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

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

Differential effects of thiopental on methacholine- and serotonin-induced bronchoconstriction in dogs

Background. Thiopental sometimes causes bronchospasm duringinduction of anaesthesia. In addition, we have reported previouslythat thiopental produced transient bronchospasm, which was blockedby atropine pretreatment, and worsened histamine-induced bronchoconstrictionin dogs. Previous in vitro reports suggest that synthesis ofcontractile cyclooxygenase products, such as thromboxane A₂,may be involved in the mechanism of bronchospasm. However, thein vivo spastic effects have not been defined comprehensively. Methods. Twenty-seven mongrel dogs were anaesthetized with pentobarbital.Bronchoconstriction was elicited with methacholine (0.5 µg kg^–1+5.0µg kg^–1 min^–1; Mch group, n=7) orserotonin (10 µg kg^–1+1 mg kg^–1 h^–1;5HT group, n=20), and assessed as percentage changes in bronchialcross-sectional area (BCA, basal=100%) using a bronchoscope.In the 5HT group, dogs were subdivided into four groups of fiveeach: S-5HT, I-5HT, 5HT-S and 5HT-A. In the S-5HT and I-5HTgroups, 30 min before serotonin infusion dogs were given salineand indomethacin respectively at 5 mg kg^–1 i.v. Inall groups, 30 min after bronchoconstrictor infusion started,dogs were given thiopental at doses between 0 (saline) and 20mg kg^–1. In the 5HT-S and 5HT-A groups, dogs weregiven saline or atropine 0.2 mg kg^–1 i.v. 5 min afterthiopental 20 mg kg^–1. Results. Methacholine and serotonin reduced BCA by about 50and 40% respectively. Thiopental 20 mg kg^–1 increasedand decreased BCA by about 20 and 10% in the Mch and 5HT groupsrespectively. Indomethacin and atropine did not attenuate thepotentiation of serotonin bronchoconstriction produced by thiopental. Conclusion. The present study indicates that thiopental mayattenuate or worsen bronchoconstriction induced by muscarinicor serotonin receptor stimulation, respectively. The synthesisof contractile cyclooxygenase products and cholinergic stimulationmay not be involved in the contractile effect of thiopentalon serotonin bronchoconstriction. Br J Anaesth 2003; 91: 379–84     

Stereoselective pharmacokinetics of ketamine and norketamine after racemic ketamine or S-ketamine administration during isoflurane anaesthesia in Shetland ponies

BACKGROUND: The arterial pharmacokinetics of ketamine and norketamine enantiomersafter racemic ketamine or S-ketamine i.v. administration wereevaluated in seven gelding ponies in a crossover study (2-monthinterval). METHODS: Anaesthesia was induced with isoflurane in oxygen via a face-maskand then maintained at each pony's individual MAC. Racemic ketamine(2.2 mg kg^–1) or S-ketamine (1.1 mg kg^–1)was injected in the right jugular vein. Blood samples were collectedfrom the right carotid artery before and at 1, 2, 4, 8, 16,32, 64, and 128 min after ketamine administration. Ketamineand norketamine enantiomer plasma concentrations were determinedby capillary electrophoresis. Individual R-ketamine and S-ketamineconcentration vs time curves were analysed by non-linear leastsquare regression two-compartment model analysis using PCNonlin.Plasma disposition curves for R-norketamine and S-norketaminewere described by estimating AUC, C_max, and T_max. Pulse rate(PR), respiratory rate (R_f), tidal volume (V_T), minute volumeventilation (V_E), end-tidal partial pressure of carbon dioxide(PE'_CO2), and mean arterial blood pressure (MAP) were also evaluated. RESULTS: The pharmacokinetic parameters of S- and R-ketamine administeredin the racemic mixture or S-ketamine administered separatelydid not differ significantly. Statistically significant higherAUC and C_max were found for S-norketamine compared with R-norketaminein the racemic group. Overall, R_f, V_E, PE'_CO2, and MAP weresignificantly higher in the racemic group, whereas PR was higherin the S-ketamine group. CONCLUSIONS: Norketamine enantiomers showed different pharmacokinetic profilesafter single i.v. administration of racemic ketamine in poniesanaesthetised with isoflurane in oxygen (1 MAC). Cardiopulmonaryvariables require further investigation.     

