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PROLONGED APNOEA AFTER SUXAMETHONIUM INJECTION ASSOCIATED WITH EYE DROPS CONTAINING AN ANTICHOLINESTERASE AGENT
Brit. J. Anaesth. (1966), 38, 408
PROLONGED APNOEA AFTER SUXAMETHONIUM INJECTION ASSOCIATED WITH EYE DROPS CONTAINING AN ANTICHOLINESTERASE AGENT A Case Report BY
Department of Anaesthesia, Negev Central Hospital, Beer-Sheva, Israel SUMMARY
Eye drops containing ecothiopate iodide, a potent anticholinesterase, produced symptoms simulating intestinal obstruction and prolonged the neuromuscular action of suxamethonium. The side effects of some drugs may simulate clinical conditions unrelated to the patient's original disease. In the following case it escaped our attention that a patient admitted as an abdominal emergency was receiving eye drops containing ecothiopate iodide (Phospholine Iodide), a strong anticholinesterase agent, because of glaucoma, and that the abdominal symptoms could have been caused by these eye drops. Previous knowledge about the eye drops and their strong anticholinesterase property would have saved the patient from surgical intervention and from serious anaesthetic complications. CASE REPORT A 72-year-old woman was admitted because of severe abdominal colic, diarrhoea and copious vomiting. Previously she had suffered from hypertension and rheumatoid arthritis. An iridectomy had been performed because of glaucoma seven years earlier, and since then she had been under treatment with eye drops. After admission the diarrhoea stopped, but the patient continued to complain of abdominal cramps, vomited copiously, and sweated profusely. The clinical picture, supported by radiological findings, suggested partial obstruction of the small intestine. Conservative treatment with parenteral fluids and gastric suction did not lead to improvement and an emergency laparotomy was decided upon because the condition of the patient was deteriorating. At this stage the following laboratory findings were available: haemoglobin 17.2 g per cent, leucocytes 5,600/cu.mm, blood sugar 80 mg/100 ml, urea 48 mg/100 ml, total protein 6.0 g/100 ml, albumin 3.2 g/100 ml, globulin 2.8 g/100 ml, bilirubin ind. 0.25 mg/100 ml, direct 0.25 mg/100 ml, transaminase f.g.o.L 24 units, transaminase s.g.p.t. 18 units, thymol turbidity 6.9 floe. + + . Urine: albumin trace, sugar nil.
Before anaesthesia the patient was sweating and restless. The arterial pressure was 180/100 mm Hg and the pulse rate 80 beats/min. Premedication consisted of pethidine 50 mg and phenergan 25 mg, atropine being omitted because of glaucoma. Anaesthesia was induced using 5 per cent thioprntone 350 mg, and after suxamethonium 50 mg the trachea was intubated. Spontaneous respiration returned, although not at its pre-operative depth. Anaesthesia was maintained with nitrous oxide and oxygen and a suxamethonium drip provided muscle relaxation and permitted mild pulmonary hyperventilation. A semiclosed circle absorber system was used. The arterial pressure and pulse rate during anaesthesia did not change significantly. The patient's colour was good and there was no clinical evidence of carbon dioxide accumulation. The sole finding at operation was a thickening of the wall of the terminal ileum with no obstruction, and after taking a biopsy of the intestine the peritoneum was closed. From the beginning of anaesthesia until the closure of peritoneum (about 1 hour) the patient was given 200 mg suxamethonium in drip form, this being the amount needed to maintain sufficient relaxation. The drip was discontinued at this point, but spontaneous respiration had not recurred 30 minutes later, when the operation was finished. After the operation, controlled ventilation with a high flow of oxygen was maintained using a semiclosed circle absorber system. In order to eliminate possible causes for the prolonged apnoea, nikethamide 2 ml and later methylphenidate (Ritalin) 20 mg were injected. To exclude a dual block a test dose of atropine 0.5 mg and neostigmine 1 mg was given 90 minutes after the termination of the operation; this had no effect. Unfortunately, a peripheral nerve stimulator was not available to help determine the cause of the apnoea, nor was edrophonium in stock. There seemed little doubt that the patient had a cholinestcrase deficiency; a blood sample was therefore sent for cholinestcrase level determination. Simultaneously a blood donor of the same group was made available in order to give a fresh blood transfusion. Three hundred ml of fresh blood did not, however, initiate spontaneous respiration, but the systolic pres-
Downloaded from http://bja.oxfordjournals.org/ at The University of British Colombia Library on June 17, 2015
THOMAS GESZTES
PROLONGED APNOEA AFTER SUXAMETHONIUM INJECTION
Cholinergic stimulation producing diarrhoea, intestinal colic, vomiting, paraesthesiae, salivation and perspiration have been reported in patients receiving ecothiopate iodide eye drops (Becker and Schaffer, 1961; Markman, Rosenberg and Dettbarn, 1964) whilst a marked reduction in true cholinesterase has been observed in seven of eight consecutive patients treated with this drug (Klendshoj and Olmstead, 1963). (Two patients being treated with ecothiopate iodide in this hospital had low cholinesterase values.) Murray McGavin (1965) warned of the potential hazard of giving suxamethonium to patients who are receiving ecothiopate iodide eye drops, and this case report would tend to substantiate this warning. The finding that the pseudocholinesterase levels rose after discontinuing the eye drops is evidence of the systemic absorption of ecothiopate iodide and the cause of the low enzyme level. It is suggested, therefore, that in the preanaesthetic visit inquiries concerning drugtaking should include all forms of medication, including eye drops. If the patient is receiving ecothiopate iodide, pseudocholinesterase levels should be determined pre-operatively and suxamethonium should be used cautiously.
