ERRATA

Delete: "During infusions of alfentanil... can be derived". Insert: "During infusions of fentanyl at 3 µg kg^–1h^–1,the plasma concentration was 3.28±0.54 ng ml^–1,from which a clearance of 15.2 litre kg^–1 min^–1can be derived." Page 123. Formula for A (ml min^–1) should be: A (ml min^–1) = Page 258, line 13. The dose of pancuronium should have been0.1 ng kg^–1 and not 0.001 ng kg^–1 as printed.      

CLEARANCE OF ATRACURIUM AND LAUDANOSINE IN THE URINE AND BY CONTINUOUS VENOVENOUS HAEMOFILTRATION

We have measured the steady state urinary clearances of atracurium,given by constant infusion, and laudanosine in eight patientsundergoing artificial ventilation; all had normal renal function(mean creatinine clearance 81 ml min^–1). Mean (so) urinaryclearance of atracurium was 0.55 (0.5) ml kg^–1 min^–1;that of laudanosine was 0.33 (0.2) ml kg^–1 min^–1.Simultaneous plasma clearances were 7.1 (1.4)ml kg^–1 min^–1and3.8 (1.5) ml kg^–1 min^–1, re-spectively. Notionalhaemofiltration clearances of the two substances were measuredalso in seven critically ill patients with renal and respiratoryfailure undergoing continuous venovenous haemofiltration. Mean(SD) clearances of atracurium and laudanosine in the haemofiltratefluid were 0.11 (0.06) ml kg^–1 min^–1 and 0.09 (0.02)ml kg^–1 min^–1, respectively whilst plasma clearanceswere atracurium 6.7 (1.8) mlkg^–1min^–1 and laudanosine4.5 (1.8) ml kg^–1 min^–1. There were no significantdifferences between the plasma clearances of the drugs in thetwo groups, despite the difference in severity of sickness.Urinary clearance rates of atracurium and laudanosine were approximately8 and 9% of that in the plasma, but the haemofiltration clearanceof both substances was only 2 %. Part of this work was presented at meetings of the AnaestheticResearch Society in April and July, 1990.     

PHARMACOKINETICS OF ATRACURIUM IN ANAESTHETIZED INFANTS AND CHILDREN

The pharmacokinetics of atracurium were studied in infants andchildren anaesthetized with isoflurane and nitrous oxide inoxygen. There were no significant differences in volume of distribution(area) (139 v. 152 ml kg^–1), clearance (5.1 v. 5.3 mlkg^–1 min^–1), T (2.1 v. 2.0 mim), or T^ß(19.1 v. 20.3 min) between children with normal hepatic andrenal function and those with moderately impaired hepatic functionpresenting for hepatic transplantation. There were significantdifferences in volume of distribution (area) (176 v. 139 mlkg^–1) and in clearance of atracurium (9.1 v.5.1 ml kg^–1min^–1) between infants and children with normal excretoryfunction. In infants the clearance of atracurium in ml m^–1min^–1 (153 v. 133) tended to be greater and the T andT^ß tended to be shorter (1.0 v. 2.0 and 13.6 v. 19.1)than in children with normal excretory function; however, thesetrends did not reach statistical significance. Plasma laudanosineconcentration was around 100 ng ml^–1 greater in patientswith liver disease than in normal children from 15–45min following a bolus of atracurium 0.5 mg kg^–1.     

INCREASED VENTILATION REQUIREMENTS DURING OBSTETRIC GENERAL ANAESTHESIA

The inspiratory fresh gas flow rate (FGF) required to producean end-tidal carbon dioxide tension (PE' _CO2)of 4kPa duringgeneral anaesthesia, neuromuscular blockade and artificial ventilation,was compared in a group of 46 obstetric patients and a matchedgroup of 50 non-pregnant female patients. The non-pregnant patientsrequired a mean (SD) inspiratory FGF of 77 (10.6) ml kg^–1min^–1, whereas the pregnant patients required a mean FGFof 121 (24.6) ml kg^–1 min^–1 before delivery (inthose who reached a stable state), and 109 (19.3) ml kg^–1min^–1 after delivery. These represent significant (P <0.0001) increases of 57% and 42%, respectively, over the non-pregnantstate. ^*Anaesthetics Unit, The London Hospital, Whitechapel, LondonEl IBB. 335, Southampton Road, Titchfield, Hants PO14 4AX. Northampton General Hospital, Whitechapel, London E1 1BB.     

