Intravenous anaesthesia and the rat microcirculation: the Dorsal Microcirculatory Chamber{dagger}

The use of the dorsal microcirculatory chamber in male Wistarrats (n=7) to study the effects of induction and maintenanceof anaesthesia on the microcirculation is described. Differentpatterns of responses were observed. At induction, arteriolardilation was found following propofol and thiopental but ketamineproduced constriction. During maintenance, constriction of arterioleswas seen with ketamine and thiopental but dilation persistedwith propofol. The dorsal microcirculatory chamber appears tobe a useful tool for the study of microcirculatory changes relatedto anaesthesia. Br J Anaesth 2000; 85: 901–3     

Effect of clonidine pre-medication on propofol requirements during lower extremity vascular surgery: a randomized controlled trial

Background. Pre-medication with clonidine reduces the requirementfor volatile agents during general anaesthesia. This may alsobe true for anaesthesia with propofol, but the amount of dosereduction has not been measured. Because clonidine also affectscardiac output and thus regional blood flow it could alter thepharmacokinetics of propofol. This randomized, double-blindplacebo-controlled trial aimed to study the effect of clonidinepre-medication on dose requirement for propofol during lowerextremity vascular surgery using the bispectral index (BIS)as a measure of anaesthetic depth. Methods. After oral pre-medication with either clonidine 3 µgkg^–1 or placebo, 39 subjects had lower limb vascular surgeryusing propofol infusion for anaesthesia. Anaesthetic depth wasadjusted to a BIS of 45. Predicted plasma propofol concentrationswere noted every 30 min from a target-controlled propofol infusionpump and arterial samples were taken at the same time for propofolmeasurements. Results. Patients in both groups were anaesthetized to similardepths of anaesthesia as indicated by BIS readings (P=0.44).The groups had comparable mean (95% CI) arterial concentrationsof propofol, 4.8 (3.5–6.1) µg ml^–1 in thepatients given clonidine, and 4.6 (3.4–5.7) µg ml^–1in the patients given placebo (P=0.81). However, the averageplasma concentration predicted by the target-controlled infusionwas less in the clonidine group [3.2 (2.9–3.5)] than inthe group given placebo [3.6 (3.3–3.9)] µg ml^–1(P<0.05). Conclusions. Pre-medication with clonidine reduces the requirementfor propofol, which is a pharmacokinetic effect and not a pharmacodynamiccentral sedative effect.     

Efficacy of prophylactic ketamine in preventing postoperative shivering

Background. Treatment with ketamine and pethidine is effectivein postoperative shivering. The aim of this study was to comparethe efficacy of low-dose prophylactic ketamine with that ofpethidine or placebo in preventing postoperative shivering. Methods. A prospective randomized double-blind study involved90 ASA I and II patients undergoing general anaesthesia. Patientswere randomly allocated to receive normal saline (Group S, n=30),pethidine 20 mg (Group P, n=30) or ketamine 0.5 mg kg^–1(Group K, n=30) intravenously 20 min before completion of surgery.The anaesthesia was induced with propofol 2 mg kg^–1, fentanyl1 µg kg^–1 and vecuronium 0.1 mg kg^–1. It wasmaintained with sevoflurane 2–4% and nitrous oxide 60%in oxygen. Tympanic temperature was measured immediately afterinduction of anaesthesia, 30 min after induction and beforeadministration of the study drug. An investigator, blinded tothe treatment group, graded postoperative shivering using afour-point scale and postoperative pain using a visual analoguescale (VAS) ranging between 0 and 10. Results. The three groups did not differ significantly regardingpatient characteristics. The number of patients shivering onarrival in the recovery room, and at 10 and 20 min after operationwere significantly less in Groups P and K than in Group S. Thetime to first analgesic requirement in Group S was shorter thanin either Group K or Group P (P<0.005). There was no differencebetween the three groups regarding VAS pain scores. Conclusion. Prophylactic low-dose ketamine was found to be effectivein preventing postoperative shivering.     

