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.     

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     

Sevoflurane anaesthesia does not induce the formation of sister chromatid exchanges in peripheral blood lymphocytes of children

Background. Compound A, a degradation product of sevoflurane,has been demonstrated to induce sister chromatid exchanges (SCE)in Chinese hamster ovary cells in vitro as a marker for possiblegenotoxicity. We investigated the formation of SCE in mitogen-stimulatedT-lymphocytes of 40 children undergoing sevoflurane anaesthesiafor minor surgical procedures. Methods. Anaesthesia was induced by inhalation of up to 8% sevofluraneand maintained at 2.5–3% in oxygen/nitrous oxide (65/35%)at a fresh gas flow of 3 litre min^–1. Soda lime (humidity12–15%) was used as a carbon dioxide absorbent. Bloodwas drawn directly before induction and after termination ofanaesthesia. Twenty-five second division metaphases of mitogen-stimulatedT-lymphocytes per blood sample were screened for SCE rates usingstandard techniques. Results. Average duration of anaesthesia was 49.6 (SD 24.0)min. Before anaesthesia induction, 7.93 (1.23) SCE per metaphasewere determined. After sevoflurane anaesthesia [1.40 (0.77)MAC h] 7.92 (1.19) SCE per metaphase were observed. Additionally,no differences were evident between male or female children. Conclusion. Short-term administration of sevoflurane anaesthesiadid not induce SCE in T-lymphocytes of children. No indicationfor a possible genotoxic effect has been observed. Br J Anaesth 2003; 90: 233–5     

Opposite effects of depressant and convulsant barbiturate stereoisomers on acetylcholine release from the rat hippocampus in vivo

Background. It has been shown that the R(–) isomer of1-methyl-5-phenyl-5-propyl barbituric acid (MPPB) induces lossof the righting reflex (LRR), while S(+)-MPPB causes pure excitatoryeffects, including convulsions, in vivo. Methods. We studied the effects of the depressant and convulsantMPPB stereoisomers on rat hippocampal acetylcholine (ACh) releasein vivo, using a brain microdialysis technique in freely movinganimals. Results. R(–)-MPPB 60 and 90 mg kg^–1 i.p. decreasedACh release from the rat hippocampus by 44.1 (8.2)% and 60.8(8.2)%, respectively. In the hippocampus, the local applicationof bicuculline, a -aminobutyric acid (GABA)_A receptor antagonist,1 µmol litre^–1 antagonized the inhibitory effectsof R(–)-MPPB 90 mg kg^–1 i.p. In contrast, R(–)-MPPB,S(+)-MPPB 60 and 90 mg kg^–1 i.p. increased ACh releaseto 151.8 (6.8)% and 169.6 (11.1)% of the basal release, respectively. Conclusions. Our results demonstrated that R(–)-MPPB decreased,while S(+)-MPPB increased, rat hippocampal ACh release and thatthe inhibitory effects of R(–)-MPPB may involve the GABA_Areceptor in vivo. These data imply that changes in hippocampalACh due to these agents may be related to their central inhibitoryand stimulatory actions in vivo. Br J Anaesth 2004; 92: 424–6     

Testing of a new pneumatic device to cause pain in humans

Background. Surgical pain typically combines superficial anddeep pain. We wished to generate pain that resembled surgicalpain, reliably and reproducibly, in volunteers. Methods. We constructed a computer-controlled pneumatic deviceto apply pressure to the anterior tibia. The reproducibilityof the pain was tested by rating the pressure that caused painrated 4–5 on a visual analogue scale (VAS) on days 0,7, and 24 in 10 volunteers. The effect of remifentanil (0.025,0.05, 0.075, and 0.1 µg kg^–1 min^–1) on paintolerance in another set of volunteers (n=11) was used as anindirect measure of the reliability of pain production. Results. The pressure needed (0.7 (0.3) to 0.9 (0.4) atm (mean(SD)) to induce pain rated 4–5 (VAS) did not vary, showinglong-term reproducibility of the method. When pressure was appliedto cause increasing pain in volunteers (n=11) 0.05 µgkg^–1 min^–1 remifentanil increased pain toleranceby 50%. An approximate doubling of the dose (0.1 µg kg^–1min^–1) increased pain tolerance significantly more. Thelinear logarithmic dose-effect relationship shows that the devicecauses pain reliably, and this can be reduced with opioid treatment. Conclusion. This pneumatic device can apply pain reliably andreproducibly. Br J Anaesth 2004; 92: 532–5     

