Postagem em destaque



sexta-feira, 4 de março de 2011

Não existe eficácia na medicação pré soroterapia, e nenhum teste cutâneo tem efeito preditivo.

Para resumir uma longa historia, e para ilustrar essa postagem, segue-se correspondência pessoal com Dr. Warrel de hoje, 04 de março de 2011. É tema de interesse público, daí sua divulgação. Em 17/02/11 relatei estar colaborando com revisão do Manual do Ministério da Saúde para Animais Peçonhentos, e estar posicionando-me CONTRA o uso rotineiro de prometazina e hidrocortisona pré-soroterapia.

Ao consultar talvez aquele que seja o mais experiente entre nós, recebo resposta clara e objetiva. Com sua licença Professor:

From: Rodrigo C. G. Souza []
Sent: 17 February 2011 5:21 PM
To: David Warrell

Dear David, we are close to finishing the revised version of the manual for the treatment of snake bites, for the Health Ministry. I've given my straight forward position about pre antivenon treatment: useless and harmfull. May I have your own opinion ?

Thanks tons,
Rodrigo C.G de Souza, M.D
Nucleo Serra Grande
CTF Ibama/MMA 495100

De:David Warrell (david.warrell@ndm.ox ...)
Enviada: sexta-feira, 4 de março de 2011 14:40:49
Para: Rodrigo C. G. Souza (

Apologies. I’ve just got back from India.

Here is my current conclusion

Since no prophylactic drug regimen has proved effective in reducing the incidence or severity of early antivenom reactions, these drugs (adrenaline, histamine H-1 blockers, corticosteroids) should not be used except in high risk patients. All patients should be watched carefully for two hours after the completion of antivenom administration and should be treated with epinephrine/adrenaline at the first sign of a reaction.

[this applies to the empirical cocktail of pre-treatment drugs recommended, against all the published evidence, by the Brazilian Ministerio de Salud]

In addition –
Skin and conjunctival “hypersensitivity” tests will reveal IgE mediated Type I hypersensitivity to horse or sheep proteins. However, since the majority of early (anaphylactic) or late (serum sickness type) antivenom reactions result from direct complement activation rather than from Ig Emediated hypersensitivity, these tests are not predictive. Since they may delay treatment and can in themselves be sensitising, these tests should not be used.

Best wishes,


Abaixo novamente Warrel, em correspondência pessoal, agora sobre corticoides pré-soroterapia. De novo o interesse público que me permite a divulgação. Com sua licença Professor:

"I disagree with the routine use of "high-dosage cortisone" before antivenom. Early reactions occur in less than a quarter of the patients and so it seems unreasonable to expose all to the general dangers of corticosteroids and possibly to increased venom toxicity. Corticosteroids are not always successful in preventing early serum reactions, but these reactions can be safely and effectively treated with adrenaline, 0 5 ml of 0 1°% solution by subcutaneous injection. The incidence of reactions due to anticomplementary activity may be reduced by diluting the antivenom and by giving it by slow intravenous infusion"

Radcliffe Infirmary,

Confira também:

Warrell, D A, et al, American Journal of Tropical
Medicine and Hygiene, 1976, 25, 517.

Warrell, D A, et al, British Medical Journal, 1975,
4, 697.

Theakston, R D G, and Reid, H A, Lancet, 1976,
2, 121.

Warrell, D A, and Ormerod, L D, American_Journal of
Tropical Medicine and Hygiene, 1976, 25, 525.

Abaixo outros dois trabalhos que ilustram a ineficácia do tratamento profilático de reações adversas na soroterapia:

Prevention of acute adverse reactions to snake antivenom after snakebite: multi-centre, randomized, controlled clinical trial

de Silva HA, Pathmeswaran A, Jayamanne S, Ariyasena H, Ratnatilaka GA, Kalupahana R, Uluwatte W, Ranasinha CD, Armitage J*, Aronson JK*, Lalloo DG**, de Silva HJ

Clinical Trials Unit, University of Kelaniya, Sri Lanka, *University of Oxford, and **Liverpool School of Tropical Medicine, UK.

