Multistudy Research Operations in the ICU: An Interprofessional Pandemic-Informed Approach.

Proliferation of COVID-19 research underscored the need for improved awareness among investigators, research staff and bedside clinicians of the operational details of clinical studies. The objective was to describe the genesis, goals, participation, procedures, and outcomes of two research operations committees in an academic ICU during the COVID-19 pandemic. DESIGN: Two-phase, single-center multistudy cohort. SETTING: University-affiliated ICU in Hamilton, ON, Canada. PATIENTS: Adult patients in the ICU, medical stepdown unit, or COVID-19 ward. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An interprofessional COVID Collaborative was convened at the pandemic onset within our department, to proactively coordinate studies, help navigate multiple authentic consent encounters by different research staff, and determine which studies would be suitable for coenrollment. From March 2020 to May 2021, five non-COVID trials continued, two were paused then restarted, and five were launched. Over 15 months, 161 patients were involved in 215 trial enrollments, 110 (51.1%) of which were into a COVID treatment trial. The overall informed consent rate (proportion agreed of those eligible and approached including a priori and deferred consent models) was 83% (215/259). The informed consent rate was lower for COVID-19 trials (110/142, 77.5%) than other trials (105/117, 89.7%; p = 0.01). Patients with COVID-19 were significantly more likely to be coenrolled in two or more studies (29/77, 37.7%) compared with other patients (13/84, 15.5%; p = 0.002). Review items for each new study were collated, refined, and evolved into a modifiable checklist template to set up each study for success. The COVID Collaborative expanded to a more formal Department of Critical Care Research Operations Committee in June 2021, supporting sustainable research operations during and beyond the pandemic. CONCLUSIONS: Structured coordination and increased communication about research operations among diverse research stakeholders cultivated a sense of shared purpose and enhanced the integrity of clinical research operations.

Heparin thromboprophylaxis in medical-surgical critically ill patients: a systematic review and meta-analysis of randomized trials.

OBJECTIVE: Venous thromboembolism prevention during critical illness is a widely used quality metric. The objective of this systematic review was to systematically review the efficacy and safety of heparin thromboprophylaxis in medical-surgical patients in the ICU. DATA SOURCES: We searched EMBASE, MEDLINE, the Cochrane Controlled Trials Register, Clinicaltrials.gov, and personal files through May 2012. STUDY SELECTION: Randomized trials in adult medical-surgical ICU patients comparing any heparin (unfractionated heparin or low-molecular-weight heparin) with each other or no anticoagulant prophylaxis, evaluating deep vein thrombosis, pulmonary embolism, major bleeding, or mortality. DATA EXTRACTION: Independently, in duplicate, we abstracted trial characteristics, outcomes, and risk of bias. DATA SYNTHESIS: Seven trials involved 7,226 patients. Any heparin thromboprophylaxis compared with placebo reduced rates of deep vein thrombosis (pooled risk ratio, 0.51 [95% CI, 0.41, 0.63]; p<0.0001; I=77%) and pulmonary embolism (risk ratio, 0.52 [95% CI, 0.28, 0.97]; p=0.04; I=0%) but not symptomatic deep vein thrombosis (risk ratio, 0.86 [95% CI, 0.59, 1.25]; p=0.43). Major bleeding (risk ratio, 0.82 [95% CI, 0.56, 1.21]; p=0.32; I=50%) and mortality (risk ratio, 0.89 [95% CI, 0.78, 1.02]; p=0.09; I=0%) rates were similar. Compared with unfractionated heparin, low-molecular-weight heparin reduced rates of pulmonary embolism (risk ratio, 0.62 [95% CI, 0.39, 1.00]; p=0.05; I=53%) and symptomatic pulmonary embolism (risk ratio, 0.58 [95% CI, 0.34, 0.97]; p=0.04) but not deep vein thrombosis (risk ratio, 0.90 [95% CI, 0.74, 1.08]; p=0.26; I=0%), symptomatic deep vein thrombosis (risk ratio, 0.87 [95% CI, 0.60, 1.25]; p=0.44; I=0%), major bleeding (risk ratio, 0.97 [95% CI, 0.75, 1.26]; p=0.83; I=0%), or mortality (risk ratio, 0.93 [95% CI, 0.82, 1.04]; p=0.20; I=31%). CONCLUSIONS: Trial evidence to date suggests that any type of heparin thromboprophylaxis decreases deep vein thrombosis and pulmonary embolism in medical-surgical critically ill patients, and low-molecular-weight heparin compared with bid unfractionated heparin decreases pulmonary embolism and symptomatic pulmonary embolism. Major bleeding and mortality rates do not appear to be significantly influenced by heparin thromboprophylaxis in the ICU setting. Trial methodology, indirectness, and the heterogeneity and imprecision of some results temper inferences from this literature.

