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.     

Comparison of three different epidural solutions in off-pump cardiac surgery: pilot study

Background. Immediate extubation using thoracic epidural analgesia(TEA) has become more popular after off-pump coronary arterybypass grafting (OPCAB). In this randomized prospective double-blindstudy, we present the first comparison of preoperative and postoperativehaemodynamics during different regimens of TEA for immediateextubation after cardiac surgery. Methods. Sixty patients undergoing OPCAB were enrolled in thisstudy. TEA was installed >1 h before application of heparinat levels T2–T4. Analgesia was provided by bupivacaine0.25%, 8 ml, 15 min before surgery and extubation, and at 10ml h^–1 during surgery and up to 72 h afterwards usingone of the following regimens: bupivacaine 0.125% alone, bupivacaine0.125% with fentanyl 3 µg ml^–1 or bupivacaine 0.125%with clonidine 0.6 µg ml^–1. Patients were block-randomizedfor one of the three treatments. Pain scores and infusion ratesof TEA were assessed up to 48 h after surgery. Respiratory functionwas assessed by Pa_O2 and Pa_O2 immediately after surgery, andhaemodynamic stability was recorded in the form of heart rateand diastolic and systolic blood pressure. Results. Patient characteristics, respiratory function and haemodynamicstability did not vary between the three groups. Pain controlwas very good and was not significantly different between thegroups using similar infusion rates after surgery. Paraesthesiain dermatomes T1 or C8 occurred equally in all three groups.There was no neurological complication related to TEA in thisstudy. Conclusions. We conclude that immediate extubation after OPCABusing TEA is feasible with different TEA regimens. Respiratoryfunction, haemodynamic stability and pain control are not differentbetween TEA with bupivacaine alone, bupivacaine with fentanylor bupivacaine with clonidine.     

Effects of haemoglobin-based oxygen carrier hemoglobin glutamer-200 (bovine) on intestinal perfusion and oxygenation in a canine hypovolaemia model

The objective of this investigation was to study the effectsof the first marketed haemoglobin-based oxygen carrier, Hemoglobinglutamer-200 (bovine) (Hb-200) (Oxyglobin^®) on splanchnicperfusion and oxygenation in a canine model of acute hypovolaemia.Twelve anaesthetized dogs [mean weight 30.8 (S.D. 1.4) kg] wereinstrumented for recordings of heart rate (HR), mean arterialpressure (MAP), central venous pressure (CVP), cardiac outputand cranial mesenteric arterial (CMA) and venous blood flows(CMV). Total and plasma haemoglobin (Hb), oxygen content andsaturation, lactate concentration, pH and blood gases were analysedin arterial, mixed venous and mesenteric venous blood samples.Measurements were made before (baseline) and after 1 hof haemorrhage, after which animals were resuscitated with eithershed blood (controls) or Hb-200 until HR, MAP and CVP returnedto prehaemorrhage levels. Recordings were repeated immediatelyand 3 h after termination of fluid resuscitation, afterwhich organ specimens were obtained for microscopic examination.Haemorrhage (average 32 ml kg^–1) reduced MAPto 50 mm Hg, increased HR and systemic vascular resistance(SVR), and was accompanied in both the systemic and the splanchniccirculation by significant decreases in blood flow, Hb contentand oxygen delivery (DO₂), and lactic acidosis. In controls,all variables recovered to baseline after isovolaemic resuscitationwith shed blood. In dogs resuscitated with a small volume ofHb-200 (10 ml kg^–1), HR, MAP, CVP and CMA andCMV blood flows returned to baseline. However, cardiac output,total Hb, oxygen content and systemic and mesenteric DO₂ remaineddepressed while SVR increased further. Mesenteric and systemicacid–base status recovered in both groups, and there wasno difference in microscopic tissue damage between groups. Thus,Hb-200 reconstituted splanchnic perfusion and oxidative metabolismin spite of pronounced systemic vasoconstriction and insufficientrestoration of CO and DO₂; it may improve diffusive oxygen transportin the microvasculature by virtue of haemodilution and its highefficiency in the uptake and release of oxygen. Br J Anaesth 2001; 86: 683–92     

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.     

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.     

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 lactated Ringer's, gelatine and blood resuscitation on intestinal oxygen supply and mucosal tissue oxygen tension in haemorrhagic shock

