Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The perfusion index of healthy term infants during transition at birth

Perfusion index is a continuous parameter provided by pulse oximetry and might be useful for evaluating hemodynamic changes at birth and identifying transitional problems. The objective was to describe perfusion index values in term infants immediately after birth. Perfusion index of 71 healthy term born infants were recorded during the first 10 min after birth, using a pulse oximetry sensor placed preductally. A Wilcoxon signed-rank test was used to compare between time points. No significant trend in perfusion index could be observed in term-delivered infants. There was a significant difference between 2 and 3 min (2.4 (1.6–5.0) vs. 2.3 (1.6–3.7), p = 0.05) and between 3 and 4 min after birth (2.3 (1.6–3.7) vs. 2.1 (1.4–3.2), p < 0.001). There was no significant change in median PI values in the following 8 min. Conclusion: Perfusion index does not change significantly during transition at birth in healthy term infants born by normal vaginal delivery or cesarean section. Large variation in perfusion index causes monitoring this parameter to have limited value

Median (IQR) pressures (cm H₂O) given of experienced and inexperienced caregivers before (dark grey) and after (light grey) two-minute training using self-inflating bag (SIB).

<p>The box plots show median values (solid black bars), IQR (margins of box), and range of data.</p

Median (IQR) mask leak (%) of experienced caregivers and inexperienced caregivers before (dark grey) and after (light grey) two-minute training using a self-inflating bag (SIB).

<p>The box plots show median values (solid black bars), IQR (margins of box), and range of data.</p

Key-points discussed during face mask training using the self-inflating bag.

<p>Key-points discussed during face mask training using the self-inflating bag.</p

An analysis of breaths generated between 9–12 minutes after birth separated into different VT ranges; VT 0–3 mL/kg (A), 3–6 mL/kg (B), 6–9 mL/kg (C) and >9 mL/kg (D).

<p>Each graph shows the frequency of different peak inspiratory flows of all breaths within the specific VT range. Open circles are CPAP success newborns. Closed circles are CPAP fail newborns.</p

The number of patient recordings analysed in each time period.

<p>The number of patient recordings analysed in each time period.</p