Propofol Levels Research Articles

Hierarchical rhythmic propagation of corticothalamic interactions for consciousness: A computational study

Clarifying the mechanisms of loss and recovery of consciousness in the brain is a major challenge in neuroscience, and research on the spatiotemporal organization of rhythms at the brain region scale at different levels of consciousness remains scarce. By applying computational neuroscience, an extended corticothalamic network model was developed in this study to simulate the altered states of consciousness induced by different concentration levels of propofol. The cortex area containing oscillation spread from posterior to anterior in four successive time stages, defining four groups of brain regions. A quantitative analysis showed that hierarchical rhythm propagation was mainly due to heterogeneity in the inter-brain region connections. These results indicate that the proposed model is an anatomically data-driven testbed and a simulation platform with millisecond resolution. It facilitates understanding of activity coordination across multiple areas of the conscious brain and the mechanisms of action of anesthetics in terms of brain regions.

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

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). 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. 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). 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.

Efficacy of propofol-supplemented cardioplegia on biomarkers of organ injury in patients having cardiac surgery using cardiopulmonary bypass: A protocol for a randomised controlled study (ProMPT2).

Cardiac surgery with cardiopulmonary bypass and cardioplegic arrest is known to be responsible for ischaemia and reperfusion organ injury. In a previous study, ProMPT, in patients undergoing coronary artery bypass or aortic valve surgery we demonstrated improved cardiac protection when supplementing the cardioplegia solution with propofol (6mcg/ml). The aim of the ProMPT2 study is to determine whether higher levels of propofol added to the cardioplegia could result in increased cardiac protection. The ProMPT2 study is a multi-centre, parallel, three-group, randomised controlled trial in adults undergoing non-emergency isolated coronary artery bypass graft surgery with cardiopulmonary bypass. A total of 240 patients will be randomised in a 1:1:1 ratio to receive either cardioplegia supplementation with high dose of propofol (12mcg/ml), low dose of propofol (6mcg/ml) or placebo (saline). The primary outcome is myocardial injury, assessed by serial measurements of myocardial troponin T up to 48hours after surgery. Secondary outcomes include biomarkers of renal function (creatinine) and metabolism (lactate). The trial received research ethics approval from South Central - Berkshire B Research Ethics Committee and Medicines and Healthcare products Regulatory Agency in September 2018. Any findings will be shared though peer-reviewed publications and presented at international and national meetings. Participants will be informed of results through patient organisations and newsletters. ISRCTN15255199. Registered in March 2019.

Environmental risk assessment of propofol in wastewater: a narrative review of regulatory guidelines.

Concerns relating to the negative environmental impacts of anaesthesia are increasing, and in recent years, there has been an environmentally motivated trend towards greater use of propofol-based total intravenous anaesthesia. Consequently, the environmental burden of propofol waste and disposal, particularly into wastewater, has gained attention. Current literature reporting levels of propofol in wastewater are scarce and the threat this presents to the environment is unclear. We review the regulatory requirements for conducting an environmental risk assessment, with a focus on the process for analysing whether drugs or drug metabolites cause harm to aquatic species. Furthermore, we present a profile for the aquatic toxicity of propofol based on available data and discuss the implications of this for future practice.

The general anaesthetic propofol prevents cerebrocortical potentiation in neocortical mouse brain slices

Propofol is well known to cause amnesia independent of its sedative effect. Memory consolidation processes in the hippocampus have been proposed as a target — however the neural substrates for propofol’s amnesic actions remain understudied and poorly described. In particular, the potential role of the cerebral cortex has not been investigated.As an in vitro experimental model of cortical memory consolidation, potentiated cerebral cortex evoked responses were generated in mouse neocortical slices using high frequency (20 Hz) stimulation to layer IV cortical grey matter or subcortical white matter. In separate experiments, slices were pretreated with propofol at two concentrations, 2 µg/mL and 4 µg/mL, to determine the effect of clinically relevant propofol levels on the potentiation response.Only grey matter stimulation induced a significant and lasting increase in cortical evoked potential amplitude in the drug-free condition. Propofol at 2 µg/mL completely inhibited cortical evoked response potentiation, while the 4 µg/mL concentration caused a small but significant depressant effect consequent to the high frequency stimulation.These findings support the hypothesis that propofol disrupts memory consolidation and actively facilitates memory decay in the cerebral cortex. The results further highlight the importance of the cerebral cortex in the early phase of long term memory consolidation.

