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Pulmonary Critical Care

I NhALEd NITRIC OxIdE TO


IMpROVE OxygENATION
FOR SAFE CRITICAL CARE
TRANSpORT OF AdULTS
WITh SEVERE hypOxEMIA
By Nicholas R. Teman, Md, Jeffrey Thomas, RN, Benjamin S. Bryner, Md,
Carl F. haas, RRT, Jonathan W. haft, Md, pauline K. park, Md, Mark J. Lowell, Md,
and Lena M. Napolitano, Md

Background Inhaled nitric oxide (iNO) is a rescue treatment


for severe hypoxemia in the intensive care unit setting.
Objective To evaluate the effectiveness and safety of iNO in
adult patients with severe hypoxemia before and during
transport to a tertiary care center.
Methods Prospective data were examined in a retrospective
cohort study. Patients with severe hypoxemia and cardiopul-
monary failure (n=139) at referring hospitals in whom conven-
tional therapy was unsuccessful were treated with iNO in the
intensive care units in anticipation of transfer to a tertiary
center. Treatment wih iNO was initiated by the critical care trans-
port team in 114 patients and continued in 25 patients. Arterial
blood gas analysis was done before and after iNO treatment.
Results Patients treated with iNO had significant improvement in
oxygenation: mean (SD) for PaO2 increased from 60.7 (20.2) to
72.3 (40.6) mm Hg (P=.008), and mean (SD) for ratio of PaO2 to
fraction of inspired oxygen (P:F) increased from 62.4 (26.1) to
73.1 (42.6) (P = .03). Use of iNO was continued through transport
in 102 patients, all of whom were transported without compli-
cation. The P:F continued to improve, with a mean (SD) of 109.7
(73.8) from 6 to 8 hours after arrival at the tertiary center (P< .001
relative to values both before and after treatment). Among
patients treated with iNO, 60.2% survived to discharge. In 35
nonresponders, iNO was discontinued, and 15 patients could
not be transferred owing to life-threatening hypoxemia; 2 were
later transferred on extracorporeal membrane oxygenation. Of
18 patients transported without iNO, 9 (50%) survived.
Conclusions Use of iNO significantly improves oxygenation
of patients with severe hypoxemia and allows safe transfer to
©2015 American Association of Critical-Care Nurses a tertiary care center. (American Journal of Critical Care. 2015;
doi: http://dx.doi.org/10.4037/ajcc2015570 24:110-117)

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A
cute respiratory distress syndrome (ARdS) affects nearly 200 000 patients in
the United States each year.1 Mortality in ARdS has steadily improved but is
still greater than 25%.2 Severe ARdS, characterized by a ratio of paO2 to fraction
of inspired oxygen (p:F) of 100 or less, is associated with 45% mortality.3 Sev-
eral treatments can improve survival in patients with ARdS, including low tidal
volume ventilation (6-8 mL/kg of ideal body weight), high positive end-expiratory pressure,
and prone positioning.4-8 The role of inhaled nitric oxide (iNO) is less clear. Inhalation of nitric
oxide can improve oxygenation in the short-term, as manifested by increased paO2 and the
p:F ratio.9-12 however, this improvement in oxygenation is transient, with no difference com-
pared with improvement associated with conventional therapy after 24 hours.13

