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1.
Acta Anaesthesiol Scand ; 53(6): 774-82, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19388889

RESUMO

BACKGROUND: The volatile anesthetic sevoflurane exhibits neuroprotective properties when assessed for motor function and histopathology after cerebral ischemia in rats. Damage of hippocampal neurons after ischemia relates to a number of cognitive deficits that are not revealed by testing animals for motor function. Therefore, the present study evaluates cognitive and behavioral function as well as hippocampal damage in rats subjected to cerebral ischemia under sevoflurane compared with fentanyl/nitrous oxide (N(2)O)/O(2) anesthesia. METHODS: Thirty-four rats were trained for 10 days using a hole-board test to detect changes in cognitive and behavioral function. Rats were randomly assigned to the following groups: (A) sham/fentanyl/N(2)O/O(2) (n=7); (B) ischemia/fentanyl/N(2)O/O(2) (n=10); (C) sham/2.0 vol% sevoflurane in O(2)/air (n=7); and (D) ischemia/2.0 vol% sevoflurane in O(2)/air (n=10). Cerebral ischemia was produced by unilateral common carotid artery occlusion combined with hemorrhagic hypotension (mean arterial blood pressure 40 mmHg for 45 min). Temperature, arterial blood gases, and pH were maintained constant. Cerebral blood flow was measured using laser-Doppler flowmetry. After surgery, cognitive and behavioral function was re-evaluated for 10 days. On day 11, the brains were removed for histopathologic evaluation (hematoxylin/eosin-staining). RESULTS: Cognitive testing revealed deficits in declarative and working memory in ischemic rats anesthetized with fentanyl/N(2)O. Rats anesthetized with sevoflurane during ischemia showed a significantly better outcome. Hippocampal damage was significantly worse with fentanyl/N(2)O. CONCLUSION: The present data add to previous investigations showing that sevoflurane prevents a deficit in cognitive function and histopathological damage induced by cerebral ischemia in rats.


Assuntos
Anestésicos/uso terapêutico , Isquemia Encefálica/complicações , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Éteres Metílicos/uso terapêutico , Desempenho Psicomotor/efeitos dos fármacos , Anestesia , Anestésicos Intravenosos/farmacologia , Animais , Gasometria , Encéfalo/patologia , Isquemia Encefálica/patologia , Transtornos Cognitivos/patologia , Interpretação Estatística de Dados , Fentanila/farmacologia , Imuno-Histoquímica , Masculino , Óxido Nitroso/farmacologia , Ratos , Ratos Sprague-Dawley , Sevoflurano
2.
J Pharmacol Exp Ther ; 325(2): 681-90, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18287214

RESUMO

We have recently proposed the hypothesis that inhibition of the cyclic nucleotide phosphodiesterase (PDE) 10A may represent a new pharmacological approach to the treatment of schizophrenia (Curr Opin Invest Drug 8:54-59, 2007). PDE10A is highly expressed in the medium spiny neurons of the mammalian striatum (Brain Res 985:113-126, 2003; J Histochem Cytochem 54:1205-1213, 2006; Neuroscience 139:597-607, 2006), where the enzyme is hypothesized to regulate both cAMP and cGMP signaling cascades to impact early signal processing in the corticostriatothalamic circuit (Neuropharmacology 51:374-385, 2006; Neuropharmacology 51:386-396, 2006). Our current understanding of the physiological role of PDE10A and the therapeutic utility of PDE10A inhibitors derives in part from studies with papaverine, the only pharmacological tool for this target extensively profiled to date. However, this agent has significant limitations in this regard, namely, relatively poor potency and selectivity and a very short exposure half-life after systemic administration. In the present report, we describe the discovery of a new class of PDE10A inhibitors exemplified by TP-10 (2-{4-[-pyridin-4-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-phenoxymethyl}-quinoline succinic acid), an agent with greatly improved potency, selectivity, and pharmaceutical properties. These new pharmacological tools enabled studies that provide further evidence that inhibition of PDE10A represents an important new target for the treatment of schizophrenia and related disorders of basal ganglia function.


Assuntos
Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/fisiologia , Pirazóis/farmacologia , Quinolinas/farmacologia , Esquizofrenia/tratamento farmacológico , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Dopamina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Inibidores de Fosfodiesterase/sangue , Inibidores de Fosfodiesterase/farmacocinética , Diester Fosfórico Hidrolases/genética , Ratos , Ratos Endogâmicos F344 , Proteínas Recombinantes/antagonistas & inibidores , Proteínas Recombinantes/genética , Reflexo de Sobressalto/efeitos dos fármacos , Esquizofrenia/metabolismo , Esquizofrenia/fisiopatologia
3.
Eur J Anaesthesiol ; 24(12): 1016-20, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17568474

