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Ketamine: Neurophysiological study of subanesthetic doses in patients with chronic pain
P Poster Presentations
134
IP-14-71 (DA)-Noradrenalini Functional State of the System DOPHA-Dophamini IP-14-S I Subanesthetic Ketamine: Neurophysiological Study of (NA}-Adremalini (A) Under Doses in Patients with Chronic Pain K. Oga I, M. Matsuura " M. Nagashima ' , T. Kojima ', J. Kato 2, S. Ogawa 2 . I Depa rtment ofNeuropsychiatry; Nihon University School of Medicine, Tokyo. Japan ; 2 Department of Anesthesiology, Nihon University School ofMedicin e, Tokyo. Japan Background: Ketamine hydrochloride, a noncompet itive NMDA antagonist, is available for the clinical treatment of pain in subanesthetic doses . This study was made to characterize phenomenological and neurophysiological effects of ketarnine at subanesthetic doses in patients with chronic pain. Subjects and methods: Seven inpatients with chronic pain, before ketamine I. V. therapy, were studied. They were fully informed the side effect of ketamine and methods of this study. They received ketamine test with single blind method. Following intravenous injections of saline (placebo), subanesthe tic doses ofketamine (5 mg) was administered three times with 5 minutes intervals. And analgesic effect of ketamine was compared with saline. We interviewed the patients to know their subjective experiences, observed behaviors, and recorded polygraph during the ketamine test. Closed eye movements were analyzed with Shimazonos' criterion. One minite EEGs were also analyzed by FFT method. Result and discussion : Spectral-a nalyzed EEG showed statiscally significant changes after ketamine, which were characterized by a decrease of alpha activity, increase of theta and delta activity. At the same time, the rapid eye movements decreased whereas the slow eye movements did not come out. These neurophysiological changes were coincident with the dreamy-like states. This electrophysiologic dissociation between EEG and oculomotor systems is thought to cause the dreamy-like states. This supports the concept that ketamine induces a functional disorganization of brain area in the thalamo-neocortical pathways, the lymbic system, and the midbrain reticular formation.
I P-14-SI TheInfluense of Ketamine Pharmacokinetics on the Activity of Neurotransmitter Systems in Humans underSurgical Stress
N.A. Davydova, R.A. Tigranian, T.E Borovkova, M.M. Abackumov, B.G. Gillis. Institute for Standardization and Conrrol of Drugs, Russian Ministry ofHealth, Moscow, Russia 50 men, aged 25-50, that were exposed to surgery, were examined. We measured blood content of E, NE I by HPLC/, 5-HT. histamin, their precussors in blood and urine, and also blood levels of AChE and ChEf fluometricaly and spectrophotometricaly/. Patients were anesthetized by i.v. injection ofketamine. Blood samples were taken 10 and 20 minutes after the onset the anesthesia and then one hour, one day and two days after the operation has been completed. We measured content ketamine and its precursors in blood and urine chromatograficaly. Blood and urine level of CA were increased at all the studied time points, while blood and urine 5-HT, histamine levels and AChT activity were reduced during the surgery and increased one hour after its completion. The activation of the studied systems persisted up to the 2nd postsurgical day. These changes did not correlate with ketamine pharmacokinet ics. The observed alteration of measured parameters in surgical stress should be attributed to the activating effect of ketanine, presumably on the sympathoadrenal system. Also changes in the patient's psychology were observed after surgical stress and their influence on biochem ical results.
Epilepsy v.A. Karlov, M,A. Gleyzer, N,D. Sorokina. Moscow Medical Stomatological Institute, Russia The aim of the investigation: the study of functional state of the system DOPHA-DA-NA-A under temporal lobe epilepsy. Methods : the estimation of the concentra tion of DOPHA, DA, NA, A in 4 portions of the daily urine as an answer to the injectio n of adrenalini, insulini, DOPHA (reactivity of system), at the same time the clinical tests for estimation of functional state of autonomic nervous system were used (tonus, reactivity, providing). Results : the safety of processes of synthesis in sympatoadrenal system was revealed and at the same time the deterioration of self-regulation in it was observed. The hypoadrenal changes under the biochemical arousing trials and deterioration of providing of autonomic nervous system in clinical tests data were marked. It is supposed the conception of deinnervated hypersensibility of katecholamin ergic neurons,
IP-14-8 ! Psychiatric Morbidity in Candidates for Normal Volunteer Trials
V. Gentil, C. Gorenstein, L. Andrade. Depts. Psychiatry + Pharmacology, Universidade Sao Paulo, Brasil Significant Psychopathology has been detected among "Normal Volunteers" and a full screening is recommended for psychopharmacological trials. We recently requested "Normal volunteers with high school or further education with mild anxiety or irritability complaints, but no significant social or work impairments , for a clinical trial of an antidepressant in normals" . Out of 254 applicants submitted to the self-report questionnaire (SRO-20), only 93 (36.6%) scored below the cut-off level. Of these, 58 were evaluated by a clinical and a PSE-l O/SCAl\' Psychiatric interview and 38 (65.5%) met criteria for one or more lifetime diagnosis (Major Depression, 55%; Dysthymia , 16%; Phobias, 13%. Panic Disorder, 5%; Cyclothmin , 5%; others, 6%). Therefo re only 8% of the applicants met the requested criteria for participation in the clinical trial. In addition, 90.5% of the candidates with present or past psychiatric diagnoses had never sought or received any psychiatric evaluation or care. Public education programmes could help.
