Survival following massive amitriptyline overdose: The use of intravenous lipid emulsion therapy and the occurrence of acute respiratory distress

Dear Editor,

While survival has been reported after ingestion of 4.25 g amitriptyline, for which intravenous lipid emulsion (ILE) therapy was administered, ¹ we recently managed a patient who made a full recovery after a 4.8 g amitriptyline overdose. Interesting features of the case were a marked response to ILE and the subsequent development of acute respiratory distress syndrome (ARDS).

Our patient had taken 96 amitriptyline 50 mg tablets (total 4.8 g or 80 mg/kg), an uncertain amount of zopiclone, alcohol and venlafaxine. In the emergency department the patient was hypotensive and unresponsive (GCS 3), with a prolonged QTc identified on ECG. Rapid sequence induction was performed followed by transfer to the intensive care unit for full supportive therapy.

Further management and key parameters are illustrated in Figure 1. Hypotension was unresponsive to fluid therapy, and noradrenaline therapy was required. Intravenous bicarbonate therapy and mild hyperventilation (with tidal volumes 6 ml/kg) were utilised, aiming to achieve a pH of 7.55. Three grand mal seizures occurred which were treated with a midazolam bolus followed by an infusion. Approximately 12 h after the drug ingestion, with escalating noradrenaline requirements, ILE was administered. The subsequent improvement in blood pressure and reduction in noradrenaline can be seen in Figure 1. OPEN IN VIEWER

Case reports detailing the successful use of ILE for the treatment of toxicity of lipophilic drugs including tricyclic antidepressants are well documented. ¹ A recent prospective, randomised, controlled trial found no benefit of ILE compared to bicarbonate in a pig model of amitriptyline toxicity. ² A rabbit model found conflicting results. ³

Various mechanisms have been suggested for the mechanism of action of ILE, but the lipid sink hypothesis describes how ILE may provide a large binding site for the drug, removing it from effective circulation. Given the pKa of amitriptyline of 9.4, prior alkalinisation, as was undertaken in this case, might be expected to augment the effect of ILE by decreasing the ionised portion of the drug.

On day 3 of their care, our patient developed criteria of ARDS with a PaO₂/FiO₂ ratio of 70 mmHg by day 5. Proning was required, tracheostomy was performed and a prolonged respiratory wean ensued with 40 days of invasive ventilation. There was no evidence of pulmonary aspiration at the scene of the overdose, during intubation or on the initial chest radiograph, though micro-aspiration cannot be excluded. Ultimately, Streptococcus pneumonia and mixed coliforms were grown from bronchoalveolar lavage of the patient’s lungs; however, concern was raised that ILE could have been linked to the ARDS. The patients subsequently made a full physical recovery.

Acute respiratory distress syndrome has been reported in three patients in a case series of nine patients treated with ILE ⁴ but, as the authors acknowledge, critically ill patients are at risk of ARDS. Furthermore, ARDS has been reported as a complication of tricyclic overdose. Nonetheless, case series into the use of lipid infusion in ARDS and septicaemia have linked it to worsening oxygenation. ⁵

We believe this to be one of the highest reported overdoses of amitriptyline that has been survived and that the use of ILE contributed to this outcome. Our experience demonstrates the potential use of ILE outside the setting of cardiac arrest or cardiovascular collapse but highlights concerns regarding its potential association with ARDS.