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Biomedical subjects

J G Bovill

Publications and source records attributed to J G Bovill.

At least 19 recordsLinked to original sources
PubMed1997

Adverse drug interactions in anesthesia.

Anesthesia often involves the administration of several drugs belonging to different classes. In addition, many patients will be taking a number of drugs related to their surgical condition or for other medical diseases. Thus, there is a considerable potential for drug interactions in the perioperative period, some of which may be potentially harmful to patients. The most common interactions involve changes in the pharmacokinetics or pharmacodynamics of one drug caused by induction or inhibition of the cytochrome P450 enzyme system by another drug. Other important interactions involve monoamine oxidase inhibitors, some antibiotics, and the tricyclic and tetracyclic antidepressants. These adverse interactions are the subject of this review.

Anesthetics↗
PubMed1997

Double-blind comparison of alizapride, droperidol and ondansetron in the treatment of post-operative nausea.

To compare the efficacy in the treatment of post-operative nausea and/or vomiting (PONV), 75 patients undergoing gynaecological procedures under general anaesthesia using N2O/enflurane who suffered from PONV in the first hour after surgery were randomly allocated to three groups containing 25 patients each to receive either alizapride 100 mg, droperidol 1 mg or ondansetron 8 mg (i.v.). Patients expressed the severity of their nausea on a Visual Analogue Scale (VAS) ranging from 0 (none) to 10 (as bad as possible). Vomiting was recorded as present or absent, and the number of emetic events was noted. Data were recorded until rescue medication was given or until 4 h after the administration of the study drug. There were no significant differences between the three groups in the average VAS scores and the presence of vomiting at the time of entry into the study. Fifteen and 30 min after the administration of the study drug, VAS decreased notably in all groups. This decreases was similar and statistically significant within each group. However, comparison between the three groups showed no statistically significant differences. There was no statistically significant difference between the three groups in the number of patients receiving rescue medication, the number of emetic events and the time from administration of the study drug until rescue medication was given. It is concluded that alizapride 100 mg, droperidol 1 mg and ondansetron 8 mg intravenously are equally effective in the treatment of PONV after gynaecological procedures and that the newer drugs alizapride and ondansetron offer no advantage over droperidol.

Adolescent↗
PubMed1997

Target-controlled infusion of alfentanil for postoperative analgesia: a feasibility study and pharmacodynamic evaluation in the early postoperative period.

We have examined the feasibility of target-controlled infusion of alfentanil (TCIA) and the pharmacodynamics of alfentanil in the early postoperative period. Patients were allocated randomly to one of the three groups to receive balanced anaesthesia with bolus injections of fentanyl (group F), sufentanil (group S) or alfentanil (group A). In the recovery room all patients received the same analgesic regimen, comprising TCIA. To evaluate the efficacy of postoperative analgesia, pain scores were measured on a visual analogue scale (VAS) and patients indicated a need for additional analgesia. EC50, the concentration at which, with a 50% probability, patients reported adequate analgesia, was estimated using logistic regression. Six patients did not complain of pain. The time from the last intraoperative bolus injection of opioid until patients complained of postoperative pain was shorter (P < 0.05) in group A (mean 68 min) than in group F (101 min) and group S (136 min). The time to onset of satisfactory analgesia was comparable in the three groups (median 18 min in group F, 15 min in group S and 14 min in group A). EC50 of alfentanil was determined in 28 patients; mean values were 26 ng ml-1 (group F), 39 ng ml-1 (group S) and 52 ng ml-1 (group A). We conclude that TCIA, under the conditions studied, resulted in a fast onset of adequate analgesia, irrespective of the opioid administered during operation. Also, there was no effect of opioids administered during operation on postoperative pharmacodynamics of alfentanil.

Adolescent↗
PubMed1997

Mechanisms of actions of opioids and non-steroidal anti-inflammatory drugs.

Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are the commonest drugs used to treat pain. Opioids mimic the actions of endogenous opioid peptides by interacting with mu, delta or kappa opioid receptors. The opioid receptors are coupled to G1 proteins and the actions of the opioids are mainly inhibitory. They close N-type voltage-operated calcium channels and open calcium-dependent inwardly-rectifying potassium channels. This results in hyperpolarization and a reduction in neuronal excitability. They also decrease intracellular cAMP which modulates the release of nociceptive neurotransmitters (e.g. substance P). Inhibition of prostaglandin synthesis by cyclooxygenase is the principal mode of the analgesic and anti-inflammatory actions of NSAIDs. Cyclo-oxygenase is inhibited irreversibly by aspirin and reversibly by other NSAIDs. The widespread inhibition of cyclo-oxygenase is responsible for many of the adverse effects of these drugs. NSAIDs also reduce prostaglandin production within the CNS. This is the main action of paracetamol.

Analgesics, Opioid↗
PubMed1996

Pulmonary distribution of alfentanil and sufentanil studied with system dynamics analysis.

We applied a system dynamics approach to the study of the pulmonary distribution of alfentanil and sufentanil in anesthetized pigs and patients, respectively. This method allows estimation of the mean transit time through the lungs and calculation of the volume of distribution of alfentanil in the lungs. In the first part of the study the pulmonary distribution of alfentanil was studied in six anesthetized pigs during three hemodynamic states (control, partial clamping of the inferior vena cave, and complete clamping of the right pulmonary artery). In the second part of the study the pulmonary distribution of sufentanil was studied in 10 patients, scheduled for elective CABG, during and after a constant rate infusion of 10 min. Pulmonary passage of the opioids was characterized by functions of transit times, derived from the pulmonary arterial and systemic arterial concentration curves. Pulmonary distribution volumes were calculated from the mean transit time and pulmonary blood flow. Pulmonary distribution volume of alfentanil during the control measurement was significantly higher (486 +/- 88 ml) than during either partial caval clamping (346 +/- 89 ml, p < 0.05) or right pulmonary artery clamping (336 +/- 56 ml, p < 0.05). There was no change in the extravascular volume of distribution of alfentanil with each hemodynamic state. Pulmonary volume of distribution of sufentanil in the patients was 22.6 (10.9) L. Pulmonary distribution of opioids can be studied using system dynamics analysis, both after bolus injection and during and after infusion. This method can be used for periods beyond the initial passage of the drug through the lungs.

Alfentanil↗
PubMed1996

Pulmonary uptake of sufentanil during and after constant rate infusion.

We have studied the pulmonary uptake of sufentanil in patients during and after a short infusion of the drug. We studied 10 patients undergoing elective coronary artery bypass surgery during anaesthesia with 0.4-0.8% enflurane, before surgery. Sufentanil 50 micrograms min-1 was given over 10 min by a constant rate infusion. During infusion and for 20 min thereafter, blood samples were obtained from the distal port of the pulmonary artery catheter and from a radial artery catheter. Uptake and release of sufentanil into and from the lungs were examined by mass balance and compartmental analyses. At the end of the infusion a mean of 48.9 (SD 18.6)% of the dose was retained in the lungs, and 20 min after infusion retention was 18.4 (22.4)%. Smokers had significantly higher pulmonary retention of sufentanil. The pulmonary volume of distribution of sufentanil, estimated from the two-compartment model, was 20.9 (7.7) litre. We conclude that pulmonary uptake of sufentanil is significant, if the drug is given as an infusion.

Anesthetics, Intravenous↗
PubMed1996

Pharmacodynamic interaction between propofol and alfentanil when given for induction of anesthesia.

