Intravenous lipid emulsion as an adjuvant therapy of acute clozapine poisoning

Abstract

Introduction: Clozapine is a frequently prescribed atypical antipsychotic drug. Various case reports documented the successful recovery of acute antipsychotics toxicity in association with the administration of intralipid emulsion (ILE). Aim: This study aimed to assess the adjuvant therapeutic role of SMOF Lipid administration on the outcomes of acute clozapine poisoning. Methods: Forty patients with acute clozapine poisoning were randomly allocated into two equal groups. The control group received the standard supportive treatment only, whereas the intervention group received the standard supportive treatment plus SMOF Lipid 20% infusion. All patients were subjected to history taking, full clinical examination, and laboratory investigations. The study outcomes were evaluated. Results: The mean Glasgow Coma Scale (GCS) at 6 hours (13.1 ± 2.3 vs 9.2 ± 2, p < 0.001) and 12 hours (14.3 ± 1.5 vs 9.6 ± 2, p < 0.001) after admission was significantly higher in the intervention group compared to the control group. The intervention group showed a significantly lower frequency of prolonged QTc interval 12 hours after admission (p = 0.003), as well as a significantly shorter hospital stay (p < 0.001). Conclusions: SMOF Lipid infusion seemed to have improved GCS, the prolonged QTc interval, and shortened the length of hospital stay. Furthermore, there were no adverse effects related to its administration.

A reply to a letter to the editor

“…The authors highlighted a difference between the effect size of lipid emulsion treatment as an antidote in acute non-local anesthetic toxicity, lipid emulsion only slightly increased the GCS (calculated Cohen’s effect size: 0.63, 95% confidence interval: −0.101 to 1.366) 1 and our findings. Our study 2 reported that lipid emulsion treatment significantly improved the GCS (Cohen’s effect size: 2.65, 95% confidence interval: 1.808–3.509) in acute clozapine poisoning. In our view, this difference is attributed to the heterogenous poison types with various inherent toxicity included in the previous study of Taftachi et al 1…”

Effect of lipid emulsion on acute clozapine poisoning-induced QT prolongation

“…S-H Ok 1,2,3 and J-T Sohn 2, 3 The article "Intravenous lipid emulsion as an adjuvant therapy of acute clozapine poisoning," recently published in Human and Experimental Toxicology, is interesting. 1 Elgazzar et al reported that lipid emulsion (SMOFlipid) increased the Glasgow Coma Scale (GCS) and reduced the incidence of QT prolongation and hospital stay in the acute clozapine (an antipsychotic drug) toxicity. 1 Such randomized clinical studies using lipid emulsions as an antidote in non-local anesthetic toxicity are rare and important in clinical toxicology, which should be complimented.…”

“…1 Elgazzar et al reported that lipid emulsion (SMOFlipid) increased the Glasgow Coma Scale (GCS) and reduced the incidence of QT prolongation and hospital stay in the acute clozapine (an antipsychotic drug) toxicity. 1 Such randomized clinical studies using lipid emulsions as an antidote in non-local anesthetic toxicity are rare and important in clinical toxicology, which should be complimented. Although there were some problems in the statistical analysis of a previous randomized controlled clinical study, lipid emulsion treatment as an antidote in acute non-local anesthetic toxicity only slightly increased the GCS (calculated Cohen's effect size: 0.63, 95% confidence interval: À0.101 to 1.366).…”

“…2 However, in the study of Elgazzar et al, lipid emulsion treatment significantly improved the GCS (Cohen's effect size: 2.65, 95% confidence interval: 1.808-3.509) in acute clozapine poisoning. 1 Acute toxicity of clozapine, which is used to treat schizophrenia, can prolong the QT interval, leading to Torsade de pointes, ventricular fibrillation, and sudden cardiac arrest. 3,4 Additionally, toxicity of other antipsychotic drugs, including risperidone, quetiapine, haloperidol, and droperidol, can cause Torsade de pointes.…”

“…The following discussion may help understand the potential mechanisms underlying the lipid emulsion-mediated inhibition of QT prolongation induced by clozapine poisoning. 1 Drug-induced prolonged QT interval causing Torsade de Pointes is due to the inhibition of human Ether-à-go-go-Related Gene (hERG)encoded rapid delayed rectifier potassium channels, leading to the inhibition of potassium efflux. 4 Local anesthetics including bupivacaine, ropivacaine, and mepivacaine inhibit hERG potassium channel encoding rapid delayed rectifier potassium channels, which is correlated with the lipid solubility of local anesthetics.…”