In a randomized trial involving 4000 patients in the ICU who required sedation for mechanical ventilation, dexmedetomidine had no benefit on 90-day mortality as compared with usual care and was ...associated with more adverse events. Additional drugs were required for prescribed sedation levels in the two groups.
The interleukin-6 receptor blockers tocilizumab and sarilumab were tested against standard care in a randomized trial involving patients newly admitted to the intensive care unit and requiring ...respiratory or blood-pressure support. The median number of organ support–free days was 10 with tocilizumab, 11 with sarilumab, and 0 with standard care.
Prehospital Tranexamic Acid for Severe Trauma Gruen, Russell L; Mitra, Biswadev; Bernard, Stephen A ...
The New England journal of medicine,
07/2023, Letnik:
389, Številka:
2
Journal Article
Recenzirano
In this trial involving adults with major trauma, treatment with tranexamic acid did not result in a greater number of patients surviving with a favorable functional outcome at 6 months than placebo.
IMPORTANCE: Proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs) are often prescribed for patients as stress ulcer prophylaxis drugs in the intensive care unit (ICU). The ...comparative effect of these drugs on mortality is unknown. OBJECTIVE: To compare in-hospital mortality rates using PPIs vs H2RBs for stress ulcer prophylaxis. DESIGN, SETTING, AND PARTICIPANTS: Cluster crossover randomized clinical trial conducted at 50 ICUs in 5 countries between August 2016 and January 2019. Patients requiring invasive mechanical ventilation within 24 hours of ICU admission were followed up for 90 days at the hospital. INTERVENTIONS: Two stress ulcer prophylaxis strategies were compared (preferential use with PPIs vs preferential use with H2RBs). Each ICU used each strategy sequentially for 6 months in random order; 25 ICUs were randomized to the sequence with use of PPIs and then use of H2RBs and 25 ICUs were randomized to the sequence with use of H2RBs and then use of PPIs (13 436 patients randomized by site to PPIs and 13 392 randomized by site to H2RBs). MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality within 90 days during index hospitalization. Secondary outcomes were clinically important upper gastrointestinal bleeding, Clostridioides difficile infection, and ICU and hospital lengths of stay. RESULTS: Among 26 982 patients who were randomized, 154 opted out, and 26 828 were analyzed (mean SD age, 58 17.0 years; 9691 36.1% were women). There were 26 771 patients (99.2%) included in the mortality analysis; 2459 of 13 415 patients (18.3%) in the PPI group died at the hospital by day 90 and 2333 of 13 356 patients (17.5%) in the H2RB group died at the hospital by day 90 (risk ratio, 1.05 95% CI, 1.00 to 1.10; absolute risk difference, 0.93 percentage points 95% CI, −0.01 to 1.88 percentage points; P = .054). An estimated 4.1% of patients randomized by ICU site to PPIs actually received H2RBs and an estimated 20.1% of patients randomized by ICU site to H2RBs actually received PPIs. Clinically important upper gastrointestinal bleeding occurred in 1.3% of the PPI group and 1.8% of the H2RB group (risk ratio, 0.73 95% CI, 0.57 to 0.92; absolute risk difference, −0.51 percentage points 95% CI, −0.90 to −0.12 percentage points; P = .009). Rates of Clostridioides difficile infection and ICU and hospital lengths of stay were not significantly different by treatment group. One adverse event (an allergic reaction) was reported in 1 patient in the PPI group. CONCLUSIONS AND RELEVANCE: Among ICU patients requiring mechanical ventilation, a strategy of stress ulcer prophylaxis with use of proton pump inhibitors vs histamine-2 receptor blockers resulted in hospital mortality rates of 18.3% vs 17.5%, respectively, a difference that did not reach the significance threshold. However, study interpretation may be limited by crossover in the use of the assigned medication. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12616000481471
In this issue of JAMA, the COVID STEROID 2 Trial Group0 reports the results of an international, multicenter randomized clinical trial that compared 2 alternative doses of glucocorticoids in ...critically ill patients with COVID-19. The investigators randomly assigned 1000 patients with confirmed SARS-CoV-2 infection who were receiving supplemental oxygen at a flow rate of at least 10 L/min or mechanical ventilation to receive, as blinded study medication, either 12 mg/d of dexamethasone or 6 mg/d of dexamethasone. The median duration of prior treatment with dexamethasone was 1 day. The primary outcome was the number of days alive without life support (defined as invasive mechanical ventilation, circulatory support, or kidney replacement therapy) censored at 28 days following randomization. The study had 85% power to demonstrate a relative reduction of 15% in 28-day mortality (from 30.0% to 25.5%) combined with a reduction of 10% in time receiving life support.
