Downloaded From: http://anesthesiology.pubs.asahq.org/pdfaccess.ashx?

url=/data/journals/jasa/931102/ on 08/23/2018 

Tidal Volume in Patients With Normal Lungs during 

General Anesthesia 
Lower the Better? 

L 
UNG low tidal protective volumes mechanical (V 
T 

ventilation strategies using 

ill patients who require mechanical ventilation for reasons ) of approximately 6 
ml/kg pre- 
other than ALI or ARDS.14,15 Studies on mechanical 
venti- dicted body weight and moderate or high positive end-expi- 
lation in perioperative settings often make use of small 
pa- atory pressures (PEEP) have been demonstrated to improve 
tient populations and focus at different (and not 
necessarily relevant outcome measures in patients with acute lung injury 
clinically relevant) outcomes, such as inflammatory 
mediators. (ALI) and acute respiratory distress syndrome (ARDS).1,2 
Such studies have revealed inhomogeneous results.13 
The im- Despite in three ARDS patients,3–5 the other fact controlled that there lowering trials is unequivocal V 
T investigating failed to improve evidence V 
T 
in outcomes that ALI me- and 
pression is, however, that major surgery (e.g., cardiac surgery), which per se causes a clinically relevant 
inflammatory response, makes the lungs more vulnerable to injury caused by mechanical chanical ventilation in 
critically ill patients has the potential 
stress.16–18This effect might be explained by a two- 
or multiple- to aggravate or, under certain circumstances, initiate lung 
hit model. Accordingly, potentially injurious 
mechanical venti- injury.6,7 In addition to mechanical ventilation with lower 
lation as a second hit requires preexisting injury 
caused by ALI/ V gies T 
,  patients  that  avoid  with  cyclic  ALI  alveolar  and  ARDS  collapse  could  and  benefit  tidal  ARDS.  Alternatively,  it 
may  also  be  a  marked  inflammatory  response  (e.g.,  triggered  by  major  surgery)  to  cause  or  aggravate  lung  injury 
and/or systemic inflammation.16–18 
 Different  studies  on  mechanical  ventilation strategies during and/or after cardiac surgery are summarized in table 
1.  The  present  study  by  Sundar  et  al.9  is  the  largest  one  in  cardiac  surgery  patients  and  it  focuses  on  clinically 
relevant  outcomes.  Although  the  authors  failed  to  show  a  significant  difference  in  time  on  mechanical  ventilation, 
the  number  of  patients  still  on  mechanical  ventilation  at  6  and  8  h  after  surgery  was  significantly  lower  in  the 
protective  ventilation  group.9 However, there are several limitations of this study: (1) it is a single-center study, thus 
its  results  cannot be gen- eralized to other centers or other groups of patients; (2) obese patients were not included in 
the  study;  (3)  the  level  of  PEEP  was  selected  according  to  a  specific  table  and  not  via  individ-  ual  physiologic 
parameters  like  gas-exchange,  compliance,  or  oxygen  delivery;  and  (4)  weaning  procedures  were  not  spe- cifically 
standardized. 
In this study, PEEP levels in both study groups were approx- imately 5 cm H 
2 from strate- recruitment, including the use of higher levels of PEEP. Meta-analysis suggest this approach can not 
only waive the need for rescue therapies as a result of life-threatening hypoxemia,7 it can also reduce mortality in 
patients with more severe ALI.8 It is still matter of discussion whether or not lung protective strat- egies could be 
beneficial in ventilated patients without ALI or ARDS as well. In this issue of A 
NESTHESIOLOGY 
, Sundaret al.9 studied erative mechanical the use of low ventilation V 
T 
ventilation among on patients duration with of postop- normal lungs who underwent elective cardiac surgery. 
