Interstitial muscle concentrations of rocuronium under steady-state conditions in anaesthetized dogs: actual versus predicted values

Introduction. The objective of this study was to compare rocuroniumeffect (C_e) and peripheral (C₂) compartment concentrations predictedby pharmacokinetic–pharmacodynamic (PK-PD) modelling withthose measured in plasma (C_p) and in the interstitial fluidof muscle tissue (C_ISF,u) by microdialysis in anaesthetizeddogs. Methods. After approval by the Animal Care Committee, eightadult male dogs with a body weight ranging from 7 to 18 kg wereanaesthetized with pentobarbital. Each dog received a 2-minrocuronium infusion of 0.15 mg kg^–1 min^–1 followedby a 118-min infusion of 60 µg kg^–1 min^–1via the right jugular vein. Arteriovenous gradient across thehindlimb was measured at 40, 60, 100 and 120 min. Three microdialysissamples were collected at 40-min intervals. Once the infusionstopped, arterial samples were collected every 2 min for thefirst 10 min and every 20 min for the next 120 min. Neuromuscularfunction was monitored using train-of-four stimulation untilfull recovery. Dogs were then killed and a biopsy of muscletissue was performed (C_m). Results. At steady state, the mean C_ISF,u value was 1353 ngml^–1. After correction for the unbound fraction in plasma,the mean C_e,corr and C_2,corr were 1681 and 1481 ng ml^–1,respectively. At the terminal sampling point, C_m was 10-foldhigher than C_p. Conclusion. Unbound concentration of rocuronium measured inthe muscle interstitial fluid under steady-state conditionsconfirms that parametric PK-PD modelling gives reliable estimatesof effect site concentrations. Rocuronium accumulates in muscletissue, probably by non-specific protein binding in the interstitialspace.     

Effect site concentrations of remifentanil and pupil response to noxious stimulation

Background. Opioid drugs block reflex pupillary dilatation inresponse to noxious stimulation. The relationship between thetarget effect site concentration (Ce_T) of remifentanil and thepupil diameter and reactivity in response to a standard noxiousstimulus were evaluated. Methods. Anaesthesia was induced with propofol TCI to obtainloss of consciousness (LOC) in 12 ASA I/II patients. Thereafter,remifentanil Ce_T was titrated by increments of 1 up to 5 ngml^–1. In the awake state, at LOC and at each plateau levelof remifentanil Ce_T, arterial pressure, heart rate, and BIS(A2000) were recorded. Pupil size and dilatation after a 100Hz tetanic stimulation (T100) were measured at LOC and at eachplateau level of remifentanil Ce_T. Results. LOC was observed at a mean propofol Ce_T of 3.53 (SD0.43) µg ml^–1. Arterial pressure and heart ratedecreased progressively from LOC to 5 ng ml^–1 remifentanilCe_T without any statistical difference between each incrementaldose of remifentanil. Mean BIS values decreased from 96 (2)in the awake state, to 46 (12) at LOC (P<0.05) and then remainedunchanged at all remifentanil Ce_T. Pupil dilatation in responseto 100 Hz tetanic stimulation decreased progressively from 1.55(0.72) to 0.01 (0.03) mm and was more sensitive than pupil diametermeasured before and after 100 Hz tetanus. An inverse correlationbetween pupil dilatation in response to 100 Hz tetanus and anincrease in remifentanil Ce_T from 0 to 5 ng ml^–1 was found(R²=0.68). Conclusions. During propofol TCI in healthy patients, the decreasein pupil response to a painful stimulus is a better measurementof the progressive increase of remifentanil Ce_T up to 5 ng ml^–1than haemodynamic or BIS measurements. Br J Anaesth 2003; 91: 347–52     

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     

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.     

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.     

