Effect-site Concentration Of Propofol Research Articles

Decrease in spectral entropy by low tidal volume ventilation-associated severe hypercapnia: a case report.

Severe hypercapnia can be predicted by a decrease in cerebral electrical activity. The authors describe a sudden decrease in spectral entropy due to severe hypercapnia-induced respiratory acidosis in a patient with chronic pulmonary obstructive disease during lung resection. After two and a half hours of low tidal volume ventilation in the lateral position, the state entropy suddenly dropped from 45 to 7, without any changes in the effect-site concentration of propofol, end-tidal carbon dioxide (CO2) tension, oxygen saturation, or arterial pressure. However, arterial blood gas analysis showed severe respiratory acidosis (pH 7.01, PaCO2 115 mmHg and PaO2 246 mmHg with FIO2 of 0.5). Immediate hyperventilation improved the state entropy and acid-base balance. Electroencephalography-based spectral entropy can detect severe hypercapnia in chronic pulmonary obstructive disease patients with a large arterial to end-tidal CO2 difference due to prolonged hypoventilation during thoracic surgery.

Probability to tolerate laryngoscopy and noxious stimulation response index as general indicators of the anaesthetic potency of sevoflurane, propofol, and remifentanil

BackgroundThe probability to tolerate laryngoscopy (PTOL) and its derivative, the noxious stimulation response index (NSRI), have been proposed as measures of potency of a propofol–remifentanil drug combination. This study aims at developing a triple drug interaction model to estimate the combined potency of sevoflurane, propofol, and remifentanil in terms of PTOL. We compare the predictive performance of PTOL and the NSRI with various anaesthetic depth monitors. MethodsData from three previous studies (n+120) were pooled and reanalysed. Movement response after laryngoscopy was observed with different combinations of propofol–remifentanil, sevoflurane–propofol, and sevoflurane–remifentanil. A triple interaction model to estimate PTOL was developed. The NSRI was derived from PTOL. The ability of PTOL and the NSRI to predict observed tolerance of laryngoscopy (TOL) was compared with the following other measures: (i) effect-site concentrations of sevoflurane, propofol, and remifentanil (CeSEVO, CePROP, and CeREMI); (ii) bispectral index; (iii) two measures of spectral entropy; (iv) composite variability index; and (v) surgical pleth index. ResultsSevoflurane and propofol interact additively, whereas remifentanil interacts in a strongly synergistic manner. The effect-site concentrations of sevoflurane and propofol at a PTOL of 50% (Ce50; se) were 2.59 (0.13) vol % and 7.58 (0.49) µg ml−1. A CeREMI of 1.36 (0.15) ng ml−1 reduced the Ce50 of sevoflurane and propofol by 50%. The common slope factor was 5.22 (0.52). The PTOL and NSRI predict the movement response to laryngoscopy best. ConclusionsThe triple interaction model estimates the potency of any combination of sevoflurane, propofol, and remifentanil expressed as either PTOL or NSRI.

Decoding motor responses from the EEG during altered states of consciousness induced by propofol

Objective. Patients undergoing general anesthesia may awaken and become aware of the surgical procedure. Due to neuromuscular blocking agents, patients could be conscious yet unable to move. Using brain–computer interface (BCI) technology, it may be possible to detect movement attempts from the EEG. However, it is unknown how an anesthetic influences the brain response to motor tasks. Approach. We tested the offline classification performance of a movement-based BCI in 12 healthy subjects at two effect-site concentrations of propofol. For each subject a second classifier was trained on the subject’s data obtained before sedation, then tested on the data obtained during sedation (‘transfer classification’). Main results. At concentration 0.5 μg ml−1, despite an overall propofol EEG effect, the mean single trial classification accuracy was 85% (95% CI 81%–89%), and 83% (79%–88%) for the transfer classification. At 1.0 μg ml−1, the accuracies were 81% (76%–86%), and 72% (66%–79%), respectively. At the highest propofol concentration for four subjects, unlike the remaining subjects, the movement-related brain response had been largely diminished, and the transfer classification accuracy was not significantly above chance. These subjects showed a slower and more erratic task response, indicating an altered state of consciousness distinct from that of the other subjects. Significance. The results show the potential of using a BCI to detect intra-operative awareness and justify further development of this paradigm. At the same time, the relationship between motor responses and consciousness and its clinical relevance for intraoperative awareness requires further investigation.

