Cerebral pressure autoregulation and carbon dioxide reactivity during propofol-induced EEG suppression

We studied cerebral pressure autoregulation and carbon dioxidereactivity during propofol-induced electrical silence of theelectroencephalogram (EEG) in 10 patients. Anaesthesia was inducedwith propofol 2.5 mg kg^–1, fentanyl 3 µg kg^–1and vecuronium 0.1 mg kg^–1, and a propofol infusion of250–300 µg kg^–1 min^–1 was used to induceEEG silence. Cerebral pressure autoregulation was tested byincreasing mean arterial pressure (MAP) by 24 (SEM 5) mm Hgfrom baseline with an infusion of phenylephrine and simultaneouslyrecording middle cerebral artery blood flow velocity (vmca)using transcranial Doppler. Carbon dioxide reactivity was testedby varying Pa_co2 between 4.0 and 7.0 kPa and recording vmcasimultaneously. Although absolute carbon dioxide reactivitywas reduced, relative carbon dioxide reactivity was within normallimits for all patients studied (mean 8.5 (SEM 0.8) cm s^–1kPa^–1 and 22 (2)% kPa^–1, respectively). No significantchange in vmca (34 (2) and 35 (2) cm s^–1) was observedwith the increase in MAP (77 (4) to 101 (4) mm Hg) during autoregulationtesting. We conclude that cerebral carbon dioxide reactivityand pressure autoregulation remain intact during propofol-inducedisoelectric EEG.     

Effects of magnesium sulphate on cerebral haemodynamics in healthy volunteers: a transcranial Doppler study

Background. Magnesium is increasingly being considered as aneuroprotective agent. We aimed to study its effects on middlecerebral artery blood flow velocity (V_mca), cerebral autoregulationand cerebral vascular reactivity to carbon dioxide (CRCO₂) inhealthy volunteers. Methods. Fifteen healthy volunteers were recruited. Using transcranialDoppler ultrasonography, V_mca was recorded continuously. Thestrength of autoregulation was assessed by the transient hyperaemicresponse test, and the CRCO₂ was measured by assessing changesin V_mca to the induced changes in end-tidal carbon dioxide.I.V. infusion of magnesium sulphate was then started (loadingdose of 16 mmol followed by an infusion at the rate of 2.7 mmolh^–1) for 45 min. The cerebral haemodynamic variables weremeasured again near the end of the infusion of magnesium sulphate. Results. Total serum magnesium levels were doubled by the infusionregimen. However, there were no significant changes in V_mca,strength of autoregulation, or CRCO₂. Five of the volunteersreported marked nausea and two developed significant hypotensionduring the loading dose. Conclusions. Infusion of magnesium sulphate, in a dose thatdoubles its concentration in plasma, does not affect V_mca, strengthof autoregulation or CRCO₂ in healthy volunteers. However, itcan be associated with nausea and hypotension. Br J Anaesth 2003; 91: 273–5     

CEREBROVASCULAR CARBON DIOXIDE REACTIVITY DURING EXPOSURE TO EQUIPOTENT ISOFLURANE AND ISOFLURANE IN NITROUS OXIDE ANAESTHESIA

We have studied the effects of hypocapnia on cerebrovascularchanges in two MAC-equivalent anaesthetic regimens, using thetranscranial Doppler technique as an index of cerebral bloodflow (CBF) in 24healthy ASA I patients undergoing spinal surgery.Eight of the patients were subjected to carbon dioxide reactivitychallenges in the awake state. Before surgery, the other 16patients received, in random order, either 1.15% isofluranein oxygen or 0.5% isoflurane with 70% nitrous oxide. Carbondioxide reactivity was calculated for each group as the increasein flow velocity per kPa change in PÉ_CO2 (cm s^–1kPa^–1). It was significantly greater for the isofluranegroup (14.09 (SD 2.44) cm s^–1 kPa^–1) and significantlyless for the isoflurane—nitrous oxide group (7.95 (1.32)cm s-^–1 kPa^–1) compared with the awake group (11.24(0.95) cm s^–1 kPa^–1). We conclude that cerebrovascularresponsiveness to changes in arterial carbon dioxide concentrationis influenced markedly by the anaesthetic procedure. Hyperventilationis more likely to affect CBF during isoflurane anaesthesia thanduring an MAC-equivalent isoflurane—nitrous oxide anaesthesia.     