Rationale Blood glucose concentrations affect outcomes in critically ill patients but the optimal target blood glucose range in those with type 2 diabetes is unknown. Objective To evaluate the ...effects of a 'liberal' approach to targeted blood glucose range during intensive care unit (ICU) admission. Methods This mutlicenter, parallel-group, open-label, randomized clinical trial included 419 adult patients with type 2 diabetes expected to be in the ICU on at least three consecutive days. In the intervention group intravenous insulin was commenced at a blood glucose >252 mg/dL and titrated to a target range of 180 to 252 mg/dL. In the comparator group insulin was commenced at a blood glucose >180 mg/dL and titrated to a target range of 108 to 180 mg/dL. The primary outcome was incident hypoglycemia (<72 mg/dL). Secondary outcomes included glucose metrics and clinical outcomes. Main Results At least one episode of hypoglycemia occurred in 10 of 210 (5%) patients assigned the intervention and 38 of 209 (18%) patients assigned the comparator (incident rate ratio: 0.21 (95% CI, 0.09 to 0.49); P<0.001). Those assigned the intervention had greater blood glucose concentrations (daily mean, minimum, maximum), less glucose variability and less relative hypoglycaemia (P<0.001 for all comparisons). By day 90, 62 of 210 (29.5%) in the intervention and 52 of 209 (24.9%) in the comparator group had died (absolute difference 4.6 percentage points (95%CI, -3.9 to 13.2%); P=0.29). Conclusions A liberal approach to blood glucose targets reduced incident hypoglycemia but did not improve patient-centered outcomes. Clinical trial registration available at www.anzctr.org.au, ID: ACTRN12616001135404.
Large randomised trials provide the most reliable evidence of effectiveness of new treatments in clinical practice. However, the time and resources required to complete such trials can be daunting. ...An overarching clinical trial platform focused on a single condition or type of surgery, aiming to compare several treatments, with an option to stop any or add in new treatment options, can provide greater efficiency. This has the potential to accelerate knowledge acquisition and identify effective, ineffective, or harmful treatments faster. The master protocol of the platform defines the study population(s) and standardised procedures. Ineffective or harmful treatments can be discarded or study drug dose modified during the life cycle of the trial. Other adaptive elements that can be modified include eligibility criteria, required sample size for any comparison(s), randomisation assignment ratio, and the addition of other promising treatment options. There are excellent opportunities for anaesthetists to establish platform trials in perioperative medicine. Platform trials are highly efficient, with the potential to provide quicker answers to important clinical questions that lead to improved patient care.
Delayed graft function (DGF) is a major adverse complication of deceased donor kidney transplantation. Intravenous fluids are routinely given to patients receiving a transplant to maintain ...intravascular volume and optimise graft function. Saline (0·9% sodium chloride) is widely used but might increase the risk of DGF due to its high chloride content. We aimed to test our hypothesis that using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce the incidence of DGF.
BEST-Fluids was a pragmatic, registry-embedded, multicentre, double-blind, randomised, controlled trial at 16 hospitals in Australia and New Zealand. Adults and children of any age receiving a deceased donor kidney transplant were eligible; those receiving a multi-organ transplant or weighing less than 20 kg were excluded. Participants were randomly assigned (1:1) using an adaptive minimisation algorithm to intravenous balanced crystalloid solution (Plasma-Lyte 148) or saline during surgery and up until 48 h after transplantation. Trial fluids were supplied in identical bags and clinicians determined the fluid volume, rate, and time of discontinuation. The primary outcome was DGF, defined as receiving dialysis within 7 days after transplantation. All participants who consented and received a transplant were included in the intention-to-treat analysis of the primary outcome. Safety was analysed in all randomly assigned eligible participants who commenced surgery and received trial fluids, whether or not they received a transplant. This study is registered with Australian New Zealand Clinical Trials Registry, (ACTRN12617000358347), and ClinicalTrials.gov (NCT03829488).