Propofol metabolism is enhanced after repetitive ketamine administration in rats: the role of cytochrome P-450 2B induction

Background. In a series of ex vivo and in vivo studies we investigatedthe ability of repetitive ketamine administration to alter themetabolism and anaesthetic effect of propofol and the role ofketamine-mediated P-450 2B induction in rats. Methods. Male Wistar rats were pretreated with 80 mg kg^–1ketamine i.p. twice daily for 4 days. Pentoxyresorufin O-dealkylation(PROD), P-450 2B protein and mRNA were determined. Residualpropofol concentration was measured after incubating hepaticmicrosomes with 100 µM propofol. Sleeping times inducedby i.p. 80 mg kg^–1 propofol were determined. Orphenadrine,a P-450 2B inhibitor, was added in both ex vivo and in vivostudies. Finally, serial whole blood propofol concentrationswere determined after i.v. infusion of 15 mg kg^–1 propofol. Results. Ketamine pretreatment produced 5.4-, 3.4- and 1.7-foldincreases in hepatic PROD activity, P-450 2B protein and mRNA,respectively. Residual propofol concentration was 46% lowerafter incubation with microsomes from ketamine-pretreated ratsthan in the control group. The addition of orphenadrine to ketamine-pretreatedmicrosomes produced an increase in residual propofol concentrationin a concentration-dependent manner. Ketamine pretreatment reducedpropofol sleeping time to 12% of the control, which was reversedby orphenadrine. The whole blood propofol concentration in ketamine-pretreatedrats was significantly lower than that of control rats at 1,2, 4 and 8 min after cessation of propofol infusion. Conclusions. Repetitive ketamine administration enhances propofolmetabolism and reduces propofol sleeping time in rats. We suggestthat P-450 2B induction may produce ketamine–propofolinteraction in anaesthetic practice.     

Anaesthesia for carotid endarterectomy: comparison of hypnotic- and opioid-based techniques

Background. Although the synergistic interaction between hypnoticsand opioids for total i.v. anaesthesia has been repeatedly demonstrated,questions about different dose combinations of hypnotics andopioids remain. The optimal combination would be based on maximalsynergy, using the lowest dose of both drugs and having thelowest incidence of side-effects. Methods. The major goal of this prospective randomized studywas to compare two different dose combinations of propofol andremifentanil (both administered by target controlled infusion(TCI)) in respect of haemodynamics during surgery and recovery,and the need for cardiovascular treatment in the recovery room.A secondary goal was to compare pain scores (VAS) and morphineconsumption in the recovery room. Anaesthesia was induced inboth groups using TCI propofol, adjusted to obtain a bispectralindex score (BIS) value between 40 and 60. TCI for remifentanilcommenced at an initial effect-site concentration of 0.5 ng ml^–1,and was adjusted according to haemodynamics. Patients were dividedinto one of two groups during anaesthesia: (i) Group H, hypnoticanaesthesia (n=23), propofol effect-site concentration maintainedat 2.4 µg ml^–1; and (ii) Group O, opioidanaesthesia (n=23), propofol effect-site concentration maintainedat 1.2 µg ml^–1. In both groups, remifentanileffect-site concentration was adjusted according to haemodynamicsand changes in BIS value. Results. In Group O, more episodes of intraoperative hypotension(P<0.02) and hypertension (P<0.01), and fewer episodesof tachycardia were observed. More patients in Group O requirednicardipine administration for postoperative hypertension (8patients in Group H vs 15 patients in Group O, P<0.04). Duringrecovery, morphine titration was necessary in     

Orally administered clonidine significantly reduces pain during injection of propofol

We examined the analgesic effects of orally administered clonidineon pain induced by injection of propofol (Diprivan; 2,6-diisopropylphenol). Female patients (n=81) were randomly allocated to oneof two groups: oral clonidine (5.5 µg kg^–1)followed by i.v. propofol and a control group given placebofollowed by i.v. propofol. The median pain score in the groupreceiving clonidine, using a four-point scale (0=no pain, 1=minimalpain, 2=moderate pain, 3=severe pain) was 1 (0–2), significantlylower than in the control group [2 (1–3), median (25–75percentiles), P<0.001]. Br J Anaesth 2001; 86: 874–6     

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.     

