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Background: Propofol accounts for a substantial proportion of medication waste. Evidence-based waste reduction methods are scarce., Methods: In a retrospective analysis of 331 procedures, the total propofol waste per surgery was compared between manual and syringe pump induction of anaesthesia during total intravenous anaesthesia (TIVA), with a syringe pump used to maintain TIVA after induction. The secondary endpoint was the amount of propofol administered. Subgroup analyses examined the influence of biological sex, age, weight or BMI, American Society of Anesthesiologists (ASA) physical status, substance use, and anaesthesia duration on propofol waste., Results: Syringe pump induction was associated with 32.8% less waste of propofol (P<0.001); this effect was most pronounced in procedures lasting 20-60 min (up to 46.9% less in procedures lasting 20-40 min, P<0.001) and 80-120 min (up to 48.8% less in procedures lasting 100-120 min, P=0.003). The amount of waste was not affected by biological sex, age, weight, BMI, or ASA physical status. Syringe pump induction was consistently associated with less waste, except in patients with obesity. Patients with active substance use had 27.6% more waste with manual induction (P=0.031) but not with syringe pump induction. In patients with and without active substance use, syringe pump induction resulted in less waste (substance use: 48.7% less, P=0.0015; without substance use: 22.7% less, P=0.0045)., Conclusions: Syringe pump induction reduced propofol waste during TIVA, regardless of patient characteristics. Manual induction using a separate syringe should be reconsidered from an environmental and economic viewpoint., Clinical Trial Registration: DRKS00032518I., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Target-controlled infusion (TCI) is a mature technology that enables the delivery of intravenous anaesthetics in the concentration domain. The accuracy of the pharmacologic models used by TCI systems is imperfect, especially regarding pharmacodynamic predictions. This shortcoming of TCI devices is not critical. That TCI systems produce steady-state effect-site concentrations at or near a specified target is a more important attribute than a high level of accuracy because anaesthesiologists titrate to a stable level of drug effect whatever the actual concentration is. In this sense, TCI functions as a 'gain switch'. Achieving a steady state is more important than perfect accuracy., (Copyright © 2024. Published by Elsevier Ltd.)

BackgroundIt remains unknown whether local anaesthetic dose is the only factor influencing continuous popliteal-sciatic nerve block effects, or whether concentration, volume, or both exert an influence as well.MethodsBilateral sciatic catheters were inserted in volunteers (n=24). Catheters were randomly assigned to ropivacaine of either 0.1% (8 ml h(-1)) or 0.4% (2 ml h(-1)) for 6 h. The primary endpoint was the tolerance to transcutaneous electrical stimulation within the tibial nerve distribution at hour 6. Secondary endpoints included current tolerance at other time points and plantar flexion maximum voluntary isometric contraction (22 h total).ResultsAt hour 6, tolerance to cutaneous stimulation for limbs receiving 0.1% ropivacaine was [mean (standard deviation)] 27.0 (20.2) vs26.9 (20.4) mA for limbs receiving 0.4% [estimated mean difference 0.2 mA; 90% confidence interval (CI) -8.2 to 8.5; P=0.02 and 0.03 for lower and upper boundaries, respectively]. Because the 90% CI fell within the prespecified tolerance ±10 mA, we conclude that the effect of the two concentration/volume combinations were equivalent. Similar negative findings were found for the secondary outcomes.ConclusionsFor continuous popliteal-sciatic nerve blocks, we found no evidence that local anaesthetic concentration and volume influence block characteristics, suggesting that local anaesthetic dose (mass) is the primary determinant of perineural infusion effects in this anatomic location. These findings suggest that for ambulatory perineural local anaesthetic infusion-for which there is usually a finite local anaesthetic reservoir-decreasing the basal rate while increasing the local anaesthetic concentration may allow for increased infusion duration without compromising postoperative analgesia.Clinical trial registrationNCT01898689.

