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Biomedical subjects

W L Way

Publications and source records attributed to W L Way.

At least 19 recordsLinked to original sources
PubMed1990

Postoperative hypoxemia after nonabdominal surgery: a frequent event not caused by nitrous oxide.

We tested whether anesthesia that includes nitrous oxide (N2O) results in the development of intraoperative and postoperative pulmonary complications, including hypoxemia. We also tested whether aging contributes to the development of such complications, particularly when anesthesia includes N2O. We randomly allocated patients having total hip replacements, carotid endarterectomies, or transsphenoidal hypophysectomies (total n = 270) to an anesthetic regimen with and without N2O (stratified within surgical group). A heat-and-moisture exchanger was included in the anesthetic circuit of all patients. Patients were monitored perioperatively and for 1 wk after surgery using intermittent and continuous pulse oximetry to determine oxyhemoglobin saturation. Intraoperatively, mean oxygen (O2) saturations were lower in patients given N2O, particularly older patients. Hypoxemia (O2 saturation less than 86%) developed in five patients receiving N2O and in one receiving O2. This difference was not significant. Administration of N2O did not decrease postoperative O2 saturation, nor did it alter the incidence of postoperative hypoxemia, cough, or sputum production.

Adult↗
PubMed1990

Nitrous oxide does not impair hepatic function in young or old surgical patients.

We investigated whether anesthesia including nitrous oxide (N2O) caused hepatic injury, and whether any adverse effect of N2O was affected by patient age. One hundred patients having total hip replacements were randomly assigned to a regimen that included or excluded N2O (50%-60%) during regional anesthesia supplemented with isoflurane and intravenous adjuvants. Using postoperative plasma levels of alanine aminotransferase, bilirubin, and alkaline phosphatase 1 and 3 days after surgery as indicators of hepatic impairment, we found no evidence that N2O causes hepatic injury in either young or old patients.

Aged↗
PubMed1988

Comparison of midazolam and diazepam for sedation during plastic surgery.

A randomized double-blind study was designed to compare midazolam, a rapid-acting water-soluble benzodiazepine, with diazepam for sedation when administered as an adjuvant to ketamine during local anesthesia. In the preliminary dose-ranging study, midazolam (0.05 to 0.15 mg/kg IV) was found to produce a spectrum of central nervous system activity (e.g., sedation, amnesia) that was similar to diazepam (0.1 to 0.3 mg/kg IV). However, the slope of midazolam's dose-response curve for sedation appeared to be steeper (i.e., a narrower therapeutic dosage range). In a comparative evaluation of their relative sedative-amnestic properties and recovery characteristics, the median effective doses of the two benzodiazepines were compared. Midazolam (0.1 mg/kg IV) was found to produce more profound sedation and amnesia than diazepam (0.2 mg/kg IV). Midazolam was associated with significantly less pain on injection and a lower incidence of postoperative venoirritation. Overall patient acceptance was higher with midazolam compared to diazepam. Finally, recovery characteristics were similar for the two benzodiazepines in our outpatient setting.

Adolescent↗
PubMed1987

Effect of propofol anesthesia on baroreflex activity in humans.

Previous studies have shown that infusions of propofol, a new intravenous anesthetic, were associated with decreased arterial pressure and slow heart rates. To evaluate the role of baroreflex mechanisms in sustaining these conditions, the effects of two infusion rates of propofol (54 and 108 micrograms.kg-1.min-1) to supplement 66% nitrous oxide in oxygen anesthesia were studied in twelve ASA class I patients having a mean age of 34 years. Baroreflex control of heart rate was studied by perturbing the patients' arterial pressure with phenylephrine or sodium nitroprusside. Valsalva maneuvers were used to assess the response of the systemic arterial system. Steady state anesthesia at both infusion rates was not associated with decreased sensitivity of the baroreflex control of heart rate, but resetting of the reflex occurred to allow lower arterial pressures for a given heart rate than in the awake state. During propofol infusions at either rate, the diastolic pressure overshoot normally associated with the relief of raised airway pressure in the Valsalva maneuver was significantly reduced. It is concluded that propofol/nitrous oxide anesthesia is not associated with impairment of baroreflex sensitivity, but that central sympatholytic and/or vagotonic mechanisms enable low heart rates to be sustained despite decreased arterial pressures.

Adult↗
PubMed1984

Placebo controls.

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Clinical Trials as Topic↗
PubMed1984

Anesthesia does not increase opioid peptides in cerebrospinal fluid of humans.