patients with severe respiratory failure benefit nitric oxide between July 2007 and August 2012.
from transfer to tertiary care centers that can provide Treatment was initiated by the critical care transport
advanced ventilation treatments and salvage thera- team of the University of Michigan Medical System,
pies.14 But transport of these critically ill patients Ann Arbor, Michigan (Survival Flight), in anticipa-
can be challenging, because most of the patients tion of a patient’s transfer to an intensive care unit
have severe hypoxemia that requires advanced in the medical system. The study was approved by
mechanical ventilation with high mean airway the appropriate institutional review board with
pressures, hypercarbia, acidosis, and hypotension waiver of informed consent.
that requires use of vasopressors. Although not cur-
rently recommended as routine therapy for ARdS, Transport Algorithm
iNO potentially has use as rescue therapy for severe In 2006, a multidisciplinary team (surgical
refractory hypoxemia to stabllize a patient’s condi- critical care, emergency medicine, adult respiratory
tion for transport to a tertiary center.15 The purpose care) established an algorithm for use by Survival
of this study was to determine the effect of iNO on Flight to stabilize the condition of adult patients
oxygenation and stabilization for transport in criti- with severe hypoxemia and ARdS for transport to a
cally ill patients with cardiopulmonary failure. tertiary center (Figure 1). Because the University of
Michigan Medical System is a
Methods regional referral center for Acute respiratory
Patients and Study Design patients with severe ARdS and
prospectively collected data in an institutional receives referrals for patients distress syndrome
database were reviewed retrospectively in a cohort with severe hypoxemia, the
study of adult patients treated with inhalation of intent of the algorithm was to
mortality has steadily
provide safe critical care during improved, but remains
transport of these patients to
About the Authors the center. The critical elements greater than 25%.
Nicholas R. Teman and Benjamin S. Bryner are general of stabilization per the algo-
surgery residents and Pauline K. Park is a professor of rithm are lung-protective ventilation with low tidal
surgery, University of Michigan Health System, Ann Arbor,
Michigan. Lena M. Napolitano is division chief, Acute volumes and positive end-expiratory pressure,
Care Surgery (Trauma, Burns, Critical Care, Emergency recruitment maneuvers, pressure-control ventilation,
Surgery), director, Trauma and Surgical Critical Care, inverse-ratio ventilation, and, when these measures
and associate chair, Department of Surgery, University
of Michigan Health System. Jeffrey Thomas is a flight are unsuccessful, inhalation of nitric oxide. The
nurse specialist mastery for University of Michigan Sur- algorithm also includes criteria based on arterial
vival Flight and Mark J. Lowell is an associate professor, blood gas analysis for safe transport (including
Department of Emergency Medicine, Carl F. Haas is a
respiratory therapy supervisor, Department of Adult arterial ph > 7.30 and paO2 > 60 mm hg).
Respiratory Care, and Jonathan W. Haft is an associate A detailed and rigorous educational program
professor of cardiac surgery and anesthesiology, Univer- on iNO for the Survival Flight transport team was
sity of Michigan Health System.
developed to ensure safety and competency in the
Corresponding author: Lena M. Napolitano, MD, FACS, FCCP,
FCCM, Department of Surgery, University of Michigan Health
use of iNO for adult patients with severe hypoxemia.
System, Rm 1C340A-UH, University Hospital, 1500 E Med- Additional educational efforts were initiated to achieve
ical Dr, Ann Arbor, MI 48109-0033 (e-mail:lenan@umich.edu). competency in advanced mechanical ventilation

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Consensus Definition of ARDS (1) Medical Management


