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     

Relationship between bispectral index,auditory evoked potential index and effect-site EC50 for propofol at two clinical end-points

Background. Many anaesthetists are deterred from using totali.v. anaesthesia because of uncertainty over the concentrationof propofol required to prevent awareness. We predicted bloodand effect-site concentrations of propofol at two clinical end-points:loss of consciousness and no response to a painful stimulus. Methods. Forty unpremedicated Caucasian patients were anaesthetizedwith i.v. propofol delivered by a Diprifusor target-controlledinfusion (TCI). Bispectral index (BIS) and auditory evoked potentialindex (AEPex) were measured and blood and effect-site propofolconcentrations were predicted. Logistic regression was usedto estimate population values for predicted blood and effect-sitepropofol concentrations at the clinical end-points and to correlatethese with BIS and AEPex. Results. The effect-site EC₅₀ at loss of consciousness was 2.8 µm ml^–1with an EC₀₅ and an EC₉₅ of 1.5 and 4.1 µm ml^–1,respectively. The predicted EC₅₀ when there was no responseto a tetanic stimulus was 5.2 µm ml^–1 withan EC₀₅ and an EC₉₅ of 3.1 and 7.2 µm ml^–1,respectively. Conclusions. Unconsciousness and lack of response to a painfulstimulus occur within a defined range of effect-site concentrations,predicted by Diprifusor TCI software. Br J Anaesth 2003; 90: 127–31     

Effects of fentanyl, alfentanil, remifentanil and sufentanil on loss of consciousness and bispectral index during propofol induction of anaesthesia

The bispectral index (BIS) and a sedation score were used todetermine and compare the effect of propofol in the presenceof fentanyl, alfentanil, remifentanil and sufentanil. Seventy-fivenon-premedicated patients were assigned randomly into five groups(15 in each) to receive fentanyl, alfentanil, remifentanil,sufentanil or placebo. Opioids were administered using a target-controlledinfusion device, to obtain the following predicted effect-siteconcentrations: fentanyl, 1.5 ng ml^–1; alfentanil, 100ng ml^–1; remifentanil, 6 ng ml^–1; and sufentanil,0.2 ng ml^–1. After this, a target-controlled infusionof propofol (Diprifusor) was started to increase concentrationgradually, to achieve predicted effect-site concentrations of1, 2, and 4 µg ml^–1. At baseline and at each successivetarget effect-site concentration of propofol, the BIS, sedationscore and haemodynamic variables were recorded. At the momentof loss of consciousness (LOC), the BIS and the effect-siteconcentration of propofol were noted. The relationship betweenpropofol effect-site concentration and BIS was preserved withor without opioids. In the presence of an opioid, LOC occurredat a lower effect-site concentration of propofol and at a higherBIS₅₀ (i.e. the BIS value associated with 50% probability ofLOC), compared with placebo. Although clinically the hypnoticeffect of propofol is enhanced by analgesic concentrations ofµ-agonist opioids, the BIS does not show this increasedhypnotic effect. Br J Anaesth 2001; 86: 523–7     

Clonidine decreases propofol requirements during anaesthesia: effect on bispectral index

Assessment of the effect of clonidine on depth of anaesthesiais difficult because clonidine combines analgesic, sedativeand direct haemodynamic effects. We thus evaluated the influenceof clonidine on the bispectral index (BIS) and its potentialdose-sparing effect on propofol. After induction of anaesthesiawith target-controlled infusion of propofol and obtaining anunchanged bispectral index (pre-BIS), clonidine 4 µg kg^–1or placebo was administered randomly to 50 patients in a double-blindmanner. Subsequently, if there was a decrease in BIS we reducedthe target concentration of propofol until pre-BIS was reached.The pre-BIS was maintained and a remifentanil infusion was addedduring surgery. The courses of the BIS, heart rate and bloodpressure were recorded and the total amounts of intra-operativepropofol and remifentanil were determined. Assessment of implicitmemory during anaesthesia was performed with an auditory implicitmemory test consisting of item sequences. Administration ofclonidine resulted in a decrease in the BIS from 45 (SD 4) to40 (6) (P<0.001), which allowed a reduction of propofol targetconcentration from 3.3 (0.6) to 2.7 (0.7) µg ml^–1(P<0.001) and measured propofol concentration from 2.9 (0.6)to 2.5 (0.7) µg ml^–1 (P=0.009) in order tomaintain the pre-BIS value. During subsequent surgery, propofolrequirements were reduced by 20% (P=0.002) in the clonidinegroup and a similar amount of remifentanil was used in eachgroup. The increase in anaesthetic depth given by clonidinecan therefore be measured with bispectral EEG analysis and allowsreduction of the propofol dose to achieve a specific depth ofanaesthesia. Br J Anaesth 2001; 86: 627–32     

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.     

