Biomedical subjects

A G Burm

Publications and source records attributed to A G Burm.

At least 55 records · Page 3Linked to original sources

PubMed1994

Plasma concentrations of alfentanil following epidural administration.

The plasma concentration-time profile of alfentanil following epidural administration was determined in eight patients undergoing lower abdominal surgery under nitrous oxide (66%)-oxygen (33%)-halothane (0.3%) anaesthesia, supplemented with intravenous sufentanil. Alfentanil (1 mg) was administered epidurally before induction of general anaesthesia. Blood samples for the determination of plasma alfentanil concentrations by capillary gas chromatography were collected at intervals until 12 h after the epidural injection. Peak plasma concentrations [mean (SD)] were 9.7 (2.3)ng.ml-1, and were attained in a median (range) time of 90 (30-120) min. The results suggest that alfentanil is slowly absorbed from the epidural space into the general circulation.

Adult↗

PubMed1994

The effect of epidural administration of alfentanil on intra-operative intravenous alfentanil requirements during nitrous oxide-oxygen-alfentanil anaesthesia for lower abdominal surgery.

The effects of epidural administration of alfentanil on the intravenous alfentanil dose requirements and the plasma concentrations required to suppress responses to surgical stimulation during nitrous oxide-oxygen-alfentanil anaesthesia in 20 patients undergoing lower abdominal surgery were studied. Before induction of anaesthesia, patients in one group (E) received an epidural injection of 1 mg alfentanil, followed by an epidural infusion of alfentanil 0.2 mg.h-1 until skin closure, whilst patients in the other group (C, control) received a continuous infusion of sodium chloride via a sham catheter in order to blind the main investigator to the treatment. Anaesthesia was induced and maintained with nitrous oxide (66%) in oxygen and a 'target'-controlled intravenous infusion of alfentanil. During surgery, the 'target' alfentanil concentration was increased or decreased according to patients' responses. The number of responses to surgical stimulation was smaller in patients from group E (median 1, range 0-3) than in patients from group C (median 4, range 1-15; p < 0.005), even though the alfentanil intravenous infusion rates were smaller in group E [mean (SD): 1.6(0.5) micrograms.kg-1 min-1] than in group C [2.9(1.2) micrograms.kg-1 min-1, p < 0.02]. Both the lowest concentrations associated with no response [133(40) ng.ml-1] and the highest concentrations associated with a response [155(65) ng.ml-1] in group E were lower than those in group C [238(100) ng.ml-1, p < 0.01 and 334(163) ng.ml-1, p < 0.05, respectively]. We concluded that epidural administration of alfentanil reduces intravenous alfentanil requirements during nitrous oxide-oxygen-alfentanil anaesthesia for lower abdominal surgery. The results indicate a spinal mechanism of action of epidural alfentanil.

Abdomen↗

PubMed1994

Pharmacokinetics of the enantiomers of bupivacaine following intravenous administration of the racemate.

1. The pharmacokinetics of R(+)-bupivacaine and S(-)-bupivacaine were investigated following a 10 min intravenous infusion of the racemate (dose 30 mg) in 10 healthy males. 2. The fractions unbound of R(+)- and S(-)-bupivacaine in pre-dose plasma were determined for each subject after in vitro addition of rac-bupivacaine (concentration of each enantiomer: approximately 300 ng ml-1). 3. The total plasma clearance of R(+)-bupivacaine (mean +/- s.d.: 0.395 +/- 0.076 l min-1) was greater (P < 0.0001) than that of S(-)-bupivacaine (0.317 +/- 0.067 l min-1). The volumes of distribution of R(+)-bupivacaine at steady state (84 +/- 29 l) and during the terminal log-linear phase (117 +/- 47 l) were larger (P < 0.0002) than those of S(-)-bupivacaine (54 +/- 20 l and 71 +/- 34 l, respectively). The terminal half-life (210 +/- 95 min) and mean residence time (215 +/- 74 min) of R(+)-bupivacaine were longer than those of S(-)-bupivacaine (157 +/- 77 min, P < 0.01, and 172 +/- 55 min, P < 0.02, respectively). 4. The free percentage of R(+)-bupivacaine (6.6 +/- 3.0 %) was greater (P < 0.0002) than that of S(-)-bupivacaine (4.5 +/- 2.1 %). 5. The plasma clearance of unbound R(+)-bupivacaine (7.26 +/- 3.60 1 min-1) was smaller (P < 0.01) than that of S(-)-bupivacaine (8.71 +/- 4.27 l min-1). Volumes of distribution based on unbound R(+)-bupivacaine concentrations (Vuss: 1576 +/- 934 l; Vu: 2233 +/- 1442 l) did not differ from those of S(-)-bupivacaine (Vuss: 1498 +/- 892 l; Vu: 1978 +/- 1302 l). 6. The enantioselective systemic disposition of bupivacaine can to a large extent be attributed to differences in the degree of plasma binding of the enantiomers.

