PubMed Health⌕ Search

Biomedical subjects

A G Burm

Publications and source records attributed to A G Burm.

At least 73 records · Page 4Linked to original sources
PubMed1991

Age does not influence the serum protein binding of bupivacaine.

The serum protein binding of bupivacaine was studied in 74 subjects, 39 males and 35 females, aged 20-90 years, without evidence of acute or chronic inflammatory disease or malignancy. Subjects were drug free for at least 1 month. The free fractions of bupivacaine did not change with age in either males or females. This is in keeping with the lack of effect of age on AAG concentrations. Free fractions of bupivacaine were slightly higher in females as compared with males. The previously observed decline in clearance of bupivacaine with age probably reflects a concomitant decline in the metabolic activity of hepatic enzymes.

Adult↗
PubMed1991

Pharmacokinetics and EEG effects of flumazenil in volunteers.

The effect of intravenous flumazenil 10 mg on the electroencephalogram (EEG) was investigated in 7 volunteers in a placebo-controlled, randomised, double-blind, crossover study. The EEG was recorded between Fp1-M1 and Fp2-M2 and analysed using an aperiodic analysis technique. Two volunteers were excluded from the study because of significant asymmetry between baseline EEG recordings of the left and right hemisphere, in the remainder there were no changes in the beta-frequency range (12 to 30 Hz) or in other ranges of the EEG during or after flumazenil or placebo administration, with regard to the parameters total number of waves per second or total amplitude per second. There were no changes in heart rate, respiratory rate or blood pressure after administration of flumazenil or placebo. Three volunteers reported feelings of 'pressure to move' during the initial 2 min of the flumazenil infusion. The pharmacokinetics of flumazenil were investigated in the same volunteers. Flumazenil 10 mg was administered intravenously over 10 min; the data from 1 volunteer were excluded from this analysis because of blood sampling problems. The plasma concentration-time data of the remaining 6 volunteers were characterised by a biexponential function. The pharmacokinetic parameters were (mean +/- SD): initial volume of distribution, 16 +/- 5.7L; volume of distribution at steady-state, 64.8 +/- 12.5L; total body clearance, 53.8 +/- 1.2 L/h; distribution half-life, 4.1 +/- 1.3 min; and elimination half-life, 70.2 +/- 9.9 min. The authors conclude that flumazenil has no significant EEG effects. The rapid distribution and elimination of flumazenil may explain its previously reported short duration of action after intravenous anaesthesia with high doses of midazolam.

Adolescent↗
PubMed1991

Pharmacokinetic-pharmacodynamic modelling of the interaction between flumazenil and midazolam in volunteers by aperiodic EEG analysis.

The CNS effects resulting from the combined administration of midazolam and flumazenil were studied in 8 healthy volunteers to develop a model of the pharmacokinetic-pharmacodynamic interaction. Electroencephalograms (EEG) were recorded between Fp1-M1 and Fp2-M2. The EEG parameter total number of waves between 12 and 30 Hz (TNW12-30) derived by aperiodic analysis was used to quantify the effect. Following a 15 min baseline EEG recording, infusion of placebo or flumazenil was started. Infusion regimens for flumazenil were designed so that 'steady-state' concentrations of 10 and 20 micrograms/L were obtained. Doses of midazolam 15, 30 and 60 mg over 5 min were given 30 min after the start of placebo infusion (session A) or flumazenil infusion to 10 micrograms/L (session B) or 20 micrograms/L (session C), respectively. Venous blood samples were taken until 8 h after the start of the flumazenil or placebo infusion. A sigmoid maximum effect (Emax) model was used to characterise the relationship between the plasma concentration of midazolam which is in equilibrium with the effect compartment concentration (Cem) [Cem/Kp] and TNW12-30. Within 2 to 5 min of starting the midazolam infusion all subjects fell asleep, with loss of eyelid reflex. They awoke between 25 and 82 min later in all 3 sessions. The mean (+/- SD) plasma drug concentrations of midazolam corresponding to half the maximum increase in TNW12-30 (EC50) were 276 +/- 64, 624 +/- 187 and 1086 +/- 379 micrograms/L in sessions A, B and C, respectively. The half-lives reflecting equilibration between plasma concentration and effect (t1/2ke0), estimated by a nonparametric method, were 2.2 +/- 1.2, 3.3 +/- 3.3 and 2.9 +/- 1.2 min for the 3 different sessions. Emax and N were not affected by flumazenil. In each subject the plot of the average measured steady-state plasma flumazenil concentration versus the EC50 of midazolam showed a linear relationship. The plasma concentration of flumazenil that doubled the EC50 of midazolam (Cf,2) was 6.5 +/- 1.0 micrograms/L. The observed interaction is consistent with the competitive nature of the antagonism of midazolam by flumazenil.