Cerebral haemodynamics in pregnancy and pre-eclampsia as assessed by transcranial Doppler ultrasonography

Background. Altered cerebral circulation, as reported duringnormal pregnancy, and in patients with pre-eclampsia, can beassociated with changes in cerebral vascular reactivity and/orcerebral autoregulation. The aim of our study was to performa comparative assessment of cerebral haemodynamics, includingvascular reactivity and autoregulation, in pre-eclamptic patients,healthy pregnant women, and healthy non-pregnant women. Methods. Thirty patients with pre-eclampsia were recruited.Age- and height-matched healthy pregnant (n=30) and non-pregnantcontrol (n=30) groups were also recruited. Monitoring includedtranscranial Doppler ultrasonography, end-tidal carbon dioxideand non-invasive arterial pressure measurement. Cerebral autoregulationwas assessed by performing the transient hyperaemic response(THR) test. The cerebrovascular reactivity to carbon dioxide(CRCO₂) was assessed by measuring middle cerebral artery bloodflow velocity (MCAFV) after induced changes in end-tidal carbondioxide. Estimated cerebral perfusion pressure (eCPP) and criticalclosing pressure (CrCP) were calculated using established formulae.Statistical analysis included ANOVA with Tukey’s pairwisecomparisons. Results. Mean arterial pressure (MAP) was increased in pre-eclampsia(P<0.05). Mean MCAFV was lower in healthy pregnancy (P<0.05),but in pre-eclampsia it was similar to the non- pregnant group.When compared with the non-pregnant group, mean eCPP was higherin the healthy pregnant and pre-eclamptic groups (P<0.05).There were no meaningful differences in cerebral autoregulationor CRCO₂. Conclusions. Healthy pregnancy increases eCPP, presumably bydecreasing CrCP. In pre-eclampsia, eCPP is maintained at thesame level as in healthy pregnancy despite an increased MAP.Pre-eclampsia has no significant effect on cerebral autoregulationor CRCO₂. Br J Anaesth 2002; 89: 687–92     

Transient hyperaemic response to assess vascular reactivity of skin; effect of locally iontophoresed sodium nitroprusside

Background. We aimed to study if brief compression (20 s) ofthe brachial artery could provoke a hyperaemic response in forearmskin. In addition, we studied the effect of pre-dilating theskin vessels with locally iontophoresed sodium nitroprussideon the hyperaemic response. Methods. Ten healthy male volunteers were studied. A custom-madeperspex iontophoresis chamber was attached to the anterior aspectof the distal forearm; this chamber allowed simultaneous administrationof drugs by iontophoresis and measurement of skin blood flowflux by the laser Doppler probe. The flow flux signal, measuredin volts, was continuously recorded onto a paper chart recorder.Three control transient hyperaemic response (THR) tests wereperformed by releasing the manual occlusion of the brachialartery maintained for 20 s. Thereafter, 2% sodium nitroprussidewas iontophoresed using a current of 100 mAmp for 240 s. TheTHR tests were repeated three more times. From the recordings,baseline blood flow flux immediately before the onset of compression(or F1) and maximum blood flow flux immediately after the releaseof compression (or F2) were taken for analysis. The THR ratio(THRR) was calculated as: THRR=F2/F1. Average values of F1 andTHRR were taken from the tests before and after iontophoresisand a paired t-test was used for analysing the changes. Results. Nine of the 10 subjects showed a hyperaemic responseat the release of compression. Iontophoresis of sodium nitroprussidesignificantly increased the baseline flow flux from 0.77 (range0.29–1.61) to 1.88 V (0.73–2.91). It also completelyabolished the THR in all subjects; THRR decreased from 1.65(1.00–2.78) to 1.00 (0.98–1.03). Conclusion. A brief compression of the brachial artery resultsin a significant hyperaemic response in the forearm skin; thisresponse is abolished by pre-dilatation of skin vessels. Thesefindings support the hypothesis that the THR test assesses truevasodilatation occurring during arterial compression. Br J Anaesth 2002; 89: 265–70     