Background: Syringe infusion pumps are used for the precise continuous administration of intravenous drugs. Their compliance and mechanical deficiencies have been found to cause considerable start-up delays, flow irregularities during vertical displacement, as well extensive delays of occlusion alarms at low infusion rates. The aim of this study was to evaluate the performance of several modern syringe infusion pumps at low infusion rates and the impact on drug concentration., Methods: Seven currently marketed syringe infusion pump assemblies were assessed in an in vitro study during start-up, vertical displacement manoeuvres, and infusion line occlusion at a set flow rate of 1 ml h -1 . The measured data were used as input for a pharmacokinetic simulation modelling plasma concentration during a standard neonatal continuous epinephrine infusion., Results: The mean time from starting the infusion pump to steady-state flow varied from 89 to 1622 s. The zero-drug delivery time after lowering the pump ranged from 145 to 335 s. In all assemblies tested, occlusion alarm delays and measured flow irregularities during vertical displacement manoeuvres resulted in relevant deviations in plasma epinephrine concentration (>25%) as calculated by the pharmacokinetic simulation model., Conclusion: Problems with the performance of syringe infusion pump assemblies can have considerable impact on plasma drug concentration when highly concentrated short-acting cardiovascular drugs are administered at low flow rates. The problems, which affected all assemblies tested, are mainly related to the functional principle of syringe infusion pumps and will only partially be solved by incremental improvements of existing equipment., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Anaesthetic medication administration errors are a significant threat to patient safety. In 2002, we began collecting data about the rate and nature of anaesthetic medication errors and implemented a variety of measures to reduce errors., Methods: Facilitated self-reporting of errors was carried out in 2002-2003. Subsequently, a medication safety bundle including 'smart' infusion pumps were implemented. During 2014 facilitated self-reporting commenced again. A barcode-based medication safety system was then implemented and the facilitated self-reporting was continued through 2015., Results: During 2002-2003, a total of 11 709 paper forms were returned. There were 73 reports of errors (0.62% of anaesthetics) and 27 reports of intercepted errors (0.23%). During 2014, 14 572 computerised forms were completed. There were 57 reports of errors (0.39%) and 11 reports of intercepted errors (0.075%). Errors associated with medication infusions were reduced in comparison with those recorded in 2002-2003 (P<0.001). The rate of syringe swap error was also reduced (P=0.001). The reduction in error rate between 2002-2003 and 2014 was statistically significant (P=0.0076 and P=0.001 for errors and intercepted errors, respectively). From December 2014 through December 2015, 24 264 computerised forms were completed after implementation of a barcode-based medication safety system. There were 56 reports of errors (0.23%) and six reports of intercepted errors (0.025%). Vial swap errors in 2014-2015 were significantly reduced compared with those in 2014 (P=0.004). The reduction in error rate after implementation of the barcode-based medication safety system was statistically significant (P=0.0045 and P=0.021 for errors and intercepted errors, respectively)., Conclusions: Reforms intended to reduce medication errors were associated with substantial improvement., (Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Manual changeover of vasoactive drug infusion pumps (CVIP) frequently lead to haemodynamic instability. Some of the newest smart pumps allow automated CVIP. The aim of this study was to compare automated CVIP with manual 'Quick Change' relays., Methods: We performed a prospective, quasi-experimental study, in a university-affiliated intensive care unit (ICU). All adult patients receiving continuous i.v. infusion of vasoactive drugs were included. CVIP were successively performed manually (Phase 1) and automatically (Phase 2) during two 6-month periods. The primary endpoint was the frequency of haemodynamic incidents related to the relays, which were defined as variations of mean arterial pressure >15 mm Hg or heart rate >15 bpm. The secondary endpoints were the nursing time dedicated to relays and the number of interruptions in care because of CVIP. A multivariate mixed effects logistic regression was fitted for analytic analysis., Results: We studied 1329 relays (Phase 1: 681, Phase 2: 648) from 133 patients (Phase 1: 63, Phase 2: 70). Incidents related to CVIP decreased from 137 (20%) in Phase 1 to 73 (11%) in Phase 2 (P<0.001). Automated relays were independently associated with a 49% risk reduction of CVIP-induced incidents (adjusted OR=0.51, 95% confidence interval 0.34-0.77, P=0.001). Time dedicated to the relays and the number of interruptions in care to manage CVIP were also significantly reduced with automated relays vs manual relays (P=0.001)., Conclusions: These results demonstrate the benefits of automated CVIP using smart pumps in limiting the frequency of haemodynamic incidents related to relays and in reducing the nursing workload.

