pressure ventilation
Cardiac failure • Diuresis and/or vasodilator therapy
Neurologic • Correction of metabolic derangements
impairment • Noise control
• Restoration of sleep cycle
25.2.1 Secretions and Cough
In the absence of other causes of airway obstruction, upper airway patency relies on
the ability to maintain the airway clear of secretions, owing to a balance between
cough strength and amount and thickness of respiratory secretions irrespective of
body weight. Cough strength has been found to be a more reliable predictor of extu-
bation outcome than the amount of endotracheal secretions. One study showed that
patients who were unable to cough on command or who had a peak expiratory flow
(PEF) rate during a cough of <35 L/min had a relative risk of 6.9 for extubation
failure, while another showed that if PEF during a cough was ≤60 L/min, the rela-
tive risk for extubation failure was 4.8 [17, 18]. Patients with PEF ≤60 L/min are
five times more likely to require reintubation [19]. Another simpler method of
assessing cough is holding a white index card held 1–2 cm from the end of the endo-
tracheal tube. Inability to moisten the card after 3–4 cough attempts is associated
with three times more likelihood of failing extubation [20]. Similarly, patients with
moderate or abundant secretions are more than eight times as likely to have unsuc-
cessful extubation as those with no or small amounts of secretions. Specifically,
patients requiring endotracheal suctioning every 2 h or less are 16 times as likely to
experience unsuccessful extubation as patients suctioned less frequently [20].
25.2.2 Post-extubation Upper Airway Obstruction
Obese patients are particularly at higher risk for post-extubation stridor [2] second-
ary to anatomic features such as short neck, large tongue, excessive palatal and
pharyngeal soft tissue, and restricted ability to open the mouth that predispose
these patients to mechanical trauma of the larynx during intubation [21, 22]. Some
of risk factors associated with early onset laryngeal edema include very large tube
size, excessive endotracheal tube mobility, aggressive suctioning, or high cuff
pressure. Those requiring extended mechanical ventilation exhibit similar lesions
242 A.A. El Solh
Table 25.2. Measurement of the cuff leak volume in mechanically ventilated patients
• Before performing the cuff leak test, first suction endotracheal and oral secretions and set
the ventilator in the assist control mode
• With the cuff inflated, record displayed inspiratory and expiratory tidal volumes to see
whether these are similar. Record cuff pressure
• Deflate the cuff
• Directly record the expiratory tidal volume over the next six breathing cycles as the
expiratory tidal volume will reach a plateau value after a few cycles
• Average the three lowest values
• The difference between the inspiratory tidal volume (measured before the cuff was
deflated) and the averaged expiratory tidal volume is the cuff leak volume
with mucosal ulcerations developing 36 h post insertion of endotracheal tube.

However, laryngeal edema can develop as early as 6 h post intubation [23]. When
upper airway obstruction occurs, it is typically manifested within 5–30 min after
extubation [24].
The gold standard for determination of laryngeal edema is direct laryngoscopy
of the airway prior to extubation. Unfortunately, this is not possible prior to extuba-
tion due to the endotracheal tube which is well below this area. Due to this fact, the
cuff leak test has been advocated as a test for the determination of possible laryngeal
edema (Table 25.2). It’s a simple test that involves placing the obese patient on a set
tidal volume by setting the mechanical ventilator on assist control mode. After the
endotracheal tube has been thoroughly suctioned, the cuff is deflated. The expira-
tory volumes are measured over the course of several breaths after the patient has
ceased coughing. The expiratory volumes are subtracted from the inspiratory vol-
umes, and this is defined as “the cuff leak volume.”
Miller and Cole were the first to attempt to correlate the volume of leak with the
possibility of post-extubation stridor [25]. A cuff leak volume <110 mL predicted a
significant risk of post-extubation failure. Other studies have used similar or higher
threshold values of cuff leak volume. Using a receiver operator characteristic curve
analysis to find out the best threshold, Jaber and colleagues [26] considered a true
positive test as a leak <130 mL or <12% of inspired VT together with post-extubation
stridor, while De Bast and coworkers [23] used a threshold of 15.5%. The absence
of a cuff leak alone is an imperfect predictor of post-extubation stridor. The cuff
leak predicts post-extubation stridor with a sensitivity of 15–85% and a specificity
of 72–99% [25–27]. Although these studies did not consistently specify the BMI of
patients who participated in the trials, the noninvasive nature of the test may still
prove of utility in this population pending validation of the data in obese patients.
With the widespread use of ultrasonographic imaging in the management of
critically ill patients, noninvasive examination of the vocal cords and the larynx is
more accessible. Using ultrasonography, the air column width (ACW), which is
defined as the width of the acoustic shadow present at the level of the vocal cords,
was introduced as a tool to predict outcome of extubation. If the ACW is measured
before and after endotracheal cuff deflation, the air column width difference
(ACWD) can be calculated. Using real-time laryngeal ultrasonography, two studies
[28, 29] showed that a lower air column width during balloon deflation was a good
predictor of post-extubation stridor. However, these results could not be consistently
replicated [30]. Because of the small sample size and the limited number of events
with post-extubation laryngeal edema, the utility of this intervention remains ques-
tionable, and its applicability in obese patients has not been tested.
Eliminating possible risk factors of post-laryngeal extubation may decrease the
incidence of post-extubation failure. It is recommended that an adequate-sized
endotracheal tube should be selected. In contrast to prevailing views, obese patients
do not have larger airways [31]. Generally accepted maximum endotracheal tube
sizes are 7.0 mm for women and 8.0 mm for men. Once the underlying causes for
respiratory failure have resolved, the endotracheal tube should be withdrawn as
soon as possible since the duration of intubation in patients with post-extubation
stridor (PES) is longer compared with patients without PES. However, there is no
data on a definitive cutoff length of intubation where by the risk for PES in obese
patients is increased.
Management of post-extubation laryngeal edema involves reestablishing a patent
airway and adequate oxygenation and relieving the distress. Though not examined
specifically in obese patients, corticosteroids have been investigated in several trials
in the prevention of laryngeal edema. Initial studies failed to show a beneficial effect
of corticosteroids on post-extubation laryngeal edema [32, 33]. In more recent stud-
ies, corticosteroids were shown to decrease the incidence of post-laryngeal edema
by more than 50% [24, 34, 35] via downregulating the inflammatory response and
decreasing capillary permeability [36]. However, the effectiveness of glucocorti-
coids in post-extubation laryngeal edema has yet to be confirmed in randomized
controlled trials because data on the most effective dose has not been determined.
That said, an argument can be made for a dosage of methylprednisolone 20–40 mg,
or dexamethasone 5 mg could be initiated 24 h before planned extubation and con-
tinued for 24–48 h after extubation [35, 37].
Epinephrine nebulization is another potentially effective therapy. Epinephrine
acts through local stimulation of α-adrenergic receptors on vascular smooth muscle
cells, thereby causing vasoconstriction and decreased blood flow, which diminishes
edema formation. There is no consensus about the potentially effective dosage of
epinephrine nebulization in obese patients. A dose of 1 mg epinephrine in 5 mL
normal saline has proved successful in some cases of upper airway obstruction in
adults [38]. Rebound edema is known to occur and close observation is essential.
Evidence for benefit of noninvasive positive pressure ventilation (NIPPV) in
laryngeal edema is lacking overall, and in the absence of any well-designed con-
trolled trials, the clinical application of NIPPV in obese patients with laryngeal
edema is not recommended.
25.2.3 Unplanned Extubation
Unplanned extubation rates range from 5 to 15%, and reintubation rates after
unplanned extubation vary between 35 and 75% [39]. There is no evidence hitherto
244 A.A. El Solh
to suggest that obese patients are at higher risk of unplanned extubation. Further,
there is no consensus on strategies for the prevention of this event [40, 41]. The
majority of studies available on this topic provide a risk assessment of the factors
associated with unplanned extubations. Understanding these factors is crucial for
identifying patients at risk and for developing interventions to reduce the frequency
of this complication. Among these, severe agitation is a long time recognized risk
factor for self-extubation. In a retrospective case-controlled study, Tung et al.
observed that ICU patients who self-extubated were more than twice as likely as
controls to be agitated [42]. Various physical restraints have been used to prevent
patients from removing their endotracheal tubes. However, the use of physical
restraints to address agitation or for any other reason requires careful evaluation,
because the use of physical restraint increases the risk for unplanned extubation by
3.11 times, and the risk increases to 12.44 times if a nosocomial infection is also
present [43]. For patients who still require mechanical ventilation, the role of seda-
tives in preventing unplanned extubation remains unclear. Studies have shown that
more than half of patients were receiving a sedative at the time of unplanned extuba-
tion [44, 45] suggesting that inadequate sedation may be partly to blame for prema-
ture extubation. A prospective study by Balon [46] demonstrated that IV boluses of
morphine sulfate, diazepam, midazolam, lorazepam, and haloperidol given “as
needed” were found to increase the incidence of unplanned extubations. Two other
studies associated the use of benzodiazepines with an increased occurrence of these
events [42, 47]. A paradoxical excitatory effect is thought to be responsible for this
association; however, the dose and schedule of administration of these sedatives
were not defined in these studies.
Because self-extubation tends to recur, constant vigilance by the ICU staff is
necessary. Proper positioning of the tip of the endotracheal tube 4–5 cm above the
carina reduce the risk of inadvertent self-extubation such as during positioning,
transport, or extension of the head and neck. Additionally, failure to identify patients
ready for liberation from ventilatory support is an important element contributing to
increased self-extubation incidence. Formal weaning protocols may reduce the inci-
dence of unplanned extubations, although self-extubation may still occur because of
the usually low sedation level during weaning [48].
Other aspects such as nurse workload and standardization of procedures (the
method of securing the endotracheal tube and the use of hand restraints) have been
reported to be useful in reducing the accidental removal of the orotracheal tube [49,
50]. Several measures can be adopted to minimize unplanned extubations and its
consequences in intubated obese patients: (1) more comprehensive approach to agi-
tated patients that include pain control and appropriate sedation; (2) verification of
the correct position of the endotracheal tube daily in patients who are orally intu-
bated; (3) strong attachment of the tracheal tube, particularly in orally intubated
patients; and (4) daily evaluation for liberation from mechanical ventilation. In one
study, the implementation of a care bundle consisting of educational courses, stan-
dardization of selected procedures such as tracheal tube fixation, tube suctioning,
patient hygiene and transport, identification of high-risk patients, and standardiza-
tion of sedation practices resulted in reducing the incidence of unplanned extuba-
tion from 2.9 to 0.6 per 100 intubation days [51].
25.2.4 Other Causes
Other reasons for extubation failure in obese patients include unrecognized myo-
cardial ischemia and congestive heart failure. Both obesity and OSA have been
associated with impairment in left ventricular function [52]. Abrupt removal of
mechanical ventilation and reinstitution of spontaneous ventilation typically
increases the pressure gradient for venous return. As a result, right ventricular dila-
tion shifts the interventricular septum toward the left ventricle, impede left ven-
tricular filling, and decrease subsequent cardiac output. In addition, right ventricular
dilation may augment right ventricular intrachamber pressure and influence the
pressure gradient for coronary blood flow. These responses are even greater in
obese individuals who exhibit increased breathing work because of the signifi-
cantly greater change in intrathoracic pressure necessary to produce gas flow into
the lungs. In a study of 74 patients who required reintubation within 72 h of extu-
bation, congestive heart failure was the reason for extubation failure in 23% of the
patients [22]. Increase in B-type natriuretic peptide levels during spontaneous
breathing trial was found to predict weaning failure from cardiac origin [53].
Reestablishing euvolemia through diuresis and/or the addition of vasodilator ther-
apy may obviate or diminish the risk of extubation failure in these patients with
reduced cardiac reserve.
Another condition that may contribute to extubation failure in critically obese
patients is delirium. Delirium remains unrecognized in as many as 66–84% of
ICU patients experiencing this complication. Delirium promotes extubation fail-
ure through alteration of consciousness, agitation and subsequent sedation, aspi-
ration, and noncompliance to treatments including NIV (42). Risk factors can be
classified into three groups: (1) host factors, (2) the acute illness itself, and (3)
iatrogenic or environmental factors. Psychoactive drugs are the leading cause for
delirium. Benzodiazepines, narcotics, phenothiazines, and other antipsychotic
medications are associated with a 3–11 times increased relative risk [54], and the
rate of adding psychoactive medications increases the risk of delirium by 4–10
times.
Prevention and management of delirium should be instituted ahead of weaning
trial to avoid extubation failure. Many prevention strategies have been studied,
including sedation protocols (such as alternative sedatives) and non-pharmacologi-
cal management such as creating an ICU environment with less noise and more
natural light, reinstituting the sleep/wake cycle (e.g., eye masks and earplugs at
night), and early mobilization [55–57]. Medications should be used only after
addressing all modifiable risk factors such as correction of electrolytes abnormali-
ties, treating underlying infections, and normalizing gas exchanges.
25.3 Noninvasive Positive Pressure Ventilation
Two randomized clinical trials failed to show benefit of NIPPV in avoiding reintu-
bation in patients who have developed respiratory failure after extubation [58, 59].
The lack of benefit in these studies was attributed to the heterogeneous study
246 A.A. El Solh
population and to the fact that NIPPV was instituted after the onset of respiratory
failure (therapeutic NIPPV). More recent evidence revealed that in obese patients
with acute respiratory failure, early extubation with immediate application of
NIPPV has a positive impact on important outcomes, turning to advantage when
compared with continuous invasive weaning [60, 61] (prophylactic NIPPV). By
applying positive pressure ventilation, NIPPV can augment patient’s native efforts
to overcome critical closing pressures and volumes. The resulting effect is a better
match regional time constant variations leading the zero pressure to move to a
more proximal point in the airway, hence minimizing atelectasis. Since obese
patients are particularly susceptible to this phenomenon, El-Solh and colleagues
[60] evaluated the application of NIPPV in critically ill morbidly obese patients
during the first 48 h post extubation. Compared with conventional therapy, the
institution of NIPPV resulted in 16% (95% confidence interval 2.9–29.3%) abso-
lute risk reduction in the rate of respiratory failure. There was also significant dif-
ference in the intensive care unit and length of hospital stay in the NIPPV group.
More importantly, hypercapnic patients showed a significant reduction in hospital
mortality when NIPPV was applied early. It is necessary to stress that NIPPV must
be applied immediately after extubation to avoid respiratory failure and consequent
reintubation after elective extubation. Keenan and colleagues [59] showed that if
NIPPV is administered to patients that develop respiratory distress after extuba-
tion, NIPPV will not be able to prevent reintubation. Whenever NIPPV is applied
post extubation, the patient must be watched carefully. A critical issue related to
the success of NIPPV is the setting of IPAP and EPAP levels according to each
patient’s needs. IPAP should be adjusted for ventilation adequacy, whereas EPAP
should be set for maintenance of airways and alveolar stability. When choosing the
NIPPV interface in obese patients, great consideration should be given to minimiz-
ing unintentional leak which impairs NIPPV efficiency [62, 63] particularly during
the first few hours of ventilation, when the patient is adapting to NIPPV, and during
sleep, due to the loss of voluntary muscle control and decreased muscle tone.
Interventions to reduce air leak include mask-support ring; ensuring proper inter-
face type, size, and securing system; and optimizing patient comfort and efficiency
with, for instance, hydrogel or foam seal, lip seal or mouth taping, and/or chin
strap.
Conclusion
The decision to extubate obese patients from mechanical ventilatory support is a
complex clinical problem. Obese patients at risk of extubation failure may ben-
efit from management with a weaning algorithm specifically tailored to mini-
mize the risk for post-extubation respiratory failure and need for reintubation.
Extubation failure has been shown to be associated with an increase in mortality
related to reintubation and the complications that develop after reintubation.
Immediate application of NIV appears to prevent post-extubation respiratory dis-
tress in obese patients at high risk of extubation failure. However, caution is
warranted, because NIPPV appears to be ineffective for established post-extuba-
tion respiratory failure.
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NIV in the Obese Patient After Surgery
26
Giuseppe Fiorentino, Antonio M. Esquinas,
and Anna Annunziata
26.1 Postoperative Respiratory Problems of Obese Patients
The risk of postoperative respiratory failure is especially greater if such patients are
made to undergo long duration, high-risk surgical procedures like upper abdominal
or thoracic surgeries [1]. General anaesthesia, by reducing the muscular tone, also
adds to pump failure. Gas exchange failure results from reduction of phrenic output,
disruption of muscle output and pain [2]. Other insults like sepsis, shock, ischaemia
and reperfusion injury and blood transfusions worsen lung injury leading to worsen-
ing of gas exchange [2]. In the morbidly obese, absorption of CO2 during pneumo-
peritoneum can lead to an increase in PaCO2 levels; however, hypercarbia is
commonly avoided with appropriate ventilatory changes. Absorption of CO2 also
alters the acid-base balance and increase in CO2 excretion load [3].
The decrease in lung and chest wall compliance may increase the work of breath-
ing in the postoperative period when patients resume spontaneous ventilation. In the
first hours after surgery, there is a 20% decrease in tidal volume, paired with a 20%
increase in respiratory rates and diaphragmatic dysfunction. This can persist for 1
week [4]. The resulting alveolar hypoventilation paired with atelectasis can contrib-
ute to the development of pneumonia.
Pulmonary atelectasis is reported to develop in 85–90% of obese patients during
the first minutes of anaesthesia and can persist for even 24 h after the end of the
surgical procedure. Several factors (reduced FRC especially in the supine position,
difficult to mobilize postoperatively and bed resting, disruption of respiratory
G. Fiorentino, M.D., F.C.C.P. (*) • A. Annunziata, M.D.

