UK Efficacy and Mechanism Evaluation Programme and National Institutes of Health.

IMPORTANCEIn patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes. OBJECTIVE To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020. INTERVENTIONS Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210). MAIN OUTCOMES AND MEASURESThe primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates. RESULTS Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, −7.6% to 11.5%]; P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, −2.1 [95% CI, −3.8 to −0.3]; P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device.CONCLUSIONS AND RELEVANCE Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference.

In adults undergoing hip fracture surgery, regional anesthesia may reduce postoperative delirium, but there is uncertainty about its effectiveness.OBJECTIVE To investigate, in older adults undergoing surgical repair for hip fracture, the effects of regional anesthesia on the incidence of postoperative delirium compared with general anesthesia. DESIGN, SETTING, AND PARTICIPANTSA randomized, allocation-concealed, open-label, multicenter clinical trial of 950 patients, aged 65 years and older, with or without preexisting dementia, and a fragility hip fracture requiring surgical repair from 9 university teaching hospitals in Southeastern China. Participants were enrolled between October 2014 and September 2018; 30-day follow-up ended November 2018.INTERVENTIONS Patients were randomized to receive either regional anesthesia (spinal, epidural, or both techniques combined with no sedation; n = 476) or general anesthesia (intravenous, inhalational, or combined anesthetic agents; n = 474).MAIN OUTCOMES AND MEASURES Primary outcome was incidence of delirium during the first 7 postoperative days. Secondary outcomes analyzed in this article include delirium severity, duration, and subtype; postoperative pain score; length of hospitalization; 30-day all-cause mortality; and complications. RESULTS Among 950 randomized patients (mean age, 76.5 years; 247 [26.8%] male), 941 were evaluable for the primary outcome (6 canceled surgery and 3 withdrew consent). Postoperative delirium occurred in 29 (6.2%) in the regional anesthesia group vs 24 (5.1%) in the general anesthesia group (unadjusted risk difference [RD], 1.1%; 95% CI, -1.7% to 3.8%; P = .48; unadjusted relative risk [RR], 1.2 [95% CI, 0.7 to 2.0]; P = .57]). Mean severity score of delirium was 23.0 vs 24.1, respectively (unadjusted difference, -1.1; 95% CI, -4.6 to 3.1). A single delirium episode occurred in 16 (3.4%) vs 10 (2.1%) (unadjusted RD, 1.1%; 95% CI, -1.7% to 3.9%; RR, 1.6 [95% CI, 0.7 to 3.5]). Hypoactive subtype in 11 (37.9%) vs 5 (20.8%) (RD, 11.5; 95% CI, -11.0% to 35.7%; RR, 2.2 [95% CI, 0.8 to 6.3]). Median worst pain score was 0 (IQR, 0 to 20) vs 0 (IQR, 0 to 10) (difference 0; 95% CI, 0 to 0). Median length of hospitalization was 7 days (IQR, 5 to 10) vs 7 days (IQR, 6 to 10) (difference 0; 95% CI, 0 to 0). Death occurred in 8 (1.7%) vs 4 (0.9%) (unadjusted RD, -0.8%; 95% CI, -2.2% to 0.7%; RR, 2.0 [95% CI, 0.6 to 6.5]). Adverse events were reported in 106 episodes in the regional anesthesia group and 102 in the general anesthesia group; the most frequently reported adverse events were nausea and vomiting (47 [44.3%] vs 34 [33.3%]) and postoperative hypotension (13 [12.3%] vs 10 [9.8%]). CONCLUSIONS AND RELEVANCEIn patients aged 65 years and older undergoing hip fracture surgery, regional anesthesia without sedation did not significantly reduce the incidence of postoperative delirium compared with general anesthesia.

IntroductionSeveral observational studies suggest that statins modulate the pathophysiology of sepsis and may prevent its progression. The aim of this study was to determine if the acute administration of atorvastatin reduces sepsis progression in statin naïve patients hospitalized with sepsis.MethodsA single centre phase II randomized double-blind placebo-controlled trial. Patients with sepsis were randomized to atorvastatin 40 mg daily or placebo for the duration of their hospital stay up to a maximum of 28-days. The primary end-point was the rate of sepsis progressing to severe sepsis during hospitalization.Results100 patients were randomized, 49 to the treatment with atorvastatin and 51 to placebo. Patients in the atorvastatin group had a significantly lower conversion rate to severe sepsis compared to placebo (4% vs. 24% p = 0.007.), with a number needed to treat of 5. No significant difference in length of hospital stay, critical care unit admissions, 28-day and 12-month readmissions or mortality was observed. Plasma cholesterol and albumin creatinine ratios were significantly lower at day 4 in the atorvastatin group (p < 0.0001 and p = 0.049 respectively). No difference in adverse events between the two groups was observed (p = 0.238).ConclusionsAcute administration of atorvastatin in patients with sepsis may prevent sepsis progression. Further multi-centre trials are required to verify these findings.Trial RegistrationInternational Standard Randomized Control Trial Registry ISRCTN64637517.

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Use of Lifesaver by school children, compared to F2F training alone, can lead to comparable learning outcomes for several key elements of successful CPR. Its use can be considered where resources or time do not permit formal F2F training sessions. The true benefits of Lifesaver can be realised if paired with F2F training.

Introduction Compliance with the ventilator care bundle affects the rate of ventilator-associated pneumonia. It was not known, however, whether compliance with sepsis care bundles has an impact on outcome. The aims of the present study were to determine the rate of compliance with 6-hour and 24-hour sepsis bundles and to determine the impact of the compliance on hospital mortality in patients with severe sepsis or septic shock.

Cerebral oximetry allows real-time, noninvasive cerebral oxygenation monitoring during cardiopulmonary resuscitation. Higher cerebral oxygenation during cardiopulmonary resuscitation is associated with return of spontaneous circulation and neurologically favorable survival to hospital discharge. Achieving higher regional cerebral oxygenation during resuscitation may optimize the chances of cardiac arrest favorable outcomes.