VECURONIUM INDUCED BRADYCARDIA FOLLOWING INDUCTION OF ANAESTHESIA WITH ETOMIDATE OR THIOPENTONE, WITH OR WITHOUT FENTANYL

To define the role of vecuronium in the occurrence of bradyarrhythmia,haemodynamic changes after the induction of anaesthesia werestudied in 96 patients undergoing coronary artery bypass grafting.Patients were assigned to one of six groups according to differentcombinations of induction agents (etomidate 0.3 mg kg^–1or thiopentone 3 mg kg^–1, with fentanyl 0.003 mg kg^–1,etomidate 0.4–0.5 mg kg^–1 or thiopentone 4–6mg kg^–1, without fentanyl) and neuromuscular blockingdrugs (vecuronium 0.112 mg kg^–1, pancuronium 0.112 mgkg^–1 or suxamethonium 1 mg kg^–1). Anaesthesia wasmaintained with enflurane and nitrous oxide in oxygen. Afterinitial diverse changes, heart rate decreased in all groups.Thirty minutes after intubation, the reduction of heart rateshowed statistically significant differences between the differentcombinations of drugs: fentanyl–etomidate–vecuronium(group I) (the largest reduction) > etomidate–vecuronium(II) = fentanyl–thiopentone–vecuronium (IV) >thiopentone–vecuronium (V) = fentanyl–thiopentone–suxamethonium(VI) = fentanyl–etomidate–pancuronium (III). Fivepatients in group I, two in group IV and one each in groupsII and V had a heart rate slower than 45 beat min^–1, whereasa similar value was never seen in groups III and VI. These resultsindicate that vecuronium has a bradycardic effect. This effectis more pronounced in association with etomidate than in associationwith thiopentone, and is augmented by the addition of fentanyl.     

DICLOFENAC FOR DAY-CARE ARTHROSCOPY SURGERY: COMPARISON WITH A STANDARD OPIOID THERAPY

Sixty unpremedicated patients presenting for day-care arthroscopysurgery were allocated randomly to receive diclofenac 1 mg kg^–1i.m., fentanyl 1 µg kg^–1 i.v. or no analgesic duringthe course of anaesthesia. Patients receiving fentanyl had slightly,although not significantly prolonged recovery times. Patientsreceiving diclofenac had significantly improved postoperativevisual analogue pain scores compared with patients receivingplacebo medication (P < 0.05). With fentanyl, pain scoreswere reduced also, but the effect was not statistically significant.Both fentanyl and diclofenac produced significant reductionin postoperative analgesic requirements (P < 0.05). We concludethat diclofenac 1 mg kg^–1 i.m. was an effective analgesicfor arthroscopic procedures on the knee and is a useful alternativeto opioids for day-care patients.     

LOWER OESOPHAGEAL REFLUX DURING PRIMING WITH VECURONIUM

We have studied the effects of vecuronium given in divided doses(priming principle) on the frequency of acid reflux into theoesophagus. Two groups of 16 patients were studied. After inductionwith thiopentone 6 mg kg^–1 and fentanyl 3 µg kg^–1,patients in one group were given vecuronium 0.01 µg kg^–1as a priming dose, followed by an intubation dose of 0.1 µgkg^–1 4 min later. Patients in the other group were givenno priming dose. Lower oesophageal pH was monitored continuouslyand acid reflux was defined as a decrease in pH to less than4.0. One patient in each group had acid reflux during the timecourse of the induction. This study suggests that vecuronium0.01 µg kg^–1 given as a priming dose does not increasethe risk of acid reflux into the oesophagus.     