UOC di Fisiopatologia e Riabilitazione Respiratoria, Monaldi Hospital Naples, Naples, Italy
e-mail: giuseppefiorentino1@gmail.com; giuseppe.fiorentino@ospedalideicolli.it
A.M. Esquinas, M.D., Ph.D., F.C.C.P.
Intensive Care Unit and Non Invasive Ventilatory Unit, Hospital Morales Meseguer,
Murcia, Spain

252 G. Fiorentino et al.
muscles as well as the reflex inhibition of the diaphragmatic excursion) contribute

to the persistence of postoperative atelectasis in obese patients [5].
In the immediate postoperative period, the risk of airway obstruction is high due
to the anatomical changes associated with obesity and possible residual anaesthesia,
neuromuscular blockade or suboptimal or excessive analgesia. This risk is increased
in the presence of obstructive apnoea syndrome (OSA) or hypopnoea syndrome.
Drug effects are more marked after short procedures and are aggravated with
increasing age. Especially upper airway muscle tone can be negatively affected by
propofol [6].
Aspiration pneumonitis following regurgitation of gastric contents under general
anaesthesia, although rare, occurring approximately 1 in every 3000 general anaes-
thetics, can result in devastating consequences. The mortality rate following aspira-
tion of gastric contents is 1 in 71,000 general anaesthetics. Obese patients have
typically been considered to have high-volume, low-pH gastric contents that may
lead to increased risk of aspiration pneumonitis, although these findings have not
been confirmed in more recent studies [7].
26.2 P
ostoperative Respiratory Management of Obese
Patients
Postoperative vigilance may be important, and the painful stimulus of blood gas
collection may have altered postoperative wakefulness; fast-track scores are too
crude for a detailed evaluation of postoperative consciousness [6].
Incentive spirometry, respiratory physiotherapy and targeted pulmonary toileting
should be instituted in the immediate postoperative stage. Supplemental oxygen is
only a symptomatic measure to prevent arterial desaturation. Pressurization of the
airway (CPAP and NIV) reduces the work of breathing (enhancing compliance by
increasing FRC, as well as inspiratory assistance) and the right ventricle afterload
(by favouring left ventricular systole), and it also improves oxygenation (reducing
atelectasis). Pressurization also keeps the upper airway open in patients with easy
collapsibility (OSA) [8].
26.3 R
ole of Positive Airway Pressure in the Postoperative
Period
26.3.1 Continuous Positive Airway Pressure (CPAP)
Continuous positive airway pressure (CPAP) therapy is often used in obese patients
after extubation in the recovery room to improve recruitment of atelectatic lungs;
maintaining patency of the upper airway improves oxygenation and reduces work
of breathing [9]. The use of CPAP during preoxygenation at the beginning of a
general anaesthetic and in the immediate postoperative period has been shown to
improve respiratory mechanics and lung function during the hospital stay [9].
26 NIV in the Obese Patient After Surgery 253
Pasquina et al. [10] reported that when CPAP was applied in patients who devel-
oped postoperative atelectasis (based on roentgenographic evidence) following
cardiac surgeries, there was considerable improvement of atelectasis, as deter-
mined by radiological scores The settings chosen are usually titrated to upper air-
way patency and can be empirically set to a start value corresponding to what is
used at home. Unfortunately, this technique is underutilized in PACU and is better
tolerated by patients who are already using a CPAP machine at home [10].
Theoretical advantages of CPAP include promoting airway patency and preventing
alveolar collapse, with a decrease in the FiO2 needed and a decrease in absorption
atelectasis. Left ventricular afterload is also decreased, with an improvement in
cardiac output [4].
26.3.2 Non-invasive Positive Pressure Ventilation (NIV)
The rationale for the use of NIV is to decrease the work of breathing by improving
ventilation (increase CO2 removal) and to decrease the amount of atelectasis, with
subsequent improvement of gas exchange, in attempt to avoid endotracheal intuba-
tion. Patient cooperation is crucial in order for this technique to be successful. NIV
combines the use of pressure support ventilation (PSV) and positive end-expiratory
pressures (PEEP). The use of end-expiratory pressure promotes upper airway
patency, while the inspiratory component is useful to control central hypoventila-
tion. Starting with low PEEP and then adding PSV can be helpful. The feasibility
and safety of NIV use in the recovery room after various types of surgery have been
demonstrated. One study showed a 16% absolute risk reduction in post-extubation
acute respiratory failure with a reduced length of ICU stay by application of 48 h of
NIV in the immediate postoperative stage for patients with a BMI above 35 kg/mq
[11]. Although there are no clinical trials that have shown the effectiveness of NIV
in the postoperative setting for the management of patients with established chronic
respiratory failure, it is considered the standard of care [11–14]. Studies have also
demonstrated that NIV is more effective if instituted as early as possible and in a
continuous way, not in an intermittent approach [8]. The most important issue in
this setting is to choose the best interface for the individual patient, even if that
requires trying various types. Improved comfort is associated with adequate syn-
chrony and increased success of NIV. NIV has been shown to significantly reduce
pulmonary dysfunction following gastroplasty in obese patients and accelerates re-
establishment of preoperative pulmonary function [15].
In morbidly obese patients undergoing abdominal surgeries, studies have clearly
demonstrated the benefits of prophylactic use of NIV in the postoperative period
[15]. Joris et al. [16] demonstrated that the application of bilevel positive airway
pressure set at 12 and 4 cm PEEP significantly improved the peak expiratory flow
rate, the forced vital capacity and the oxygen saturation on the first postoperative
day. In these patients, the beneficial effects of NIV were attributed to an improve-
ment in lung inflation, prevention of alveolar collapse and reduced inspiratory
threshold load.
Together these data suggest that postoperative prophylactic use of NIV could
improve outcome of morbidly obese patients. Its use is recommended in morbidly
obese patients at high risk of postoperative pulmonary complications after tho-
racic or abdominal surgery. These include the more severely obese (BMI > 45),
those with preexisting respiratory disease and those who remain hypoxaemic
despite chest physiotherapy and low flow supplemental oxygen via a nasal
cannula [16].
Aguilo et al. [17] investigated early effects of NIV after lung surgery in compari-
son with the conventional treatment. NIV improved arterial oxygenation after 1-h
application, and this effect continued one more hour after the cessation of the ven-
tilator support and carbon dioxide level, and physiological dead space did not
change at that moment. The procedure was feasibly tolerable, and only one of the
patients had considerable pleural air leak.
Perrin et al. [18] applied prophylactic NIV in both preoperative and postopera-
tive periods of the same patients and compared it to oxygen therapy. They tested
whether NIV ensures a better gas exchange and pulmonary function on lung resec-
tion in patients with a forced expiratory volume lower than 70% of predicted. Gas
exchange and spirometer values were better, and hospital stay was lower in NIV
group [18].
Lefebvre et al. [19] reported that of the patients at risk for severe complications
following lung resection surgeries, 16.3% eventually developed acute respiratory
failure, which were both hypoxaemic and hypercapnic types. The overall success
rate of NIV in this group was 85.3%; however, the mortality associated with NIV
failure was 46.1%. In the same study, the presence of cardiac comorbidities and lack
of initial response to NIV were found to be independently associated with NIV
failure.
Matte et al. [20] reported that when preventive NIV was used in 96 patients in the
first 2 days after cardiac surgery, there was improved oxygenation and lower reduc-
tion of lung volumes. However, the incidence of atelectasis was similar (12–15%)
to the non-NIV group.
There have been only a few studies reporting the use of NIV for treatment of
respiratory failure following cardiac surgeries. Olper et al. [21] studied 85 patients
who received NIV for treatment of respiratory failure following cardiac surgery and
reported that NIV was a safe and feasible solution for postoperative acute respira-
tory failure, even when applied after discharge from the ICU.
26.4 Mechanical Setting
NIV in the postoperative period should always be provided in appropriately mon-

itored locations. It is important to explain the procedure to the patient and reas-
sure the patient before initiating NIV. The patient must be propped up at least 30°
and have received adequate analgesia. It is advisable to begin with low PS as it
usually takes a few minutes for the patient to accommodate to the pressure
applied and synchronize his breathing with that of the machine. Once the patient
starts to feel comfortable and breathing begins to improve, it is easier to gradu-

ally increase the PS till there is improvement in symptoms, reduced respiratory
rates and good synchrony. The end points of the PS applied must be always indi-
vidualized. An arterial blood gas should be obtained by 1–2 h to verify clinical
improvements. Normally, a sensible inspiratory trigger (1–2 L/min or 1–2 cm of
H2O) is applied, with moderate to maximal slope. EPAP levels of 4 cm and IPAP
of 8 cm of H2O (4 cm above EPAP) are normally used at initiation. These may be
gradually increased by increments of 1–2 cm till a maximum EPAP of 10 and
IPAP of 25 cm of H2O [22]. The end points of the PS applied must be always
individualized. An arterial blood gas should be obtained by 1–2 h to verify clini-
cal improvements. Pelosi et al. [23] demonstrated that the addition of PEEP at
10 cm H2O in morbidly obese patients increased elastance and improved oxygen-
ation compared with nonobese subjects. If higher pressures are required, it may
be necessary to change the interface and adjust mask fit. The expiratory trigger is
generally fixed at 0.8–1 s or between 40 and 60% of the peak flow rate. The most
appropriate tidal volume of the patient should be based on ideal and not actual
body weight to avoid high peak and plateau airway pressures and barotrauma.
Because of the reduced chest wall compliance of respiratory system in obesity,
inflation pressures should be interpreted with caution with the initial target tidal
volume calculated from the IBW and then adjusted according to gas exchange.
The use of a low tidal volume and a high fraction of inspired oxygen in the obese
population can lead to progressive formation of atelectasis, with secondary
hypoxaemia and hypercapnia [24]. The goal for mechanical ventilation in this
patient population should focus on the use of peak inspiratory pressures high
enough to open collapsed lung regions and the use of PEEP to keep the alveoli
open at the end of expiration [23].
It is important to carefully monitor these patients and recognize those who are
not responding adequately. One may need to consider other factors like leaks in
circuit, poor mask fit, inadequate trigger levels, etc., which may be readjusted for
better results.
26.5 Interfaces
The most important factor to be taken into consideration while choosing the right
mask is a good fit, patient comfort and mask tolerance. Tolerance of a tightly held
facemask was previously rated identically before and after surgery. As the mask
must be held tightly to avoid leaks and to maintain maximal FiO2, it seems impor-
tant to reassure patients before and during preoxygenation of their ability to breathe
with the facemask. While there is no evidence favouring the use of any one over the
other, oronasal masks are more commonly used than others [25]. Holanda et al. [26]
observed that while the full facemask avoided pain over the bridge of the nose and
prevented air leaks around the eyes and mouth, they caused more oronasal dryness
and claustrophobia. Kwok et al. [27] noted that in the dyspnoeic patient, nasal
masks are less well tolerated than are oronasal masks.
26.6 Side Effects
Most of the patients were unfamiliar with long-term support for sleep apnoea, but
this did not reduce tolerance. We did not find any significant cardiovascular depres-
sant effects of NIV with respect to BP and heart rate. Gastric distension was greater
after NIV, but the increase was modest. O2 administration with PEEP alone did not
increase gastric air insufflation, suggesting that the pressure support component
promoted gastric distension during NIV. Positive-pressure ventilation may increase
gastric air content and hence may promote pulmonary aspiration during endotra-
cheal intubation. There is a risk with an insufflation pressure of more than
20 cm H2O, which can be easily obtained using manual ventilation. There may be
some concerns gastrointestinal increased anastomotic leakage in patients who
receive NIV after gastrointestinal anastomoses, especially following upper gastro-
intestinal anastomosis, where use of NIV may be considered a relative contraindica-
tion [28]. However, several studies on the use of NIV in patients who had undergone
procedures like oesophagectomies, digestive surgeries, gastrectomies and colosto-
mies showing increased benefits and reduced morbidity with the use of NIV postop-
eratively have not reported any problems with suture integrity [28]. Gastric inflation
pressures should be carefully monitored as the risk of anastomotic leakage seems to
be more if very high insufflation pressures are applied (more than 25 cm H2O). NIV
is contraindicated in case of upper GI surgery, where it could contribute to leaks at
the anastomosis site. Increased secretions can cause an increased work of breathing
and decrease the efficacy of NIV.
Conclusion
Standard perioperative medications (anaesthetics, sedatives, opioids and
neuromuscular-blocking agents), interventions (patient positioning, mechanical
ventilation and surgical trauma) and diseases (lung hyperinflation, obesity and
obstructive sleep apnoea) have differential effects on the respiratory muscle.
These effects on the upper airway dilators and respiratory pump muscles impair
their coordination and function and can result in respiratory failure. Perioperative
management strategies can help decrease the incidence of postoperative respira-
tory muscle dysfunction. In the past decade, the NIV has proven to be an effec-
tive alternative to invasive ventilation in the setting of moderate and severe
acute postoperative respiratory failure. The use of NIV has not only reduced
intubation rates with the attendant complications associated with mechanical
ventilation but has also reduced morbidity, length of hospital stay and mortality
in these patients. The effect lasted 24 h after discontinuation of NIV. Patient
selection is necessary in order to establish clinically relevant improvements.
This translates to huge benefits in costs of treatment too, especially in a country
like ours where resources are limited and costs of therapy play a major role in
deciding treatment options.
Early initiation of short-term NIV during the postoperative promotes more
rapid recovery of postoperative lung function and oxygenation in the obese.
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1. Branson RD. The scientific basis for the postoperative respiratory care. Respir Care.
2013;58:1974–84.
2. Levi D, Goodman ER, Patel M, Savransky Y. Critical care of the obese and bariatric surgical
patient. Crit Care Clin. 2003;19(1):11–32.
3. Nguyen NT, Wolfe BM. The physiologic effects on pneumoperitoneum in the morbidly obese.
Ann Surg. 2005;241(2):219–26.
4. Jaber S, Michelet P, Chanques G. Role of non-invasive ventilation (NIV) in the perioperative
period. Best Pract Res Clin Anaesthesiol. 2010;24(2):253–65.
5. Eichenberger AS, Proietti S, Wicky S, Frascarolo P, Suter M, Spahn DR, et al. Morbid obe-
sity and postoperative pulmonary atelectasis: an underestimated problem. Anesth Analg.
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with Obstructive Sleep Apnea. Practice guidelines for the perioperative management of
patients with obstructive sleep apnea. Anesthesiology. 2014;120(2):1–19.
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lation for obesity hypoventilation syndrome. Chest. 2010;138:84–90.
14. Masa JF, Celli BR, Riesco JA, et al. The obesity hypoventilation syndrome can be treated with
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15. Martí-Valeri C, Sabaté A, Masdevall C, Dalmau A. Improvement of associated respira-
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2007;17(8):1102–10.
16. Joris JL, Sottiaux TM, Chiche JD, Desaive CJ, Lamy ML. Effect of bi-level positive airway
pressure (BiPAP) nasal ventilation on the postoperative pulmonary restrictive syndrome in
obese patients undergoing gastroplasty. Chest. 1997;111:665–70.
17. Aguilo R, Togores B, Pons S, et al. Noninvasive ventilatory support a er lung resectional sur-
gery. Chest. 1997;112:117–21.
18. Perrin C, Jullien V, Venissac N, Berthier F, Padovani B, Guillot F, et al. Prophylactic use
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2007;101:1572–8.
19. Lefebvre A, Lorut C, Alifano M, Dermine H, Roche N, Gauzit R, Regnard JF, Huchon G,
Rabbat A. Noninvasive ventilation for acute respiratory failure after lung resection: an obser-
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Determinants of NIV Success or Failure
27
Antonello Nicolini, Ines Maria Grazia Piroddi,
Cornelius Barlascini, Gianluca Ferraioli, and Paolo Banfi
Patients who are likely to benefit from noninvasive ventilation (NIV) need to be
identified early [1, 2]. Failure to do so often results in increased morbidity and mor-
tality as well as inappropriate use of limited resources [2].
Before starting NIV, it is crucial to identify good candidates [1]. The best way to
do this is to look for predictors of failure [3]. The absence of the essential qualifica-
tions of alertness and ability to follow instructions excludes many patients.
Hypotension, pneumothorax, gastric insufflation, vomiting, and risk of aspiration
must be evaluated. The risk of NIV failure determines the intensity of monitoring
needed [3]. Moreover, knowing the factors affecting the likelihood of success of
NIV may help to decide also the duration of NIV trial. One approach to determining
the need for monitoring is to assess the patient’s risk of NIV failure [4]. Some of
these are simple bedside assessments, such as ease of arousability, agitation, cough
integrity, and respiratory rate. Other methods require simple laboratory tests, such
as determination of arterial blood gas. Other methods require proven evaluation
protocols: Acute Physiology and Chronic Health Evaluation (APACHE) II or
Simplified Acute Physiology Score (SAPS) II. When a quick decision is required,
reliance on simple bedside observations and rapidly obtained laboratory values such
as pH is best choice [4, 5].
A. Nicolini (*) • I.M.G. Piroddi