Modelling of the Sedative Effects of Propofol in Patients undergoing Spinal Anaesthesia: A Pharmacodynamic Analysis.

Sedation can increase patient comfort during spinal anaesthesia. Understanding the relationship between the propofol effect-site concentration (Ce) and patient sedation level could help clinicians achieve the desired sedation level with minimal side effects. We aimed to model the relationship between the propofol Ce and adequate and deep sedation and also incorporate covariates. Thirty patients scheduled for orthopaedic surgery received spinal anaesthesia with 0.5% bupivacaine. Propofol was administered via an effect-site target-controlled infusion device using the Schnider pharmacokinetic model. The pharmacodynamic models for both adequate sedation [Observer's Assessment of Alertness/Sedation (OAA/S) scores of 3-4] and deep sedation (OAA/S scores of 1-2) were developed using nonlinear mixed-effects modelling. Increments in the propofol Ce were associated with increased depths of sedation. In the basic model, the estimated population Ce50 values for adequate and deep sedation were 0.94 and 1.52 μg/ml, respectively. The inclusion of the patient's age and sensory block level for adequate sedation and of age for deep sedation as covariates significantly improved the basic model by decreasing the objective function's minimum value from 10696.72 to 10677.92 (p = 0.0003). The simulated Ce50 values for adequate sedation in 20-year-old patients with a T12 sensory level and in 80-year-old patients with a T4 level were 1.63 and 0.53 μg/ml, respectively. Both age and sensory block level should be considered for adequate sedation, and the propofol concentration should be reduced for elderly patients with a high spinal block to avoid unnecessarily deep levels of sedation.

Spectral Gini Index for Quantifying the Depth of Consciousness.

We propose indices that describe the depth of consciousness (DOC) based on electroencephalograms (EEGs) acquired during anesthesia. The spectral Gini index (SpG) is a novel index utilizing the inequality in the powers of the EEG spectral components; a similar index is the binarized spectral Gini index (BSpG), which has low computational complexity. A set of EEG data from 15 subjects was obtained during the induction and recovery periods of general anesthesia with propofol. The efficacy of the indices as indicators of the DOC was demonstrated by examining Spearman's correlation coefficients between the indices and the effect-site concentration of propofol. A higher correlation was observed for SpG and BSpG (0.633 and 0.770, resp., p < 0.001) compared to the conventional indices. These results show that the proposed indices can achieve a reliable quantification of the DOC with simplified calculations.

Correlation Between Body Movements and Salivary Secretion During Sedation.

During dental sedation, control of the cough reflex is crucial for a safe and smooth procedure. Accumulated saliva is one of the predisposing factors for coughing. Body movements during dental sedation appear to enhance salivation. Therefore, the aim of this study was to investigate the difference in salivary secretion between the with-movements state and the without-movements state during sedation. Salivary weight for 1 min was measured 3 times in 27 patients with intellectual disability during dental treatment under deep sedation with midazolam and propofol. The observed variables were body movements, bispectral index (BIS), and predicted propofol effect-site concentration. A total of 81 measurements were classified into the with-movements state (n = 39; ie, measurements during which body movements were observed) or the without-movements state (n = 42; ie, measurements during which no body movements were observed). The median salivary weight was significantly smaller in the without-movements state compared with the with-movements state (0.03 vs 0.11 g, P < .0001). The BIS was significantly lower in the without-movements state. There was no significant difference in the predicted propofol effect-site concentration between the 2 states. Significant correlation was observed between salivary weight and BIS in the with-movements state (r = 0.44, P = .004). The findings indicate that salivary secretion decreased according to deep sedation. Furthermore, immobility also reduced salivary secretion. We concluded that one reason that immobility is beneficial is because of the resulting decreased salivary secretion during dental treatment under deep sedation.

