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ECT emergence agitation and methohexital-succinylcholine interaction
Brief Report This section will carry communications of work in progress, preliminary research reports, or interesting and unusual vignettes. Such reports will be considered for their practical clinical relevance or heuristic value.
ECT Emergence Agitation and Methohexital-Succinylcholine Interaction Case Report Conrad Melton Swartz, Ph.D., M.D.
Abstract: Two separate methods of preventing post-ECT emergence agitation are increasing the succinylcholine dose to about 2.2 mgjkg and adding a methohexital bolus about 0.67 mglkg immediately at seizure end. These methods can work separately and additively without any expectation ofdiminishing treatment efficacy. A relevant case is described.
of
Introduction Prevention of the restlessly agitated state of emergence agitation that tends to occur in mesomorphic and lean patients after a programmed seizure (electroconvulsive therapy, ECT) can often be achieved by administration of higher doses of succinylcholine, the muscle paralytic agent routinely used at ECT [I]. Others have confirmed this observation 1241. Prevention or mitigation of emergence agitation is important because the discomfort can last for hours and provoke patients to discontinue treatment. Succinylcholine acts only to paralyze muscle and thereby prevent accumulation of the products of muscle metabolism such as lactate and carbon dioxide. Thus, emergence agitation has biochemical similarities to the agitation chemically induced by carbon dioxide or lactate infusion [5,61. Occurrence of emergence agitation after 1.0-1.1 mg/kg succinylcholine presumably means that the patient has a low responsivity to succinylcholine, a high sensitivity to the products of muscle metabolism, or Department of Psychiatric Medicine, East Carolina University School of Medicine, Greenville, North Carolina Address reprint requests to: Dr. Conrad Swartz, Department of Psychiatric Medicine, ECU School of Medicine, Greenville, NC 27858-4354.
General Hospital Psych&y 15, 339-341, 1993 8 1993 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010
an unusually large release of these metabolites 111.
Such occurrences raise questions about whether succinylcholine dose is irrelevant to those patients and what the clinical alternatives are; a recent case provided relevant information.
Case Report This 63-year-old, 95-kg, melancholic, mesomorphic male ex-marine mentioned severe emergence agitation with ECTs for previous depressive episodes. We administered six unilateral brief-pulse ECTs, with anesthesia by intravenous glycopyrrolate, methohexital, succinylcholine, and hyperoxygenation. After the first ECT, with 60 mg methohexital and 70 mg succinylcholine, the patient was mildly agitated but needed no sedation. After the second ECT he was severely agitated and mildly irritable; 10 mg diazepam i.v. calmed him about 50%. Increase of succinylcholine to 100 mg was met by only marginally less severe agitation; midazolam 2 mg i.v. calmed him about 50%. Replacement of methohexital with etomidate 0.6 mg at ECT #4 and continuation of 100 mg succinylcholine was followed by the most severe emergence agitation seen, which included severe irritability; the patient was constantly hollering and trying to fight. This state surprisingly showed no attenuation with three sequential lo-mg i.v. boluses of diazepam over 5 minutes; all boluses were properly infused. At ECT #5, the anesthesiologist infused 75 mg methohexital and 65 mg succinylcholine without discussion. Immediately at the end of cuffed-limb motor seizure activity we infused a 45-mg methohexital bolus.
339 ISSN 01658343/93/$6.00
C. M. Swartz
The patient then showed no emergence agitation. ECT #6 was conducted in the same way as ECT #5 except the succinylcholine dose was 50 mg (0.53 mg/kg), and the patient again showed problematic emergence agitation.