SELECTIVE DEPRESSION BY ALFENTANIL OF GROUP III AND IV SOMATOSYMPATHETIC REFLEXES IN THE DOG

The effect of alfentanil on sympathetic reflexes evoked by supramaximalelectrical stimulation of the radial nerve has been observedin five dogs anaesthetized with -chloralose, paralysed withsuxamethonium and artificially ventilated. In five dogs duringthe infusion of alfentanil at a rate of 20 µg kg^–1min^–1 the late long latency sympathetic response evokedby unmyelinated fibres (group IV, C) was abolished at a meandose of 68.8 (SE 2.85) µg kg^–1. The infusion ratewas then increased to 200 µg kg^–1 min^–1 andthe early, short latency response evoked by small myelinatedfibres (group III, A) was eliminated at mean total dose of 809(SE 72) µg kg^–1. When the infusion was stopped thegroup III reflex returned within 1–5 min and recoveryto approximately 50% of control for both reflexes occurred within15–60 min in different preparations. Mean arterial pressureand mean heart rate decreased from 140 (6) mm Hg and 132 (11)beat min^–1 to 100 (7) mm Hg and 70 (6) beat min^–1,respectively, by the time the group IV response was eliminated;that is, after a mean infusion time of 3.4 min. Thereafter,there was no further cardiovascular depression. Within 3 minof the administration of naloxone 2 mg i.v., the sympatheticreflexes, arterial pressure and heart rate returned to withincontrol values.     

Do fluid administration and reduction in norepinephrine dose improve global and splanchnic haemodynamics?

We studied global and splanchnic haemodynamics in patients withseptic shock, while reducing norepinephrine doses by progressivefluid loading administration. Ten patients (six female, fourmale, aged 39–86 yr, mean 61 yr) were assessed using atranspulmonary thermo-dye dilution technique to measure cardiacoutput, intrathoracic blood volume and total blood volume. Splanchnicblood flow was measured by the steady state indocyanine greentechnique using a hepatic venous catheter. Gastric mucosal bloodflow was estimated by regional carbon dioxide tension (P_CO2). Hydroxyethylstarch was infused in two stageswhile maintaining mean arterial pressure, allowing a reductionin norepinephrine dose from 0.54 to 0.33 to 0.21 µg kg^–1min^–1. Mean () heart rate significantly decreased, from 104 (13) to 94 (15) beats min^–1. Totalblood volume index (mean ()) increased from 2650 (638) to 3655 (885) ml m^–2, intrathoracic blood volumeindex from 888 (204) to 1050 (248) ml m^–2 and cardiacindex from 3.6 (1.0) to 4.0 (0.9) litres min^–1 m^–2.Splanchnic blood flow did not change significantly–eitherabsolute (from 0.81 to 0.98 litres min^–1 m^–2) orfractional (from 22.3% to 23.9%). Gastric mucosal (P_CO2) increased from 7.5 (2.5) to 9.0 (2.8) kPa. TheP₂ gap, i.e. the difference between regionaland end-tidal P₂, increased from 3.1 (2.5)to 4.0 (2.9) kPa. Marked individual variation in responses suggeststhat norepinephrine dose reduction by fluid loading in patientswith stabilized septic shock does not necessarily increase globalor splanchnic blood flow.     

HEART RATE RESPONSE TO AN I.V. TEST DOSE OF ADRENALINE AND LIGNOCAINE WITH AND WITHOUT ATROPINE PRETREATMENT

In order to evaluate the sensitivity of an adrenaline test dosefor detecting intravascular injection and the effect of atropinepretreatment, 90 ASA physical status I and II patients wereallocated randomly to two groups, to receive i.v. saline 1 ml(n = 46) or i.v. atropine 0.5 mg (n = 44). Five minutes later,all patients received an i.v. test does of 2% lignocaine 3 mlwith adrenaline 15 µg at a rate of 1 ml s^–1. Thegroups were similar with respect to basal heart rate (HR). HRremained unchanged after saline injection, but increased slightly5 min after atropine injection (mean 78 (SD 15) beat min^–1vs 87 (20) beat min^–1 (P <0.05). After the test doseof lignocaine with adrenaline, HR increased significantly inboth groups at 30 s, 1 and 2 min, and remained increased at3 min in the atropine group. The maximum increase in HR wasgreater in the atropine group than in the saline group (31 (4)beat min^–1 vs 26 (11) beat min^–1 (P < 0.05).However, when individual maximum HR changes are considered,five patients in the saline group and four in the atropine grouphad an increase 10 beat min^–1, and three patients in thesaline group had no change or a decrease in HR. Defining a positiveresult to a test dose as an increase in HR of > 10 beat min^–1,the sensitivity of the adrenaline test dose was 83 (5.5)% inthe saline group and 91 (3.5)% in the atropine group (ns). Thusa test dose containing 2% lignocaine 3 ml and adrenaline 15µg was not very sensitive for detecting intravascularinjection, as moderate or false negative responses occurredfrequently.     

