Low dose subcutaneous adrenaline to prevent acute adverse reactions to antivenom serum in people bitten by snakes: randomised,placebo controlled trialBMJ 1999; 318 doi: https://doi.org/10.1136/bmj.318.7190.1041 (Published 17 April 1999) Cite this as: BMJ 1999;318:1041
All rapid responses
EDITOR: Premawardhena et al have listed medical contraindications to
adrenaline premed administration to prevent acute adverse reactions to
polyspecific antivenom serum in snake bite victims (1).
I suggest that potential drug interactions should also be considered.
Patients taking nonselective beta adrenergic receptor blockers could
be at risk of an increased hypertensive response to parenteral adrenaline.
Most patients on beta blockers would be excluded because of the underlying
condition such as hypertension or ischaemic heart disease. Patients on
beta blockers for migraine prophylaxis could be included.
Patients taking drugs with alpha adrenergic receptor blocking
activity could theoretically, via the reverse adrenaline effect, have a
hypotensive response to parenteral adrenaline (2,3).Patients taking
prazosin for hypertension would be excluded. Patients taking prazosin for
bladder neck obstruction would not be excluded.
There are very few published reports of clinical misadventure as a
result of the reverse adrenaline effect (3). I suspect however that the
many unexplained deaths in children (4,5) and adults on tricyclic
antidepressants and/or phenothiazines are related to the fact that both of
these groups of drugs have major alpha adrenergic receptor blocking
It is conceivable from accepted pharmacological principles that
patients taking alpha adrenergic blockers who have a hypotensive collapse
(from whatever cause- anaphylaxis, septicaemia, snake bite, vasovagal)
would further drop their blood pressure as a result of a physiological
endogenous adrenaline surge. Physician administered parenteral adrenaline
in such patients could also exacerbate the hypotension possibly with fatal
In summary snake bite victims taking adrenergic blockers may merit
exclusion from adrenaline premed because of possible adverse drug
1. Premawardhena AP, de Silva CE, Fonseka MMD, Gunatilake SB, de
Silva HJ. Low dose subcutaneous adrenaline to prevent acute adverse
reactions to antivenom serum in people bitten by snakes: randomised,
placebo controlled trial. BMJ 1999;318:1041-1043 (17 April).
2. Watson A. Don't get stung with the adrenergic blockers (beta or
alpha). Australian Family Physician Vol. 24, No.10, October 1995 1879
3. Watson A. Alpha adrenergic blockers and adrenaline- a mysterious
collapse. Australian Family Physician Vol. 27 No. 8, August 1998 714-715.
4. Popper CW, Zimnitzky B. Sudden death putatively related to
desipramine treatment in youth: a fifth case and a review of speculative
mechanisms. Journal Of Child And Adolescent Psychopharmacology Vol. 5, No.
5. Varley CK, McLennan J. Case study: two additional sudden deaths
with tricyclic antidepressants. J.Am.Acad.Child Adolesc. Psychiatry 36:3,
March 1997 390-394.
Competing interests: No competing interests
Premawardhene et al have demonstrated that low dose adrenaline can be
safely administered by the sub-cutaneous route prophylactically prior to
the administration of antivenom serum(1).
They did not see an acute rise in blood pressure or other adverse
sequelae. Fatal intracranial bleeding has however been documented
following sub-cutaneous administration of adrenaline (2). Intravenous
administration of adrenaline certainly does cause marked hypertension
(3,4) which, as the sub cutaneous route can be catastrophic (5). We are
also aware of a local case where the use of 2ml 1:10 000 Adrenaline given
intravenously in a patient with moderate hypotension resulted in fatal
Adrenaline is currently being extensively used in the treatment of
established anaphylaxis and cardiopulmonary arrest. Its use in a
prophylactic role has now been described(1). We are deeply concerned that
the medical profession is beginning to lose sight of the fact that
adrenaline is a highly potent drug and must be used judiciously.
Distinction should be made between the different routes of administration,
although serious sequelae can ensue from its subcutaneous route these are
far more likely if the intravenous route is chosen. Certainly, at present
its use as a prophylactic agent should only be considered after detailed
local protocols have been drawn up.
1.Premawardhena AP, de Silva CE, Fonseka MMD, Gunatilake, SB, de Silva HJ.
Low dose subcutaneous adrenaline to prevent acute adverse reactions to
antivenom serum in people bitten by snakes:randomised placebo controlled
trial. BMJ 1999;318:730-3(17 April)
2.Horowitz BZ, Jadallah S, Derlet RW. Fatal intracranial bleeding
associated with prehospital use of epinephrine. Ann Emerg Med 1996;28:725-
3.[Accidental administration of racemic adrenaline. Three life-threatening
cases after intravenous injection in children]. Tidsskr Nor Laegeforen
4. Hoffman BB, Lefkowitz RJ. Catecholamines, Sympathomimetic Drugs and
Adrenergic Receptor Antagonists. In: Hardman JG, Limbird LE, eds. Goodman
and Gilman’s, The Pharmacological Basis of Therapeutics. 9th Ed: New York.
McGraw Hill 1996: 199-248.
5. Delodovici ML, Cavaletti G, Crespi V, Sanguineti I. Intracerebral
hemorrhage following intravenous administration of epinephrine. Riv Neurol
Competing interests: No competing interests