Target-controlled Infusion Of Propofol Research Articles

Comparison of arterial hypotension incidence during general anesthesia induction – target-controlled infusion vs. bolus injection of propofol: a randomized clinical trial

BackgroundThe incidence of arterial hypotension during induction of general anesthesia is influenced by the method of propofol administration, but there is a dearth of randomized clinical trials comparing bolus injection and target-controlled infusion in relation to arterial hypotension. This study seeks to compare the incidence of arterial hypotension between these two methods of propofol administration. MethodsThis prospective, randomized, single-center, non-blinded study included 60 patients (aged 35 to 55 years), classified as ASA physical status I or II, who were undergoing non-cardiac surgeries. They were randomly allocated using a computer to two groups based on the method of propofol administration during the induction of general anesthesia: the Target Group, receiving target-controlled infusion at 4 μg.mL−1, and the Bolus Group, receiving a bolus infusion of 2 mg.kg−1. Both groups also received midazolam 2 mg, fentanyl 3 μg.kg−1, and rocuronium 0.6 mg.kg−1. Over the first 10 minutes of anesthesia induction, Mean Arterial Pressure (MAP), Heart Rate (HR), level of Consciousness (qCON), and Suppression Rate (SR) were recorded every 2 minutes. ResultsTwenty-seven patients remained in the TCI group, while 28 were in the Bolus group. Repeated measure analysis using mixed-effects models could not reject the null hypothesis for the effect of group-time interactions in MAP (p = 0.85), HR (p = 0.49), SR (p = 0.44), or qCON (p = 0.72). The difference in means for qCON (60.2 for TCI, 50.5 for bolus, p < 0.001), MAP (90.3 for TCI, 86.2 for bolus, p < 0.006), HR (76.2 for TCI, 76.9 for bolus, p = 0.93), and SR (0.01 for TCI, 5.5 for bolus, p < 0.001), irrespective of time (whole period means), revealed some significant differences. ConclusionPatients who received propofol bolus injection exhibited a lower mean arterial pressure, a greater variation in the level of consciousness, and a higher suppression rate compared to those who received it as a target-controlled infusion. However, the interaction effect between groups and time remains inconclusive.

Effect of Remimazolam Supplementation on Propofol Requirements During Hysteroscopy: A Double-Blind, Dose-Response Study.

Propofol is commonly used for procedural sedation but may increase side effects in a dose-dependent manner. Remimazolam, an ultrashort-acting benzodiazepine, has been approved for procedural sedation but may delay awakening. This study tested the hypothesis that remimazolam as a supplement reduces effect-site propofol concentration (Ceprop) required to suppress response to cervical dilation in patients undergoing hysteroscopy. One hundred and fifty patients who were scheduled for hysteroscopy were randomized to receive 0, 0.05, 0.1, 0.15, or 0.2 mg·kg-1 intravenous remimazolam, followed by a bolus of sufentanil 0.15 μg⋅kg-1, and a target-controlled propofol infusion. The initial target Ceprop was 3.5 μg·mL-1 and was increased or decreased in subsequent patients by steps of 0.5 μg·mL-1 according to whether there was loss of response to cervical dilation in the previous patient. We used up-down sequential analysis to determine values of Ceprop that suppressed response to cervical dilation in 50% of patients (EC50). The EC50 of propofol for suppressing response to cervical dilation was lower in patients given 0.1 mg·kg-1 (2.08 [95% confidence interval, CI, 1.88-2.28] μg·mL-1), 0.15 mg⋅kg-1 (1.83 [1.56-2.10] μg·mL-1), and 0.2 mg⋅kg-1 (1.43 [1.27-1.58] μg·mL-1) remimazolam than those given 0 mg⋅kg-1 (3.67 [3.49-3.86] μg·mL-1) or 0.05 mg⋅kg-1 (3.47 [3.28-3.67] μg·mL-1) remimazolam (all were P < .005). Remimazolam at doses of 0.1, 0.15, and 0.2 mg·kg-1 decreased EC50 of propofol by 43.3% (95% CI, 41.3%-45.5%), 50.3% (48.0%-52.8%), and 61.2% (58.7%-63.8%), respectively, from baseline (remimazolam 0 mg⋅kg-1). Propofol consumption was lower in patients given 0.1 mg⋅kg-1 (4.15 [3.51-5.44] mg·kg-1), 0.15 mg⋅kg-1 (3.54 [3.16-4.46] mg·kg-1), and 0.2 mg⋅kg-1 (2.74 [1.73-4.01] mg·kg-1) remimazolam than those given 0 mg⋅kg-1 (6.09 [4.99-7.35] mg·kg-1) remimazolam (all were P < .005). Time to anesthesia emergence did not differ significantly among the 5 groups. For women undergoing hysteroscopic procedures, remimazolam at doses from 0.1 to 0.2 mg·kg-1 reduced the EC50 of propofol inhibiting response to cervical dilation and the total propofol requirement. Whether the combination could improve perioperative outcomes deserves further investigation.

