Download Management of Scorpion Envenomation : Need For A

Editorial
Management of Scorpion Envenomation : Need For
A Standard Treatment Protocol Using Drugs and
Antivenom
Dilip R Karnad
physicians like Dr Bawaskar from Mahad, Maharashtra, have
helped develop regimen involving use of vasodilators like the
alpha-blocking drug prazosin, which can be easily used in
primary care facilities. 9,14 While afterload reduction will help
reverse several of the cardiovascular derangements in mild
(hypertensive) or moderate envenomation (pulmonary edema),
it does little to improve cardiac contractility which is a major
abnormality in patients with cardiogenic shock. Inotropic agents
are required at this stage15 and the study by Patil et al in this issue
of the journal shows how dobutamine is successful when used
in these patients. Besides afterload and myocardial contractility,
the need for attention to preload has been highlighted by our
studies. 10,16 Unless the patient is adequately hydrated, use of
afterload reducing drugs or diuretics can cause precipitous
hypotension.10,16 Inotropic drugs too may not achieve the desired
hemodynamic effects in dehydrated hypovolemic patients.
Scorpion venoms are a complex mixture of proteins.1-4 The
short chain peptides (22 to 47 amino acids) interfere with the
function of potassium ion channels while long-chain peptides
(59 to 76 amino acid residues) modify the channel gating
properties of the sodium channel.2 Other venoms identified
include those that act on the calcium and chloride ion channels,
hyaluronidases, lysozymes and phospholipases. 2 Many of
the toxins act on ion channels that play an important role in
maintaining resting membrane potential of excitable cells like
neurons and myocytes.1-4 They produce persistent depolarization
of autonomic nerves with release of neurotransmitters from the
adrenal medulla and parasympathetic and sympathetic nerve
endings (the “autonomic storm”). These neurotransmitters are
largely responsible for the toxic cardiovascular manifestations.5
The toxin may also directly affect myocardial contractility and
excitability. Central nervous system effects include irritability,
muscle rigidity, altered consciousness and convulsions.4
The regimen commonly followed in our ICU involves
proper restoration of fluid volume as the first step.8 Intravenous
fluids are necessary in most patients. After fluid resuscitation,
patients with a systolic arterial pressure > 90 mmHg receive
oral prazosin or captopril for afterload reduction. 8,10 Some
patients who have improvement in pulmonary edema but a
drop in blood pressure require further fluid infusion. 8 Patients
with severe envenomation and cardiogenic shock should not be
treated with vasodilators; inotropic agents like dobutamine,15 or
vasopressors like dopamine must be infused immediately8 and
vasodilators introduced only after the shock is reversed.8 Few
patients who have respiratory fatigue and exhaustion require
mechanical ventilation. A recent report from Turkey describes
the successful use of noninvasive ventilation in these patients;17
this could be tried in conscious patients who are not vomiting.
While there is considerable data from uncontrolled studies
showing that a protocol like this could reduce mortality. 8,9
This has also been confirmed by two controlled studies using
historical controls.13,18
Scorpion envenomation following sting of the Indian red
scorpion, Mesobuthus tumulus is a common emergency in several
parts of rural India. This and all other venomous scorpions of
clinical importance belong to the Buthidae family of scorpions,
which are widely distributed in warmer parts of the old and new
worlds.1 Majority of deaths following scorpion envenomation
in most parts of the world occur due to cardiovascular
dysfunction. 1 Neurological complications are more common
than cardiovascular manifestations after sting by scorpions of
the Centruroides species found in North America,6 but also occur
in a few cases stung by other species of scorpions, especially
children.7 Hemodynamic and observational studies show that
mild envenomation results in severe vasoconstriction resulting
in hypertension. 1,8 More severe cases have left ventricular
dysfunction, with increased pulmonary wedge pressure and
pulmonary oedema.1,2,8-11 Systolic as well as diastolic ventricular
dysfunction has been demonstrated by echocardiography and
radionucleide studies. 11,12 In patients who are dehydrated due
to sweating, vomiting or diuretic therapy, pulmonary edema
may be absent but low cardiac output with hypotension may
predominate. 8,10 In well hydrated patients, blood pressure
and cardiac output may be normal but pulmonary edema is
prominent.8,10 The most severely affected patients present with
low cardiac output, elevated pulmonary artery wedge pressures,
pulmonary edema and severe cardiogenic shock.1,7,8,10,13
Despite drug therapy, mor tality following scorpion
envenomation remains high. 1,8,13,18 Factors associated with
increased mortality include age <5 years, weight <25 kg, long
interval between envenomation and hospitalization, altered
consciousness (GCS ≤8/15), azotemia, acidosis and leucocytosis
(>25000 cells/mm3).7,8
Administration of scorpion antivenom to patients presenting
with cardiovascular manifestations of envenomation has not
been conclusively shown to be of benefit.1 While uncontrolled
studies have shown promise,19 a large randomized controlled
study in Tunisia failed to show any benefit of serotherapy.20 On
the other hand, antivenom against the predominantly neurotoxic
North American Centruroides species has been found to be useful
in preventing morbidity and mortality.6 Experimental studies on
While severe cases require intensive care, ICU facilities are
commonly lacking in rural areas where scorpion stings are
common. Fortunately, work of observant and enterprising
Professor of Medicine, Seth G S Medical College & K E M Hospital,
Mumbai; Adjunct Professor of Medicine, Baylor College of Medicine,
Houston, Texas.
