PROPOFOL AND ALFENTANIL IN CHILDREN: INFUSION TECHNIQUE AND DOSE REQUIREMENT FOR TOTAL I.V. ANAESTHESIA

We estimated the dose of propofol (initial dose followed bya stepped infusion) when given with two different infusion ratesof alfentanil for total i. v. anaesthesia in 59 children aged3–12 yr. Patients in series 1 (four groups) received analfentanil loading dose of 85g kg^–1 and an infusion of65 g kg^–1 h^–1. Patients in series 2 (groups 5 and6) received an alfentanil loading dose of 65 g kg^–1 andinfusion of 50 g kg^–1 h^–1. Parents gave their informedconsent. Premedication comprised temazepam 0.3 mg kg^–1.Glycopyrronium 5 g kg^–1 was administered and anaesthesiainduced and maintained with alfentanil (loading dose and infusion)followed by propofol (loading dose and three-stage manual infusionscheme). Suxa-methonium 1 mg kg^–1 was used to facilitatetracheal intubation and the lungs were ventilated artificiallyto normocapnia with 30% oxygen in air. Probit analysis was usedto determine the dose requirement of propofol. In series 1.the ED₅₀ was 6.0 mg kg^–1 h^–1 (95% confidence limits5.5-6.2 mg kg^–1 h^–1) and ED₉₅ 8.6 (6.8-7.8) mg kg^–1h^–1. Corresponding values for series 2 were ED₅₀ 7.5 (8.0-9.8)mg kg^–1 h^–1 and ED₉₅ 10.5 (9.6^–13.1) mg kg^–1h^–1. ^*Department of Anaesthesia, University of Newcastle upon Tyne,Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP.      

TOTAL I.V. ANAESTHESIA WITH PROPOFOL AND ALFENTANIL FOR CORONARY ARTERY BYPASS GRAFTING

The haemodynamic effects of total i.v. anaesthesia with a combinationof propofol and alfentanil infusions were studied in eight patientswith good left ventricular function undergoing coronary arterybypass surgery. Haemodynamic indices were measured before anaesthesiaand at specified intervals before cardiopulmonary bypass. Thetechnique resulted in haemodynamic changes comparable to thosereported with opioid-based anaesthesia for coronary artery surgery,and has potential advantages.     

PHARMACOKINETICS OF ALFENTANIL IN TOTAL I. V. ANAESTHESIA

Alfentanil was administered, together with midazolam, as partof a total i.v. anaesthetic technique. The pharmacokineticsof alfentanil were determined in 10 female patients undergoinglower abdominal surgery. The dose regimen of alfentanil, basedon simulation studies, consisted of a two-stage infusion followingan initial bolus dose. The kinetics of alfentanil were describedby a linear twocompartment open model. The total plasma clearanceranged between 93 and 431 ml min^–1 (mean 249 ml min^–1).The apparent volume of distribution at steady-state ranged between0. 27 and 0. 64 litre kg^–1 (mean 0.44 litre kg^–11).The apparent volume of distribution (Vd^ß) was 0.58litre kg^–1, resulting in a terminal half-life of 112 min.Alfentanil concentrations at the time of extubation and postoperativeanalgesic requirements were also monitored. Good correlationbetween respiratory depression and plasma alfentanil concentrationwas found. Neither lower abdominal surgery nor the simultaneousadministration of midazolam seemed to affect the kinetics ofalfentanil as compared with results from studies in healthyvolunteers. The short haIf-life of alfentanil, resulting froma small volume of distribution, makes it suitable as part ofa total i.v. technique. Consideration must be paid, however,to interindividual differences in the pharmacodynamic responseand in plasma clearance. Presented in part at the third World Conference on ClinicalPharmacology and Therapeutics, Stockholm, Sweden, July 27-August1, 1986.     