DISCUSSION
The management of a patient who has apnoea following the use of muscle relaxants has been described by'Churchill-Davidson and Wise (1960) and this patient was treated along the lines advocated, though unfortunately no nerve stimulator was available. Vickers (1963) described a case of prolonged apnoea after administration of suxamethonium to a patient possessing atypical pseudocholinesterase and questioned the rationale of giving neostigmine to these patients because of the danger of prolonging the apnoea. The subject of the present report received a small dose of neostigmine 120 minutes after discontinuing the suxamethonium drip, which should be well outside the limits of too early administration. It is believed, therefore, that the dose of neostigmine given to this patient did not influence the length of the apnoea. The return of spontaneous respirations may have been related to the administration of fresh blood, since they reappeared during the transfusion.
ACKNOWLEDGEMENTS
I would Like to thank Drs. Gottfried, Gliksman, Sober and Lehmann for their help and comment. REFERENCES
Becker, B., and Shaffer, R. N. (1961). Diagnosis and Therapy of the Glaucomas, p. 218. St. Louis: Mosby. Churchill-Davidson, H. C , and Wise, R. P. (1960). Prevention) diagnosis and treatment of prolonged apnoea. Brit. J. Anaesth., 32, 384. Klendshoj, N. C , and Olmsted, E. P. (1963). Observation of dangerous side effects of phospholine iodide in glaucoma therapy. Amer. J. Ophthal., 56, 247. Markman, H. D., Rosenberg, P., and Dettbarn, W. D. (1964). Eye drops and diarrhea: diarrhea as the first symptom of echothiophate iodide toxicity. New Engl. J. Med., 271, 197. Murray McGavin, H. M (1965). Correspondence: Depressed levels of serum-pseudocholinesterase with ecothiopate iodide eye drops. Lancet, 2, 272. Vickers, M. D. A. (1963). The mismanagement of suxamethonium apnoea. Brit. J. Anaesth., 35, 260.
Downloaded from http://bja.oxfordjournals.org/ at The University of British Colombia Library on June 17, 2015
sure rose to 220 mm Hg. In view of the pre-operative haemoglobin value of 17.2 g/100 ml, a phlebotomy of the same amount of blood was done in order to obtain the "normal" blood pressure value of 180/100 mm Hg. In the meantime the pseudocholinesterase level was reported to be 0.15ApH units /hour according to the Michel method (normal 0.5 to 1.2ApH units/hour). Accordingly 4 hours later, a further 400 ml of fresh blood was given over a period of 1 hour, and during this time spontaneous respiration reappeared. At the end of the transfusion the patient was breathing adequately and was extubated. The postanaesthetic course was uneventful apart from a slight sore throat due to the presence of the endotracheal tube for 8 hours. The patient was apnoeic for 5i hours after discontinuing the suxamethonium infusion. Oxygen alone was used for pulmonary ventilation and although the patient appeared to react on addressing her, there was complete amnesia for the postoperative period. Further cholinesterase level estimations with the Michel and with dibucaine number methods demonstrated that the low cholinesterase level was not of genetic origin. Investigation of the cause of the cholinesterase deficiency then revealed that the patient was receiving eye drops containing ecothiopate iodide, a drug having strong and prolonged anticholinesterase action, and which is absorbed through the conjunctiva. This provided an explanation for the intestinal symptoms noted in the patient. The cholinesterase level 14 hours after operation was 0.15ApH units/hour; three days after operation (i.e. three days after the eye drops had been discontinued) 0.32ApH units/hour; on the fifth postoperative day 0.36 units; and at the end of hospitalization (seven weeks later) 0.45ApH units/hour.