Adult↗
PubMed1990

The effect of age on serum concentrations of albumin and alpha 1-acid glycoprotein.

1. Human serum albumin (HSA) concentrations and alpha 1-acid glycoprotein (AAG) concentrations were measured in 68 subjects, 35 males and 33 females, aged 20-90 years without evidence of acute or chronic inflammatory disease or malignancy. Subjects were drug free for at least 1 month. HSA and AAG concentrations were measured using rate nephelometry. 2. Age had no effect on alpha 1-acid glycoprotein concentration, whereas plasma albumin levels decreased as a function of age in both sexes. We observed no differences between males and females in the plasma concentrations of HSA and AAG. 3. These data show that in healthy subjects the HSA concentration decreases with increasing age, whereas age, uncomplicated by disease does not influence AAG concentration.

Adult↗
PubMed1990

Single-dose interpleural versus intercostal blockade: nerve block characteristics and plasma concentration profiles after administration of 0.5% bupivacaine with epinephrine.

Analgesic effects and plasma concentration profiles after interpleural (IP) or intercostal (IC) administration of 21 mL of 0.5% bupivacaine with epinephrine (5 micrograms/mL) were studied in 24 patients (IP group: n = 12; IC group: n = 12) who had undergone cholecystectomy or renal surgery. The number of blocked dermatomes, as assessed by pinprick, was more variable between patients in the IP group (2-9 dermatomes) than in the IC group (6-8 dermatomes). The mean time intervals from the injection to two-dermatome regression and to first need for additional pain medication were 4 h (IP) and 5.5 h (IC) (P less than 0.02) and 5.3 h (IP) and 9.8 h (IC) (P = 0.002), respectively. The degree of postoperative pain was evaluated by means of a visual analogue scale. This gradually increased during the first 4 h in the IP group (P less than 0.001), but not in the IC group. Peak bupivacaine concentrations in arterial plasma were approximately 10% higher than those in venous plasma and were attained more rapidly. Peak arterial plasma concentrations after IP injection (2.07 +/- 0.53 micrograms/mL) were significantly higher (P less than 0.005) than those after IC administration (1.36 +/- 0.48 micrograms/mL). Peak venous plasma concentrations showed a similar difference (IP: 1.86 +/- 0.45 micrograms/mL; IC: 1.21 +/- 0.48 micrograms/mL; P less than 0.005). Peak concentrations were attained later after IP injection both in arterial (IP: 16.3 +/- 4.6 min; IC: 8.8 +/- 5.4 min; P less than 0.002) and venous plasma (IP: 20.0 +/- 7.1 min; IC 13.3 +/- 6.9 min; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Comparison of midazolam and propofol in combination with alfentanil for total intravenous anesthesia.

Hemodynamic function during induction of anesthesia, the alfentanil and naloxone requirements, and the speed of recovery from total intravenous anesthesia with alfentanil/midazolam (group M, n = 10) or alfentanil/propofol (group P, n = 10) were compared in patients undergoing lower limb surgery. Twenty patients were randomly assigned to receive either 2 mg/kg propofol in 5 min followed by 9 mg.kg-1.h-1 for 30 min and 4.5 mg.kg-1.h-1 until skin closure, or 0.42 mg/kg midazolam in 5 min followed by 0.125 mg.kg-1.h-1 until skin closure. Simultaneously, a variable-rate infusion of alfentanil was given. Patients were ventilated with 30% oxygen in air. In both groups blood pressure and heart rate decreased significantly (P less than 0.02) and to a similar extent during induction. The total dose of alfentanil was similar in both groups. No patient in group P and nine patients in group M needed naloxone (average dose 130 +/- 70 micrograms, P less than 0.001). Recovery, as judged by psychomotor tests (90% score was reached at 1 h in the P group and at about 4 h in the M group, P less than 0.001), sedative scores, and orientation in time and place, was shorter in group P than in group M. The conclusion is reached that propofol is superior to midazolam in total intravenous anesthesia with alfentanil.

