Secondary Logo

Journal Logo

Patient Safety: Original Clinical Research Report

Apneic Oxygenation During Prolonged Laryngoscopy in Obese Patients: A Randomized, Controlled Trial of Buccal RAE Tube Oxygen Administration

Heard, Andrew FRCA*; Toner, Andrew J. FRCA*; Evans, James R. FRCA*; Aranda Palacios, Alberto M. FRCA*†; Lauer, Stefan MD*‡

Author Information
doi: 10.1213/ANE.0000000000001564
  • Free

Obesity is increasingly prevalent in the surgical population1 and is an established risk factor for difficulty with both ventilation and intubation.2 In such high-risk groups, strategies that extend the apneic time without significant hypoxemia allow airway techniques to be better executed, using advanced equipment and additional expertise as required. Preoxygenation before anesthetic induction is the archetypal approach toward prolonging the safe apnea time – commonly defined as apneic duration with Spo2 ≥ 95%.3 Notwithstanding some opposition to routine preoxygenation for all patients,4,5 this has become standard of care in many health care systems.

Preoxygenation in healthy subjects extends the safe apnea time to not more than 9 minutes, as oxygen reserves deplete from high baseline levels.6,7 Obese patients undergoing best-practice preoxygenation exhibit significant hypoxemia after only 2–4 minutes of apnea.3,8,9 Techniques to augment functional residual capacity through head-up positioning10 and noninvasive ventilatory support11 only marginally improve the duration of safe apnea. Even in healthy nonobese volunteers undergoing full preoxygenation, apnea induced by a variety of induction regimes does not reverse in time to prevent significant falls in Spo2.12,13 Thus, preoxygenation offers limited protection in the event of severe airway difficulties.

To extend the safe apnea time beyond the limits of preoxygenation, methods of apneic oxygenation are required where ambient oxygen in the upper airway replaces oxygen uptake in the lung, in the absence of ventilation but in the presence of a partially patent airway.14 Numerous studies of apneic oxygenation during induction of anesthesia are described in the literature using modified laryngoscopes,15 nasopharyngeal catheters,7,16,17 and nasal prongs.3,18 Nasal approaches in particular are increasing in popularity but are contraindicated in certain patient groups, eg, trauma. Furthermore, some nasal catheter techniques have been associated with significant harm19 and randomized efficacy trials exploring alternative routes remain few. We, therefore, set out to validate a novel method of increasing the ambient oxygen fraction in the upper airway using a continuous oral route. We hypothesized that buccal oxygen administration via a modified Ring-Adair-Elwyn (RAE) tube would effectively extend safe apnea during prolonged laryngoscopy in obese patients.


The study protocol was approved by the local Human Research Ethics Committee. Eligible patients were approached by the research team in the surgical admission unit and informed consent was obtained for all participants. Registration with the Australia and New Zealand Clinical Trials Registry occurred on June 26, 2013; ACTRN 12613000697785; Principal Investigator: Dr Andrew Heard. Trial reporting was in accordance with the 2010 CONSORT statement.

Trial Design

This was an open-label, parallel-arm, randomized-controlled, efficacy trial conducted at a single University Hospital site in Western Australia, assessing buccal oxygenation for superiority over standard care. Block randomization in a 1:1 ratio occurred by computerized sequence generation and the sealed opaque envelope method. Forty patients were recruited (20 in each arm) between June 27, 2013 and March 3, 2015. Eligibility criteria included the following: patients ≥18 years requiring general anesthesia with endotracheal intubation for scheduled surgery, BMI between 30 and 40, ASA physical status I–II. Patients were deemed ineligible if they had chronic respiratory disease, arterial hemoglobin saturation <98% after preoxygenation, previous or anticipated difficult intubation, uncontrolled hypertension, ischemic heart disease, congestive heart failure, increased intracranial pressure, gastroesophageal reflux disease, or a known allergy or contraindication to propofol, remifentanil, rocuronium, or midazolam.

Buccal Oxygen Delivery Device

Figure 1.:
Adapted 3.5-mm south-facing Ring-Adair-Elwyn (RAE) tube for administration of buccal oxygen. Pictures from left to right show intact apparatus, connector removed, and distal tube cut above Murphy eye, modified apparatus with auxiliary oxygen tubing attached to cut end.
Figure 2.:
Adapted Ring-Adair-Elwyn (RAE) tube secured for oxygen delivery to the left buccal space.