© JAPI • APRIL 2009 • VOL. 57 299
pharmacokinetics of the venom show that the relatively small
peptides are rapidly distributed in the blood and tissues, unlike
polyvalent antibodies in antivenom. 21 A recently concluded
study showed that intravenous rather than intramuscular
administration, 21 and use of larger doses of commercially
available antivenom against the Indian red scorpion may be of
benefit (Natu VS, personal communication).
More recently, proteomic analysis using sophisticated
chromatographics techniques and mass spectroscopy has
been performed on venom of many species of scorpions
including Tityus, Androctonus spp, and the Asian black scorpion
(Heterometrus longimanus).2 This has spurred research to identify
epitopes that could be targets for antibodies in antivenom. The
efficacy of equine antivenom containing polyclonal antibodies
has been disappointing. Use of smaller antibody fragments like
the Fab or F(ab’)2 may hold the key to find specific antidotes
that neutralize the toxins from scorpion venom. 22 With faster
redistribution in vascular and extravascular compartments,
these smaller molecules may potentially be able to neutralize
toxins at sites that were hitherto inaccessible. An effective equine
F(ab’)2 antibody against Centruroides spp is already commercially
available (Acramynin™) in Mexico.2 Research on development of
a similar antibody against the cardiotoxic venom of Androctonus
australis hector has already reached an advanced stage.22 Even
smaller fragments of antibodies include single chain antibody
fragments (ScFv) and nanobodies.2 Development of antivenom
made from these novel antibody fragments which can be safely
administered intravenously and devoid of risk of anaphylaxis or
allergy may considerably reduce morbidity and mortality from
scorpion envenomation in the near future. More importantly,
prophylactic use of these antivenoms in patients stung by
venomous scorpions could even prevent development of toxic
manifestations. Ability to detect scorpion venom in serum or
urine of envenomated victims could further aid in identifying
patients who require serotherapy.23
2.
Espino-Solis GP, Riaño-Umbarila L, Becerril B, Possani LD.
Antidotes against venomous animals: State of the art and
prospective. J Proteomics 2009;72:183-99.
3.
Gazarian KG, Gazarian T, Hernandez R, Possani LD. Immunology
of scorpion toxins and perspectives for generation of anti-venom
vaccines. Vaccine 2005;23: 3357–68.
4.
Joshi SR, Sapatnekar SM. Stings and hopes: toxinomics and
autonomic storm in the Indian red scorpion (Mesobuthus tamulus
concanesis, Pocock). J Assoc Physicians India 2007;55:11-3.
5.
300
7.
Bouaziz M, Bahloul M, Kallel H, et al. Epidemiological, clinical
characteristics and outcome of severe scorpion envenomation
in South Tunisia: multivariate analysis of 951 cases. Toxicon
2008;52:918-26.
8.
Krishnan A, Sonawane RV, Karnad DR. Captopril in the Treatment
of Cardiovascular Manifestations of Indian Red Scorpion
(Mesobuthus Tamulus Concanesis Pocock) Envenomation. J Assoc
Physicians Ind 2007;55:22-6.
9.