Discussion After the prevention of emergence agitation at ECT #5, its reappearance at ECT #6 with only a decrease in succinylcholine dose is consistent with the previous report that succinylcholine increase prevents emergence agitation [ll. The failure of 1.05 mg/kg succinylcholine to block emergence agitation at ECT #3 suggests that this patient showed relatively low responsivity to succinylcholine or especially high sensitivity to the products of muscle metabolism. The prevention of emergence agitation at ECT #5 appears to have followed the combination of two influences: a sufficient dose of succinylcholine and the immediacy of methohexital administration at the end of the seizure. The former is shown by comparison with ECT #6 and the latter by comparison with ECTs #14. The apparent effectiveness of methohexital when given immediately at the end of the seizure contrasts with the ineffectuality of heavy diazepam doses given after the emergence agitation had started. In turn, this suggests that high pre-ECT doses of barbiturates might prevent emergence agitation because of their presence immediately at the end of the seizure. Indeed, the exacerbation of emergence agisubstitution of etomidate for tation by methohexital at ECT #4 is consistent with prevention of emergence agitation by pre-ECT barbiturate administration. Administration of sedatives immediately postictal has the advantage over additional pre-ECT sedatives of not interfering with the expected source of therapeutic benefit, the seizure itself. The greater postictal action of anesthetic barbiturates that persist longer than methohexital, such as thiopental, might likewise prevent or diminish emergence agitation without additional dosage after the seizure. Once emergence agitation develops after the opportunity to prevent it has passed, possible intravenous sedatives include continuous 2% methohexital infusion or bolus 10 mg diazepam, 1 mg midazolam, or 2 mg lorazepam [71; lorazepam has the slowest onset but lowest apnea risk. 340
Anticonvulsant action is probably the simplest mechanism to explain the anti-agitation effects of increasing the pre-ECT barbiturate dosage 181, i.e., additional barbiturate decreases the total amount of seizure activity and its consequences, including emergence agitation. Unfortunately, an increase in pre-ECT barbiturate also increases risks of cutting treatment efficacy and exacerbating cognitive sideeffects. Anesthetic barbiturates inhibit ECT seizure 19-121 and are recommended to terminate long ECT seizures [13]; 30 mg of methohexital seems to work rapidly. High-dose (1.5 mg/kg) methohexital probably predisposed to the notorious absence of benefit from bilateral ECT in the Northwick Park trial [141. Exposure to benzodiazepines, similar agents, impairs ECT efficacy [151. Although simple seizure duration ordinarily has little relationship to efficacy [16], in the presence of inhibitory influences, a decrease in seizure duration evidences treatment obstruction, as seen with pre-ECT lidoCaine [171 and propofol 1181. Thus, the shortened seizure durations seen after increased pre-ECT barbiturates in the second and third cases of Devanand and Sackeim [81 may be seen as undesirable. In addition, larger doses of pre-ECT methohexital have been associated with greater memory impairment [191. Unlike pre-ECT barbiturates, higher doses of succinylcholine do not shorten seizures. New examination of clinical records from a prior study 111 reveals that motor seizure duration averaged 59.4 (SD 12.3) seconds with 1.0-1.1 mg/kg succinylcholine and 63.8 (SD 22.1) seconds with 0.7 mg/kg; the difference is insignificant p = 0.59 and explainable by the customary fall of seizure duration along the course of treatment [201. The survey statistic that shorter seizures correlate with larger succinylcholine doses [19] is simply attributable to the larger barbiturate doses received by the heavier patients and the consequently shorter seizures also noted; individual patients were not repeatedly measured after differing succinylcholine doses. If patients who receive large succinylcholine doses were to waken still partially paralyzed, they could be readily managed by administering additional methohexital after seizure completion, which can also be given prophylactically. In summary, increasing the succinylcholine dose to about 1.1 mg/kg and adding a methohexital bolus of about 2/3 mg/kg immediately at seizure end are two separate methods of preventing emergence agitation that can work additively without any expectation of diminishing treatment efficacy.
ECT Emergence Agitation
Addendum Recently a second case was seen in which intravenous methohexital immediately after the seizure prevented emergence agitation. A 41-year-old 120 kg female with a psychotic mixed manic-depressive episode showed severe agitated restlessness after her first ECT with 70 mg methohexital and 60 mg succinylcholine. The same postictal agitated restlessness occurred after the next ECT, with 100 mg succinylcholine; three intravenous boluses of diazepam 10 mg did not observably calm the patient. From the third through the sixth and final ECT she received an additional 30 mg methohexital bolus immediately after the seizure; no agitation or restlessness followed and no further sedatives were needed or given.
