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Biomedical subjects

J W Sear

Publications and source records attributed to J W Sear.

At least 19 recordsLinked to original sources
PubMed1992

Effects of different hepatic pathologies on disposition of alfentanil in anaesthetized patients.

We have studied the influence of different hepatic pathologies on the disposition of alfentanil in 23 unpremedicated patients (six healthy control subjects, six patients with liver dysfunction of alcoholic aetiology and 11 patients with non-alcohol related liver disease). All patients received a bolus of alfentanil 500 micrograms i.v. as supplement to 67% nitrous oxide and isoflurane in oxygen anaesthesia. Plasma drug concentrations were measured in venous blood samples at intervals up to 24 h by radio-immunoassay and protein binding was determined by equilibrium dialysis. Kinetic estimates were determined using non-compartmental analysis. Patients with non-alcoholic liver disease had lesser plasma clearance (114.8 (range 66.8-213.5) ml min-1) than the alcoholic group (158.8 (100.0-220.7) ml min-1) or controls (187.4 (125.2-269.5) ml min-1). In all three groups, there was considerable intersubject variability, with a bimodal distribution in the non-alcoholic group. This group also had a smaller apparent volume of distribution at steady state. Mean residence time was prolonged in the alcoholic group compared with controls (284.9 (217.8-362.2) min vs 226.8 (201.2-250) min). Protein binding was decreased in the alcoholic group compared with controls (84.9 (SD 4.2)% vs 89.3 (2.1)%); this was attributable to a lesser plasma alpha 1-acid glycoprotein concentration (0.55 (0.18) g litre-1 vs 0.89 (0.21) g litre-1). Free drug clearance was reduced in both liver dysfunction groups compared with controls.

Adult↗
PubMed1992

Effect of graded infusion rates of propofol on regional and global left ventricular function in the dog.

We have studied the effects of graded infusion rates of propofol (0.2-0.5 mg kg-1 min-1) on left ventricular global and regional function, in eight acutely instrumented dogs. Global function was assessed by measurement of aortic and left ventricular pressure, LV dP/dtmax, aortic blood acceleration and stroke volume. Regional function was assessed by measurement of systolic shortening and the end-systolic pressure-length relationship. The response of the coronary circulation to short periods of occlusion was also assessed. Administration of propofol significantly reduced left ventricular preload, as indicated by reductions in end-diastolic pressure and length; contractility was depressed, the depression being greater in the apex than in the base of the left ventricle. High infusion rates impaired relaxation. Regulation of coronary blood flow was not disrupted. Reductions in preload and contractility contributed to the propofol-induced hypotension. After 60 min, recovery from the greatest infusion rate was incomplete.

Animals↗
PubMed1992

Pregnanolone: a new steroid intravenous anaesthetic. Dose-finding study.

The intravenous steroid anaesthetic pregnanolone has been investigated as an induction agent in 60 fit adults premedicated with morphine and atropine. The drug was given in a stepwise fashion starting with 0.5 mg.kg-1; following a successful induction, the next patient received 15% less, while the subsequent patient received 15% more if anaesthesia was not achieved. Taking loss of eyelash reflex as the end point, 31 patients were satisfactorily induced; the AD50 in these patients was 0.44 mg.kg-1 (95% CI 0.41-0.47). A further 23 patients were induced satisfactorily as assessed by cessation of counting. Induction was trouble free with minimal changes in heart rate and arterial blood pressure, a low incidence of apnoea and few involuntary movements; pain on injection was not a feature. Loss of eyelash reflex is not a good end point for assessment of loss of consciousness following pregnanolone.

Adult↗
PubMed1992

Thoracic electrical bioimpedance measurement of cardiac output and cardiovascular responses to the induction of anaesthesia and to laryngoscopy and intubation.

Noninvasive methods of determining cardiac output (by thoracic electrical bioimpedance) and arterial pressure (by intermittent oscillometry) were used to record minute-by-minute changes in heart rate, mean arterial pressure, stroke volume, cardiac output and systemic vascular resistance following induction of general anaesthesia and laryngoscopy and intubation in 60 healthy female patients who were either unpremedicated, or premedicated with temazepam or papaveretum-hyoscine. Anaesthesia was induced with a sleep dose (3-5 mg.kg-1) of thiopentone and maintained with 70% nitrous oxide in oxygen with 0.5-1% enflurane. Tracheal intubation was facilitated by administration of vecuronium 0.1 mg.kg-1. Mean arterial pressure and cardiac output decreased maximally 5 min after induction in all premedication groups by mean estimates of 21-25% and 14-22% respectively. Heart rate increased initially one minute after induction, but decreased to less than the baseline value 5 min after induction. Systemic vascular resistance was unchanged. The stimulus of laryngoscopy and tracheal intubation was accompanied by a significant pressor response and tachycardia one minute after intubation (with mean increases in mean arterial pressure and heart rate of 29-34% and 22-33% respectively). The increase in mean arterial pressure was secondary to an increase in systemic vascular resistance (36-57%), and was accompanied by a decrease in stroke volume (-25 to -31%). These changes were significant in all three groups. Cardiac output decreased only in unpremedicated patients. There were wide variations in the different haemodynamic indices.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Practical treatment recommendations for the safe use of anaesthetics.

