Plasma Propofol Concentrations Research Articles

Electroencephalographic indices for clinical endpoints during propofol anesthesia in infants-an early phase propofol biomarker-finding study.

Unlike expired sevoflurane concentration, propofol lacks a biomarker for its brain effect site concentration (Ce), leading to dosing imprecision particularly in infants. Electroencephalography (EEG) monitoring can serve as a biomarker for propofol Ce, yet proprietary EEG indices are not validated in infants. We evaluated spectral edge frequency (SEF95) as a propofol anesthesia biomarker in infants. We hypothesized that the SEF95 targets will vary for different clinical stimuli and an inverse relationship existed between SEF95 and propofol plasma concentration. This prospective study enrolled infants (3-12 months) to determine the SEF95 ranges for three clinical endpoints of anesthesia (consciousness-pacifier placement, pain-electrical nerve stimulation, and intubation-laryngoscopy) and correlation between SEF95 and propofol plasma concentration at steady state. Dixon's Up-Down method was used to determine target SEF95 for each clinical endpoint. Centered isotonic regression determined the dose-response function of SEF95 where 50% and 90% of infants (ED50 and ED90) did not respond to the clinical endpoint. Linear mixed-effect model determined the association of propofol plasma concentration and SEF95. Of 49 enrolled infants, 44 evaluable (90%) showed distinct SEF95 for endpoints: pacifier (ED50 21.4Hz, ED90 19.3Hz), electrical stimulation (ED50 12.6Hz, ED90 10.4Hz), and laryngoscopy (ED50 8.5Hz, ED90 5.2Hz). From propofol 0.5-6 μg/ml, a 1 Hz SEF95 increase was linearly correlated to a 0.24 (95% CI: 0.19 - 0.29, p<0.001) μg/mL decrease in plasma propofol concentration (marginal R 2 = 0.55). SEF95 can be a biomarker for propofol anesthesia depth in infants, potentially improving dosing accuracy and utilization of propofol anesthesia in this population.

Development of extended pharmacokinetic models for propofol based on measured blood and brain concentrations

Propofol’s pharmacokinetics have been extensively studied using human blood samples and applied to target-controlled infusion systems; however, information on its concentration in the brain remains scarce. Therefore, this study aimed to simultaneously measure propofol plasma and brain concentrations in patients who underwent awake craniotomy and establish new pharmacokinetic model. Fifty-seven patients with brain tumors or brain lesions who underwent awake craniotomy were sequentially assigned to model-building and validating groups. Plasma and brain (lobectomy or uncapping margins) samples were collected at five time-points. The concentration of propofol was measured using high-performance liquid chromatography. Population pharmacokinetic analysis was conducted through a nonlinear mixed-effects modeling program using a first-order conditional estimation method with interactions. Propofol’s brain concentrations were higher than its plasma concentrations. The measured brain concentrations were higher than the effect site concentrations using the previous models. Extended models were constructed based on measured concentrations by incorporating the brain/plasma partition coefficient (Kp value). Extended models showed good predictive accuracy for brain concentrations in the validating group. The Kp value functioned as a factor explaining retention in the brain. Our new pharmacokinetic models and Kp value can predict propofol’s brain and plasma concentrations, contributing to safer and more stable anesthesia.

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).

Exhaled breath is found to be better than blood samples for determining propofol concentrations in the brain tissues of rats

The correlation between propofol concentration in exhaled breath (C E) and plasma (C P) has been well-established, but its applicability for estimating the concentration in brain tissues (C B) remains unknown. Given the impracticality of directly sampling human brain tissues, rats are commonly used as a pharmacokinetic model due to their similar drug-metabolizing processes to humans. In this study, we measured C E, C P, and C B in mechanically ventilated rats injected with propofol. Exhaled breath samples from the rats were collected every 20 s and analyzed using our team’s developed vacuum ultraviolet time-of-flight mass spectrometry. Additionally, femoral artery blood samples and brain tissue samples at different time points were collected and measured using high-performance liquid chromatography mass spectrometry. The results demonstrated that propofol concentration in exhaled breath exhibited stronger correlations with that in brain tissues compared to plasma levels, suggesting its potential suitability for reflecting anesthetic action sites’ concentrations and anesthesia titration. Our study provides valuable animal data supporting future clinical applications.