Rapacuronium recovery characteristics and infusion requirements during inhalation versus propofol-based anaesthesia

We examined the effect of four maintenance anaesthetics on theneuromuscular blocking activity and spontaneous recovery characteristicsafter a short-term infusion of rapacuronium. Eighty ASA I–IIIadult patients undergoing elective surgery were studied at fourcentres. Anaesthesia was induced with propofol 1.5–2.5 mg kg^–1and fentanyl 1–2 µg kg^–1, followedby a bolus of rapacuronium 1.5 mg kg^–1. Thepatients were randomized to receive either desflurane (2–4%end-tidal, ET), sevoflurane (0.75–1.5% ET), isoflurane(0.4–0.8% ET), or a propofol infusion (75–150 µg kg^–1 min^–1)for maintenance of anaesthesia in combination with nitrous oxide(60–70%) in oxygen. When the first twitch (T₁) of a train-of-fourstimulus (using the TOF Guard^® accelerometer) returned to5%, an infusion of rapacuronium was started at 3 mg kg^–1 h^–1and adjusted to maintain T₁/T₀ at 10%. The duration of infusionlasted between 45 and 60 min, and the average infusionrates of rapacuronium were similar in all groups, ranging from1.6 to 2.5 mg kg^–1 h^–1. There wereno significant differences among the groups in the times forT₁/T₀ to return to 25%, 75% or 90%, or for T₄/T₁ to return to70% and 80% upon discontinuation of the infusion. When potentinhalation anaesthetics are used in clinically relevant concentrationsfor maintenance of anaesthesia, the neuromuscular recovery profileof rapacuronium administered as a variable-rate infusion forup to 1 h is similar to that found with a propofol-basedanaesthetic technique. Br J Anaesth 2000; 85: 302–5     

Comparison of relaxant effects of propofol on methacholine-induced bronchoconstriction in dogs with and without vagotomy

Propofol has been suggested to have in vivo airway relaxanteffects, although the mechanism is still unclear. In this study,we determined whether propofol could antagonize methacholine-inducedbronchoconstriction and determined whether vagotomy modifiesthis relaxant effect. Fourteen mongrel dogs anaesthetized withpentobarbital and pancuronium were assigned to a control group(n=7) and a vagotomy group (n=7). The trachea was intubatedwith a special endotracheal tube that had a second lumen forinsertion of the bronchoscope. Bronchial cross-sectional area,which was monitored continuously through the bronchoscope, wasmeasured with image analysis software. Bronchoconstriction waselicited with methacholine (0.5 µg kg^–1 + 5.0 µg kg^–1 min^–1)until the end of the experiment. Thirty minutes after the startof methacholine infusion, propofol 0, 0.2, 2.0 and 20 mg kg^–1was administered. Changes in bronchial cross-sectional areawere expressed as percentages of the basal area. Plasma concentrationsof propofol and catecholamine were measured by high-performanceliquid chromatography. Maximal inhibition (bronchoconstriction= 0%, baseline = 100%) and IC₅₀ (concentration producing 50%inhibition of maximal effect) produced by propofol was obtainedfrom each concentration–response curve using a curve-fittingprogram. Methacholine decreased bronchial cross-sectional areato 49.3% (95% confidence interval 38.5–60.1%) and 45.3%(34.8–55.7%) of the baseline value. Propofol 20 mg kg^–1significantly reversed this effect: bronchial cross-sectionalarea was reduced to 77.8% (66.2–89.6%) and 75.9% (64.0–87.9)in the control and vagotomy groups respectively. The two groupsdid not differ significantly in the maximal inhibitory effectof propofol [control group, 61.1% (46.3–75.9%), vagotomygroup, 64.2% (40.1–88.3%)] or pIC₅₀ [control group 5.03(4.55–5.51), vagotomy group 4.86 (4.49–5.24)]. Therefore,the relaxant effects of propofol on methacholine-induced bronchoconstrictionmay not be mediated centrally. Propofol may relax airway smoothmuscles directly or through the peripheral vagal pathway. Br J Anaesth 2001; 86: 249–53     