Patient diagnosed with ARDS
• PaO2 to FIO2, ratio ≤ 200 • Check ionized calcium
• Bilateral infiltrates consistent – If <1.3 and patient is hypotensive,
with pulmonary edema on give calcium gluconate or calcium
Assumption: all other nonrespira-
frontal chest radiograph chloride
tory medical management
• Requirement for positive pressure • Check arterial pH
issues are being addressed (1)
ventilation via endotracheal tube – If < 7.3, consider administering
• No clinical evidence of left atrial sodium bicarbonate (PCO2 < 60) or
hypertension. If measured, pul- Tham (Pco2 > 60) after consultation
Mimic current ventilator settings
monary artery wedge pressure with receiving medical staff
established at the OSH (2)
≤ 18 mm Hg. • If mean arterial BP < 60
• All criteria must occur together – Initiate Levophed infusion
within a 24-hour interval – Consider vasopressor infusion
Try to establish lung protective
at 0.04 units/min
Calculating a P:F Ratio settings (3)
• Assess adequacy of sedation and
Arterial PaO2 divided by FIO2 neuromuscular blockade
Example: PaO2 = 90, FIO2 = 0.60 – fentanyl, Versed, Nimbex PRN
90/0.6 = P:F ratio of 150 Adequate oxygenation (4)
(2) Mimic Settings
PEEP = Anti-derecruitment Pressure • If on VCV, target expired, not set
tidal volume (ensure no leak)
Clamp the Endotracheal Tube Recruitment maneuver (5)
(3) Lung-Protective Ventilator Settings
• During all circuit change intervals • Pplat < 30-35 cm H2O
• Before and after opening the Yes • VT 6 mL/kg ideal body weight
ventilator circuit for recruitment Adequate oxygenation? • PEEP 12-15 cm H2O
maneuvers and medication
administration No (4) Oxygen Target
• Clamp the tube for ≤10 sec O2 sat ≥ 88% and or Pao2 ≥ 60 mm Hg
Increase PEEP
Consider placement of an arte- (5) Recruitment Maneuver
rial catheter • Use an anesthesia bag with pressure
Yes
Adequate oxygenation? manometer
Chest Tubes • Apply a moderate amount of pressure
• For Survival Flight patients, No (40 cm H2O) for an extended time
empiric chest tube placement (40 sec) while monitoring the
At maximum PEEP? (6)
may be required for patients patient’s status
in unstable condition because Yes • Abort procedure if patient decom-
chest radiographs may not be pensates
readily available Convert to pressure-control
ventilation (if not already on (6) Maximum PEEP
(9) Inhaled Nitric Oxide pressure mode) • Highest level patient will tolerate
• Use the Inovent delivery system (hemodynamic parameters)
• LTV is the only ventilator Sur- • Maximum level of PEEP that the
vival Flight will use for nurse- Lengthen inspiratory time from ventilator is able to deliver
administered NO in adults and I:E of 1:2 to 1:1 to 1.5:1 to 2:1 • LTV max PEEP = 20 cm H2O
children to 2.5:1 to 3:1 (7) (7) Inverse-Ratio Ventilation
• Administer 40 ppm as a test dose • Do not exceed 3:1 I:E ratio with
• Definition of a positive iNO inverse-ratio ventilation (minimize
response: Yes
Adequate oxygenation? auto-PEEP)
– > 10% increase in P:F ratio
– Decrease in PA pressures of 20% No (8) Auto-PEEP
– “Subjective response” • Measurement procedure
Check for auto-PEEP (8) – Press the “Insp/Exp Hold” until
• Discontinue iNO if no objective
or no subjective response it displays “Exp Hold”
• If response to iNO is positive, Yes – Press again and hold the button
titrate the drug dose down in Auto-PEEP present? down until an auto-PEEP value
10-ppm increments is displayed
No Reduce – Release button
• If patient’s status deteriorates No
Maximum I:E inspiratory – If patient effort is detected or
during titration, increase iNO
time high-pressure alarms are detected,
dose to the previous effective Yes
level this procedure is aborted
• Minimum dose for transport 20 Stop lengthening inspiratory time • Interventions for auto-PEEP
ppm unless tried on a lower – Slow respiratory rate, shorten
dose at the referring institution inspiratory time, bronchodilators
Consider iNO Continue with – Monitor for cardiovascular
Contact respiratory care supervisor current settings compromise if auto-PEEP
(pager 1550) for consultation refractory to interventions