PHARMACOKINETICS OF FENTANYL IN THE ELDERLY

The pharmacokinetics of fentanyl were determined in seven elderly(71–82 yr) and seven younger adults (18–41 yr) anaesthetizedwith thiopentone, nitrous oxide in oxygen and morphine. Fentanylwas administered as a 2-min i.v. infusion at doses of 15 µgkg^–1 for elderly patients and 20 µg kg^–1 forthe younger patients. Plasma samples were obtained for 4 h andfentanyl concentrations determined by radio-immunoassay. Fentanylconcentration, per µg kg^–1 administered, was higherin elderly than in young patients at 2 min (7.73±3.14v. 4.54 ± 1.83 ng ml^–1 (mean±SD), respectively)and at 4 min after the start of infusion (3.26 ± 1.44v. 1.78 ±0.72 ng ml^–1, respectively). Concentrationswere similar at all other sampling times. Pharmacokinetic variableswere determined by non-compartmental techniques. Total plasmaclearance was similar for the two age groups. Volume of distributionat steady-state (VD^ss) was smaller in elderly patients (1.36± 0.44 v. 2.27 ± 0.82 litre kg ^–1). Despiteage-related changes in VD^ss, plasma fentanyl concentrationsfor the two groups were similar throughout the 4-h samplingperiod except immediately following administration. These resultssuggest that, if there are age-related differences in responseto fentanyl, the likely pharmacokinetic explanation is the higherconcentration of fentanyl in the elderly immediately followingits administration.     

EFFECT OF THIOPENTONE, ETOMIDATE AND PROPOFOL ON SYSTEMIC VASCULAR RESISTANCE DURING CARDIOPULMONARY BYPASS

We have studied the effect of thiopentone, etomidate and propofolon systemic vascular resistance (SVR) during cardiopulmonarybypass with constant pump flow in 30 patients undergoing electivecoronary artery bypass surgery. SVR decreased to 78% of controlvalues after thiopentone 4 mg kg^–1, to 72% of controlafter etomidate 0.3 mg kg^–1, and to 68% of control afterpropofol 2 mg kg^–1; it returned to control values 10 minafter administration of thiopentone and propofol and 7 min afteradministration of etomidate. Analysis of variance showed thatthere were no significant differences in the changes in SVRbetween the groups.     

EFFECTS OF ALFENTANIL AND FENTANYL ON INDUCTION OF ANAESTHESIA IN PATIENTS WITH SEVERE PREGNANCY-INDUCED HYPERTENSION

Forty patients with severe pregnancy-induced hypertension presentingfor Caesarean section under general anaesthesia were allocatedrandomly to receive either fentanyl 2.5 µg kg^–1or alfentanil 10 µg kg^–1 as part of the anaestheticinduction sequence. In all patients, the cardiovascular responseto tracheal intubation was measured. Both drugs attenuated theresponse equally but did not abolish it in all patients. Alfentanil10 µg kg^–1 is a suitable alternative to fentanyl2.5 µg kg^–1 for patients with pregnancy-inducedhypertension.     

FENTANYL BY CONSTANT RATE I.V. INFUSION FOR POSTOPERATIVE ANALGESIA

Fentanyl by continuous i.v. infusion (1.5 µg kg^–1min^–1 or 0.5 µg kg^–1 min^–1) was comparedwith placebo infusion as an analgesic regimen for 24 h afterhysterectomy. The drugs were infused using a new disposabledevice which required no external power source. All patientswere allowed morphine i.m. if they experienced pain. Patientsin the higher dose fentanyl group demanded less i.m. morphineand had better pain relief after operation, without importantrespiratory depression. ^* Present address: University Department of Anaesthesia, MedicalSchool, Beech Hill Road, Sheffield S10 2RX.     

EFFECT OF INDUCTION OF ANAESTHESIA WITH ETOMIDATE ON CORTICOSTEROID SYNTHESIS IN MAN

The effects of a single bolus dose of etomidate 0.3 mg kg^–or thiopentone 5 mg kg^– on the synthesis of corticosteroidhormones and adrenocorticotrophic hormone (ACTH), were comparedfor 24 h in 12 patients, undergoing minor surgery under generalanaesthesia. Following opioid premedication i.m. and generalanaesthesia, plasma cortisoi concentrations decreased transientlywithin the first hour of anaesthesia in all 12 patients. Thesix patients who received etomidate had statistically higherplasma 11-deoxycorticosterone concentrations at 4 and 24 h thanthose who had received thiopentone (P < 0.01). Throughoutthe study, no difference in plasma cortisoi, corticosteroneor ACTH concentrations were found between the two groups. Wehave demonstrated a biochemical effect of a single bolus doseof etomidate consistent with incomplete inhibition of adrenocorticalmitochondrial 11 ß-hydroxylase activity, but no clinicallysignificant adrenocortical suppression. ^*Present address: Department of Anaesthesia, Sheffield UniversityMedical School, Beech Hill Road, Sheffield S10 2RX.     