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     

Inhaled olprinone improves contractility of fatigued canine diaphragm

Background. Diaphragmatic fatigue is implicated as a cause ofrespiratory failure. This study was undertaken to evaluate theeffects of inhaled olprinone, a newly developed phosphodiesteraseIII inhibitor, on the contractility of fatigued diaphragm indogs. Methods. Diaphragmatic fatigue was induced by intermittent supramaximalbilateral electrophrenic stimulation at a frequency of 20 Hzstimulation applied for 30 min. When fatigue was established,group I (n=8) received inhaled vehicle; group II (n=8) receivedinhaled olprinone 1 mg; group III (n=8) received inhaled olprinone2 mg. Diaphragmatic contractility was assessed by transdiaphragmaticpressure (Pdi, cm H₂O). Results. In the presence of fatigue, in each group, Pdi at low-frequency(20 Hz) stimulation decreased from baseline values (P<0.05),whereas Pdi at high-frequency (100 Hz) stimulation did not change.In groups II and III, during olprinone administration, Pdi atboth stimuli increased from fatigued values (20 Hz stimulation:group II (mean (SD)) 10.8 (1.0) to 12.5 (1.3), group III 10.9(1.7) to 15.0 (3.0); 100 Hz stimulation: group II 20.1 (1.9)to 22.6 (1.3), group III 20.6 (2.0) to 24.5 (2.0), P<0.05).The increase in Pdi was larger in group III than in group II(P<0.05). Conclusions. Inhaled olprinone produces a dose-dependent improvementin contractility of fatigued canine diaphragm. Br J Anaesth 2002; 88: 408–11     

Evaluation of effects of magnesium sulphate in reducing intraoperative anaesthetic requirements

Background. The present randomized, placebo-controlled, double-blindstudy was designed to assess the effect of peroperatively administeredi.v. magnesium sulphate on anaesthetic and analgesic requirementsduring total i.v. anaesthesia. Methods. Eighty-one patients (36 women, 45 men) undergoing electivespinal surgery were included in one of two parallel groups.The magnesium group received magnesium sulphate 30 mg kg^–1as a bolus before induction of anaesthesia and 10 mg kg^–1h^–1 by continuous i.v. infusion during the operation period.The same volume of isotonic solution was administered to thecontrol group. Anaesthesia was maintained with propofol (administeredaccording to the bispectral index) and remifentanil (adjustedaccording to heart rate and arterial blood pressure) infusions. Results. A significant reduction in hourly propofol consumptionwas observed with magnesium administration. For example, themean infusion rate of propofol in the second hour of the operationwas 7.09 mg kg^–1 h^–1 in the controlgroup vs 4.35 mg kg^–1 h^–1 in themagnesium group (P<0.001). The magnesium group required significantlyless remifentanil (P<0.001) and vecuronium (P<0.001).No side-effects were observed with magnesium administration. Conclusion. The administration of magnesium led to a significantreduction in the requirements for anaesthetic drugs during totali.v. anaesthesia with propofol, remifentanil and vecuronium. Br J Anaesth 2002; 89: 594–8     

Suppressive effect of nitrous oxide on motor evoked potentials can be reversed by train stimulation in rabbits under ketamine/fentanyl anaesthesia, but not with additional propofol

The effect of nitrous oxide on myogenic motor evoked potentials(MEPs) after multipulse stimulation is controversial. We investigatedthe effects of propofol in this paradigm. MEPs were elicitedelectrically by a single pulse and by trains of three and fivepulses in rabbits anaesthetized with ketamine and fentanyl.Nitrous oxide 30–70% was given and MEPs were recorded.After washout of nitrous oxide, propofol was given as a bolusof 10 mg kg^–1 followed by 0.8 (n=9) or 1.6 mg kg^–1 min^–1(n=8) as a continuous infusion. Nitrous oxide was then readministeredand MEPs were recorded. Without propofol, nitrous oxide significantlyreduced the amplitude of MEPs dose-dependently, but this effectwas reversed by multipulse stimulation. Administration of low-dosepropofol enhanced nitrous oxide-induced suppression, and thiseffect was reversed by five-pulse stimulation. However, high-dosepropofol produced a greater increase in suppression, such thateven five-pulse stimulation did not overcome the suppression.The results suggest that the degree of reversal of nitrous oxide-inducedMEP suppression produced by multipulse stimulation is affectedby the administration of propofol. Br J Anaesth 2001; 86: 395–402     

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     

Differential effects of propofol, ketamine, and thiopental anaesthesia on the skeletal muscle microcirculation of normotensive and hypertensive rats in vivo

