High-dose versus low-dose intravenous nitroglycerine for sympathetic crashing acute pulmonary edema: a randomised controlled trial.

OBJECTIVES: Sympathetic crashing acute pulmonary edema (SCAPE) is a subset of heart failure with a dramatic presentation. The unique physiology of this condition requires a different management strategy from the conventional practice. The trial objective was to compare the efficacy of high-dose and low-dose GTN in patients with SCAPE. METHODS: This was an open-label randomised control trial conducted in a tertiary care teaching hospital in India from 11 November 2021 to 30 November 2022. Consenting participants were randomised to high-dose GTN or conventional low-dose GTN. The primary outcome was symptom resolution at 6 hours and 12 hours. Secondary outcomes included intubation rates, admission rates, length of hospital stay, and any short-term adverse effects of GTN and major adverse cardiac events (MACE) at 30 days. RESULTS: Fifty-four participants were included (26 high-dose GTN, 26 low-dose GTN). At 6 hours, symptom resolution was seen in 17 patients (65.4%) in the 'high-dose' group, compared with 3 (11.5%) in the 'low-dose' group (p<0.001). At 12 hours, 88.5% of patients had a clinical resolution in the 'high-dose' arm versus 19.5% in 'low-dose' arm . The low-dose group had longer median hospital stay (12 hours vs 72 hours), more frequent MACE (3.8% vs 26.9%, p=0.02) and a higher intubation rate (3.8% vs 19.2%, p=0.08). The only short-term adverse effect seen was a headache in both the groups. CONCLUSION: In SCAPE, patients receiving high-dose GTN (>100 mcg/min) had earlier symptom resolution compared with the conventional 'low dose' GTN without any significant adverse effects. TRIAL REGISTRATION: Clinical trial registry of India (CTRI/2021/11/037902).

Taming the Tiger: Ultra high dose nitroglycerin in managing sympathetic crashing acute pulmonary edema patient.

INTRODUCTION: Sympathetic Crashing Acute Pulmonary Edema (SCAPE) lies on the end of the acute heart failure syndrome spectrum with pulmonary edema in all lung zones. NTG at lower doses (10-20 µg/min) cause preload reduction, and at higher doses (> 100 µg/min) causes after-load reduction by arterial dilatation. The main aim is to decrease the afterload at the earliest to cut the vicious cycle caused by sudden sympathetic upsurge. To our knowledge, this is the highest nitroglycerin dose usage in the literature. CASE: A 60-year-old male with no known prior co-morbidities presented to our Emergency with complaints of acute onset severe shortness of breath, which was also associated with extreme diaphoresis, agitation, anxiety, and palpitations. On Examination, the patient was hypoxic and hypertensive with severe tachypnea and tachycardia. On Auscultation, diffuse bilateral crackles in all areas were heard. Point of care ultrasound showed bilateral B-profile in all lung zones, inferior vena cava was >50% collapsible. We managed the patient with non-invasive ventilation and ultrahigh dose nitroglycerin/ highest ever- 9 mg intravenous bolus with 76 mg infusion. The patient had improved within hours and did not require oxygen. The patient was discharged from the emergency after a few hours of observation. DISCUSSION: SCAPE occurs due to a vicious spiral involving increasing sympathetic outflow, excessive afterload, and worsening heart failure. The central, defining pathophysiological feature of SCAPE is pathologically elevated afterload due to systemic vasoconstriction and hypertension. SCAPE patients may be euvolemic, hypovolemic or hypervolemic. The problem is shift of fluid into the lungs rather than hypervolemia. The emphasis on treating pulmonary edema has shifted from diuretics to vasodilators, especially high-dose nitrates, combined with non-invasive positive pressure ventilation. CONCLUSION: This is the first report describing the safe and effective administration of ultra-high dose bolus/ highest dose ever and prolonged high-dose infusion for SCAPE, along with Non-invasive ventilation, which has prevented mechanical ventilation and mortality. High doses of intravenous NTG are extremely effective and safe for SCAPE patients.