1,354,642 research outputs found
Clinical Validation Of The Eleveld Propofol Pharmacokinetic-pharmacodynamic Model Used In General Anaesthesia
No full textBackground: Target-controlled infusion (TCI) systems are used to facilitate anesthetic drug administration. Current systems use pharmacokinetic models developed for specific patient groups. Their use in patients with different characteristics to that of the development population is therefore discouraged. Recently, Eleveld et al1 developed a propofol PK-PD model for broad application. The aim of the current study was to validate it in a broad range of patients, from children to the elderly, and in obese adults. Methods: The medical ethics committee of the University Medical Center Groningen (reference METc2018/216) approved the study. Four groups of 25 patients undergoing an elective surgical procedure were included. Eligibility criteria for the four groups were: children (age ≥ 3 years and <18 years), adults (age 18 - <70 years; body mass index (BMI) <30 kg/m2), elderly patients (age ≥ 70 years) and obese adults (age 18 - <70 years; BMI ≥30 kg/m2). Arterial blood samples were collected at 5, 10, 20, 30, 40 and 60 minutes after start of propofol TCI, and every 30 minutes thereafter until end of surgery or 10 samples total had been collected. Bilateral bispectral index (BIS) was recorded and anesthesiologists were instructed to adjust the target propofol concentration to maintain the BIS in the range 40-60. Predictive performance of the model was assessed using the Varvel criteria2. Results: For PK predictive accuracy, the Eleveld model showed acceptable bias (<±20%) in children, adults and the obese (-4.4%, -14.1%, -14.1% respectively) but there was some bias (-27%) for the elderly. Precision was acceptable (<30%) for all groups. None of the other PK models tested (Schnider, Marsh, Cortinez, Paedfusor and Kataria) performed better than the Eleveld model at a significance level of P<0.01. For BIS, bias and precision was smaller than ±2 and 10 BIS units, respectively, for all groups. The median (5-95 percentile) observed BIS during the procedure was 46 (33-63) and the target concentration was 3.1 (2.2-4.2) µg/ml which was 102% (85-138) of the age-adjusted concentration for 50% drug effect (Ce50). Conclusion: The Eleveld PK-PD model is sufficiently accurate to achieve clinically relevant BIS values using effect-site target concentrations close to the individual Ce50. There is some bias in PK predictions for the elderly, but this does not appear to be a limitation for clinical practic
Environmental forcing of aquatic ecosystem variability: A matter of perspective
Full text linkVerburg, P.H. [Promotor]Simis, S.G.H. [Copromotor]Eleveld, M.A. [Copromotor
Prospective clinical validation of the Eleveld propofol pharmacokinetic-pharmacodynamic model in general anaesthesia
No full textBackground: Target-controlled infusion (TCI) systems incorporating pharmacokinetic (PK) or PK-pharmacodynamic (PKPD) models can be used to facilitate drug administration. Existing models were developed using data from select populations, the use of which is, strictly speaking, limited to these populations. Recently a propofol PK-PD model was developed for a broad population range. The aim of the study was to prospectively validate this model in children, adults, older subjects, and obese adults undergoing general anaesthesia.
Methods: The 25 subjects included in each of four groups were stratified by age and weight. Subjects received propofol through TCI with the Eleveld model, titrated to a bispectral index (BIS) of 40e60. Arterial blood samples were collected at 5, 10, 20, 30, 40, and 60 min after the start of propofol infusion, and every 30 min thereafter, to a maximum of 10 samples. BIS was recorded continuously. Predictive performance was assessed using the Varvel criteria.
Results: For PK, the Eleveld model showed a bias < ±20% in children, adults, and obese adults, but a greater bias ( 27%) in older subjects. Precision was <30% in all groups. For PD, the bias and wobble were <5 BIS units and the precision was close to 10 BIS units in all groups. Anaesthetists were able to achieve intraoperative BIS values of 40e60 using effect-site target concentrations about 85e140% of the age-adjusted Ce50.
