The American Journal of Surgery (2013) 205, 492-499
North Pacific Surgical Association
Adult refractory hypoxemic acute respiratory distress syndrome treated with extracorporeal membrane oxygenation: the role of a regional referral center Andrew J. Michaels, M.D.*, Jonathan G. Hill, M.D., William B. Long, M.D., Brian P. Young, M.D., Bernie P. Sperley, D.O., Tanya R. Shanks, R.N., Lori J. Morgan, M.D. Legacy Emanuel Medical Center, Portland, OR, USA KEYWORDS: Extracorporeal membrane oxygenation; ECMO; ARDS; Referral center; Transport
Abstract BACKGROUND: The investigators present a series of adults with severe acute respiratory distress syndrome (ARDS) who were treated with extracorporeal membrane oxygenation (ECMO) at a regional referral center. METHODS: Patients with refractory hypoxic ARDS received ECMO until they recovered lung function or demonstrated futility. ECMO was initiated at the referring facility if necessary, and aggressive critical care was maintained throughout. RESULTS: ARDS due to multiple etiologies was managed with ECMO in 36 adults. The pre-ECMO ratio of partial pressure of oxygen to fraction of inspired oxygen was 48.3 6 2.2. Regional facilities referred 89% of these patients, and 69% required ECMO for transport. The mean duration of ECMO was 7.1 6 .9 days for survivors, and the mean post-ECMO ratio of partial pressure of oxygen to fraction of inspired oxygen was 281.2 6 11. ECMO was successfully weaned in 67% of patients, and 60% survived to discharge. CONCLUSIONS: ECMO provides support that prevents ventilator-induced lung injury while the lungs heal. The investigators present a series of 36 adults with refractory hypoxemic ARDS (ratio of partial pressure of oxygen to fraction of inspired oxygen ,50) from 17 different facilities who, treated with ECMO at a single referral center, had a 60% survival rate. Ó 2013 Elsevier Inc. All rights reserved.
Acute respiratory distress syndrome (ARDS) was first described in 19671 and, despite evolutions in definition2–4 and therapy,5–9 continues to have very high mortality. For profound refractory hypoxemic ARDS, which is defined
The authors declare no conflicts of interest. * Corresponding author. Tel.: 11-503-413-2211; fax: 11-503-4132219. E-mail address: amichael@lhs.org Manuscript received November 26, 2012; revised manuscript January 17, 2013 0002-9610/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjsurg.2013.01.025
as lung failure with a ratio of partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) ,100, survival is ,55%.4,10 Despite controversy regarding the utility of extracorporeal membrane oxygenation (ECMO) for adult ARDS due to early studies involving techniques that are no longer clinically relevant,11,12 we have used ECMO for resuscitation and refractory hypoxemia in a protocolized fashion for many years.13,14 Recent reports have suggested that adults cared for at centers that can provide ECMO have improved survival from generic ARDS15 and lung failure caused by the H1N1
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493
Figure 1 Management protocol for adults with ARDS. ALI 5 acute lung injury; APRV 5 airway pressure release ventilation; CPAP 5 continuous positive airway pressure; CT 5 computed tomographic; eSIGH 5 extended sigh; HFOV 5 high-frequency oscillatory ventilation; LIP 5 lower inflection point; PEEP 5 positive end-expiratory pressure; P/F 5 PaO2/FiO2; PTX 5 pneumothorax; VDR 5 Volumetric Diffusive Respiration.
virus.16 Currently, ECMO is considered a valid and valuable adjunct to aggressive pulmonary critical care when the limits of standard care have been reached.17–21 We have considered the role of regionalized care for high-reliability procedures and the importance of transport capability for an ECMO referral center.15,22–28 Our first experience with ECMO was for resuscitation and hypothermia29 in 1986. Since then, we have used ECMO for a variety of indications, including emergency cardiopulmonary support, drowning, refractory shock, hypothermia, myocardial stun, and traumatic lung injury. This report details a recent cohort of patients with refractory hypoxemic ARDS treated with modern ECMO techniques and equipment at a single regional referral center.