Respiratory Diseases Unit, Hospital of Sestri Levante, Sestri Levaente, Italy
e-mail: antonellonicolini@gmail.com
C. Barlascini
Hygiene and Health Medicine Unit, Hospital of Sestri Levante, Sestri Levaente, Italy
G. Ferraioli
Emergency and Internal Medicine Unit, Hospital of Lavagna, Lavagna, Italy
P. Banfi
Pulmonology Department, Don Gnocchi Foundation IRCSS, Milan, Italy

260 A. Nicolini et al.
The risk of NIV failure determines the level of monitoring required. A patient
with multiple risk factors for NIV failure should be in a closely monitored setting
such as an ICU or step-down respiratory unit.
Three critical moments identify NIV failure: (1) immediate failure (within min-
utes to <1 h), (2) early failure (1–48 h), and (3) late failure (after 48 h) [6–8].
27.1 Immediate NIV Failure
Immediate NIV failure refers to failure within 60 min [9]. Predictors of failure in this
period have never been systematically analyzed. A weak cough reflex leading to inef-
ficient clearance of excessive secretions from airways is a common cause of immediate
NIV failure. The inability to spontaneously remove secretions is considered a contrain-
dication to NIV, e.g., patients with impaired consciousness and depressed cough reflex.
Hypercapnic encephalopathy syndrome (HES) is often considered a cause of immedi-
ate NIV failure because of poor compliance due to confusion and/or agitation. It is a
relative contraindication because of the increased risk of aspiration [3, 8, 9]. The risk of
aspiration has been shown to be minimized by the rapid improvement of neurological
status. Patient tolerance has been shown to be critical for NIV success, especially in the
first few minutes while the patient adapts to this “new mode” of breathing [10].
27.2 Early NIV Failure
Nearly 65% of NIV failures occur within 1–48 h of NIV use. This time interval has
received more attention in assessments of NIV failure than any other. Several inves-
tigators have tried to assess the best predictors of NIV failure. Confalonieri et al.
found that subjects likely to fail NIV had more severe respiratory acidosis and a
lower level of consciousness, were older and more hypoxemic, and had a higher
respiratory rate on presentation [4]. Clinical signs that are only equivocal on presen-
tation become more definitively predictive of failure if they persist after 2 h of
NIV. It is important to assess clinical trajectory after 1–2 h of initiation of NIV to
identify response. However, even on presentation, subjects who have a pH < 7.25,
an APACHE II score >29, and a Glasgow coma score <11 have failure rates ranging
from 64 to 82%. Patients with excessive respiratory secretions or without improve-
ment after 60 min of NIV have high risk of failure [4, 11].
27.3 Late NIV Failure
Late NIV failure (after 48 h) is an event occurring after an initial good response to
NIV. It is more likely in subjects who, at the time of admission, showed functional
limitations evaluated using a score correlated to home activities of daily living
(ADL), the number of comorbidities, a lower pH at baseline, and the underlying
cause of acute respiratory failure (ARF), e.g., pneumonia [6, 8, 12].
27 Determinants of NIV Success or Failure 261
27.4 Obesity Hypoventilation Syndrome
Obesity hypoventilation syndrome (OHS) is defined as a combination of obesity

(BMI > 30 kg/m2), daytime hypercapnia, PaCO2 < 45 mmHg, and sleep-disordered
breathing during sleep [13, 14]. OHS is a chronic disease associated with respira-
tory and cardio-metabolic impairments leading to a decrease in activities of daily
life and social involvement as well as a higher risk of hospitalization and death.
About more than 30% of patients are diagnosed when hospitalized for acute on
chronic respiratory failure [1, 7]. Patients with OHS often respond well to NIV. The
pathophysiology of OHS results from complex interactions between various sleep
breathing disorders (obstructive sleep apnea, REM sleep hypoventilation), increased
work of breathing due to a decreased thoracoabdominal compliance, and altered
ventilatory drive [15]. These mechanisms can be successfully corrected by
NIV. Patients with OHS can be treated in an acute care setting with better results
than other diseases such as COPD. NIV reduces the respiratory load, increases min-
ute volume for a given breathing effort, and provides ventilation during central
apneic events [16].
Only a few studies have investigated NIV success or failure in OHS patients [1,
7, 16]. Several observations have emerged from these works: (a) In OHS NIV rarely
failed in reversing ARF. (b) Obese patients who exhibited early NIV failure had a
high severity score and a low HCO3 level at admission and were likely to have
hypoxemic ARF caused by pneumonia. (c) Factors associated with a successful
response to NIV included high paCO2 at admission and a diagnosis of idiopathic
hypercapnic decompensation of OHS. (d) More than half of hypercapnic patients
with decompensated OHS exhibited a delayed response to NIV with late NIV
failure.
The authors concluded that in obese patients with ARF, both pH and paCO2 may
not accurately predict patient response to NIV, especially in the first hours of NIV
treatment [7]. The decreased responsiveness in hypoxic and hypercapnic ventilatory
drive that characterizes this last category may explain why they need more time than
expected to correct respiratory acidosis compared to all other patients [1, 7].
No ventilatory mode has been shown to lead to better outcome than others [17–
20]. Numerous modes have been implemented: continuous positive airway pressure
[CPAP], bilevel positive airway pressure [BiPAP], pressure support ventilation
[PSV], pressure control ventilation [PCV], Bilevel Positive Airway Pressure
[BiPAP] spontaneous-timed [ST] with AVAPS [average volume-assured pressure
support], and airway pressure release ventilation [APRV] [7, 14, 16, 21–24].
The setting of ventilator is very important because the delay in the reduction of
PaCO2 may be due to:
1. Inadequate level of inspiratory (IPAP) or expiratory (EPAP) pressure: in obese

patients, IPAP should range from 12 to 30 H2O or greater and EPAP from 8 to
12 cm H2O.
2. Inadequate duration of NIV: the obese patients as previously explained require
longer NIV therapy than non-obese patients especially during the night; their
262 A. Nicolini et al.
apneas or hypoventilation worsen during hours of sleep. These findings suggest

that NIV setting needs to be titrated more aggressively in OHS than other syn-
dromes when acute illness precipitates respiratory decompensation (especially
pneumonia) [7, 21].
Although few studies are available concerning morbidly obese patients with
decompensation of OHS, they suggest that these patients have similar mortality and
intubation rates compared to non-obese patients. OHS patients require more aggres-
sive NIV settings and a longer time to reduce paCO2 levels below 50 mmHg and
more frequently have late NIV failure. The best ventilatory strategy is to treat each
patient as unique using flexibility and vigilance.
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failure of noninvasive ventilation in chronic obstructive pulmonary disease with acute exacer-
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Chronic Ventilation in Obese Patients
28
Jean Christian Borel, Jean-Paul Janssens, Renaud Tamisier,
Olivier Contal, Dan Adler, and Jean-Louis Pépin
28.1 Introduction
Obesity is defined by a body mass index (BMI) of ≥30 kg/m2.The general increase

in prevalence of obesity is a major challenge facing governments and health-care
systems worldwide [1]. The prevalence of severe obesity (class III), defined as a
BMI ≥40 kg/m2, is increasing at a much faster rate than other classes of obesity [2].
Obesity is associated with an increased rate of death from cardiovascular diseases
and a higher cancer incidence [3] and also has a major impact on respiratory health.
Morbid obesity is one of the main causes for severe hypercapnic respiratory failure
requiring ICU admission [4–6]. Obesity-related respiratory impairment is complex,
involving thoraco-pulmonary mechanic abnormalities, central respiratory control
alterations, and sleep breathing disorders. Obstructive sleep apnea syndrome
(OSAS) is commonly associated with obesity [7]. However, beyond OSAS, obesity
hypoventilation syndrome (OHS) is a specific entity defined as a combination of
obesity (BMI ≥ 30 kg/m2), daytime hypercapnia (PaCO2 ≥ 45 mmHg), and
J.C. Borel (*)

HP2 Laboratory, INSERM U1042, University Grenoble Alps, Grenoble, France
EFCR Laboratory, Grenoble Alps University Hospital, Grenoble, France
AGIR à dom. Association, 36 bd du Vieux Chêne, 38240 Meylan, France
e-mail: J.borel@agiradom.com
J.-P. Janssens • D. Adler
Division of Pulmonary Diseases, Geneva University Hospital, Geneva, Switzerland
R. Tamisier • J.-L. Pépin
HP2 Laboratory, INSERM U1042, University Grenoble Alps, Grenoble, France
EFCR Laboratory, Grenoble Alps University Hospital, Grenoble, France
O. Contal
Haute Ecole de Santé de Vaud, HESAV, Lausanne, Switzerland

266 J.C. Borel et al.
sleep-disordered breathing after ruling out other disorders that may cause alveolar
hypoventilation. Although this condition remains often underdiagnosed [4, 5, 8],
patients with OHS are characterized by a higher morbidity-mortality than eucapnic
obese patients. OHS has become the primary cause for long-term home noninvasive
mechanical ventilation [9].
In this chapter, we will discuss (1) the main pathophysiological mechanisms
leading to obesity-related chronic respiratory failure and their implications for treat-
ment decision, (2) the need to improve early diagnosis in these patients, and (3)
treatment modalities, mainly use of long-term noninvasive positive airway pressure
therapies. We will finally discuss the importance of screening for comorbidities and
the need to offer combined treatment strategies including weight loss strategies as
well as changes in lifestyle habits and rehabilitation programs to improve long-term
outcomes.
28.2 P
hysiopathology of Obesity-Related Chronic
Respiratory Failure
Hypoventilation is defined by an inadequate alveolar ventilation for a given meta-

bolic activity and production of CO2 (VCO2) resulting in hypoxemia and hypercap-
nia. In obese patients, hypoventilation results from the conjunction/combination of
several factors which interact to overwhelm the compensatory mechanisms of CO2
homeostasis.
28.2.1 Respiratory Mechanics
A decrease in pulmonary volumes (vital capacity, total lung capacity, functional

residual capacity (FRC), and expiratory reserve volume (ERV)) has been reported
as a determinant of hypoventilation in obese patients [10–15]. This restrictive ven-
tilatory defect, mainly related to fat deposits [16, 17], is also associated with
decreases in chest wall compliance, expiratory flow limitation [18, 19], and intrinsic
positive end-expiratory pressure [20]. This contributes to an increase in total work
of breathing. The reduced expiratory reserve volume may lead to abnormalities in
distribution of ventilation (ventilation/perfusion mismatches) and therefore of gas
exchanges [21]. The central fat distribution (intrathoracic and abdominal) pheno-
type is a strong determinant of lung volume restriction [22, 23]. It may also be a
cause of the development of chronic hypoventilation [24]. Although there is a cor-
relation between inspiratory muscle strength and the development of hypoventila-
tion, hypercapnic obese patients are usually able to temporarily correct
hypoventilation with voluntary breathing [12]. Additionally, during spontaneous
breathing [25], transdiaphragmatic pressures are preserved compared to eucapnic
patients [25, 26]. This suggests that muscle function may be slightly impaired but,
mainly, respiratory muscles cannot cope with the overload imposed on the respira-
tory system.
28 Chronic Ventilation in Obese Patients 267
28.2.2 Sleep Breathing Disorders
Most patients with obesity and chronic respiratory failure suffer from severe
OSAS [27, 28]. OSAS is multifactorial, but fat deposits surrounding upper air-
ways, reduced lung volume [29], and fluid overload shifting from the legs to the
neck in recumbent position [30] contribute to obstructive events during sleep.
The severity of OSAS is a key component in the development of hypoventilation
[31] and, more specifically, occurrence of prolonged apneas/hypopneas [32] and
insufficient post-event ventilatory compensation [33] (Fig. 28.1). Apart from
OSAS, periods of central hypoventilation during sleep, characterized by a sus-
tained reduction in ventilation associated with reduced respiratory drive [34, 35],
are encountered in obese patients. These periods are more pronounced during
REM sleep [34] (Fig. 28.2). Their repetitive occurrence and severity induce renal
bicarbonate retention which may not be fully cleared during waking hours, lead-
ing to a gradual depression of respiratory drive and daytime hypoventilation
[35–37].
5 minutes epoch
SpO2
THO
ABD
THERM
FLOW
PTT
HYPN
CO2 excretion
Blunted ventilatory responses
CO2 (mL/breath)
CO2 CO2 Load Metabolic

Load Insufficient post-event
production
ventilatory
compensation
Time Diurnal Hypoventilation
Fig. 28.1 (a) Polysomnographic pattern of obstructive sleep apnea syndrome. SpO2 Oxygen
blood saturation, THO thoracic movements, ABD abdominal movements, THERM bucconasal
thermistor, FLOW nasal pressure, EOG electrooculogram, ECG electrocardiogram, PTT pulse
transit time (an indirect measure of respiratory effort). (b) Schematic representation of insufficient
post-event ventilatory compensation (From Borel et al. Respirology 2012; 17: 601–610)
5 minute epoch : sustained reduction in airflow amplitude during REM sleep
A2-C3 Arousal
EOG
THER
FLOW
THO
ABD
SpO 2
ECG
W
REM
S1
Hypnogram
S2
S3
S4
REM
SpO 2, %
↓ SpO 2
↑ PtCO 2
PtCO 2, mmHg
Overnight
Fig. 28.2 Polysomnographic pattern of REM sleep hypoventilation. (a) 5 min epoch. A2-C3
Electroencephalogram, SpO2 oxygen blood saturation, THO thoracic movements, ABD abdominal
movements, THERM bucconasal thermistor, FLOW nasal pressure, EOG electrooculogram, ECG
electrocardiogram. (b) Overnight hypnogram (see the increase in PtCO2 during REM sleep) (From
Borel et al. Respirology 2012; 17: 601–610)
These distinct pathophysiological phenotypes are clinically relevant for identify-

ing OHS subtypes responding to different PAP modalities. This has been recently
demonstrated in clinical trials specifically dedicated to OHS with prominent OSAS
or REM hypoventilation, respectively [27, 38].
28.3 I mproving Early Diagnosis in Patients with Obesity-

Related Chronic Respiratory Failure
In a stable state, the clinical presentation of OHS patients differs slightly from
eucapnic obese patients referred to the sleep laboratory for suspicion of sleep-
related breathing disorders. OHS patients are more likely to have class III obesity,
to complain of severe sleepiness, and to exhibit multi-morbid conditions [39, 40].
However, a third of obese patients with chronic respiratory failure are diagnosed
during an episode of acute respiratory failure [41–43]. This emphasizes the under-
diagnosis of these patients before the end stage of the disease, hence the necessity
for early identification [8]. An increase in venous bicarbonate concentration
[HCO3-v] has recently been proposed as a simple biomarker for identifying OHS
patients. A threshold of [HCO3-v] > 27 mMol L−1 has been shown to be highly sen-
sitive for the identification of OHS patients [13]. Furthermore, the presence of a
Table 28.1 Staging of hypoventilation in obesity

