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Editor,—We read with great interest the haemodynamic pattern in patients with scorpion envenomation.1 We have studied this acute time sensitive medical emergency since 1976 and have tried various regimens including antiscorpion venom.2 Since the advent of prazosin (1983–84)—an α adrenergic blocker which acts as an antidote to venom—the mortality of scorpion sting victims is less than 1%.3
In the pre-prazosin era (1961–83) a fatality rate of 25–30% was reported from western India,4 acute pulmonary oedema causing death. We were therefore surprised by the 25% mortality reported by Karnad,1 and that two victims died on the third day of hospitalisation; we has similar findings in 1978–82—that is, before prazosin treatment.5
We have reported that the severity of scorpion sting depends on the victim’s age, the season, and the time between sting and administration of prazosin. The symptoms following the sting are hypertension, tachycardia, pulmonary oedema, and shock (autonomic storm).6 We believe that the transport of Karnad’s patients to the nearest major hospital contributed to their deaths5; seven of eight had acute pulmonary oedema owing to a delay in reaching a tertiary care hospital.1
Scorpion venom inhibits angiotensin converting enzyme (ACE), resulting in accumulation of bradykinin, which is implicated in the development of pulmonary oedema and acute reversible pancreatitis.7Captopril (an ACE inhibitor) has a similar action resulting in hypotension resistant to dopamine agonists.1 Bradykinin further enhances noradrenaline (norepinephrine) release by a presynaptic mechanism.8
Alpha receptor stimulation plays a major role in the pathogenesis of pulmonary oedema.9 It causes hyperkalaemia and hyperglycaemia (inhibition of insulin secretions). Angiotensin II stimulates α adrenergic receptors in the myocardium and hypoxia results from coronary spasm as well as accumulation of free fatty acids and free radicals injurious to myocardium leading to cardiac arrhythmias and sudden death.1
At a general hospital at Mahad we successfully treated 658 cases of severe scorpion sting with oral rehydration, oral prazosin, and oxygen and aminophylline: 362 (55%) had hypertension, 178 (27%) had pulmonary oedema, 118 (18%) had tachycardia; no patient had lethal arrhythmias. Seventeen patients who died on the way to Mahad had been referred 24 hours after being stung while 13 cases were admitted with multiorgan failure and were moribund and comatose; they died 30–60 minutes after admission despite treatment with dopamine, nitroprusside, oxygen, and insulin–glucose drip. The remaining 56 cases with massive pulmonary oedema recovered after treatment with intravenous sodium nitroprusside.
We travelled throughout western Maharashtra whereMesobuthus tamulus scorpion flourish, and taught all peripheral doctors how to treat scorpion sting victims. There has not been any deaths over the past two years due to scorpion sting reported from this region. Moreover, only two patients had massive pulmonary oedema, which was treated with intravenous sodium nitroprusside. Captopril failed to correct haemodynamic abnormalities in two cases who had cardiac arrhythmias.1 Prazosin treatment would have been life saving in the two patients treated with captopril who died in Karnad’s report.1 As a potent inhibitor of phospodiesterase, prazosin causes accumulation of cGMP, a second messenger of nitric oxide, in vascular endothelium and myocardium, inhibits the formation of inositol triphosphate, and activates venom inhibited calcium dependent potassium channels.
Thus prazosin reverses both inotropic (hypertension), and hypokinetic (pulmonary oedema, hypotension, tachycardia) phases evoked by scorpion envenoming.10
Editor,—The study by Karnad1-1 on the haemodynamic patterns encountered in scorpion envenomation raises important concerns. Karnad claims that the mechanism of pulmonary oedema observed in scorpion envenomation had not previously been established as pulmonary artery wedge pressure (PAWP) had not been measured. However, the haemodynamic mechanism of pulmonary oedema in scorpion envenomation was suggested in animal studies as early as 19801-2 and confirmed by numerous series in human subjects. All of these series performed a haemodynamic study and measured PAWP.1-3-1-5 We are therefore not surprised with Karnad’s findings and observe that they are consistent with our previous reports suggesting similar effects of the Indian red scorpionMesobuthus tamulus and the yellow scorpion of North Africa (Androctonus australis).
We are particularly concerned by Karnad’s interpretation of the haemodynamic records in the envenomated patients and the treatment strategy he suggests. Numerous haemodynamic, echocardiographic, and angioscintigraphic studies have shown that severe scorpion envenomation impairs left and right ventricles to the same extent.1-3-1-5Echocardiographic studies showed that LV systolic function might be deeply depressed with a mean LV fractional shortening as low as 12%.1-3 Regarding the right ventricle, in eight patients we recorded a mean RV ejection fraction of 24%.1-5 In fact, severe scorpion envenomation evokes acute heart failure which tends to recover in a few days. The heart failure might be concealed in some patients by the simultaneous hypovolaemia that occurs in envenomated patients as a consequence of vomiting and sweating. Hence, the patterns II, III, and IV described by Karnad should not be regarded differently from the multiple facets of the same and only haemodynamic feature that is the profile of acute heart failure (patterns II and IV) that might be mitigated by simultaneous hypovolaemia (pattern III). Moreover, the three reported patients who had simultaneous hypovolaemia exhibited a worsening in their pulmonary oedema with fluid infusion, suggesting an exaggerated increase in PAWP resulting from altered LV function.