References CM: Electroconvulsive therapy emergence agitation and succinylcholine dose. J Nerv Ment Dis 178:455+57, 1990 2. Schrift M: Personal communication, May 1991 3. Bornstein P: Personal communication, May 1991 1. Swartz
4. Jowsey SG: The effect of medications on ECT. Psychiatric Ann 23:33-37, 1993 5. Liebowitz MR, Fyer AJ, Gorman JM, et al: Lactate provocation of panic attacks. Arch Gen Psychiatry 41: 764-770, 1984 6. Woods SW, Chamey DS, Loke J, Goodman WK, Redmond DE, Heninger GR: Carbon dioxide sensitivity in panic disorder. Arch Gen Psychiatry 43:900-909, 1986 7. Abrams R: Electroconvulsive Therapy, 2nd ed. New York, Oxford Press, 1992, pp 173-174 8. Devanand DP, Sackeim HA: Use of increased anesthetic dose prior to electroconvulsive therapy to pre-
vent postictal excitement. Gen Hosp Psychiatry 14: 345-349, 1992 9. Enderle JD, Staton RD, Gerst JW, Barr CE, Brumback RA: The electroencephalographic pattern during electroconvulsive treatment. Clin Electroencephalogr 17:66-77, 1986 10. Staton RD, Enderle JD, Gerst JW: The electroencephalographic pattern during electroconvulsive therapy. IV. Spectral energy distributions with methohexital, innovar and ketamine anesthesias. Clin Electroencephalogr 17~203-215, 1986 11. Witztum J, Baker M, Woodruff RA, Pitts FN: Electrotherapy: the effects of methohexital on electrocardiogram. Dis Nerv Syst 31:193-195,197O 12. Ayd FJ: Methohexital (Brevital): a new anesthetic for electroconvulsive therapy. Dis Nerv Syst 22:388-390, 1961 13. American Psychiatric Association: The Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training, and Privileging. Washington DC, American Psychiatric Association, 1990 14. Johnstone EC, Deakin JF, Lawler P, et al: The Northwick Park electroconvulsive therapy trial. Lancet 2(8208-8209):1317-20, 1980 15. Pettinati HM, Stephens SM, Willis KM, Robin SE: Evidence for less improvement in depression in patients taking benzodiazepines during unilateral ECT. Am J Psychiatry 147~1029-1035, 1990 16. Swartz CM: Beyond seizure duration as a measure of ECT quality. Convulsive Ther 9:1-7, 1993 17. Cronholm B, Ottosson JO: Experimental studies of the therapeutic action of electroconvulsive therapy in endogenous depression. Acta Psychiatr Stand 35
(Suppl 145):69-102, 1960
18. Swartz CM: Propofol anesthesia in electroconvulsive therapy. Convulsive Ther (in press) 19. Miller AL, Faber RA, Hatch JP, Alexander HE: Factors affecting amnesia, seizure duration, and efficacy in ECT. Am J Psychiatry 142:692-696,1985 20. Sackeim HA, Devanand DP, Prudic J: Stimulus intensity, seizure threshold, and seizure duration: impact on the efficacy and safety of electroconvulsive therapy. Psychiatr Clin North Am 14:803-844, 1991
341
ECT Emergence Agitation and Methohexital-Succinylcholine Interaction Case Report Conrad Melton Swartz, Ph.D., M.D.
Abstract: Two separate methods of preventing post-ECT emergence agitation are increasing the succinylcholine dose to about 2.2 mgjkg and adding a methohexital bolus about 0.67 mglkg immediately at seizure end. These methods can work separately and additively without any expectation ofdiminishing treatment efficacy. A relevant case is described.
of
Introduction Prevention of the restlessly agitated state of emergence agitation that tends to occur in mesomorphic and lean patients after a programmed seizure (electroconvulsive therapy, ECT) can often be achieved by administration of higher doses of succinylcholine, the muscle paralytic agent routinely used at ECT [I]. Others have confirmed this observation 1241. Prevention or mitigation of emergence agitation is important because the discomfort can last for hours and provoke patients to discontinue treatment. Succinylcholine acts only to paralyze muscle and thereby prevent accumulation of the products of muscle metabolism such as lactate and carbon dioxide. Thus, emergence agitation has biochemical similarities to the agitation chemically induced by carbon dioxide or lactate infusion [5,61. Occurrence of emergence agitation after 1.0-1.1 mg/kg succinylcholine presumably means that the patient has a low responsivity to succinylcholine, a high sensitivity to the products of muscle metabolism, or Department of Psychiatric Medicine, East Carolina University School of Medicine, Greenville, North Carolina Address reprint requests to: Dr. Conrad Swartz, Department of Psychiatric Medicine, ECU School of Medicine, Greenville, NC 27858-4354.
General Hospital Psych&y 15, 339-341, 1993 8 1993 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010
an unusually large release of these metabolites 111.
Such occurrences raise questions about whether succinylcholine dose is irrelevant to those patients and what the clinical alternatives are; a recent case provided relevant information.
