- Email: [email protected]
The use of midazolam for hypnosedative interviews
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.
The Use of Midazolam for Hypnosedative Interviews Mark Hyatt, M.D., Nancy Braun, M.D., Greg Briscoe, M.D., and Lesley Dickson, M.D. Abstract: The authors describe three cases in which midazolam was successfully used in diagnostic kypnosedative interviews. A discussion comparing and contrasting midazolam to other intravenous kypnosedatives is presented. The authors suggest that midazolam is an effecfive agent for diagnostic hypnosedative interviews and may be preferable to other agents when posthypnotic recollection of interview content is undesirable.
Introduction The use of intravenous hypnotics can be helpful in differentiating catatonic from organic states [1,2]. These agents have also been successfully employed in narcoanalysis [II and in the diagnosis and treatment of conversion disorders [3,41 and psychogenic amnesia 151. The barbiturates amobarbital and pentobarbital, and the benzodiazepine diazepam are most commonly used. However, there are some potentially serious complications from intravenous use of these drugs. All three agents can cause lifethreatening respiratory depression 161. Barbiturates have a low therapeutic index, which decreases even more as hypnosedative tolerance increases 161. Residual drowsiness and central nervous system (CNS) depression (up to 24 hours postinfusion) are common with barbiturates 161. Barbiturates are only mediocre anxiolytics, and not uncommonly produce paradoxical excitement 161; therefore, they may be of little benefit in an anxious patient. Although diazepam is an excellent anxiolytic with a University of Kentucky College of Medicine, Lexington, Kentucky. Address reprint requests to: Mark Hyatt, M.D., Chief of Psychiatry, Veteran’s Affairs Medical Center, 116-A, Lexington, KY 40511.
260 ISSN 0163-8343/93/!$6.00
generous therapeutic index, it too is associated with significant postinfusion drowsiness and CNS depression [6,71. Intravenous diazepam can also be painful upon infusion and is accompanied by a high incidence (5%-30%) of thrombophlebitis at the infusion site [6-81. Midazolam is a relatively new parenteral benzodiazepine that has been used successfully for conscious sedation and induction of general anesthesia 16-81. It is a highly lipophilic compound which, when administered intravenously, has a more rapid onset of action (2-5 minutes), shorter duration of action (mean 2 hours), and shorter halflife (mean 2 hours) than diazepam 17-91. As with other benzodiazepines, midazolam is an excellent anxiolytic hypnosedative with a favorable therapeutic index, but it may cause significant respiratory depression and apnea if infused too quickly or when used concomitantly with opioids or in patients taking other hypnosedative agents [9,10]. Unlike intravenous diazepam, midazolam produces near-complete amnesia for the procedure and is associated with less postinfusion drowsiness 171. There is also little or no venous irritation, so infusion pain and thrombophlebitis (0.4%) are rare 1781. For complete details regarding the administration of intravenous midazolam for conscious sedation, refer to the package insert.’ The manufacturer recommends that for otherwise healthy individuals under the age of 60, an initial dose of O.l0.15 mg/kg be administered slowly over l-2 minutes (no more than 2.5 mg should be adminis-
‘Versed, Roche Laboratories GeneralHospitalPsychiafy 15, 260-262, 1993 8 1993 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010
Midazolam for Hypnosedative Interviews
Wed over 2 minutes). Maintenance doses of 25% of the initial dose may be used to sustain the desired level of sedation. In general, additional doses should be administered no sooner than 2 minutes after the preceding dose. For most procedures where conscious sedation is desired, a total of 5 mg of midazolam will usually suffice [B]. We present three cases in which intravenous midazolam was employed for diagnostic purposes: one case of suspected conversional dysphonia and two cases of suspected catatonia.
Case 1 A 32-year-old Caucasian male presented to the emer-
gency room with dysphoria, suicidal ideation, and poIysubstance abuse. His depressive symptoms were largely situational and accentuated by a bout of heavy
drinking prior to admission. Within a few days of admission he became euthymic and inquired about the possibility of getting some help for his “voice problem,” which had begun 3 years prior to admission. Scheduled to give a class presentation, he had begun losing his voice a few hours before class, and by classtime, was totally aphonic and unable to make his presentation. Within 24 hours of onset of the aphonia, his voice had returned, but as a squeaky, high-pitched dysphonia. All physical evaluations of his oropharynx and larynx were normal, and speech therapy and biofeedback proved unhelpful. Suspecting conversional dysphonia, a barbiturate interview was conducted. Unfortunately, due to his extreme tolerance to hypnosedatives, adequate hypnosis was not achieved with barbiturates (pentobarbital 300 mg iv. over 15 minutes; phenobarbital 180 mg i.v. over 15 minutes). The next day midazolam 7 mg was administered i.v. over a 20-minute period with complete resolution of the dysphonia. The dysphonia remained quiescent for approximately 30 minutes after the midazolam administration had terminated, but was followed by a gradual return over the next 12 hours.