Conclusions: The Eleveld propofol PK-PD model showed predictive precision <30% for arterial plasma concentrations and BIS predictions with a low (population) bias when used in TCI in clinical anaesthesia practice
Welfare to Work and the Question of Social Justice: An Interdisciplinary Normative Perspective on Welfare Policies. An introduction
No full textHet verbod op verplichte arbeid en het recht op vrije arbeidskeuze bij re-integratie en tegenprestatie
No full textClinical Validation Of The Eleveld Propofol Pharmacokinetic-pharmacodynamic Model Used In General Anaesthesia
No full textBackground: Target-controlled infusion (TCI) systems are used to facilitate anesthetic drug administration. Current systems use pharmacokinetic models developed for specific patient groups. Their use in patients with different characteristics to that of the development population is therefore discouraged. Recently, Eleveld et al1 developed a propofol PK-PD model for broad application. The aim of the current study was to validate it in a broad range of patients, from children to the elderly, and in obese adults. Methods: The medical ethics committee of the University Medical Center Groningen (reference METc2018/216) approved the study. Four groups of 25 patients undergoing an elective surgical procedure were included. Eligibility criteria for the four groups were: children (age ≥ 3 years and <18 years), adults (age 18 - <70 years; body mass index (BMI) <30 kg/m2), elderly patients (age ≥ 70 years) and obese adults (age 18 - <70 years; BMI ≥30 kg/m2). Arterial blood samples were collected at 5, 10, 20, 30, 40 and 60 minutes after start of propofol TCI, and every 30 minutes thereafter until end of surgery or 10 samples total had been collected. Bilateral bispectral index (BIS) was recorded and anesthesiologists were instructed to adjust the target propofol concentration to maintain the BIS in the range 40-60. Predictive performance of the model was assessed using the Varvel criteria2. Results: For PK predictive accuracy, the Eleveld model showed acceptable bias (<±20%) in children, adults and the obese (-4.4%, -14.1%, -14.1% respectively) but there was some bias (-27%) for the elderly. Precision was acceptable (<30%) for all groups. None of the other PK models tested (Schnider, Marsh, Cortinez, Paedfusor and Kataria) performed better than the Eleveld model at a significance level of P<0.01. For BIS, bias and precision was smaller than ±2 and 10 BIS units, respectively, for all groups. The median (5-95 percentile) observed BIS during the procedure was 46 (33-63) and the target concentration was 3.1 (2.2-4.2) µg/ml which was 102% (85-138) of the age-adjusted concentration for 50% drug effect (Ce50). Conclusion: The Eleveld PK-PD model is sufficiently accurate to achieve clinically relevant BIS values using effect-site target concentrations close to the individual Ce50. There is some bias in PK predictions for the elderly, but this does not appear to be a limitation for clinical practic
Schnider and Eleveld Models for Propofol Target-Controlled Infusion Anesthesia: A Clinical Comparison
Full text linkBackground: Various pharmacokinetic/pharmacodynamic (PK/PD) models have been developed to accurately dose propofol administration during total intravenous anesthesia with target-controlled infusion (TIVA-TCI). We aim to clinically compare the performance of the Schnider model and the new and general-purpose Eleveld PK/PD model during TIVA-TCI. Methods: We conducted a prospective observational study at a single center, enrolling 78 female patients, including 37 adults (aged < 65 years) and 41 elderly patients (aged ≥ 65 years). These patients underwent breast surgery with propofol-remifentanil TIVA-TCI guided by the bispectral index (BIS) for depth of anesthesia monitoring (target value 40–60) and the surgical plethysmographic index (SPI) for antinociception monitoring (target value 20–50) without neuromuscular blockade. The concentration at the effect site of propofol (CeP) at loss of responsiveness (LoR) during anesthesia maintenance (MA) and at return of responsiveness (RoR), the duration of surgery and anesthesia (min), the time to RoR (min), the propofol total dose (mg), the deepening of anesthesia events (DAEs), burst suppression events (BSEs), light anesthesia events (LAEs) and unwanted spontaneous responsiveness events (USREs) were considered to compare the two PK/PD models. Results: Patients undergoing BIS-SPI-guided TIVA-TCI with the Eleveld PK/PD model showed a lower CeP at LoR (1.7 (1.36–2.25) vs. 3.60 (3.00–4.18) μg/mL, p < 0.001), higher CePMA (2.80 (2.55–3.40) vs. 2.30 (1.80–2.50) μg/mL, p < 0.001) and at RoR (1.48 (1.08–1.80) vs. 0.64 (0.55–0.81) μg/mL, p < 0.001) than with the Schnider PK/PD model. Anesthetic hysteresis was observed only in the Schnider PK/PD model group (p < 0.001). DAEs (69.2% vs. 30.8%, p = 0.001) and BSEs (28.2% vs. 5.1%, p = 0.013) were more frequent with the Eleveld PK/PD model than with the Schnider PK/PD model in the general patient population. DAEs (63.2% vs. 27.3%, p = 0.030) and BSEs (31.6% vs. 4.5%, p = 0.036) were more frequent with the Eleveld PK/PD model than with the Schnider PK/PD model in the elderly. Conclusions: The Schnider and Eleveld PK/PD models impact CePs differently. A greater incidence of DAEs and BSEs in the elderly suggests more attention is necessary in this group of patients undergoing BIS-SPI-guided TIVA-TCI with the Eleveld PK/PD than with the Schnider model
Prospective clinical validation of the Eleveld propofol pharmacokinetic-pharmacodynamic model in general anaesthesia
Full text linkBACKGROUND: Target-controlled infusion (TCI) systems incorporating pharmacokinetic (PK) or PK-pharmacodynamic (PK-PD) models can be used to facilitate drug administration. Existing models were developed using data from select populations, the use of which is, strictly speaking, limited to these populations. Recently a propofol PK-PD model was developed for a broad population range. The aim of the study was to prospectively validate this model in children, adults, older subjects, and obese adults undergoing general anaesthesia.METHODS: The 25 subjects included in each of four groups were stratified by age and weight. Subjects received propofol through TCI with the Eleveld model, titrated to a bispectral index (BIS) of 40-60. Arterial blood samples were collected at 5, 10, 20, 30, 40, and 60 min after the start of propofol infusion, and every 30 min thereafter, to a maximum of 10 samples. BIS was recorded continuously. Predictive performance was assessed using the Varvel criteria.RESULTS: For PK, the Eleveld model showed a bias < ±20% in children, adults, and obese adults, but a greater bias (-27%) in older subjects. Precision was <30% in all groups. For PD, the bias and wobble were <5 BIS units and the precision was close to 10 BIS units in all groups. Anaesthetists were able to achieve intraoperative BIS values of 40-60 using effect-site target concentrations about 85-140% of the age-adjusted Ce50.CONCLUSIONS: The Eleveld propofol PK-PD model showed predictive precision <30% for arterial plasma concentrations and BIS predictions with a low (population) bias when used in TCI in clinical anaesthesia practice.</p
- …