0 At risk BMI > 30 kg m−2 OSA No hypercapnia
I Obesity- BMI > 30 kg m−2 OSA/ Intermittent hypercapnia
associated sleep hypoventilation during sleep, full recovery
hypoventilation during sleep during sleep (PaCO2 or
PtcCO2 morning~evening)
II Obesity- BMI > 30 kg m−2 OSA/ Serum bicarbonate
associated sleep hypoventilation <27 mmol L−1 when awake,
hypoventilation during sleep intermittent hypercapnia
during sleep (PaCO2 or
PtcCO2 morning > evening)
III Obesity BMI > 30 kg m−2 OSA/ Serum HCO3 ≥27 mmol L−1
hypoventilation hypoventilation when awake, HCO3
during sleep increased during day
Sustained hypercapnia
(PaCO2 > 45 mmHg while
awake)
IV Obesity BMI > 30 kg m−2 OSA/ Sustained hypercapnia
hypoventilation hypoventilation while awake,
syndrome during sleep cardiometabolic
comorbidities
From [45]; Randerath W et al. Eur Respir J. 2016
raised base excess without diurnal hypercapnia could represent an early stage of
obesity-related hypoventilation [44]. This concept of a gradual spectrum in obesity-
related hypoventilation, recently included in a European Respiratory Society Task
Force statement (Table 28.1) [45], could have important implications for the early
identification and management of OHS patients: indeed, a treatment initiated earlier
may have more impact than at the end stage of OHS with established
comorbidities.
28.4 T
reatment Modalities in Patients with Obesity-Related
Chronic Respiratory Failure
28.4.1 Positive Airway Pressure Therapies
Positive airway pressure therapies (CPAP or NIV) represent the cornerstone of

treatment for sleep breathing disorders. As previously described, most patients with
obesity-related chronic respiratory failure suffer from severe OSAS: in these
patients, CPAP efficiently reverses diurnal hypoventilation [27, 46, 47] and improves
sleep parameters and clinical symptoms [27] when followed 2–3 months. Piper
et al. [47] showed that failure of CPAP to normalize nocturnal gas exchanges (i.e.,
persistent oxygen desaturation during CPAP titration) does not preclude its efficacy
after 3 months. NIV has also been envisaged as first-line therapy to treat sleep
breathing disorders [48], raising the question of the optimal treatment between
CPAP and NIV. Although no long-term studies have demonstrated whether NIV is

more beneficial than CPAP on outcomes such as cardiovascular events, hospitaliza-
tion, or mortality, three randomized controlled trials have compared the efficacy of
these two modalities over 2–3 months [27, 47, 49]. Neither study has demonstrated
the superiority of one modality to another with respect to daytime PaCO2 or rate of
treatment failure (defined as hospital admission, persistent or worsening ventilatory
failure, or nonadherence). NIV may have a more favorable impact than CPAP on
health-related quality of life [27] and functional [27] or psychomotor criteria [47];
however, these results should be interpreted with caution since issued from explor-
atory analyses (secondary outcomes) in the studies. Moreover, two of these three
trials [38, 47] did not include patients with less severe forms of OSAS [27] or with
severe continuous and non-apneic oxygen desaturation under CPAP [47] who are
more likely to respond to NIV [38].
In clinical practice (Fig. 28.3), in patients with obesity-related chronic respira-
tory failure and severe OSAS, an initial CPAP trial conducted for a duration of
2–4 weeks is recommended [50]. An assessment of CPAP efficacy should at least
include nocturnal oximetry, ideally completed by transcutaneous PCO2, and respira-
tory polygraphy or polysomnography [51]. In case of persisting sleep-related
hypoventilation despite adequate CPAP therapy, shifting to NIV is justified.
Patient with Obesity-related Hypoventilation
Severe OSAS
(AHI ≥30 events/hour)
Yes No
CPAP trial for 2 to 4 weeks Non-Invasive

with assessment of CPAP efficacy Ventilation
Poly(somno)graphy+ PtcCO2
Persistant hypoventilation despite

adequate CPAP therapy? Yes
No
Continue treatment with

CPAP
Fig. 28.3 Proposed algorithm for choosing the appropriate PAP therapy in patients with obesity-
related hypoventilation. NIV Noninvasive ventilation, AHI apnea and hypopnea index, and CPAP
continuous positive airway pressure
According to the AASM rules for scoring respiratory events in sleep, hypoventila-
tion is scored when (1) arterial PCO2 is > 55 mmHg for ≥ 10 min or (2) there is an
increase in arterial PCO2 ≥ 10 mmHg (in comparison to an awake supine value) to
a value exceeding 50 mmHg for ≥ 10 min [52]. Finally, clinicians should be aware
that auto-CPAP modes have not been designed to detect and report hypoventilation.
Therefore, analysis of residual events based on built-in software of auto-CPAP
devices may be falsely reassuring in spite of persistent hypoventilation and oxygen
desaturation, particularly during REM sleep [53].
In the particular phenotype of obese patients who are mostly hypoventilators
without severe obstructive sleep apnea and in patients with failure of a CPAP trial,
NIV is the most common modality of treatment to control sleep breathing disorders
[38]. NIV is more expensive and more complex to set up than CPAP, with a large
range of ventilatory modes which require knowledge and experience in choice of
appropriate modes and titration procedure.
28.4.2 Selecting the Mode of NIV and Titration Procedures
Currently NIV is mainly applied by bilevel positive airways pressure (BiPAP)

with three main modes [9]: (1) the spontaneous mode “S” in which each pressur-
ization by the ventilator is triggered and cycled by the patient; (2) the spontane-
ous/timed “S/T” mode in which, if the patient fails to trigger the ventilator, a
pressurization within a given time frame is automatically delivered based on a
backup respiratory rate; and (3) the timed mode “T” in which the NIV device
delivers pressurizations at a preset respiratory rate, during a preset inspiratory
time. Although there is a lack of data comparing these different modes on long-
term outcome, the S/T mode is generally admitted as the most appropriate for
these patients [27, 38, 41, 43, 54]. The spontaneous mode may promote central
sleep apnea [55] and ineffective efforts (for triggering the ventilator) rendering it
less effective than the S/T mode.
In the S/T mode, a sufficient expiratory positive airway pressure (EPAP) should
be set to prevent upper airway obstruction. Inspiratory positive airway pressure
(IPAP) should be increased until abolition of hypoventilation. Table 28.2 reports the
main settings applied in the most recent RCT published in the field. Under NIV, and
particularly in S/T mode, asynchronies between patient and ventilator may occur.
Patient-ventilator asynchronies can have a negative impact on sleep quality or cor-
rection of hypoventilation [56, 57]. This justifies a systematic overnight monitoring
under NIV with the aim of adjusting ventilator settings and interface to suppress
abnormal residual events [51, 58].
Manufacturers have developed other types of ventilatory modes such as volume-
assured pressure support (VAPS) [59, 60] and auto-titrating noninvasive ventilation
[61, 62]. By automatically adapting EPAP, IPAP, or backup respiratory rate (accord-
ing to each specific algorithm), these modes have in theory the ability to provide
appropriate ventilation during the different phases of sleep and body positions.
Although two studies [59, 60] have reported greater improvements in nocturnal
Table 28.2 NIV settings applied in patients with OHS according to the recent published RCTs
EPAP IPAP Backup
Ventilatory mean (SD), respiratory rate,
Reference mode cmH2O mean (SD), cmH2O mean (SD)
Piper et al. S 10 (2) 16 (2) –
[47] CPAP 14 (3) – –
Borel et al. S/T 11 (2) 18 (3) 13 (2)
[48]
Murphy S/T 10 (2) 25 (3) 14 (1)
et al. [63] S/T with 9 (1) Set IPAP = EPAP + [4 – 30] 14 (1)
VAPS mean Vte = 657 (96) mL
Masa et al. S/T with 7.8a Set IPAP = [18–22] 14a
[27] VAPS Mean IPAP = 20
CPAP 11a
Masa et al. S/T with 7.1a 18.2a 15a
[38] VAPS
Howard S/T 11.9 (2.3) 19.3 (2.8) 15 (2.7)
et al. [49] CPAP 15.2 (2.8)
S Spontaneous, S/T spontaneous/timed, VAPS volume-assured pressure support
a
SD non available
hypoventilation using VAPS mode, the largest RCT prospectively comparing VAPS
ventilation to classical S/T mode did not find any difference in terms of correction
of PaCO2 or health-related quality of life after 3 months of treatment [63]. Regarding
auto-titrating noninvasive ventilation, two RCTs including clinical and medico-
economic outcomes are currently ongoing in patients with OHS (NCT01757444;
NCT02342899). The clinical relevance of these specific modes (volume-assured
pressure support and auto-titrating NIV) has thus yet to be clarified [64].
28.5 L
ong-Term Follow-Up of Patients with Obesity-Related
Chronic Respiratory Failure: The Need to Screen
Comorbidities and to Propose Multimodal
Therapeutic Strategies
Uncontrolled studies have consistently reported a lower mortality rate in patients

with obesity-related chronic respiratory failure treated with long-term NIV [43, 54,
65] compared to untreated patients [8, 14, 66]. However, mortality rate of these
patients remains substantially higher than that of patients with simple obstructive
sleep apnea [42]. Cardiovascular [41] and metabolic comorbidities [42] remain the
major determinant of mortality in these patients treated by NIV. Thus, NIV should be
combined with other modalities of treatment to further improve these risk factors.
Interventional studies designed to allow weight loss in obese patients have shown
that weight loss achieved either by bariatric surgery [67] or by lifestyle intervention
[68] was associated with improvements in sleep-related breathing disorders and
diurnal hypoventilation [69–72].
Increasing physical activity in patients with obesity-related respiratory failure is

likely to be an essential lever for improving outcomes. However, these patients often
have a very limited social activity and lack motivation regarding rehabilitation pro-
grams [73]. The implementation of NIV could be an appropriate time to initiate a
rehabilitation program since nocturnal NIV itself may increase exercise tolerance
[74]; in that way, a trial aimed at comparing the effect of an exercise and nutrition
program in addition to NIV versus NIV alone is currently ongoing (https://clinicaltri-
als.gov/ct2/show/NCT01483716). Modalities of exercise training in this population
require further studies. For instance, in patients who hypoventilate during exercise,
NIV during exercise training may increase performance and efficacy of training [75].
Combining respiratory muscle training with a low-calorie diet and a physical activity
program may improve dyspnea and exercise capacity more than physical activity and
diet alone [76]. Finally, home-based neuromuscular electrical stimulation might help
morbidly obese patients to return to at least a minimal level of physical activity.
Conclusion
Positive airway pressure therapies (CPAP and/or NIV) are the cornerstone treat-
ment of patients with obesity-related chronic respiratory failure. In the absence
of long-term studies showing which ventilator mode is most effective, the choice
of nocturnal CPAP or NIV should be based on obtaining the best control of
underlying sleep-related respiratory abnormalities. However, nocturnal pressure
therapies cannot be considered as the only strategy: (1) there is a need to identify
as early as possible patients at risk of developing obesity-related chronic
hypoventilation and (2) to implement multimodal therapeutic approaches before
the occurrence of less reversible comorbidities and unfavorable outcomes.
Conflicts of Interest: Jean Christian Borel is employed by AGIR à dom, a nonprofit home care
provider. The other authors have no conflict of interest in relation to this chapter.
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Part V
How to Support Nutritionally the Critically Ill
Obese Patient
Nutritional Support in the Critically Ill
Obese Ventilated Patient 29
Kasuen Mauldin and Janine W. Berta
29.1 Introduction
About 25–30% of patients admitted to an intensive care unit (ICU) are obese per
body mass index (BMI, calculated as weight in kilograms divided by height in
meters squared) greater than or equal to 30.0 kg/m2, and these patients have a
higher risk of having malnutrition in the ICU setting [1, 2]. Obesity is a chronic
condition that is often characterized by low-grade systemic inflammation and asso-
ciated with metabolic alterations that result in glucose intolerance, altered fuel
utilization, and greater potential for loss of lean body mass [2, 3]. Critical illness is
characterized by catabolic stress, indicating greater nutritional needs, especially
protein, in critically ill obese patients [2, 3]. Critically ill obese patients requiring
mechanical ventilation tend to have greater complications, such as acute respira-
tory distress syndrome and acute renal failure, during the course of ventilation [4].
This group of patients is also at risk for missed or delayed detection of malnutri-
tion, which can result in increased hospital morbidity and longer lengths of stays
[1, 2]. In the ICU setting, chronic disease-related malnutrition such as sarcopenic
obesity, defined as loss of muscle mass with reduced physical function in the con-
text of excess body fat, is of concern, and timely, tailored nutrition support can
improve clinical outcomes [1, 3].
K. Mauldin, Ph.D., R.D. (*) • J.W. Berta, M.S., R.D., C.N.S.C.

Department of Nutrition, Food Science, and Packaging, San José State University,
San José, CA, USA
Department of Clinical Nutrition, Stanford Health Care, Palo Alto, CA, USA
e-mail: kasuen.mauldin@sjsu.edu; jberta@stanfordhealthcare.org

282 K. Mauldin and J.W. Berta
In nutrition assessment of the critically ill obese patient, current guidelines recom-
mend clinician focus on evidence of comorbidities that can make clinical manage-
ment more difficult. Factors that put the obese ICU patient at highest risk are the
presence of central adiposity, metabolic syndrome (evaluated by blood pressure and
serum glucose, triglyceride, and cholesterol concentrations), and sarcopenia [2].
A nutrition-focused physical assessment of critically ill obese patients can help
detect central adiposity, sarcopenic obesity, and malnutrition in obese mechanically
ventilated patients and help guide nutrition interventions. Emerging methods such
as computed tomography (CT) and ultrasound scans have been used to assess body
composition or the analysis of lean versus fat mass, especially in the abdominal
region. CT can identify low muscle volume and poor muscle quality, but it does
require expensive equipment and exposure to radiation, and very obese patients may
be difficult to analyze [5]. Ultrasound scans can be conducted at bedside, with low
patient burden, to measure muscle thickness, but recommendations for use in prac-
tice have yet to be established [6]. Other body composition analysis methods, such
as bioelectrical impedance analysis, dual-energy X-ray absorptiometry, dilution
techniques with isotopic water, air displacement plethysmography, and underwater
weighing, are not appropriate or feasible in this patient population [3]. If possible,
measuring waist circumference, as a proxy for central adiposity, may be more rele-
vant to clinical outcomes than just calculating BMI [2].
The guidelines for assessing energy and protein needs in critically ill obese indi-
viduals have undergone several revisions within the past decade. Current guidelines
are still based primarily on expert consensus and low-grade evidence. Further revi-
sions to predictive equations can be expected as this body of evidence continues to
evolve.
Indirect calorimetry (IC) is heralded as the gold standard for measuring energy
needs. There are several indications for indirect calorimetry (see Table 29.1).
Particularly, obese critically ill patients may benefit from IC as predictive equations
for this population are problematic. However, use of IC remains low, 0.8% of avail-
able cases [7]. Cost and lack of trained staff to conduct the measurement remain
major barriers to implementation of this technology in clinical practice. When IC is
available, the American Society for Parenteral and Enteral Nutrition (ASPEN) and
Society of Critical Care Medicine (SCCM) recommend targeting enteral nutrition
(EN) support at 65–70% of measured energy needs in order to promote steady
weight loss [2]. As energy needs change with clinical condition progression, the IC
measurement should be repeated as regularly as is feasible.
Predictive equations for critically ill obese patients are designed to provide hypo-
caloric, high-protein nutritional regimens with the goal of steady weight loss and
positive nitrogen balance. Hypocaloric feeding should be used with caution in
patients who have renal or hepatic function impairment.
When IC is not available, ASPEN and SCCM recommend targeting nutrition sup-
port regimens at 11–14 kcal/kg actual body weight for BMI between 30 and 50 kg/m2
and 22–25 kcal/kg ideal body weight for BMI > 50 kg/m2 (Table 29.2) with concurrent
29 Nutritional Support in the Critically Ill Obese Ventilated Patient 283
Table 29.1 Indications and contraindications for IC measurement [8]

Contraindications or reasons to delay
Indications for IC measurement IC measurement
• Acute or chronic respiratory syndrome • FiO2 greater than 60%
• Large or open wounds • Acute changes in ventilation
• Trauma within 1–2 h of the study
• Multi-organ failure • Excessive moisture in the circuit
• Post-op transplant • Inhaled nitric oxide or anesthetic
• Sepsis, SIRS gas delivery
• Use of sedation or paralytics • Patient instability
• Malnutrition with altered body composition – Hemodynamics
– Obesity – Body temperature
– Underweight – Agitation
– Ascites – PEEP > 16 cm H2O
– Peripheral edema – Painful procedure within the
– Limb amputation hour prior to the study
• Failure to respond to nutrition support based on
– General anesthesia 6–8 h
predictive equations
before study is completed
• Evaluation of whether under/overfeeding is
contributing to metabolic or respiratory distress – Hemodialysis 3–4 h before the
study is completed
– Nursing care cannot be avoided
during the study
• Leak in system > 1 L/min
Table 29.2 Weight-based BMI range Equation to estimate daily energy requirement

equations for estimating 30–50 kg/m2 11–14 kcal/kg actual body weight
energy requirements for
> 50 kg/m2 22–25 kcal/kg ideal body weight
various BMI ranges [2]
Table 29.3 Weight-based BMI range Equation to estimate daily protein requirement

