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     

Esmolol prevents movement and attenuates the BIS response to orotracheal intubation

Background. Beta-adrenergic agonists enhance behavioural andelectroencephalographic arousal reactions. We explored whetheradding esmolol, a short-acting ß₁-adrenoceptor antagonist,to propofol anaesthesia modified the bispectral index (BIS)during induction of anaesthesia and orotracheal intubation. Methods. Fifty patients were randomly allocated, in a double-blindfashion, to receive esmolol 1 mg kg^–1 followed by 250µg kg^–1 min^–1 or saline (control). Esmololor saline was started 6 min after a target-controlled infusion(TCI) of propofol (effect-site concentration 4 µg ml^–1).After loss of consciousness, and before administration of vecuronium0.1 mg kg^–1, a tourniquet was applied to one arm and inflatedto 150 mm Hg greater than systolic pressure. Eleven minutesafter the TCI began, the trachea was intubated; gross movementwithin the first min after orotracheal intubation was recorded.BIS was recorded at 10-s intervals. Mean arterial pressure (MAP)and heart rate were measured non-invasively every min. Results. There were no intergroup differences in BIS, heartrate or MAP before laryngoscopy. BIS increased significantlyafter orotracheal intubation (compared with the pre-laryngoscopyvalues) in the control group only, with a maximum increase of40 (SD 18)% vs 8 (11)% in the esmolol group (P<0.01). Maximumchanges in heart rate [45 (19)% vs 23 (14)%] and MAP [62 (24)%vs 45 (23)%] with orotracheal intubation were also significantlygreater in the control group than in the esmolol group. Morepatients in the control than in the esmolol group moved afterorotracheal intubation (23 vs 12, P<0.01). Conclusion. Esmolol not only attenuated haemodynamic and somaticresponses to laryngoscopy and orotracheal intubation, but alsoprevented BIS arousal reactions in patients anaesthetized withpropofol. Br J Anaesth 2002; 89: 857–62     

Bispectral index changes following etomidate induction of general anaesthesia and orotracheal intubation

Background. Etomidate-associated hypnosis has only been studiedusing standard clinical criteria and raw EEG variables. We conducteda BIS-based investigation of etomidate induction of generalanaesthesia. Methods. Thirty hydroxyzine-premedicated ASA I patients wererandomly allocated to receive etomidate 0.2, 0.3, or 0.4 mgkg^–1 intravenously over 30 s. The BIS was continuouslyrecorded. A tourniquet was placed on a lower limb to recordpurposeful movements and myoclonia. Tracheal intubation wasfacilitated using rocuronium 0.6 mg kg^–1 when the BISvalue was 50. The times to disappearance of the eyelash reflex,to a decrease in the BIS to 50, and to tracheal intubation werecompared. The BIS values 30 s following tracheal intubation,and mean arterial pressure (MAP) and heart rate (HR) at alltime points were also recorded. Results. The BIS value decreased to 50 for tracheal intubationwith no purposeful movement in all but one patient in the 0.2mg kg^–1 group. There was no difference between the etomidategroups (0.2, 0.3, and 0.4 mg kg^–1) in regards to timeto loss of the eyelash reflex (103 (67), 65 (34), 116 (86) s,P=0.2), or to a decrease in BIS to 50 (135 (81), 82 (36), 150(84) s, P=0.1). Also, the BIS value 30 s after intubation (41(10), 37 (4), 37 (4), P=0.4), and plasma etomidate concentrations(161 [29–998], 308 [111–730], 310 [90–869]ng ml^–1, P=0.2) did not differ between groups. The timeto loss of the eyelash reflex was 12–140 s shorter thanthe time to a decrease in BIS to 50 in three patients in eachgroup who received etomidate 0.2 and 0.4 mg kg^–1, andin four patients who received 0.3 mg kg^–1. No awarenesswas recorded. MAP and HR increases following tracheal intubationwere comparable between groups. Conclusions. Etomidate induction doses do not predict the timefor BIS to decrease to 50 as this variable varies markedly followingthree etomidate dose regimen. Br J Anaesth 2003; 91: 341–6     