General anaesthesia is the reversible depression of central nervous system function. There is still no agreement over what constitutes depth of anaesthesia, and the clinical anaesthetist must thus titrate drug input according to clinical signs (heart rate, blood pressure, somatic movement, autonomic responses). The potency of inhalational agents may be expressed in terms of the MAC (minimum alveolar concentration); comparable end-points (including blood concentrations) have been proposed for the intravenous agents. Kinetic infusion regimens can be constructed for the intravenous agents to achieve the ED95 concentrations required to provide clinically adequate anaesthesia. However, because of individual differences in drug kinetics and dynamics, as well as the influences of disease states and intercurrent therapy, the clinician will titrate the dose according to response. Administration of volatile or intravenous anaesthetics by fixed regimens may result in either overdosage or the risk of patient awareness. The choice of anaesthetic drug is usually based on the nonhypnotic side effects of the different agents--including their central and regional cardiovascular effects, the speed and completeness of recovery, and the need to provide intraoperative analgesia. In addition, special techniques and drugs are often needed for neurosurgical, cardiothoracic and obstetric anaesthesia. All anaesthetic agents (inhalation and intravenous) have other side effects (such as cardiorespiratory depression and organ toxicity related to the liver or kidney). Both halothane and enflurane may be responsible for postoperative hepatic dysfunction, while the metabolism of enflurane can also result in nephrotoxicity in patients with pre-existing renal dysfunction. Isoflurane has been reported to cause 'coronary steal' in patients with ischaemic heart disease through its coronary vasodilator properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1992

Propofol to provide sedation after coronary artery bypass surgery. A comparison of two fixed rate infusion regimens.

Propofol (2,6, di-isopropylphenol) was given by continuous intravenous infusion to provide sedation following coronary artery bypass surgery. The need for additional sedation, analgesia and hypotensive agents was assessed at two propofol infusion rates (10 or 25 micrograms/kg/min). Both rates provided clinically satisfactory conditions. There were no differences in the requirements for analgesia or vasodilators between the groups. The higher infusion rate of 25 micrograms/kg/min was associated with a lower requirement for additional sedation but a more frequent need to stop the infusion temporarily to prevent hypotension.

Adult↗
PubMed1991

Preoperative silent myocardial ischaemia: incidence and predictors in a general surgical population.

We have studied before operation 156 patients aged more than 40 yr presenting for elective vascular or non-vascular surgery, using ambulatory ECG monitoring to detect silent myocardial ischaemia (SMI). The prevalence of SMI was 18.2% in the vascular group (n = 102) and 7.6% in the non-vascular group (n = 54). A history of ischaemic heart disease, or an abnormal ECG suggestive of a previous myocardial infarction, predicted a high risk of SMI (28% compared with 9% in the absence of these variables). However, a significant amount of SMI (36% of the total) occurred in patients without one of the defined risk factors. In addition, 24 of the patients with abdominal aortic disease underwent cardiac gated blood pool (MUGA) scans. Abnormal ventricular wall function was observed in 62.5% of the patients. Twenty-nine percent of the patients studied with MUGA scans had SMI and 21% had ejection fractions less than 40%. A significant association (P less than 0.05) existed between the presence of SMI and a ventricular ejection fraction of less than 40%.

Adult↗
PubMed1991

First pass lung uptake of bupivacaine: effect of acidosis in an intact rabbit lung model.

The first pass uptake, metabolism and recovery of bupivacaine were examined in an intact rabbit lung model using a multiple indicator technique with rapid sequential sampling. The rabbits were allocated to an acidotic group (pH 7.0-7.1) (n = 8) and a control group (n = 10) with normal pH. Bupivacaine recovery rates were not significantly different: median 93.2% (range 48.9-116.5%) and 94.5% (54.9-123.1%) in control and acidotic groups, respectively. Median peak percentage fractional concentrations of bupivacaine were greater in the acidotic group: 6.22% (2.5-7.65%) vs 4.1% (2.5-6.7%) (P less than 0.05). Median maximum instantaneous pulmonary percentage extraction was less in the acidotic animals than in animals with normal pH: 81.2% (47.1-91.9%) vs 91.0% (82.6-94.5%) (P less than 0.01). Median normalized mean percentage transit time was less in the acidotic group (245.3% (163.4-465.3%)) than in the control group (423.9% (313.9-740.4%)) (P less than 0.01). There was no evidence for bupivacaine metabolism by the lung. The results suggest that acidosis reduced bupivacaine lung uptake and increased its rate of passage through the lung, but did not influence overall drug recovery rates. This has clinical implications for bupivacaine related cardiac and cerebral toxicity.