Cerebrovascular response to carbon dioxide during sodium nitroprusside- and isoflurane-induced hypotension

We have examined the cerebrovascular response to carbon dioxideduring normotension, sodium nitroprusside (SNP)-induced hypotensionand high dose isoflurane-induced hypotension in 10 patientswho received a standardized general anaesthetic. Carbon dioxidereactivity was determined by varying Pa_co2 between 3.0 and 8.0kPa and recording simultaneously blood flow velocity from themiddle cerebral artery (vmca). The paired vmca-Pa_co2 data wereanalysed using linear regression to determine carbon dioxidereactivity. During hypotension, both high-dose isoflurane andSNP reduced significantly mean absolute (from 17.4 (SEM 2.3)to 13.0 (1.7) and 8.8 (1.3) cm s^–1 kPa^–1 respectively;P < 0.05) and relative (from 32.5 (3.8) to 23.6 (2.0) and15.5 (1.3) % kPa^– respectively; P < 0.05) cerebrovascularreactivity to carbon dioxide. This reduction was greater duringSNP-induced hypotension (P < 0.05). We conclude that cerebrovascularreactivity to carbon dioxide was attenuated during isofluraneand SNP-induced hypotension, and that it was better preservedduring isoflurane-induced hypotension. (Br. J. Anaesth. 1995;74: 296–300) Present addresses: Department of Anaesthesia, The Ipswich Hospital,Ipswich IP4 5PD, UK. Present addresses: Phoenix Anesthesia Group, 2950 North 7thSt, Phoenix, AZ 85014, USA. Present addresses: University of Basel/Kantonsspital, Departmentof Anesthesia, CH-4031, Basel, Switzerland.     

Effects of halothane, sevoflurane and propofol on left ventricular diastolic function in humans during spontaneous and mechanical ventilation

Background. There is limited knowledge of the effects of anaestheticson left ventricular (LV) diastolic function in humans. Our aimwas to evaluate these effects in humans free from cardiovasculardisease. Methods. Sixty patients (aged 18–47 yr) who had no historyor signs of cardiovascular disease were randomized to receivegeneral anaesthesia with halothane, sevoflurane or propofol.Echocardiography was performed at baseline and during spontaneousrespiration at 1 minimum alveolar concentration (MAC) of theinhalational agents or propofol 4 µg ml^–1 (step1), and repeated during positive-pressure ventilation with 1and 1.5 MAC of the inhalational agents or with propofol 4 and6 µg ml^–1 (steps 2A and 2B). Analysis of echocardiographicmeasurements focused on heart rate corrected isovolumic relaxationtime (IVRT_c) and early diastolic peak velocity of the lateralmitral annulus (E_a). Results. IVRT_c decreased from baseline to step 1 in the halothanegroup (82 [95% CI, 76–88] ms and 74 [95% CI, 68–80]ms respectively; P=0.02), remained stable in the sevofluranegroup (78 [95% CI, 72–83] ms and 73 [95% CI, 67–81]ms; n.s.) and increased in the propofol group (80 [95% CI, 74–86]ms and 92 [95% CI, 84–102] ms; P=0.02). E_a decreased inthe propofol group only (18.8 [95% CI, 16.5–19.9] cm s^–1and 16.0 [95% CI, 14.9–17.9] cm s^–1; P=0.003). Fromstep 2A to step 2B, IVRT_c increased further in the propofolgroup (109 [95% CI, 99–121] ms and 119 [95% CI, 99–135]ms; P=0.04) but remained stable in the other two groups. E_adid not change from step 2A to step 2B. Conclusions. Halothane and sevoflurane did not impair LV relaxation,whereas propofol caused a mild impairment. However, the impairmentby propofol was of a magnitude that is unlikely to cause clinicaldiastolic dysfunction.      