Adult↗

PubMed1994

Alfentanil pharmacokinetics in cardiac surgical patients.

There is growing interest in early tracheal extubation and intensive care unit. (ICU) discharge of cardiac surgical patients. Among the opioids currently available, alfentanil seems to be particularly suited to these goals because of its pharmacokinetic and pharmacodynamic characteristics. However, the pharmacokinetics of alfentanil after cardiopulmonary bypass (CPB) have not been fully characterized. Eight patients undergoing coronary artery bypass grafting (CABG) with hypothermic CPB received alfentanil 125 micrograms/kg intravenously (IV) at the induction of anesthesia and again 5 h later after the completion of CPB. Arterial blood samples were analyzed for alfentanil (n = 8) and for plasma proteins (n = 3). Arterial blood samples were obtained from another six patients for measurements of the concentrations of plasma proteins at various stages of the perioperative period. Compared to the pre-CPB period as well as to patients not exposed to CPB, CABG patients after CPB exhibited an increased elimination half-time (t1/2 beta = 180 +/- 55 min SD), central distribution volume (Vc = 0.25 +/- 0.07 L/kg), and total volume of distribution (Vdss 0.63 +/- 0.08 L/kg; Vd area 0.92 +/- 0.23 L/kg) which reflected a 33%-50% decrease in alpha 1-acid glycoprotein, the principal plasma protein to which alfentanil is bound. There was no substantial change in the concentration of free alfentanil at the start of CPB. The clearance of total alfentanil was not affected significantly by CPB. We conclude: 1) Alfentanil pharmacokinetics in CABG patients before CPB are similar to those found in noncardiac surgical patients and volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Spinal anesthesia with ropivacaine: a double-blind study on the efficacy and safety of 0.5% and 0.75% solutions in patients undergoing minor lower limb surgery.

The purpose of this study was to determine the clinical efficacy and safety of ropivacaine as a local anesthetic for spinal anesthesia. Forty patients between the ages of 18 and 75 yr, scheduled for minor lower limb surgery, were studied. They were randomly allocated to receive either 3 mL glucose-free 0.5% (15 mg) or 0.75% (22.5 mg) ropivacaine in a double-blind fashion. The subarachnoid puncture was performed with a 26-gauge Quincke-point needle at the L3-4 interspace with the patients in the sitting position. The onset of analgesia to pinprick was similar with both concentrations. The median (range) upper level of analgesia obtained with the 0.5% solution was T11 (L4-T5) and was T10-11 (L4-T4) with the 0.75% solution. The duration of analgesia at T12 (P < 0.01) and the total duration of analgesia (P < 0.002) were longer in the 0.75% group. In addition, the area under the number of blocked segments versus time curve was larger with the 0.75% ropivacaine solution (P < 0.001). The incidence of complete motor block of the lower limbs was higher (P < 0.02) and the total duration of motor block longer (P < 0.002) in the 0.75% group. No unexpected adverse events were registered. We conclude that subarachnoid injection of glucose-free ropivacaine solutions results in a variable spread of analgesia, mostly accompanied by a good quality of motor block, in particular with the 0.75% solution.

Adolescent↗

PubMed1993

Preoperative interpleural administration of sufentanil or bupivacaine reduces intraoperative intravenous sufentanil requirements during thoracotomy.

