Study of Two Sedative Protocols for Drug-Induced Sleep Endoscopy: Propofol versus Propofol-Remifentanil Combination, Delivered in Target-Controlled Infusion Mode.

Background and Objectives: Obstructive sleep apnea (OSA) is a prevalent sleep-disordered breathing pathology with significant clinical consequences, including increased cardiovascular risk and cognitive decline. Continuous positive airway pressure (CPAP) is the gold-standard treatment, but alternative strategies are sometimes needed for patients intolerant to CPAP. Drug-induced sleep endoscopy (DISE) is a key diagnostic tool for assessing upper airway obstruction in OSA patients and subsequently tailoring a surgical approach, with sedation protocols playing a crucial role in its efficacy and results accuracy. This study aimed to investigate the effect of adding remifentanil to a propofol target-controlled infusion (TCI) regimen on the sedation parameters and procedural outcomes of DISE. Materials and Methods: The study was conducted at the Central University and Emergency Military Hospital "Dr. Carol Davila" and Ria Clinic in Bucharest between July 2021 and October 2023. Thirty-one patients were enrolled and randomised into two groups: a propofol group (P group, n= 11) and a remifentanil-propofol group (R-P group, n = 20). DISE was performed using standardised protocols, sedative drugs were administered in TCI mode, and data on sedation levels, respiratory and cardiovascular parameters, and procedural incidents were collected. Results: The addition of remifentanil at 1 ng/mL effect-site concentration significantly reduced the effect-site concentration of propofol required for adequate sedation (3.4 ± 0.7 µg/mL in the P group vs. 2.8 ± 0.6 µg/mL in the R-P group, p = 0.035). The time to achieve adequate sedation was also shorter in the R-P group (7.1 ± 2.5 min vs. 9.5 ± 2.7 min, p = 0.017). The incidence of cough, hypoxemia, and cardiovascular events did not significantly differ between the two groups. Conclusions: Adding remifentanil to a propofol TCI regimen for DISE effectively reduces the required propofol effect-site concentration and shortens sedation time without increasing the risk of adverse events. This combination may enhance the safety and efficiency of DISE, offering a promising alternative for patients undergoing this procedure.

Expiratory Velopharyngeal Obstruction: Sleep Endoscopy-Guided Treatment Strategies to Prevent Oral Breathing During Sleep.

OBJECTIVE: Obstructive sleep apnea (OSA) is a prevalent disorder, with oral breathing influencing its severity. Expiratory velopharyngeal obstruction (EVO), observed during drug-induced sleep endoscopy (DISE), may contribute to oral breathing in OSA patients. EVO results in obstruction between the pharynx and nasal cavity during expiration. This study aims to identify factors associated with positive EVO during DISE. STUDY DESIGN: Case series. SETTING: Tertiary Medical Center. METHODS: Seventy-two OSA patients underwent clinical evaluation, polysomnography, and DISE, utilizing interventions like intraoral negative airway pressure (iNAP), mouth closure, and oral appliances (OAs) in supine positions with head rotation. The findings, classified under velopharynx, oropharynx, tongue base, epiglottis, included the presence of EVO. RESULTS: The results demonstrated that interventions including mouth closure and iNAP were associated with increased observation of EVO (43.1% and 34.7%) compared to OA (20.1%). However, head rotation was associated with decreased presence of EVO during DISE compare to supine (26% vs 35.8%). Noticeably, per 1 year increase of age was associated with an increased odds of EVO (odds ratio: 1.03, 95% confidence interval: 1.01-1.06). However, no other baseline characteristics were significantly associated the odds of EVO. CONCLUSION: Our study reveals the effectiveness of head rotation and OA in reducing EVO and improving mouth breathing in OSA patients, offering valuable insights for future treatment strategies.

Design of a pharmacokinetic/pharmacodynamic model for administration of low dose peripheral norepinephrine during general anaesthesia.