Methods Our approach to ARDS is protocolized and, as much as possible, evidence based. Our goals are to use the lowest
level of support to provide adequate oxygen delivery14 (Fig. 1). We use a full spectrum of ventilator modes, including ARDS Network lung-protective strategies, airway pressure release ventilation, and high-frequency percussive ventilation (HFPV) with the Volume Diffusive Respirator (VDR-4 critical care ventilator; Percussionaire Corporation, Sandpoint, ID). We also use numerous ancillary methods, including computed tomographic imaging, positional therapy, pulmonary artery catheter–directed care, euvolemic resuscitation, inhaled agents, and targeted diuresis, and renal replacement therapy. If, despite and after the above measures, a patient cannot achieve an oxygen index (PaO2/FiO2 ratio) .100 on ‘‘safe’’ settings (ie, FiO2 , 80%, peak inspiratory pressure , 40 cm H2O, and tidal volume ,6 to 8 cm3/kg), the patient is considered for ECMO support. An established protocol (Fig. 1) outlines the framework to guide the increasing intensity of pulmonary support. It is recognized that ARDS can lead to rapid patient deterioration and refractory hypoxemia.
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The protocol escalates the treatment of ARDS on the basis of evidence-based guidelines using low–tidal volume, lungprotective mechanical ventilation as the initial strategy. The protocol is designed to rapidly apply increasingly intense methods of pulmonary support and to identify patients who demonstrate failure to respond to ARDS Network10 ventilation strategies, airway pressure release ventilation, and the VDR while they are in the early stages of ARDS before ventilator-induced lung injury and secondary complications ensue. Indications for ECMO and relative contraindications are listed in Table 1. Referral calls are evaluated by attending surgeons with ECMO credentials. Patients who are considered appropriate for ECMO service care are brought to Legacy Emanuel Medical Center and cared for in a single surgical intensive care unit (ICU). Patients are transferred by standard means with transport crews and ventilators if they can tolerate that level of care. Patients requiring higher levels of support are transported by the ECMO mobile surgical transport team. This team consists of 2 attending surgeons, a respiratory therapist, a perfusionist, and 2 registered nurses, one an operating room cardiac nurse and the other a trauma resuscitation nurse with ECMO experience. All transports are done by ground. A protocolized set of activitiesd administrative, logistic, and clinicaldoccurs simultaneously so that the mobile surgical transport team can arrive at the bedside in the referral center as rapidly as possible and immediately begin advanced critical care. The
team evaluates the patient, briefs the family, places monitoring lines, initiates ECMO support, switches to a travel VDR ventilator (Bronchotron; Percussionnaire) and returns to the Legacy Emanuel Medical Center in Portland, Oregon. Before the initiation of ECMO, if not already present, an oximetric pulmonary artery catheter is positioned through the left subclavian or internal jugular vein. A venovenous route is used for ECMO initiation when possible and is the preferred mode for ARDS even in the presence of inotropic support or secondary organ dysfunction. Cannulation by a venoarterial route is used for patients with severe hemodynamic instability complicating pulmonary failure and selectively for very unstable patients requiring interhospital transport. All initial cannulations are conducted percutaneously at the bedside of the patient. Patients are converted from venoarterial to venovenous perfusion as soon as possible. Several different cannulas are used, including Biomedicus (Medtronic, Inc, Minneapolis, MN), Edwards single lumen catheters (Edwards Lifesciences, Irvine, CA), and Avalon 2-stage dual-lumen cannulas (Avalon Laboratories, LLC, Rancho Dominguez, CA). All cannula placements are facilitated using vascular ultrasonography with the Sonosite device (Sonosite, Bothell, WA). The Avalon 2-stage cannulas are placed with transesophageal echocardiographic and/or fluoroscopic guidance. A simple circuit uses a Quadrox oxygenator (Maquet Medical Systems USA, Wayne, NJ) and a Rotaflow centrifugal
Table 1
Adult patient selection criteria for ECMO
Criteria are due to either Refractory noncardiogenic hypoxemia Refractory respiratory acidosis with protective ventilation Despite and after optimal care Protective ventilation Advanced modes of airway pressure release ventilation and/or HFOV or HFPV Euvolemia Positional therapy iNO and/or prostacyclin CESAR criteria Age 18–65 y Murray lung injury score .3.0 or hypercapnia with pH ,7.20 ELSO criteria Consider ECMO when the risk for mortality is R50% PaO2/FiO2 ,150 on FiO2 .90% and/or Murray score 2–3 Initiate ECMO when the risk for mortality is R80% PaO2/FiO2 ,80 on FiO2 .90% and/or Murray score 3–4 Relative contraindications Increasing age .65 y Intracranial hemorrhage or other concern for anticoagulation Underlying terminal condition not related to ARDS Prolonged high-pressure/high-FiO2 ventilation (.7–10 d) Inability to safely transport Morbid obesity that would require .5 L/min of ECMO flow for support Limitations to care (‘‘code status’’) ECMO 5 extracorporeal membrane oxygenation; ELSO 5 Extracorporeal Life Support Organization; HFOV 5 high-frequency oscillatory ventilation; HFPV 5 high-frequency percussive ventilation; iNO 5 inhaled nitric oxide.
