Propofol Target-controlled Infusion System Research Articles

Pharmacokinetic Analysis of Propofol Target-Controlled Infusion Models in Chinese Patients with Hepatic Insufficiency.

BackgroundEffects of liver dysfunction on target-controlled infusion (TCI) with Marsh parameters of propofol remain poorly documented. The purpose of this study was to evaluate the performance of propofol TCI in a cohort of Chinese patients with severe hepatic insufficiency.Material/MethodsWe assigned 32 patients who underwent liver transplantation to 3 groups according to Child-Turcotte-Pugh (CTP) score. Anesthesia, preceding liver transplantation, was induced and maintained with TCI of 3 μg/mL propofol. Plasma propofol concentration was assessed. Propofol TCI system performance was analyzed in terms of error size, bias, and divergence. Data on plasma propofol concentrations were analyzed, and population pharmacokinetic parameters of propofol were fitted by NONMEM software.ResultsIn the CTP C group, measured concentrations of propofol were much higher than those of predictive concentrations, with significantly higher overshoots compared to CTP A patients. Overall, TCI system performance was significantly lower in CTP C patients. Linear regression equations of Cm vs. Cp and a regression model of pharmacokinetics were obtained.ConclusionsPropofol TCI device performance with Marsh parameters was clinically acceptable in CTP A patients but may not be suitable for patients with severe hepatic impairment.

Assessment of the Berlin Questionnaire for evaluation of hypoxemia risk in subjects undergoing deep sedation for screening gastrointestinal endoscopy.

BackgroundSubjects with obstructive sleep apnea (OSA) are vulnerable to sedation-related complications during endoscopic procedures. A significant portion of subjects undergoing routine endoscopy is at high risk of OSA, but most are undiagnosed. The purpose of this study was to estimate the prevalence of high risk for OSA among Chinese subjects undergoing deep sedation for screening gastrointestinal endoscopy and to evaluate the hypoxemia risk of these examinees stratified by Berlin Questionnaire (BQ).Patients and methodsWe performed a prospective cohort study in subjects undergoing deep sedation with monitored anesthesia care for combined esophagogastroduodenoscopy plus colonoscopy. Subjects who were Chinese were stratified into high- and low-risk groups for OSA by administration of BQ. Deep sedation was achieved via a propofol target-controlled infusion system. Hypoxemia was defined as pulse oximetry reading of less than 90%. The frequency of hypoxemia was compared between high- and low-risk groups for OSA.ResultsA total of 615 Chinese subjects were recruited during the study period, and 614 subjects were included for analysis. Two hundred eighteen (35.5%) subjected were classified to be at high risk of OSA, and 396 (64.5%) were stratified to be at low risk of OSA by BQ. Hypoxemia occurred in 83 (13.5%) subjects during endoscopy procedures. The risk of developing hypoxemia in the high-risk group was significantly higher when compared to that of the low-risk group subjects (24.8% vs 7.3%; relative risk, 3.37; 95% CI, 2.22–5.13).ConclusionAbout one-third Chinese subjects undergoing deep sedation for screening endoscopy were at high risk of OSA. Subjects at high risk of OSA are associated with an increased risk of hypoxemia in comparison to the low-risk group when undergoing deep sedation for screening gastrointestinal endoscopy.

Safety of Target-Controlled Propofol Infusion by Gastroenterologists in Patients Undergoing Endoscopic Resection.

A target-controlled infusion (TCI) of a propofol system uses a pharmacokinetic model to achieve and maintain a selected target blood propofol concentration. The aim of this study was to assess whether the propofol TCI system could be safely used by gastroenterologists in patients undergoing endoscopic resection including endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) compared with a manually controlled infusion (MCI) system. A total of 431 patients undergoing therapeutic endoscopy (178 ESD and 253 EMR) were consecutively included from November 2011 to August 2014. The patients were divided into the MCI (271) and TCI (160) propofol infusion groups. We compared adverse event rates in MCI and TCI groups and assessed independent risk factors for adverse events. The total sedation-related adverse event rate was 5.8% (25/431). Most of the events were minor, and the rate of major events was 0.5% (2/431). There was no significant difference in adverse event rate between the MCI and TCI groups [5.5% (15/271) vs. 6.3% (10/160); P=0.759]. In univariate analysis, the propofol infusion time was significantly associated with adverse events (94.88 vs. 59.45min, P=0.017). In the multivariate analysis, there were no significant factors associated with adverse events. TCI was not an independent risk factor for adverse events despite the fact that the TCI had a longer duration of infusion and higher total infusion dose (95% CI, 0.343-2.216; P=0.773). TCI of propofol by gastroenterologists may provide safe sedation in patients undergoing ESD and EMR under careful respiratory monitoring.

