What is the toxidrome associated with carbamate overdose
Carbamate toxicity, as manifested by the cholinergic toxidrome, largely resembles OP toxicity but with an important difference: Both OPs and carbamates function by binding to and inhibiting AChE; however, the carbamate-AChE bond undergoes spontaneous hydrolysis, thereby reactivating the enzyme. Consequently, the clinical effects of carbamate toxicity, though potentially severe, are self-limited and usually only last 24 hours or less.4
How should this patient be managed?
The general approach to a patient with medical carbamate toxicity is similar to that of a patient with OP poisoning. Dermal exposure, as is the case with this patient, should prompt skin decontamination to minimize ongoing exposure. Patch removal is necessary but is not sufficient to prevent ongoing absorption, since a depot of medication typically forms in the dermal tissue. In the presence of significant or life-threatening muscarinic effects (eg, bronchorrhea, bronchospasm, seizure), an antimuscarinic agent such as atropine is indicated. Various dosing schemes of atropine exist; at our institution, we recommend an initial dose of 1 to 3 mg intravenously (IV), with escalating doses every 5 minutes until reversal of bronchorrhea and bronchospasm occur.4 This is followed by initiation of an atropine infusion at a rate of 10% to 20% of the total loading dose per hour (to a maximum of 2 mg/h).4
Pralidoxime (2-PAM) and other oximes, accelerate the reactivation of carbamate-inhibited AChE and have effects at both the nicotinic and muscarinic synapses. Reactivation results in the enhanced metabolism of intrasynaptic ACh and decreased clinical cholinergic effects. Since atropine is only effective at muscarinic receptors, oximes were administered in this case to reverse neuromuscular weakness.
Although early administration of 2-PAM is indicated in the setting of significant OP poisoning (due to irreversible inhibition of AChE), its use for medical carbamate toxicity is controversial. Early animal studies of carbamate toxicity suggested that treatment with oximes worsened outcomes; however, this has not been demonstrated in more recent studies.5,6 Therefore, although 2-PAM may be beneficial in treating cases of clinically significant carbamate poisoning (which can be prolonged and severe), these benefits should be weighed against the potential risks.
Case Conclusion
Upon arrival to the ED, the patient’s skin was cleansed thoroughly. As he did not exhibit muscarinic findings of bradycardia, bronchoconstriction, or bronchorrhea, atropine was not indicated. He was treated conservatively with IV fluid hydration and admitted to the medicine floor. Since he continued to exhibit profound extremity weakness with no improvement 12 hours from the onset of symptoms, pralidoxime 1 g IV was administered over a 30-minute period. Shortly thereafter, patient’s motor strength improved from 2/5 to 4/5 in both upper and lower extremities. No complications were noted, and the patient‘s weakness and tremulousness continued to resolve. He was transferred to a skilled nursing facility on hospital day 6.
Dr Laskowski is a medical toxicology fellow in the department of emergency medicine at New York University Langone Medical Center. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.