Background: In open TCI and anaesthesia display systems, the choice of pharmacokinetic (PK) parameter sets of opioids is clinically relevant. Accuracy and bias of the PK models may be affected by administration mode and the co-administered hypnotic drug. We retrospectively evaluated the performance of eight PK parameter sets for alfentanil in two data sets (infusion and bolus application)., Methods: With the dosing history from two studies in orthopaedic patients anaesthetized with propofol or inhalation anaesthetics the alfentanil plasma concentration over time was calculated with eight PK parameter sets. Median absolute performance error (MDAPE), log accuracy, median performance error (MDPE), log bias, Wobble, and Divergence were computed. Mann-Whitney rank test with Bonferroni correction was used for comparison between bolus and infusion data, repeated measures analysis of variance on ranks was used for comparison among parameter sets., Results: The parameters by Scott (original and weight adjusted) and Fragen had a MDAPE ≤30% and a median log accuracy <0.15 independent of the administration mode, while MDPE was within ±20% and log bias nearly within ±0.1, respectively. The sets by Maitre and Lemmens were within these limits only in the bolus data. All other parameter sets were outside these limits., Conclusions: In healthy orthopaedic patients, the PK parameters by Scott and by Maitre were equally valid when alfentanil was given as repeated boluses. When given as infusion, the Maitre parameters were less accurate and subject to a significant bias. We cannot exclude that the difference between bolus and infusion is partially because of the different hypnotics used.

Background: In the ideal pharmacokinetic-dynamic (PK-PD) model for calculating the predicted effect-site concentration of propofol (Ce(PROP)), for any Ce(PROP), the corresponding hypnotic effect should be constant. We compared three PK-PD models (Marsh PK with Shüttler PD, Schnider PK with fixed ke0, and Schnider PK with Minto PD) in their ability to maintain a constant bispectral index (BIS), while using the respective effect-site-controlled target-controlled infusion (TCI) algorithms., Methods: We randomized 60 patients to Group M (Marsh's model with k(e0)=0.26 min(-1)), Group S1 or Group S2 (Schnider's model with a fixed k(e0)=0.456 min(-1) or a k(e0) adapted to a fixed time-to-peak effect=1.6 min, respectively). All patients received propofol at a constant rate until loss of consciousness. The corresponding Ce(PROP), as calculated by the respective models, was set as a target for effect-site-controlled TCI. We observed BIS for 20 min. We hypothesized that BIS remains constant, if Ce(PROP) remains constant over time., Results: All patients in Group M woke up, one in Group S1 and none in Group S2. In Groups S1 and S2, BIS remained constant after 11 min of constant Ce(PROP), at a more pronounced level of hypnotic drug effect than intended., Conclusions: Targeting Ce(PROP) at which patients lose consciousness with effect-site-controlled TCI does not translate into an immediate constant effect.

Background: This study has compared the predictive performance of four pharmacokinetic models, two of which are currently incorporated in commercial target-controlled infusion pumps for the administration of propofol., Methods: Arterial propofol concentrations and patient characteristic data were available from nine patients who, in a published study, had received a standardized infusion of propofol. Predicted concentrations with 'Diprifusor' (Marsh), 'Schnider', 'Schuttler', and 'White' models were obtained by computer simulation. The predictive performance of each model was assessed overall and over the following phases: rapid infusion (1-5 min), early (1-21 min), maintenance (21-min end-infusion), and recovery (2-20 min post-infusion)., Results: The overall assessment, based on 29-36 samples from each patient, indicated that all four models were clinically acceptable. However, the negligible bias (-0.1%) with the 'Schnider' model was accompanied by overprediction in the rapid infusion phase and underprediction during recovery. This changing bias over time was not detected as 'divergence' when assessed on absolute performance error (APE), (1.4% h(-1)) but became significant (13.2% h(-1)) when based on changes in signed PE over time. The 'Schuttler' model performed well at most phases but overpredicted concentrations during recovery. The White model led to a marginal improvement over 'Diprifusor' and would be expected to reduce the positive bias usually seen with 'Diprifusor' systems., Conclusions: In assessing the predictive performance of pharmacokinetic models, additional information can be obtained by analysis of bias at different phases of an infusion. The evaluation of divergence should involve linear regression analysis of both absolute and signed PEs.