A 3.5-mm internal diameter, south-facing RAE (Portex Polar Preformed Tracheal Tube) endotracheal tube was adapted to deliver buccal oxygenation (Figure 1). The distal end of the RAE tube was cut above the Murphy eye, before connecting standard oxygen tubing from the cut end to the auxiliary oxygen outlet on the anesthetic machine. After removal of the tube connector, the blunt proximal end was placed in the buccal space with the tube angle apposed to the left side of the mouth (Figure 2). If patient discomfort was encountered, the adapted oral end was shortened by 1 cm at a time, until well tolerated. Fixation with sleek tape to the external cheek maintained the modified RAE tube in position.

Conduct of Anesthesia

On the operating table before induction of general anesthesia, all patients had IV access secured and monitoring with bispectral index, 3-lead electrocardiogram, Spo2, and noninvasive blood pressure set at 1-minute cycles. Midazolam 2 mg IV was administered. The buccal oxygen delivery device was applied in patients randomly assigned to the intervention, but no flow was commenced. Preoxygenation was conducted with patients spontaneously ventilating (adjustable pressure limiting valve fully open) in the 30° reverse Trendelenburg position with a continuous end-tidal carbon dioxide (Etco2) trace.

At the first reading of end-tidal oxygen (Eto2) ≥ 80%, buccal oxygenation was started at 10 L/min in the intervention arm, and total intravenous anesthesia (TIVA) was commenced in all patients with target-controlled infusions (TCI) of propofol (7.0 μg/mL, Schnider model, effect-site concentration) and remifentanil (4.0 ng/mL, Minto model, effect-site concentration). Time zero was recorded at the point both TCI infusions were running. Rocuronium 0.9 mg/mL was injected at 60 seconds (or as soon afterward that verbal contact was lost) and automated train-of-four monitoring was established at 20-second intervals.

At 2.5 minutes, laryngoscopy was performed with the GlideScope AVL Single Use video laryngoscope (Verathon Ltd). A laryngeal view consistent with straightforward intubation was required for study continuation. Once confirmed, laryngoscopy force was reduced to the minimum required to maintain a small space between epiglottis and posterior pharyngeal wall as seen on the video screen (equivalent to a grade 3 view), thus simulating the partially obstructed airway. This position was sustained until a study end point of Spo2 < 95% or 750 seconds was reached. Meanwhile Propofol TCI was adjusted to maintain a bispectral index value of 40–60, and systolic blood pressure was kept within 20% of the baseline value with boluses of vasoactive agents. At the study end point, the attending anesthetist proceeded with intubation utilizing the in situ GlideScope, followed by rapid reoxygenation with high tidal volume ventilation.

Data Collection

The primary outcome was time to reach Spo2 < 95% during 750 seconds of apnea. Patients who did not reach this level were censured at 750 seconds – a period with the potential to demonstrate meaningful efficacy while maintaining participant safety. Patient age, sex, weight, height, BMI, intubating position, and fat distribution (central, peripheral, or even) were documented on the case report form (CRF). Arterial hemoglobin saturations (Spo2) were recorded at baseline on room air, at induction after preoxygenation (time-zero), and then at the following time-points: 60 seconds, 150 seconds, and every minute thereafter until a study end point was reached. At study end, the peak Etco2 value and the lowest Spo2 value were recorded.

Statistical Analysis

Sample size was calculated for a comparison of means of 2 independent groups. A recent study investigating apneic oxygenation by nasal prongs reported improvements in mean time to desaturation <95% of approximately 90 seconds, with a standard deviation up to 80 seconds.3 To replicate these findings with type I and type II errors of 5% and 20%, respectively, 14 patients per group were required. To allow sufficient power for statistical tests in the event of abnormal distributions, the sample size was inflated by 15%. To allow for withdrawals in the event of Spo2 < 98% after preoxygenation or difficult laryngoscopy, a further inflation of 20% was applied. Therefore, 20 patients were required in each group.

The primary outcome was analyzed using Kaplan-Meier survival curves, and log-rank tests were applied. Apnea times with Spo2 ≥ 95% were reported in each group for comparison with preceding studies – differences were assessed with the Mann-Whitney U test. Analyses were performed on an intention-to-treat basis using GraphPad Prism 6.0, with a statistical significance level of P < .05 on 2-tailed testing.