Altitude effect on Propofol Pharmacokinetics in Rats.

Propofol is an intravenous agent for clinical anesthesia. As the influence of the hypobaric- hypoxic environment (Qinghai-Tibetan region, altitude: 2800-4300 m, PaO2: 15.1-12.4 kPa) on the metabolism of Propofol is complex, the research results on the metabolic characteristics of Propofol in high-altitude areas remain unclear. This study aimed to investigate the pharmacokinetic characteristics of Propofol in a high-altitude hypoxic environment using animal experiments. Rats were randomly divided into three groups: high-altitude, medium-altitude, and plain groups. The time of disappearance and recovery of the rat righting reflex was recorded as the time of anesthesia induction and awakening, respectively. The plasma concentration of Propofol was determined by gas chromatography- mass spectrometry. A pharmacokinetic analysis software was used to analyze the blood-drug concentrations and obtain the pharmacokinetic parameters. We observed that when Propofol anesthetizes rats, the anesthesia induction time was shortened, and the recovery time was prolonged with increased altitude. Compared with the plain group, the clearance of Propofol decreased, whereas the half-life, area under the concentration-time curve, peak plasma concentration, and average residence time extension increased. The pharmacokinetic characteristics of Propofol are significantly altered in high-altitude hypoxic environments.

Effect of acute normovolemic hemodilution on anesthetic effect, plasma concentration, and recovery quality in elderly patients undergoing spinal surgery

ObjectiveTo explore the effect of acute normovolemic hemodilution (ANH) on the anesthetic effect, plasma concentration, and postoperative recovery quality in elderly patients undergoing spinal surgery.MethodsA total of 60 cases of elderly patients aged 65 to 75 years who underwent elective multilevel spinal surgery were assigned randomly into the ANH group (n = 30) and control group (n = 30). Hemodynamic and blood gas analysis indexes were observed and recorded before ANH (T1), after ANH (T2), immediately after postoperative autologous blood transfusion (T3), 10 min (T4), 20 min (T5), 30 min (T6), 40 min (T7), and 50 min (T8) after the transfusion, and at the end of the transfusion (i.e., 60 min; T9). At T3 ~ 9, bispectral index (BIS) and train-of-four (TOF) stimulation were recorded and the plasma propofol/cisatracurium concentration was determined. The extubation time and recovery quality were recorded.ResultsThe ANH group presented a lower MAP value and a higher SVV value at T2, and shorter extubation and orientation recovery time (P < 0.05) compared with the control group. BIS values at T8 and T9 were lower in the ANH group than those in the control group (P < 0.05). TOF values at T7 ~ 9 were lower in the ANH group than those in the control group (P < 0.05). There were no statistically significant differences in the postoperative plasma concentrations of propofol and cisatracurium between the groups (P > 0.05).ConclusionDuring orthopedic surgery, the plasma concentration of elderly patients is increased after autologous blood transfusion of ANH, and the depth of anesthesia and muscle relaxant effect are strengthened, thus leading to delayed recovery of respiratory function and extubation.

Rocuronium-neuromuscular blockade does not influence the patient state index in anesthetized dogs.

To evaluate the effects of rocuronium and sugammadex on the patient state index (PSI) in dogs anesthetized with propofol. 6 intact healthy male Beagles. Anesthesia was induced with and maintained on a propofol infusion. The estimated plasma propofol concentration (ePC) was recorded. Baseline PSI and train-of-four ratio (TOFR) readings were collected for 2 minutes in stable general anesthesia. Neuromuscular blockade (NMB) was induced with 0.6 mg/kg, IV, rocuronium, and full NMB was confirmed with a TOFR of 0. After 5 minutes, the neuromuscular function was restored with 4 mg/kg sugammadex, IV (reversal), and monitored for 5 minutes. Throughout the data collection, ePC, PSI, and TOFR were recorded every 15 seconds and compared with mixed-effect ANOVA. Baseline ePC, PSI, and TOFR were 3.63 ± 0.38, 41 ± 6, and 0.97 ± 0.08 µg/mL, respectively. There was no difference between the baseline of ePC and PSI from NMB or reversal. Compared to the baseline, the TOFR decreased to 0 with NMB (P < .001) and returned to 0.96 ± 0.08 (P = .721) on reversal. After 5 minutes, sugammadex fully reversed 5 out of 6 dogs to TOFR > 0.90 and partially reversed 1 animal to TOFR = 0.80. There was no evidence that NMB with rocuronium and sugammadex-induced reversal interfered with PSI readings under steady-state total intravenous anesthesia with propofol. Further evaluation of PSI is warranted to assess its utility in a clinical population to detect changes in levels of consciousness during NMB.

