Low-dose versus high-dose intravenous nitroglycerin in the treatment of sympathetic crashing acute pulmonary oedema: a systematic review and meta-analysis focusing on efficacy, safety and outcomes
Bibliographic record
Abstract
Objectives Sympathetic crashing acute pulmonary oedema (SCAPE) is a menacing medical emergency and a severe form of acute heart failure that requires urgent intervention. Nitroglycerin (NTG) is commonly used in SCAPE management, but the optimal dosing remains uncertain. This meta-analysis compared the efficacy and safety of high-dose vs low-dose NTG in SCAPE patients, assessing mechanical ventilation need, symptom resolution, hospital stay and major adverse cardiovascular events (MACE). Design Systematic review and meta-analysis conducted per Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, registered in Prospective Register of Systematic Reviews (CRD42024527486). Data sources A comprehensive search in PubMed, Europe PMC and ScienceDirect up to November 2024. Reference lists of included studies were also reviewed. Eligibility criteria Randomised controlled trials (RCTs) and observational studies comparing high-dose NTG (≥100 mcg/min) with low-dose NTG (<100 mcg/min) in SCAPE patients were included. Key inclusion criteria were acute dyspnoea (<6 hours), systolic blood pressure (SBP) ≥160 mmHg, mean arterial pressure (MAP) ≥120 mmHg, respiratory rate (RR) ≥30 breaths/min and sympathetic activation. Exclusion criteria included non-cardiogenic pulmonary oedema, immediate intubation, NTG contraindications, pregnancy and acute coronary syndrome. Data extraction and synthesis Two authors independently screened the titles and abstracts of identified studies for eligibility. Full texts of potentially relevant articles were then reviewed. Any discordance or disagreements were resolved through discussion, with final decisions made by consensus. Risk of bias was assessed using the Newcastle–Ottawa Scale. Meta-analysis was performed using STATA 17.0 and Review Manager 5.4. The Mantel–Haenszel method was applied for dichotomous outcomes, and the inverse variance approach for continuous outcomes. Heterogeneity was assessed via I-squared (I) 2 , with a random-effects model applied when needed. Results Four studies (one RCT, three observational) with 185 SCAPE patients met inclusion criteria. High-dose NTG reduced mechanical ventilation need (RR=0.31, 95% CI: 0.10 to 0.96; p=0.04, I 2 =0%, high certainty) and increased symptom resolution within 6 hours (RR=3.88, 95% CI: 1.95 to 7.71; p<0.001, I 2 =27%, moderate certainty). Hospital stay was shorter (MD=−47.49 hours, 95% CI: −93.76 to −1.21; p=0.04, I 2 =78%, low certainty). No significant difference was found in MACE risk (RR=0.41, 95% CI: 0.06 to 2.68; p=0.35, I 2 =72%, very low certainty). Hypotension incidence was 0% in both groups. Conclusions High-dose NTG improved clinical outcomes in SCAPE, reducing mechanical ventilation need, symptom duration and hospital stay without increased adverse events. These findings suggest high-dose NTG as a promising treatment strategy. Further large-scale studies are needed to optimise dosing protocols.
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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 | 0.009 | 0.020 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.019 | 0.035 |
| Bibliometrics | 0.005 | 0.005 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".