Abstract
Introduction
Most hospitals lack a sufficient supply of atropine to treat, simultaneously, patients poisoned with multiple organophosphorous compound (OC) or nerve agent. The presence of a ubiquitous alternate antidote would prove useful if mass poisoning occurred. Our objective was to evaluate the effect of ophthalmic homatropine (Isopto Homatropine 5%) on survivability in a rat model of significant, acute OC poisoning.
Methods
Sprague-Dawley rats were randomized to one of five pre-treatment groups (N = 10 per group). Prior to experimentation, animals were pre-treated with intramuscular (IM) injections of either atropine 5 mg/kg, atropine 10 mg/kg, homatropine 10 mg/kg, or homatropine 20 mg/kg. The control group received 0.3 mL normal saline IM. Five minutes later, 25 mg/kg of dichlorvos was subcutaneously administered. Mortality rates were compared using Fisher’s Exact test. Kaplan-Meier survival curves with Logrank analysis was also performed. If alive at 120 minutes, survival was assumed, and the study was terminated.
Results
All rats pre-treated with normal saline, atropine 5 mg/kg, and homatropine 10 mg/kg died. Survival in the homatropine (20 mg/kg) and atropine (10 mg/kg) groups was 30% and 40% respectively. Times to death ranged between 4 and 12 minutes. Overall comparison of time to death revealed a statistically significant improvement for groups pre-treated with homatropine (20 mg/kg) and atropine (10 mg/kg).
Conclusions
Pre-treatment with homatropine (20 mg/kg) was comparable with atropine (10 mg/kg) in preventing lethality in this rat model of acute OC poisoning.
Keywords: antidote, terrorism, homatropine, atropine, dichlorvos
Full Text
The Full Text of this article is available as a PDF (134.2 KB).
Footnotes
Poster Presentation (Abstract): 2005 NACCT, Orlando, FL
Funding provided by 2004 ACMT/ATSDR Grant for Chemical Terrorism or Mass Chemical Exposure Incident Preparedness
References
- 1.Tsao TCY, Juang YC, Lan RS, et al. Respiratory Failure of Acute Organophosphate and Carbamate Poisoning. Chest. 1990;98:631–636. doi: 10.1378/chest.98.3.631. [DOI] [PubMed] [Google Scholar]
- 2.Skofield S, Lambert D, Tomassoni A, et al. Inadequate Regional Supplies of Antidotes and Medications for Poisoning Emergencies (abstract) Journal of Toxicology Clinical Toxicology. 1997;35:467–575. [Google Scholar]
- 3.Dart RC, Stark Y, Fulton B, et al. Insufficient Stocking of Poisoning Antidotes in Hospital Pharamacies. JAMA. 1996;276:1508–1510. doi: 10.1001/jama.276.18.1508. [DOI] [PubMed] [Google Scholar]
- 4.Hopmann G, Wanke H. Maximum Dose Atropine Treatment in Severe Organophosphate Poisoning. Dtsch Med Wochenschr. 1974;99:2106–2108. doi: 10.1055/s-0028-1108097. [DOI] [PubMed] [Google Scholar]
- 5.Holstege CP, Kirk M, Sidell FR. Chemical Warfare. Nerve Agent Poisoning. Critical Care Clinics. 1997;13:923–942. doi: 10.1016/S0749-0704(05)70374-2. [DOI] [PubMed] [Google Scholar]
- 6.Bird SB, Gaspari RJ, Lee WJ, et al. Diphenhydramine as a Protective Agent in a Rat Model of Acute, Lethal Organophosphate Poisoning. Academic Emergency Medicine. 2002;9:1369–1372. doi: 10.1111/j.1553-2712.2002.tb01604.x. [DOI] [PubMed] [Google Scholar]
- 7.Bania TC, Chu J, Bailes D, et al. Jimson Weed Extract as a Protective Agent in Severe Organophosphate Toxicity. Academic Emergency Medicine. 2004;11:335–338. doi: 10.1197/j.aem.2003.12.002. [DOI] [PubMed] [Google Scholar]
- 8.Faris GA, Mohammad FK. Prevention and Treatment of Dichlorvos-Induced Toxicosis in Mice by Diphenhydramine. Veterinary and Human Toxicology. 1997;39:22–25. [PubMed] [Google Scholar]
- 9.Schier JG, Ravikumar PR, Nelson LS, et al. Preparing for Chemical Terrorism: Stability of Injectable Atropine Sulfate. Academic Emergency Medicine. 2004;11:329–334. doi: 10.1111/j.1553-2712.2004.tb01447.x. [DOI] [PubMed] [Google Scholar]
- 10.Geller RJ, Lopez GP, Cutler S, et al. Atropine Availability as an Antidote for Nerve Agent Casualties: Validated Rapid Reformulation of High-Concentration Atropine From Bulk Powder. Annals of Emergency Medicine. 2003;41:453–456. doi: 10.1067/mem.2003.103. [DOI] [PubMed] [Google Scholar]
- 11.Perrone J, Henretig Sims M, et al. A Role for Ipratropium in Chemical Terrorism Preparedness. Academic Emergency Medicine. 2003;10:290–290. doi: 10.1111/j.1553-2712.2003.tb02008.x. [DOI] [PubMed] [Google Scholar]
- 12.Stein CM, Neill P. Atropine or Hyoscine in Treatment of Acute Organophosphate Poisoning? Lancet. 1985;8432:823–824. doi: 10.1016/S0140-6736(85)91487-4. [DOI] [PubMed] [Google Scholar]
- 13.Franz DN. Antimucarinc and Antispasmodic Drugs. In: Gennaro AR, editor. Remington, The Science and Practice of Pharmacy. 19th ed. Easton, PA: Mack Publishing Company; 1995. pp. 1020–1026. [Google Scholar]
- 14.Reilly KM, Chan L, Mehta NJ, et al. Systemic Toxicity From Ocular Homatropine. Academic Emergency Medicine. 1996;9:868–871. doi: 10.1111/j.1553-2712.1996.tb03533.x. [DOI] [PubMed] [Google Scholar]
