Br.J. Anaesth. (1977), 49, 1065
USE OF NEOSTIGMINE AFTER SNAKE BITE R. W. NAPHADE AND R. N. SHETTI SUMMARY
Cobra venom consists of a neurotoxin which is responsible for respiratory paralysis simulating that associated with a non-depolarizing muscle relaxant. A combination of artificial respiration and neostigmine has been useful in resuscitating a child bitten by a snake.
R. W. NAPHADE, M.B., B.S., D.A.; R. N. SHETTI, M.B., B.S.,
D.A.,
M.S.(ANAESTH.),
F.I.C.S.;
Department
of
Anaes-
thesiologyj Mahatma Gandhi Institute of Medical Sciences, Sevagram—442102, India. Correspondence to R. N. S.
patients (Harrison et al., 1966) and this has been confirmed by other workers (Ghosh and Mandal, 1964; Santosh and Usagaonkar, 1968; Banerjee et al., 1972). We present here a case of snake bite successfully treated with artificial ventilation and neostigmine. CASE REPORT
The anaesthetist received an urgent call to a 10-yr-old child with marked cyanosis and no respiratory activity. Ventilation was being assisted manually. Immediate tracheal intubation was performed and oxygen-enriched air was administered with the help of an Ambu resuscitator. Within a few minutes the child's colour improved. However, respiration was inadequate still and continued artificial ventilation was required. The child, who had been in good health, had been bitten on the dorsum of the left foot by a snake 3-4 h earner. His father had applied a tourniquet immediately and made an incision on the dorsum of the foot. The child was then rushed to a hospital, about 50 km from our hospital, where he was given tetanus toxoid and antibiotics. On clinical examination, the heart rate was 160 beat.min" 1 . The pupils were dilated and reacted sluggishly to light, and the patient was in a state of cardiovascular collapse. Dextrose in saline, hydrocortisone acetate, mephenteramine and sodium bicarbonate were administered i.v. Anti-snake venom was given i.v. However, there was no improvement in the child's respiration and assisted ventilation was continued with an Ambu bag. As respiratory failure associated with neurotoxin was considered it was thought that neostigmine might be effective. Initially, neostigmine 0.5 mg, diluted to 5 ml with distilled water, was given slowly i.v. After a few minutes the heart rate was 120 beat.min" 1 and there was a marked improvement in respiration. Encouraged by this response, we repeated the same
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Snakes and cretes are found all over the world except in the Arctic region, New Zealand and Ireland (Deoras, 1965). Although the number of persons bitten by snakes is not known exactly, it is estimated that, in India, about 2 million are bitten annually, of whom nearly 15 000 die (Swaroop and Grab, 1954; Ahuja and Singh, 1956; Banerjee and Bhattacharya, 1960; Minton, 1963; Santosh and Usagaonkar, 1968). The global death rate for snake bite is about 30 000 per annum, the tropical regions of Asia and Africa alone contributing nearly 65% of the mortality because of the presence of poisonous snakes in these zones. Although the death rate from snake bites is 5.4% in India, this relates to human lives only as there are no data about the losses to live-stock and other domestic animals (Deoras, 1965). The treatment of snake bite is controversial because there is no completely successful method (Lockhart, 1965). The management of snake bite poisoning involves first aid methods (tourniquet, excision, incision and suction) and specific therapy (antivenom serum and antibiotics). Cryotherapy with refrigeration for the extremities is efficient in controlling enzyme destruction of tissues following a bite by the rattlesnake (Mullins, 1960; Lockhart, 1965). It was demonstrated by Kellaway and Holden (1932) that snake venom has an action on the neuromuscular junction which resembles a non-depolarizing block, thereby producing skeletal muscular paralysis. This led to the belief that artificial ventilation should form an important part of therapy. This was shown to be so by Gode, Tandon and Bhide (1968) in experimental cobra envenomation in dogs and was confirmed by Mehta, Kelkar and Parikh (1968) in human subjects. It was postulated also that neostigmine may be of help in resuscitating these
