3 Early Experience with Intravenous Milrinone Therapy. A Novel Adjunct in Severe Pulmonary Hypertension of the Newborn (PPHN)
Bibliographic record
Abstract
Inhaled Nitric Oxide (iNO) is the pulmonary vasodilator of choice however some neonates are non-responders or have suboptimal improvements in oxygenation. Milrinone is a phosphodi-esterase III inhibitor which acts by increasing cAMP in cardiac myocytes thus augmenting contractile force (inotropy), improving myocardial relaxation (lusitropy) and inducing relaxation of both pulmonary and systemic vascular smooth muscle. Experimental animal data suggest that the synergistic effects of combined Milrinone and iNO therapy may produce more potent pulmonary vasodilatation, however there is little literature related to use of Milrinone in newborns. To investigate the effects of intravenous Milrinone on efficacy of oxygenation and hemodynamic stability in neonates with severe PPHN. All patients admitted to the NICU over an 18 month period with severe PPHN [Oxygenation index (OI) > 20 & echocardiographic evidence of elevated pulmonary artery systolic pressure with right-left shunting] who received Milrinone therapy were identified. Control patients were matched for birth weight, gestational age, postnatal age and oxygenation index (OI). The effect of intravenous milrinone on OI, iNO requirement, heart rate and blood pressure was examined over a 72 hour period. Secondary endpoints examined included duration of iNO and duration of respiratory support. 9 full term babies who received Milrinone and 14 control patients with severe PPHN were compared. There was no significant difference in gestation (37.4±10.36 vs. 39.25±2.76 wks), birth weight (3602.3±866.3 vs. 3668±649.1 gms) and baseline OI (32.4±8.72 vs. 28.7±6.01) for the Control & Milrinone groups respectively. The average time of commencement of Milrinone was 25.3±13.6 hrs and patients were treated for 77.1±38.9 hrs. There was a significant reduction in OI in both groups over the 72 hour period, however OI was significantly lower in patients who received Milrinone at 2 hrs (p<0.01) and 24 hours (p<0.05) respectively. There was no difference in temporal iNO requirements between the groups. Infants who received Milrinone had a non-significant trend towards improved blood pressure. There was a non-significant trend towards earlier extubation in the Milrinone group (26.1±54.2 hrs vs. 53.8±9.6 hrs, p=0.09) but an increased duration of iNO therapy (p<0.05). Intravenous Milrinone produces early improvements in oxygenation without compromising systemic blood pressure. The ideal inotropic agent for neonatal PPHN remains unknown. Based on this pilot data a prospective randomized controlled trial of intravenous Milrinone therapy is warranted because of its inodilator properties.
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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 | 0.000 | 0.001 |
| 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 | 0.000 | 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".