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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
PubMed2006

Intravenous anesthesia for the patient with left ventricular dysfunction.

Patients with heart failure have a diminished cardiac reserve capacity that may be further compromised by anesthesia. In addition to depression of sympathetic activity, most anaesthetics interfere with cardiovascular performance, either by a direct myocardial depression or by modifying cardiovascular control mechanisms. Etomidate causes the least cardiovascular depression. It is popular for induction of anesthesia in cardiac-compromised patients; however, it is not suitable for maintenance of anesthesia because it depresses adrenocortical function. Ketamine has a favorable cardiovascular profile related to central sympathetic stimulation and inhibition of neuronal catecholamine uptake. These counteract its direct negative inotropic effect. In patients with a failing myocardium, however, the negative inotropic effects may be unmasked, resulting in deterioration in cardiac performance and cardiovascular instability. Propofol is the most popular intravenous anesthetic for maintenance of anesthesia. It does have a negative inotropic effect, but the net effect on myocardial contractility is insignificant at clinical concentrations, probably because of a simultaneous increase in the sensitivity of the myofilaments to Ca2+. Propofol protects the myocardium against ischemia-reperfusion injury, an action derived from its antioxidant and free-radical-scavenging properties as well as the related inhibition of the mitochondrial permeability transition pore. For intravenous anesthesia, propofol is always combined with an opioid. Opioids have relatively few cardiovascular side effects and, in particular, do not cause myocardial depression. Indeed, they are cardioprotective, with antiarrhythmic activity, and induce pharmacologic preconditioning of the myocardium by a mechanism similar to the inhalational anesthetics.

Anesthesia, Intravenous↗
PubMed2005

Effect of three different anaesthetic agents on the postoperative production of cardiac troponin T in paediatric cardiac surgery.

BACKGROUND: Paediatric cardiac surgery is associated with some degree of myocardial injury. Ischaemic preconditioning (IP) has been investigated widely in the adult population. Volatile agents have been shown to simulate IP providing extra protection to the myocardium during adult cardiopulmonary bypass (CPB) while propofol seems to act through different mechanisms. IP has not been investigated in the paediatric population to the same extent. Cardiac troponin T (cTnT) is a reliable marker of myocardial injury in neonates and children. We have investigated the relationship between three anaesthetic agents, midazolam, propofol, and sevoflurane, and postoperative production of cTnT. METHODS: Ninety patients undergoing repair of congenital heart defect with CPB were investigated in a prospective randomized study. cTnT was measured four times during the first 24 h following admission to the paediatric intensive care unit. Other variables measured included arterial blood gases, lactate, fluid balance, use of inotropic drugs, PaO2/FiO2 ratio and ventilator hours. RESULTS: cTnT was elevated in all three groups throughout the study period. The differences between the three groups were not statistically significant. Eight hours after admission to the intensive care unit cTnT concentrations tended to be higher in the midazolam group [mean (95% confidence intervals)]; 2.7 (1.9-3.5) ng ml(-1). Patients receiving a propofol-based anaesthesia had similar concentrations 2.6 (1.7-3.5) ng ml(-1) while those receiving sevoflurane tended to have a lower cTnT production 1.7 (1.3-2.2) ng ml(-1). CONCLUSIONS: Midazolam, propofol, and sevoflurane appear to provide equal myocardial protection in paediatric cardiac surgery when using cTnT as a marker of myocardial damage.

Anesthetics, Inhalation↗
PubMed2004

Gut permeability in paediatric cardiac surgery.

