Geoffrey K Isbister1, Colin B Page2, Nicholas A Buckley3, Daniel M Fatovich4, Ovidiu Pascu5, Stephen P J MacDonald6, Leonie A Calver7, Simon G A Brown4. 1. School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia; Department of Clinical Toxicology and Pharmacology, Calvary Mater Newcastle, Newcastle, New South Wales, Australia. Electronic address: geoff.isbister@gmail.com. 2. Department of Clinical Toxicology and Pharmacology, Calvary Mater Newcastle, Newcastle, New South Wales, Australia; Emergency Department, Princess Alexandra Hospital, Brisbane, Queensland, Australia. 3. Discipline of Pharmacology, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia. 4. Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute for Medical Research and the University of Western Australia, and the Department of Emergency Medicine, Royal Perth Hospital, Perth, Western Australia, Australia. 5. Emergency Department, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia. 6. Emergency Department, Armadale Health Service, Perth, Western Australia, Australia. 7. School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
Abstract
STUDY OBJECTIVE: Latrodectism is the most important spider envenomation syndrome worldwide. There remains considerable controversy over antivenom treatment. We aimed to investigate whether antivenom resulted in resolution of pain and systemic effects in patients with latrodectism who received standardized analgesia. METHODS: In a multicenter randomized placebo-controlled trial of redback spider antivenom for latrodectism, 224 patients (>7 years) with a redback spider bite and severe pain, with or without systemic effects, were randomized to receive normal saline solution (placebo) or antivenom after receiving standardized analgesia. The primary outcome was a clinically significant reduction in pain 2 hours after trial medication compared with baseline. A second primary outcome for the subgroup with systemic features of envenomation was resolution of systemic features at 2 hours. Secondary outcomes were improved pain at 4 and 24 hours, resolution of systemic features at 4 hours, administration of opioid analgesics or unblinded antivenom after 2 hours, and adverse reactions. RESULTS: Two hours after treatment, 26 of 112 patients (23%) from the placebo arm had a clinically significant improvement in pain versus 38 of 112 (34%) from the antivenom arm (difference in favor of antivenom 10.7%; 95% confidence interval -1.1% to 22.6%; P=.10). Systemic effects resolved after 2 hours in 9 of 41 patients (22%) in the placebo arm and 9 of 35 (26%) in the antivenom arm (difference 3.8%; 95% confidence interval -15% to 23%; P=.79). There was no significant difference in any secondary outcome between antivenom and placebo. Acute systemic hypersensitivity reactions occurred in 4 of 112 patients (3.6%) receiving antivenom. CONCLUSION: The addition of antivenom to standardized analgesia in patients with latrodectism did not significantly improve pain or systemic effects.
RCT Entities:
STUDY OBJECTIVE: Latrodectism is the most important spider envenomation syndrome worldwide. There remains considerable controversy over antivenom treatment. We aimed to investigate whether antivenom resulted in resolution of pain and systemic effects in patients with latrodectism who received standardized analgesia. METHODS: In a multicenter randomized placebo-controlled trial of redback spider antivenom for latrodectism, 224 patients (>7 years) with a redback spider bite and severe pain, with or without systemic effects, were randomized to receive normal saline solution (placebo) or antivenom after receiving standardized analgesia. The primary outcome was a clinically significant reduction in pain 2 hours after trial medication compared with baseline. A second primary outcome for the subgroup with systemic features of envenomation was resolution of systemic features at 2 hours. Secondary outcomes were improved pain at 4 and 24 hours, resolution of systemic features at 4 hours, administration of opioid analgesics or unblinded antivenom after 2 hours, and adverse reactions. RESULTS: Two hours after treatment, 26 of 112 patients (23%) from the placebo arm had a clinically significant improvement in pain versus 38 of 112 (34%) from the antivenom arm (difference in favor of antivenom 10.7%; 95% confidence interval -1.1% to 22.6%; P=.10). Systemic effects resolved after 2 hours in 9 of 41 patients (22%) in the placebo arm and 9 of 35 (26%) in the antivenom arm (difference 3.8%; 95% confidence interval -15% to 23%; P=.79). There was no significant difference in any secondary outcome between antivenom and placebo. Acute systemic hypersensitivity reactions occurred in 4 of 112 patients (3.6%) receiving antivenom. CONCLUSION: The addition of antivenom to standardized analgesia in patients with latrodectism did not significantly improve pain or systemic effects.
Authors: Timothy P Jenkins; Shirin Ahmadi; Matyas A Bittenbinder; Trenton K Stewart; Dilber E Akgun; Melissa Hale; Nafiseh N Nasrabadi; Darian S Wolff; Freek J Vonk; Jeroen Kool; Andreas H Laustsen Journal: PLoS Negl Trop Dis Date: 2021-12-02