Effects of sevoflurane and propofol on left ventricular diastolic function in patients with pre-existing diastolic dysfunction

Background. The effects of anaesthetics on left ventricular(LV) diastolic function in patients with pre-existing diastolicdysfunction are not well known. We hypothesized that propofolbut not sevoflurane will worsen the pre-existing LV diastolicdysfunction. Methods. Of 24 randomized patients, 23 fulfilled the predefinedechocardiographic criterion for diastolic dysfunction. Theyreceived general anaesthesia with sevoflurane 1 MAC (n=12) orpropofol 4 µg ml^–1 (n=11). Echocardiographic examinationswere performed at baseline and in anaesthetized patients underspontaneous breathing and under positive pressure ventilation.Analysis focused on peak early diastolic velocity of the mitralannulus (E_a). Results. During spontaneous breathing, E_a was higher in thesevoflurane than in the propofol group [mean (95% CI) 7.0 (5.9–8.1)vs 5.5 (4.7–6.3) cm s^–1; P<0.05], reflectingan increase of E_a from baseline only in the sevoflurane group(P<0.01). Haemodynamic findings were similar in both groups,but the end-tidal carbon dioxide content was more elevated inthe propofol group (P<0.01). During positive pressure ventilation,E_a was similarly low in the sevoflurane and propofol groups[5.3 (4.2–6.3) and 4.4 (3.6–5.2) cm s^–1, respectively]. Conclusions. During spontaneous breathing, early diastolic functionimproved in the sevoflurane but not in the propofol group. However,during positive pressure ventilation and balanced anaesthesia,there was no evidence of different effects caused by the twoanaesthetics.     

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).     

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.     

Impact of peripheral elimination on the concentration-effect relationship of remifentanil in anaesthetized dogs

Background. This study elucidates the impact of sampling sitewhen estimating pharmacokinetic-pharmacodynamic (PK-PD) parametersof drugs such as remifentanil that undergo tissue extractionin the biophase. The interrelationship between the concentrationsof remifentanil predicted for the effect compartment and thosemeasured in arterial, venous, and cerebrospinal fluid were investigatedunder steady-state conditions. Methods. Following induction of anaesthesia with pentobarbital,an arterial cannula (femoral) and two venous catheters (jugularand femoral) were inserted. Electrodes were placed for EEG recordingof theta wave activity. Each dog received two consecutive 5-mininfusions for the PK-PD study and a bolus followed by a 60-mininfusion was started for the steady-state study. Cerebrospinalfluid, arterial and venous blood samples were drawn simultaneouslyafter 30, 40, and 50 min. At the end of the infusion, arterialblood samples were collected for pharmacokinetic analysis. Results. Remifentanil PK-PD parameters based on theta wave activitywere as follows: apparent volume of distribution at steady-state(V_ss) (231±37 ml kg^–1), total body clearance (Cl)(63±16 ml min^–1 kg^–1), terminal eliminationhalf-life (t_1/2ß) (7.71 min), effect compartment concentrationat 50% of maximal observed effect (EC₅₀) (21±13 ng ml^–1),and equilibration rate constant between plasma and effect compartment(k_e0) (0.48±0.24 min). The mean steady-state cerebrospinalfluid concentration of 236 ng ml^–1 represented 52 and74% of that in arterial and venous blood, respectively. Conclusions. Our study re-emphasizes the importance of a samplingsite when performing PK-PD modelling for drugs undergoing eliminationfrom the effect compartment. For a drug undergoing tissue eliminationsuch as remifentanil, venous rather than arterial concentrationswill reflect more exactly the effect compartment concentrations,under steady-state conditions. Declaration of interest. Remifentanil was provided by AbbottLaboratories.     

Non-selective and cyclo-oxygenase-2-specific non-steroidal anti-inflammatory drugs impair the hyperaemic response of skin to brief axillary artery occlusion

