Population pharmacokinetics of intravenous clonidine for sedation during paediatric extracorporeal membrane oxygenation and continuous venovenous hemofiltration
Bibliographic record
Abstract
AIMS: Clonidine is used for sedation in the paediatric intensive care unit. Extracorporeal membrane oxygenation (ECMO) provides temporary support if respiratory and cardiac function is threatened. ECMO influences the pharmacokinetics of drugs. Clonidine during paediatric ECMO cannot be effectively titrated as PK data are lacking. The aim of this study is to describe clonidine PK in a particular ECMO system and propose dosing guidelines for children on this particular ECMO circuit. METHODS: All children below the age of 18 years who received clonidine during ECMO were eligible. The pharmacokinetic analysis was conducted by nonlinear mixed effect modelling, which enables to establish the separate influences of determinants on drug blood level and to provide individualized dosing. RESULTS: Twenty-two patients, median age 1 month (IQR 6.4) and weight at inclusion 4 kg (IQR 3.1) were included of whom 90% in addition to ECMO received pre-emptive continuous venovenous hemofiltration to optimize fluid balance. The clonidine clearance rate was two-fold that measured in patients not on ECMO. Clearance increased steeply with postnatal age: at days 6, 8 and 10, respectively 30%, 50% and 70% of the adult clearance rate was reached. The use of diuretics was associated with a lower clearance. The volume of distribution increased by 55% during ECMO support. CONCLUSION: Our findings suggest that a higher dose of clonidine may be needed during ECMO. The PK parameters on ECMO and the dosing guidelines proposed hold the potential to improve sedation practices on ECMO but need to be repeated with different ECMO systems.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".