Comparison of accuracy of Marsh model versus Schnider model for propofol target-controlled infusion system

Objective To compare the accuracy of Marsh model and Schnider model for propofol target-controlled infusion (TCI) system. Methods Eighty patients, aged 20-60 yr, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, with body mass index of 17.5-28.0 kg/m2, scheduled for elective gynecological operation under general anesthesia, were equally and randomly divided into either Marsh model group (group M) or Schnider model group (group S) using a random number table.The target plasma concentration was set at 3 μg/ml in both groups.During TCI and at different time points after the end of TCI, the blood samples were collected for determination of blood propofol concentrations by high performance liquid chromatography with fluorescence detector.The difference between measured and predicted concentrations (△C) at each time point was calculated.The median performance error (MDPE), median absolute performance error (MDAPE), and wobble of propofol TCI system were calculated in each group. Results In M and S groups, the MDPE was 9.90% and 14.00%, respectively; the MDAPE was 11.43% and 14.49%, respectively; the wobble was 7.77% and 7.79%, respectively.There was no significant difference in △C at each time point during TCI between group M and group S (P>0.05). After TCI was stopped, △C at each time point was significantly lower in group M than in group S (P<0.05). Conclusion Marsh model provides higher accuracy than Schnider model for propofol TCI system in the patients undergoing gynecological operation. Key words: Propofol; Drug delivery systems; Pharmacokinetics

Drug-induced sleep endoscopy in adults with sleep-disordered breathing: Technique and the VOTE Classification system

Drug-induced sleep endoscopy (DISE) offers an unique evaluation of the upper airway. After pharmacologic induction of unconscious sedation, it is possible to evaluate endoscopically the structures contributing to upper airway obstruction in sleep disordered breathing. The authors describe DISE techniques and the VOTE classification system for reporting of DISE findings. The VOTE classification focuses on the primary structures that contribute to upper airway obstruction and represents a common language to describe the patterns of obstruction during DISE. The latter can facilitate the scientific evaluation of DISE, including its role in directing treatment.

Evaluation of predictive performance of propofol target-controlled infusion system incorporating the Schnider pharmacokinetic parameters

Objective To evaluate the predictive performance of propofol target-controlled infusion (TCI) system incorporating the Schnider pharmacokinetic parameters in Chinese patients. Methods Forty ASA Ⅰ or Ⅱ patients, aged 25-45 yr, with body mass index 20-25 kg/m2 , scheduled for gynecological laparoscopic surgery un der general anesthesia, were enrolled in this study. Anesthesia was induced with TCI of propofol (target plasma concentration (Cp) 3 μg/ml) and remifentanil (Cp 4 ng/ml) . Propofol was infused by Orchestra TCI system incorporating the Schnider pharmacokinetic parameters. Tracheal intubation was facilitated with rocuronium 0.6 mg/kgafter the patients lost consciousness. The patients were mechanically ventilated. PETCO2 was maintained at 30-40 mm Hg. Anesthesia was maintained with TCI of remifentanil (Cp 4 ng/ml) and propofol (Cp 3-5 μg/ml) and intermittent iv boluses of atracurium 0.2 mg/kg. BIS value was maintained at 40-45. Venous blood samples were obtained at 15, 30, 45 and 60 min after pneumoperitoneum for measurement of blood propofol concentrations by high performance liquid chromatography with fluorescence detector. Performance error, median prediction performance error, median absolute performance error, wobble and divergence of propofol TCI system were calculated. Results The value for performance error was 21 % (13%), for median prediction performance error 6.7 % (37.4%),for median absolute performance error 19% (18%), for divergence - 0.65%/h (0.82%/h) and for wobble 16.3% (15.2% ) . Conclusion The accuracy of propofol TCI system incorporating the Schnider pharmacokinetic parameters is high in Chinese patients and its predictive performance is acceptable clinically. Key words: Propofol; Pharmacokinetics; Drug deliver systems