equations for estimating 30–40 kg/m2 2.0 g protein/kg ideal body weight
protein requirements for
≥40 kg/m2 Up to 2.5 g protein/kg ideal body weight
various BMI ranges [2]
protein provision in a range from 2.0 g/kg ideal body weight for BMI 30–40 kg/m2 up
to 2.5 g/kg ideal body weight for BMI ≥ 40 kg/m2 (Table 29.3) [2].
Early enteral feeding is a well-established practice in critical care. ASPEN and
SCCM recommend initiating EN within 24–48 h in critically ill patients who are
unable to maintain volitional intake, provided that the patient is hemodynamically
stable. In the presence of a functional gastrointestinal tract, EN is always preferred
as it provides many physiologic and cost benefits over parenteral nutrition (PN) [2].
Until recently, meeting the correct ratio of energy and protein for patients on
hypocaloric, high-protein feeds required the addition of protein modulars, as the
ratio of calories to protein in most standard enteral formulas was designed for the
normal-weight patient population. Within the past 5 years, two formulas have
been developed for use in the critically ill obese population, Peptamen Bariatric
(Nestle) and Vital High Protein (Abbott). Both feature an energy-to-protein ratio
that meets the needs of most patients with a BMI between 30 and 40 kg/m2 with-
out the use of additional protein modulars. Both of these formulas are peptide-
based, which may not be necessary for critically ill patients; however, the
practicality of providing a ready to hang formula as opposed to a standard formula
with additional protein modulars often outweighs the lack of indication for a pep-
tide-based formula [2].
Standard practice for any hospitalized patient receiving EN therapy includes
monitoring of energy and protein provision, fluid status, weight, stooling patterns,
electrolytes, glycemic control, and micronutrients for long-term nutrition support
patients. Obese critically ill patients are predisposed to metabolic derangements and
should be closely monitored for hyperglycemia, hyperlipidemia, fluid overload, and
hepatic fat accumulation [2]. Adequacy of protein provision can be monitored via
nitrogen balance studies, provided that confounding losses from large wounds or
drains are absent or quantifiable. Appropriate energy provision can be confirmed
with repeat IC measurements.
Patients who have undergone bariatric surgery are at risk for malabsorption and
micronutrient deficiencies. These patients require lifelong daily micronutrient sup-
plementation at twice the standard dose and routine biochemical monitoring of vita-
min and mineral levels [9]. Bariatric and standard enteral formulas contain
insufficient levels of vitamins and minerals to meet these increased needs. Additional
supplementation via the parenteral route would not require an increase from the
standard dose, as the gastrointestinal tract is bypassed, and therefore, malabsorption
is not a concern.
Initial enteral access is often achieved through a temporary nasoenteric feeding
tube. If a patient requires enteral feeding for longer than 4 weeks, long-term surgi-
cal or endoscopic access should be considered. Selection of the device (gastros-
tomy, jejunostomy, gastrostomy-jejunostomy) and method of placement should
meet the individualized needs of the patient [9]. Patients who have undergone a
Roux-en-Y gastric bypass may tolerate gastrostomy placement into the remnant
stomach without risk of aspiration. Jejunostomy tubes may be more appropriate for
patients who have had a sleeve gastrectomy; however, gastric feeding has been
reported successfully. Special consideration must be taken to properly secure the
enteral access device, as dislodgement is an increased risk in patients with a large
pannus [9].
EN is the preferred method of nutrition support, but there are certain conditions,
such as gastrointestinal ischemia, intestinal obstruction, intractable vomiting and/or
diarrhea, paralytic ileus, and any other situations where gastrointestinal rest is
desired and where enteral feeding may not be possible [9]. In this case, PN may be
initiated but only if PN support is planned for greater than 7 days. In general, a per-
cutaneously inserted central venous catheter is placed into the superior vena cava to
provide parenteral nutrition. The components of PN include water, electrolytes,
vitamins, trace minerals, and energy-yielding macronutrients in the form of dex-
trose, amino acids, and fat emulsion [9]. All patients receiving PN should be moni-
tored daily for potential catheter-related infections, hepatobiliary complications
(steatosis and/or cholestasis), fluid overload, hypercapnia, hyperglycemia, and/or
29 Nutritional Support in the Critically Ill Obese Ventilated Patient 285
hypertriglyceridemia [2, 9]. Attention should also be paid to the rate of PN advance-
ment, weight changes (not masked by fluid shifts), and nutrition adequacy.
The target blood glucose range for critically ill patients is 140–180 mg/dL, and
to prevent hyperglycemia, the carbohydrate (dextrose) content of PN should not
exceed 7 g per kg body weight per day [9]. In addition, to prevent hypertriglyceri-
demia and associated complications (possibly pancreatitis, immunosuppression,
and altered pulmonary function), the lipid content of PN should not exceed 1.0 g per
kg body weight per day [10]. If serum triglyceride levels exceed 400 mg/dL but not
greater than 500 mg/dL, then intravenous fat emulsion should be dosed at the mini-
mum amount required to prevent essential fatty acid deficiency (typically 250 mL
20% lipid given once to twice per week) [10]. If serum triglyceride levels exceed
500 mg/dL, daily fat emulsion should be discontinued until triglyceride levels are
below 500 mg/dL [10]. The electrolyte and micronutrient levels in parenteral
solutions should be adjusted based on laboratory values checked per hospital
protocols [9].
Given the benefits of EN over PN, repeated efforts should be made to transition
the critically ill obese patient to enteral feeding when clinically feasible. During the
transition, the amount of calories delivered by both EN and PN should not exceed
total target estimated needs. As tolerance to EN improves, the amount of PN calo-
ries should be decreased and eventually discontinued when EN therapy exceeds
60% of target calorie requirements [2].
Of concern in critically ill obese mechanically ventilated patients is obesity
hypoventilation syndrome, characterized by low blood oxygen (pO2 < 75 mmHg)
and high blood CO2 (pCO2 > 45 mmHg) levels, and about 10–20% of patients with
obesity are presumed to have this condition [4]. In patients with respiratory failure,
who may be prone to CO2 retention, current guidelines stress the importance of
avoiding overfeeding (i.e., nutrition support energy provision exceeds energy
requirements) due to the risk of hypercapnia [2]. Overfeeding promotes lipogenesis,
a metabolic process that produces significant CO2. Also of concern in this popula-
tion is fluid overload, as extreme obesity tends to increase circulating blood volume
and possible cardiovascular alterations that can impair fluid balance [4]. It is also
recommended that energy-dense EN formulas (providing 1.5–2 kcal/mL) be con-
sidered for patients with acute respiratory failure, especially if they are in a state of
volume overload and require fluid restriction [2]. Lastly, current guidelines also
recommend serum phosphate levels be monitored when nutrition support (EN or
PN) is initiated in the ICU patient with pulmonary failure. Hypophosphatemia may
contribute to respiratory muscle weakness, so close monitoring and prompt reple-
tion are needed to optimize respiratory function in ventilated patients [2].
Conclusion
Critically ill obese mechanically ventilated patients are at risk for chronic
disease-related malnutrition and metabolic alterations. When providing nutrition
care to this population, proper evaluation and documentation of nutrition assess-
ment factors of concern will help guide the nutrition intervention. The goal of
nutrition support for this population is to provide high-protein, hypocaloric
feeding, preferably via enteral access, in an effort to preserve lean body mass,
promote lipolysis, and minimize the metabolic complications of overfeeding.
29.3 Key Recommendations
1. In nutrition assessment, evaluate for and document central adiposity, metabolic

syndrome, and sarcopenia.
2. Use indirect calorimetry to assess energy needs. If indirect calorimetry is unavail-
able, use suggested weight-based equations based on BMI range.
3. Enteral nutrition is preferred over parenteral nutrition support.
4. Nutrition support regimen should not exceed 65–70% of target energy needs as
measured by indirect calorimetry.
5. Nutrition support regimen should provide high protein in a range from 2.0 g
protein per kg ideal body weight per day for patients with BMI of 30–40 kg/m2
up to 2.5 g protein per kg ideal body weight per day for patients with BMI greater
or equal to 40 kg/m2.
References
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critically ill patients. Crit Care Nurse. 2015;35(4):24–30.
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nutrition support therapy in the adult critically ill patient—Society of Critical Care Medicine
(SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN). JPEN J Parenter
Enteral Nutr. 2016;40(2):159–211.
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care in the intensive care unit. JPEN J Parenter Enteral Nutr. 2011;35(5 suppl):21S–8S.
4. Dickerson RN. Management of the obese patient. In: Seres DS, Van Way CW, editors. Nutrition
support for the critically ill. Cham: Humana Press; 2016. p. 173–93.
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6. McGhee B, Roosevelt H. Application of ultrasonography for measuring change in lean body
mass in acute care. Support Line. 2015;37(3):3–5.
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ger the orphan of energy estimation. Nutr Clin Pract. 2015;31:30–8.
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Long-Term Outcomes
After Mechanical Ventilation 30
Rose Franco and Rahul Nanchal
30.1 Introduction
Twenty-five years ago, the standard measure for outcomes after critical illness was the
28-day all-cause mortality. Long-term outcomes were a nascent field of investigation;
the first organized report of 1-year outcomes after acute respiratory distress syndrome
(ARDS) was published in the year 2003 [1]. In the past decade, the expanding arma-
mentarium of therapies for critical illness and refinements in understanding its patho-
physiology have led to improved survival rates but have created an increasing number
of survivors that suffer from the long-term sequelae of critical illness. Manifestations
of these long-term outcomes span a constellation of physical, cognitive, and mental
domains and are collectively termed post-intensive care syndrome (PICS). Caregivers
of survivors may be overwhelmed with this drastic life-changing event and can become
affected with mood disorders, a phenomenon known as PICS-Family (PICS-F) [2, 3].
Close to two million hospitalizations each year in the USA alone are for acute
respiratory failure, and approximately half require invasive mechanical ventilation
[4]. Although steady improvements have been observed in short-term mortality rates,
likely secondary to advances in general ICU supportive care, survivors remain at
heightened risk for late mortality and morbidity. Survivors of acute respiratory dis-
tress syndrome (ARDS) typically have prolonged ICU stays and have been the most
extensively studied group. However, recent additional studies on other at risk groups
of patients such the elderly, survivors of sepsis and those requiring prolonged
mechanical ventilation not ARDS related have slowly emerged. This chapter will
review the physical, neurologic, and neurocognitive outcomes for survivors of criti-
cal illness and touch on the impact on caregivers. We will examine predictors of poor
R. Franco, M.D. • R. Nanchal, M.D., M.S. (*)

Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin,
Milwaukee, WI 53226, USA
e-mail: Rnanchal@mcw.edu

288 R. Franco and R. Nanchal
long-term outcomes (patient characteristics, burden of comorbidities, and ICU prac-

tice patterns). Lastly we will review the current state of research into interventions
that might change the outcomes and quality of life for patients and their families.
30.2 Impact on Health-Related Quality of Life
Health-related quality of life (HRQOL) measures have emerged as important

patient-centric metrics of recovery post critical illness. HRQOL is a multidimen-
sional concept that includes domains pertinent to physical, mental, emotional, neu-
rocognitive, and social functioning. These domains are determined through the
administration of questionnaires and comparison with published normative data.
The Medical Outcomes Study 36-Item Short Form Health Survey, Standard Form
(SF-36) is the most commonly used tool to measures HRQOL is survivors of critical
illness. SF-36 comprises 36 items and measures both physical and mental health.
The first report that prospectively evaluated the link between pulmonary dysfunc-
tion and functional disability in ARDS survivors was published by McHugh et al.,
who noted that scores for the Sickness Impact Profile (a crude quality of life mea-
sure) significantly improved 3 months post extubation but appeared to plateau there-
after up to 1 year. They also found that only a small proportion of the decreased
physical functioning could be attributed to pulmonary dysfunction [5]. Weinert
et al. used SF-36 in a small cohort of acute lung injury survivors 6–41 months post
hospitalization to evaluate HRQOL [6]. They reported decrements in all domains
compared to the general population with significantly more impairment in social
functioning and mental health domains than those with chronic medical disorders.
Several investigators across continents have subsequently demonstrated reduced
HRQOL in survivors of critical illness; most cohorts received mechanical ventila-
tion while hospitalized [7–11]. Although there appears to be a long-term cost to an
acute episode of severe critical illness, other factors such as age, pre-illness func-
tional status, chronic organ dysfunctions, and physiological reserve likely play an
important role in determining post-illness trajectory of health and quality of life
[12–15]. HRQOL comparisons of ARDS survivors to patients with chronic respira-
tory illnesses such as cystic fibrosis have suggested global physical functioning
rather than pulmonary dysfunction as the etiology of decreased scores [16].
The lingering physical, emotional, cognitive, and social impacts of critical ill-
ness are key factors leading to reduced quality of life. Common physical manifesta-
tions of critical illness-related sequela include heterotopic ossifications, alopecia,
tracheal stenosis, ischemic digits, striae, hearing loss, neuropathy, and muscle atro-
phy leading to weakness, frozen joints, and contractures. Equally important aspects
of reduced HRQOL are mental health issues and neurocognitive impairment. These
brain impairments may be slow to recover and more importantly lead to residual
permanent disability [17–20].
Prolonged mechanical ventilation is a significant risk for post critical illness physical
impairment and mortality [8, 21, 22]. The major factor affecting HRQOL in the initial
months after critical illness requiring prolonged mechanical ventilation appears to be
diminished physical capacity as a consequence of ICU-acquired weakness. Longer-term
30 Long-Term Outcomes After Mechanical Ventilation 289
studies of functional outcomes demonstrate that survivors even after 5 years have not
returned to their normal predicted level of functioning and continue to experience new
or persistent physical and neuropsychological impairments [19]. A 5-year cohort study
of survivors of critical illness reported by Cuthbertson et al. found that during the 5 years
after survivorship, the cumulative quality-adjusted life years remained significantly
lower than that expected for the general population and suggested, based on these find-
ings, survivors of critical illness be considered to have a lifelong diagnosis of critical
illness associated with ICU admission with subsequent associated excess mortality,
morbidity, and the requirement for ongoing health-care support [23]. Survivorship from
critical illness may result in frequent physician visits, assistance with cares, and even
continuous skilled nursing care. This creates additional health-care-associated costs that
are on par with that seen with chronic disease states [19, 23, 24].
Lone et al. studied over 5500 survivors of acute illness and over 5 years after
initial hospital discharge compared those requiring ICU care to those who did not.
At 5 years, the ICU cohort had higher mortality, used more hospital resources, and
had 51% higher mean 5-year hospital costs [25]. Excess resource use and mortality
was greatest for younger patients without significant comorbidity [26]. Additional
collateral costs, financial due to lost income and reductions in HRQOL for both
survivors and their caregivers, are likely underreported and frequently under-recog-
nized by the health professionals caring for them [27–31].
Thus, our understanding of HRQOL post ICU has progressed beyond simple
correlations of pulmonary function to quality of life to novel risk factors and the
spectrum of long-term functional and neurocognitive limitations that lead to subse-
quent increased costs and health-care utilization.
Subsequent sections in this chapter detail physical, neurocognitive, and caregiver
burdens of survivorship from critical illness.
30.3 Physical Manifestations
Physical limitations are common after critical illness. Some are permanent. See
Table 30.1.
30.3.1 Pulmonary Function
ARDS survivors are the best-studied cohort of mechanically ventilated patients in

terms of subsequent pulmonary function and outcomes. Most studies report good
pulmonary recovery with normal or near normal function achieved by 6 months to
1 year after the acute episode [1, 19]. Pulmonary function tests often demonstrate
mild restriction or obstruction with an associated decreased diffusion capacity [32,
33]. When mild pulmonary function abnormalities are present beyond 1 year fol-
lowing the acute illness, they are associated with decreased HRQOL and in some
studies are likely to remain permanent [9]. However, this mild degree of pulmonary
dysfunction does not explain functional impairments in survivors [34]. In fact most
survivors do not attribute their reduced quality of life and physical compromise to
Table 30.1 Complications Physical

of critical illness. Weakness due to critical illness neuropathy/myopathy
Contractures/frozen joints
Ischemic digits
Residual renal impairment
Post-inflammatory pulmonary fibrosis/bronchiectasis
Ventilator dependence
Tracheal stenosis
Scars (cosmesis)
Alopecia
Heterotopic ossifications
Striae
Hearing loss
Taste changes
Cognitive
Attention deficits
Executive function impairments
Worsening dementia
Psychological
Depression
Anxiety
Post-traumatic stress disorder
Addiction (narcotics/sedatives)
Financial
Uncovered/underinsured cost of care acute care and rehab
care for first year
Lost income disabled from occupation
Delay in income disability support from all work
Cost of additional home assistance or in home skilled nursing
care
Ongoing therapy costs
Assist devices (ventilator, bed, canes, etc.)
Family loss of income (caregiver)
breathing difficulties [19, 35]. Lung imaging studies of ARDS survivors demon-
strate reticular patterns, pulmonary fibrosis, and other parenchymal changes such as
interlobular septal thickening which are more pronounced in the nondependent lung
regions. These imaging abnormalities persist even at 5 years post ARDS; however,
they are minor and constitute less than 10% of the lung parenchyma [36–38].
30.3.2 Neuromuscular Dysfunction
Weakness associated with critical illness (or ICU-acquired weakness (ICU-AW))

was recognized as one of the major sources of morbidity and mortality even as long
ago as the late 1800s by Sir William Osler [39]. Studies have demonstrated that
muscle weakness develops even within the first hours after mechanical ventilation
is initiated [40]. ICU-AW is a significant morbidity affecting up to one third of criti-
cally ill and may exceed 50% of those with ARDS and multi-organ failure [41].
Bolton et al. in 1984 reported on five ventilator-dependent patients who by electro-
physiologic testing demonstrated a primary axonopathy which manifested as a
mixed sensorimotor neuropathy [42]. An extensive meta-analysis of 24 studies uti-
lizing all available testing (electromyogram, nerve conduction studies, and/or mus-
cle and nerve histology) of 1421 critically ill patients found that 46% of patients
demonstrated critical illness neuromyopathy [43]. ICU-AW is a major factor inhib-
iting the ability to liberate patients from mechanical ventilation and when present is
associated with prolonged mechanical ventilation, longer ICU and hospital stays,
and higher overall health-related costs as well as increased risk of death. It is also a
key driver of long-term functional limitations experienced by survivors [44–48].
An international working recently proposed a simple and clinically relevant clas-
sification system that uses basic clinical evaluations and bedside testing. It catego-
rizes ICU-AW as a broad diagnosis of exclusion. The basic tenets include onset of
diffuse, symmetrical generalized weakness during critical illness, ventilator depen-
dence, and bedside muscle testing that demonstrates weakness (Medical Research
Council or MRC Score) [49]. They further defined, critical illness polyneuropathy
as ICU-AW in conjunction with electrophysiologic testing consistent with a senso-
rimotor axonal polyneuropathy. Finally they proposed using the term critical illness
myopathy for those with ICU-AW and electromyographic or muscle biopsy proven
myopathic features; presence of both muscle and nerve dysfunction was classified
as critical illness myoneuropathy [50].
30.3.3 Etiology of Critical Illness Polyneuropathy and Myopathy
Table 30.2 lists factors that contribute to the development of critical illness-
associated polyneuropathy and myopathy.
Many investigators have reported a strong association of sepsis and systemic
inflammatory response syndrome with the development critical illness polyneurop-
athy and myopathy [49]. Microcirculatory changes may create relative ischemia of
the tissue and result in axonal injury and degeneration [51].
Table 30.2 Sources of Sepsis/SIRS

critical illness Glucose metabolism derangement
polyneuropathy and
Medications
myopathy
Corticosteroids
Neuromuscular blockers
Synergistic effects with other medications
Inactivity/disuse atrophy
Catabolism
Channelopathy
Elevated glucose levels can negatively impact mitochondrial function and there-
fore contribute to oxidative stress and cell death [52]. Hyperglycemia, in both surgi-
cal and medical critical illness, has been associated with ICU-acquired weakness.
Van Den Berghe et al. demonstrated a significant reduction in the number of patients
with neurophysiologic testing confirmed critical illness polyneuropathy with tight
glycemic control [53–55]. However, in a large well-designed randomized trial,
aggressive glucose control was shown to increase the risk of death in critically ill
patients; therefore, intensive insulin therapy solely for the purpose of preventing
critical illness polyneuropathy is not recommended [56].
30.3.4 Medications in Critical Illness Linked to Neuromuscular

