Midazolam infusions for therapeutic management of pediatric refractory status epilepticus: a systematic review
Bibliographic record
Abstract
Objective We aim to determine the optimal dosing of midazolam continuous intravenous infusions for the treatment of pediatric refractory status epilepticus (RSE). Data sources We searched Medline ALL, Embase, Embase Classic, Cochrane CENTRAL, and Web of Science in March 2023 and again in February 2024. Study selection Randomized and non-randomized studies involving pediatric patients who received continuous midazolam for the treatment of RSE were eligible. Two authors independently conducted screening, full-text review, and data extraction. All methods followed PRISMA reporting guidelines. A narrative data synthesis was performed due to data heterogeneity. Data extraction and synthesis Nineteen studies (448 patients) proved eligible; 3 were randomized control trials, while 16 were non-randomized studies. All studies had concerns regarding the risk of bias. Overall, midazolam aborted seizures in 363/448 (81%) participants, with mean effective doses of 1.7–13.0 μg/kg/min (0.17–0.78 mg/kg/h). The remaining 85 participants (19%) who did not achieve seizure cessation received maximum doses of 1.7–32.0 μg/kg/min (0.17–1.92 mg/kg/h) prior to transitioning to another agent. Only 4 studies specified that boluses were given with each titration. Twelve studies reported that seizure cessation occurred at a mean time of 1.4–546.0 min (range 0–720 min) after midazolam initiation. In 8 of these studies, effective midazolam doses clustered at 2.0–5.0 μg/kg/min (0.12–0.30 mg/kg/h), with seizure cessation occurring within 10–70 min in 204/221 (92%) participants. Treatment-associated adverse events included intubation in 42/221 (19%) and hypotension requiring fluids or no intervention in 18/221 (8%). The studies did not differentiate between intubations performed as part of the study protocol or prior to midazolam infusion initiation nor did they specify whether hypotension was related to the co-administration of phenytoin or phenobarbital. Conclusion Data supporting midazolam continuous infusion dosing are limited and heterogeneous. Our findings suggest a potential therapeutic window at rates of 2.0–5.0 μg/kg/min (0.12–0.30 mg/kg/h), with limited adverse risks. Earlier seizure cessation may be achieved by targeting this therapeutic window by starting treatment with higher doses than the typically used 1.0 μg/kg/min (0.06 mg/kg/h) or by rapidly escalating the dose. Systematic Review Registration: PROSPERO, identifier CRD42023413038.
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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 | 0.008 | 0.026 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.011 | 0.007 |
| Bibliometrics | 0.009 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".