409
410
BRITISH JOURNAL OF ANAESTHESIA
APNEE PROLONGEE APRES UNE INJECTION DE SUXAMETHONIUM ASSOCIEE A UN COLLYRE CONTENANT UN AGENT ANTICHOLINESTERASE: RAPPORT D'UNE OBSERVATION
VERLANGERTE APNOE NACH INJEKTION VON SUXAMETHONIUM IM ZUSAMMENHANG MIT AUGENTROPFEN, DIE EINEN CHOLINESTERASEHEMMER ENTHALTEN: EIN FALLBERICHT
SOMMAIRE
Augentropfen, die Ecothiopatjodid, einen stark wirksamen Cholinesterasehemmer, enthalten, riefen Darmverschlufi-vortauschende Symptome und eine anbaltende neuromuskulare Wirkung des Suxamethoniujns hervor.
ZUSAMMENFASSUNG
THE ROYAL SOCIETY OF MEDICINE Registrars' Prize (Anaesthetics) Applications are invited by the Royal Society of Medicine, Section of Anaesthetics, for a prize of £50 provided by Messrs. May and Baker Ltd., for a paper written by a medical practitioner of Senior Registrar or Registrar status holding an appointment in anaesthesia in a department or hospital, or in the armed forces of the Commonwealth or of the Republics of South Africa or Eire. Fellowship of the Royal Society of Medicine is not necessary for entry. The subject will be of the author's choice, but must be connected with anaesthesia. All papers for the 1967 award must be submitted in triplicate by January 1, 1967. Further details and rules of the prize can be obtained from the Assistant Secretary, ROYAL SOCIETY OF MEDICINE, 1 WIMPOLE STREET, LONDON,
W.I.
A further prize of £25 may be awarded on the recommendation of the judges.
Downloaded from http://bja.oxfordjournals.org/ at The University of British Colombia Library on June 17, 2015
Des collyres contenant de l'iodure d'ecothiopate, puissant agent anti-cholinesterase, ont produit des symptomes simulant une obstruction intestinale et prolong^ l'action neuro-musculaire du suxamethonium.
PROLONGED APNOEA AFTER SUXAMETHONIUM INJECTION ASSOCIATED WITH EYE DROPS CONTAINING AN ANTICHOLINESTERASE AGENT A Case Report BY
Department of Anaesthesia, Negev Central Hospital, Beer-Sheva, Israel SUMMARY
Eye drops containing ecothiopate iodide, a potent anticholinesterase, produced symptoms simulating intestinal obstruction and prolonged the neuromuscular action of suxamethonium. The side effects of some drugs may simulate clinical conditions unrelated to the patient's original disease. In the following case it escaped our attention that a patient admitted as an abdominal emergency was receiving eye drops containing ecothiopate iodide (Phospholine Iodide), a strong anticholinesterase agent, because of glaucoma, and that the abdominal symptoms could have been caused by these eye drops. Previous knowledge about the eye drops and their strong anticholinesterase property would have saved the patient from surgical intervention and from serious anaesthetic complications. CASE REPORT A 72-year-old woman was admitted because of severe abdominal colic, diarrhoea and copious vomiting. Previously she had suffered from hypertension and rheumatoid arthritis. An iridectomy had been performed because of glaucoma seven years earlier, and since then she had been under treatment with eye drops. After admission the diarrhoea stopped, but the patient continued to complain of abdominal cramps, vomited copiously, and sweated profusely. The clinical picture, supported by radiological findings, suggested partial obstruction of the small intestine. Conservative treatment with parenteral fluids and gastric suction did not lead to improvement and an emergency laparotomy was decided upon because the condition of the patient was deteriorating. At this stage the following laboratory findings were available: haemoglobin 17.2 g per cent, leucocytes 5,600/cu.mm, blood sugar 80 mg/100 ml, urea 48 mg/100 ml, total protein 6.0 g/100 ml, albumin 3.2 g/100 ml, globulin 2.8 g/100 ml, bilirubin ind. 0.25 mg/100 ml, direct 0.25 mg/100 ml, transaminase f.g.o.L 24 units, transaminase s.g.p.t. 18 units, thymol turbidity 6.9 floe. + + . Urine: albumin trace, sugar nil.
