Alchemists, philosophers and physicians for millennia have been looking for the so-called “universal antidote” or panacea, a remedy that would counteract all poisons and make the owner immune to toxic injury. King Mithridates of Pontus (143-63 BC), whose father was assassinated by poison, invented a version of this panacea containing up to 65 ingredients, including acacia juice, costmary, parsley, and poppy. Existing scientific literature does not reflect if his concoction was effective.
A later recipe for a universal antidote called for activated charcoal, magnesium oxide, and tannic acid. This formula eventually fell out of favor, but activated charcoal is still widely used for gastrointestinal decontamination and enhanced elimination.
The closest thing today's toxicologist has to a universal antidote is sodium bicarbonate, however. Certainly it is not beneficial in all poisonings, but NaHCO3 is effective in treating an amazingly wide range of overdoses.
It is ironic that supplies of this generally safe and inexpensive drug have recently been scarce or not available at all in some hospitals. The shortage has eased somewhat recently, but was still listed by the FDA as being in short supply as of this writing.
Sodium bicarbonate boluses are the treatment of choice for conduction abnormalities and hemodynamic instability associated with any drug that causes sodium-channel blockade and a widened QRS interval. (See table.) This includes, most importantly, the tricyclic antidepressants (TCAs). A prolonged QRS interval in TCA toxicity heralds the onset of seizures and potentially lethal cardiac dysrhythmias. Most authorities recommend administering boluses of sodium bicarbonate when the QRS exceeds 0.10 seconds. This will provide not only a sodium load to help overcome channel blockade, but also decrease the ionized for toxic fraction of a drug by alkalinizing the serum.
Sodium bicarbonate is also essential in treating salicylate toxicity where it does double duty. Alkalinizing the urine increases salicylate excretion while getting the serum pH to about 7.50-7.55 (but no higher) minimizes entry of salicylate into the central nervous system. A crucial therapeutic goal in these cases is to avoid an increasing brain salicylate level, which is associated with a poor clinical outcome.
But, as they say in the infomercials, there's more. Sodium bicarbonate is a useful adjunct in overdose from phenobarbital and methotrexate. It helps reverse, at least temporarily, potentially lethal acidemia in ethylene glycol and methanol poisoning. It also can alleviate symptoms of airway irritation in patients exposed to chlorine gas when administered by nebulized inhaler.
Given its importance, it is unfortunate that sodium bicarbonate ended up on the burgeoning list of drugs in short supply. Sixty-one drugs made that list in 2005, a number that increased by a factor of three by 2010, according to the Department of Health and Human Services. These shortages have involved critical, lifesaving medications such as antibiotics, cancer drugs, and atropine. The sheer number of drugs involved seems to have declined recently, but the situation continues to cause immense problems. The pharmacy must scramble to maintain supplies when a drug becomes scarce while deciding if and how its use should be restricted and if alternatives are available.
Many factors contribute to making drugs difficult to acquire, with quality control and safe manufacturing practices heading the list, especially as more injectable products come out in generic formulations. Ironically, the Drug Shortage Prevention Act of 2012, by requiring an early warning system to spread the word about impending drug shortages, encouraged drug hoarding and only exacerbated the problem.
So the question remains: what alternatives do we have when sodium bicarbonate is unavailable? A recent article suggests that sodium acetate is safe and effective in correcting acidemia for a number of medical and surgical conditions, including diarrhea, uremia, and trauma. (J Med Toxicol 2013 Apr 30 [Epub ahead of print].) Adverse events, including hemodynamic instability, have occurred when sodium acetate was used as a dialysate buffer, but this results in much higher acetate levels than would be produced by slow infusion.
The authors suggest that when bicarbonate is unavailable, sodium acetate can be used in a similar fashion on an equimolar basis, but there is one caveat. The metabolism of sodium acetate is considerably more complicated than sodium bicarbonate, and administering sodium acetate as a rapid bolus may result in unsafe blood levels. This is largely theoretical, but few data are available on using sodium acetate for toxicologic indications. The authors recommend that sodium acetate be infused over 15-20 minutes, not pushed over a minute or two, for a prolonged QRS interval.
Patients who need initial rapid treatment for QRS widening, cardiac arrhythmias, and salicylism should receive 1-2 mEq per kg of sodium bicarbonate bolus over 1-2 minutes but 1 mEq per kg of sodium acetate bolus over 15-20 minutes. Patients who need serum pH maintained at 7.50-7.55 should receive 150 mEq to 1 L of sodium bicarbonate with D5W infused at twice the maintenance rate but 150 mEq sodium acetate diluted to 1L with D5W at twice the maintenance rate. (J Med Toxicol 2013 Apr 30 [Epub ahead of print].)
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