Dysfunction
It is difficult to replicate the true risk associated with specific drugs and drug-drug
interactions likely because of confounding influence of other conditions such as
renal replacement therapy, nutritional deficiencies, liver dysfunction, and medica-
tions that either directly or indirectly affect muscle and nerve function like amino-
glycosides and vasopressors in those with systemic inflammatory response syndrome
and severe sepsis.
In animal models, administration of corticosteroids can produce selective muscle
atrophy, particularly of fast-twitch fibers [57]. Critical illness myopathy is a non-
necrotizing diffuse process with fatty degeneration of the muscle fibers, fiber atro-
phy, and fibrosis [58]. In studies of the critically ill, where a muscle biopsy was used
as the gold standard, the incidence is reported anywhere from 48 to 96% [59]. These
lesions have also been linked to corticosteroids and paralytic exposure [58]. Thick-
filament myopathy is a selective loss of myosin filaments seen with exposure to
corticosteroid or paralytic agents and immobility [60]. Acute necrotizing myopathy
microscopically characterized by extensive myonecrosis with vacuolization and
phagocytosis of muscle fibers has also been linked to use of corticosteroids and
paralytic agents and multisystem organ dysfunction [61].
In an ARDS study with ongoing evaluations over 1 year, the investigators
reported that those patients who received systemic corticosteroids were more likely
to have an associated decrease in 6 min walk distance at 3 months and diminished
proximal weakness of the shoulder and hip girdle regions [1]. In a randomized study
of corticosteroids for persistent ARDS, there was no improvement in 60-day mortal-
ity, but there were cases of neuromyopathy reported only in treatment arm receiving
methylprednisolone [62].
Neuromuscular blockers, given to help with ventilator synchrony in ARDS, were
traditionally considered a source of acquired neuromuscular weakness, but a well-
designed prospective trial by Papazian et al. found that there was no added risk
above that created by the etiology of the ARDS [63]. Further, the arm receiving
neuromuscular blockade had significantly better survival thought to be related to
attenuation of ventilator-induced lung injury (VILI) through enhanced patient-
ventilator synchrony. The combined exposure to neuromuscular blockers with
systemic corticosteroids does appear to result in higher likelihood of residual neu-

romuscular weakness. Behbehani et al. found a threefold increase in the risk for
significant weakness in patents with status asthmaticus who received treatment with
both paralytics and systemic corticosteroids (10% vs. 30% for those receiving both
agents) [64].
30.3.5 Role of Immobility and Other Factors
Factors that contribute to the development of myopathy in critical illness include

inactivity, catabolism, inflammation, and derangement of membrane excitability.
Lack of movement in the critically ill patient stimulates protein loss from the
muscle beds. The role of nutrition in reducing the muscle loss and myopathy remains
in question. Animal models suggest that rather than the nutritional status being a
major factor, it is in fact the disuse of the muscle group that has the most deleterious
impact [65]. Critical illness particularly sepsis rapidly induces a catabolic state with
skeletal muscle wasting. Depressed protein synthesis and elevation of protein break-
down relative to protein synthesis resulting in a net catabolic state resulting in early
skeletal muscle wasting in critically ill patients were demonstrated in an elegant
study by Puthucheary et al. [66]. These findings were more severe in patients with
multiple organ failure as compared to single organ failure. Other measures demon-
strating a net catabolic state such as urinary nitrogen loss, low protein, and gluta-
mine and DNA levels in muscle biopsies and upregulation of calpain and ubiquitin
proteolytic pathways as well as increased apoptosis have been documented [67].
Acquired channelopathy may also be a significant contributor to the pathology of
myopathy in critical illness. Allen et al. reported on acquired sodium channel dys-
function resulting in alteration in muscle-fiber excitability [68].
An important facet of failure to wean from mechanical ventilation and myopathy
is diaphragmatic dysfunction related to mechanical ventilation and critical illness.
The diaphragm is exquisitely susceptible to rest and the effects of sepsis on its func-
tion [69, 70]. Within hours of initiation of controlled ventilation, there is objective
evidence of muscle breakdown and atrophy of the muscle [71, 72]. Preserving dia-
phragm function through selection of spontaneous ventilation modes would seem to
intuitively counteract these effects; yet to date no study has shown this as a tangible
reality.
30.3.6 Additional Physical Morbidities
Entrapment Neuropathy: The Toronto ARDS Outcomes study reported 6% preva-

lence of peroneal and ulnar nerve palsy. The presence of these complicates rehabili-
tation and prolongs time to recovery [1]..
Heterotopic Ossification: Deposition of para-articular ectopic bone has been
reported in the setting of trauma, burns, pancreatitis, and ARDS. Development of
this condition is associated with paralysis and prolonged immobilization. In the
Toronto ARDS Outcomes Study, the prevalence was 5% [1]. This condition while
remediable with surgical intervention, if left undetected/treated, can also hamper
patients’ recovery.
Cosmesis/Scars: The physical transformative nature of critical illness which may
include scars from laparotomy, burns, striae from volume overload, tracheostomy,
and central line scars have been reported by survivors to contribute to social isola-
tion and sexual dysfunction [1].
30.4 Neurocognitive and Psychiatric Manifestations
Hopkins et al. in 1999 in an ARDS cohort first reported cognitive impairment in

30% of patients at 1 year [73]. Longer-term studies suggest that some of this may be
permanent with some reporting deficits out to 6 years after the acute illness [74].
While initial improvements can occur within the first 6–12 months, many continue
to have significant chronic impairments years after discharge [75]. A prospective
study of long-term effects after ICU care involving mechanical ventilated patients
who prior to their illness did not have known cognitive impairments demonstrated
neurocognitive impairment in 11 of 34 (32%) patients that persisted for at least
6 months after illness. The areas with most involvement were the psychomotor
speed, visual and working memory, verbal fluency, and visuo-construction [76, 77].
The etiology of cognitive impairment in critical illness is complex. Many factors
such as hypoxemia, hypotension, delirium, glucose dysregulation, medication
effects of sedatives and hypnotics, and the direct effects of sepsis and systemic
inflammatory response can potentially serve as the source or contributor to brain
injury and cognitive impairments in critical illness. See Table 30.3.
Hypoxemia: Hopkins et al. found mean oxygen saturation (Spo2) and the extent
of hypoxemia correlated significantly with neurocognitive dysfunction [73].
Hypoxemia has been associated with cortical atrophy and ventricular enlargement
(suggesting neuronal loss) [78].
Hypotension: The contribution of low blood pressure is less clear. A mean blood
pressure <50 mmHg and memory impairment at hospital discharge has been
reported. Others have reported only a modestly correlated impairment with duration
of hypotension and this does not persist beyond 1 year of follow-up [79].
Delirium: Delirium affects 60–80% of ventilated patients and may go unrecog-
nized when there is not systematic screening [80]. Delirium has emerged as a strong
risk factor for ICU and hospital length of stay and increased cost as well as long-
term neurocognitive impairment and death [20, 81–84].
Table 30.3 Sources of Hypoxemia

cognitive impairment Hypotension
Sepsis/SIRS
Delirium
Glucose dysregulation
Sedatives/analgesics
Glucose Dysregulation: Blood glucose dysregulation and neurocognitive func-

tion have been found to have an important association. In a study of ARDS survi-
vors, the presence of moderate hyperglycemia while in ICU was associated with
poorer neurocognitive outcomes [85]. Hypoglycemia was also associated with three
times the risk for depression in patient with ARDS [86].
Sedatives/Analgesics: The study of impact of agents including sedatives, narcot-
ics, and anesthetics on long-term neurocognitive function has not provided strong
evidence of causality. There may be some populations that are more at risk such as
the elderly and those with prior neurocognitive impairment [87, 88]. In a prospec-
tive controlled trial of mechanically ventilated patients, there were no differences
seen in long-term cognitive outcomes when daily sedation interruptions were insti-
tuted [89].
Systemic Inflammatory Response Syndrome and Sepsis: The brain is at risk from
both the direct deleterious effects on the microcirculation from the cytokines (IL 1
and IL 6) as well as the direct effects on neuronal function that these cytokines may
have. Animal models have demonstrated excess levels of these cytokines in the pre-
frontal and hippocampal areas and impact on learning and memory. Long-term out-
comes study of sepsis survivors demonstrates impairments that persist years after
hospital discharge [90–92].
The cumulative effect of these insults may result in brain damage and combined
with the psychological reaction to the stresses of critical illness, medications, pain,
altered sensory inputs, and an unfamiliar environment may contribute to develop-
ment of neuropsychiatric sequelae.
The impact of critical illness and neurocognitive decline in the elderly is an area
of study that could provide significant insight for providers and patients and their
families when grappling with the questions of critical illness care and the after care.
A longitudinal study in older adults without premorbid neurocognitive impairments
or dementia using objective measures of neurocognitive function demonstrated that
those requiring acute care or critical illness hospitalization had a greater decline in
neurocognitive function and new incident dementia compared to those who were
not hospitalized [93].
Iwashyna et al. used the Health and Retirement Study (HRS) database to study
over 1100 older Americans 7 years prior to and 8 years after critical illness. They
found that severe sepsis was three times more likely to result in moderate to severe
cognitive impairments that would add substantial health and social costs for the care
of the aged. The cognitive impairments were a key factor in the inability to continue
to live independently [18].
Psychiatric disorders are common among survivors of critical illness. Depression
and anxiety in survivors range in prevalence from 10 to 58% [94].
In a systematic review of psychiatric morbidity related to ARDS survivors in
2008 [95], Davydow et al. reported a point prevalence of clinically significant
depression ranging from 17% in a prospective study [96] to 43% in a retrospective
study [6]. Age, sex, and severity of illness were not predictive of depression, but
early post-ICU depressive symptoms were strongly predictive of reduction in qual-
ity of life and further depressive symptoms [26].
In ARDS survivors the prevalence of depression is higher compared to that in the

general critically ill population. Hopkins et al. found that the risk factors for depres-
sion included duration of mechanical ventilation, ICU length of stay, sedation, alco-
hol dependence, female gender, and younger age [97]. They also reported on
predictors of ongoing anxiety at 1-year post ARDS finding more risk with a higher
lung injury score and with a longer duration of mechanical ventilation.
More recently focus has turned to recognizing the development of post-trau-
matic stress disorder (PTSD) in those surviving critical illness after the report in
1998 by Schelling et al. In this study of 80 survivors, 28% met criteria for diagno-
sis of PTSD up to 4 years after the acute illness [98]. PTSD usually develops fol-
lowing an event that triggers serious personal threat in which the subject experiences
helplessness and intense fear. The symptoms are grouped into three clusters:
hyperarousal symptoms, intrusive recollections, and avoidance/numbing symp-
toms. In another study, Kapfhammer et al. found 44% of ICU survivors at dis-
charge from hospital had PTSD, and 24% still had symptoms 8 or more years later
and that pre-existing psychopathology, higher benzodiazepine use, memories of
frightening/psychotic experiences in ICU, and the absence of any ICU memory
were risk factors for post-ICU PTSD [99]. Disturbing dreams and persecutory
delusions experienced as part of delirium are also important risks for long-term
development of PTSD [100].
Factual memories do not protect survivors from )PTSD. Myhren et al. evaluated
194 survivors and found 27% had post-traumatic stress, and the predictors for PTSD
were higher education, optimism, factual recall, and memory of pain [28].
Pre-existing psychiatric disease may predispose some to ICU-related PTSD).
Patel et al. prospectively assessed 160 ICU survivors (a mix of veterans and civil-
ians) over 1 year after acute illness. Pre-existing PTSD and depression were strong
markers for ICU-related PTSD risk [101]. Interventions to prevent or reduce psy-
chological sequelae are being investigated. Jones et al. in a randomized controlled
trial reported that ICU diaries may reduce the incidence of PTSD. They reported
only 5% of their intervention cohort had clinically significant PTSD compared to
13% of controls [102]. The greatest benefit came from those who experienced
symptoms earlier.
30.5 R
isk Factors for Poor Functional Outcomes After Critical
Illness
The degree of functional impairment prior to the critical illness, the age of the
patient, and the severity of the critical illness are all factors that have substantial
impact on predicting long-term outcomes. See Table 30.4.
Chelluri et al. reported on 817 patients who were studied for 1 year after requir-
ing prolonged mechanical ventilation. Surviving to discharge was more likely if
they had less comorbidity, lower severity of illness scores, and better functional
status prior to critical illness. At 1 year follow-up, 57% still needed caregiver
assistance [103].
Table 30.4 Risk factors for Age

poor functional outcomes Pre-event health and functional status
Severity of the critical illness
Length of ICU stay
Duration of ventilator support
Iwashyna et al. reported that after critical illness, neurocognitive and physical
decline persisted for at least 8 years after an episode of sepsis, and this impairment
altered patients’ ability to live independently. In fact even at 8 years post event, the
likelihood of significant cognitive impairment was fourfold higher (32%) than
matched controls for the elderly [18].
Increased age by itself may not have as much of an impact on outcomes as sug-
gested by some studies. There results on outcome of mortality are mixed. In a study
of 484 patients, Khouli et al. reported that at 6 months post discharge, one third had
died. Predictors of death at 6 months were number of days of physical health not
good in the 30 days prior to admission, a higher Acute Physiology and Chronic
Health Evaluation (APACHE) II score, and chronic pulmonary disease. The oldest
survivors had the worse health-related quality of life [15]. Unroe et al. studied 126
patients who required prolonged mechanical ventilation (more than 21 days of ven-
tilator support). Older age and more comorbid conditions predicted the need for
discharge to a post-acute care facility. This single-center cohort contained on aver-
age sicker people with most not working, retired or disabled at time of illness, and
with two comorbid conditions on average. At 1 year only 11 people (9%) were
without functional dependence. The mean cost of care per patient was 306, 135 US
dollars (SD: 285,467), and the total cohort cost of care was 38.1 million, with
3.5 million per independently functioning survivor at 1 year [21]. For this same
cohort at the time of placement of tracheostomy, Cox et al. assessed expectations
from both physicians as well as surrogates for patients (often family). The cohort of
126 had only 11 (9%) who were alive and independently functioning at 1 year. The
patient surrogates projected survival at 93% and functional status and quality of life
at 71% and 83%, respectively. Physicians also overestimated survivorship at 43%
but were more realistic on functional status and quality of life (6% and 4%). Yet
only 26% of surrogates reported that the physicians had discussed what to expect
for survival, general health, and caregiving needs [104].
30.6 Caregiver and Family Burden
Caregiver burden has been studied over the last several decades, and any summary
chapter on the long-term outcomes after critical illness would fall woefully short
without consideration of this area. There is a physical and psychological toll that
begins as soon as their family member becomes critically ill. Bedside vigils fol-
lowed by assuming almost all responsibility for medical and psychological care for
new more complex needs are a burden that without assistance could cause complete
collapse of their health and well-being as well as that of the family unit. PTSD
symptoms are common with reports ranging from 13 to 56% [105]. A task force of
the Society of Critical Care Medicine in 2010 that met to explore these issues for
family and patients proposed the term post-intensive care syndrome-family (PICS-F)
and recommended that active assessment for and initiation of interventions to
improve outcomes begin during the hospital stay [2, 3]. Based on the current evi-
dence, limitations in active communication and understanding during the hospital-
ization contribute to some of the ongoing stress and even development of PICS-F
[106]. Interventions trialed with some benefit include structured communication
and active involvement of the family with care decisions during hospitalization
[107] to setting up after ICU care clinics to address both patient and family needs.
Yet the best path forward is not entirely clear. A recent multicenter study of 286
critically ill patients using a nurse-led intensive follow-up versus usual care found
no difference in long-term outcomes with the nurse-led program yet costing signifi-
cantly more [108].
More than half of ICU survivors who needed prolonged mechanical ventilation
still required assistance of a family caregiver 1 year after their critical illness. This
caregiver status implies that the caregiver as well as the survivor has not returned to
full-time work status and the family unit suffers financial stressors as well as psy-
chological and physical stressors that come with the caregiver status. Griffiths et al.
reported a negative impact on family income by 33% of all patients at 6 months and
28% at 12 months [109]. Among all patients receiving care, 26% reported requiring
greater than 50 h a week. More than 70% of survivors of critical illness receive their
care from family members and as such are not compensated and are likely not in a
position where they can be relieved of their responsibilities regularly such as one
does in an structured care facility. As a result the caregivers have higher risk for
PTSD, emotional distress, depression, and anxiety [103, 104, 110].
30.7 Potential Strategies to Optimize Long-Term Outcomes
Appropriate rehabilitation post ICU stay requires attention. In systematic compara-