Adult↗
PubMed1990

Quantification of the EEG effect of midazolam by aperiodic analysis in volunteers. Pharmacokinetic/pharmacodynamic modelling.

The effects of midazolam on the EEG were related to plasma midazolam concentrations in 8 healthy male volunteers in order to develop a pharmacokinetic-pharmacodynamic model. The EEG parameters were derived by aperiodic analysis. The EEG was recorded between Fp1-M1 and Fp2-M2. Following a 15-minute baseline EEG registration, midazolam 15 mg was given intravenously over 5 minutes. Venous blood samples were taken until 8 hours after the start of the infusion. Within 2 to 4 minutes of starting the infusion all subjects became asleep, with loss of eyelid reflex. The most obvious EEG changes, in the beta frequency range (12 to 30 Hz), were observed within 2 minutes of the start of drug administration. Seven subjects awoke 60 to 70 minutes after the start of the infusion and 1 awoke after 45 minutes. The EEG parameter that best characterised the effect of midazolam was the total number of waves per second in the frequency range 12 to 30 Hz (TNW12-30). This was used as the effect parameter in the pharmacokinetic-pharmacodynamic modelling. The plasma concentration-time data were characterised by a triexponential function for all subjects. To allow for a possible delay between plasma midazolam concentration and EEG effect, a hypothetical effect compartment was included in the pharmacokinetic-pharmacodynamic model. A sigmoid maximum effect (Emax) model was used to characterise the effect compartment midazolam concentration-TNW12-30 data. The plasma drug concentration corresponding to half the maximum increase in TNW12-30 (EC50) was 290 +/- 98 micrograms/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Influence of age on the pharmacokinetics of alfentanil. Gender dependence.

Studies on the effects of age on the pharmacokinetics of alfentanil are inconclusive. A possible factor in explaining the differences between various studies could be the effect of gender. The authors studied the effects of age on the pharmacokinetics of alfentanil in female (n = 21) and male (n = 15) patients undergoing lower abdominal surgery under nitrous oxide alfentanil anaesthesia. There was a significant negative correlation (r = -0.79, p less than 0.001) between plasma alfentanil clearance (CL) and age in women (less than 50y, median CL 24.84 L/h; greater than 50y, median CL 14.52 L/h), but not in men (less than 50y, median CL 19.44 L/h; greater than 50y, median CL 16.2 L/h). The conclusion is drawn that the effects of age on the pharmacokinetics of alfentanil are gender-dependent.

Adult↗
PubMed1989

Alcohol consumption alters the pharmacodynamics of alfentanil.

Two groups of women, ASA physical status 1, undergoing surgery for primary breast cancer, were studied to assess the effect of alcohol intake on alfentanil pharmacodynamics. Patients in group 1 (n = 6) had an average daily consumption of 20-40 g alcohol. Patients in group 2 (n = 8) were life-long abstainers or drank only occasionally (less than 60 g per year). Anesthesia was induced and maintained with 66% N2O in O2 and alfentanil. Alfentanil was administered by a computer-controlled infusion pump. If during surgery the patient exhibited somatic, hemodynamic, or other autonomic signs of inadequate anesthesia (response), the target alfentanil plasma concentration was increased by 50-100 ng/ml. If there was no response during a 15-min period, the target concentration was decreased by 50-100 ng/ml. Arterial blood samples were taken before any change of the target concentration, 4 min after a new predicted target concentration was achieved, and at extubation. Plasma concentrations were determined by capillary gas chromatography. Alfentanil protein binding was measured by equilibrium dialysis. Plasma alfentanil concentration-effect data were analyzed by nonlinear regression, where effect was either response or no response to surgical stimuli. The average total alfentanil requirement was significantly (P less than 0.005) higher in group 1 (3.7 +/- 1.2 micrograms.kg-1.min-1) than in group 2 (1.9 +/- 0.4 micrograms.kg-1.min-1). The average Cp50 (the plasma concentration for which the probability of no response during surgery is 50%) was significantly (P less than 0.001) higher in group 1 (522 +/- 104 ng/ml) than in group 2 (208 +/- 26 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMed1989

Alfentanil requirement in Crohn's disease. Increased alfentanil dose requirement in patients with Crohn's disease.