BACKGROUND: Intestinal mucosal ischaemia can occur in infants and children during and after cardiac surgery. Severe decreases in mucosal perfusion may cause complications such as necrotizing enterocolitis and postoperative mortality. We investigated gut permeability in paediatric patients undergoing cardiac surgery using the dual sugar permeability test and absorption of two other saccharides. METHODS: Thirty-four patients undergoing palliative or corrective surgical procedures with and without cardiopulmonary bypass were investigated. Intestinal permeability was measured using 3-O-methyl-D-glucose, D-xylose, L-rhamnose and lactulose, given orally after induction of anaesthesia and 12 and 24 h later. RESULTS: Lactulose/rhamnose ratios were raised from the outset [median 0.39 (confidence interval 0.07-1.8 for patients undergoing operations without cardiopulmonary bypass and 0.30 (0.02-2.6) with cardiopulmonary bypass]. The highest lactulose/rhamnose ratios were recorded 12 h after surgery 0.32 (0.07-6.9), when cardiopulmonary bypass was used. This is approximately seven times the value expected in healthy children. There was an improvement in patients not undergoing cardiopulmonary bypass: 0.22 (0.03-0.85) 12 h and 0.11 (0-0.48) 24 h after induction of anaesthesia. Patients undergoing repair of aortic coarctation showed the fastest recovery: 0.09 (0.03-0.31) 12 h and 0.07 (0.04-0.35) 24 h after induction of anaesthesia. CONCLUSIONS: Patients with congenital heart defects have abnormal gut permeability when compared with healthy children of similar age. Cardiopulmonary bypass seems to affect the intestinal barrier morphologically (lactulose and rhamnose absorption) and functionally (3-O-methyl-D-glucose and D-xylose absorption).

Cardiopulmonary Bypass↗
PubMed2001

Gender differences in the pharmacokinetics of propofol in elderly patients during and after continuous infusion.

Differences in the pharmacokinetics of propofol between male and female patients during and after continuous infusion have not been described in detail in patients aged 65 yr and older. To increase our insight into the pharmacokinetics of propofol in this patient population and to obtain pharmacokinetic parameters applicable in target controlled infusion (TCI), the pharmacokinetics of propofol during and after continuous infusion were studied in 31 ASA class 1 and 2 patients, aged 65-91 yr, scheduled for general surgery. Patients received propofol 1.5 mg kg(-1) i.v. in 1 min followed by 7 mg kg(-1) h(-1) until skin closure in the presence of a variable rate infusion of alfentanil during oxygen-air ventilation. On the basis of arterial blood samples that were taken up to 24 h post-infusion, the pharmacokinetics of propofol were evaluated in a two-stage manner. Multiple linear regression analysis was used to explore the effect of age, weight, gender and lean body mass as covariates. Gender significantly affected the pharmacokinetics of propofol. V3, Cl1 and Cl2 were significantly different between male and female patients, weight only affected Cl1. The pharmacokinetic parameters were: V1=4.88 litre, V2=24.50 litre, V3 (litre)=115+147 x gender (gender: male=1, female=2), Cl1 (litre min(-1))=-0.29+0.022 x weight+0.22 x gender, Cl2 (litre min(-1))=2.84-0.65 x gender (male=1, female=2), and Cl3=0.788 litre min(-1).

Aged↗
PubMed2001

Recirculatory pharmacokinetics and pharmacodynamics of rocuronium in patients: the influence of cardiac output.

BACKGROUND: Recirculatory models are capable of accurately describing first-pass pharmacokinetics and the influence of cardiac output (CO), which is important for drugs with a fast onset of effect. The influence of CO on pharmacokinetic and pharmacodynamic parameters of rocuronium in patients was evaluated using a recirculatory pharmacokinetic model. METHODS: Fifteen patients were included to study rocuronium pharmacokinetics and pharmacodynamics. Bolus doses of rocuronium (0.35 mg/kg) and indocyanine green (25 mg) were injected simultaneously via a peripheral intravenous catheter. Blood samples were taken for 240 min from the radial artery. The force of contraction of the adductor pollicis after a train-of-four at 2 Hz every 12 s was measured. Arterial concentration-time curves of rocuronium and indocyanine green were analyzed using a recirculatory model. Pharmacodynamics were described using a sigmoid maximum effect (Emax) model. RESULTS: The CO of the patients varied from 2.43 to 5.59 l/min. Total distribution volume of rocuronium was 17.3 +/- 4.8 l (mean +/- SD). The CO showed a correlation with the fast tissue clearance (Cl(T_f); r2 = 0.51), with the slow tissue clearance (Cl(T_s); r2 = 0.31) and with the mean transit times of rocuronium except for the mean transit time of the slow tissue compartment. The blood-effect site equilibration constant (k(e0)) was strongly correlated with CO (r2 = 0.70). CONCLUSIONS: Cardiac output influences the pharmacokinetics, including k(e0), for rocuronium in patients. For drugs with a fast onset of effect, a recirculatory model, which includes CO, can give a good description of the relation between concentration and effect, in contrast to a conventional compartmental pharmacokinetic model.