Before anaesthesia the patient was sweating and restless. The arterial pressure was 180/100 mm Hg and the pulse rate 80 beats/min. Premedication consisted of pethidine 50 mg and phenergan 25 mg, atropine being omitted because of glaucoma. Anaesthesia was induced using 5 per cent thioprntone 350 mg, and after suxamethonium 50 mg the trachea was intubated. Spontaneous respiration returned, although not at its pre-operative depth. Anaesthesia was maintained with nitrous oxide and oxygen and a suxamethonium drip provided muscle relaxation and permitted mild pulmonary hyperventilation. A semiclosed circle absorber system was used. The arterial pressure and pulse rate during anaesthesia did not change significantly. The patient's colour was good and there was no clinical evidence of carbon dioxide accumulation. The sole finding at operation was a thickening of the wall of the terminal ileum with no obstruction, and after taking a biopsy of the intestine the peritoneum was closed. From the beginning of anaesthesia until the closure of peritoneum (about 1 hour) the patient was given 200 mg suxamethonium in drip form, this being the amount needed to maintain sufficient relaxation. The drip was discontinued at this point, but spontaneous respiration had not recurred 30 minutes later, when the operation was finished. After the operation, controlled ventilation with a high flow of oxygen was maintained using a semiclosed circle absorber system. In order to eliminate possible causes for the prolonged apnoea, nikethamide 2 ml and later methylphenidate (Ritalin) 20 mg were injected. To exclude a dual block a test dose of atropine 0.5 mg and neostigmine 1 mg was given 90 minutes after the termination of the operation; this had no effect. Unfortunately, a peripheral nerve stimulator was not available to help determine the cause of the apnoea, nor was edrophonium in stock. There seemed little doubt that the patient had a cholinestcrase deficiency; a blood sample was therefore sent for cholinestcrase level determination. Simultaneously a blood donor of the same group was made available in order to give a fresh blood transfusion. Three hundred ml of fresh blood did not, however, initiate spontaneous respiration, but the systolic pres-
Downloaded from http://bja.oxfordjournals.org/ at The University of British Colombia Library on June 17, 2015
THOMAS GESZTES
PROLONGED APNOEA AFTER SUXAMETHONIUM INJECTION
Cholinergic stimulation producing diarrhoea, intestinal colic, vomiting, paraesthesiae, salivation and perspiration have been reported in patients receiving ecothiopate iodide eye drops (Becker and Schaffer, 1961; Markman, Rosenberg and Dettbarn, 1964) whilst a marked reduction in true cholinesterase has been observed in seven of eight consecutive patients treated with this drug (Klendshoj and Olmstead, 1963). (Two patients being treated with ecothiopate iodide in this hospital had low cholinesterase values.) Murray McGavin (1965) warned of the potential hazard of giving suxamethonium to patients who are receiving ecothiopate iodide eye drops, and this case report would tend to substantiate this warning. The finding that the pseudocholinesterase levels rose after discontinuing the eye drops is evidence of the systemic absorption of ecothiopate iodide and the cause of the low enzyme level. It is suggested, therefore, that in the preanaesthetic visit inquiries concerning drugtaking should include all forms of medication, including eye drops. If the patient is receiving ecothiopate iodide, pseudocholinesterase levels should be determined pre-operatively and suxamethonium should be used cautiously.
DISCUSSION
The management of a patient who has apnoea following the use of muscle relaxants has been described by'Churchill-Davidson and Wise (1960) and this patient was treated along the lines advocated, though unfortunately no nerve stimulator was available. Vickers (1963) described a case of prolonged apnoea after administration of suxamethonium to a patient possessing atypical pseudocholinesterase and questioned the rationale of giving neostigmine to these patients because of the danger of prolonging the apnoea. The subject of the present report received a small dose of neostigmine 120 minutes after discontinuing the suxamethonium drip, which should be well outside the limits of too early administration. It is believed, therefore, that the dose of neostigmine given to this patient did not influence the length of the apnoea. The return of spontaneous respirations may have been related to the administration of fresh blood, since they reappeared during the transfusion.
ACKNOWLEDGEMENTS
I would Like to thank Drs. Gottfried, Gliksman, Sober and Lehmann for their help and comment. REFERENCES
Becker, B., and Shaffer, R. N. (1961). Diagnosis and Therapy of the Glaucomas, p. 218. St. Louis: Mosby. Churchill-Davidson, H. C , and Wise, R. P. (1960). Prevention) diagnosis and treatment of prolonged apnoea. Brit. J. Anaesth., 32, 384. Klendshoj, N. C , and Olmsted, E. P. (1963). Observation of dangerous side effects of phospholine iodide in glaucoma therapy. Amer. J. Ophthal., 56, 247. Markman, H. D., Rosenberg, P., and Dettbarn, W. D. (1964). Eye drops and diarrhea: diarrhea as the first symptom of echothiophate iodide toxicity. New Engl. J. Med., 271, 197. Murray McGavin, H. M (1965). Correspondence: Depressed levels of serum-pseudocholinesterase with ecothiopate iodide eye drops. Lancet, 2, 272. Vickers, M. D. A. (1963). The mismanagement of suxamethonium apnoea. Brit. J. Anaesth., 35, 260.
Downloaded from http://bja.oxfordjournals.org/ at The University of British Colombia Library on June 17, 2015
sure rose to 220 mm Hg. In view of the pre-operative haemoglobin value of 17.2 g/100 ml, a phlebotomy of the same amount of blood was done in order to obtain the "normal" blood pressure value of 180/100 mm Hg. In the meantime the pseudocholinesterase level was reported to be 0.15ApH units /hour according to the Michel method (normal 0.5 to 1.2ApH units/hour). Accordingly 4 hours later, a further 400 ml of fresh blood was given over a period of 1 hour, and during this time spontaneous respiration reappeared. At the end of the transfusion the patient was breathing adequately and was extubated. The postanaesthetic course was uneventful apart from a slight sore throat due to the presence of the endotracheal tube for 8 hours. The patient was apnoeic for 5i hours after discontinuing the suxamethonium infusion. Oxygen alone was used for pulmonary ventilation and although the patient appeared to react on addressing her, there was complete amnesia for the postoperative period. Further cholinesterase level estimations with the Michel and with dibucaine number methods demonstrated that the low cholinesterase level was not of genetic origin. Investigation of the cause of the cholinesterase deficiency then revealed that the patient was receiving eye drops containing ecothiopate iodide, a drug having strong and prolonged anticholinesterase action, and which is absorbed through the conjunctiva. This provided an explanation for the intestinal symptoms noted in the patient. The cholinesterase level 14 hours after operation was 0.15ApH units/hour; three days after operation (i.e. three days after the eye drops had been discontinued) 0.32ApH units/hour; on the fifth postoperative day 0.36 units; and at the end of hospitalization (seven weeks later) 0.45ApH units/hour.
409
410
BRITISH JOURNAL OF ANAESTHESIA
APNEE PROLONGEE APRES UNE INJECTION DE SUXAMETHONIUM ASSOCIEE A UN COLLYRE CONTENANT UN AGENT ANTICHOLINESTERASE: RAPPORT D'UNE OBSERVATION
VERLANGERTE APNOE NACH INJEKTION VON SUXAMETHONIUM IM ZUSAMMENHANG MIT AUGENTROPFEN, DIE EINEN CHOLINESTERASEHEMMER ENTHALTEN: EIN FALLBERICHT
SOMMAIRE
Augentropfen, die Ecothiopatjodid, einen stark wirksamen Cholinesterasehemmer, enthalten, riefen Darmverschlufi-vortauschende Symptome und eine anbaltende neuromuskulare Wirkung des Suxamethoniujns hervor.
ZUSAMMENFASSUNG
THE ROYAL SOCIETY OF MEDICINE Registrars' Prize (Anaesthetics) Applications are invited by the Royal Society of Medicine, Section of Anaesthetics, for a prize of £50 provided by Messrs. May and Baker Ltd., for a paper written by a medical practitioner of Senior Registrar or Registrar status holding an appointment in anaesthesia in a department or hospital, or in the armed forces of the Commonwealth or of the Republics of South Africa or Eire. Fellowship of the Royal Society of Medicine is not necessary for entry. The subject will be of the author's choice, but must be connected with anaesthesia. All papers for the 1967 award must be submitted in triplicate by January 1, 1967. Further details and rules of the prize can be obtained from the Assistant Secretary, ROYAL SOCIETY OF MEDICINE, 1 WIMPOLE STREET, LONDON,
W.I.
A further prize of £25 may be awarded on the recommendation of the judges.
Downloaded from http://bja.oxfordjournals.org/ at The University of British Colombia Library on June 17, 2015
Des collyres contenant de l'iodure d'ecothiopate, puissant agent anti-cholinesterase, ont produit des symptomes simulant une obstruction intestinale et prolong^ l'action neuro-musculaire du suxamethonium.