RESUMO
Intravenous infusion of morphine sulfate in rats for 24 hours produced marked opioid dependence, manifested by a series of well-documented signs appearing after injection of the opiate antagonist naloxone. Treatment of rats with naloxonazine significantly reduced the analgesia associated with the morphine infusions for more than 24 hours. Furthermore, 14 of 16 withdrawal signs observed in naloxonazine-treated rats were virtually identical to those in rats that received morphine alone. These results raise the possibility that different receptor mechanisms mediate morphine analgesia and many of the withdrawal signs associated with morphine dependence.
Assuntos
Analgesia , Morfina/farmacologia , Naloxona/análogos & derivados , Transtornos Relacionados ao Uso de Substâncias , Animais , Humanos , Masculino , Naloxona/farmacologia , Ratos , Ratos Endogâmicos , Síndrome de Abstinência a SubstânciasRESUMO
In the aftermath of the devastating Haitian earthquake, we became the primary relief service for a large group of severely injured earthquake victims. Finding ourselves virtually isolated with extremely limited facilities and a group of critically injured patients whose needs vastly outstripped the available resources we employed a disaster triage system to organize their clinical care. This report describes the specific injury profile of this group of patients, their clinical course, and the management philosophy that we employed. It provides useful lessons for similar situations in the future.
Assuntos
Planejamento em Desastres/organização & administração , Terremotos , Serviços Médicos de Emergência/organização & administração , Traumatismo Múltiplo/terapia , Triagem/organização & administração , Ferimentos e Lesões/terapia , Feminino , Haiti/epidemiologia , Humanos , Masculino , Incidentes com Feridos em Massa , Traumatismo Múltiplo/epidemiologia , Úlcera por Pressão/epidemiologia , Úlcera por Pressão/terapia , Sepse/epidemiologia , Ferimentos e Lesões/epidemiologiaRESUMO
We tested whether the existence of saturable binding sites for anesthetics causes the solubility of halothane or isoflurane in rabbit brain not to obey Henry's law. For each anesthetic, we measured brain/gas partition coefficients (paired samples) at approximately 0.05 MAC and 5 MAC at 38.5 degrees C. In addition, for halothane, brain/gas partition coefficients (paired samples) were determined at 0.05 MAC and 2 MAC. The values for halothane at 0.05 MAC, 2 MAC, and 5 MAC did not differ; values for isoflurane at 0.05 MAC and 5 MAC did not differ. Over the range of anesthetic partial pressures studied, no evidence for saturable binding was found. We conclude that the solubility of halothane and isoflurane in brain is independent of the partial pressure applied; inhaled anesthetics obey Henry's law.
Assuntos
Encéfalo/metabolismo , Halotano/metabolismo , Isoflurano/metabolismo , Anestesia por Inalação , Animais , Sítios de Ligação , Fenômenos Químicos , Físico-Química , Cromatografia Gasosa , Halotano/análise , Técnicas In Vitro , Isoflurano/análise , Masculino , Pressão Parcial , Coelhos , SolubilidadeRESUMO
Findings on plain chest radiographs of patients with aortic dissection are variable and often overlap those of patients without dissection. To determine which findings were most useful in predicting aortic dissection, plain chest radiographs from 36 patients with aortographically proven aortic dissection and 36 patients from a control population were randomized and analyzed independently by five radiologists for the presence of various radiographic features associated with this condition. A widened aortic knob, widened descending aorta, and widened mediastinum showed the greatest interobserver agreement (p less than .001) although the overall interobserver agreement was poor. The final conclusion of the radiologists was a better predictor of dissection than any of the individual radiographic features alone. Widening of the mediastinum (p less than .001) and widening of the aortic knob (p less than .012) were the only two radiographic features of significance in predicting dissection. In a stepwise multiple logistic regression model, the radiologists achieved an overall accuracy of 85%, a sensitivity of 81%, and a specificity of 89%. Although this illustrates the usefulness of plain chest radiographs in diagnosing aortic dissection, poor interobserver agreement dictates that further definitive investigation be undertaken.
