Total intravenous anaesthesia with propofol,alfentanil, and oxygen-air: three different dosage schemes

Three different dosage schemes of propofol infusions combined with a fixed-rate alfentanil infusion were investigated in total intravenous anaesthesia. In 30 premedicated patients, divided at random into three groups, anaesthesia was induced with propofol 2 mg.kg-1 immediately followed by an alfentanil infusion 10 micrograms.kg-1.min-1 as a loading dose which was decreased after ten minutes to a maintenance dose of 1 microgram.kg-1.min-1. Vecuronium bromide 0.1 mg.kg-1 was used as the muscle relaxant. After induction of anaesthesia a propofol infusion 2 mg.kg-1.hr-1 was started in group A, 3 mg.kg-1.hr-1 in group B and 4 mg.kg-1 hr-1 in group C. At signs of light anaesthesia supplementary bolus doses of 20 mg propofol and 1 mg alfentanil were given. The patients' lungs were ventilated with air-oxygen (FIO2 0.35). The mean systolic and diastolic blood pressures showed no statistical significant differences between the three groups. A significant (P less than 0.01) decrease of the mean systolic and diastolic blood pressures was present after induction of anaesthesia and tracheal intubation. Recovery was uneventful in all but one patient, who had ventilatory depression that responded to naloxone (0.2 mg IV). Awareness did not occur in any patient. The only difference between the three groups was the higher number of supplementary bolus doses of propofol and alfentanil needed in group A (P less than 0.01). In total intravenous anaesthesia propofol 3 and 4 mg.kg-1.hr-1 as a maintenance dose combined with a two-step fixed-rate alfentanil infusion provided smooth anaesthesia and uneventful rapid recovery.     

Continuous opioid infusions for neurosurgical procedures: a double-blind comparison of alfentanil and fentanyl

The ability of continuous infusions of opioids to control hypertension at the end of neurosurgical procedures without compromising prompt emergence was studied in patients undergoing craniotomy for supratentorial tumours. Four infusion regimens were compared in a randomized double-blind fashion; three of alfentanil and one of fentanyl. Low-dose alfentanil was administered to nine patients (35.1 micrograms.kg-1 then a continuous infusion of 16.2 micrograms.kg-1.hr-1); mid-dose alfentanil to eight patients (70.2 micrograms.kg-1 then 32.4 micrograms.kg-1.hr-1); high-dose alfentanil to eight patients (105.3 micrograms.kg-1 then 48.6 micrograms.kg-1.hr-1). Eight additional patients were given fentanyl (8.3 micrograms.kg-1 then 1.6 micrograms.kg-1.hr-1). Using published values for the pharmacokinetic variables of alfentanil and fentanyl, modelling predicted stable concentrations of 60, 120, 180 ng.ml-1 for the alfentanil infusion regimens respectively and 2 ng.ml-1 with the fentanyl regimen. Maintenance anaesthesia comprised the opioid infusion, 50% N2O in O2 and isoflurane titrated to control mean arterial pressure (MAP) within 20% of ward MAP. Isoflurane was discontinued after closure of the dura. Nitrous oxide was discontinued at the same time as reversal of neuromuscular blockade. The opioid infusion was discontinued with closure of the galea. A greater time-averaged isoflurane concentration was required to control MAP within the prescribed limits in the low alfentanil group (ANOVA; P less than 0.05). The PaCO2 at two, five and 30 min after extubation were not different among groups. The times from discontinuing N2O to eye opening and tracheal extubation were not different. The time to follow commands was longer in the low alfentanil group (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics and pharmacodynamics of alfentanil infusions during general anesthesia

The pharmacokinetic and pharmacodynamic properties of alfentanil were studied in 64 surgical patients. Alfentanil was administered as a loading infusion (25-130 micrograms/kg) followed by a maintenance infusion (0.25-1.3 micrograms X kg-1 X min-1) as part of a nitrous oxide-narcotic-muscle relaxant technique. Although alfentanil doses of at least 50 micrograms/kg (in combination with thiopental, 2 mg/kg) were required to prevent hemodynamic changes during intubation, apnea or chest wall rigidity frequently occurred with alfentanil loading infusions exceeding 75 micrograms/kg. The alfentanil clearance rate was significantly lower in patients with liver dysfunction (2.3 +/- 1.3 vs 4.2 +/- 2.0 ml X kg-1 X min-1, mean +/- SD). In addition, the patients who required opioid antagonists to reverse postoperative respiratory depression had lower clearance rates (1.5 +/- 0.7 vs 4.1 +/- 1.9 ml X kg-1 X min-1) and longer elimination half-life values (406 +/- 304 vs 87 +/- 53 min). For maintenance of hemodynamic stability during superficial and intraabdominal operations, alfentanil serum concentration-response curves revealed ED95 values exceeding 300 ng/ml and 400 ng/ml, respectively. Our study also demonstrated a wide range of clinical responses to fixed doses of alfentanil. At equivalent doses, some patients required supplemental anesthetics, whereas others required an opioid antagonist. Careful titration of the alfentanil maintenance infusion is recommended to minimize the possibility of postoperative respiratory depression.     

The enflurane-sparing effect of alfentanil in dogs

Some investigators believe that the dog is less sensitive than are humans to the anesthetic/analgesic actions of opioids. The alfentanil plasma concentration [ALF] vs anesthetic effect relationship has been determined for humans undergoing surgery. This study was designed to determine the [ALF] vs anesthetic relationship for alfentanil in the enflurane-anesthetized dog and thereby to provide data by which the [ALF] vs anesthetic effect relationships in the dog and in humans could be compared. Mongrel dogs (n = 10) were anesthetized with enflurane, and enflurane MAC (EMAC) was determined in each dog. After this, each dog received at least three incremental infusions of alfentanil using infusion rates of 0.625, 1.6, 8, 32, or 80 micrograms.kg-1.min-1. EMAC and [ALF] were determined during each infusion rate. There was a linear increase in [ALF] produced by incremental infusions of alfentanil (r = 0.999). Administration of alfentanil produced a dose-dependent reduction of EMAC up to a maximum of 72.5 +/- 3.7% (mean +/- SEM) at 32 micrograms.kg-1.min-1 ([ALF] = 960 +/- 86 ng/ml); a ceiling effect was evident. The degree of EMAC reduction (69%) produced by an infusion rate of 8 micrograms.kg-1.min-1 ([ALF] = 223 +/- 13 ng/ml) was not statistically different from the EMAC reductions produced by infusion rates of 32 (73% reduction at [ALF] = 960 +/- 86 ng/ml) or 80 micrograms.kg-1.min-1 (70% reduction at [ALF] = 2613 +/- 247 ng/ml) (P greater than 0.05). The relative potency of alfentanil was one-seventh to one-tenth that of fentanyl studied under identical conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alfentanil sedation for cardiac catheterization of children with Fontan shunts

After Fontan operation, prolonged invasive cardiac assessment is often needed. This study is a clinical evaluation of the effectiveness of flunitrazepam premedication, EMLA cream, and alfentanil continuous infusion for management of children undergoing such catheterization. Fourteen consecutive subjects aged 5-20 yr with Fontan shunts (right atrium to pulmonary artery) undergoing elective haemodynamic and electrophysiological catheterization were sedated with an individually titrated alfentanil infusion. After oral premedication with flunitrazepam 2 mg, the mean induction dose and mean maintenance requirement of alfentanil were 4.4 +/- 2.7 micrograms.kg-1 and 10.3 +/- 8.6 micrograms.kg-1 x hr-1, respectively. Mean oxygen consumption during haemodynamic catheterization was 4.1 +/- 0.4 ml.kg-1 x min-1 with an average individual variation of 10%. For every patient, tranquil and stable conditions during catheterization could be produced. It is concluded that alfentanil infusion is a method of sedation of children and adolescents with Fontan shunts during haemodynamic and electrophysiologic catheterization. However, continuous monitoring of ventilation and an understanding of the slow circulation time after Fontan operation are essential with such sedation in these patients.     

Pharmacokinetics and placental transfer of intravenous and epidural alfentanil in parturient women

Alfentanil was administered as a 30 micrograms/kg single intravenous injection to five healthy women scheduled for elective cesarean section (group A). In five pregnant women normal vaginal delivery was supported by epidural analgesia with a 30 micrograms/kg loading dose followed by a 30 micrograms/kg-1/hr-1 infusion of alfentanil (group B). Five healthy nonpregnant women scheduled for minor general surgery received 120 micrograms/kg alfentanil intravenously as a bolus before surgical incision (group C). In groups A and B plasma alfentanil concentrations, alfentanil plasma protein binding, and alpha 1-acid glycoprotein (alpha 1-AGP) concentrations were measured in maternal and umbilical arterial or venous blood samples at delivery. Multiple arterial sampling in groups A and C for measurement of alfentanil plasma concentration decay analysis indicated three-compartmental characteristics in most patients. In the pregnant population terminal half-life (t1/2 beta), volume of distribution at steady state (Vdss), and total plasma clearance (Clp) amounted to 103 +/- 67 min, 541 +/- 155 ml/kg and 6.48 +/- 0.85 ml/kg-1/min-1, respectively (mean +/- SD), and did not differ significantly in nonpregnant patients. In groups A and B the fetal-maternal ratios indicated a concentration gradient for the total plasma alfentanil content (ratio of total alfentanil concentrations in umbilical venous and maternal blood (Uv/M), 0.31 +/- 0.08 and 0.28 +/- 0.06 (mean +/- SD) in groups A and B respectively) with a larger protein binding capacity in maternal plasma (group A, 85 +/- 3%; group B, 90 +/- 1%) (mean +/- SD).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics and pharmacodynamics of the three isomers of mivacurium in health, in end-stage renal failure and in patients with impaired renal function

We have studied the pharmacokinetics of cis-trans, trans-trans and cis- cis mivacurium in nine healthy patients (creatinine clearance 66-133 ml min-1), in seven patients with end-stage renal failure requiring dialysis (creatinine clearance 4-11 ml min-1) and in seven patients with impaired renal function (creatinine clearance 32-49 ml min-1), during thiopentone-fentanyl-midazolam-nitrous oxide-oxygen anaesthesia. Mivacurium chloride was infused at a rate of 15 micrograms kg-1 min-1 for 10 min, 7.5 micrograms kg-1 min-1 for a further 10 min, and then at a rate adjusted to maintain T1/T0 at 5%. The minimum duration of infusion was 60 min (range 60-235 min). The plasma concentration of the three isomers was measured at regular intervals throughout the infusion, and for up to 300 min after the infusion was stopped. Compartmental analysis of the resulting isomer profiles was undertaken: one- and two-compartment models were fitted to derive clearance, volume of distribution and terminal elimination half-life. Clearance of the cis-cis isomer was reduced significantly in the renal failure (median 2.4 (range 2.1-2.6) ml kg-1 min-1) and intermediate renal function groups (2.1 (2.0-2.9) ml kg-1 min-1), compared with healthy patients (3.8 (2.6-4.9) ml kg-1 min-1) (P < 0.01 in each case). There was no significant difference, within the sample size studied, between the clearance of the cis-trans isomer, in health (106 (26-147) ml kg-1 min-1), in renal failure (80 (22-135) ml kg-1 min-1) or with impaired renal function (87 (58-101) ml kg-1 min-1); or of the trans-trans isomer (57 (18-79) ml kg-1 min-1), (47 (16-88) ml kg-1 min-1) and (44 (40-55) ml kg-1 min-1), respectively). Clearance of each isomer correlated significantly with plasma cholinesterase activity (cis-trans, r = 0.55, P < 0.01; trans-trans, r = 0.62, P < 0.01), although this could be demonstrated only in healthy patients for the cis-cis isomer (r = 0.67, P < 0.05). There was no significant difference in the terminal half-lives of any isomer between the groups: cis-cis, healthy (68 (41-204) min), renal failure (80 (55-153) min), impaired renal function (101 (66-157) min); cis-trans, healthy (2.0 (1.3-4.4) min), renal failure (4.3 (2.3-7.8) min), impaired renal function (3.5 (1.4-10.4) min; trans-trans, healthy (2.3 (1.6-8.1) min), renal failure (4.2 (2.4-7.3) min), impaired renal function (13.4 (2.1-50) min). Volume of distribution was similar for each isomer in all three groups. The median infusion rate required to maintain T1/T0 at 5% was significantly increased in the impaired renal function group, at 10.0 micrograms kg-1 min-1, compared with both healthy patients (5.9 micrograms kg-1 min-1) and renal failure patients (5.0 micrograms kg-1 min-1) (P < 0.05 in each case).      