Background: A computer controlled infusion device for S(+) ketamine was used in combination with a Diprifusor device to provide anaesthesia for 20 ASA I or II patients undergoing elective colonoscopy. The aim of the study was to assess the performance of the pharmacokinetic model for S(+) ketamine used in the delivery algorithm of the device., Results: It was observed that during the first 30 min of infusion there was systematic underprediction by the delivery system of the measured levels of S(+) ketamine. New pharmacokinetic constants were derived from the observed data which provided, on pharmacokinetic simulation, improved prediction of the measured values of S(+) ketamine. Prospective application of this modified model for S(+) ketamine in a further nine study patients was performed and the pharmacokinetic performance of the model was reassessed. The data from all 29 patients was subsequently used to calculate the population distribution of S(+) ketamine clearance. The distribution was found to be normal only in the logarithmic domain. In the normal domain the mode of S(+) ketamine clearance was found to be 35.8 ml kg(-1) min(-1) with 5 and 95% confidence limits of, respectively, 11.5 and 111.1 ml kg(-1) min(-1)., Conclusion: It was necessary to modify the original published pharmacokinetic parameters incorporated into the S(+) ketamine delivery system in order to simulate improved PK performance during short procedures (<1 h duration) where propofol was concurrently administered. This improved performance was confirmed in a further prospective study.

Background: State entropy (SE) is a newly available monitor for depth of anaesthesia. We investigated whether the relationship between predicted effect-site propofol concentration and both bispectral index (BIS) and SE values is useful for predicting loss of verbal contact and loss of consciousness during steady-state conditions., Methods: Twenty unpremedicated patients undergoing elective major abdominal surgery were recruited. A target-controlled infusion of propofol was administered using Schneider's pharmacokinetic model. The propofol infusion was set at an initial site-effect concentration of 1.0 microg ml(-1), and increased by 1.0 microg ml(-1) steps every 4 min, up to 6.0 microg ml(-1). A 4-min interval was chosen to ensure that steady-state site-effect concentrations were obtained. Propofol site-effect concentrations and BIS and SE values were recorded at loss of verbal contact (LVC) and loss of consciousness (LOC). Population values for predicted effect-site concentrations at the clinical endpoints were estimated and correlated with BIS and SE values., Results: For LVC, the effect-site concentration for 90% of patients was 1.1 (1.1-3.2) microg ml(-1) and for LOC 2.8 (2.8-5.65) microg ml(-1). LVC occurred in 90% of patients at a BIS value of 70.2 (70.2-90.2) and an SE value of 60.3 (60.3-75.5) and LOC occurred at a BIS value of 38.2 (38.2-70.4) and an SE value of 42.2 (42.2-60.4)., Conclusions: LVC and LOC occurred within a defined range of predicted effect-site concentrations. SE had a smaller range than BIS and higher correlation with effect-site concentration and may be more useful than BIS in predicting both LVC and LOC.

Background: The purpose of this study is to test precision and systematic bias of a target controlled infusion (TCI) of propofol in human volunteers at two sedative concentrations., Methods: We studied the 'Diprifusor' model (Marsh Pharmacokinetics and a Graseby 3400 infusion pump) in 18 human volunteers at two sedative target plasma concentrations (0.5 and 1.0 microg ml(-1)). Twenty minutes after infusion start or change and 20 min after discontinuation of the infusion plasma propofol concentrations were measured using liquid chromatography-mass spectroscopy (LC-MS). Plasma propofol concentrations were compared with concentrations predicted by the TCI system. Agreement of those two measures (precision and bias) was determined using regression analysis., Results: We found little systematic bias but poor precision. When setting the TCI system to deliver a plasma concentration of 1.0 microg ml(-1) one can predict the actual plasma concentration with 95% confidence only within a range of 0.44-1.38 microg ml(-1)., Conclusions: This finding helps to explain differences in responses to propofol sedation; pharmacokinetic variability appears to be an important factor.

