Predictive performance of computer-controlled infusion of remifentanil during propofol/remifentanil anaesthesia

Background. The predictive performance of the available pharmacokineticparameter sets for remifentanil, when used for target-controlledinfusion (TCI) during total i.v. anaesthesia, has not been determinedin a clinical setting. We studied the predictive performanceof five parameter sets of remifentanil when used for TCI ofremifentanil during propofol anaesthesia in surgical patients. Methods. Remifentanil concentration–time data that hadbeen collected during a previous pharmacodynamic interactionstudy in 30 female patients (ASA physical status I, aged 20–65 yr)who received a TCI of remifentanil and propofol during lowerabdominal surgery were used in this evaluation. The remifentanilconcentrations predicted by the five parameter sets were calculatedon the basis of the TCI device record of the infusion rate–timeprofile that had actually been administered to each individual.The individual and pooled bias [median performance error (MDPE)],inaccuracy [median absolute performance error (MDAPE)], divergenceand wobble of the remifentanil TCI device were determined fromthe pooled and intrasubject performance errors. Results. A total of 444 remifentanil blood samples were analysed.Blood propofol and remifentanil concentrations ranged from 0.5to 11 µg ml^–1 and 0.1 to 19.6 ng ml^–1respectively. Pooled MDPE and MDAPE of the remifentanil TCIdevice were –15 and 20% for the parameter set of Mintoand colleagues (Anesthesiology 1997; 86: 10–23), 1 and21%, –6 and 21%, and –6 and 19% for the three parametersets described by Egan and colleagues (Anesthesiology 1996;84: 821–33, Anesthesiology 1993; 79: 881–92, Anesthesiology1998; 89: 562–73), and –24 and 30% for the parameterset described by Drover and Lemmens (Anesthesiology 1998; 89:869–77). Conclusions. Remifentanil can be administered by TCI with acceptablebias and inaccuracy. The three pharmacokinetic parameter setsdescribed by Egan and colleagues resulted in the least biasand best accuracy. Br J Anaesth 2003; 90: 132–41     

Narcotrend-assisted propofol/remifentanil anaesthesia for prevention of awareness

Editor—I read with interest about the comparison of theuse of Narcotrend and clinical assessment in judging the depthof anaesthesia while using total i.v. anaesthesia (TIVA).¹ Ifully agree with the authors that the use of clinical assessmentalone would lead to a greater deviation from a defined targetwhile     

Bispectral index-guided administration of anaesthesia: comparison between remifentanil/propofol and remifentanil/isoflurane

BACKGROUND AND OBJECTIVE: The bispectral index of the electroencephalogram is a measure of the hypnotic component of anaesthesia and can be used to guide the administration of anaesthesia. This study compares bispectral index-guided anaesthesia with remifentanil and either propofol or isoflurane. METHODS: Eighty consenting patients were randomly assigned to two groups. Following induction with propofol and remifentanil, anaesthesia was maintained with remifentanil/propofol or remifentanil/isoflurane. Remifentanil infusion rates were guided by haemodynamic responses--maintaining mean arterial pressure and heart rate within 20% of baseline. Propofol and isoflurane administration was guided using the bispectral index (45-60). Thirty minutes before the end of surgery, morphine was administered (0.15 mg kg(-1) intravenously). Fifteen minutes before end of surgery, propofol and isoflurane were reduced (bispectral index 60-75). At the end of surgery, the anaesthetic agents were discontinued. Groups were compared for recovery, remifentanil doses and signs of inadequate anaesthesia using the chi2-test and ANOVA (P < 0.05). RESULTS: The duration of surgery was longer in the propofol/remifentanil group (121 +/- 53 versus 94 +/- 40 min). Recovery data were not different between groups. The remifentanil infusion rate was significantly lower with additional isoflurane (0.18 +/- 0.06 microg kg(-1) min(-1)) than with additional propofol (0.31 +/- 0.20 microg kg(-1) min(-1)). The propofol infusion rate was 123 +/- 48 microg kg(-1) min(-1); isoflurane concentration was 0.66 +/- 0.13%. CONCLUSIONS: Bispectral index-guided anaesthesia with remifentanil plus propofol or isoflurane results in the absence of postoperative recall and a fast recovery with both drug combinations. In our patients, at comparable bispectral index-levels, haemodynamic control requires higher doses of remifentanil with propofol than with isoflurane.     

