Recovery after remifentanil and sufentanil for analgesia and sedation of mechanically ventilated patients after trauma or major surgery

We investigated the analgesic effect and the neurological recoverytime after administration of remifentanil in mechanically ventilatedpatients in an intensive care unit. Twenty patients, after traumaor major surgery with no intracranial pathology, were randomizedto receive either remifentanil/propofol (n=10) or sufentanil/propofol(n=10). A sedation score and a simplified pain score were usedto assess adequate sedation and analgesia. Medication was temporarilystopped after 24 h. Immediately before and 10 and 30 min after,the degree of sedation and pain score were evaluated. Adequateanalgesia and sedation was achieved with remifentanil 10.6 µgkg^–1 h^–1 and propofol 2.1 mg kg^–1 h^–1,or sufentanil 0.5 µg kg^–1 h^–1 and propofol1.3 mg kg^–1 h^–1. The difference in propofol dosebetween groups was significant. Ten minutes after terminatingthe medication, the degree of sedation decreased significantlyafter remifentanil and all patients could follow simple commands.During the following 20 min, all patients with remifentanilemerged from sedation and complained of considerable pain. Bycontrast, in the sufentanil group, only six (7) responded tocommands after 10 (30) min and their pain score remained essentiallyunchanged during the 30-min observation period. We concludethat, in contrast to sufentanil, remifentanil facilitates rapidemergence from analgesia and sedation, allowing a clinical neurologicalexamination within 10–30 min in mechanically ventilatedpatients with no intracranial pathology. Br J Anaesth 2001; 86: 763–8     

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     

Sedative, haemodynamic and respiratory effects of dexmedetomidine in children undergoing magnetic resonance imaging examination: preliminary results

Background. We evaluated the sedative, haemodynamic and respiratoryeffects of dexmedetomidine and compared them with those of midazolamin children undergoing magnetic resonance imaging (MRI) procedures. Methods. Eighty children aged between 1 and 7 yr were randomlyallocated to receive sedation with either dexmedetomidine (groupD, n=40) or midazolam (group M, n=40). The loading dose of thestudy drugs was administered for 10 min (dexmedetomidine 1 µgkg^–1 or midazolam 0.2 mg kg^–1) followed by continuousinfusion (dexmedetomidine 0.5 µg kg^–1 h^–1or midazolam 6 µg kg^–1 min^–1). Inadequatesedation was defined as difficulty in completing the procedurebecause of the child's movement during MRI. The children whowere inadequately sedated were given a single dose of rescuemidazolam and/or propofol intravenously. Mean arterial pressure(MAP), heart rate (HR), peripheral oxygen saturation (     

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     

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.     

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.     

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     

Comparison of the role of endothelin, vasopressin and angiotensin in arterial pressure regulation during sevoflurane anaesthesia in dogs

Background. In this study we aimed to clarify the role of endothelinin arterial pressure regulation during anaesthesia with increasingconcentrations of sevoflurane (1–3 MAC) and compare itwith those of vasopressin and angiotensin. Methods. After an awake control period, on different days, sixdogs underwent each of the following four interventions: sevofluraneanaesthesia alone (1–3 MAC), sevoflurane after block ofeither endothelin receptors using tezosentan (3 mg kg^–1followed by 3 mg kg^–1 h^–1), vasopressinV_1a receptors using [d(CH₂)₅Tyr(Me²)]AVP (40 µg kg^--1)or angiotensin receptors using losartan (6 mg kg^–1 h^–1).Plasma concentrations of endothelin, big endothelin, vasopressinand renin were measured. Effects of sevoflurane in the presenceand absence of the respective receptor block were analysed andcompared using analysis of variance for repeated measures (ANOVAfollowed by Fisher’s PLSD (protected least significantdifference) (P<0.05)). Results. Mean arterial pressure decreased in a dose-dependentmanner with sevoflurane during all interventions. At 1 MAC,this decrease was greatest during angiotensin receptor block(mean (SEM), –41 (3) mm Hg), intermediate duringvasopressin and endothelin receptor block (–31 (4) and–30 (2) mm Hg respectively), and least during sevofluranealone (–24 (3) mm Hg). The course of systemic vascularresistance mirrored the course of arterial pressure, while cardiacoutput did not differ between groups. Plasma concentrationsof endothelin, big endothelin and renin did not change duringany intervention, whereas vasopressin concentration increasedfrom     

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.     