BACKGROUND: Propofol and alfentanil often are combined during induction of anesthesia. However, the interaction between these agents during induction has not been studied in detail. The influence of alfentanil on the propofol concentration-effect relationships was studied for loss of eyelash reflex, loss of consciousness, and hemodynamic function in 20 unpremedicated ASA physical status 1 patients aged 20-55 yr. METHODS: Patients were randomly divided into four groups to receive a computer- controlled infusion of alfentanil with target concentrations of 0, 50, 200, or 400 ng/ml (groups A, B, C, and D, respectively). While the target concentration of alfentanil was maintained constant, patients received a computer- controlled infusion of propofol, with an initial target concentration of 0.5-1 microgram/ml, that was increased every 12 min by 0.5-1 microgram/ml. Every 3 min, the eyelash reflex and state of consciousness were tested an an arterial blood sample was taken for blood propofol and plasma alfentanil determination. The propofol-alfentanil concentration-response relationships for loss of eyelash reflex and loss of consciousness were determined by nonlinear regression, and for the percentage of change in systolic blood pressure and heart rate by logistic regression. RESULTS: The patient characteristics did not differ significantly among the four groups. The patients in groups A and B continued to breathe adequately, whereas all patients in groups C and D required assisted ventilation. End-tidal carbon dioxide partial pressure remained less than 46 mmHg in all patients. With plasma alfentanil concentrations increasing from 0 to 500 ng/ml, the EC(50) of propofol decreased from 2.07 to 0.83 microgram/ml for loss of eyelash reflex and from 3.62 to 1.55 microgram/ml for loss of consciousness. With plasma alfentanil concentrations increasing from 0 to 500 ng/ml, the blood propofol concentrations associated with a 10% decrease in systolic blood pressure and heart rate decreased from 1.68 to 0.17 microgram/ml and from 2.36 to 0.04 microgram/ml, respectively. CONCLUSIONS: Alfentanil significantly reduces blood propofol concentrations required for loss of eyelash reflex and loss of consciousness. In addition, alfentanil enhances the depressant effects of propofol on systolic blood pressure and heart rate. Hemodynamic stability, therefore, does not increase in patients receiving propofol in combination with alfentanil compared to those receiving propofol as the sole agent for induction of anesthesia.

Adult↗
PubMed1996

Comparison of sufentanil/propofol versus isoflurane/nitrous oxide anaesthesia on mesenteric artery blood flow.

Duplex sonography was used to determine the changes in mesenteric arterial blood flow occurring in patients undergoing aortic surgery, anaesthetised either by total intravenous anaesthesia with propofol and sufentanil (group A) or inhalational anaesthesia with isoflurane and nitrous oxide (group B). Sixteen patients were studied. Measurements were performed immediately before and 15 min after induction of anaesthesia, before surgery. There was a 38% decrease (p = 0.015) in the superior mesenteric artery end diastolic velocity in group A and a 23% decrease (p = 0.033) in the superior mesenteric artery peak systolic velocity in group B. There were no changes in any of the other sonography parameters in either group. We conclude that neither total intravenous anaesthesia with propofol and sufentanil nor inhalational anaesthesia with isoflurane and nitrous oxide have any clinically significant influence on mesenteric blood flow in the absence of surgical stimulation.

Aged↗
PubMed1995

First-pass pulmonary retention of sufentanil at three different background blood concentrations of the opioid.

Using a double-indicator technique, we have studied, in 10 patients undergoing aorto-coronary bypass surgery, first-pass pulmonary retention of sufentanil. Pulmonary retention was studied at three pseudo steady-state background blood concentrations of 2.8 (0.66), 6.9 (1.2) and 15.9 (2.6) ng ml-1, respectively, produced by a computer-controlled infusion. Mean first-pass pulmonary retentions at these concentrations were 68 (95% confidence intervals 62-73), 65 (60-70) and 60 (52-67)%, respectively. First-pass pulmonary retention of sufentanil was significantly lower at the highest background concentration compared with the lowest background concentration. First-pass pulmonary retention of sufentanil was partly saturable in the range of concentrations used for clinical purposes.

Coronary Artery Bypass↗
PubMed1995

Computer-controlled infusion of alfentanil versus patient-controlled administration of morphine for postoperative analgesia: a double-blind randomized trial.