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     

Effect of prophylactic bronchodilator treatment with i.v. carperitide on airway resistance and lung compliance after tracheal intubation

Background. Lung resistance increases after induction of anaesthesia.We hypothesized that prophylactic bronchodilation with i.v.carperitide before tracheal intubation would decrease airwayresistance and increase lung compliance after placement of thetracheal tube in both smokers and nonsmokers. Methods. Ninety-seven adults aged between 24 and 59 yr wererandomized to receive i.v. normal saline (0.9% saline) (control)or carperitide, 0.2 µg kg^–1 min^–1 throughoutthe study. The 97 patients included smokers and nonsmokers.Thus the patients were allocated to one of the four groups:smokers who received normal saline (n=21), nonsmokers who receivednormal saline (n=27), smokers who received carperitide (n=19)or nonsmokers who received carperitide (n=30). Thirty minutesafter starting normal saline or carperitide infusion, we administeredthiamylal 5 mg kg^–1 and fentanyl 5 µg kg^–1to induce general anaesthesia and vecuronium 0.3 mg kg^–1for muscle relaxation. Continuous infusion of thiamylal 15 mgkg^–1 h^–1 followed anaesthetic induction. Mean airwayresistance (R_awm), expiratory airway resistance (R_awe) and dynamiclung compliance (C_dyn) were determined 4, 8, 12 and 16 min aftertracheal intubation and compared between the four groups. Results. At 4 min after intubation, R_awm and R_awe were higherand C_dyn lower in smokers than in nonsmokers in the controlgroup. R_awm and R_awe were lower and C_dyn higher in smokers inthe carperitide group than in smokers in the control group.R_awm and R_awe were lower in nonsmokers in the carperitide groupthan in nonsmokers in the control group. Conclusions. Marked bronchoconstriction occurred in the controlgroups (smokers and nonsmokers) 4 min after tracheal intubation.Prophylactic treatment with carperitide before induction ofanaesthesia and tracheal intubation was advantageous, particularlyin smokers.     

Influence of acute normovolaemic haemodilution on the dose-response relationship, time-course of action and pharmacokinetics of rocuronium bromide

Background. Acute normovolaemic haemodilution (ANH) is an effectivestrategy for avoiding or reducing allogeneic blood transfusion.We aimed to study its effect on the pharmacological profileof rocuronium. Methods. In two study centres, 28 patients undergoing majorsurgery with ANH were matched with 28 control patients. In thedose–response groups, using the mechanomyograph, neuromuscularblock of six consecutive incremental doses of rocuronium 50µg kg^–1, followed by 300 µg kg^–1, wasevaluated. In the pharmacokinetics groups, serial arterial bloodsamples were withdrawn for rocuronium assay after a single doseof rocuronium 600 µg kg^–1. Results. ANH resulted in a shift to the left of rocuronium dose–responsecurve. Rocuronium effective dose₉₅ (ED₉₅) was 26% lower (P<0.05)in the ANH group [283.4 (92.0) µg kg^–1] comparedwith the control group [383.5 (127.3) µg kg^–1].Times from administration of last incremental dose until 25%of first response of train-of-four (TOF) recovery (Dur₂₅) and0.8 TOF ratio recovery (Dur_0.8) were 28% longer in the ANH group[39.9 (8.4), 66.7 (14.2) min] compared with the control group[31.1 (6.6), 52.1 (15.8) min] (P<0.01, P<0.05), respectively.Volume of distribution was higher (P<0.01), central clearancewas lower (P<0.05) and terminal elimination half-life waslonger (P<0.0001) in the ANH group [234.97 (47.11) ml kg^–1,4.70 (0.94) ml kg^–1 min^–1, 77.29 (12.25) min] comparedwith the control group [181.22 (35.73) ml kg^–1, 5.71 (1.29)ml kg^–1 min^–1, 56.86 (10.05) min, respectively]. Conclusion. ANH resulted in prolongation of rocuronium time-courseof action, thus careful monitoring of neuromuscular block isrecommended in patients who undergo ANH.     