Case 2 A 33-year-old Caucasian male presented to the emergency room in a manic state. He had a long history of schizoaffective disorder with catatonia and psychotropic noncompliance. His usual medications (molindone, lithium, and propranolol) were restarted, and by hospital day 3, his mania had largely remitted. However, the next day he developed a catatonic state that did not resolve with parenterai administration of neuroleptic (thiothixene). After 48 hours of unremitted catatonia, a midazolam intravenous infusion (4 mg) was conducted over a 20-minute period. His pro-
found catatonic stupor dissipated, and he became verbal and cooperative with no further episodes of catatonia during his IO-day hospitalization.
Case 3 A 39-year-old Caucasian male presented to the neurology service with a recent history of fever, chills, cough, progressive changes in personality, and catatonic behavior. His past psychiatric history was unremarkable and neurologic exam was nonfocal. Initially he received empiric acyclovir for presumed herpes encephalitis, anticonvulsant therapy for seizure prophylaxis, and antibiotic treatment for pneumonia. Extensive workup for suspected encephalopathy proved to be unremarkable. Believing now that his catatonia was functional, anticonvulsant therapy and acyclovir were discontinued. A midazolam interview was conducted to help clarify his clinical picture; midazolam 4mg was infused intravenously over a lo-minute period. He became animated with spontaneous and appropriate responses to questions, but this period of lucidity was transient, diminishing a few hours after the midazolam infusion. He was subsequently transferred to the psychiatry service, but was lost to follow-up when his wife wanted him hospitalized closer to home.
Discussion Although more clinical experience is needed, these three cases demonstrate that midazolam may be an effective agent for diagnostic hypnosedative interviews. Narcoanalysis or hypnotherapy was not an intent of these interventions, yet it is interesting to note that in one patient, catatonia completely resolved as a result of the midazolam interview. Due to the near complete procedural amnesia seen in patients having undergone intravenous midazolam infusion, one might speculate that it would be a particularly useful drug when posthypnotic recollection of interview content might be undesirable. As an intravenous hypnosedative, midazolam has major advantages over the more traditional agents in that it has a rapid onset of action, favorable therapeutic index (when administered slowly), less postinfusion CNS depression, and minimal venous irritation. Because intravenous infusion of midazolam is not without potential complications (respiratory depression and apnea), it should be administered slowly and only in the presence of appropriate monitoring (pulse oximetry and ECG) and resuscitative devices. 261
M. Hyatt et al.
References 1. Gorman JM, Davis JM: Antianxiety drugs. In Kaplan HI, Sadock BJ feds), Comprehensive Textbook of Psychiatry. Baltimore, Williams and Wilkins, pp. 15791591, 1989 2. Stoudemire GA: The differential diagnosis of catatonic states. Psychosomatics 23:245-252, 1982 3. Barsky AJ: Somatoform disorders. In Kaplan HI, Sadock BJ (ed), Comprehensive Textbook of Psychiatry. Baltimore, Williams and Wilkins, 1989 pp. 1009-1027 4. Stoudemire GA: Somatoform disorders, factitious disorders, and malingering. In Talbott JA, Hales RE, Yudofsky SC (eds), Textbook of Psychiatry. Washington, DC, American Psychiatric Press, 1988, pp. 533-556 5. Kluft RI’: The dissociative disorders. In Talbott JA, Hales RE, Yudofsky SC teds), Textbook of Psychia-
262
6.
7.
8.
9.
10.
try. Washington, DC, American Psychiatric Press, 1988, pp. 557-585 The Pharmacological Basis of Therapeutics, 8th ed. Gilman AG, Rall TW, Nies AS, Taylor P teds). Elmsford, NY, Pergamon Press, 1990 Reves JG, Fragen RJ, Vinik HR, et al: Midazolam: pharmacology and uses. Anesthesiology 62:310-324, 1985 American Hospital Formulary Service Drug Information 1992. American Society of Hospital Pharmacists, Bethesda, MD, 1992 Nuotto EJ, Korttila KT, Lichtor JL, et al: Sedation and recovery of psychomotor function after intravenous administration of various doses of midazolam and diazepam. Anesth Analg 74:265-271, 1992 Kissin I, Vinik HR, Casillo, et al: Alfentanil potentiates midazolam-induced unconsciousness in subanalgesic doses. Anesth Analg, 71:65-69, 1990
The Use of Midazolam for Hypnosedative Interviews Mark Hyatt, M.D., Nancy Braun, M.D., Greg Briscoe, M.D., and Lesley Dickson, M.D. Abstract: The authors describe three cases in which midazolam was successfully used in diagnostic kypnosedative interviews. A discussion comparing and contrasting midazolam to other intravenous kypnosedatives is presented. The authors suggest that midazolam is an effecfive agent for diagnostic hypnosedative interviews and may be preferable to other agents when posthypnotic recollection of interview content is undesirable.