RESUMO

BACKGROUND AND OBJECTIVES: The purpose of this study was to determine whether brain oxyhaemoglobin-deoxyhaemoglobin coupling was altered by anaesthesia or intubation-induced stress. METHODS: This was a prospective observational study in the operating room. Thirteen patients (ASA I and II) undergoing spinal or peripheral nerve procedures were recruited. They were stabilized before surgery with mask ventilation of 100% oxygen. Anaesthesia was induced with 2 microg kg(-1) fentanyl and 3 mg kg(-1) thiopental. Laryngoscopy and intubation were performed 4 min later. After intubation, desflurane anaesthesia (FiO2=1.0) was adjusted to maintain response entropy of the electroencephalogram at 40-45 for 20 min. Prefrontal cortex oxyhaemoglobin and deoxyhaemoglobin were determined every 2 s using frequency domain near-infrared spectroscopy. Blood pressure, heart rate and response entropy were collected every 10 s. RESULTS: Awake oxyhaemoglobin and deoxyhaemoglobin were 18.9 +/- 2.3 micromol (mean +/- SD) and 12.7 +/- 0.8 micromol, respectively, and neither changed significantly during induction. Intubation increased oxyhaemoglobin by 37% (P < 0.05) and decreased deoxyhaemoglobin by 16% (P < 0.05), and both measures returned to baseline within 20 min of desflurane anaesthesia. Blood pressure, heart rate and electroencephalogram response entropy increased during intubation, and the increase in heart rate correlated with the increase in brain oxygen saturation (r = 0.48, P < 0.05). CONCLUSIONS: Intubation-related stress increased oxyhaemoglobin related to electroencephalogram and autonomic activation. Stress-induced brain stimulation may be monitored during anaesthesia using frequency domain near-infrared spectroscopy.


Assuntos
Encéfalo/metabolismo , Intubação Intratraqueal/efeitos adversos , Oxigênio/farmacologia , Oxiemoglobinas/metabolismo , Estresse Psicológico/metabolismo , Adulto , Anestésicos/farmacologia , Anestésicos/uso terapêutico , Sistema Nervoso Autônomo/metabolismo , Pressão Sanguínea/fisiologia , Desflurano , Feminino , Fentanila/farmacologia , Fentanila/uso terapêutico , Frequência Cardíaca/fisiologia , Hemoglobinas/metabolismo , Humanos , Isoflurano/análogos & derivados , Isoflurano/farmacologia , Isoflurano/uso terapêutico , Laringoscopia , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória/métodos , Estudos Prospectivos , Tiopental/farmacologia , Tiopental/uso terapêutico
4.
Pediatr Dent ; 27(6): 500-4, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16532892

RESUMO

PURPOSE: Pediatric oral rehabilitation patients who receive presedation with oral Versed and general anesthesia (GA) occasionally experience prolonged sedation and delayed discharge. The Bispectral Index System (BIS) is an EEG monitor that measures the anesthesia level. The purpose of this study was to compare the effects of monitoring the BIS to not monitoring the BIS on time from discontinuation of GA to extubation and to discharge. METHODS: Twenty-nine children were enrolled. BIS was monitored from admission until discharge. Each child received 0.7 mg/kg of oral Versed. In the operating room, GA with sevoflurane (IH), rocuronium 1 mg/kg (IV), fentanyl 1 microg/kg (IV), and ondansetron 0.15 mg/kg (IV) was administered. Randomly, in half the patients, the anesthesiologist maintained the level of anesthesia and BIS by adjusting sevoflurane. In the rest, the anesthesiologist did not know BIS. The time from turning off sevoflurane to discharge was compared. RESULTS: Group 1 patients were extubated 5+/-2 minutes sooner than group 2 patients (P=.04). The post-anesthesia care unit stay for group 1 patients was 47+/-17 minutes compared to 63+/-17 minutes in group 2. (p=0.02). CONCLUSIONS: Monitoring anesthesia with BIS promotes earlier extubation and discharge for pediatric dental patients who receive oral Versed and sevoflurane GA.


Assuntos
Período de Recuperação da Anestesia , Anestesia Dentária/métodos , Anestesia Geral/métodos , Monitorização Intraoperatória/instrumentação , Medicação Pré-Anestésica , Administração Oral , Procedimentos Cirúrgicos Ambulatórios , Anestesia Dentária/instrumentação , Anestesia Geral/instrumentação , Anestésicos Inalatórios/administração & dosagem , Pressão Sanguínea , Pré-Escolar , Dentística Operatória , Cuidado Periódico , Feminino , Frequência Cardíaca , Humanos , Hipnóticos e Sedativos/administração & dosagem , Masculino , Éteres Metílicos/administração & dosagem , Midazolam/administração & dosagem , Monitorização Intraoperatória/métodos , Estudos Prospectivos , Sevoflurano , Método Simples-Cego , Titulometria
5.
Pediatr Dent ; 26(3): 256-60, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15185808

RESUMO

PURPOSE: Pediatric patients who receive both intramuscular (i.m.) sedation and general anesthesia (GA) for oral rehabilitation occasionally experience prolonged sedation and delayed discharge. The Bispectral Index System (BIS) is an EEG monitor that measures the level of sedation. The authors compared discharge times of patients who had BIS monitoring to those who did not to determine if the use of BIS speeded discharge. METHODS: After IRB approval, 20 children were enrolled. BIS was monitored continuously from admission until discharge. Each child received ketamine, midazolam, and glycopyrrolate i.m. Once sedated, the patient was transferred to the operating room, monitored, and i.v. access was established. GA proceeded with sevoflurane, rocuronium, and fentanyl. Randomly, in half the patients, the anesthesiologist knew and maintained the BIS at GA level of sedation by adjusting sevoflurane. In the rest, the anesthesiologist did not know BIS. Time from turning of sevoflurane to discharge was noted and compared. RESULTS: Patients where the BIS was known and used were discharged 60+/-13 minutes after the end of GA. Patients where BIS was unknown were discharged 90+/-11 minutes after the end of GA (P<.001). CONCLUSIONS: Based on the data, the authors recommend the use of BIS to facilitate faster discharge of pediatric patients who require i.m. sedation and GA for oral rehabilitation.