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pump (Maquet Medical Systems USA) and is managed by perfusionists. Once adequate ECMO support is instituted, the ventilators are set to low ‘‘recruitment’’ settings. All patients are maintained with the VDR-4 critical care ventilator. VDR settings during ECMO support consist of FiO2 of 40%, a pulsatile flow rate (inspiratory pressure) in the mid–20 cm H2O range, an oscillatory positive end-expiratory pressure of 12 6 2 cm H2O, a pulse frequency of 500 beats/min, and a rate of 15 cycles/min with an inspiratory/expiratory ratio of 1:1. These lung-protective recruitment settings are not adjusted during the entirety of the ECMO course. As the patients recover and ‘‘trials off’’ ECMO are attempted, a convective pressure rise is added to the ventilator management as clinically indicated. Once the patient is stable on ECMO, standard procedure includes direct evaluation by computed tomography of the head without contrast and, if not already done, of the chest, abdomen, and pelvis with contrast. The head computed tomographic study adds a baseline and identifies intracranial lesions that might affect the degree of anticoagulation targeted. Afterward, patients are transported to either the operating room for indicated procedures or to the ICU. Bronchoscopy with diagnostic and therapeutic bronchoalveolar lavage is performed on all patients on admission. Anticoagulation is monitored at the bedside with a target activated clotting time of 180 6 20 seconds. Sedation is maintained with benzodiazepine and narcotic drugs. Neuromuscular blockade is instituted episodically for procedures, recalcitrant agitation, and pulmonary hypertension. Enteric nutrition is used when possible, and if this is insufficient, parenteral nutrition is implemented. Fluid balance is managed by the use of intravenous diuretics and continuous venovenous hemofiltration as clinically indicated. Bleeding during ECMO is managed by a protocol addressing specific problems in the clotting cascade. The first maneuver involves decreasing the systemic heparinization so that the activated clotting time is reduced to 150 seconds. Liberal transfusion thresholds maintain a fibrinogen level R100 mg%, a platelet count R100,000, and an international normalized ratio ,1.5. Episodes of massive transfusion are conducted with an equal ratio of packed cells, fresh frozen plasma, and platelets. In addition, desmopressin acetate and aminocaproic acid are used if platelet dysfunction or fibrinolysis is suspected. If bleeding continues despite these measures, heparin is stopped, and a backup circuit is placed at the bedside. Finally, if no other measures are effective, factor VIIa is given. Operative interventions are both timed and conducted with the recognition of the anticoagulated nature of the patient. Early operation and compulsive hemostasis, and modified techniques supplemented with the generous use of topical hemostatic agents (Fibrillar [Ethicon Endo-Surgery Inc, Somerville, NJ], Floseal [Baxter Healthcare Corporation, Deerfield, IL], Surgicel [Ethicon Endo-Surgery Inc, Somerville, NJ], and packing), reduce the incidence and consequence of surgical bleeding.