Forty patients were recruited with no exclusions for Spo2 < 98% after preoxygenation or difficult laryngoscopy. Perioperative patient characteristics were similar in the 2 study arms (Table), including fat distribution that can impact respiratory physiology.20 All patients achieved the preoxygenation target of Eto2 ≥ 80%. No patients reported buccal RAE tube discomfort. Two patients in the intervention arm inadvertently commenced buccal oxygenation before standard preoxygenation, thus interfering with Eto2 monitoring. This was acknowledged by the study investigators after commencement of TIVA and noted on the CRF (apnea time 223 seconds and 330 seconds). One additional buccal oxygenation patient developed transient supraventricular tachycardia and hypotension on induction, with associated loss of the oxygen saturation trace (apnea time of 180 seconds documented at loss of trace). These patients are included on an intention-to-treat basis. There were no missing data points.

Perioperative Characteristics
Figure 3.:
(A) Standard care, (B) buccal oxygenation. Arterial oxygen saturation profiles during study period including lowest recorded value after study termination.
Figure 4.:
Proportion of patients with Spo 2 ≥ 95% during 750 s apnea (95% confidence bands shown with dashed lines). Hazard ratio for Spo 2 < 95% 0.159, 95% confidence interval 0.044–0.226, P < .0001.
Figure 5.:
Apnea time with Spo 2 ≥ 95%, horizontal line = median.

Spo2 at baseline and on induction were no different across study arms (Table). Thereafter, individual patient Spo2 profiles varied considerably (Figure 3). Patients in the buccal oxygenation arm were less likely to reach Spo2 < 95% in the first 750 seconds of apnea; hazard ratio 0.159, 95% confidence interval 0.044–0.226, P < .0001 (Figure 4). This manifested in a longer median (IQR) safe apnea time; 750 seconds (389–750) vs 296 seconds (244–314), P < .0001 (Figure 5). Of note, 11 of 20 patients in both arms had at least the first twitch (T1) of the train-of-four present 150 seconds after rocuronium administration. At the end of the study, no difficult airways were encountered. Median Spo2 values briefly dropped in the standard care arm before reoxygenation occurred – the median (IQR) of the lowest observed Spo2 values was higher in the buccal oxygenation arm; 97 (92–99) vs 91 (89–92), P < .001. Peak end-tidal CO2 levels remained within a safe range. All patients had uneventful surgery and met recovery discharge criteria in the expected time course.


This study demonstrates a median safe apnea time of 12.5 minutes in obese patients receiving buccal RAE tube oxygenation; a 2.5-fold increase compared with standard care and the longest safe apnea time reported in a randomized trial. In the only comparable study in obese patients (BMI 31), low-flow oxygen via Salter type nasal prongs extended safe apnea by 1.8 minutes, with only 8 of 15 patients maintaining Spo2 ≥ 95% for the duration of a 6-minute apnea test.3 The long duration of efficacy with buccal oxygenation is consistent with clinical studies in nonobese patients,16 animal experiments,21 and physiologic simulators.22

The benefits of an extended period of safe apnea with buccal oxygenation are multiple. First, sufficient time can be allowed for full neuromuscular junction blockade before intubation attempts, even if ventilation difficulties are encountered—an issue highlighted in the current study by rocuronium onset times slower than values accepted in the literature.23 Second, once the feasibility of facemask ventilation is established, the need for further ventilation can be eliminated even during prolonged intubation attempts. This is particularly relevant where facemask ventilation may encourage aspiration, eg, during rapid sequence induction. Third, mitigating the stress of evolving hypoxemia in the unanticipated difficult airway will likely improve operator performance.24 The buccal RAE tube system can deliver these benefits with equipment that is well tolerated, inexpensive, and widely available across standard anesthetic departments.