Effect of the new propofol target controlled infusion system in children undergoing high ligation of hernial sac

To discuss the effect of the new target controlled infusion (TCI) system in Chinese children undergoing minor operation and compared with TCI system with Marsh parameters. Ninety ASA I, aged 3 - 5 yrs children undergoing elective unilateral high ligation of hernial sac under general anesthesia were randomly divided into group L (n = 45) and group M (n = 45) 2 groups. All subjects were unpremedicated. Systolic blood pressure (SBP), diastolic blood pressure (DBP), ECG, SpO2 and BIS were monitored. Patients of Group L and group M were anesthetized with propofol by Lian propofol TCI system and Marsh system respectively, combined with regional block. The target plasma concentration of TCI system was set at 6 microg/ml initially and up-regulated 1 microg/ml gradually if obvious body movement occurred while skin incision. If the target plasma concentration up to 8 microg/ml but there still had body movement, the TCI venous anesthesia was replaced by inhaled anesthesia. HR, RR, SBP, DBP and BIS were recorded in time points of baseline (T(0)), after the induction (T(1)), skin incision (T(2)), 3, 5 min after skin incision (T(3), T(4)), the end of operation (T(5)). Complications, the awakening time and the number of cases which anesthetized with different propofol plasma concentrations or inhaled anesthesia were recorded respectively as well. The number of cases which completed the operation under TCI plasma concentration 6 microg/ml in group L were significantly more than those in group M (P < 0.01). There were significantly different of T(1)-T(4) values of HR, RR, SBP, DBP and BIS in group M (P < 0.05), but not in group L. Compared with group L, T(2)-T(4) values of HR, RR, SBP, DBP and BIS were higher in group M (P < 0.05 or 0.01). Complications were lower in group L than those in group M. Compared with Marsh system, propofol 6 microg/ml plasma concentration with the new target controlled infusion system applied in Chinese children undergoing unilateral high ligation of hernial sac could maintain stable hemodynamics, less stress reaction and complications.

Comparison of remifentanil-propofol and remifentanil-sevoflurane anaesthesia for laparoscopic cholecystectomy

Objective To examine recovery profile and haemodynamic differences using remifentanil infusion with either propofol target controlled infusion system or sevoflurane inhalation for laparoscopic choleeystectomy. Methods Forty-eight adult patients, ASAⅠ～Ⅱgrade, undergoing elective laparoseopie cholecystectomy were randomly divided into two groups(n=24). Group R P received propofol target controlled infusion system and remifentanil; Group RS received sevoflurane and remifentanil for maintenance of anaesthesia. The amount of narcotie medication during the oporation, mean arterial pressure (MAP) and heart rate (HR) at each time point during anesthesia and awake time for patients after surgery of the two grous were recorded. Results No statistically significant differences between the two groups with tegards to the haemodynamic changes(P>O.05). Recovery times were considerably shorter after remifentanil-sevoflurane (7.0±3.4)min in comparison with remifentanil-prpofol (13.1±7.8) min target controlled infusion system group (P<0.01). Conclusion Remifentanil-propofol and sevoflurane-remifentanil combinations provide a similar adequate haemodynamic stability. However, sevoflurane-remifentanil gives a faster recovery compared with propofol target controlled infusion system with remifentanil for laparoscopic cholecystectomy. Key words: Propofol; Sevoflurane; Remifentanil; Target control infusion; Anaesthesia; Laparoscopic cholecystectomy

Comparison of thoracic epidural anesthesia combined intravenous and total intravenous anesthesia in thoracic surgery

