Effect of renal failure and cirrhosis on the pharmacokinetics and neuromuscular effects of rapacuronium administered by bolus followed by infusion.
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BACKGROUND: Recent trials indicate that rapacuronium's pharmacokinetic characteristics are influenced by both renal failure and cirrhosis but the time course of a single bolus dose of 1.5 mg/kg is affected minimally. The authors reassessed these pharmacokinetic findings and examined the time course of the same bolus dose followed by a 30-min infusion. METHODS: During nitrous oxide-isoflurane anesthesia, patients with normal renal and hepatic function (n = 25), those with renal failure (n = 28), and those with cirrhosis (n = 6) received a bolus dose of rapacuronium (1.5 mg/kg) followed by a 30-min infusion adjusted to maintain 90-95% twitch depression. At 25% recovery, neostigmine was administered. Blood was sampled until 8 h after the infusion to determine concentrations of rapacuronium and its active metabolite ORG9488. Rapacuronium's pharmacokinetic parameters were determined using mixed-effects modeling. RESULTS: Onset and facilitated recovery of twitch depression were similar in the three groups. Patients with renal failure required 22% less rapacuronium to maintain target twitch depression during the infusion. Rapacuronium's plasma clearance was 24% smaller in renal failure and decreased 0.5%/yr of age; rapid distribution clearance was 51% smaller in men than in women. After the infusion, ORG9488 concentrations decreased markedly more slowly in patients with renal failure. Cirrhosis did not alter the pharmacokinetics of rapacuronium. CONCLUSION: Rapacuronium's plasma clearance and infusion requirement were decreased by renal failure. By dosing to maintain target twitch depression, recovery was not prolonged. Cirrhosis does not affect the pharmacokinetics or neuromuscular effects of rapacuronium. Persistence of ORG9488 in patients with renal failure might prolong recovery after rapacuronium if target twitch depression is not maintained or with administration of rapacuronium for more than 30 min. (+info)
Occupational exposure to inhaled anesthetic. Is it a concern for pregnant women?
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QUESTION: Two of my pregnant patients are exposed to inhaled anesthetic on the job. One is an anesthetist, and the other is a veterinarian. They have both expressed concern about this exposure. How should I advise them? ANSWER: Occupational exposure to waste anesthetic gas is not associated with increased risk of major malformations. Risk of spontaneous abortion might be slightly increased, however. This risk can be reduced, if not eliminated, by good gas scavenging systems. (+info)
Psychological studies of human performance as affected by traces of enflurane and nitrous oxide.
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Thirty human subjects were exposed for four hours to 500 ppm N-2O and 15 ppm enflurane in air and then, within five minutes, given a 35-minute battery of psychological tests. Performance of a divided-attention audiovisual task and a digit-span memory test were significantly decreased compared with control data following exposure to air. A tachistoscopic task, four tests from the Wechsler memory scale, and five others from the Wechsler Adult Intelligence Scale were unaffected. Thirty subjects exposed to 500 ppm N-2-O in air only scored significantly lower on the digit-span test only. (+info)
Hemodynamic and ventilatory responses to fentanyl, fentanyl-droperidol, and nitrous oxide in patients with acquired valvular heart disease.
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Fentanyl (10 mug/kh) or fentanyl (10 mug/kg) plus droperidol (100 mug/kg) administered intravenously during 20 minutes to adult patients with acquired valvular heart disease produced minimal circulatory changes. The trend during drug infusion was for mean arterial pressure and systemic vascular resistance to decrease, and for cardiac index and stroke volume index to increase without change in heart rate. Central venous pressure increased during drug infusion (P less than 0.05) but decreased to awake levels following controlled ventilation and skeletal-muscle paralysis, probably reflecting thoracoabdominal-muscle rigidity rather than a circulatory response. Hypoventilation during drug infusion necessitated assisted or controlled ventilation, with or without skeletal muscle paralysis, in 14 of 16 patients. Addition of 60 per cent nitrous oxide following fentanyl or fentanyl-droperidol infusion significantly decreased mean arterial pressure, heart rate, and cardiac index. All circulatory changes were similar in direction and extent to those previously found during morphine-nitrous oxide anesthesia. (Key words: Anesthetics, intravenous, fentanyl; Anesthetics, gases, nitrous oxide; Heart, effect of fentanyl, dorperidol, and nitrous oxide.). (+info)
Cone dark adaptation: the influence of halothane anesthesia.