Swallowing Impairment During Propofol Target-Controlled Infusion

Sedatives can impair the swallowing process. We assessed the incidence and severity of swallowing impairment in patients sedated with propofol at clinically relevant doses. We also identified factors that were predictive of swallowing impairment. In 80 patients scheduled to undergo elective gastrointestinal endoscopy under target-controlled infusion (TCI) propofol sedation, swallowing was evaluated by glottis videoendoscopy, using the Dysphagia Severity Score (DSS) and the Penetration and Aspiration Scale (PAS). The level of sedation was assessed with the Observer's Assessment of Alertness/Sedation (OAAS) scale. Evaluations were obtained within each patient at 3 target effect-site propofol concentrations of 2, 3, and 4 μg/mL (Marsh model). At 2 μg/mL TCI, the OAAS score was 2 in 21 (26.25%) patients and 1 in 59 (73.75%). The OAAS score was 1 in all patients at 3 and 4 μg/mL TCI target. At 3 μg/mL TCI target, 19 (24.36%) patients had a DSS = 3 and 18 patients (23.08%) had a PAS = 7-8 (severe swallowing impairment). DSS was associated with increasing age (5-year odds ratio [OR] 1.53 [1.22-1.93]; P < 0.001), body mass index (BMI; OR 1.24 [1.08-1.42]; P = 0.002), and TCI target (OR 15.80 [7.76-32.20]; P < 0.001). In an alternative model incorporating OAAS instead of TCI target, DSS was associated with increasing age (5-year OR 1.13 [1.02-1.24]; P = 0.014) and BMI (OR 1.08 [1.02-1.15]; P = 0.006) and decreasing OAAS (OR 0.05 [0.006-0.36]; P = 0.003). PAS was associated with increasing age (5-year OR 1.09 [1.04-1.15]; P < 0.001), BMI (OR 1.23 [1.07-1.41]; P = 0.003), and TCI target (OR 15.23 [7.45-31.16]; P < 0.001). In an alternative model incorporating OAAS instead of TCI target, PAS was associated with increasing age (5-year OR 1.14 [1.04-1.26]; P = 0.007) and BMI (OR 1.09 [1.02-1.15]; P = 0.006) and decreasing OAAS (OR 0.05 [0.006-0.41]; P = 0.005). Aspiration due to swallowing impairment may occur during deep sedation produced by propofol at commonly used TCI targets. TCI targets are predictors of swallowing impairment; increased age and high BMI are concomitant risk factors.

A Pharmacokinetics-Neural Mass Model (PK-NMM) for the Simulation of EEG Activity during Propofol Anesthesia.

Modeling the effects of anesthetic drugs on brain activity is very helpful in understanding anesthesia mechanisms. The aim of this study was to set up a combined model to relate actual drug levels to EEG dynamics and behavioral states during propofol-induced anesthesia. We proposed a new combined theoretical model based on a pharmacokinetics (PK) model and a neural mass model (NMM), which we termed PK-NMM—with the aim of simulating electroencephalogram (EEG) activity during propofol-induced general anesthesia. The PK model was used to derive propofol effect-site drug concentrations (C eff) based on the actual drug infusion regimen. The NMM model took C eff as the control parameter to produce simulated EEG-like (sEEG) data. For comparison, we used real prefrontal EEG (rEEG) data of nine volunteers undergoing propofol anesthesia from a previous experiment. To see how well the sEEG could describe the dynamic changes of neural activity during anesthesia, the rEEG data and the sEEG data were compared with respect to: power-frequency plots; nonlinear exponent (permutation entropy (PE)); and bispectral SynchFastSlow (SFS) parameters. We found that the PK-NMM model was able to reproduce anesthesia EEG-like signals based on the estimated drug concentration and patients’ condition. The frequency spectrum indicated that the frequency power peak of the sEEG moved towards the low frequency band as anesthesia deepened. Different anesthetic states could be differentiated by the PE index. The correlation coefficient of PE was 0.80±0.13 (mean±standard deviation) between rEEG and sEEG for all subjects. Additionally, SFS could track the depth of anesthesia and the SFS of rEEG and sEEG were highly correlated with a correlation coefficient of 0.77±0.13. The PK-NMM model could simulate EEG activity and might be a useful tool for understanding the action of propofol on brain activity.