Although attractive from a pathophysiological standpoint, Karnad challenges the usefulness of inotropic drugs and claims that they improve only transiently the circulatory failure observed in scorpion envenomation with no effect on mortality. We are unaware of any study specifically dedicated to address this issue. Nevertheless, owing to the clearly established haemodynamic pattern of severe scorpion envenomation and on the basis of a pathophysiological approach, we and others have usually treated envenomated patients exhibiting pulmonary oedema and/or peripheral circulatory failure with dobutamine. The physiological effects were as expected, those usually observed in the treatment of heart failure: an increase in cardiac output as a consequence of an increase in stroke volume with enhanced LV performance, a substantial decrease in PAWP, and an increase of arterial pressure.1-6
Finally, Karnad suggests that RV failure occurs late in the terminal phase of scorpion envenomation and combines with pre-existing LV failure to produce severe cardiogenic shock. This speculation is not supported by Nouira et al who used a modified Swan–Ganz catheter equipped with a fast response thermistance.1-5 This study showed that scorpion envenomation evokes simultaneous impairment of the LV as well as the RV, the latter being depressed to the same extent as the former. Infusion of dobutamine enhances RV as well as LV performance.1-6
In conclusion, scorpion envenomation kills thousands of patients in developing countries. First line clinicians need comprehensive and meaningful insights regarding the pathophysiology and valuable treatments of this dreaded accident. The clearer and simpler the message on this issue the better the effect in daily clinical practice.
These letters were shown to the author, who replies as follows:
The efforts of Bawaskar and Bawaskar in popularising prazosin treatment in western India are truly commendable, and the effect on mortality following scorpion envenomation is impressive. They cite their personal experience of 658 patients treated with prazosin, of whom only 30 (4.5%) died. They had previously reported 526 patients treated with prazosin up to 1992; in this series 28 patients (5%) died.2-1 They are surprised that two of the eight patients reported in my paper died. However, it must be understood that as the objective of my paper was to describe haemodynamic patterns, only eight patients in whom detailed serial haemodynamic data were available were reported; these cases are not the entire experience of our unit with captopril in scorpion envenomation.
In India, scorpion envenomation occurs almost exclusively in rural areas, and is particularly common in the coastal regions of western India where Dr Bawaskar’s hospital is located. Patients stung by scorpions are likely to consult local doctors first, especially if envenomation is mild, explaining why 18% of patients had tachycardia alone and 55% had hypertension. Pulmonary oedema, resulting from more severe envenomation, was seen in 27% of patients. In contrast, our experience is from a tertiary referral centre in Bombay. Most patients treated in our unit were referred from rural areas 80 to 150 km away, 6–36 hours after the sting. Moreover, these patients had not improved despite receiving treatment at primary care centres. Consequent to this referral pattern, a greater proportion of our patients had severe envenomation and presented late—18 of 31 patients treated in our unit with captopril in the past 10 years had pulmonary oedema with hypotension. Four patients (all had severe pulmonary oedema with hypotension) died. In Dr Bawaskar’s series, 178 patients with pulmonary oedema were treated with prazosin and 30 (17%) died. This is not significantly different from the 22% mortality in our experience with captopril.
I agree with Abroug and colleagues that patterns II, III, and IV described in my paper are facets of the same underlying abnormality. For this reason, they were all grouped under the category of predominant myocardial effects. Haemodynamic abnormalities in patterns II and III differ only in terms of the patients’ fluid balance, but the clinical features of the two patterns were so different as to need separate discussion. Pattern II is characterised by severe pulmonary oedema and mild or no hypotension. Pattern III is seen in dehydrated patients and manifests as severe hypotension, with little or no pulmonary oedema.
Abroug et al have, in a previous study, shown that left ventricular ejection fraction measured by echocardiography was severely depressed (26%) following scorpion envenomation. They showed a threefold improvement to 75% during recovery.2-2 In another study, they assessed right ventricular function using a pulmonary artery catheter; right ventricular ejection fraction was 24% following envenomation and improved to 39% during recovery.2-3 Unfortunately simultaneous right and left ventricular functions have not been studied.
Our patients with pattern II showed severely raised PAWP and subnormal left ventricular stroke work index, while right ventricular stroke work index and right atrial pressures were normal, suggesting that the left ventricle was more severely affected than the right. In pattern IV, however, left as well as right ventricular stroke work indices were severely depressed and both PAWP and right atrial pressures were grossly raised suggesting that at this stage right ventricular function was also severely deranged.
Abroug et al mention that they have been using dobutamine in scorpion envenomation with good results. Their patients also received antivenom, which is not available in India. It may be possible that antivenom favourably alters the response to inotropic catecholamines. The experience of Bawaskar and Bawaskar suggests that inotropic treatment given to patients who have not received antivenom does not decrease mortality. Although no controlled studies exist, studies using historical controls treated conventionally, including inotropic drugs, have shown that vasodilators are beneficial in the treatment of cardiovascular manifestations of scorpion envenomation.2-1 2-4 2-5 Vasodilators like prazosin, calcium channel blockers, ACE inhibitors, and sodium nitroprusside have been used.2-1 2-4 2-5 However, whether any one of them is superior has not been studied. Currently available evidence indicates that these are equally effective and the suggestion that prazosin may have been effective in patients who did not improve with captopril as suggested by Bawaskar can only be considered speculative.