Pharmacodynamic Safety Endpoints for Propofol Anesthesia in Children by Age and Sex: A Multicohort Observational Study
Bibliographic record
Abstract
BACKGROUND: Propofol is a commonly used intravenous sedative and general anesthetic, with rapid onset and short duration of action. It has a narrow therapeutic index and significant interindividual variability in dosing requirements, which may elevate risks of its use, particularly in children. AIMS: We aimed to quantify the doses required to induce loss of consciousness and apnea in children by age and sex to contribute to tailored propofol dosing recommendations for improved safety and efficacy in pediatric anesthesia. METHODS: for 20 s) up to a maximum dose of 10 mg/kg. We measured the propofol dose required to reach pharmacodynamic endpoints, including loss of eyelash reflex (LOER) and apnea, and estimated the effect of sex and age on these doses. RESULTS: Data were available for 318 participants, with 162 females and a median (interquartile range) age of 8.1 (5.3-12.9) years. The mean (SD) propofol dose to LOER was 2.65 (0.69) mg/kg with no effect of sex (-0.10 mg/kg for male, 95% confidence interval (CI) -0.26 to 0.05, p = 0.183) or age (0.0 mg/kg per year, 95% CI -0.02 to 0.02, p = 0.876). The mean (SD) propofol dose to apnea was 6.82 (1.64) mg/kg, with significant effects of both sex (+0.67 mg/kg for male, 95% CI 0.30 to 1.03, p < 0.001) and age (-0.14 mg/kg per year, 95% CI -0.19 to -0.1, p < 0.001). Apnea was not reached in 62 participants. CONCLUSIONS: Older and female children exhibited narrower therapeutic indices for the margin between LOER and apnea. This requires heightened vigilance, especially when maintaining spontaneous respiration. A planned genome-wide association study may identify pharmacogenetic-pharmacodynamic relationships and correlations with genetic ancestry. TRIAL REGISTRATION: The trial was registered on clinicaltrials.gov before enrolment (NCT04164264; date of registration 2019-11-15).
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.003 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| 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".