Comparison of remifentanil and alfentanil during anaesthesia for patients undergoing direct laryngoscopy without intubation

Background. Remifentanil and alfentanil are opioids often usedduring direct laryngoscopy (DL). This prospective, randomizedstudy compared these agents with respect to haemodynamic andBispectral Index (BIS) responses, glottic visualization, andrapidity of recovery (spontaneous ventilation, eye opening)in DL without intubation. Methods. A total of 60 patients undergoing DL were randomizedinto two groups: remifentanil (R) and alfentanil (A). Anaesthesiawas induced with propofol 2.5 mg kg^–1 and the opioid wasadministered 1 min later (R=2 µg kg^–1 or A=30 µgkg^–1 over 30 s). DL was commenced 1 min after (correspondingto 3 min after the beginning of induction). Glottic visualization,opioid and/or propofol re-injection, spontaneous ventilationrecovery, and eye opening were recorded. Results. During DL, mean arterial pressure (MAP) increased by6% in the R group vs 20% in the A group (P<0.05) when comparedwith post-induction values without affecting heart rate or BIS.No significant difference was observed between groups with respectto glottic exposure, opioid and/or propofol re-injection, andspontaneous ventilation recovery (mean (SEM) 3.8 (0.6) min,R group vs 3.2 (0.7) min, A group, NS) or eye opening (7.1 (1.1)min, R group vs 7.4 (0.9) min, A group, NS). Thirty minutesafter postanaesthesia care unit (PACU) admission, MAP returnedto its pre-induction value in the R group (104 (3) vs 109 (3)at baseline, NS), whereas in the A group MAP remained significantlylower at this time point (96 (4) vs 106 (3) at baseline, P<0.05). Conclusion. This study showed that only remifentanil preventedMAP increase without adverse effects such as bradycardia duringDL, and prevented MAP decrease 30 min after PACU admission. Br J Anaesth 2003; 91: 421–3     

Influence of peroperative opioid on postoperative pain after major abdominal surgery: sufentanil TCI versus remifentanil TCI. A randomized, controlled study

Background. Sufentanil and remifentanil are characterized bytwo different pharmacokinetic profiles. The aim of this studywas to compare the effects of sufentanil and remifentanil administeredusing target-controlled infusion (TCI) on recovery and postoperativeanalgesia after major abdominal surgery. Methods. Thirty adult patients scheduled for open colorectalsurgery were included in a prospective, randomized study. SufentanilTCI (sufentanil group) or remifentanil TCI (remifentanil group)was administered during surgery. In the remifentanil group,30 min before the anticipated end of surgery, morphine 0.15mg kg^–1 was administered i.v. In the sufentanil group,an effect-site concentration of 0.25 ng ml^–1 wastargeted at extubation. In both groups, postoperative pain wascontrolled by titration of i.v. morphine and then patient-controlledanalgesia with morphine. Results. The extubation time was similar in the two groups (mean(SD) 13 (6) and 14 (6) min in the sufentanil and remifentanilgroups respectively). Visual analogue scale scores were significantlygreater during the first 2 h after tracheal extubation in theremifentanil group than in the sufentanil group. The time tofirst analgesic request in the postanaesthesia care unit wassignificantly longer in the sufentanil group than in the remifentanilgroup (55 (64) (range 2–240) vs 11 (7) (1–29) min;P<0.001). The cumulative morphine dose for titration wassignificantly greater in the remifentanil group (P<0.01).The cumulative morphine dose used during titration and patient-controlledanalgesia was significantly greater in the remifentanil group4, 12 and 24 h after extubation (P<0.05). Conclusion. TCI sufentanil (0.25 ng ml^–1 effect-siteconcentration at extubation) is more effective than the intraoperativecombination of remifentanil TCI infusion with morphine bolus(0.15 mg kg^–1) for postoperative pain relief aftermajor abdominal surgery and does not compromise extubation andrecovery. Br J Anaesth 2003; 91: 842–9     