Assuntos
Aneurisma Aórtico/diagnóstico por imagem , Dissecção Aórtica/diagnóstico por imagem , Estatística como Assunto , Adolescente , Adulto , Idoso , Aortografia , Feminino , Humanos , Masculino , Mediastino/diagnóstico por imagem , Pessoa de Meia-Idade , Radiografia Torácica , SoftwareRESUMO
We studied the ventilatory effects of desflurane (formerly I-653) with and without N2O in healthy male volunteers. After insertion of venous and arterial (radial and pulmonary) catheters, baseline measurements of tidal volume (VT), respiratory rate (RR), ventilatory response to CO2, and arterial and mixed venous blood gases were made. Subjects were randomly assigned to receive either desflurane with O2 (n = 6) or with O2 and 60% N2O (n = 6). Anesthesia was induced by inhalation of desflurane followed by tracheal intubation without muscle relaxants. In each volunteer, at end-tidal concentrations totaling 0.83, 1.24, and 1.66 MAC, we repeated measurements of VT, RR, response to CO2, and arterial and mixed venous blood gases. As depth of anesthesia increased, VT significantly (P less than 0.05) decreased from 363 +/- 22 ml awake to 76 +/- 22 ml at 1.66 MAC without N2O and from 473 +/- 70 ml awake to 128 +/- 6 ml at 1.66 MAC with N2O (mean +/- SE). Similarly, RR increased from 15 +/- 0.5 breaths per min awake to 32 +/- 2 breaths per min at 1.66 MAC without N2O and from 14 +/- 0.5 breaths per min awake to 40 +/- 3 breaths per min at 1.66 MAC with N2O. Desflurane without N2O depressed the ventilatory response to CO2 to 45 +/- 9, 31 +/- 5, and 11 +/- 4% of the awake values at 0.83, 1.24, and 1.66 MAC, respectively. With N2O, values were 52 +/- 14, 23 +/- 5, and 26 +/- 9% of the awake value at 0.83, 1.24, and 1.66 MAC, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Anestesia por Inalação , Isoflurano/análogos & derivados , Respiração/efeitos dos fármacos , Adulto , Dióxido de Carbono/sangue , Depressão Química , Desflurano , Humanos , Isoflurano/farmacologia , Masculino , Óxido Nitroso , Oxigênio , Consumo de Oxigênio/efeitos dos fármacos , Pressão Parcial , Valores de Referência , Volume de Ventilação Pulmonar/efeitos dos fármacosRESUMO
Pretreating rats 24 hr earlier with naloxonazine (10 mg/kg i.v.) virtually eliminates the analgesic response observed with morphine at 3.5 mg/kg (i.v.) and significantly reduces the elevation in tail-flick latencies seen with higher morphine doses. Full dose-response curves show a 4-fold shift to the right (P less than .001) following naloxonazine treatment. At 3.5 mg/kg (i.v.), morphine depresses respiratory function, as determined by arterial blood gas (pO2, pCO2 and pH) measurements. Unlike analgesia, prior treatment of rats with naloxonazine does not alter the respiratory depressant actions of morphine. This inability of naloxonazine to antagonize the respiratory depressant actions of morphine is supported by full dose-response curves. Thus, prior treatment of rats with the mu-1-selective antagonist naloxonazine selectively antagonizes analgesia without affecting respiratory depression, implying different receptor mechanisms for the analgesic and respiratory depressant effects of morphine. Further comparisons of the analgesic and respiratory depressant effects of morphine and two opioid peptides, metkephamid and D-Ala2-D-Leu5-enkephalin, strongly suggest the involvement of mu-2 rather than delta mechanisms in opioid respiratory depression.
Assuntos
Analgesia , Morfina/farmacologia , Naloxona/análogos & derivados , Receptores Opioides/fisiologia , Respiração/efeitos dos fármacos , Animais , Gasometria , Relação Dose-Resposta a Droga , Encefalina Leucina/análogos & derivados , Encefalina Leucina/farmacologia , Leucina Encefalina-2-Alanina , Encefalina Metionina/análogos & derivados , Encefalina Metionina/farmacologia , Encefalinas/farmacologia , Masculino , Naloxona/farmacologia , Ratos , Ratos EndogâmicosRESUMO
We studied the percutaneous losses of sevoflurane and isoflurane during administration and elimination in seven healthy male volunteers. Anesthesia was induced and maintained with fentanyl, midazolam, and/or thiopental, and nitrous oxide for 30 min, after which 1% sevoflurane and 0.4% isoflurane in 65% nitrous oxide were administered for 30 min. Inspired, end-tidal, and mixed-expired gas samples were collected during administration and for 5-7 days of elimination. To measure percutaneous loss, each subject's arm was enclosed in a glass cylinder sealed at both ends and with two ports, one for flushing with nitrogen and one for obtaining gas samples during the 30 min of administration and the first 150 min of elimination. Anesthetic concentrations in all samples were determined using gas chromatography. The surface area of the arm was measured and the total surface area was calculated. During administration and elimination, percutaneous loss of isoflurane was significantly greater than that of sevoflurane (P less than 0.05). For both volatile agents, losses during elimination were greater than during administration (P less than 0.05), but even when combined, these losses were too small to affect kinetic or metabolic studies based on mass balance.