Bawaskar HS, Bawaskar PH. Prazosin therapy and scorpion
envenomation. J Assoc Physician India 2000;48:1175-80.
11. Abroug F, Ayari M, Nouira S, et al. Assessment of left ventricular
function in severe scorpion envenomation: combined hemodynamic
and echo-Doppler study. Intensive Care Med 1995;21: 629-35.
12. Cupo P, Figueiredo AB, Filho AP, et al. Acute left ventricular
dysfunction of severe scorpion envenomation is related to
myocardial perfusion disturbance. Int J Cardiol 2007;116:98-106.
13. Biswal N, Bashir RA, Murmu UC, Mathai B, Balachander J,
Srinivasan S. Outcome of scorpion sting envenomation after a
protocol guided therapy. Indian J Pediatr 2006;73:577-82.
14. Bawaskar HS, Bawaskar PH. Utility of Scorpion Antivenin in the
Management of Severe Mesobuthus tamulus (Indian Red Scorpion)
Envenoming at Rural Setting. J Assoc Physicians Ind 2007;55:14-21.
15. Elatrous S, Nouira S, Besbes-Ouanes L, et al. Dobutamine in severe
scorpion envenomation. Effects on standard hemodynamics, right
ventricular performance and tissue oxygenation. Chest 1999;116:74853.
16. Karnad DR, Deo AM, Apte N, Lohe AS, Thatte S, Tilve GH.
Captopril for correcting diuretic induced hypotension in pulmonary
edema after scorpion sting. Br Med J 1989;298:1430-1.
17. Yildizdas D, Yilmaz HL, Erdem S. Treatment of cardiogenic
pulmonary edema by helmet-delivered non-invasive pressure
support ventilation in children with scorpion sting envenomation.
Ann Acad Med Singapore 2008;37:230-4.
18. Gupta V. Prazosin: a pharmacological antidote for scorpion
envenomation. J Trop Pediatr 2006;52:150-1.
19. Natu VS, Murthy RK, Deodhar KP. Efficacy of species specific antiscorpion venom serum (AScVS) against severe, serious scorpion
stings (Mesobuthus tamulus concanesis Pocock)·an experience
from rural hospital in western Maharashtra. J Assoc Physicians India
2006;54:283-7.
References
Chippaux JP, Goyffon M. Epidemiology of scorpionism: a global
appraisal. Acta Trop 2008;107:71-9.
Riley BD, LoVecchio F, Pizon AF. Lack of scorpion antivenom
leads to increased pediatric ICU admissions. Ann Emerg Med
2006;47:398-9.
10. Karnad DR. Haemodynamic patterns in patients with scorpion
envenomation. Heart 1998;79:485-89.
Research along these lines at premier Indian centers for
immunology and vaccine research directed towards developing
safe and effective antivenom preparations is the need of the hour.
This would decrease the need for drug therapy and intensive
care which are often inaccessible in rural areas.24
1.
6.
20. Abroug F, Elatrous S, Nouira S, Habib H, Touzi N, Bouchoucha S.
Serotherapy in scorpion envenomation : a randomized controlled
trial. Lancet 1999;354:906-9.
21. Krifia MN, Savinb S, Debrayd M, Bonb C, El Ayebc M, Choumetb
V. Pharmacokinetic studies of scorpion venom before and after
antivenom immunotherapy. Toxicon 2005;45:187–98.
22. Sami-Merah S, Hammoudi-Triki D, Martin-Eauclaire M, LarabaDjebari F. Combination of two antibody fragments F(ab′)2/Fab:
An alternative for scorpion envenoming treatment. International
Immunopharmacology 2008; 8:1386–94.
23. Chase P, Boyer-Hassen L, McNally J, Vazquez HL, Theodorou
AA, Walter FG, Alagon A. Serum levels and urine detection of
Centruroides sculpturatus venom in significantly envenomated
patients. Clin Toxicol (Phila) 2009; 47:24-8.
Teixeira Jr AL, Fontoura BF, Freire-Maia L, Machado CRS, Camargos
ERS, Teixeira MM. Evidence for a direct action of Tityus serrulatus
scorpion venom on the cardiac muscle. Toxicon 2001;39:703-9.
24. Adhisivam B. Of prazosin and purses. Lancet 2006; 368:1870.
© JAPI • APRIL 2009 • VOL. 57