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partial. However, anti-cholinesterases have very little effect on a fully established block in vitro (Meldrum, 1965). Paralysis occurs in the muscles of the mouth, throat and breathing in that order (Mehta, Kelkar and Parikh, 1968). The neurotoxin fraction of the venom is relatively heat-stable (Sarkar, 1947) and it is thought that heating crude venom solution at 90 °C for 30 min leaves the neurotoxin unaffected while destroying the other fractions (Ramachandra, Kaul and Gode, 1974). The other enzymes in the venom are: proteases, erepsin, cholinesterase, hyaluronidase (a solubilizing enzyme which acts on the intracellular substance of the connective tissue facilitating spread of the toxin), DISCUSSION ribonuclease and desoxyribonuclease, and ophioSnake venom is a highly concentrated digestive juice oxidase (which promotes autolysis and putrefaction which, on drying, forms fine needle-like crystals. The (Porges, 1953)). The histopathological lesions depend upon the dose crude cobra venom consists of three active ingredients (Kellaway and Holden, 1932; De and Ghosh, 1937; of venom and consist of changes in Nissls granules, Ghosh, De and Choudhary, 1941; Sarkar, 1951; Lee fragmentation of the reticulum of the nerve cells, and Peng, 1961; Meldrum, 1965; Vick, Cinechta and opacity of the nuclei and the fragmentation and swelling of the nucleoli. Sometimes acute granular Polley, 1965): (a) A haemolysin. Phosphatidase produces enzymatic degeneration may be seen also (Mehta, Kelkar and destruction of cell walls, tissues and the endothelium Parikh, 1968). Without treatment, death occurs from 20 min to of the blood vessels. Consequently there is lysis of red blood cells, haemorrhage and acute haemolytic 6 h after a bite, depending upon the site, the amount of venom at the site and the rate of absorption. It is anaemia. (b) A cardiotoxin. The effect of this fraction has believed that 12 mg of dried cobra venom may be been studied extensively (for example: Chopra and fatal (Deoras, 1965). Cardiovascular collapse may have been caused by Ishwariah, 1931; Gottdenkar and Wachsteinum, 1940; Sarkar, 1947, 1948, 1951; Sarkar and Maitra, the cardiotoxin (Chopra and Ishwariah, 1931; 1950; Bhanganada and Perry, 1963). It was found Gottdenkar and Wachsteinum, 1940; Sarkar, 1948; that small doses of venom increased the force of Bhanganada and Perry, 1963). Hydrocortisone myocardial contraction, cardiac output and arterial was administered to combat shock (Feldberg and pressure, while with large doses there was depression Kellaway, 1937) along with dextrose saline and of the myocardium, leading to asystole. The hypo- mephenteramine sulphate i.v. tension which occurs may be a result of a direct In the present case report, cyanosis was observed depressant effect on myocardium, depression of the nearly 3.5 h after the bite. Although first aid had been vasomotor centre (Chopra and Ishwariah, 1931) or given initially it seems likely that some toxin remained paralysis of the peripheral vasculature (Bhanganada and, after the release of the tourniquet, was absorbed and Perry, 1963). slowly producing a neuromuscular block and resulting (c) A neurotoxin. This acts on the neuromuscular in respiratory paralysis similar to that following a junction, producing a curare-like effect and muscle non-depolarizing muscle relaxant (Kellaway, Chenny paralysis (Kellaway and Holden, 1932; Lee and Peng, and Williams, 1932). 1961; Vick, Cinechta and Polley, 1965). However, Doubt exists, however, as to whether the neurothere are distinct differences between the actions of muscular block is a result of neurotoxin or antivenom the neurotoxin and those of curare. The neurotoxin is serum (Mehta, Kelkar and Parikh, 1968). Since, in slower in onset and the block cannot be antagonized this patient, the antivenom was given after admission by washing out the end-plate. Also, the block is to the hospital, when the patient was already in sustained for several hours after exposure to toxins. respiratory failure, it seems likely that the neuroThe neurotoxin block may be antagonized or muscular block was caused by the neurotoxin. decreased by anticholinesterases as long as it is only Neurological assessment of such patients is difficult
dose 10 min later and again after a further 20 min. By this time the heart rate was 90 beat.min""1 and respiration was adequate. The tracheal tube remained in position for a further period of 2 h. When the child was unable to tolerate the tube it was removed following suction to the throat. Thereafter respiration remained satisfactory; the child remained in hospital for the treatment of cellulitis. Neither haematuria nor bleeding from any other site were noted. On the day following the bite, the bleeding time was 1 min 15 s and the clotting time was 6 min. The child has since successfully undergone desloughing and skin grafting procedures.