Assuntos
Anestésicos/metabolismo , Éteres/metabolismo , Isoflurano/metabolismo , Éteres Metílicos , Pele/metabolismo , Adulto , Anestesia por Inalação , Anestésicos/análise , Éteres/análise , Fentanila , Humanos , Isoflurano/análise , Masculino , Midazolam , Óxido Nitroso , Sevoflurano , TiopentalRESUMO
The electroencephalographic (EEG) effects of a new inhaled anesthetic are of interest because of the potential of such agents to produce excitatory (convulsant) activity and because of the potential usefulness of the EEG as an indicator of anesthetic depth and cerebral activity. Accordingly, we examined the EEG in 12 healthy, young male volunteers during desflurane anesthesia. Each subject had a baseline recording and then steady-state exposure to 6, 9, and 12% (0.83, 1.24, and 1.66 MAC) desflurane in O2 alone, and to 3, 6, and 9% desflurane in O2 with 60% N2O. The sequence of doses and the presence of N2O were randomized. We used mechanical ventilation to maintain normocapnia at each dose level. We also tested the effects of hypercapnia secondary to spontaneous ventilation. Additionally, at 1.24 MAC, subjects' lungs were hyperventilated to a PCO2 of 25.8 +/- 0.7 mmHg and exposed to rhythmic, loud clapping to attempt to provoke excitatory phenomena. Finally, after at least 6 h exposure to desflurane, we repeated measurements at 0.83 and 1.66 MAC to assess possible tolerance. Four channels of EEG were monitored visually, and at each dose, a quantitative EEG analysis was performed. Desflurane produced EEG changes comparable to those observed with equipotent levels of isoflurane. No epileptiform activity was seen. Desflurane significantly suppressed EEG activity; prominent burst suppression was seen at 1.24 MAC and higher. Substitution of N2O for 0.42 MAC desflurane reduced the degree of EEG suppression relative to the equipotent administration of desflurane and O2. Quantitative EEG measures for the early doses and for the later, repeated exposures did not differ.
Assuntos
Anestesia por Inalação , Eletroencefalografia/efeitos dos fármacos , Isoflurano/análogos & derivados , Adulto , Desflurano , Relação Dose-Resposta a Droga , Humanos , Isoflurano/farmacologia , Masculino , Óxido Nitroso , Oxigênio , Valores de ReferênciaRESUMO
The authors used in vivo 19F nuclear magnetic resonance spectroscopy to determine rates of cerebral uptake and elimination of desflurane, isoflurane, and halothane in rabbits. After anesthetizing animals by intramuscular and intravenous injection of methohexital and inhalation of 70% nitrous oxide, intravenous and intraarterial catheters were inserted and a tracheostomy and craniotomy performed. Ventilation was controlled to maintain arterial carbon dioxide tension (PaCO2) from between 35 and 45 mmHg. A 2-2.5-cm diameter circle of dura was exposed, over which a 0.9 x 1.0-cm elliptical surface coil was placed. Cerebral anesthetic concentrations (CC) were estimated from spectra acquired on a 4.7-Tesla spectrometer. Alveolar uptake and elimination also were assessed, using inspired (FI) and end-tidal (denoted FA0 at the end of administration) concentrations measured by gas chromatography. After baseline spectra were obtained, volatile agents were administered for 30 min, followed by a 120-min period of elimination. Our findings demonstrate that cerebral uptake and elimination correlate with solubility: they are most rapid for desflurane, next most rapid for isoflurane, and least rapid for halothane. During administration, cerebral uptake of desflurane (CC/FI = 0.690 +/- 0.049 at 9 min) was approximately 1.7 times faster than isoflurane (CC/FI = 0.691 +/- 0.020 at 15 min) and 3 times faster than halothane (CC/FI = 0.662 +/- 0.040 at 27 min). Similarly, elimination rates for desflurane (CC/FA0 = 0.238 +/- 0.015 at 9 min) were 1.7 times faster than isoflurane (CC/FA0 = 0.236 +/- 0.017 at 15 min) and three times faster than halothane (CC/FA0 = 0.212 +/- 0.033 at 27 min).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Encéfalo/metabolismo , Halotano/farmacocinética , Isoflurano/análogos & derivados , Isoflurano/farmacocinética , Animais , Desflurano , Espectroscopia de Ressonância Magnética , Coelhos , SolubilidadeRESUMO