Objectives. To evaluate the effects on intestinal oxygen supply,and mucosal tissue oxygen tension during haemorrhage and afterfluid resuscitation with either blood (B; n=7), gelatine (G;n=8), or lactated Ringer's solution (R; n=8) in an autoperfused,innervated jejunal segment in anaesthetized pigs. Methods. To induce haemorrhagic shock, 50% of calculated bloodvolume was withdrawn. Systemic haemodynamics, mesenteric venousand systemic acid–base and blood gas variables, and lactatemeasurements were recorded. A flowmeter was used for measuringmesenteric arterial blood flow. Mucosal tissue oxygen tension(PO₂muc), jejunal microvascular haemoglobin oxygen saturation(HbO₂) and microvascular blood flow were measured. Measurementswere performed at baseline, after haemorrhage and at four 20min intervals after fluid resuscitation. After haemorrhage,animals were retransfused with blood, gelatine or lactated Ringer'ssolution until baseline pulmonary capillary wedge pressure wasreached. Results. After resuscitation, no significant differences inmacrohaemodynamic parameters were observed between groups. Systemicand intestinal lactate concentration was significantly increasedin animals receiving lactated Ringer's solution [5.6 (1.1) vs3.3 (1.1) mmol litre^–1; 5.6 (1.1) vs 3.3 (1.2) mmol litre^–1].Oxygen supply to the intestine was impaired in animals receivinglactated Ringer's solution when compared with animals receivingblood. Blood and gelatine resuscitation resulted in higher HbO₂than with lactated Ringer's resuscitation after haemorrhagicshock [B, 43.8 (10.4)%; G, 34.6 (9.4)%; R, 28.0 (9.3)%]. PO₂mucwas better preserved with gelatine resuscitation when comparedwith lactated Ringer's or blood resuscitation [20.0 (8.8) vs13.8 (7.1) mm Hg, 15.2 (7.2) mm Hg, respectively]. Conclusion. Blood or gelatine infusion improves mucosal tissueoxygenation of the porcine jejunum after severe haemorrhagewhen compared with lactated Ringer's solution.     

Pharmacokinetics of levobupivacaine 0.25% following caudal administration in children under 2 years of age

Background. Levobupivacaine, the S(–)enantiomer of racemicbupivacaine is less cardiotoxic than racemic bupivacaine andthe R(+)enantiomer dexbupivacaine, while retaining similar localanaesthetic properties and potency to racemic bupivacaine. Thepharmacokinetic profiles of the two bupivacaine enantiomersdiffers and that of racemic bupivacaine may be age dependent.We examined the pharmacokinetics of levobupivacaine after itssingle shot caudal epidural administration in children. Methods. An open-label phase 2 study was undertaken to examinethe pharmacokinetics of levobupivacaine 0.25% 2 mg kg^–1in 49 children aged less than 2 yr, after single shot caudalepidural administration. Plasma concentrations were determinedat intervals up to 60 min after caudal injection. Results. Time to peak plasma concentration (T_max) ranged between5 and 60 min (median 30 min) and was reached later in childrenaged less than 3 months (P<0.005). Peak plasma concentration(C_max) ranged between 0.41 and 2.12 µg ml^–1 (median0.80, mean (SD) 0.91 (0.40) µg ml^–1). Conclusion. After the caudal epidural administration of levobupivacaine2 mg kg^–1 in children less than 2 yr of age, C_max waswithin the accepted safe range for racemic bupivacaine. T_maxvaried and occurred later in some children, particularly thoseaged less than 3 months. Sampling in future pharmacokineticstudies in this age group should extend beyond 60 min. Br J Anaesth 2004; 92: 218–22     

Relation between fentanyl dose and predicted EC50 of propofol for laryngeal mask insertion

Background. This study sought to determine the effective concentrationfor 50% of the attempts to secure laryngeal mask insertion (predictedEC_50LMA) of propofol using a target-controlled infusion (Diprifusor^TM)and investigated whether fentanyl influenced these requiredconcentrations, respiratory rate (RR) and bispectral index (BIS). Methods. Sixty-four elective unpremedicated patients were randomlyassigned to four groups (n = 16 for each group) and given saline(control) or fentanyl 0.5, 1 or 2 µg kg^–1.Propofol target concentration was determined by a modificationof Dixon’s up-and-down method. Laryngeal mask airway insertionwas attempted without neuromuscular blocking drugs after equilibrationhad been established for >10 min. Movement was defined aspresence of bucking or gross purposeful muscular movement within1 min after insertion. EC_50LMA values were obtained by calculatingthe mean of 16 patients in each group. Results. Predicted EC_50LMA of the control, fentanyl 0.5, 1 and2 µg kg^–1 groups were 3.25 (0.20), 2.06 (0.55),1.69 (0.38) and 1.50 (0.54) µg ml^–1 respectively;those of all fentanyl groups were significantly lower than thatof control. RR was decreased in relation to the fentanyl doseup to 1 µg kg^–1. BIS values after fentanyl1 and 2 µg kg^–1 were significantly greaterthan in the control and 0.5 µg kg^–1 groups. Conclusions. A fentanyl dose of 0.5 µg kg^–1is sufficient to decrease predicted EC_50LMA with minimum respiratorydepression and without a high BIS value. Br J Anaesth 2004; 92: 238–41     

Beta2 adrenergic antagonist inhibits cerebral cortical oxygen delivery after severe haemodilution in rats

