Abstract
Introduction
Frostbite is an injury caused by exposure of tissue to freezing temperatures. Severe frostbite may result in amputation, leading to considerable morbidity.
Objective
The objective was to identify and synthesize, via systematic literature review (SLR) and meta-analysis (MA), evidence published on patient-level historical amputation rates in adults with severe frostbite treated with and without iloprost.
Methods
The SLR was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. It identified English-language articles published from January 1, 2000 to July 31, 2022, reporting amputation rates associated with iloprost and standard of care (SoC) treatments in severe frostbite. Study designs of interest were clinical trials (randomized and single arm), observational studies, and case series with at least 10 patients. Meta-analyses of proportions of patients with amputation as well as MAs of odds ratios of risk of amputation in comparative studies were conducted.
Results
The SLR identified 17 primary studies; 16 were deemed eligible for the MAs of proportions, and 2 studies were deemed eligible for MAs of odds ratios. Results for pooled MA arm-level data for SoC estimated a 52 to 62% risk of a patient undergoing at least 1 amputation. Results for pooled arm-level data for iloprost analyses found a 15 to 18% risk of amputation. Comparisons across MAs consistently showed a 34 to 46% reduction in amputation for iloprost over SoC, with all differences being statistically significant, although there was statistical heterogeneity in effect estimates. Similar significant findings existed in the comparative MA. Safety events associated with the administration of iloprost were generally mild, especially relative to the severity of the condition.
Conclusions
Our review of studies of the treatment of severe frostbite with either iloprost or SoC found a substantial rate of amputation with SoC and, comparatively, a significant reduction in amputation rate in patients treated with iloprost.
Keywords: amputation, surgical, statistics & numerical data, frostbite, surgery, therapy, humans, iloprost, therapeutic use, outcome and process assessment, healthcare
Disclosures: C-LV, AW, KC, and WB are employees of Eicos Sciences. KF and RH are employees of Evidera, a vendor contracted by Eicos to conduct the analyses. CD is a consultant for Eicos Sciences.
Funding: This study was funded by Eicos Sciences, Inc.