Evaluating the Effects and Safety of Intravenous Lipid Emulsion on Haloperidol-Induced Neurotoxicity in Rabbit

Abstract

There are many reports on the effect of intravenous lipid emulsion (ILE) as an antidote in drugs related toxicities. We determined the effects of ILE on neurotoxicity of haloperidol (HA), a highly lipophilic antipsychotic, as a model of antipsychotics poisoning. We used six groups of five male rabbits. Two groups received distilled water intravenously followed by infusions of either 18 mL/kg of normal saline or ILE 20%, after 30 minutes. The third group received 18 mL/kg of normal saline after HA (2.6 mg/kg) administration. The three other groups received ILE 20% solution (6, 12, and 18 mL/kg) following HA injection. Catalepsy scores, temperature, pupil size, and mortality rate were measured at 0, 0.5, 1, 2, 3, 4, 8, and 24 hours after HA administration began. Blood and tissue samples were taken from all animals at 24 hours or at death time for biochemical, cell count, and pathological studies. ILE reversed cataleptic scores, miotic pupils, and hypothermia of HA intoxication much faster than normal saline (P < 0.001). Biochemical complications and mortality rate of the animals were significantly higher in the HA + 18 mL/Kg ILE group. ILE reversed sings of HA neurotoxicity; however, synergistic effect of high dose of ILE and HA increased complications and mortality.

Effect of Intravenous Lipid Emulsion on Clozapine Acute Toxicity in Rats

“…Previous animal tests support the effect of ILE in reveling lipophilic drugs induced hypotension. In a study ILE has shown significant positive effects for primary or secondary hemodynamic endpoints in metoprolol, verapamil, tramadol and haloperidol intoxication [2, 7, 28–30]. There is a suggested mechanism for ILE in revealing drugs-induced hypotension, the lipid sink theory.…”

Pharmacokinetics and Pharmacodynamics Evaluation of Tramadol in Thermoreversible Gels

“…Both pupils were measured and the mean value was used as reference. The measurements occurred in the same location and under similar brightness of light at all evaluation times [ 14 ].…”

Intravenous Lipid Emulsion as an Adjuvant Therapy of Acute Antipsychotic Poisoning: A randomized Controlled Trial

“…This agrees with Finn et al (2009) who observed a rapid improvement in the level of consciousness immediately after ILE administration in a case of quetiapine overdose. As well, it has been reported that ILE could reverse altered consciousness levels in patients with local anesthetic CNS toxicity (Moshiri et al, 2014). A previous RCT investigated the effect of 10 cc/ kg ILE 10% in the management of acute non-local anesthetic drug toxicity, they reported significant improvement of GCS 6 hours after admission in the intervention group compared to the control group (Taftachi et al, 2012).…”

“…The most accepted mechanism of ILE's protective effect against intoxication by lipophilic drugs by general is the "lipid sink" theory. It suggests that lipophilic agents, like antipsychotic drugs, are redistributed from their site of action to a new inert compartment caused by the ILE itself in the vessels (Moshiri et al, 2014). Moreover, ILE provides highenergy essential fatty acids as well as polyunsaturated fatty acids that are essential for the brain's metabolism and the production of bioactive chemicals.…”