Antimuscarinic agents (e.g. diphenhydramine) are one of the commonly ingested substances in the US. Lorazepam is frequently used to treat delirium and agitation associated with antimuscarinic toxicity. Although physostigmine is also effective, its use is infrequent due to concerns of safety and provider’s limited experience with physostigmine.

A small blinded randomized clinical trial was conducted to compare physostigmine vs lorazepam for the treatment of antimuscarinic toxicity -delirium/agitation. 

Inclusion criteria

• Age: 10-17 years old
• At least one central and 2 peripheral antimuscarinic symptoms
• Delirium and moderate agitation

 

Intervention

1. Lorazepam 0.05 mg/kg IV bolus (max 2 mg). this dose could be repeated at 10 min if needed. then a 4 hr normal saline infusion 
2. Physostigmine 0.02 mg/kg IV bolus (max 2 mg; over 3-5 min). this dose could be repeated at 10 min if needed. then 0.02 mg/kg/hr (max 2 mg/h) physostigmine infusion for 4 hours.

Plus administration of lorazepam (0.05 mg/kg) IV bolus (max 2 mg) every 2 hours as needed for continued agitation or delirium (at the discretion of treatment team)

 

Delirium and agitation were assessed by Confusion Assessment Method for the Intensive Care Unit score (CAM-ICU) and Richmond Agitation Sedation Score

 

Result

Study duration: March 20, 2017 to June 30, 2020

• 175 patients presented with xenobiotic ingestion. But 19 patients were enrolled
• Physostigmine arm: 9 (47%)
• Lorazepam arm: 10 (53%)

Antimuscarinic agent ingested

• Diphenhydramine: 16 (84%)
• Dicyclomine: 1 (5%)
• Doxylamine: 1 (5%)
• Hyoscyamine: 1 (5%)

Proportion of subject with delirium by CAM-ICU

Prior to first bolus (p >0.99)

• Lorazepam arm: 9/10 (90%)
• Physostigmine arm: 9/9 (100%)

After 1^st bolus (p=0.01)

• Lorazepam: 10/10 (100%)
• Physostigmine: 4/9 (44.4%)

End of 4 hr infusion (p <0.001)

• Lorazepam: 10 (100%
• Physostigmine: 2 (22.2%)

No adverse events noted in both group

 

Conclusion

• Although this is a small study, it showed that physostigmine is better than lorazepam in treating antimuscarinic delirium and agitation.
• This study provides additional support to the finding from a prior retrospective study (Bruns MJ et al. Ann Emerg Med. 2000;35(4):374-381), which also showed the benefits of physostigmine over benzodiazepines in the management of antimuscarinic overdose associated delirium.

References

Wang GS et al. A randomized trial comparing physostigmine vs lorazepam for treatment of antimuscarinic (anticholinergic) toxidrome. Clin Toxicol (Phila.) 2020. Dec 9. Online ahead of print. https://doi.org/10.1080/15563650.2020.1854281