VARIATION IN THE DISPOSITION OF MORPHINE AFTER I.M. ADMINISTRATION IN SURGICAL PATIENTS

The disposition of morphine when administered by i.m. injectionwas studied in 36 patients receiving morphine as part of premedicationbefore general anaesthesia, and in five patients who receivedmorphine as a postoperative analgesic after median sternotomyfor coronary artery surgery (PCA group). Maximum plasma concentrationof morphine (Cp_max) was 75.3 ± 6.0 (mean±standarderror (SEM)) ng ml^–1 (range 30–160 ng ml(^–1),mean elimination rate constant (k) 4.85 x 10^–3 min^–1and half-life (T₁₂) = 143 min for the preanaesthetic group.The corresponding values for PCA group were Cp_max = 58.0 ±18.0 ng ml^–1 (range 30–130 ng ml^–1), k = 5.63x 10^–3 min^–1 and T₁₂ = 123 min. Analysis of varianceshowed no differences between the groups. Within the preanaestheticgroup, there was a significant difference in k between males(k = 4.01 x 10^–3 min^–1) and females (6.30 x 10^–3min^–1, P<0.01). The corresponding T₁₂ for males was173 min; and 110 min for females. The variation in the dispositionof morphine is thought to be the result of variations in restingmuscle blood flow and inadvertent injection into adipose tissue.There were no significant differences between males and femalesin the preanaesthetic group with respect to age, CP_max timefrom injection to Cp_max.     

PHARAMACOKINETICS OF PROPOFOL IN YOUNG CHILDREN AFTER A SINGLE DOSE

The pharmacokinetics of propofol were studied following a singlebolus injection (2.5 mg kg^–1) in 10 healthy children (4–7yr). Propofol was distributed rapidly and extensively (Vss 10.9(1.2) litre kg^–1) and cleared rapidly from the body (Cl30.6 (2.9) ml min^–1 kg^–1). With the exception ofa larger central compartment volume (V 722 (113) ml kg^–1).these data are similar to those reported for young adults whoreceived an identical dose and who underwent sampling over thesame period. The larger value of V is consistent with the higherinduction dose requirement reported for children.     

Treatment of cardiogenic shock with levosimendan in combination with beta-adrenergic antagonists

Levosimendan, a calcium sensitizer, was used in combinationwith ß-adrenergic antagonists in a man aged 56 yrwith cardiogenic shock, complicating acute myocardial infarction,who developed severe tachycardia after dobutamine administration.The patient's trachea was intubated, his lungs were ventilated,and he was started on dopamine 5 µg kg^–1 min^–1and dobutamine 5 µg kg^–1 min^–1, titrated toa mean arterial pressure 65 mm Hg. He progressively became tachycardiac(>120 beats min^–1) with a cardiac index (CI) of 1.4litre min^–1 m^–2 despite adequate preload. Levosimendan6 µg kg^–1 was administered intravenously over 10min followed by a continuous infusion of 0.2 µg kg^–1min^–1 for 24 h. Within 30 min, the patient's CI increasedto 2.2 litre min^–1 m^–2, but the heart rate (HR)also increased from 142 to 155 beats min^–1. Esmolol 1mg kg^–1 i.v. was administered with a consequent transientdecrease in HR to 110 beats min^–1 without adverse haemodynamiceffects; however, HR increased again shortly afterwards. Carvedilol3.125 mg orally twice a day was then administered, and the dosewas increased to 6.25 mg orally twice daily on the followingday. Subsequently, HR decreased over time and both catecholamineswere discontinued 14 h after starting levosimendan infusion.The trachea was extubated within 20 h and the patient was dischargedto the ward on day 4 after admission. In conclusion, levosimendanin combination with a ß-adrenergic antagonist mayhave beneficial effects in patients with cardiogenic shock whoexhibit tachycardia in response to inotropic agents.     