Pharmacological effects of intravenous melatonin: comparative studies with thiopental and propofol

Background. Possible utility of high-dose i.v. melatonin asan anaesthetic adjuvant has not been studied. This study comparedits effects with thiopental and propofol. Methods. Sprague Dawley rats were assigned to receive bolusor cumulative i.v. doses of melatonin, thiopental or propofol.Righting reflex, hindpaw withdrawal to a noxious stimulus, responseto tail clamping and haemodynamic effects were assessed. Results. Melatonin caused a dose-dependent increase in paw withdrawalthreshold and the percent of rats displaying loss of the rightingreflex. Melatonin was comparable to thiopental and propofolin terms of its rapid onset of hypnosis. The mean ED₅₀ valuesfor loss of righting reflex were 5.4 (SEM 1.2), 12.5 (1.1) and178 (1.1) mg kg^–1 for propofol, thiopental and melatonin,respectively. The percent of rats displaying loss of responseto tail clamping was greater with propofol than with melatonin(P<0.05). Haemodynamic changes produced by melatonin or propofolwere similar in onset and magnitude. Conclusions. I.V. melatonin can exert hypnotic effects similarto those observed with thiopental and propofol. Melatonin exhibitedsignificant antinociceptive effects but was less effective inabolishing the response to tail clamping. Br J Anaesth 2003; 90: 504–7     

Anoxic depolarization of rat hippocampal slices is prevented by thiopental but not by propofol or isoflurane

Background. There is strong evidence to suggest that anoxicdepolarization (AD) is an important factor in hypoxia/ischaemia-inducedneural damage. Treatments that prevent the occurrence of ADmay be useful in providing neuronal protection against hypoxia.The current study was designed to determine whether generalanaesthetics which have been suggested to ‘induce prophylaxis’against hypoxia can attenuate the incidence of AD. Methods. The effects of anoxia (3 min) on evoked extracellularlyrecorded field potentials of CA1 neurons in rat hippocampalslices were assessed in the absence and presence of the i.v.general anaesthetics thiopental and propofol and the volatileanaesthetic isoflurane. Results. In the absence of anaesthetics, AD occurred in 81%of the preparations tested. Thiopental (2x10^–4 M) significantlyreduced the incidence of AD (16%, P=0.0006). In comparison,propofol (2x10^–4 M) and isoflurane (1.5 vol%) were ineffective(69% and 60%, respectively). Furthermore, in the presence ofthiopental, the population spike amplitude recovered with andwithout AD (90% and 94% of pre-anoxic value, respectively) following3 min anoxia. Conclusion. The prophylactic effect of thiopental against hypoxiamight be induced, in part, by preventing the generation of AD.     

Ketamine and thiopental sodium: individual and combined neuroprotective effects on cortical cultures exposed to NMDA or nitric oxide

Background. An N-methyl-D-aspartate (NMDA) blocker, ketamine,has been shown to be neuroprotective both in vivo and in vitro.However, ketamine is not commonly recommended for use in patientssuffering from cerebral ischaemia because of its adverse neurologicaleffects. We hypothesized that combined administration of ketamineand thiopental sodium (TPS) would be highly effective in protectingcerebral cortical neurones from ischaemia, with possibly reduceddosages. Methods. We examined the degree of neuroprotection providedby various concentrations of ketamine and TPS, alone and incombination, in cortical cultures exposed to NMDA or a nitricoxide-releasing compound (NOC-5) for 24 h. The survival rate(SR) of E16 Wistar rat cortical neurones was evaluated usingphotomicrographs before and after exposure to these compounds. Results. The SRs of cortical neurones exposed to 30 µMNMDA or NOC-5 were 15.0 (3.8)%, 12.8 (3.1)%, respectively. Higherdoses (5, 10 and 50 µM) but not lower doses (<1 µM)of ketamine improved SRs [57.9 (2.2)%, 61.1 (5.4)%, 76.7 (3.0)%,respectively] against NMDA but not NOC. Enhanced survival wasobserved with combined administration of 5 or 10 µM ketamineand 50 µM TPS [SR 71.3 (4.8)%, 74.7 (3.7)%, respectively,P<0.05 if ketamine alone, P<0.01 if TPS alone], againstNMDA-induced neurotoxicity in vitro. Only the highest dose ofTPS (50 µM) improved survival after NOC exposure. Thisneuroprotection was not influenced by ketamine. Conclusions. These data indicate that a low, clinically relevantdose of ketamine offer significant neuroprotection during prolongedexposure to NMDA but not to NOC. Combinations of reduced dosesof ketamine and TPS exhibited enhanced neuroprotection againstNMDA-induced neurotoxicity. Hence, combinations of these twocommon i.v. anaesthetics agents could be developed to protectthe brain from ischaemia.     

Midazolam versus propofol for reducing contractility of fatigued canine diaphragm

The effects of midazolam and propofol on the contractility offatigued canine diaphragm were examined. Diaphragmatic fatiguewas induced by intermittent supramaximal bilateral electrophrenicstimulation at a frequency of 20 Hz applied for 30 min.After fatigue had been induced, group I (n=10) receivedno study drug, group II (n=10) was given a propofol infusion(0.1 mg kg^–1 loading dose plus 1.5 mg kg^–1 h^–1maintenance dose) and group III (n=10) was given a midazolaminfusion (0.1 mg kg^–1 loading dose plus 0.1 mg kg^–1 h^–1maintenance dose). Diaphragmatic contractility was assessedby measuring transdiaphragmatic pressure (P_di). After the fatigue-inducingperiod in each group, P_di at low-frequency (20 Hz) stimulationwas lower than the baseline values (P<0.05), whereas no changein P_di at high-frequency (100 Hz) stimulation was observed.In group II, P_di at 20 Hz stimulation was lower than fatiguedvalues (P<0.05); P_di at 100 Hz stimulation did not change.In group III, P_di at both stimulation frequencies was lowerthan fatigued values (P<0.05). Compared with group I, P_diat 20 Hz stimulation was lower than fatigued values (P<0.05)during administration of the study drug in groups II and III.The decrease in P_di was greater in group III than in group II(P<0.05). In conclusion, midazolam compared with propofolis associated with an inhibitory effect on contractility inthe fatigued canine diaphragm. Br J Anaesth 2001; 86: 879–81     

Comparative effects of thiopental and propofol on atrial vulnerability: electrophysiological study in a porcine model including acute alcoholic intoxication

Background. Atrial tachyarrhythmias (AT) frequently complicatethe perioperative period. Alcohol intoxication is a recognizedcausative factor for dysrrhythmias. We studied the effects ofpropofol and thiopental on atrial electrophysiology and vulnerabilityto AT in a closed-chest porcine model in which AT are facilitatedby ethanol. Methods. Thirty-eight pigs were randomly assigned to thiopental(T-group, n=19) or propofol (P-group n=19). All animals wereassigned to undergo a right atrial electrical stimulation protocol(RASP) at baseline. Thirty pigs were assigned to undergo additionalRASP during ethanol infusion, while the remaining eight wereassigned to undergo additional RASP during saline infusion (controlgroup). We analysed effective refractory period (ERP), and intra-atrialconduction interval (ICI) (between atrial sites 4 cm apart),at several cycle lengths (CL). Results. There were no significant differences at baseline.During ethanol infusion, propofol produced a greater rate-dependentdecrease in excitability, manifested by a longer minimum pacedCL with 1:1 atrial capture: 145 (11) vs 164 (27) ms in the T-and P-group, respectively (P=0.01). Propofol was associatedwith a greater rate-related slowing in conduction: differencebetween ICI at CL of 300 ms and ICI at minimum CL: 30 ms inP-group and 22 ms in T-group (P<0.03). In the P-group weobserved a longer duration of induced arrhythmias (145 (131)vs 74 (91) s, P<0.03) and a higher proportion with atrialflutter (AFl) (76 vs 19%, P<0.001). Conclusions. Propofol in this model was more arrhythmogenicthan thiopental, as manifested by a longer duration of inducedarrhythmias, particularly AFl. This work has been presented at the 9th Annual Meeting of EuropeanSociety of Anaesthesiology, 7–10 April 2001, Gothenburg,Sweden.     

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     

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.     