EEG microstate dynamics indicate a U-shaped path to propofol-induced loss of consciousness

Evidence suggests that the stream of consciousness is parsed into transient brain states manifesting themselves as discrete spatiotemporal patterns of global neuronal activity. Electroencephalographical (EEG) microstates are proposed as the neurophysiological correlates of these transiently stable brain states that last for fractions of seconds. To further understand the link between EEG microstate dynamics and consciousness, we continuously recorded high-density EEG in 23 surgical patients from their awake state to unconsciousness, induced by step-wise increasing concentrations of the intravenous anesthetic propofol. Besides the conventional parameters of microstate dynamics, we introduce a new implementation of a method to estimate the complexity of microstate sequences. The brain activity under the surgical anesthesia showed a decreased sequence complexity of the stereotypical microstates, which became sparser and longer-lasting. However, we observed an initial increase in microstates’ temporal dynamics and complexity with increasing depth of sedation leading to a distinctive “U-shape” that may be linked to the paradoxical excitation induced by moderate levels of propofol. Our results support the idea that the brain is in a metastable state under normal conditions, balancing between order and chaos in order to flexibly switch from one state to another. The temporal dynamics of EEG microstates indicate changes of this critical balance between stability and transition that lead to altered states of consciousness.

A "Smart" Biosensor-Enabled Intravascular Catheter and Platform for Dynamic Delivery of Propofol to "Close the Loop" for Total Intravenous Anesthesia.

Target-controlled infusion anesthesia is used worldwide to provide user-defined, stable, blood concentrations of propofol for sedation and anesthesia. The drug infusion is controlled by a microprocessor that uses population-based pharmacokinetic data and patient biometrics to estimate the required infusion rate to replace losses from the blood compartment due to drug distribution and metabolism. The objective of the research was to develop and validate a method to detect and quantify propofol levels in the blood, to improve the safety of propofol use, and to demonstrate a pathway for regulatory approval for its use in the USA. We conceptualized and prototyped a novel "smart" biosensor-enabled intravenous catheter capable of quantifying propofol at physiologic levels in the blood, in real time. The clinical embodiment of the platform is comprised of a "smart" biosensor-enabled catheter prototype, a signal generation/detection readout display, and a driving electronics software. The biosensor was validated in vitro using a variety of electrochemical methods in both static and flow systems with biofluids, including blood. We present data demonstrating the experimental detection and quantification of propofol at sub-micromolar concentrations using this biosensor and method. Detection of the drug is rapid and stable with negligible biofouling due to the sensor coating. It shows a linear correlation with mass spectroscopy methods. An intuitive graphical user interface was developed to: (1) detect and quantify the propofol sensor signal, (2) determine the difference between targeted and actual propofol concentration, (3) communicate the variance in real time, and (4) use the output of the controller to drive drug delivery from an in-line syringe pump. The automated delivery and maintenance of propofol levels was demonstrated in a modeled benchtop "patient" applying the known pharmacokinetics of the drug using published algorithms. We present a proof-of-concept and in vitro validation of accurate electrochemical quantification of propofol directly from the blood and the design and prototyping of a "smart," indwelling, biosensor-enabled catheter and demonstrate feedback hardware and software architecture permitting accurate measurement of propofol in blood in real time. The controller platform is shown to permit autonomous, "closed-loop" delivery of the drug and maintenance of user-defined propofol levels in a dynamic flow model.

Application of a benchtop colorimetric method for quantification of blood propofol levels.