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     

Psychomotor performance after short-term anaesthesia

BACKGROUND AND OBJECTIVE: The aim was to examine the immediate effects of short-term anaesthesia on the different components of psychomotor performance of the upper extremity and cognitive functions, and to find out if there were any differences in the sensitivities of the different tests. The measured psychomotor aspects were simple reaction time, choice reaction time, speed of movement, index finger-tapping speed, co-ordination, visual spatial memory capacity, digit-symbol substitution and the Maddox Wing test. METHODS: The subjects were 30 female patients aged 24-50 yr who had been through a minor gynaecological operation. Anaesthesia had been induced with propofol and alfentanil. The measurements were mainly made with the HPM/BEP system, and the tests were performed 1 h before the anaesthesia and immediately after the wake-up. RESULTS: Short-term anaesthesia prolonged the simple reaction time by 7% and the choice reaction times by 25% (one-choice) and 7% (two-choice) and decreased the speed of movement by 10% (one-choice) and 19% (two-choice), index finger-tapping speed by 7% and co-ordination by 7%. In addition, visual spatial memory capacity decreased by 21%, digit-symbol substitution increased by 5% and the Maddox Wing test increased by 68%. CONCLUSIONS: Based on the results, it seems that short-term anaesthesia reduces both signal processing at the central level, and motor control and co-ordination of movements at the peripheral level, and has a decreasing effect on motor performance in the above-mentioned aspects measured immediately after wake-up.     

Absence of implicit and explicit memory during propofol/remifentanil anaesthesia

BACKGROUND AND OBJECTIVE: High doses of opioid associated with low doses of hypnotic is a popular anaesthetic technique since the use of remifentanil has become widespread. This type of anaesthesia could result in a higher incidence of implicit memory. METHODS: Ten patients were anaesthetised with a target-controlled infusion of remifentanil (target concentration of 8 ng mL(-1)) combined with a target-controlled infusion of propofol with progressive stepwise increases until loss of consciousness was reached. A tape containing 20 words was then played to the patients. Bispectral index (BIS, Aspect Medical Systems, Newton, MA, USA) was continuously monitored during the whole study period. Implicit and explicit memories were tested between 2 and 4 h after recovery. RESULTS: Loss of consciousness was obtained with a mean calculated propofol plasma concentration of 1.3 +/- 0.4 microg mL(-1). At this low hypnotic concentration no implicit or explicit memory was found in the three postoperative memory tests. Median (range) BIS value during word presentation was 93 (80-98). CONCLUSIONS: In our group of young American Society of Anesthesiologists (ASA) I/II patients, no explicit or implicit memory was found when the calculated concentration of propofol combined with a high concentration of remifentanil was maintained at the level associated with loss of consciousness with high BIS values.     

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.     

Psychomotor recovery following propofol or isoflurane anaesthesia for day-care surgery

A newly developed test for the assessment of psychomotor recovery--the perceptive accuracy test (PAT)--is described. Seventy-four subjects who performed the test though that it was easy to perform and some were motivated to try it on a number of occasions. Eight persons performed the test on different days and at different periods of time; the results were consistent and reproducible. Eight more persons were then asked to do the test 4 times at 15-min intervals; no 'learning' was seen with this test. A randomized, prospective study was then performed in two groups of 15 patients, undergoing arthroscopic procedures of the knee. Anaesthesia was induced with propofol and maintained with an infusion of propofol 12 mg/kg/h for the first 15 min, followed by 8 mg/kg/h subsequently in the propofol group. In the isoflurane group, anaesthesia was also induced with propofol, but isoflurane (0.5-2%) was used to maintain anaesthesia. Alfentanil was the analgesic used in both groups of patients. Results were compared with a third group of unanaesthetised controls, who were asked to perform psychomotor tests including choice reaction time and PAT at 30-min intervals for 2.5 h. There was a significant difference (P less than 0.01) in psychomotor recovery on the PAT-200 between the propofol group and control groups, but not in the isoflurane and control groups at 30 min. Both groups had returned to baseline values at 60 min in the PAT-60 and PAT-200. The choice reaction time showed no significant difference in either group 30 min after the anaesthetic.(ABSTRACT TRUNCATED AT 250 WORDS)     

Less postoperative nausea and vomiting after propofol + remifentanil versus propofol + fentanyl anaesthesia during plastic surgery