Effect of acute hypervolemic hemodilution of 6% hydroxyethyl starch 130/0.4 on the EC50 of propofol at two clinical endpoints in patients.

Preoperative acute hypervolemic hemodilution (AHHD) is a technique used in anesthesia to reduce the number of blood cells lost during intraoperative bleeding. The aim of the present study was to evaluate the effect of the hypervolemic hemodilution of 6% hydroxyethyl starch 130/0.4 on the EC50 of propofol at two clinical endpoints. A total of 20 patients undergoing AHHD following epidural anesthesia were studied, and 20 patients who did not receive hemodilution were used as a control group. All patients were American Society of Anesthesiologists grade I, aged 20–40 years and undergoing hip arthroplasty surgery. In the AHHD group, 10 ml/kg lactated Ringer's solution was infused over 20 min at the same time as the epidural test dose. The infusion was followed by the infusion of 6% hydroxyethyl starch 130/0.4 over 30 min. Patients in the control group received 10 ml/kg Ringer's solution over 50 min. Propofol was then delivered by a Diprifusor target-controlled infusion. The predicted blood and effect-site propofol concentrations were recorded at loss of consciousness (LOC) and return of consciousness (ROC). Probit analysis was used to estimate the values for predicted blood and effect-site concentrations at the two clinical endpoints. The results showed that the potency of propofol was decreased during AHHD. Compared with the controls, the predicted blood and effect-site concentrations of propofol at LOC were higher in patients of the hemodilution group, resulting in higher EC50 values (P=0.001 and 0.025, respectively). At ROC, the effect-site EC50 was 2.9 µg/ml [95% confidence interval (CI), 2.8–3.0] in hemodilution patients and 2.5 µg/ml (95% CI, 2.2–2.6) in control patients (P=0.001). With AHHD, the LOC time was significantly longer and the propofol dose was higher, while ROC times were comparable. In conclusion, AHHD increases the requirement for propofol at LOC and prolongs LOC time. Patients with AHHD recovered consciousness at higher effect-site concentrations of propofol. Thus, the induction dose of propofol should be increased during AHHD.

A comparison of different synchronization measures in electroencephalogram during propofol anesthesia

Electroencephalogram (EEG) synchronization is becoming an essential tool to describe neurophysiological mechanisms of communication between brain regions under general anesthesia. Different synchronization measures have their own properties to reflect the changes of EEG activities during different anesthetic states. However, the performance characteristics and the relations of different synchronization measures in evaluating synchronization changes during propofol-induced anesthesia are not fully elucidated. Two-channel EEG data from seven volunteers who had undergone a brief standardized propofol anesthesia were then adopted to calculate eight synchronization indexes. We computed the prediction probability (P K ) of synchronization indexes with Bispectral Index (BIS) and propofol effect-site concentration (C eff ) to quantify the ability of the indexes to predict BIS and C eff . Also, box plots and coefficient of variation were used to reflect the different synchronization changes and their robustness to noise in awake, unconscious and recovery states, and the Pearson correlation coefficient (R) was used for assessing the relationship among synchronization measures, BIS and C eff . Permutation cross mutual information (PCMI) and determinism (DET) could predict BIS and follow C eff better than nonlinear interdependence (NI), mutual information based on kernel estimation (KerMI) and cross correlation. Wavelet transform coherence (WTC) in α and β frequency bands followed BIS and C eff better than that in other frequency bands. There was a significant decrease in unconscious state and a significant increase in recovery state for PCMI and NI, while the trends were opposite for KerMI, DET and WTC. Phase synchronization based on phase locking value (PSPLV) in δ, θ, α and γ1 frequency bands dropped significantly in unconscious state, whereas it had no significant synchronization in recovery state. Moreover, PCMI, NI, DET correlated closely with each other and they had a better robustness to noise and higher correlation with BIS and C eff than other synchronization indexes. Propofol caused EEG synchronization changes during the anesthetic period. Different synchronization measures had individual properties in evaluating synchronization changes in different anesthetic states, which might be related to various forms of neural activities and neurophysiological mechanisms under general anesthesia.

