Local anesthesia toxicity review.
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We compared the incidence of postoperative nausea and vomiting after total intravenous propofol-fentanyl anesthesia (TIVA group) and that after thiamylal-nitrous oxide-isoflurane anesthesia (GOI group) in 60 ASA physical I and II patients for elective abdominal simple total hysterectomy. When the patients returned to the ward, the incidence of nausea was lower in TIVA group than in GOI group (P < 0.05), but no difference was found in the incidence of vomiting between the two groups. There were no differences in the incidence of nausea and vomiting 6 hours after the operation and on the next morning between the two groups. Postoperative pain scores were similar between the two groups, while total postoperative evaluation scores (nausea, vomiting, pain, fever, and sleep disturbance) were lower in TIVA group (P < 0.05). We conclude that TIVA with propofol-fentanyl reduced the incidence of nausea and improved total evaluation scores in the immediate postoperative period.
We experienced a case of difficult tracheal intubation in a 15-year-old boy with von Recklinghausen disease scheduled for resection of a right neck tumor. His scoliosis made it difficult to intubate and to manage airway because he easily developed dyspnea. We tried nasotracheal intubation with the patient awake under sedation using a bronchofiberscope, but we found an unexpected tumor jeopardizing his airway patency near his vocal cord. Preoperative examination of a tumor in the airway is essential in the anesthetic management of the patients with von Recklinghausen disease.
We compared the patient's response to laryngeal mask (LM) insertion and hemodynamics among three anesthesia induction methods; S group used sevoflurane and slowly increased to 5% in 50% nitrous oxide; I group used isoflurane and slowly increased to 3% in 50% nitrous oxide; and P group used 2.5 mg.kg-1 propofol with 0.2 microgram.kg-1 fentanyl. Thirty patients, 35 to 65 years, for elective mastectomy were the subjects of study in each of the three groups. Preanesthetic medication was composed of i.m. injection of 0.5 mg atropine and 5 mg midazolam 30 min. prior to the induction. The number of patients with difficult insertion or demonstrating body movement or gagging in each group was in the order of P group > I group > S group. Blood pressure (BP), heart rate (HR) and rate pressure product (RPP) in the P group were significantly lower than those in the other two groups. I group showed significant increase in BP, HR and RPP. It was concluded that sevoflurane enabled the most smooth insertion of LM among the three methods of anesthesia with the least hemodynamic change.
A new gas-liquid chromatographic method was developed for the determination of diethylether in whole blood. Ether was quantitated by peak area ratio analysis with n-propanol as the internal standard using a flame ionization detector. Blood ether concentrations were determined in cats undergoing inhalational anesthesia by ether in oxygen. In normal spontaneously breathing cats, anesthesia began at ether concentrations of about 0.6 g/l, and respiratory arrest occurred at 2.4 g/l and above. Mean arterial blood pressure was well maintained throughout the entire anesthetic range. In spinal artificially respired animals, mean arterial blood pressure correlated inversely with blood ether concentration. The data suggest that decline in blood pressure may be a useful sign of ether toxicity in spinal cats.
The laryngeal mask airway (LMA) was clinically evaluated using capnogram in patients who breathed spontaneously under the combination of general and spinal anesthesia. Using the LMA, the airway was maintained without jaw lift and no remarkable hemodynamic change was observed during its insertion and removal. Capnogram was useful to confirm the intact airway and to monitor the respiration. Respiratory depression was observed after thiopental administration and enflurane inhalation. The respiration recovered promptly following the increase of respiratory rate (RR) and tidal volume at first, and it made a further recovery following increase in RR. The use of the LMA under light inhalation anesthesia is hence a useful combination with regional anesthesia.
STUDY OBJECTIVES: To evaluate the decomposition of sevoflurane in soda lime during prolonged sevoflurane anesthesia in humans. To evaluate for evidence of renal or hepatotoxicity as a result of exposure to these sevoflurane degradation compounds. DESIGN: Prospective evaluation in healthy volunteers. SETTING: Clinical research unit and postanesthesia care unit of a university hospital. PATIENTS: Six healthy male volunteers. INTERVENTIONS: Subjects were anesthetized with sevoflurane 1 to 1.2 minimum alveolar concentration for greater than 9 hours with a semiclosed circuit anesthetic technique (5-liter total flow) with fresh soda lime as the absorbent. MEASUREMENTS AND MAIN RESULTS: Laboratory tests of renal and hepatic function were performed before anesthesia and 1 and 5 days after anesthesia. During sevoflurane anesthesia, inhalation and exhalation circuit limb gas samples were obtained for degradation compound analysis. Only one degradation product, fluoromethyl-2,2-difluoro-1-(trifluoromethyl) vinyl ether (compound A), was detected. Inhalation concentration was maximal (7.6 +/- 1.0 ppm) at 2 hours and did not increase further after this time point. There were no differences in preanesthesia and postanesthesia tests of hepatic and renal function. CONCLUSIONS: Levels of the degradation compound (compound A) produced in semiclosed circuit sevoflurane anesthesia with soda lime are well below potential toxic levels and thus appear safe. When sevoflurane is administered under these conditions for prolonged anesthesia, concentrations of compound A do not continue to increase throughout anesthesia.