Comparison of propofol/remifentanil and sevoflurane/remifentanil for maintenance of anaesthesia for elective intracranial surgery

Background. Propofol and sevoflurane are suitable agents formaintenance of anaesthesia during neurosurgical procedures.We have prospectively compared these agents in combination withthe short-acting opioid, remifentanil. Methods. Fifty unpremedicated patients undergoing elective craniotomyreceived remifentanil 1 µg kg^–1 followed by an infusioncommencing at 0.5 µg kg^–1 min^–1 reducing to0.25 µg kg^–1 min^–1 after craniotomy. Anaesthesiawas induced with propofol, and maintained with either a target-controlledinfusion of propofol, minimum target 2 µg ml^–1 orsevoflurane, initial concentration 2%_ET. Episodes of mean arterialpressure (MAP) more than 100 mm Hg or less than 60 mm Hg formore than 1 min were defined as hypertensive or hypotensiveevents, respectively. A surgical assessment of operating conditionsand times to spontaneous respiration, extubation, obey commandsand eye opening were recorded. Drug acquisition costs were calculated. Results. Twenty-four and twenty-six patients were assigned topropofol (Group P) and sevoflurane anaesthesia (Group S), respectively.The number of hypertensive events was comparable, whilst morehypotensive events were observed in Group S than in Group P(P=0.053, chi-squared test). As rescue therapy, more labetolol[45 (33) vs 76 (58) mg, P=0.073] and ephedrine [4.80 (2.21)vs 9.78 (5.59) mg, P=0.020] were used in Group S. Between groupdifferences in recovery times were small and clinically unimportant.The combined hourly acquisition costs of hypnotic, analgesic,and vasoactive drugs appeared to be lower in patients maintainedwith sevoflurane than with propofol. Conclusion. Propofol/remifentanil and sevoflurane/remifentanilboth provided satisfactory anaesthesia for intracranial surgery.     

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.     

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.     

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     

Sedation during spinal anaesthesia in infants

Background. Neuraxial anaesthesia in adults decreases the doseof i.v. or inhalational anaesthetic needed to reach a desiredlevel of sedation. Furthermore, spinal anaesthesia alone hasa sedative effect. The mechanism behind this phenomenon is presumedto be decreased afferent stimulation of the reticular activatingsystem after sympatholysis. We hypothesized that this mechanismis equally active in infants undergoing spinal anaesthesia. Methods. In total, 20 unpremedicated former preterm infantsunderwent surgery under spinal anaesthesia with hyperbaric bupivacaine0.5% 1 mg kg^–1 with epinephrine 10 µg kg^–1.No additional sedatives or anaesthetics were administered. Sedationwas evaluated using the bispectral index (BIS) score and the95% spectral edge frequency (SEF₉₅). Results. After spinal anaesthesia, mean (SD) BIS began to decreasesignificantly from baseline 97.0 (1.1) to 83.9 (14.4) after15 min (P=0.006). BIS decreased further, reaching the lowestvalues after 30 min [62.2 (14.0); P<0.00001]. Mean (SD) SEF₉₅declined from baseline 26.1 (1.8) Hz to 24.3 (3.1) after 5 min(P=0.02) and further to 9.9 (3.8) after 30 min (P<0.00001).Mean arterial pressure also decreased significantly from 66.5(4.7) mm Hg within 10 min to 56.1 (5.6) after spinal anaesthesia(P=0.0002), while heart rate remained stable. Conclusions. These results suggest that sedation after spinalanaesthesia in infants is at least as pronounced as in adults.The sedative effect of spinal anaesthesia should be kept inmind when additional sedatives are administered, especiallyin former preterm infants.     

