A Swine Model of Severe Propranolol Toxicity Permitting Direct Measurement of Brain Tissue Oxygenation

High-dose insulin (HDI) therapy has been used successfully for beta-blocker toxicity, but needs further study when hypotension persists despite HDI. The objective was to develop a model of propranolol toxicity with persistent hypotension despite HDI and to develop means to measure cerebral oxygen tension (PbrO₂).

Eight anesthetized Yorkshire pigs were instrumented with a tracheostomy, Swan-Ganz catheter, arterial catheter, and intra-cerebral pressure and oxygen monitor. Intravenous propranolol was given until the initial point of toxicity (POT); 25% reduction from baseline mean arterial pressure (MAP) × heart rate (HR). At the initial POT, normal saline (NS) bolus and infusion along with HDI infusion were started. The propranolol infusion was titrated up slowly to induce hypotension. Group 2 pigs received a norepinephrine (NE) infusion after a secondary POT defined as a MAP < 50 mmHg. NE was titrated to maintain subsequent MAPs > 50 mmHg. Cardiac output, HR, MAP, PbrO₂, and intracranial pressure were then recorded every 5 min until death or 4 h. Systemic vascular resistance, potassium, and glucose were also measured. Surviving pigs were euthanized.

Two pigs received unique doses for protocol development. One pig developed a tachyarrhythmia prior to protocol, one failed to reach secondary POT, leaving 2 pigs in each group reaching secondary POT. The range of PbrO₂ recordings for group 1 was 12.7-48.5 mmHg and 9.2-26.2 mmHg for group 2.

We report a pilot study swine model of propranolol toxicity with hypotension despite HDI, in which physiologic measures including PbrO₂ are achieved. Our toxicity model can be used in the future, and the hemodynamic and brain monitoring model may prove important for subsequent research in various contexts.