The efficacy of interpleural administration of sufentanil, 50 micrograms, was compared with that of 150 mg of bupivacaine, 0.5%, with epinephrine, 5 micrograms/mL, or saline, in 30 patients (N = 10 in each group) undergoing lateral thoracotomy. Sufentanil, bupivacaine, or saline was administered interpleurally after induction of anesthesia with sufentanil, 1 microgram/kg intravenously, and thiopental, 2 to 5 mg/kg. Anesthesia was maintained with nitrous oxide, 66%, and halothane, 0.3% inspired concentration. Supplementary intravenous sufentanil, 25 micrograms, was given whenever the systolic arterial blood pressure increased more than 15 mmHg above the preoperative value, heart rate exceeded 90 beats/min in the absence of hypovolemia, or when other autonomic or somatic signs of inadequate anesthesia occurred. The additional intravenous sufentanil requirement and the incidence of hypotension were compared between the groups. All patients in the placebo group needed supplementary sufentanil. Significantly fewer patients in the interpleural sufentanil (N = 1, P < 0.0002) and bupivacaine (N = 1, P < 0.0002) groups required supplementary sufentanil compared to the placebo group (N = 10). The time from interpleural administration of the study drug to the first administration of postoperative analgesic was significantly longer (P < 0.001) in the sufentanil group (228 +/- 72 min) and bupivacaine group (242 +/- 76 min) compared to the placebo group (141 +/- 50 min). It was concluded that interpleural administration of either sufentanil or bupivacaine contributes to intraoperative analgesia during thoracotomy.

Adult↗

PubMed1993

Influence of Crohn's disease on the pharmacokinetics and pharmacodynamics of alfentanil.

We have compared the dose requirements, pharmacokinetics and pharmacodynamics of alfentanil in 12 patients with Crohn's disease and 10 control patients undergoing abdominal surgery. Plasma concentrations of alpha 1-acid glycoprotein (AAG) and alfentanil protein binding were also measured. Anaesthesia was induced with alfentanil 100 micrograms kg-1 and thiopentone, and maintained with nitrous oxide in oxygen and alfentanil 25-200 micrograms kg-1 h-1. Arterial blood samples were obtained before and after each change in the alfentanil infusion rate and for 6 h after stopping the infusion. Pharmacokinetic data were derived using non-compartmental methods. Alfentanil concentration-effect data were evaluated by non-linear regression, where effect was either response or no response to surgical stimulation. Mean intraoperative alfentanil requirement was greater in patients with Crohn's disease (2.48 micrograms kg-1 min-1) than in control patients (1.35 micrograms kg-1 min-1) (P < 0.01). Mean elimination half-life, total plasma clearance and steady state distribution volume in patients with Crohn's disease were comparable to those in control patients (80 vs 81 min, 5.7 vs 6.4 ml kg-1 min-1 and 0.70 vs 0.68 litre kg-1, respectively). Mean plasma concentration at which the probability of no response was 50% for the intra-abdominal period of surgery was greater in the Crohn group (359 ng ml-1) than in the control group (199 ng ml-1) (P < 0.02). Plasma AAG concentrations were greater in the Crohn group, but the free fraction of alfentanil was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Pharmacodynamics of alfentanil as a supplement to propofol or nitrous oxide for lower abdominal surgery in female patients.