AIMS: Intraoperative hypotension is a risk factor for kidney, heart and cognitive postoperative complications. Literature suggests that the use of low-dose peripheral norepinephrine (NOR) reduces organ dysfunction, yet its administration remains unstandardized. In this work we develop a pharmacokinetic (PK)/pharmacodynamic (PD) model of NOR and its effect on mean arterial pressure (MAP). METHODS: From June 2018 to December 2021, we included patients scheduled for elective neurosurgery and requiring vasopressors for intraoperative hypotension management at Lariboisière Hospital, Paris. Low doses of NOR were administered peripherally, and successive arterial blood samples were collected to track its plasmatic concentration. We used a compartmental modelling approach for NOR PK. We developed and compared 2 models for NOR PD on MAP. Model comparison was done using Bayes information criteria. The resulting PK/PD model parameters were fitted over the entire population and linked to age, weight, height and sex. RESULTS: We included 29 patients (age 52 [46-64] years, 69% female). NOR median time to peak effect on MAP was 74 [53-94] s. After bolus administration, MAP increased by 24% (15-31%). A 2-comparment model with depot best captured NOR PK. NOR PD effect on MAP was well represented by both Emax and Windkessel models, with better results for the former. We found that age, height and weight as well as history of smoking and hypertension were correlated with model parameters. CONCLUSION: We have developed a PK/PD model to accurately track norepinephrine plasma concentration and its effect on MAP over time, which could serve for target-controlled infusion.

Is target-controlled infusion better than manual controlled infusion during TIVA for elective neurosurgery? Results of a single-centre pilot study.

INTRODUCTION: Maintaining optimal systemic circulatory parameters is essential to ensure adequate cerebral perfusion (CPP) during neurosurgery, especially when autoregulation is impaired. AIM OF STUDY: To compare two types of total intravenous anaesthesia i.e. target controlled infusion (TCI) and manually controlled infusion (MCI) with propofol and remifentanil in terms of their control of cardiovascular parameters during neurosurgical resection of intracranial pathology. MATERIAL AND METHODS: Patients with supratentorial intracranial pathology were selected for the study. Patients in ASA grades III and IV and those with diseases of the circulatory system were excluded. Patients were randomly divided into two equal groups according to the method of general anaesthesia used i.e. TCI or MCI. During the neurosurgery, the values of mean arterial pressure (MAP), heart rate (HR), bispectral index (BIS) and central venous pressure were monitored and recorded at the designated 14 relevant (i.e. critical from the anaesthetist's and neurosurgeon's points of view) measurement points. RESULTS: Fifty patients (25 TCI and 25 MCI) were enrolled in the study. The groups did not differ with respect to sex, age and BMI, operation time or volume of removed lesions. TCI-anaesthetised patients had better MAP stability at the respective time points. CONCLUSIONS: Due to the greater stability of MAP, which has a direct effect on CPP, TCI appears to be the method of choice in anaesthesia for intracranial surgery.

Target-controlled infusion: A comparative, prospective, observational study of the conventional TCI pump and the novel smartphone-based application iTIVA.

Background and Aims: Empirically adjusted, standard drug doses fail to address interindividual pharmacokinetic and pharmacodynamics variability. Target-controlled infusion (TCI) delivers drugs in calibrated boluses to achieve and maintain a selected target plateau drug level (plasma or effect site). Interactive total intravenous anesthesia (iTIVA™) smartphone software simulates TCI and employs 31 established pharmacokinetic models for 11 different intravenous agents and is coupled with standard volumetric infusion pumps for administering TCI. Material and Methods: This prospective, observational, study investigates the degree of agreement between iTIVA and a conventional TCI pump (CTP) for the volume of propofol infused using the Schnider pharmacokinetic model in adult patients of either sex undergoing oncosurgery lasting 1-3 h under total intravenous anesthesia. Bland-Altman analysis of 124 data pairs from 30 patients provided bias, precision, and limits of agreement between the volumes infused by CTP and iTIVA (V-CTP and V-iTIVA) during specific identical time periods. Spearman's rho and Kendall's tau rank correlation coefficients provided the degree of association between V-CTP and V-iTIVA. Results: Spearman's rho and Kendall's tau were 0.996 and 0.964, respectively. Bias or the mean of differences was -0.02, while the limits of agreement were 0.58 and -0.63, respectively (Bland-Altman plot). The maximum allowed difference of 2 ml was much larger than the 95% confidence intervals for the limits of agreement. The Mountain plot was short tailed (-1.28 to 1.55) and centred over zero (0.01). Conclusion: The volume of propofol infused using TCI pump was similar to that calculated by iTIVA in identical time periods, confirming the clinical applicability of iTIVA.

