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

A 12-Month Clinical Audit Comparing Point-of-Care Lactate Measurements Tested by Paramedics with In-Hospital Serum Lactate Measurements

Objective Prehospital point-of-care lactate (pLA) measurement may be a useful tool to assist paramedics with diagnosing a range of conditions, but only if it can be shown to be a reliable surrogate for serum lactate (sLA) measurement. The aim of this study was to determine whether pLA is a reliable predictor of sLA. Methods This was a retrospective study of adult patients over a 12-month period who had pLA measured by paramedics in an urban Australian setting and were transported by ambulance to a tertiary hospital where sLA was measured. Patients were excluded if they suffered a cardiopulmonary arrest at any time, had missing data, or if sLA was not measured within 24 hours of arrival. Levels of agreement were determined using methods proposed by Bland and Altman. Results A total of 290 patients were transported with a pLA recorded. After exclusions, there were 155 patients (55.0% male; age 71 [SD=18] years) remaining who had sLA recorded within 24 hours. Elevated pLA (>2.0mMol/L) was associated with sLA measurement (76.1% vs 23.9%; OR 3.18; 95% CI, 1.88-5.37; P<.0001). Median time between measurements was 89 minutes (IQR=75). Overall, median pLA was higher than sLA (3.0 [IQR=2.0] mMol/L vs 1.7 [IQR=1.3]; P<.001). Bland-Altman analysis on all participants showed a mean difference of 1.48 mMol/L (95% CI, -3.34 to 6.31). Normal pLA was found to be a true negative in 82.9% of cases, and elevated pLA was a true positive in 48.3% of cases. When the time between measurements was less than 60 minutes (n=25), normal pLA predicted normal sLA with 100% accuracy, with a false-positive rate of 18.2%. As time between measurements increased, accuracy diminished and the false-positive rate increased. Conclusions Overall, the level of agreement between pLA and sLA was poor. Accuracy of pLA diminished markedly as the time between the two measurements increased. It may be possible to use pLA as a screening tool; when considered this way, pLA performed much better, though larger prospective trials would be needed to confirm this

The relationship between elevated prehospital point-of-care lactate measurements, intensive care unit admission, and mortality: A retrospective review of adult patients

Objective To determine whether prehospital point-of-care lactate (pLA) is associated with mortality, admission, and duration of hospital stay. Design A retrospective clinical audit, where elevated lactate was defined as ≥2 mmol/L. Setting The ambulance service and primary referral hospital in the Australian Capital Territory from 1st July 2014 to 30th June 2015. Participants Adult patients (≥18 years) who had pLA measured and were transported to the primary referral hospital. Main outcome measures Mortality, admission, and duration of hospital stay. Results Two hundred fifty-three patients with a median pLA of 2.5 mmol/L (interquartile range [IQR]: 1.5–3.7) were analysed. Overall mortality was 8.3%; 68% were admitted to the hospital; 8.3% to the intensive care unit (ICU). pLA was non-significantly higher in those who died compared to survivors (3.5 [IQR: 2.75–5.85] vs 2.4 [1.5–3.6]; W = 1631.5; p = 0.053). pLA was higher for those admitted to the hospital (2.9 [1.9–3.9] vs 2.0 [1.4–3.1]; W = 5094.5, p = 0.001) and the ICU (3.2 [2.4–5.7] vs 2.4 [1.5–3.6]; W = 1578.5; p = 0.008). There was no relationship between pLA and duration of stay. Considered as a screening tool, at a cut-off of 2.5 mmol/L, pLA had a likelihood ratio+ of 1.61 for mortality and 1.44 for ICU admission; the odds ratio for mortality was 3.76 (95% confidence interval = 1.30, 13.89). Conclusions Elevated prehospital lactate was associated with significantly increased ICU and hospital admissions. There may be value in pLA as a screening tool

A 12-Month Clinical Audit Comparing Point-of-Care Lactate Measurements Tested by Paramedics with In-Hospital Serum Lactate Measurements

Objective Prehospital point-of-care lactate (pLA) measurement may be a useful tool to assist paramedics with diagnosing a range of conditions, but only if it can be shown to be a reliable surrogate for serum lactate (sLA) measurement. The aim of this study was to determine whether pLA is a reliable predictor of sLA. Methods This was a retrospective study of adult patients over a 12-month period who had pLA measured by paramedics in an urban Australian setting and were transported by ambulance to a tertiary hospital where sLA was measured. Patients were excluded if they suffered a cardiopulmonary arrest at any time, had missing data, or if sLA was not measured within 24 hours of arrival. Levels of agreement were determined using methods proposed by Bland and Altman. Results A total of 290 patients were transported with a pLA recorded. After exclusions, there were 155 patients (55.0% male; age 71 [SD=18] years) remaining who had sLA recorded within 24 hours. Elevated pLA (>2.0mMol/L) was associated with sLA measurement (76.1% vs 23.9%; OR 3.18; 95% CI, 1.88-5.37; P<.0001). Median time between measurements was 89 minutes (IQR=75). Overall, median pLA was higher than sLA (3.0 [IQR=2.0] mMol/L vs 1.7 [IQR=1.3]; P<.001). Bland-Altman analysis on all participants showed a mean difference of 1.48 mMol/L (95% CI, -3.34 to 6.31). Normal pLA was found to be a true negative in 82.9% of cases, and elevated pLA was a true positive in 48.3% of cases. When the time between measurements was less than 60 minutes (n=25), normal pLA predicted normal sLA with 100% accuracy, with a false-positive rate of 18.2%. As time between measurements increased, accuracy diminished and the false-positive rate increased. Conclusions Overall, the level of agreement between pLA and sLA was poor. Accuracy of pLA diminished markedly as the time between the two measurements increased. It may be possible to use pLA as a screening tool; when considered this way, pLA performed much better, though larger prospective trials would be needed to confirm this

Vancomycin-resistant enterococci surveillance of intensive care patients: incidence and outcome of colonisation

Background Vancomycin-resistant enterococci (VRE) colonisation serves as a reservoir and increases the risk of developing an infection with VRE. Treatment difficulties and infection control measures associated with vancomycin-resistant enterococci presen

A prospective controlled trial of the effect of a multi-faceted intervention on early recognition and intervention in deteriorating hospital patients

Aim: To determine whether the introduction of a multi-faceted intervention (newly designed ward observation chart, a track and trigger system and an associated education program, COMPAS

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc