-Letter to the Editor
Asystole Following Neostigmine Administration during Carotid Sinus Stimulation To the Editor: Changes in heart rate (HR) occur following reversal of muscle relaxants by anticholinergic anticholinesterase mixtures.‘-.’ A greater degree of bradycardia has been reported when a mixture is used,” particularly with rapid injection. (i Following is a case of profound bradycardia followed by asystole after neostigminei during carotid sinus administration atropine stimulation.
Case Report A 34-year-old woman presented for a right thyroid lobectomy to remove a right thyroid mass. Her medical history included hypothyroidism for which she took levothyroxine sodium 0.1 mg daily; at the time of presentation, she was clinically euthyroid. She took no other medications and reported no allergies. Her only previous anesthetic was uneventful. On physical examination, she was a 75 kg healthy female with a 3- by 3-cm right neck mass. Her blood pressure (BP) was 100/60 mmHg, and HR was 68 beats/minute. The patient was premeditated with midazolam 2 mg intramuscularly (IM). Anesthesia was induced with fentanyl 250 pg and thiopental sodium 250 mg. Vecuronium bromide 8 mg IV was given to facilitate intubation. Maintenance of anesthesia included N,O/ 0, 50%, enflurane 0.5% to 1.870, and vecuronium. Surgery was uneventful, with an HR range of 80 to 110 beats/minute, and duration of surgery was 1 hour 45 minutes. The patient demonstrated a T, to T, ratio of 0.8 during facial nerve stimulation and was breathing spontaneously. After skin staples were applied, a mixture of neostigmine bromide 2.5 mg and atropine 1 mg IV was given over 10 seconds. At that time, the patient’s HR was 96 beats/minute, and BP was 120/ 70 mmHg. The surgical team began an intense, vigorous cleansing of the area of the wound on the anterior neck. The patient’s HR dropped abruptly to 40 beatsimin212
J. Clin. Anesth., vol. 2, May/June 1990
ute, with a BP of 80/50 mmHg. Atropine 0.5 mg IV was administered rapidly. Bradycardia progressed until there was no electrical activity on the clectrocardiogram (EKG) and the patient was pulseless. Chest compressions were initiated. After approximately 20 to 30 seconds ot cardiopulmonary resuscitation ((:PR), the patient’s pulse became palpable at 1 10 beatsiminutc. with a BP of I Z38180mmHg. ‘l‘he patient emerged from anesthesia uneventfully. Postoperatively, I IIC chest radiograph was normal, and cardiac isoenivmes were within normal limits. ‘I%e patient was informed of the intraoperative events and discharged lvithout complication on the first postoperative dav.
Discussion While there have been reports of cardiac arrest following reversal of neuromuscular blockade with mixtures of neostigmine and atropine, many studies have established its safety. This practice, however, is associated with hemodynamic changes. Harper et al.” compared a fixed-dose reversal with a weight-related dose at different rates of injection. There was more bradycardia with rapid administration. Mirakhur e/ nl.’ studied varying doses of atropine and glycopyrrolate mixed with neostigmine and also given 6 minutes before neostigmine. With atropine at 20 kg/kg, 34 patients had bradycardia requiring additional atropine. Takkunen et ~1.~ studied reversal with atropine or glycopyrrolate followed rapidly by neostigmine. There was significantly more bradycardia in the atropine group. Cardiac arrest following intentional use of anticholinesterase to slow the rate of atria1 tachycardia has been reported.g Carotid sinus massage slows conduction through the A-V node and has been useful in the slowing of atria1 fibrillation, atria1 flutter, and other atria1 tachycardias. This maneuver theoretically could be potentiated by anticholinesterases. Prolonged bradycardia has been reported after neostigmine administration in patients taking beta antagonists. Eldor et al. ‘” and Seidl and Martini1 reported severe bradycardia refractory to all intervention except epinephrine administration. Diabetic neuropathy with vagal dysfunction has been reported to
Letter to the Editor cause
deep,
esterase nervation carotid
refractory
bradycardia
administration.‘*
Drug
may be analogous sinus interaction
In summary,
after
synergy
4.
to the anticholinesterase-
in the current
this case
anticholinor vagal de-
of profound
case. bradycardia
leading to cardiac arrest is best explained by carotid sinus stimulation during the onset of muscarinic stimulation
by an anticholinesterase.
The
carotid sinus stimuli by anticholinesterase John E. Tetzlaff, Staff
potentiation
of
5. 6.
is postulated.
MD
7.
Anesthesiologist
Michael J. Choban, Resident
MD
in Anesthesiology
Department of General Anesthesiology Cleveland Clinic Foundation Cleveland,
OH 44195,
8.
USA 9.
References 10. Hollander AA, Dewaehter, Deville A, Vaisiere D: Haemodynamic changes associated with atropineineostigmine administration. Acta Anaesth Stand 1981;25: 18792. Mirakhur RK, Dundee JW, Clarke RSJ: Glycopyrrolateneostigmine mixture for antagonism of neuromuscular block: comparison with atropine-neostigmine mixture. Br J Anaesth 1977;49:825-8. Azar 1, Pham AN, Karambelkar DJ, Lear E: The heart rate following edrophonium-atropine and edrophon-
11.
12.
ium-glycopyrrolate mixtures. Anesthesiology 1983; 59:139-41. Gottlieb JD, Sweet RB: The antagonism of curare: the cardiac effects of atropine and neostigmine. Can Anaesth Sot J 1963;10:114-21. Ovassapian A: Effects of administration of atropine and neostigmine in man. Anesth Analg 1968;48:219-23. Harper KW, Bali IM, Gibson FM, et al: Reversal of neuromuscular block. Heart rate changes with slow injection of neostigmine and atropine mixtures. Anaesthesia 1984;39:772-5. Mirakhur RK, Dundee JW, Jones CJ, Coppel DL, Clarke RSJ: Reversal of neuromuscular blockade: dose determination in studies with atropine and glycopyrrolate given before or in a mixture with neostigmine. Anesth Analg 1981;60:557-62. Takkunen 0, Salmenpera M, Heinonen J: Atropine vs glycopyrrolate during reversal of pancuronium block in patients anesthetized with halothane. Acta Anaesth Stand 1984;28:377-80. Youngberg JA: Cardiac arrest following treatment of paroxysmal atria1 tachycardia with edrophonium. Anesthesiology 1979;50:234-5. Eldor J, Hoffman B, Davidson JT: Prolonged bradycardia and hypotension after neostigmine administration in a patient receiving atenolol. Anaesthesia 1987; 42: 1294-7. Seidl DC, Martin DE: Prolonged bradycardia after neostigmine administration in a patient taking nadolol. Anesth Analg 1984;63:365-7. Triantafillou AN, Tseuda K, Berg J, Wieman TJ: Refractory bradycardia after reversal of muscle relaxant in a diabetic with vagal neuropathy. Anesth Analg 1986;65:1237-41.
J. Clin. Anesth., vol. 2, May/June 1990
213
Asystole Following Neostigmine Administration during Carotid Sinus Stimulation To the Editor: Changes in heart rate (HR) occur following reversal of muscle relaxants by anticholinergic anticholinesterase mixtures.‘-.’ A greater degree of bradycardia has been reported when a mixture is used,” particularly with rapid injection. (i Following is a case of profound bradycardia followed by asystole after neostigminei during carotid sinus administration atropine stimulation.
Case Report A 34-year-old woman presented for a right thyroid lobectomy to remove a right thyroid mass. Her medical history included hypothyroidism for which she took levothyroxine sodium 0.1 mg daily; at the time of presentation, she was clinically euthyroid. She took no other medications and reported no allergies. Her only previous anesthetic was uneventful. On physical examination, she was a 75 kg healthy female with a 3- by 3-cm right neck mass. Her blood pressure (BP) was 100/60 mmHg, and HR was 68 beats/minute. The patient was premeditated with midazolam 2 mg intramuscularly (IM). Anesthesia was induced with fentanyl 250 pg and thiopental sodium 250 mg. Vecuronium bromide 8 mg IV was given to facilitate intubation. Maintenance of anesthesia included N,O/ 0, 50%, enflurane 0.5% to 1.870, and vecuronium. Surgery was uneventful, with an HR range of 80 to 110 beats/minute, and duration of surgery was 1 hour 45 minutes. The patient demonstrated a T, to T, ratio of 0.8 during facial nerve stimulation and was breathing spontaneously. After skin staples were applied, a mixture of neostigmine bromide 2.5 mg and atropine 1 mg IV was given over 10 seconds. At that time, the patient’s HR was 96 beats/minute, and BP was 120/ 70 mmHg. The surgical team began an intense, vigorous cleansing of the area of the wound on the anterior neck. The patient’s HR dropped abruptly to 40 beatsimin212
J. Clin. Anesth., vol. 2, May/June 1990
ute, with a BP of 80/50 mmHg. Atropine 0.5 mg IV was administered rapidly. Bradycardia progressed until there was no electrical activity on the clectrocardiogram (EKG) and the patient was pulseless. Chest compressions were initiated. After approximately 20 to 30 seconds ot cardiopulmonary resuscitation ((:PR), the patient’s pulse became palpable at 1 10 beatsiminutc. with a BP of I Z38180mmHg. ‘l‘he patient emerged from anesthesia uneventfully. Postoperatively, I IIC chest radiograph was normal, and cardiac isoenivmes were within normal limits. ‘I%e patient was informed of the intraoperative events and discharged lvithout complication on the first postoperative dav.
Discussion While there have been reports of cardiac arrest following reversal of neuromuscular blockade with mixtures of neostigmine and atropine, many studies have established its safety. This practice, however, is associated with hemodynamic changes. Harper et al.” compared a fixed-dose reversal with a weight-related dose at different rates of injection. There was more bradycardia with rapid administration. Mirakhur e/ nl.’ studied varying doses of atropine and glycopyrrolate mixed with neostigmine and also given 6 minutes before neostigmine. With atropine at 20 kg/kg, 34 patients had bradycardia requiring additional atropine. Takkunen et ~1.~ studied reversal with atropine or glycopyrrolate followed rapidly by neostigmine. There was significantly more bradycardia in the atropine group. Cardiac arrest following intentional use of anticholinesterase to slow the rate of atria1 tachycardia has been reported.g Carotid sinus massage slows conduction through the A-V node and has been useful in the slowing of atria1 fibrillation, atria1 flutter, and other atria1 tachycardias. This maneuver theoretically could be potentiated by anticholinesterases. Prolonged bradycardia has been reported after neostigmine administration in patients taking beta antagonists. Eldor et al. ‘” and Seidl and Martini1 reported severe bradycardia refractory to all intervention except epinephrine administration. Diabetic neuropathy with vagal dysfunction has been reported to
Letter to the Editor cause
deep,
esterase nervation carotid
refractory
bradycardia
administration.‘*
Drug
may be analogous sinus interaction
In summary,
after
synergy
4.
to the anticholinesterase-
in the current
this case
anticholinor vagal de-
of profound
case. bradycardia
leading to cardiac arrest is best explained by carotid sinus stimulation during the onset of muscarinic stimulation
by an anticholinesterase.
The
carotid sinus stimuli by anticholinesterase John E. Tetzlaff, Staff
potentiation
of
5. 6.
is postulated.
MD
7.
Anesthesiologist
Michael J. Choban, Resident
MD
in Anesthesiology
Department of General Anesthesiology Cleveland Clinic Foundation Cleveland,
OH 44195,
8.
USA 9.
References 10. Hollander AA, Dewaehter, Deville A, Vaisiere D: Haemodynamic changes associated with atropineineostigmine administration. Acta Anaesth Stand 1981;25: 18792. Mirakhur RK, Dundee JW, Clarke RSJ: Glycopyrrolateneostigmine mixture for antagonism of neuromuscular block: comparison with atropine-neostigmine mixture. Br J Anaesth 1977;49:825-8. Azar 1, Pham AN, Karambelkar DJ, Lear E: The heart rate following edrophonium-atropine and edrophon-
11.
12.
ium-glycopyrrolate mixtures. Anesthesiology 1983; 59:139-41. Gottlieb JD, Sweet RB: The antagonism of curare: the cardiac effects of atropine and neostigmine. Can Anaesth Sot J 1963;10:114-21. Ovassapian A: Effects of administration of atropine and neostigmine in man. Anesth Analg 1968;48:219-23. Harper KW, Bali IM, Gibson FM, et al: Reversal of neuromuscular block. Heart rate changes with slow injection of neostigmine and atropine mixtures. Anaesthesia 1984;39:772-5. Mirakhur RK, Dundee JW, Jones CJ, Coppel DL, Clarke RSJ: Reversal of neuromuscular blockade: dose determination in studies with atropine and glycopyrrolate given before or in a mixture with neostigmine. Anesth Analg 1981;60:557-62. Takkunen 0, Salmenpera M, Heinonen J: Atropine vs glycopyrrolate during reversal of pancuronium block in patients anesthetized with halothane. Acta Anaesth Stand 1984;28:377-80. Youngberg JA: Cardiac arrest following treatment of paroxysmal atria1 tachycardia with edrophonium. Anesthesiology 1979;50:234-5. Eldor J, Hoffman B, Davidson JT: Prolonged bradycardia and hypotension after neostigmine administration in a patient receiving atenolol. Anaesthesia 1987; 42: 1294-7. Seidl DC, Martin DE: Prolonged bradycardia after neostigmine administration in a patient taking nadolol. Anesth Analg 1984;63:365-7. Triantafillou AN, Tseuda K, Berg J, Wieman TJ: Refractory bradycardia after reversal of muscle relaxant in a diabetic with vagal neuropathy. Anesth Analg 1986;65:1237-41.
J. Clin. Anesth., vol. 2, May/June 1990
213