Acidosis↗
PubMed1991

Non-invasive measurement of cardiac output by thoracic electrical bioimpedance: a study of reproducibility and comparison with thermodilution.

The performance and reproducibility of the BoMED NCCOM3 thoracic electrical bioimpedance cardiograph (TEB) has been evaluated in volunteers and patients. In resting supine volunteers, we determined the coefficient of variability over short time periods (30 min) and over several days, and examined the effects of differences in electrode type and electrode placement. The mean (range) intra-subject coefficients of variation (CV) for thoracic fluid index (TFI) and stroke volume (SV) were 1.0% (0.4-1.8%) and 4.7% (2.1-8.5%), respectively over a 30-min period. The corresponding CV were 5.6% (2.3-10.9%) and 10.9% (6.1-14.8%) for measurements made at rest on four separate occasions. Use of different electrode types (RedDot and Medicotest) resulted in differences in TFI (P less than 0.01), but not in mean values for SV or cardiac output (Q); their use in individual subjects revealed differences of up to 20% in SV and Q. Alterations in electrode placement by 5 cm in the horizontal and diagonal planes produced no significant changes in TFI, SV or Q; changes in the longitudinal plane produced a graded change. Increases of 5 cm and 10 cm in thoracic length produced mean increases in TFI of 9.8% and 39.8%, respectively, and mean decreases in Q of 8.4% and 16.7% and SV of 7.5% and 15.8%. TEB measurements of Q and SV were compared with thermodilution (TD) in 16 intensive care patients. Mean (SEM) Q by TEB was 5.63 (1.10) litre min-1 compared with TD 4.38 (0.72) litre min-1 (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1979

Cytotoxicity of i.v. anaesthetic agents on the isolated rat hepatocyte.

The isolated rat hepatocyte model has been used to assess the hepatotoxicity of a number of i.v. anaesthetic induction agents. Ketamine, Althesin and CCI 12923 (minaxolone) all inhibited gluconeogenesis and urea formation from alanine. There was also a decrease in the cell ATP concentration, and a dose-related increase in leakage of LDH. Of these indices of cell toxicity, gluconeogenesis from alanine was found to be the most sensitive. Fifty per cent inhibition of gluconeogenesis for all three agents occurred in the range 150--300 mumol. The effects of these agents on the isolated hepatocyte may be attributed to a primary impairment of mitochondrial function through a change in the ATP concentration. The plasma concentration of anaesthetic agents measured during their clinical use is at least one order of magnitude less than that required to cause 50% inhibition of gluconeogenesis.

Adenosine Triphosphate↗
PubMed1979

Plasma concentrations of alphaxalone during continuous infusion of Althesin.

Plasma concentrations of alphaxalone have been measured during various rates of continuous infusion of Althesin used to supplement nitrous oxide-oxygen anaesthesia in man. There was an approximately linear relationship between the plasma concentration of alphaxalone and the rate of infusion of Althesin. The rate of uptake of alphaxalone into the liver did not appear to be impaired in the presence of the steroid myoneural blocking agent pancuronium, or in patients with hepatic cirrhosis.

Alfaxalone Alfadolone Mixture↗
PubMed1979

Dose-related haemodynamic effects of continuous infusions of Althesin in man.

The cardiovascular effects of infusions of Althesin at various rates to supplement nitrous oxide anaesthesia have been studied in seven spontaneously breathing patients and11 patients ventilated artificially to normal PaCO2. During spontaneous breathing, increasing rates of Althesin infusion were associated with increases in heart rate and cardiac output. The modest decrease in arterial pressure (-5%) was the result of a decrease in vascular resistance. Increasing rates of Althesin rates of Althesin infusion (up to eight times the minimum infusion rate) caused dose-dependent decreases of arterial pressure and systemic vascular resistance, whereas heart rate and cardiac output were increased slightly at all rates of infusion.

Alfaxalone Alfadolone Mixture↗
PubMed1979

Cardiovascular studies during induction with minaxolone.

The cardiovascular effects of induction of anesthesia with minaxolone, a new water soluble steroid agent, have been studied in 12 normotensive patients and 5 patients with treated hypertension. The arterial pressure, heart rate and ECG were continuously recorded before and during induction of anesthesia with Minaxolone 0.5 mg kg-1. Cardiac output measurements were made in the awake patient, at 3 minutes after the induction of anesthesia and 2 minutes after an increment of the drug. In both groups of patients, induction of anesthesia led to a decrease in systolic arterial pressure and a smaller decrease in diastolic arterial pressures. This was coupled with an increase in the heart rate. The decrease in cardiac output was similar in both the normal and treated hypertensive patients. Administration of an increment of minaxolone (0.1 mg kg-1) did not produce further significant changes in the cardiovascular variables. The results of this study show that the changes in hemodynamic variables with minaxolone are comparable with those seen following induction of anesthesia with other intravenous agents, with the one difference in that there was only minimal change in the diastolic arterial pressure.

Anesthesia, Intravenous↗