This study is a retrospective review of the effect of nutritional support on duration of hospitalization in patients undergoing radical cystectomy. Thirty-five patients were randomly assigned to receive either 5% dextrose (D5W) solution plus electrolytes or total parenteral nutrition (TPN) following operation. The assigned nutritional regimen was continued for 1 week after operation until oral intake resumed. If the patients receiving D5W remained incapable of oral intake after 1 week, TPN was instituted. The group receiving immediate postoperative TPN had a median duration of hospitalization of 17 days, while the median duration for the group receiving 5% dextrose solution was 24 days. All other patient characteristics, such as age, sex, stage/grade of tumor, and extent of preoperative radiotherapy, were similar in the two groups. These results demonstrate that immediate postoperative institution of nutritional support reduced hospitalization time following radical cystectomy. This indicates that the routine use of 5% dextrose as postoperative nutrition should be reevaluated.
Assuntos
Tempo de Internação , Nutrição Parenteral Total , Cuidados Pós-Operatórios , Idoso , Ensaios Clínicos como Assunto , Eletrólitos/administração & dosagem , Feminino , Glucose/administração & dosagem , Humanos , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/normas , Distribuição Aleatória , Estudos Retrospectivos , Fatores de Tempo , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
Using magnetic resonance spectroscopy, the authors tested whether cerebral concentrations of inhaled anesthetics do not increase proportionately at inspired concentrations exceeding 3% 1) because anesthetics bind to and saturate specific sites in the brain or 2) because anesthetic-induced depression of ventilation limits the increase in alveolar anesthetic partial pressure. New Zealand White rabbits were anesthetized with methohexital, 70% nitrous oxide, and local infiltration of 1% lidocaine. Cerebral concentrations of anesthetic were determined from 19F spectra acquired with nuclear magnetic resonance (NMR). Inspired, end-tidal, and arterial anesthetic concentrations, and end-tidal and arterial partial pressure of carbon dioxide were measured. Blood/gas partition coefficients were determined and used to convert arterial anesthetic concentration to partial pressures. In seven spontaneously breathing animals, halothane (1%; n = 5) or isoflurane (0.8%; n = 2) was administered at a constant inspired concentration for 20 min; NMR spectra were acquired between 10 and 20 min. Thereafter, the inspired concentration was increased and the process repeated until apnea occurred. Two additional rabbits were anesthetized with isoflurane and studied similarly but with higher inspired concentrations during mechanical ventilation. In spontaneously breathing animals, ventilatory depression occurred, documented by marked increases in PaCO2, and cerebral concentrations of anesthetic did not increase proportionately at inspired concentrations exceeding 3%. In contrast to an absence of a correlation of inspired and cerebral concentrations during spontaneous ventilation, arterial and cerebral concentrations correlated linearly during both spontaneous and mechanical ventilation (R2 greater than 0.969). These results are consistent with depression of ventilation, rather than binding to specific cerebral sites as an explanation for the nonlinear relationship between cerebral and inspired anesthetic concentrations.