EFFECT OF I.V. ANAESTHESIA WITH PROPOFOL ON DRUG DISTRIBUTION AND METABOLISM IN THE DOG

We have studied the effect of i.v. anaesthesia with propofolin the emulsion (Intralipid) formulation on drug distributionand metabolism in six dogs using dual-route administration ofpropranolol as a model compound. Each dog was studied on twoconsecutive days: day 1 awake and day 2 during propofol anaesthesia(6 mg kg^–1 followed by an infusion of 0.8 mg kg^–1min^–1). Propofol anaesthesia was associated with reducedintrinsic clearance by 40% (P < 0.05) but no significantdifference in systemic clearance or hepatic plasma flow. Propofolproduced marked changes in drug distribution; volume of distribution(V^ss) of propranolol increased 54% from 82.5 (SEM 7.3) litreawake to 127.3 (27) litre during propofol anaesthesia (P <0.05). This change was accompanied by an increase (P < 0.05)in the free fraction of propranolol from 8.5 (0.7)% in awaketo 14.0 (0.7)% in propofol-anaesthetized dogs. The combinationof the effects of both drug clearance and protein binding resultedin a 65% decrease in the intrinsic clearance of unbound drug(P < 0.05). In contrast with the effects of propofol on drugdistribution, infusion of Intralipid alone in another groupof six dogs had no significant effects on drug distribution,protein binding or drug metabolism. We conclude that propofolis a modest inhibitor of drug metabolism, but has major effectson propranolol distribution, possibly by changing plasma proteinbinding.     

RECOVERY FROM DAY-CASE ANAESTHESIA: COMPARISON OF TOTAL I.V. ANAESTHESIA USING PROPOFOL WITH AN INHALATION TECHNIQUE

A prospective, double-blind study was conducted to compare postoperativerecovery after either total i.v. anaesthesia (TIVA: propofoland alfentanil) or an inhalation technique (propofol and alfentanilfollowed by nitrous oxide and isoflurane) in 50 patients undergoingday-case gynaecological surgery. Psychomotor performance wasassessed at 1 and 2 h after surgery using the Critical FlickerFusion Threshold (CFFT), Simple Reaction Time (SRT) and ChoiceReaction Time (CRT). Subjective recovery and side effects afterdischarge from hospital were assessed using a postal questionnaire.Recovery occurred significantly earlier in the TIVA group asassessed by CFFT and SRT (P < 0.01 ); there were no significantdifferences (P > 0.05) between the two groups in CRT, subjectiveduration of recovery or side effects. ^* Stoke Mandcville Hospital, Mandeville Road, Aylesbury, BucksHP21 8AN      

COMPARISON OF THE CARDIORESPIRATORY EFFECTS OF KETOROLAC AND ALFENTANIL DURING PROPOFOL ANAESTHESIA

The cardiorespiratory effects of a new nonopioid analgesic,ketorolac tromethamine, were compared with alfentanil as partof a balanced technique in which anaesthesia was maintainedby a constant infusion of propofol. Twenty patients were allocatedrandomly to receive a single dose of either ketorolac 30 mgor alfentanil 0.5 mg. The study medication was given duringthe anaesthetic when the rate of ventilation had been stable(±1 b.p.m.) for 5 min. Measurements of ventilatory rate,end-tidal carbon dioxide partial pressure, arterial oxygen saturation(Sa_O2), heart rate and systemic arterial pressure were madeat 1-min intervals for 15 min following the test drug. Patientshaving alfentanil developed significant decreases in ventilatoryrate, heart rate and mean arterial pressure. A significant increasein end-tidal carbon dioxide partial pressure occurred also.No changes occurred in any of the measured variables in theketorolac group. ^*Present address: Royal Infirmary, Edinburgh.     

EFFECT OF DOSE AND PREMEDICATION ON INDUCTION COMPLICATIONS WITH ETOMIDATE

The induction characteristics of etomidate, a new i.v. hypnoticagent, were studied in 400 patients. Two hundred were premedicatedwith atropine and anaesthesia was induced with 0.2, 0.25, 0.3or 0.35 mg/kg of etomidate. The remainder received one of fourstandard premedications and anaesthesia was induced with etomidate0.3 mg/kg. Involuntary muscle movements occurred in more than60% of patients receiving atropine alone. The frequency wasreduced in the second group, but remained unacceptable in over8% of patients. The incidence of other excitatory phenomena,such as cough and hiccup, was 10% approximately. Cardiovascularchanges were minimal and no serious allergic phenomena wereobserved. Nausea and vomiting occurred after surgery in up to30% of patients and was unrelated to the dose of etomidate orto premedication. Pain on injection occurred in up to 80% ofpatients when the drug was injected into small peripheral veinsand occurred in more than % when using more proximal veins     