Mechanical  ventilation  is  often  mandatory  for  patients  who  undergo  surgery, especially cardiac surgery. Despite 
its  life-saving  necessity,  mechanical  ventilation  adds  mechanical  stress  to  lung  tissues  and  may  cause  damage on a 
cellular  level.  Potential  mechanisms  include:  (1)  stress  failure  of  plasma  membrane  (necrosis,  release  of  mediators 
and  cytosol  from  damaged  cells),  (2)  stress  failure  of  endothelial  and  epithelial  barriers  (loss  of 
compartmentalization,  hemorrhage,  accu-  mulation  of  lung  leukocytes),  (3)  damage  of  the  extracellular  matrix,  (4) 
overdistension  without  tissue  destruction,  (5)  ef-  fects  on  the  vasculature  independent  of  stretch  and  rupture 
(increased intraluminal pressure and shear stress).10,11 In contrast with results from small animal models—in which 
mechanical stress induced by high V 
T 
O. Low PEEP levels might increase regional shear stress and lung injury by causing opening and closing of lung 
units within a ventilatory cycle (atelectrauma), even in absence of high plateau pressures.19Tidal recruitment and 
dere- cruitment can be minimized by using PEEP levels of 10 cm and low (or no) PEEP has caused lung injury in 
normal lungs (and which have been 
H Although 2 
O during it anesthesia, is at least in healthy nonobese patients.20 uncertain whether ventilation strategies recently 
effects of seen short-term in larger perioperative animals in the mechanical context of ventilation high V 
T) 
12— on 
that use higher levels of PEEP during the intraoperative period are beneficial to these patients,17,21 higher levels of 
pulmonary integrity in patients are less well defined.13 Two 
PEEP could reduce intraoperative atelectasis, 
decreasing retrospective analyses identified high airway pressures and 
repetitive collapse and reexpansion of dependent lung 
V 
T 
as independent risk factors for ALI and ARDS in critically 
Accepted  for  publication  February  14,  2011.  The  authors  are  not  supported  by,  nor  maintain  any  financial  interest  in,  any 
commercial activity that may be associated with the topic of this article. 
Copyright © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology 2011; 
114:1011–3 
♦  This  Editorial  View  accompanies  the  following  article:  Sundar  S,  Novack  V,  Jervis K, Bender SP, Lerner A, Panzica P, Mah- 
mood F, Malhotra A, Talmor D: Influence of low tidal volume ventilation on time to extubation in cardiac surgical patients. A 
NESTHESIOLOGY 
2011; 114:1102–10. 
Anesthesiology, V 114 • No 5 1011 
May 2011 
 
Downloaded From: http://anesthesiology.pubs.asahq.org/pdfaccess.ashx?url=/data/journals/jasa/931102/ on 08/23/2018 
Editorial Views 
Table 1. Randomized and Controlled Trials Comparing High versus Low V 
T 
Ventilation in Cardiac Surgery Patients 
Respiratory V 
T 
Rate, l/min PEEP, cm H 
2 
O 
Outcomes for Intervention Trial 
Year N Setting* Low High Low High Low High (ProtectiveStrategy) Chaney MA 
et al.25 
Anesthesiology 2011; 114:1011–3 1012 
H. Wrigge and P. Pelosi , ml/kg 2000 25 OR 6 12 16 8 5 5 Better lung mechanics, less shunt 
Koner O 
et al.26 
2004 44 OR 6 10 15 9 5 5 or 0 No difference: plasma IL-6, TNF, 
ventilation time, hospital length of stay Wrigge H et al.17 
2005 44 ICU 6 12 21 10 9 7 No difference: plasma mediators; 
lower TNF in broncho-alveolar lavage; subgroup showed faster plasma TNF decline Zupancich E 
et al.16 
2005 40 OR 6.8 10.9 12–15 12–15 9.1 2.1 LowerIL-6andIL-8inplasma and broncho-alveolar lavage Reis Miranda D et al.18 
2005 62 OR/ICU 4–6 6–8 NA NA 14–15 5.5 Faster decline in plasma 
IL-8 (IL-10) Sundar S 
et al.9 
2011 149 OR 6.2 10.0 17 12 5.0 4.9 No difference: ventilation time; fewer patients ventilated 6 h after operation; fewer 
reintubations 
* Clinical setting at start of study. High room; PEEP high V 
T 
group; positive ICU end-expiratory intensive care pressure; unit; IL TNF interleukin; tumor necrosis low low factor-α; V 
T 
group; V T 
NA tidal not volume. 