BACKGROUND: Although propofol and alfentanil are given in combination in clinical practice, the pharmacodynamic interaction between these drugs has not been described. METHODS: The pharmacodynamics of alfentanil when given as a supplement to propofol were studied in 10 ASA physical status 1 female patients (group P) undergoing lower abdominal surgery and compared to the pharmacodynamics of alfentanil when given as a supplement to nitrous oxide (group N, n = 10). Anesthesia was induced by either computer-controlled infusion of propofol and alfentanil at target concentrations of 3 micrograms/ml and 100 ng/ml (group P) or computer-controlled infusion of 400 ng/ml alfentanil as a supplement to nitrous oxide and oxygen (ratio 2:1; group N). The target concentration of alfentanil was varied to patient responses, and the nitrous oxide and propofol concentrations were maintained constant. A sigmoid Emax model was fitted to response/no response data versus plasma alfentanil concentrations at intubation, skin incision, and the opening of the peritoneum in both groups and for the intraabdominal part of surgery in the individual patients. In addition, the speed of recovery in both groups was determined by a deletion-of-p's test. RESULTS: The EC50 (the concentration at which, with a 50% probability, the patients did not respond to the surgical stimuli) of alfentanil during propofol anesthesia was 92 ng/ml for intubation, 55 ng/ml for skin incision, 84 ng/ml for the opening of the peritoneum, and 66 +/- 38 ng/ml (mean +/- SD) for the intraabdominal part of surgery. The corresponding values during nitrous oxide anesthesia were significantly higher: 429 ng/ml for intubation, 101 ng/ml for skin incision, and 206 +/- 65 ng/ml for the intraabdominal part of surgery (P < 0.001). The speed of recovery was similar in both groups. CONCLUSIONS: The alfentanil requirements in ASA physical status 1 female patients undergoing lower abdominal surgery are less when given as a supplement to propofol (4 micrograms/ml) compared to 66% N2O.

Abdomen↗

PubMed1993

Computer-controlled infusion of alfentanil for postoperative analgesia. A pharmacokinetic and pharmacodynamic evaluation.

BACKGROUND: Although computer-controlled infusion (CCI) of alfentanil has been shown to be effective intraoperatively, this technique has not been validated for postoperative use. Therefore, the authors examined the efficacy of this technique in providing postoperative pain relief. The study comprised both a validation of published pharmacokinetic data sets and the definition of the minimum effective analgesic concentrations after major orthopedic surgery. METHODS: The bias and inaccuracy of the implemented pharmacokinetic data set were examined, in 20 patients who had undergone major orthopedic surgery, by determination of the median performance error (MDPE) and median absolute performance error (MDAPE). The performance of two other published pharmacokinetic data sets was also examined by simulating the plasma concentrations that would have been predicted, had these data sets been implemented. The minimum effective analgesic concentrations (MEAC) were determined at the following time points: at the onset of pain, at 9:00 PM on the day of surgery, and at 9:00 AM and 9:00 PM on the first postoperative day. RESULTS: Measured plasma concentration-time profiles generally were parallel to the target concentration-time profiles. The MDPE and MDAPE obtained were 12% and 28%, respectively. The MEACs ranged from < 1 to 175 ng/ml and showed substantial interindividual variability. The median MEACs at the four study times were 59, 52, 65, and 43 ng/ml. The MEAC at 9:00 PM on the first postoperative day was significantly lower than those at the other study times (P < 0.05). CONCLUSION: Computer-controlled infusion of alfentanil provides adequate postoperative analgesia. The study demonstrated that pharmacokinetic data sets that are useful for intraoperative CCI of alfentanil are equally valid in the postoperative phase. Although required plasma concentrations of alfentanil are reasonably stable in time, interindividual variations are large, necessitating individual titration.

Adult↗

PubMed1993

Pharmacokinetics of alfentanil administered at a variable rate during three types of surgery.

To determine if the pharmacokinetics of alfentanil varied with the type of surgery (site of operation and intensity of surgical stimulation) or with the mode of administration, three groups of patients were given a variable-rate infusion of alfentanil (supplemented with bolus injections) as an adjunct to nitrous oxide-oxygen anaesthesia for breast surgery, lower abdominal surgery, or upper abdominal surgery. A two-compartment pharmacokinetic model adequately characterized the plasma concentration profiles of alfentanil for 31 of 34 patients. Mean distribution half-life (6 min), elimination half-life (87 min), initial volume of distribution (10 litres), steady state volume of distribution (31 litres), total body clearance (308 ml min-1), and distribution clearance (656 ml min-1) did not vary with the type of surgery. The pharmacokinetics could not be determined for three patients undergoing upper abdominal surgery, probably because of nonstationarity. Comparison of our data with those obtained after a single bolus injection or a constant-rate infusion indicates that the pharmacokinetics of alfentanil do not vary with the mode of administration.

