02845nas a2200349   4500000000100000008004100001260003700042653002600079653001900105653002500124653003900149100001800188700001700206700001500223700001600238700001800254700001400272700001500286700001400301700001600315700001800331700001700349700001500366700001700381700001800398245017500416856007900591300000900670490000700679520179500686022001402481       2025                            d  bPublic Library of Science (PLoS)10aCold and heat therapy10aBothrops atrox10aSnakebite envenoming10arandomized controlled trials (RCT)1 ade Almeida MC1 aCarvalho KMP1 aMendes YDS1 aOliveira DN1 aCarvalho ÉDS1 aSartim MA1 aAraújo FQ1 aSachett A1 aVissoci JRN1 aAlmeida-Val F1 ade Castro DB1 aMonteiro W1 aSachett JDAG1 aGutiérrez JM00aLimited efficacy of cold and heat therapy as adjunctive treatments for local and functional outcomes of Bothrops atrox snakebite envenomation: A randomized clinical trial  uhttps://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0013423  a1-150 v193 a<p><strong>Background</strong> Bothrops atrox envenomation can cause significant local and systemic effects. Adjunctive therapies, such as cold and heat applications, are proposed to enhance antivenom efficacy, but their clinical value remains unclear.</p>

<p><strong>Methods</strong> This randomized, three-arm clinical trial included 94 patients allocated in a 1:1:1 ratio to Cold Therapy Group (CTG, n = 30), Heat Therapy Group (HTG, n = 31), or Control Group (CG, n = 33). All participants received standard antivenom therapy, with CTG and HTG receiving additional interventions applied for 24 hours post-admission. Primary outcomes included changes in creatine kinase (CK) levels. Secondary outcomes assessed pain intensity, edema, local temperature, and functional recovery using the World Health Organization Disability Assessment Schedule (WHODAS 2.0) assessed four to six months after hospital discharge. Kaplan-Meier survival analysis evaluated time-to-event outcomes.</p>

<p><strong>Findings</strong> Baseline characteristics were comparable across groups. CK levels decreased similarly in all groups at 48 hours (p = 0.89). No significant differences were observed in the reduction of limb circumference, edema extent and bite site temperature, either the ITT or PP analysis. CTG showed a significant reduction in pain within 24 hours in the per-protocol analysis (Log-rank p = 0.04). Disability assessed by WHODAS 2.0 revealed no significant differences between groups after 6 months of follow-up. No adverse events were associated with the interventions.</p>

<p><strong>Interpretation</strong> Adjunctive HTG had no efficacy in treating local effects of B. atrox envenomation. Adjunctive CTG demonstrated benefits observed in pain reduction.</p>
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