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.      

Effects of ketamine and propofol on inflammatory responses of primary glial cell cultures stimulated with lipopolysaccharide

Background. Ketamine has been reported to exert anti-inflammatoryeffects on macrophages stimulated with lipopolysaccharide (LPS)in vitro and in vivo. Several studies have reported conflictingresults regarding the effects of propofol on cytokine productionfrom immune cells. However, there have been no reports of theeffects of these agents on inflammatory responses in glial cells.We investigated the effects of ketamine and propofol on LPS-inducedproduction of nitric oxide, tumour necrosis factor-     

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.     

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     

Predictive performance of the Domino, Hijazi, and Clements models during low-dose target-controlled ketamine infusions in healthy volunteers

Background: Healthy volunteers received low-dose target-controlled infusions(TCI) of ketamine controlled by the Domino model while cognitivefunction tests and functional neuroimaging were performed. Theaim of the current study was to assess the predictive performanceof the Domino model during these studies, and compare it withthat of three other ketamine models. Methods: Fifty-eight volunteers received ketamine administered by a TCIdevice on one or more occasions at target concentrations ofeither 50, 100, or 200 ng ml^–1. At each target concentration,two or three venous blood samples were withdrawn during infusion,with a further sample after the infusion ended. Ketamine assayswere performed by gas chromatography. The plasma concentrationtime courses predicted by the Hijazi, Clements 125, and Clements250 models were calculated retrospectively, and the predictiveperformance of each of the models was assessed using Varvelmethodology. Results: For the Domino model, bias, inaccuracy, wobble, and divergencewere – 2.7%, 33.9%, 24.2%, and 0.1463 % h^–1, respectively.There was a systematic increase in performance error over time.The Clements 250 model performed best by all criteria, whereasthe Hijazi model performed least well by all criteria exceptfor bias. Conclusions: Performance of the Domino model during control of low-dose ketamineinfusions was sub-optimal. The Clements 250 model may be a bettermodel for controlling low-dose TCI ketamine administration     

Propofol and halothane versus sevoflurane in paediatric day-case surgery: induction and recovery characteristics

Background. The aim of this study was to compare the inductionand recovery characteristics associated with propofol inductionand halothane maintenance with sevoflurane anaesthesia in paediatricday surgery. Methods. In total, 322 children were assigned randomly to i.v.propofol induction and halothane/nitrous oxide maintenance orsevoflurane/nitrous oxide alone. The patients’ age, sex,and type of surgery were recorded, as were the times requiredfor anaesthetic induction, maintenance, recovery and time todischarge home. Postoperative nausea and vomiting, and the incidenceof adverse events during induction and recovery were also noted. Results. No significant differences were detected in age, sex,type of surgery performed or intraoperative opioid administration.Excitatory movement was more common during induction with sevoflurane.The mean time required for induction with propofol was 3.1 mincompared with 5 min in the sevoflurane group (P<0.001). Therecovery time was shorter in the sevoflurane group comparedwith propofol/halothane (23.2 vs 26.4 min, P<0.002). Theincidence of delirium in recovery was greater in the sevofluranegroup (P<0.001). There was no difference between groups inthe time spent on the postoperative ward before discharge home.On the postoperative ward the incidence of both nausea and vomitingwas significantly higher in the sevoflurane group (P=0.034).Five children were admitted to hospital overnight, none foranaesthetic reasons. Conclusions. The increased incidence of adverse events duringinduction, postoperative nausea and vomiting and postoperativedelirium in the sevoflurane group suggests that sevofluraneis not ideal as a sole agent for paediatric day case anaesthesia. Br J Anaesth 2003; 90: 461–6     

Effect of low-dose ketamine on inflammatory response in off-pump coronary artery bypass graft surgery

Background: Off-pump coronary artery bypass graft surgery (OPCAB) is stillassociated with a marked systemic inflammatory response. Theaim of this study was to investigate whether pre-emptive, lowdose of ketamine, which has been reported to have anti-inflammatoryactivity in on-pump coronary artery bypass surgery, could reduceinflammatory response in low-risk patients undergoing OPCAB. Methods: In this prospective randomized-controlled trial, 50 patientswith stable angina and preserved myocardial function undergoingOPCAB were randomly assigned to receive either 0.5 mg kg^–1of ketamine (Ketamine group, n=25) or normal saline (Controlgroup, n=25) during induction of anaesthesia. Inflammatory markersincluding C-reactive protein (CRP), interleukin (IL)-6, tumournecrosis factor- (TNF-), and cardiac enzymes were measured previousto induction (T1), 4 h after surgery (T2), and the first andsecond days after the surgery (T3 and T4). Results: There were no significant intergroup differences in the serumconcentrations of the CRP, IL-6, and TNF- and cardiac enzymes.Pro-inflammatory markers and cardiac enzymes, except TNF-, wereall increased after the surgery compared with baseline valuesin both groups. Conclusions: Low-dose ketamine administered during anaesthesia inductiondid not exert any evident anti-inflammatory effect in termsof reducing the serum concentrations of pro-inflammatory markersin low-risk patients undergoing OPCAB.     