Background. This study utilized the dorsal microcirculatorychamber (DMC) model to determine differential effects of i.v.propofol, ketamine, and thiopental anaesthesia on the skeletalmuscle microcirculation (10–180 µm) of normotensive(Male Wistar Kyoto, WKY) and hypertensive (spontaneously hypertensiveHarlan, SHR) rats, importantly, comparing responses to a consciousbaseline. Methods. Three weeks following implantation of the DMC in WKY(n=8) and SHR (n=6) (130 g) 0.25 ml 100 g^–1 FITC–BSA(i.v.) was administered and the microcirculation viewed usingfluorescent in vivo microscopy for a 30 min baseline (t=0–30min). This was followed by either propofol, thiopental, ketamine,or saline (i.v. bolus induction over 5 min (t=30–35 min)),then maintenance step-up infusion for 60 min (t=45–105min), so that animals received all four agents 1 week apart(56 experiments). Results. Dilation of A3 arterioles (15–30 µm) andV3 venules (20–40 µm) with propofol was greaterin SHR (t=95 min, A3 36.7 (12)%, V3 15.5 (2.3)%) than WKY (t=95min, A3 19.4 (7.4)%, V3 8.0 (2.3)%) (P<0.05). Constrictionof A3 with ketamine was greater in SHR (t=95 min, A3 –29.1(6.4)%) than WKY (A3 –17.5 (8.8)%) (P<0.05). This wasaccompanied by hypotension with propofol in SHR (–32%decrease in systolic arterial pressure), but not WKY (–6%)and hypertension with ketamine in WKY (–15%) and SHR (–24%)(P<0.05). During thiopental anaesthesia there was dilationof A1 (80–180 µm), A3, and V3 in WKY (P<0.05).Conversely, in SHR dilation of venules (29.2 (8.7)%) was accompaniedby constriction of A1 and A3 (t=95 min, A1 –25.1 (5.9)%,A3 –45.2 (3.1)%) (P<0.05). Conclusion. Within the skeletal muscle microcirculation of hypertensiverats there is enhanced dilation with propofol and constrictionwith ketamine, associated with exaggerated changes in arterialpressure. Thus, dysfunctional control mechanisms at the levelof the microcirculation alter responses to anaesthesia duringhypertension.      

RETRACTED ARTICLE: Effects of dobutamine on the fatigued diaphragm: A comparison with dopamine

We examined the effects of dopamine (DOA) 10 μg·kg⁻¹·min⁻¹ I.V. and dobutamine (DOB) 10 μg·kg⁻¹. min⁻¹ I.V. on the contractility of the fatigued diaphragm in 26 anesthetized, mechanically ventilated dogs. Animals were divided into two groups of 13 each: the DOA and DOB groups. Diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. Diaphragmatic contractility was assessed from changes in transdiaphragmatic pressure (P_di). After diaphragmatic fatigue, P_di at low-frequency (20 Hz) stimulation decreased significantly compared with the prefatigue value (P<0.05), whereas no change in P_di was observed at high-frequency (100 Hz) stimulation. In the fatigued diaphragm, P_di at both stimuli increased with an infusion of either DOA (P<0.05) or DOB (P<0.05). The increase of P_di at 20 Hz stimulation was significantly larger in the DOB group compared with that of the DOA group (P<0.05). In each group, P_di at both stimuli decreased after the cessation of administration. The integrated diaphragmatic electric activity (E_di) in the two groups did not change at any frequency of stimulation throughout the study. We conclude that DOB in comparison with DOA is more effective in improving the contractility of the fatigued diaphragm.     

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     

Effect site concentrations of remifentanil and pupil response to noxious stimulation

