Jeffrey Maudlin

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Journals/Publications

• Caron, E., Manock, S., Maudlin, J., Koleski, J., Theakston, R., Warrell, D., & Smalligan, R. (2009). Apparent marked reduction in early antivenom reactions compared to historical controls: Was it prophylaxis or method of administration?. Toxicon, 54(6). doi:10.1016/j.toxicon.2009.06.001
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  Objective: Serious morbidity and mortality following snakebite injuries are common in tropical regions of the world. Although antivenom administration is clinically effective, it carries an important risk of early anaphylactic reactions, ranging from relatively benign nausea, vomiting, and urticaria to life-threatening angioedema, bronchospasm and hypotension. Currently, no adequately powered study has demonstrated significant benefit from the use of any prophylactic drug. A high rate of anaphylactic reactions observed during a trial of three different antivenoms in Ecuador prompted adoption of premedication with intravenous (IV) hydrocortisone and diphenhydramine together with dilution and slower administration of antivenom. Design: In a rural mission hospital in Eastern Ecuador, 53 consecutive snakebite victims received a new antivenom regimen in 2004-2006, comprising prophylactic drugs and IV infusion of diluted antivenom over 60 min. They were compared to an historical control cohort of 76 patients treated in 1997-2002 without prophylactic drugs and with IV "push" injection of undiluted antivenom over 10 min. All these patients had incoagulable blood on admission and all were treated with Brazilian Instituto Butantan polyspecific antivenom. Results: Baseline characteristics of the historical control and premedicated groups were broadly similar. In the historical group, early reaction rates were as follows: 51% of patients had no reaction; 35% had mild reactions; 6% moderate; and 6% severe. In the premedicated/slow IV group, 98% of patients had no reaction; 0 mild; 0 moderate; and 2% severe. The difference in reaction rates was statistically significant (p < 0.001). Conclusions: Premedication with intravenous hydrocortisone and diphenhydramine together with dilution of antivenom and its administration by IV infusion over 60 min appeared to reduce both the frequency and severity of anaphylactic reactions. A randomized blinded controlled trial is needed to confirm these encouraging preliminary findings. © 2009 Elsevier Ltd. All rights reserved.
• Smalligan, R., Cole, J., Brito, N., Laing, G., Mertz, B., Manock, S., Maudlin, J., Quist, B., Holland, G., Nelson, S., Lalloo, D., Rivadeneira, G., Barragan, M., Dolley, D., Eddleston, M., Warrell, D., & Theakston, R. (2004). Crotaline snake bite in the Ecuadorian Amazon: Randomised double blind comparative trial of three South American polyspecific antivenoms. British Medical Journal, 329(7475). doi:10.1136/bmj.329.7475.1129
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  Objective: To compare the efficacy and safety of three polyspecific antivenoms for bites from pit vipers. Design: Randomised double blind comparative trial of three antivenoms. Setting: Shell, Pastaza, southeastern Ecuador. Participants: 210 patients with incoagulable blood were recruited from 221 consecutive patients admitted with snake bite between January 1997 and December 2001. Intervention: One of three antivenoms manufactured in Brazil, Colombia, and Ecuador, chosen for their preclinical potency against Ecuadorian venoms. Main outcome measures: Permanent restoration of blood coagulability after 6 and 24 hours. Results: The snakes responsible for the bites were identified in 187 cases: 109 patients (58%) were bitten by Bothrops atrox, 68 (36%) by B bilineatus, and 10 (5%) by B taeniatus, B brazili, or Lachesis muta. Eighty seven patients (41%) received Colombian antivenom, 82 (39%) received Brazilian antivenom, but only 41 (20%) received Ecuadorian antivenom because the supply was exhausted. Two patients died, and 10 developed local necrosis. All antivenoms achieved the primary end point of permanently restoring blood coagulability by 6 or 24 hours after the start of treatment in > 40% of patients. Colombian antivenom, however, was the most effective after initial doses of 20 ml (two vials), < 70 ml, and any initial dose at both 6 and 24 hours. An initial dose of 20 ml of Colombian antivenom permanently restored blood coagulability in 64% (46/72) of patients after 6 hours (P = 0.054 compared with the other two antivenoms) and an initial dose of < 70 ml was effective at 6 hours (65%, P = 0.045) and 24 hours (99%, P = 0.06). Early anaphylactoid reactions were common (53%, 73%, and 19%, respectively, for Brazilian, Colombian, and Ecuadorian antivenoms, P < 0.0001) but only three reactions were severe and none was fatal. Conclusions: All three antivenoms can be recommended for the treatment of snakebites in this region, though the reactogenicity of Brazilian and Colombian antivenoms is a cause for concern.