Assuntos
Anestesia Dentária , Anestesia Geral , Sedação Consciente , Eletroencefalografia/métodos , Monitorização Fisiológica/métodos , Reabilitação Bucal , Adjuvantes Anestésicos/administração & dosagem , Adolescente , Assistência Ambulatorial , Período de Recuperação da Anestesia , Anestésicos Dissociativos/administração & dosagem , Anestésicos Inalatórios/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Criança , Pré-Escolar , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Injeções Intramusculares , Masculino , Alta do Paciente , Processamento de Sinais Assistido por Computador , Fatores de Tempo
6.
Acta Anaesthesiol Scand ; 47(2): 221-5, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12631053

RESUMO

BACKGROUND: Reports show that glyburide, an adenosine triphosphate sensitive potassium (K+ATP) channel blocker, will reverse the myocardial protective effect of inhalational anesthesia. We evaluated the effect of glyburide on myocardial tissue oxygen pressure (PmO2) in dogs anesthetized with desflurane. METHODS: Twelve dogs were anesthetized with 8% end-tidal desflurane for baseline anesthesia. A flow probe was placed on the left anterior descending (LAD) artery. A probe that measured PmO2 was inserted into the middle myocardium in the LAD region. After baseline measures, six dogs received i.v. 1 mg kg(-1) of glyburide and six dogs received sham vehicle treatment. After the glyburide or sham treatment, each dog received an i.v. infusion of adenosine 0.1 microg kg(-1) x min(-1), sodium nitroprusside (SNP) 2-4 microg kg(-1) x min(-1) and 14% end-tidal desflurane in random order. RESULTS: Glyburide decreased LAD artery flow from 59 +/- 9 ml min(-1) to 30 +/- 6 ml min(-1) (P < 0.05) and PmO2 from 44 +/- 16 mmHg to 30 +/- 9 mmHg (P < 0.05). Adenosine infusion increased LAD artery blood flow 180% in the sham-treated dogs but produced no change in the glyburide-treated dogs. Sodium nitroprusside infusion increased LAD artery flow and decreased PmO2 in both the glyburide- and sham-treated dogs. Desflurane (14%) did not reverse the glyburide-induced vasoconstriction but increased PmO2 to 38 +/- 20 mmHg (P < 0.05). CONCLUSION: Glyburide produced myocardial tissue hypoxia, which was not changed by adenosine, worsened by SNP and improved by 14% desflurane. The improvement in PmO2 with desflurane occurred without a change in myocardial blood flow.


Assuntos
Glibureto/farmacologia , Isoflurano/análogos & derivados , Miocárdio/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/farmacologia , Adenosina/farmacologia , Anestésicos Inalatórios/farmacologia , Animais , Gasometria , Pressão Sanguínea/efeitos dos fármacos , Circulação Coronária/efeitos dos fármacos , Depressão Química , Desflurano , Cães , Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Isoflurano/farmacologia , Masculino , Nitroprussiato/farmacologia , Vasodilatadores/farmacologia
7.
J Neurosurg Anesthesiol ; 13(4): 303-9, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11733661

RESUMO

Myocardial tissue oxygen pressure (PmO2 ) and left anterior descending (LAD) artery blood flow were measured in dogs anesthetized with 1.5% isoflurane, and were then compared to brain tissue oxygen pressure (PbO2 ) and middle cerebral artery (MCA) blood flow during normocapnia, hypocapnia, and hypercapnia. A craniotomy was performed and a tissue probe (Codman, Inc.) that measures PO2, PCO2, and pH was inserted into the brain cortex in the MCA region (n = 8). Separately, after a thoracotomy, a probe was inserted into the middle myocardium of the left ventricle, within the distribution of the LAD, in eight dogs. Blood flow probes were placed on the LAD or MCA. Blood flow and tissue gases were measured during normocapnia (PaCO2 = 38 mm Hg), hypocapnia (PaCO2 = 26 mm Hg), and hypercapnia (PaCO2 = 53 mm Hg). Mean arterial pressure, heart rate, arterial gases, and pH were not different between brain and heart measurements. PbO2 was 21 +/- 9 mm Hg (mean +/- SD ), 40 +/- 16 mm Hg, and 47 +/- 11 mm Hg. PmO2 was 35 +/- 12 mm Hg, 40 +/- 14 mm Hg, and 48 +/- 15 mm Hg during hypocapnia, normocapnia, and hypercapnia respectively. During hypercapnia, LAD and MCA flow increased 50% and tissue oxygenation increased 20% ( P < .05). During hypocapnia, MCA flow and PbO2 decreased 50% ( P < .05), but LAD flow and PmO2 did not significantly change. These results indicated that LAD flow and myocardial PO2 were less responsive to hypocapnia than MCA flow and PbO2.


