Abstract
Randomized Controlled Trial of Intravenous Antivenom Versus Placebo for Latrodectism: The Second Redback Antivenom Evaluation (RAVE-II) Study
Latrodectism is a severe spider envenomation syndrome caused by the widow spider (Latrodectus spp). The primary symptoms include local pain at the site of envenomation, generalized pain, muscle rigidity, sweating, and vomiting. Both the regional distribution and type of widow spider affect the severity of symptoms. Although patients may experience severe pain, latrodectism is rarely fatal to humans. Although there are variations in clinical practice for treating latrodectism, mainstays are supportive care and pain control; however, an equine-derived antivenom is also available. The purpose of this study was to investigate the ability of the antivenom to reduce pain and the systemic effects after moderate to severe envenomation by the redback widow spider.
This multicenter, randomized, placebo-controlled trial recruited patients from 20 emergency departments in Australia from 2009 to 2013 after envenomation by a redback widow spider. All patients received the standard analgesia with paracetamol, ibuprofen, and oxycodone, and were then randomly assigned to either placebo or antivenom administration. In all, 224 patients were enrolled, and each study arm had similar baseline characteristics. The primary outcomes were reduction in pain and systemic symptoms 2 hours after placebo or antivenom administration. It was found that the placebo arm had a 23% pain reduction whereas the antivenom arm had a 34% pain reduction; however, this was not statistically significant (95% confidence interval: −1.1% to 22.6%; P = .10). Additionally, systemic effects resolved for 22% of patients in the placebo arm and for 26% of patients in the antivenom arm (95% confidence interval: −15% to 23%; P = .079).
The RAVE-II trial expanded on prior research from 3 latrodectism antivenom trials. The investigators conclude that antivenom administration for redback widow spider envenomation does not significantly improve pain or systemic effects when given with standard analgesia. Although treatment effects were not statistically significant, the investigators recognize that a limitation of the study is the small sample size, limiting the power of the study. Moreover, standard analgesia treatment, with or without antivenom, relieved pain in only one quarter of patients after 2 hours. The researchers recognize that further treatment options, including calcium, magnesium, muscle relaxants, or neuropathic medications, should be investigated to identify alternative options to ultimately improve patient outcomes.
(Ann Emerg Med. 2014;64:620–628) GK Isbister, CB Page, NA Buckley, et al.