Adjunct treatment in snakebite envenoming: a systematic review of randomised controlled trials

Adjunct therapy in snakebite may be lifesaving if administered appropriately or can be harmful if non-judicious use leads to avoidable delays in administering antivenom. This systematic review analyses the evidence from randomised controlled trials (RCTs) on the efficacy of adjunct treatment administered with antivenom. PubMed, EMBASE, Scopus, Cochrane library and CINAHL were searched for RCTs enrolling patients with snakebite envenoming where a treatment other than antivenom has been assessed for its efficacy within the last 25 y. Fifteen studies met the inclusion criteria. The interventions assessed were categorised as adjunct therapies (heparin or fresh frozen plasma) to reverse haemotoxicity (three studies), antibiotics to prevent local infections (three studies), steroids to reduce local swelling (one study), premedication (adrenaline, steroids and antihistamines, either alone or in combination) to reduce hypersensitivity reactions to antivenom (five studies) and other interventions (three studies). Apart from a beneficial effect of low-dose adrenaline (1:1000, 0.25 ml administered subcutaneously) in preventing antivenom-induced hypersensitivities (OR: 0.54, 95% CI 0.32 to 0.93, two RCTs, 354 participants, moderate certainty evidence) in Sri Lanka, evidence for any other adjunct therapy is either non-existent or needs confirmation by larger better designed trials.