TRACHEAL INTUBATION AFTER INDUCTION OF ANAESTHESIA WITH PROFOL, ALFENTANIL AND I.V. LIGNOCAINE

We have assessed trachea/ intubating conditions in 60 AS A Ior II patients after induction of anaesthesia with propofol2.5 mg kg^-1 and alfentanil 10 or 20 fig kgr' with or withouti. v. lignocaine 1 mg kg1. No neuromuscular blocking agentswere administered. Patients were allocated randomly to fourgroups: group 1 = propofol-alfentanil 10 fig kg^-1; group 2 =propofol-alfentanil 10 fig kg^-1-lignocaine Imgkgr1; group 3= propofol-alfentanil 20 jig kg^-1; group 4 = propofol-alfentanil20 fig kg^-1-lignocaine 1 mgkgr. Intubating conditions were assessedas acceptable or unacceptable on the basis of a scoring systemdependent on ease of faryngoscopy, vocal cord position and coughingon insertion of the trachea/ tube. Intubating conditions wereacceptable in 20% 73, 73% and 93% of patients in groups 1–4,respectively. Intubating conditions were better and there wasless coughing in the lignocaine group. (Br. J. Anaesth. 1993;70: 163–166)     

OESOPHAGEAL CONTRACTILITY DURING TOTAL I.V. ANAESTHESIA WITH AND WITHOUT GLYCOPYRRONIUM

Somatic movement and spontaneous and provoked oesophageal contractionswere noted at time of incision in 51 patients receiving totali.v. anaesthesia with alfentanil and propofol. Probit analysisof the dose of propofol required to prevent spontaneous movementrevealed an ED₅₀ (95% confidence limits) of 2.5 (1.8-2.9) mgkg^–1 h^–1 and ED₉₅ of 4.7 (4.0-7.5) mg kg^–1h^–1. Corresponding venous blood concentrations gave anEC₅₀ of 1.2 (0.4-1.6) µg ml^–1 and an EC₉₅ of 4.0(2.8-18.5) µg ml^minus;1. ED₅₀ of propofol for preventingspontaneous oesophageal contraction was 3.0 (1.9-3.6) mg kg^–1h^–1. ED₉₅ was 6.9 (5.0-27.3) mg kg^–1 h^–1;EC₅₀ for oesophageal contractions was 1.7 (0.7-2.3) µgml^–1 and EC₉₅ was 5.9 (3.7-70.6) µg ml^–1.Another group of 10 patients were given glycopyrronium 5 µgkg^–1 at induction; oesophageal contractility was significantlyreduced in this group. Preliminary results of this research were presented to the AnaestheticResearch Society, Nottingham, July 1990. ^*Department of Anaesthesia, Derriford Hospital, Plymouth, DevonPL6 8DH. Department of Anaesthesia, Darlington Memorial Hospital, Darlington,Durham DL3 6HX.     

DOSE REQUIREMENTS OF PROPOFOL BY INFUSION DURING NITROUS OXIDE ANAESTHESIA IN MAN: I: Patients Premedicated with Morphine Sulphate

The study was performed to determine the ED₅₀ and ED₉₅ of acontinuous infusion of the emulsion formulation of propofolduring 67% nitrous oxide anaestheisa in 57 patients premed-icatedwith morphine sulphate 0.15 mg kg^–1. Anaesthesia was inducedwith propofol 2 mg kg^–1, and maintained before incisionwith a fixed-rate infusion of propofol to supplement nitrousoxide. The response to the first surgical incision, made atleast 30 min after induction of anaesthesia, was observed. TheED₅₀; was 53.5 µg kg^–1 min^–1 and the ED₉₅was 112.2 µg kg^–1 min^–1. At the time of thefirst surgical incision, the venous whole blood concentrationsof propofol at the ED₅₀ and ED₉₅ infusion rates (EC₅₀and EC₉₅were 1.66 µg ml^–1 and 3.39 fig ml^–1 respectively.The satisfactory maintenance of anaesthesia provided by nitrousoxide supplemented with propofol was associated with stabilityand rapid, uncomplicated recovery.     

I.V. ANAESTHESIA WITH PROPOFOL USING A TRAGET-CONTROLLED INFUSION SYSTEM: COMPARISON WITH INHALATION ANAESTHESIA FOR GENERAL SURGICAL PROCEDURES IN CHILDREN

We studied 40 children undergoing general surgical procedures.They were allocated randomly to receive induction of anaesthesiawith propofol 3–5 mg kg^-1 followed by maintenance withhalo-thane and an appropriate regional block, or induction andmaintenance of anaesthesia with a computerized, target-controlledinfusion of propofol with a regional block. All patients breatheda mixture of 67% nitrous oxide in oxygen via a laryngeal maskairway. Both techniques provided adequate anaesthesia and operatingconditions. There were no significant differences between thegroups in heart rate, mean arterial pressure and end-expiredcarbon dioxide concentration during anaesthesia. There was nosignificant difference in the recovery times of the two groups.(Br. J. Anaesth. 1993; 70: 542–545) ^*Present Address: Military Hospital, Aldershot, Hants GUII 2AN.     