Assuntos
Química Encefálica/fisiologia , Dióxido de Carbono/sangue , Miocárdio/metabolismo , Consumo de Oxigênio/fisiologia , Animais , Gasometria , Cães , Hemodinâmica/fisiologia , Concentração de Íons de Hidrogênio , Hipercapnia/metabolismo , Hipocapnia/metabolismo , Masculino
8.
Anesth Analg ; 93(1): 166-70, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11429359

RESUMO

UNLABELLED: We compared sodium nitroprusside (SNP)-induced hypotension with 3% isoflurane-induced hypotension with regard to brain tissue oxygen pressure (PtO(2)), middle cerebral artery (MCA) blood flow, and cerebral arteriovenous shunting. Eight dogs were anesthetized with 1.5% isoflurane. After a craniotomy, a probe was inserted into the left frontoparietal brain cortex to mea-sure tissue gases and pH. Blood flow was measured in a secondary branch of the MCA by a flowprobe. Measurements were made during baseline 1.5% isoflurane, during 1.5% isoflurane and SNP-induced hypotension or 3% isoflurane-induced hypotension to a mean pressure of 60-65 mm Hg, and during continued treatment with SNP or 3% isoflurane with blood pressure support to baseline levels with phenylephrine. Shunting was calculated from arterial, sagittal sinus, and tissue (indicating capillary) oxygen content. During hypotension with SNP, PtO(2) decreased 50%, and shunting increased 50%. During hypotension with 3% isoflurane, PtO(2) and shunting did not change. Blood pressure support increased PtO(2) and MCA flow during both SNP and 3% isoflurane treatment. These results show that SNP is a cerebrovasodilator but that hypotension will decrease PtO(2), probably because of an increase in arteriovenous shunting and a decrease in capillary perfusion. IMPLICATIONS: We measured brain arteriovenous shunting and tissue oxygen pressure(PtO(2))during a 40% decrease in blood pressure induced by sodium nitroprusside (SNP)or 3% isoflurane. Large-dose isoflurane maintainedPtO(2) with no change in shunting. SNP infusion decreasedPtO(2) 50%and increased shunting 50%. This suggests that SNP-induced hypotension decreases PtO(2) because of a decrease in capillary perfusion.


Assuntos
Anestésicos Inalatórios/farmacologia , Anti-Hipertensivos/farmacologia , Fístula Arteriovenosa/induzido quimicamente , Química Encefálica/efeitos dos fármacos , Hipotensão/induzido quimicamente , Isoflurano/farmacologia , Nitroprussiato/farmacologia , Consumo de Oxigênio/efeitos dos fármacos , Animais , Gasometria , Temperatura Corporal/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Cães , Hemodinâmica/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Hipotensão/fisiopatologia , Artéria Cerebral Média/fisiologia
9.
J Neurosurg Anesthesiol ; 13(2): 74-8, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11294461

RESUMO

During rapid opioid detoxification, increased sympathetic activity and a greater median frequency (MF) of activity on electroencephalography (EEG) have been reported. The purpose of this study was to evaluate a new index for detoxification that combines sympathetic activity and MF data. After informed consent was obtained, eight patients were sedated with propofol. The MF of EEG activity derived from frontal electrodes was determined. Heart rate variability was evaluated in 256-second segments by power spectral analysis, and sympathetic activity was determined by the low frequency component. The Hoffman Index for narcotic detoxification was weighted 70% to sympathetic activity and 30% to MF to normalize the difference in scales and to provide adequate weight to the sympathetic component. Opioid detoxification was produced by infusion of 25 mg naloxone for 30 minutes, followed by a 24-hour infusion of 1 mg per hour. The MF showed a rapid increase during high-dose infusion of naloxone, but the peak response occurred 1 to 2 hours later. Sympathetic activation and the Hoffman Index increased more slowly after the start of naloxone infusion, but peak increases in all components occurred at approximately the same time. The peak increases in Hoffman Index (110% of baseline), MF (260%), and sympathetic activity (304%) during administration of naloxone were significant and correlated with respect to time (r = 0.89-0.94). The Hoffman Index showed an early increase related to MF and a well-defined peak response indicative of sympathetic and MF activity. The behavior of the Hoffman Index in relation to the MF and sympathetic activity more clearly indicated the onset of opioid detoxification and the maximum response to opioid reversal than did MF or sympathetic activity alone.


Assuntos
Eletroencefalografia , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Transtornos Relacionados ao Uso de Opioides/terapia , Sistema Nervoso Simpático/fisiologia , Eletrocardiografia , Humanos , Hipnóticos e Sedativos/farmacologia , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Propofol/farmacologia
10.
J Addict Dis ; 19(4): 59-64, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11110065

RESUMO

Orogastric naltrexone is used for opioid detoxification, but it is not known how gastric absorption affects plasma concentrations of the drug. We measured plasma naltrexone during orogastric naltrexone, given in repeated doses of 12.5 mg, 25 mg, 50 mg and 50 mg. Plasma naltrexone was measured after each naltrexone dose. The increase in plasma naltrexone was highly variable between patients during orogastric administration. Adequate detoxification was questioned in 4 of 10 patients because plasma naltrexone did not increase above 5 ng/ml. There was a negative correlation between plasma naltrexone and the presence of withdrawal symptoms on the day after the procedure (r = -0.78, P < 0.05). These results show that the increase in plasma naltrexone is variable during orogastric administration and this may impair successful detoxification.


