Low-Dose Adrenaline, Promethazine, and Hydrocortisone in the Prevention of Acute Adverse Reactions to Antivenom following Snakebite: A Randomised, Double-Blind, Placebo-Controlled Trial

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Background:
Envenoming from snakebites is most effectively treated by antivenom. However, the antivenom available in South Asian countries commonly causes acute allergic reactions, anaphylactic reactions being particularly serious. We investigated whether adrenaline, promethazine, and hydrocortisone prevent such reactions in secondary referral hospitals in Sri Lanka by conducting a randomised, double-blind placebo-controlled trial.

Methods and Findings:
In total, 1,007 patients were randomized, using a 2×2×2 factorial design, in a double-blind, placebo-controlled trial of adrenaline (0.25 ml of a 1∶1,000 solution subcutaneously), promethazine (25 mg intravenously), and hydrocortisone (200 mg intravenously), each alone and in all possible combinations. The interventions, or matching placebo, were given immediately before infusion of antivenom. Patients were monitored for mild, moderate, or severe adverse reactions for at least 96 h. The prespecified primary end point was the effect of the interventions on the incidence of severe reactions up to and including 48 h after antivenom administration. In total, 752 (75%) patients had acute reactions to antivenom: 9% mild, 48% moderate, and 43% severe; 89% of the reactions occurred within 1 h; and 40% of all patients were given rescue medication (adrenaline, promethazine, and hydrocortisone) during the first hour. Compared with placebo, adrenaline significantly reduced severe reactions to antivenom by 43% (95% CI 25–67) at 1 h and by 38% (95% CI 26–49) up to and including 48 h after antivenom administration; hydrocortisone and promethazine did not. Adding hydrocortisone negated the benefit of adrenaline.

Conclusions:
Pretreatment with low-dose adrenaline was safe and reduced the risk of acute severe reactions to snake antivenom. This may be of particular importance in countries where adverse reactions to antivenom are common, although the need to improve the quality of available antivenom cannot be overemphasized.

Trial registration:
www.ClinicalTrials.gov NCT00270777

: Please see later in the article for the Editors' Summary

Vyšlo v časopise: Low-Dose Adrenaline, Promethazine, and Hydrocortisone in the Prevention of Acute Adverse Reactions to Antivenom following Snakebite: A Randomised, Double-Blind, Placebo-Controlled Trial. PLoS Med 8(5): e32767. doi:10.1371/journal.pmed.1000435
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1000435

Souhrn

Trial registration:
www.ClinicalTrials.gov NCT00270777

: Please see later in the article for the Editors' Summary

Zdroje

1. KasturiratneA

WickremasingheAR

de SilvaN

GunawardenaNK

PathmeswaranA

2008 The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths. PLoS Med 5 e218 doi:10.1371/journal.pmed.0050218

2. ChippauxJP

2008 Estimating the global burden of snakebite can help to improve management. PLoS Med 5 e221 doi:10.1371/journal.pmed.0050221

3. KasturiratneA

PathmeswaranA

FonsekaMMD

LallooDG

BrookerS

2005 Estimates of disease burden due to land-snake bite in Sri Lankan hospitals. Southeast Asian J Trop Med Public Health 36 733 740

4. Sri Lankan Ministry of Health 2005 Annual health bulletin

5. GutiérrezJM

TheakstonRD

WarrellDA

2006 Confronting the neglected problem of snake bite envenoming: the need for a global partnership. PLoS Med 3 e150 doi:10.1371/journal.pmed.0030150

6. MalasitP

WarrellDA

ChanthavanichP

ViravanC

MongkolsapayaJ

1986 Prediction, prevention, and mechanism of early (anaphylactic) antivenom reactions in victims of snake bites. Br Med J (Clin Res Ed) 292 17 20

7. LallooD

TheakstonRDG

2003 Snake antivenoms. J Toxicol Clin Toxicol 41 277 290; 317-327

8. TheakstonRDG

WarrellDA

GriffithsE

2003 Report of a WHO workshop on the standardization and control of antivenoms. Toxicon 41 541 557

9. SampsonHA

Munoz-FurlongA

CampbellRL

AdkinsonNFJr

BockSA

2006 Second symposium on the definition and management of anaphylaxis: summary report—Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol 117 391 397