Figure 1 Algorithm for stabilization and management of patients with ARDS in preparation for transport.
Abbreviations: ARDS, acute respiratory distress syndrome; FIO2, fraction of inspired oxygen; I:E, ratio of inspiratory time to expiratory time; iNO, inhaled
nitric oxide; LTV, lap-top ventilator; OSH, outside hospital; PEEP, positive end-expiratory pressure; Pplat, plateau pressure; PRN, as needed; sat, satura-
tion; VCV, volume control ventilation; VT, tidal volume.
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Table 1
Baseline demographics of 139 patients
treated with inhaled nitric oxide
techniques, including recruitment maneuvers. The
Survival Flight staff are dually licensed as registered Characteristic Valuea
nurses and paramedics. In addition to requiring a
Age (n = 139), mean (SD), y 45.3 (15.7)
minimum of 5 years of clinical nursing experience
(mean staff nursing clinical experience > 20 years), Men (n = 139) 84 (60)
Survival Flight has an extensive 6-month competency- White (n = 93) 74 (80)
based education for new hires. A specific detailed Hypertension 50 (41)
ARdS educational curriculum, including the admin-
Dyslipidemia 28 (23)
istration and pharmacological properties of iNO
and advanced mechanical ventilation treatments Diabetes mellitus 26 (21)
for severe hypoxemia, is part of the orientation for Previous known heart failure 14 (12)
all critical care transport staff. Coronary artery disease 26 (21)
Ongoing educational efforts for the Survival
Pulmonary hypertension 6 (5)
Flight team include a weekly grand rounds case
review of each ARdS case with the medical director Chronic obstructive pulmonary disease 15 (12)
and transport team with input from the critical care History of smoking 48 (40)
team on strategies that can be used to optimize safe Current smoker 34 (28)
transport of patients. Mandatory biannual advanced
Body mass indexb (n = 110), mean (SD) 35.9 (11.7)
respiratory workshops are led by 2 Survival Flight
a
staff members who are also licensed as respiratory Unless indicated otherwise, all values are number (%) of patients, and n = 121.
b Calculated as weight in kilograms divided by height in meters squared.
therapists. In these sessions, iNO and advanced
mechanical ventilation treatments are reviewed in
detail, including converting patients from modes Flight team. Individual patient data from the Sur-
that cannot be used with the transport ventilator to vival Flight transport record were transferred to a
transport modes that can be used to achieve optimal prospective institutional database, and outcome
alveolar recruitment. Additional multidisciplinary data were included.
meetings are held with the critical care team to
review and revise the ARdS transport algorithm. Statistical Analysis
In order to determine a patient’s response to
Protocol for Inhalation of Nitric Oxide iNO, results of arterial blood gas analysis done
The transport ventilators used during the time before iNO treatment was started were compared
of prospective data collection were the pulmonetic with the results of the first arterial blood gas analysis
LTV 1000 and 1200 (pulmonetic Systems). Nitric after iNO began. Categorical variables between sur-
oxide was delivered via the INOmax dSIR (Ikaria, vivors and nonsurvivors were compared by using c2
Inc). Initially, a test dose of 40 ppm of nitric oxide analysis. Two-sample t tests or Wilcoxon rank-sum
was administered. An objectively positive response tests were used to compare respiratory values before
was defined as an increase in paO2 greater than 10%. and after iNO therapy. Statistical significance was
A subjectively positive response was at the discretion defined as a 2-sided P value less than .05. All statis-
of the Survival Flight team and was defined as an tical analyses were performed by using SpSS, version
improvement in a patient’s clinical appearance, 20, software (SpSS IBM).
hemodynamic status, or oxygen saturation, without
a corresponding increase in paO2. If a patient did Results
not have a positive response, iNO therapy was dis- Survival Flight treated 139 patients with iNO at
continued. If a patient had a positive response, the referring hospitals, initiating iNO in 114 patients
dose was decreased in 10-ppm increments to a min- (82%) and continuing therapy that had previously
imum of 20 ppm. Inhalation of nitric oxide was not been started in 25 patients (18%). Baseline charac-
discontinued if the treatment had been started before teristics of the patients treated with iNO are shown
arrival of the Survival Flight team or if the gas had in Table 1. The underlying pathophysiological con-
been administered for longer than 30 minutes. dition requiring iNO during transport was ARdS in
79% of patients, cardiac failure in 16%, and other
Data Collection causes in 5%. A total of 74% of patients had severe
prospective data were collected for all adult ARdS (p:F ratio ≤ 100) (Table 2).
critically ill patients with severe hypoxemia or car- Figure 2 is the consort flow diagram of the
diopulmonary failure transported by the Survival patients included in the study, including outcomes.