Case Report This 63-year-old, 95-kg, melancholic, mesomorphic male ex-marine mentioned severe emergence agitation with ECTs for previous depressive episodes. We administered six unilateral brief-pulse ECTs, with anesthesia by intravenous glycopyrrolate, methohexital, succinylcholine, and hyperoxygenation. After the first ECT, with 60 mg methohexital and 70 mg succinylcholine, the patient was mildly agitated but needed no sedation. After the second ECT he was severely agitated and mildly irritable; 10 mg diazepam i.v. calmed him about 50%. Increase of succinylcholine to 100 mg was met by only marginally less severe agitation; midazolam 2 mg i.v. calmed him about 50%. Replacement of methohexital with etomidate 0.6 mg at ECT #4 and continuation of 100 mg succinylcholine was followed by the most severe emergence agitation seen, which included severe irritability; the patient was constantly hollering and trying to fight. This state surprisingly showed no attenuation with three sequential lo-mg i.v. boluses of diazepam over 5 minutes; all boluses were properly infused. At ECT #5, the anesthesiologist infused 75 mg methohexital and 65 mg succinylcholine without discussion. Immediately at the end of cuffed-limb motor seizure activity we infused a 45-mg methohexital bolus.
339 ISSN 01658343/93/$6.00
C. M. Swartz
The patient then showed no emergence agitation. ECT #6 was conducted in the same way as ECT #5 except the succinylcholine dose was 50 mg (0.53 mg/kg), and the patient again showed problematic emergence agitation.
Discussion After the prevention of emergence agitation at ECT #5, its reappearance at ECT #6 with only a decrease in succinylcholine dose is consistent with the previous report that succinylcholine increase prevents emergence agitation [ll. The failure of 1.05 mg/kg succinylcholine to block emergence agitation at ECT #3 suggests that this patient showed relatively low responsivity to succinylcholine or especially high sensitivity to the products of muscle metabolism. The prevention of emergence agitation at ECT #5 appears to have followed the combination of two influences: a sufficient dose of succinylcholine and the immediacy of methohexital administration at the end of the seizure. The former is shown by comparison with ECT #6 and the latter by comparison with ECTs #14. The apparent effectiveness of methohexital when given immediately at the end of the seizure contrasts with the ineffectuality of heavy diazepam doses given after the emergence agitation had started. In turn, this suggests that high pre-ECT doses of barbiturates might prevent emergence agitation because of their presence immediately at the end of the seizure. Indeed, the exacerbation of emergence agisubstitution of etomidate for tation by methohexital at ECT #4 is consistent with prevention of emergence agitation by pre-ECT barbiturate administration. Administration of sedatives immediately postictal has the advantage over additional pre-ECT sedatives of not interfering with the expected source of therapeutic benefit, the seizure itself. The greater postictal action of anesthetic barbiturates that persist longer than methohexital, such as thiopental, might likewise prevent or diminish emergence agitation without additional dosage after the seizure. Once emergence agitation develops after the opportunity to prevent it has passed, possible intravenous sedatives include continuous 2% methohexital infusion or bolus 10 mg diazepam, 1 mg midazolam, or 2 mg lorazepam [71; lorazepam has the slowest onset but lowest apnea risk. 340
Anticonvulsant action is probably the simplest mechanism to explain the anti-agitation effects of increasing the pre-ECT barbiturate dosage 181, i.e., additional barbiturate decreases the total amount of seizure activity and its consequences, including emergence agitation. Unfortunately, an increase in pre-ECT barbiturate also increases risks of cutting treatment efficacy and exacerbating cognitive sideeffects. Anesthetic barbiturates inhibit ECT seizure 19-121 and are recommended to terminate long ECT seizures [13]; 30 mg of methohexital seems to work rapidly. High-dose (1.5 mg/kg) methohexital probably predisposed to the notorious absence of benefit from bilateral ECT in the Northwick Park trial [141. Exposure to benzodiazepines, similar agents, impairs ECT efficacy [151. Although simple seizure duration ordinarily has little relationship to efficacy [16], in the presence of inhibitory influences, a decrease in seizure duration evidences treatment obstruction, as seen with pre-ECT lidoCaine [171 and propofol 1181. Thus, the shortened seizure durations seen after increased pre-ECT barbiturates in the second and third cases of Devanand and Sackeim [81 may be seen as undesirable. In addition, larger doses of pre-ECT methohexital have been associated with greater memory impairment [191. Unlike pre-ECT barbiturates, higher doses of succinylcholine do not shorten seizures. New examination of clinical records from a prior study 111 reveals that motor seizure duration averaged 59.4 (SD 12.3) seconds with 1.0-1.1 mg/kg succinylcholine and 63.8 (SD 22.1) seconds with 0.7 mg/kg; the difference is insignificant p = 0.59 and explainable by the customary fall of seizure duration along the course of treatment [201. The survey statistic that shorter seizures correlate with larger succinylcholine doses [19] is simply attributable to the larger barbiturate doses received by the heavier patients and the consequently shorter seizures also noted; individual patients were not repeatedly measured after differing succinylcholine doses. If patients who receive large succinylcholine doses were to waken still partially paralyzed, they could be readily managed by administering additional methohexital after seizure completion, which can also be given prophylactically. In summary, increasing the succinylcholine dose to about 1.1 mg/kg and adding a methohexital bolus of about 2/3 mg/kg immediately at seizure end are two separate methods of preventing emergence agitation that can work additively without any expectation of diminishing treatment efficacy.