NEOSTIGMINE AFTER SNAKE BITE
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Banerjee, R. N., Sahani, A. L., Chatko, K. A.,and Vijaykumar (1972). Neostigmine in the treatment of Elapidae bites. j . Assoc. Physicians India, 20, 503. Bhanganada, K., and Perry, J. F. (1963). Cardiovascular effects of cobra venom. J.A.M.A., 183, 257. Chopra, R. N., and Ishwariah, V. (1931). An experimental investigation into the action of Indian cobra (Naja-naja triperdians). Indian J. Med. Res., 18, 1113. De, S. S., and Ghosh, V. N. (1937). Studies in absorption of the neurotoxin and haemolysin of cobra (Naja-naja) venom by various absorbents at different pH with a view to their isolation. Indian J. Med. Res., 24, 318. Deoras, P. J. (1965). Snakes in India. National Book Trust, India. Feldberg, W., and Kellaway, C. H. (1937). Circulatory effects of the Indian cobra {Naja-naja) in dogs. Aust. J. Exp. Biol. Med. Sci., 15, 441. Ghosh, B. N., De, S. S., and Choudhary, D. K. (1941). Separation of neurotoxin from the crude venom and study of the action of a number of reducing agents on it. Indian J. Med. Res., 29, 367. Ghosh, M. M., and Mandal, P. C. (1964). A case of cobra bite. Armed Forces Med. J. India, 20, 79. Gode, G. R., Tandon, G. C , and Bhide, N. K. (1968). Role of artificial ventilation in experimental cobra envenomation in dogs. Br. J. Anaesth., 40, 850. Gottdenkar, F., and Wachsteinum, M. (1940). Circulatory effects of venom of the Indian cobra (Naja-naja). J. Pharmacol., 69, 117. Harrison, T. R., Adams, R. D., Dennet, I. L., Resnik, W. N., Thosan, G. W., and Wintrobe, M. M. (1966). Disorders caused by venoms, bites and stings; in Principles of Internal Medicines, 6th edn, p. 692. Tokyo: Kogakusha Co. Kellaway, C. H., Chenny, R. O., and Williams, F. E. (1932). Peripheral action of Australian snake venoms. I I : The curare-like action in mammals. Aust. J. Exp. Biol. Med. Sci., 10, 181. Holden, H. F. (1932). Peripheral action of the Australian snake venoms. I: The curare-like action on frogs. Aust. J. Exp. Biol. Med. Sci.,10, 167. Lee, G. Y., and Pang, M. T. (1961). An analysis of the respiratory failure produced by the formasan Elepid venoms. Arch. /nf. Pharmacodyn. Ther., 83, 180. Lockhart, W. E. (1965). Treatment of snake bite. J.A.M.A. 193, 336. Mehta, S. S., Kelkar, P. N., and Parikh, P. N. (1968). Respiratory failure after snake bite poisoning successfully ACKNOWLEDGEMENTS treated with prolonged artificial ventilation. Indian J. We express our thanks to the district surgeon, Civil Hospital, Anaesth., 6, 273. Wardha; the Principal and the physicians of the Department of Medicine, Mahatma Gandhi Institute of Medical Meldrum, B. S. (1965). Action of snake venom on nerve and muscle. Pharmacol. Rev., 17, 393. Sciences, Sevagram, for their kind permission to publish this report. The secretarial assistance of Shri Kuljit Singh is Minton, S. A., jr (1963). Snake bite; in Textbook of Medicine (eds R. K. Cecil and R. F. Loab), 11th edn, p. 1797. acknowledged gratefully. Philadelphia and London: Saunders. REFERENCES Mullins, J. F. (1960). Successful management of cobra bite with cryotherapy. J.A.M.A., 174, 1677. Ahuja, M. L., and Singh, G. (1956). Snake bite in India; in Venoms (eds E. E. Buckley and N. Porges), p. 341. Porges, N. (1953). Snake venoms. Their biochemistry and mode of action. Science, 117, 47. Washington, D.C.: American Association for the Ramachandra, A. R., Kaul, H. I., and Gode, G. R. (1974). Advancement of Science. Banerjee, J. C , and Bhattacharya, P. B. (1960). Handbook An experimental study of the action of neurotoxin, a of Tropical Diseases, 4th edn, p. 402. Calcutta: Academic component of cobra venom, in dog. Indian J. Anaesth., 22, Publishers. 43. as there is paralysis of all the cranial and peripheral nerves (Harrison et al., 1966). Since the occulomotor nerves are affected also, both light and accommodation reflexes are lost and widely dilated pupils need not indicate intracranial pathology. In addition, it is difficult to assess levels of consciousness since the patient cannot react appropriately to painful stimuli. Since the site of action of the toxin is now known to be at the neuromuscular junction, it follows that artificial ventilation should form part of the treatment (Gode, Tandon and Bhide, 1968; Mehta, Kelkar and Parikh, 1968). In this case the child's general condition improved after artificial ventilation with oxygenenriched air. The therapeutic response to neostigmine depends upon the following factors (Banerjee et al., 1972): (a) Degree of neuromuscular block (whether partial or complete) (b) Blood concentration of neostigmine and its continued maintenance until complete neutralization of the neurotoxin (c) The dose of cardiotoxin absorbed which is totally unresponsive to the anticholinesterase In earlier studies the usefulness of neostigmine has been demonstrated by improved survival and more rapid recovery (Santosh and Usagaonkar, 1968; Banerjee et al.. 1972). Our findings are in agreement with earlier observations that the combination of neostigmine and atropine sulphate is safe, although in the present patient atropine was not given as the heart rate was in excess of 160 beat.min" 1 . It would appear that the dose of venom absorbed was small, as only 1.5 mg of neostigmine was required to neutralize the effects of the toxin and it was not found necessary to continue the drug treatment. The immediate application of the tourniquet and the incision of the site of bite by the father appears to have been a contributory factor in the low absorption of venom.
