A biomarker reflecting the severity of a Calcium Channel Blocker (CCB) OD is degree of hyperglycemia. If serum glucose is greater than 320 mg/dL, calcium channels are blocked and mortality is increased.
The cause of CCB-induced hyperglycemia is twofold. Firstly, blocked L-type calcium channels in the beta cells of the pancreas prevent glucose-induced insulin release (so called insulin resistance). Secondly, CCBs inhibit glucose uptake in peripheral tissues via interference with glucose transporters (GLUTs)- a family of passive transporters that mediate glucose uptake. But the different CCB vary in the degree they block GLUTs. Verapamil inhibits GLUTs in a dose-dependent manner in adipose, skeletal, cardiac myocytes and neuronal cells. But in the few studies that have been done, diltiazem did not reduce glucose transport at any concentration in skeletal muscle in rats. Because we see far more Verapamil OD patients with significant hyperglycemia (they have insulin resistance and blocked GLUTs), we are accustomed to administering hi-dose insulin. But we may need to be cautious with hi-dose insulin for other CCBs as these patients may be more responsive to insulin (unblocked GLUTS). A 16-year-old female with sole diltiazem OD was hypotensive with a glucose of 115 mg/dL. She was extremely sensitive to low-dose insulin and was intermittently hypoglycemic even with co-administration of glucose. She did not tolerate any insulin administration. So be careful. The last thing these hypotensive patients need is hypoglycemia.
So how does insulin ameliorate the hypotension caused by CCB OD? Insulin stimulates myocardial metabolism of carbohydrate (CHO) instead of fatty acids. Remember, last week’s question noted that CCB-induced hypotension shifted the myocardial energy substrate preference from FFA to CHO. Additionally, insulin improves myocardial contractility (independent of myocardial CHO usage) by increasing intracellular calcium. This positive inotropic insulin effect is also dependent on extracellular calcium concentration and is maximal at physiologic calcium concentrations. But when the channel is blocked, extracellular calcium is high which may be a problem as higher calcium concentrations reduce the inotropic effect of insulin which may even become negative. So though it is reasonable to give these patients some calcium, this is not the time to get aggressive with the calcium vials.
Are catecholamine pressors of benefit? They can be. Many ICU protocols use catecholamine pressors as the initial approach to CCB-induced hypotension. But if hypotension persists, HIE should be initiated. Recommended doses vary up to 1-2 units/kg with varying amounts of dextrose administered. If it is a verapamil OD, this should work well. With other CCB ODs, make sure and monitor serum glucose.
This question was prepared by Donna Seger MD
A note from the Medical Director: Hospitals in our state may be stocking Anavip for administration following snake envenomation. The Poison Center will help with the management of the envenomation if either anavip or crofab is being stocked in your hospital. Rebecca Bruccoleri MD Medical Director TPC
I am interested in any questions you would like answered in the Question of the Week. Please email me with any suggestion at donna.seger@vumc.org.
Donna Seger, MD
Executive Director
Tennessee Poison Center www.tnpoisoncenter.org
Poison Help Hotline: 1-800-222-1222