Relationship between decrement time and recovery time in pediatric total intravenous anesthesia with propofol and remifentanil.

Propofol target-controlled infusion is now used in many countries for the administration of total intravenous anesthesia (TIVA) and uses population pharmacokinetic data incorporated into the target-controlled infusion pump to administer a dose which will achieve a target concentration selected by the practitioner. Modern target-controlled infusion pumps can include an estimate of how long it will take for the plasma propofol concentration to fall to a value programmed into the pump, once the propofol infusion is stopped. This is known as decrement time. Many users consider decrement time to be equivalent to recovery time for the patient, despite the several assumptions that makes. To determine if the decrement time estimated by the target-controlled infusion pumps at the end of anesthesia could be reliably used to predict recovery time for individual patients. Target-controlled infusion pumps at Birmingham Children's Hospital are programmed with a propofol decrement concentration of 1.5 μg.mL-1 . Patients for a variety of surgical procedures were anesthetised with propofol-remifentanil TIVA. Eye opening was used as a surrogate of recovery time. Data were analyzed using median absolute deviation, Mann-Whitney U test, and linear regression to see if there was any correlation with decrement time and recovery time, total dose of propofol administered, duration of anesthesia and patient age. A total of 55 patients were audited. Median age was 7.2 years (range 0.9-15.9), and median weight was 26 kg (range 8.5-77). Median decrement time was 11.8 min (IQR 8.3-21), while median recovery time was 15 min (IQR 9-20). Recovery time was the same as decrement time in 2% of patients, less than in 40% of patients and more in 58% of patients. Two thirds of patients opened eyes at an estimated plasma propofol concentration between 1.2 and 1.8 μg.mL-1 . The median absolute deviation for the difference between decrement time and recovery time was 5.7 min, from a median of 1 min. Analysis demonstrated there was no statistical correlation between decrement time to 1.5 μg.mL-1 and recovery time, age, total propofol dose administered, or duration of anesthesia, for individual patients. There was variation between decrement time to 1.5 μg.mL-1 and recovery time of over 5 min in nearly half of patients. Decrement time to 1.5 μg.mL-1 must be used with caution when trying to predict recovery time for individual patients following TIVA.

Pharmacokinetics of intravenous propofol in southern white rhinoceros (Ceratotherium simum simum) after intramuscular etorphine-butorphanol-medetomidine-azaperone.

To determine the pharmacokinetics of a single bolus of intravenous (IV) propofol after intramuscular administration of etorphine, butorphanol, medetomidine, and azaperone in 5 southern white rhinoceros to facilitate reproductive evaluations. A specific consideration was whether propofol would facilitate timely orotracheal intubation. 5 adult, female, zoo-maintained southern white rhinoceros. Rhinoceros were administered etorphine (0.002 mg/kg), butorphanol (0.02 to 0.026 mg/kg), medetomidine (0.023 to 0.025 mg/kg), and azaperone (0.014 to 0.017 mg/kg) intramuscularly (IM) prior to an IV dose of propofol (0.5 mg/kg). Physiologic parameters (heart rate, blood pressure, respiratory rate, and capnography), timed parameters (eg, time to initial effects and intubation), and quality of induction and intubation were recorded following drug administration. Venous blood was collected for analysis of plasma propofol concentrations using liquid chromatography-tandem mass spectrometry at various time points after propofol administration. All animals were approachable following IM drug administration, and orotracheal intubation was achieved at 9.8 ± 2.0 minutes (mean ±SD) following propofol administration. The mean clearance for propofol was 14.2 ± 7.7 ml/min/kg, the mean terminal half-life was 82.4 ± 74.4 minutes, and the maximum concentration occurred at 2.8 ± 2.9 minutes. Two of 5 rhinoceros experienced apnea after propofol administration. Initial hypertension, which improved without intervention, was observed. This study provides pharmacokinetic data and insight into the effects of propofol in rhinoceros anesthetized using etorphine, butorphanol, medetomidine, and azaperone. While apnea was observed in 2 rhinoceros, propofol administration allowed for rapid control of the airway and facilitated oxygen administration and ventilatory support.