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Sarkar, N. K. (1947). Isolation of cardiotoxin from cobra venom. Indian J. Chem. Soc, 24, 227. (1948). Existence of cardiotoxic principles in cobra venom. Ann. Biol. Exp. Med., 8, 11. (1951). Action, mechanisms of cobra venom cardiotoxin and allied substances on muscle contraction. Proc. Soc. Exp. Biol. N.Y., 78, 4691. Maitra, S. R. (1950). Action of cobra venom and cardiotoxin on gastrocnemius-sciatic preparation of frog. Am. J. Physiol., 163, 209. Santosh, K., and Usagaonkar, R. S. (1968). Myasthenia gravis-like picture resulting from snake bite. J. Indian Med. Assoc, 50, 428. Swaroop, S., and Grab, B. (1954). Snake bite. Bull. W.H.O., 10, 35. Vick, J. A., Cinechta, H. P., and Polley, E. H. (1965). The effect of cobra venom on the respiratory mechanisms of the frog. Arch. Int. Pharmacodyn. Ther., 153, 425.
relaxant musculaire non depolarisant. La combinaison de respiration artificielle et de neostigmine a permis de reanimer un enfant qui avait ete mordu par un serpent.
USAGE DE LA NEOSTIGMINE APRES UNE MORSURE DE SERPENT
El veneno de cobra consiste de una neurotoxina que es responsable de paralisis respiratorio, simulando aquel asociado con un relajador de musculo no despolarizante. Una combinacion de respiraci6n artificial y neoestigmina ha sido util en la resucitacion de un menor picado por una vfbora.
ZUSAMMENFASSUNG
Kobragift besteht aus einem Neurotoxin, das eine sonst durch ein nichtdepolarisierendes Muskelentspannungsmittel hervorgerufene Atmungslahmung bewirkt. Eine Verbindung von kunstlicher Atmung und Neostigmin envies sich bei der Wiederbelebung eines von einer Schlange gebissenen Kindes als niitzlich. EMPLEO DE NEOESTIGMINA DESPUES DE PICADURA DE VIBORA SUMARIO
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RESUME
Le venin du cobra contient une neurotoxine qui provoque une paralysie respiratoire semblable a celle associee a un
VERWENDUNG VON NEOSTIGMIN NACH SCHLANGENBISS
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A s a hypotensive agent sodium nitroprusside has much to recommend it: rapid onset of action, direct relaxation of vascular smooth muscle, predictable and easy control of blood pressure, relative absence of toxicity in the usual dose range, and a short-lasting effect. Not to mention a reputation for being highly effective. Use of this valuable drug, although increasing in the last few years, has been somewhat problematical due to the lack of a standard and acceptable pharmaceutical presentation. This has been a matter of concern for doctors and pharmacists alike. It has also been a matter of concern for Roche. So much so that we decided to devote our resources to solving this problem. Happily, our efforts have been successful and we are pleased to announce that the need for a standard formulation of sodium nitroprusside can now be met-with Nipride.
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XXV
HALOTHANE-M&B justifiably takes pride of place
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In most types of surgery
USE OF NEOSTIGMINE AFTER SNAKE BITE R. W. NAPHADE AND R. N. SHETTI SUMMARY
Cobra venom consists of a neurotoxin which is responsible for respiratory paralysis simulating that associated with a non-depolarizing muscle relaxant. A combination of artificial respiration and neostigmine has been useful in resuscitating a child bitten by a snake.