Introduction The use of intravenous hypnotics can be helpful in differentiating catatonic from organic states [1,2]. These agents have also been successfully employed in narcoanalysis [II and in the diagnosis and treatment of conversion disorders [3,41 and psychogenic amnesia 151. The barbiturates amobarbital and pentobarbital, and the benzodiazepine diazepam are most commonly used. However, there are some potentially serious complications from intravenous use of these drugs. All three agents can cause lifethreatening respiratory depression 161. Barbiturates have a low therapeutic index, which decreases even more as hypnosedative tolerance increases 161. Residual drowsiness and central nervous system (CNS) depression (up to 24 hours postinfusion) are common with barbiturates 161. Barbiturates are only mediocre anxiolytics, and not uncommonly produce paradoxical excitement 161; therefore, they may be of little benefit in an anxious patient. Although diazepam is an excellent anxiolytic with a University of Kentucky College of Medicine, Lexington, Kentucky. Address reprint requests to: Mark Hyatt, M.D., Chief of Psychiatry, Veteran’s Affairs Medical Center, 116-A, Lexington, KY 40511.
260 ISSN 0163-8343/93/!$6.00
generous therapeutic index, it too is associated with significant postinfusion drowsiness and CNS depression [6,71. Intravenous diazepam can also be painful upon infusion and is accompanied by a high incidence (5%-30%) of thrombophlebitis at the infusion site [6-81. Midazolam is a relatively new parenteral benzodiazepine that has been used successfully for conscious sedation and induction of general anesthesia 16-81. It is a highly lipophilic compound which, when administered intravenously, has a more rapid onset of action (2-5 minutes), shorter duration of action (mean 2 hours), and shorter halflife (mean 2 hours) than diazepam 17-91. As with other benzodiazepines, midazolam is an excellent anxiolytic hypnosedative with a favorable therapeutic index, but it may cause significant respiratory depression and apnea if infused too quickly or when used concomitantly with opioids or in patients taking other hypnosedative agents [9,10]. Unlike intravenous diazepam, midazolam produces near-complete amnesia for the procedure and is associated with less postinfusion drowsiness 171. There is also little or no venous irritation, so infusion pain and thrombophlebitis (0.4%) are rare 1781. For complete details regarding the administration of intravenous midazolam for conscious sedation, refer to the package insert.’ The manufacturer recommends that for otherwise healthy individuals under the age of 60, an initial dose of O.l0.15 mg/kg be administered slowly over l-2 minutes (no more than 2.5 mg should be adminis-
‘Versed, Roche Laboratories GeneralHospitalPsychiafy 15, 260-262, 1993 8 1993 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010
Midazolam for Hypnosedative Interviews
Wed over 2 minutes). Maintenance doses of 25% of the initial dose may be used to sustain the desired level of sedation. In general, additional doses should be administered no sooner than 2 minutes after the preceding dose. For most procedures where conscious sedation is desired, a total of 5 mg of midazolam will usually suffice [B]. We present three cases in which intravenous midazolam was employed for diagnostic purposes: one case of suspected conversional dysphonia and two cases of suspected catatonia.
Case 1 A 32-year-old Caucasian male presented to the emer-
gency room with dysphoria, suicidal ideation, and poIysubstance abuse. His depressive symptoms were largely situational and accentuated by a bout of heavy
drinking prior to admission. Within a few days of admission he became euthymic and inquired about the possibility of getting some help for his “voice problem,” which had begun 3 years prior to admission. Scheduled to give a class presentation, he had begun losing his voice a few hours before class, and by classtime, was totally aphonic and unable to make his presentation. Within 24 hours of onset of the aphonia, his voice had returned, but as a squeaky, high-pitched dysphonia. All physical evaluations of his oropharynx and larynx were normal, and speech therapy and biofeedback proved unhelpful. Suspecting conversional dysphonia, a barbiturate interview was conducted. Unfortunately, due to his extreme tolerance to hypnosedatives, adequate hypnosis was not achieved with barbiturates (pentobarbital 300 mg iv. over 15 minutes; phenobarbital 180 mg i.v. over 15 minutes). The next day midazolam 7 mg was administered i.v. over a 20-minute period with complete resolution of the dysphonia. The dysphonia remained quiescent for approximately 30 minutes after the midazolam administration had terminated, but was followed by a gradual return over the next 12 hours.