The effect of preoperative sleep quality on the target plasma concentration of propofol and postoperative sleep in patients undergoing painless gastroscopy

BackgroundThis study aims to investigate the effect of preoperative sleep quality on the target plasma concentration of propofol and postoperative sleep in patients undergoing painless gastroscopy.MethodsNinety-three outpatients aged 45 to 64 years with body mass index (BMI) of 18.5–30 kg/m2 and ASA grades of I or II, who underwent painless gastroscopy, were selected. All patients were evaluated by the Athens insomnia scale (AIS) before the painless gastroscopy. The patients were divided into two groups according to the AIS score evaluated before painless gastroscopy: normal sleep group (group N, AIS score < 4 points, 47 cases) and sleep disorder group (group D, AIS score > 6 points, 46 cases). The target-controlled infusion (TCI) of propofol (Marsh model) was used for general anesthesia, the Bispectral index (BIS) was used to monitor the depth of anesthesia, and the BIS was maintained between 50 and 65 during the painless gastroscopy. The target plasma concentration (Cp) of propofol was recorded when the patient’s eyelash reflex disappeared (T1), before the painless gastroscopy (T2), at the time of advancing the gastroscope (T3) and during the painless gastroscopy (T4), and the infusion rate per body surface area of propofol was calculated. The patient’s AIS score was followed up by telephone at day 1, day 3, 1 week, and 1 month after the painless gastroscopy to assess the postoperative sleep of the patient. The occurrence of adverse reactions during the painless gastroscopy was recorded; the patient’s satisfaction and the endoscopist’s satisfaction with the anesthesia effect were compared between the two groups.ResultsCompared with group N, the Cp at each time point and the infusion rate per body surface area of propofol in group D was increased significantly (P < 0.05); compared with the AIS scores before the painless gastroscopy, the AIS scores of the two groups of patients were significantly increased day 1 after the painless gastroscopy (P < 0.05); there were no significant differences in the AIS scores of the two groups at day 3, 1 week, and 1 month after the painless gastroscopy (P > 0.05). There were no statistically significant differences in the occurrence of adverse reactions and the patient’s satisfaction and the endoscopist’s satisfaction with the anesthesia effect between the two groups (P > 0.05).ConclusionThe preoperative sleep disturbance will increase the Cp and the infusion rate per body surface area of propofol in patients undergoing painless gastroscopy. Propofol only affects the patients’ sleep for day 1 after the painless gastroscopy.Trial registrationChinese Clinical Trial Registry (ChiCTR2100045332) on 12/04/2021.

Clinical observation of different dosages of dexmedetomidine combined with a target-controlled infusion of propofol in hysteroscopic submucosal myomectomy.

This study aimed to explore the clinical effects of different dosages of dexmedetomidine (Dex) combined with a target-controlled infusion of propofol in hysteroscopic submucosal myomectomy. Ninety patients who underwent hysteroscopic submucosal myomectomy between September 2021 and March 2022 were enrolled and randomly divided into three groups, with 30 patients in each group. Patients in Groups A, B, and C received injections of 0.25, 0.5, or 0.75 µg/kg of Dex, respectively, by intravenous pump over 10 min. After this time, a maintenance dosage of 0.5 µg/kg/h was administered by intravenous infusion until the end of the surgery. Anesthesia was induced using 1.5 mg/kg of propofol and 0.3 µg/kg of sufentanil that were introduced through a laryngeal mask. The plasma concentration of propofol was maintained at 3 µg/ml by target-controlled infusion until the end of the surgery. The mean arterial pressure (MAP), heart rate (HR), and electroencephalographic bispectral index (BIS) were observed when the patient entered the operating room (T0), after catheter indwelling for anesthesia (T1), at the time of cervical dilation (T2), at the time of hysteroscopic surgery (T3), and at the end of the surgery (T4) in all three groups. The total dosage of propofol for induction and maintenance, anesthesia awakening time, orientation recovery time, Visual Analog Scale (VAS) score of the post-awakening uterine contraction pain, and adverse reactions were recorded. The intraoperative reductions of MAP and HR in patients were significant in Group C when compared with those in Groups A and B (P < 0.05), and BIS was significantly lower in Group C at T2 and T3 when compared with the baseline measurement at T0 (P < 0.05). The dosage of propofol was significantly higher for Group A than for Groups B and C (P < 0.05). The anesthesia awakening time and orientation recovery time were significantly longer for patients in Group C when compared with patients in Groups A and B (P < 0.05). Within 5-30 min after awakening, the VAS scores in Groups B and C were significantly lower than those for Group A (P < 0.05). The incidence of adverse reactions in Group B was significantly less than that for Groups A and C (P < 0.05). The continuous pumping of 0.5 µg/kg of Dex combined with a target-controlled infusion of propofol in hysteroscopic submucosal myomectomy resulted in positive anesthetic and analgesia effects and fewer adverse reactions. It therefore has high clinical significance.

