PATIENT-CONTROLLED ANALGESIA WITH LOW DOSE BACKGROUND INFUSIONS AFTER LOWER ABDOMINAL SURGERY IN CHILDREN

Forty-five children (aged 6–12 yr) undergoing appendicectomyreceived one of three analgesic regimens using patient-controlledanalgesia (PCA) with morphine: no background infusion (BO);background infusion 4 µg kg^–1 h^–1 (B4); backgroundinfusion 10 µh^–1 h^–1 (B10). Total consumptionof morphine was greater in group B10 compared with groups BO(P<0.01) and B4 (P<0.05). There was no significant differencein morphine consumption in groups BO and B4. All three groupsself-administered similar amounts of morphine and there wereno significant differences in pain scores or incidence of excessivesedation. Group B4 suffered less hypoxaemia compared with groupsBO (P<0.01) and B10 (P<0.001). Group B10 suffered morenausea and vomiting than groups BO (P<0.001) and B4 (P<0.001),but there was no significant difference in the incidence ofnausea and vomiting between groups BO and B4. Groups B4 andB10 spent more time at night asleep than group BO (P<0.05).There were no significant differences between the groups inthe amount of time spent asleep during the day. Inclusion ofa background infusion of morphine 4 µg kg^–1 h^–1in a PCA regimen for children did not increase the incidenceof side effects and was associated with less hypoxaemia anda better sleep pattern than no background infusion. (Br. J.Anaesth. 1993; 71: 818–822)     

Haemodynamic effects of the lateral decubitus position and the kidney rest lateral decubitus position during anaesthesia

We measured the haemodynamic effects of changing from the supineposition to the lateral decubitus (lateral) position, and thento the kidney rest lateral decubitus (kidney) position in 12patients undergoing nephrectomy under isoflurane anaesthesia.Eight control patients undergoing pulmonary surgery remainedin the lateral position. The lateral position produced no significantchanges. In the kidney position, however, significant reductionsoccurred in the mean arterial (P<0.01), right atrial (P<0.05)and pulmonary artery wedge pressures (P<0.01). There werealso significant reductions in cardiac index (from 3.04 ( 0.21) to 2.44 (0.26) litre min^–1 m^–2,P<0.01) and stroke volume index (from 40 (5) to 31 (5) mlbeat^–1 m^–2, P<0.01). The systemic vascular resistanceindex increased significantly (P<0.05). Cardiac output wasprobably reduced by a decrease in venous return and an increasein systemic vascular resistance.     

CLINICAL AND HAEMODYNAMIC EFFECTS OF MILRINONE IN THE TREATMENT OF LOW CARDIAC OUTPUT AFTER CARDIAC SURGERY

We have studied the haemodynamic effects of i.v. milrinone.a newphosphodiesterase inhibitor, in patients with low cardiacoutput after cardiac surgery. Thirty-five patients with a cardiacindex (Cl) < 2.5 litre min^–1 m^–2 and a pulmonarycapillary wedge pressure (PCWP) > 8 mm Hg were given a loadingdose of milrinone 50 µg kg^–1 followed by an infusionat one of three rates: 0.375 fig kg^–1 min^–1, 0.5fig kg^–1 min^–1 or 0.75 µg kg^–1 min^–1for 12 h. After 1 h there were increases in Cl (35%) (P<0.001), heart rate (13%) (P< 0.01) and stroke volume index(19%) (P< 0.005). There were decreases in mean arterial pressure(12%) (P< 0.01), systemic vascular resistance (35%) (P<0.001) and PCWP (24%) (P< 0.05). Pulmonary vascular resistancewas unchanged or reduced and left ventricular stroke work indexwas unchanged or increased. The haemodynamic improvements weresustained throughout the infusion period. Milrinone was toleratedwell: three patients developed tachycardia > 125 beat min^–1,one patient developed atrial fibrillation and one patient hada short run of atrial bigemini. We conclude that milrinone isa useful agent in the treatment of patients with a reduced cardiacoutput after cardiac surgery.     

