Effects of Cardiopulmonary Bypass on Sufentanil Pharmacokinetics in Patients Undergoing Coronary Artery Bypass Surgery
Bibliographic record
Abstract
BACKGROUND: Complete pharmacokinetic modeling, including assessment of the effect of cardiopulmonary bypass (CPB) on sufentanil disposition, has not been reported. The aims of this investigation were to define a model that accurately predicted sufentanil concentrations during and after cardiac surgery and to determine if CPB had a clinically significant impact on sufentanil pharmacokinetics. METHODS: Population pharmacokinetic modeling was applied to data from 21 patients undergoing coronary artery bypass grafting. The predictive ability of models was assessed by calculating bias, accuracy, and measured:predicted concentration ratios versus time. A simple three-compartment model, without covariates, was initially compared with models having weight or gender as covariates and was subsequently used as the foundation for multiple CPB-adjusted models (allowing step-changes of parameters at the start or end of CPB). The primary criterion for choosing more complex models was a significant improvement in log-likelihood; secondary criteria were significant improvement in bias or accuracy. RESULTS: Neither covariate (weight or gender) models improved bias or accuracy compared with the simple three-compartment model. A final CPB-adjusted model with V2 and Cl3 changing at the start of CPB and V1, Cl2, and Cl3 changing at the end of CPB had significantly greater log-likelihood values when compared with the simple three-compartment model and with less elaborate CPB-adjusted models. However, bias and accuracy for this final model were not significantly different from the simple three-compartment model. CONCLUSIONS: When sufentanil is infused at a constant rate, with initiation of CPB, a pharmacokinetic model adjusted for CPB predicts that the sufentanil concentration will decrease approximately 17% and that it will begin to return to the prebypass concentration 12 min after initiation of CPB. At the end of CPB, this model also predicts a brief spike of the sufentanil concentration. These predictions reflect changes in the measured sufentanil concentrations. However, compared with a simple, three-compartment model, incorporating step-changes of pharmacokinetic parameters at the start or end of cardiopulmonary bypass (or both) did not significantly improve overall perioperative prediction of measured sufentanil concentrations. This suggests that CPB has clinically insignificant effects on sufentanil kinetics in adults.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".