Quantification of plasma propofol (2,6-diisopropylphenol) in the context of clinical anaesthesia is challenging because of the need for offline blood sample processing using specialised laboratory equipment and techniques. In this study we sought to refine a simple procedure using solid phase extraction and colorimetric analysis into a benchtop protocol for accurate blood propofol measurement.The colorimetric method based on the reaction of phenols (e.g. propofol) with Gibbs reagent was first tested in 10% methanol samples (n = 50) containing 0.5-6.0µg/mL propofol. Subsequently, whole blood samples (n = 15) were spiked to known propofol concentrations and processed using reverse phase solid phase extraction (SPE) and colorimetric analysis.The standard deviation of the difference between known and measured propofol concentrations in the methanol samples was 0.11µg/mL, with limits of agreement of - 0.21 to 0.22µg/mL. For the blood-processed samples, the standard deviation of the difference between known and measured propofol concentrations was 0.09µg/mL, with limits of agreement - 0.18 to 0.17µg/mL.Quantification of plasma propofol with an error of less than 0.2µg/mL is achievable with a simple and inexpensive benchtop method.

Multi-drug therapy for epilepsy influenced bispectral index after a bolus propofol administration without affecting propofol\u2019s pharmacokinetics: a prospective cohort study

Some previous studies have indicated that valproate (VPA) might change the pharmacokinetics and enhance the effects of propofol. We evaluated whether clinical VPA therapy affected the propofol blood level, the protein-unbound free propofol level, and/or the anesthetic effects of propofol in the clinical setting. The subjects were divided into the control group (not medicated with antiepileptics), the mono-VPA group (medicated with VPA alone), and the poly-VPA group (medicated with VPA, other antiepileptics, and/or psychoactive drugs). General anesthesia was induced via the administration of a single bolus of propofol and a remifentanil infusion, and when the bispectral index (BIS) exceeded 60 sevoflurane was started. There were no significant differences in the total blood propofol level at 5, 10, 15, and 20 min or the protein-unbound free propofol level at 5 min after the intravenous administration of propofol between the 3 groups. However, the minimum BIS was significantly lower and the time until the BIS exceeded 60 was significantly longer in the poly-VPA group. In the multivariate regression analysis, belonging to the poly-VPA group was found to be independently associated with the minimum BIS value and the time until the BIS exceeded 60. Clinical VPA therapy did not influence the pharmacokinetics of propofol. However, multi-drug therapy involving VPA might enhance the anesthetic effects of propofol.

Literature Review for Office-Based Anesthesia.

Literature Review for Office-Based Anesthesia.

Measuring the accuracy of propofol target-controlled infusion (TCI) before and after surgery with major blood loss.

Target-controlled infusion (TCI) is based on pharmacokinetic models designed to achieve a desired drug level in the blood. TCI's predictive accuracy of plasma propofol levels at the end of surgery with major blood loss has not been well established. This prospective observational study included adult patients (BMI 20-35kg/m2) undergoing surgery with expected blood loss ≥ 1500mL. The study was conducted with the Schnider TCI propofol model (Alaris PK Infusion Pump, CareFusion, Switzerland). Propofol levels were assessed in steady-state at the end of anaesthesia induction (Tinitial) and before the end of surgery (Tfinal). Predicted propofol levels (CTCI) were compared to measured levels (Cblood). Twenty-one patients were included. The median estimated blood loss was 1600mL (IQR 1000-2300), and the median fluid balance at Tfinal was + 3200mL (IQR 2320-4715). Heart rate, mean arterial blood pressure, and blood lactate did not differ significantly between Tinitial and Tfinal. The median bispectral index (0-100) was 50 (IQR 42-54) and 49 (IQR 42-56) at the two respective time points. At Tinitial, median CTCI was 2.2µmol/L (IQR 2-2.45) and Cblood was 2.0µmol/L (bias 0.3µmol/L, limits of agreement - 1.1 to 1.3, p = 0.33). CTCI and Cblood at Tfinal were 2.0µmol/L (IQR 1.6-2.2) and 1µmol/L (IQR 0.8-1.4), respectively (bias 0.6µmol/L, limits of agreement - 0.89 to 1.4, p < 0.0001). Propofol TCI allows clinically unproblematic conduct of general anaesthesia. In cases of major blood loss, the probability of propofol TCI overestimating plasma levels increases.Trial registration German Clinical Trials Register (DRKS; DRKS00009312).