This study compared the efficacy of computer-controlled infusion of alfentanil (CCiA) with patient-controlled administration of morphine (PCAM) for postoperative analgesia. Twenty patients were randomly allocated to one of the two study groups to receive either an intravenous CCiA or PCAM regimen. Pain scores measured on a visual analog scale (VAS) and the number of valid demands were used as variables to evaluate the efficacy of the postoperative analgesic therapy. In addition, the bias and inaccuracy of the pharmacokinetic data set of alfentanil used in the CCiA program were examined by determining the median performance error (MDPE), and the median absolute performance error (MDAPE). The onset of satisfactory analgesia was faster (P < 0.05) in the CCiA group (median: 20 min) than in the PCAM group (median: 50 min). The total number of demands was lower (21 vs 34, P < 0.05) and the time when the VAS score was > 3.0 was shorter (P < 0.05, 12% of the time) in the CCiA group than in the PCAM group (21% of the time). The MDPE and MDAPE were 8% and 22%, respectively. The maximum alfentanil concentrations associated with pain and the minimum effective analgesic concentrations of alfentanil varied considerably both inter- and intraindividually. In conclusion, compared to a standard intravenous PCAM regimen, a CCiA is faster in onset of analgesia and is as effective in providing postoperative analgesia.

Adolescent↗
PubMed1995

Performance of computer-controlled infusion of propofol: an evaluation of five pharmacokinetic parameter sets.

Computer-controlled infusion of propofol is used with increasing frequency for the induction and maintenance of anesthesia. The performance of computer-controlled infusion devices is highly dependent on how well the implemented pharmacokinetic parameter set matches the pharmacokinetics of the patient. This study examined the performance of a computer-controlled infusion device when provided with five different pharmacokinetic parameter sets of propofol in female patients. The infusion rate-time data that had been stored on a disk from 19 female patients who had been given propofol by computer-controlled infusion, using the pharmacokinetic parameter set from Gepts et al. (Anesth Analg 1987;66:1256-63), were entered into a computer simulation program to recalculate predicted propofol concentrations that would have been obtained with four other pharmacokinetic parameter (Shafer et al., Anesthesiology 1988;69:348-56; Kirkpatrick et al., Br J Anesth 1988;60:146-50; Cockshott et al., Br J Anesth 1987;59:941P; Tackley et al., Br J Anesth, 1989;62:46-53) sets of propofol, had these been implemented. The performance error (PE) was determined for each measured blood propofol concentration, on the basis of each of the five pharmacokinetic parameter sets. Then, for each of the five pharmacokinetic parameter sets, the performance in the population was determined by the median absolute performance error (MDAPE), the median performance error (MDPE), the wobble (the median absolute deviation of each PE from the MDPE), and the divergence (the percentage change of the absolute PE with time). The MDPE and MDAPE were compared between the parameter sets by the multisample median test. The initially used pharmacokinetic parameter set from Gepts et al. resulted in a MDPE of 24% and MDAPE of 26%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The pharmacodynamic interaction of propofol and alfentanil during lower abdominal surgery in women.

BACKGROUND: Propofol and alfentanil are frequently combined to provide general anesthesia. The purpose of this study was to characterize the pharmacodynamic interaction between propofol and alfentanil for several clinically relevant end points. METHODS: Twenty-one women, aged 20-55 yr, scheduled for lower abdominal surgery, were randomly assigned in a double-blind manner to one of three groups to receive a computer-controlled infusion of propofol with target concentrations of 2, 4, or 6 micrograms/ml. In addition, all patients received computer-controlled infusion of alfentanil (initial target concentration 50 ng/ml). While the target concentration of propofol was maintained constant, the target concentration of alfentanil was varied in steps of 10-50 ng/ml according to the presence or absence of patient responses to perioperative stimuli. Arterial blood samples for alfentanil and propofol determination were taken at clinically relevant stimuli. Alfentanil-propofol interactions for laryngoscopy, intubation, skin incision, the opening of the peritoneum, and awakening were determined by logistic regression over the three groups (n = 21). The alfentanil concentrations associated with a 50% probability (EC50s) of suppression of responses to intraabdominal surgical stimuli, as determined by logistic regression in the individual patients, were related to corresponding mean blood propofol concentrations by nonlinear regression analysis. RESULTS: With blood propofol concentrations increasing from 2 to 10 micrograms/ml, the EC50 of alfentanil decreased from 170 to 25 ng/ml for laryngoscopy, from 280 to 23 ng/ml for intubation, from 259 to 9 ng/ml for the opening of the peritoneum, and from 209 to 16 ng/ml for the intraabdominal surgical stimuli. With plasma alfentanil concentrations increasing from 10 to 150 ng/ml, the EC50 of propofol for the regaining of consciousness decreased from 3.8 to 0.8 microgram/ml. DISCUSSION: We defined the pharmacodynamic interaction between propofol and alfentanil for suppression of responses to perioperative stimuli during lower abdominal surgery. We conclude that propofol reduces alfentanil requirements for all studied clinical end points. In addition, alfentanil decreases propofol concentrations at which patients regain consciousness.