PREMEDICATION DETERMINES THE CIRCULATORY RESPONSES TO RAPID SEQUENCE INDUCTION WITH SUFENTANIL FOR CARDIAC SURGERY

Thirty-three patients undergoing elective aortocoronary bypasswere allocated randomly to receive morphine 0.1 mg kg^–1i.m. and either lorazepam 50 µg kg^–1 by mouth orhyoscine 6 µg kg^–1 i.m. before rapid sequence inductionof anaesthesia with sufentanil 5 µg kg^–1 i.v. andsuxamethonium 1 mg kg^–1 i.v. Following induction and trachealintubation, patients premedicated with hyoscine had a significantlyhigher mean heart rate, mean arterial pressure, cardiac indexand left ventricular stroke-work index than patients premedicatedwith lorazepam. The incidence of new myocardial ischaemia waslow in both groups.     

COMPARISON OF CUMULATIVE AND SINGLE BOLUS DOSE TECHNIQUES FOR DETERMINING THE POTENCY OF VECURONIUM

The potency of vecuronium was determined using single bolusdose administrations of 10–50 µg kg^–1in 28patients anaesthetized with thiopentone, nitrous oxide, oxygenand fentanyl. The results were compared with those previouslyobtained using a cumulative dose technique in a comparable groupof 10 patients. The 50% and 95% blocking doses (ED₅₀and ED₉₅)of vecuronium were found to be 23.1 and 39.6 µg kg^–1,respectively. These were significantly lower than the 30.5 and56.7µg kg^–1 obtained previously using the cumulativedose technique. We recommend the use of single bolus dose methodof determining potency for relatively shorter-acting drugs likevecuronium.     

PREVENTION OF HISTAMINE-INDUCED CARDIOVASCULAR REACTIONS DURING THE INDUCTION OF ANESTHESIA FOLLOWING PREMEDICATION WITH H1- + H2-ANTAGONISTS I. M.

In a prospective controlled double-blind study, 60 electivesurgical patients were randomly assigned to three premedicationgroups. Twenty patients received promethazine 0. 5 mg kg^–1i.m. 45 min before induction of anaesthesia; a further 20 patientsreceived an additional i. m. injection of cimetidine 400 mg120 min before induction. The third group (n = 20) served asthe control group. Following vecuronium 0.02 mg kg^–1,anaesthesia was induced with fentanyl, and etomidate. All patientsthen received suxamethonium 1.5 mg kg^–1 i. v. The combinedadministration of H₁- + H₂-antagonists as premedication ledto a significant reduction in the increase in heart rate whencompared with the effects in the other groups.     

INTERACTION OF KETAMINE WITH ATRACURIUM

The effect of ketamine on the duration of atracurium-inducedneuromuscular blockade was studied in 40 healthy patients anaesthetizedwith midazolam, fentanyl and nitrous oxide. Twenty received,in addition, i.v. ketamine 2 mg kg^–1 followed by an infusionof 2 mg kg^–1 h^–1. Atracurium 0.5 mg kg^–1 wasinjected i.v. and the time to 25% recovery of the twitch heightwas measured. It was 8.0 min longer in the ketamine group (P< 0.005), with a 95% confidence interval of from 2.3 to 11.8min.     

CARDIAC EFFECTS OF ATROPINE AND GALLAMINE IN PATIENTS RECEIVING SUXAMETHONIUM

Eighty healthy patients were randomly allocated to four groups.Atropine 0.01 mg kg^–1 i.v. (group I), gallamine 0.3 mgkg^–1 i.v. (group II), atropine 0.01 mg kg^–1 i.m.and gallamine 0.3 mg kg^–1 i.v. (group III), or atropine0.01 mg kg^–1 i.v. and gallamine 0.3 mg Lrg^–1 i.v.(group IV) were given before operation. After induction of anaesthesiawith thiopentone, suxamethonium 1 mg kg^–1 was given i.v.The lungs were ventilated with halothane in nitrus oxide inoxygen. Five minutes later the same dose of suxamrthonium wasrepeated. E.c.g. was monitored continuously. No serious bradycardiawas observed following a second injection of suxamethonium inany group. The results suggest that thiopentone protects againstsuxamethonium-induced bradycardia during halothane anaesthesia.     