Background. Opioid drugs block reflex pupillary dilatation inresponse to noxious stimulation. The relationship between thetarget effect site concentration (Ce_T) of remifentanil and thepupil diameter and reactivity in response to a standard noxiousstimulus were evaluated. Methods. Anaesthesia was induced with propofol TCI to obtainloss of consciousness (LOC) in 12 ASA I/II patients. Thereafter,remifentanil Ce_T was titrated by increments of 1 up to 5 ngml^–1. In the awake state, at LOC and at each plateau levelof remifentanil Ce_T, arterial pressure, heart rate, and BIS(A2000) were recorded. Pupil size and dilatation after a 100Hz tetanic stimulation (T100) were measured at LOC and at eachplateau level of remifentanil Ce_T. Results. LOC was observed at a mean propofol Ce_T of 3.53 (SD0.43) µg ml^–1. Arterial pressure and heart ratedecreased progressively from LOC to 5 ng ml^–1 remifentanilCe_T without any statistical difference between each incrementaldose of remifentanil. Mean BIS values decreased from 96 (2)in the awake state, to 46 (12) at LOC (P<0.05) and then remainedunchanged at all remifentanil Ce_T. Pupil dilatation in responseto 100 Hz tetanic stimulation decreased progressively from 1.55(0.72) to 0.01 (0.03) mm and was more sensitive than pupil diametermeasured before and after 100 Hz tetanus. An inverse correlationbetween pupil dilatation in response to 100 Hz tetanus and anincrease in remifentanil Ce_T from 0 to 5 ng ml^–1 was found(R²=0.68). Conclusions. During propofol TCI in healthy patients, the decreasein pupil response to a painful stimulus is a better measurementof the progressive increase of remifentanil Ce_T up to 5 ng ml^–1than haemodynamic or BIS measurements. Br J Anaesth 2003; 91: 347–52     

Effects of 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.     

RETRACTED ARTICLE: Nicardipine inhibits amrinone-enhanced contractility in fatigued diaphragm

The purpose of this study was to examine the effect of amrinone, a bipyridine derivative, with and without nicardipine, a calcium channel blocker, on the contractility of fatigued diaphragm in dogs. Twenty dogs were divided into two groups of ten each: amrinone group (group A) and combined amrinone and nicardipine group (group AN). Diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. Diaphragmatic contractility was assessed from changes in transdiaphragmatic pressure (P_di). In group A, after producing fatigue, amrinone (0.75 mg·kg⁻¹ loading dose plus 10 μg·kg⁻¹·min⁻¹ maintenance dose) was administered iv. In group AN, nicardipine 5 μg·kg⁻¹·min⁻¹ was infused iv simultaneously with amrinone during this period. After diaphragmatic fatigue, P_di at low-frequency (10–30 Hz) stimulation decreased compared with the prefatigue values (P<0.05), whereas no change in P_di was observed at high-frequency (50–100 Hz), stimulation. The P_di at each stimulus were increased compared with the fatigued values (P<0.05) by administering amrinone, and returned to these values after this agent was discontinued. The P_di values at any frequency of stimulation did not change when amrinone was administered with nicardipine. Our results suggest that amirinone may enhance contractility in fatigued diaphragm via its effect on transmembrane calcium movement.     

Impact of depth of propofol anaesthesia on functional residual capacity and ventilation distribution in healthy preschool children

Background: Propofol is commonly used in children undergoing diagnosticinterventions under anaesthesia or deep sedation. Because hypoxaemiais the most common cause of critical deterioration during anaesthesiaand sedation, improved understanding of the effects of anaestheticson pulmonary function is essential. The aim of this study wasto determine the effect of different levels of propofol anaesthesiaon functional residual capacity (FRC) and ventilation distribution. Methods: In 20 children without cardiopulmonary disease mean age (SD)49.75 (13.3) months and mean weight (SD) 17.5 (3.9) kg,anaesthesia was induced by a bolus of i.v. propofol 2 mg kg^–1followed by an infusion of propofol 120 µg kg^–1 min^–1(level I). Then, a bolus of propofol 1 mg kg^–1was given followed by a propofol infusion at 240 µg kg^–1 min^–1(level II). FRC and lung clearance index (LCI) were calculatedat each level of anaesthesia using multibreath analysis. Results: The FRC mean (SD) decreased from 20.7 (3.3) ml kg^–1at anaesthesia level I to 17.7 (3.9) ml kg^–1at level II (P < 0.0001). At the same time, mean (SD) LCIincreased from 10.4 (1.1) to 11.9 (2.2) (P = 0.0038), whereasbispectral index score values decreased from mean (SD) 57.5(7.2) to 35.5 (5.9) (P < 0.0001). Conclusions: Propofol elicited a deeper level of anaesthesia that led toa significant decrease of the FRC whereas at the same time theLCI, an index for ventilation distribution, increased indicatingan increased vulnerability to hypoxaemia.     

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.     

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

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

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