External validation of the modified Marsh and Schnider models for medium-chain triglyceride propofol in target-controlled infusion anesthesia

BackgroundPropofol formulated with medium- and long-chain triglycerides (MCT/LCT propofol) has rapidly replaced propofol formulated with long-chain triglycerides (LCT propofol). Despite this shift, the modified Marsh and Schnider pharmacokinetic models developed using LCT propofol are still widely used for target-controlled infusion (TCI) of propofol. This study aimed to validate the external applicability of these models by evaluating their predictive performance during TCI of MCT/LCT propofol in general anesthesia.MethodsAdult patients (n = 48) undergoing elective surgery received MCT/LCT propofol via a TCI system using either the modified Marsh or Schnider models. Blood samples were collected at various target propofol concentrations and at specific time points, including the loss of consciousness and the recovery of consciousness (13 samples per patient). The actual plasma concentration of propofol was determined using high-performance liquid chromatography. The predictive performance of each pharmacokinetic model was assessed by calculating four parameters: inaccuracy, bias, divergence, and wobble.ResultsBoth the modified Marsh and Schnider models demonstrated predictive performances within clinically acceptable ranges for MCT/LCT propofol. The inaccuracy values were 24.4% for the modified Marsh model and 26.9% for the Schnider model. Both models showed an overall positive bias, 16.4% for the modified Marsh model and 16.6% for the Schnider model. The predictive performance of MCT/LCT propofol was comparable to that of LCT propofol, suggesting formulation changes might exert only a minor impact on the reliability of the TCI system during general anesthesia. Additionally, both models exhibited higher bias and inaccuracy at target concentrations ranging from 3.5 ~ 5 ug/ml than at concentrations between 2 ~ 3 ug/ml.ConclusionsThe modified Marsh and Schnider models, initially developed for LCT propofol, remain clinically acceptable for TCI with MCT/LCT propofol.Trial registrationThis study was registered at the Clinical Research Information Service of the Korean National Institute of Health (https://cris.nih.go.kr; registration number: KCT0002191; 06/01/2017).

General purpose propofol target-controlled infusion using the marsh model with adjusted weight input.

We report a simple method for adjusting the weight input of the Marsh target-controlled infusion (TCI) model such that the resulting infusion regime closely mimics the behaviour of the Eleveld model, thereby making the Marsh model more precise for patients at the extremes of age and body mass index. To assess the performance of our method, we simulated 2768 subjects with diverse combinations of age, weight, height and sex undergoing a hypothetical four-hour propofol TCI using both the Marsh model with our weight adjustment and the Eleveld model. The weight adjusted Marsh model produced infusion regimes and corresponding effect site concentrations closely mimicking that of the Eleveld model at all time points, with median and maximum absolute performance errors less than 8.1% and 20.3%, respectively, across the entire cohort. Our weight adjustment method is a simple and robust way of improving the precision of the Marsh model in patients at extremes of age and body mass index, until general purpose TCI models for propofol, such as the Eleveld model, become more widely available in commercial infusion pumps.

Comparison between remimazolam and propofol anaesthesia for interventional neuroradiology: a randomised controlled trial

BackgroundGeneral anaesthesia can immobile patients during interventional neuroradiology to improve image quality. Remimazolam, an ultrashort-acting benzodiazepine, is advantageous for haemodynamic stability. This study compared remimazolam and propofol anaesthesia during neuroradiology procedures regarding intraoperative hypotensive events and rapid recovery. MethodsThis single-masked randomised-controlled study included 76 participants who underwent elective endovascular embolisation in a single centre. Patients were randomised between a continuous remimazolam infusion (n = 38) or a target-controlled propofol infusion group (n = 38). In the remimazolam group, flumazenil (0.2 mg) was administered at the end of the procedure. Phenylephrine was titrated to maintain the mean arterial pressure within ± 20% of the baseline value. The primary outcome was the total phenylephrine dose during the procedure. ResultsThe total phenylephrine dose was 0.0 [0.0–30.0] μg in the remimazolam group and 30.0 [0.0–205.0] μg in the propofol group (p = 0.001). Hypotensive events were observed in 11 (28.9%) patients in the remimazolam group and 23 (60.5%) patients in the propofol group (p = 0.001). Recovery times to spontaneous breathing, eye-opening, extubation, and orientation were shorter in the remimazolam group than in the propofol group (all p < 0.001). ConclusionsRemimazolam anaesthesia showed superior haemodynamic stability compared with propofol anaesthesia during neuroradiology procedures. Systematic use of flumazenil enabled rapid recovery from remimazolam anaesthesia. RegistrationUniversity Hospital Medical Information Network Clinical Trials Registry; Registration number: UMIN000047384; URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000054046

