Propofol and fentanyl anaesthesia.
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Anesthesia↗
Biomedical subjects
C S Reilly
Publications and source records attributed to C S Reilly.
Comparison of the effects of isoflurane or fentanyl-nitrous oxide anaesthesia on propranolol disposition in dogs.
The disposition of propranolol was studied, using dual-route administration, in two groups of six dogs. Each dog was studied on three consecutive days: day 1 awake, day 2 during anaesthesia, and day 3, 24 h after anaesthesia. Anaesthesia was with isoflurane 2.0 MAC (in oxygen) in one group and with a fentanyl-nitrous oxide-atracurium regimen in the other group. In the group receiving fentanyl, anaesthesia caused a significant decrease (63%) in intrinsic clearance from the day 1 value (P less than 0.05) and a 45% decrease in systemic clearance (P less than 0.05). Hepatic plasma flow decreased by 27% (ns). A similar pattern was found with isoflurane: intrinsic clearance decreased by 53% (P less than 0.05) and systemic clearance by 40% (P less than 0.05). Hepatic plasma flow decreased by 40% (ns). In both groups, the values 24 h after anaesthesia were not significantly different from those obtained on day 1. Anaesthesia with either fentanyl-nitrous oxide-atracurium or isoflurane has a marked, but short-lasting effect on the disposition of propranolol, in part as a result of a decrease in intrinsic clearance.
Anesthesia, General↗
New intravenous anaesthetics and neuromuscular blocking drugs. A review of their properties and clinical use.
The newer neuromuscular blocking drugs include vecuronium and atracurium. Vecuronium is a competitive neuromuscular blocking drug with a steroid nucleus. A dose of 0.1 mg/kg has an onset time of 2 minutes and provides surgical paralysis for 20 minutes. Recovery to 90% twitch height occurs in 40 to 50 minutes. Vecuronium has few adverse effects and its use is associated with cardiovascular stability. Atracurium is a competitive neuromuscular blocking drug which undergoes Hofmann degradation and ester hydrolysis in plasma. A dose of 0.6 mg/kg has an onset time of around 2 minutes and provides surgical paralysis for 20 to 30 minutes. Recovery to 90% twitch height occurs in 60 to 80 minutes. Histamine release, usually only localised, has been reported in association with the use of atracurium. The organ-independent metabolism of atracurium allows its use in standard dosage in patients with renal or hepatic disease. Edrophonium, although not a new drug, has recently been re-evaluated for reversal of neuromuscular blockade. In a dose of 0.5 mg/kg it has been shown to be as effective as neostigmine at reversing neuromuscular blockade after recovery has started (greater than 25% twitch height recovery). However, if blockade is profound (less than 10% recovery), edrophonium is less effective. Among the newer intravenous anaesthetics are propofol (disoprofol) and midazolam. In a dose of 1.5 to 2.5 mg/kg, propofol produces sleep rapidly with a prompt recovery in 4 to 6 minutes. Induction of anaesthesia may be associated with a transient apnoea and a fall in systolic pressure. The rapid recovery has led to its use for maintenance of anaesthesia. Midazolam is a water-soluble benzodiazepine which has been used as an anaesthetic agent. The dose needed to induce sleep varies widely (0.15 to 0.5 mg/kg); onset is slow (1.5 to 5 minutes), and recovery may be prolonged. Midazolam is also used in lower doses as a sedative. Ketamine, an intravenous induction agent, has recently been used intrathecally and extradurally to provide analgesia.
Anesthesia, Intravenous↗
Enprostil, in contrast to cimetidine, does not inhibit propranolol metabolism.
Enprostil, an orally active prostaglandin E2 analog, is undergoing clinical trials in the treatment of peptic ulcer disease. Because results of animal studies suggested that prostaglandins might affect both hepatic drug metabolizing ability and hepatic blood flow, the effects of enprostil on drug elimination were studied and compared with those of the standard antiulcer drug cimetidine in a double-blind, randomized, crossover study of nine normal subjects. Cimetidine reduced the oral clearance of propranolol by 50%, consistent with the inhibition of drug metabolism reported in previous studies. On the other hand, enprostil had no effect on propranolol elimination. Neither drug altered liver blood flow as assessed either by the clearance of indocyanine green or by the technique of dual route of administration of propranolol. Thus in contrast to cimetidine, enprostil had no effect on hepatic drug metabolism.