Infusion of amino acid enriched solution hastens recovery from neuromuscular block caused by vecuronium

We investigated the effect of an amino acid infusion on neuromuscularblock produced by vecuronium, and on rectal temperature andsurface temperature over the adductor pollicis muscle. Sixtyadult patients undergoing general anaesthesia were randomlydivided into four groups of 15 patients each: amino acid (AA)-post-tetaniccount (PTC); AA-train-of-four (TOF); control (C)-PTC; or C-TOFgroup. In the AA-PTC and AA-TOF groups, after a bolus of vecuronium0.1 mg kg^–1, a continuous infusion of an 18 amino acidenriched solution (AMIPAREN^®) was started at a rate of 166kJ h^–1. In the C-PTC and C-TOF groups, normal saline wasadministered. Time from vecuronium to the return of the PTCin the AA-PTC group was significantly shorter than in the C-PTCgroup (mean (SD), 13.3 (4.5) versus 18.0 (5.6) min, P<0.05).Times to return of T1, T2, T3, and T4 (first, second, third,and fourth twitch of TOF) in the AA-TOF group were significantlyshorter than in the C-TOF group (21.1 (4.5) versus 28.0 (8.2)min for T1, P<0.05). PTC in the AA-PTC group was significantlygreater than in the C-PTC group; 25–35 min after administrationof vecuronium (P<0.05). T1/T0 and T4/T1 in the AA-TOF groupwere significantly higher than in the C-TOF group, 40–120and 50–120 min after vecuronium respectively (P<0.05).Rectal temperature and surface temperature over the adductorpollicis muscle in the AA-PTC and AA-TOF groups were significantlyhigher than in the control groups 50–120 and 100–120min after vecuronium respectively (P<0.05). Infusion of aminoacid enriched solution hastens recovery from neuromuscular block. Br J Anaesth 2001; 86: 814–21     

Dietary Fish Oil Supplements Preserve Renal Function in Renal Transplant Recipients with Chronic Vascular Rejection

The effect of dietary fish oil supplements on renal failureand lipid abnormalities was studied in 14 adult renal transplantrecipients with chronic vascular rejection. The rate of declineof renal function (assessed by studying the slope of reciprocalplasma creatinine plots) slowed significantly during a 6-monthperiod on fish oil supplements compared with the preceding 6-monthcontrol period (slope 1/cr during supplementation –3.6x 10^–5 µmol/l per month compared with –13.5x 10^–5 before, the difference in slope being –9.8x 10^–5, 95% confidence interval (CI) –16.2 x 10^–5,–3.5 x 10^–5, P<0.05). Total plasma triglycerideconcentrations decreased during supplementation (mean change–1.15 mmol/l, 95% CI –1.84, –0.47, P<0.003),but there was no change in total plasma cholesterol concentrationor urinary protein excretion. Platelet function was studiedin nine patients. Platelet aggregation induced by adrenalineand collagen was reduced by fish oils (median change in percent aggregation), adrenaline 2 µmol/ –36% (95%CI –68%, –8%, P<0.05), collagen 1 mg/l, –13%(95% CI –44%, –2%, P<0.05). Platelet thromboxaneA₂ release in response to these agents was also significantlyreduced. These results demonstrate that fish oils preserve residualfunction in renal graft failure due to chronic vascular rejection.     

Effects of cyclosporin A withdrawal on renal function and renal stimulation in liver transplant patients treated with triple-drug immunosuppression for over 2 years

The influence of CsA withdrawal on the glomerular filtrationrate (GFR) and the effective renal plasma flow (ERPF) was prospectivelystudied in nine stable liver transplant recipients. Before CsAwithdrawal (test 1), and 6 months thereafter (test 2) the renalfunction was determined by measuring GFR and the ERPF with ¹²⁵I-iothalamateand ¹³¹I-hippuran respectively. The renal function was alsostimulated with dopamine, with an amino-acid infusion and acombination of both. After CsA withdrawal the GFR increased,median from 74 ml min^–1 to 90 ml min^–1, (P<0.04).The ERPF also increased, median from 310 ml min^–1 to 380ml min^–1, (P<0.03). In test 1 as well as in test 2the renal function could be stimulated, especially with dopamine.GFR and ERPF improved, even after more than 2 years of CsA treatment.These results suggest that long-term CsA treatment impairs therenal function, though in these liver transplant patients CsAtreatment did not prevent afferent and efferent arteriolar vasodilatationafter renal stimulation. This reversible intrarenal vasoconstrictionduring CsA treatment may predict renal improvement after CsAwithdrawal.     