Onset and duration of mivacurium-induced neuromuscular block in patients with Duchenne muscular dystrophy

Background. To determine the response to mivacurium, we prospectivelystudied onset time and complete spontaneous recovery from mivacurium-inducedneuromuscular block in patients with Duchenne muscular dystrophy(DMD). Methods. Twelve boys with DMD, age 5–14 yr, seven of themwheelchair-bound, ASA II–III, and 12 age- and sex-matchedcontrols (ASA I) were enrolled in the study. Anaesthesia wasinduced with fentanyl 2–3 µg kg^–1 and propofol3–4 mg kg^–1 titrated to effect, and maintained bycontinuous i.v. infusion of propofol 8–12 mg kg^–1and remifentanil as required. The lungs were ventilated withoxygen in air. Neuromuscular transmission was assessed by acceleromyographyusing train-of-four (TOF) stimulation every 15 s. After baselinereadings, a single dose of mivacurium 0.2 mg kg^–1 wasgiven. The following variables were recorded: (i) lag time;(ii) onset time; (iii) peak effect; (iv) recovery of first twitchfrom the TOF response to 10, 25 and 90% (T₁₀, T₂₅, T₉₀) relativeto baseline; (v) recovery index (time between 25 and 75% recoveryof first twitch); and (vi) recovery time (time between 25% recoveryof first twitch and recovery of TOF ratio to 90%). For comparisonbetween the groups the Mann–Whitney U-test was applied. Results. There were no differences between the groups in lagtime, onset time and peak effect. However, all recorded recoveryindices were significantly (P<0.05) prolonged in the DMDgroup. The median (range) for time points T₁₀, T₂₅ and T₉₀ inthe DMD and control group was 12.0 (8–16) vs 8.4 (5–15)min, 14.1 (9–20) vs 10.5 (7–17) min and 26.9 (15–40)vs 15.9 (12–23) min, respectively. The recovery indexand recovery time were similarly prolonged in the DMD group. Conclusions. These results support the assumption that mivacurium-inducedneuromuscular block is prolonged in patients with DMD. This study was presented at the Annual Meeting of the AmericanSociety of Anaesthesiologists, Las Vegas, October 2004. These authors contributed equally to this work.     

Haemodynamic effects of remifentanil in children with and without intravenous atropine. An echocardiographic study

Background. Remifentanil is known to cause bradycardia and hypotension.We aimed to characterize the haemodynamic profile of remifentanilduring sevoflurane anaesthesia in children with or without atropine. Methods. Forty children who required elective surgery receivedinhalational induction of anaesthesia using 8% sevoflurane.They were allocated randomly to receive either atropine, 20µg kg^–1 (atropine group) or Ringer's lactate (controlgroup) after 10 min of steady-state 1 MAC sevoflurane anaesthesia(baseline). Three minutes later (T0), all children receivedremifentanil 1 µg kg^–1 injected over a 60 s period,followed by an infusion of 0.25 µg kg^–1 min^–1for 10 min then 0.5 µg kg^–1 min^–1 for 10 min.Haemodynamic variables and echocardiographic data were determinedat baseline, T0, T5, T10, T15 and T20 min. Results. Remifentanil caused a significant decrease in heartrate compared with the T0 value, which was greater at T20 thanT10 in the two groups: however, the values at T10 and T20 werenot significantly different from baseline in the atropine group.In comparison with T0, there was a significant fall in bloodpressure in the two groups. Remifentanil caused a significantdecrease in the cardiac index with or without atropine. Remifentanildid not cause variation in stroke volume (SV). In both groups,a significant increase in systemic vascular resistance occurredafter administration of remifentanil. Contractility decreasedsignificantly in the two groups, but this decrease remainedmoderate (between –2 and +2 SD). Conclusion. Remifentanil produced a fall in blood pressure andcardiac index, mainly as a result of a fall in heart rate. Althoughatropine was able to reduce the fall in heart rate, it did notcompletely prevent the reduction in cardiac index.     

