Impact of Noninvasive Respiratory Support in Patients With COVID-19 Requiring V-V ECMO

Abstract

Qamar ahmad ,* adam Green , † abhimanyu Chandel , ‡ James lantry, § mehul desai, § Jikerkhoun simou, § erik osborn , § ramesh sinGh , ¶ nitin Puri, † PatriCk moran , ¶ǁ heidi dalton , § alan sPeir , ¶ and ChristoPher kinG §The impact of the duration of noninvasive respiratory support (RS) including high-flow nasal cannula and noninvasive ventilation before the initiation of extracorporeal membrane oxygenation (ECMO) is unknown. We reviewed data of patients with coronavirus disease 2019 (COVID-19) treated with V-V ECMO at two high-volume tertiary care centers. Survival analysis was used to compare the effect of duration of RS on liberation from ECMO. A total of 78 patients required ECMO and the median duration of RS and invasive mechanical ventilation (IMV) before ECMO was 2 days (interquartile range [IQR]: 0, 6) and 2.5 days (IQR: 1, 5), respectively. The median duration of ECMO support was 24 days (IQR: 11, 73) and 59.0% (N = 46) remained alive at the time of censure. Patients that received RS for ≥3 days were significantly less likely to be liberated from ECMO (HR: 0.46; 95% CI: 0.26-0.83), IMV (HR: 0.42; 95% CI: 0.20-0.89) or be discharged from the hospital (HR: 0.52; 95% CI: 0.27-0.99) compared to patients that received RS for <3 days. There was no difference in hospital mortality between the groups (HR: 1.12; 95% CI: 0.56-2.26). These relationships persisted after adjustment for age, gender, and duration of IMV. Prolonged duration of RS before ECMO may result in lung injury and worse subsequent outcomes.

Prognostic factors associated with mortality among patients receiving venovenous extracorporeal membrane oxygenation for COVID-19: a systematic review and meta-analysis

“…Of 2888 studies identified ( figure ), we selected 123 for full-text review. We included 42 observational cohort studies 13 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 involving 17 449 patients ( table 1 ), predominantly from North America or Europe. We did not identify any randomised controlled trials that met our eligibility criteria.…”

“… 35 , 36 , 37 , 38 , 39 Studies were judged to be at some risk of bias for confounding adjustment and for statistical analysis and reporting if they did not account for clinically important confounders using either logistic regression or Cox proportional hazards models. 15 , 39 , 44 , 46 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 Studies reporting adjusted analyses were judged to be at some risk of bias for statistical analysis 35 , 36 , 37 , 40 , 41 , 42 , 43 , 44 , 45 , 46 if they did not adhere to methodological standards set by the PROGRESS guidelines, 19 , 20 , 21 , 22 in particular with regards to a priori selection of clinically important confounders and consideration of an appropriate sample size to minimise potential overfitting. 28 , 76 The composition and methodological quality of individual prediction models for each study and funnel plots used to evaluate for publication bias among variables that were assessed in at least ten studies are included in the appendix (p 36–41 ).…”

“… 45 Similarly, when the effect of age was measured in 10-year increments in eight studies, 35 , 40 , 41 , 42 , 44 , 60 , 69 , 73 older age remained associated with mortality (aOR 1·19 [95% CI 1·11–1·27]). Of the 26 studies 36 , 37 , 39 , 40 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 58 , 60 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 71 , 74 that included sex as a prognostic factor, male sex was found to be probably associated with increased mortality (uOR 1·34 [95% CI 1·20–1·49]; moderate certainty) and of the three studies 13 , 35 , 71 that included lung disease as a prognostic factor, chronic lung disease was found to be probably associated with increased mortality (aHR 1·55 [95% CI 1·20–2·00]; moderate certainty). In the 14 studies 35 , 41 , 49 , 51 , 54 , 55 , 61 , 62 , 66 , 67 , 68 , 72 , 73 , 74 that included obesity as a prognostic factor, obesity may have been associated with decreased mortality (uOR 0·84 [0·72–0·97]), although this finding was based on low-certainty evidence with a serious risk of bias and imprecision.…”

Respiratory indications for ECMO: focus on COVID-19

“…It is unclear if the duration of non-invasive respiratory support before intubation and ECMO, also relates to outcomes. Data from a small retrospective analysis support this concern—patients who received non-invasive respiratory support for ≥ 3 days had poorer outcomes than patients who received non-invasive respiratory support for < 3 days [ 53 ]. Likewise, in the ELSO registry, the later cohort (with higher mortality) was noted to have greater use of non-invasive respiratory support prior to ECMO compared with the early cohort [ 34 ].…”

Impact of Noninvasive Respiratory Support in Patients With COVID-19 Requiring Veno-Venous Extracorporeal Membrane Oxygenation: A Question of Time?

“…However, this remarkable observation, consistent with lower ECMO survival rates observed by other authors in this setting after prolonged noninvasive oxygenation strategies, 2 needs further confirmation due to some limits of the current study. 1 First, among baseline characteristics, there are no clear biochemical or radiological markers of illness severity, such as static respiratory system compliance, PaO 2 /FiO 2 ratio (PF ratio), D-dimer concentrations, and signs (i.e., pneumothorax or pneumomediastinum) suggestive of barotrauma at CT-scan imaging, collected within 24 hours of patient admission. The lack of triage criteria does not allow the detection of high-risk patients, which most likely benefit from early treatment with V-V ECMO.…”