PHARMACOKINETICS OF ATRACURIUM AND LAUDANOSINE IN PATIENTS WITH HEPATIC CIRRHOSIS

The pharmacokinetic profiles of atracurium and one of its derivatives,laudanosine were studied following an i.v. bolus of atracurium0.6 mg kg^–1 administered to eight patients with hepaticcirrhosis and to seven healthy controls. The central volumeof distribution of atracurium was greater in the patients withcirrhosis (104.6 ml kg^–1) compared with the controls (69.6ml kg^–1) (P < 0.05), as was the total volume of distribution(281.8 ml kg^–1 and 202.1 ml kg^–1, respectively)(P < 0.05). There was no significant difference in the eliminationhalf-life of atracurium between the two groups. The total volumeof distribution of laudanosine was increased in cirrhotic patients(2.68 litre kg^–1) compared with healthy controls (1.97litre kg^–1) (P < 0.05), as was its elimination half-life(277 min in cirrhotic individuals; 168 min in controls) (P <0.05). There was no significant difference in the clearanceof laudanosine between the two groups.     

Renal tubular responses to low-dose infusion of angiotensin II in type 1 diabetes mellitus; relation to chronic glycaemic control

Renal responses to low-dose infusion of angiotensin II (ANGII,1.25 and 2.5 ng.kg^–1 min^–1) were examined in 15patients with type 1 diabetes and in 10 control subjects afterpretreatment with lithium carbonate (750 mg, 20 mmol). Meanarterial pressure rose during ANGII infusion in both groups.The renal haemodynamic response to angiotensin II was not abnormalin the diabetic patients. Absolute proximal reabsorption ofsodium was increased at baseline in the diabetic group, andfell during ANGII. Fractional lithium excretion was reducedin the diabetic patients at baseline (P<0.05), and the fallin fractional lithium excretion during ANGII was less than inthe control group (P=0.012). In the diabetic group correlationsexisted between glycated haemoglobin and baseline glomerularfiltration rate (P<0.05), baseline fractional lithium excretion(P=0.03), and the fall in fractional lithium excretion duringangiotensin II infusion (P=0.013). There was no correlationbetween glycated haemoglobin and absolute lithium clearance.Some indices of sodium reabsorption by the proximal renal tubulein diabetic patients correlate with prevailing chronic glycaemiccontrol, largely reflecting changes in glomerular filtrationrate. Reduced fractional proximal tubular responsiveness toexogenous angiotensin II is consistent with a role for endogenousangiotensin II as one mediator of increased tubular reabsorptionof sodium in type I diabetes, but the data does not excludealternative mechanisms.     

NON-INVASIVE MEASUREMENT OF CARDIAC OUTPUT DURING INDUCTION OF ANAESTHESIA AND TRACHEAL INTUBATION: THIOPENTONE AND PROPOFOL COMPARED

We have investigated the haemodynamic changes in response toinduction of anaesthesia and tracheal intubation in patientswho received either thiopentone 5 mg kg^–1 or propofol3 mg kg^–1 followed by atracurium 0.5 mg kg^–1 andfentanyl 1.5 µg kg^–1. Anaesthesia was maintainedwith 0.6% enflurane and 50% nitrous oxide in oxygen with assistedventilation. Cardiac output and heart rate (HR) were monitoredcontinuously with a transthoracic impedence monitor. Mean HRdid not change after induction in each group, but increasedafter tracheal intubation in both groups (P < 0.01). Meancardiac index (CI) decreased after induction (P < 0.05) anddecreased further after tracheal intubation in both groups (P< 0.05). There was no difference between the two groups withrespect to changes in CI and HR. Mean arterial pressure (MAP)and systemic vascular resistance (SVR) did not change significantlyafter induction in the thiopentone group. Both variables increasedfrom preinduction values 1 min after tracheal intubation (P< 0.001). In contrast, both MAP and SVR decreased after inductionin the propofol group (P < 0.001) and did not differ frompreinduction values 1 min after tracheal intubation. MAP andSVR were greater in the thiopentone group compared with thepropofol group after induction and tracheal intubation (P <0.01).     

Borderline hypertensive autosomal dominant polycystic kidney disease patients have enhanced production of renal dopamine. Normalization of renal haemodynamics by DOPA infusion

BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD) thepathophysiology of hypertension, which is frequently observedbefore loss of renal function, is not well understood. We investigatedintrarenal dopamine, the renin-angiotensi n-aldosterone system(RAAS), and plasma endothelin in relation to sodium homeostasisas potential hypertensive factors in this disease. METHOD: Eight borderline hypertensive ADPKD patients with (near) normalrenal function and seven matched healthy control subjects wereinvestigated at three levels of daily dietary sodium intake:150, 50 and 450 mmol. In the 450-mmol sodium intake period westudied the effects of renally formed dopamine by infusing itsprecursor DOPA (DOPA_i.v., 7 µg kg^–1 min^–1).In the 50-mmol sodium intake period we studied the influenceof the RAAS by administering enalaprilate (42 µg kg^–1followed by angiotensin II (12 ng kg^–1 min^–1) intravenously.GFR and ERPF were measured by continuous infusion of inulinand PAH. RESULTS: At all levels of sodium intake sodium balances were equal, butdaily urinary excretions of dopa mine and DOPA were higher (P<0.01)in the ADPKD patients than in the controls. Renal vascular resistance,filtration fraction and blood pressure were higher in the ADPKDpatients (all P<0.05) while plasma renin activity was similar.DOPA^i.v. normalized renal haemodynamics and increased plasmaendothelin in ADPKD patients (all P<0.05), while stimulationof natriuresis was equal in both groups. Enalaprilate increasedplasma endothelin in the ADPKD patients and only partially normalizedrenal haemodynamics. CONCLUSION: In borderline hypertensive ADPKD patients: (1) urinary dopamineexcretion is increased at all levels of sodium intake, suggestingthat this may be needed to maintain sodium balance; (2) stimulationof renal dopamine production is able to normalize renal haemodynamics,making dopamine receptor agonism a potential therapeutic option;(3) the activity of the RAAS is not clearly enhanced; (4) renalvasodilatation increases plasma endothelin levels.     

PHARMACOKINETICS OF GLYCOPYRRONIUM IN URAEMIC PATIENTS

We studied the pharmacokinetics of glycopyrronium 11 uraemicpatients undergoing cadaveric renal transplantation and in sevenASA I control patients undergoing general surgery. Glycopyrronium4 µg kg^–1 was given i.v. before induction of anaesthesia.Blood and urine samples were collected for up to 24 h for measurementof glycopyrronium concentrations using a radioreceptor assay.Volume of distribution in the elimination phase (V^ß)was similar in both groups, the elimination half-life was longer (P <0.05), area underthe plasma concentration-time curve (AUC) larger (P <0.01)and plasma clearance (Cl) smaller (P < 0.01) in the uraemicpatients. In 3 h, mean 0.7 (range 0–3) % and 50 (21–82)% of glycopyrronium was excreted in the urine in the uraemicand healthy patients, respectively (P <0.001). The 24-h renalexcretion was 7 (0–25) % in uraernic and 65 (30–99)% in control patients (P <0.001). We conclude that the eliminationof glycopyrronium is severely impaired in uraemic patients.     

METABOLIC CHANGES DURING DOPAMINE INFUSION IN DOGS

The effects were investigated, in 12 dogs, of the infusion ofdopamine 10 or 30 µg kg^–1 min^–1 on circulatingglucose, glycerol, lactate and potassium concentrations. Bothdoses of dopamine produced an initial increase in blood glucoseconcentration (P < 0.05) followed by hypoglycaemia (P<0.05).Lipolysis was stimulated as shown by an increase in plasma glycerolconcentrations with dopamine 10 µg kg^–1 min^–1(P<0.05) and dopamine 30 µg kg^–1 min^–1(P<0.01). Blood lactate concentrations increased slightlyin both groups, but this was significant (P < 0.05) onlyin the dogs infused with dopamine 10 µg kg^–1min^–1.Dopamine had no significant effect on the plasma potassium concentration.     

Effects of remifentanil and alfentanil on the cardiovascular responses to induction of anaesthesia and tracheal intubation in the elderly

Background. We compared the effects of remifentanil and alfentanilon arterial pressure and heart rate at induction of anaesthesiaand tracheal intubation in 40 ASA I–III patients agedgreater than 65 yr, in a randomized double-blind study. Methods. Patients received either remifentanil 0.5 µgkg^–1 over 30 s, followed by an infusion of 0.1 µgkg min^–1 (group R) or alfentanil 10 µg kg^–1over 30 s, followed by an infusion of saline (group A). Anaesthesiawas then induced with propofol, rocuronium, and 1% isofluranewith 66% nitrous oxide in oxygen. Results. Systolic arterial pressure (SAP) and mean arterialpressure (MAP) decreased after the induction of anaesthesia(P<0.05) and increased for 3 min after intubation in bothgroups (P<0.05), but remained below baseline values throughout.Heart rate remained stable after induction of anaesthesia butincreased significantly from baseline after intubation for 1and 4 min in groups R and A, respectively (P<0.05). Therewere no significant between-group differences in SAP, MAP, andheart rate. Diastolic pressure was significantly higher in groupA than group R at 4 and 5 min after intubation (P<0.05).Hypotension (SAP <100 mm Hg) occurred in four patients ingroup R and three patients in group A. Conclusions. Remifentanil and alfentanil similarly attenuatethe pressor response to laryngoscopy and intubation, but theincidence of hypotension confirms that both drugs should beused with caution in elderly patients. Br J Anaesth 2002; 88: 430–3     

