Dose Derivation of Once-Daily Dosing Guidelines for Gentamicin in Critically Ill Pediatric Patients
Bibliographic record
Abstract
OBJECTIVES: To determine dose and eligibility criteria for once-daily dosing (ODD) of gentamicin in critically ill pediatric patients. METHODS: Retrospective chart review of patients admitted to the Pediatric Intensive Care Unit or Cardiac Critical Care Unit at The Hospital for Sick Children (SickKids) who received traditionally dosed intravenous (IV) gentamicin (January 2008 to June 2010). Statistically significant patient characteristics associated with gentamicin pharmacokinetic (PK) parameters were determined by multiple linear regression. Binary partitioning was used to set critical values for these characteristics to derive dose for ODD of gentamicin. Feasibility of implementing ODD of gentamicin in critically ill children was assessed using individualized PK parameters to simulate area under the concentration-time curves and drug-free intervals while targeting a maximum concentration (C(max)) of 16-20 mg/L. Eligibility criteria were determined by patient characteristics that had a statistically significant impact on gentamicin PK. RESULTS: Volume of distribution (V(d)) and elimination rate constant (k(e)) were calculated for 140 patients. Weight and admission unit were significantly associated with weight-normalized V(d) (Vd/kg), whereas age and serum creatinine (SCr) were significantly associated with k(e). Weight <5 kg and SCr ≥20% over age-specific upper normal limit before gentamicin initiation were associated with prolonged gentamicin elimination. Gentamicin 6 mg/kg IV every 24 hours, the dose at which the highest percentage of patients achieved C(max), area under the curve, and drug-free interval within target ranges simultaneously, was selected as the proposed ODD regimen. CONCLUSIONS: A regimen of gentamicin 6 mg/kg IV every 24 hours for Pediatric Intensive Care Unit/Cardiac Critical Care Unit patients at SickKids weighing ≥5 kg with SCr <20% above age-specific upper normal limit before initiation of gentamicin is proposed.
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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 | 0.004 | 0.030 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".