A number of alternative apneic oxygenation devices are employed in clinical practice. Nasopharyngeal catheters deliver oxygen close to the laryngeal inlet, maximizing efficacy by maintaining a high supralaryngeal oxygen fraction22 and yielding near-perfect oxygenation in randomized trials.7,16,17 However, if oxygen flows do not vent through the mouth or nose after induction of anesthesia, significant barotrauma can occur—19 such cases spanning 5 decades were recently described.19 The use of nasal prongs rather than nasal catheters has also been investigated. Moderate gains in apnea times have been reported with low-flow oxygen delivery,3,16 and efficacy may be limited in obese patients by retropalatal obstruction under anesthesia.25 In contrast, high-flow nasal cannulae (HFNC) deliver flows up to 70 L/min and in the process generate continuous positive airway pressure (CPAP)—a feature that can overcome retropalatal obstruction and augment functional residual capacity.26 Indeed, Patel and colleagues successfully used HFNC at 70 L/min in a case series of 25 patients undergoing ear, nose, and throat surgery with known difficult airways,18 reporting a median apnea time (range) with Spo2 ≥ 90% of 14 (5–65) minutes and enhanced carbon dioxide clearance. Nevertheless, randomized studies of HFNC during intubation of critically ill patients have not reported efficacy,27,28 pharyngeal pressures can rise when the oral29–31 and nasal32 escape routes are attenuated, and bag-mask ventilation necessitates equipment removal, potentially rendering this an intermittent technique.

The buccal approach was designed to integrate seamlessly with existing airway management algorithms,33 to eliminate the risk of barotrauma, and to offer a viable alternative when nasal instrumentation is contraindicated. Importantly, the RAE tube positioned within the left buccal space allows normal use of Guedel, nasopharyngeal, and laryngeal mask airways, minimal interruption of facemask seal and unimpeded laryngoscopy. This position also ensures that any rise of pharyngeal pressure is vented through the oral escape route, comprising the sum interdental gap area during facemask application and the open mouth during prolonged laryngoscopy. In a lung model for jet ventilation, we have previously shown end-expiratory lung pressures to be under 1 cm H2O when oxygen is applied to the trachea continuously at 15 L/min in the presence of a 1.1-cm2 surface area expiratory pathway (published as abstract).34 By reducing the flow rate to 10 L/min for buccal oxygenation, we aimed to generate negligible CPAP while maintaining a high supralaryngeal oxygen fraction and a patent airway through sustained laryngoscopy. In contrast to HFNC, the benefits of 10 L/min are likely restricted to pure apneic oxygenation with little contribution from CPAP or ventilatory exchange. Where sustained laryngoscopy is judged inappropriate, alternative techniques to maintain airway patency (eg, jaw thrust, Guedel airway) could be deployed and warrant further investigation.

A third of patients receiving buccal oxygenation did not maintain Spo2 ≥ 95% for the full study duration. Potential explanations include protocol deviations and a failure to maintain either a high supralaryngeal oxygen fraction or a patent airway, despite good views on video laryngoscopy. The observed incidence of early study termination is also consistent with the high incidence of atelectasis and subsequent pulmonary shunt that occurs in obese populations under general anesthesia.35,36 Even when apneic oxygenation techniques are perfectly implemented in animals, large shunt values associate with rapid desaturation at the onset of apnea.37 In such models of shunt, arterial oxygen values equilibrate at a higher plateau with apneic oxygenation,22,37 suggesting patients with shunt may still derive benefit from buccal oxygen delivery despite early desaturation below Spo2 of 95%. Minimizing atelectasis and pulmonary shunt on induction of anesthesia will likely maximize the efficacy of apneic oxygenation, highlighting the importance of the reverse Trendelenburg position and the potential advantages of techniques that generate CPAP.18 High shunt may also explain the apparent lack of utility of apneic oxygenation during intubation of critically ill patients.27,28

There are a number of limitations to the current work. First, this was a nonblinded, single-center study with associated risks of investigator bias. Given the hard end point of time to Spo2 < 95%, these risks were minimized. A blinded design was deemed impractical at this stage of investigation, because buccal oxygen administration is both audible and visible, and cannot easily be substituted with an alternative gas flow that is physiologically neutral. Blinding in future studies may be achievable by using sham RAE tubes or a concealed 3-way tap directing oxygen or air flow toward or away from the oral cavity. Second, the rationale for an oxygen flow rate of 10 L/min was based on limited data. Although this rate proved effective, experimental designs with measurement of pharyngeal pressure generation, oxygen fraction above the larynx, and carbon dioxide clearance are required to better inform optimal flow rates. Third, although apneic oxygenation is functional across very small apertures, the utility of buccal oxygenation in patients that develop severe airway obstruction cannot be inferred. Finally, our study population did not include super morbidly obese patients, a particularly at-risk group during the induction of anesthesia.

