Comparison of alfentanil,fentanyl and enflurane as supplements to general anaesthesia for outpatient gynaecologic surgery

We compared two narcotic/N2O anaesthetic techniques and an inhalational anaesthesia/N2O technique for outpatient surgery in 59 women undergoing short gynaecological procedures. All patients received droperidol 0.625 mg IV, thiopentone and 70 per cent N2O in O2 plus either alfentanil (15 micrograms.kg-1), fentanyl (1.5 microgram.kg-1) or enflurane. The narcotics were given in a double-blind fashion and all anaesthetic techniques were assigned randomly. Cardiorespiratory parameters remained stable in all groups, with few clinically important changes occurring. Recovery was significantly faster in the group receiving alfentanil, with the time to respond to verbal commands and the time to establish alertness significantly faster than with either fentanyl or enflurane. All techniques provided satisfactory anaesthesia; however, the patients receiving alfentanil had significantly more adverse events than those receiving fentanyl.     

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.     

Effect of total intravenous anaesthesia with midazolam/alfentanil on the adrenocortical and hyperglycaemic response to abdominal surgery

The effect of anaesthesia on the hyperglycaemic and adrenocortical response induced by surgery was studied in patients undergoing abdominal hysterectomy. The study group was anaesthetized with midazolam and alfentanil using a totally intravenous anaesthetic technique. A reference group received anaesthesia with thiopentone, alfentanil and nitrous oxide. Midazolam 0.42 mg.kg-1 was given as a loading infusion followed by a maintenance infusion of 0.125 mg.kg-1.h-1. Alfentanil was given as a bolus dose of 0.075 mg.kg-1 in both groups, followed by a loading infusion of 0.3 mg.kg-1.h-1 for 15 min and a maintenance infusion of 0.065 mg.kg-1.h-1. Increments of alfentanil were given whenever heart rate or systolic blood pressure exceeded pre-induction values by more than 10%. During anaesthesia mean arterial pressure and heart rate were similar in both groups and there was no difference in alfentanil requirement. An immediate increase in blood glucose concentrations was seen following incision, but maximum concentrations were measured in the early postoperative period. Serum cortisol concentrations decreased after induction of anaesthesia. During surgery they returned to pre-induction values, and in the postoperative period they increased to about twice the pre-induction values. It is concluded that midazolam/alfentanil anaesthesia is as effective as anaesthesia induced by thiopentone, alfentanil and nitrous oxide in suppressing the stress-response to surgery until the postoperative period. No signs of prolonged adrenocortical depression were observed.     

Cardiovascular response of a continuous variable rate alfentanil infusion for abdominal aortic surgery

A prospective study was undertaken to determine the cardiovascular response of a continuous alfentanil infusion during abdominal aortic surgery (AAS). Each subject (n = 20) received a beta-blocking drug preoperatively, and was premedicated with oral lorazepam. Anaesthesia was induced with alfentanil 50 micrograms.kg-1 and thiopentone 3 mg.kg-1, and was maintained with a variable rate infusion of alfentanil and 66 per cent nitrous oxide in oxygen. During the infusion, boluses of alfentanil, 7.5 micrograms.kg-1, were administered to maintain heart rate and blood pressure within 20 per cent of awake baseline values. Haemodynamic stability during surgery was achieved with infusion rates varying between 0.5 and 2.5 micrograms.kg-1, which resulted in mean alfentanil serum concentrations ranging from 186 +/- 53 to 315 +/- 98 ng.ml-1. The mean cumulative alfentanil dose was 15.4 +/- 6.2 mg.patient-1 for surgery which lasted an average of 141 +/- 41 min. Throughout surgery, no patient required inhalational anaesthetic agents or vasoactive drugs. Fifteen of the 20 patients had perioperative Holter monitoring. No myocardial ischaemia was detected during the intraoperative period. However, there was a 33 per cent incidence of myocardial ischaemia on the first postoperative day. There were no myocardial infarcts and no deaths. We conclude that in beta-blocked patients undergoing aortic reconstructive surgery, a variable rate alfentanil infusion administered with 66 per cent nitrous oxide provides anaesthesia characterized by good haemodynamic control without the need for supplemental agents or vasoactive drugs.     

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.     

Placental transfer of alfentanil at caesarean section

Twenty-one women about to undergo elective Caesarean section were given intravenous alfentanil 10 micrograms kg-1 1 min prior to induction of anaesthesia in order to obtund the pressor response to laryngoscopy and endotracheal intubation. Compared with a control group of 16 patients, alfentanil significantly reduced the pressor response to endotracheal intubation (P less than 0.01), without any detectable adverse effect upon the neonate. At delivery, mean maternal alfentanil plasma concentration was 23.5 ng ml-1 (SD 7.5, range 9.8-41.2 ng ml-1) and the mean maternal venous plasma alpha 1-acid glycoprotein (alpha 1-AGP) was 576 mg l-1 (SD 208, range 230-1200 mg l-1). Mean neonatal umbilical venous alfentanil plasma concentration was 7.5 ng ml-1 (SD 1.8, range 3.6-10.6 ng ml-1), while the mean umbilical venous alpha 1-AGP concentration was 189 mg l-1 (SD 76, range 80-410 mg l-1). At delivery, the calculated unbound maternal and foetal plasma alfentanil concentrations were similar.     

