Neostigmine and Atropine in Snake Bite
Neostigmine and atropine are NOT recommended for the treatment of snake bites in North America, as the definitive treatment is antivenom, and first aid measures should focus on rapid transport to emergency care rather than pharmacological interventions. 1
Evidence Against Use in Snake Envenomation
The 2024 American Heart Association and American Red Cross guidelines for first aid explicitly state that the definitive treatment for snake bite is antivenom, which is not available in the first aid setting, and emphasize that prompt medical attention is the priority. 1 More specifically, the use of neostigmine in snake bites is not recommended, except in specific cases of coral snake envenomation where reversible blockade is documented, and should be combined with appropriate antivenom administration. 2
Clinical Evidence from Neurotoxic Snake Bites
Research from actual snake bite cases reveals significant limitations:
In a study of 72 patients with Indian common krait (Bungarus caeruleus) bites, neostigmine was completely ineffective—none of the patients showed any improvement following treatment with 2.5 mg neostigmine at 30-minute intervals after atropine administration, and all patients developed respiratory paralysis requiring assisted ventilation. 3
A 10-year retrospective analysis from rural Maharashtra documented that while neurotoxic envenomation required 40-320 ml of antisnake venom, the primary effective treatment was antivenom itself, not anticholinesterase agents. 4
Another study comparing antivenom doses found that low-dose antivenom (150 ml) was as effective as high-dose protocols in severe neurotoxic envenomation, with similar durations of mechanical ventilation, but made no mention of neostigmine having therapeutic benefit. 5
Why Neostigmine Fails in Most Snake Bites
The mechanism explains the failure: Neostigmine works by inhibiting acetylcholinesterase to increase acetylcholine at the neuromuscular junction, which is designed to reverse competitive neuromuscular blockade from anesthetic agents, not the irreversible or presynaptic blockade caused by most snake venoms. 6
Critical Distinctions
Train-of-four monitoring should not be used to guide neostigmine dosing in snake bites, as this monitoring is designed for anesthetic reversal, not envenomation. 2
The FDA-approved indication for neostigmine is specifically for reversal of non-depolarizing neuromuscular blocking agents (rocuronium, vecuronium, pancuronium) used in anesthesia, not for toxin-induced paralysis. 6
Neostigmine's elimination half-life is only 24-113 minutes, far too short to counteract the prolonged effects of snake venom. 6
Limited Experimental Evidence
While one pilot study showed that intranasal neostigmine improved survival in mice injected with Naja naja (Indian cobra) venom—with 67% survival at 2.5× LD50 compared to 0% in controls 7—and another case report suggested reversal of experimental paralysis in a human 8, these experimental findings have not translated to clinical efficacy in actual snake bite victims, as demonstrated by the complete failure in the krait bite study. 3
Recommended Approach for North American Snake Bites
Emergency services should be activated for any person bitten by a venomous or possibly venomous snake. 1
Appropriate First Aid Measures
It is reasonable to rest and immobilize the bitten extremity and minimize exertion if it does not delay access to emergency medical care. 1
Remove rings and other constricting objects from the bitten extremity. 1
Contraindicated Interventions
The following are potentially harmful and should NOT be used: 1
- Tourniquets
- Pressure immobilization bandaging
- Suction devices
- Ice application
- Electric shock
Clinical Context: When Neostigmine IS Appropriate
Neostigmine with atropine is indicated for reversal of non-depolarizing neuromuscular blockade in anesthesia, where: 6
The recommended dose is 0.03-0.07 mg/kg IV neostigmine with atropine (0.02 mg/kg) or glycopyrrolate administered prior to or concomitantly. 1, 6
Atropine must be given to prevent bradycardia and other muscarinic side effects from neostigmine. 6, 9
This achieves a train-of-four ratio ≥0.9 within 10-20 minutes when used for its approved indication. 1, 6
This anesthetic context is fundamentally different from snake envenomation and the principles do not transfer.