ALFENTANIL AND PROPOFOL INFUSIONS FOR SURGERY IN THE BURNED PATIENT

We have studied combinations of alfentanil and propofol fortotal i.v. anaesthesia in 24 severely burned patients. No inhalationagents were used. After a loading dose of alfentanil 100 µgkg^–1, the intraoperative requirement was 1.24 (SEM 0.7)µg kg^–1 min^–1, and after a propofol inductiondose of 2 mg kg^–1 the maintenance rate was 100 µgkg^–1 min^–1. Initial hypotension occurred after inductionof anaesthesia, but during the operation, cardiovascular variableswere stable. After adequate antagonism of neuromuscular block,respiratory depression persisted in three patients when thetwo agents were discontinued simultaneously; this was not seenwhen alfentanil was discontinued 15 min before propofol. Qualityof recovery was good, and satisfactory postoperative analgesiawas present in the majority of patients 2 h after operation.This study indicates that total i.v. anaesthesia with a combinationof alfentanil and propofol appears to be satisfactory in burnedpatients.     

COMPARISON OF ORTHODOX WITH FIBREOPTIC OROTRACHEAL INTUBATION UNDER TOTAL I.V. ANAESTHESIA

Fibreoptic orotracheal intubation was compared with orthodoxlaryngoscopy and tracheal intubation using a total i.v. techniquewith propofol in 60 ASA I and II patients. There was no significantdifference between the two techniques in haemodynamic profile(before, during and following the intubation procedure) andincidence of postoperative sore throat. Minimal oxygen saturationwas 96% during the study; maximal end-tidal PCO₂ after intubationwas 5.4 kPa. Intubation time was faster (P < 0.01) in theorthodox group (30.7 (SEM 2.3) s) than in the fibreoptic group(52.7 (4.8) s).     

USE OF ALFENTANIL WITH PROPOFOL FOR NASOTRACHEAL INTUBATION WITHOUT NEUROMUSCULAR BLOCK

We have investigated the effect of augmentation of propofolwith alfentanil for nasotracheal intubation without neuromuscularblock in 60 patients undergoing short elective maxillo-facialprocedures as outpatients. After administration of glycopyrronium5 fig kg^–1 i.v., anaesthesia was induced with propofol2.5 mg kg^–1, or alfentanil 20 µg kg^–1 andprofopol 2.5 mg kg^–1. The alfentanil group had improvedjaw relaxation (P < 0.001) and vocalcord conditions (P <0.005). Tracheal intubation was successful in 83% of patientsreceiving alfentanil, and in 73% of patients receiving propofolonly. This difference was not significant. The cardiovascularresponse to intubation was attenuated in the alfentanil group.(Br. J. Anaesth. 1993; 70: 89–91)     

EFFECT OF ALFENTANIL ANAESTHESIA ON THE ADRENOCORTICAL AND HYPERGLYCAEMIC RESPONSE TO ABDOMINAL SURGERY

Plasma concentrations of cortisol and glucose were measuredfrom before to 9 h after skin incision in 24 patients undergoingabdominal hysterectomy. The patients were randomly allocatedto receive either high-dose alfentanil anaesthesia (150 µgkg^–1 initially, followed by continuous infusion at a rateof 3 µg kg^–1 min^–1) or neurolept anaesthesia(droperidol 0.25 mg kg^–1 plus fentanyl 5 µg kg^–1initially, followed by intermittent incremental doses of fentanyl50 µg). The intraoperative and initial postoperative increasesin plasma cortisol and glucose concentrations were inhibited(P < 0.05) by alfentanil but, later in the postoperativeperiod, both groups showed identical increases in cortisol andglucose concentrations. Mean arterial pressure and heart ratewere more stable in the alfentanil group. The concept of "stress-free"anaesthesia during highdose opiate administration seems to bevalid during operation and for the initial 1–3 h intothe postoperative period.     

PHARMACOKINETICS OF MIDAZOLAM IN TOTAL I. V. ANAESTHESIA

The pharmacokinetics of midazolam during total i.v. anaesthesiawere determined in 15 female i patients undergoing major surgery.Midazolam was administered together with an analgesic drug anda neuromuscu/ar blocking drug. The dose regimen of midazolam.based on simula-tions, included two consecutive infusions fol-lowing a bolus injection at the induction of anaesthesia. Multipleblood amples were drawn and a two-compartment open model wasfitted to the measured plasma concentrations. Plasma clearance(483 ml min^–l), apparent volume of distribution (1.94litre kg^–l) and terminal half-life (3.1 h) were in agreementwith other reports. Thus, there was no obvious evidence thatthe surgical procedure or the concomitant use of other drugs,or both, influenced the pharmaco- kinetics of midazolam. Therelatively rapid elimination makes midazolam suitable for useby infusion in a total i.v. technique.     