Changes in topographic electroencephalogram during deepening levels of propofol sedation based on alertness/sedation scale under bispectral index guidance.

Sedation has been associated with numerous changes on electroencephalogram (EEG) but there is a need to clarify specific alterations in relation to deepening levels of sedation with different agents. We aimed to evaluate the effect of deepening levels of sedation induced by propofol and how they compare to natural sleep. Fifty consecutive neurologically normal patients who underwent upper gastrointestinal endoscopy while sedated with propofol were included. Topographic EEG spectral maps and the bispectral index (BIS) values were obtained at four time points: wakefulness, mild sedation, deep sedation and recovery. Observer's Assessment of Alertness and Sedation (OAA/S) score was used to assess sedation levels. Propofol induced increased delta (0.5-3.5 Hz) and gamma (25-40 Hz) power throughout sedation. In addition, there was decreased alpha power (9-11.5 Hz) in the occipital area and increased global beta (12-25 Hz)/gamma (25-40 Hz) power during mild sedation. Deep sedation was associated with increased theta (4-7 Hz)/alpha (9-11.5 Hz)/beta (12-25 Hz) power, which was maximal frontally. There are distinct changes associated with deepening levels of propofol induced sedation that distinguish it from natural sleep. This suggests that different mechanisms are involved in them and warrants further investigations to clarify the nature of these changes.

Changes in transcranial motor evoked potentials during hemorrhage are associated with increased serum propofol concentrations.

Transcranial motor evoked potentials (TcMEPs) monitor the integrity of the spinal cord during spine surgery. Propofol-based anesthesia is favored in order to enhance TcMEP quality. During intraoperative hemorrhage, TcMEP amplitudes may be reduced. The serum concentration of propofol may increase during hemorrhage. No study has determined whether changes in TcMEPs due to hemorrhage are related to changes in propofol blood levels. We monitored TcMEPs, mean arterial pressure (MAP), and cardiac output (CO) and hemoglobin in pigs (n = 6) undergoing controlled progressive hemorrhage during a standardized anesthetic with infusions of propofol, ketamine, and fentanyl. We recorded TcMEPs from the rectus femoris (RF) and tibialis anterior (TA) muscles bilaterally. A pulmonary artery catheter was placed to measure CO. Progressive hemorrhage of 10% blood volume increments was done until TcMEP amplitude decreased by >60% from baseline. Serum propofol levels were also measured following removal of each 10% blood volume increment. TcMEP responses were elicited every 3min using constant stimulation parameters. We removed between 20 and 50% of total blood volume in order to achieve the >60% reduction in TcMEP amplitude. MAP and CO decreased significantly from baseline. At maximum hemorrhage, TcMEP amplitude decreased in the RF and TA by an average of 73 and 62% respectively from baseline (P < 0.01). Serum propofol levels varied greatly among animals at baseline (range 410-1720ng/mL) and increased in each animal during hemorrhage. The mean propofol concentration rose from 1190 ± 530 to 2483 ± 968ng/mL (P < 0.01). The increased propofol concentration correlated with decreased CO. Multivariate analysis using hierarchical linear models indicated that the decline of TcMEP amplitude was primarily associated with rising propofol concentrations, but was also independently affected by reduced CO. We believe that the decrease in blood volume and CO during hemorrhage increased the serum concentration of propofol by reducing the volume of distribution and/or rate of hepatic metabolism of the drug. Despite wide acceptance of propofol as the preferred anesthetic when using TcMEPs, intravenous anesthetics are vulnerable to altered pharmacokinetics during conditions of hemorrhage and could contribute to false-positive TcMEP changes.

Drug-Induced Sleep Endoscopy (DISE) with Target Controlled Infusion (TCI) and Bispectral Analysis in Obstructive Sleep Apnea.