The effect of ephedrine on intubating conditions and haemodynamics during rapid tracheal intubation using propofol and rocuronium

Background: We compared the effect of pre-treatment with ephedrine 75, 100,150 µg kg^–1 and saline on intubating conditionsand haemodynamics during rapid tracheal intubation using propofoland rocuronium. Methods: One hundred adult patients randomized into one of the four groups—PE75, PE 100, PE 150, and saline (control) groups—were pre-treatedwith i.v. ephedrine 75, 100, 150 µg kg^–1 or saline,respectively, 1 min before rapid tracheal intubation using propofol2.5 mg kg^–1 and rocuronium 0.6 mg kg^–1. A blindedanaesthesiologist assessed the intubating conditions. Heartrate and mean arterial pressure were recorded before anaesthesiainduction (baseline), post-induction, and every minute afterintubation for 5 min. A 20% change in haemodynamic variablesfrom baseline was regarded as clinically significant. Data wereanalysed using ANOVA test with post hoc Tukey's test and ² orFisher's exact test. P < 0.05 was regarded as significant. Results: Patient characteristics, baseline heart rate, and mean arterialpressure were comparable between the groups. Intubating conditionswere significantly better in the PE 75 (P = 0.003) and PE 100(P = 0.001) groups. A significant increase in heart rate wasobserved in the PE 75 and PE 150 groups when compared with thesaline group. A statistically significant difference in meanarterial pressure was noted between PE 75 and PE 150 groupsand between PE 150 and saline groups at most of the time intervals.However, when considering the clinical significance of these,all groups were comparable (P > 0.05). Conclusions: Ephedrine either 75 or 100 µg kg^–1 given beforerapid tracheal intubation using propofol and rocuronium bromideimproves the intubation conditions. It is not effective in preventingthe hypotension which follows ensuing induction of anaesthesia.     

Early recovery after remifentanil-pronounced compared with propofol-pronounced total intravenous anaesthesia for short painful procedures

Background. We compared recovery from high-dose propofol/low-doseremifentanil (‘propofol-pronounced’) compared withhigh-dose remifentanil/low-dose propofol (‘remifentanil-pronounced’)anaesthesia. Methods. Adult patients having panendoscopy, microlaryngoscopy,or tonsillectomy were randomly assigned to receive either propofol-pronounced(propofol 100 µg kg^–1 min^–1; remifentanil0.15 µg kg^–1 min^–1) or remifentanil-pronounced(propofol 50 µg kg^–1 min^–1; remifentanil 0.45µg kg^–1 min^–1) anaesthesia. In both groups,the procedure was started with remifentanil 0.4 µg kg^–1,propofol 2 mg kg^–1, and mivacurium 0.2 mg kg^–1.Cardiovascular measurements and EEG bispectral index (BIS) wererecorded. To maintain comparable anaesthetic depth, additionalpropofol (0.5 mg kg^–1) was given if BIS values were greaterthan 55 and remifentanil (0.4 µg kg^–1) if heartrate or arterial pressure was greater than 110% of pre-anaestheticvalues. Results. Patient and surgical characteristics, cardiovascularmeasurements, and BIS values were similar in both groups. Therewere no differences in recovery times between the groups (timeto extubation: 12.7 (4.5) vs 12.0 (3.6) min, readiness for transferto the recovery ward: 14.4 (4.4) vs. 13.7 (3.6) min, mean (SD)). Conclusions. In patients having short painful surgery, lesspropofol does not give faster recovery as long as the same anaestheticlevel (as indicated by BIS and clinical signs) is maintainedby more remifentanil. However, recovery times were less variablefollowing remifentanil-pronounced anaesthesia suggesting a morepredictable recovery. Br J Anaesth 2003; 91: 580–2     

Propofol-alfentanil vs propofol-remifentanil for posterior spinal fusion including wake-up test