A SYSTEM FOR THE CONTINUOUS MEASUREMENT OF OXYGEN UPTAKE AND CARBON DIOXIDE OUTPUT IN ARTIFICIALLY VENTILATED PATIENTS

A continuous, non-invasive system is described for measuringoxygen uptake () and carbon dioxide output () in mechanically ventilated patients. Inspiratory and mixed expiratory gas sampleswere pumped through fine-bore tubing to a remote mass spectrometerfor analysis. The expiratory flow transducer of a Siemens Servo900B ventilator was used for expiratory flow measurement andinspiratory flow was calculated from this using the Haldanetransformation. A desk-top computer calculated , and respiratory quotient. The system has been validated against standard methodsof gas analysis and flow measurement ( mean difference –lOml min^–1: SD9.13; mean difference 8.12ml min^–1:SD4.66). Comparison with Douglas bag measurements in patientshas been made ( mean difference 10.7ml min^–1: SD9.8; mean difference –1.07ml min^–1: SD4.7).     

Volume kinetics of glucose 2.5% solution and insulin resistance after abdominal hysterectomy

Background. We hypothesized that volume kinetics can be usedto predict the rate of infusion of glucose 2.5% solution requiredto yield any predetermined plasma glucose level and degree ofplasma dilution during the postoperative period. Methods. In 15 women, mean age 50 yr (range 37–63), 2days after an abdominal hysterectomy, a volume kinetic analysiswas performed on an i.v. infusion of 12.5 ml kg^–1 (900ml) of glucose 2.5% given over 45 min. The insulin resistancewas measured by a glucose clamp, and it was compared with dailybioimpedance analyses, which indicated the hydration of theintra/extracellular body fluid spaces. Results. The clearance of glucose was 0.42 litre min^–1(0.60 litre min^–1 is normal) while the other five parametersin the kinetic model were similar to those obtained in healthyvolunteers. Computer simulations indicated that in a 70-kg female,at steady state, the rate of infusion (ml min^–1) shouldbe three times the allowed increase in plasma glucose (mmollitre^–1). To maintain a predetermined plasma dilutionthe corresponding rate factor was 160. The glucose uptake duringclamping was 3.9 mg kg^–1 min^–1 (7.0 is normal),which, during the second day after hysterectomy, correlatedwith the dehydration of the intracellular space (r=0.77; P<0.002)and with the protein catabolism as indicated by the urinaryexcretion of 3-methylhistidine (r=–0.76, P<0.002). Conclusion. The anaesthetist can prescribe postoperative administrationof glucose 2.5% to reach any desired plasma glucose level anddilution by using the two presented nomograms. Insulin resistancecorrelated with intracellular dehydration and protein catabolism.     

PHARMACOKINETICS OF GALANTHAMINE (A LONG-ACTING ANTICHOLINESTERASE DRUG) IN ANAESTHETIZED PATIENTS

The pharmacokinetics of the long-acting anti-cholinesterasedrug, galanthamine, were investi-gated in eight patients. Afteri.v. injection of 0.3 mg kg^–1, the decrease in the serumconcen-tration of galanthamine followed a biexponential curve.The serum concentration decreased rapidly from 543±47ng ml^–1 to 128±14 ng ml^–1 be-tween 2 and30 min with a T of 6.42 ± 2.15 min, and then declinedmore slowly with a T^ß of 264±28min. Total serumclearance of galanthamine amounted to 5.37±0.87ml min^–1kg^–1, and the renal clearance was 1.36±0.10 mlmin^–1 kg^–1. The cumulative urinary excretion ofgalanthamine between 0 and 48 h after injection amounted to28.0±5.4% of the administered dose. The biliary excretionof galanthamine during 24 h amounted to 0.2 ±0.1% ofthe dose. There was no evidence of glucuronide or sulphate conjugationof galanthampine.     

