Could Intravenous Lipid Emulsion Improve the Level of Consciousness in Acute Sedative and Antipsychotic Poisoning? A Review of Randomised Human Trials

Abstract

Introduction: Sedative and antipsychotic (SAP) agents are amongst the most common overdoses seen clinically, with few available antidotes. The proposed “lipid shuttle” mechanism of action for intravenous lipid emulsion (ILE) could augment the redistribution of SAP agents from the central nervous system in overdoses. We reviewed randomised controlled clinical trials to evaluate the effect of intravenous lipid emulsion when the indication for use was a reduction in the level of consciousness in SAP overdoses. Methods: We searched for human randomized controlled trials comparing the use of ILE to placebos in SAP drug overdoses. Animal and non-randomised human studies were excluded. Relevant databases were searched with two independent reviewers assessing studies for inclusion and risk of bias using the ROB 2 tool. Results: Five identified studies enrolled 270 patients in total, of whom 226 had isolated tramadol or clozapine toxicity. One study was assessed as having serious concerns for bias, and the other four as having some potential for bias. In all studies, there was a statistically significant increase in the Glasgow Coma Scale (GCS), favouring the ILE groups. This effect does not appear to have been due to changes in haemodynamics. Secondary outcomes on length of stay and QT interval were also positive. No patient died in any study. Conclusions: In the five reported randomised human trials of the effect of ILE on level of consciousness post-SAP overdose, patients receiving ILE had a greater increase in GCS over time. The potential for bias existed in all studies, and trial results may be true but specific to the intoxicants and situations studied, which prevents the generalisability of findings. More research is both feasible and necessary in this area.

Keywords

• intravenous lipid emulsions
• poisoning
• antidotes