134
IP-14-71 (DA)-Noradrenalini Functional State of the System DOPHA-Dophamini IP-14-S I Subanesthetic Ketamine: Neurophysiological Study of (NA}-Adremalini (A) Under Doses in Patients with Chronic Pain K. Oga I, M. Matsuura " M. Nagashima ' , T. Kojima ', J. Kato 2, S. Ogawa 2 . I Depa rtment ofNeuropsychiatry; Nihon University School of Medicine, Tokyo. Japan ; 2 Department of Anesthesiology, Nihon University School ofMedicin e, Tokyo. Japan Background: Ketamine hydrochloride, a noncompet itive NMDA antagonist, is available for the clinical treatment of pain in subanesthetic doses . This study was made to characterize phenomenological and neurophysiological effects of ketarnine at subanesthetic doses in patients with chronic pain. Subjects and methods: Seven inpatients with chronic pain, before ketamine I. V. therapy, were studied. They were fully informed the side effect of ketamine and methods of this study. They received ketamine test with single blind method. Following intravenous injections of saline (placebo), subanesthe tic doses ofketamine (5 mg) was administered three times with 5 minutes intervals. And analgesic effect of ketamine was compared with saline. We interviewed the patients to know their subjective experiences, observed behaviors, and recorded polygraph during the ketamine test. Closed eye movements were analyzed with Shimazonos' criterion. One minite EEGs were also analyzed by FFT method. Result and discussion : Spectral-a nalyzed EEG showed statiscally significant changes after ketamine, which were characterized by a decrease of alpha activity, increase of theta and delta activity. At the same time, the rapid eye movements decreased whereas the slow eye movements did not come out. These neurophysiological changes were coincident with the dreamy-like states. This electrophysiologic dissociation between EEG and oculomotor systems is thought to cause the dreamy-like states. This supports the concept that ketamine induces a functional disorganization of brain area in the thalamo-neocortical pathways, the lymbic system, and the midbrain reticular formation.
I P-14-SI TheInfluense of Ketamine Pharmacokinetics on the Activity of Neurotransmitter Systems in Humans underSurgical Stress
N.A. Davydova, R.A. Tigranian, T.E Borovkova, M.M. Abackumov, B.G. Gillis. Institute for Standardization and Conrrol of Drugs, Russian Ministry ofHealth, Moscow, Russia 50 men, aged 25-50, that were exposed to surgery, were examined. We measured blood content of E, NE I by HPLC/, 5-HT. histamin, their precussors in blood and urine, and also blood levels of AChE and ChEf fluometricaly and spectrophotometricaly/. Patients were anesthetized by i.v. injection ofketamine. Blood samples were taken 10 and 20 minutes after the onset the anesthesia and then one hour, one day and two days after the operation has been completed. We measured content ketamine and its precursors in blood and urine chromatograficaly. Blood and urine level of CA were increased at all the studied time points, while blood and urine 5-HT, histamine levels and AChT activity were reduced during the surgery and increased one hour after its completion. The activation of the studied systems persisted up to the 2nd postsurgical day. These changes did not correlate with ketamine pharmacokinet ics. The observed alteration of measured parameters in surgical stress should be attributed to the activating effect of ketanine, presumably on the sympathoadrenal system. Also changes in the patient's psychology were observed after surgical stress and their influence on biochem ical results.
Epilepsy v.A. Karlov, M,A. Gleyzer, N,D. Sorokina. Moscow Medical Stomatological Institute, Russia The aim of the investigation: the study of functional state of the system DOPHA-DA-NA-A under temporal lobe epilepsy. Methods : the estimation of the concentra tion of DOPHA, DA, NA, A in 4 portions of the daily urine as an answer to the injectio n of adrenalini, insulini, DOPHA (reactivity of system), at the same time the clinical tests for estimation of functional state of autonomic nervous system were used (tonus, reactivity, providing). Results : the safety of processes of synthesis in sympatoadrenal system was revealed and at the same time the deterioration of self-regulation in it was observed. The hypoadrenal changes under the biochemical arousing trials and deterioration of providing of autonomic nervous system in clinical tests data were marked. It is supposed the conception of deinnervated hypersensibility of katecholamin ergic neurons,
IP-14-8 ! Psychiatric Morbidity in Candidates for Normal Volunteer Trials
V. Gentil, C. Gorenstein, L. Andrade. Depts. Psychiatry + Pharmacology, Universidade Sao Paulo, Brasil Significant Psychopathology has been detected among "Normal Volunteers" and a full screening is recommended for psychopharmacological trials. We recently requested "Normal volunteers with high school or further education with mild anxiety or irritability complaints, but no significant social or work impairments , for a clinical trial of an antidepressant in normals" . Out of 254 applicants submitted to the self-report questionnaire (SRO-20), only 93 (36.6%) scored below the cut-off level. Of these, 58 were evaluated by a clinical and a PSE-l O/SCAl\' Psychiatric interview and 38 (65.5%) met criteria for one or more lifetime diagnosis (Major Depression, 55%; Dysthymia , 16%; Phobias, 13%. Panic Disorder, 5%; Cyclothmin , 5%; others, 6%). Therefo re only 8% of the applicants met the requested criteria for participation in the clinical trial. In addition, 90.5% of the candidates with present or past psychiatric diagnoses had never sought or received any psychiatric evaluation or care. Public education programmes could help.