By Richard Kallet, MS, RRT, FCCM

Director of Quality Assurance, Respiratory Care Services, Department of Anesthesia, San Francisco General Hospital

Mr. Kallet reports he is a major stockholder of and a business advisory board member for the Asthma & Allergy Prevention Company and receives grant/research support from Nihon-Kohden.

SYNOPSIS: Despite credible evidence from a large, randomized, controlled trial and numerous meta-analyses demonstrating improved outcomes, prone position is seldom attempted prior to initiating extracorporeal membrane oxygenation to treat severe acute respiratory distress syndrome.

SOURCE: Li X, Scales DC, Kavanagh BP. Unproven and expensive before proven and cheap — Extracorporeal membrane oxygenation vs. prone position in ARDS. Am J Respir Crit Care Med 2018 Jan 9. doi: 10.1164/rccm.201711-2216CP. [Epub ahead of print].

The authors of this retrospective investigation examined 17 studies involving 672 patients who received extracorporeal membrane oxygenation (ECMO) between 1997 and 2017 for severe acute respiratory distress syndrome (ARDS). Overall, 15 studies were published after 2010. These studies represented only 28% of those meeting inclusion criteria because only correspondence with those study investigators could confirm whether a prone position (PP) trial preceded ECMO initiation. Only 208 of 672 patients received PP prior to ECMO. Interestingly, more patients received PP prior to publication of the landmark 2013 PROSEVA study, which showed that PP decreased 28-day and 90-day mortality than after: 124/220 vs. 84/452, respectively (P < 0.05). Li et al were unable to ascertain from their inquiries why so few patients receiving ECMO after 2013 did not first receive a trial of PP.

COMMENTARY

The justification for ECMO in ARDS is based largely on the 2009 CESAR trial1 and the ANZ-ECMO case series during the H1N1 influenza pandemic. Unfortunately, neither study provided high-level evidence that would advocate using this extraordinarily invasive and costly therapy that carries greater risks than PP.2 The CESAR trial did not use explicit, well-defined methods, particularly regarding mechanical ventilation in the control group.2 In essence, ECMO at a single treatment center was compared to ill-defined, usual care practice at referral hospitals. Moreover, in contrast to other multi-center, randomized, controlled trials of ARDS, the authors of the CESAR trial didn’t publish detailed mechanical ventilation data from the first three to seven study days. Thus, the degree to which lung protective ventilation was achieved remains unknown. However, it’s telling that only 70% of the control group received treatment by low volume-low pressure ventilation “at any time” compared to 93% of those randomized to receive ECMO. Numerous studies strongly suggest that mortality risk in ARDS increases when tidal volume exceeds 6 mL/kg and plateau pressure exceeds 30 cm H2O or driving pressure exceeds 15 cm H2O. Therefore, it is impossible to accurately assess mortality differences reported in the CESAR trial, as in large measure these differences may have reflected failure to provide adequate lung protective ventilation. So why is there such a discrepancy between using a simple, highly effective, and economically prudent therapy supported by high-level evidence in favor of one that doesn’t? Perhaps the contemporaneous publication of the CESAR trial with the H1N1 influenza pandemic may have generated an illusion of superiority (or suspension of skepticism), engendered in part by emotionally fraught circumstances in dealing with a particularly severe form of influenza. Another aspect that illuminates this discussion relates to the extraordinary advancement in our understanding of lung recruitment that began approximately two decades ago. In severe ARDS, recruiting the dorsal-caudal lung while in the supine position (primarily responsible for severe refractory hypoxemia) requires brief exposure to threshold opening pressures of 40-50 cm H2O with a positive end-expiratory pressure (PEEP) of 20-30 cm H2O. This is of interest because a cursory review of studies cited by Li et al reveals that, when reported, mean PEEP prior to ECMO was 12-16 cm H2O, with plateau pressures of 30-35 cm H2O. Therefore, this strategy alone would not be expected to substantially improve gas exchange. Moreover, it also perpetuates the impression (or bias) that ECMO is the only viable therapeutic alternative in these circumstances. Incorporating PP enhances the recruiting and stabilizing effects of plateau pressure and PEEP by adding ~5 cm H2O of transpulmonary pressure while also improving ventilation-perfusion relationships, global alveolar stability, and secretion mobilization regardless of whatever recruitment might be achieved.3 However, it’s easier to manage severe ARDS with ECMO than it is to implement mechanics-based treatment strategies using these techniques. ECMO becomes all the more seductive if it’s readily available and also generates considerable revenue. Clinician angst from unfamiliarity is a substantial barrier to implementing PP. This continues to be an issue at my institution, despite 20 years of experience with PP and employing both respiratory care practitioners and nurses who are highly competent in its practice. Essentially, it remains a physician leadership issue, as those experienced in using PP are not hesitant to use it. There is always trepidation when first using PP, which dissipates as experience increases. Thus, the problem essentially is a circular one. In addition, as long as strong financial incentives to pursue ECMO exist, the initial uneasiness to pursue PP in the treatment of ARDS is unlikely to change.

Finally, we’ve devised an effective strategy to prevent overuse of ECMO by first requiring at least 16 hours of bundled therapies to reverse refractory hypoxemia, including: tidal volume of < 6 mL/kg with a minimum PEEP of 16 cm H2O in combination with PP, neuromuscular blockade, inhaled vasodilators, and, in some instances, full alveolar recruitment maneuvers (the caveat: absence of heart failure or contraindications to these therapies). We have found that such an approach prior to referral to an ECMO center is both fiscally sound and clinically prudent.

REFERENCES

  1. Peek GJ, Mugford M, Tiruvoipati R, et al. 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;374:1351-1363.
  2. Morris AH, Hirshberg E, Miller RR 3rd, et al. Counterpoint: Efficacy of extracorporeal membrane oxygenation in 2009 Influenza A(H1N1). Sufficient evidence? Chest 2010;138:778-784.
  3. Kallet RH. A comprehensive review of prone positioning in acute respiratory distress syndrome. Respir Care 2015;60:1660-1688.