Low-dose ketamine affects immune responses in humans during the early postoperative period

Background: Anaesthesia and surgery are associated with impairment of theimmune system expressed as an excessive proinflammatory immuneresponse and suppression of cell-mediated immunity that mayaffect the course of the postoperative period. Addition of anaestheticagents capable of attenuating the alterations in perioperativeimmune function may exert a favourable effect on patients’healing. We have assessed the effect of preoperative administrationof a sub-anaesthetic dose of ketamine on the mitogen responseand production of interleukin (IL)-1ß, IL-2, IL-6,and tumour necrosis factor (TNF)- by peripheral blood mononuclearcells (PBMCs), as well as natural killer cell cytotoxicity (NKCC)in patients undergoing abdominal surgery. Methods: Seventeen patients admitted for elective abdominal surgery weregiven ketamine 0.15 mg kg^–1 i.v. 5 min before inductionof general anaesthesia. Nineteen patients received a similarvolume of isotonic saline 5 min before induction of the anaesthesia.PBMCs were isolated from venous blood before and 4, 24, 48,and 72 h after operation for IL-1ß, IL-2, IL-6, andTNF- secretion, and NKCC assessment. Results: Four hours after operation, the cells from patients in the ketaminegroup showed a significantly suppressed production of IL-6 (P< 0.01) compared with controls. The production of IL-2 didnot change from that of the preoperation samples. TNF- secretionwas significantly elevated in the control group 4 h after operation(P < 0.05). Conclusions: Addition of small doses of ketamine before induction of anaesthesiaresulted in attenuation of secretion of the proinflammatorycytokines IL-6 and TNF-, and in preservation of IL-2 productionat its preoperative level. It is suggested that this anaestheticmay be of value in preventing immune function alterations inthe early postoperative period.     

EEG-controlled closed-loop dosing of propofol in rats

Background. Based on previous pharmacokinetic and pharmacodynamicstudies, we have developed an EEG-controlled closed-loop systemfor the i.v. hypnotic agent propofol in rats. Methods. Seven adult male Sprague–Dawley rats (weight423–584 g) were included in the study. EEG was recordedwith occipito–occipital needle electrodes and the EEGpower spectrum was estimated. The median frequency (MEF) wasextracted from the power spectrum and was modified MEF (mMEF)to account for the occurrence of spikes and burst suppressionpatterns in the EEG. Propofol infusion was controlled by a model-basedadaptive control algorithm to maintain a set point of mMEF=3.0(SD 0.5) Hz. The performance of the feedback system was characterizedby the median performance error MDPE=median{(mMEF–setpoint)/set point} and the median absolute performance error(MDAPE). The effective therapeutic infusion (ETI) to maintainthe set point was determined from the resulting infusion rates. Results. In all rats a feedback period of 90 min could be performed.Mean MDPE was 1.2 (SE 0.4)% and MDAPE was 13.9 (0.3)%. The ETIwas 0.73 (SD 0.20) mg kg^–1 min^–1. Mean arterialpressure before propofol infusion was 148 (14) mm Hg, with thelowest value during closed-loop infusion being 110 (20) mm Hg. Conclusions. The feedback system presented here may be a usefultool not only for automatic drug control to maintain a definedhypnotic effect but may also be a powerful device in pharmacologicalstudies such as the determination of dose requirements or theassessment of drug–drug interactions. Br J Anaesth 2004; 92: 564–9     

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.     

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     

Propofol 1% versus propofol 2% in children undergoing minor ENT surgery

Background. The induction characteristics of propofol 1% and2% were compared in children undergoing ENT surgery, in a prospective,randomized, double-blind study. Methods. One hundred and eight children received propofol 1%(n=55) or 2% (n=53) for induction and maintenance of anaesthesia.For induction, propofol 4 mg kg^–1 was injectedat a constant rate (1200 ml h^–1), supplementedwith alfentanil. Intubating conditions without the use of aneuromuscular blocking agent were scored. Results. Pain on injection occurred in 9% and 21% of patientsafter propofol 1% and 2%, respectively (P=0.09). Loss of consciousnesswas more rapid with propofol 2% compared with propofol 1% (47 svs 54 s; P=0.02). Spontaneous movements during inductionoccurred in 22% and 34% (P=0.18), and intubating conditionswere satisfactory in 87% and 96% (P=0.19) of children receivingpropofol 1% or 2%, respectively. There were no differences betweenthe two groups in respect of haemodynamic changes or adverseevents. Conclusions. For the end-points tested, propofol 1% and propofol2% are similar for induction of anaesthesia in children undergoingminor ENT surgery. Br J Anaesth 2003: 90: 375–7     

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.     