Recovery from propofol anaesthesia supplemented with remifentanil

We have examined the effects on recovery end-points of supplementationof a propofol-based anaesthetic with remifentanil. After inductionof anaesthesia with propofol and remifentanil 1.0 µg kg^–1,15 patients each were randomly allocated to target plasma propofolconcentrations of 2, 3, 4 or 5 µg ml^–1for maintenance of anaesthesia. Remifentanil was administeredby infusion for supplementation in doses required for maintenanceof adequate anaesthesia. All patients received 50% nitrous oxidein oxygen and ventilation was controlled. The total amount ofdrugs used and times to different recovery end-points were recorded.Cognitive function was also assessed using a Mini-Mental Statequestionnaire. The median dose of remifentanil for maintenanceof adequate anaesthesia (excluding the initial bolus dose) inthe four groups was 0.21, 0.15, 0.11 and 0.13 µg kg^–1 min^–1respectively (P=0.0026). The median times to eye opening andorientation were shortest in the 2 µg ml^–1group [6.0 and 6.5 min, 8.5 and 10.8 min, 13.4 and15.8 min, and 14.2 and 19.5 min respectively in thepropofol 2, 3, 4, and 5 µg ml^–1 groups respectively(P<0.001)]. The times to discharge from the recovery wardand the Mini-Mental State scores were not significantly different. Br J Anaesth 2001; 86: 361–5     

Predicted values of propofol EC50 and sevoflurane concentration for insertion of laryngeal mask Classic and ProSeal

Background. A new laryngeal mask airway, the ProSeal^TM (PLMA),is said to be more difficult to insert than the laryngeal maskairway Classic^TM (CLMA) using propofol anaesthesia. Therefore,we expected a greater dose of propofol and sevoflurane to berequired to insert the PLMA compared with the CLMA. We determinedthe effective concentration 50% (EC₅₀) of propofol and end-tidalsevoflurane to allow insertion of the PLMA and the CLMA. Methods. Seventy-six elective female patients (aged 20–60yr and ASA I–II) were randomly assigned to one of fourgroups. Either a PLMA or a CLMA was inserted using either propofoltarget controlled infusion or sevoflurane. Both propofol andsevoflurane targets were determined with a modified Dixon’sup-and-down method. After equilibration between the predeterminedblood and effect site concentrations, which had been held steadyfor more than 10 min, LMA insertion was attempted without neuromuscularblock. Results. The predicted EC_50CLMA and EC_50PLMA for propofol were3.14 (0.33) and 4.32 (0.67) µg ml^–1. E'_CLMAand E'_PLMA of sevoflurane (mean (SD)) were 2.36 (0.22) and 2.82(0.45)% (P<0.01 and 0.05, respectively). Conclusions. The estimated concentration of propofol and thesevoflurane concentration needed to allow insertion of the ProSeal^TMare respectively 38 and 20% greater than those needed for insertionof the Classic LMA. Br J Anaesth 2004; 92: 242–5     

Comparing the effects of stimulation and propofol infusion rate on implicit and explicit memory formation

Doubt remains about the conditions under which learning persistsdespite anaesthesia. This study investigated the relative importanceof dose of anaesthetic and stimulation for learning during propofolinfusion before surgery. Thirty-six patients were randomly assignedto three groups. Group 1 received two word lists (category examplesand nonsense words) during infusion of propofol to a targetconcentration of 2 µg ml^–1. Groups 2 and3 received the word lists during infusion of propofol 5 µg ml^–1.Group 2 received nonsense words before tracheal intubation andcategory examples during intubation; Group 3 heard categoryexamples before and nonsense words during intubation. Bispectralindex was recorded as a measure of depth of sedation/anaesthesia.We assessed explicit memory on recovery using a structured interviewand a recognition test. We assessed implicit memory using acategory generation test and a preference rating task. To establishbaseline, a control group of 12 patients completed the categorygeneration test without receiving the category examples duringanaesthesia. Overall, there was no evidence for learning duringpropofol infusion, though the category generation task showeda trend towards more implicit memory for words presented duringintubation than during anaesthesia. We conclude that learningdoes not occur during anaesthesia without surgery. Br J Anaesth 2001; 86: 189–95     