Background. Wake-up test can be used during posterior spinalfusion (PSF) to ensure that spinal function remains intact.This study aims at assessing the characteristics of the wake-uptest during propofol–alfentanil (PA) vs propofol–remifentanil(PR) infusions for PSF surgery. Methods. Sixty patients with scoliosis and candidates for PSFsurgery were randomly allocated in either alfentanil (PA) orremifentanil (PR) group. After an i.v. bolus of alfentanil 30µg kg^–1 in the PA group or remifentanil 1 µgkg^–1 in the PR group, anaesthesia was induced with thiopentaland atracurium. During maintenance, opioid infusion consistedof alfentanil 1 µg kg^–1 min^–1 or remifentanil0.2 µg kg^–1 min^–1, in the PA group and thePR group, respectively. All patients received propofol 50 µgkg^–1 min^–1. Atracurium was given to maintain therequired surgical relaxation. At the surgeon's request, allinfusions were discontinued. Patients were asked to move theirhands and feet. Time from anaesthetic discontinuation to spontaneousventilation (T₁), and from then until movement of the handsand feet (T₂), and its quality were recorded. Results. The average T₁ and T₂ were significantly shorter inthe PR group [3.6 (2.5) and 4.1 (2) min] than the PA group [6.1(4) and 7.5 (4.5) min]. Quality of wake-up test, however, didnot show significant difference between the two groups studied. Conclusion. Wake-up test can be conducted faster with remifentanilcompared with alfentanil infusion during PSF surgery.     

Optimal rocuronium dose for intubation during inhalation induction with sevoflurane in children

Background. We studied 120 children aged 2–7 yr in a prospective,randomized, assessor-blinded fashion to define the optimal rocuroniumdose which provides a 95% probability of acceptable intubationconditions (ED_95TI) during inhalation induction with sevoflurane. Methods. After inhalation induction with 8% sevoflurane in 60%nitrous oxide and 40% oxygen, and loss of the eyelash reflex,we administered rocuronium (0.1, 0.15, 0.22, 0.3, or 0.6 mgkg^–1) or placebo. We quantified neuromuscular functionby stimulation of the ulnar nerve at 0.1 Hz to produce contractionof the adductor pollicis muscle using accelerometry. Intubationconditions were assessed 2 min after test drug injection. Theoptimal rocuronium dose was defined as the lowest dose, whichallowed acceptable intubation conditions in 95% of children(ED_95TI). Results. Two minutes after injection of placebo or rocuronium,intubation conditions were acceptable in 35, 45, 80, 90, 95,and 100% of children, respectively. Rocuronium 0.07 [CI 0.02–0.11],0.24 [0.19–0.31], and 0.29 [0.23–0.38] mg kg^–1provided 50, 90, and 95% probability of acceptable intubatingconditions. When thumb acceleration was depressed by 50% ormore, intubating conditions were considered acceptable in 97%of children. Recovery of the train-of-four ratio to 0.8 averaged12 (7), 16 (7), 24 (7), 24 (8), and 50 (22) min after the respectivedose of rocuronium. Conclusions. During inhalation induction with 8% sevofluranein 60% nitrous oxide, rocuronium 0.29 mg kg^–1 (ED₉₅) optimizesintubation conditions for surgery of short duration. Br J Anaesth 2002; 89: 277–81     

Pre-emptive lidocaine inhibits arterial vasoconstriction but not vasopressin release induced by a carbon dioxide pneumoperitoneum in pigs