Analgesia nociception index is an indicator of laparoscopic trocar insertion-induced transient nociceptive stimuli.

Objective: This study aimed to investigate whether analgesia nociception index (ANI) could be an indicator of perioperative pain during laparoscopic trocar insertion. Methods: A total of 280 participants of anesthesia receiving laparoscopic surgery were enrolled. Anesthesia induction and maintenance were performed using the Marsh model for target propofol and the Minto model for remifentanil. Systolic blood pressure (SBP), heart rate (HR), and ANI were recorded at skin incision, the first-, second, the last-trocar insertion, and 5 min after the last trocar insertion. Results: ANI was significantly different among the five groups in the last four time points (all P < 0.05). Pearson's correlation showed that ANI was negatively correlated with SBP (r = -0.114, P = 0.077) and HR (r = -0.247, P < 0.001). The area under the curve of ANI was positively correlated with those of SBP (r = 0.493, P < 0.001) and HR (r = -0.420, P < 0.001). Multivariate logistic regression showed that the ANI was an independent factor associated with intraoperative hemodynamic adverse events only at 5 min after the last trocar insertion. Conclusions: Under general anesthesia, the change in ANI was consistent with changes in the balance between analgesia and nociceptive stimuli. The ANI can reflect the extent of transient pain but had a poor predictive performance for hemodynamic adverse events.

Pharmacokinetics of propofol in severely obese surgical patients.

BACKGROUND: Existing PK models of propofol include sparse data from very obese patients. The aim of this study was to develop a PK model based on standardised surgical conditions and spanning from normal-weight up to, and including, a high number of very obese patients. METHODS: Adult patients scheduled for laparoscopic cholecystectomy or bariatric surgery were studied. Anaesthesia was induced with propofol 2 mg/kg adjusted body weight over 2 min followed by 6 mg/kg/h adjusted body weight over 30 min. For the remainder of the operation anaesthesia was maintained with sevoflurane. Remifentanil was dosed according to clinical need. Eight arterial samples were drawn in a randomised block sampling regimen over a span of 24 h. Time-concentration data were analysed by population PK modelling using non-linear mixed-effects modelling. RESULTS: Four hundred and seventy four serum propofol concentrations were collected from 69 patients aged 19-60 years with a BMI 21.6-67.3 kg/m2. Twenty one patients had a BMI above 50 kg/m2. A 3-compartment PK model was produced wherein three different body weight descriptors and sex were included as covariates in the final model. Total body weight was found to be a covariate for clearance and Q3; lean body weight for V1, V2 and Q2; predicted normal weight for V3 and sex for V1. The fixed allometric exponent of 0.75 applied to all clearance parameters improved the performance of the model. Accuracy and precision were 1.4% and 21.7% respectively in post-hoc performance evaluation. CONCLUSION: We have developed a new PK model of propofol that is suitable for all adult weight classes. Specifically, it is based on data from an unprecedented number of individuals with very high BMI.

Dexmedetomidine target controlled infusion for awake craniotomy†.

A 73-year-old woman underwent an awake craniotomy for the resection of a supratentorial brain tumour. We provided sedation for the surgery using a dexmedetomidine target controlled infusion using the Dyck pharmacokinetic model. Using a target controlled infusion allowed more rapid titration to the desired plasma level compared with a manual infusion, without any unexpected cardiovascular, respiratory or other complications. Rapid titration of sedation during awake craniotomy is desirable, allowing deeper sedation during stimulating parts of the surgery, followed by lighter sedation - or absence of sedation - during cortical mapping. While this can be performed manually, we found utilising the Dyck model in this case simple and quick to use, avoiding the need to manually calculate infusion rates. We believe this is the first report of using a target controlled infusion model to administer dexmedetomidine for awake craniotomy, and suggest it could be considered as an alternative to administering a manual infusion.

