VetSRev
Database of veterinary systematic reviews
Database of veterinary systematic reviews
Clin Toxicol (Phila) (2021) 59: 1–11
DOI: 10.1080/15563650.2020.1814316
INTRODUCTION: Clinicians utilize lipid emulsion to treat local anesthetic toxicity and non-local anesthetic toxicities, a practice supported by animal experimentation and clinical experience. Prior meta-analysis confirmed a mortality benefit of lipid emulsion in animal models of local anesthetic toxicity but the benefit of lipid emulsion in models of non-local anesthetic toxicity remains unanswered. Further, swine suffer an anaphylactoid reaction from lipid emulsions calling into question their role as a model system to study lipid, so we examined swine and non-swine dependent outcomes in models of intravenous lipid emulsion. METHODS: We conducted a systematic review and meta-analysis examining the use of lipid emulsion therapy in animal models of cardiac toxicity. We quantified mortality using a random-effects odds-ratio method. Secondary outcomes included survival in the following subgroups: local-anesthetic systemic toxicity, non-local anesthetic toxicity, swine-based models, and non-swine models (e.g., rat, rabbit and dog). We assessed for heterogeneity with Cochran’s Q and I(2). We examined bias with Egger’s test & funnel plot analysis. RESULTS: Of 2784 references screened, 58 met criteria for inclusion. Treatment with lipid emulsion reduced chance of death in all models of toxicity with an odds ratio of death of 0.26 (95% CI 0.16-0.44, Z-5.21, p \textless 0.00001, Cohen’s-d = 0.72, n = 60). Secondary outcomes confirmed a reduced chance of death in models of local anesthetic toxicity (OR 0.16 {95% CI 0.1-0.33}) and non-local anesthetic toxicity (OR 0.43 {95% CI 0.22-0.83}). Heterogeneity (Cochran’s Q 132 {df = 59, p \textless 0.01}, I (2) = 0.55) arose primarily from animal-model and disappeared (I (2) \textless = 0.12) when we analyzed swine and non-swine subgroups independently. Swine only benefited in models of local anesthetic toxicity (OR 0.28 {95% CI 0.11-0.7}, p = 0.0033) whereas non-swine models experienced a homogeneous benefit across all toxins (OR 0.1 {95% CI 0.06-0.16}, p \textless 0.00001). Egger’s test identified risk of bias with outliers on funnel plot analysis. DISCUSSION: Lipid emulsion therapy reduces mortality in animal models of toxicity. Heterogeneity arises from the animal-model used. Swine only benefit in models of local anesthetic toxicity, potentially due to lipid dose, experimental design or swine’s anaphylactoid reaction to lipid. Outlier analysis reinforced the need for appropriate dosing of lipid emulsion along with airway management and chest compressions in the setting of cardiac arrest.
Fettiplace, M. R., & Pichurko, A. B. (2021). Heterogeneity and bias in animal models of lipid emulsion therapy: a systematic review and meta-analysis. Clin Toxicol (Phila), 59(1), 1–11. https://doi.org/10.1080/15563650.2020.1814316 pig, swine, meta-analysis, toxicity, systematic review, heterogeneity, Intravenous lipid emulsion, porcine