Abdomen↗

PubMed1992

Pharmacokinetics of alfentanil before and after cardiopulmonary bypass in pediatric patients undergoing cardiac surgery: Part I.

Changes induced by cardiopulmonary bypass (CPB) may markedly affect the pharmacokinetics of drugs. Therefore, the pharmacokinetics of alfentanil before and after CPB were compared in infants and children undergoing cardiac surgery, who had been anesthetized with nitrous oxide in oxygen and low inspiratory concentrations of halothane. Six infants and six children were investigated. Before CPB, alfentanil, 200 micrograms/kg, and after CPB, alfentanil, 80 micrograms/kg, was infused in 10 minutes. Arterial blood samples were obtained before and after CPB for determination of plasma alfentanil concentrations. Bi-exponential functions were fitted to the plasma concentration-time data using weighted least-squares nonlinear regression analysis. A correction was made to account for the contribution of the first infusion to the plasma concentrations measured during and after the second infusion. Total sampling time before CPB (45 to 75 minutes) was too short to allow full characterization of the pharmacokinetics of alfentanil, but allowed estimation of the initial volume of distribution. The initial volume of distribution before CPB was smaller (68 +/- 37 mL/kg in infants and 80 +/- 32 mL/kg in children) than after CPB (235 +/- 58 mL/kg in infants and 179 +/- 99 mL/kg in children; P less than 0.001). The normalized area under the plasma concentration-time curve from 0 to 45 minutes was larger before CPB (17.9 +/- 2.9 mg.min/L in infants and 18.3 +/- 5.4 mg.min/L in children) than after CPB (11.1 +/- 2.9 mg.min/L in infants and 12.9 +/- 3.4 mg.min/L in children; P less than 0.001). Despite intravenous administration of atropine, arterial blood pressure and heart rate decreased significantly after alfentanil was given.

Alfentanil↗

PubMed1992

Pharmacokinetics of alfentanil before and after cardiopulmonary bypass in pigs: Part II.

The pharmacokinetics of alfentanil before and after cardiopulmonary bypass (CPB) were investigated in six pigs undergoing mitral valve replacement. Before bypass, alfentanil, 100 micrograms/kg, was infused in 10 minutes and after bypass, alfentanil, 40 micrograms/kg, was infused in 10 minutes. Low inspiratory concentrations of halothane were given concomitantly. Arterial blood was obtained before and after CPB for determination of plasma alfentanil concentrations by gas chromatography. Bi-exponential functions were fitted to the plasma concentration-time data using weighted least-squares nonlinear regression analysis. The steady-state volume of distribution (Vss; 258 +/- 70 mL/kg), elimination clearance (Cle; 10.7 +/- 3.0 mL/kg/min), and distribution clearance (Cld; 6.8 +/- 3.3 mL/kg/min) before CPB were smaller than the Vss (1,107 +/- 373 mL/kg; P less than 0.01), Cle (20.0 +/- 3.0 mL/kg/min; P less than 0.002), and Cld (23.0 +/- 6.7 mL/kg/min; P less than 0.02) after CPB. The distribution half-life (t1/2 lambda 1; 2.8 +/- 0.8 minutes) was longer and the elimination half-life (t1/2 lambda 2; 36 +/- 8 minutes) was shorter before CPB than the t1/2 lambda 1 (1.7 +/- 0.2 minutes; P less than 0.05) and t1/2 lambda 2 (68 +/- 20 minutes; P less than 0.02) after CPB.

Alfentanil↗

PubMed1992

Uptake of sufentanil, alfentanil and morphine in the lungs of patients about to undergo coronary artery surgery.