Glycopyrrolate during sevoflurane-remifentanil-based anaesthesia for cardiac catheterization of children with congenital heart disease

Background. Remifentanil is recommended for use in procedureswith painful intraoperative stimuli but minimal postoperativepain. However, bradycardia and hypotension are known side-effects.We evaluated haemodynamic effects of i.v. glycopyrrolate duringremifentanil–sevoflurane anaesthesia for cardiac catheterizationof children with congenital heart disease. Methods. Forty-five children undergoing general anaesthesiawith remifentanil and sevoflurane were randomly allocated toreceive either saline, glycopyrrolate 6 µg kg^–1or glycopyrrolate 12 µg kg^–1. After induction ofanaesthesia with sevoflurane, i.v. placebo or glycopyrrolatewas administered. An infusion of remifentanil at the rate of0.15 µg kg^–1min^–1 was started, sevofluranecontinued at 0.6 MAC and cisatracurium 0.2 mg kg^–1 wasgiven. Heart rate (HR) and non-invasive arterial pressures weremonitored and noted every minute for the first 10 min and thenevery 2.5 min for subsequent maximum of 45 min. Results. Baseline HR [mean (SD)] of 117 (20) beats min^–1decreased significantly from 12.5 min onwards after startingthe remifentanil infusion in the control group [106 (18) at12.5 min and 99 (16) beats min^–1 at 45 min]. In the groupsreceiving glycopyrrolate, no significant decrease in HR wasnoticed. Glycopyrrolate at 12 µg kg^–1 induced tachycardiabetween 5 and 9 min after administration. Systolic and diastolicarterial pressures decreased gradually, but there were no significantdifferences in the pressures between groups. Conclusion. I.V. glycopyrrolate 6 µg kg^–1 preventsbradycardia during general anaesthesia with remifentanil andsevoflurane for cardiac catheterization in children with congenitalheart disease. Administering 12 µg kg^–1 of glycopyrrolatetemporarily induces tachycardia and offers no additional advantage.     

Pretreatment with remifentanil to prevent withdrawal after rocuronium in children

Background. Pain from rocuronium injection is a common side-effectreported to occur in 50–80% of the patients. This randomized,double-blind, placebo-controlled study was designed to evaluatethe efficacy of pretreatment with i.v. remifentanil on preventionof withdrawal response during rocuronium injection in paediatricpatients. Methods. After obtaining parental consents, 70 paediatric patientswere randomly allocated into two groups to receive either i.v.remifentanil 1 µg kg^–1 (remifentanil group, n=35)or i.v. saline 5 ml (saline group, n=35). Anaesthesia was inducedwith thiopental sodium 2.5% (5 mg kg^–1) and the test drugwas injected over 30 s. One minute after the test drug injection,rocuronium 1% (0.6 mg kg^–1) was injected over 5 s andthe response was recorded. Mean arterial pressure (MAP) andheart rate were recorded on arrival in the operating theatre,before and 1 min after the tracheal intubation. Results. The overall incidence of withdrawal movements was significantlyhigher in the saline group (33 patients; 94%) than that in theremifentanil group (8 patients; 23%) (P<0.001). No patientin the remifentanil group showed generalized movement, whereas51% of patients in the saline group did. Remifentanil preventedsignificant increase in MAP after intubation. Conclusion. This study demonstrated that pretreatment with remifentanil1 µg kg^–1 provided a safe and simple method forreducing the incidence of rocuronium-associated withdrawal movementwith haemodynamic stability in children.     

Remifentanil and nitrous oxide reduce changes in cerebral blood flow velocity in the middle cerebral artery caused by pain

Background. Cerebral blood flow is affected by painful stimuli,and analgesic agents may alter the response of cerebral bloodflow to pain. We set out to quantify the effects of remifentaniland nitrous oxide on blood flow changes caused by experimentalpain. Methods. We simulated surgical pain in 10 conscious volunteersusing increasing mechanical pressure to the tibia. We measuredchanges in cerebral blood flow velocity in the middle cerebralartery (CBFV_MCA) caused by the pain, using transcranial Dopplersonography. We gave increasing doses of remifentanil (0.025,0.05 and 0.1 µg kg^–1 min^–1)or nitrous oxide [20%, 35% and 50% end-tidal concentration (FE'_N2O)]and compared these effects on blood flow changes. Results. Nitrous oxide increased CBFV_MCA only when given at50% FE'_N2O. Remifentanil did not affect CBFV_MCA. Pain increasedCBFV_MCA. Both agents attenuated this pain-induced change inCBFV_MCA with the exception of nitrous oxide at 20% FE'_N2O. Conclusions. Inhalation of nitrous oxide or adminstration ofremifentanil attenuated pain-induced changes in CBFV_MCA. Br J Anaesth 2003: 90: 296–9     