Effect of high flow nasal catheter oxygen to prevent hypoxemia in endoscopic retrograde cholangiopancreatography surgery in aged

Objective: To explore the effect of high-flow nasal catheter oxygen inhalation in preventing hypoxemia during endoscopic retrograde cholangiopancreatography (ERCP) surgery in elderly patients. Methods: From September 2021 to September 2022, 116 elderly patients (aged ≥ 70 years) who underwent elective ERCP in the Northern Theater General Hospital were prospectively selected, then divided into general nasal catheter oxygen inhalation group [group C, 31 males and 27 females, aged (79.8±6.4) years] and high-flow nasal catheter oxygen inhalation group [group H, 33 males and 25 females, aged (81.4±6.7) years], with 58 patients in each group. All patients were monitored for anesthesia by target-controlled infusion of propofol and remifentanil. The main outcome index was the incidence of intraoperative subclinical hypoxemia (90% ≤ SpO2 < 95%, duration >5 s), hypoxemia (75% < SpO2 < 90%, 5 s < duration ≤ 60 s) and severe hypoxemia (SpO2 < 75% or SpO2 < 90%, duration > 60 s). Secondary observation measures were SpO2 from T0 to T5 (T0, before anesthesia induction; T1, immediately after anesthesia induction; T2, endoscopic introduction; T3, duodenal papula intubation; T4, endoscopic withdrawal; T5, postoperative awakening), the arterial oxygen partial pressure (PaO2), carbon dioxide partial pressure (PaCO2) and pH at T0, 15 min after the induction and T5. Results: The incidence of intraoperative subclinical hypoxemia in group C and group H was 12.0% (7/58) and 3.4% (2/58) respectively, which showed no significant statistical difference (P=0.165) from each other. The incidence of intraoperative hypoxemia in group H was 8.6% (5/58), which was significantly lower than 31.0% (18/58) of group C (P=0.003). Neither group had intraoperative severe hypoxemia. SpO2 of group H were (98.2±0.9)%, (98.2±0.9)%, (97.8±1.7)% and (97.7±1.7)% at T1, T2, T3, T4, which were higher than (96.8±2.1)%, (96.4±3.0)%, (96.1±2.9)% and (96.4±3.4)% in group C (all P<0.05). PaO2 at 15 min after induction in group H was (240.5±46.7) mmHg (1 mmHg=0.133 kPa), which was higher than that of group C (170.6±33.4) mmHg (P<0.001). There was no statistically significant difference in pH and PaCO2 between the two groups of patients at each timepoint. Conclusion: High flow nasal catheter oxygen can effectively reduce the incidence of hypoxemia in ERCP in elderly patients.

A Deep Learning Framework for Anesthesia Depth Prediction from Drug Infusion History.

In the target-controlled infusion (TCI) of propofol and remifentanil intravenous anesthesia, accurate prediction of the depth of anesthesia (DOA) is very challenging. Patients with different physiological characteristics have inconsistent pharmacodynamic responses during different stages of anesthesia. For example, in TCI, older adults transition smoothly from the induction period to the maintenance period, while younger adults are more prone to anesthetic awareness, resulting in different DOA data distributions among patients. To address these problems, a deep learning framework that incorporates domain adaptation and knowledge distillation and uses propofol and remifentanil doses at historical moments to continuously predict the bispectral index (BIS) is proposed in this paper. Specifically, a modified adaptive recurrent neural network (AdaRNN) is adopted to address data distribution differences among patients. Moreover, a knowledge distillation pipeline is developed to train the prediction network by enabling it to learn intermediate feature representations of the teacher network. The experimental results show that our method exhibits better performance than existing approaches during all anesthetic phases in the TCI of propofol and remifentanil intravenous anesthesia. In particular, our method outperforms some state-of-the-art methods in terms of root mean square error and mean absolute error by 1 and 0.8, respectively, in the internal dataset as well as in the publicly available dataset.