R. W. NAPHADE, M.B., B.S., D.A.; R. N. SHETTI, M.B., B.S.,
D.A.,
M.S.(ANAESTH.),
F.I.C.S.;
Department
of
Anaes-
thesiologyj Mahatma Gandhi Institute of Medical Sciences, Sevagram—442102, India. Correspondence to R. N. S.
patients (Harrison et al., 1966) and this has been confirmed by other workers (Ghosh and Mandal, 1964; Santosh and Usagaonkar, 1968; Banerjee et al., 1972). We present here a case of snake bite successfully treated with artificial ventilation and neostigmine. CASE REPORT
The anaesthetist received an urgent call to a 10-yr-old child with marked cyanosis and no respiratory activity. Ventilation was being assisted manually. Immediate tracheal intubation was performed and oxygen-enriched air was administered with the help of an Ambu resuscitator. Within a few minutes the child's colour improved. However, respiration was inadequate still and continued artificial ventilation was required. The child, who had been in good health, had been bitten on the dorsum of the left foot by a snake 3-4 h earner. His father had applied a tourniquet immediately and made an incision on the dorsum of the foot. The child was then rushed to a hospital, about 50 km from our hospital, where he was given tetanus toxoid and antibiotics. On clinical examination, the heart rate was 160 beat.min" 1 . The pupils were dilated and reacted sluggishly to light, and the patient was in a state of cardiovascular collapse. Dextrose in saline, hydrocortisone acetate, mephenteramine and sodium bicarbonate were administered i.v. Anti-snake venom was given i.v. However, there was no improvement in the child's respiration and assisted ventilation was continued with an Ambu bag. As respiratory failure associated with neurotoxin was considered it was thought that neostigmine might be effective. Initially, neostigmine 0.5 mg, diluted to 5 ml with distilled water, was given slowly i.v. After a few minutes the heart rate was 120 beat.min" 1 and there was a marked improvement in respiration. Encouraged by this response, we repeated the same
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Snakes and cretes are found all over the world except in the Arctic region, New Zealand and Ireland (Deoras, 1965). Although the number of persons bitten by snakes is not known exactly, it is estimated that, in India, about 2 million are bitten annually, of whom nearly 15 000 die (Swaroop and Grab, 1954; Ahuja and Singh, 1956; Banerjee and Bhattacharya, 1960; Minton, 1963; Santosh and Usagaonkar, 1968). The global death rate for snake bite is about 30 000 per annum, the tropical regions of Asia and Africa alone contributing nearly 65% of the mortality because of the presence of poisonous snakes in these zones. Although the death rate from snake bites is 5.4% in India, this relates to human lives only as there are no data about the losses to live-stock and other domestic animals (Deoras, 1965). The treatment of snake bite is controversial because there is no completely successful method (Lockhart, 1965). The management of snake bite poisoning involves first aid methods (tourniquet, excision, incision and suction) and specific therapy (antivenom serum and antibiotics). Cryotherapy with refrigeration for the extremities is efficient in controlling enzyme destruction of tissues following a bite by the rattlesnake (Mullins, 1960; Lockhart, 1965). It was demonstrated by Kellaway and Holden (1932) that snake venom has an action on the neuromuscular junction which resembles a non-depolarizing block, thereby producing skeletal muscular paralysis. This led to the belief that artificial ventilation should form an important part of therapy. This was shown to be so by Gode, Tandon and Bhide (1968) in experimental cobra envenomation in dogs and was confirmed by Mehta, Kelkar and Parikh (1968) in human subjects. It was postulated also that neostigmine may be of help in resuscitating these