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

BACKGROUND: Propofol 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. METHODS: Adult 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. RESULTS: Both 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. CONCLUSIONS: The modified Marsh and Schnider models, initially developed for LCT propofol, remain clinically acceptable for TCI with MCT/LCT propofol. TRIAL REGISTRATION: This 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).

Propofol sedation in routine endoscopy: A case series comparing target controlled infusion vs manually controlled bolus concept.

BACKGROUND: Many studies have addressed safety and effectiveness of non-anaesthesiologist propofol sedation (NAPS) for gastrointestinal (GI) endoscopy Target controlled infusion (TCI) is claimed to provide an optimal sedation regimen by avoiding under- or oversedation. AIM: To assess safety and performance of propofol TCI sedation in comparison with nurse-administered bolus-sedation. METHODS: Fouty-five patients undergoing endoscopy under TCI propofol sedation were prospectively included from November 2016 to May 2017 and compared to 87 patients retrospectively included that underwent endoscopy with NAPS. Patients were matched for age and endoscopic procedure. We recorded time of sedation and endoscopy, dosage of medication and adverse events. RESULTS: There was a significant reduction in dose per time of propofol administered in the TCI group, compared to the NAPS group (8.2 ± 2.7 mg/min vs 9.3 ± 3.4 mg/min; P = 0.046). The time needed to provide adequate sedation levels was slightly but significantly lower in the control group (5.3 ± 2.7 min vs 7.7 ± 3.3 min; P < 0.001), nonetheless the total endoscopy time was similar in both groups. No differences between TCI and bolus-sedation was observed for mean total-dosage of propofol rate as well as adverse events. CONCLUSION: This study indicates that sedation using TCI for GI endoscopy reduces the dose of propofol necessary per minute of endoscopy. This may translate into less adverse events. However, further and randomized trials need to confirm this trend.

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.

Evaluating inter-individual variability captured by the Eleveld pharmacokinetics model.

Inter-individual variability in Pharmacokinetic (PK) and Pharmacodynamic (PD) models significantly affects the accuracy of Target Controlled Infusion and closed-loop control of anesthesia. We hypothesize that the novel Eleveld PK model captures more inter-individual variability relevant to both open-loop and closed-loop control design, resulting in reduced variability in PD models identified using the Eleveld PK model's plasma prediction compared to the Schuttler or Schnider PK model. We used a dataset of propofol infusion rates and Depth of Hypnosis measurements across three demographic groups: elderly, obese, and adult. PD models are identified based on plasma concentration prediction using three PK models (Schuttler, Schnider, and Eleveld). Validation methods are presented to confirm acceptable predictive performance and comparable PK-PD model variability within each demographic group. To test our hypothesis, we compared coefficient variations in step responses for open-loop control and multiplicative uncertainty of PD model sets for closed-loop control. Validated PKPD models using the Schuttler and Schnider PK model showed no significant differences in predictive response and multiplicative uncertainty compared to the Eleveld PK model. The coefficient variations in step responses of PD model sets and the frequency ranges, corresponding to uncertainty below one, were comparable for all three PK models. The comparison of the accumulated coefficient of variation in the step-response and the uncertainty of the PD model sets indicated that the Eleveld PK model does not offer any advantage for the design of open-loop or closed-loop control of anesthesia.

Potential Treatments for Epiglottic Collapse in Obstructive Sleep Apnea: How Modified Drug-Induced Sleep Endoscopy Help?