SITE OF ACTION OF FENTANYL IN INHIBITING THE PITUITARY-ADRENAL RESPONSE TO SURGERY IN MAN

To determine the site of action of fentanyl in attenuating thepituitary—adrenal response to surgery, we have measuredserum concentrations of cortisol and growth hormone during andafter a standardized surgical procedure in two groups of patients.One group received fentanyl 15µg kg^–1 i.v. immediatelybefore the start of surgery; a second group received fentanyl15 µg kg^–1 i.v. together with corticotrophin releasingfactor 100 µg i.v., growth hormone releasing hormone 100µgi. v. and arginine vasopressin 10 units i.m. The concomitantadministration of the releasing factors with the opioid resultedin a significantly greater serum concentration of cortisol 30,60, 120 and 240 min after surgery commenced, compared with thegroup which received fentanyl alone. Similarly, the growth hormoneresponse in the combined group was significantly greater thanin the fentanyl-alone group 30 min after the start of surgery.We conclude that the inhibitory effect of fentanyl on surgically-inducedsecretion of pituitary hormone was mediated directly or indirectlyvia the hypothalamus.     

HAEMODYNAMIC EFFECTS OF VECURONIUM, PANCURONIUM AND ATRACURIUM IN PATIENTS WITH CORONARY ARTERY DISEASE

Thirty patients with ischaemic heart disease scheduled for coronaryartery bypass grafting were randomly allocated to three equalgroups. Following morphine, hyoscine and pentobarbi-tone premedication,anaesthesia was induced with diazepam 0.3 mg kg¹. Five minuteslater neuromuscular blockade was induced with pancuronium 0.1mg kg¹, vecuronium 0.1 mg^–1 or atracurium 0.5 mg kg^–1,followed after 6 min by fentanyl 25 µg kg^–1. Pancuroniumand atracurium caused significant increases in heart rate, whilevecuronium induced little change. Systemic vascular resistancedecreased significantly from 1515 dyn s cm^–6 to 1200 dyns cm^–5 following atracurium. Cardiac index was increasedtransiently in the atracurium group, but a more sustained increasewas observed following pancuronium. Nine patients in the atracuriumgroup showed skin flushing and one developed skin weals.     

DEXMEDETOMIDINE ATTENUATES SYMPATHOADRENAL RESPONSES TO TRACHEAL INTUBATION AND REDUCES THE NEED FOR THIOPENTONE AND PEROPERATIVE FENTANYL

The effects of the new, highly selective alpha₂-adrenergic agonist,dexmedetomidine, were studied in a randomized, placebo-controlled,double-blind trial in 24 ASA I patients. Dexmedetomidine 0.6µg kg^–1 or saline was given i.v. 10 min before inductionof anaesthesia. The required dose of thiopentone was significantly(P < 0.001) smaller in the dexmedetomidine group (mean 4.4(SD 0.9) mg kg^–1) than in the control group (6.9 (1.6)mg kg^–1), and the drug attenuated the cardiovascular responsesto laryngoscopy and tracheal intubation. The concentration ofnoradrenaline in mixed venous plasma was smaller in the dexmedetomidinegroup during all phases of induction (P < 0.01). During surgery,fentanyl was required in a dose of 0.5 (0.6) mg kg^–1 and2.8(2.6) mg kg^–1 in the dexmedetomidine and control groups,respectively (P < 0.001). During 2h postoperative follow-up,oxycodone 0.06 (0.06) mg kg^–1 and 0.16 (0.1) mg kg^–1(P < 0.05) was given to the two groups respectively.     

Postoperative extradural analgesia in children: comparison of morphine with fentanyl

We have compared the efficacy and side effects of extraduralmorphine with extradural fentanyl for postoperative pain relief.Thirty children (ages 1–16 yr) were allocated randomlyto receive, after extradural administration of 0.5% bupivacaine0.75 ml kg^–1 and before surgical incision, extreduralmorphine 0.75 µg kg^–1 (group M), with an additionaldose administered 24 h later or extradural fentanyl 2 µgkg^–1 (group F) followed by a continuous extradural infusion(during 48 h). There was no major complication (respiratorydepression). Pain scores were satisfactory in both groups for48 h. Ventilatory frequency was greater in group M 20, 21, 22,23 and 25 h after the beginning of analgesia (P < 0.05).Pruritus, nausea and vomiting were less common with extraduralfentanyl (20% vs 53%, P < 0.05 and 0% vs 33%, P < 0.05)than with morphine. Urinary retention occurred with equal frequency(25%) in the two groups. After a bolus of 2 µg kg^–1,continuous extradural infusion of fentanyl 5 µg kg^–1day^–1 provided analgesia comparable to that from a dailybolus of extradural morphine 0.75 mg kg^–1 and producedfewer side effects.      