available (not reported); OR operating 
parts, and thereby attenuating pulmonary inflammation 
ing potential cardiovascular impairment as a result of 
de- and coagulation.22,23 Individual factors such as obesity, 
 creased venous return as associated with higher PEEP. 
In pneumoperitoneum, preexisting disease, and some surgi- fact, cal interventions may aggravate atelectasis 
formation. 
risks it and is often benefits required of protective when using mechanical lower V 
ventilation T 
. Balancing during the 
Furthermore, although some positive clinical indication on 
anesthesia should include an assessment of 
preoperative pa- ventilation-free hours or reduced reintubation rate were ob- 
tient status and expected amount and duration of 
surgical served, clinical decisions regarding patient need for reintubation 
trauma, among other individual factors. There is an 
increas- (or any other intervention) were made by these teams based on 
ing body of evidence from relatively small studies 
directly or theirclinicalassessments.Therateofintubationwasdetermined 
indirectly suggesting a potential benefit of protective 
venti- mainly by bleeding, arrhythmia, and pancreatitis not specifically 
latory strategies for patients without lung injury. This 
find- related to ventilation management. 
ing is especially true for patients during cardiac and 
thoracic Inflammatory responses to cardiac surgery are variable 
surgery (e.g., esophagectomy, which is often 
associated with a and may depend on individual patient factors, such as co- 
clinically relevant systemic inflammatory response to 
surgical morbidities, genetic predisposition, previous tissue injury 
procedures). Systematic patient scoring methodologies 
may (e.g., cardiac shock), or surgical trauma depending on type of 
be useful in assisting clinicians identify patients at risk 
of surgery, amount of ischemia-reperfusion injury, and blood 
postoperative complications.24 Future studies might 
con- loss. Because high-risk patients are usually not included in 
sider stratifying patients to include those with more 
severe studies on perioperative ventilation, the issue of protective 
illness or injury. This stratification, however, assumes 
that mechanical ventilation may be even more relevant in daily 
the more ill a patient is, the more relevant a protective 
ven- practice when one treats these patients. Despite an accurately 
tilatory strategy may be. performed sample size 
calculation in the study by Sundar et al.,9 the number of patients undergoing routine elective car- diac surgery to be 
studied might be higher to see differences in relevant outcomes depending on mechanical ventilation 
Hermann Wrigge, M.D.,* Paolo Pelosi, M.D.† *Depart- ment of Anesthesiology and Intensive Care Medicine, Uni- versity of 
Leipzig, Germany. hermann.wrigge@medizin.uni- leipzig.de. †Department of Surgical Sciences and Integrated strategy. 
Diagnostics, University of Genoa, Italy. When using lung 
protective mechanical ventilation more extensively in patients without ALI/ARDS, adverse effects 
References such as hypercapnia, atelectasis formation, 
and increased re- quirements for higher fractional inspired oxygen tension and PEEP should be considered. 
Increased fluid administration 
1. Ventilation with lower tidal volumes as compared with tra- ditional tidal volumes for acute lung injury and the acute 
respiratory distress syndrome. The Acute Respiratory Dis- tress Syndrome Network. N Engl J Med 2000; 342:1301–8 or even use 
of catecholamines might be necessary when treat- 
2. Parsons PE, Eisner MD, Thompson BT, Matthay MA, Ancuk- 
 
Downloaded From: http://anesthesiology.pubs.asahq.org/pdfaccess.ashx?url=/data/journals/jasa/931102/ on 08/23/2018 
EDITORIAL VIEWS 
iewicz M, Bernard GR, Wheeler AP, NHLBI Acute Respiratory 
Ventilator-associated lung injury in patients without acute 
Distress Syndrome Clinical Trials Network: Lower tidal vol- 
lung injury at the onset of mechanical ventilation. Crit Care 
ume ventilation and plasma cytokine markers of inflamma- 
Med 2004; 32:1817–24 tion in patients with acute lung 
injury. Crit Care Med 2005; 33:1–6 
15. Gajic O, Frutos-Vivar F, Esteban A, Hubmayr RD, Anzueto A: Ventilator settings as a risk factor for acute respiratory dis- 3. 