EFFECTS OF DIFFERENT HEPATIC PATHOLOGIES ON DISPOSITION OF ALFENTANIL IN ANAESTHETIZED PATIENTS

We have studied the influence of different hepatic pathologieson the disposition of alfentanil in 23 unpremedicated patients(six healthy control subjects, six patients with liver dysfunctionof alcoholic aetiology and 11 patients with non-alcohol relatedliver disease). All patients received a bolus of alfentanil500 fig i.v. as supplement to 67% nitrous oxide and isofluranein oxygen anaesthesia. Plasma drug concentrations were measuredin venous blood samples at intervals up to 24 h by radio-immunoassayand protein binding was determined by equilibrium dialysis.Kinetic estimates were determined using non-compartmental analysis.Patients with non-alcoholic liver disease had lesser plasmaclearance (114.8 (range 66.8–213.5) ml min^–1) thanthe alcoholic group (158.8 (100.0–220.7) ml min^–1)or controls (187.4 (125.2–269.5) ml min^–1). In allthree groups, there was considerable intersubject variability,with a bimodal distribution in the non-alcoholic group. Thisgroup also had a smaller apparent volume of distribution atsteady state. Mean residence time was prolonged in the alcoholicgroup compared with controls (284.9 (217.8–362.2) minvs 226.8 (201.2–250) min). Protein binding was decreasedin the alcoholic group compared with controls (84.9 (SD 4.2)%vs 89.3 (2.1)%); this was attributable to a lesser plasma a,-acidglycoprotein concentration (0.55 (0.18) g litre^–1 vs 0.89(0.21) g litre^–1). Free drug clearance was reduced inboth liver dysfunction groups compared with controls. ^*Department of Anesthesiology, Bowman-Gray Medical School, WinstonSalem, North Carolina, U.S.A. Department of Anaesthesia, Freeman Hospital, Newcastle uponTyne. Presented in part at the Anaesthetic Research Society meeting,Cardiff July 1989 [1].     

FENTANYL PHARMACOKINETICS IN ANAESTHETIZED PATIENTS WITH CIRRHOSIS

Fentanyl kinetics were studied in patients with cirrhosis andin patients with normal hepatic and renal function undergoingsurgery under general anaesthesia, the latter group served asthe controls. Plasma fentanyl concentrations declined bi-exponentiallyin the controls with an average elimination half-life (T^ß)of 263 mm; total plasma clearance (C7) was 10.8mlmin^–1kg^–1,and total apparent volume of distribution (V^ß) 3 81litre kg^–1. No significant change was observed in patientswith cirrhosis: T( T^ß) was 304mm, Cl 11.3 ml min^–1kg^–1 and V^ß 4.41 litre kg^–1. These datasuggest that the elimination half-life of fentanyl is not primarilyinfluenced by the rate at which it is metabolized in the liver.     

CONTINUOUS I.V. INFUSION OF LABETALOL FOR POSTOPERATIVE HYPERTENSION: Haemodynamic Effects and Plasma Kinetics

Labetalol is a combined -and ß-adrenoreceptor blockingagent. A loading dose may be used to antagonize sympatheticoveractivity rapidly after surgery and be followed by a continuousinfusion to achieve a stable effect. The haemodynamic effectsand pharmacokinetics of this method of labetalol administrationwere studied in six rewarmed, extubated and sedated patients15±2 h after aortobifemoral bypass surgery. Patientswere monitored with radial and thermistor-tipped pulmonary arterycatheters. Labetalol 1.5 mg kg^–1 was injected i.v. over5 min and a maintenance infusion of 0.2 mg kg ^–1 h^–1was started 30 min later and continued for 5.5 h. Within 5 minof the loading dose, i.v. labetalol induced significant (P <0.05) decreases in mean arterial pressure (–32 ±11%),in heart rate (–20±11%) and in cardiac index (–26± 15%) that lasted throughout the infusion. Changes insystemic vascular resistance were not uniform, but an increasewas not observed in any patient. Mean stroke volume index andventricular filling pressures were not significantly affectedby labetalol administration. The mean measured steady stateplasma concentration (C^ss) (264 ±46 ng ml^–1) washigher than predicted (170 ng ml^–1) because the clearance(13.1 ±2.4 ml kg^–1 min^–1) was lower thanthat used to calculate the infusion rate. We conclude that labetalolis an effective antihypertensive agent in the postoperativeperiod. A C^ss can be achieved rapidly by such i.v. administrationand this offers the advantage of inducing rapid and stable haemodynamiceffects. However, calculation of the infusion rate must be basedon a clearance of 13 ml kg^–1 min^–1.     