OBJECTIVE: In patients with obstructive sleep apnea (OSA), epiglottic collapse (EC) constitutes a major factor in the failure of continuous positive airway pressure therapy and uvulopalatopharyngoplasty. This study explored treatments that can improve EC in patients with OSA through drug-induced sleep endoscopy with target-controlled infusion (TCI-DISE). STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary center. METHODS: This study screened 352 OSA patients who underwent TCI-DISE between 2016 and 2022. Fifty-four patients with EC were included in the final analysis. EC severity was assessed multiple times through TCI-DISE with different interventions. RESULTS: The application of these interventions in patients with anteroposterior epiglottic collapse (apEC) led to a significant decrease in apEC severity from total to partial or no obstruction in 60.0% of patients by head rotation, in 53.6% by mouth closure, in 47.4% who received oral appliances (OA), and in 28.0% who received intermittent negative airway pressure (iNAP). With simultaneous head rotation, apEC severity decreased more significantly from total to partial or no obstruction in 77.8% of patients by mouth closure, in 70.3% who received OA, and in 68.0% who received iNAP. Lateral epiglottic collapse (latEC) severity decreased in 53.8% of patients after OA use and in 61.5% of patients with OA use and head rotation. CONCLUSION: This study identified head rotation with mouth closure as the most effective treatment for apEC through TCI-DISE. Patients with latEC had higher weight, apnea-hypopnea index, and body mass index compared with patients with apEC. OA use with head rotation appeared more effective in latEC through TCI-DISE.

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.

Hypotension after Anesthesia Induction: Target-Controlled Infusion Versus Manual Anesthesia Induction of Propofol.

BACKGROUND: Post-induction hypotension frequently occurs and can lead to adverse outcomes. As target-controlled infusion (TCI) obviates the need to calculate the infusion rate manually and helps safer dosing with prompt titration of the drug using complex pharmacokinetic models, the use of TCI may provide a better hemodynamic profile during anesthesia induction. This study aimed to compare TCI versus manual induction and to determine the hemodynamic risk factors for post-induction hypotension. METHODS: A total of 200 ASA grade 1-3 patients, aged 24 to 82 years, were recruited and randomly assigned to the TCI (n = 100) or manual induction groups (n = 100). Hemodynamic parameters were monitored with the pressure-recording analytic method. The propofol dosage was adjusted to keep the Bispectral Index between 40 and 60. RESULTS: Post-induction hypotension was significantly higher in the manual induction group than in the TCI group (34% vs. 13%; p < 0.001, respectively). The propofol induction dose did not differ between the groups (TCI: 155 (135-180) mg; manual: 150 (120-200) mg; p = 0.719), but the induction time was significantly longer in the TCI group (47 (35-60) s vs. 150 (105-220) s; p < 0.001, respectively). In the multivariable Cox regression model, the presence of hypertension, stroke volume index (SVI), cardiac power output (CPO), and anesthesia induction method were found to predict post-induction hypotension (p = 0.032, p = 0.013, p = 0.024, and p = 0.015, respectively). CONCLUSION: TCI induction with propofol provided better hemodynamic stability than manual induction, and the presence of hypertension, a decrease in the pre-induction SVI, and the CPO could predict post-induction hypotension.

Effect-site concentrations of remifentanil for smooth emergence from combined epidural-general anesthesia or general anesthesia in patients using video double-lumen tube: A randomized trial.

Objective: The present study aimed to determine the effect-site concentration of remifentanil of 90% (EC90) for smooth emergence in patients with a video DLT (VDLT) under sevoflurane-maintained general anesthesia and to investigate whether the EC90 was affected by epidural anesthesia. Methods: One hundred and twenty patients who underwent video-assisted thoracic surgery (VATS) were enrolled. Patients received either general anesthesia combined with epidural anesthesia (PEA group, n = 60) or general anesthesia (GA group, n = 60). The primary outcome was the EC90 for smooth emergence in both groups. The secondary outcomes were intraoperative emergence, smooth emergence, recovery, and hemodynamic profiles in both groups. Result: The EC90 values for smooth emergence in patients using VDLT were 3.5 ng/ml (95% confidence interval [CI], 3.3-4.4 ng/ml) in the PEA group and 2.7 ng/ml (95% CI, 2.5-3.2 ng/ml) in the GA group. The total amount of remifentanil infusion during emergency was significantly higher in the PEA group (164.6 ± 47.9 µg) than in the GA group (127.1 ± 30.4 µg) (P < 0.001). The number of patients who experienced hypotension during emergency in the PEA group was higher than that in the GA group (46.7% versus 13.3%, P < 0.001). Conclusion: The EC90 of remifentanil for smooth emergence in patients with VDLT under general anesthesia combined with epidural anesthesia (3.5 ng/ml) was higher than that under general anesthesia (2.7 ng/ml). Trial registration: Chinese Clinical Trial Registry, ChiCTR2100054230.