PURPOSE: Sevoflurane and isoflurane have been reported to exert protective effects against ischemia-reperfusion injury (IRI) in various organs. To compare the effect of sevoflurane anesthesia on liver IRI with that of isoflurane anesthesia, we performed the present study in pigs. METHODS: Nineteen pigs were assigned to either the sevoflurane ( n = 9) or the isoflurane group ( n = 10). Hepatic warm ischemia was produced by 30-min hepatic artery and portal vein clamping beginning 90 min after the start of the inhalation anesthesia; this was followed by a 240-min reperfusion. To extend our evaluation, we evaluated the degree of IRI using various parameters (plasma alpha-glutathione-S-transferase [alpha-GST], lipid peroxide, and lactate concentrations), in addition to the conventionally used liver damage markers. RESULTS: The lactate level was significantly higher under isoflurane than under sevoflurane at 120 min after reperfusion (4.0 +/- 0.4 mmol.l(-1) vs 2.5 +/- 0.3 mmol.l(-1); P < 0.05). How-ever, this difference had disappeared after 240 min of reperfusion. No significant differences between the two groups were observed in values for alpha-GST, lipid peroxides, aspartate aminotransferase, alanine aminotransferase, or lactic dehydrogenase. CONCLUSION: The extent of the hepatic IRI seen under sevoflurane anesthesia in pigs did not differ significantly from that seen under isoflurane, as judged from measurements of a number of parameters over a 240-min reperfusion period.
The mechanisms of inhalation anesthesia may include inhibiting non NMDA excitatory amino acid neurotransmission. This possibility was addressed by measuring the effect of three anesthetics at clinically relevant concentration on kainate-induced glutamate release from cerebellar granule cells. Cerebellar granule cells were obtained from 8-day-old SD rats and maintained in vitro for 9-14 days. Medium glutamate concentrations were measured by HPLC after 90 minutes incubation with kainate or NMDA. Inhalation anesthetics were introduced by holding the cells under a continuous flow of air/anesthetic mixtures. All anesthetics tested did not effect NMDA-induced glutamate release. Halothane (1 MAC), isoflurane (1 MAC) inhibited kainate-induced glutamate release from the cultured cells whereas enflurane (1 MAC) had no effect on kainate-induced glutamate release. The difference between enflurane and the other anesthetics tested suggests that anesthesia is dependent on more than one process and the extent at which each function is perturbed is dependent on the specific anesthetic used. Halothane inhibition of kainate-induced glutamate release was not reversible by increasing kainate concentration, indicating halothane does not directly compete with kainate at its receptor.
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To determine whether naloxone when perfused through the cerebroventricular system would modify the circulatory and hypnotic effects of halothane, the authors studied its effect in six trained dogs. Naloxone, 20 microgram/ml, was perfused through the fourth cerebral ventricle in three and through the third cerebral and lateral ventricles in three other dogs when awake and during halothane anesthesia (0.75--0.82 vol per cent in oxygen). Blood pressure, heart rate, and circulatory responses to bilateral occlusion of the carotid arteries were measured. The state of consciousness was evaluated by the animals behavior and the EEG. Arterial hypotension, bradycardia, depressed baroreceptor responses, and EEG synchronization associated with halothane anesthesia were reversed when naloxone was perfused through the fourth ventricle. To maintain comparable depths of anesthesia the halothane concentration had to be doubled during naloxone perfusion. No change in the circulatory or hypnotic effects of halothane occurred when the third ventricle was perfused with naloxone. It is concluded that opiate receptors in structures bordering the fourth cerebral ventricle may be important modulators of inhalational anesthesia.
BACKGROUND: Patients with asthma who require general anesthesia and tracheal intubation are at increased risk for the development of bronchospasm during induction. The incidence of wheezing during induction with different intravenously administered agents is unknown. A randomized, double-blinded prospective study was undertaken to evaluate the incidence of wheezing in asymptomatic asthmatic and nonasthmatic patients receiving three commonly used intravenous anesthetic agents for induction of anesthesia. METHODS: Fifty-nine asymptomatic asthmatic and 96 nonasthmatic patients of ASA physical status 1 and 2 were studied. All patients received 1.5 micrograms/kg fentanyl, oxygen, followed by either 5 mg/kg thiopental or thiamylal, 1.75 mg/kg methohexital or 2.5 mg/kg propofol, 1.5 mg/kg succinylcholine, tracheal intubation, and inhalational anesthesia. Wheezing was assessed by an independent blinded observer, auscultating the lungs at 2 and 5 min postintubation. Data were analyzed by Pearson's chi-squared, Fisher's exact test, and multiple logistic regression with significance set at P < 0.05. RESULTS: Both asthmatic and nonasthmatic patients who received a thiobarbiturate for induction had a greater incidence of wheezing than did patients receiving propofol. In asthmatic patients, 45% (23, 67) (mean and 95% confidence interval) who received a thiobarbiturate, 26% (8, 44) who received an oxybarbiturate, and none (0, 17) who received propofol wheezed after intubation. In nonasthmatic patients, 16% (3, 28) who received thiobarbiturate and 3% (0, 9) who received propofol wheezed. CONCLUSIONS: This study suggests that propofol should be considered for induction of anesthesia in patients, particularly those with asthma, who require timely intubation.
