Abstract

BACKGROUND In previous studies of predictors of gastrointestinal (GI) bleeding in the intensive care unit (ICU), most patients received pharmacological stress ulcer prophylaxis (SUP). We aimed to assess associations between potential predictors of clinically important GI bleeding (CIB) and overt GI bleeding in adult ICU patients, while considering the effect and potential interaction with use of SUP. METHODS We included 3291 acutely admitted adult ICU patients with risk factors for GI bleeding randomised to SUP (pantoprazole) or placebo in the SUP-ICU trial. We used logistic regression models adjusted for allocation to SUP to estimate associations between 23 potential predictors and CIB (primary outcome) and overt GI bleeding (secondary outcome). Further, we assessed associations between potential predictors and both outcomes in each allocation group and assessed potential interaction with allocation to SUP. RESULTS Increasing SAPS II and SOFA scores, use of circulatory support and renal replacement therapy were associated with increased risk of CIB and overt GI bleeding; chronic lung disease was associated with increased risk of overt GI bleeding. Results for the remaining potential predictors were compatible with both no difference or increased and decreased risks. We found no strong evidence for any interaction between treatment allocation and any potential predictors. CONCLUSION In adult ICU patients at risk of GI bleeding, severity of illness, use of circulatory support and renal replacement therapy were associated with higher odds of CIB, with no strong evidence of interaction with SUP.

Abstract

PURPOSE With the publication of a large randomized-controlled trial (RCT) suggesting that tranexamic acid (TXA) may improve head-injury-related deaths, we aimed to determine the safety and efficacy of TXA in acute traumatic brain injury (TBI). METHODS In this systematic review and meta-analysis, we searched MEDLINE, PubMed, EMBASE, CINHAL, ACPJC, Google Scholar, and unpublished sources from inception until June 24, 2020 for randomized-controlled trials comparing TXA and placebo in adults and adolescents (≥ 15 years of age) with acute TBI. We screened studies and extracted summary estimates independently and in duplicate. We assessed the quality of evidence using the grading of recommendations assessment, development, and evaluation approach. This study is registered with PROSPERO (CRD42020164232). RESULTS Nine RCTs enrolled 14,747 patients. Compared to placebo, TXA had no effect on mortality (RR 0.95; 95% CI 0.88-1.02; RD 1.0% reduction; 95% CI 2.5% reduction to 0.4% increase, moderate certainty) or disability assessed by the Disability Rating Scale (MD, - 0.18 points; 95% CI - 0.43 to 0.08; moderate certainty). TXA may reduce hematoma expansion on subsequent imaging (RR 0.77; 95% CI 0.58-1.03, RD 3.6%, 95% CI 6.6% reduction to 0.5% increase, low certainty). Risks of adverse events (all moderate, low, or very low certainty) were similar between placebo and TXA. CONCLUSIONS In patients with acute TBI, TXA probably has no effect on mortality or disability. TXA may decrease hematoma expansion on subsequent imaging; however, this outcome is likely of less importance to patients. The use of TXA probably does not increase the risk of adverse events.

Abstract

PURPOSE Motivated by a new randomized trial (the PEPTIC trial) that raised the issue of an increase in mortality with proton pump inhibitors (PPIs) relative to histamine-2 receptor antagonists (H2RAs), we updated our prior systematic review and network meta-analysis (NMA) addressing the impact of pharmacological gastrointestinal bleeding prophylaxis in critically ill patients. METHODS We searched for randomized controlled trials that examined the efficacy and safety of gastrointestinal bleeding prophylaxis with PPIs, H2RAs, or sucralfate versus one another or placebo or no prophylaxis in adult critically ill patients. We performed Bayesian random-effects NMA and conducted analyses using all PEPTIC data as well as a restricted analysis using only PEPTIC data from high compliance centers. We used the GRADE approach to quantify absolute effects and assess the certainty of evidence. RESULTS Seventy-four trials enrolling 39 569 patients proved eligible. Both PPIs (risk ratio (RR) 1.03, 95% credible interval 0.93 to 1.14, moderate certainty) and H2RAs (RR 0.98, 0.89 to 1.08, moderate certainty) probably have little or no impact on mortality compared with no prophylaxis. There may be no important difference between PPIs and H2RAs on mortality (RR 1.05, 0.97 to 1.14, low certainty), the 95% credible interval of the complete analysis has not excluded an important increase in mortality with PPIs. Both PPIs (RR 0.46, 0.29 to 0.66) and H2RAs (RR 0.67, 0.48 to 0.94) probably reduce clinically important gastrointestinal bleeding; the magnitude of reduction is probably greater in PPIs than H2RAs (RR 0.69, 0.45 to 0.93), and the difference may be important in higher, but not lower bleeding risk patients. PPIs (RR 1.08, 0.88 to 1.45, low certainty) and H2RAs (RR 1.07, 0.85 to 1.37, low certainty) may have no important impact on pneumonia compared with no prophylaxis. CONCLUSION This updated NMA confirmed that PPIs and H2RAs are most likely to have a similar effect on mortality compared to each other and compared to no prophylaxis; however, the possibility that PPIs may slightly increase mortality cannot be excluded (low certainty evidence). PPIs and H2RAs probably achieve important reductions in clinically important gastrointestinal bleeding; for higher bleeding risk patients, the greater benefit of PPIs over H2RAs may be important. PPIs or H2RAs may not result in important increases in pneumonia but the certainty of evidence is low.