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partial. However, anti-cholinesterases have very little effect on a fully established block in vitro (Meldrum, 1965). Paralysis occurs in the muscles of the mouth, throat and breathing in that order (Mehta, Kelkar and Parikh, 1968). The neurotoxin fraction of the venom is relatively heat-stable (Sarkar, 1947) and it is thought that heating crude venom solution at 90 °C for 30 min leaves the neurotoxin unaffected while destroying the other fractions (Ramachandra, Kaul and Gode, 1974). The other enzymes in the venom are: proteases, erepsin, cholinesterase, hyaluronidase (a solubilizing enzyme which acts on the intracellular substance of the connective tissue facilitating spread of the toxin), DISCUSSION ribonuclease and desoxyribonuclease, and ophioSnake venom is a highly concentrated digestive juice oxidase (which promotes autolysis and putrefaction which, on drying, forms fine needle-like crystals. The (Porges, 1953)). The histopathological lesions depend upon the dose crude cobra venom consists of three active ingredients (Kellaway and Holden, 1932; De and Ghosh, 1937; of venom and consist of changes in Nissls granules, Ghosh, De and Choudhary, 1941; Sarkar, 1951; Lee fragmentation of the reticulum of the nerve cells, and Peng, 1961; Meldrum, 1965; Vick, Cinechta and opacity of the nuclei and the fragmentation and swelling of the nucleoli. Sometimes acute granular Polley, 1965): (a) A haemolysin. Phosphatidase produces enzymatic degeneration may be seen also (Mehta, Kelkar and destruction of cell walls, tissues and the endothelium Parikh, 1968). Without treatment, death occurs from 20 min to of the blood vessels. Consequently there is lysis of red blood cells, haemorrhage and acute haemolytic 6 h after a bite, depending upon the site, the amount of venom at the site and the rate of absorption. It is anaemia. (b) A cardiotoxin. The effect of this fraction has believed that 12 mg of dried cobra venom may be been studied extensively (for example: Chopra and fatal (Deoras, 1965). Cardiovascular collapse may have been caused by Ishwariah, 1931; Gottdenkar and Wachsteinum, 1940; Sarkar, 1947, 1948, 1951; Sarkar and Maitra, the cardiotoxin (Chopra and Ishwariah, 1931; 1950; Bhanganada and Perry, 1963). It was found Gottdenkar and Wachsteinum, 1940; Sarkar, 1948; that small doses of venom increased the force of Bhanganada and Perry, 1963). Hydrocortisone myocardial contraction, cardiac output and arterial was administered to combat shock (Feldberg and pressure, while with large doses there was depression Kellaway, 1937) along with dextrose saline and of the myocardium, leading to asystole. The hypo- mephenteramine sulphate i.v. tension which occurs may be a result of a direct In the present case report, cyanosis was observed depressant effect on myocardium, depression of the nearly 3.5 h after the bite. Although first aid had been vasomotor centre (Chopra and Ishwariah, 1931) or given initially it seems likely that some toxin remained paralysis of the peripheral vasculature (Bhanganada and, after the release of the tourniquet, was absorbed and Perry, 1963). slowly producing a neuromuscular block and resulting (c) A neurotoxin. This acts on the neuromuscular in respiratory paralysis similar to that following a junction, producing a curare-like effect and muscle non-depolarizing muscle relaxant (Kellaway, Chenny paralysis (Kellaway and Holden, 1932; Lee and Peng, and Williams, 1932). 1961; Vick, Cinechta and Polley, 1965). However, Doubt exists, however, as to whether the neurothere are distinct differences between the actions of muscular block is a result of neurotoxin or antivenom the neurotoxin and those of curare. The neurotoxin is serum (Mehta, Kelkar and Parikh, 1968). Since, in slower in onset and the block cannot be antagonized this patient, the antivenom was given after admission by washing out the end-plate. Also, the block is to the hospital, when the patient was already in sustained for several hours after exposure to toxins. respiratory failure, it seems likely that the neuroThe neurotoxin block may be antagonized or muscular block was caused by the neurotoxin. decreased by anticholinesterases as long as it is only Neurological assessment of such patients is difficult
dose 10 min later and again after a further 20 min. By this time the heart rate was 90 beat.min""1 and respiration was adequate. The tracheal tube remained in position for a further period of 2 h. When the child was unable to tolerate the tube it was removed following suction to the throat. Thereafter respiration remained satisfactory; the child remained in hospital for the treatment of cellulitis. Neither haematuria nor bleeding from any other site were noted. On the day following the bite, the bleeding time was 1 min 15 s and the clotting time was 6 min. The child has since successfully undergone desloughing and skin grafting procedures.