Background: Target-controlled infusions (TCI) are used to simplify administration and increase precision of i.v. drugs during general anaesthesia. However, there is a limited relationship between preset targets and measured concentrations of drugs and between measured concentrations and measures of brain function, such as the bispectral index (BIS)., Methods: We set out to evaluate the performance of TCI devices for propofol (Diprifusor) and remifentanil (Remifusor, prototype), during laparoscopic cholecystectomy in 21 patients. We also checked if there was any correlation between serum concentrations of propofol and BIS during individually adjusted anaesthesia., Results: The Diprifusor and Remifusor had a median absolute performance error of 60% and 25% respectively. Propofol concentrations were underpredicted by a median of 60%, and remifentanil concentrations were slightly overpredicted by a median of 7%. When anaesthesia was adjusted to keep BIS values between 45 and 60, no correlation existed between measured concentrations of propofol and the corresponding BIS values, although both BIS and serum propofol concentration discriminated well between the awake and asleep states. Emergence was rapid and uneventful in all patients. Female patients had a more rapid emergence than male patients (6.6 and 11.6 min respectively)., Conclusions: TCI devices for remifentanil and propofol result in large variation in measured serum concentrations. The lack of correlation between BIS and serum concentrations of propofol adds to the debate about whether BIS measures hypnosis as a graded state during surgery. This study confirms that women wake up faster than men, but provides no explanation for this repeatedly shown difference.

Background: Direct or indirect acting cholinergic muscarinic agonists such as neostigmine, are potent antinociceptives when administered intrathecally (i.t.). This study examines whether spinal neostigmine tolerance and cross-tolerance to spinal morphine occurs., Methods: Rats (32/group) were implanted with miniosmotic pumps delivering either i.t. saline 1 microl h(-1) (S), morphine 10 nmol microl(-1) h(-1) (M), or neostigmine 3 nmol microl(-1) h(-1) (N). Latencies (infrared thermal withdrawal rear paw) were measured daily for 6 days after which four animals from each group were given one i.t. challenge dose of morphine (m) 0.1, 1, 10, or 100 nmol, or neostigmine (n) 0.3, 3, 10, or 30 nmol., Results: Neostigmine and morphine-infused animals both developed tolerance to spinal neostigmine, but neostigmine-infused animals showed no significant cross-tolerance to spinal morphine; mean ED(50) nmol (CI 95%) dose-response values were Sn 2.6 (1.9-3.5), Mn 15.6 (9.9-24.6)*, Nn 18.7 (11.7-29.8)*, Sm 0.7 (0.4-1.1), Nm 1.2 (0.8-2.0), Mm 152 (50-461)* (*significance vs saline infused control group)., Conclusion: Thus, unidirectional cross-tolerance from morphine to neostigmine was evident. Previous studies suggest morphine has a cholinergic mechanism of action partially accounting for its antinociceptive effect, which may explain this observed unidirectional cross-tolerance.

We have assessed the efficacy and safety of a system which allowed 20 patients undergoing day-case anaesthesia to operate a target-controlled infusion of propofol to provide anxiolytic premedication. A target-controlled infusion of propofol was started with a target blood concentration of 1 microgram ml-1, and the patient was allowed to increase the target by 0.2 microgram ml-1 by operating a control button. There was a lockout time of 2 min and a maximum target concentration of 3 micrograms ml-1. There were significant reductions in anxiety scores from presedation baseline values and those measured at 15 min after the start of sedation. Values remained low until induction of anaesthesia. Median blood target concentration of propofol varied from 1.0 to 1.2 micrograms ml-1 and mean propofol consumption was 50.3 (SD 17.6) micrograms kg-1 min-1. No patient became oversedated and all remained cardiovascularly stable. Two individuals required low-dose supplementary oxygen for mild arterial oxygen desaturation but there were no instances of airway obstruction. Patient satisfaction with the system was high.

The performance of a fuzzy controller for atracurium-induced neuromuscular block was assessed. Ten ASA I or II patients undergoing surgery anticipated to last at least 120 min were studied. A Datex Relaxograph was used to monitor neuromuscular block. Initially the T1 set point was set at 10% of baseline for at least 30 min (phase I). The T1 set point was then increased to 20% and then returned to 10% for two further periods of at least 30 min duration (phases II and III). The mean (SD) of the mean T1 error in 10 patients for phases I, II and III were 1.1 (1.4)%, -0.43 (1.2)% and 0.28 (0.94)%, respectively. The results show that a simple fuzzy logic controller can provide good accuracy with insensitivity to set point changes despite the considerable inter-individual variation in infusion rate required.