The effect of selenium therapy on mortality in patients with sepsis syndrome: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Patients with sepsis syndrome commonly have low serum selenium levels. Several randomized controlled trials have examined the efficacy of selenium supplementation on mortality in patients with sepsis. OBJECTIVE: To determine the efficacy and safety of high-dose selenium supplementation compared to placebo for the reduction of mortality in patients with sepsis. SOURCES OF DATA: We searched Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, SciFinder, and Clinicaltrials.gov. SELECTION CRITERIA: Randomized controlled parallel group trials comparing selenium supplementation in doses greater than daily requirement to placebo on the outcome of mortality in patients with sepsis syndrome. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcome was mortality; secondary outcomes were ICU length of stay, nosocomial pneumonia, and adverse events. Trial authors were contacted for additional or clarifying information. RESULTS: Nine trials enrolling a total of 792 patients were included. Selenium supplementation in comparison to placebo was associated with lower mortality (odds ratio, 0.73; 95% CI, 0.54, 0.98; p = 0.03; I = 0%). Among patients receiving and not receiving selenium, there was no difference in ICU length of stay (mean difference, 2.03; 95% CI, -0.51, 4.56; p = 0.12; I = 0%) or nosocomial pneumonia (odds ratio, 0.83; 95% CI, 0.28, 2.49; p = 0.74; I = 56%). Significant heterogeneity among trials in adverse event reporting precluded pooling of results. CONCLUSIONS: In patients with sepsis, selenium supplementation at doses higher than daily requirement may reduce mortality. We observed no impact of selenium on ICU length of stay or risk of nosocomial pneumonia.

Proton pump inhibitors versus histamine 2 receptor antagonists for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis.

BACKGROUND: Critically ill patients may develop bleeding caused by stress ulceration. Acid suppression is commonly prescribed for patients at risk of stress ulcer bleeding. Whether proton pump inhibitors are more effective than histamine 2 receptor antagonists is unclear. OBJECTIVES: To determine the efficacy and safety of proton pump inhibitors vs. histamine 2 receptor antagonists for the prevention of upper gastrointestinal bleeding in the ICU. SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, ACPJC, CINHAL, online trials registries (clinicaltrials.gov, ISRCTN Register, WHO ICTRP), conference proceedings databases, and reference lists of relevant articles. SELECTION CRITERIA: Randomized controlled parallel group trials comparing proton pump inhibitors to histamine 2 receptor antagonists for the prevention of upper gastrointestinal bleeding in critically ill patients, published before March 2012. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcomes were clinically important upper gastrointestinal bleeding and overt upper gastrointestinal bleeding; secondary outcomes were nosocomial pneumonia, ICU mortality, ICU length of stay, and Clostridium difficile infection. Trial authors were contacted for additional or clarifying information. RESULTS: Fourteen trials enrolling a total of 1,720 patients were included. Proton pump inhibitors were more effective than histamine 2 receptor antagonists at reducing clinically important upper gastrointestinal bleeding (relative risk 0.36; 95% confidence interval 0.19-0.68; p = 0.002; I = 0%) and overt upper gastrointestinal bleeding (relative risk 0.35; 95% confidence interval 0.21-0.59; p < 0.0001; I = 15%). There were no differences between proton pump inhibitors and histamine 2 receptor antagonists in the risk of nosocomial pneumonia (relative risk 1.06; 95% confidence interval 0.73-1.52; p = 0.76; I = 0%), ICU mortality (relative risk 1.01; 95% confidence interval 0.83-1.24; p = 0.91; I = 0%), or ICU length of stay (mean difference -0.54 days; 95% confidence interval -2.20 to 1.13; p = 0.53; I = 39%). No trials reported on C. difficile infection. CONCLUSIONS: In critically ill patients, proton pump inhibitors seem to be more effective than histamine 2 receptor antagonists in preventing clinically important and overt upper gastrointestinal bleeding. The robustness of this conclusion is limited by the trial methodology, differences between lower and higher quality trials, sparse data, and possible publication bias. We observed no differences between drugs in the risk of pneumonia, death, or ICU length of stay.