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Banerjee, R. N., Sahani, A. L., Chatko, K. A.,and Vijaykumar (1972). Neostigmine in the treatment of Elapidae bites. j . Assoc. Physicians India, 20, 503. Bhanganada, K., and Perry, J. F. (1963). Cardiovascular effects of cobra venom. J.A.M.A., 183, 257. Chopra, R. N., and Ishwariah, V. (1931). An experimental investigation into the action of Indian cobra (Naja-naja triperdians). Indian J. Med. Res., 18, 1113. De, S. S., and Ghosh, V. N. (1937). Studies in absorption of the neurotoxin and haemolysin of cobra (Naja-naja) venom by various absorbents at different pH with a view to their isolation. Indian J. Med. Res., 24, 318. Deoras, P. J. (1965). Snakes in India. National Book Trust, India. Feldberg, W., and Kellaway, C. H. (1937). Circulatory effects of the Indian cobra {Naja-naja) in dogs. Aust. J. Exp. Biol. Med. Sci., 15, 441. Ghosh, B. N., De, S. S., and Choudhary, D. K. (1941). Separation of neurotoxin from the crude venom and study of the action of a number of reducing agents on it. Indian J. Med. Res., 29, 367. Ghosh, M. M., and Mandal, P. C. (1964). A case of cobra bite. Armed Forces Med. J. India, 20, 79. Gode, G. R., Tandon, G. C , and Bhide, N. K. (1968). Role of artificial ventilation in experimental cobra envenomation in dogs. Br. J. Anaesth., 40, 850. Gottdenkar, F., and Wachsteinum, M. (1940). Circulatory effects of venom of the Indian cobra (Naja-naja). J. Pharmacol., 69, 117. Harrison, T. R., Adams, R. D., Dennet, I. L., Resnik, W. N., Thosan, G. W., and Wintrobe, M. M. (1966). Disorders caused by venoms, bites and stings; in Principles of Internal Medicines, 6th edn, p. 692. Tokyo: Kogakusha Co. Kellaway, C. H., Chenny, R. O., and Williams, F. E. (1932). Peripheral action of Australian snake venoms. I I : The curare-like action in mammals. Aust. J. Exp. Biol. Med. Sci., 10, 181. Holden, H. F. (1932). Peripheral action of the Australian snake venoms. I: The curare-like action on frogs. Aust. J. Exp. Biol. Med. Sci.,10, 167. Lee, G. Y., and Pang, M. T. (1961). An analysis of the respiratory failure produced by the formasan Elepid venoms. Arch. /nf. Pharmacodyn. Ther., 83, 180. Lockhart, W. E. (1965). Treatment of snake bite. J.A.M.A. 193, 336. Mehta, S. S., Kelkar, P. N., and Parikh, P. N. (1968). Respiratory failure after snake bite poisoning successfully ACKNOWLEDGEMENTS treated with prolonged artificial ventilation. Indian J. We express our thanks to the district surgeon, Civil Hospital, Anaesth., 6, 273. Wardha; the Principal and the physicians of the Department of Medicine, Mahatma Gandhi Institute of Medical Meldrum, B. S. (1965). Action of snake venom on nerve and muscle. Pharmacol. Rev., 17, 393. Sciences, Sevagram, for their kind permission to publish this report. The secretarial assistance of Shri Kuljit Singh is Minton, S. A., jr (1963). Snake bite; in Textbook of Medicine (eds R. K. Cecil and R. F. Loab), 11th edn, p. 1797. acknowledged gratefully. Philadelphia and London: Saunders. REFERENCES Mullins, J. F. (1960). Successful management of cobra bite with cryotherapy. J.A.M.A., 174, 1677. Ahuja, M. L., and Singh, G. (1956). Snake bite in India; in Venoms (eds E. E. Buckley and N. Porges), p. 341. Porges, N. (1953). Snake venoms. Their biochemistry and mode of action. Science, 117, 47. Washington, D.C.: American Association for the Ramachandra, A. R., Kaul, H. I., and Gode, G. R. (1974). Advancement of Science. Banerjee, J. C , and Bhattacharya, P. B. (1960). Handbook An experimental study of the action of neurotoxin, a of Tropical Diseases, 4th edn, p. 402. Calcutta: Academic component of cobra venom, in dog. Indian J. Anaesth., 22, Publishers. 43. as there is paralysis of all the cranial and peripheral nerves (Harrison et al., 1966). Since the occulomotor nerves are affected also, both light and accommodation reflexes are lost and widely dilated pupils need not indicate intracranial pathology. In addition, it is difficult to assess levels of consciousness since the patient cannot react appropriately to painful stimuli. Since the site of action of the toxin is now known to be at the neuromuscular junction, it follows that artificial ventilation should form part of the treatment (Gode, Tandon and Bhide, 1968; Mehta, Kelkar and Parikh, 1968). In this case the child's general condition improved after artificial ventilation with oxygenenriched air. The therapeutic response to neostigmine depends upon the following factors (Banerjee et al., 1972): (a) Degree of neuromuscular block (whether partial or complete) (b) Blood concentration of neostigmine and its continued maintenance until complete neutralization of the neurotoxin (c) The dose of cardiotoxin absorbed which is totally unresponsive to the anticholinesterase In earlier studies the usefulness of neostigmine has been demonstrated by improved survival and more rapid recovery (Santosh and Usagaonkar, 1968; Banerjee et al.. 1972). Our findings are in agreement with earlier observations that the combination of neostigmine and atropine sulphate is safe, although in the present patient atropine was not given as the heart rate was in excess of 160 beat.min" 1 . It would appear that the dose of venom absorbed was small, as only 1.5 mg of neostigmine was required to neutralize the effects of the toxin and it was not found necessary to continue the drug treatment. The immediate application of the tourniquet and the incision of the site of bite by the father appears to have been a contributory factor in the low absorption of venom.