Comparison of C₅₀ for Propofol-remifentanil Target-controlled Infusion and Bispectral Index at Loss of Consciousness and Response to Painful Stimulus in Elderly and Young Patients.

Background:In this prospective randomized study, we compared the predicted blood and effect-site C50 for propofol and remifentanil target-controlled infusion (TCI) and the bispectral index (BIS) values at loss of consciousness (LOC) and response to a standard noxious painful stimulus (LOS) in elderly and young patients, respectively. We hypothesized that the elderly patients will require lower target concentration of both propofol and remifentanil at above two clinical end-points.Methods:There were 80 American Society of Anesthesiologists (ASA) physical status I–II unpremedicated patients enrolled in this study, they were divided into elderly group (age ≥65 years, n = 40) and young group (aged 18–64 years, n = 40). Propofol was initially given to a predicted blood concentration of 1.2 μg/ml and thereafter increased by 0.3 μg/ml every 30 s until Observer's Assessment of Alertness and Sedation score was 1. The propofol level was kept constant, and remifentanil was given to provide a predict blood concentration of 2.0 ng/ml, and then increased by 0.3 ng/ml every 30 s until loss of response to a tetanic stimulus. BIS (version 3.22, BIS Quattro sensor) was also recorded.Results:In elderly group, the propofol effect-site C50 at LOC of was 1.5 (1.4–1.6) μg/ml, was significantly lower than that of young group, which was 2.2 (2.1–2.3) μg/ml, the remifentanil effect-site C50 at LOS was 3.5 (3.3–3.7) ng/ml in elderly patients, was similar with 3.7 (3.6–3.8) ng/ml in young patients. Fifty percent of patients lost consciousness at a BIS value of 57.3 (56.4–58.1), was similar with that of young group, which was 55.2 (54.0–56.3).Conclusion:In elderly patients, the predicted blood and effect-site concentrations of propofol at LOC were lower than that of young patients. At same sedation status, predicted blood and effect-site concentrations of remifentanil required at LOS were similar in elderly and young patients. BIS were not affected by age. Low-propofol/high-opioid may be optional TCI strategy for elderly patients.

Population pharmacokinetic-pharmacodynamic modeling and dosing simulation of propofol maintenance anesthesia in severely obese adolescents.

Optimal dosing of propofol to maintain appropriate anesthetic depth is challenging in severely obese (SO) adolescents. We previously reported that total body weight (TBW) is predictive of propofol clearance. This study was aimed at characterizing pharmacokinetics (PK) and pharmacodynamics (PD) of propofol in SO adolescents, using bispectral index (BIS), and toward developing PK/PD model-based dosing guidelines. A prospective PK/PD study was conducted in 26 SO children and adolescents aged 9-18 years (body mass index 31-69 kg·m(-2)), undergoing surgery with intravenous propofol anesthesia clinically titrated by providers blinded to BIS. BIS data and propofol infusion schemes were recorded. Venous blood samples collected during and after propofol infusion were assayed for propofol concentrations. A propofol PK/PD model was developed using NONMEM and model-based simulations were performed to determine propofol dosing regimens targeting BIS of 50 ± 10. A three-compartment PK model linked to a sigmoidal inhibitory Emax PD model by a first-order rate constant, adequately described the propofol concentration (n = 375) and BIS (n = 3334) data. TBW was the most predictive covariate for propofol clearance [CL (l·min(-1) ) = 1.65 × (TBW/70)(0.75)]. An effect-site propofol concentration of 3.19 μg·ml(-1) was estimated for half-maximal effect, with no identifiable predictive covariates. The proposed maintenance dosing regimen targeted to a BIS of 50 ± 10, based on our PK/PD model, was able to predict desired propofol concentrations and BIS in a representative obese teen when used in conjunction with accepted PK/PD models for children/obese adults (PK:Eleveld/PD: Cortinez), further supporting evidence for the dosing based on TBW. This is the first study to describe the PK/PD of propofol in SO adolescents. The proposed maintenance dosing regimen for propofol uses TBW in an allometric function as a dosing scalar, with an exponent of 0.75. Our results suggest no relevant effect of obesity on the propofol concentration-BIS relationship.