EFFECTS OF FENTANYL-DIAZEPAM-NITRIOUS OXIDE ANAESTHESIA ON ARTERIAL BAROREFLEX CONTROL OF HEART RATE IN MAN

The effects of fentanyl 7.5 µg kg^–l (group I), 10.0µg kg^–1 (group Il) and 12.5 µg kg^–1(group lll) with diazepam 0.25 mg kg^–l and 70% nitrousoxide on baroreflex control of heart rate in humans were investigated.Phenylephrine (the pressor test), sodium nitroprusside (thedepressor test) and graded neck suction provoked baroreflexresponses. In group I the pressor, depressor and neck suctionbaroreflex slopes decreased during anaesthesia. In groups IIand III the depressor test slopes were also decreased duringanaesthesia. However, the slopes derived from the pressor andneck suction tests did not decrease. These data suggest thatbaroreflex control of heart rate is attenuated during low dosesof fentanyl (7.5 µg kg^–1). Baroreflex mediated tachycardiais decreased by higher doses of fentanyl (10.0 and 12.5 µgkg^–1). However, baroreflex-mediated bradycardia is maintainedduring the higher doses of fentanyl. We suggest this effectis the result of enhanced vagal efferent activity mediated byfentanyl.     

METHOHEXITONE ANAESTHESIA FOR MICROLARYNGOSCOPY: CIRCULATORY MODULATION WITH METROPROLOL AND DIHYDRALAZINE

Anaesthesia for microlaryngoscopy was induced and maintainedwith fentanyl 3 µg kg^– and methohexitone (initialbolus of 1–1.5 mg-kg^–1 plus subsequent infusionof 4 mg kg^–1 h^–1). Suxamethonium was used to induceneuro-muscular blockade. Twenty minutes before induction ofanaesthesia, previously normotensive patients (n = 35), andpatients with hypertension well controlled by beta-receptorantagonists (n = 16) were pretreated with metoprolol (M) 0.2mg kg^–1i.v. and dihydralazine (DH) 0.2 mg kg^–1i.v.,dihydralazine 0.2 mg kg^–1 i.v. alone, or saline. Arterialpressure (AP) and heart rate (HR) were monitored: any arrhythmiaand ST₆₀T changes were noted. After the methohexitone infusionwas stopped, the times for emergence and full recovery wereshort (median 2 min 15s and 5 min later, respectively). Pretreatmentwith M+DH abolished increases in AP and HR during endoscopy.Arrhythmias were observed in fewer pretreated patients thanin controls (P < 0.05). ST₆₀-Tchanges in the ECG indicatingmyocardial ischaemia were found in two of 19 M+DH and in sixof 21 saline-pretreated patients. One of these six patientsdeveloped a myocardial infarction. Pretreatment with dihydralazinealone attenuated the pressor response to microlaryngoscopy,but was associated with consistently high HR and an incidenceof arrhythmias as well as ST₆₀T changes similar to that foundafter saline.     

Comparison of intravenous and oral ketoprofen for postoperative pain after adenoidectomy in children

One hundred children, aged 1–9 yr, undergoing adenoidectomywere randomized to receive ketoprofen 1 mg kg^–1either i.v. with an oral placebo (n=40) or ketoprofen 1 mg kg^–1orally with an i.v. placebo (n=40), or both oral and i.v. placebo(n=20). The study design was prospective and double blind withparallel groups. The pain was assessed at rest and during swallowingusing the Maunuksela pain scale (0=no pain, 10=worst possiblepain) after surgery for 3 h. Fentanyl 0.5 µg kg^–1i.v. was given for rescue analgesia. Children in the i.v. groupneeded significantly less doses (1, 1–3; median and 10th/90thpercentiles) of rescue analgesic compared with the oral group(2, 1–3; P=0.024). Of those who needed rescue analgesic,three out of 30 children in the i.v. group required three ormore doses of fentanyl compared with 10 out of 28 children inthe oral group. There were no differences between the groupswith respect to pain scores, operation times, perioperativebleeding or frequency of adverse events. Br J Anaesth 2000; 85: 224–7 ^* Corresponding author