Alfentanil infusion for sedation in infants and small children during cardiac catheterization

We have analyzed several sedation techniques for paediatric cardiac catheterization which offer stable conditions for a few hours investigation, and maintain spontaneous breathing. In the present study, after premedication with oral flunitrazepam 0.1 mg.kg-1, 14 children aged 1-17 mo were sedated with an individually titrated alfentanil infusion. Every patient was sedated to a level which produced no reaction to pain or any discomfort. The induction dose and the maintenance requirement of alfentanil were 24 +/- 8 micrograms.kg-1 and 32 +/- 8 micrograms.kg-1.hr-1 (mean +/- SD), respectively. These doses were less in cyanotic than in acyanotic patients: 21 +/- 6 vs 28 +/- 8 micrograms.kg-1 and 29 +/- 10 vs 34 +/- 3 micrograms.kg-1.hr-1, respectively (P less than 0.05). The mean plasma concentration of alfentanil during maintenance of sedation was 79 +/- 23 ng.ml-1. Ventilation of two children was assisted for a short time after an incremental bolus of alfentanil. It is concluded that an alfentanil infusion technique with close monitoring of breathing is a practical sedation method for paediatric cardiac catheterization.     

The influence of hepatic plasma flow on alfentanil plasma concentration plateaus achieved with an infusion model in humans: measurement of alfentanil hepatic extraction coefficient

In a group of seven patients undergoing intracranial surgery under neurolept anesthesia, an alfentanil infusion was initiated with a loading dose of 235 micrograms/kg over 5 min, followed by a maintenance infusion rate of 1.8 microgram X kg-1 X min-1 in order to obtain a steady state plasma concentration (Css) of 400 ng/ml-1 according to an infusion model. The mean values of Css (446 +/- 209 ng/ml) were close to the predicted ones. Nevertheless, an important intersubject variability in Css values was observed. A positive linear correlation existed between alfentanil steady state clearance and indocyanine green clearance (r = 0.88) and between alfentanil steady state clearance and cardiac index (r = 0.93). In three patients, a catheter was inserted into an hepatic vein to determine the alfentanil hepatic extraction coefficient. Alfentanil plasma clearance did not differ from alfentanil hepatic clearance and alfentanil hepatic extraction coefficient values ranged from 0.32-0.53. We conclude that alfentanil is a drug with an intermediate hepatic extraction coefficient and that alfentanil plasma clearance depends on hepatic plasma flow, which is thus one of the factors accounting for individual variability in plasma concentration plateaus achieved with an infusion model.     

Comparaison de l’incidence sur le saignement de deux techniques anesthésiques midazolam-alfentanil versus propofol-alfentanil lors de la cure d’otospongiose

This study was performed to compare the incidence of bleeding associated with two anaesthetic techniques during otolaryngological microsurgery. Twenty-eight venous interpositions for otospongiosis have been carried out at random either under local anaesthesia combined with light sedation (midazolam 0.1 mg.kg-1 and alfentanil 0 micrograms.kg-1) or using general anaesthesia (propofol 2.5 mg.kg-1, then 9 mg.kg-1.hr-1 and alfentanil 30 micrograms.kg-1, then 15 micrograms.kg-1). The patients' lungs were mechanically ventilated. Every ten minutes, heart rate, arterial blood pressure and FETCO2 were observed. Bleeding was assessed on a four-point scale and evaluated according to its duration and the annoyance that it caused. General anaesthesia was clinically better tolerated. Heart rate and arterial blood pressure were lower than with general anaesthesia. The end-expiratory CO2 was 4.7 +/- 0.2 per cent. Bleeding was less frequent, lasted less time, but when it occurred the surgical disturbance was identical in the two groups. General anaesthesia produced a less bloody operating field and local anaesthesia required the cooperation of the patient.     