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     

Reduction of pain during induction with target-controlled propofol and remifentanil

BACKGROUND: Pain on injection of propofol is unpleasant. We hypothesized that propofol infusion pain might be prevented by infusing remifentanil before starting the propofol infusion in a clinical setting where target-controlled infusions (TCI) of both drugs were used. A prospective, randomized, double-blind, placebo-controlled trial was performed to determine the effect-site concentration (Ce) of remifentanil to prevent the pain without producing complications. METHODS: A total of 128 patients undergoing general surgery were randomly allocated to receive normal saline (control) or remifentanil to a target Ce of 2 ng ml(-1) (R2), 4 ng ml(-1) (R4), or 6 ng ml(-1) (R6) administered via TCI. After the target Ce was achieved, the infusion of propofol was started. Remifentanil-related complications were assessed during the remifentanil infusion, and pain caused by propofol was evaluated using a four-point scale during the propofol infusion. RESULTS: The incidence of pain was significantly lower in Groups R4 and R6 than in the control and R2 groups (12/32 and 6/31 vs 26/31 and 25/32, respectively, P<0.001). Pain was less severe in Groups R4 and R6 than in the control and R2 groups (P<0.001). However, both incidence and severity of pain were not different between Groups R4 and R6. No significant complications were observed during the study. CONCLUSIONS: During induction of anaesthesia with TCI of propofol and remifentanil, a significant reduction in propofol infusion pain was achieved without significant complications by prior administration of remifentanil at a target Ce of 4 ng ml(-1).     

Propofol sparing effect of remifentanil using closed-loop anaesthesia

Background. General anaesthesia is a balance between hypnosisand analgesia. We investigated whether an increase in remifentanilblood concentration would reduce the amount of propofol requiredto maintain a comparable level of anaesthesia in 60 patientsundergoing ambulatory surgery. Methods. Patients were allocated randomly to receive remifentanilto a target blood concentration of 2 ng ml^–1 (low), 4ng ml^–1 (medium), or 8 ng ml^–1 (high), administeredby target-controlled infusion (TCI). After equilibration, propofolTCI was commenced in closed-loop control, with auditory evokedpotentials (AEPex) as the input signal, aiming for an AEPexof 35. This was to ensure a comparable and unbiased level ofanaesthesia in all patients. Results. We found a dose-dependent decrease in propofol requirementswith increasing remifentanil concentrations. The mean (95% CI)propofol target blood concentration during adequate anaesthesiawas 4.96 (3.85–6.01) µg ml^–1 in the low, 3.46(2.96–3.96) µg ml^–1 in the medium, and 3.01(2.20–3.38) µg ml^–1 in the high group. Therewas no significant difference when recovery end points wereachieved between the groups. Cardiovascular changes were moderate,but most pronounced in the high concentration group, with adecrease in heart rate of 21% compared with baseline. The meancalculated effect site propofol concentration at loss of consciousnesswas 2.08 (1.85–2.32) µg ml^–1, and at recoveryof consciousness was 1.85 (1.68–2.00) µg ml^–1. Conclusions. This study confirms a synergistic interaction betweenremifentanil and propofol during surgery, whereas the contributionof remifentanil in the absence of stimulation seems limited.In addition, our results suggest that the propofol effect siteconcentration provides a guide to the value at which the patientrecovers consciousness. Br J Anaesth 2003; 90: 623–9     

Adding ketamine to morphine for patient-controlled analgesia after thoracic surgery: influence on morphine consumption, respiratory function, and nocturnal desaturation