tive studies on rehabilitative interventions in the post-ICU patients, ICU diaries had
the best potential effectiveness in reducing PTSD for patients [111, 112]. While
structured nurse-supervised post-ICU care may be more resource draining without
clear benefits above usual care, a self-help manual with instructions for physical
therapy improved 6-month outcomes in physical function [113].
Based on the neurocognitive and physical residual impairments of critical ill-
ness, the next wave of research should focus on interventions to change these out-
comes. In fact, some of the currently accepted ICU practices may contribute to the
burden for rehabilitation. Sedating and “resting” the patient during the initial
period of critical illness very likely contribute to residual weakness at discharge.
The lighting, the sounds of the ICU, and care staff may contribute to delirium and
risk for psychiatric dysfunction. Some experts have commented that rehabilitation
should begin when the patient is admitted to the ICU. Early mobilization of the
critical ill may have a significant protective effect in reducing critical illness mor-
bidity related to weakness [114] especially when coupled with interruption in seda-
tion, delirium [115, 116]. The weight of evidence in favor of early mobilization is
such that the European Respiratory Society and European Society of Intensive
Care Medicine Task Force on Physiotherapy for Critically Ill Patients advocate for
mobilization and muscle training instituted early [117]. The use of paralytics, the
role of steroids, the control of glucose levels, and the ever present risk/benefit role
of sedatives and analgesics in preventing and controlling delirium are all areas of
investigation.
Ongoing collaborative multicenter interventional studies in critical illness
designed to study how we can improve the outcomes stated above are the current
priority for International Critical Care and Medical societies. As we learn more and
more about the care choices made for the patient with critical illness, the model for
best practices during the acute stay and the post-ICU care will undergo future trans-
formation that will lead to improvements in quality of life for patients and their
families as well as further improve the associated morbidity and mortality of surviv-
ing critical illness.
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doi:10.1002/14651858.CD010468.pub2.
113. Jones C, Skirrow P, Griffiths RD, Humphris GH, Ingleby S, Eddleston J, Waldmann C,
Gager M. Rehabilitation after critical illness: a randomized, controlled trial. Crit Care Med.
2003;31(10):2456–61.
114. Adler J, Malone D. Early mobilization in the intensive care unit: a systematic review.
Cardiopulm Phys Ther J. 2012;23(1):5–13.
115. Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, Taichman DB,
Dunn JG, Pohlman AS, Kinniry PA, Jackson JC, Canonico AE, Light RW, Shintani AK,
Thompson JL, Gordon SM, Hall JB, Dittus RS, Bernard GR, Ely EW. Efficacy and safety
of a paired sedation and ventilator weaning protocol for mechanically ventilated patients
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116. Schweickert WD, Pohlman MC, Pohlman AS, Nigos C, Pawlik AJ, Esbrook CL, Spears L,
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Index
A Acute respiratory failure (ARF), 139, 142,

Abdominal compartment syndrome (ACS), 67, 143, 207, 208
68, 71, 72 Adiposity, 46
definitions, 65, 66 Adjuvants
clinical features alpha-agonist, 115
hemodynamics, 67 gabapentinoids, 115
imaging, 68 ketamine, 114
laboratory, 68 magnesium, 115
physical examination, 67 Adult respiratory distress syndrome
symptoms, 67 (ARDS), 153
consequences, 69 clinical data, 160
definitions, 66 Air column width (ACW), 242
diagnosis, 68, 69 Airway passage, 51
etiologies, 67 Airway pressure release ventilation (APRV)
invasive mechanical ventilation advantages, 168
PEEP, 72 disadvantages, 168
plateau pressure, 72 fixed modes, 169
recruitment maneuvers, 72 in obese critical care patients, 168
tidal volume, 72 personalised modes, 169
ventilator mode, 71 pressure control ventilation, 168
management, 70 protective lung ventilation, 168
noninvasive ventilation, 71 sedation requirements, 168
obesity, 69 timing, 169
positioning, 72–73 treatment, 168
pulmonary physiology, 70 Airway resistance, 205
Absolute humidity, 217 Airway size, 152
Acetazolamide, 83 Alpha-agonist, 115
Acute exacerbations of COPD (AECOPD), Alveolar collapse, 52
230 Analgesia, 114, 115
Acute hypercapnic respiratory failure (AHRF) adjuvants
asthma, 232 alpha-agonist, 115
causes of, 229, 230 gabapentinoids, 115
contraindications, 230, 231 ketamine, 114
COPD, 230, 232 magnesium, 115
extra-pulmonary restrictive lung diseases, central adverse effects, 110
233 central neuraxial blocks, 117
indications, 230, 231 flupirtine, 114
non-CF bronchiectasis, 233 intraoperative non-opioid analgesic
OHS, 234, 235 regimen vs. fentanyl-based
Acute necrotizing myopathy, 292 analgesia, 112

Obese Patient, https://doi.org/10.1007/978-3-319-49253-7
308 Index
Analgesia (cont.) Cardiogenic shock, 61

intraperitoneal infusions, 117 Cardiovascular events (CVEs), 46, 47, 146
multimodal approach, 112 Central neuraxial blocks, 117
neurocognitive and psychiatric Central sleep apnea (CSA)
manifestations, 295 respiratory drive, 83
NSAIDs, 113 treatment, 83
paracetamol, 113–114 Cephalad displacement, 141
peripheral blocks, 116–117 Chemical control of breathing, 4–6
peripheral mechanisms, 110 in eucapnic obesity
postoperative complications, 109 chemosensitivity, 5
regional anesthesia, 116 compensatory mechanisms, 4
surgical site infusions, 117 external elastic loading, 4
Apnea-Hypopnea Index, 78 HOVR, 5
Apneic oxygenation, 103 with OSA, 6
Apnoeas, 152 without OSA, 4, 5
Apocynin, 159 in hypercapnic obesity, 6–8
Aspiration pneumonitis, 252 Chemosensitivity, 5–9
Assist control (AC), 201 Chest wall deformity, 233
Asthma, 232 Cheyne-Stokes breathing, 83
Atelectasis Chronic obstructive pulmonary disease
causes, 51–52 (COPD), 153
definition, 51 Chronic respiratory failure (CRF), 207, 209
meta-analysis, 53 Comorbidities
outcomes, 52 adiposity, 46
PEEP, 53 asthma, 47
predicted body weight formula, 53 cardiovascular events, 46, 47
prevention, 52 chronic kidney disease, 47
recruitment maneuvers, 53 chronic obstructive pulmonary disease, 47
tidal volume setting, 52 coronary artery disease, 47
treatment, 53 heart failure, 46
Atelectrauma, 153 hypertension, 46
Auto-titrating noninvasive ventilation, 271 left ventricular hypertrophy, 46
Average volume-assured pressure support microalbuminuria or proteinuria, 47
(AVAPS) mode, 81, 82, 169, 200 obesity hypoventilation syndrome, 47
obstructive and central sleep apnea, 47
percutaneous coronary intervention studies,
B 44, 45, 47
Barotrauma, 146, 148 PICO strategy, 44
Bedside test, 159 Sao Paulo Epidemiologic Sleep Study, 47
Bi-level positive airway pressure Sleep Heart Health Study, 48
(BPAP/BiPAP), 81, 82, 154, 194, Wisconsin Sleep Cohort Study, 47
200, 201, 207 Congestive heart failure (CHF), see Heart
devices, 202 failure
OHS (see Obesity hypoventilation Continuous positive airway pressure (CPAP),
syndrome (OHS)) 81, 82, 154, 194, 201, 252
respiratory mechanics and physiology, 207 treatment modality, with OSA, 207
Biotrauma, 153 Conventional oxygen therapy (COT)
Breathing pattern, 158 FiO2, dilution of, 216
inspired gases, humidification and heating,
217
C rational for, 216
Carbon monoxide diffusion capacity Coronary artery disease, 47
(DLCO), 206 Critical illness, 289–296
Cardiac chair position, 142 caregiver and family burden, 297, 298
Index 309
neurocognitive and psychiatric post-extubation laryngeal edema, 243

manifestations post-laryngeal extubation, 243
cognitive impairment, 294 receiver operator characteristic curve
delirium, 294 analysis, 242
glucose dysregulation, 295 risk factors, 240, 241, 245
hypotension, 294 secretions and cough, 241
hypoxemia, 294 unplanned extubation, 243–244
psychiatric disorders, 295 upper airway obstruction, 242
PTSD, 296 Cyclical waxing, 83
sedatives/analgesics, 295
sepsis, 295
systemic inflammatory response D
syndrome, 295 Decannulation process
physical manifestations non-invasive ventilation, 188
acquired channelopathy, 293 percutaneous dilatational vs. surgical
acute necrotizing myopathy, 292 tracheotomy, 188
complications, 289, 290 positioning, 188
corticosteroids, 292 spontaneous breathing, 187, 188
cosmesis/scars, 294 Delirium, 294
diaphragm, 293 prevention and management, 245
entrapment neuropathy, 293 psychoactive medications, 245
factors, 293 Dexmedetomidine, 110
heterotopic ossification, 293
neuromuscular blockers, 292
neuromuscular dysfunction, 290–291 E
polyneuropathy and myopathy, 291 End-expiratory lung volumes (EELV), 29
pulmonary function, 289–290 Enteral nutrition (EN), 283
systemic corticosteroids, 292, 293 Entrapment neuropathy, 293
thick-filament myopathy, 292 Epinephrine nebulization, 243
risk factors, 296, 297 Eucapnic obesity, 4–6
strategy, 298, 299 chemical control of breathing
Critically ill obese patient, 52, 239–245 chemosensitivity, 5
atelectasis compensatory mechanisms, 4
body weight formula prediction, 53 external elastic loading, 4
causes, 51–52 HCVR, 5
meta-analysis, 53 with OSA, 6
outcomes, 52 without OSA, 4–6
PEEP, 53 respiratory drive, 4
prevention, 52 Expiratory positive airway pressure (EPAP),
recruitment maneuvers, 53 200, 207
tidal volume setting, 52 Expiratory reserve volume (ERV), 152
treatment, 53 Extracorporeal membrane oxygenation
post-extubation failure (ECMO), 159
ACW, 242 Extraparenchymal restrictive respiratory
clinical background, 239 disorders, 153
congestive heart failure, 245 Extra-pulmonary restrictive lung diseases, 233
cuff leak test, 242
delirium, 245
high airway resistance, 240 F
low respiratory system compliance, 240 Fiberoptic bronchoscopy, 53
myocardial ischemia, 245 Flexible bronchoscopy, 53
NIPPV, 245 Flupirtine, 114
pathophysiologic mechanism, 240 Fraction of alveolar oxygen (FAO2), 100
PES, 243 Fraction of expired oxygen (FEO2), 101
310 Index
Fraction of inspired oxygen (FiO2), 196 PEEP, 219

Functional residual capacity (FRC), PIP, 219
146, 152 indications
hypoxemic acute respiratory failure,
220
G post-extubation support, 221
Gabapentinoids, 115 postoperative period, 221
Gas exchange, 17, 29, 33, 34 preoxygenation, before endotracheal
Gel masks, 194 intubation, 222
Glucose dysregulation, 295 in obese patients, 223
technical characteristics, 217, 218
High tidal volume, 146
H Humidification, 203, 217
Head-elevated laryngoscopy (HELP) Hybrid modes, 201
position, 140, 141 Hypertension, 46
Health and Retirement Study (HRS) Hypophosphatemia, 285
database, 295 Hypopnoea syndrome, 152, 252
Health-related quality of life (HRQOL) Hypotension, 294
ARDS vs. patients with chronic respiratory Hypoventilation, 266
illness, 288 Hypoxemia, 158, 159, 294
critical illness, 288
domains, 288
functional outcomes, 289 I
physical manifestations, 288 ICU-acquired weakness (ICU-AW), 290
prolonged mechanical ventilation, 288 Indirect calorimetry (IC), 282, 283
recovery post critical illness, 288 Inspiratory positive airway pressure (IPAP),
SF-36, 288 200, 202, 207
Sickness Impact Profile, 288 Intelligent volume-assured pressure support
survivorship, 289 (iVPAPS), 200
Heart failure, 46 Intra-abdominal hypertension (IAH), 67, 68
cardiogenic shock, 61 clinical features
definition, 57, 58 hemodynamics, 67
diagnosis, 58 imaging, 68
myocardial infarction, 61 laboratory, 68
obesity paradox, 60 physical examination, 67
pathophysiology, 58, 59 symptoms, 67
right ventricular functional and consequences, 69
morphologic alterations, 59 definitions, 65, 66
therapy, 60–61 diagnosis, 68, 69
weight loss, 61 etiologies, 67
Heart failure with preserved ejection fraction obesity, 69
(HFpEF), 58 pulmonary physiology, 70–71
Heart failure with reduced ejection fraction Intra- and postoperative respiratory
(HFpEF), 58 complications, 145
Heat and moisture exchangers (HME, 203 Intraoperative ventilation
Heated humidifiers (HH), 203 PEEP, 146, 147
Hemodynamics, 67 RM, 147, 148
Heterotopic ossification, 293 Intraperitoneal infusions, 117
High-flow nasal cannula (HFNC) oxygen Intrinsic positive end-expiratory pressure
therapy, 219–222 (iPEEP), 151, 158
advantages, 223 Isothermic saturation, 217
dead space washout, 220
FiO2 dilution, 219
gas mixture, humidification and K
heating, 219–220 Ketamine, 114
Index 311
L N
Lateral decubitus position, 141 N-acetylcysteine, 159
Leptin, 8, 9 Neuromuscular blockers, 292
Lorrain-Smith effect, 159 Neuromuscular diseases (NMD), 233
Lungs Nocturnal breathing disorders, 59
atelectasis, 203 Nocturnal polysomnography, 79
elastance and resistance, 30 Non-CF bronchiectasis, 233
mechanics, 151 Non-communicable disease (NCD), 15
posterior and basal segments, 52 Noninvasive positive pressure ventilation
recruitment, 147 (NIPPV), 155
volumes and functions, 18, 19, 29, 152 with acute hypercapnia failure, 169, 170
advantage, 170
APACHE II score, 170
M in laryngeal edema, 243
Magnesium, 115 obesity arm, 170
Masks post-extubation failure, 245
helmets, 194, 195 preoxygenation, 101–102
nasal, 194, 195 prolonged inspiratory time, 170
nasal pillows, 194 respiratory failure, 170
oral, 194 role, 169
oronasal, 194 spontaneous/time ventilatory mode, 169
total face, 194, 195 time-mode options, 169
Mechanical ventilation, 32–35, 139 Noninvasive ventilation (NIV), 194–196,
airway management, 32 229–235
complication, 152 AHRF
due to derecruitments, 153 asthma, 232
duration, 154, 155 causes of, 229, 230
effects, 159 contraindications, 230, 231
extubation and weaning period, 35 COPD, 230, 232
indications, tracheotomy, 36 extra-pulmonary restrictive lung
liberating process, 154 diseases, 233
respiratory pathophysiological changes, indications, 230, 231
164 non-CF bronchiectasis, 233
ventilatory support OHS, 233–235
aspects, 32 atelectasis, 53
body positioning, 35 beneficial effects, 253
driving pressure, 32 bilevel positive airway pressure, 253
gas exchange, 33–34 close double-tube circuit, 196
ling protection, 32 CPAP, 252
lung protection, 32 dead space, 196
monitoring respiratory mechanics, decannulation, 188
33–34 early, 260
PEEP functions, 34 exercise training, 273
plateau pressure, 33 expensive and complex, 271
pleural pressure, 33 feasibility and safety, 253
Mechanoreceptors, 110 gas exchange and spirometer values, 254
Medical Outcomes Study 36-Item Short Form immediate, 260
Health Survey, 288 implementation, 273
Medroxyprogesterone, 83 interfaces, 255
Monitoring Respiratory Mechanics, late, 260
33–34 lung resection surgeries, 254
Morbidity obesity, 139, 140, 142, masks
151, 202 fitting, 196
Mucolytics, 54 helmets, 194, 195
Myocardial infarction, 61 nasal, 194, 195
312 Index
Noninvasive ventilation (NIV) (cont.) severe hypercapnic respiratory failure, 265