495 All patients receive broad-spectrum antibiotics (piperacillin/tazobactam, metronidazole, vancomycin, and azithromycin) and an enhanced dose of oseltamivir at double the standard dose and double the duration (150 mg twice daily for 10 days) if H1N1 or another virus is considered causative. Frequently, fluconazole is added if broadspectrum antibiotics are used or fungal organisms are isolated. Because patients on ECMO do not demonstrate thermal variation, aggressive infection surveillance is the standard. Routine blood cultures and bronchoscopy with bronchoalveolar lavage are conducted on all patients. Infectious disease consultants are involved in all cases. Patients without signs of active infection, especially if a component of autoimmune disease is suspected, receive steroids. Bedside rounds, conducted twice a day, include attending surgeons and intensivists, respiratory therapists, perfusionists and/or ECMO specialists, infectious disease specialists, nephrologists when indicated, pharmacists, social workers, and bedside nurses. The nursing ratio for these patients is 2:1, and a perfusionist attends each circuit. When a patient begins to show evidence of pulmonary recovery, he or she is given a ‘‘trial off’’ consisting of a protocolized evaluation of native pulmonary function. The ventilator is set for optimal levels of pulsatile flow rate and oscillatory positive end-expiratory pressure, and inspired oxygen is set at 100%. Then, the ECMO circuit gas exchange is stopped while flows are maintained. At this point, there is no extracorporeal oxygenation or carbon dioxide removal. If the patient’s hemodynamics and gas exchange are adequate on the VDR, inspired oxygen on the ventilator is reduced to 50%. If the patient is able to tolerate this, and all other factors suggest that complete removal from extracorporeal support is indicated, the patient is decannulated. Decannulation of venous access sites can be managed with bedside removal and direct pressure for 15 to 30 minutes. Arterial sites or complicated venous sites of long duration were managed with operative removal and vascular repair. All patients receive venous ultrasound after decannulation. Data are reported as numbers, percentages and mean 6 SEM. Paired t tests were used for comparisons of means. P values ,.05 were considered statistically significant.
Results Between January 2009 and September 2012, 36 adults (aged .17 years) were treated with ECMO for ARDS at the Legacy Emanuel Medical Center. All patients were cared for by the ECMO service primarily, a surgically directed multidisciplinary team of cardiac and critical care surgeons, intensivists and specialists, perfusionists, and therapists. Thirty-two of these patients (89%) were referred from regional hospitals. Twenty-five patients (69% of the total cohort or 78% of referrals) required ECMO support to
496 ensure safe transport. These patients were cannulated in the ICU of the referral facilities and transported by the ECMO mobile surgical transport team. Fifty percent of patients were men, and the mean age was 40.0 6 6.0 years (range, 17 to 70 years). Twenty-four (67%) recovered lung function and were successfully weaned from ECMO. The duration of mechanical ventilation before the initiation of ECMO was 2.83 6 .36 days (range, 1 to 11 days), and the mean PaO2/FiO2 ratio was 51.9 6 3.2 (range, 23 to 130). The ventilation modes for these patients before cannulation for ECMO included lung-protective ARDS Network strategies, airway pressure release ventilation, and high-frequency ventilation, both oscillatory and percussive. For the entire cohort, patients spent 163.1 6 20.1 hours (range, 4 to 546 hours) on ECMO, while those who weaned successfully from ECMO recovered in 150.38 6 18.2 hours (range, 45.8 to 350.3 hours). The mean post-ECMO PaO2/ FiO2 ratio was 282.6 6 10.2 (range, 164 to 385). Patients who recovered spent 18.7 6 3.8 days on the ventilator (range, 2 to 83 days) after weaning from ECMO, 26.0 6 3.9 days in the ICU (range, 6 to 97 days), and 35.4 6 5.4 days in the hospital (range, 8 to 129 days). Full outcomes data are missing for 3 patients who recovered because they were transferred back to the referring institutions while still on the ventilator. The primary etiology of ARDS was infectious in general. The H1N1 virus accounted for the single largest group of patients, and viral agents were responsible for 44% of the series. Bacterial pneumonia caused 5 cases (14%), and sepsis of abdominal origin caused 3 