Adult↗
PubMed2001

Modeling population pharmacokinetics of lidocaine: should cardiac output be included as a patient factor?

BACKGROUND: Inclusion of cardiac output and other physiologic parameters, in addition to or instead of, demographic variables might improve the population pharmacokinetic modeling of lidocaine. METHODS: Thirty-one patients were included in a population pharmacokinetic study of lidocaine. After bolus injection of lidocaine (1 mg/kg), 22 or 10 blood samples per patient were taken from a radial artery. During the experiment, cardiac output was measured using a thoracic electrical bioimpedance method. The following four population pharmacokinetic models were constructed and their performances investigated: a model with no covariates, a model with cardiac output as covariate, a model with demographic covariates, and a model with both cardiac output and demographic characteristics as covariates. Model discrimination was performed with the likelihood ratio test. RESULTS: Inclusion of cardiac output resulted in a significant improvement of the pharmacokinetic model, but inclusion of demographic covariates was even better. However, the best model was obtained by inclusion of both demographic covariates and cardiac output in the pharmacokinetic model. CONCLUSIONS: When population pharmacokinetic models are used for individualization of dosing schedules, physiologic covariates, e.g., cardiac output, can improve their ability to predict the individual kinetics.

Adult↗
PubMed2001

Propofol alters the pharmacokinetics of alfentanil in healthy male volunteers.

BACKGROUND: The influence of propofol on the pharmacokinetics of alfentanil is poorly understood. The authors therefore studied the effect of a pseudo-steady state concentration of propofol on the pharmacokinetics of alfentanil. METHODS: The pharmacokinetics of alfentanil was studied on two occasions in eight male volunteers in a randomized crossover manner with a 3-week interval. While breathing 30% O2 in air, 12.5 microg/kg intravenous alfentanil was given in 2 min, followed by 25 microg.kg(-1).h(-1) for 58 min (sessions A and B). During session B, a target controlled infusion of propofol (target concentration, 1.5 microg/ml) was given from 10 min before the start until 6 h after termination of the alfentanil infusion. Blood pressure, cardiac output, electrocardiogram, respiratory rate, oxygen saturation, and end-tidal carbon dioxide were monitored. Venous blood samples for determination of the plasma alfentanil concentration were collected until 6 h after termination of the alfentanil infusion. Nonlinear mixed-effects population pharmacokinetic models examining the influence of propofol and mean arterial pressure were constructed. RESULTS: A three-compartment model, including a lag time accounting for the venous blood sampling, adequately described the concentration-time curves of alfentanil Propofol decreased the elimination clearance of alfentanil by 15%, rapid distribution clearance by 68%, slow distribution clearance by 51%, and lag time by 62%. Mean arterial pressure and systemic vascular resistance were significantly lower in the presence of propofol. Scaling the pharmacokinetic parameters to the mean arterial pressure instead of propofol improved the model. CONCLUSIONS: Propofol alters the pharmacokinetics of alfentanil. Hemodynamic changes induced by propofol may have an important influence on the pharmacokinetics of alfentanil.

Adult↗
PubMed2000

Effect of epidural and intravenous clonidine on the neuro-endocrine and immune stress response in patients undergoing lung surgery.

The effects of intravenous and epidural clonidine, 4 microg kg-1, combined with epidural morphine, 40 microg kg-1, on the neuro-endocrine and immune stress responses to thoracic surgery are reported. A control group received only epidural morphine. Anaesthesia was induced and maintained with propofol. Catecholamines, vasopressin, cortisol, beta-endorphin concentrations and leucocyte counts were measured before drug administration, immediately after intubation of the trachea, after thoracotomy and at the end of surgery. Catecholamines did not change in any of the groups. The other stress hormones increased during surgery, the pattern being similar in the three groups. Total leucocyte and neutrophil counts were increased in all groups at the end of surgery, but the increase was least in the epidural clonidine group. The number of lymphocytes was reduced at the end of surgery in the epidural and intravenous group, compared with the control group in which the number of lymphocytes did not change. The effects are more pronounced with epidural than with intravenous administration. We conclude that clonidine can modulate the immune stress response to thoracic surgery.