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     

Blood propofol concentration and psychomotor effects on driving skills

We studied psychomotor performance in 10 healthy volunteersduring recovery after a target-controlled infusion of propofol.Choice reaction time, dual task tracking with secondary reactiontime and a within-list recognition task were assessed at targetblood propofol concentrations of 0.8, 0.4 and 0.2 µg ml^–1.Performance was impaired most at the highest blood propofolconcentration (choice reaction time increased by a mean of 247ms and secondary reaction time by a mean of 178 ms). Choicereaction time and dual task tracking with secondary reactiontime were the most sensitive and reliable methods of assessment(significant difference from baseline (P<0.05) at a propofolconcentration of 0.2 µg ml^–1 with choice and secondaryreaction time testing). Within-list recognition assessment ofmemory was not sufficiently sensitive at very low propofol concentrations.The impairment in choice and secondary reaction time with ablood propofol concentration of 0.2 µg ml^–1 wasless than that observed with a blood alcohol concentration of50 mg 100 ml^–1 and no greater than that observed witha blood alcohol concentration of 20 mg 100 ml^–1 in a previousstudy involving healthy volunteers. Br J Anaesth 2000; 85: 396–400 ^* Corresponding author     

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     

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

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

Assessment of the cough reflex after propofol anaesthesia for colonoscopy

Background. Dysfunction of the cough reflex as a result of thelingering effects of anaesthetics may lead to aspiration pneumoniaor retained secretions after general anaesthesia. It is unknownwhether low concentrations of propofol alter the cough reflexin the early period after anaesthesia. The objective of thisstudy was to investigate the effect of low concentrations ofpropofol on the cough reflex sensitivity as assessed by thecough reflex threshold to an inhaled irritant. Methods. Fifteen, ASA I–II, non-smoking patients undergoingelective colonoscopy were studied. Anaesthesia was induced andmaintained with a blood target-controlled propofol infusion.Cough reflex threshold was measured with citric acid. Increasingconcentrations of nebulized citric acid (2.5, 5, 10, 20, 40,80, 160, 320, and 640 mg ml^–1) were delivered during inspirationuntil a cough was evoked. The citric acid concentration elicitingone cough (C1) was defined as the cough reflex threshold. C1was log transformed for statistical analysis (Log C1). Log C1was measured before anaesthesia and during the recovery periodwith estimated decreasing propofol concentrations of 1.2, 0.9,0.6, and 0.3 µg ml^–1. Results. Log C1 (median; interquartile range) measured withpropofol concentrations of 1.2, 0.9, 0.6, 0.3, and 0 µgml^–1 were 1.9 (0.6), 1.9 (1.0), 1.9 (1.1), 1.9 (0.6),and 1.9 (0.7) mg ml^–1 (NS), respectively. However, lightsedation was observed with propofol concentrations of 1.2 and0.9 µg ml^–1. Conclusion. This study indicates that residual sedation afterpropofol anaesthesia for colonoscopy does not adversely affectthe cough reflex.     

High plasma ropivacaine concentrations after fascia iliaca compartment block in children

Background. The pharmacokinetic profile of local anaestheticsis influenced by the mode of administration. We sought to comparethe pharmacokinetics of two doses of ropivacaine after fasciailiaca compartment (FIC) block in children. Methods. In this prospective, double-blind study, children receivedan FIC block as a part of their anaesthetic management duringelective orthopaedic surgery on the thigh. They were randomizedto receive ropivacaine 0.7 ml kg^–1 using either a0.375% or 0.5% solution. Venous blood samples were drawn upto 6 h after injection. Plasma concentrations of ropivacainewere measured by gas–liquid chromatography. Results. Six children (10.2 (range 5–15) yr, 35.6 (SD10) kg were included. FIC block provided satisfactory peroperativepain relief. No signs of toxicity were observed, but high maximalplasma concentrations (C_max 4.33–5.6 µg ml^–1),were observed for three of four patients in the ropivacaine0.5% group. The two patients in the 0.375% group showed valueswithin the safe range (C_max 0.66 and 0.98 µg ml^–1respectively). Even though no toxic effects were observed, theseresults led us to discontinue the study. Conclusions. The administration of ropivacaine 3.5 mg kg^–1can be associated with sustained high plasma concentrationsof ropivacaine, outside the tolerable range. In view of theseresults, we recommend the use of lower ropivacaine dosage duringFIC block in children. Br J Anaesth 2004: 92: 416–18     