The dose requirement of alfentanil as a supplement to nitrous oxide anaesthesia was studied in 13 patients with Crohn's disease and seven control patients all of whom underwent laparotomy. Alfentanil was administered as a variable rate infusion with supplemental bolus injections titrated to the patient's needs. The alfentanil requirement was independent of the duration of surgery and was significantly higher in patients with Crohn's disease than in control patients. The results indicate that Crohn's disease alters the dose requirement of alfentanil.

Adjuvants, Anesthesia↗
PubMed1989

Clinical pharmacokinetics of epidural and spinal anaesthesia.

Epidural and spinal anaesthesia results from the interaction of local anaesthetics with nerve structures, primarily those located within the subarachnoid space. Local anaesthetics can reach the sites of action along various distribution pathways. Uptake into extraneural tissues (in particular epidural fat) and systemic absorption compete with neural tissue distribution and thereby affect the clinical potency and duration of action. Consequently, epidural doses must be much higher than spinal doses. The systemic absorption of lignocaine (lidocaine), bupivacaine and etidocaine following lumbar epidural administration has been shown to be biphasic, with a rapid initial absorption phase followed by a much slower absorption phase. Initial absorption rates of lignocaine and bupivacaine following subarachnoid injection are much slower, but the late absorption rates are similar to those after epidural administration. The tissue distribution characteristics of various amide-type agents are similar, because more extensive plasma binding offsets the greater tissue affinity of the more lipophilic compounds bupivacaine and etidocaine. The amide-type agents are predominantly eliminated by hepatic metabolism, except prilocaine, which is also metabolised elsewhere in the body. Ester-type agents are rapidly hydrolysed in blood and liver and are eliminated much faster than amide-type agents. The blood concentrations attained depend primarily upon the dose administered. The addition of adrenaline (epinephrine) reduces the peak plasma drug concentrations; similarly, the age of the patient, disease states and drug interactions may alter the pharmacokinetics to various extents. Because of the low dose requirements, systemic toxicity is not a problem during spinal anaesthesia. During epidural anaesthesia, however, the safety margin is relatively small, and systemic toxicity is very likely to occur after inadvertent intravascular injection of an epidural dose.

Anesthesia, Epidural↗
PubMed1988

The effects on ventilation of ketorolac in comparison with morphine.

We have compared the effect on ventilation of ketorolac, an injectable non-steroidal analgesic, with that of morphine in a randomized, double-blind, cross-over study, using two doses of ketorolac (10 and 90 mg i.m.) and one of morphine (10 mg i.m.). The effect on ventilation was measured with a CO2 rebreathing technique. As a measure of the effect we studied the increase in PETCO2 (CO2 shift) that caused a respiratory minute volume (RMV) equal to the RMV in the control period at 8 kPa PETCO2. Ketorolac caused insignificant CO2 shifts of about 0.10 kPa, while morphine caused a significant CO2 shift of 0.86 kPa. We conclude that ketorolac in analgesic and supra-analgesic doses has no effect on the ventilatory response to CO2 under circumstances in which significant effects are seen with morphine.

Adult↗
PubMed1988

Alfentanil in infants and children with congenital heart defects.

The use of an alfentanil infusion as a supplement to a nitrous oxide-halothane anesthetic and the pharmacokinetics of alfentanil were evaluated in infants and children undergoing surgery for correction of congenital heart defects. Eleven patients, six infants and five children, were studied. Anesthesia was induced with nitrous oxide-halothane and pancuronium, 0.15 mg/kg. After intubation, anesthesia was maintained with nitrous oxide-oxygen and halothane to a maximum inspired concentration of 0.6%. After administration of atropine, 20 micrograms/kg, alfentanil, 20 micrograms/kg, was given, followed by a continuous infusion of 1 microgram/kg/min, which was stopped after closure of the sternum. Supplemental boluses of alfentanil, 5 micrograms/kg, were given when, during surgery, blood pressure and/or heart rate increased more than 20% above control values. At the end of surgery, after antagonism of residual neuromuscular blockade, the patients were extubated. Arterial blood samples were collected at regular intervals during surgery and for six hours thereafter for determination of alfentanil plasma concentrations by gas chromatography. Pharmacokinetic data were calculated using the method of residuals and noncompartmental moment analysis. Although atropine was administered, heart rate decreased significantly (2.5% to 15%) in all infants after administration of alfentanil. In the older children, blood pressure decreased 10% to 35%. In the period before bypass, three infants and four children needed supplemental boluses of alfentanil. During and after bypass, anesthesia was adequate. All patients could be extubed within 34 minutes of stopping the alfentanil infusion. Naloxone was not required in any patient, and postoperative respiratory depression did not occur. In the infants and children, total plasma clearance was 8.2 +/- 2.2 mL/kg/min and 6.3 +/- 0.8 mL/kg/min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Alfentanil↗
PubMed1988