Between Jan 26, 2018, and Aug 10, 2020, 808 participants were randomly assigned to balanced crystalloid (n=404) or saline (n=404) and received a transplant (512 63% were male and 296 37% were female). One participant in the saline group withdrew before 7 days and was excluded, leaving 404 participants in the balanced crystalloid group and 403 in the saline group that were included in the primary analysis. DGF occurred in 121 (30%) of 404 participants in the balanced crystalloid group versus 160 (40%) of 403 in the saline group (adjusted relative risk 0·74 95% CI 0·66 to 0·84; p<0·0001; adjusted risk difference 10·1% 95% CI 3·5 to 16·6). In the safety analysis, numbers of investigator-reported serious adverse events were similar in both groups, being reported in three (<1%) of 406 participants in the balanced crystalloid group versus five (1%) of 409 participants in the saline group (adjusted risk difference –0·5%, 95% CI –1·8 to 0·9; p=0·48).
Among patients receiving a deceased donor kidney transplant, intravenous fluid therapy with balanced crystalloid solution reduced the incidence of DGF compared with saline. Balanced crystalloid solution should be the standard-of-care intravenous fluid used in deceased donor kidney transplantation.
Medical Research Future Fund and National Health and Medical Research Council (Australia), Health Research Council (New Zealand), Royal Australasian College of Physicians, and Baxter.
IMPORTANCE: The efficacy of vitamin C for hospitalized patients with COVID-19 is uncertain. OBJECTIVE: To determine whether vitamin C improves outcomes for patients with COVID-19. DESIGN, SETTING, ...AND PARTICIPANTS: Two prospectively harmonized randomized clinical trials enrolled critically ill patients receiving organ support in intensive care units (90 sites) and patients who were not critically ill (40 sites) between July 23, 2020, and July 15, 2022, on 4 continents. INTERVENTIONS: Patients were randomized to receive vitamin C administered intravenously or control (placebo or no vitamin C) every 6 hours for 96 hours (maximum of 16 doses). MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of organ support–free days defined as days alive and free of respiratory and cardiovascular organ support in the intensive care unit up to day 21 and survival to hospital discharge. Values ranged from –1 organ support–free days for patients experiencing in-hospital death to 22 organ support–free days for those who survived without needing organ support. The primary analysis used a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented efficacy (improved survival, more organ support–free days, or both), an OR less than 1 represented harm, and an OR less than 1.2 represented futility. RESULTS: Enrollment was terminated after statistical triggers for harm and futility were met. The trials had primary outcome data for 1568 critically ill patients (1037 in the vitamin C group and 531 in the control group; median age, 60 years IQR, 50-70 years; 35.9% were female) and 1022 patients who were not critically ill (456 in the vitamin C group and 566 in the control group; median age, 62 years IQR, 51-72 years; 39.6% were female). Among critically ill patients, the median number of organ support–free days was 7 (IQR, −1 to 17 days) for the vitamin C group vs 10 (IQR, −1 to 17 days) for the control group (adjusted proportional OR, 0.88 95% credible interval {CrI}, 0.73 to 1.06) and the posterior probabilities were 8.6% (efficacy), 91.4% (harm), and 99.9% (futility). Among patients who were not critically ill, the median number of organ support–free days was 22 (IQR, 18 to 22 days) for the vitamin C group vs 22 (IQR, 21 to 22 days) for the control group (adjusted proportional OR, 0.80 95% CrI, 0.60 to 1.01) and the posterior probabilities were 2.9% (efficacy), 97.1% (harm), and greater than 99.9% (futility). Among critically ill patients, survival to hospital discharge was 61.9% (642/1037) for the vitamin C group vs 64.6% (343/531) for the control group (adjusted OR, 0.92 95% CrI, 0.73 to 1.17) and the posterior probability was 24.0% for efficacy. Among patients who were not critically ill, survival to hospital discharge was 85.1% (388/456) for the vitamin C group vs 86.6% (490/566) for the control group (adjusted OR, 0.86 95% CrI, 0.61 to 1.17) and the posterior probability was 17.8% for efficacy. CONCLUSIONS AND RELEVANCE: In hospitalized patients with COVID-19, vitamin C had low probability of improving the primary composite outcome of organ support–free days and hospital survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT04401150 (LOVIT-COVID) and NCT02735707 (REMAP-CAP)
Simvastatin in Critically Ill Patients with Covid-19 Hills, Thomas E; Lorenzi, Elizabeth; Berry, Lindsay R ...
New England journal of medicine/The New England journal of medicine,
12/2023, Letnik:
389, Številka:
25
Journal Article
Recenzirano
Odprti dostop
In this trial of simvastatin involving critically ill patients with Covid-19, which was stopped owing to reduced cases, simvastatin did not meet the prespecified criteria for superiority to control ...treatment.
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