Norepinephrine Intermittent Intravenous Boluses to Prevent Hypotension During Spinal Anesthesia for Cesarean Delivery: A Sequential Allocation Dose-Finding Study
Bibliographic record
Abstract
BACKGROUND: The use of phenylephrine as the first-line agent for prevention and treatment of maternal hypotension during cesarean delivery (CD) may reduce cardiac output, posing a theoretical risk to mother and fetus. Norepinephrine has been suggested as a potential alternative, because its β-adrenergic effects might result in greater heart rate and cardiac output than phenylephrine. The use of norepinephrine to prevent and treat hypotension during CD is new, and its use as a bolus has not been fully determined in this context. The purpose of this study was to determine the effective norepinephrine dose, when given as intermittent intravenous (IV) boluses, to prevent postspinal hypotension in 90% of women undergoing elective CD (ED90). METHODS: This was a prospective, double-blind sequential allocation dose-finding study, using the biased coin up-and-down design. Forty-term pregnant women undergoing elective CD under spinal anesthesia received a set intermittent norepinephrine bolus of either 3, 4, 5, 6, 7, or 8 µg every time their systolic blood pressure (SBP) fell to below 100% of baseline. The primary outcome was the success of the norepinephrine regimen to maintain SBP at or above 80% of baseline, from induction of spinal anesthesia to delivery of the fetus. Secondary outcomes included nausea, vomiting, hypertension (SBP > 120% of baseline), bradycardia (<50 bpm), upper sensory level of anesthesia to ice cold and umbilical artery and vein blood gases. The ED90 and 95% confidence intervals (CIs) were estimated using both truncated Dixon and Mood and isotonic regression methods. RESULTS: The estimated ED90 of norepinephrine was 5.49 µg (95% CI, 5.15-5.83) using the truncated Dixon and Mood method and 5.80 µg (95% CI, 5.01-6.59) using the isotonic regression method. CONCLUSIONS: The use of intermittent IV norepinephrine boluses to prevent spinal-induced hypotension in elective CD seems feasible and was not observed to be associated with adverse outcomes. Practically, we suggest an ED90 dose of 6 µg. Further work is warranted to elucidate the comparative effects of intermittent IV bolus doses of phenylephrine and norepinephrine, in terms of efficacy and safety.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".