Predictors for delayed awakening in adult glioma patients receiving awake craniotomy under monitored anesthesia care

PurposeDelayed awakening after anesthetic discontinuation during awake craniotomy is associated with somnolence during functional brain mapping. However, predictors of delayed awakening in patients receiving monitored anesthesia care for awake craniotomy are unknown.MethodsThis retrospective cohort study analyzed 117 adult patients with supratentorial glioma in or near eloquent areas who received monitored anesthesia care for awake craniotomy between July 2020 and January 2023 at Linkou Chang Gung Memorial Hospital. These patients were divided into two groups according to their time to awakening (ability to speak their names) after propofol cessation: longer or shorter than 20 min (median duration). Because propofol was solely used anesthetic from skin incision to dural opening, parameters in Schnider model for propofol target-controlled infusion, such as age, sex, and BMI, were adjusted or propensity-matched to compare their anesthetic, surgical, and histopathological profiles.ResultsAfter propensity-matched comparisons of age and BMI, significant predictors of delayed awakening included IDH1 wild-type tumors and repeated craniotomies. Subgroup analysis revealed that older age and larger T2 volume were predictors in patients undergoing the first craniotomy, while lower preoperative Karnofsky performance scale scores and depression were predictors in repeated craniotomy cases. Delayed awakening was also associated with somnolence and a lower gross total resection rate.ConclusionOur retrospective analysis of patients receiving monitored anesthesia care for awake craniotomy revealed that delayed awakening after propofol discontinuation occurred more often in patients with IDH1 wild-type tumors and repeated craniotomies. Also, delayed awakening was associated with somnolence during functional mapping and a lower gross total resection rate.

Effect of general anaesthesia with remimazolam versus propofol on postoperative quality of recovery in patients undergoing ambulatory arthroscopic meniscus repair: a randomised clinical trial

BackgroundThe type of anaesthesia and choice of anaesthetic drugs may affect the quality of recovery after surgery. Remimazolam is a new benzodiazepine with rapid onset and offset, specifically antagonised by flumazenil. This study aimed to compare remimazolam with propofol on the quality of recovery in patients undergoing ambulatory arthroscopic surgery. MethodsPatients aged 18–65 yr and scheduled for ambulatory arthroscopic meniscus repair were recruited and randomly assigned to receive either continuous i.v. infusion of remimazolam or plasma target-controlled infusion of propofol. The quality of recovery-15 (QoR-15) scale was administered on postoperative day 1 (POD1) as the primary outcome. Secondary outcomes included the Athens Insomnia Scale (AIS) scores and cardiovascular variables. ResultsIn total, 120 patients were randomly assigned to the remimazolam or propofol groups and 114 patients were included in the analysis. The remimazolam group had higher total QoR-15 scores on POD1 (125 [120–127.5] vs 121.5 [119–124], with a median difference of 3 (95% confidence interval: 1–5; P=0.002). Physical independence and psychological support were higher in the remimazolam group (8.5 [8–10] vs 8 [7–9], P=0.043; 17 [13–17] vs 12.5 [12–14], P<0.001). Remimazolam lowered the number of awakenings during the first postoperative night (P=0.042) and the incidence of hypotension (P=0.04). ConclusionsRemimazolam-based total i.v. anaesthesia was associated with small improvements in the quality of recovery; however, the improvement was less than the minimally clinically important difference. Clinical trial registrationChiCTR2100053014.

Schnider and Eleveld Models for Propofol Target-Controlled Infusion Anesthesia: A Clinical Comparison.

Various pharmacokinetic/pharmacodynamic (PK/PD) models have been developed to accurately dose propofol administration during total intravenous anesthesia with target-controlled infusion (TIVA-TCI). We aim to clinically compare the performance of the Schnider model and the new and general-purpose Eleveld PK/PD model during TIVA-TCI. We conducted a prospective observational study at a single center, enrolling 78 female patients, including 37 adults (aged < 65 years) and 41 elderly patients (aged ≥ 65 years). These patients underwent breast surgery with propofol-remifentanil TIVA-TCI guided by the bispectral index (BIS) for depth of anesthesia monitoring (target value 40-60) and the surgical plethysmographic index (SPI) for antinociception monitoring (target value 20-50) without neuromuscular blockade. The concentration at the effect site of propofol (CeP) at loss of responsiveness (LoR) during anesthesia maintenance (MA) and at return of responsiveness (RoR), the duration of surgery and anesthesia (min), the time to RoR (min), the propofol total dose (mg), the deepening of anesthesia events (DAEs), burst suppression events (BSEs), light anesthesia events (LAEs) and unwanted spontaneous responsiveness events (USREs) were considered to compare the two PK/PD models. Patients undergoing BIS-SPI-guided TIVA-TCI with the Eleveld PK/PD model showed a lower CeP at LoR (1.7 (1.36-2.25) vs. 3.60 (3.00-4.18) μg/mL, p < 0.001), higher CePMA (2.80 (2.55-3.40) vs. 2.30 (1.80-2.50) μg/mL, p < 0.001) and at RoR (1.48 (1.08-1.80) vs. 0.64 (0.55-0.81) μg/mL, p < 0.001) than with the Schnider PK/PD model. Anesthetic hysteresis was observed only in the Schnider PK/PD model group (p < 0.001). DAEs (69.2% vs. 30.8%, p = 0.001) and BSEs (28.2% vs. 5.1%, p = 0.013) were more frequent with the Eleveld PK/PD model than with the Schnider PK/PD model in the general patient population. DAEs (63.2% vs. 27.3%, p = 0.030) and BSEs (31.6% vs. 4.5%, p = 0.036) were more frequent with the Eleveld PK/PD model than with the Schnider PK/PD model in the elderly. The Schnider and Eleveld PK/PD models impact CePs differently. A greater incidence of DAEs and BSEs in the elderly suggests more attention is necessary in this group of patients undergoing BIS-SPI-guided TIVA-TCI with the Eleveld PK/PD than with the Schnider model.