An open, randomized comparison of alfentanil, remifentanil and alfentanil followed by remifentanil in anaesthesia for craniotomy

We studied 52 adults undergoing elective craniotomy, allocated randomly to one of three opioid treatments: alfentanil 50 micrograms kg-1 followed by 0.833 microgram kg-1 min-1 until dural closure (group Alf.); alfentanil 50 micrograms kg-1 followed by 0.833 microgram kg-1 min-1 for 2 h, then remifentanil 0.25 microgram kg-1 min-1 (group Alf.- Remi.); or remifentanil 1 microgram kg-1 followed by 0.5 microgram kg-1 min-1 reducing to 0.25 microgram kg-1 min-1 after craniotomy (group Remi.). Anaesthesia was maintained with infusion of propofol and 66% nitrous oxide in oxygen. Infusions of propofol and remifentanil were stopped at head bandaging. Group Remi. had the least intraoperative haemodynamic responses and group Alf. the most (P < 0.05). Times to tracheal extubation and obey commands were similar in all groups. In all patients in group Alf.-Remi. and group Remi., the trachea was extubated 27 min from the end of anaesthesia; three patients in group Alf. were slower to recover. Use of analgesia in the recovery room and time to transfer to the neurosurgical unit were similar in the three groups.      

Metoclopramide does not decrease the incidence of nausea and vomiting after alfentanil for outpatient anaesthesia

Sixty patients were studied in a randomized, double-blind manner to determine whether metoclopramide added to droperidol decreased further the incidence of emetic symptoms (nausea, retching, vomiting) in outpatients receiving alfentanil anaesthesia for nasal surgery. Group 1 (n = 30) received metoclopramide 0.15 mg.kg-1 and Group 2 (n = 30) received placebo. In addition, both groups received droperidol 0.02 mg.kg-1 immediately before anaesthesia which was supplemented by alfentanil 20 micrograms.kg-1 at induction followed by an infusion of 0.25-1 micrograms.kg-1.min-1. Emetic symptoms were assessed 0-3 hr, 3-6 hr and 6-24 hr after surgery. Both groups received similar doses of alfentanil (mean +/- SD; Group 1 4641 +/- 1894 micrograms, Group 2 4714 +/- 1640 micrograms). The percentage of patients who had either nausea or vomiting at 0-3, 3-6 or 6-24 hr was 23%, 14% and 13% in Group 1; and 20%, 17% and 10% in Group 2. The overall incidence for each group was 8/30 (27%). There was no difference in the incidence of emetic symptoms between the groups at any time interval or throughout the study. Metoclopramide did not improve upon the antiemesis of droperidol during alfentanil anaesthesia for outpatient nasal surgery.     

Alfentanil v. isoflurane for outpatient arthroscopy

Alfentanil by continuous intravenous infusion and isoflurane have been compared as anaesthetic agents for outpatient arthroscopy. In 42 patients, divided at random into two groups, anaesthesia was induced with methohexitone and vecuronium bromide, and, after intubation, maintained with nitrous oxide 66% in oxygen combined with alfentanil or isoflurane. Alfentanil was given before intubation (1 mg), as a loading dose before starting surgery (50 micrograms kg-1) and by a continuous infusion at a rate of 1 microgram kg-1 min-1. Isoflurane was given in a concentration of 0.9% as a maintenance dose. Awakening from anaesthesia was more rapid with alfentanil than with isoflurane. Recovery tests were applied in the recovery room. Both anaesthetic techniques provided satisfactory anaesthesia and rapid recovery. All patients but one were content with the anaesthesia. The patients who received isoflurane scored better in the recovery tests in the first 3 h, but after 3 h there was no difference between the groups. The alfentanil group showed a higher incidence of nausea and/or vomiting: 45% compared to 14% in the isoflurane group.     

Analgesia for appendectomy: comparison of fentanyl and alfentanil in children

During etomidate-N2O vecuronium anaesthesia for appendectomy, three groups of 13 children received fentanyl as a 10 micrograms.kg-1 loading dose and 2 micrograms.kg-1 increments in Group F, alfentanil as a 100 micrograms.kg-1 initial loading dose and either 20 micrograms.kg-1 increments in Group AB or 1 microgram.kg-1.min-1 continuous infusion in Group AI. On the basis of intraoperative heart rate changes, the opioid regimen was less efficient in Group AB (P less than 0.05). Based upon equianalgesic cumulative dosage, the alfentanil/fentanyl potency ratio was in the range of 1/10 to 1/13. The awakening time was similar in all groups, as were the duration of postoperative analgesia, the incidence of postoperative pain and the incidence of nausea and vomiting. We conclude that high-dose alfentanil is as efficient as fentanyl for intra and postoperative analgesia in children undergoing appendectomy.     