One theory of narcosis postulates that inhaled anesthetics produce general anesthesia by causing the release of endogenous opioid peptides. In the present study, however, the concentration of immunoreactive beta-endorphin-like material (eight patients) or leu-enkephalin (four patients) did not increase in cerebrospinal fluid of patients 5 min after induction of anesthesia with thiopental, 2-5 mg/kg and N2O 70%; after an additional 10 min, during which halothane was added; at 5, 15, and 60 min after surgical incision; or after 30 min in the recovery room. Therefore, any contribution of the endorphin system to the production of general anesthesia does not appear to require the release of beta-endorphin.

Analgesia↗
PubMed1983

The effects of intravenous lorazepam alone and with meperidine on ventilation in man.

The respiratory effects of lorazepam (a 1, 4 benzodiazepine) were studied using a modified Read rebreathing technique in healthy adult males about to undergo elective surgery. Lorazepam 0.05 mg/kg (IV) produced an increase in slope and a shift to the left of the CO2 response curve. These effects were also detectable but of smaller magnitude when the same lorazepam dose (IV) was given with meperidine (IV). End-expiratory CO2 (PeCO2), which was significantly elevated in all drug groups, is not a sensitive indicator of either the time course or the degree of respiratory depression.

Adult↗
PubMed1979

d-Propoxyphene kinetics after single oral and intravenous doses in man.

d-Propoxyphene kinetics was studied in 8 healthy male subjects after single oral doses of d-propoxyphene at 65, 130, and 190 mg and after slow intravenous infusion of 65 mg. Total urinary excretion (7 days) indicated complete oral absorption but systemic availability was reduced corresponding to fist-pass elimination of 30% to 70%. There was linearity between oral dose and the corresponding area under the plasma concentration/time curve of d-propoxyphene and the metabolite norpropoxyphene. The kinetic measurements showed 2- to 3-fold interindividual variations: oral clearance, 1.3 to 3.6 1/min; systemic clearance, 0.6 to 1.2 1/min; apparent volume of distribution, 700 to 1,800 1; d-propoxyphene half-life (t1/2), 8 to 24 hr; and norpropoxyphene t1/2, 18 to 29 hr. There were pronounced intraindividual dose-dependent variations in oral clearance in some subjects. The intravenous concentration curves indicated a 3-compartment distribution model.

Administration, Oral↗
PubMed1979

Entrance into brain of dextropropoxyphene and the toxic metabolite norpropoxyphene.

Several studies show that dextropropoxyphene after oral administration is intensively biotransformed to norpropoxyphene by first pass metabolism in the liver. While dextropropoxyphene is analgesic, cardiotoxic and shows CNS toxicity with convulsions and respiratory depression, norpropoxyphene is cardiotoxic to the same degree as dextropropoxyphene, but is without analgesic or CNS-toxic effects (Lund-Jacobsen, 1978). This principal difference between the effects of dextropropoxyphene and norpropoxyphene might be due to differences in penetration into the brain. We investigated the penetration of the two compounds in 14C-labelled moities into the brain of rats by the technique originally described by Oldendorf (1970). By this method the extraction of dextropropoxyphene was found extremely high, while it was much lower for the metabolite. The extraction percentage for dextropropoxyphene after 5 and 10 S was 350 +/- 34.1 and 164 +/- 15.2, respectively, while the values for norpropoxyphene was 62 +/- 6.2 and 44 +/- 4.1 (mean +/- S.E.M.), respectively. This difference may at least partly explain the missing CNS-symptoms with the metabolite.

Animals↗
PubMed1978

Comparative pharmacology of the optical isomers of ketamine in mice.

Relative pharmacological potencies of the optical isomers of ketamine have been estimated in ICR mice. The (+)-isomer was 3X more potent than (-)-ketamine as an analgesic using the phenylquinone writhing test, only 1.5X more potent in terms of hypnotic activity and 1.8X more potent in causing locomotor stimulation. At equianalgesic doses (+)-ketamine caused less stimulation of locomotor activity than the (-)-isomer. These potency differences did not appear to be due to differences in biodisposition although stereoselective metabolism was demonstrated in vivo. Analgesia induced by ketamine was reversed by 10 mg/kg of naloxone.

Analgesics↗
PubMed1976

Effects of halothane anesthesia on the biodisposition of ketamine in rats.

