Revisiting vasodilator strategy in sympathetic crashing acute pulmonary edema: A meta-analysis of high-dose nitroglycerin efficacy and safety

AIM: To evaluate the efficacy and safety of high-dose intravenous nitroglycerin compared with conventional low-dose strategies in patients with SCAPE. METHODS: A comprehensive search of PubMed, Scopus, Web of Science, and Cochrane Library databases was performed from inception to March 2026. Eligible studies included randomized controlled trials (RCTs) and observational studies assessing high-dose NTG (≥100 μg/min or equivalent bolus regimens) in adult patients with SCAPE. RESULTS: Six studies (n = 534 in comparative analysis) were included. No significant differences were observed in intubation rates (RR 0.91; 95% CI, 0.11-7.73), intensive care unit (ICU) admission (RR 0.92; 95% CI, 0.81-1.05), or ICU length of stay (MD -31.29 h; 95% CI, -330.32 to 267.73). Notably, high-dose NTG showed numerically higher estimates of achieving the target systolic blood pressure reduction compared with low-dose NTG (RR 1.70; 95% CI, 0.36-8.10; p = 0.15). High-dose NTG was associated with a modest increase in hypotension risk (RR 1.41; 95% CI, 1.02-1.94). Single-arm analysis demonstrated high rates of symptom resolution (95%) and relatively low intubation (10%) and ICU admission (12%) rates. Subgroup analyses showed rapid improvements in blood pressure, respiratory rate (RR), and oxygenation. CONCLUSION: High-dose intravenous nitroglycerin provides rapid hemodynamic and symptomatic improvement in SCAPE. However, these benefits do not clearly translate into reductions in intubation or ICU utilization and are accompanied by a modest increase in hypotension risk. Interpretation is constrained by variable low-dose comparator definitions, differing high-dose regimens, and inconsistent reporting of co-interventions.