Pharmacokinetics of alfentanil and clinical responses during cardiac surgery

This study assessed the pharmacokinetic and pharmacodynamic behaviour of alfentanil during and after coronary artery bypass grafting (CABG). Twenty-eight patients with good ventricular function having CABG were divided into three groups and premedicated with morphine 0.1 mg.kg-1 IM, scopolamine 0.005 mg.kg-1 IM and diazepam 0.1 mg.kg-1 PO. Group I patients received an infusion of 250 micrograms.kg-1 of alfentanil over one hour coincidental with a second infusion at 2.5 micrograms.kg-1.min-1 which was continued to the end of surgery. Patients in group II received 300 micrograms.kg-1 and 3.0 micrograms.kg-1.min-1 and patients in group III 350 micrograms.kg-1 and 3.5 micrograms.kg-1.min-1. The tracheas of all patients were intubated after receiving alfentanil 96 micrograms.kg-1 and pancuronium 0.15 micrograms.kg-1. Haemodynamic responses to intubation and surgical stimuli (greater than or equal to 20 per cent increase in heart rate and/or systolic blood pressure from control) were treated with isoflurane, one to two per cent inspired, until abolished. Blood samples were taken during and after surgery for plasma alfentanil concentrations which were determined by radioimmunoassay. After surgery the times to awakening and extubation, and alfentanil elimination half-life (t1/2B = 0.693/-k) were determined for each patient. Haemodynamic responses occurred in 20 patients. There were no significant differences in any variable among the groups. The times to awakening and extubation for all patients were 3.2 +/- 0.6 and 8.8 +/- 1.2 hr (mean +/- SEM) respectively. The elimination half-life for all patients was 5.1 +/- 1.0 hr (mean +/- SEM).(ABSTRACT TRUNCATED AT 250 WORDS)     

CBF and CMRO2 during Continuous Etomidate Infusion Supplemented with N2O and Fentanyl in Patients with Supratentorial Cerebral Tumour. A Dose-Response Study

In 14 patients with supratentorial cerebral tumours with midline shift below 10 mm, CBF and CMRO2 were measured (Kety & Schmidt) during craniotomy. The anaesthesia was continuous etomidate infusion supplemented with nitrous oxide and fentanyl. The patients were divided into two groups. In Group 1 etomidate infusion of 30 micrograms kg-1 min-1 was used throughout the anaesthesia, and CBF and CMRO2 were measured twice. In this group CMRO2 (means +/- s.d.) averaged 2.31 +/- 0.43 ml O2 100 g-1 min-1 70 min after induction and 2.21 +/- 0.38 ml O2 100 g-1 min-1 130 min after induction. In Group 2 the etomidate infusion was increased from 30 to 60 micrograms kg-1 min-1 after the first study and a significant fall in CMRO2 from 2.52 +/- 0.56 to 1.76 +/- 0.40 ml O2 100 g-1 min-1 was found. Simultaneously, a significant fall in CBF was observed. The CO2 reactivity was preserved during anaesthesia.     

Bupivacaine 0.125% produces motor block and weakness with fentanyl epidural analgesia in children

PURPOSE: Epidural infusions of fentanyl (2 micrograms.ml-1) alone or combined with bupivacaine 0.125% were compared for perioperative analgesia, motor block and other side-effects in children who underwent urological surgery. METHODS: In a prospective, double-blind study, 42 children, ASA I-II, 1-16 yr, were randomly allocated to receive either epidural F (fentanyl bolus 2 micrograms.kg-1 in 0.5 ml.kg-1 saline followed by 2 micrograms.ml-1 fentanyl infusion) or epidural F-B (fentanyl bolus 2 micrograms.kg-1 in 0.5 ml.kg-1 bupivacaine 0.25% followed by 2 micrograms.ml-1 fentanyl infusion in bupivacaine 0.125%) after induction of general anaesthesia. Adequacy of analgesia, lower limb motor block and side-effects were assessed four hourly postoperatively. RESULTS: Both infusion regimens provided excellent analgesia (median objective pain scores = 0). Epidural infusion rates were similar in the F (0.29 +/- 0.07 ml.kg-1.hr-1) and F-B (0.26 +/- 0.05 ml.kg-1.hr-1) groups. Three children in the F group and all children in the F-B group developed lower limb weakness. (P < 0.05) Bromage scores were different in the F group (median 0, range 0-0.66) compared with the F-B group (median 0.33, range 0-1) (P < 0.001). Other side-effects did not differ. CONCLUSION: Postoperative epidural fentanyl infusion provides equipotent analgesia to administration of a solution including both fentanyl and bupivacaine 0.125% and causes less lower limb weakness. No reduction in the fentanyl requirement resulted from the addition of bupivacaine 0.125%.     