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Cone dark adaptation (da) (measured with an electroretinogram [ERG] method) is found to be severely retarded when the subject (human and macaque monkey) is under halothane anesthesia. The degree of retardation depends both on the halothane level and on the bleach history. The effect of bleach history shows a great similarity with psychophysical findings concerning foveal da. Interpretation of halothane effects, therefore, is possible in terms of an existing model on cone pigment kinetics. (+info)
Intracranial pressure during hypotension and subsequent vasopressor therapy in anesthetized cats.
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The effects of vasopressor therapy on intracranial pressure (ICP) during hypotension were evaluated in 45 adult cats anesthetized with pentobarbital and hyperventilated via an endotracheal tube with nitrous oxide, 70 per cent, and oxygen, 30 per cent, to maintain Paco2 25 plus or minus 5 torr. Hypotension was induced by intravenous administration of trimethaphan camsylate or sodium nitroferricyanide and by hemorrhage. Vasopressor (norepinephrine, ephedrine, or isoproterenol) administration in the absence of hypotension caused slight transient increases in ICP. Trimethaphan produced increases in ICP averaging 4.3 mm Hg, while sodium nitroferricyanide caused no change and hemorrhage decreased ICP by 3.9 mm Hg. After hypotension was established, vasopressors caused increases in ICP of 1-21 mm Hg. The greatest increase was seen with norepinephrine administration during sodium nitroferricyanide-induced hypotension. Increases in ICP were pronounced in absolute magnitude and rapidity of rise but were of short duration (2 to 5 minutes). The elevation of pressure might be of clinical significance in patients who have pre-existing intracranial hypertension or space-occupying lesions. (+info)
Anesthetic biotransformation and renal function in obese patients during and after methoxyflurane or halothane anesthesia.
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Anesthetic biotransformation and renal function were studied in obese adult patients (148 plus or minus 8 kg; mean plus or minus SE) anesthetized for three hours with 60 per cent nitrous oxide plus either methoxyflurane or halothane for elective jejunoileal small-bowel-bypass operations. There was no evidence of persistent renal dysfunction in any patient postoperatively, but serum osmolality was elevated 72 hours after methoxyflurane anesthesia. Urine concentrating ability was not determined. Peak serum ionic fluoride concentration was 55.8 plus or minus 5.8 muM/1 two hours after discontinuation of methoxyflurane. Urinary ionic fluoride and oxalate excretions increased postoperatively. Compared with previously reported data from nonobese patients, serum ionic fluoride concentrations in obese patients increased more rapidly during methoxyflurane anesthesia and peaked higher and sooner after discontinuation of methoxyflurane. The peak serum ionic fluoride concentration was 10.4 plus or minus 1.5 muM/1 at the conclusion of halothane anesthesia, significantly more than the corresponding value in nonobese patients. Intraoperative liver biopsies from 23 of 27 patients showed moderate to severe fatty metamorphosis. Fatty liver infiltration may have increased hepatic anesthetic uptake and exposed more methoxyflurane or halothane to hepatic microsomal enzymes. The more rapid elevation and higher peak levels of serum ionic fluoride following methoxyflurane, and to a lesser extent following halothane, may reflect increased anesthetic biotransformation in obese compared with nonobese patients. To avoid excessive serum ionic fluoride elevations the authors recommended limiting low-dose methoxyflurane anesthesia delivered to obese patients with potential fatty liver infiltration to no more than three hours. (+info)
Sevoflurane and isoflurane reduce oxygen saturation in infants.
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Volatile anesthetics are generally known to exert several influences on the respiratory system, but their direct effect on oxygen saturation as measured by pulse oximetry (SpO2) in infants remains unknown. In this study, 70 infants under 2 years of age who received general anesthesia were examined to determine the effects of several volatile anesthetics and nitrous oxide on SpO2. After endotracheal intubation, the subjects were ventilated using a Jackson-Rees circuit with oxygen, nitrous oxide, and either sevoflurane, enflurane, or isoflurane adjusted to twice the adult minimum alveolar concentration (MAC) for the agents when used in combination with 67% nitrous oxide. In all cases, the end-tidal carbon dioxide tension (PetCO2) was maintained within the same range (28-35 mm Hg). Significantly lower SpO2 values (paired t test, P < .05) were observed when the subjects were ventilated with oxygen, 67% nitrous oxide, and sevoflurane or isoflurane--but not with oxygen, 67% nitrous oxide, and enflurane--than when they were administered oxygen, 50% nitrous oxide, and the original concentration of each volatile anesthetic. These results suggest that sevoflurane and isoflurane have different effects from enflurane on gas exchange systems. (+info)