A randomized controlled study comparing high-dose insulin to vasopressors or combination therapy in a porcine model of refractory propranolol-induced cardiogenic shock

Abstract

Context: Although cerebral perfusion (CP) is preserved across a wide range of mean arterial pressures (MAP) through cerebral-vascular autoregulation, the relationship between MAP and CP in refractory poison-induced cardiogenic shock (PICS) has never been studied. We compared the effects of therapies used in PICS: high-dose insulin (HDI), HDI plus norepinephrine (NE), and vasopressors alone (NE plus epinephrine (Epi)) on cerebral tissue oxygenation (P_tO₂).

Methods: Fifteen swine were randomized to either HDI, HDI + NE, or NE + Epi. All animals received a propranolol infusion using an established model of toxicity. At primary toxicity (P₁), defined as a 25% reduction in heart rate (HR) multiplied by MAP, the HDI and HDI + NE groups received HDI and the NE + Epi group received NE. Once a sustained MAP < 55 mmHg was reached (P₂), the HDI group received saline (NS), the HDI + NE group received NE and the NE + Epi group received Epi until death or censoring. P_tO₂ and hemodynamic parameters including MAP, cardiac output (CO) and central venous pressure (CVP) were measured every 10 minutes. Glucose and potassium were measured at predetermined intervals.

Results: Animals treated with HDI + NE maintained P_tO₂ over time more than the HDI-alone group. Due to rapid hemodynamic collapse, we were unable to analyze P_tO₂ data in the vasopressor only animals. Mean survival time was 1.9, 2.9 and 0.1 hours for the HDI, HDI + NE and NE + Epi groups, respectively. Survival time from P₂ (sustained MAP <55 mmHg) to death or censoring was not different between HDI and HDI + NE groups.

Conclusions: HDI + NE treatment was superior to HDI-alone at preserving P_tO₂ when MAP < 55 mmHg. We were unable to compare the P_tO₂ between the NE + Epi to the HDI or HDI + NE due to rapid decline in CO and death. If MAP is sustained at < 55 mmHg after maximizing HDI, adjunctive treatment with NE should be considered to preserve P_tO₂.

Keywords:

• Overdose
• beta-adrenergic blockers
• cardiogenic shock
• cerebral perfusion
• high-dose insulin
• vasopressors

Acknowledgements

We would like to thank Katherine Faltesek, CVT, RLATG, and the HealthPartners Institute for support, use of their facilities, and technical assistance.

Disclosure statement

The authors confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

Additional information

Funding

Funding for this work was provided by grants from the HealthPartners Institute and the American College of Medical Toxicology Foundation.