Assuntos
Naltrexona/sangue , Antagonistas de Entorpecentes/sangue , Entorpecentes/farmacocinética , Síndrome de Abstinência a Substâncias/sangue , Administração Oral , Relação Dose-Resposta a Droga , Humanos , Inativação Metabólica , Naltrexona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Entorpecentes/efeitos adversos , Fatores de Tempo
11.
Neurol Res ; 22(6): 620-2, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11045027

RESUMO

Brain tissue oxygen reactivity is a measure of the increase in tissue oxygen pressure (PtO2) relative to an increase in arterial oxygen pressure (PaO2). Clinical studies show that PtO2 reactivity is increased after cerebral injury. However, the impact of patient ventilation on these measures is not known. We determined whether changes in end tidal carbon dioxide pressure (ETCO2) would affect PtO2 reactivity in dogs. After a craniotomy, a Neurotrend probe that measures PtO2 was inserted into the cerebral cortex of eight dogs. PtO2 reactivity was measured at five concentrations of inspired oxygen (room air, 40%, 60%, 80%, 95%) at three levels of ETCO2 (20 mmHg, 40 mmHg, 60 mmHg) in random order. PtO2 reactivity at ETCO2 of 20 mmHg was 0.2 and increased to 0.3 when ETCO2 was 40 mmHg was 0.4 when ETCO2 was 60 mmHg (p < 0.05). These results show that PtO2 reactivity increases from hypocapnia to normocapnia. It is important to consider the ventilation state of each patient when evaluating PtO2.


Assuntos
Encéfalo/metabolismo , Dióxido de Carbono/sangue , Consumo de Oxigênio , Oxigênio/sangue , Animais , Gasometria/instrumentação , Gasometria/métodos , Calibragem , Cães , Humanos , Pressão Parcial , Valores de Referência , Respiração
12.
Neurol Res ; 22(6): 642-4, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11045031

RESUMO

Neurosurgical monitoring devices have recently become available which are capable of measuring cerebral tissue gas tensions and pH. Brain tissue sensors have not been conclusively demonstrated to correlate with other measurements of regional cerebral gas tensions or pH. The present study was undertaken to correlate sensor values for pO2, pCO2 and pH with blood samples taken concurrently from local cerebral veins. Adult mongrel dogs were anesthetized and a craniotomy was performed. A small gyral vein was isolated and cannulated. Adjacent to the venous catheter tip, a Neurotrend brain tissue probe was inserted in an intracortical location. Each subject received a sequence of manipulations in inspired oxygen and end tidal carbon dioxide conditions. Under each experimental condition, samples of arterial and gyral venous blood were obtained and blood gas analysis performed. Concurrent brain probe measurements of tissue pO2, pCO2 and pH were recorded. Statistical analysis determined that local tissue and cerebral venous blood values for pO2, pCO2 and pH were highly correlated (R(s) = 0.62-0.82; p < 0.001). This indicates that there exists a confirmable monotonic relationship between tissue values and conditions in the post-capillary venous bed. Tissue sensors such as the Neurotrend probe can offer reliable trend indications in brain tissue gas tensions and pH.


Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Dióxido de Carbono/sangue , Veias Cerebrais/fisiologia , Concentração de Íons de Hidrogênio , Oxigênio/sangue , Animais , Gasometria/instrumentação , Gasometria/métodos , Cães , Masculino , Oxigênio/análise , Pressão Parcial , Reprodutibilidade dos Testes
13.
Anesth Analg ; 91(3): 637-41, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10960391

RESUMO

UNLABELLED: We tested the possibility that large-dose isoflurane will produce a loss of brain tissue oxygen regulation in dogs. A total of 12 dogs were anesthetized with isoflurane, a craniotomy was performed, and a probe was inserted to measure brain tissue oxygen pressure (PtO(2)), carbon dioxide, and pH. Baseline measures were made during 1.5% end-tidal isoflurane with 30% oxygen ventilation, followed by 95% oxygen ventilation. Six dogs (Group 1) were treated with 3% isoflurane and 30% oxygen, followed by a second oxygen challenge with 95% O(2). Six dogs (Group 2) received propofol to produce a similar suppression of the electroencephalogram as in Group 1, followed by 95% oxygen ventilation. Brain tissue oxygen reactivity was calculated by the increase in PtO(2) divided by the increase in arterial PO(2). During 1.5% isoflurane and propofol anesthesia, PtO(2) increased from 42 to 62 mm Hg with oxygen ventilation, and brain tissue oxygen reactivity was 0.14% per mm Hg(-1). Brain tissue oxygen reactivity did not change during propofol anesthesia. With 3% isoflurane, PtO(2) increased from 52 to 113 mm Hg and brain tissue oxygen reactivity was 0.36% per mm Hg(-1) (P: < 0.05). These results suggest that the cerebrovasodilator and vasoplegic effects of large-dose isoflurane attenuate brain oxygen regulation. IMPLICATIONS: We evaluated the ability of oxygen ventilation to increase brain tissue oxygen pressure in dogs anesthetized with 1.5% and 3% isoflurane and propofol. Increases in tissue oxygen were significantly greater during 3% isoflurane compared with 1.5% isoflurane and propofol.