Administration, Oral↗
Ultra-short-acting beta-blockade: a comparison with conventional beta-blockade.
Esmolol is a beta 1-selective adrenoceptor blocker that is rapidly metabolized by blood and liver esterases. The beta-receptor and hemodynamic effects of esmolol were determined in a group of 12 healthy men and were compared with those induced by both oral and intravenous propranolol. Esmolol was rapidly effective in inducing at least 90% of steady-state beta-blockade within 5 minutes of either initiating or changing the esmolol infusion rate. More importantly, when esmolol infusion was discontinued the beta-blockade had totally disappeared by 18 minutes after esmolol, 300 micrograms/kg/min, and had been reduced by 50% after 750 micrograms/kg/min. In contrast, 30 minutes after discontinuation of a propranolol infusion, there was no change in the level of beta-blockade. Propranolol was much more potent at blocking isoproterenol-induced tachycardia (dose ratio 33.5 +/- 2.5) than was even the highest dose (750 micrograms/kg/min) of esmolol (dose ratio 13.1 +/- 1.0). The same dose of intravenous propranolol was approximately equipotent to oral propranolol, 40 mg every 8 hours (dose ratio 33.5 +/- 2.5 and 34.5 +/- 3.6, respectively). In contrast, propranolol, 40 mg every 8 hours, and esmolol, 300 micrograms/kg/min, were equipotent in antagonizing exercise-induced tachycardia (40.1% +/- 2.3% and 42.7% +/- 3.2%, respectively). Esmolol had striking hypotensive effects. Systolic blood pressure fell by 20 mm Hg during esmolol infusions of 750 micrograms/kg/min. Esmolol appears to be a potent beta 1-selective adrenoceptor antagonist with a particularly strong hypotensive effect. It is likely to be very useful in the treatment of hemodynamically unstable patients and may be useful in the emergency treatment of hypertension.
Adrenergic beta-Antagonists↗
The effect of halothane on drug disposition: contribution of changes in intrinsic drug metabolizing capacity and hepatic blood flow.
Several studies have shown that halothane may influence drug disposition in animals and humans, but the mechanism remains unclear. The relative contributions of changes in metabolizing capacity and hepatic blood flow to altered drug disposition were investigated during halothane anesthesia, using propranolol as a model compound. The studies were performed on six dogs on three separate days; first, the day before anesthesia, second, during halothane (2.0 MAC) anesthesia, and third, 24 h after anesthesia. Each dog simultaneously received 40 mg unlabeled propranolol directly into the portal vein and 200 mCi of 3H-propranolol intravenously via chronically implanted catheters. Blood samples were taken every 5 min for the first hour and then every 15 min for a further 3 h for the measurement of unlabeled and 3H-propranolol concentrations. During halothane anesthesia, intraportal-intrinsic clearance was decreased by 62% (P less than 0.05) from 2,110 +/- 298 to 799 +/- 233 ml/min, while systemic clearance was decreased (P less than 0.05) from 470 +/- 33 ml/min preanesthesia to 280 +/- 38 ml/min during halothane anesthesia. The intravenous elimination half-life was increased (P less than 0.05) from 87 +/- 12 to 155 +/- 23 min during anesthesia. Although halothane anesthesia tended to lower liver plasma flow from 642 +/- 80 to 473 +/- 47 ml/min, this change was not significant. The large change in portal or intrinsic clearance indicates that halothane anesthesia markedly inhibits drug-metabolizing ability. The authors therefore conclude that the alterations in drug disposition observed during halothane anesthesia are mainly due to inhibition of drug-metabolizing capacity in the liver.
