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Noninvasive Ventilation Plus Extracorporeal CO2 Removal in High-Risk Conditions: A Forthcoming Tool?

To the Editor: Currently, intubation and mechanical ventilation are the only practical treatment options for high-risk patients with hypercapnic respiratory failure that does not respond to noninvasive mechanical ventilation (NIV), as evidenced by selected cases of early endotracheal intubation (ETI) (1, 2). Under these circumstances, the addition of extracorporeal Co 2 removal to NIV is a physiologically attractive and innovative strategy (3). We have read with great interest the article by Del Sorbo et al (4) in which NIV plus extracorporeal Co 2 removal is compared with NIV alone in hypercapnic patients for the endpoint of reducing the cumulative prevalence of ETI in a multicenter matched-cohort study employing historical controls. Compared with patients treated only with NIV, those who received NIV plus extracorporeal Co 2 removal had a substantially reduced risk of ETI (hazard ratio, 0.27; 95% CI, 0.07–0.98; p = 0.047). The latter approach is a rational alternative; however, some aspects of the study warrant additional comment so that the authors’ observations may be generalizable to other institutions. First, from a methodological perspective, it is important to know whether factors other than those chosen by the authors were present or would likely be present in a “high-risk hypercapnic population.” The authors added extracorporeal Co 2 removal when NIV was at risk of failing, defined by an arterial pH less than or equal to 7.30 with arterial Pco 2 greater than 20% of baseline, respiratory rate greater than or equal to 30 breaths/ min, or the use of accessory muscles/paradoxical abdominal movements. This definition may be somewhat restrictive, as there are additional criteria for ETI that the authors did not include. For example, level of consciousness is a strong predictor of NIV failure and ETI (4). Thus, altered sensorium should also be considered in the decision-making process around adding extracorporeal Co 2 removal to NIV. Second, the authors matched cases of combined NIV and extracorporeal Co 2 use to historical controls treated only with NIV on the basis of age, forced expiratory volume, Simple Acute Physiology Score II, arterial pH, and Charlson comorbidity index. However, two additional determinants of NIV failure were not considered. The first of these is the underlying cause of acute hypercapnic respiratory failure, especially given that NIV outcomes are distinctly different in cases of pneumonia or cardiogenic pulmonary edema (2, 5). The second of these is a history of admissions and/or readmissions to the ICU. Consideration should be given to these determinants of NIV failure in the development of recommendations about the addition of extracorporeal Co 2 removal to NIV (6). Third, it would be useful to know how long the authors used extracorporeal Co 2 removal in combination with NIV, how long it took them to observe satisfactory Co 2 clearance, and the blood flow removal rate they used (3). We think that it remains an open question as to whether the same effect of extracorporeal Co 2 removal plus NIV on ETI risk would be seen in cases of more severe acidosis when arterial hypotension could develop. In the latter circumstance, higher flow removal (600–900 mL) and larger cannula (200–300 mL) may be needed. Before the addition of extracorporeal Co 2 removal to NIV can be broadly implemented, a more precise understanding of its effects on healthcare costs, resource utilization, safety, and nurse workload is necessary. These considerations should be incorporated as endpoints in future prospective clinical trials in order to ensure the safe and effective dissemination of Co 2 removal as a complementary therapy in high-risk hypercapnic respiratory failure. The authors have disclosed that they do not have any potential conflicts of interest.