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Table 2
Diagnosis or cause for transfer of 139
patients treated with inhaled nitric oxide
before the arrival of the Survival Flight team). Among
Characteristic No. (%) the responders to iNO, 2 died before transport, but
the remaining 102 patients were transported to the
Acute respiratory distress syndrome 110 (79)
tertiary care center successfully without complication.
Severe acute respiratory distress syndromea 103 (74) Among the 102 patients, the mode of transport
Cardiac failure 22 (16) was helicopter in 66 (65%), ground in 33 (32%),
Other 7 (5) and fixed-wing in 3 (3%). Mean iNO dose at trans-
a
port was 33 (Sd, 23) ppm. After arrival at the terti-
Ratio of PaO2 to fraction of inspired oxygen ≤ 100 mm Hg.
ary care center, 81 patients (79%) had treatment
with iNO continued past the first day of admission.
Of the patients who had iNO therapy started by A total of 22 patients (22%) treated with iNO during
the Survival Flight team, 63 had a positive objective transport required extracorporeal membrane oxy-
response (55%), 16 had a positive subjective response genation (ECMO) during admission at the tertiary
(14%), and 35 did not have a response (31%). care center; 9 of the 22 (41%) survived. Ultimately,
Inhalation of nitric oxide was discontinued in the 62 (60%) of the 102 patients treated with iNO
35 nonresponders and continued in 104 patients during transport survived to discharge, including
(the 79 patients with an objective or subjective 67% of those who had cardiac failure and 60% of
response plus the 25 patients treated with iNO those who had ARdS.

139 Patients
25 Started on iNO
by outside hospital

114 Started on
iNo by Survival
Flight team

35 Nonresponders
12 survived (48%)
13 died (52%)
15 Not transferred 79 Responders

50 survived (63%)

2 Transferred later 29 died (37%)


on ECMO

104 Continued
18 Transported on iNO
without iNO
2 Died at outside hospital

9 survived (50%)
102 Transported
9 died (50%)
on iNO
22 Later treated
with ECMO

80 Not treated 9 survived (41%)


with ECMO 13 died (59%)

53 survived (66%)
27 died (34%)

Figure 2 Consort diagram of patients treated with inhaled nitric oxide at referring hospitals by Survival Flight team.
Abbreviations: ECMO, extracorporeal membrane oxygenation; iNO, inhaled nitric oxide.

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A
80
P = .008
Of the 35 patients who had iNO therapy discon-

Mean partial pressure, mm Hg


70
tinued, 18 were transferred without iNO treatment
60
after further stabilization of their condition, and 17 P = .42
could not be transferred at that time. A total of 2 of 50
the 17 were subsequently transported with ECMO
40
support; 3 others were transported at a later date
after clinical improvement. 30
Changes in arterial blood gas measurements
20
from before iNO therapy to after iNO therapy are
shown in Figure 3. Oxygenation improved signifi- 10
cantly after iNO therapy was started, with an increase
0
in mean paO2 from 60.7 (Sd, 20.2) mm hg before PaO2 PacO2
to 72.3 (Sd, 40.6) mm hg after (P=.008) and a
Before iNO After iNO
mean increase in the p:F ratio from 62.4 (Sd, 26.1)
before to 73.1 (Sd. 42.6) after (P=.03). The p:F B
ratio continued to improve, with a mean of 109.7 120
P < .001
(Sd, 73.8) according to arterial blood gas analysis
of blood obtained 6 to 8 hours after arrival at the 100
tertiary care center (P < .001 relative to values before
P = .03
and after iNO therapy). No significant changes 80
Mean ratio

occurred in paCO2 or ph. Mean paCO2 was 52.2


(Sd, 14.8) mm hg before iNO therapy and 50.6 60
(Sd, 14.4) mm hg after therapy (P = .42), and mean
ph was 7.32 (Sd, 0.11) before and 7.34 (Sd, 0.10) 40
after (P = .14).
20
Discussion
Transport of critically ill patients with severe 0
Before iNO After iNO 6-8 hours
hypoxemia to a regional center for advanced care is after arrival at
complex and potentially life-threatening, and critical medical center
C
care transport teams face marked challenges to
7.50
provide safe transport. Our results suggest that iNO
therapy improves oxygenation, allowing for safe 7.45
transport. We found significant increases in paO2
7.40
and the p:F ratio in patients treated with iNO. The P = .14
increases persisted throughout transport to the 7.35
Mean pH