Population pharmacokinetic and pharmacodynamic model of propofol externally validated in Korean elderly subjects.

The Eleveld propofol pharmacokinetic (PK) model, which was developed based on a broad range of populations, showed greater bias (- 27%) in elderly subjects in a previous validation study conducted by Vellinga and colleagues. We aimed to develop and externally validate a new PK-pharmacodynamic (PK-PD) model of propofol for elderly subjects. A population PK-PD model was constructed using propofol plasma concentrations and bispectral index (BIS) values that were obtained from 31 subjects aged 65years older in previously published phase I studies. The predictive performance of the newly-developed PK-PD model (Choi model) was assessed in a separate Korean elderly population and compared with that of the Eleveld model. A three-compartment mammillary model using an allometric expression and a sigmoid Emax model well-described the time courses of propofol concentrations and BIS values. The V1, V2, V3, Cl, Q1, Q2, E0, Emax, Ce50, γ, and ke0 of a 60-kg subject were 8.36, 58.0, 650 L, 1.26, 0.917, 0.669 L/min, 92.1, 18.7, 2.21μg/mL, 2.89, and 0.138 /min, respectively. In the Choi model and Eleveld model, pooled biases (95% CI) of the propofol concentration were 7.78 (3.09-12.49) and 16.70 (9.46-23.93) and pooled inaccuracies were 22.84 (18.87-26.81) and 24.85 (18.07-31.63), respectively. The Choi PK model was less biased than the Eleveld PK model in Korean elderly subjects (age range: 65.0-79.0yr; weight range: 45.0-75.3kg). Our results suggest that the Choi PK model, particularly, is applicable to target-controlled infusion in non-obese Korean elderly subjects.

The Preventive Effect of Transcutaneous Electrical Acupoint Stimulation on Postoperative Delirium in Elderly Patients with Time Factors: A Randomized Trial

Objectives: There is currently no exact and effective treatment for postoperative delirium (POD). The purpose of this study was to observe the effect of transcutaneous electrical acupoint stimulation (TEAS) before surgery and during surgery in elderly patients with POD. Materials and Methods: A total of 90 patients were randomly divided into three groups: a preoperative TEAS group (group E1), an intraoperative TEAS group (group E2), and a control group (group C). In group E1, TEAS was applied at the Shenting, Baihui, bilateral Neiguan, and Hegu points for 30 min 1 day before surgery and before the induction of anesthesia. In group E2, TEAS was applied during surgery. In group C, electrodes were applied to the points just cited, but no electric stimulation was administered. The incidence of delirium was assessed within 5 days after surgery, and the plasma concentration of propofol at bispectral index (BIS) = 50 was recorded. Blood samples were collected to measure neuron-specific enolation (NSE), tumor necrosis factor-α (TNF-α), and interleukin (IL)-1β 1 day before surgery and 1 and 5 days after surgery. Results: The incidence of delirium in group E1 was decreased in comparison with group C and group E1 (both p < 0.05). The propofol plasma concentration at BIS = 50 in group E1 was also decreased in comparison with group C and group E2 (both p < 0.05). Compared with group C, the concentrations of NSE, TNF-α, and IL-1β in plasma were decreased in group E1 and group E2 1 and 5 days after surgery (both p < 0.05), and the concentrations of NSE and IL-1β in plasma in group E1 were decreased 1 and 5 days after surgery in comparison with group E2. Conclusion: The TEAS can reduce the dosage of propofol required during surgery and the occurrence of delirium after surgery. Its mechanism may be related to inhibiting inflammation response and alleviating brain injury. Compared with intraoperative application, the effect of preconditioning with TEAS before surgery is better. Clinical Trial Registration: ChiCTR-INR-17012501. Date of registration: August 29, 2017.