Stewart TE, Meade MO, Cook DJ, Granton JT, Hodder RV, 
tress syndrome in mechanically ventilated patients. Intensive 
Lapinsky SE, Mazer CD, McLean RF, Rogovein TS, Schouten 
Care Med 2005; 31:922–6 BD, Todd TR, Slutsky AS: 
Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. 
Pressure- and Volume-Limited Ventilation Strategy Group. N Engl J Med 1998; 338:355–61 4. Brochard L, Roudot-Thoraval F, 
Roupie E, Delclaux C, Chas- tre J, Fernandez-Mondéjar E, Clémenti E, Mancebo J, Factor P, Matamis D, Ranieri M, Blanch L, 
Rodi G, Mentec H, Dreyfuss D, Ferrer M, Brun-Buisson C, Tobin M, Lemaire F: Tidal volume reduction for prevention of 
ventilator-induced lung injury in acute respiratory distress syndrome. The Mul- ticenter Trail Group on Tidal Volume reduction 
in ARDS. Am J Respir Crit Care Med 1998; 158:1831–8 5. Brower RG, Shanholtz CB, Fessler HE, Shade DM, White P Jr, 
Wiener CM, Teeter JG, Dodd-o JM, Almog Y, Piantadosi S: Prospective, randomized, controlled clinical trial comparing 
traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients. Crit Care Med 1999; 
27:1492–8 
16. Zupancich E, Paparella D, Turani F, Munch C, Rossi A, Massaccesi S, Ranieri VM: Mechanical ventilation affects in- 
flammatory mediators in patients undergoing cardiopulmo- nary bypass for cardiac surgery: A randomized clinical trial. J Thorac 
Cardiovasc Surg 2005; 130:378–83 17. Wrigge H, Uhlig U, Baumgarten G, Menzenbach J, Zinserling J, Ernst M, Drömann D, 
Welz A, Uhlig S, Putensen C: Me- chanical ventilation strategies and inflammatory responses to cardiac surgery: A prospective 
randomized clinical trial. In- tensive Care Med 2005; 31:1379–87 18. Reis Miranda D, Gommers D, Struijs A, Dekker R, Mekel 
J, Feelders R, Lachmann B, Bogers AJ: Ventilation according to the open lung concept attenuates pulmonary inflammatory 
response in cardiac surgery. Eur J Cardiothorac Surg 2005; 28:889–95 19. Mols G, Priebe HJ, Guttmann J: Alveolar recruitment 
in acute 
lung injury. Br J Anaesth 2006; 96:156–66 6. Tremblay 
LN, Slutsky AS: Ventilator-induced injury: From 
20. Neumann P, Rothen HU, Berglund JE, Valtysson J, Magnus- 
barotrauma to biotrauma. Proc Assoc Am Physicians 1998; 
son A, Hedenstierna G: Positive end-expiratory pressure 
pre- 110:482–8 
vents atelectasis during general anaesthesia even in the 
pres- 7. Putensen C, Theuerkauf N, Zinserling J, Wrigge H, Pelosi P: Meta-analysis: Ventilation strategies and outcomes of the 
ence of a high inspired oxygen concentration. Acta Anaesthesiol Scand 1999; 43:295–301 acute respiratory distress syndrome 
and acute lung injury. 