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Sarkar, N. K. (1947). Isolation of cardiotoxin from cobra venom. Indian J. Chem. Soc, 24, 227. (1948). Existence of cardiotoxic principles in cobra venom. Ann. Biol. Exp. Med., 8, 11. (1951). Action, mechanisms of cobra venom cardiotoxin and allied substances on muscle contraction. Proc. Soc. Exp. Biol. N.Y., 78, 4691. Maitra, S. R. (1950). Action of cobra venom and cardiotoxin on gastrocnemius-sciatic preparation of frog. Am. J. Physiol., 163, 209. Santosh, K., and Usagaonkar, R. S. (1968). Myasthenia gravis-like picture resulting from snake bite. J. Indian Med. Assoc, 50, 428. Swaroop, S., and Grab, B. (1954). Snake bite. Bull. W.H.O., 10, 35. Vick, J. A., Cinechta, H. P., and Polley, E. H. (1965). The effect of cobra venom on the respiratory mechanisms of the frog. Arch. Int. Pharmacodyn. Ther., 153, 425.
relaxant musculaire non depolarisant. La combinaison de respiration artificielle et de neostigmine a permis de reanimer un enfant qui avait ete mordu par un serpent.
USAGE DE LA NEOSTIGMINE APRES UNE MORSURE DE SERPENT
El veneno de cobra consiste de una neurotoxina que es responsable de paralisis respiratorio, simulando aquel asociado con un relajador de musculo no despolarizante. Una combinacion de respiraci6n artificial y neoestigmina ha sido util en la resucitacion de un menor picado por una vfbora.
ZUSAMMENFASSUNG
Kobragift besteht aus einem Neurotoxin, das eine sonst durch ein nichtdepolarisierendes Muskelentspannungsmittel hervorgerufene Atmungslahmung bewirkt. Eine Verbindung von kunstlicher Atmung und Neostigmin envies sich bei der Wiederbelebung eines von einer Schlange gebissenen Kindes als niitzlich. EMPLEO DE NEOESTIGMINA DESPUES DE PICADURA DE VIBORA SUMARIO
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RESUME
Le venin du cobra contient une neurotoxine qui provoque une paralysie respiratoire semblable a celle associee a un
VERWENDUNG VON NEOSTIGMIN NACH SCHLANGENBISS
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A s a hypotensive agent sodium nitroprusside has much to recommend it: rapid onset of action, direct relaxation of vascular smooth muscle, predictable and easy control of blood pressure, relative absence of toxicity in the usual dose range, and a short-lasting effect. Not to mention a reputation for being highly effective. Use of this valuable drug, although increasing in the last few years, has been somewhat problematical due to the lack of a standard and acceptable pharmaceutical presentation. This has been a matter of concern for doctors and pharmacists alike. It has also been a matter of concern for Roche. So much so that we decided to devote our resources to solving this problem. Happily, our efforts have been successful and we are pleased to announce that the need for a standard formulation of sodium nitroprusside can now be met-with Nipride.
Nipride References Verner.l.R., Postgrad.med.J.,1974,50,576 Kohll.R.K., and Elwood.C.M., Amer.Fam.Phycn.,1977,/5,141 Tlnker.J.H., and Michenlelder.J.D., Anesthesiology,1976,45,No.3,340 Palmer,R.F., and Lasseter.K.C, New Engl.J.Med.,197S.292.294 Nipride is the trade mark lor Roche pharmaceutical preparations containing sodium nitroprusside
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XXV
HALOTHANE-M&B justifiably takes pride of place
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In most types of surgery