tertiary care center. All patients who received iNO


7.30
therapy during transport survived the transport, and
some required ECMO or other rescue therapies for 7.25
ongoing treatment of severe refractory hypoxemia.
7.20
Inhaled nitric oxide is a selective pulmonary
vasodilator. It improves oxygenation via vasodi- 7.15
latation of the ventilated part of the lungs, resulting 7.10
in decreased shunting and improved ventilation- pH
perfusion matching.16 Because iNO has no effect on
Before iNO After iNO
the systemic circulation, it does not cause hypoten-
sion or increased perfusion to the shunted part of
the lungs.16 however, iNO is also associated with Figure 3 Change in arterial blood gas measurements after ini-
tiation of inhaled nitric oxide (iNO). A, Arterial PaO2 and PaCO2.
increased renal dysfunction.9,10 Because of this asso- B, Ratio of PaO2 to fraction of inspired oxygen. C, Arterial pH.
ciation and the lack of a proven mortality benefit,
iNO is not recommended as routine therapy for
ARdS,9 rather it is considered a rescue therapy for strategies for treatment of severe ARdS, then inhala-
severe refractory hypoxemia. When the p:F ratio tion of nitric oxide is started by determining whether
cannot be maintained at more than 60 with other or not the patient responds to the inhaled gas. In iNO

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responders, improved oxygenation facilitates more while receiving ECMO,26 this practice necessitates a
timely and safer transport to the ARdS referral cen- substantially increased workload related to the
ter. patients who are iNO nonresponders with a equipment required and also requires a physician
persistent p:F ratio less than 60 may ultimately not to perform cannulation.
be able to be transported. We found no previous published reports of
Our patients experienced no adverse events adult ARdS patients transported while receiving iNO
related to iNO use during transport, and all trans- therapy. Reily et al27 presented a case of a young
ported patients survived to arrival at the referral adult with ARdS who was transported while receiv-
center. The importance of transporting critically ill ing inhaled prostacyclin therapy, in part because
patients to tertiary hospitals for advanced care has the delivery system for inhalation of nitric oxide
been well described. gebremichael et al17 showed was too large for the helicopter. The delivery system
that critically ill patients can be transported safely we use is compact and fits in a helicopter, airplane,
and that transfer of patients with severe respiratory or ambulance, allowing consistent administration of
failure to tertiary care centers has a survival advantage. iNO therapy during transport. Our findings indicate
Ridley and Carter18 reported that patients have a that use of a regionally based critical care transport
predictable physiological response to transfer, inde- team with equipment for iNO therapy for transport
pendent of the severity of the underlying disease; of adult critically ill patients with severe hypoxemia
that is, patients with higher critical illness scores did is feasible, safe, and associated with reasonable sur-
not have worse outcomes during transport. Ridley vival after transport.
and Carter also showed that patients transferred from The limitations of our study stem from its ret-
outside institutions had similar mortality to patients rospective nature. We did not have data on the total
admitted directly to the tertiary center ICU, conclud- number of ARdS patients who were evaluated for
ing that the risks of transport are generally lower transport or who did not receive iNO therapy during
than the risks of the underlying disease and that transport. Also, the treatment algorithm is meant
patients should be transferred if more advanced as a guide for treatment by the Survival Flight team;
care is available at another medical center. no clear criteria exist for progression to each next
Use of specialized transport teams is beneficial step in the algorithm, allowing flexibility but leading
in the transport of critically ill patients. Bellingan to variability in patient management. We also did
et al19 found that patients transported by specialized not know the clinical course or outcome of the
ICU teams had less hypotension, less acidosis, and patients who were not transported to our institution.
lower mortality than did patients despite these limitations, our results support
Our patients transported by traditional ambu- the use of iNO therapy as an additional tool in the
lance. The transport of patients management of severe hypoxemia in adult critically
had no adverse with ARdS requires specialized ill patients with cardiopulmonary failure who require
teams, exemplified by the Acute transport to a regional referral center for advanced
events related to Lung Rescue Team.20,21 Using clinical care. A significant improvement in oxygena-
iNO, and all sur- advanced ventilator strategies tion, even if transient, makes iNO therapy valuable
and ECMO, the team has suc- for the transport of critically ill patients, partly by
vived to arrival. cessfully transported patients mitigating the physiological challenges posed by
with ARdS from the combat the- transport of patients with severe hypoxemia. In our
ater to military hospitals. Uusaro et al22 described a experience at the University of Michigan Medical
series of 66 patients, most of whom had ARdS, System, use of iNO therapy allowed transport of
who were successfully transferred via ground to a critically ill adult patients who otherwise were not
tertiary ICU and concluded that transfers of even considered in stable enough condition for transport
the most critically ill patients are safe. to our facility for advanced critical care.
despite the benefit of iNO on oxygenation and
the safety of transport, few data are available on Conclusions
transport of adult patients who receive iNO therapy Initiation of iNO therapy before transport
during transport. Much of the existing literature23-25 improves oxygenation in critically ill patients with
is about iNO therapy in infants and children. In severe hypoxemia, allowing stabilization of the
these patients, iNO therapy can improve oxygenation patients’ condition and safe transport. Although
and allow stabilization of hypoxemic newborns to prospective randomized studies have indicated that
facilitate transport. Although adult ARdS patients with iNO leads to improved oxygenation in patients
severe hypoxemia have been successfully transported with ARdS, no previous studies have shown the