Assuntos
Sítios de Ligação/fisiologia , Encéfalo/fisiologia , Halotano/metabolismo , Isoflurano/metabolismo , Animais , Encéfalo/metabolismo , Espectroscopia de Ressonância Magnética , Coelhos , Respiração ArtificialRESUMO
We examined the potential toxicity of desflurane in 13 young 25.0 +/- 2.3 (mean +/- SD) yr-old men, given 7.35 +/- 0.81 MAC-hours of desflurane anesthesia. Hepatic and renal function tests, serum electrolytes, and standard urine and hematologic tests were performed before, during, and after anesthesia. No toxicity was found. There were no changes in tests of hepatocellular integrity (plasma alanine transferase activity), synthetic function (serum albumin, prothrombin time, partial thromboplastin time), or renal function (serum creatinine concentration, blood urea nitrogen concentration). Decreases in red blood cell count, hematocrit, and blood hemoglobin concentration during and immediately after anesthesia were attributed to blood sampling and infusion of intravenous electrolyte solution. These values returned by 4 days after anesthesia to values not different from those before anesthesia. Increased white blood cell counts and blood glucose concentrations noted during anesthesia with other inhaled anesthetics were also seen in these volunteers. Desflurane appears to have no greater toxicity than currently used inhaled anesthetics and, because of its lesser metabolism, may have lesser or not toxicity.
Assuntos
Anestésicos/toxicidade , Isoflurano/análogos & derivados , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Adulto , Análise Química do Sangue , Doença Hepática Induzida por Substâncias e Drogas , Desflurano , Humanos , Isoflurano/toxicidade , Rim/fisiologia , Nefropatias/sangue , Nefropatias/induzido quimicamente , Fígado/fisiologia , Hepatopatias/sangue , Masculino , Valores de ReferênciaRESUMO
We determined the cardiovascular effects of 0.91, 1.34, and 1.74 MAC of desflurane/nitrous oxide anesthesia (60% inspired nitrous oxide contributed 0.5 MAC at each level) in 12 healthy, normocapnic male volunteers. Desflurane/nitrous oxide anesthesia decreased systemic blood pressures, cardiac index, stroke volume index, systemic vascular resistance, and left ventricular stroke work index, and increased pulmonary arterial pressures and central venous pressure in a dose-dependent fashion, while heart rate was 10%-12% and mixed venous oxygen tension was 2-4 mm Hg higher at all MAC levels than at baseline (awake). Desflurane/nitrous oxide anesthesia modestly increased left ventricular end-diastolic cross-sectional area (preload) and decreased velocity of left ventricular circumferential fiber shortening, systolic wall stress (afterload), and area ejection fraction; this combination of changes indicates myocardial depression. At approximately comparable MAC levels, heart rate was lower and systemic blood pressures, central venous pressure, left ventricular stroke work index, and systemic vascular resistance usually were significantly higher during anesthesia with desflurane and nitrous oxide than during desflurane anesthesia alone (same volunteers, data collected in crossover design). After 7 h of anesthesia, regardless of the background gas, somewhat less cardiovascular depression and/or modest stimulation was apparent: cardiac index, area ejection fraction, and velocity of left ventricular circumferential fiber shortening recovered to or toward awake values, whereas heart rate was further increased. Evidence of circulatory insufficiency did not develop in any volunteers during the study. Segmental left ventricular function was normal at baseline, and no segmental wall-motion abnormalities, ST-segment change, or dysrhythmias developed.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Anestésicos/farmacologia , Hemodinâmica/efeitos dos fármacos , Isoflurano/análogos & derivados , Óxido Nitroso/farmacologia , Administração por Inalação , Adulto , Desflurano , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Humanos , Isoflurano/farmacologia , MasculinoRESUMO
We investigated the cardiovascular actions of desflurane (formerly I-653) during spontaneous ventilation. We gave 0.8-0.9, 1.2-1.3, and 1.6-1.7 MAC desflurane in oxygen (n = 6) and in 60% nitrous oxide, balance oxygen (n = 6) to unmedicated healthy male volunteers. Both anesthetic regimens decreased ventilation, increased partial pressure of arterial carbon dioxide, and produced similar cardiovascular changes. In comparison with values obtained when the volunteers were conscious, desflurane anesthesia with spontaneous ventilation decreased systemic vascular resistance and mean arterial blood pressure. Cardiac index, heart rate, stroke volume index, and central venous blood pressure increased. Left ventricular ejection fraction increased at 0.83 MAC desflurane in oxygen, and otherwise did not differ from the conscious value. The velocity of ventricular circumferential fiber shortening, estimated by echocardiography, increased with desflurane in oxygen but did not change with desflurane in nitrous oxide. Oxygen consumption increased during desflurane and oxygen anesthesia, but not when nitrous oxide plus oxygen was the background gas. Desflurane increased oxygen transport, the ratio of oxygen transport to oxygen consumption, mixed venous partial pressure of oxygen, and oxyhemoglobin saturation. The cardiovascular changes with desflurane during spontaneous ventilation differ from those during controlled ventilation. With both background gases, spontaneous ventilation, in comparison with controlled ventilation, increased cardiac index, stroke volume, central venous pressure, left ventricular ejection fraction, velocity of circumferential fiber shortening, oxygen transport, and the ratio of oxygen transport to oxygen consumption but did not change mean arterial blood pressure except at 1.66 MAC desflurane in oxygen (when it was higher with spontaneous than with controlled ventilation).