Background. Cyclo-oxygenase-2 (COX-2)-specific inhibitors aremarketed as safer analgesics than non-selective non-steroidalanti-inflammatory drugs. However, there has been conflictingevidence concerning endothelial function and cardiovascularrisk after COX-2 inhibitor use. We investigated forearm skinvascular reactivity to brief axillary artery occlusion in healthyvolunteers after a single dose of the non-steroidal anti-inflammatorydrugs ibuprofen (non-selective) and rofecoxib (COX-2 specific). Methods. Ten healthy male volunteers were studied. Forearm skinblood flow was measured using laser Doppler flowmetry. Two non-invasiveprobes were placed on the volar surface of the forearm. Themagnitude of hyperaemic response to brief (20 s) and prolonged(5 min) occlusion of the axillary artery was measured beforeand 2–3 h after administration of ibuprofen 800 mg orrofecoxib 25 mg. The transient hyperaemic response ratio (THRR),defined as the net peak hyperaemic flow-flux divided by thenet baseline flow-flux, was calculated. Each volunteer receivedboth drugs in random order at least 1 week apart. Results. Ibuprofen and rofecoxib increased net baseline bloodflow (median (range): ibuprofen, from 23.3 (12.1–40.8)to 31.5 (17.4–77.3); rofecoxib, from 22.0 (14.6–41.0)to 29.9 (19.5–112.0); P<0.01). The net hyperaemic peakflow-flux after brief and prolonged occlusion was unchangedafter both drugs. THRR was reduced by both drugs (ibuprofen,from 2.92 (2.38–3.86) to 2.09 (1.45–3.54); rofecoxib,from 3.36 (2.06–5.16) to 2.67 (1.15 –3.84); P<0.01). Conclusions. Both COX-2 and non-selective non-steroidal anti-inflammatorydrugs, when given to healthy volunteers as single therapeuticdoses, decrease skin microvascular tone but do not impair maximalvasodilatory ability. Br J Anaesth 2003; 91: 353–6     

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.     

Effects of desflurane on cerebral autoregulation

The aim of this study was to determine the effects of desflurane,at 1 and 1.5 MAC, on cerebral autoregulation. Data were analysedfrom eight patients undergoing non-neurosurgical procedure.The blood flow velocity in the middle cerebral artery was measuredby transcranial Doppler ultrasound and cerebral autoregulationwas assessed by the transient hyperaemic response test. Partialpressure of the end-tidal carbon dioxide (PE'_CO2) and mean arterialpressure were measured throughout the study. Anaesthesia wasinduced with propofol and was maintained with desflurane atend-tidal concentrations of 7.4% (1 MAC) or 10.8% (1.5 MAC).The order of administration of the desflurane concentrationswas determined randomly and a period of 15 min was allowed forequilibration at each concentration. The transient hyperaemicresponse tests were performed before induction of anaesthesiaand after equilibration with each concentration of desflurane.An infusion of phenylephrine was used to maintain pre-inductionmean arterial pressure and ventilation was adjusted to maintainthe pre-induction value of PE'_CO2 throughout the study. Twoindices derived from the transient hyperaemic response test(the transient hyperaemic response ratio and the strength ofautoregulation) were used to assess cerebral autoregulation.Desflurane resulted in a marked and significant impairment incerebral autoregulation; at concentrations of 1.5 MAC, autoregulationwas almost abolished. Br J Anaesth 2001; 87: 193–7     

The suppression of spinal F-waves by propofol does not predict immobility to painful stimuli in humans

Background. The immobilizing effects of volatile anaestheticsare primarily mediated at the spinal level. A suppression ofrecurrent spinal responses (F-waves), which reflect spinal excitability,has been shown for propofol. We have assessed the concentration-dependentF-wave suppression by propofol and related it to the logisticregression curve for suppression of movement to noxious stimuliand the effect on the bispectral index^TM (BIS^TM). The predictivepower of drug effects on F-waves and BIS for movement responsesto noxious stimuli was tested. Methods. In 24 patients anaesthesia was induced and maintainedwith propofol infused by a target controlled infusion pump atstepwise increasing and decreasing plasma concentrations between0.5 and 4.5 mg litre^–1. The F-waves of the abductor hallucismuscle were recorded at a frequency of 0.2 Hz. BIS values wererecorded continuously. Calculated propofol concentrations andF-wave amplitude and persistence were analyzed in terms of apharmacokinetic–pharmacodynamic (PK/PD) model with a simplesigmoid concentration–response function. Motor responsesto tetanic electrical stimulation (50 Hz, 60 mA, 5 s, volarforearm) were tested and the EC_50tetanus was calculated usinglogistic regression. Results. For slowly increasing propofol concentrations, computerfits of the PK/PD model for the suppression by propofol yieldeda median EC₅₀ of 1.26 (0.4–2.3) and 1.9 (1.0–2.8)mg litre^–1 for the F-wave amplitude and persistence, respectively.These values are far lower than the calculated EC₅₀ for noxiouselectrical stimulation of 3.75 mg litre^–1. This differenceresults in a poor prediction probability of movement to noxiousstimuli of 0.59 for the F-wave amplitude. Conclusions. F-waves are almost completely suppressed at subclinicalpropofol concentrations and they are therefore not suitablefor prediction of motor responses to noxious stimuli under propofolmono-anaesthesia. Presented in part at the annual meeting of the American Societyof Anesthesiologists 2004 in Las Vegas.     