Predictive performance of computer-controlled infusion of remifentanil during propofol/remifentanil anaesthesia

Background. The predictive performance of the available pharmacokineticparameter sets for remifentanil, when used for target-controlledinfusion (TCI) during total i.v. anaesthesia, has not been determinedin a clinical setting. We studied the predictive performanceof five parameter sets of remifentanil when used for TCI ofremifentanil during propofol anaesthesia in surgical patients. Methods. Remifentanil concentration–time data that hadbeen collected during a previous pharmacodynamic interactionstudy in 30 female patients (ASA physical status I, aged 20–65 yr)who received a TCI of remifentanil and propofol during lowerabdominal surgery were used in this evaluation. The remifentanilconcentrations predicted by the five parameter sets were calculatedon the basis of the TCI device record of the infusion rate–timeprofile that had actually been administered to each individual.The individual and pooled bias [median performance error (MDPE)],inaccuracy [median absolute performance error (MDAPE)], divergenceand wobble of the remifentanil TCI device were determined fromthe pooled and intrasubject performance errors. Results. A total of 444 remifentanil blood samples were analysed.Blood propofol and remifentanil concentrations ranged from 0.5to 11 µg ml^–1 and 0.1 to 19.6 ng ml^–1respectively. Pooled MDPE and MDAPE of the remifentanil TCIdevice were –15 and 20% for the parameter set of Mintoand colleagues (Anesthesiology 1997; 86: 10–23), 1 and21%, –6 and 21%, and –6 and 19% for the three parametersets described by Egan and colleagues (Anesthesiology 1996;84: 821–33, Anesthesiology 1993; 79: 881–92, Anesthesiology1998; 89: 562–73), and –24 and 30% for the parameterset described by Drover and Lemmens (Anesthesiology 1998; 89:869–77). Conclusions. Remifentanil can be administered by TCI with acceptablebias and inaccuracy. The three pharmacokinetic parameter setsdescribed by Egan and colleagues resulted in the least biasand best accuracy. Br J Anaesth 2003; 90: 132–41     

Cerebral haemodynamics in patients with chronic renal failure: effects of haemodialysis

Background. We measured middle cerebral artery (MCA) flow velocity(FV), dynamic pressure autoregulation, and carbon dioxide reactivity(CRCO₂) in patients with chronic renal failure before and afterhaemodialysis using transcranial Doppler ultrasonography. Methods. Twelve patients on long-term haemodialysis were recruited.MCA FV was measured continuously. The transient hyperaemic responsetest was used to assess cerebral autoregulation, and per centchange in FV per kPa change in end-tidal carbon dioxide wascalculated to assess CRCO₂. All measurements were recorded beforeand after haemodialysis. Results. MCA FV (mean [SD]) decreased from 57 (10) cm s^–1before to 46 (13) cm s^–1 after haemodialysis (P<0.01).The transient hyperaemic response ratio (THRR) was (mean [SD])1.29 (0.13) before haemodialysis and did not change significantlyfollowing haemodialysis (1.36 [0.10]). CRCO₂ was 21.7 (8.3)%kPa^–1 before haemodialysis and remained unchanged afterwards(20.9 [3.8]% kPa^–1). Values in normal subjects for MCAFV, THRR and CRCO₂ are 56 (12) cm s^–1, 1.26 (0.13) and22 (6)% kPa^–1, respectively. Conclusions. MCA FV decreases significantly after haemodialysis.Dynamic pressure autoregulation and CRCO₂ remain normal in patientswith chronic renal failure, and are not altered significantlyby haemodialysis. Presented at the European Society of Anaesthesiologists AnnualCongress Amsterdam, May 1999.     