Assuntos
Anestésicos/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Isoflurano/análogos & derivados , Óxido Nitroso/farmacologia , Respiração/efeitos dos fármacos , Administração por Inalação , Adulto , Desflurano , Combinação de Medicamentos , Humanos , Isoflurano/farmacologia , Masculino , Oxigênio/metabolismoRESUMO
We asked if desflurane with or without nitrous oxide at 0.83, 1.24, and 1.66 MAC prevented cardiovascular responses to stimulation. We measured cardiac output, heart rate, systemic arterial blood pressure, central venous pressure, pulmonary arterial blood pressure, and systemic vascular resistance in six healthy male volunteers before (control) and at 0, 1, 2, 4, and 6 min after tetanic electrical stimulation (50, 100, and 200 Hz) of the ulnar nerve. At 0.83 and 1.24 MAC, cardiac output, mean systemic arterial blood pressure, heart rate, and pulmonary arterial blood pressure increased. Peak changes averaged 13%-20% and most frequently occurred 0-2 min after stimulation (P less than 0.05) with return to control values at 4-6 min (except for pulmonary arterial blood pressure). At 1.66 MAC, heart rate and systemic blood pressure responses were attenuated, but this level of anesthesia had equivocal effects on the cardiac output and pulmonary blood pressure responses. The addition of nitrous oxide attenuated the peak response of heart rate and cardiac output but not the peak response of mean systemic arterial blood pressure. In summary, 0.83 and 1.24 MAC desflurane did not abolish cardiovascular responses to stimulation, but 1.66 MAC attenuated the responses.
Assuntos
Anestésicos/farmacologia , Circulação Sanguínea/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Isoflurano/análogos & derivados , Administração por Inalação , Adulto , Desflurano , Estimulação Elétrica , Hemodinâmica/efeitos dos fármacos , Humanos , Isoflurano/farmacologia , Óxido Nitroso/farmacologia , Nervo UlnarRESUMO
Desflurane (formerly I-653) is a new inhalaticnal anesthetic with a promising pharmacokinetic profile that includes low solubility in blood and tissue, including fat. Since its lipid solubility is less than that of other volatile agents, it may have lower potency. Low solubility would be expected to increase the rate at which alveolar concentration approaches inspired concentration during induction as well as to increase the rate of elimination of desflurane from blood at emergence. We determined the minimum alveolar concentration (MAC) of desflurane in 44 unpremedicated ASA physical status 1 or 2 patients undergoing elective surgery. We prospectively studied four patient groups distinguished by age and anesthetic regimen: 18-30 versus 31-65 yr and desflurane in 60% N2O/40% O2 versus desflurane in O2. Anesthesia was induced with desflurane or desflurane in 60% N2O/40% O2. MAC was determined by a modification of Dixon's up-and-down method with increments of 0.5% desflurane. The MAC of desflurane in O2 was 7.25 +/- 0.0 (mean +/- SD) in the 18-30-yr age group, and 6.0 +/- 0.29 in the 31-65-yr group; the addition of 60% N2O reduced the MAC to 4.0 +/- 0.29 and 2.83 +/- 0.58, respectively. The median time from discontinuation of desflurane to an appropriate response to commands was 5.25 min. Desflurane appears to be a mild airway irritant but was well tolerated by all patients.