Adrenergic alpha-Agonists↗
PubMed2000

The influence of the alpha2-adrenoceptor agonist, clonidine, on the EEG and on the MAC of isoflurane.

We investigated the influence of intravenous clonidine 2, 4 and 6 microg kg-1 on the electroencephalogram and on the minimal alveolar concentration of isoflurane in 40 patients aged 20-60 years undergoing elective surgery. Minimal alveolar concentration was determined using the Dixon 'up-and-down' method. Thirty min after the clonidine infusion anaesthesia was induced with etomidate, 0.25 mg kg-1. Skin incision was made after stable end-tidal isoflurane concentrations had been maintained for at least 15 min. Clonidine caused significant decreases in the spectral edge (95%) and median power frequency of the electroencephalogram and in the bispectral index. The minimal alveolar concentration of isoflurane decreased in a dose-dependent manner from 1.32% (95% CI, 1.28%-1.36%) in the control group to 1.03% (0.9%-1.18%) in patients given clonidine 6 microg kg-1. Clonidine 4 and 6 microg kg-1 was associated with a moderate reduction in heart rate and arterial systolic blood pressure. We recommend the use of clonidine intravenously as an adjunct to general anaesthesia in a dose of 4 microg kg-1 given 15 min before induction of anaesthesia.

Adrenergic alpha-Agonists↗
PubMed2000

A comparison of the effects of propofol and midazolam on memory during two levels of sedation by using target-controlled infusion.

UNLABELLED: We examined memory during sedation with target-controlled infusions of propofol and midazolam in a double-blinded five-way, cross-over study in 10 volunteers. Each active drug infusion was targeted to sedation level 1 (asleep) and level 4 (lethargic) as determined with the Observer Assessment of Alertness/Sedation scale. At the target level of sedation, drug concentration was clamped for 30 min, during which time neutral words were presented. After 2 h, explicit memory was assessed by recall, and implicit memory by using a wordstem completion test. Venous drug concentrations (mean +/- SD) were 1350 ng/mL (+/-332 ng/mL) for propofol and 208 ng/mL (+/-112 ng/mL) for midazolam during Observer Assessment of Alertness/Sedation scale level 4; and 1620 ng/mL (+/-357 ng/mL) and 249 ng/mL (+/-82 ng/mL) respectively during level 1. The wordstem completion test frequencies at low level sedation were significantly higher than spontaneous frequencies (8.7% + 2.4%; P: < 0.05 in all cases), and lower than during placebo (33.6% + 23%) (P: < 0.05 in all cases, except P: = 0.076 for propofol at level 4). Clinically distinct levels of sedation were accompanied by small differences in venous propofol or midazolam concentrations. This indicates steep concentration-effect relationships. Neutral information is still memorized during low-level sedation with both drugs. The memory effect of propofol and midazolam did not differ significantly. IMPLICATIONS: Implicit memory can occur during different states of consciousness and might lead to psychological damage. In 10 volunteers, implicit memory was investigated during sedation with propofol and midazolam in a double-blinded, placebo-controlled study. To compare the effects of both drugs, they were titrated using a computer-controlled infusion system to produce similar high and low levels of sedation.

Adult↗
PubMed1999

Effect-site modelling of propofol using auditory evoked potentials.

Auditory evoked potentials (AEP) were used to monitor central nervous system effects during induction and recovery from anaesthesia produced by infusion of propofol 30 mg kg-1 h-1 in 22 healthy male patients. Non-parametric and parametric modelling techniques were used successfully to calculate the parameter keo which linked pharmacokinetic with pharmacodynamic aspects of drug action in only 15 of the study patients. In the non-parametric analysis, keo was found to have a mean value of 0.2 (range 0.1-0.36) min-1. Estimation of keo allowed calculation of the effect-site concentration (Ce50) associated with 50% of AEP effect for the population (2.08 micrograms ml-1; 95% confidence limits 1.7-2.45). There were no significant differences between keo values calculated by non-parametric and individual parametric modelling techniques. During recovery, 50% of patients demonstrated evidence of waking at an effect-site concentration of 2.28 micrograms ml-1.