cases (8%). Trauma, autoimmune disorders, mycoplasma pneumoniae, and noncardiogenic post–cardiopulmonary bypass lung injury accounted for 2 cases (6%), respectively. A wide spectrum of complications is listed in Table 2. Fifteen patients did not survive to discharge. Of these, 3 recovered lung function and were weaned from ECMO, 1 surviving several months only to ultimately succumb to a chronic inflammatory state and inanition. Of those who expired, 80% had support withdrawn for perceived futility. The most common cause of death was neurologic catastrophe, with 2 patients experiencing global anoxia, 2 acute ischemic insults, and 2 cerebral hemorrhage. Four patients died secondary to bleeding. Three of these deaths were due to multifactorial coagulopathies, and 1 was secondary to an acute intra-abdominal hemorrhage from unsuspected splenitis with profound hemorrhagic shock. Three patients had recalcitrant sepsis and could not be supported even with venoarterial ECMO, and 1 patient had a sudden cardiac event and could not be resuscitated before significant cerebral insult had occurred. Overall, the only significant differences between groups was that those who recovered did not require ECMO for transport as frequently (58% vs 92%, P 5 .017). All patients who were placed on ECMO at referral institutions survived evaluation, cannulation, and transport. A full spectrum of procedures was conducted on these patients. These procedures included percutaneous and
The American Journal of Surgery, Vol 205, No 5, May 2013 Table 2
Adult ECMO for ARDS: complications
Complication
n
%
Cannula problems Oxygenator clots Oxygenator failure Cannulas-site bleeding Surgical-site bleeding DIC Hemolysis GI hemorrhage CNS infarct CNS hemorrhage Brain death Cr 1.5–3.0 mg/dL Cr .3.0 mg/dL CVVH Hemofiltration Pneumothorax Pulmonary hemorrhage Inotropes on ECMO Vasodilators on ECMO Cardiac tamponade CPR on ECMO Arrhythmia New infection on ECMO Glucose .240 mg/dL pH ,7.20 Hyperbilirubinemia
4 5 6 5 6 7 6 2 2 2 1 4 2 17 2 6 8 18 6 1 4 9 3 15 1 2
11 14 17 14 17 19 17 6 6 6 3 11 6 47 6 17 22 50 17 3 11 25 8 42 3 6
ARDS 5 acute respiratory distress syndrome; CNS 5 central nervous system; CPR 5 cardiopulmonary resuscitation; Cr 5 creatinine; CVVH 5 continuous venovenous hemofiltration; DIC 5 disseminated intravascular coagulopathy; ECMO 5 extracorporeal membrane oxygenation; GI 5 gastrointestinal.
complex cannulations, tracheostomies, decompressive laparotomies, splenectomies, thoracotomies, sternotomies, lung resections, vascular repairs and revisions, and calf fasciotomies. All patients had pulmonary artery catheters, and more than half had renal replacement therapy.
Comments The use of ECMO for adults with profound and refractory hypoxemic ARDS remains controversial despite significant advances in technology, practice, and evidence. First reported for posttraumatic ARDS30 in 1972, the early randomized trials of Zapol et al11 in 1979 and Morris et al12 in 1994 failed to show improved survival in the ECMO groups. These studies were conducted using equipment, techniques, patient selection and critical care methods that are not comparable with today’s standards. In 2009, the Conventional Ventilation or ECMO for Severe Adult Respiratory Failure (CESAR) trial, conducted by Peek et al15 in the United Kingdom, demonstrated ‘‘significantly improved survival without severe disability’’ with ECMObased management for adults with ARDS. The study was stopped for early demonstration of efficacy after 180
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patients but has been criticized despite this. The criticisms are primarily because although the trial was a randomized prospective design, it was a single-center treatment study with relatively uncontrolled care in the conventional therapy arm and because the patients in the ‘‘treatment’’ arm did not all receive ECMO. Nevertheless, the disabilityfree survival of 63% vs 47% demonstrates that transfer to a high-volume regional referral center that uses a protocolized approach to severe ARDS that includes ECMO improved the patient important outcome of disability-free survival. Our center has a long history of aggressive protocolized care for adult patients with ARDS, including ECMO,13,14,31,32 and has served as a regional referral center for critical care and pulmonary failure as well as for trauma. Our first experience with ECMO for adults29 was in 1986, and our first mobile ECMO/surgical transport was in 1988. We have maintained a strong