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     

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 three different L-type Ca2+ entry blockers on airway constriction induced by muscarinic receptor stimulation

Background. The crucial role of L-type Ca²⁺ channels in airwaysmooth muscle contraction suggests that these channels couldbe an important therapeutic target. There are three separatedrug binding sites on this channel: those for dihydropyridines,benzothiazepines and phenyl alkylamines. In this study, we examinedthe effects of the dihydropyridines nifedipine and nicardipine,the benzothiazepine diltiazem, and the phenylalkylamine verapamilon airway constriction. Methods. Tension of guinea-pig tracheal strips was measuredisometrically in vitro with a force displacement transducer.Strips were precontracted with carbachol 10^–7 M with orwithout 4-aminopyridine 10^–3 M, a voltage-sensitive K⁺channel blocker. Then, nifedipine 10^–8–10^–4M, diltiazem 10^–8–3x10^–4 M or verapamil 10^–8–3x10^–4M was added cumulatively to the organ bath (n=6 each). The bronchialcross-sectional area of pentobarbital-anaesthetized dogs wasassessed using a bronchoscopy method. Bronchoconstriction waselicited with methacholine 0.5 µg kg^–1 plus 5 µgkg^–1 min^–1, and then nicardipine 0–1000 µgkg^–1, diltiazem 0–3000 µg kg^–1 or verapamil0–3000 µg kg^–1 were given i.v. (n=7 each). Results. In the in vitro experiments, nifedipine and diltiazemfully reversed carbachol-mediated tracheal contraction withlogIC₅₀ values of 4.76 (SEM 0.22) (mean 17.5 µM) and 4.60(0.33) (mean 24.8 µM), respectively. Although verapamil10^–6–10^–4 M reversed the contraction by 87.2%,strip tension re-increased by 18.1% following maximal relaxationwith verapamil 3x10^–4 M. This re-increase was almost fullyabolished by pretreatment with 4-aminopyridine. In the in vivoexperiments, nicardipine and diltiazem dose-dependently reversedmethacholine-induced bronchoconstriction, with logID₅₀ valuesof 3.22 (0.05) (mean 0.60 mg kg^–1) and 1.85 (0.32) (mean14.0 mg kg^–1), respectively. Verapamil worsened methacholine-inducedbronchoconstriction. Conclusions. Although supraclinical doses of dihydropyridinesand benzothiazepines can produce airway relaxant effects, theseagents are unlikely to be used in the treatment of bronchoconstriction.In addition, verapamil may aggravate airway constriction. Br J Anaesth 2003; 90: 671–5     

Dynamic aspects of acute tolerance to allopregnanolone evaluated using anaesthesia threshold in male rats