The requirement of propofol for induction of anesthesia in patients with traumatic brain injury determined using bilateral bispectral index and target controlled infusion - An observational cohort study.

Background and Aims: Patients with traumatic brain injury (TBI) frequently require emergency surgery. There is a paucity of literature with regard to anesthetic requirements in these patients. The aim of the study was to compare the dose of propofol required for induction of anesthesia in patients with different grades of TBI. Material and Methods: This prospective, observational study included patients with mild, moderate, and severe grades of TBI undergoing emergency surgery within 48 h of injury. Bispectral Index (BIS) values were recorded using a bilateral BIS sensor. Anesthesia was induced with a target controlled infusion (TCI) pump. Once BIS reached 40, plasma (Cp) and effect-site (Ce) concentration and total dose of propofol required were noted from the TCI pump. Results: Of the 96 patients recruited, 27, 36, and 33 patients belonged to mild, moderate, and severe TBI (sTBI) groups, respectively. The Ce of propofol in mild, moderate, and sTBI groups was 6 ± 0.9, 5.82 ± 0.98, and 4.48 ± 1.5 µg/mL (P < 0.001), and the dose of propofol required was 1.9 ± 0.2, 1.8 ± 0.4, 1.41 ± 0.5 mg/kg, respectively (P < 0.001). Baseline BIS on the injured side was 80 ± 7.8, 71 ± 9.4, 55 ± 11.6, and on the uninjured side was 89 ± 5.5, 81 ± 8.4, and 65 ± 12 in mild, moderate, and sTBI groups, respectively. Conclusions: The requirement of propofol was reduced in patients with sTBI. The dose of propofol required for induction of anesthesia as determined using Ce was significantly lower only between sTBI and mild TBI and not between patients with sTBI and moderate TBI or between mild and moderate head injury. BIS values were significantly different between the groups (highest in mild TBI and lowest in sTBI) and between normal and injured sides within each group.

Does Propofol Effect Site (Brain) Concentration Predicted by Target-Controlled Infusion Correlate with Propofol Measured in the Brain? An Exploratory Study in Neurosurgical Patients.

BACKGROUND: Total intravenous anesthesia with propofol can be administered by target-controlled infusion pumps, which work on the principles of pharmacokinetic modeling. While designing this model, neurosurgical patients were excluded as the surgical site and drug action site remained the same (brain). Whether the predicted set propofol concentration and the actual brain site concentration correlate, especially in neurosurgical patients with impaired blood-brain barrier (BBB), is still unknown. In this study we compared the set propofol effect-site concentration in the target-controlled infusion pump with actual brain concentration measured by sampling the cerebrospinal fluid (CSF). METHODS: Consecutive adult neurosurgical patients requiring propofol infusion intraoperatively were recruited. Blood and CSF samples were collected simultaneously when patients received propofol infusion at 2 different target effect-site concentrations-2 and 4 ug/mL. To study BBB integrity, CSF-to-blood albumin ratio and imaging findings were compared. The propofol level in the CSF was compared with set concentration using the Wilcoxon signed-rank test. RESULTS: Fifty patients were recruited, and the data were analyzed from 43 patients. There was no correlation between propofol concentration set in TCI and propofol concentration measured in blood and CSF. Though imaging findings were suggestive of BBB disruption in 37/43 patients, the mean (±standard deviation) CSF-to-serum albumin ratio was 0.0028 ± 0.002, suggesting intact BBB integrity (ratio >0.3 was considered as disrupted BBB). CONCLUSIONS: CSF propofol level did not correlate with set concentration in spite of acceptable clinical anesthetic effect. Also, the CSF-to-blood albumin measurement did not provide information on the BBB integrity.