Sevoflurane and propofol decrease intraocular pressure equally during non-ophthalmic surgery and recovery

Background. To provide good control of intraocular pressure(IOP) during anaesthesia and surgery, we conducted a study comparingthe effects on IOP during maintenance and recovery of sevofluranevs propofol anaesthesia in 33 patients (ASA I–II) undergoingelective non- ophthalmic surgery. Methods. Anaesthesia was induced with propofol 2 mg kg^–1,fentanyl 2 µg kg^–1 and vecuronium 0.1 mg kg^–1.Patients were allocated randomly to receive either propofol4–8 mg kg^–1 h^–1 (group P; n=16)or 1.5–2.5 vol% sevoflurane (group S; n=17) for maintenanceof anaesthesia. Fentanyl 2–4 µg kg^–1was added if necessary. The lungs were ventilated with 50% airin oxygen. Blood pressure, heart rate, oxygen saturation andend-tidal carbon dioxide were measured before and throughoutanaesthesia and in the recovery room. IOP was determined withapplanation tonometry (Perkins) by one ophthalmologist blindedto the anaesthetic technique. Results. There was a significant decrease in IOP after inductionand during maintenance of anaesthesia in both groups. No significantdifferences in IOP between the two groups was found. Conclusion. Sevoflurane maintains the IOP at an equally reducedlevel compared with propofol. Br J Anaesth 2002; 89: 764–6     

Effects of propofol on cerebral oxygenation and metabolism after head injury

Background. Flow-metabolism coupling is thought to be derangedafter traumatic brain injury, while the effects of propofolon flow-metabolism coupling are controversial. We have useda step increase in target plasma propofol concentration in headinjured patients to explore flow-metabolism coupling in thesepatients. Methods. Ten patients with a moderate to severe head injuryreceived a step increase in propofol target controlled infusionof 2 µg ml^–1. Cerebral tissue gas measurements wererecorded using a multimodal sensor, and regional chemistry wasassessed using microdialysis. Arterial-jugular venous oxygendifferences (AVDO₂) were measured and all patients had corticalfunction monitoring (EEG). Results. The step increase in propofol led to a large increasein EEG burst-suppression ratio (0% (range 0–1.1) to 46.1%(range 0–61.7), P<0.05); however, this did not significantlychange tissue gas levels, tissue chemistry, or AVDO₂. Conclusions. Flow-metabolism coupling remains intact duringa step increase in propofol after traumatic brain injury. TheEEG burst-suppression induced by propofol after traumatic braininjury does not appear to be a useful therapeutic tool in reducingthe level of regional ischaemic burden. Br J Anaesth 2003; 91: 781–6     

Ketamine, but not propofol, anaesthesia is regulated by metabotropic glutamate 5 receptors

Background. Group I metabotropic glutamate receptors (mGluRs)have been reported to regulate N-methyl-D-aspartate (NMDA) receptorfunction in various brain regions. The selective mGluR5 antagonist2-methyl-6-(phenylethynyl)-pyridine (MPEP) can potentiate NMDAantagonists such as PCP and MK-801-induced behavioural responses.In the present study, the role of group I mGluRs on ketamine-and propofol-induced general anaesthesia was examined. Methods. Mice were pretreated with various doses of the groupI mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG), selectivemGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG),mGluR1 antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylateethyl ester (CPCCOEt) and mGluR5 antagonist MPEP followed byadministration of ketamine (120 mg kg^–1) or propofol (140mg kg^–1) to induce anaesthesia. The duration of loss ofrighting reflex was recorded. Results. DHPG and CHPG antagonized and MPEP potentiated ketamine-inducedanaesthesia in a dose-dependent manner. CPCCOEt was ineffective.However, propofol-induced anaesthesia was not affected aftermanipulating mGluR1 and mGluR5 receptors. Conclusions. mGluR5 receptors play an important role in modulationof anaesthesia induced by ketamine, but not propofol.     