Background. It is unclear if allopregnanolone (AlloP) anaesthesiacan induce tolerance. Acute tolerance is defined as alteredsensitivity to a drug during a single continuous exposure. Methods. Induction of acute tolerance to AlloP was studied inmale rats using a threshold technique of deep anaesthesia. AlloPwas infused at a dose rate of 4.0 mg kg^–1 min^–1.The infusion was stopped when a burst suppression of 1 s ormore (the ‘silent second’, SS) occurred in the EEG.To maintain anaesthesia, the infusion was restarted when noSS had been seen in the EEG for 1 min. This interrupted targetedinfusion towards an EEG end-point (SS) was continued until 30,60 or 90 min of anaesthesia had been reached. At these timesthe rats were killed and AlloP concentrations in serum, muscle,fat and different brain regions were determined by radioimmunoassay. Results. Maintenance dose rate (MDR) was calculated using 20-minintervals. During anaesthesia the MDR increased (P<0.001)from 0.67 (SEM 0.03) mg kg^–1 min^–1 (in the interval10–30 min) to 0.98 (0.04) mg kg^–1 min^–1 (inthe interval 65–85 min). After 60 min a slight increasein MDR was observed. After 90 min of anaesthesia the AlloP concentrationsin the hippocampus and brainstem had increased by more than50% compared with control values of 25.2 (1.13) and 52.7 (5.81)nmol g^–1 respectively, and after 60 min to around 40%.At 30 min no increase was seen in any brain region analysed. Conclusions. Measurements in vivo and in vitro record acutetolerance to AlloP occurring with a delay.     

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     

Treatment of ischaemic left ventricular dysfunction with milrinone or dobutamine administered during coronary artery stenosis in the presence of beta blockade in pigs

Background. This study examines the effects of phosphodiesterasetype III (PDEIII) inhibition vs beta stimulation on global functionof the left ventricle (LV) and systemic haemodynamics in a porcinemodel of acute coronary stenosis with beta blockade. Methods. A total of 18 adult swine were anaesthetized. Micromanometer-tippedcatheters were placed in the ascending aorta and LV. Two pairsof ultrasonic dimension transducers were placed in the subendocardiumon the short axis proximal to a left anterior descending (LAD)artery occluder and the long axis of the LV. Before ischaemia,i.v. esmolol was infused to decrease baseline heart rate (HR)by approximately 25%, and all animals received an esmolol infusion(150 µg kg^–1 min^–1). Ischaemia was producedby reducing the flow in the LAD artery by approximately 80%,from 17(4) to 3(2) ml min^–1. Animals were randomized toreceive (after esmolol) one of the following: no drug, shamonly (Group 1, n=6), control (C); 50 µg kg^–1 i.v.milrinone (Group 2, n=6) followed by 0.375 µg kg^–1min^–1 (M); or incremental doses of dobutamine (Group 3,n=6) every 10 min (5, 10 and 20 µg kg^–1 min^–1)(D). Left ventricular function data obtained included HR, arterialand LV pressures, cardiac output (CO), Emax and dP/dT. Measurementswere taken during five time periods: before ischaemia (at baseline,after esmolol) and every 10 min during ischaemia (at 10, 20and 30 min). Results. The effects of beta blockade and ischaemia had a significantimpact on contractility (Emax) in Group M and myocardial performance(left ventricular end-diastolic pressure, LVEDP) in all groups.Left ventricular function (Emax, CO, LVEDP and SVR) was betterpreserved when milrinone was added in Group M. A moderate doseof dobutamine (10 µg kg^–1 min^–1) increasedCO. Only the high dose (20 µg kg^–1 min^–1)improved contractility (Emax), but at the expense of increasedSVR. Also, LVEDP with either dose of dobutamine remained highand unchanged. Conclusions. From our limited findings, it would appear thatthere may, theoretically, be some benefit for using milrinonein preference to other inotropic drugs in the presence of betablockade. Milrinone administration should be considered in patientswith acute ischaemic LV dysfunction and preexisting beta blockadebefore using other inotropic drugs such as beta stimulants. Presented in part at: the 27th Annual Meeting of the Societyof Cardiovascular Anesthesiologists, May 14–18, 2005,Baltimore, MD, USA (Anesth Analg 2005; 100: 5CA60).     

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.     

Comparison of the haemodynamic effects of mivacurium and atracurium during fentanyl anaesthesia

We have measured the haemodynamic effects of mivacurium 0.15and 0.2 mg kg^–1, and atracurium 0.5 mg kg^–1 administeredover 10–15 s in patients undergoing coronary artery bypasssurgery under fentanyl anaesthesia. There were no significanthaemodynamic changes in the atracurium group, other than a transientdecrease in pulmonary arterial wedge pressure. Changes in heartrate were small in all three groups. Mivacurium 0.15 mg kg^–1produced changes of only small magnitude (12% decrease in meanarterial pressure and 16% decrease in systemic vascular resistanceindex) however, mivacurium 0.2 mg kg^–1 produced a 25%reduction in mean arterial pressure, a 14% increase in cardiacindex and a 35% decrease in systemic vascular resistance index.Erythema developed in two, three and seven patients after atracurium,mivacurium 0.15mgkg^–1 and mivacurium 0.2 mg kg^–1,respectively. One patient exhibited a 54% decrease in mean arterialpressure, generalized erythema and bronchospasm after mivacurium0.2mg kg^–1. The haemodynamic changes with mivacurium suggestedhistamine release. (Br. J. Anaesth. 1995; 74: 330–332)     

Correlating in vivo anaesthetic effects with ex vivo receptor density data supports a GABAergic mechanism of action for propofol, but not for isoflurane

If the in vivo effects of anaesthesia are mediated through aspecific receptor system, then a relationship could exist betweenthe regional changes in brain metabolism caused by a particularagent and the underlying regional distribution of the specificreceptors affected by that agent. Positron emission tomographydata from volunteers studied while unconscious during propofol(n=8) or isoflurane (n=5) anaesthesia were used retrospectivelyto explore for evidence of relationships between regional anaestheticeffects on brain glucose metabolism and known (ex vivo) regionaldistribution patterns of human receptor binding sites. The regionalmetabolic reductions caused by propofol differed significantlyfrom those of isoflurane. Propofol’s reductions negativelycorrelated most significantly with the regional distributionof [³H]diazepam and [³H]flunitrazepam (benzodiazepine) bindingsite densities (r=–0.86, P<0.0005; r=–0.79, P<0.005,respectively) and less strongly with [³H]naloxone (opioid) bindingdensity (r=–0.69, P<0.05). Isoflurane’s reductionspositively correlated only with muscarinic (acetylcholine) bindingdensity (r=0.85, P<0.05). These findings are consistent withthe hypothesis that some of propofol’s in vivo anaestheticeffects may be mediated through a GABAergic mechanism and suggestsome of isoflurane’s in vivo effects might involve antagonismof central acetylcholine functioning. Br J Anaesth 2001; 86: 618–26     

Volume kinetics of glucose 2.5% solution during laparoscopic cholecystectomy

Background. Analyses of the distribution and elimination ofglucose 2.5% solutions can be used to suggest combinations ofinfusion rates and infusion times which yield a predeterminedplasma glucose level and degree of plasma dilution during surgery. Methods. Twelve patients aged between 27 and 51 (mean 40) underwentlaparoscopic cholecystectomy. An i.v. infusion of 1.4 litresof glucose 2.5% over 60 min was started when surgery began.A volume kinetic model was fitted to measurements of the plasmaglucose concentration and the degree of haemodilution. Nomogramswere constructed based on the kinetic results. Results. The volume of distribution for the glucose and infusedfluid and the plasma insulin levels were similar to the onesrecorded in previous volunteer studies, but 50–70% lowervalues were obtained for the clearance of glucose (mean 0.21litres min^–1), endogenous glucose production (1.1 mmolmin^–1) and the elimination rate constant for the infusedfluid (median 37 ml min^–1). Urinary excretion was markedlydepressed and amounted to 9% of the infused fluid volume 4 hafter starting surgery. To prevent hyperglycaemia, nomogramssuggested that the infusion should be directed towards a ‘target’glucose concentration and then slowed down in a controlled way.At steady state, the infused fluid maintains a 3.5% plasma dilutionfor each mmol that plasma glucose remains above baseline. Conclusion. Metabolic changes warrant careful balancing of infusionrates of glucose 2.5% during laparoscopic cholecystectomy, whichis facilitated by a nomogram. Volume expansion from the infusedfluid volume should be recognized. Br J Anaesth 2004; 92: 485–92     