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.     

Comparison of Alaris AEP index and bispectral index during propofol-remifentanil anaesthesia

Background. The Alaris AEP monitor^TM (Alaris, UK, version 1.4)is the first commercially available auditory evoked potential(AEP) monitor designed to estimate the depth of anaesthesia.It generates an ‘Alaris AEP index’ (AAI), whichis a dimensionless number scaled from 100 (awake) to 0. Thisstudy was designed to compare AAI and BIS^TM (Aspect, USA, versionXP) values at different levels of anaesthesia. Methods. Adult female patients were premedicated with diazepam0.15 mg kg^–1 orally on the morning of surgery. Electrodesfor BIS and Alaris AEP monitoring and a headphone to give auditorystimuli were applied as recommended by the manufacturers. Anaesthesiawas induced with remifentanil (0.4 µg kg^–1 min^–1)and a propofol target-controlled infusion (Diprifusor^TM TCI,AstraZeneca, Germany) to obtain a predicted concentration ofinitially 3.5 µg ml^–1. After loss of consciousnessthe patients were given 0.5 mg kg^–1 of atracurium. Aftertracheal intubation, remifentanil was given at 0.2 µgkg^–1 min^–1 and the propofol infusion was adjustedto obtain BIS target values of 30, 40, 50, and 60. AAI and BISvalues were recorded and matched with the predicted propofoleffect-site concentrations. Prediction probability was calculatedfor consciousness vs unconsciousness. Values are mean (SD). Results. Fifty female patients, 53 (15), range 18–78 yr,ASA I or II were studied. Mean values before induction of anaesthesiawere 95 (4), range 99–82 for BIS and 85 (12), range 99–55for AAI. With loss of eyelash reflex both values were significantlyreduced to 64 (13), range 83–39 for BIS (P<0.05) and61 (22), range 99–15 for AAI (P<0.05). The predictionprobability P_K for consciousness vs unconsciousness (i.e. lossof eyelash reflex) was better for BIS (P_K=0.99) than for AAI(P_K=0.79). At a BIS of 30, 40, 50, and 60 the correspondingAAI values were 15 (6), 20 (8), 28 (11), and 40 (16), and thesewere significantly different. Conclusions. During propofol-remifentanil anaesthesia a decreaseof the depth of anaesthesia as indicated by BIS monitoring isaccompanied by corresponding effects shown by the AAI. However,wide variation in the awake values and considerable overlapof AAI values between consciousness and unconsciousness, suggestsfurther improvement of the AAI system is required. Br J Anaesth 2003; 91: 336–40     

Sedative, analgesic and cognitive effects of clonidine infusions in humans

This placebo-controlled, randomized study evaluated, on separatedays, the dose–response relationship for 1 h infusionsof clonidine 1, 2 and 4 µg kg^–1 h^–1,in eight healthy volunteers aged 22–30 yr. Responseend-points included sedation (bispectral index, visual analoguescale and observer assessment of sedation), analgesia to a coldpressor test, memory (recall of word lists), cognitive function(digit symbol substitution test (DSST)), respiratory function(respiratory rate, end-tidal carbon dioxide, oxygen saturation)and haemodynamic stability (heart rate and mean arterial pressure).Clonidine infusions resulted in significant and progressivesedation, but all subjects were easily awoken to perform testsand evaluations. Statistically significant analgesia, memoryimpairment and reduced performance on the DSST occurred during4 µg kg^–1 h^–1 infusions (resultingin a plasma concentration of 2 ng ml^–1. There were nostatistically significant changes in cardiorespiratory variablesthroughout the study. Br J Anaesth 2001; 86: 5–11     

Pharmacokinetics of dexmedetomidine infusions for sedation of postoperative patients requiring intensive caret