HEPATIC AND RENAL DISPOSITION OF PANCURONIUM AND GALLAMINE IN PATIENTS WITH EXTRAHEPATIC CHOLESTASIS

The plasma clearance of pancuronium in patients with extrahepaticcholestasis was 16% lower than in a control group (1.47±0.11ml min^–1 kg^–1 v. 1.76±0.21 ml min^–1kg^–1), but the difference was not significant. A significantincrease in the elimination half-life T^ß of pancuronium(from 141 to 224 min) and a significant increase in the volumeof the peripheral compartment (V₂ was found in patients withextrahepatic cholestasis when compared with control patients.There was a significantly lower cumulative biliary excretionof pancuronium (0.3±0.3% v. 10.9±3.2% in the controls)during the 48-h period of observation. The biotransformationand cumulative urinary excretion patterns of pancuronium revealedno significant differences between the two groups of patients.The increase of T^ß pancuronium in patients with extrahepaticcholestasis was mainly a consequence of the increase in thevolume of distribution. No significant differences in the plasmaclearance, T^ß or in the volume of distribution wereobserved with gallamine in the patients with extrahepatic cholestasiswhen compared with the control patients. The cumulative urinaryexcretion of gallamine during 48 h in both groups of patientswas approximately 100%. We concluded that in patients with cholestasisand normal glomerular filtration, gallamine is probably morereliable than pancuronium for neuromuscular blockade.     

ENCLOSED AFFERENT RESERVOIR BREATHING SYSTEMS: Description and Clinical Evaluation

A new group of breathing systems, namely the Enclosed AfferentReservoir (EAR) systems, is described. They allow for the selectiveelimination of alveolar gas in association with both spontaneousand controlled ventilation. A comparison with the Bain systemin controlled ventilation demonstrates greater efficiency ineliminating carbon dioxide. A fresh gas flow (F) of 70 ml kg^–1 min^–1 using an EAR systemgave mild hypocarbia which equated to a F of 100 ml kg^–1 min^–1 using the Bainsystem. Smaller minute volumes of ventilation are required foroptimal performance than with the Bain system. The minimum recommendedminute volume of ventilation (l) should equal F plus anatomical deadspace ventilation (D^anat).The pattern of ventilation appears to have little influenceupon the efficiency of carbon dioxide elimination when usingan EAR system, whereas the Bain system does appear to be affected.     

Comparison of three devices for oxygen administration in the late postoperative period

We have evaluated three different devices for oxygen administrationin the surgical ward, the Hudson face mask (oxygen 3 litre min^–1air 12 litre min^–1) the nasal prong (oxygen 3 litre min^–1)and the binasal catheter (oxygen 3 litre min^–1) We evaluatedthe three devices in random order for periods of 30 mm eachin 25 patients with postoperative hypoxaemia (Sp^o2 94%). Arterialoxygen saturation was measured by continuous pulse oximetryand comfort was evaluated with a questionnaire after each treatmentperiod. The three systems increased arterial oxygen saturationto similar levels, but the highest degree of comfort was foundwith the binasal catheter. Use of the binasal catheter is recommendedfor oxygen administration in the late postoperative period.(Br. J. Anaesth. 1995; 74: 607–609)     

Tramadol does not modify the Bispectral Index during anaesthesia with sevoflurane and remifentanil

Background. The aim of this study was to investigate the effectsof tramadol administered with ketorolac on the Bispectral Index(BIS) during anaesthesia with sevoflurane and remifentanil. Methods. Forty-six adult patients, ASA I–III, scheduledfor elective minor surgical procedures were studied. Patientswere premedicated with remifentanil infusion 0.4 µg kg^–1min^–1 and anaesthesia was induced 4–5 min laterwith propofol 1.5 mg kg^–1 and maintained with air–oxygen( 0.4), remifentanil 0.1–0.15 µg kg^–1 min^–1 and sevoflurane, adjusted to keep theBIS between 40 and 50. After 20 min of stable anaesthesia, thesubjects were allocated randomly to receive i.v. tramadol 1.5mg kg^–1 and i.v. ketorolac 0.3 mg kg^–1 (tramadolgroup) or saline (control group). BIS values, mean arterialpressure, heart rate and end-tidal carbon dioxide were recordedevery 5 min for 20 min. Results. Mean BIS values after tramadol administration werenot significantly different from those recorded in patientsreceiving saline throughout the period of observation. Therewere no patients who presented explicit recall of events underanaesthesia. No significant changes in mean arterial pressure,heart rate and end-tidal carbon dioxide were noted after tramadolinjection. Conclusion. Tramadol, given with ketorolac to prevent postoperativepain, during anaesthesia maintained with sevoflurane and remifentanilat BIS between 40 and 50, does not modify the BIS value.