An assessment of the in vivo effects of intravenous lipid emulsion on blood drug concentration and haemodynamics following oro-gastric amitriptyline overdose

Background . Overdose with lipophilic drugs, such as amitriptyline, may cause cardiotoxicity in overdose. Severe poisoning can be resistant to traditional treatments. Intravenous lipid emulsion (ILE) has been recommended as a novel therapy for the treatment of such overdoses; however, a little is known about the effects of ILE-infusion on drug concentration and haemodynamics in the early/absorptive phase after oral poisoning. Method . Thirty minutes after oro-gastric administration of amitriptyline (70 mg/kg), either 20 intravenous lipid emulsion (ILE), 8.4 sodium bicarbonate or Hartmann ? s solution was infused to anaesthetized and ventilated rodents (n 10 per group). Heart rate, blood pressure, cutaneous ECG ? QRS interval duration (QRS-d), and survival were serially recorded over 120 min. Blood drug concentrations were also collected during this period. Continuous variables were compared using one-way ANOVA. Results . ILE infusion signifi cantly decreased the survival compared to other treatments (10 ILE vs 70 bicarbonate vs 70 Hartmann ? s solution, p 0.005). There was a gradual prolongation of QRS-d and fall in blood pressure over time compared to baseline (T0) measurement for both ILE and Hartmann ? s solution treatments. This was associated with signifi cantly increased blood AMI concentration with ILE treatment at T60, T90 and T120 min to the other treatments (p 0.02). Conclusion . Administration of ILE early after oral amitriptyline overdose resulted in worse survival and no improvement in haemodynamics. In addition, blood amitriptyline concentrations were higher in the ILE-treated group. This suggests that either drug absorption from the gastrointestinal-tract was facilitated or drug redistribution was retarded when ILE was given early after oral poisoning.