We report a case of profound neurologic and cardiovascular manifestations of tricyclic antidepressant intoxication following self-poisoning with multiple pharmaceuticals including amitriptyline in excess of 43 mg/kg, in a 51-year-old male. Institution of mechanical ventilation, volume expansion, systemic alkalinisation (pH 7.51), and intermittent bolus metaraminol resulted in QRS narrowing but failed to resolve the developed shock. One 100-ml bolus of 20% lipid emulsion followed by a further 400 ml over 30 min was administered with restoration of haemodynamic stability, thereby curtailing the need for ongoing vasopressor medications. Assayed blood levels were consistent with the 'lipid sink' being a major effecter in the observed improvement.

The use of intravenous lipid emulsions (ILEs) as antidote in local anaesthetic systemic toxicity has gained widespread support following convincing data from animal models, and successful case reports in humans. Proposed beneficial mechanisms of action for ILEs include intravascular sequestration of intoxicant and subsequent enhanced redistribution to biologically inert tissues, augmentation of fatty acid utilisation for ATP synthesis in the context of metabolic poisoning, and direct cardiotonic and ion channel effects. The evidence base for use of ILEs in acute drug intoxication is evolving. The present evidence supports use of ILEs only in local anaesthetic systemic toxicity and in lipophilic cardiotoxin intoxication when there is an immediate threat to life, and other therapies have proven ineffective.

Intravenous lipid emulsion (ILE) has been demonstrated to be an effective treatment for systemic toxicity associated with local anaesthetics and increasingly non-local anaesthetic agents of high lipophilicity. Effect for ILE has been demonstrated in animal models of propranolol poisoning; however, any benefit for ILE in more hydrophilic β-blockers remains uncertain. We determined to examine the effect of ILE on haemodynamic recovery following induction of hypotension with the relatively hydrophilic β-blocker, metoprolol. Twenty sedated, invasively monitored and mechanically ventilated adult New Zealand white rabbits underwent metoprolol infusion to mean arterial pressure (MAP) 60% baseline. Intravenous rescue was given according to the following groups: 6 mL/kg 20% lipid emulsion or 6 mL/kg 0.9% saline solution over 4 min. Haemodynamic parameters were obtained in 15 min. MAP was 70 (interquartile range (IQR), 58–82) mmHg saline group and 79 (IQR, 72–89) mmHg ILE group at baseline, and 38 (IQR, 33–40) mmHg saline group and 41 (IQR, 40–43) mmHg ILE group, respectively, following metoprolol infusion. No statistically significant difference between ILE and saline-treated groups was observed in MAP, or pulse rate, at any time point following rescue therapy. ILE was not effective in reversal of metoprolol-induced hypotension in this rabbit model. These findings lend inferential support for the ‘lipid sink’ as principal mechanism for the beneficial effect observed with ILE administration in other models of lipophilic β-blocker-induced toxicity.

Context. The use of intravenous lipid emulsion (ILE) as an antidote in non-local, anaesthetic drug toxicity has generated considerable interest. Flecainide is a lipophilic anti-arrhythmic with a significant cardiotoxic profile, with blockade of sodium and potassium channels causing arrhythmias and shock in severe toxicity. ILE has been proposed as a treatment option in severe flecainide toxicity refractory to other modalities. Objective. We compared the effects of ILE and hypertonic sodium bicarbonate in a rabbit model of flecainide toxicity. Materials and methods. Twenty sedated and ventilated New Zealand White Rabbits received flecainide infusion titrated to a mean arterial pressure (MAP) of 60% baseline, which was defined as toxicity. The rabbits then received either sodium bicarbonate or ILE, and the flecainide infusion was reduced in an attempt to model ongoing enteric absorption. MAP and heart rate were recorded every minute for 15 min and plasma flecainide concentration was measured at toxicity and 15 min. ECG QRS duration was recorded at baseline, toxicity and at 5, 10 and 15 min post-toxicity. Results. No difference was observed in heart rate (p = 0.2804), MAP (p = 0.1802) or QRS duration (p = 0.7471) between groups. The immediate rate of rise in MAP was greatest in the bicarbonate group in the 5 min immediately post-toxicity. Conclusions. In this study, no differences were observed between an active control of hypertonic sodium bicarbonate and ILE for the primary endpoint of MAP at 15 min nor for QRS duration at any timepoint. There was a transient rapid increase in blood pressure seen in the sodium bicarbonate group that was not sustained. No increase was seen in blood concentration of flecainide in the ILE group, suggesting no ‘lipid sink’ for flecainide in this model. More research is warranted to define any role for ILE in flecainide toxicity.