Abstract

PURPOSE Hemodynamic management of adults with distributive shock often includes the use of catecholamine-based vasoconstricting medications. It is unclear whether adding vasopressin or vasopressin analogues to catecholamine therapy is beneficial in the management of patients with distributive shock. The purpose of this guideline was to develop an evidence-based recommendation regarding the addition of vasopressin to catecholamine vasopressors in the management of adults with distributive shock. METHODS We summarized the evidence informing this recommendation by updating a recently published meta-analysis. Then, a multidisciplinary panel from the Canadian Critical Care Society developed the recommendation using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. RESULTS The updated systematic review identified 25 randomized controlled trials including a total of 3,737 patients with distributive shock. Compared with catecholamine therapy alone, the addition of vasopressin or its analogues was associated with a reduced risk of mortality (relative risk [RR], 0.91; 95% confidence interval [CI], 0.85 to 0.99; low certainty), reduced risk of atrial fibrillation (RR, 0.77; 95% CI, 0.67 to 0.88; high certainty), and increased risk of digital ischemia (RR, 2.56; 95% CI, 1.24 to 5.25; moderate certainty). CONCLUSIONS After considering certainty in the evidence, values and preferences, cost, and other factors, the expert guideline panel suggests using vasopressin or vasopressin analogues in addition to catecholamines over catecholamine vasopressors alone for the management of distributive shock (conditional recommendation, low certainty evidence).

Abstract

PURPOSE To systematically identify predictors of gastrointestinal (GI) bleeding in adult intensive care unit (ICU) patients. METHODS We conducted a systematic review and meta-analysis of cohort studies including trial cohorts. We searched MEDLINE, EMBASE, and trial registries up to March 2019. Eligible studies assessed potential predictors of clinically important GI bleeding (CIB; primary outcome) or overt GI bleeding (secondary outcome), had > 20 events, and presented adjusted effect estimates. Two reviewers assessed study eligibility, extracted data, and assessed risk of bias and certainty of evidence using GRADE. We meta-analysed adjusted effect estimates if data from ≥ 2 studies were available. RESULTS We included 8 studies (116,497 patients). 4 studies (including 74,456 patients) assessed potential predictors of CIB, and we meta-analysed 12 potential predictors from these. Acute kidney injury (relative effect [RE] 2.38, 95% confidence interval [CI] 1.07-5.28, moderate certainty) and male gender (RE 1.24, 95% CI 1.03-1.50, low certainty) were associated with increased incidence of CIB. After excluding high risk of bias studies, coagulopathy (RE 4.76, 95% CI 2.62-8.63, moderate certainty), shock (RE 2.60, 95% CI 1.25-5.42, low certainty), and chronic liver disease (RE 7.64, 95% CI 3.32-17.58, moderate certainty) were associated with increased incidence of CIB. The effect of mechanical ventilation on CIB was unclear (RE 1.93, 0.57-6.50, very low certainty). CONCLUSIONS We identified predictors of CIB and overt GI bleeding in adult ICU patients. These findings may be used to identify ICU patients at higher risk of GI bleeding who are most likely to benefit from stress ulcer prophylaxis.

Abstract

BACKGROUND Fluid resuscitation is the cornerstone of sepsis treatment. However, whether balanced or unbalanced crystalloids or natural or synthetic colloids confer a survival advantage is unclear. PURPOSE To examine the effect of different resuscitative fluids on mortality in patients with sepsis. DATA SOURCES MEDLINE, EMBASE, ACP Journal Club, CINAHL, HealthSTAR, the Allied and Complementary Medicine Database, and the Cochrane Central Register of Controlled Trials through March 2014. STUDY SELECTION Randomized trials that evaluated different resuscitative fluids in adult patients with sepsis or septic shock and death. No language restrictions were applied. DATA EXTRACTION Two reviewers extracted data on study characteristics, methods, and outcomes. Risk of bias for individual studies and quality of evidence were assessed. DATA SYNTHESIS 14 studies (18916 patients) were included with 15 direct comparisons. Network meta-analysis at the 4-node level showed higher mortality with starches than with crystalloids (high confidence) and lower mortality with albumin than with crystalloids (moderate confidence) or starches (moderate confidence). Network meta-analysis at the 6-node level showed lower mortality with albumin than with saline (moderate confidence) and low-molecular-weight starch (low confidence) and with balanced crystalloids than with saline (low confidence) and low- and high-molecular-weight starches (moderate confidence). LIMITATIONS These trials were heterogeneous in case mix, fluids evaluated, duration of fluid exposure, and risk of bias. Imprecise estimates for several comparisons in this network meta-analysis contribute to low confidence in most estimates of effect. CONCLUSION Among patients with sepsis, resuscitation with balanced crystalloids or albumin compared with other fluids seems to be associated with reduced mortality. PRIMARY FUNDING SOURCE The Hamilton Chapter of the Canadian Intensive Care Foundation and the Critical Care Medicine Residency Program and Critical Care Division Alternate Funding Plan at McMaster University.