Objective To compare thoracic epidural anesthesia (TEA)combined with general anesthesia (GA)and total-IV anesthesia (TIVA)with respect to haemodynamic differences, maintenance dosage of narcotic, recovery profile and postoperative pain.Methods Sixty-four patients, ASA physical status Ⅰ-Ⅲ undergoing thoracotomy were randomly allocated to two groups: thoracic epidural anesthesia(TEA)combined with general anesthesia (GA) group(group A) and total-IV anesthesia(TIVA) group(group B).Patients in the A group received 10 ml of 0.25% bupivacaine and fentanyl 0.1mg via the epidural route prior to skin incision, followed by an infusion of bupivacaine 0.25% and fentanyl 10 μg/ml at 5 ml/h. Group B received propofol target controlled infusion system and remifentanil. Results No statistically significant differences between the two groups with regards to the haemodynamic changes.Maintenance of anesthesia in TEA combined with GA group neither muscle relaxants nor opioid anesthetics were required. Extubate times were considerably shorter after TEA combined with GA (11±4) min in comparison with TIVA (23±16) min target controlled infusion system group (P<0.05). The emerge of postoperative pain time were considerably longer after TEA combined with GA (7.4±2.6) min in comparison with TIVA (0.5±0.3) min target controlled infusion system group (P<0.01). Conclusion Thoracic epidural anesthesia combined with general anesthesia for thoracotomy is rapid, safe, economic and effective method, moreover, in favor of the patients' postoperative recovery. Key words: Thoracic epidural anesthesia; General anesthesia; Thoracotomy

A comparison of the effects of two different doses of ketamine used for co-induction of anaesthesia with a target-controlled infusion of propofol in dogs

ObjectiveTo assess the cardiorespiratory and hypnotic-sparing effects of ketamine co-induction with target-controlled infusion of propofol in dogs. Study designProspective, randomized, blinded clinical study. AnimalsNinety healthy dogs (ASA grades I/II). Mean body mass 30.5 ± SD 8.6 kg and mean age 4.2 ± 2.6 years. MethodsAll dogs received pre-anaesthetic medication with acepromazine (0.03 mg kg−1) and morphine (0.2 mg kg−1) administered intramuscularly 30 minutes prior to induction of anaesthesia. Heart rate and respiratory rate were recorded prior to pre-medication. Animals were allocated into three different groups: Group 1 (control) received 0.9% NaCl, group 2, 0.25 mg kg−1 ketamine and group 3, 0.5 mg kg−1 ketamine, intravenously 1 minute prior to induction of anaesthesia, which was accomplished using a propofol target-controlled infusion system. The target propofol concentration was gradually increased until endotracheal intubation was possible and the target concentration at intubation was recorded. Heart rate, respiratory rate and noninvasive blood pressure were recorded immediately prior to induction, at successful intubation and at 3 and 5 minutes post-intubation. The quality of induction was graded according to the amount of muscle twitching and paddling observed. Data were analysed using a combination of chi-squared tests, Fisher's exact tests, Kruskal–Wallis, and anova with significance assumed at p< 0.05. ResultsThere were no significant differences between groups in the blood propofol targets required to achieve endotracheal intubation, nor with respect to heart rate, noninvasive blood pressure or quality of induction. Compared with the other groups, the incidence of post-induction apnoea was significantly higher in group 3, but despite this dogs in this group had higher respiratory rates overall. Conclusions and clinical relevanceUnder the conditions of this study, ketamine does not seem to be a useful agent for co-induction of anaesthesia with propofol in dogs.

Accuracy of target-controlled infusion of propofol for cardiac valve replacement performed under cardioplmonary bypass

Objective To investigate the performance of target-controlled infusion(TCI)of propofol for cardiac valve replacement performed under cardiopulmonary bypass(CPB).Methods Twenty ASA Ⅱ or Ⅲ patients aged 25-64 yr weighing 50-70 kg undergoing cardiac valve replacement under CPB were enrolled in this study.Anesthesia Was induced with intravenous midazolam,fentanyl and recuronium and maintained with intravenous midazolam infusion(0.05-0.1 mg·kg-1·h-1),TCI of propofol(target plasma concentration War set at 1 μ/ml),intermittent iv boluses of fentanyl and iv recuronium infusion(0.05-0.1 mg·kg-1·h-1).Propofol Was administered with a specific TCI system incorporating the Tackley pharmacokinetic parameters.Blood samples were obtained from radial artery before CPB(T1,baseline),at 1,5,10,20,40,60 min of CPB(T2-7)and 5,10 min after CPB(T8,9)for measurement of propofol plasma concentration by HPLC.Median prediction performance error (MDPE),median absolute performance error(MDAPE),wobble and divergence of propofol TCI system were calculated.Results The measured plasma concentrations of propofol were significantly higher at T1 than the target plasma concentration(Cp)but there were no significant differences between the measured plasma concentrations and Cp of propofol at T2-4.The measured plasma concentrations of pmpefol were significantly higher than Cp at T5-9.The MDPE,MDAPE,wobble and divergence of propofol TCI system were 21%.29%,21%and-0.06%/h respectively.Conclusion The accuracy of the TCI system incorporecting the Tackley pharmacoki-netic parameters exceeds the clinically acceptable scopein patients undergoing cardiac valve replacement under CPB. Key words: Cardiopulmonary bypass; Drug delivery systems; Propofol; Plasma concentration; Pharmacokinetica