Adult↗
PubMed1999

Target-controlled infusion of alfentanil for postoperative analgesia: contribution of plasma protein binding to intra-patient and inter-patient variability.

We have examined the influence of plasma protein binding on inter-individual and intra-individual variability in the effective postoperative analgesic concentration (EAC) of alfentanil and on the performance of the target-controlled infusion system used. Ten patients received standardized anaesthesia and target-controlled alfentanil for postoperative analgesia. Analgesia was assessed using a visual analogue scale (VAS). Plasma protein binding of alfentanil was assessed at four different times (on arrival in the recovery room, at 21:00 on the day of surgery and at 09:00 and 21:00 on the first postoperative day). Bias and inaccuracy were examined on the day of surgery and on the first postoperative day. Unbound fractions of alfentanil varied from 5 to 15% and varied in time. In general, the unbound fractions on the day of surgery were higher than those on the first postoperative day. Thirty-nine percent of inter-individual variability in the EAC of alfentanil (range 33-140 ng ml-1) at the onset of therapy could be explained by protein binding. At the other observation times, correlations between unbound fraction and EAC were only moderate. Bias on the day of surgery was -19% and 12% on the first postoperative day (ns). Inaccuracy was 23% and 18%, respectively (ns). We conclude that inter-individual variations in plasma protein binding can explain a significant portion of inter-individual variability in the EAC of alfentanil in the early postoperative phase.

Adolescent↗
PubMed1999

Pharmacodynamic interaction of eltanolone and alfentanil during lower abdominal surgery in female patients.

We have studied the influence of eltanolone on intraoperative alfentanil requirements in 18 female patients undergoing lower abdominal surgery receiving target-controlled infusions of eltanolone and alfentanil. While target concentrations of eltanolone were maintained constant, target concentrations of alfentanil changed in response to the presence or absence of responses. With serum eltanolone concentrations increasing from 500 to 2000 ng ml-1, the EC50 of alfentanil for suppression of responses to surgical stimulation decreased from 233 to 9 ng ml-1. The findings suggest that the interaction between eltanolone and alfentanil is synergistic.

Abdomen↗
PubMed1999

Recirculatory and compartmental pharmacokinetic modeling of alfentanil in pigs: the influence of cardiac output.

BACKGROUND: Cardiac output (CO) is likely to influence the pharmacokinetics of anesthetic drugs and should be accounted for in pharmacokinetic models. The influence of CO on the pharmacokinetic parameters of alfentanil in pigs was evaluated using compartmental and recirculatory models. METHODS: Twenty-four premedicated pigs were evaluated during halothane (0.6-2%) anesthesia. They were assigned randomly to one of three groups. One group served as control. In the other groups, the baseline CO was decreased or increased by 40% by pharmacologic intervention (propranolol or dobutamine). Boluses of alfentanil (2 mg) and indocyanine green (25 mg) were injected into the right atrium. Blood samples were taken for 150 min from the right atrium and aortic root. Arterial concentration-time curves of indocyanine green and alfentanil were analyzed using compartmental models (two-stage and mixed-effects approach) and a recirculatory model, which can describe lung uptake and early distribution. RESULTS: The CO of individual pigs varied from 1.33 to 6.44 l/min. Three-compartmental modeling showed that CO is a determinant of the central compartment volume (V1, r2 = 0.54), fast peripheral compartment volume (V2, r2 = 0.29), steady state distribution volume (Vss, r2 = 0.29), fast distribution clearance (Cl12, r2 = 0.39), and elimination clearance (Cl10, r2 = 0.51). Recirculatory modeling showed that CO is a determinant of total distribution volume (r2 = 0.48), elimination clearance (r2 = 0.54), and some distribution clearances. The pulmonary distribution volume was independent of CO. CONCLUSIONS: Cardiac output markedly influences the pharmacokinetics of alfentanil in pigs. Therefore, accounting for CO enhances the predictive value of pharmacokinetic models of alfentanil.

Alfentanil↗