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     

Comparative evaluation of the cerebral state index and the bispectral index during target-controlled infusion of propofol

Background. Cerebral state index (CSI) has recently been introducedas an intra-operative monitor of anaesthetic depth. We comparedthe performance of the CSI to the bispectral index (BIS) inmeasuring depth of anaesthesia during target-controlled infusion(TCI) of propofol. Methods. Twenty Chinese patients undergoing general anaesthesiawere recruited. CSI and BIS, and predicted effect-site concentrationof propofol were recorded. The level of sedation was testedby Modified Observer's Assessment of Alertness/Sedation Scale(MOAAS) every 20 s during stepwise increase (TCI, 0.5 µgml^–1) of propofol. The loss of verbal contact (LVC) andloss of response (LOR) were defined by MOAAS values of 2–3and less than 2, respectively. Baseline variability and theprediction probability (P_K) were calculated for the BIS andCSI. The values of BIS₀₅ and CSI₀₅, BIS₅₀ and CSI₅₀, BIS₉₅ andCSI₉₅ were calculated at each end-point (LVC and LOR). Results. Baseline variability of CSI was more than that of BIS.Both CSI and BIS showed a high prediction probability for thesteps awake vs LVC, awake vs LOR, and LVC vs LOR, and good correlationswith MOAAS values. Conclusion. Despite larger baseline variation, CSI performedas well as BIS in terms of P_K values and correlations with stepchanges in sedation.     

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     

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     

Sedative, analgesic and cognitive effects of clonidine infusions in humans

This placebo-controlled, randomized study evaluated, on separatedays, the dose–response relationship for 1 h infusionsof clonidine 1, 2 and 4 µg kg^–1 h^–1,in eight healthy volunteers aged 22–30 yr. Responseend-points included sedation (bispectral index, visual analoguescale and observer assessment of sedation), analgesia to a coldpressor test, memory (recall of word lists), cognitive function(digit symbol substitution test (DSST)), respiratory function(respiratory rate, end-tidal carbon dioxide, oxygen saturation)and haemodynamic stability (heart rate and mean arterial pressure).Clonidine infusions resulted in significant and progressivesedation, but all subjects were easily awoken to perform testsand evaluations. Statistically significant analgesia, memoryimpairment and reduced performance on the DSST occurred during4 µg kg^–1 h^–1 infusions (resultingin a plasma concentration of 2 ng ml^–1. There were nostatistically significant changes in cardiorespiratory variablesthroughout the study. Br J Anaesth 2001; 86: 5–11     

Comparison of intubating conditions following propofol and succinylcholine with propofol and remifentanil 2 micrograms kg-1 or 4 micrograms kg-1

We evaluated the intubating conditions, haemodynamic responsesand duration of apnoea in 60 healthy adult patients after propofol2 mg kg^–1 combined with either a bolus of remifentanil2 µg kg^–1 or 4 µg kg^–1,or succinylcholine 1 mg kg^–1. Patients intubatedfollowing remifentanil showed dose-dependent intubating conditions,similar at 4 µg kg^–1 to the conditionsproduced with succinylcholine. Post-induction mean arterialpressure decreased from baseline values by 21% (P<0.0001),28% (P<0.0001) and 8% (P>0.05) in the remifentanil 2 µg kg^–1,remifentanil 4 µg kg^–1 and succinylcholine1 mg kg^–1 groups, respectively. The mean (SD)duration of apnoea following induction was 9.3 (2.6) minand 12.8 (2.9) min in the remifentanil 2 µg kg^–1and 4 µg kg^–1 groups, and 6.0 (0.9) minin the succinylcholine group (P<0.001 between groups). Br J Anaesth 2000; 85: 623--5