Animals↗
Variability of fentanyl pharmacokinetics in man. Computer predicted plasma concentrations for three intravenous dosage regimens.
The derived pharmacokinetic data for the intravenous administration of fentanyl obtained from seven previous studies were compared using computer simulation of predicted plasma concentrations following three intravenous dosage regimens. There was wide discrepancy between the reported calculated pharmacokinetic constants from the various studies, such that the volume of distribution ranged from 4.4 to 59.7 litres, estimates of terminal elimination half-life ranged from 141 to 853 minutes while total body clearance values ranged from 160 to 1530 ml/minute. The differences in predicted plasma concentrations were marked. The peak concentration following a bolus of 500 micrograms ranged from 8.4-113.6 ng/ml and took from 2.9 to 18.9 hours to fall to 0.5 ng/ml. The steady state plasma concentration reached with an infusion of 0.3 microgram/kg/minute varied from 12.2-119.9 ng/ml and the plateau level attained with a two-rate infusion (2.7 micrograms/kg/minute for 20 minutes then 0.3 micrograms/kg/minute) ranged from 10.6-50.8 ng/ml. The aim of descriptive pharmacokinetics is to allow the clinician to predict the plasma concentration achieved by a given dose and to facilitate dosage choice and adjustment. Recent interest has centred on the use of pharmacokinetics to calculate continuous intravenous infusion dosage regimens. The clinical application of current pharmacokinetic data for fentanyl is questionable.
Adult↗
Drug absorption after general anaesthesia for minor surgery.
Paracetamol absorption after oral administration was studied in eleven patients immediately after a short general anaesthetic for cystoscopy and also in eight healthy volunteers. There were no statistical differences between the rate of paracetamol absorption in the two groups. This suggests that oral medication may be given immediately following a short general anaesthetic when opioid drugs are avoided.
Acetaminophen↗
Comparison of cephazolin and gentamicin in the prophylactic treatment of infection in out-patient urinary tract endoscopy.
Previous studies have shown that the incidence of rigors following urinary tract endoscopy in out-patients may be as high as 16% and that this incidence can be significantly lowered to about 7% by the administration of intramuscular cephazolin sodium at the time of endoscopy. In order to reduce further the rigor rate, a comparison of intramuscular cephazolin with gentamicin has been carried out with 200 patients in each group. There was a rigor rate correlation between an infected urine and the occurrence of a rigor. Cephazolin sodium remains the drug of choice in this situation because of its low toxicity.
Cefazolin↗
Adverse effects of general anaesthetics.
This review deals with the adverse reactions associated with general anaesthetic agents in current use. These reactions fall into 2 categories; those which are more common, predictable and often closely related, and those which are rare, unpredictable and carry a high mortality. Both inhalational and intravenous anaesthetic agents affect the central nervous and cardio-respiratory systems in a dose-related manner. Neuronal inhibition results in decreasing levels of consciousness and depression of the medullary vital centres which can lead to cardiorespiratory failure. Both groups of agents have some depressant effect on the myocardium and vascular smooth muscle leading to a fall in cardiac output and hypotension. Centrally-mediated respiratory depression is common to both groups and the inhalational agents have a direct effect on lung physiology. The most important idiosyncratic reactions to the volatile agents are malignant hyperpyrexia and 'halothane hepatitis'. Malignant hyperpyrexia has an incidence of 1:12,000 with a mortality of about 24%. It is triggered most often by halothane together with suxamethonium. Post halothane hepatic necrosis is rare. Evidence points to 2 distinct syndromes; direct toxicity from the products of reductive metabolism, and a more serious illness, immunologically mediated via haptens formed by liver proteins and the products of oxidative metabolism. Prolonged nitrous oxide exposure can cause bone marrow depression and life-threatening pressure effects by expansion of air-filled spaces within the body. The idiosyncratic reactions to the intravenous agents include anaphylactoid reactions (which are rare) and triggering of acute porphyria. Etomidate is immunologically 'clean', but it inhibits cortisol synthesis.
Anesthesia, Inhalation↗