New Orleans—Emergency pharmacists and clinicians need to take high-dose insulin and lipid emulsion therapy seriously for the treatment of severe calcium channel blocker (CCB) and β-blocker (BB) toxicity, two experts told attendees of the American Society of Health-System Pharmacists (ASHP) 2012 Midyear Clinical Meeting.

Slim ‘but Convincing’ Evidence

Phillippe Mentler, PharmD, pointed to a slim “but convincing” body of evidence showing that high-dose insulin, or hyperinsulinemia-euglycemia (HIE), is profoundly effective for severe CCB and BB toxicity, whereas IV fluids, atropine, calcium, vasopressors and glucagon are not. “More than 80 cases have been published to date, and all have shown that HIE is consistently superior to other treatments,” said Dr. Mentler, an emergency medicine pharmacist at Durham Regional Hospital, in North Carolina.

Dr. Mentler explained that HIE provides glucose and energy to the stressed myocardium, bypassing the need for a functioning pancreas (Clin Toxicol 2011;49:277-283). Given that CCB and BB toxicity account for the second highest number of deaths among cardiovascular medication–related mortalities (Clin Toxicol 2011;49:910-941), the 85% survival rate among these patients treated with HIE should be taken seriously, he suggested. Moreover, he noted, the survival rate may be even higher when an initial bolus of high-dose insulin is administered earlier (see e.g., Clin Toxicol 2011;49:653-658).

Dr. Mentler said that HIE is underused primarily because of a psychological barrier that prevents clinicians who are not familiar with the treatment from administering the unusually high doses of insulin required. A typical treatment protocol calls for an initial IV bolus injection of 1 unit/kg, followed by an infusion of 0.5 to 1 unit/kg per hour, titrated every 15 minutes up to a maximum of 10 units/kg per hour (Clin Toxicol 2011;49:277-283; Clin Toxicol 2011;49:653-658).

“Clinicians might look at you as if you are insane for recommending this dose,” Dr. Mentler said. But Daniel Hays, PharmD, who moderated the ASHP session at which Dr. Mentler spoke, said, “Clinicians need to look past the high doses of insulin and realize the tremendous benefits from this therapy. In patients with known toxicity due to ingestion of calcium channel blockers and β-blockers, insulin therapy should be the first line of treatment,” added Dr. Hays, the clinical coordinator of emergency pharmacy services in the Departments of Pharmacy and Emergency Medicine at the University of Arizona Health Network, in Tucson.

A standardized order set like one developed by pharmacists in Minnesota (see related article, page 8) may help emergency department clinicians and nurses feel more comfortable with the protocol, he told Pharmacy Practice News.

‘A Miraculous Intervention’

Another highly effective but underused treatment for severe CCB and BB toxicity is lipid emulsion therapy, Zlatan Coralic, PharmD, an emergency department clinical pharmacist at the University of California, San Francisco, told attendees during the ASHP session.

“Although the data we have are limited to case reports, they do suggest that lipid emulsion therapy is a miraculous intervention,” Dr. Coralic said. “The treatment has brought patients from active chest compressions to full recovery with minimal to no long-term sequelae.”

According to Dr. Coralic, lipid emulsion therapy has been used for some time to treat toxicity related to other lipid-binding medications such as local anesthetic agents (Clin Toxicol 2011;49:801-809).

Although the treatment’s precise mechanism of action is under debate, its efficacy is likely due to the lipid sink effect it exerts, swallowing drug molecules in the intravascular space. Like insulin therapy, it also provides energy to the stressed heart via fatty acids, and it increases intracellular fatty acid content, provides intracellular cytoprotection and increases calcium ion uptake (Anesthesiology 2012;117:180-187).

Dr. Coralic said the treatment does carry “at least a theoretical risk” for pancreatitis, hyperlipidemia and interference with laboratory test results, but published case reports have found no serious complications. He said that although case reports should be cautiously interpreted given the potential for overrepresentation of positive results in the literature, the benefits of treatment outweigh any risks.

“The potential adverse effects of lipid therapy are minimal when compared with the morbidity and mortality from severe CCB toxicity,” Dr. Coralic told Pharmacy Practice News.

“Emergency department pharmacists and clinicians need to be aware of both HIE and lipid therapy as these are inexpensive, easily available and extremely efficacious treatments,” concluded Dr. Hays.

For more detail on the rationale, evidence and treatment protocols for both HIE and lipid emulsion therapy, see “New Treatments Tested for Cardiac Drug Poisonings” in the April 2012 issue of Pharmacy Practice News. For more information on lipid therapy, visit lipidrescue.org.

—David Wild


Drs. Mentler, Coralic and Hays reported no relevant financial conflicts of interest.