Remifentanil or propofol for sedation during carotid endarterectomy under cervical plexus block

Background. During carotid endarterectomy under regional anaesthesia,patients often require medication to control haemodynamic instabilityand to provide sedation and analgesia. Propofol and remifentanilare used for this purpose. However, the benefits, side-effects,and optimal dose of these drugs in such patients are unclear. Methods. Sixty patients were included in a prospective, randomized,single blinded study. All patients received a deep cervicalplexus block with 30 ml ropivacaine 0.75% and were randomizedto receive either remifentanil 3 µg kg^–1 h^–1or propofol 1 mg kg^–1 h^–1. The infusions were startedafter performing the regional block and were stopped at theend of surgery. Arterial pressure, ECG, ventilatory rate, andPa_CO2 were measured continuously and recorded at predeterminedtimes. Twenty-four hours after surgery, patient comfort, andsatisfaction were also evaluated. Results. In three patients, the infusion of remifentanil hadto be stopped because of severe respiratory depression or bradycardia.No significant differences were found between the two groupsin haemodynamic variables or sedative effects, but there wasa significantly greater decrease in ventilatory frequency andincrease in Pa_CO2 in the remifentanil group. The patient’ssubjective impressions and pain control were excellent in bothgroups. Conclusion. As a result of the higher incidence of adverse respiratoryeffects with remifentanil and similar sedative effects, propofolis preferable for sedation during cervical plexus block in elderlypatients with comorbid disease at the dosage used. Br J Anaesth 2002; 89: 637–40     

Maternal and neonatal side-effects of remifentanil patient-controlled analgesia in labour

Background. Remifentanil has been suggested as an ideal opioidfor patient-controlled analgesia (PCA) in labour, but the safetyprofile has not been established. The aims of this preliminaryprospective observational study were to investigate the maternalside-effects and early neonatal effects, and to assess the placentaltransfer of remifentanil PCA during labour. Methods. Women with no known obstetric complications or contraindicationto remifentanil were recruited (n=50). Remifentanil was administeredat a bolus dose of 0.5 µg kg^–1 and a lockout periodof 2 min. A visual analogue scale was used to assess pain, nauseaand itching. Maternal observations were recorded hourly andfetal heart rate trace was assessed every 2 h. Umbilical cordgases, 1 and 5 min Apgar scores and neurological evaluationof the neonate were recorded. Maternal venous blood and umbilicalartery and vein cord blood samples were collected for analysisof remifentanil concentration. Results. Fifty women enrolled in the study (24 multiparous,26 primiparous). There was no evidence of cardiovascular instabilityor respiratory depression. Pain scores decreased significantly,but there was no significant change in nausea after initiatingthe PCA. A statistically significant increase in itching wasfound to be clinically mild and 22 women were slightly drowsy(95% confidence interval [CI], 30–58.7%) but alert tovoice. Ten fetal heart rate traces demonstrated changes in thefirst 20 min, but did not require intervention (95% CI, 10–33.7%).The median 1 and 5 min Apgar scores were 9. The mean umbilicalcord gases and neurological examination were within normal limits.Maternal vein and umbilical vein cord samples demonstrated placentaltransfer of remifentanil, and small amounts were detected inumbilical artery samples. Conclusions. At the bolus dose used remifentanil PCA has anacceptable level of maternal side-effects and minimal effecton the neonate. Remifentanil crosses the placenta and appearsto be either rapidly metabolized or redistributed in the neonate.     

Predicted effect compartment concentration of thiopental at loss of eyelash reflex

We derived the predicted effect compartment concentration ofthiopental, at loss of the eyelash reflex, following three differentinjection regimens. Sixty patients were given thiopental forinduction of anaesthesia. Twenty patients received multiplesmall boluses, 20 patients received a single bolus and 20 patientsreceived an infusion. Computer simulation was then used to derivethe effect compartment concentration. The median concentrationwas not significantly different between the three groups. EC₅₀,derived after combining all three groups was 11.3 µg ml^–1.The EC₀₅–EC₉₅ range was 6.9–18.3 µg ml^–1,suggesting wide inter-individual variation. Br J Anaesth 2001; 86: 422–4     

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     

Effects of thoracic epidural anaesthesia on microvascular gastric mucosal oxygenation in physiological and compromised circulatory conditions in dogs