Spontaneous Ventilation Combined with Double-Lumen Tube Intubation during Thoracic Surgery: A New Anesthesiologic Method Based on 141 Cases over Three Years.

Non-intubated thoracic surgery has not achieved widespread acceptance despite its potential to improve postoperative outcomes. To ensure airway safety, our institute has developed a technique combining spontaneous ventilation with double-lumen tube intubation (SVI). This study aimed to verify the feasibility and limitations of this SVI technique. For the SVI method, anesthesia induction involves fentanyl and propofol target-controlled infusion, with mivacurium administration. Bispectral index monitoring was used to ensure the optimal depth of anesthesia. Short-term muscle relaxation facilitated double-lumen tube intubation and early surgical steps. Chest opening preceded local infiltration, followed by a vagal nerve blockade to prevent the cough reflex and a paravertebral blockade for pain relief. Subsequently, the muscle relaxant was ceased. The patient underwent spontaneous breathing without coughing during surgical manipulation. Between 10 March 2020 and 28 October 2022, 141 SVI surgeries were performed. Spontaneous respiration with positive end-expiratory pressure was sufficient in 65.96% (93/141) of cases, whereas 31.21% (44/141) required pressure support ventilation. Only 2.84% (4/141) of cases reversed to conventional anesthetic management, owing to technical or surgical difficulties. Results of the 141 cases: The mean maximal carbon dioxide pressure was 59.01 (34.4-92.9) mmHg, and the mean lowest oxygen saturation was 93.96% (81-100%). The mean one-lung, mechanical and spontaneous one-lung ventilation time was 74.88 (20-140), 17.55 (0-115) and 57.73 (0-130) min, respectively. Spontaneous ventilation with double-lumen tube intubation is safe and feasible for thoracic surgery. The mechanical one-lung ventilation time was reduced by 76.5%, and the rate of anesthetic conversion to relaxation was low (2.8%).

Effectiveness and safety of an atropine/midazolam and target controlled infusion propofol-based moderate sedation protocol during percutaneous endoscopic transgastric jejunostomy procedures in Parkinson's disease: a real-life retrospective observational study.

Patients with Parkinson's disease (PD), often elderly with various comorbidities, may require a continuous intestinal infusion of carbidopa/levodopa gel by the placement of a percutaneous endoscopic gastrostomy (PEG) with a jejunal tube (PEG-J) to improve their motor outcome and quality of life. However, it is unclear what is the best procedural sedation protocol for PEG-J procedures. Fifty patients with PD and indication for PEG-J procedure (implantation, replacement, removal) underwent, from 2017 to 2022, a sedation protocol characterized by premedication with atropine (0.01 mg/Kg i.v.), midazolam (0.015-0.03 mg/Kg i.v.) and induction with bolus propofol (0.5-1 mg/Kg i.v.) as well as, finally, sedation with continuous infusion propofol (2-5 mg/Kg/h i.v.) by Target Controlled Infusion (TCI) technique. Ninety-eight per cent of patients experienced no intraprocedural or peri-procedural adverse events. All the procedures were technically successful. A good discharge time was recorded. The vital parameters recorded during the procedure did not vary significantly. A PEG-J procedure conducted within 30 min showed a significant advantage over end-tidal carbon dioxide (EtCO2). Indeed, the latter showed some predictive behavior (OR: 1.318, 95% CI 1.075-1.615, p = 0.008). In the real world, this sedation protocol showed a good safety and effectiveness profile, even with reduced doses of midazolam and a TCI propofol technique in moderate sedation.