The aim of this study was to establish a standardized protocol for drug-induced sleep endoscopy (DISE) to differentiate obstruction patterns in obstructive sleep apnea (OSA). Target-controlled infusion (TCI) of the sedative propofol was combined with real-time monitoring of the depth of sedation using bispectral analysis. In an observational study 57 patients (mean age 44.8 years, ± SD 10.5; mean apnea hypopnea Index (AHI) 30.8/hr, ± SD 21.6, mean BMI 28.2 kg/m2, ± SD 5.3) underwent cardiorespiratory polysomnography followed by DISE with TCI and bispectral analysis. Sleep was induced solely by the intravenous infusion of propofol with a TCI-pump, with an initial target plasma level of 2.0 µg/ml. Under continuous monitoring of the patient's respiration, state of consciousness and value of the bispectral analysis, the target plasma propofol level was raised in steps of 0.2 µg/ml/2 min until the desired depth of sedation was reached. The mean value of the bispectral analysis at the target depth of sedation was determined and the obstruction patterns during DISE-TCI-bispectral analysis then classified according to the VOTE-system. Subsequently the results were analyzed according to polysomnographic and anthropometric data. The occurrence of multilevel obstruction sites across all degrees of severity of OSA clarifies the need for sleep endoscopy prior to upper airway surgery. The advantage of this technique is the reproducibility of the protocol even for heterogeneous groups of patients. In addition, the gradual controlled and standardized increase of the plasma level of propofol with real-time control of the bispectral index leads to a precisely controllable depth of sedation. The DISE-TCI-bispectral analysis procedure is a step towards a required reproducible protocol of sleep endoscopy - capable of standardization. However it is not yet known whether these observed obstruction patterns also correspond to findings in natural sleep.

Cerebral responses to local and global auditory novelty under general anesthesia

Primate brains can detect a variety of unexpected deviations in auditory sequences. The local-global paradigm dissociates two hierarchical levels of auditory predictive coding by examining the brain responses to first-order (local) and second-order (global) sequence violations. Using the macaque model, we previously demonstrated that, in the awake state, local violations cause focal auditory responses while global violations activate a brain circuit comprising prefrontal, parietal and cingulate cortices. Here we used the same local-global auditory paradigm to clarify the encoding of the hierarchical auditory regularities in anesthetized monkeys and compared their brain responses to those obtained in the awake state as measured with fMRI. Both, propofol, a GABAA-agonist, and ketamine, an NMDA-antagonist, left intact or even enhanced the cortical response to auditory inputs. The local effect vanished during propofol anesthesia and shifted spatially during ketamine anesthesia compared with wakefulness. Under increasing levels of propofol, we observed a progressive disorganization of the global effect in prefrontal, parietal and cingulate cortices and its complete suppression under ketamine anesthesia. Anesthesia also suppressed thalamic activations to the global effect. These results suggest that anesthesia preserves initial auditory processing, but disturbs both short-term and long-term auditory predictive coding mechanisms. The disorganization of auditory novelty processing under anesthesia relates to a loss of thalamic responses to novelty and to a disruption of higher-order functional cortical networks in parietal, prefrontal and cingular cortices.

Morbid Obesity Alters Both Pharmacokinetics and Pharmacodynamics of Propofol: Dosing Recommendation for Anesthesia Induction.

The prevalence of obesity has markedly increased worldwide. Obese patients pose significant challenges to anesthesiologists with regard to accurate dosing of anesthetics due to potentially altered pharmacokinetics (PK). Here we determined the PK and pharmacodynamics (PD) of propofol for anesthesia induction in morbidly obese (MO) subjects (body mass index >35 kg/m(2)) at two dosing regimens: dosing based on total body weight and lean body weight (LBW), respectively. The propofol pharmacokinetic profile was well fitted with a two-compartment model. Both elimination clearance (223%-243% of controls, who had a body mass index <25 kg/m(2); P < 0.01) and peripheral compartment volume (156%-180% of controls; P < 0.01) were significantly increased in MO subjects, resulting in an equal or decreased propofol level in plasma (total body weight-based dosing). Furthermore, propofol PD (measured by the bispectral index) was adequately described by a PK/PD model that linked an effect compartment to the two-compartment PK model through a sigmoidal Emax model. All PD parameters except EC50 values (the half maximal effect concentration) were similar (P > 0.05) between MO subjects and controls. Morbid obesity led to a significant decrease (37.9%-38.6%; P < 0.01) in EC50 values, which suggests increased brain sensitivity to propofol in the MO population. Moreover, dose reduction (i.e., dosing based on LBW) generated identical anesthetic effects in MO subjects compared with controls. In conclusion, morbid obesity significantly altered both PK and PD of propofol. LBW was a better weight-based dosing scalar for anesthesia induction with propofol in MO subjects.