Alfentanil pharmacokinetics in patients with cirrhosis

The pharmacokinetics of alfentanil were studied in 11 patients with alcoholic cirrhosis and 10 control patients during general anesthesia. All patients received 50 micrograms . kg-1 alfentanil as an intravenous bolus injection. Plasma concentrations were measured at intervals up to 10 h, using a specific radioimmunoassay technique. Protein binding was measured by equilibrium dialysis. Patients with cirrhosis had a significantly lower (P less than 0.01) plasma clearance of alfentanil of 1.6 +/- 1.0 ml . min-1 . kg-1 (mean +/- SD) instead of 3.1 +/- 1.6 ml . min-1 . kg-1 in the controls. The total apparent volume of distribution was similar in the two groups. The elimination half-life was prolonged from 90 +/- 18 min in the controls to 219 +/- 128 min in the cirrhotics (P less than 0.01). Patients with cirrhosis had a higher (P less than 0.01) alfentanil plasma-free fraction (18.6 +/- 9.4%) compared with the control patients (11.5 +/- 3.9%). When kinetic parameters were corrected for protein binding, the unbound volume of distribution and the free drug clearance were decreased significantly in patients with cirrhosis. Since the concentration alpha 1-glycoprotein to which alfentanil mainly is bound in plasma did not differ in the two groups, it is suggested that the increase in the free fraction is caused by an alteration of binding sites of this protein in patients with cirrhosis. Owing to its delayed elimination and increased free fraction, alfentanil will exert a prolonged and pronounced effect in patients with cirrhosis.     

Preinduction atropine or glycopyrrolate and hemodynamic changes associated with induction and maintenance of anesthesia with propofol and alfentanil

Total intravenous anesthesia by infusions of propofol and alfentanil may be associated with decreases in heart rate and blood pressure. The effects of two vagolytic agents on these hemodynamic changes were studied in 24 ASA physical status 1 patients undergoing body surface surgery. Patients were randomly allocated to receive atropine 10 micrograms/kg, glycopyrrolate, 5 micrograms/kg, or 0.9% sodium chloride, intravenously, 5 min before induction of anesthesia with loading doses of alfentanil, 50 micrograms/kg and propofol 1 mg/kg. Anesthesia was maintained with infusions of alfentanil 50 micrograms.kg-1.hr-1, and propofol 10 mg.kg-1.hr-1 for the first 10 min, 8 mg.kg-1.hr-1 for the next 10 min, and 6 mg.kg-1.hr-1 thereafter. Patients given glycopyrrolate before anesthesia had significantly higher arterial pressures than did patients receiving either atropine or saline, even though heart rates increased equally after glycopyrrolate and atropine.     

Alfentanil-midazolam anaesthesia has no electrophysiological effects upon the normal conduction system or accessory pathways in patients with Wolff-Parkinson-White syndrome

The effects of alfentanil-midazolam anaesthesia upon the electrophysiologic (EP) properties of normal atrioventricular (A-V) and accessory pathway (AP) conduction were studied in eight patients with Wolff-Parkinson-White syndrome during accessory pathway surgical ablation. The presence of an AP was confirmed by preoperative EP studies. Anaesthesia was induced with alfentanil (50 micrograms.kg-1) and midazolam (0.15 mg.kg-1) and maintained with an alfentanil infusion (2 micrograms.kg-1.min-1) and intermittent boluses of midazolam (1-2 mg q 15 min, PRN). Following sternotomy, a baseline EP study was performed which consisted of effective refractory period (ERP) and shortest cycle length (SCC) measurement during antegrade conduction in the AV and AP, as well as during retrograde conduction in the AP. Comparison with preoperative EP studies indicated that the administration of alfentanil-midazolam anaesthesia had no effect upon conduction or ERP in either pathway. Haemodynamic stability occurred throughout the surgical procedure with no tachyarrhythmias. We conclude that a combination of alfentanil-midazolam is suitable for general anaesthesia in patients undergoing ablative procedures for accessory pathways.