Ketamine, a highly lipophilic drug, was rapidly distributed into highly vascular organs and subsequently redistributed to less well perfused tissues, with concurrent hepatic metabolism and urinary and biliary excretion, after both i. m. and i. v. administration in the rat. Halothane, a potent cardiovascular depressant, was found to prolong the plasma and brain half-life of ketamine (50 mg/kg i.m.) and also increased the duration of ketamine-induced ataxia when the two drugs were administered concomitantly. Halothane anesthesia (0.8% halothane in oxygen) produced a decrease in the rate of uptake and delayed distribution and redistribution of ketamine (50 mg/kg i. m.), while the rate of urinary excretion of ketamine was not significantly altered. Similarly, redistribution of intravenously administered ketamine (30 mg/kg i. v.) was slowed in the presence of halothane. In vitro hepatic microsomal metabolism of ketamine and its principle N-demethylated metabolite, metabolite I, was inhibited noncompetitively by halothane with inhibitor constants (Ki) for halothane estimated to be 1.56 and 1. 64 mM,respectively. The gas anesthetic also decreased the overall rate of in vivo metabolism of ketamine (30 mg/kg i. v.) in a concentration-dependent manner. Thus halothane anesthesia by decreasing uptake, distribution, redistribution and metabolism of intramuscularly administered ketamine produced significant prolongation of its pharmacologic action on the central nervous system. Our results imply that concomitant use of inhalational anesthetics may prolong pharmacologic actions of other agents via effects on distribution/redistribution processes as well as on metabolism.

Anesthesia↗
PubMed1976

Biodisposition of ketamine in the rat: self-induction of metabolism.

Four pharmacologic actions of intravenous ketamine (30 mg/kg) were studied in the rat. To elucidate the mechanism(s) terminating the pharmacologic effects, animals were pretreated with ketamine and agents anticipated to modify hepatic microsomal metabolism, including phenobarbital and SKF 525A. SKF 525A pretreatment markedly prolonged ataxia, analgesia and agitation, in addition to significantly elevating brain and plasma ketamine levels subsequent to the initial 10 minutes following injection; thus hepatic metabolism appeared to play a prominent role in the termination of the posthypnotic effects of the drug. While significantly shortening the durations of the three posthypnotic events, phenobarbital and ketamine pretreatments also lowered the brain and plasma levels of ketamine. With all pretreatments, brain ketamine levels were almost identical at the cessation of hypnosis (25 mug/g of tissue) and ataxia (8-10 mug/g of tissue). No pretreatment altered either the duration of loss of righting reflex (hypnosis) or brain and plasma ketamine levels during the initial 10 minutes after injection. Approximately 70% of the injected drug was recovered from four tissues, skeletal muscle, gut, skin and liver, at 10 minutes after injection; thus redistribution from brain to other tissues appeared to play a major role in the cessation of hypnosis. Ketamine pretreatment caused a 2-fold increase in the rate of its in vitro hepatic microsomal metabolism. Brain and plasma ketamine levels 30 minutes after injection were nearly identical in rats pretreated with ketamine and phenobarbital, although phenobarbital pretreatment resulted in a 4-fold increase in in vitro ketamine hepatic metabolism.

Analgesia↗
PubMed1975

The effect of acid-base balance on neostigmine antagonism of d-tubocurarine-induced neuromuscular blockade.

d-Tubocurarine (dTc) was infused intravenously into 35 cats anesthetized with chloralose and urethane at a constant continuous rate to produce and maintain 90 per cent depression of twitch height of the anterior tibial muscle following supramaximal stimulation of the peroneal nerve. The mean infusion rates that produced 90 per cent depression were not significantly altered by respiratory acid-base changes. Metabolic alkalosis decreased (32.5 per cent) and metabolic acidosis increased (27.7 per cent) the required infusion rate of dTc. When pH and Paco2 were maintained at 7.37 and 38 torr, respectively, the addition of a bolus of neostigmine, 10.5 mug/kg, intravenously, to the continuing infusion of dTc produced 50 per cent antagonism of the dTc-depressed twitch. Respiratory alkalosis and metabolic acidosis did not alter the dose of neostigmine needed to produce 50 per cent antagonism. However, during respiratory acidosis (pH 7.13, Paco2 66 torr) and metabolic alkalosis (pH 7.59, Paco2 36 torr) 20.0 and 18.0 mug/kg neostigmine, respectively, were needed to produce 50 per cent antagonism. Still larger doses of neostigmine (75 mug/kg) could not completely antagonize the block unless pH and Paco2 were returned to 7.30-7.50 and 35-45 torr, respectively. It is concluded that respiratory acidosis and metabolic alkalosis limit and oppose antagonism of dTc by neostigmine.

Acid-Base Equilibrium↗