presence for mobile surgical outreach and critical care transport for many years,31–34 and the 25 patients transported on ECMO in this series reflect the maturity of this program. Several regional ECMO referral centers35–37 have strong transport capabilities. Because many patients are too moribund to survive standard transport levels of care by the time referral is finally made, a transport program is essential for a regional ECMO center. The concept of regionalization of low-frequency, highreliability, and time-dependent care is not novel or unique to the extremes of ARDS and ECMO. Perhaps the best example of this approach is seen with the American model of trauma care24,38,39 which has been shown to improve outcomes and is regulated at the state level and monitored by the American College of Surgeons Committee on Trauma. Improved outcomes after protocolization and regionalization of care has also been seen with acute myocardial infarction,22 stroke,23 pediatric critical care, and advanced surgical procedures.25,26,40 Perceived and historical barriers to regionalized care include financial, regulatory, quality, patient, and family-related social and resource allocation issues.41 Nevertheless, advanced critical care for profound ARDS, including ECMO, represents the type of time-dependent and high-reliability practice that might best be provided in a focused setting in which the provider and systems aspects of performance would benefit from a high density of experience. These patients were referred to Legacy Emanuel Medical Center from 18 different medical centers, as well as several patients from our own institution. Our series compares favorably with other recently published series of adults treated with ECMO for ARDS.15,24,36 Our recovery rate of 67% and survival rate of 60% are similar to the recovery rate of 64% and survival rate of 55% listed for the Extracorporeal Life Support Organization’s international registry for adult respiratory failure.42 In addition to comparable outcomes, our process of care for ECMO for adult ARDS is associated with significantly shorter durations of ECMO support.43,44
497 Because this was a retrospective review of a single institutional experience, it represents no more than a case series, and our study had limitations. Most important, we have no information concerning the care or outcomes of the many patients with ARDS treated by conventional means in our region. We do have reason to believe that patients such as those we treated in this series would have a mortality far in excess of the 40% we experienced4,10 if managed by current best practices that did not include ECMO. In conclusion, our practice is to provide the most aggressive critical care possible for ARDS, and if we cannot deliver oxygen adequately on safe levels of support, we move rapidly to ECMO. Our principles of ARDS care are centered on adequate resuscitation, euvolemia, evidence-based ventilator management, use of a DO2/VO2 focused paradigm and ‘‘early/routine’’ as opposed to ‘‘rescue’’ use of prone positioning, inhaled nitric oxide, prostacyclin, steroids, and renal replacement therapy. If, despite and after these measures, our patients require high pressures and/or FiO2 and demonstrate poor oxygenation, poor oxygen delivery/consumption ratios, or respiratory acidosis, we place them on ECMO and rest their lungs before ventilator-induced lung injury occurs. We have found that a regional referral center for ECMO should have several optimal resources. A strong critical care team with a surgical core is essential. Institutional experience with multidisciplinary collaboration for evidence-based and protocolized care of ARDS is ideal. A culture of continuous quality improvement and commitment to education are important, as is a collaborative practice approach, to include routine debriefings and human resource maintenance. The essential role of an experienced and immediately available transport team cannot be overemphasized. And ultimately, relationships within the institution and among institutions in the region are culture defining. The nature of these cases is such that any institution is taxed by their care, and the decision to transfer to another institution is frequently difficult. Ideally, practitioners from the referring facilities in the region would rotate on the ECMO service in the regional center, share in the care of these patients, and identify with this integrated regional resource in an inclusive and collaborative fashion.
