A prospective study of acute propranolol overdose defining dose thresholds of severe toxicity (ATOM - 9)

Propranolol is a beta-adrenoceptor blocking drug with sodium channel-blocking properties that can cause life-threatening toxicity in overdose. Limited research defines dose thresholds of toxicity. We aimed to investigate propranolol overdose and dose thresholds for severe toxicity.

This is a prospective series of patients with acute propranolol overdose ≥360 mg from August 2014 to December 2023 enrolled through the Australian TOxicology Monitoring (ATOM) collaboration. Severe toxicity was defined as seizure, coma, inotrope therapy, electrocardiographic evidence of sodium channel blockade, or cardiac arrest.

There were 209 presentations in 165 patients (median age 30 years [range 15-80 years]; 117 females, 71%). The median reported dose ingested was 1,000 mg (IQR: 600-2,000 mg; range 360-16,000 mg). Co-ingestion occurred in 155 (74%) patients, most commonly involving benzodiazepines (n = 52). Bradycardia (heart rate <50 beats/min) occurred in 41 (20%), and hypotension (systolic blood pressure <90 mmHg) in 88 (42%). Severe toxicity occurred in 51 patients (24%), with 17 (8%) having a seizure and 29 (14%) developing coma. Forty-one (20%) received inotropes, including 31(15%) who were given epinephrine and 20 (10%) high-dose insulin. Electrocardiographic evidence of sodium channel blockade occurred in 16 (8%). Seven (3%) had a cardiac arrest (reported dose range 2,400-16,000 mg), with two deaths following the ingestion of propranolol 4,000 mg and 16,000 mg. The median length of stay was 17 h (IQR: 11-32 h). In 79 patients who ingested only propranolol, the lowest reported propranolol dose for hypotension was 400 mg and for bradycardia, 800 mg. The lowest reported dose for severe toxicity was propranolol 2,000 mg. In those ingesting propranolol only, 17 of 32 (53%) patients who ingested ≥2,000 mg had severe toxicity.

Severe toxicity was common, occurring in a quarter of all propranolol overdoses and half of the isolated propranolol ingestions (≥2,000 mg). The outcome was usually favourable with good supportive care, even in severe toxicity.

The dose threshold for severe toxicity in isolated propranolol overdose appeared to be 2,000 mg.