Toxicology
Selected Papers from the 1999 Society for Academic Emergency Medicine Meetings
CONFERENCE COVERAGE
Toxicology
Calcium and Digoxin Toxicity
In the current experiment, digoxin toxic guinea pigs were randomized to receive either calcium or normal saline and then observed for dysrhythmias and death. All animals developed hyperkalemia, demonstrating classic digoxin toxicity. Although there were no statistical differences between the calcium and the saline groups, there was a trend toward decreased rates of death and dysrhythmia in the calcium-treated animals.
Comment by Robert Hoffman, MD
Digoxin toxicity produces extracellular hyperkalemia and intracellular hypercalcemia, all as a direct result of blocking the Na-K-ATPase pump. The hyperkalemia is often profound, prompting clinicians to treat it aggressively, often before the diagnosis of digoxin toxicity is known. While standard emergency therapies with insulin, dextrose, and bicarbonate are all safe and effective, concern has been expressed about the use of calcium. This concern dates back to early animal investigations that demonstrated that intravenous calcium could be fatal in the setting of digoxin toxicity, probably as a result of profound intracellular hypercalcemia.
While this is a very interesting and provocative model, unfortunately the results suffer from the limitations of a small sample size. The failure to achieve statistical significance here means that the data can not be interpreted. While a power analysis would probably demonstrate that the sample size was too small, it is unclear if the trend would persist in a larger sample. The authors should be encouraged to repeat the study with a larger sample. For the time being, however, I would caution against using this paper to suggest that the use of calcium salts in the treatment of digoxin-induced hyperkalemia in humans is either indicated, effective, or safe. (Source: Ghaemmaghami CA, Harchelroad F. Dangers of intravenous calcium chloride in the treatment of digoxin-induced hyperkalemia—Fact or fiction [abstract]? Acad Emerg Med 1999;6:378.)
Digoxin in Verapamil Toxicity
Since calcium channel blockers work largely through a reduction of intracellular calcium, the present investigation evaluated the effect of digoxin (which increases intracellular calcium) in verapamil toxicity. Dogs poisoned with verapamil were randomized to receive either calcium or calcium plus a high therapeutic dose of digoxin, and their hemodynamics were followed. Digoxin plus calcium produced a significant increase in systolic blood pressure and mean arterial blood pressure, as well as a non-significant trend toward decreased mortality, when compared to calcium alone.
Comment by Robert Hoffman, MD
Calcium channel blocker overdose is among the leading causes of fatal ingestions of prescription medications reported to poison control centers. The severe toxicity of calcium channel blockers results largely from their combined negative inotropy and negative chronotropy. Sustained release formulations further compound toxicity by prolonging the absorptive phase. Although many therapies (including calcium, glucagon, phosphodiesterase inhibitors, and catecholamines) are available, they are often insufficient in severe toxicity.
Although these results were hampered by the small sample size, the findings are clear. What remains somewhat problematic is whether it is safe and advisable to administer digoxin (a drug known to produce bradycardia) to people who are at risk for profound bradycardia and hypotension. If this study can be verified in another model, human trials should follow promptly. (Source: Bania TC, et al. Calcium plus digoxin versus calcium alone for verapamil toxicity [abstract]. Acad Emerg Med 1999;6:378.)
In the study by Bania et al on the effect of digoxin on dogs made toxic with verapamil:
a. dogs receiving calcium plus digoxin had significant increases in mortality.
b. dogs receiving calcium plus digoxin had significant increases in mean arterial pressure.
c. dogs receiving calcium plus digoxin had significant increases in bradyasystolic deaths.
d. dogs receiving calcium plus digoxin had increased rates of heart block.
Antidote Stocking in the ED
The present study evaluated stocking of N-acetylcysteine, naloxone, cyanide antidote, deferoxamine, digoxin Fab, fomepizole, ethanol, pralidoxime, crotalid antivenom, and pyridoxine in hospitals in Oregon and Nevada. Not surprisingly, only 50% of hospitals surveyed had 24-hour quantities of all antidotes. Only 60% had six-hour quantities of all 10 antidotes. When these values were corrected for frequency of use, stock levels appeared better. Lee and colleagues note that for less than $10,000 a hospital can be sufficiently stocked to be prepared for routine care of even infrequent poisonings.
Comment by Robert Hoffman, MD
The ability to respond to poisoned patients often requires the use of specialized antidotes. Many of these antidotes are expensive, infrequently used, and have no other indications. Probably as a direct result of these factors, several previous studies have demonstrated that many hospitals are inadequately prepared to care for poisoned patients.
This study raises significant public health concerns. Hospitals are going to have to make the commitment to be adequately stocked, or else enter into cooperative agreements with other area facilities. Alternatively, it seems reasonable to have central supplies of antidotes in referral hospitals, poison centers, or poison treatment centers, and to move patients or antidotes depending on clinical necessity. Regardless of the solution, it is essential for communities to develop plans that assure that patients will have access to antidotes. (Source: Lee JH, et al. Antidote stocking in Oregon and Nevada: Are EDs inadequately prepared [abstract]? Acad Emerg Med 1999;6:392.)
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