The SedUROscopy Project: Sedation conducted by nurses supervised by the anaesthetist at a Lithotripsy and Endourology Unit in Spain

AbstractThe increased demand for simple, yet invasive and sometimes painful urological procedures in our unit, coupled with a relative lack of anaesthetists, prompted the search for appropriate safe alternatives to current practice, so to enable efficient, satisfactory, and safe interventions for patients. In response to this need, the Four‐Phase SedUROscopy Project has been developed, a plan in which identified Urology nurses take on a more active role in the anaesthetic procedure at the Lithotripsy and Endourology Unit. The aim of the project is to establish a specific care model that ensures the safety and satisfaction of patients undergoing minor endourological procedures, whilst also optimizing resources and empowering nurses and their practice. The SedUROscopy Project started with the training of five nurses (Phase 1: Theory). Subsequently, one of the nurses then began her practical course (Phase 2: up to 200 sedations). She carried out 90 sedations in patients in preparation for minor procedures. Remifentanil and Propofol were administrated using Target Controlled Infusion (TCI) pumps. The initial target plasma propofol concentration was 2 μg/ml, and the remifentanil one was 1 μg/ml. Doses were adjusted to achieve the right sedation. ECG, pulse oximetry, non‐invasive blood pressure and end‐tidal CO2 were monitored. Up to 10 different procedures were carried out. There were 37 oxygen desaturation events (41%), however they were solved with chin lift manoeuvres and mandibular subluxation (8.88%), use of Guedel tube (21.1%) and manual ventilation (11.1%). The intervention of the anaesthetist was not required in any of the cases, and all the patients involved in the sample were discharged the same day, free of any anaesthetic problem at all (100%). As the surveys indicated, the levels of satisfaction expressed by both patient and staff performing the technique were high (98%). The sedation performed by trained urology nurses using TCI has resulted in a provision of safe and effective procedures. Likewise, the patients' satisfaction was ensured. In conclusion, this model represents an optimal use of resources: not only because just a single anaesthetist could supervise two operation theatres, but also nurses could control the patients pain due to their knowledge of endourological procedures and the sedation technique.

Evaluation of the anesthetic depth and bispectral index during propofol sequential target-controlled infusion in dogs.

Background and Aim:The use of anesthetic infusions based on pharmacokinetic values associated with anesthetic plan and bispectral index in dogs have not been well-documented in the literature. This study aimed to evaluate the bispectral index (BIS) change based on pre-propofol and establish clinical anesthetic depth changes during propofol sequential target-controlled infusion (STCI) in dogs with a plasma target of 5 μg/mL.Materials and Methods:Twenty healthy male dogs aged 1-3 years and weighing 9.8-44 kg were recruited. These dogs were pre-medicated intramuscularly with methadone (0.2 mg/kg) and acepromazine (0.03 mg/kg). After 30 min, propofol anesthetic induction and maintenance were initiated using STCI according to dog pharmacokinetic (PK) parameters. Subsequently, the target plasma concentration of propofol was set at 5 μg/mL for both anesthetic induction and the 120 min maintenance. Then, TivaTrainer v.9.1 software was used to calculate anesthetic infusion rates in a TCI plasmatic concentration mode using the PKs model optimized by covariates for propofol TCI in dogs. The BIS value was recorded every 5 min from the beginning of induction until the end of anesthesia. Finally, analysis of variance was performed on numerical data using the Friedman test, followed by the Bonferroni adjustment (p<0.05).Results:A statistical difference was observed between the baseline BIS value (T0), with a median value of 84.5 (81-97), and BIS after every 15 min (T15) of inducing anesthesia. Surgical anesthetic depth was also reached in 18 of 20 dogs after 10 min of infusion and in all dogs after 20 min, with a median BIS value of 72 (53-89) at the time of surgical anesthesia depth. Results also showed no BIS variation (p<0.05) between anesthetic moments after anesthetic induction with a substantial amplitude of BIS in the surgical anesthetic depth. Moreover, the maximum depth of anesthesia in all dogs by clinical evaluation was reached after 20 min of anesthesia and then remained stable throughout the anesthetic period.Conclusion:This study suggested that most dogs (90%) attained a surgical depth of anesthesia within 15 min of STCI onset, with a plasma target of 5 μg/mL and no change in anesthetic depth throughout the period anesthesia lasted. Furthermore, median BIS values remained high even after dogs reached the surgical depth of anesthesia, indicating that the comparison of BIS values of dogs and humans should not be considered for classifying anesthetic and hypnotic depths in dogs.