Cardiovascular responses caused by the combination of lidocaine and vecuronium in the induction of general anaesthesia

Fentanyl, vecuronium and enflurane may cause bradyarrhythmias during anaesthesia. Lidocaine administered before endotracheal intubation may interact synergistically with these agents. In this randomized and double-blind study, lidocaine 1 mg kg-1 (24 patients) or saline (20 patients) was given, immediately after glycopyrrolate 5 micrograms kg-1, fentanyl 1.5 micrograms ml-1 and thiopentone 3-5 mg kg-1, together with vecuronium 0.1 mg kg-1 as a rapid i.v. injection to healthy (ASA 1) surgical patients. Enflurane 0.8% was included in the inhaled gases 10 min and enflurane 1.6% 25 min after lidocaine administration. The plasma concentrations of lidocaine rose to a mean level of 3.1 micrograms ml-1 (maximum 7.1 micrograms ml-1) which may affect the electrical conduction at various sites in the heart. There were no statistically significant differences in arterial blood pressures or heart rates during anaesthesia between the groups. The incidence of junctional rhythm was 7/24 patients in the lidocaine group and 5/20 patients in the saline group. Three patients in the lidocaine group, and two patients in the control group developed junctional rhythm immediately after intubation. The plasma concentrations of vecuronium were unaffected by lidocaine. The ratio of the unbound lidocaine to plasma protein bound lidocaine was at the expected level and did not differ significantly 2 and 10 min after the injection.     

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.     

Pharmacokinetics of propofol injected after deliberate preoperative hemodilution

The effects of acute isovolaemic haemodilution (AIH) on propofol pharmacokinetics were studied in 16 male patients scheduled for prostatectomy. They were all ranked ASA 1, and were randomly allocated to two groups, group I (n = 8), who did not undergo any haemodilution, and group II (n = 8), in whom AIH was carried out. Anaesthesia was induced with a single 2.5 mg.kg-1 propofol bolus given in 30 s; maintenance was achieved with fentanyl 2 micrograms.kg-1, atracurium 1 mg.kg-1, and a ventilation with a mixture of nitrous oxide in oxygen 50 %, with enflurane 1 %. Those patients due to be haemodiluted had blood withdrawn before surgery (1,387.5 +/- 423.3 ml), at the same time as they were given the same volume of modified fluid gelatin (Plasmion). The volume of blood to be withdrawn was calculated according to the initial haematocrit, and that required. Haematocrit was decreased to 32.3 +/- 3.9 % (extremes 27 and 37 %). Thereafter blood samples were then collected over a 24 h period, which included surgery. Propofol was assayed in whole blood using high performance liquid chromatography. Analysis with a three-compartment model was carried out. The AIH only altered the central compartment volume (65.5 +/- 15.6 l in the control group vs 83.6 +/- 13.3 l in group II, p less than 0.01). Initial concentrations were not significantly different in the two groups (2,892 +/- 762 ng.ml-1 in controls vs 2,373 +/- 589 ng.ml-1 in the others). Clinically, anaesthesia and recovery were uneventful. It is concluded that the induction dose of propofol in patients scheduled for haemodilution does not require any alteration.     

Comparison of Alfentanil and Fentanyl as Supplements to Induction of Anaesthesia with Thiopentone

In 120 premedicated patients undergoing general surgery, anaesthesia was induced with thiopentone 3 mg kg-1, preceded by alfentanil 4.5, 9.0 or 13.5 micrograms kg-1 or fentanyl 1.5 micrograms kg-1. The largest alfentanil dose attenuated the arterial blood pressure response to laryngoscopy and intubation better than the smaller doses of alfentanil. Changes in frontal muscle electromyogram or plasma cortisol and prolactin levels were not dependent on the adjuvant used. After thiopentone, 30, 7 and 17% of the patients given alfentanil 9.0 and 13.5 micrograms kg-1 and fentanyl 1.5 micrograms kg-1, respectively, reacted to pinching of the lower abdomen. Patients given alfentanil 4.5 micrograms kg-1 did not tolerate the endotracheal tube after recovery from suxamethonium block and their heart rate was increased 12 min after alfentanil administration. We conclude that the antinociceptive effect of alfentanil is distinctly shorter than that of fentanyl. The analgesic potency of alfentanil is between one sixth and one ninth of that of fentanyl.     