Background. Haemodilution has been associated with neurologicalmorbidity in surgical patients. This study tests the hypothesisthat inhibition of cerebral vasodilatation by systemic ß₂adrenergic blockade would impair cerebral oxygen delivery leadingto tissue hypoxia in severely haemodiluted rats. Methods. Under general anaesthesia, cerebral tissue probes wereplaced to measure temperature, regional cerebral blood flow(rCBF) and tissue oxygen tension (P_BrO₂) in the parietal cerebralcortex or hippocampus. Baseline measurements were establishedbefore and after systemic administration of either a ß₂antagonist (10 mg kg^–1 i.v., ICI 118, 551) or saline vehicle.Acute haemodilution was then performed by simultaneously exchanging50% of the estimated blood volume (30 ml kg^–1) with pentastarch.Arterial blood gases (ABGs), haemoglobin concentration (co-oximetry),mean arterial blood pressure (MAP) and heart rate (HR) werealso measured. Data were analysed using a two-way ANOVA andpost hoc Tukey's test [mean (SD)]. Results. Haemodilution reduced the haemoglobin concentrationcomparably in all groups [71 (9) g litre^–1]. There wereno differences in ABGs, co-oximetry, HR and MAP measurementsbetween control and ß₂ blocked rats, either beforeor 60 min after drug or vehicle administration. In rats treatedwith the ß₂ antagonist there was a significant reductionin parietal cerebral cortical temperature, regional blood flowand tissue oxygen tension, relative to control rats, 60 minafter haemodilution (P<0.05 for each). These differenceswere not observed when probes were placed in the hippocampus. Conclusion. Systemic ß₂ adrenergic blockade inhibitedthe compensatory increase in parietal cerebral cortical oxygendelivery after haemodilution thereby reducing cerebral corticaltissue oxygen tension.     

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.     

Effects of sustained post-traumatic shock and initial fluid resuscitation on extravascular lung water content and pulmonary vascular pressures in a porcine model of shock

Background. The temporal evolution of lung injury followingpost-traumatic shock is poorly understood. In the present studywe have tested the hypothesis that manifestations of pulmonaryvascular dysfunction may be demonstrable within the first hourafter the onset of shock. Methods. Twenty-nine anaesthetized pigs (mean weight 27.4 kg;(SD) 3.2) were randomly allocated to three groups: control (C,n=9), shock resuscitated with either NaCl 0.9% (S, n=10), or4% gelatine (G, n=10). Shock was maintained for 1 h followedby fluid resuscitation with either normal saline or 4% gelatinesolution. Cardiac output (CO), mean arterial pressure (MAP),mixed venous saturation (Sv_O2), blood lactate concentration,mean pulmonary artery pressure (MPAP), MPAP/MAP, pulmonary vascularresistance (PVR), extravascular lung water index (EVLWi), Pa_O2/FI_O2,venous admixture (Q^·_S/Q^·_T), and dynamic lung compliance(C_dyn) were measured at baseline, beginning of shock phase,end of shock phase, and post-resuscitation. Results. At the end of volume resuscitation CO was restoredto control values in both shock groups. MAP remained significantlybelow control values (95% CI: C=70–95, S=28–52,G=45–69 mm Hg) in both shock groups. MPAP/MAP was significantlygreater in both shock groups at the end of the shock phase (95%CI; C=0.15–0.24, S=0.28–0.38, G=0.32–0.42)and at the post-resuscitation phase (95% CI: C=0.12–0.30,S=0.43–0.61, G=0.32–0.49) indicating the presenceof relative pulmonary hypertension. This was associated witha significant increase in PVR in Group S (F=3.9; P<0.05).There were no significant changes in Pa_O2/FI_O2, Q^·_S/Q^·_T,EVLWi, or C_dyn. In a small cohort of animals a measurable increasein EVLWi (>30%) and reduction in C_dyn (>10%) were observed. Conclusions. Pulmonary vascular injury manifesting as relativepulmonary hypertension and increased PVR may occur within thefirst hour after the onset of shock. These changes may not beaccompanied by overt changes in oxygenation, compliance, orEVLWi. Br J Anaesth 2003; 91: 224–32     

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.     

Esmolol prevents movement and attenuates the BIS response to orotracheal intubation

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

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.      

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     

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     

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     

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     

Effects of phenylephrine and prostaglandin E on ventriculo-arterial matching during halothane anaesthesia

We have investigated the effects of phenylephrine alone andcombined with prostaglandin E₁ (PGE₁) on ventriculo-arterialmatching during halothane anaesthesia in dogs. The ratio ofleft ventricular end-systolic elastance (Ees) to effective arterialelastance (Ea) was used as an index of ventriculo-arterial matching.In group 1 (n = 7), measurements were performed at control,1.5% halothane, halothane+phenylephrine 1–10 µgkg^–1 min^–1, and halothane + phenylephrine + PGE₁,0.2–1.0 or 1.0–2.0 µg kg^–1 min^–1.In group 2 (n = 5), dobutamine 2 and 5 µg kg^–1 min^–1was infused during halothane anaesthesia. Halothane 1.5% decreasedmean arterial pressure (MAP), cardiac output and Ees. Phenylephrinerestored MAP, but further decreased cardiac output. The decreasein Ees produced by halothane was reversed by phenylephrine.PGE₁ increased cardiac output and reversed the increases inEa and Ea/Ees during phenylephrine infusion. Dobutamine alsoreversed halothane-induced decreases in MAP, cardiac outputand Ees, and improved Ea/Ees. Our results indicate that combineduse of PGE₁ with phenylephrine can eliminate the vasoconstrictiveproperty of phenylephrine, resulting in an improvement in ventriculo-arterialmatching.