BACKGROUND: The effect of different opioids on postoperative nausea and vomiting (PONV) has not been conclusively determined yet, thus the aim of this study was to compare the incidence of PONV in propofol-anaesthetized patients receiving either fentanyl or remifentanil as opioid supplement. METHODS: Sixty ASA physical status I and II patients scheduled for plastic surgery gave their written informed consent for this prospective, randomized, double-blind study. Anaesthesia was induced with propofol, rocuronium and fentanyl (n = 30; 2 microg kg(-1)) or remifentanil (n = 30; 1 microg kg(-1)). After tracheal intubation, anaesthesia was maintained with propofol, oxygen in air and an infusion of the opioid studied, which was modified according to clinical criteria. Baseline postoperative analgesia was achieved with intravenous propacetamol + metamizol. Intravenous morphine was given if visual analogic scale (VAS) for pain was > or = 4 (scale 0-10) and metoclopramide was administered if a patient presented > or = 2 PONV episodes (nausea or vomiting) in less than 30 min. Postoperatively (2, 12 and 24 h), we registered VAS, rescue morphine consumption, number of patients with episodes of PONV and number of patients requiring metoclopramide. P < 0.05 was considered significant. RESULTS: There were no significant differences between groups in the demographic parameters, ASA physical status, propofol dose, VAS, and rescue morphine requirements. Fourteen patients in the fentanyl group and four in the remifentanil group presented PONV episodes 2-12 h postoperative hours' interval; (P < 0.05). Ten patients in the fentanyl group and four in the remifentanil group presented vomiting episodes in the same period (P < 0.05); and eight patients in the fentanyl group and one in the remifentanil group required metoclopramide; (P < 0.05). The number of postoperative PONV episodes were low, both in the 0-2-h period (n = 2 vs. n = 1, fentanyl and remifentanil, respectively) and in the 12-24-h period (n = 3 vs. n = 1). CONCLUSION: Propofol + fentanyl anaesthesia resulted in a higher incidence of PONV and requirements of antiemetic drugs in the period between 2 and 12 postoperative hours compared with propofol + remifentanil, in patients undergoing plastic surgery.     

SNAP index and Bispectral index during different states of propofol/remifentanil anaesthesia

The accuracy of the new SNAP index with the Bispectral index (BIS) to distinguish different states of propofol/remifentanil anaesthesia was compared in 19 female patients who were undergoing minor gynaecological surgery. Comparisons of the SNAP index, BIS, spectral edge frequency, mean arterial blood pressure and heart rate were performed. The ability of all parameters to distinguish between the steps of anaesthesia -awake vs. loss of response, awake vs. anaesthesia, anaesthesia vs. first reaction and anaesthesia vs. extubation - were analysed with the prediction probability. The prediction probability to differentiate between two interesting nuances of anaesthetic states -loss of response vs. first reaction - was calculated. Only the BIS showed no overlap between the investigated steps of anaesthesia. Both the SNAP index and BIS failed to differentiate the nuances of anaesthesia. The SNAP index and BIS were superior to mean arterial blood pressure and heart rate and spectral edge frequency in distinguishing between different steps of anaesthesia with propofol and remifentanil and provided useful additional information.     

Bronchial mucus transport velocity in patients receiving anaesthesia with propofol and morphine or propofol and remifentanil

In vitro morphine does not reduce cilia beat frequency, a key factor determining bronchial mucus transport velocity. There are no reports about the effect of remifentanil on bronchial mucus transport. We compared the bronchial mucus transport velocity in patients having total intravenous anaesthesia with either propofol and morphine, or propofol and remifentanil. Twenty patients scheduled for elective surgery were randomly allocated to the two groups. Fifteen minutes after insertion of the laryngeal mask airway, bronchial mucus transport velocity was assessed by fibreoptic observation of the movement of methylene blue dye applied to the right main bronchus. Compared with morphine, bronchial mucus transport velocity was significantly reduced in patients receiving remifentanil (morphine mean (SD) 9.2 (5.8) vs remifentanil 4.2 (3.0) mm.min(-1), p = 0.028). Anaesthesia with remifentanil may lead to significantly impaired bronchociliary clearance in comparison to morphine. This could have clinical implications, in particular in patients at risk.     

Pharmacokinetic-based total intravenous anaesthesia using remifentanil and propofol for surgical myocardial revascularization