21. Wrigge H, Uhlig U, Zinserling J, Behrends-Callsen E, Ot- 
Ann Intern Med 2009; 151:566–76 
tersbach G, Fischer M, Uhlig S, Putensen C: The effects 
of 8. Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD, Slutsky AS, Pullenayegum E, Zhou Q, Cook D, Brochard 
L, Richard JC, Lamontagne F, Bhatnagar N, Stewart TE, 
different ventilatory settings on pulmonary and systemic inflammatory responses during major surgery. Anesth Analg 2004; 
98:775–81 Guyatt G: Higher vs lower positive end-expiratory pressure 
22. Choi G, Wolthuis EK, Bresser P, Levi M, van der Poll T, in 
patients with acute lung injury and acute respiratory 
Dzoljic M, Vroom MB, Schultz MJ: Mechanical ventilation 
distress syndrome: Systematic review and meta-analysis. 
with lower tidal volumes and positive end-expiratory pres- 
JAMA 2010; 303:865–73 
sure prevents alveolar coagulation in patients without 
lung 9. Sundar S, Novack V, Jervis K, Bender SP, Lerner A, Panzica P, 
injury. A 
NESTHESIOLOGY Mahmood F, Malhotra A, 
Talmor D: Influence of low tidal volume ventilation on time to extubation in cardiac surgical patients. A 
NESTHESIOLOGY 
Anesthesiology 2011; 114:1011–3 1013 
H. Wrigge and P. Pelosi 2006; 105:689–95 23. Wolthuis EK, Choi G, Dessing MC, Bresser P, Lutter 
R, 
2011; 114:1102–10 
Dzoljic M, van der Poll T, Vroom MB, Hollmann M, Schultz MJ: Mechanical ventilation with lower tidal volumes and 10. Uhlig 
S: Ventilation-induced lung injury and mechanotrans- 
positive end-expiratory pressure prevents pulmonary inflam- 
duction: Stretching it too far? Am J Physiol Lung Cell Mol 
mation in patients without preexisting lung injury. A 
NESTH
E Physiol 2002; 282:L892–6 11. Pelosi P, Negrini D: Extracellular matrix and mechanical ventilation in healthy lungs: Back to 
baro/volotrauma? Curr Opin Crit Care 2008; 14:16–21 12. Protti A, Cressoni M, Santini A, Langer T, Mietto C, Febres D, 
Chierichetti M, Coppola S, Conte G, Gatti S, Leopardi O, Masson S, Lombardi L, Lazzerini M, Rampoldi E, Cadringher P, 
Gattinoni L: Lung stress and strain during mechanical ventilation: Any safe threshold? Am J Respir Crit Care Med 2011 [Epub 
ahead of print Feb. 4] 13. Schultz MJ, Haitsma JJ, Slutsky AS, Gajic O: What tidal vol- umes should be used in patients without 
acute lung injury? A 
NESTHESIOLOGY 
- SIOLOGY 
2008; 108:46–54 24. Canet J, Gallart L, Gomar C, Paluzie G, Valle`s J, Castillo J, Sabaté S, Mazo V, Briones Z, 
Sanchis J, ARISCAT Group: Prediction of postoperative pulmonary complications in a population-based surgical cohort. A 
NESTHESIOLOGY 
2010; 113: 1338–50 25. Chaney MA, Nikolov MP, Blakeman BP, Bakhos M: 
Protective ventilation attenuates postoperative pulmonary dysfunction in patients undergoing cardiopulmonary bypass. J 
Cardiotho- rac Vasc Anesth 2000; 14:514–8 26. Koner O, Celebi S, Balci H, Cetin G, Karaoglu K, Cakar N: 
2007; 106:1226–31 
Effects of protective and conventional mechanical ventila- tion on pulmonary function and systemic cytokine release 14. Gajic O, 
Dara SI, Mendez JL, Adesanya AO, Festic E, Caples 
 after cardiopulmonary bypass. Intensive Care Med 2004; 
SM, Rana R, St Sauver JL, Lymp JF, Afessa B, Hubmayr RD: 
30:620–6