Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the International Severe Acute Respiratory and Emerging Infection Consortium WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study

Due to the large number of patients with severe coronavirus disease 2019 (COVID-19), many were treated outside the traditional walls of the intensive care unit (ICU), and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the International Severe Acute Respiratory and Emerging Infection Consortium World Health Organization COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or noninvasive mechanical ventilation, high-flow nasal cannula, inotropes or vasopressors. A logistic generalised additive model was used to compare clinical outcomes among patients admitted or not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median (interquartile range (IQR), 67 (55-78) years), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 (5-19) days and was longer in patients admitted to an ICU than in those who were cared for outside the ICU (12 (6-23) days versus 8 (4-15) days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% (5797 out of 18 831) versus 39.0% (7532 out of 19 295), p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR 0.70, 95% CI 0.65-0.75; p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside an ICU

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

Sodium bicarbonate infusion to reduce cardiac surgery-associated acute kidney injury: a phase II multicenter double-blind randomized controlled trial

OBJECTIVE

A multicenter, randomized, controlled Phase IIb trial of avoidance of hyperoxemia during cardiopulmonary bypass

Background: Cardiac surgery utilizing cardiopulmonary bypass (CPB) is one of the most common forms of major surgery. Cardiac surgery–associated multiorgan dysfunction (CSA-MOD) is well recognized and includes acute kidney injury (AKI), hepatic impairment, myocardial damage, and postoperative neurologic deficit. Pathophysiology of CSA-MOD involves numerous injurious pathways linked to the use of CPB including oxidative stress and formation of reactive iron species. During cardiac surgery with CPB, arterial return blood is oxygenated to supranormal levels. This study aimed to determine whether the avoidance of arterial hyperoxemia decreased oxidative stress and reduced the severity of the multiorgan dysfunction in patients undergoing cardiac surgery utilizing CPB. Methods: The study was a multicenter, open-label, parallel-group, randomized controlled study of the avoidance of arterial hyperoxemia versus usual care in patients undergoing cardiac surgery involving CPB. Primary outcome was the incidence and severity of AKI. Secondary outcomes included serum biomarkers for CSA-MOD, duration of mechanical ventilation, and length of intensive care and hospital stay. Results: A total of 298 patients were randomized and analyzed at two hospitals in New Zealand and Australia. Mean Pao2 was significantly different between groups during CPB. There was no difference in the development of AKI (intervention arm 72.0% vs. usual care 66.2%; difference, −5.8% [95% CI, −16.1 to 4.7%]; P = 0.28), other markers of organ damage, or intensive care unit and hospital length of stay. Conclusions: Avoiding modest hyperoxemia during CPB failed to demonstrate any difference in AKI, markers of organ damage, or length of stay.Shay P. McGuinness, Rachael L. Parke, Kate Drummond, Tim Willcox, Michael Baile

What happens to nutrition intake in the post-intensive care unit hospitalization period? An observational cohort study in critically ill adults

BACKGROUND: Little is currently known about nutrition intake and energy requirements in the post-intensive care unit (ICU) hospitalization period in critically ill patients. We aimed to describe energy and protein intake, and determine the feasibility of measuring energy expenditure during the post-ICU hospitalization period in critically ill adults. METHODS: This is a nested cohort study within a randomized controlled trial in critically ill patients. After discharge from ICU, energy and protein intake was quantified periodically and indirect calorimetry attempted. Data are presented as n (%), mean (SD), and median (interquartile range [IQR]). RESULTS: Thirty-two patients were studied in the post-ICU hospitalization period, and 12 had indirect calorimetry. Mean age and BMI was 56 (18) years and 30 (8) kg/m2 , respectively, 75% were male, and the median estimated energy and protein requirement were 2000 [1650-2550] kcal and 112 [84-129] g, respectively. Oral nutrition either alone (n = 124 days, 55%) or in combination with enteral nutrition (n = 96 days, 42%) was the predominant mode. Over 227 total days in the post-ICU hospitalization period, a median [IQR] of 1238 [869-1813] kcal and 60 [35-89.5] g of protein was received from nutrition therapy. In the 12 patients who had indirect calorimetry, the median measured daily energy requirement was 1982 [1843-2345] kcal and daily energy deficit was -95 [-1050 to 347] kcal compared with the measured energy requirement. CONCLUSIONS: Energy and protein intake in the post-ICU hospitalization period was less than estimated and measured energy requirements. Oral nutrition provided alone was the most common mode of nutrition therapy

Device-related pressure injuries in adult intensive care unit patients: An Australian and New Zealand point prevalence study

Background: Device-related pressure injuries (DRPIs) are an ongoing iatrogenic problem evident in intensive care unit (ICU) settings. Critically ill patients are at high risk of developing pressure injuries caused by devices. Objective: The aim of the study was to determine the prevalence of DRPI in critically ill patients in intensive care and the location, stage, and attributable device of DRPI and describe the products and processes of care used to prevent these injuries. Methods: This was a prospective, multicentre, cross-sectional point prevalence study of patients aged more than 16 years in Australian and New Zealand ICUs. The study was part of the Australian and New Zealand Intensive Care Society Clinical Trials Group Point Prevalence Program coordinated by The George Institute for Global Health. Main outcome measure: Identification of DRPI on the study day was the main outcome measure. Results: Of the 624 patients included from 44 participating ICUs, 27 were found to have 35 identified DRPIs, giving a point prevalence DRPI rate of 4.3% (27/624). Study patients had a mean age of 59 years, and 60.3% were men. Patients with DRPI compared with patients without DRPI were significantly heavier (median: 92 kg versus 80 kg, respectively, p = 0.027), were less likely to survive the ICU (63.0% versus 85.9%, respectively, p = 0.015), had higher Acute Physiology and Chronic Health Evaluation II scores at admission to the ICU (median: 20 versus 16, respectively, p = 0.001), received mechanical ventilation more often (88.9% versus 43.5%, respectively, p < 0.001), and were more frequently diagnosed with respiratory conditions (37.0% versus 18.6%, respectively, p = 0.022). Processes of care activities were surveyed in 42 ICUs. Most DRPIs were attributed to endotracheal tubes and other respiratory devices. Forty-two ICUs reported processes of care to prevent DRPI, and just more than half of the participating sites (54.8%, 23/44) reported a dedicated ICU-based protocol for prevention of DRPI. Conclusion: DRPIs pose a burden on patients in the ICU. Our study showed a DRPI prevalence comparable with other studies. Prevention strategies targeting DRPI should be included in ICU-specific pressure injury prevention guidelines or protocols.</p