Characteristics of Delirium and Its Association with Sedation and In-Hospital Mortality in COVID-19 Patients on Veno-venous Extracorporeal Membrane Oxygenation (preprint)

Background Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has been used in patients with COVID-19 acute respiratory distress syndrome (ARDS). We aim to assess the characteristics of delirium and describe its association with sedation and in-hospital mortality. Methods We retrospectively reviewed adult patients on VV-ECMO for severe COVID-19 ARDS in the Johns Hopkins Hospital ECMO registry in 2020-2021. Delirium was assessed by the Confusion Assessment Method for the ICU when patients scored -3 or above on Richmond Agitation-Sedation Scale (RASS). Primary outcomes were delirium prevalence while on VV-ECMO and categorization of VV-ECMO days based on delirium status. Results Of 47 patients (median age=51) with 6 in a persistent coma, 40 of the remaining 41 patients (98%) had ICU delirium. Delirium in the survivors (n=21) and non-survivors (n=26) was first detected at a similar time point (day 9.5[5, 14] vs. 8.5[5, 21], p=0.56) with similar total delirium days (9.5[3.3, 16.8] vs. 9.0[4.3, 28.3], p=0.43), but the RASS scores on VV-ECMO were numerically lower in non-survivors (-3.72[-4.42, -2.96] vs. -3.10[-3.91, -2.21], p=0.06). Non-survivors had significantly prolonged median delirium days (27.3[17.4, 46.4] vs. 17.0[9.9, 28], p=0.04), delirium-unassessable days on VV-ECMO with a RASS of -4/-5 (23.0[16.3, 38.3] vs. 17.0[6, 23], p=0.03), and total VV-ECMO days (44.5[20.5, 74.3] vs. 27.0[21, 38], p=0.04). The proportion of delirium-present days correlated with RASS (r=0.64, p<0.001), proportion of days with a neuromuscular blocker (r=-0.59, p=0.001) and delirium-unassessable exams (r=-0.69, p<0.001), but not with overall ECMO duration (r=0.01, p=0.96). Average daily dosage of delirium-related medications on ECMO days did not differ significantly between survivors and non-survivors. On multivariable logistic regression, proportion of delirium days was not associated with mortality. Conclusions Longer duration of delirium was associated with lighter analgosedation and shorter paralysis, but the condition did not discern in-hospital mortality. Future studies should evaluate analgosedation and paralytic strategies to optimize delirium, sedation level, and outcomes.

Cerebrovascular Complications of COVID-19 on Venovenous Extracorporeal Membrane Oxygenation (preprint)

Background: Evidence of cerebrovascular complications in Coronavirus disease 2019 (COVID-19) requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO) is limited. The aim of our study is to characterize the prevalence and risk factors of stroke secondary to COVID-19 in patients on V-V ECMO. Methods: We analyzed prospectively collected observational data of adults from 380 institutions of 53 countries in the COVID-19 Critical Care Consortium (COVID Critical) registry. We used univariable and multivariable survival modeling to identify risk factors for stroke during ECMO. Cox proportional hazards and Fine-Gray models were used, with death and discharge treated as competing risks. Results: 595 patients (median age [IQR]: 51 years [42-59]; male: 70.8%) had V-V ECMO support. Forty-three patients (7.2%) suffered strokes, 83.7% of which were hemorrhagic. In multivariable survival analysis, obesity [adjusted Hazard Ratio (aHR)=2.19, 95% CI=1.05–4.59] and use of vasopressors before ECMO (aHR=2.37, 95% CI =1.08–5.22) were associated with an increased risk of stroke. Relative ΔPaCO2 of negative 26% and relative ΔPaO2 of positive 24% at 48-hours of ECMO initiation were observed in stroke patients in comparison to relative ΔPaCO2 of negative 17% and relative ΔPaO2 of positive 7% in the non-stroke group. Patients with acute stroke had a 79% in-hospital mortality compared with a 45% mortality for stroke-free patients.Conclusion: Our study highlights the association of obesity and pre-ECMO vasopressor use with the development of stroke in COVID-19 patients on V-V ECMO. Also, the importance of relative decrease in PaCO2 and moderate hyperoxia within 48-hours after ECMO initiation were additional risk factors.

Risk Factors for 28-Day in-Hospital Mortality in Mechanically Ventilated Patients with COVID-19: An International Cohort Study (preprint)

Background: Risk factors associated with mortality in patients with coronavirus disease 2019 (COVID-19) on mechanical ventilation are still not fully elucidated. Thus, we aimed to identify patient-level factors, readily available at the bedside, associated with the risk of in-hospital mortality within 28 days from commencement of invasive mechanical ventilation (28-day IMV mortality) in patients with COVID-19. Methods: Prospective observational cohort study in 148 intensive care units in the global COVID-19 Critical Care Consortium . Patients with clinically suspected or laboratory confirmed COVID-19 infection admitted to the intensive care unit (ICU) from February 2 nd through December 29th, 2020, requiring IMV. No study-specific interventions were performed. Patient characteristics and clinical data were assessed upon ICU admission, the commencement of IMV and for 28 days thereafter. We primarily aimed to identify time-independent and time-dependent risk factors for 28-day IMV mortality. Results: : A total of 1713 patients were included in the survival analysis, 588 patients died in hospital within 28 days of commencing IMV (34.3%). Cox-regression analysis identified associations between the hazard of 28-day IMV mortality with age (HR 1.27 per 10-year increase in age, 95% CI 1.17 to 1.37, P<0.001), PEEP upon commencement of IMV (HR 0.78 per 5-cmH 2 O increase, 95% CI 0.66-0.93, P=0.005). Time-dependent parameters associated with 28-day IMV mortality were serum creatinine (HR 1.30 per doubling, 95% CI 1.19-1.42, P<0.001), lactate (HR 1.16 per doubling, 95% CI 1.06-1.27 P=0.001), PaCO 2 (HR 1.31 per doubling, 95% CI 1.05-1.64, P=0.015), pH (HR 0.82 per 0.1 increase, 95% CI 0.74-0.91, P<0.001), PaO 2 /FiO 2 (HR 0.56 per doubling, 95% CI 0.50-0.62, P<0.001) and mean arterial pressure (HR 0.92 per 10 mmHg increase, 95% CI 0.88-0.97, P=0.002). Conclusions: : This international study establishes that in mechanically ventilated patients with COVID-19, older age and clinically relevant variables monitored at the bedside are risk factors for 28-day IMV mortality. Further investigation is warranted to validate any causative roles these parameters might play in influencing clinical outcomes.