ABSTRACT
Hypotension affects approximately 40% of critically ill patients undergoing emergency intubation and is associated with an increased risk of death. The objective of this study was to examine the association between prophylactic vasopressor administration and the incidence of peri-intubation hypotension and other clinical outcomes. DESIGN: A secondary analysis of two multicenter randomized clinical trials. The clinical effect of prophylactic vasopressor administration was estimated using a one-to-one propensity-matched cohort of patients with and without prophylactic vasopressors. SETTING: Seven emergency departments and 17 ICUs across the United States. PATIENTS: One thousand seven hundred ninety-eight critically ill patients who underwent emergency intubation at the study sites between February 1, 2019, and May 24, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was peri-intubation hypotension defined as a systolic blood pressure less than 90 mm Hg occurring between induction and 2 minutes after tracheal intubation. A total of 187 patients (10%) received prophylactic vasopressors prior to intubation. Compared with patients who did not receive prophylactic vasopressors, those who did were older, had higher Acute Physiology and Chronic Health Evaluation II scores, were more likely to have a diagnosis of sepsis, had lower pre-induction systolic blood pressures, and were more likely to be on continuous vasopressor infusions prior to intubation. In our propensity-matched cohort, prophylactic vasopressor administration was not associated with reduced risk of peri-intubation hypotension (41% vs 32%; p = 0.08) or change in systolic blood pressure from baseline (-12 vs -11 mm Hg; p = 0.66). CONCLUSIONS: The administration of prophylactic vasopressors was not associated with a lower incidence of peri-intubation hypotension in our propensity-matched analysis. To address potential residual confounding, randomized clinical trials should examine the effect of prophylactic vasopressor administration on peri-intubation outcomes.
ABSTRACT
Rationale: Optimal infusion rate for fluid challenges in critically ill patients is unknown. A large clinical trial comparing two different infusion rates yielded neutral results. Conditional average treatment effect (CATE) assessment may aid in tailoring therapy. Objectives: To estimate CATE in patients enrolled in the BaSICS trial and to assess the effects of receiving CATE model-recommended treatment in terms of hospital mortality. Methods: Post hoc analysis of the BaSICS trial assessing the effect of two infusion rates for the fluid challenge (fast, 999 ml/h, control group; vs. slow, 333 ml/h, intervention group) on hospital mortality. CATE was estimated as the difference in outcome for treatment arms in counterfactuals obtained from a Bayesian model trained in the first half of the trial adjusted for predictors hypothesized to interact with the intervention. The model recommended slow or fast infusion or made no recommendation in the second half. A threshold greater than 0.90 probability of benefit was considered. Results: A total of 10,465 patients were analyzed. The model was trained in 5,230 patients and tested in 5,235 patients. A recommendation could be made in the test set in 19% of patients (14% were recommended the control group and 5% the treatment group); for 81% of patients, no recommendation could be made. Slow infusion was more frequently recommended in cases of planned admissions in younger patients; fast infusion was recommended for older patients with sepsis. Slow infusion rate in the subgroup of patients in the test set in which slow infusion was recommended by the model was associated with an odds ratio of 0.58 (95% credible interval of 0.32-0.90; 0.99 posterior probability of benefit) for hospital mortality. Fast infusion in the subgroup in which the model recommended fast infusion was associated with an odds ratio of 0.72 (credible intervals from 0.54 to 0.91; probability of benefit >0.99). Conclusions: Estimation of CATEs from counterfactual probabilities in data from BaSICS provided additional information on trial data. Agreement between treatment recommendation and actual treatment was associated with lower hospital mortality. Clinical trial registered with clinicaltrials.gov (NCT02875873).
Subject(s)
Critical Care , Critical Illness , Humans , Bayes Theorem , Critical Illness/therapy , Fluid Therapy/adverse effects , Fluid Therapy/methods , Research DesignABSTRACT
Objective: It remains unclear whether balanced solutions improve patient-centred outcomes in critically ill patients overall and whether the treatment effect is heterogeneous, with evidence that some populations of patients may be helped and others harmed. To provide the most up-to-date and comprehensive assessment of the totality of the evidence, we will perform an ongoing living systematic review with aggregated and individual patient data meta-analysis (IPDMA) comparing the use of balanced solutions with saline in critically ill adults. Design: Living systematic review using aggregated and individual patient data from randomised controlled trials. Data sources: We will conduct annual searches of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials. gov, the Australian New Zealand Clinical Trials Registry (ANZCTR), Japan's University Hospital Medical Information Network (UMIN) Center, and the Brazilian Registry of Clinical Trials (ReBEC). The first search was completed on 1 March 2022 and will be repeated annually. Authors of eligible trials will be invited to provide individual data for the IPDMA. The initial analysis will use all data received up to 30 June 2022. Review methods: We will include randomised controlled trials in adults treated in an intensive care unit that allocated individuals or clusters of patients to a balanced crystalloid solution or 0.9% saline for intravenous fluid therapy. Studies that used colloids as part of the intervention or that recruited only elective surgical patients will be excluded. The primary endpoint will be in-hospital mortality. The key secondary endpoint will be survival at longest follow-up for each trial. Data will be synthesised using both a random effect Bayesian meta-analysis and using hierarchical Bayesian models for individual patient data. Discussion: The use of balanced crystalloid solutions may reduce mortality and improve other outcomes in some critically ill patients. We will assess the totality of current and future evidence by performing an ongoing living systematic review with aggregated data and IPDMA. Protocol registration: CRD42022299282.
ABSTRACT
BACKGROUND: To assess whether use of low-chloride solutions in unselected critically ill or perioperative adult patients for maintenance or resuscitation reduces mortality and renal replacement therapy (RRT) use when compared to high-chloride fluids. METHODS: Systematic review and meta-analysis with random-effects inverse variance model. PubMed, Cochrane library, EMBASE, LILACS, and Web of Science were searched from inception to October 2016. Published and unpublished randomized controlled trials in any language that enrolled critically ill and/or perioperative adult patients and compared a low- to a highchloride solution for volume maintenance or resuscitation. The primary outcomes were mortality and RRT use. We conducted trial sequential analyses and assessed risk of bias of individual trials and the overall quality of evidence. Fifteen trials with 4067 patients, most at low risk of bias, were identified. Of those, only 11 and 10 trials had data on mortality and RRT use, respectively. A total of 3710 patients were included in the mortality analysis and 3724 in the RRT analysis. RESULTS: No statistically significant impact on mortality (odds ratio, 0.90; 95% confidence interval, 0.69-1.17; P = .44; I = 0%) or RRT use (odds ratio, 1.12; 95% confidence interval, 0.80-1.58; P = .52; I = 0%) was found. Overall quality of evidence was low for both primary outcomes. Trial sequential analyses highlighted that the sample size needed was much larger than that available for properly powered outcome assessment. CONCLUSIONS: The current evidence on low- versus high-chloride solutions for unselected critically ill or perioperative adult patients demonstrates no benefit, but suffers from considerable imprecision. We noted a limited exposure volume for study fluids and a relatively low risk of the populations in each study. Together with the relatively small pooled sample size, these data leave us underpowered to detect potentially important differences. Results from well-conducted, adequately powered randomized controlled trials examining sufficiently large fluid exposure are necessary.