Confounding factors to predict the awakening effect-site concentration of propofol in target-controlled infusion based on propofol and fentanyl anesthesia.

We conducted a large retrospective study to investigate the confounding factors that predict Ce ROC under propofol-based TIVA with TCI. We recorded sex, age, height, weight, Ce LOC, Ce ROC, total propofol and fentanyl consumption dose, and anesthetic time. Simple linear regression models were used to identify potential predictors of Ce ROC, and multiple linear regression models were used to identify the confounding predictors of Ce ROC. We found that Ce ROC correlated with age, sex, Ce LOC, and both total fentanyl and propofol consumption dose. The prediction formula was: Ce ROC = 0.87 - 0.06 × age + 0.18 × Ce LOC + 0.04 (if fentanyl consumption > 150 μg; if not, ignore this value) + 0.07 × (1 or 2, according to the total propofol consumption dose, 1 for a propofol amount 1000-2000 mg and 2 for a propofol amount > 2000 mg). We simplified the formula further as Ce ROC = 0.87 - 0.06 × age + 0.18 × Ce LOC. In conclusion, Ce ROC can be predicted under TCI with propofol- and fentanyl-based TIVA. The confounding factors that predicted propofol Ce ROC are age, sex, Ce LOC, and total consumption dose of propofol and fentanyl.

The Concentration for Loss of Consciousness by Propofol does not differ between Morning and Afternoon

Background: Circadian rhythms influence the pharmacology and effects of anesthetic agents such as local anesthetics, general anesthetics, and muscle relaxants. However, the influences of the circadian rhythm on new anesthetics such as propofol are unknown. Method: Propofol, one of popular intravenous anesthetics, was administered intravenously using the Diprifusor™ system, which is a target-controlled infusion system of propofol. The propofol infusion started with an initial effect-site concentration of 4μg/mL for 3 min and increased in increments of 0.5μg/mL every 30 sec after the first 3 min until the patient lost the eyelash reflex and exhibited no response to verbal commands. The predicted blood concentration and the predicted effect-site concentration of propofol required for loss of consciousness (LOC) were recorded. Results: Thirty-seven patients underwent induced anesthesia at 8:30. Twenty-eight patients were induced between 14:00 and 16:00.There was no significant difference between the two groups in the predicted blood concentration, the predicted effect-site concentration and the time for LOC. Conclusion: The concentration for LOC by propofol is not influenced by the time of day, at least during the human active period.

Pharmacokinetics and pharmacodynamics of propofol in cancer patients undergoing major lung surgery.

Despite the growing number of cancer cases and cancer surgeries around the world, the pharmacokinetics (PK) and pharmacodynamics (PD) of anesthetics used in this population are poorly understood. Patients operated due to cancer are usually in severe state and often require chemotherapy. It might affect the PK/PD of drugs used in this population. Therefore, in this study we explored the PK/PD of propofol in cancer patients having a major lung surgery. 23 patients that underwent a propofol–fentanyl total intravenous anesthesia were included in the analysis. A large set of demographic, biochemical and hemodynamic parameters was collected for the purpose of covariate analysis. Nonlinear mixed effect modeling in NONMEM was used to analyze the collected data. A three-compartment model was sufficient to describe PK of propofol. The anesthetic effect (AAI index) was linked to the propofol effect site concentrations through a sigmoidal E max model. A slightly higher value of clearance, a lower value of distribution clearance, and a decreased volume of peripheral compartment were observed in our patients, as compared with the literature values reported for healthy volunteers by Schnider et al. and by Eleveld et al. Despite these differences, both models led to a clinically insignificant bias of −8 and −1 % in concentration predictions, as reflected by the median performance error. The C e50 and propofol biophase concentration at the time of postoperative orientation were low and equaled 1.40 and 1.13 mg/L. The population PK/PD model was proposed for cancer patients undergoing a major lung surgery. The large body of studied covariates did not affect PK/PD of propofol significantly. The modification of propofol dosage in the group of patients under study is not necessary when TCI-guided administration of propofol by means of the Schnider model is used.Electronic supplementary materialThe online version of this article (doi:10.1007/s10928-015-9404-6) contains supplementary material, which is available to authorized users.