We have studied the pulmonary extraction and retention of sufentanil, alfentanil and morphine using a double indicator technique in 30 patients undergoing elective aortocoronary bypass surgery. Patients were allocated to three groups (10 each) to receive sufentanil 43 micrograms, alfentanil 672 micrograms or morphine 1887 micrograms, mixed with indocyanine green as indicator. After sufentanil, mean peak extraction was 93.7% (95% confidence interval 87.1-100.4%) and release occurred after 16.1 (13.8-18.4) s; first-pass retention was 61.1 (51.3-70.9)%. After alfentanil, peak extraction was 67.4 (42.7-92.0)% and release occurred after 9.9 (8.5-11.3) s; first-pass retention was 10.1 (3.5-16.7)%. After morphine, peak extraction was 58.3 (44.4-72.2)% and release occurred after 7.2 (4.4-10.1) s; first-pass retention was 7.1 (-4.7-19.9)%. Both peak extraction and first-pass retention were significantly greater after sufentanil. There was no significant difference in the peak extraction and first-pass retention between alfentanil and morphine.

Alfentanil↗

PubMed1992

Pharmacodynamics of alfentanil. The role of plasma protein binding.

The role of protein binding in relation to the pharmacodynamics of alfentanil was investigated in 15 female and 13 male patients, aged 21-85 yr, ASA physical status 1 or 2, undergoing upper abdominal surgery. All patients had normal cardiac, hepatic, renal, and pulmonary function. None was receiving medication or had a history of alcohol or other drug abuse. Anesthesia was induced and maintained with 66% nitrous oxide in oxygen and alfentanil. Alfentanil was administered by a computer-controlled infusion pump. If, during surgery, the patient exhibited signs of inadequate anesthesia (i.e., 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 and 4 min after the computer had indicated that the new target concentration had been reached. In addition, blood samples were taken before intubation, skin incision, and in the patients in whom ventilation recovered spontaneously before extubation. In the remaining patients a blood sample was taken before the administration of naloxone. Plasma alfentanil concentrations were determined by capillary gas chromatography. Alfentanil protein binding was determined by equilibrium dialysis in an arterial blood sample taken before induction of anesthesia. Alfentanil concentration-effect data were evaluated by logistic regression, where effect was either response or no response to perioperative stimuli. The average free fraction of alfentanil was 9.3 +/- 3.9% (range 3.7-19.1%). For intubation, skin incision, and postanesthesia ventilation, it was not possible to characterize the concentration-effect curves based on total plasma concentrations with logistic regression.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

PubMed1992

Pharmacodynamics of propofol in female patients.

Although the clinical properties of propofol have been studied extensively, the pharmacodynamics have not yet been described fully. We studied the propofol concentration-effect relationships for loss of eyelash reflex, loss of consciousness, and hemodynamic changes in 18 female patients, ASA physical status 1, aged 20-49 yr. Propofol was given by computer-controlled infusion. The initial target concentration of 0.5-1 microgram/ml was increased every 12 min by 0.5-1 microgram/ml until the patients lost consciousness. Every 3 min, loss of eyelash reflex and loss of consciousness were tested and an arterial blood sample was taken for analysis of the blood propofol concentration. The concentration-response relationships for loss of eyelash reflex and loss of consciousness were defined by fitting a sigmoid Emax function (where Emax = the maximum effect that can be reached; i.e., 100% of the patients showing loss of eyelash reflex or loss of consciousness) to the response/no response data versus the propofol concentration, using nonlinear regression. The effect of propofol on hemodynamic parameters was analyzed by linear regression. The propofol concentrations at which 50% and 90% of the patients showed loss of eyelash reflex were 2.07 and 2.78 micrograms/ml, respectively. The corresponding values for loss of consciousness were 3.40 and 4.34 micrograms/ml. The systolic and diastolic blood pressure decreased with increasing blood propofol concentration. The correlation coefficients for the decrease in systolic and diastolic blood pressure versus the blood propofol concentration were r2 = -0.663 and r2 = -0.243, but heart rate did not change. In conclusion, propofol concentrations inducing loss of eyelash reflex are less than those inducing loss of consciousness.

Adult↗

PubMed1992

The effect of age on the systemic absorption, disposition and pharmacodynamics of bupivacaine after epidural administration.