10. PremawardenaAP

de SilvaCE

FonsekaMMD

GunatilakeSB

de SilvaHJ

1999 Low dose subcutaneous adrenaline to prevent acute adverse reactions to antivenom serum in snake bite: a randomised placebo-controlled trial. BMJ 318 730 733

11. AriaratnamCA

SjostromL

RaziekZ

AbeyasingheS

KularatneM

2001 An open, randomised controlled trial of two antivenoms for the treatment of envenoming by Sri Lankan Russell's viper (Daboia russelli russelli). Trans R Soc Trop Med Hyg 95 74 80

12. GawarammanaIB

AbeysingheS

KularatneM

DissanayakeWP

KumarasiriRPV

2004 Parallel infusion of hydrocortisone ± chlorpheniramine bolus injection to prevent acute adverse reactions to antivenom for snakebites: a randomised, double-blind, placebo-controlled study. Med J Aust 180 20 23

13. KhannaR

HawkinsWJ

1999 Replies to “Low dose subcutaneous adrenaline to prevent acute adverse reactions to antivenom serum in people bitten by snakes: randomised,placebo controlled trial”: A plea for caution in the use of adrenaline. BMJ Available: http://www.bmj.com/content/318/7190/1041/reply. Accessed 5 April 2011

14. WilliamsDJ

JensenJD

NimorakiotakisB

MullerR

WinkelKD

2007 Antivenom use, premedication and early adverse reactions in the management of snake bites in rural Papua New Guinea. Toxicon 49 780 792

15. IsbisterGK

BrownSGA

MacDonaldE

WhiteJ

CurrieBJ

2008 Current use of Australian snake antivenoms and frequency of immediate-type hypersensitivity reactions and anaphylaxis. Med J Aust 188 473 476

16. FanHW

MarcopitoLF

CardosoJL

FrancaFOS

MalaqueCMS

1999 Sequential randomised and double blind trial of promethazine prophylaxis against early anaphylactic reactions to antivenom for Bothrops snake bites. BMJ 318 1451 1452

17. BrownSGA

2004 Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol 114 371 376

18. DassanayakeAS

KarunanayakeP

KasturiratneKT

FonsekaMMD

WijesiriwardenaB

2002 Safety of subcutaneous adrenaline as prophylaxis against acute adverse reactions to anti-venom serum in snakebite. CMJ 47 48 49

19. HorowitzBZ

JadallahS

DerletRW

1996 Intracranial bleeding associated with prehospital use of epinephrine. Ann Emerg Med 28 725 727

20. SutherlandSK

1977 Serum reactions: an analysis of commercial antivenoms and the possible role of anticomplementary activity in de-novo reactions to antivenom and venom. Med J Aust 1 613 615

21. PughRN

TheakstonRDG

1987 Antivenom reactions and complement depletion in snake bite. Ann Trop Med Parasitol 81 73 75

22. TheakstonRDG

SmithDC

1997 Antivenoms: a review of current status and future developments. Biopharmaceuticals 7 366 375

23. Otero-PatinoR

CardosoJL

HigashiHG

NunezV

DiazA

1998 A randomized, blinded, comparative trial of one pepsin-digested and two whole IgG antivenoms for Bothrops snake bites in Uraba, Colombia. The Regional Group on Antivenom Therapy Research (REGATHER). Am J Trop Med Hyg 58 183 189

24. OteroR

GutierrezJM

RojasG

NunezV

DiazA

1999 A randomized blinded clinical trial of two antivenoms, prepared by caprylic acid or ammonium sulphate fractionation of IgG, in Bothrops and Porthidium snakebites in Colombia: correlation between safety and biochemical characteristics of antivenoms. Toxicon 37 895 908

25. ThiansookonA

RojnuckarinP

2008 Low incidence of early reactions to horse-derived F(ab')(2) antivenom for snakebites in Thailand. Acta Trop 105 203 205

26. World Health Organization WHO guidelines for the production, control and regulation of snake antivenom immunoglobulins. Geneva World Health Organization Available: http://www.who.int/bloodproducts/snake_antivenoms/snakeantivenomguide/en/index.html. Accessed 5 April 2011