Effects of Etomidate on Postintubation Hypotension, Inflammatory Markers, and Mortality in Critically Ill Patients with COVID-19: An International, Multicenter, Retrospective Study.

OBJECTIVE: To evaluate the association of etomidate with postintubation hypotension, inflammation, and mortality in critically ill patients with COVID-19. DESIGN: International, multicenter, retrospective study. PARTICIPANTS: Critically ill patients hospitalized specifically for COVID-19 from three major academic institutions in the US and Europe. MAIN OUTCOME AND MEASURES: Patients were allocated into the etomidate (ET) group or another induction agent (OA) group. The primary outcome was postintubation hypotension. Secondary outcomes included postintubation inflammatory status, in-hospital mortality, and mortality at 30 days. RESULTS: 171 patients with a median age of 68 (IQR 58-73) years were included (ET, n = 98; OA, n = 73). Etomidate was associated with lower postintubation mean arterial pressure [74.33 (64-85) mm Hg versus 81.84 (69.75-94.25) mm Hg, p = 0.005] compared to other agents. No statistically significant differences were generally observed in inflammatory markers between the two groups at 7- and 14-days after admission to the intensive care unit. In-hospital mortality [77 (79%) versus 41 (56%), p = 0.003] and mortality at 30-days [78 (80%) versus 43 (59%), p = 0.006] were higher in the ET group. In multivariate logistic regression analysis, only etomidate (p = 0.009) and postintubation mean arterial pressure (p < 0.001) had a statistically significant effect on mortality, in contrast to stress-dose steroids (p = 0.301), after adjusting for creatinine (p = 0.695), blood urea nitrogen (p = 0.153), age (p = 0.055), oxygen saturation of hemoglobin (SpO2) (p = 0.941), and fraction of inspired oxygen (FiO2) (p = 0.712). CONCLUSIONS: Administration of a single-bolus dose of etomidate in critically ill patients with COVID-19 is associated with lower postintubation mean arterial pressure and higher in-hospital and 30-day mortality compared to other induction agents.

Critical warm ischemia time point for cardiac donation after circulatory death.

Donation after circulatory death (DCD) represents a promising opportunity to overcome the relative shortage of donors for heart transplantation. However, the necessary period of warm ischemia is a concern. This study aims to determine the critical warm ischemia time based on in vivo biochemical changes. Sixteen DCD non-cardiac donors, without cardiovascular disease, underwent serial endomyocardial biopsies immediately before withdrawal of life-sustaining therapy (WLST), at circulatory arrest (CA) and every 2 min thereafter. Samples were processed into representative pools to assess calcium homeostasis, mitochondrial function and cellular viability. Compared to baseline, no significant deterioration was observed in any studied parameter at the time of CA (median: 9 min; IQR: 7-13 min; range: 4-19 min). Ten min after CA, phosphorylation of cAMP-dependent protein kinase-A on Thr197 and SERCA2 decreased markedly; and parallelly, mitochondrial complex II and IV activities decreased, and caspase 3/7 activity raised significantly. These results did not differ when donors with higher WLST to CA times (≥9 min) were analyzed separately. In human cardiomyocytes, the period from WLST to CA and the first 10 min after CA were not associated with a significant compromise in cellular function or viability. These findings may help to incorporate DCD into heart transplant programs.