Propofol injection pain in children: a prospective randomized double-blind trial of a new propofol formulation versus propofol with added lidocaine

Background. The incidence of pain on injection of propofol remainsunacceptably high in children, despite various strategies toreduce it. A new drug formulation of propofol has, in adultstudies, been reported to cause less injection pain comparedwith other propofol solutions. The aim of the present prospectiverandomized double-blind clinical trial was to compare the incidenceof pain-free injection following the use of this new formulationwith that following the use of propofol with added lidocainein children undergoing day case surgery. Methods. Eighty-three children (age range 2–18 yr) wererandomized to receive 3 mg kg^–1 of either Propofol-Lipuro®(propofol dissolved in a mixture of medium- and long-chain triglycerides[MCT–LCT]; group pL, n=42) or Diprivan® (propofoldissolved in long-chain triglycerides [LCT]) with added lidocaine(0.3 mg kg^–1) (group pD, n=41). A specially trained nurseanaesthetist assessed the occurrence of injection pain usinga four-graded pain scale. Results. Significantly fewer patients had an entirely pain-freepropofol injection in group pL (33.3%) than in group pD (61.0%)(P=0.016). Conclusions. A new MCT–LCT propofol formulation as a plainsolution was associated with a higher incidence of injectionpain than LCT propofol with added lidocaine when used for inductionof anaesthesia in children.     

Comparison of isoflurane and propofol-fentanyl anaesthesia in a swine model of asphyxia

Background. There have been few studies comparing the responseto asphyxia and the effectiveness of typical cardiopulmonaryresuscitation (CPR) using exogenous epinephrine administrationand manual closed-chest compression between total intravenousanaesthesia (TIVA) and inhalational anaesthesia. Methods. Twenty pigs were randomly assigned to two study groupsanaesthetized using either 2% end-tidal isoflurane (n=10) orpropofol (12 mg kg^–1 h^–1)–fentanyl (50 µgkg^–1) (n=10). Asphyxia was induced by clamping the trachealtube until the mean arterial pressure (MAP) decreased to 40%of the baseline value (40% MAP time). The tracheal tube wasdeclamped at that point, and CPR was performed. Haemodynamicparameters and blood samples were obtained before the inductionof asphyxia, at 1-min intervals during asphyxia, and 1, 2, 3,5, 10, 30 and 60 min after asphyxia. Results. TIVA maintained the MAP against hypoxia–hypercapniastress significantly longer than isoflurane anaesthesia (mean(SD) 40% MAP time 498 (95) and 378 (104) s respectively). Inall animals in the isoflurane group, spontaneous circulationreturned within 1 min of the start of CPR. In six of the TIVAanimals, spontaneous circulation returned for 220 (121) s; spontaneouscirculation did not return within 5 min in the remaining fouranimals. Conclusions. Although TIVA is less prone than isoflurane anaesthesiato primary cardiovascular depression leading to asphyxia, TIVAis associated with reduced effectiveness of CPR in which resuscitationbecause of asphyxic haemodynamic depression occurs. Br J Anaesth 2003; 91: 871–7     

Bispectral index is a topographically dependent variable in patients receiving propofol anaesthesia

Background. As very strong agreement has been reported betweenbispectral index (BIS) values measured from the occipital andfrontal skull areas, we compared BIS values measured from centraland parietal areas with those from frontal area to investigatewhether BIS is really a topographically dependent or topographicallyindependent variable. Methods. Twenty patients, ASA I–II, non-obese, aged 18–62yr and with no neurological disorders were enrolled. Based onthe 10–20 international landmarks, five silver dome electrodeswere positioned: F7, C3, P7, Cz (common reference) and Fp1 (ground).Using frontal (F7–Cz), central (C3–Cz) and parietal(P7–Cz) electrode montages, the corresponding BIS valueswere simultaneously recorded with an Aspect A-1000 monitor (softwarev3.12). The BIS values were recorded at the propofol concentrationallowing laryngeal mask insertion, which was maintained duringthe 10 min data collection period in absence of additional externalstimuli. Data were analysed using the Kruskall–Wallis,Wilcoxon paired sign with Bonferroni correction, Bland–Altmanand linear correlation tests. Results. At the predicted effect target propofol concentration4–8 µg ml^–1, the 10 min mean BIS (median [min–max])were 32 [20–44], 46 [28–68] and 58 [41–72]for the frontal, central and parietal leads, respectively. Differencesbetween these BIS recordings were statistically significant(P<0.0001, Kruskall–Wallis; P<0.005, Wilcoxon pairedsign test). Conclusions. The present results provide evidence that BIS indexis a topographically dependent variable in patients receivingpropofol anaesthesia.