Evaluation of effects of magnesium sulphate in reducing intraoperative anaesthetic requirements

Background. The present randomized, placebo-controlled, double-blindstudy was designed to assess the effect of peroperatively administeredi.v. magnesium sulphate on anaesthetic and analgesic requirementsduring total i.v. anaesthesia. Methods. Eighty-one patients (36 women, 45 men) undergoing electivespinal surgery were included in one of two parallel groups.The magnesium group received magnesium sulphate 30 mg kg^–1as a bolus before induction of anaesthesia and 10 mg kg^–1h^–1 by continuous i.v. infusion during the operation period.The same volume of isotonic solution was administered to thecontrol group. Anaesthesia was maintained with propofol (administeredaccording to the bispectral index) and remifentanil (adjustedaccording to heart rate and arterial blood pressure) infusions. Results. A significant reduction in hourly propofol consumptionwas observed with magnesium administration. For example, themean infusion rate of propofol in the second hour of the operationwas 7.09 mg kg^–1 h^–1 in the controlgroup vs 4.35 mg kg^–1 h^–1 in themagnesium group (P<0.001). The magnesium group required significantlyless remifentanil (P<0.001) and vecuronium (P<0.001).No side-effects were observed with magnesium administration. Conclusion. The administration of magnesium led to a significantreduction in the requirements for anaesthetic drugs during totali.v. anaesthesia with propofol, remifentanil and vecuronium. Br J Anaesth 2002; 89: 594–8     

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.      

USE OF ATRACURIUM IN CARDIAC SURGERY INVOLVING CARDIOPULMONARY BYPASS WITH INDUCED HYPOTHERMIA

Atracurium was administered by infusion to 12 anaesthetizedpatients undergoing cardiac surgery with cardiopulmonary bypassand induced hypothermia. Following an initial bolus dose of0.6 mg kg^–1, an infusion of atracurium was continued atan average rate of 0.0066±0.0003 mg kg^–1 min^–1(0.4 mg kg^–1 h^–1) which was sufficient to maintain90–95% block of the single twitch or train-of-four responsesbefore bypass. Adequate surgical arinn was provided with approximatlyhalf the rate of infusion of 0.0034±0.0003 mg kg^–1min^–1 (0.2 mg kg^–1h^–1) during cardiopulmonarybypass with included hypothermia (25–26°C for 70–166min.This rate of infmnon during hypothermia was significantly slower(P<0.001) than that during normothermia. Thus, atracuriumappeared to be suitable for use by continuous infininn in cardiacsurgery and the temperature-dependent inactivatkm of atracuriumwas used to advantage because less drug was required duringinduced hypothermia     

Prevention of postoperative nausea and vomiting by continuous infusion of subhypnotic propofol in female patients receiving intravenous patient-controlled analgesia

In this prospective, randomized, double-blind, placebo-controlledstudy, the use of continuous subhypnotic propofol infusion asan antiemetic in fentanyl intravenous patient-controlled analgesia(i.v. PCA) was investigated during the first 24 h after surgery.One hundred female patients, ASA I–II, aged 20–71yr, undergoing major gynaecological or orthopaedic surgery,were included. Either propofol 10 mg or placebo (1 ml of Intralipid)was given and one of the following five regimens was maintainedfor 24 h: propofol 5, 10, 15 or 20 µg kg^–1 min^–1or Intralipid 1 ml h^–1 as a placebo. Fentanyl i.v. PCAwas started in the postanaesthesia care unit for postoperativeanalgesia. Significantly more of the patients given propofol15 and 20 µg kg^–1 min^–1 experienced no nauseaor vomiting compared with those given placebo (65% and 70% versus25%; P<0.05). Patients given propofol 20 µg kg^–1min^–1 reported more sedation than those in the other groups4 h after surgery (P<0.05). Br J Anaesth 2000; 85: 898–900     

INFLUENCE OF CROHN'S DISEASE ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF ALFENTANIL