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5. Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342:1301–8. 6. Mercat A, Richard JC, Vielle B, et al, Expiratory Pressure (EXPRESS) Study Group. Positive endexpiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA 2008;299:646–55. 7. Papazian L, Forel JM, Gacouin A, et al, ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med 2010;363:1107–16. 8. Sud L, Sud M, Friedrich JO, et al. High frequency oscillation in patients with acute lung injury and acute respiratory distress syndrome (ARDS): systematic review and meta-analysis. BMJ 2010;340:c2327. 9. Gattinoni L, Carlesso E, Taccone P, et al. Prone positioning improves survival in severe ARDS: a pathophysiologic review and individual patient meta-analysis. Minerva Anestesiol 2010;76:448–54. 10. Meade MO, Cook DJ, Guyatt GH, et al. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive endexpiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA 2008;299:637–45. 11. Zapol WM, Snider MT, Hill JD, et al. Extracorporeal membrane oxygenation in severe acute respiratory failure. A randomized prospective study. JAMA 1979;242:2193–6. 12. Morris AH, Wallace CJ, Menlove RL, et al. Randomized clinical trial of pressure controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome. Am J Respir Crit Care Med 1994;149:295–305. 13. Michaels AJ, Wanek SM, Dreifuss BA, et al. A protocolized approach to pulmonary failure and the role of intermittent prone positioning. J Trauma 2002;52:1037–47. 14. Perchinsky MJ, Long WB, Hill JG, et al. Extracorporeal cardiopulmonary life support with heparin-bonded circuitry in the resuscitation of massively injured trauma patients. Am J Surg 1995;169:488–91. 15. Peek GJ, Mugford M, Tiruvoipati R, et al, CESAR Trial Collaboration. Efficacy and economic assessment of Conventional Ventilatory Support Versus Extracorporeal Membrane Oxygenation for Severe Adult Respiratory Failure (CESAR): a multicentre randomized controlled trial. Lancet 2009;374:1351–63. 16. Noah MA, Peek GJ, Finney SJ, et al. Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A (H1N1). JAMA 2011;306:1659–68. 17. Brodie D, Bacchetta M. Extracorporeal membrane oxygenation for ARDS in adults. N Engl J Med 2011;365:1905–14. 18. Raoof S, Goulet K, Esan A, et al. Severe hypoxemic respiratory failure: part 2dnonventilatory strategies. Chest 2010;137:1437–48. 19. Pipeling MR, Fan E. Therapies for refractory hypoxemia in acute respiratory distress syndrome. JAMA 2010;304:2521–7. 20. Park PK, Napolitano LM, Bartlett RH. Extracorporeal membrane oxygenation in adult acute respiratory distress syndrome. Crit Care Clin 2011;27:627–46. 21. MacLaren G, Combes A, Bartlett RH. Contemporary extracorporeal membrane oxygenation for adult respiratory failure: life support in the new era. Intensive Care Med 2012;38:210–20. 22. Smith LG, Duval S, Tannenbaum MA, et al. Are the results of a regional ST-elevation myocardial infarction system reproducible? Am J Cardiol 2012;109:1582–8. 23. Gropen T, Magdon-Ismail Z, Day D, et al. Regional implementation of the stroke systems of care model: recommendations of the northeast cerebrovascular consortium. Stroke 2009;40:1793–802. 24. MacKenzie EJ, Rivara FP, Jurkovich GJ, et al. A national evaluation of the effect of trauma-center care on mortality. N Engl J Med 2006;354: 366–78. 25. Wang HE, Yealy DM. Distribution of specialized care centers in the United States. Ann Emerg Med 2012;60:632–7. 26. Birkmeyer JD, Siewers AE, Finlayson EV, et al. Hospital volume and surgical mortality in the United States. N Engl J Med 2002;346: 1128–37.