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)     

Fentanyl-oxygen versus fentanyl-N2O/oxygen anaesthesia in children undergoing cardiac surgery

Fentanyl-oxygen (fentanyl-O2) anaesthesia was compared to fentanyl-nitrous oxide/oxygen (fentanyl-N2O/O2) anaesthesia in 14 children undergoing cardiac surgery. Children were randomly assigned to one of the two techniques studied, with seven patients in each group. The mean age (mean +/- SE) was 3.9 +/- 0.75 years (0.5-8.25 years) and mean weight 14.7 +/- 2 kg (3.5-29.5 kg). Patients were premedicated with IM atropine 0.02 mg . kg-1 and morphine 0.2 mg . kg-1 1 hour preoperatively. They received a fentanyl bolus of 30 micrograms . kg-1 with a concomitant continuous infusion of 0.3 micrograms . kg-1 . min-1. Pancuronium 0.1 mg . kg-1 was administered immediately following the fentanyl bolus. Fifty per cent nitrous oxide was given with oxygen in one group and 100 per cent oxygen was administered to the other group. Fentanyl plasma concentrations were similar in the two groups at the various stages of surgery. There were no significant differences between the two treatment groups in systolic and diastolic blood pressure or in heart rate in response to induction, intubation, and incision. There was a significantly greater increase in systolic blood pressure after sternotomy in the fentanyl-O2 group. In addition, in six of seven patients receiving fentanyl-O2 there were events of sudden increase in blood pressure during various stages of surgery before the bypass, necessitating an additional fentanyl bolus or the addition of droperidol in four cases. Similar phenomena were not documented in the fentanyl-N2O/O2 group. Our studies suggest that fentanyl-O2 anaesthesia in the schedule described, in children undergoing elective cardiac surgery for Tetralogy of Fallot, A-V canal, and transposition of the great arteries, is not sufficient to prevent elevation in systolic blood pressure despite fentanyl plasma concentrations in excess of 20 ng X ml-1. The addition of nitrous oxide prevents this phenomenon.     

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)     

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)     

Concentrations of thiopentone in mature breast milk and colostrum following an induction dose

In two groups of eight patients, concentrations of thiopentone in mature breast milk and colostrum following anaesthesia induction with 5.4 and 5.0 mg kg-1 b.w. (mean), respectively, were measured in the first 36 h postoperatively. Blood concentrations were measured simultaneously. The maximal concentrations were: in mature breast milk, 3.4 +/- 0.68 mumol l-1 (mean +/- s.e. mean) (0.090 mg 100 ml-1), and in colostrum, 1.3 +/- 0.5 mumol l-1 (0.034 mg 100 ml-1). The milk/plasma ratio was less than 1.0 in both groups. The above concentrations may be regarded as negligible and therefore non-toxic for the nursing infant.     

Cerebrospinal fluid concentrations of propofol during anaesthesia in humans

The concentration of propofol in and surrounding the human brain during propofol anaesthesia is unknown. We measured simultaneously the concentration of propofol in cerebrospinal fluid (CSF) from an indwelling intraventricular catheter and the concentration in arterial blood in five neurosurgical patients before, during induction (at 2.5 and 5 min) and during a maintenance propofol infusion (at 15 and 30 min). After induction of anaesthesia with propofol 2 mg kg-1, anaesthesia was maintained with an infusion of 8 mg kg-1 h-1 for 15 min and then reduced to 6 mg kg-1 h-1. The plasma concentration of propofol increased rapidly during induction and reached a plateau concentration of mean 2.24 (SD 0.66) micrograms ml-1 after 5 min. The concentration of propofol in CSF showed a slower increase during induction and remained almost constant at 35.5 (19.6) ng ml-1 at 15-30 min after induction. The CSF concentration of propofol that we measured was 1.6% of the plasma concentration and consistent with the high protein binding of the drug in plasma.      

Total intravenous anaesthesia with propofol and alfentanil protects against postoperative nausea and vomiting

The incidence of postoperative nausea and vomiting and requirements for anti-emetic medication were assessed in 80 female patients undergoing day-case anaesthesia during assisted conception therapy. Anaesthesia was induced with alfentanil 50 micrograms.kg-1 and propofol 1 mg.kg-1; atracurium 0.5 mg.kg-1 was given to facilitate tracheal intubation. The patients were allocated to receive either total intravenous maintenance of anaesthesia with an infusion of propofol and increments of alfentanil (Group P) or inhalational maintenance of anaesthesia with nitrous oxide and enflurane (Group E). Postoperative nausea, retching, vomiting, requirements for anti-emetic therapy, and unplanned admission for overnight stay in hospital were recorded. Overall incidence of nausea was 64% in group E and 39% in Group P (P less than 0.05). Incidence of vomiting was 67% in Group E and 34% in Group P (P less than 0.05). Metoclopramide was requested by 62% of patients in Group E, and 32% of those in Group P (P less than 0.05); 21% of the patients in Group E were admitted to hospital overnight, while only 5% of the patients in Group P required unscheduled admission to hospital (P less than 0.05). We conclude that total intravenous anaesthesia with propofol and alfentanil is superior to inhalational maintenance with nitrous oxide and enflurane in that it is associated with less nausea and vomiting, less requirement for anti-emetic medication, and a lower probability of unplanned admission to hospital after day-care gynaecological surgery.     