Background. The effects of thoracic epidural anaesthesia (TEA)on gastric mucosal microvascular haemoglobin oxygenation (µHbO₂)are unclear. At the splanchnic level, reduction of sympathetictone may promote vasodilation and increase µHbO₂. However,these splanchnic effects are counteracted by systemic effectsof TEA (e.g., decreased cardiac output (CO) and mean arterialpressure (MAP)), thus making the net effect on µHbO₂ difficultto predict. In this respect, effects of TEA on µHbO₂ maydiffer between physiological and compromised circulatory conditions,and additionally may depend on adequate fluid resuscitation.Furthermore, TEA may alter the relationship between regionalµHbO₂ and systemic oxygen-transport (DO₂). Methods. Chronically instrumented dogs (flow probes for CO measurement)were anaesthetized, their lungs ventilated and randomly receivedTEA with lidocaine (n=6) or epidural saline (controls, n=6).Animals were studied under physiological and compromised circulatoryconditions (PEEP 10 cm H₂O), both with and without fluid resuscitation.We measured gastric mucosal µHbO₂ by reflectance spectrophotometry,systemic DO₂, and systemic haemodynamics (CO, MAP). Results. Under physiological conditions, TEA preserved µHbO₂(47 (3)% and 49 (5)%, mean (SEM)) despite significantly decreasingDO₂ (11.3 (0.8) to 10.0 (0.7) ml kg^–1 min^–1) andMAP (66 (2) to 59 (3) mm Hg). However, during compromised circulatoryconditions, TEA aggravated the reduction in µHbO₂ (to32 (1)%), DO₂ (to 6.7 (0.8) ml kg^–1 min^–1) and MAP(to 52 (4) mm Hg), compared with controls. During TEA, fluidresuscitation completely restored these variables. TEA preservedthe correlation between µHbO₂ and DO₂, compared with controls. Conclusions. TEA maintains µHbO₂ under physiological conditions,but aggravates the reduction of µHbO₂ induced by cardiocirculatorydepression, thereby preserving the relationship between gastricmucosal and systemic oxygenation. Presented in part at the German Anaesthesia Congress 2003 (April9–12, Munich, Germany) and the European Society of IntensiveCare Congress 2003 (October 5–8, Amsterdam, The Netherlands).     

Spectral entropy measurement of patient responsiveness during propofol and remifentanil. A comparison with the bispectral index

Background. We compared two spectral entropies, state entropy(SE) and response entropy (RE), based on the irregularity ofthe EEG, to measure loss of response to verbal command (LOR_verbal)and noxious stimulus (LOR_noxious) with the bispectral index(BIS) during propofol infusion with and without remifentanil. Methods. Three groups of 20 patients received an effect-sitecontrolled propofol infusion (Ce_PROP) starting at 1 µgml^–1 and increased in steps of 0.5 µg ml^–1at 4 min intervals. In addition, a remifentanil infusion wasmaintained at a group-dependent, fixed effect-site target concentration(Ce_REMI) (0, 2 or 4 ng ml^–1). The ability of BIS, SE orRE to predict LOR_verbal and LOR_noxious were compared with thechanges in BIS, SE and RE using logistic regression, predictionprobability (P_K), and sensitivity/specificity. Results. In all groups, BIS, SE and RE decreased with increasingCe_PROP. However, BIS decreased more smoothly than SE and REat deeper levels of sedation. At LOR_verbal, BIS₅₀, SE₅₀ andRE₅₀ increased with increasing Ce_REMI. BIS, SE and RE all detectedLOR_verbal accurately but BIS performed better at 100% sensitivity.Sensitivity/specificity for detection of LOR_verbal decreasedfor all methods with increasing Ce_REMI. LOR_noxious was poorlydescribed by all measures. Conclusion. LOR_verbal was detected accurately by BIS, SE andRE except for 100% sensitivity, where BIS performed better.Though BIS, SE and RE were influenced by remifentanil duringpropofol administration, their ability to detect LOR_verbal remainedaccurate. None of the measures predicted LOR_noxious.