27. Hemmila MR, Rowe SA, Boules TN, et al. Extracorporeal life support for severe acute respiratory distress syndrome in adults. Ann Surg 2004;240:595–605. 28. Davies A, Jones D, Bailey M, et al. Extracorporeal membrane oxygenation for 2009 influenza A (H1N1) acute respiratory distress syndrome. JAMA 2009;302:1888–95. 29. Hauty MG, Esrig BC, Hill JG, et al. Prognostic factors in severe accidental hypothermia: experience from the Mt. Hood tragedy. J Trauma 1987;27:1107–12. 30. Hill JD, De Leval MR, Fallat RJ, et al. Acute respiratory insufficiency. Treatment with prolonged extracorporeal oxygenation. J Thorac Cardiovasc Surg 1972;64:551–62. 31. Sasadeusz KJ, Long III WB, Kemalyan N, et al. Successful treatment of a patient with multiple injuries using extracorporeal membrane oxygenation and inhaled nitric oxide. J Trauma 2000;49:1126–8. 32. Bennett JB, Hill JG, Long III WB, et al. Interhospital transport of the patient on extracorporeal cardiopulmonary support. Ann Thorac Surg 1994;57:107–11. 33. Wick JM, Wade J, Datena SJ, et al. Mobile surgical transport team. AORN J 1998;67:346–52. 34. Long WB, Michaels AJ, Hill JG, et al. The mobile surgical transport team: level I outreach. Presented at: 33rd Annual Meeting of the Western Trauma Association; Snowbird, UT; February 2003. 35. Ciapetti M, Cianchi G, Zagl G, et al. Feasibility of inter-hospital transportation using extra-corporeal membrane oxygenation (ECMO) support of patients affected by severe swine-flu (H1N1)-related ARDS. Scand J Trauma Resusc Emerg Med 2011;19:32. 36. Forrest P, Ratchford J, Burns B, et al. Retrieval of critically ill adults using extracorporeal membrane oxygenation: an Australian experience. Intensive Care Med 2011;37:824–30. 37. Coppola CP, Tyree M, Larry K, et al. A 22-year experience in global transport extracorporeal membrane oxygenation. J Pediatr Surg 2008; 43:46–52. 38. Kahn JM, Branas CC, Schwab CW, et al. Regionalization of medical critical care: what can we learn from the trauma experience? Crit Care Med 2008;36:3085–8. 39. Mullins RJ, Veum-Stone J, Helfand M, et al. Outcome of hospitalized injured patients after institution of a trauma system in an urban area. JAMA 2008;271:1919–24. 40. Carr BG, Matthew Edwards J, Martinez R, et al. Regionalized care for time-critical conditions: lessons learned from existing networks. Acad Emerg Med 2010;17:1354–8. 41. Kahn JM, Asch RJ, Iwashyna TJ, et al. Physician attitudes toward regionalization of adult critical care: a national survey. Crit Care Med 2009;37:2149–54. 42. Extracorporeal Life Support Organization. ECLS registry report: international summary. Available at: http://www.elsonet.org/index.php/registry/ statistics/limited.html. Accessed March 13, 2013. 43. Michaels AJ, Hill JG, Long WB, et al. Reducing the time on ECMO with the use of the Volume Diffusive Respirator (VDR) for adults with H1N1 pneumonia, Am J Surg 2013;205:500–4. 44. Michaels AJ, Hill JG, Long WB, et al. The protocolized use of percussive ventilation reduces the cost and risk of ECMO for refractory hypoxemic ARDS in adults. Presented at: 84th Annual Meeting of the Pacific Coast Surgical Association; Kauai, HI; 2013.
Discussion Martin Schreiber, M.D. (Portland, OR): Dr Michaels and colleagues report a series of 36 severely hypoxic ARDS patients who were treated with extracorporeal membrane oxygenation (ECMO) utilizing a well-defined evidenced based algorithm. Their outcomes are consistent with prior reports with a 60% survival rate. Their work is unique because 89% of the patients were transferred to their
A.J. Michaels et al.
Regional ECMO center for ARDS
facility for ECMO and 69% were transferred on ECMO. I have several comments and questions. 1. I would question the practice of maintaining the HCT between 34 and 40. Large prospective randomized trials have shown no benefit of transfusion threshold of 10 g/ dL vs 7 g/dL in critical care patients. Blood transfusions have been independently associated with increased mortality in trauma patients and our group has shown that transfusion of blood that is older than 21 days is associated with decreased end organ perfusion. I would make a similar argument with respect to attempts to achieve flow independence. This practice has been largely abandoned due to associated complications such as secondary abdominal compartment syndrome due to aggressive fluid resuscitation as reported in this series. 2. What is the purpose of the CT of the head, chest, abdomen and pelvis in all of these patients?
499 3. Do all patients truly receive the broad spectrum antibiotics described or is this only done in patients with a suspected infectious etiology of their ARDS? 4. For the most part, techniques such as prone positioning and the use of inhaled nitric oxide have been associated with improved oxygenation and not improved survival. Why are these techniques necessary if patients are being oxygenated using ECMO? 5. You have divided the bleeding complications into several different categories. Did all of these bleeding complications occur in different patients or did some occur in the same patients. Overall, were bleeding complications the most common complication? Can ECMO be performed without full anticoagulation? Overall, this paper is a very nice addition to the literature especially due its regional referral emphasis.