Determination of total and unbound propofol in patients during intensive care sedation by ultrafiltration and LC–MS/MS

For the quantification of propofol total and unbound drug concentrations a sensitive and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated. To separate unbound propofol an ultrafiltration step before sample preparation was performed. Both the ultrafiltrate and plasma samples were extracted with solid-phase extraction and substituted with deuterated propofol as an internal standard. Separation was performed by gradient elution using UPLC-like system and analyzed by MS/MS consisting of an electrospray ionization source. To detect low and high concentration levels of propofol two calibration curves were identified and showed linearity within the range of 1–50ng/ml and 50–20000ng/ml. The lower limit of quantification was 1ng/ml. Intra- and interassay precision and accuracy did not exceed ±15%. The method was applied to a clinical study during intensive care treatment of patients after coronary artery bypass grafting.

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.

Performance of target-controlled infusion of propofol using two different pharmacokinetic models in open heart surgery - a randomised controlled study

We compared the performance of a propofol target-controlled infusion (TCI) using Marsh versus PGIMER models in patients undergoing open heart surgery, in terms of measured plasma levels of propofol and objective pharmacodynamic effect. Twenty-three, ASA II/III adult patients aged 18-65 years and scheduled for elective open heart surgery received Marsh or PGIMER (Postgraduate Institute of Medical Education and Research) pharmacokinetic models of TCI for the induction and maintenance of anaesthesia with propofol in a randomized, active-controlled, non-inferiority trial. The plasma levels of propofol were measured at specified time points before, during and after bypass. The performances of both the models were similar, as determined by the error (%) in maintaining the target plasma concentrations: MDPE of -5.0 (-12.0, 5.0) in the PGIMER group vs -6.4 (-7.7 to 0.5) in the Marsh group and MDAPE of 9.1 (5, 15) in the PGIMER group vs 8 (6.7, 10.1) in the Marsh group. These values indicate that both models over-predicted the plasma propofol concentration. The new pharmacokinetic model based on data from Indian patients is comparable in performance to the commercially available Marsh pharmacokinetic model.

Measured versus predicted blood propofol concentrations in children during scoliosis surgery.

Propofol anesthesia is preferred during scoliosis surgery because it suppresses evoked potential spinal cord function less than other drugs and better enables the detection of spinal cord ischemia. In this study, we determined the difference between the true and predicted blood propofol levels during target-controlled infusions in children during scoliosis surgery. Arterial blood propofol measured concentrations (Cm) were compared with predicted concentrations (Cp) approximately every 30 minutes during the maintenance phase of anesthesia in 20 children. Whole blood propofol concentrations were measured using a point-of-care blood propofol analyzer. Anesthesia management was not affected by the study. The median performance error, median absolute performance error, wobble, and divergence were calculated. Children were aged 9 to 17 years and weighed 26.5 to 95 kg. The Paedfusor model was used in 16 children and the Marsh model in 4 children. In 154 blood propofol measurements, the mean difference between the Cm and Cp was 1.5 µg·mL (limits of agreement, -1.4 to 4.5 µg·mL), and the mean performance error was 44.7% (limits of agreement, -40.1% to 130.2%). The median performance error and median absolute performance error for the whole group were 39.8% (range, -20.9% to 103.3%) and 39.8% (range, 20%-103.3%), respectively. The performance errors improved with increase in duration of infusion (divergence, -2.2 [range, -1.03 to 0.13]). Cm was almost always larger than Cp except in 2 children who had consistently lower Cm than Cp (lowest Cm(s) were 1.74 and 1.96 µg·mL when the Cp was 3 µg·mL); both had the Paedfusor model and their body weights were 28 and 33 kg. Propofol target-controlled infusion models had poor performance characteristics in children undergoing scoliosis surgery. Point-of-care propofol assay may enable adjustment of the infusion to better achieve the intended blood level.