BACKGROUND AND OBJECTIVE: We investigated the following aspects of pharmacokinetic-guided total intravenous anaesthesia with remifentanil and propofol in patients undergoing surgical myocardial revascularization: anaesthetic efficacy, haemodynamic effects, impact on extubation of the trachea and analgesia after operation. METHODS: Thirty-two patients undergoing on-pump coronary bypass surgery received intravenous anaesthesia with remifentanil and propofol. Both drugs were dosed and titrated based on computer-assisted pharmacokinetic models to maintain constant plasma concentrations. The propofol target plasma concentration was 1.2 microg mL(-1) throughout the procedure. A remifentanil target plasma concentration of 8 ng mL(-1) was achieved over 2 min for induction. After tracheal intubation, the opioid plasma concentration was reduced to 4 ng mL(-1), and then titrated up to 8 ng mL(-1) during surgery. Postoperative analgesia was managed with remifentanil infusion until 4 h after tracheal extubation, and a continuous infusion of tramadol was started 1 h before the remifentanil was stopped. RESULTS: After induction of anaesthesia, heart rate (-20%) and cardiac index (-6%) decreased significantly. No hypotensive episodes (mean arterial pressure < 60 mmHg) occurred. Intraoperative haemodynamics were stable. Three cases of myocardial ischaemia were detected: two by transoesophageal echocardiography and one with ST-segment monitoring. The duration of postoperative mechanical ventilation of the lungs was 95 +/- 13 min and the time to extubation was 150 +/- 18 min. Postoperative analgesia was satisfactory in all patients. CONCLUSIONS: Pharmacokinetic-based total intravenous anaesthesia with remifentanil and propofol provides adequate anaesthesia during coronary surgery with cardiopulmonary bypass and allows safe early extubation after operation.     

Mood change after anaesthesia with remifentanil or alfentanil

BACKGROUND AND OBJECTIVE: There are anecdotal reports of dysphoria occurring in patients on the first day after anaesthesia with remifentanil. This study was performed to investigate this allegation and to find a possible relationship to postoperative shivering or to nausea and vomiting. METHODS: Patients undergoing otorhinolaryngeal surgery took part in a prospective, randomized, double-blind study comparing total intravenous anaesthesia with propofol (2 mg kg(-1) bolus injection then 100 microg kg(-1) min(-1)) and remifentanil (1 microg kg(-1) bolus then 0.1-0.5 microg kg(-1) min-1) or alfentanil (30 microg kg(-1) bolus then 0.16-0.83 microg kg((-1) min(-1)). The patients were carefully insulated and actively warmed by convective heating and rectal temperature was monitored continuously. Postoperative shivering was graded on a three-point scale, and the cumulative incidence of nausea and vomiting were registered at 24 h after surgery. Pre- and postoperative mood was measured with the von Zerssen mood scale (Befindlichkeits-Skala) and changes tested for significance. High scores reflect discontent and dysphoria. RESULTS: The data of 98 patients (49 in each group, ASA I-II, age 42 +/- 13 yr, anaesthesia time 141 +/- 60 min; mean +/- SD; intergroup P values > 0.1) were evaluated. Core temperature did not change perioperatively (before 36.6 +/- 0.2 degrees C; after 36.8 +/- 0.3 degrees C, inter- and intragroup P > 0.1). The incidence of nausea was the same in each group; vomiting occurred with equal frequency (6/49 vs. 7/49). Shivering was significantly more frequent after remifentanil (41% vs. 10%, P < 0.001). The patients' mood remained stable after remifentanil but worsened after alfentanil (von Zerssen score from 9.3 +/- 2.5 to 13.9 +/- 3.6; mean +/- 95% confidence intervals; P < 0.01). DISCUSSION: Postoperative shivering was more frequent after remifentanil but was unrelated to intraoperative heat loss. Contrary to preliminary informal observations, there was no evidence that remifentanil caused postanaesthetic dysphoria on the day one after surgery.     

Effect of tramadol on Bispectral Index during intravenous anaesthesia with propofol and remifentanil

The aim of this study was to investigate the effects of tramadol on the Bispectral Index (BIS) during total intravenous propofol-remifentanil anaesthesia. Forty-four adult ASA Physical status I-II patients, scheduled for elective general surgical procedures were included in a prospective observational randomized study. Doses for anaesthetics and opioids were adjusted to keep the BIS value at 50 +/- 5. After 20 minutes of stable anaesthesia, the subjects were randomly allocated to receive intravenous saline (control group) or tramadol 1.5 mg/kg (tramadol group). BIS values, mean arterial pressure, and heart rate were recorded every five minutes for 20 minutes. Mean BIS values after tramadol administration were not significantly different from those following saline, throughout the observation period (P > 0.05). There were no patients in whom BIS values were more than 60 or who presented explicit recall of events under anaesthesia. There were no significant changes in mean arterial pressure, SpO2, or heart rate (P > 0.05). The results indicate that the administration of tramadol during stable total intravenous anaesthesia with propofol-remifentanil does not affect BIS values. The clinical relevance is that tramadol can be safely administered pre- and intraoperatively as pre-emptive or preventive analgesia without modification of the depth of anaesthesia.