Effect of two anaesthetic regimens on airway nitric oxide production in horses

There is evidence that halothane inhibits nitric oxide synthasein vitro, but the effect of intravenous anaesthetic agents isless clear. This study was undertaken to compare the rate ofexhaled nitric oxide production (V_NO) in spontaneously breathinghorses anaesthetized with halothane or an intravenous regimen.Seven adult horses were studied twice in random order. Afterpremedication with romifidine 100 µg kg^–1,anaesthesia was induced with ketamine 2.2 mg kg^–1and maintained with halothane in oxygen (HA) or by an intravenousinfusion of ketamine, guaiphenesin and romifidine (IV). Inhaledand exhaled nitric oxide (NO) concentrations, respiratory minuteventilation (V_E), pulmonary artery pressure (P_PA), fractionalinspired oxygen concentration (FI_O2), end-tidal carbon dioxideconcentration (E'_CO2), cardiac output (Q) and partial pressuresof oxygen and carbon dioxide in arterial blood (Pa_O2, Pa_CO2)were measured. Exhaled nitric oxide production rate was significantlylower (40 min, P<0.01; 60 min, P<0.02) duringHA [40 min, 1.4 (SD 1.4) pmol l^–1 kg^–1 min^–1;60 min, 0.7 (0.7) pmol l^–1 kg^–1 min^–1]than during IV [40 min, 9.3 (9.9) pmol l^–1 kg^–1min^–1; 60 min, 12.5 (13.3) pmol l^–1 kg^–1min^–1). Mean pulmonary artery pressure was significantlyhigher (40 min, P<0.01; 60 min, P<0.001) during HA[40 min, 5.9 (1.1) kPa; 60 min, 5.9 (0.9) kPa] comparedwith IV (40 min, 4.4 (0.4) kPa; 60 min, 4.4 (0.5) kPa].NO is reduced in the exhalate of horses anaesthetized with halothanecompared with an intravenous regimen. It is suggested that increasedmean pulmonary artery pressure during halothane anaesthesiamay be linked to the differences in NO production. Br J Anaesth 2001; 86: 127–30     

Low-dose remifentanil infusion does not impair natural killer cell function in healthy volunteers

Background. Mu opioid agonists suppress natural killer (NK)cell activity in animal models. Studies in human volunteers,however, have yielded conflicting results, with morphine suppressingand fentanyl increasing NK cell activity. This study evaluatedthe effect of a constant 8-h infusion of remifentanil on NKcell number and function in human volunteers. Methods. After IRB approval and informed consent was obtained,10 healthy volunteers underwent an 11 pm to 7 am infusion ofsaline, and at least 1 week later an infusion of 0.02–0.04µg kg^–1 min^–1 remifentanil. Blood was collectedat 7 am for measurement of NK cell cytotoxicity using a ⁵¹Crrelease assay and measurement of NK cell number using fluorescentflow cytometry. Results. Median and range of the total NK cell cytoxicity (KUml^–1) was 745.0 (498.3–1483.6) on the control morningand 818.6 (238.5–1454.5) on the morning following theremifentanil infusion. Neither the number of NK cells ml^–1(2.5x10⁵ (1.4x10⁵–4.2x10⁵) vs 2.7x10⁵ (1.1x10⁵–4.4x10⁵))nor the cytotoxicity per 1000 NK cells (KU 1000 NK cells^–1)(3.0 (1.8–5.2) vs 2.9 (0.9–6.7)) changed betweenthe control and remifentanil conditions. Conclusions. An 8-h infusion of remifentanil did not affectNK cell activity in normal volunteers. This result differs fromprevious findings of morphine-induced NK cell activity suppressionand fentanyl-induced NK cell activity enhancement in normalvolunteers. Br J Anaesth 2003; 91: 805–9     

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.     

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 (