The influence of age on the systemic absorption and disposition of bupivacaine following epidural administration in 20 male patients (22 to 81 years) was examined using a stable isotope method to determine whether pharmacokinetics play a role in age-related pharmacodynamic changes seen with the drug. After epidural bupivacaine administration a deuterium-labelled analogue was administered intravenously. Bi- and triexponential functions were fitted to plasma concentration-time data of deuterium-labelled bupivacaine. The systemic absorption was described by 2 parallel first-order absorption processes. The upper level of analgesia and the duration of analgesia at dermatome T-12 increased with age (r = 0.68, p less than 0.001; r = 0.56, p less than 0.01, respectively). The time to maximal caudad spread of analgesia and the time to onset of motor block decreased with age (r = -0.76, p less than 0.0001; r = -0.72, p less than 0.001, respectively). Age did not influence systemic absorption or disposition of bupivacaine. We conclude that the changes in the clinical profile of bupivacaine with age are not due to altered pharmacokinetics, but may be related to changes in the pharmacodynamics of the drug.

Absorption↗

PubMed1992

Continuous interpleural infusion of bupivacaine for postoperative analgesia after surgery with flank incisions: a double-blind comparison of 0.25% and 0.5% solutions.

Postoperative analgesia, as assessed by visual analogue scale scores (0-10) and patient-controlled analgesia morphine requirements, pulmonary function (forced vital capacity and forced expiratory volume in 1 s), and plasma bupivacaine concentrations were studied in patients receiving interpleural blockade with bupivacaine after surgery with a flank incision. Two groups of 10 patients received either 0.5% or 0.25% bupivacaine, both with epinephrine (5 micrograms/mL). Pain relief was initiated when patients had visual analogue scale scores greater than or equal to 4. Patients received 21 mL of bupivacaine 0.25% or 0.5% in a double-blind fashion. One hour later, a continuous infusion of 5 mL/h of the study solution was started. At the same time, patient-controlled analgesia became accessible to the patients. The onset time of pain relief and the area under the visual analogue scale score-time curves over the first 8 h were similar in both groups. Patient-controlled analgesia morphine use was also similar in the 0.25% (21.3 +/- 14.6 mg) and 0.5% (21.0 +/- 16.0 mg) groups (mean +/- SD). In both groups, forced vital capacity and forced expiratory volume in 1 s improved significantly within 60 min (P less than 0.05). Peak plasma concentrations (Cmax) and the area under the plasma concentration-time curve (AUC) over 24 h were higher (P less than 0.001) in the 0.5% group (Cmax, 1.47 +/- 0.37 micrograms/mL; AUC, 1511 +/- 323 micrograms.mL-1.min) than those in the 0.25% group (Cmax, 0.55 +/- 0.22 micrograms/mL; AUC, 680 +/- 118 micrograms.mL-1.min) (mean +/- SD).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

The effect of age on systemic absorption and systemic disposition of bupivacaine after subarachnoid administration.

In order to evaluate the role of the pharmacokinetics of the age-related changes in the clinical profile of spinal anesthesia with bupivacaine, we studied the influence of age on the systemic absorption and systemic disposition of bupivacaine after subarachnoid administration in 20 male patients (22-81 yr), ASA Physical Status 1 or 2, by a stable isotope method. After subarachnoid administration of 3 ml 0.5% bupivacaine in 8% glucose, a deuterium-labeled analog (13.4 mg) was administered intravenously. Blood samples were collected for 24 h. Plasma concentrations of unlabeled and deuterium-labeled bupivacaine were determined with a combination of gas chromatography and mass fragmentography. Biexponential functions were fitted to the plasma concentration-time data of the deuterium-labeled bupivacaine. The systemic absorption was evaluated by means of deconvolution. Mono- and biexponential functions were fitted to the data of fraction absorbed versus time. The maximal height of analgesia and the duration of analgesia at T12 increased with age (r = 0.715, P less than 0.001; r = 0.640, P less than 0.01, respectively). In 18 patients the systemic absorption of bupivacaine was best described by a biexponential equation. The half-life of the slow systemic absorption process (r = -0.478; P less than 0.05) and the mean absorption time (r = -0.551; P less than 0.02) decreased with age. The total plasma clearance decreased with age (r = -0.650, P less than 0.002), whereas the mean residence time and terminal half-life increased with age (r = 0.597, P less than 0.01; r = 0.503, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