Background. We assessed the preventive effects of i.v. or i.p.lidocaine administration on increases in vascular resistanceproduced by carbon dioxide pneumoperitoneum and related thisto vasopressin release. Methods. Carbon dioxide pneumoperitoneum (14 mm Hg intra-abdominalpressure) was performed in 32 anaesthetized young pigs and monitoredusing a pulmonary artery catheter. Animals received lidocaine0.5% (0.5 mg kg^–1) i.v. (n=9) or 2 ml kg^–1 i.p.(n=9) or saline (n=5) 15 min before the pneumoperitoneum andwere compared with a control group (n=9). Results. I.V. and i.p. lidocaine inhibited increases in meansystemic vascular resistance induced by the pneumoperitoneum[2109 (SD 935) and 2282 (895), respectively, vs 3013 (1067)dyne s^–1 cm^–5 in the control group]. Cardiac outputwas increased. Plasma lidocaine concentrations were threefoldhigher after i.p. administration than after i.v. administration.After pneumoperitoneum insufflation, plasma lysine-vasopressinconcentrations increased in all groups (control 74%, saline65%, i.p. lidocaine 57%, i.v. lidocaine 74%). Conclusions. I.V. and i.p. lidocaine blunted systemic vascularresponses to carbon dioxide pneumoperitoneum in pigs, but withoutinfluencing vasopressin release. Br J Anaesth 2003; 90: 343–8     

Effect of remifentanil infusion rate on stress response to the pre-bypass phase of paediatric cardiac surgery

Background. Opioids are used routinely to eliminate the stressresponse in the pre-bypass phase of paediatric cardiac surgery.Remifentanil is a unique opioid allowing a rapidly titratableeffect. No data are available regarding a suitable remifentanildose regimen for obtunding stress and cardiovascular responsesto such surgery. Methods. We recruited 49 infants and children under 5 yr oldwho were randomized to receive one of four remifentanil infusionrates (0.25, 1.0, 2.5, or 5.0 µg kg^–1 min^–1).Blood samples were obtained at induction, pre-surgery, 5 minafter opening the chest, and immediately pre-bypass. Whole bloodglucose was measured at all time points while cortisol and neuropeptideY (NPY) were measured in the first and last samples. Heart rateand arterial pressure were also recorded. Results. There was a significant increase in whole blood glucose5 min after opening the chest and pre-bypass (P=0.009, P=0.002)in patients receiving remifentanil 0.25 µg kg^–1min^–1, but not in those receiving higher doses. Increasedremifentanil dosage was associated with reduced plasma cortisolduring surgery (P<0.001). Baseline NPY showed considerablevariation and there was no association between pre-bypass NPYand remifentanil dose. There was a significantly higher heartrate at the pre-bypass stage of surgery in the remifentanil0.25 µg kg^–1 min^–1 group compared with higherdoses (P=0.0006). Four out of five neonates with complex cardiacconditions showed severe bradycardia associated with remifentanil. Conclusions. In infants and children under 5 yr, remifentanilinfusions of 1.0 µg kg^–1 min^–1 and greatercan suppress the glucose increase and tachycardia associatedwith the pre-bypass phase of cardiac surgery, while 0.25 µgkg^–1 min^–1 does not. Remifentanil should be usedwith caution in neonates with complex congenital heart disease. Br J Anaesth 2004; 92: 187–94     

Effects of xenon anaesthesia on the circulatory response to hypoventilation

Background. Circulatory response to hypoventilation is aimedat eliminating carbon dioxide and maintaining oxygen delivery(DO₂) by increasing cardiac output (CO). The hypothesis thatthis increase is more pronounced with xenon than with isofluraneanaesthesia was tested in pigs. Methods. Twenty pigs received anaesthesia with xenon 0.55 MAC/remifentanil0.5 µg kg^–1 min^–1 (group X, n=10) or isoflurane0.55 MAC/remifentanil 0.5 µg kg^–1min^–1 (groupI, n=10). CO, heart rate (HR), mean arterial pressure (MAP)and left ventricular fractional area change (FAC) were measuredat baseline, after 5 and 15 min of hypoventilation and after5, 15 and 30 min of restored ventilation. Results. CO increased by 10–20% with both anaesthetics,with an equivalent rise in HR, maintaining DO₂ in spite of a20% reduction in arterial oxygen content. Decreased left ventricular(LV) afterload during hypoventilation increased FAC, and thiswas more marked with xenon (0.60–0.66, P<0.05 comparedwith baseline and isoflurane). This difference is attributedto negative inotropic effects of isoflurane. Increased pulmonaryvascular resistance during hypoventilation was found with bothanaesthetics. Conclusion. The cardiovascular effects observed in this modelof moderate hypoventilation were sufficient to maintain DO₂.Although the haemodynamic response appeared more pronouncedwith xenon, differences were not clinically relevant. An increasein FAC with xenon is attributed to its lack of negative inotropiceffects.     