Pro-Con Debate: Should All General Anesthesia Be Done Using Target-Controlled Propofol Infusion Guided by Objective Monitoring of Depth of Anesthesia?

In this Pro-Con commentary article, we discuss whether all general anesthesia should be done using target-controlled propofol anesthesia guided by monitoring of depth of anesthesia. This is an ongoing debate since more than 25 years, representing a scientific, cultural as well as geographical divide in the anesthesia community. The Pro side argues that total intravenous anesthesia causes less postoperative nausea and higher patient satisfaction than anesthesia using volatile anesthetics. Target-controlled infusion (TCI) of anesthetic agents allows for better titration of intravenous anesthesia using pharmacokinetic models. Processed EEG monitors, such as bispectral index monitoring, allows for better assessing the effect of TCI anesthesia than solely assessment of clinical parameters, such as ECG or blood pressure. The combination of TCI propofol and objective depth of anesthesia monitoring allows creating a pharmacokinetic-pharmacodynamic profile for each patient. Finally, anesthesia using volatile anesthetics poses health risks for healthcare professionals and contributes to greenhouse effect. The Con side argues that for procedures accompanied with ischemia and reperfusion injury of an organ or tissue and for patients suffering from a severe inflammation' the use of volatile anesthetics might well have its advantages above propofol. In times of sudden shortage of drugs, volatile anesthetics can overcome the restriction in the operating theater or even on the intensive care unit, which is another advantage. Volatile anesthetics can be used for induction of anesthesia when IV access is impossible, end-tidal measurements of volatile anesthetic concentration allows confirmation that patients receive anesthetics. Taking environmental considerations into account, both propofol and volatile anesthetics bear certain harm to the environment, be it as waste product or as greenhouse gases. The authors therefore suggest to carefully considering advantages and disadvantages for each patient in its according environment. A well-balanced choice based on the available literature is recommended. The authors recommend careful consideration of advantages and disadvantages of each technique when tailoring an anesthetic to meet patient needs. Where appropriate, anesthesia providers are encouraged to account for unique features of anesthetic drug behavior, patient-reported and observed postoperative outcomes, and economic and environmental considerations when choosing any of the 2 described techniques.

Variability of predicted propofol concentrations and measured sevoflurane concentrations during general anaesthesia: a single-centre retrospective cohort study

BackgroundVariability is high in predicted propofol concentrations during clinical anaesthesia titrated by target-controlled infusion (TCI) to maintain a processed EEG parameter (bispectral index [BIS]) within a specified range. We have shown that the potential for improving the pharmacokinetic model is minimal. The drug titration paradox revealed that titration challenges the classical relationship between drug dose and effect in both individuals and the population. We hypothesised that dynamic factors during surgery beyond the static genetic, epigenetic, and other factors such as age, height, and weight affect the necessary dose. We compared the variability of measured end-tidal sevoflurane concentrations with predicted effect-site propofol concentrations when titrated to a BIS range of 40–60, with the hypothesis that the variability in measured sevoflurane concentrations would not be less than the variability in estimated propofol concentrations. MethodsClinical data from 2280 surgical procedures >1 h in duration were included in the analysis. Anaesthesia with sevoflurane or propofol was based on an institutional protocol. The titration performance for both drugs was assessed by comparing BIS values 30 min after skin incision. The variability of the required concentrations at the same time point was calculated and compared. ResultsThe achieved 30-min post-incision BIS ranges were not significantly different for sevoflurane or propofol TCI (30 [99% CI: 28–33] and 31 [99% CI: 27–36], respectively). The variability of sevoflurane concentrations was not significantly different from measured predicted propofol concentrations during BIS-guided anaesthesia (normalized concentration range of 0.89 [99% CI: 0.78–0.99] and 0.93 [99% CI 0.87–1.02). ConclusionsImprovements in prediction accuracy of pharmacokinetic models beyond that of those already in clinical use are unlikely to reduce variability in target anaesthetic concentrations across patients in clinical practice.

Comparison of Sedation With Ketamine-Propofol Versus Propofol-Fentanyl for Elderly Patients Undergoing Prostate Biopsy: A Retrospective Observational Study.