Case 2 A 33-year-old Caucasian male presented to the emergency room in a manic state. He had a long history of schizoaffective disorder with catatonia and psychotropic noncompliance. His usual medications (molindone, lithium, and propranolol) were restarted, and by hospital day 3, his mania had largely remitted. However, the next day he developed a catatonic state that did not resolve with parenterai administration of neuroleptic (thiothixene). After 48 hours of unremitted catatonia, a midazolam intravenous infusion (4 mg) was conducted over a 20-minute period. His pro-
found catatonic stupor dissipated, and he became verbal and cooperative with no further episodes of catatonia during his IO-day hospitalization.
Case 3 A 39-year-old Caucasian male presented to the neurology service with a recent history of fever, chills, cough, progressive changes in personality, and catatonic behavior. His past psychiatric history was unremarkable and neurologic exam was nonfocal. Initially he received empiric acyclovir for presumed herpes encephalitis, anticonvulsant therapy for seizure prophylaxis, and antibiotic treatment for pneumonia. Extensive workup for suspected encephalopathy proved to be unremarkable. Believing now that his catatonia was functional, anticonvulsant therapy and acyclovir were discontinued. A midazolam interview was conducted to help clarify his clinical picture; midazolam 4mg was infused intravenously over a lo-minute period. He became animated with spontaneous and appropriate responses to questions, but this period of lucidity was transient, diminishing a few hours after the midazolam infusion. He was subsequently transferred to the psychiatry service, but was lost to follow-up when his wife wanted him hospitalized closer to home.
Discussion Although more clinical experience is needed, these three cases demonstrate that midazolam may be an effective agent for diagnostic hypnosedative interviews. Narcoanalysis or hypnotherapy was not an intent of these interventions, yet it is interesting to note that in one patient, catatonia completely resolved as a result of the midazolam interview. Due to the near complete procedural amnesia seen in patients having undergone intravenous midazolam infusion, one might speculate that it would be a particularly useful drug when posthypnotic recollection of interview content might be undesirable. As an intravenous hypnosedative, midazolam has major advantages over the more traditional agents in that it has a rapid onset of action, favorable therapeutic index (when administered slowly), less postinfusion CNS depression, and minimal venous irritation. Because intravenous infusion of midazolam is not without potential complications (respiratory depression and apnea), it should be administered slowly and only in the presence of appropriate monitoring (pulse oximetry and ECG) and resuscitative devices. 261
M. Hyatt et al.
References 1. Gorman JM, Davis JM: Antianxiety drugs. In Kaplan HI, Sadock BJ feds), Comprehensive Textbook of Psychiatry. Baltimore, Williams and Wilkins, pp. 15791591, 1989 2. Stoudemire GA: The differential diagnosis of catatonic states. Psychosomatics 23:245-252, 1982 3. Barsky AJ: Somatoform disorders. In Kaplan HI, Sadock BJ (ed), Comprehensive Textbook of Psychiatry. Baltimore, Williams and Wilkins, 1989 pp. 1009-1027 4. Stoudemire GA: Somatoform disorders, factitious disorders, and malingering. In Talbott JA, Hales RE, Yudofsky SC (eds), Textbook of Psychiatry. Washington, DC, American Psychiatric Press, 1988, pp. 533-556 5. Kluft RI’: The dissociative disorders. In Talbott JA, Hales RE, Yudofsky SC teds), Textbook of Psychia-
262
6.
7.
8.
9.
10.
try. Washington, DC, American Psychiatric Press, 1988, pp. 557-585 The Pharmacological Basis of Therapeutics, 8th ed. Gilman AG, Rall TW, Nies AS, Taylor P teds). Elmsford, NY, Pergamon Press, 1990 Reves JG, Fragen RJ, Vinik HR, et al: Midazolam: pharmacology and uses. Anesthesiology 62:310-324, 1985 American Hospital Formulary Service Drug Information 1992. American Society of Hospital Pharmacists, Bethesda, MD, 1992 Nuotto EJ, Korttila KT, Lichtor JL, et al: Sedation and recovery of psychomotor function after intravenous administration of various doses of midazolam and diazepam. Anesth Analg 74:265-271, 1992 Kissin I, Vinik HR, Casillo, et al: Alfentanil potentiates midazolam-induced unconsciousness in subanalgesic doses. Anesth Analg, 71:65-69, 1990