Pharmacokinetics of controlled release morphine (MST) in patients with liver carcinoma

Background. There are no studies reported on the pharmacokineticsof controlled release morphine (MST) in patients with hepatocellularcarcinoma, the fifth most common cancer in the world. Methods. We have studied the pharmacokinetic profile of MST(30 mg) in 15 patients with liver carcinoma (eight with primarycarcinoma on top of chronic hepatitis C, and seven with secondarymetastatic liver malignancy as a result of other primary) comparedwith our previously published data for 10 healthy controls.Plasma morphine concentrations were measured in venous bloodsamples at intervals up to 12 h by high-pressure liquid chromatography.Total body clearance (Cl) and systemic bioavailability wereestimated using a compartmental method. Results. Morphine bioavailability showed a substantial increasein patients with primary liver and secondary metastatic carcinomathan that of controls (64.8, 62.1, and 16.8%, respectively).The area under the serum concentration–time curve increased4-fold in primary carcinoma (416 [SEM25] µg h^–1litre^–1) and 3-fold (303 [21] µg h^–1 litre^–1)in metastatic liver patients compared with healthy control (92.5[3] µg h^–1 litre^–1). No significant differencewas found in T_max between the two malignant groups but C_maxwas significantly greater in primary liver carcinoma patients.Impaired morphine elimination was noted in primary carcinomaonly (t_1/2 5.99 [0.39] h). Conclusion. Careful administration of morphine is recommendedin patients with liver cancer.     

Transient hyperaemic response to assess vascular reactivity of skin: effect of locally iontophoresed acetylcholine,bradykinin, epinephrine and phenylephrine

Background. Recently, the transient hyperaemic response (THR)to brief compression (20 s) of the brachial artery has beendescribed as a way to assess vascular reactivity of the forearmskin. We studied the effects of locally iontophoresed vasoactiveagents on this response in 20 male volunteers. Methods. An iontophoresis chamber attached to the anterior forearmpermitted simultaneous administration of drugs by iontophoresisand measurement of skin blood flow-flux by laser Doppler probe.Three THR tests were performed before and after iontophoresisby compressing the brachial artery with digital pressure for20 s and then releasing. The following were iontophoresed: saline0.9% (iontophoresis vehicle control), acetylcholine, bradykinin,epinephrine and phenylephrine. The THR ratio (THRR) was calculatedas F2/F1 where F1 was baseline blood flow-flux immediately beforecompression and F2 was peak blood flow-flux after release. Results. When compared with saline 0.9%, acetylcholine and bradykininincreased median F1 from 9.2 (range 5.2–23.8) to 22.1(8.7–61.5) and from 4.8 (3.0–23.2) to 15.0 (2.5–31.8),respectively, and reduced THRR from 1.26 (1.07–2.2) to0.99 (0.93–1.04) and from 1.63 (1.06–2.58) to 1.09(0.93–1.19), respectively. Epinephrine, but not phenylephrine,caused a significant reduction in F1 from 9.2 (5.2–23.8)to 4.0 (1.5–22.3). Neither epinephrine nor phenylephrinehad significant effect on THRR. Conclusions. Iontophoresed acetylcholine and bradykinin significantlyincrease the flow-flux and impair THR in forearm skin, furthervalidating the concept that THR represents true vasodilatationduring arterial occlusion. In addition, iontophoresis of vasoconstrictorsdoes not appear to have any consistent effect. Br J Anaesth 2003; 90: 446–51     