We studied 160 ASA I-II patients, anaesthetized with propofol by infusion, using either a manually controlled or target-controlled infusion system. Patients were anaesthetized by eight consultant anaesthetists who had little or no previous experience of the use of propofol by infusion. In addition to propofol, patients received temazepam premedication, a single dose of fentanyl and 67% nitrous oxide in oxygen. Each consultant anaesthetized 10 patients in sequential fashion with each system. Use of the target-controlled infusion resulted in more rapid induction of anaesthesia and allowed earlier insertion of a laryngeal mask airway. There was a tendency towards less movement in response to the initial surgical stimulus and significantly less movement during the remainder of surgery. Significantly more propofol was administered during both induction and maintenance of anaesthesia with the target-controlled system. This was associated with significantly increased end-tidal carbon dioxide measurements during the middle period of maintenance only, but recovery from anaesthesia was not significantly prolonged in the target-controlled group. With the exception of a clinically insignificant difference in heart rate, haemodynamic variables were similar in the two groups. Six of the eight anaesthetists found the target-controlled system easier to use, and seven would use the target-controlled system in preference to a manually controlled infusion. Anaesthetists without prior experience of propofol infusion anaesthesia quickly became familiar with both manual and target-controlled techniques, and expressed a clear preference for the target-controlled system.

I have evaluated in vitro methods of increasing the flow rate of clear fluids through an i.v. cannula at room temperature. These included, alone and in combination: increasing the height of a gravity-fed system; increasing the i.v. cannula diameter, manual compression of the lower drip chamber and the use of pressure bags. Flow rate was measured using a uroflowmeter, which was found to be reliable and reproducible. The most effective methods of increasing flow were the use of a 14-gauge cannula rather than a 16-gauge cannula, which resulted in a 50% increase, and the use of a 300-mm Hg pressure bag with automatic adjustable pressure regulator, which doubled the flow rate. The combination of these two tripled the overall flow to nearly 600 ml min-1. Manual compression of the drip chamber, despite producing peak pressures of more than 100 cm H2O, was an inefficient method of improving flow compared with an external pressure bag.

A computerized infusion system was used to determine mivacurium infusion requirements to maintain 95% and 50% neuromuscular block in 15 infants less than 1 yr of age. Neuromuscular block was measured by adductor pollicis EMG and anaesthesia maintained with 66% nitrous oxide in oxygen and alfentanil 50-100 micrograms kg-1 h-1. Neuromuscular block was produced by repeated bolus doses of mivacurium 0.1 mg kg-1; subsequently the target neuromuscular block was maintained by a closed loop infusion. Dose potency of mivacurium was similar to that previously published in children with a similar anaesthetic technique. Mean mivacurium requirement for 95% neuromuscular block was 820 (SD 300) micrograms kg-1 h-1, which represented an hourly requirement of 6.6 (1.5) individual ED95 doses. Infusion requirement for 50% neuromuscular block was 320 (150) micrograms kg-1 h-1. These infusion rates were similar to those in children. No side effects of mivacurium were noticed.

A computerized infusion system was used to determine requirement for a mivacurium infusion to maintain a 95% and a 50% neuromuscular block in 21 children aged 1-15 yr. Neuromuscular block was measured by adductor pollicis EMG and anaesthesia maintained with 66% nitrous oxide in oxygen and alfentanil 50-100 micrograms kg-1 h-1. The targeted neuromuscular block was reached within mean 5 (SD 3) min from initiation of an infusion. Mivacurium requirement for 95% neuromuscular block was 950 (350) micrograms kg-1 h-1, which represented an hourly requirement of 6.8 (1.6) individual ED95 doses. Infusion requirement for 50% neuromuscular block averaged 350 (150) micrograms kg-1 h-1. There was a significant negative correlation between infusion rate and age of a patient. Great individual variation of the infusion rate makes a computerized infusion an easy method to achieve and maintain a desired level of neuromuscular block. No side effects of mivacurium were noticed.