ECT Emergence Agitation
Addendum Recently a second case was seen in which intravenous methohexital immediately after the seizure prevented emergence agitation. A 41-year-old 120 kg female with a psychotic mixed manic-depressive episode showed severe agitated restlessness after her first ECT with 70 mg methohexital and 60 mg succinylcholine. The same postictal agitated restlessness occurred after the next ECT, with 100 mg succinylcholine; three intravenous boluses of diazepam 10 mg did not observably calm the patient. From the third through the sixth and final ECT she received an additional 30 mg methohexital bolus immediately after the seizure; no agitation or restlessness followed and no further sedatives were needed or given.
References CM: Electroconvulsive therapy emergence agitation and succinylcholine dose. J Nerv Ment Dis 178:455+57, 1990 2. Schrift M: Personal communication, May 1991 3. Bornstein P: Personal communication, May 1991 1. Swartz
4. Jowsey SG: The effect of medications on ECT. Psychiatric Ann 23:33-37, 1993 5. Liebowitz MR, Fyer AJ, Gorman JM, et al: Lactate provocation of panic attacks. Arch Gen Psychiatry 41: 764-770, 1984 6. Woods SW, Chamey DS, Loke J, Goodman WK, Redmond DE, Heninger GR: Carbon dioxide sensitivity in panic disorder. Arch Gen Psychiatry 43:900-909, 1986 7. Abrams R: Electroconvulsive Therapy, 2nd ed. New York, Oxford Press, 1992, pp 173-174 8. Devanand DP, Sackeim HA: Use of increased anesthetic dose prior to electroconvulsive therapy to pre-
vent postictal excitement. Gen Hosp Psychiatry 14: 345-349, 1992 9. Enderle JD, Staton RD, Gerst JW, Barr CE, Brumback RA: The electroencephalographic pattern during electroconvulsive treatment. Clin Electroencephalogr 17:66-77, 1986 10. Staton RD, Enderle JD, Gerst JW: The electroencephalographic pattern during electroconvulsive therapy. IV. Spectral energy distributions with methohexital, innovar and ketamine anesthesias. Clin Electroencephalogr 17~203-215, 1986 11. Witztum J, Baker M, Woodruff RA, Pitts FN: Electrotherapy: the effects of methohexital on electrocardiogram. Dis Nerv Syst 31:193-195,197O 12. Ayd FJ: Methohexital (Brevital): a new anesthetic for electroconvulsive therapy. Dis Nerv Syst 22:388-390, 1961 13. American Psychiatric Association: The Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training, and Privileging. Washington DC, American Psychiatric Association, 1990 14. Johnstone EC, Deakin JF, Lawler P, et al: The Northwick Park electroconvulsive therapy trial. Lancet 2(8208-8209):1317-20, 1980 15. Pettinati HM, Stephens SM, Willis KM, Robin SE: Evidence for less improvement in depression in patients taking benzodiazepines during unilateral ECT. Am J Psychiatry 147~1029-1035, 1990 16. Swartz CM: Beyond seizure duration as a measure of ECT quality. Convulsive Ther 9:1-7, 1993 17. Cronholm B, Ottosson JO: Experimental studies of the therapeutic action of electroconvulsive therapy in endogenous depression. Acta Psychiatr Stand 35
(Suppl 145):69-102, 1960
18. Swartz CM: Propofol anesthesia in electroconvulsive therapy. Convulsive Ther (in press) 19. Miller AL, Faber RA, Hatch JP, Alexander HE: Factors affecting amnesia, seizure duration, and efficacy in ECT. Am J Psychiatry 142:692-696,1985 20. Sackeim HA, Devanand DP, Prudic J: Stimulus intensity, seizure threshold, and seizure duration: impact on the efficacy and safety of electroconvulsive therapy. Psychiatr Clin North Am 14:803-844, 1991
341