Xenon increases total body oxygen consumption during isoflurane anaesthesia in dogs

Background. This study was designed to examine whether the couplingbetween oxygen consumption (V^·O₂) and cardiac output(CO) is maintained during xenon anaesthesia. Methods. We studied the relationship between V^·O₂ (indirectcalorimetry) and CO (ultrasound flowmetry) by adding xenon toisoflurane anaesthesia in five chronically instrumented dogs.Different mixtures of xenon (70% and 50%) and isoflurane (0–1.4%)were compared with isoflurane alone (1.4% and 2.8%). In addition,the autonomic nervous system was blocked (using hexamethonium)to study its influence on V^·_O2 and CO during xenon anaesthesia. Results. Mean (SEM) V^·O₂ increased from 3.4 (0.1) ml kg^–1 min^–1during 1.4% isoflurane to 3.7 (0.2) and 4.0 (0.1) ml kg^–1 min^–1after addition of 70% and 50% xenon, respectively (P<0.05),whereas CO and arterial pressure remained essentially unchanged.In contrast, 2.8% isoflurane reduced both, V^·O₂ [from3.4 (0.1) to 3.1 (0.1) ml kg^–1 min^–1]and CO [from 96 (5) to 70 (3) ml kg^–1 min^–1](P<0.05). V^·O₂ and CO correlated closely during isofluraneanaesthesia alone and also in the presence of xenon (r²=0.94and 0.97, respectively), but the regression lines relating COto V^·_O2 differed significantly between conditions, withthe line in the presence of xenon showing a 0.3–0.6 ml kg^–1 min^–1greater V^·O₂ for any given CO. Following ganglionic blockade,50% and 70% xenon elicited a similar increase in V^·O₂,while CO and blood pressure were unchanged. Conclusions. Metabolic regulation of blood flow is maintainedduring xenon anaesthesia, but cardiovascular stability is accompaniedby increased V^·O₂. The increase in V^·_O2 is independentof the autonomic nervous system and is probably caused by directstimulation of the cellular metabolic rate. Br J Anaesth 2002; 88: 546–54     

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.     

Effects of candesartan and enalaprilat on the organ-specific microvascular permeability during haemorrhagic shock in rats

Background. To counteract the contribution of angiotensin IIto shock-induced ischaemic organ damage pharmacologic blockadeof the renin–angiotensin-system (RAS) is currently underinvestigation. To evaluate potential side-effects of RAS blockaderegarding capillary leak, we studied alterations in microvascularpermeability in various organs during haemorrhagic shock (HS)in rats pretreated with candesartan (AT₁-receptor antagonism)or enalaprilat (ACE-inhibition). Methods. Thirty-eight instrumented and anaesthetized animalsreceived either candesartan, enalaprilat or placebo. Withineach of the three groups 6–7 animals were exposed to HSand 6 animals of each group served as normovolaemic controls.After 30 min of shock, 50 mg kg^–1 Evans blue (EB) wasinjected i.v. followed by a distribution period of 20 min. Exsanguinationwas performed with saline, before harvesting organs to quantifyalbumin-bound EB extravasation. Results. To reduce cardiac output from 37.5 (1.3) to 20.4 (1.1)ml min^–1 [mean (SEM)] in the shock groups, withdrawalof 4.0 (0.25) ml [mean (SEM)] blood was necessary. Simultaneouslymean arterial pressure decreased from 77.5 (3.2) to 36.1 (2)mm Hg. Serum lactate increased significantly from 1.3 (0.1)to 3.5 (0.24) mmol litre^–1. Treatment with candesartanincreased EB extravasation in the kidney in normovolaemic controls.Specific AT₁ and ACE-blockade before acute nonresuscitated HSsignificantly increased EB extravasation in the rat ileum by53 and 66%, respectively. Conclusion. This observation of increased microvascular albuminextravasation should be borne in mind for any interventionaluse of candesartan or enalaprilat during circulatory stress.