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.     

Differential effects of thiopental on methacholine- and serotonin-induced bronchoconstriction in dogs

Background. Thiopental sometimes causes bronchospasm duringinduction of anaesthesia. In addition, we have reported previouslythat thiopental produced transient bronchospasm, which was blockedby atropine pretreatment, and worsened histamine-induced bronchoconstrictionin dogs. Previous in vitro reports suggest that synthesis ofcontractile cyclooxygenase products, such as thromboxane A₂,may be involved in the mechanism of bronchospasm. However, thein vivo spastic effects have not been defined comprehensively. Methods. Twenty-seven mongrel dogs were anaesthetized with pentobarbital.Bronchoconstriction was elicited with methacholine (0.5 µg kg^–1+5.0µg kg^–1 min^–1; Mch group, n=7) orserotonin (10 µg kg^–1+1 mg kg^–1 h^–1;5HT group, n=20), and assessed as percentage changes in bronchialcross-sectional area (BCA, basal=100%) using a bronchoscope.In the 5HT group, dogs were subdivided into four groups of fiveeach: S-5HT, I-5HT, 5HT-S and 5HT-A. In the S-5HT and I-5HTgroups, 30 min before serotonin infusion dogs were given salineand indomethacin respectively at 5 mg kg^–1 i.v. Inall groups, 30 min after bronchoconstrictor infusion started,dogs were given thiopental at doses between 0 (saline) and 20mg kg^–1. In the 5HT-S and 5HT-A groups, dogs weregiven saline or atropine 0.2 mg kg^–1 i.v. 5 min afterthiopental 20 mg kg^–1. Results. Methacholine and serotonin reduced BCA by about 50and 40% respectively. Thiopental 20 mg kg^–1 increasedand decreased BCA by about 20 and 10% in the Mch and 5HT groupsrespectively. Indomethacin and atropine did not attenuate thepotentiation of serotonin bronchoconstriction produced by thiopental. Conclusion. The present study indicates that thiopental mayattenuate or worsen bronchoconstriction induced by muscarinicor serotonin receptor stimulation, respectively. The synthesisof contractile cyclooxygenase products and cholinergic stimulationmay not be involved in the contractile effect of thiopentalon serotonin bronchoconstriction. Br J Anaesth 2003; 91: 379–84     

Pharmacokinetics of remifentanil and its major metabolite, remifentanil acid, in ICU patients with renal impairment

Background. The pharmacokinetics of remifentanil, an opioidanalgesic metabolized by non-specific esterases, and its principalmetabolite, remifentanil acid (RA), which is excreted via thekidneys, were assessed as part of an open-label safety studyin intensive care unit (ICU) patients with varying degrees ofrenal impairment. Methods. Forty adult ICU patients with normal/mildly impairedrenal function (creatinine clearance [CL_cr] 62.9 (SD) 14.5 mlmin^–1; n=10) or moderate/severe renal impairment (CL_cr14.7 (15.7) ml min^–1; n=30) were included. Remifentanilwas infused for up to 72 h, at a starting rate of 6–9µg kg^–1 h^–1 titrated to achieve a target sedationlevel, with additional propofol (0.5 mg kg^–1 h^–1)if required. Intensive arterial sampling was performed for upto 72 h after infusion. Pharmacokinetic parameters obtainedby simultaneous modelling of remifentanil and RA data were statisticallycompared between the two groups. Results. Remifentanil pharmacokinetics were not significantlyaffected by renal status. RA clearance in the moderate/severegroup was reduced to about 25% that of the normal/mild group(41 (29) vs 176 (49) ml kg^–1 h^–1, P<0.0001).Metabolic ratio, a predictor of the ratio of RA to remifentanilconcentrations at steady state, was approximately eight-foldhigher in the moderate/severe group relative to the normal/mildgroup (116 (110) vs 15 (4), P<0.0001). Maximum RA levelsapproached 700 ng ml^–1 in the moderate/severe group. Conclusions. Although RA accumulates in patients with moderate/severerenal impairment, pharmacokinetic modelling predicts that RAconcentrations during a 9 µg kg^–1 h^–1 remifentanilinfusion for up to 15 days would not exceed those reported inthe present study, for which no associated prolongation of µ-opioideffects was observed. Br J Anaesth 2004; 92: 493–503     