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effectiveness of iNO therapy for ARdS when initi- Inhaled Nitric Oxide in ARDS Study Group. Crit Care Med.
1998;26(1):15-23.
ated at referring hospitals by a nonphysician critical 12. Dupont H, Le Corre F, Fierobe L, Cheval C, Moine P, Timsit
care transport team. We have demonstrated the role JF. Efficiency of inhaled nitric oxide as rescue therapy dur-
ing severe ARDS: survival and factors associated with the
of iNO in our ARdS treatment algorithm for safe first response. J Crit Care. 1999;14(3):107-113.
transport of these critically ill patients with severe 13. Michael JR, Barton RG, Saffle JR, et al. Inhaled nitric oxide
versus conventional therapy: effect on oxygenation in ARDS.
hypoxemia. Specialized critical care transport teams Am J Respir Crit Care Med. 1998;157(5 pt 1):1372-1380.
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prostacyclin in acute respiratory distress syndrome: what
FINANCIAL DISCLOSURES is the evidence? Crit Care Clin. 2011;27(3):561-587.
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WM. Inhaled nitric oxide for the adult respiratory distress
syndrome. N Engl J Med. 1993;328(6):399-405.
17. Gebremichael M, Borg U, Habashi NM, et al. Interhospital
eLetters
transport of the extremely ill patient: the mobile intensive
Now that you’ve read the article, create or contribute to an
care unit. Crit Care Med. 2000;28(1):79-85.
online discussion on this topic. Visit www.ajcconline.org
18. Ridley S, Carter R. The effects of secondary transport on
and click “Responses” in the second column of either the
critically ill patients. Anaesthesia. 1989;44(10):822-827.
full-text or PDF view of the article.
19. Bellingan G, Olivier T, Batson S, Webb A. Comparison of a
specialist retrieval team with current United Kingdom prac-
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Med. 2000;26(6):740-744.
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To purchase electronic or print reprints, contact the
acute lung injury in children and adults. Cochrane Database
Syst Rev. 2010;(7):CD002787. American Association of Critical-Care Nurses, 101
11. Dellinger RP, Zimmerman JL, Taylor RW, et al. Effects of Columbia, Aliso Viejo, CA 92656. Phone, (800) 899-1712
inhaled nitric oxide in patients with acute respiratory dis- or (949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail,
tress syndrome: results of a randomized phase II trial. reprints@aacn.org.

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