Efficacy and safety of damage control in experimental animal models of injury: protocol for a systematic review and meta-analysis

Abstract

BackgroundAlthough abbreviated surgery with planned reoperation (damage control surgery) is now widely used to manage major trauma patients, the procedure and its component interventions have not been evaluated in randomized controlled trials (RCTs). While some have suggested the need for such trials, they are unlikely to be conducted because of patient safety concerns. As animal studies may overcome several of the limitations of existing observational damage control studies, the primary objective of this study is to evaluate the efficacy and safety of damage control versus definitive surgery in experimental animal models of injury.Methods/designWe will search electronic databases (Medline, Embase, PubMed, Web of Science, Scopus, and the Cochrane Library), conference abstracts, personal files, and bibliographies of included articles. We will include RCTs and prospective cohort studies that utilized an animal model of injury and compared damage control surgery (or specific damage control interventions or adjuncts) to definitive surgery (or specific definitive surgical interventions). Two investigators will independently evaluate the internal and external/construct validity of individual studies. The primary outcome will be all-cause mortality. Secondary outcomes will include blood loss amounts; blood pressures and heart rates; urinary outputs; core body temperatures; arterial lactate, pH, and base deficit/excess values; prothrombin and partial thromboplastin times; international normalized ratios; and thromboelastography (TEG) results/activated clotting times. We will calculate summary relative risks (RRs) of mortality and mean differences (for continuous outcomes) using DerSimonian and Laird random effects models. Heterogeneity will be explored using subgroup meta-analysis and meta-regression. We will assess for publication bias using funnel plots and Begg’s and Egger’s tests. When evidence of publication bias exists, we will use the Duval and Tweedie trim and fill method to estimate the potential influence of this bias on pooled summary estimates.DiscussionThis study will evaluate the efficacy and safety of damage control in experimental animal models of injury. Study results will be used to guide future clinical evaluations of damage control surgery, determine which animal study outcomes may potentially be generalizable to the clinical setting, and to provide guidelines to strengthen the conduct and relevance of future pre-clinical studies.

Outcomes of selective nonoperative management of civilian abdominal gunshot wounds: a systematic review and meta-analysis

“…Using this method, small outlying studies were first “trimmed” (removed until funnel plots were symmetric). The remaining study results were then used to re-estimate the theoretically unbiased center of the plot before it was “filled” (the missing outlying study results and their theoretical counterparts were replaced around the re-estimated center), permitting calculation of a publication bias-adjusted pooled risk estimate [ 26 – 29 ]. Stata version 13 (Stata Corp., College Station, TX, USA) was used for all analyses.…”

Outcomes After Receipt of Neuraxial or Regional Anesthesia Instead of General Anesthesia for Lower Limb Revascularization Surgery: Protocol for a Systematic Review and Meta-Analysis

“…We will evaluate for the presence of small study effects potentially due to publication bias for each outcome by visually inspecting produced funnel plots and using Begg's and Egger's tests (p-value <0.05 considered signi cant) [42]. When evidence of small study effects exists, we will use the Duval and Tweedie "trim and ll" method to estimate the potential in uence of this type of bias on our pooled estimates [43][44][45]. In this method, small outlying studies are rst "trimmed" (removed until the funnel plot is symmetrical) and then the remaining symmetrical studies are used to re-estimate the "true" center of the plot [43][44][45].…”

“…Statistical analyses will be performed using Stata MP version 13.1 (Stata Corporation, College Station, Texas, USA) by a trained meta-analyst [43][44][45].…”

“…When evidence of small study effects exists, we will use the Duval and Tweedie "trim and ll" method to estimate the potential in uence of this type of bias on our pooled estimates [43][44][45]. In this method, small outlying studies are rst "trimmed" (removed until the funnel plot is symmetrical) and then the remaining symmetrical studies are used to re-estimate the "true" center of the plot [43][44][45]. The plot is then " lled" (the missing, outlying study results and their theoretical balancing counterparts are replaced around the new center) and a small study effects-adjusted center is recalculated.…”

Outcomes After Receipt of Neuraxial or Regional Anesthesia Instead of General Anesthesia for Lower Limb Revascularization Surgery: Protocol for a Systematic Review and Meta-analysis

“…We will evaluate for the presence of small study effects potentially due to publication bias for each outcome by visually inspecting produced funnel plots and using Begg and Egger tests (P value<.05 considered significant) [38]. When evidence of small study effects exists, we will use the Duval and Tweedie "trim and fill" method to estimate the potential influence of this type of bias on our pooled estimates [39][40][41]. In this method, small outlying studies are first "trimmed" (removed until the funnel plot is symmetrical) and then the remaining symmetrical studies are used to re-estimate the "true" center of the plot [39][40][41].…”