Background: I.V. patient-controlled analgesia (PCA) with morphine is oftenused for postoperative analgesia after thoracic surgery, butthe required doses may increase postoperative respiratory disorders.Adjunction of ketamine could reduce both doses and related respiratoryside-effects. Methods: The main objective of this prospective, randomized double-blindedstudy was to evaluate the influence of adding ketamine to PCAon morphine consumption and postoperative respiratory disorders.Consecutive patients undergoing lobectomy (n = 50) were randomlyassigned to receive, during the postoperative period, eitheri.v. morphine 1 mg ml^–1 or morphine with ketamine 1 mgml^–1 for each. Morphine consumption was evaluated by cumulativedoses every 12 h for the three postoperative days. Postoperativerespiratory disorders were assessed by spirometric evaluationand recording of nocturnal desaturation. Results: The adjunction of ketamine resulted in a significant reductionin cumulative morphine consumption as early as the 36th postoperativehour [43 (SD 18) vs 32 (14) mg, P = 0.03] with a similar visualanalogue scale. In the morphine group, the percentage of timewith desaturation < 90% was higher during the three nights[1.80 (0.21–6.37) vs 0.02 (0–0.13), P < 0.001;2.15 (0.35–8.65) vs 0.50 (0.01–1.30), P = 0.02;2.46 (0.57–5.51) vs 0.55 (0.21–1.00), P = 0.02].The decrease in forced expiratory volume in 1 s was less markedin the ketamine group at the first postoperative day [1.04 (0.68–1.22)litre vs 1.21 (1.10–0.70) litre, P = 0.039]. Conclusions: Adding small doses of ketamine to morphine in PCA devices decreasesthe morphine consumption and may improve respiratory disordersafter thoracic surgery.     

Feasibility study for the administration of remifentanil based on the difference between response entropy and state entropy

Background: Facial electromyography (FEMG) may have utility in the assessmentof nociception during surgery. The difference between stateentropy (SE) and response entropy (RE) is an indirect measureof FEMG. This study assesses an automated algorithm for remifentaniladministration that is based on maintaining an entropy difference(ED) that is less than an upper boundary condition and greaterthan a lower boundary condition. Methods: The algorithm was constructed with a development set (n = 40),and then automated and studied with a validation set (n = 20)of patients undergoing anterior cruciate ligament repair. Thepercentage of time that the ED was maintained between the twoboundary conditions was determined. Remifentanil and propofolpredicted effect-site concentrations (Ce) were determined atsurgical milestones and, after drug discontinuation, the timeto response to verbal stimulation and orientation was measured. Results: The median (25th–75th percentile) per cent of time thatthe ED was recorded between the boundary conditions was 99.3%(98.1–99.8%). Predicted propofol (µg ml^–1)and remifentanil (ng ml^–1) Ce (SD), respectively, were3.5 and 4.0 at induction, 1.9 (0.8) and 7.2 (3.7) at the endof surgery, and 1.1 (0.5) and 3.2 (2.2) at eye opening. Themedian time to eye opening and orientation was 3.8 and 6.8 min,respectively. Conclusion: This feasibility study supports the concept that remifentanilmay be delivered using an algorithm that maintains the differencebetween SE and RE between the upper and lower boundary condition.     

Effects of sevoflurane and propofol on ischaemia-reperfusion injury after thoracic-aortic occlusion in pigs

Background: Thoraco-abdominal-aneurysm surgery predicts high mortality.Propofol and sevoflurane are commonly used anaesthetics forthis procedure. Halogenated anaesthetics induce organ protectionsimilar to ischaemic preconditioning. We investigated whichanaesthetic regimen would lead to a better protection againstischaemia–reperfusion injury induced by temporary thoracic-aorticocclusion. Methods: Following initial fentanyl–midazolam anaesthesia for surgicalpreparation, 18 pigs were randomly assigned to two groups: groupone received propofol (n = 9) and group two sevoflurane (n =9) before, during, and after lower body ischaemia in an investigatorblinded fashion. Ten animals without aortic occlusion servedas time controls (propofol, n = 5; sevoflurane, n = 5). Forinduction of ischaemia, the thoracic aorta was occluded by aballoon-catheter for 90 min. After 120 min of reperfusion, thestudy anaesthetics were discontinued and fentanyl–midazolamre-established for an additional 180 min. Goal-directed therapywas performed during reperfusion. Fluid and catecholamine requirementswere assessed. Serum samples and intestinal tissue specimenswere obtained. Results: Severe declamping shock occurred in both study groups. Whilenorepinephrine requirements in the sevoflurane group were significantlyreduced during reperfusion (P < 0.05), allowing cessationof catecholamine support in 4/9 animals, all 9/9 animals werestill catecholamine dependent at the end of the experiment inthe propofol group. Serum activities of lactate dehydrogenase,aspartate transaminase, and alanine aminotransferase were lowerwith sevoflurane (P < 0.05). Small intestine tissue specimensdid not differ histologically. Conclusions: Use of sevoflurane compared with propofol attenuated the haemodynamicsequelae of reperfusion injury in our model. Release of serummarkers of cellular injury was also attenuated.     

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.