Procedural sedation is increasingly used for elderly patients, but there is no established ideal method for elderly patients who are prone to respiratory and circulatory depression. This study aims to investigate the association of respiratory complications and the combination of ketamine-propofol versus fentanyl-propofol in elderly patients undergoing prostate biopsy requiring deep sedation. This was a single-center, retrospective, observational study conducted from April 2020 to March 2021. We included male patients aged 65 years and older scheduled for prostate biopsy under procedural sedation. Ketamine-propofol and fentanyl-propofol were administered at the discretion of the anesthesiologist. The primary outcome was the need for assisted ventilation. The secondary outcome was the duration ofoxygen saturation (SpO2)below 90%. We enrolled 120 patients over 65 years, and 92 patients were included in the final analysis. The anesthesiologist administered an initial dose of ketamine and propofol of 1:1 to 1:4 of 1.0 mg kg-1 (interquartile range: 0.98 to 1.17) or administered an initial dose of fentanyl of 0.05 to 0.1 mg and a target-controlled infusion of propofol of 2.8 μg ml-1 (interquartile range: 2.0 to 3.0) followed by additional doses at the discretion of the anesthesiologist. Ketamine-propofol was associated with a reduced need for assisted ventilation and a shorter duration of SpO2 below 90% than propofol-fentanyl (95.7% vs. 4.3%, P < 0.05; 0.64 minutes vs. 0.17 minutes, P = 0.26). Ketamine-propofol is associated with a significantly reduced need for assisted ventilation compared topropofol-fentanyl during procedural sedation and analgesia for procedures requiring deep sedation for the elderly.

Comparison of propofol vs. remimazolam on emergence profiles after general anesthesia: A randomized clinical trial

Study objectiveThe emergence profiles in patients undergoing total intravenous anesthesia with either propofol or remimazolam with flumazenil reversal were compared. DesignA prospective, double-blind, randomized trial. SettingAn operating room and a post-anesthesia care unit (PACU). PatientsAdult patients (n = 100) having American Society of Anesthesiologists (ASA) physical status of I-III undergoing general anesthesia were enrolled and randomly assigned to the propofol or the remimazolam group. InterventionsThe propofol group received target-controlled infusion of propofol, and the remimazolam group received continuous infusion of remimazolam. Continuous infusion of remifentanil was used in both groups. For emergence, flumazenil was used in increments of 0.2 mg in the remimazolam group. MeasurementsThe primary outcome was the time required for the patient to obey verbal commands. The secondary outcomes included the time to bispectral index (BIS) over 80, the time to laryngeal mask airway (LMA) removal, the Richmond Agitation-Sedation Scale (RASS) scores in the PACU, and adverse events throughout the study period. Main resultsThe time taken to obey verbal commands was significantly longer in the propofol group than the remimazolam group (14 [9, 19]) vs. 5 [3, 7]) minutes, P < 0.001; median difference -9, 95% confidence interval -11 to -6). The times to BIS over 80 and to LMA removal were also significantly longer in the propofol group. In addition, the RASS score upon arrival to the PACU differed significantly between the two groups (P = 0.006). Re-sedation in the PACU was observed in 11 (22%) of the patients in the remimazolam group. ConclusionsRemimazolam-based total intravenous anesthesia with flumazenil reversal may be effective in reducing emergence time, but a significant incidence of re-sedation was observed in the PACU. Further studies are needed to determine adequate dose and timing of routine flumazenil use and minimize the risk of re-sedation.

Total intravenous anaesthesia in neonatal surgery: a case series using the Eleveld model

The practice of total intravenous anaesthesia (TIVA) target-controlled infusion of propofol (TCI-propofol) during neonatal surgery was limited by the lack of an appropriate pharmacokinetic-pharmacodynamic model and safety concerns. This is due to the physiological differences between the adult and neonate populations as well as inter-individual pharmacodynamic variation. Eleveld is the latest propofol pharmacokinetic model commercially available and the only model with the neonatal population in its algorithm design. We present a case series of neonates that underwent neonatal surgery under TIVA TCI-propofol utilising the Eleveld pharmacokinetic model. There was no observable clinically significant hypotension intraoperatively. Careful titration of TCI-propofol was necessary for timely emergence and maintaining haemodynamic stability. All neonates were extubated well postoperatively and recovered uneventfully. These demonstrated good and desirable anaesthetic effects using TCI-propofol without undesirable short-term side effects, especially clinically significant hypotension.