Background: Polyvalent antivenom (PAV) is the most effective treatment for snakebite envenoming. Acute adverse reactions to the PAV are common; anaphylactic reactions are particularly serious. 

Objective: To determine whether promethazine, hydrocortisone, and low-dose adrenaline, alone and in all possible combinations, prevent reactions to antivenom.

Methods: The study was conducted in 3 hospitals in Sri Lanka from March 2005 to April 2008. It required 1000 patients to detect a 25% reduction in reactions at p<0.01 with 80% power. After informed consent, patients were randomized in a 2x2x2 factorial blinded design to receive each active intervention versus matching placebo immediately before administration of PAV. They were monitored for adverse reactions categorized as mild, moderate, severe, for at least 96 hours. The pre-specified primary analyses were of effects of each intervention on the incidence of severe reactions over 48 hours.

Results: Of 1007 randomised subjects 776 (77.2%) were males, mean (sd) age 36.5 (13.6) yrs. Median time between snakebite and PAV administration was 4.25 hours. 752 (75%) patients developed acute reactions to PAV; 9% mild, 48% moderate, 43% severe. None of the drugs significantly reduced severe reactions to PAV at any time point. There was an 18.4% reduction in the rate of severe reactions at 1 hour with adrenaline (p=0.052), and a 33.3% reduction in signs of allergy (pruritus, urticaria, facial oedema, bronchospasm) with promethazine at 1 and 24 hours ( p<0.001).

Conclusions: Pre-treatment with promethazine, hydrocortisone, and low-dose adrenaline alone and in different combinations do not significantly reduce acute reactions to PAV.

BMJ 1999; 318 : 1451 (Published 29 May 1999)

Sequential randomised and double blind trial of promethazine prophylaxis against early anaphylactic reactions to antivenom for bothrops snake bites

  1. Hui Wen Fan, doctor (,
  2. Luiz F Marcopito, associate professorb,
  3. João Luiz C Cardoso, doctora,
  4. Francisco O S França, doctora,
  5. Ceila M S Malaque, doctora,
  6. Ronnei A Ferrari, doctora,
  7. Robert David G Theakston, associate professorc,
  8. David A Warrell, associate professor
+ Author Affiliations
  1. a Hospital Vital Brazil, Instituto Butantan, Avenue Vital Brazil 1500, 05503-900, São Paulo, Brazil
  2. b Division of Epidemiology, Escola Paulista de Medicina, Unifesp, 04039-032, São Paulo, Brazil
  3. c Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA
  4. d Centre for Tropical Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU
  1. Correspondence to: Dr H W Fan

    Objective: To investigate the efficacy of the H1 antihistamine promethazine against early anaphylactic reactions to antivenom.

    Design: sequential randomised, double blind, placebo controlled trial.

    Setting: Public hospital in a venom research institute, São Paulo, Brazil.

    Participants: 101 patients requiring antivenom treatment after being bitten by bothrops snakes.

    Intervention: Intramuscular injection of promethazine (25 mg for adults and 0.5/kg for children) or placebo given 15-20 min before starting intravenous infusion of antivenom.
    Main outcome measures: Incidence and severity of anaphylactic reactions occurring within 24 hours after antivenom.

    Results: Reactions occurred in 12 of 49 patients treated with promethazine (24%) and in 13 of 52 given placebo (25%); most were mild or moderate. Continuous sequential analysis indicated that the study could be interrupted at the 22nd untied pair, without preference for promethazine or placebo.

    Conclusion: Prophylaxis with promethazine does not prevent early reactions. Patients should be observed carefully during antivenom infusion and the subsequent few hours.

    Mestre Abade em quadro anafilático pós soroterapia anti laquética. Ficou no exantema. A adrenalina deteve a reação.


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