Online exhaled propofol monitoring in normal-weight and obese surgical patients.

BackgroundIon mobility spectrometry (IMS) allows for online quantification of exhaled propofol concentrations. We aimed to validate a bedside online IMS device, the Edmon®, for predicting plasma concentrations of propofol in normal‐weight and obese patients.MethodsPatients with body mass index (BMI) >20 kg/m2 scheduled for laparoscopic cholecystectomy or bariatric surgery were recruited. Exhaled propofol concentrations (CA), arterial plasma propofol concentrations (CP) and bispectral index (BIS) values were collected during target‐controlled infusion (TCI) anaesthesia. Generalised estimation equation (GEE) was applied to all samples and stable‐phase samples at different delays for best fit between CP and CA. BMI was evaluated as covariate. BIS and exhaled propofol correlations were also assessed with GEE.ResultsA total of 29 patients (BMI 20.3–53.7) were included. A maximal R 2 of 0.58 was found during stable concentrations with 5 min delay of CA to CP; the intercept a = −0.69 (95% CI −1.7, 0.3) and slope b = 0.87 (95% CI 0.7, 1.1). BMI was found to be a non‐significant covariate. The median absolute performance error predicting plasma propofol concentrations was 13.4%. At a CA of 5 ppb, the model predicts a CP of 3.6 μg/ml (95% CI ±1.4). There was a maximal negative correlation of R 2 = 0.44 at 2‐min delay from CA to BIS.ConclusionsOnline monitoring of exhaled propofol concentrations is clinically feasible in normal‐weight and obese patients. With a 5‐min delay, our model outperforms the Marsh plasma TCI model in a post hoc analysis. Modest correlation with plasma concentrations makes the clinical usefulness questionable.

Intraoperative hand strength as an indicator of consciousness during awake craniotomy: a prospective, observational study

Awake craniotomy enables mapping and monitoring of brain functions. For successful procedures, rapid awakening and the precise evaluation of consciousness are required. A prospective, observational study conducted to test whether intraoperative hand strength could be a sensitive indicator of consciousness during the awake phase of awake craniotomy. Twenty-three patients who underwent awake craniotomy were included. Subtle changes of the level of consciousness were assessed by the Japan Coma Scale (JCS). The associations of hand strength on the unaffected side with the predicted plasma concentration (Cp) of propofol, the bispectral index (BIS), and the JCS were analyzed. Hand strength relative to the preoperative maximum hand strength on the unaffected side showed significant correlations with the Cp of propofol (ρ = − 0.219, p = 0.007), the BIS (ρ = 0.259, p = 0.002), and the JCS (τ = − 0.508, p = 0.001). Receiver operating characteristic curve analysis for discriminating JCS 0–1 and JCS ≥ 2 demonstrated that the area under the curve was 0.76 for hand strength, 0.78 for Cp of propofol, and 0.66 for BIS. With a cutoff value of 75% for hand strength, the sensitivity was 0.76, and the specificity was 0.67. These data demonstrated that hand strength is a useful indicator for assessing the intraoperative level of consciousness during awake craniotomy.

To ascertain the plasma concentration of propofol to achieve bispectral index-guided sedation using a target-controlled infusion in patients undergoing elective surgeries under neuraxial anaesthesia.