Use of a target-controlled infusion system for propofol does not improve subjective assessment of anaesthetic depth by inexperienced anaesthesiologists*

Target-controlled infusion, via the calculated effect compartment concentrations, may help anaesthesiologists to titrate anaesthetic depth and to shorten recovery from anaesthesia. In this prospective, randomized clinical study, we compared the performance of six inexperienced anaesthesiologists with <1 yr of training when using target- or manually controlled infusion of propofol, combined with manual dosing of fentanyl. Ninety-two premedicated ASA I-III patients undergoing minor elective urological or gynaecological surgery were assigned to the manual- or target-controlled infusion group. Bispectral index was recorded in a blinded manner. Subjective assessment of anaesthetic depth on a 10 point numerical scale (1 = very deep anaesthesia, 10 = awake) was asked at regular intervals and the correlation with the blinded bispectral index was analysed using the prediction probability, PK. The propofol concentration profile was calculated post hoc. Propofol administration was similar in both groups with no significant difference for the administered amount and concentrations of propofol. Recovery times were also not different. In both groups, a large percentage of the bispectral index data points recorded during surgery showed bispectral index values below the recommended value of 40, but in the target-controlled infusion group there were significantly less bispectral index values above the recommended upper limit of 60 (2.5% vs. 5.1%). A target-controlled infusion system does not help inexperienced anaesthesiologists to assess anaesthetic depth or to shorten recovery times, but may reduce episodes of overly light anaesthesia and thus help to prevent awareness.

Clinical comparison of remifentanil–sevoflurane vs. remifentanil–propofol for endoscopic endonasal transphenoidal surgery

Endoscopic endonasal transphenoidal surgery has been recently proposed as a minimally invasive procedure for the treatment of pituitary adenomas. The main objective of the anaesthesiologist is to induce sufficient haemodynamic control together with rapid recovery at the end of surgery. The aim of this study was to examine recovery profile, surgical operative conditions and haemodynamic differences using remifentanil infusion with either propofol target controlled infusion system or sevoflurane. Forty-four adult patients were enrolled in a prospective, randomized, single-blind, two-group study: Group P received propofol target controlled infusion system and remifentanil; Group S received sevoflurane and remifentanil for maintenance of anaesthesia. No statistically significant differences between the two groups with regards to the haemodynamic changes, operative conditions as assessed by a four-step bleeding score (0-3), were obtained. Recovery times were considerably shorter after remifentanil-sevoflurane in comparison with remifentanil-propofol target controlled infusion system group (7.4 vs. 12.8 min, P < 0.01). This study demonstrates that sevoflurane-remifentanil gives a faster recovery and equivalent intraoperative status compared with propofol target controlled infusion system with remifentanil for the endoscopic endonasal transphenoidal approach.

Predictive performance of ‘Servin's formula’ during BIS®-guided propofol-remifentanil target-controlled infusion in morbidly obese patients

The aim of this study was to assess the predictive performance of 'Servin's formula' for bispectral index (BIS)-guided propofol-remifentanil target-controlled infusion (TCI) in morbidly obese patients. Twenty patients (ASA physical status II-III, age 32-64 yr) undergoing bilio-intestinal bypass surgery, were recruited. Anaesthesia was induced by using a TCI of propofol with an initial target plasma concentration of 6 microg ml(-1), then adapted to maintain stable BIS values ranging between 40 and 50. A TCI of remifentanil was added to achieve pain control and haemodynamic stability. For propofol, weight was corrected as suggested by Servin and colleagues. With ideal body weight (IBW) corrected according to formula suggested by Lemmens and colleagues. For remifentanil, weight was corrected according to IBW. Arterial blood samples for the determination of blood propofol concentrations were collected at different surgical times. The predictive performance of propofol TCI was evaluated by examining performance accuracy. Median prediction error and median absolute prediction error were -32.6% (range -53.4%; -2.5%) and 33.1% (10.8%; 53.4%), respectively. Wobble median value was 5.9% (2.5%; 25.2%) while divergence median value was -1.5% h(-1) (-7.7; 33.8% h(-1)). Significant bias between predicted and measured plasma propofol concentrations was found while the low wobble values suggest that propofol TCI system is able to maintain stable drug concentrations over time. As already suggested before, a computer simulation confirmed that the TCI system performance could be significantly improved when total body weight is used.