Assuntos
Anestesia por Inalação , Isoflurano/análogos & derivados , Procedimentos Cirúrgicos Operatórios , Adulto , Envelhecimento/fisiologia , Período de Recuperação da Anestesia , Desflurano , Humanos , Pessoa de Meia-Idade , Óxido Nitroso , Oxigênio , Estudos ProspectivosRESUMO
We studied the percutaneous losses of the new inhaled anesthetic, desflurane (I-653), and of isoflurane and halothane during anesthetic administration and elimination in seven healthy male volunteers. Anesthesia was induced and maintained with midazolam, thiopental, and fentanyl. We administered 70% N2O for 30 min, and then administered 2% desflurane, 0.4% isoflurane, and 0.2% halothane concurrently with 65% N2O for 30 min. Inspired, end-tidal, and mixed-expired gas samples were collected during administration of the volatile agents and for 5-7 days of elimination. The right arm and hand of each subject was enclosed in a sealed glass cylinder having a port at each end, one for sampling and both for flushing with N2 after anesthetic administration and every 15 min thereafter. We sampled gases from the cylinder during administration and for the 150 min of elimination and analyzed their anesthetic concentrations by gas chromatography. The surface area of the enclosed portion of the arm was measured, and the total body surface area was calculated. All values were normalized to (i.e., divided by) the end-tidal (alveolar) concentration at the end of administration. During administration, percutaneous loss of halothane was 3.5 times that of desflurane and 2 times that of isoflurane. During elimination, the loss of halothane was 6 times and 2 times greater than the loss of desflurane and isoflurane, respectively. Percutaneous loss of halothane significantly exceeded that of isoflurane. The elimination values included an estimate of elimination after 150 min. The percutaneous loss of each anesthetic was 2- to 3-fold greater during elimination than administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Anestesia por Inalação , Halotano/farmacocinética , Isoflurano/análogos & derivados , Isoflurano/farmacocinética , Fenômenos Fisiológicos da Pele , Adulto , Desflurano , Difusão , Humanos , Masculino , Valores de ReferênciaRESUMO
The low solubility of desflurane in blood and tissues suggests that the partial pressures of this agent in blood and tissues should approach the inspired partial pressure more rapidly than would the blood and tissue partial pressures of other potent inhaled anesthetics. We tested this prediction, comparing the pharmacokinetics of desflurane with those of isoflurane, halothane, and nitrous oxide in eight volunteers. We measured the rate at which the alveolar (endtidal) (FA) concentration of nitrous oxide increased towards an inspired (FI) concentration of 65-70%, and then measured the concurrent increase in FA and mixed expired concentrations (FM) of desflurane, isoflurane, and halothane at respective FI values of 2.0%, 0.4%, 0.2%. Minute ventilation (VE) was measured concurrently with the measurements of anesthetic concentrations. The potent vapors were administered for 30 min; administration of nitrous oxide continued throughout the period of anesthesia. For the potent agents, we also measured VE, FA, and FM for 5-7 days of elimination. We used FA/FI and FA/FA0 (FA0 = the last FA during the administration of each anesthetic) to define the rate of increase of anesthetic in the lungs and the rate of elimination of anesthetic, respectively. FA/FI values at 30 min of administration were: (mean +/- SD) nitrous oxide 0.99 +/- 0.01, desflurane 0.90 +/- 0.01, isoflurane 0.73 +/- 0.03, and halothane 0.58 +/- 0.04. FA/FA0 values after 5 min of elimination were: desflurane 0.14 +/- 0.02, isoflurane 0.22 +/- 0.02, and halothane 0.25 +/- 0.02. Recovery (volume of anesthetic recovered during elimination per volume taken up) of desflurane (105 +/- 25%) equalled recovery of isoflurane (102 +/- 13%) and exceeded recovery of halothane (64 +/- 9%). Time constants for a five-compartment mammillary model for halothane and isoflurane differed for the lungs, fat group, and hepatic metabolism, and exceeded those for desflurane for all compartments. In summary, we found that FA/FI of desflurane increases more rapidly and that FA/FA0 decreases more rapidly in humans than do these variables with other available potent anesthetics. We also found that desflurane resists biodegradation in humans and so may have little or no toxic potential.