Abdomen↗
PubMed1995

The effect of midazolam premedication on implicit memory activation during alfentanil-nitrous oxide anaesthesia.

Eighty-three patients were given midazolam 0.1 mg.kg-1 by intramuscular injection as premedication before general anaesthesia with alfentanil-nitrous oxide. During anaesthesia patients were presented (through headphones) with either statements about common facts of some years ago (group A) (n = 43) or new verbal associations, e.g. names of fictitious, nonfamous people (group B) (n = 40). In a previous study with the same anaesthetic technique, but without premedication there was significant activation of implicit memory (p < 0.001). In this study we found no explicit or implicit memory for the auditory information presented during anaesthesia. Midazolam premedication can prevent implicit memory activation during alfentanil-nitrous oxide anaesthesia.

Adult↗
PubMed1994

The Leiden anaesthesia simulator.

We describe an anaesthesia simulator capable of simulating all possible situations during anaesthesia. The Leiden anaesthesia simulator (LAS) may be used with most commercially available anaesthesia equipment and monitors, which are connected to the simulated patient as they are to a patient. A commercially available intubation manikin attached to an electromechanical lung model represents the patient. The lung allows both spontaneous and mechanical ventilation. Compliance, resistance, tidal volume and ventilatory frequency may be altered by a controlling computer. Carbon dioxide production and oxygen uptake are simulated. Physiological signals (ECG, arterial, pulmonary arterial and central venous pressure waveforms) generated by a signal generator under software control provide input to the monitors. All types of ECG disturbances may be simulated. There are facilities for simulating non-invasive arterial pressure measurement and pulse oximetry. A series of physiological models is being developed to control interactions between the cardiovascular and respiratory variables. During a simulation session, a pre-defined scenario is presented to the trainee. The task of the trainee is to diagnose and treat the problem as if in real life. The simulator experiences on the LAS were judged as highly realistic by 28 subjects. This simulator is currently being used for teaching and training of anaesthetists, trainees and anaesthesia personnel and for research.

Anesthesiology↗
PubMed1994

Does training on an anaesthesia simulator lead to improvement in performance?

We have used the Leiden anaesthesia simulator, which makes use of a standard anaesthesia machine and monitors, and realistically simulates the anaesthesia work place. After obtaining informed consent, 28 anaesthetists and anaesthesia trainees in one hospital took part in the study. All participants were exposed to a pre-scripted simulated "control" scenario of anaphylactic shock (phase 1). The sessions were videotaped and the performances of individual participants were evaluated using a standardized scoring scheme. During phase 2, the participants were allocated randomly to undergo training in the management of either anaphylactic shock (group A, n = 13) or malignant hyperthermia (group B, n = 15) on the simulator. After 4 months, each participant underwent a blinded evaluation session with a pre-scripted "test" scenario of malignant hyperthermia (phase 3). These sessions were also videotaped and evaluated as for phase 1. The participants in group B responded more quickly, treated better and deviated less from the accepted procedure during phase 3 than those in group A. The total performance of participants in group B during phase 3 was significantly better than those in group A. We conclude that training on an anaesthesia simulator does improve the performance of anaesthetists in dealing with emergencies during anaesthesia.

Anaphylaxis↗