Efficacy of intraoperative thoracoscopic intercostal nerve blocks in nonintubated and intubated video-assisted thoracic surgery: A randomized study

The efficacy of thoracoscopic intercostal nerve blocks (TINBs) for noxious stimulation from video-assisted thoracic surgery (VATS) remains unclear. The efficacy of TINBs may also be different between nonintubated VATS (NIVATS) and intubated VATS (IVATS). We aim to compare the efficacy of TINBs on analgesia and sedation for NIVATS and IVATs intraoperatively. Sixty patients randomized to the NIVATS or IVATS group (30 each) received target-controlled propofol and remifentanil infusions, with bispectral index (BIS) maintained at 40-60, and multilevel (T3-T8) TINBs before surgical manipulations. Intraoperative monitoring data, including pulse oximetry, mean arterial pressure (MAP), heart rate, BIS, density spectral arrays (DSAs), and propofol and remifentanil effect-site concentration (Ce) at different time points. A two way ANOVA with post hoc analysis was applied to analyze the differences and interactions of groups and time points. In both groups, DSA monitoring revealed burst suppression and α dropout immediately after the TINBs. The Ce of the propofol infusion had to be reduced within 5min post-TINBs in both NIVATS (p<0.001) and IVATS (p=0.252) groups. The Ce of remifentanil infusion was significantly reduced after TINBs in both groups (p<0.001), and was significantly lower in NIVATS (p<0.001) without group interactions. The surgeon-performed intraoperative multilevel TINBs allow reduced anesthetic and analgesic requirement for VATS. With lower requirement of remifentanil infusion, NIVATS presents a significantly higher risk of hypotension after TINBs. DSA is beneficial for providing real-time data that facilitate the preemptive management, especially for NIVATS.

Administration of Oxycodone Hydrochloride by Target Controlled Infusion - Does the Timing Matter?

Background: In spite of long-term clinical experience with oxycodone hydrochloride/OxyNorm (OH), analgesic concentrations of OH in acute postoperative pain management have not been established. There are assumably different opinions regarding intraoperative timing of OH administration among anaesthesiologists and nurse anaesthetists, hence different practices. Aim: The aim of the study was to determine to which extent intraoperative timing of OH administration affects the need for postoperative OH during target-controlled propofol and remifentanil infusion (TCI) for patients undergoing laparoscopic cholecystectomy. Method: Anesthetic and postoperative journals from 100 patients were included in this retrospective observational study. Patients in category 1 (n = 20) received OH towards the end in addition to the introduction/maintenance of TCI. Patients in category 2 (n = 66) received OH in the beginning/during the maintenance of TCI, but not towards the end. Patients in category 3 (n = 14) received OH only towards the end of TCI. Multiple regression models were used to analyze the data. Result: Mean total postoperative doses of OH and standard deviations (SD) were 4.7 (3.1), 6.9 (5.1) and 4.7 (3.4) mg for patients in categories 1–3, respectively; with an overall p-value for equality of group means of 0.032. Adjusting for age, gender, weight, operating time and medications given during operation did not affect the results substantially (p = 0.012). In total during the per- and postoperative course, observed means (SD) of OH administered were 11.0 (2.9), 12.1 (5.5) and 9.0 (3.5) mg for patients in categories 1- , respectively (p = 0.039). The estimated group differences were only slightly affected by adjusting for patient and operational variables, however the result was no longer statistically significant (p = 0.057). Conclusion: Our retrospective analysis suggested that intraoperative timing of OH administration affects the need for OH postoperatively after laparoscopic cholecystectomy with TCI anaesthesia. To reduce the total amount of OH, it may be beneficial to administer OH only towards the end of anaesthesia.

Accuracy of closed-loop and open-loop propofol delivery systems by bispectral index monitoring in breast surgery patients: a prospective randomized trial

BackgroundThis randomized and controlled prospective study tested the hypothesis that closed-loop Target-Controlled Infusion (TCI) of propofol would be associated with better system performance when compared with open-loop controlled delivery of propofol. MethodsPatients scheduled for elective breast surgery were randomly assigned to two groups: a closed-loop group, in which propofol infusion was performed by a closed-loop TCI system that used the Bispectral Index (BIS) as a feedback parameter to titrate the rate of propofol infusion, and an open-loop group, in which propofol infusion was performed manually and guided by the bispectral index. ResultsA total of 156 patients were recruited for this study (closed-loop group n = 79; open-loop group n = 77). The Global Score (GS) of the closed-loop group was lower than that of the open-loop group (34.3 and 42.2) (p = 0.044). The proportions of time with a BIS value between 40 and 60 were almost identical in the closed-loop group and the open-loop group (68.7 ± 10.6% and 66.7 ± 13.3%) (p = 0.318). The individuals in the closed-loop group consumed more propofol compared with those in the open-loop group (7.20 ± 1.65 mg.kg−1.h−1 vs. 6.03 ± 1.31 mg.kg−1.h−1, p < 0.001). No intraoperative recall, somatic events or adverse events occurred. No significant difference in heart rate was observed between the two groups (p = 0.169). ConclusionThe closed-loop protocol was associated with lower BIS variability and lower out-of-range BIS values, at the cost of a greater consumption of propofol when compared to the open loop group. Register numberChiCTR-INR-17010399.