Assuntos
Anestésicos Inalatórios/farmacologia , Química Encefálica/efeitos dos fármacos , Isoflurano/farmacologia , Consumo de Oxigênio/efeitos dos fármacos , Algoritmos , Anestesia , Anestésicos Intravenosos/farmacologia , Animais , Gasometria , Pressão Sanguínea/efeitos dos fármacos , Cães , Eletroencefalografia/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Propofol/farmacologia
14.
J Neurosurg Anesthesiol ; 12(2): 95-8, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10774602

RESUMO

It is reported that high dose desflurane can increase brain tissue oxygen pressure (PtO2) in patients during cerebral aneurysm surgery. The purpose of this study was to determine whether high dose isoflurane anesthesia can produce a similar effect in dogs and the importance of cerebral perfusion pressure in mediating this effect. Six dogs were anesthetized, and ventilated with isoflurane inspired oxygen concentration of 40%. Following a craniotomy, a catheter was inserted into the sagittal sinus for cerebral venous blood samples and a Neurotrend probe was inserted into cortex brain tissue to measure PtO2, carbon dioxide pressure (PtCO2), and pH (pHt). Brain tissue and arterial and sagittal sinus blood gas tensions and pH were measured under the following conditions: 1 = baseline 1.5% isoflurane, 2 = 1.5% isoflurane + increase mean arterial pressure (MAP) by 50 mm Hg, 3 = 3% isoflurane anesthesia, 4 = 3% isoflurane anesthesia + increase MAP 55 mm Hg, 5 = 1.5% isoflurane anesthesia, 6 = 1.5% isoflurane anesthesia + increase MAP 35 mm Hg. In the first and second trial with 1.5% end-tidal isoflurane, PtO2 increased 15% during an increase in MAP without a change in sagittal sinus oxygenation. At 3% isoflurane, PtO2 increased 90% and sagittal sinus PO2 increased 38% during an increase in MAP. These results show that the cerebral metabolic depression and cerebrovasodilatory effects of high dose isoflurane can enhance brain tissue oxygenation. Normal brain vascular regulation that limits hyperperfusion and hyperoxygenation of brain tissue is antagonized by high dose isoflurane.


Assuntos
Anestesia por Inalação , Córtex Cerebral/metabolismo , Isoflurano/farmacologia , Consumo de Oxigênio/efeitos dos fármacos , Oxigênio/sangue , Anestésicos Inalatórios/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Dióxido de Carbono/sangue , Córtex Cerebral/efeitos dos fármacos , Cães , Frequência Cardíaca/efeitos dos fármacos
15.
Anesthesiology ; 92(2): 442-6, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10691231

RESUMO

BACKGROUND: Subarachnoid hemorrhage can lead to cerebral ischemia and irreversible brain injury. The purpose of this study was to determine whether subarachnoid hemorrhage produces changes in brain tissue oxygen pressure, carbon dioxide pressure, or pH during surgery for cerebral aneurysm clipping. METHODS: After institutional review board approval and patient consent, 30 patients undergoing craniotomy for cerebral aneurysm clipping were studied, 15 without and 15 with subarachnoid hemorrhage. Patients with subarachnoid hemorrhage were prospectively separated into groups with modest (Fisher grade 1 or 2; n = 8) and severe bleeds (Fisher grade 3; n = 7). After a craniotomy, a probe was inserted into cortex tissue supplied by the artery associated with the aneurysm. Baseline measures were made in the presence of a 4% end-tidal desflurane level. The end-tidal desflurane level was increased to 9% before clipping of the aneurysm, and a second tissue measurement was made. RESULTS: The median time of surgery after subarachnoid hemorrhage was 2 days, ranging from 1 to 13 days. During baseline anesthesia, brain tissue oxygen pressure was 17+/-9 mm Hg (mean +/- SD) in control patients, 13+/-9 mm Hg in those with Fisher grade 1 or 2 hemorrhage, and 7+/-6 mm Hg in those with Fisher grade 3 hemorrhage (P<0.05 compared with control). Brain tissue pH was 7.10+/-0.10 in control patients, 7.14+/-0.13 in those with Fisher grade 1 or 2 hemorrhage, and 6.95+/-0.18 in those with with Fisher grade 3 hemorrhage (P<0.05). At a 9% end-tidal desflurane level, brain tissue oxygen pressure increased to 19+/-9 mm Hg and brain tissue pH increased to 7.11+/-0.11 in patients with Fisher grade 3 hemorrhage (P<0.05 for both increases). CONCLUSION: These results show that subarachnoid hemorrhage can significantly decrease brain tissue oxygen pressure and pH related to the severity of the bleed. Increasing the desflurane concentration to 9% increased brain tissue oxygen pressure in all patients and brain tissue pH in patients with subarachnoid hemorrhage with baseline acidosis.