Haemodynamic effects of haemorrhage during xenon anaesthesia in pigs

Background. It was hypothesized that xenon would stabilize meanarterial pressure (MAP) in haemorrhagic shock, recovery, andvolume resuscitation, because a higher MAP has been observedwith xenon, when compared with isoflurane anaesthesia. The responsesto haemorrhage and subsequent volume replacement were thereforecompared between xenon and isoflurane anaesthesia, in pigs. Methods. Pigs were randomized to anaesthesia with xenon 0.55MAC (group Xe, n=9) or isoflurane 0.55 MAC (group Iso, n=9),each with remifentanil 0.5 µg kg^–1 min^–1.MAP, heart rate, cardiac output (CO), and left ventricular fractionalarea change (FAC) were collected at control (1), after haemorrhage(20 ml kg^–1) (2), after 10 min of recovery (3), aftervolume replacement (4), and 30 min later (5). Data were analysedby two-way repeated measures ANOVA. Results. Blood loss decreased MAP (Xe: 103 [21] to 53 [24] mmHg; Iso: 92 [18] to 55 [14] mm Hg) and CO (Xe: 4.1 [0.8] to2.6 [0.5] litre min^–1; Iso: 5.1 [1.1] to 3.8 [1.2] litremin^–1), in spite of significant tachycardia. MAP and COrecovered to about 75% of control, and subsequent volume replacementcompletely reversed symptoms in both groups, but increased FAConly with xenon. Conclusion. Haemodynamic response to acute haemorrhage appearedfaster with xenon/remifentanil than with isoflurane/remifentanilanaesthesia. In particular MAP decrease and short-term recoverywere more marked with xenon (P<0.02). In the xenon group,volume replacement increased FAC compared with control and isoflurane(P<0.02).     

Effects of intramuscular administration of lidocaine or bupivacaine on induction and maintenance doses of propofol evaluated by bispectral index

Background. Interest in combining local and general anaesthesiahas lead to studies investigating possible interactions. Ina prospective, randomized, double-blind study, we tested whetherlocal anaesthetics administered i.m. potentiate the hypnoticeffect of propofol. Methods. Sixty patients (three groups, n=20) undergoing lowerabdominal surgery with total i.v. propofol anaesthesia wereinvestigated. Patients in Group B received i.m. bupivacaine(5 mg ml^–1) 1 mg kg^–1, patients in Group Lreceived i.m. lidocaine (100 mg ml^–1) 2 mg kg^–1and patients in Group C received i.m. saline 5 ml beforeoperation. Hypnosis was measured with bispectral index (BIS). Results. The induction (BIS <45), and the maintenance dosesof propofol (BIS between 40 and 50) were significantly lessin Group B and Group L compared with the control group. Inductiondoses were 1.58 (SD 0.39), 1.56 (0.24) and 2.03 (0.33) mg kg^–1respectively; P<0.0001. Maintenance doses were 6.33 (2.06),7.08 (1.23) and 9.95 (2.02) mg kg^–1 respectively in thefirst hour; P<0.0001. Groups B and L were associated withan attenuated haemodynamic response to both induction and intubation. Conclusion. I.M. administered local anaesthetics are associatedwith a decrease in both the induction and maintenance dosesof propofol during total i.v. anaesthesia and a reduction inhaemodynamic responses. Br J Anaesth 2002; 89: 849–52