Spinal anaesthesia with hyperbaric bupivacaine. Effects of age on neural blockade and pharmacokinetics.

Effects of ageing were studied on the neural blockade and the pharmacokinetics after subarachnoid administration of 0.5% bupivacaine 3 ml in 8% glucose in two groups of 15 male patients, between 20 and 55 yr and older than 55 yr, respectively. The blockade was performed with the patient in the sitting position. Two minutes after the injection the patient was placed in the supine position. The time to maximum cephalad spread and the upper level of analgesia increased with advancing age, whereas the time to onset of motor blockade decreased with advancing age. Effects of age on the total duration of analgesia and motor blockade could not be demonstrated. Age had no effect on the peak plasma concentration of bupivacaine. The time to peak concentration and the terminal half-life increased, whereas the total plasma clearance decreased with advancing age.

Adult↗
PubMed1988

Pharmacodynamics of alfentanil as a supplement to nitrous oxide anaesthesia in the elderly patient.

The pharmacodynamics of alfentanil given as a supplement to nitrous oxide anaesthesia were studied in 10 elderly patients undergoing lower abdominal surgery. Plasma alfentanil concentration-effect curves for perioperative stimuli and for the probability of needing naloxone at the end of surgery were fitted by logistic regression. The concentration at which the probability of no response was 0.5 (Cp50) for laryngoscopy was 356 ng ml-1, for opening the peritoneum 295 ng ml-1 and for closing the peritoneum 254 ng ml-1. The average Cp50 for the intra-abdominal part of the operation was 268 +/- 97 ng ml-1. The Cp50 for needing naloxone was 174 ng ml-1. These findings are similar to published values for young healthy females undergoing lower abdominal surgery. Our findings suggest that the pharmacodynamics of alfentanil in the elderly are similar to those in younger adults.

Adjuvants, Anesthesia↗
PubMed1988

Pharmacokinetics of lidocaine and bupivacaine following subarachnoid administration in surgical patients: simultaneous investigation of absorption and disposition kinetics using stable isotopes.

The pharmacokinetics of lidocaine and bupivacaine following subarachnoid administration were studied in 12 surgical patients using a stable isotope method. After subarachnoid administration of the agent to be evaluated, a deuterium-labelled analogue was administered intravenously. Blood samples were collected for 24 h. Plasma concentrations of the unlabelled and the deuterium-labelled local anesthetics were determined using a combination of capillary gas chromatography and mass fragmentography. Bi-exponential functions were fitted to the plasma concentration-time data of the deuterium-labelled local anesthetics. The progression of the absorption was evaluated using deconvolution. Mono- and bi-exponential functions were then fitted to the fraction absorbed versus time data. The distribution and elimination half-lives of the deuterium-labelled analogues were 25 +/- 13 min (mean +/- SD) and 121 +/- 31 min for lidocaine and 19 +/- 10 min and 131 +/- 33 min for bupivacaine. The volumes of the central compartment and steady-state volumes of distribution were: lidocaine 57 +/- 10 l and 105 +/- 25 l, bupivacaine 25 +/- 6 l and 63 +/- 22 l. Total plasma clearance values averaged 0.97 +/- 0.21 l/min for lidocaine and 0.56 +/- 0.14 l/min for bupivacaine. The absorption of lidocaine could be described by a single first order absorption process, characterized by a half-life of 71 +/- 17 min in five out of six patients. The absorption of bupivacaine could be described adequately assuming two parallel first order absorption processes in all six patients. The half-lives, characterizing the fast and slow absorption processes of bupivacaine, were 50 +/- 27 min and 408 +/- 275 min, respectively. The fractions of the dose, absorbed in the fast and slow processes, were 0.35 +/- 0.17 and 0.61 +/- 0.16, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