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Catastrophe conditions for anesthesia and the treatment of pain arise when otherwise conventional techniques and procedures, including supervision of the patient, can only be carried out incompletely or not at all. Pain must be controlled with analgesics which have the least possible side-effects. When supplies of energy and gas fail, inhalation anesthesia can only be carried out under certain circumstances. In its place intravenous anesthesia can be used, with or without relaxation, with air breathing or artificial respiration. Reports in the literature of studies and experience attribute particular importance to ketamine in this respect.
Cardiac output distribution and regional blood flow in 18 dogs during isoflurane and halothane anesthesia were studied in dose-related fashion. Surgical preparation consisted of left thoracotomy and placement of catheters in the left atrium and aorta through a femoral artery. Regional blood flow was studied one week after surgical preparation using a microsphere technique at the three stages: awake, 1 MAC, and 2 MAC of inhalation anesthesia. At each stage of the experiment, two sets of microspheres (15- and 9-micron diameter), labeled with different isotopes, were used simultaneously. Both anesthetics increased cerebral blood flow, decreased blood flow through preportal area, and preserved renal blood flow. Isoflurane increased hepatic artery blood flow at both levels of anesthesia, while halothane preserved the flow during 1 MAC and decreased it at 2 MAC. Apparently, isoflurane provided better oxygenation to the liver than halothane. Myocardial blood flow was increased during isoflurane (despite decrease in blood pressure and cardiac output) and decreased during halothane anesthesia. Isoflurane appears to be a coronary vasodilator with potential beneficial (improvement in myocardial blood supply) as well as hazardous ("steal effect") effects on the heart.
The relative efficacies and cardiorespiratory effects of three injectable anesthetic combinations containing medetomidine were evaluated in ring-tailed lemurs (Lemur catta). In addition, the direct effects of medetomidine on heart rate and blood pressure were evaluated in lemurs anesthetized with isoflurane. For injectable anesthesia, captive adult ring-tailed lemurs were anesthetized with medetomidine and ketamine (0.04-0.06 mg/kg, i.m. and 3 mg/kg, i.m., respectively), medetomidine, butorphanol, and ketamine (0.04 mg/kg, i.m., 0.4 mg/kg, i.m., and 3 mg/kg, i.m., respectively), or medetomidine, butorphanol, and midazolam (0.04 mg/kg, i.m., 0.4 mg/kg, i.m., and 0.3 mg/kg, i.m., respectively). For inhalation anesthesia, lemurs were mask-induced and maintained with isoflurane for 30 min before receiving medetomidine (0.04 mg/kg, i.m.). Sedation produced by medetomidine-ketamine was unpredictable and of short duration. Both medetomidine-butorphanol-ketamine (MBK) and medetomidine-butorphanol-midazolam (MBMz) provided adequate anesthesia for routine physical exams; however, the effects of MBMz lasted longer than those of MBK. Heart rates and respiratory rates were within clinically normal ranges for all groups, and lemurs remained normotensive throughout the study. Common side effects such as hypertension and bradycardia associated with the use of alpha2-adrenergic receptor agonist combinations in other species were not observed. Likewise, medetomidine administration had no effect on HR in lemurs receiving isoflurane. Lemurs in all groups were well ventilated and remained well oxygenated throughout the procedures, though arterial partial pressure of O2 was lowest in the MBMz group. All three injectable medetomidine combinations were effective in ring-tailed lemurs but only MBK and MBMz provided adequate depth and duration of anesthesia for use as sole regimes. For many clinical procedures in lemurs, MBMz offers advantages over MBK because of its longer duration of action and its rapid and more complete reversibility with specific antagonists.
PURPOSE: The population PK/PD approach was prospectively used to determine the PK/PD of cisatracurium in various subgroups of healthy surgical patients. METHODS: Plasma concentration (Cp) and neuromuscular block data from 241 patients in 8 prospectively-designed Phase I-III trials were pooled and analyzed using NONMEM. The analyses included limited Cp-time data randomly collected from 186 patients in efficacy/safety studies and full Cp-time data from 55 patients in pharmacokinetic studies. The effects of covariates on the PK/PD parameters of cisatracurium were evaluated. The time course of neuromuscular block was predicted for various patient subgroups. RESULTS: The population PK/PD model for cisatracurium revealed that anesthesia type, gender, age, creatinine clearance, and presence of obesity were associated with statistically significant (p < 0.01) effects on the PK/PD parameters of cisatracurium. These covariates were not associated with any clinically significant changes in the predicted recovery profile of cisatracurium. Slight differences in onset were predicted in patients with renal impairment and patients receiving inhalation anesthesia. Based on the validation procedure, the model appears to be accurate and precise. CONCLUSIONS: The prospective incorporation of a population PK/PD strategy into the clinical development of cisatracurium generated information which influenced product labeling and reduced the number of studies needed during development.