In conclusion, buccal oxygen delivery is an inexpensive, readily available, and effective method of apneic oxygenation during prolonged laryngoscopy in obese patients. Importantly, it offers a viable alternative to the nasal route. Future studies should focus on larger, multicenter designs, with reporting of extended safety profiles and clinically relevant outcomes in high-risk patients.


Name: Andrew Heard, FRCA.

Contribution:This author helped conceive and design the trial, collect the data, and write the manuscript.

Name: Andrew J. Toner, FRCA.

Contribution:This author helped collect and analyze the data, and write the manuscript.

Name: James R. Evans, FRCA.

Contribution:This author helped collect and analyze the data.

Name: Alberto M. Aranda Palacios, FRCA.

Contribution:This author helped design the trial and collect the data.

Name: Stefan Lauer, MD.

Contribution:This author helped design the trial, collect the data, and write the manuscript.

This manuscript is handled by: Richard C. Prielipp, MD.


1. Tjeertes EK, Tjeertes EE, Hoeks SE, et al. Obesity–a risk factor for postoperative complications in general surgery? BMC Anesthesiol. 2015;15:112.
2. Kheterpal S, Martin L, Shanks AM, Tremper KK. Prediction and outcomes of impossible mask ventilation: a review of 50,000 anesthetics. Anesthesiology. 2009;110:891–897.
3. Ramachandran SK, Cosnowski A, Shanks A, Turner CR. Apneic oxygenation during prolonged laryngoscopy in obese patients: a randomized, controlled trial of nasal oxygen administration. J Clin Anesth. 2010;22:164–168.
4. Bell MD. Routine pre-oxygenation - a new ‘minimum standard’ of care? Anaesthesia. 2004;59:943–945.
5. Lumb AB. Just a little oxygen to breathe as you go off to sleep. Is it always a good idea? Br J Anaesth. 2007;99:769–771.
6. Gambee AM, Hertzka RE, Fisher DM. Preoxygenation techniques: comparison of three minutes and four breaths. Anesth Analg. 1987;66:468–470.
7. Teller LE, Alexander CM, Frumin MJ, Gross JB. Pharyngeal insufflation of oxygen prevents arterial desaturation during apnea. Anesthesiology. 1988;69:980–982.
8. Baraka AS, Taha SK, Siddik-Sayyid SM, et al. Supplementation of pre-oxygenation in morbidly obese patients using nasopharyngeal oxygen insufflation. Anaesthesia. 2007;62:769–773.
9. Berthoud MC, Peacock JE, Reilly CS. Effectiveness of preoxygenation in morbidly obese patients. Br J Anaesth. 1991;67:464–466.
10. Altermatt FR, Muñoz HR, Delfino AE, Cortínez LI. Pre-oxygenation in the obese patient: effects of position on tolerance to apnoea. Br J Anaesth. 2005;95:706–709.
11. Baillard C, Fosse JP, Sebbane M, et al. Noninvasive ventilation improves preoxygenation before intubation of hypoxic patients. Am J Respir Crit Care Med. 2006;174:171–177.
12. Heier T, Feiner JR, Lin J, Brown R, Caldwell JE. Hemoglobin desaturation after succinylcholine-induced apnea: a study of the recovery of spontaneous ventilation in healthy volunteers. Anesthesiology. 2001;94:754–759.
13. Stefanutto TB, Feiner J, Krombach J, Brown R, Caldwell JE. Hemoglobin desaturation after propofol/remifentanil-induced apnea: a study of the recovery of spontaneous ventilation in healthy volunteers. Anesth Analg. 2012;114:980–986.
14. Frumin MJ, Epstein RM, Cohen G. Apneic oxygenation in man. Anesthesiology. 1959;20:789–798.
15. Mitterlechner T, Herff H, Hammel CW, et al. A dual-use laryngoscope to facilitate apneic oxygenation. J Emerg Med. 2015;48:103–107.
16. Achar SK, Pai AJ, Shenoy UK. Apneic Oxygenation during simulated prolonged difficult laryngoscopy: comparison of nasal prongs versus nasopharyngeal catheter: a prospective randomized controlled study. Anesth Essays Res. 2014;8:63–67.
17. Taha SK, Siddik-Sayyid SM, El-Khatib MF, Dagher CM, Hakki MA, Baraka AS. Nasopharyngeal oxygen insufflation following pre-oxygenation using the four deep breath technique. Anaesthesia. 2006;61:427–430.