Assuntos
Halotano/farmacocinética , Isoflurano/análogos & derivados , Isoflurano/farmacocinética , Adulto , Desflurano , Halotano/sangue , Humanos , Isoflurano/sangue , Masculino , Modelos Biológicos , Óxido Nitroso/sangue , Óxido Nitroso/farmacocinética , Pressão Parcial , Valores de Referência , SolubilidadeRESUMO
The low solubility of sevoflurane in blood suggests that this agent should enter and leave the body more rapidly than isoflurane. However, the closeness of sevoflurane and isoflurane tissue/blood partition coefficients suggests that the rates of equilibration with and elimination from tissues should be similar. We tested both predictions, comparing sevoflurane with isoflurane and nitrous oxide in seven volunteers. We measured the rate at which the alveolar (end-tidal) (FA) concentration of nitrous oxide increased toward an inspired (FI) concentration of 65%-70%, then measured the concurrent rise in FA and mixed expired concentrations (FM) of sevoflurane and isoflurane at respective FI values of 1.0% sevoflurane and 0.6% isoflurane for 30 min. Minute ventilation (VE) was measured concurrently with the measurements of anesthetic concentrations. For the potent agents, we also measured VE, FA, and FM for 6-7 days of elimination. FA/FI values at 30 min of administration were as follows: nitrous oxide, 0.986 +/- 0.003 (mean +/- SD); sevoflurane, 0.850 +/- 0.018; and isoflurane, 0.733 +/- 0.027. FA/FA0 (FA0 = the last FA during administration) values after 5 min of elimination were as follows: sevoflurane, 0.157 +/- 0.020; isoflurane, 0.223 +/- 0.024. Recovery (volume of anesthetic recovered during elimination/volume taken up) of sevoflurane (101% +/- 7%) equaled recovery of isoflurane (101% +/- 6%). Time constants for a five-compartment mammillary model for sevoflurane were smaller than those for isoflurane for the lungs but were not different from isoflurane for the other compartments.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Anestésicos/farmacocinética , Éteres/farmacocinética , Isoflurano/farmacocinética , Éteres Metílicos , Administração por Inalação , Adulto , Humanos , Masculino , Óxido Nitroso/farmacocinética , Sevoflurano , Distribuição TecidualRESUMO
The cardiovascular actions of three concentrations of desflurane (formerly I-653), a new inhalation anesthetic, were examined in 12 unmedicated normocapnic, normothermic male volunteers. We compared the effects of 0.83, 1.24, and 1.66 MAC desflurane with measurements obtained while the same men were conscious. Desflurane caused a dose-dependent increase in right-heart filling pressure and a decrease in systemic vascular resistance and mean systemic arterial blood pressure. As measured by echocardiography, left ventricular end-diastolic area did not change except for a small increase at 1.66 MAC desflurane, and systolic wall stress was less at all concentrations of desflurane than during the conscious state. Desflurane did not change cardiac index or left ventricular ejection fraction. Heart rate did not change at 0.83 MAC, but progressively increased with deeper desflurane anesthesia. Stroke volume index was less at all concentrations of desflurane than while the men were conscious, but desflurane did not alter the velocity of ventricular circumferential fiber shortening. Mixed venous blood PO2 and oxyhemoglobin saturation were higher during all concentrations of desflurane anesthesia than during the conscious state. No volunteer developed a metabolic acidosis. We conclude that desflurane with controlled ventilation and constant PaCO2 causes cardiovascular depression, as indicated by the increased cardiac filling pressure and decreased stroke volume index and by no change in the velocity of circumferential fiber shortening in the presence of decreased systolic wall stress. However, cardiac output is well maintained, and heart rate does not increase at light levels of anesthesia. The cardiovascular actions of 0.83 and 1.66 MAC desflurane were also reexamined in 6 of the 12 men during the seventh hour of anesthesia. Prolonged desflurane anesthesia resulted in lesser cardiovascular depression than was evidenced during the first 90 min. The measures of cardiac filling (central venous pressure and left ventricular end-diastolic cross-sectional area) did not differ between the early and late periods of anesthesia. Systemic vascular resistance decreased further during the late period, but systolic wall stress did not differ between the two time periods. During the seventh hour of desflurane anesthesia, heart rate and cardiac index were higher at both anesthetic concentrations than during the first 90 min of anesthesia. Left ventricular ejection fraction and velocity of fiber shortening did not change with duration of desflurane anesthesia. Oxygen consumption, oxygen transport, the ratio of the two, mixed venous PO2, and mixed venous oxyhemoglobin saturation (SO2) increased late in the anesthetic in comparison with the first 90 min.