nasal pillows, 194 Obesity hypoventilation syndrome (OHS),
oral, 194 151–155
oronasal, 194 AHRF, 234, 235
total face, 194, 195 ARF, 207–209
upper airway obstruction, 195–196 arterial blood gas, 79
mechanical setting, 254–255 causes, 78
OHS, 261–262 clinical evaluation, 79
open single-tube circuit, 196 vs. COPD, 171
oxygen supply and interface, 196–197 CRF, 207, 209–211
positive end-expiratory pressures, 253 definition, 77, 206, 261
postoperative prophylactic use, 254 definitive test, 79
postoperative respiratory failure, 251–252 duration, 171
postoperative respiratory management, 252 long-term management, 171
pressure support ventilation, 253 mechanisms, 261
prevention, 254 morbidity, 207
prophylactic, 254 mortality, 207
settings, 272 nocturnal polysomnography, 79
side effects, 256 organ system derangements, 80
sleep breathing disorders, 269 outcomes, 171
treatment modality, 271 pathophysiology, 78, 80, 207, 261
Non-pulmonary-associated alterations, 28–29 preoperative and postoperative
Nonsteroidal anti-inflammatory drugs cardiopulmonary complications, 80
(NSAIDs), 113 prevalence, 206
Nutritional support, 282–285 pulmonary function test, 79
in critically ill obese patients risks, 80
body composition analysis methods, sleep disordered breathing, 23
282 symptoms, 79, 206
central adiposity, 282 ventilator modes, 261
computed tomography, 282 Obesity paradox, 60
energy and protein provision, 284 Obesity supine death syndrome, 139
energy requirement estimation, 283 Obesity-related chronic respiratory failure,
energy-to-protein ratio, 283 266–272
enteral access device, 284 cardiovascular and metabolic
enteral nutrition, 283, 284 comorbidities, 272
factors, 282 hypoventilation, staging of, 269
hypophosphatemia, 285 long-term follow up, 272–273
indirect calorimetry, 282, 283 morbidity, 151
lipogenesis, 285 physiopathology
malnutrition, 282 OSAS, 267
metabolic process, 285 REM sleep, 267, 268
micronutrient supplementation, 284 respiratory mechanics, 266
overfeeding, 285 treatment modalities
parenteral nutrition, 284, 285 NIV settings, 271, 272
peptide-based formula, 284 positive airway pressure therapies, 269,
protein requirement estimation, 283 270
sarcopenic obesity, 282 spontaneous mode (S), 271
ultrasound scans, 282 timed mode, 271
titration procedure, 271
Obstructive sleep apnea syndrome (OSAS),
O 151, 152, 154, 155, 252, 265, 267
Obesity daytime symptoms, 78
definition, 265 definition, 78
prevalence, 265 OSA-induced nocturnal hypoxemia, 80
Index 313
pathophysiology, 81 fat deposition, 100

preoperative and postoperative FEO2, 101
cardiopulmonary complications, 80 FRC, 100
prevalence, 78 general anesthesia, 104
risk factors, 80 increased oxygen consumption and
sleep disordered breathing, 22 alterations, 100
Oxygenation, 159 intubation, 100
life-threatening complications, 100
noninvasive positive pressure ventilation,
P 101
Paracetamol, 113 patient positioning, 104
Parenchymal restrictive respiratory disorders, respiratory system, 99
153 SAP, 100
Parenteral nutrition (PN), 284, 285 slow method, 101
Percutaneous dilational tracheostomy (PDT), SpO2, 101
182 Pressure-controlled ventilation (PCV)
Peripheral blocks, 116 in critical care, 165
Peripheral oxygen saturation (SpO2), 101 theoretical advantage, 165
Permissive hypercapnia, 34 vs. VCV, 166
Pickwickian’ syndrome, 23 Pressure-controlled ventilation volume
Population, intervention, comparator, and guaranteed (PCV-VG), 166
outcome (PICO) strategy, 44 Pressure-regulated controlled volume (PRCV),
Positive airway pressure (PAP) therapies, 81, 166
83, 269–271 Pressure support ventilation (PSV), 167, 201,
Positive end-expiratory pressure (PEEP), 146, 253
154, 159, 202, 253 Prone position, 141, 159, 174
HFNC, 219 Proportional assist ventilation (PAV), 201
Positive inspiratory pressure (PIP), HFNC, Psychiatric disorders, 295
219 Pulmonary atelectasis, 251
Post-extubation failure Pulmonary consequences
ACW, 242 breathing work, 30, 31
clinical background, 239–240 gas exchange, 29
congestive heart failure, 245 lung elastance and resistance, 30
cuff leak test, 242 lung volume, 29
delirium, 245 respiratory efficiency, 30, 31
high airway resistance, 240 upper airway anatomy, 29
low respiratory system compliance, 240 Pulmonary function tests, 206
myocardial ischemia, 245 Pulmonary physiology, 70
NIPPV, 245
pathophysiologic mechanism, 240
PES, 243 R
post-extubation laryngeal edema, 243 Ramped position, 140, 141
post-laryngeal extubation, 243 Real-time ultrasound guidance (RUSG), 184
receiver operator characteristic curve Recruitment-derecruitment phenomenon, 153
analysis, 242 Recruitment maneuvers (RM), 147,
risk factors, 240, 241, 245 148, 172
secretions and cough, 241 ACS, 72
unplanned extubation, 243 atelectasis, 53
upper airway obstruction, 242 Refractory hypoxemia, 202
Post-extubation stridor (PES), 243 Regional anesthesia, 116
Post-traumatic stress disorder (PTSD), 296 REM sleep, 267
Preoxygenation Respiratory comorbidities, 52
apneic oxygenation, 103 Respiratory complications, 146
fast method, 101 Respiratory cycle, 153
314 Index
Respiratory mechanics, 266 prevalence, 78

background, 15 risk factor, 80
compliance, 18 treatments, 81
continuous positive airway pressure, 18 Sleep Heart Health Study, 48
functional residual capacity, 18 Sleep-disordered breathing, 152–154
gas exchange, 17 fat distribution, 21–22
human diaphragm, 16 leptin resistance, 22
lung volumes, 18, 19 obesity hypoventilation syndrome
NCD, 15 (OHS), 23
pressure–volume curves, 18, 20 OSA, 22
respiratory muscle pump, 16, 17 weight gain, 22
Respiratory neural drive, 4 Sleep-related breathing disorders (SRBD), 59
Respiratory physiology, 154 Sniff position, 140
Respiratory physiotherapy, 146 Standard Form (SF-36), 288
Respiratory system compliance, 151, 152 STOP-BANG score, 81
Reverse Trendelenburg positiin, 173 Supine position, 139
Rigid bronchoscopy-guided tracheostomy, 183 Surgical tracheostomy, 182, 185
Systemic corticosteroids, 292, 293
Systemic inflammatory disorder, 152
S Systemic inflammatory response
Safe apnea period (SAP), 100 syndrome, 295
Sao Paulo Epidemiologic Sleep Study, 47
Sedation, neurocognitive and psychiatric
manifestations, 295 T
Sepsis, 295 Thick-filament myopathy, 292
Sickness Impact Profile, 288 Total lung capacity (TLC), 151, 152
Sitting position, 142, 143 Total respiratory system compliance, 205
Sleep apnea, 59 Tracheostomy, 81, 82
Sleep breathing disorders, 77–81, 83 anatomic variations, 181
CSA complication rates, 182
respiratory drive, 83 contraindications, 180
treatment, 83 indications, 180
OHS optimal timing, 181
arterial blood gas, 79 patient’s anatomy and comorbidities, 181
causes, 78 PDT, 182, 183
clinical evaluation, 79 rigid bronchoscopy-guided tracheostomy,
definition, 77 182–184
definitive test, 79 RUSG, 184
nocturnal polysomnography, 79 surgical, 182, 185
organ system derangements, 80 Transpulmonary pressure (TPP), 33, 153
pathophysiology, 78, 80 Trendelenburg position, 139, 140
preoperative and postoperative
cardiopulmonary complications, 80
pulmonary function test, 79 U
risks, 80 Upper airway anatomy, 29
symptoms, 79
OSA
daytime symptoms, 78 V
definition, 78 Ventilation modes, 147, 165, 166, 172, 173
nocturnal hypoxemia, 80 APRV, 168–169
pathophysiology, 81 NIPPV, 168–170
preoperative and postoperative oesophageal pressure-guided mechanical
cardiopulmonary complications, 80 ventilation
Index 315
optimum PEEP, 172 pressure support ventilation, 201

recruitment manoeuvres, 172–173 proportional assist ventilation, 201
respiratory failure, 172 respiratory rate, 202
in supine position, 172 reverse Trendelenburg position, 201
OHS, 169–171 sitting position, 201
open lung ventilation, 167 tidal volume, 202
PCV volume-controlled NIV, 202
in critical care, 165 Ventilator-induced lung injury (VILI)
theoretical advantage, 165 characterization, 157–158
vs. VCV, 166 clinical data, 160
PCV-VG, 166 fatty deposition, 158
PRCV, 166 medical treatment, 159
proning, 174 respiratory mechanics, 158
PSV, 167 ventilation-perfusion mismatch, 158
reverse Trendelenburg position, 173 Ventilatory support
VCV aspects, 32
vs. PCV, 166 body positioning, 35
target volume, 165 driving pressure, 32
Ventilation perfusion mismatch, 206 gas exchange, 33–34
Ventilation-perfusion ratio (shunt effect), 141 lung protection, 32
Ventilator, 201–203 PEEP functions, 34
assist-control mode, 200 plateau pressure, 33
hybrid mode, 200 pleural pressure, 33
ICU, 200 respiratory mechanics, 33–34
NIV modes, 200 Volume-assured pressure support (VAPS), 271
pressure-cycled, 200 Volume-controlled ventilation (VCV)
settings vs. PCV, 166
assist control, 201 target volume, 165
BPAP, 201 Volutrauma, 157
continuous positive airway pressure,
201
humidification, 203 W
hybrid modes, 201 Waning pattern, 83
low initial pressures, 202 Wisconsin Sleep Cohort Study, 47

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Mechanical Ventilation

in the Critically Ill Obese

ISBN 978-3-319-49252-0 ISBN 978-3-319-49253-7 (eBook)

Library of Congress Control Number: 2017955688

© Springer International Publishing AG 2018

Printed on acid-free paper

This Springer imprint is published by Springer Nature

Lens, France Malcolm Lemyze, M.D.

Part I Effects of Obesity on Respiratory Physiology

1 Control of Ventilation in Obesity������������������������������������������������������������ 3

Part II Causes of Acute Respiratory Failure in the Obese Patient

4 Obesity and Comorbidities��������������������������������������������������������������������� 43

Part III Invasive Mechanical Ventilation in the Critically

10 Preoxygenation Before Intubation in the Critically

Part IV Noninvasive Ventilation and Oxygen Delivery in the Critically

20 The Choice of Interface �������������������������������������������������������������������������� 193

23 High-Flow Nasal Cannula Therapy: Principles and Potential Use

Part V How to Support Nutritionally the Critically Ill Obese Patient

29 Nutritional Support in the Critically Ill Obese Ventilated Patient������ 281

ABG Arterial blood gas

FRC Functional residual capacity

The literature on the control of ventilation in obesity suggests a fundamental dichot-

N. Markou, M.D. (*) • H. Stefanatou, M.D.

© Springer International Publishing AG 2018 3

1.2 Respiratory Neural Drive at Rest in Obesity

In otherwise healthy eucapnic obese adults, measurements of P0,1 and EMGdi

1.3 Chemical Control of Breathing in Eucapnic Obesity

In normal volunteers, the application of external elastic loading results in compen-

Yet, perhaps because of methodological differences, not all studies on chemo-

1.4  hemical Control of Breathing in Eucapnic Obesity

An interplay between weight increase and sex on chemosensitivity is further cor-

1.5  hemical Control of Breathing in Eucapnic Obesity

1.6  hemical Control of Breathing in Hypercapnic Obesity

1.7  he Role of Leptin in Alterations of Chemosensitivity

Neurohormonal changes may also be implicated in alterations of chemosensitivity

4 4. Lourenco RV. Diaphragm activity in obesity. J Clin Invest. 1969;48:1609–14.

Culadeeban Ratneswaran, Patrick Murphy, Nicholas Hart,

2.1 Respiratory Mechanics and Obesity

2.1.2 Non-communicable Disease

According to the World Health Organization (WHO), non-communicable disease

© Springer International Publishing AG 2018 15

2.1.3 The Respiratory Muscle Pump

Effects of obesity can impact on the respiratory mechanics, as well as on neural

Contraction of the diaphragm results in caudal movement of the dome-like struc-

2.1.4 Gas Exchange in Obesity

cavity, particularly in supine posture, and contribute to a ventilation-perfusion mis-

2.1.5 Lung Volumes in Obesity

2.1.6 Respiratory Mechanics and Changes in Obesity

Lung Volume (L)

100 TLC 100

Lung Volume (%predTLC)

-40 -30 -20 -10 0 10 20 30 40 50

Transpulmonary Pressure (cmH20)

Sitting Supine Supine+CPAP

Pgas Pgas Pgas

2.2 Sleep-Disordered Breathing

2.2.1 Fat Distribution

Sleep-disordered breathing relates to abnormal breathing when asleep; the most

2.2.3 Obstructive Sleep Apnoea

2.2.4 Obesity Hypoventilation Syndrome

Obesity hypoventilation syndrome (OHS) [42] was historically known as the

© Springer International Publishing AG 2018 27

3.2  natomic and Physiologic Considerations

Lens, France Malcolm Lemyze, M.D.

1 Control of Ventilation in Obesity�� 3

4 Obesity and Comorbidities�� 43

Part III Invasive Mechanical Ventilation in the Critically

10 Preoxygenation Before Intubation in the Critically

Part IV Noninvasive Ventilation and Oxygen Delivery in the Critically

20 The Choice of Interface �� 193

23 High-Flow Nasal Cannula Therapy: Principles and Potential Use

29 Nutritional Support in the Critically Ill Obese Ventilated Patient�� 281

1.2 Respiratory Neural Drive at Rest in Obesity

1.3 Chemical Control of Breathing in Eucapnic Obesity

1.4 hemical Control of Breathing in Eucapnic Obesity

1.5 hemical Control of Breathing in Eucapnic Obesity

1.6 hemical Control of Breathing in Hypercapnic Obesity

1.7 he Role of Leptin in Alterations of Chemosensitivity

2.1 Respiratory Mechanics and Obesity

2.1.2 Non-communicable Disease

2.1.3 The Respiratory Muscle Pump

2.1.4 Gas Exchange in Obesity

2.1.5 Lung Volumes in Obesity

2.1.6 Respiratory Mechanics and Changes in Obesity

2.2 Sleep-Disordered Breathing

2.2.1 Fat Distribution

2.2.3 Obstructive Sleep Apnoea

2.2.4 Obesity Hypoventilation Syndrome

3.2 natomic and Physiologic Considerations

3.2.1 Non-pulmonary-Associated Alterations

3.2.2 Pulmonary Consequences of Obesity

3.2.2.1 Upper Airway Anatomy

3.2.2.2 Lung Volume

3.2.2.3 Gas Exchange

3.2.2.4 Lung Elastance and Resistance

3.2.2.5 Respiratory Efficiency and Work of Breathing

3.3 Mechanical Ventilation of the Obese Patient

3.3.1 Airway Management

3.3.2 Ventilatory Support

3.3.2.1 Importance of Monitoring Respiratory Mechanics

3.3.2.2 PEEP Setting

3.3.2.3 Effects of Body Positioning

3.3.3 Extubation and Weaning Period

3.3.4 Indications for Tracheotomy

4.1.1 Obesity and Comorbidities

4.2 Discussion and Analysis

4.3 Key Major Recommendations

5.2 Discussion and Analysis

5.2.1 Causes of Atelectasis in Critically Ill Obese Patients

5.2.2 Outcomes of Atelectasis in Critically Ill Obese Patients

6.2 Definition and Diagnosis of Left Heart Failure

6.3 athophysiology of Heart Failure with

6.4 Association of Obesity and Right Ventricular Function

6.5 Obesity Paradox

6.6 Therapy of Heart Failure in Obese Patients

6.7 eaning of Obesity in Cardiogenic Shock

6.8 Key Major Recommendations

7.4 Clinical Features

7.4.2 Physical Examination