18. Patel A, Nouraei SA. Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE): a physiological method of increasing apnoea time in patients with difficult airways. Anaesthesia. 2015;70:323–329.
19. Yao HH, Tuck MV, McNally C, Smith M, Usatoff V. Gastric rupture following nasopharyngeal catheter oxygen delivery-a report of two cases. Anaesth Intensive Care. 2015;43:244–248.
20. Wannamethee SG, Shaper AG, Whincup PH. Body fat distribution, body composition, and respiratory function in elderly men. Am J Clin Nutr. 2005;82:996–1003.
21. Draper WB, Whitehead RW, Spencer JN. Studies on diffusion respiration: alveolar gases and venous blood pH of dogs during diffusion respiration. Anesthesiology. 1947;8:524–533.
22. McNamara MJ, Hardman JG. Hypoxaemia during open-airway apnoea: a computational modelling analysis. Anaesthesia. 2005;60:741–746.
23. Magorian T, Flannery KB, Miller RD. Comparison of rocuronium, succinylcholine, and vecuronium for rapid-sequence induction of anesthesia in adult patients. Anesthesiology. 1993;79:913–918.
24. Cooper JB, Newbower RS, Long CD, McPeek B. Preventable anesthesia mishaps: a study of human factors. Anesthesiology. 1978;49:399–406.
25. Isono S, Tanaka A, Tagaito Y, Sho Y, Nishino T. Pharyngeal patency in response to advancement of the mandible in obese anesthetized persons. Anesthesiology. 1997;87:1055–1062.
26. Riera J, Pérez P, Cortés J, Roca O, Masclans JR, Rello J. Effect of high-flow nasal cannula and body position on end-expiratory lung volume: a cohort study using electrical impedance tomography. Respir Care. 2013;58:589–596.
27. Semler MW, Weavind L, Hooper MH, et al. An electronic tool for the evaluation and treatment of sepsis in the ICU: a randomized controlled trial. Crit Care Med. 2015;43:1595–1602.
28. Vourc’h M, Asfar P, Volteau C, et al. High-flow nasal cannula oxygen during endotracheal intubation in hypoxemic patients: a randomized controlled clinical trial. Intensive Care Med. 2015;41:1538–1548.
29. Chanques G, Riboulet F, Molinari N, et al. Comparison of three high flow oxygen therapy delivery devices: a clinical physiological cross-over study. Minerva Anestesiol. 2013;79:1344–1355.
30. Groves N, Tobin A. High flow nasal oxygen generates positive airway pressure in adult volunteers. Aust Crit Care. 2007;20:126–131.
31. Parke R, McGuinness S, Eccleston M. Nasal high-flow therapy delivers low level positive airway pressure. Br J Anaesth. 2009;103:886–890.
32. Sivieri EM, Gerdes JS, Abbasi S. Effect of HFNC flow rate, cannula size, and nares diameter on generated airway pressures: an in vitro study. Pediatr Pulmonol. 2013;48:506–514.
33. Frerk C, Mitchell VS, McNarry AF, et al.: Difficult Airway Society intubation guidelines working group. Difficult Airway Society 2015 guidelines for management of unanticipated difficult intubation in adults. Br J Anaesth. 2015;115:827–848.
34. Heard AMB, Calder CA, Day RE. Expiration following cannula cricothyroidotomy: a bench study of different jet oxygenation devices. Anaesthesia. 2012;67:559.
35. Gander S, Frascarolo P, Suter M, Spahn DR, Magnusson L. Positive end-expiratory pressure during induction of general anesthesia increases duration of nonhypoxic apnea in morbidly obese patients. Anesth Analg. 2005;100:580–584.
36. Gunnarsson L, Tokics L, Gustavsson H, Hedenstierna G. Influence of age on atelectasis formation and gas exchange impairment during general anaesthesia. Br J Anaesth. 1991;66:423–432.
37. Engström J, Hedenstierna G, Larsson A. Pharyngeal oxygen administration increases the time to serious desaturation at intubation in acute lung injury: an experimental study. Crit Care. 2010;14:R93.
Copyright © 2016 International Anesthesia Research Society