Background. The pharmacokinetics of the alpha-2 adrenoceptoragonist dexmedetomidine were studied in 10 patients requiringpostoperative sedation and mechanical ventilation in the intensivecare unit (ICU), and compared with previous volunteer data. Methods. On arrival in the ICU, sedation with dexmedetomidinewas commenced with a loading dose of 2.5 µg kg^–1 h^–1over 10 min followed by a maintenance infusion of 0.7 µg kg^–1 h^–1into a central vein. Blood samples for measurement of plasmadexmedetomidine concentrations were taken during and after sedativeinfusions at predetermined intervals. Pharmacokinetic variableswere estimated using non-compartmental methods. In addition,non-linear mixed effects modelling was used to obtain variableestimates not readily attainable from non-compartmental methods.Respiratory and haemodynamic data were recorded to enable correlationof any adverse events with the calculated pharmacokinetic profile. Results. The harmonic mean distribution half-life of dexmedetomidinewas 8.6 min and the harmonic mean terminal half-life was3.14 h. Steady-state volume of distribution averaged 173 litres,clearance averaged 48.3 litres h^–1, and themean residence time averaged 3.86 h. Conclusions. Mean dexmedetomidine pharmacokinetic variablesseen in postoperative, intensive care patients were similarto those previously found in volunteers, with the exceptionof the steady-state volume of distribution. A small loadingdose provided effective sedation with no adverse events. Br J Anaesth 2002; 88: 669–75     

Haemodynamic effects of three doses of dihydroergotamine during spinal anaesthesia

We performed a randomized study comparing the haemodynamic effectsof three doses of the vasopressor dihydroergotamine (DHE) (5,10 and 15 µg kg^–1) in 30 ASA 1 and 2 patients,aged 53–87 yr, undergoing spinal anaesthesia. Non-invasivesystolic arterial pressure (SAP), heart rate and central venouspressure (CVP) were recorded continuously for 25 min. Intravenousfluids were withheld during this period. All three doses ofDHE reversed the lowering effects of spinal anaesthesia on SAPand CVP (P<0.0001), and these effects were smooth in onsetand sustained. Whereas the lowest (5 µg kg^–1)dose restored SAP and CVP to near prespinal values, the higher(10 and 15 µg kg^–1) doses resulted inabove-baseline increases in SAP of 7% and in CVP of 2.7 cm H₂O(P<0.05). The haemodynamic profile of DHE makes it a usefulagent for managing hypotension during spinal anaesthesia. Adose of 5–10 µg kg^–1 is recommended. Br J Anaesth 2001; 87: 499–501     

Cerebrospinal fluid and blood propofol concentration during total intravenous anaesthesia for neurosurgery

Background. The aim of this paper is to compare the propofolconcentration in blood and cerebrospinal fluid (CSF) in patientsscheduled for different neurosurgical procedures and anaesthetizedusing propofol as part of a total intravenous anaesthesia technique. Methods. Thirty-nine patients (ASA I–III) scheduled forelective intracranial procedures, were studied. Propofol wasinfused initially at 12 mg kg^–1 h^–1 and thenreduced in steps to 9 and 6 mg kg^–1 h^–1. Duringanaesthesia, bolus doses of fentanyl and cis-atracurium wereadministered as necessary. After tracheal intubation the lungswere ventilated to achieve normocapnia with an oxygen-air mixture(FI_O2=0.33). Arterial blood and CSF samples for propofol examinationwere obtained simultaneously directly after intracranial drainageinsertion and measured using high-performance liquid chromatography.The patients were divided into two groups depending on the typeof neurosurgery. The Aneurysm group consisted of 13 patientswho were surgically treated for ruptured intracranial aneurysm.The Tumour group was composed of 26 patients who were undergoingelective posterior fossa extra-axial tumour removal. Results. Blood propofol concentrations in both groups did notdiffer significantly (P>0.05). The propofol concentrationin CSF was 86.62 (SD 37.99) ng ml^–1 in the Aneurysm groupand 50.81 (26.10) ng ml^–1 in the Tumour group (P<0.005). Conclusions. Intracranial pathology may influence CSF propofolconcentration. However, the observed discrepancies may alsoresult from quantitative differences in CSF composition andfrom restricted diffusion of the drug in the CSF. Br J Anaesth 2003; 90: 84–6