Sedation improves patient satisfaction, comfort and acceptance of regional anaesthesia. Propofol using bispectral index (BIS)/target-controlled infusion (TCI) system can be an optimal method of sedation, as it combines objective measurement of sedation using BIS along with maintenance of a steady plasma concentration of propofol with the TCI device. The aim of this study was to ascertain the dose and safety of propofol using BIS/TCI system for sedation in patients undergoing surgeries under neuraxial anaesthesia. One hundred and seven adult patients, undergoing elective surgical procedures under spinal or combined spinal epidural anaesthesia, were recruited. Propofol infusion was started with TCI at an initial target plasma concentration (Cpt) of 1.2 μg/mL, and after equilibration between Cpt and effect site concentration (Ce), propofol was then adjusted in increments and/or decrements of 0.2 μg/mL in order to maintain a BIS value between 60 and 80. The average time to reach BIS = 80 after starting infusion was 7.32 ± 3.13 minutes. The objective was to calculate mean Cpt value maintaining BIS between 60 and 80 and to observe recovery time and complications. Mean Cpt value was 1.13 ± 0.17 mg/mL with 95% confidence interval (1.10-1.16 μg/mL). In 85% of patients, a BIS value of 60-80 was maintained at Cpt ≤ 1.2 μg/mL. No patient had severe complications requiring stoppage of infusion. Propofol sedation using BIS/TCI system can provide safe and convenient sedation during neuraxial anaesthesia at very low plasma concentration, Cpt ≤ 1.2 μg/mL in majority of patients. There were no periprocedural complications, and recovery was rapid.

Intravenous propofol, ketamine (ketofol) and rocuronium after sevoflurane induction provides long lasting anesthesia in ventilated rats.

Rats are commonly used animals for laboratory experiments and many experiments require general anesthesia. However, the lack of published and reproducible intravenous anesthesia protocols for rats results in unnecessary animal use to establish new anesthesia techniques across institutions. We therefore developed an anesthesia protocol with propofol, ketamine, and rocuronium for mechanically ventilated rats, and evaluated vital parameters and plasma concentrations. 15 male Sprague-Dawley rats underwent inhalation induction with sevoflurane and tracheal, venous and arterial cannulation. After established venous access, sevoflurane was substituted by propofol and ketamine (ketofol). Rocuronium was added under mechanical ventilation for 7 h. Drug dosages were stepwise reduced to prevent accumulation. All animals survived the observation period and showed adequate depth of anesthesia. Mean arterial pressure and heart rate remained within normal ranges. Median propofol plasma concentrations remained stable: 1, 4, 7 h: 2.0 (interquartile range (IQR): 1.8–2.2), 2.1 (1.8–2.2), 1.8 (1.6–2.1) µg/ml, whereas median ketamine concentrations slightly differed after 7 h compared to 1 h: 1, 4, 7 h: 3.7 (IQR: 3.5–4.5), 3.8 (3.3–4.1), 3.8 (3.0–4.1) µg/ml. Median rocuronium plasma concentrations were lower after 4 and 7 h compared to 1 h: 1, 4, 7 h: 3.9 (IQR: 3.5–4.9), 3.2 (2.7–3.3), 3.0 (2.4–3.4) µg/ml. Our anesthesia protocol provides stable and reliable anesthesia in mechanically ventilated rats for several hours.

Obesity and anesthetic pharmacology: simulation of target-controlled infusion models of propofol and remifentanil.

The prevalence of obesity is increasing, resulting in an increase in the number of surgeries performed to treat obesity and diseases induced by obesity. The associated comorbidities as well as the pharmacokinetic and pharmacodynamic changes that occur in obese patients make it difficult to control the appropriate dose of anesthetic agents. Factors that affect pharmacokinetic changes include the increase in adipose tissue, lean body weight, extracellular fluid, and cardiac output associated with obesity. These physiological and body compositional changes cause changes in the pharmacokinetic and pharmacodynamic parameters. The increased central volume of distribution and alterations in the clearance of drugs affect the plasma concentration of propofol and remifentanil in the obese population. Additionally, obesity can affect pharmacodynamic properties, such as the 50% of maximal effective concentration and the effect-site equilibration rate constant (ke0). Conducting a simulation of target-controlled infusions based on pharmacokinetic and pharmacodynamic models that include patients that are obese can help clinicians better understand the pharmacokinetic and pharmacodynamic changes of anesthetic drugs associated with this population.