We have compared the dose requirements, pharma cokinetics andpharmacodynamics of alfentanil in 12 patients with Crohn's diseaseand 10 control patients undergoing abdominal surgery. Plasmaconcentrations of ₁-acid glycoprotein (AAG) and alfentanil proteinbinding were also measured. Anaesthesia was induced with aifentanil100 µg kg^–1 and thiopentone, and maintained withnitrous oxide in oxygen and aifentanil 25–200 µgkg^–1 h^–1 Arterial blood samples were obtained beforeand after each change in the aifentanil infusion rate and for6 h after stopping the infusion. Pharmacokinetic data were derivedusing non-compartmental methods. Alfentanil concen tration—effectdata were evaluated by non-linear regression, where effect waseither response or no response to surgical stimulation. Meanintra operative aifentanil requirement was greater in patientswith Crohn's disease (2.48 µg kg^–1 min^–1)than in control patients (1.35 µg kg^–1 min^–1)(P< 0.01). Mean elimination half-life, total plasma clearanceand steady state distribution volume in patients with Crohn'sdisease were comparable to those in control patients (80 vs81 min, 5.7 vs 6.4 ml kg^–1 min^–1 and 0.70 vs 0.68litre kg^–1, respectively). Mean plasma concentration atwhich the probability of no response was 50% for the intra-abdominalperiod of surgery was greater in the Crohn group (359 ng ml^–1)than in the control group (199 ng ml^–1 (P<0.02). PlasmaAAG concentrations were greater in the Crohn group, but thefree fraction of aifentanil was similar in both groups. Thisstudy indicates that the increased alfentanil requirement inpatients with Crohn's disease may be attributed to a changein pharmacodynamics. (Br. J. Anaesth. 1993; 71: 827–834)     

PHARMACOKINETICS AND CLINICAL EXPERIENCE OF 20-H INFUSIONS OF METHOHEXITONE IN INTENSIVE CARE PATIENTS WITH POSTOPERATIVE PYREXIA

We have studied the pharmacokinetics of 20-h infusions of methohexitonein young patients with postoperative fever undergoing artificialventilation of the lungs. The infusion rate was adjusted sothat patients were unresponsive to vocal stimulation but reactedto tracheal suction. The mean steady state concentration ofmethohexitone required was 2.6 mg litre^–1 (unbound 0.53mg litre^–1). The mean (SD) total clearance of methohexitonewas 16.3 (4.2) ml min^–1 kg^–1, which is greater thanthat for volunteers or normal surgical patients. The unboundclearance correlated positively with body temperature duringthe infusion (r = 0.796, P = 0.017). The terminal half-lifeof methohexitone was 6.3 (3.8) h and that of the 4'-hydroxymetabolite 5.8 (2.1) h. There were no marked haemodynamic effectsof the infusion, and no excessive sedation after the infusion.However, the clearance of methohexitone was high and variable,possibly as a direct effect of postoperative fever. Consequently,the need for individual titration of the rate of infusion isemphasized.     

TOTAL I.V. ANAESTHESIA WITH PROPOFOL AND ALFENTANIL: DOSE REQUIREMENTS FOR PROPOFOL AND THE EFFECT OF PREMEDICATION WITH CLONIDINE

We determined in 51 healthy patients undergoing body surfacesurgery the dose requirements for propofol, as part of a totali.v. anaesthesia technique with an alfentanil infusion. Afterpremedication with temazepam, patients received alfentanil 50µg kg^–1 followed by an infusion of 50 µg kg^–1h^–1. Patients were anaesthetized with a loading dose ofpropofol followed by a three-stage infusion designed to reachone of five preselected blood concentrations of propofol. Themotor response to the initial surgical incision was noted andprobit analysis was used to derive the ED₅₀ (2.94 mg kg^–1h^–1; 95% confidence limits: 2.35–3.37 mg kg^–1h^–1). and ED₉₅ (4.98 mg kg^–1 h^–1; 95% limits:4.13–8.8 mg kg^–1 h^–1) for the final propololinfusion rate under these conditions. Whole blood concentrationof propofol at the time of the incision was related linearlyto the infusion rate and the EC₅₀ and EC₉₅ (probit analysis)were derived as 1.44 (95% confidence limits 0.62–1.87)and 4.05 (95% confidence limits 2.78–30.5) µg ml^–1,respectively. Postoperative recovery was rapid, uncomplicatedand uneventful. In a subgroup of eight patients, the additionof clonidine 0.6mg to the premedication significantly decreasedthe requirement for propofol (P <0.05) during surgery, butresulted in prolonged recovery times. Pilot study presented to the Anaesthetic Research Society, June24, 1988 [1].