Target-controlled propofol infusion during monitored anesthesia in patients undergoing ERCP

Background A target-controlled infusion system automatically adjusts the rate of infusion of propofol to maintain a desired (target) concentration. The aim of this study was to determine whether administration of propofol with a target-controlled infusion system could improve the sedation of patients undergoing ERCP. Methods A total of 205 consecutive patients undergoing ERCP were sedated by using a propofol target-controlled infusion system by an anesthesiologist. The target plasma concentration of propofol ranged from 2 to 5 μg/mL. A bolus dose of fentanyl (50-100 mcg) was administered if signs of insufficient analgesia were observed at the maximum target concentration of propofol allowed. The technical difficulty of ERCP was graded on a scale from 1 (least difficult) to 5 (most difficult). Results The mean dosages of propofol and fentanyl administered were 465 (245) mg and 59 (23) mcg, respectively. The total dose of propofol administered and the mean duration of ERCP were related to the degree of difficulty of the procedure. No severe complication was observed; mean time to discharge was 31 (12) minutes. Time to discharge was not influenced by the difficulty of ERCP or by the total dose of propofol administered. Conclusions A target-controlled infusion system for administration of propofol provides safe and effective sedation during ERCP. Further studies are needed to determine the cost-effectiveness and the safety profile for infusion of propofol with a target-controlled infusion system by a nonanesthesiologist during ERCP.

Closed-loop control of anesthesia using Bispectral index: performance assessment in patients undergoing major orthopedic surgery under combined general and regional anesthesia.

The Bispectral Index (BIS) is an electroencephalogram-derived measure of anesthetic depth. A closed-loop anesthesia system was built using BIS as the control variable, a proportional-integral-differential control algorithm, and a propofol target-controlled infusion system as the control actuator. Closed-loop performance was assessed in 10 adult patients. Ten adult patients scheduled to undergo elective hip or knee surgery were enrolled. An epidural cannula was inserted, and 0.5% bupivacaine was used to provide anesthesia to T8 before general anesthesia was induced using the propofol target-controlled infusion system under manual control. After the start of surgery, when anesthesia was clinically adequate, automatic control of anesthesia was commenced using the BIS as the control variable. Adequacy of anesthesia during closed-loop control was assessed clinically and by calculating the median performance error, the median absolute performance error, and the mean offset of the control variable. The median performance error and the median absolute performance error were 2.2 and 8.0%, respectively. Mean offset of the BIS from the set point was 0.9. Cardiovascular parameters were stable during closed-loop control. Operating conditions were adequate in all patients but one, who began moving after 45 min of stable anesthesia. No patients reported awareness or recall of intraoperative events. In three patients, there was oscillation of the measured BIS around the set point. The system was able to provide clinically adequate anesthesia in 9 of 10 patients. Further studies are required to determine whether control performance can be improved by alterations to the gain factors or by using an effect site-targeted, target-controlled infusion propofol system.

Performance of Closed-loop Anesthesia System Assessed during Orthopedic Surgery.