Assuntos
Química Encefálica/fisiologia , Hipóxia Encefálica/metabolismo , Hemorragia Subaracnóidea/metabolismo , Adulto , Idoso , Anestésicos Inalatórios/administração & dosagem , Temperatura Corporal/fisiologia , Dióxido de Carbono/metabolismo , Desflurano , Feminino , Humanos , Concentração de Íons de Hidrogênio , Hipóxia Encefálica/etiologia , Aneurisma Intracraniano/cirurgia , Isoflurano/administração & dosagem , Isoflurano/análogos & derivados , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Estudos Prospectivos , Hemorragia Subaracnóidea/complicações
16.
Surg Neurol ; 54(6): 432-7; discussion 438, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11240169

RESUMO

BACKGROUND: The purpose of the present study was to assess brain tissue monitoring for detection of ischemia due to vasospasm in aneurysmal subarachnoid hemorrhage (SAH) patients. METHODS: After obtaining informed consent, a burr hole was made in 10 patients and a Neurotrend 7 probe was inserted ipsilateral to the region of SAH. In eight patients the probe was inserted during surgery for clipping the aneurysm and in two patients the probe was inserted in the neurosurgery ICU. Brain tissue gases and pH were collected over 6-hour periods for 7 to 10 days until the termination of monitoring. The onset of vasospasm was confirmed by angiography and xenon computed tomography (Xe/CT) cerebral blood flow studies. RESULTS: Seven patients did not develop vasospasm during monitoring and were considered as controls. In this group, brain tissue oxygen pressure (PO(2)) remained above 20 mmHg, carbon dioxide pressure (PCO(2)) stabilized at 40 mmHg and pH remained between 7.1 and 7.2. In three patients who developed vasospasm during monitoring, PO(2) was not different from the control group. However, PCO(2) increased to 60 mmHg and pH decreased to 6.7 (p < 0.001). CONCLUSION: In this study, patients with SAH who developed vasospasm had significantly lower brain tissue pH and higher PCO(2) compared to controls. However, there was no significant change in PO(2) levels associated with vasospasm. Brain tissue monitoring can provide an indication of ischemia during vasospasm.


Assuntos
Isquemia Encefálica/diagnóstico , Encéfalo/metabolismo , Dióxido de Carbono/metabolismo , Hidrogênio/metabolismo , Oxigênio/metabolismo , Hemorragia Subaracnóidea/complicações , Vasoespasmo Intracraniano/metabolismo , Idoso , Isquemia Encefálica/etiologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Aneurisma Intracraniano/complicações , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Pressão Parcial , Vasoespasmo Intracraniano/complicações
17.
J Neurosurg ; 91(6): 1050-4, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10584856

RESUMO

Quantitative measurement of blood flow in cerebral vessels during aneurysm surgery can help prevent ischemic injury and improve patient outcome. The authors report a case of a superior cerebellar artery (SCA) aneurysm in which perivascular microflow probes were used to measure blood flow quantitatively in both the SCA and the posterior cerebral artery before and after aneurysm clipping. Following aneurysm clipping, blood flow in the SCA was reduced to less than 25% of its initial baseline value. Prompt detection of compromised blood flow gave the surgeon the opportunity to adjust the clip and restore SCA flow to its preclipping value within 5 minutes of initial clip placement. Quantitative vessel-flow measurements were integral to the safe progression of the operation and may have prevented an adverse neurological outcome in this patient. The recommended surgical technique and the principle of operation are described.


Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Aneurisma Intracraniano/cirurgia , Fluxometria por Laser-Doppler/instrumentação , Monitorização Intraoperatória/instrumentação , Idoso , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/prevenção & controle , Cerebelo/irrigação sanguínea , Feminino , Humanos , Aneurisma Intracraniano/fisiopatologia , Complicações Intraoperatórias/fisiopatologia , Complicações Intraoperatórias/prevenção & controle , Artéria Cerebral Posterior/fisiopatologia , Instrumentos Cirúrgicos
18.
J Neurosurg Anesthesiol ; 11(4): 255-9, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10527144

RESUMO

Sympathetic heart rate variability is correlated with the increase in plasma catecholamines during rapid opioid detoxification. We evaluated whether the bispectral index, median frequency, or 95% spectral edge of the electroencephalogram are sensitive to the sympathetic response seen during reversal of opioid dependence. Eight patients undergoing rapid opioid detoxification gave informed consent. Two-channel frontal electroencephalogram was measured. Sympathetic heart rate variability was measured in 256 second segments by Fourier transform of continuous heart rate and the low frequency segment (0.02-0.13 Hz) analyzed for sympathetic function. Patients were anesthetized with propofol infusion. After a 30-60 min steady state, naloxone was infused intravenously at a rate of 25 mg/30 min, followed by an infusion of 1 mg/hr. During induction of anesthesia, sympathetic heart rate variability decreased from 1.80 to 0.3, bispectral index from 86 to 47, median frequency from 10.2 to 3.4, spectral edge from 23.5 to 16.7 (all P<.05). During naloxone infusion, the median percent increase in sympathetic heart rate variability was 487% (P<.05), median frequency increased 163% (P<.05), bispectral index (10%), and spectral edge (7%) did not significantly change. The increase in median frequency was delayed compared to sympathetic heart rate variability and median frequency remained elevated after sympathetic heart rate variability returned to anesthetized baseline in 5 of 8 cases. Our results show that median frequency and sympathetic heart rate variability increase during opioid detoxification, but the time course of each response is different. Median frequency is a more sensitive electroencephalogram indicator of opioid reversal than bispectral index or spectral edge.