Comparison of Pharmacokinetic Models for Hypnosis Control Based on Effect-Site Propofol Concentration to Maintain Appropriate Hypnosis

This paper studies an appropriate pharmacokinetic (PK) model for hypnosis control based on effect-site anesthetic concentration. For maintaining hypnosis, methods to keep plasma or effect-site concentration of propofol, an anesthetic drug, calculated using PK models at a target level are often used. In order to realize a desirable hypnosis control by such methods an accurate estimation of propofol concentration corresponding to the threshold of unconsciousness is critical. Since time variation of the calculated propofol concentration depends on the PK model, the performance of maintaining hypnosis also depends on it. In this paper, we compare the existing PK models of propofol focusing on sensitivity and specificity for detecting consciousness during anesthesia by a criterion based on cal ulated propofol concentration and measured aepEX, a hypnosis index. The results show that Barr model provides the highest sensitivity and specificity, and that Marsh, modified Marsh, and Schnider models, which are often used in target controlled infusion systems give fairly high sensitivity and specificity.

Estimation of effect-site concentration of propofol for laryngeal mask airway insertion using fentanyl or morphine as adjuvant.

Background and Aims:Insertion of laryngeal mask airway (LMA) requires adequate depth of anaesthesia, which provides jaw relaxation and suppression of upper airway reflexes. Propofol can provide these conditions especially when combined with narcotics. This study had been designed to find out the effect-site concentration (EC50) of propofol using target controlled infusion (TCI) when fentanyl or morphine is added as an adjuvant.Methods:Patients satisfying inclusion criteria were divided into fentanyl and morphine groups. Intravenous glycopyrrolate 0.2 mg was given 15 min before induction. Patients were given either intravenous fentanyl (1 μg/kg) or morphine (0.1 mg/kg) before propofol infusion depending on the group. Patients in either groups were induced by continuous infusion of propofol at an EC of 6 μg/mL by TCI with Schneider pharmacokinetic model. The LMA supreme of appropriate size was inserted 1 min after achieving target concentration. Patient movement at LMA insertion or within 1 min of insertion was classified as failure. For subsequent patients, the target EC was increased/decreased depending on previous patients' response. Dixons up and down method was used to determine the EC50. The EC50 is defined as the mean of crossover midpoints in each pair of failure to success.Results:The EC50 of propofol in the fentanyl group for LMA insertion was 5.95 ± 0.6 μg/ml and morphine group was 5.75 ± 0.8 μg/ml. No significant difference in insertion conditions was noticed between the two groups (P = 0.3).Conclusion:We conclude that there was no significant difference in propofol EC50 for insertion of LMA and insertion conditions were similar when fentanyl or morphine was used as an adjuvant drug.

Pharmacodynamic Estimate of Propofol-Induced Sedation and Airway Obstruction Effects in Obstructive Sleep Apnea-Hypopnea Syndrome.