Performance of Closed-loop Anesthesia System Assessed during Orthopedic Surgery. Absalom et al. (page 67)In this study of 10 patients undergoing elective hip or knee replacement, Absalom et al. evaluated the performance of custom-made software to monitor and to automatically control propofol infusion in a closed-loop anesthesia system. Using the Bispectral Index (BIS) as the control variable, the system provides data management in the “monitor” mode, requesting electroencephalographic data at 5-s intervals and providing a graphical display of current and trend values. In “automatic” mode, the system automatically controls the propofol infusion after the operator has entered a target BIS value, a minimum propofol concentration, and the American Society of Anesthesiologists physical status of the patient. The system will not operate in automatic mode if the American Society of Anesthesiologists status is IV or V.Patients received 0.5% epidural bupivacaine at T8 to provide preinduction anesthesia. General anesthesia was induced using the propofol target-controlled infusion system under manual control in monitor mode. When anesthesia was deemed to be clinically adequate and surgery had begun, the system was switched to automatic mode using BIS as the control variable. The adequacy of anesthesia was then assessed throughout the remainder of the procedure, both clinically and by calculating the median performance error, the median absolute performance error, and the mean offset of the control variable.One anesthesiologist was in charge of clinical management of the patient, and another monitored the research equipment while also manually recording BIS, physiologic data, and blood and effect-site propofol concentrations at 5-min intervals. The target-controlled infusion system was switched back to manual mode when the surgeon began final closing, and the target propofol concentration was set to zero. Patients remained in the operating room until they had regained consciousness, laryngeal mask airways had been removed, and they could correctly state their date of birth. After surgery, none of the patients reported explicit recall of intraoperative events.Operating conditions were adequate in 9 of the 10 patients. One began moving after hip manipulation by the surgeon, after about 45 min of stable anesthesia. In three patients, the research team found oscillation of the measured BIS around the set point. The median performance error and median absolute performance error were 2.2 and 8.0%, respectively, and the mean offset of the BIS from the set point was 0.9. The researchers urge further study to determine whether control performance could be improved by alterations to the gain factors or by using an effect site–targeted, target-controlled infusion propofol system.

Theoretical basis of target controlled anaesthesia: history, concept and clinical perspectives

The technique of target controlled infusion (TCI) has influenced the development of intravenous anaesthesia substantially and opened the possibility of many new and exciting applications in peri-operative anaesthetic care. The launch of ‘Diprifusor™’ as the first commercially available TCI system for propofol in 1996 was the cornerstone of a successful research period within the last decade, which evaluated the pharmacokinetic foundations of computer assisted intravenous drug delivery. We are now in a period where TCI technology is becoming a part of the routine anaesthetic techniques for the practitioner rather than a research tool for specialists and enthusiasts. This review gives an overview of the history of target controlled anaesthesia, the rational pharmacokinetic basis of TCI development, the preliminary clinical experience with the new technique, the performance and accuracy of available TCI devices and the potential technical pitfalls in clinical routine. Although these developments were predominantly made with intravenous anaesthetic drugs, the knowledge of target controlled anaesthesia can principally be transferred to the administration of inhalational drugs, especially in the advent of new quantitative anaesthesia machines. As well as the clinical application of TCI with propofol and, in the near future, with remifentanil, target controlled systems are expected to play a significant role as research tools in the evaluation of drug interactions in anaesthesia, in the development of novel control techniques for the administration of sedative and analgesic drugs in the peri-operative period, and in optimizing the accuracy of feedback control systems.

Target controlled infusion (TCI)--status and clinical perspectives

The technique of target controlled infusion (TCI) has influenced the development of intravenous anaesthesia substantially and opens the possibility of many new and exciting applications in peri-operative anaesthetic care. The launch of "Diprifusor" as the first commercially available TCI system for propofol was the cornerstone of a successful research period within the last decade, which evaluated the pharmacokinetic foundations of computer assisted intravenous drug delivery. We are now in a period where TCI technology is becoming a part of routine anaesthesia technique for the practitioner rather than a research tool for specialists and enthusiasts. This review gives an update on the rational pharmacokinetic basis of TCI development, the preliminary clinical experience with the new technique, the performance and accuracy of TCI devices and potential technical pitfalls in clinical routine. Besides clinical application in anaesthesia with "Diprifusor" TCI, target controlled systems are expected to play a significant role as research tools in the evaluation of drug interactions in anaesthesia and in the development of novel control techniques for the administration of sedative and analgesic drugs in the peri-operative period.

Target controlled infusions

Target controlled infusion (TCI) combines a real-time pharmacokinetic model with an infusion pump and allows the administration and maintenance of a constant blood concentration of drug. TCI also allows alterations in the blood concentration to be made rapidly and easily. A TCI system for propofol, the ‘Diprifusor’, is now available and has greatly simplified the administration of propofol for maintenance of anaesthesia. TCI systems for other drugs exist, such as alfentanil and remifentanil, but are not yet commercially available. TCI propofol for maintenance of anaesthesia offers several benefits compared to volatile agents, including rapid recovery with a low incidence of nausea and vomiting. This review explores the development of TCI and discusses its advantages and disadvantages.