Assuntos
Anestesia Intravenosa , Eletroencefalografia , Frequência Cardíaca , Síndrome de Abstinência a Substâncias/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Eletroencefalografia/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Naloxona , Transtornos Relacionados ao Uso de Opioides/reabilitação , Propofol/farmacologia , Sensibilidade e Especificidade , Fatores de Tempo
19.
Anesth Analg ; 89(3): 679-83, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10475305

RESUMO

UNLABELLED: Cerebral venous blood gas values have been used to indicate brain tissue oxygenation. However, it is not clear how cerebral tissue and venous measures may vary under physiologic conditions caused by arteriovenous shunt. The purpose of this study was to measure brain tissue and local cerebral venous oxygen (PO2) and carbon dioxide (P(CO2)) partial pressure during changes in ventilation and to calculate shunt fraction. Eight dogs were anesthetized with isoflurane. After a craniotomy, a Neurotrend probe (Diametrics Inc., St. Paul, MN) that measures P(O2), P(CO2), pH, and temperature was inserted into brain tissue, and a small vein that drained the same tissue was catheterized. Arterial, cerebral venous, and brain tissue P(O2) and Pco2 were measured during random changes in ventilation to produce five different levels of inspired oxygen (room air, 40%, 60%, 80%, 95%) at each of three different end-tidal Pco2 (20 mm Hg, 40 mm Hg, 60 mm Hg). Arteriovenous shunt was calculated from oxygen and C(O2) content in artery, vein, and tissue, representing capillary. Tissue P(CO2) was 8 mm Hg greater than vein Pco2 during hypocapnia and this difference increased to 20 mm Hg during hypercapnia. Vein P(O2) was 8 mm Hg higher than tissue P(O2) during hypocapnia, and this difference increased to 40 mm Hg during hypercapnia. Shunt fraction increased from 10%-20% during hypocapnia to 50%-60% during hypercapnia. These results show that brain vein and tissue P(O2) and P(CO2) differ because of arteriovenous shunting and this difference is increased as end-tidal P(CO2) increases. IMPLICATIONS: We found, in dogs, that the gradient between brain venous and tissue P(O2) and PCO2 is increased with increased arterial P(CO2). The divergence between tissue and venous gases can be described by arterial to venous shunting.


Assuntos
Derivação Arteriovenosa Cirúrgica , Química Encefálica/fisiologia , Circulação Cerebrovascular/fisiologia , Animais , Gasometria , Temperatura Corporal/fisiologia , Dióxido de Carbono/sangue , Veias Cerebrais , Cães , Concentração de Íons de Hidrogênio , Oxigênio/sangue , Mecânica Respiratória/fisiologia
20.
J Neurosurg Anesthesiol ; 11(3): 195-9, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10414675

RESUMO

It has been shown that rapid opioid detoxification is associated with increased sympathetic activity (SYMP) and plasma catecholamines. Heart rate (HR) variability may provide a noninvasive method of evaluating withdrawal and sympathetic activation caused by the reversal of opioid binding in patients who are opioid dependent. The purpose of this study was to evaluate the relationship between HR variability and plasma catecholamines during opioid detoxification. Patients were anesthetized with propofol, intubated, paralyzed with rocuronium infusion, and ventilated. The bispectral index (BIS) of the electroencephalogram was recorded with the patient awake as well as during propofol anesthesia. SYMP was determined by power spectral analysis of HR variability. Plasma epinephrine and norepinephrine were measured at baseline propofol anesthesia and during naltrexone treatment in eight opioid-dependent patients. Nonopioid-dependent controls (n = 7) were monitored during surgery without naltrexone treatment or measurement of plasma catecholamines. Compared with an awake status, propofol anesthesia significantly decreased the BIS and SYMP in both groups of patients. Controls showed no change from baseline anesthetized levels during surgery. Plasma norepinephrine and epinephrine as well as SYMP increased 300 to 400% (P < .05) during naltrexone treatment in opioid-dependent patients, and the time to peak increase in plasma norepinephrine correlated with the increase in SYMP (r = 0.89, P < .01). These results confirm that opioid detoxification increases plasma catecholamines and SYMP in a similar manner. HR rate variability may provide a low-cost real-time noninvasive method of evaluating the reversal of opioid binding in opioid-dependent patients.


Assuntos
Epinefrina/sangue , Frequência Cardíaca/fisiologia , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Norepinefrina/sangue , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Simpatomiméticos/sangue , Adulto , Análise de Variância , Anestésicos Intravenosos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Eletroencefalografia/efeitos dos fármacos , Feminino , Humanos , Masculino , Propofol/administração & dosagem , Processamento de Sinais Assistido por Computador , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Sistema Nervoso Simpático/efeitos dos fármacos , Vigília
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