Alfentanil anaesthesia in gall-bladder surgery

Five different dosage schemes for alfentanil administration supplemented with thiopentone, pancuronium and N2O/O2 have been studied in 25 patients undergoing elective cholecystectomy. Six patients in the high dosage group experienced stiff chest during induction and five patients developed respiratory arrest on the recovery ward. The effects of the different schedules in blocking the surgical stress response have been elucidated by serial measurements of serum cortisol and glucose, heart rate and systolic blood pressure. There were no significant changes in serum cortisol, heart rate and blood pressure during anaesthesia and surgery in any group. All patients showed a significant increase in serum cortisol 2 h postoperatively. There was significant elevation of serum glucose after 1 h of surgery in two groups (maintenance dose 1 microgram/kg/min of alfentanil) and in all groups except one (maintenance dose 3.0 micrograms/kg/min) 2 h postoperatively. High dosage of alfentanil resulted in frequent stiff chest during induction and respiratory arrest postoperatively. High dosage did not seem to give any additional benefits in blocking the surgical stress response in this type of surgery.     

Alfentanil infusion in the elderly

The use of a computer-assisted infusion of alfentanil, combined with 66% nitrous oxide in oxygen, for induction and maintenance of anaesthesia was evaluated in 18 elderly patients. The target alfentanil concentration for induction was varied between 300 and 475 ng/ml, to be achieved in 2 minutes. During maintenance, the alfentanil concentration was increased or decreased according to each patient's responses. Arterial blood samples were taken for measurement of alfentanil concentration. There were high incidences of muscle rigidity, bradycardia and hypotension during induction. Hypotension was dose- and concentration-dependent. Signs of light anaesthesia during maintenance were controlled rapidly by increasing the target plasma concentration. Nine patients required naloxone at the end of surgery. Ventilatory depression recurred in three of these. The use of published alfentanil pharmacokinetic data from elderly patients to predict plasma concentrations during prolonged infusion resulted in significant prediction errors, notably in the higher concentration range.     

Plasma concentrations of alfentanil required to supplement nitrous oxide anesthesia for general surgery

To design an efficient infusion regimen from pharmacokinetic data, it is necessary to know the alfentanil plasma concentrations required for satisfactory anesthesia. In 37 patients about to undergo lower abdominal gynecologic, upper abdominal, or breast surgery, anesthesia was induced with alfentanil 150 micrograms/kg iv and 66% N2O in oxygen. Thereafter, N2O anesthesia was supplemented with a continuous infusion of alfentanil that was varied between 25 and 150 micrograms X kg-1 X h-1, as indicated by the patient's responses to surgical stimulation. Small bolus doses of alfentanil 7 or 14 micrograms/kg were administered and the infusion rate increased to suppress precisely defined somatic, autonomic, and hemodynamic responses. Arterial plasma concentrations of alfentanil were measured during the operation when the patient did and did not respond to noxious stimulation. Logistic regression was used to determine plasma concentration-effect curves for different stimuli. Plasma alfentanil concentrations required along with 66% N2O to obtain responses to single episodes of stimulation in 50% of the 37 patients (Cp50 +/- SE) were: 475 +/- 28 ng/ml for tracheal intubation, 279 +/- 20 ng/ml for skin incision, and 150 +/- 23 ng/ml for skin closure. Between skin incision and closure, multiple determinations of response/no response were made for each patient and an individual Cp50 was estimated. The Cp50 (mean +/- SD) for the three surgical procedures were: breast, 270 +/- 63 ng/ml (n = 12); lower abdominal, 309 +/- 44 ng/ml (n = 14); and upper abdominal, 412 +/- 135 ng/ml (n = 11). The Cp50 for satisfactory spontaneous ventilation after the discontinuation of N2O was 223 +/- 13 ng/ml. These data demonstrate that different perioperative stimuli require different alfentanil concentrations to suppress undesirable responses. Thus, the alfentanil infusion rate should be varied according to the patient's responsiveness to stimulation in order to maintain satisfactory anesthetic and operative conditions and to provide rapid recovery of consciousness and spontaneous ventilation.