PurposeSedatives must be carefully titrated for patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) as oversedation may lead to disastrous respiratory outcomes. This study aimed to investigate the relations between the effect-site concentration (Ce) of propofol and sedation and airway obstruction levels in patients with OSAHS.Materials and MethodsIn 25 patients with OSAHS, sedation was induced by 2% propofol using target-controlled infusion. Sedation and airway obstruction levels were assessed using the Observer's Assessment of Alertness/Sedation Scale and a four-category scale, respectively. The relationships between propofol Ce and sedation and airway obstruction were evaluated using a sigmoid Emax model. Pharmacodynamic modeling incorporating covariates was performed using the Nonlinear Mixed Effects Modeling VII software.ResultsIncreased propofol Ce correlated with the depth of sedation and the severity of airway obstruction. Predicted Ce50(m) (Ce associated with 50% probability of an effect≥m) for sedation scores (m≥2, 3, 4, and 5) and airway-obstruction scores (m≥2, 3, and 4) were 1.61, 1.78, 1.91, and 2.17 µg/mL and 1.53, 1.64, and 2.09 µg/mL, respectively. Including the apnea-hypopnea index (AHI) as a covariate in the analysis of Ce50(4) for airway obstruction significantly improved the performance of the basic model (p<0.05).ConclusionThe probability of each sedation and airway obstruction score was properly described using a sigmoid Emax model with a narrow therapeutic range of propofol Ce in OSAHS patients. Patients with high AHI values need close monitoring to ensure that airway patency is maintained during propofol sedation.

Frontal-temporal synchronization of EEG signals quantified by order patterns cross recurrence analysis during propofol anesthesia.

Characterizing brain dynamics during anesthesia is a main current challenge in anesthesia study. Several single channel electroencephalogram (EEG)-based commercial monitors like the Bispectral index (BIS) have suggested to examine EEG signal. But, the BIS index has obtained numerous critiques. In this study, we evaluate the concentration-dependent effect of the propofol on long-range frontal-temporal synchronization of EEG signals collected from eight subjects during a controlled induction and recovery design. We used order patterns cross recurrence plot and provide an index named order pattern laminarity (OPL) to assess changes in neuronal synchronization as the mechanism forming the foundation of conscious perception. The prediction probability of 0.9 and 0.84 for OPL and BIS specified that the OPL index correlated more strongly with effect-site propofol concentration. Also, our new index makes faster reaction to transients in EEG recordings based on pharmacokinetic and pharmacodynamic model parameters and demonstrates less variability at the point of loss of consciousness (standard deviation of 0.04 for OPL compared with 0.09 for BIS index). The result show that the OPL index can estimate anesthetic state of patient more efficiently than the BIS index in lightly sedated state with more tolerant of artifacts.

Remifentanil requirements for preventing motor response to skin incision in healthy women anesthetized with combinations of propofol and dexmedetomidine titrated to similar Bispectral Index (BIS) values.

It is unclear whether the sedative, analgesic or sympatholytic effects of adjunctive dexmedetomidine contribute to reduced analgesic requirements in general anesthesia. This study aimed to assess the analgesic effect of dexmedetomidine on intraoperative opioid requirements using body movement as observation indicator at similar BIS-guided sedative depth in propofol anesthesia. Ninety patients were randomly divided into three groups to receive administration of saline, and dexmedetomidine at 0.5 and 1.0 µg kg(-1) over 10 min, followed by saline and dexmedetomidine at infusion rates of 0.17 and 0.33 µg kg(-1) h(-1), respectively. After dexmedetomidine and saline bolus administration, propofol was titrated to maintain the BIS values at 45-55. When BIS values reached the predetermined range, remifentanil was administered by target-controlled infusion. Five minutes following remifentanil treatment, skin was incised and the motor response observed. Then, the concentration of remifentanil blunting the motor response in 50% of patients (Ce50) was determined using a modified Dixon's sequential 'up-and-down' method. Dexmedetomidine significantly decreased effect-site concentrations of propofol for maintaining the preset BIS range (P < 0.01). The Ce50 (95% CI) of remifentanil were 0.93 (0.82-1.03), 1.03 (0.89-1.17) and 0.91 (0.77-1.06) ng ml(-1) in the 0 (saline), 0.5 and 1.0 µg kg(-1) dexmedetomidine groups, respectively, indicating non-statistically significant differences among groups (P > 0.0167). Propofol and its combination with dexmedetomidine have similar opioid requirements for preventing motor response to skin incision when titrated to similar BIS values. These findings indicate that adjunctive dexmedetomidine for general anesthesia has sedative but no opioid sparing effects.