DREAMING ASSOCIATED WITH ANAESTHESIA: THE INFLUENCE OF MORPHINE PREMEDICATION AND TWO VOLATILE ADJUVANTS

An investigation is described into the problems of dreamingand recall under anaesthesia. One hundred and twenty patientswere divided into four equal groups. Group 1 were anaesthetizedusing thiopentone for induction and nitrous oxide for the maintenanceof anaesthesia, muscle relaxation being provided by tubocurarineand no premedicant or volatile anaesthetic agent being used.The three other groups received modifications of this technique:group 2 received pre-anaesthetic medication with morphine (1mg/stone body weight (6.3 kg) 30–60 min before operation);group 3 received small concentrations (0.5–0.3 per cent)of halothane as an adjuvant, and group 4 small concentrations(0.3–0.1 per cent) of methoxyflurane. The incidence ofdreaming in association with anaesthesia was high in the caseof group 1 (57 per cent) but significantly less in group 2 (23per cent; P<0.02), group 3 (0 per cent; P<0.001), andgroup 4 (23 per cent; P<0.02). There was no unequivocal evidenceof awareness of the surgical procedure, but there were a numberof dreams which appeared to be connected with the site of theoperation. The significance of this is discussed.     

PHARMACOKINETICS AND EFFECTS OF I.M. ALFENTANIL AS PREMEDICATION FOR DAY-CASE OPHTHALMIC SURGERY IN ELDERLY PATIENTS

We have studied the pharmacokinetics and effects of i.m. alfentanilas premedication for peribulbar block in 90 patients undergoingelective day-case cataract surgery. We compared alfentanil 12.5µg kg^–1 injected into the deltoid (n = 30) or glutealmuscle (n = 30)15 min before the peribulbar block, and placebo(n = 30). The alfentanil concentrations were significantly greaterin the deltoid group during the study and the mean peak concentrationoccurred more rapidly in this group. Only alfentanil injectedinto the deltoid muscle reduced pain (assessed with a visualanalogue scale (VAS)) associated with the peribulbar block.A mild sedative effect (VAS) was found in both alfentanil groups.We conclude that i.m. alfentanil appears to be a suitable premedicantfor short, painful procedures because it has a short durationof action and is not associated with any clinically significantside effects. (Br. J. Anaesth. 1993; 71: 507–511)     

LORAZEPAM AND MORPHINE FOR I.V. SURGICAL PREMEDICATION

The effects of i.v. lorazepam alone, in doses of 2 mg and 4mg, and combined with morphine 5 mg, were studied. Sedation,relief of anxiety, lack of recall, patient acceptance, physicianacceptance and side-effects were evaluated. The addition ofmorphine to lorazepam significantly improved sedation and reliefof anxiety. Physician acceptance and patient acceptance showedno significant difference between any of the combinations. Lackof recall was enhanced by increasing the dose of lorazepam from2 mg to 4 mg, independent of the addition of morphine. The onlysignificant side-effect was restlessness which occurred in 15%of patients receiving lorazepam 4 mg and 3% of patients receivinglorazepam 2 mg, again independent of the addition of morphine.     

DOSE REQUIREMENTS OF PROPOFOL BY INFUSION DURING NITROUS OXIDE ANAESTHESIA IN MAN: II: Patients Premedicated with Lorazepam

The infusion rate of propofol required to supplement 67% nitrousoxide in oxygen to maintain surgical anaesthesia was determinedin 72 patients premedicated with lorazepam. Following an inductiondose of propofol 2 mg kg^–1, groups of eight patients receivedan infusion of propofol varying from 60 to 200 µg kg^–1.Probit analysis was used to determine the ED₅₀ (130 µgkg^minus;1 min^–1; 95% confidence limits: 106–167µg kg^–1 min^–1) and ED₉₅ (348 µg kg^–1min^–1; 95% confidence limits: 233–1296 µgkg^–1 min^–1;) for propofol infusion. Whole bloodpropofol concentrations at the time of surgical incision correlatedstrongly with the infusion rate, giving an EC₅₀ value of 2.5µg ml ^–1, and an EC₉₅ value of 5.92 µg ml^–1.There was no significant correlation between the rate of infusionof propofol, or the total propofol dose, and the times to responseto command, or to recall of birthdate.