Washington University Emergency Medicine Journal Club- May 2024


It’s nine o’clock on a Saturday, and the regular crowd shuffles in (you know…Charles, Tiffany, Jason) when EMS brings Mr. H to TCC-1. Per report Mr. H has a history of congestive heart failure and hypertension and presents with acute onset of shortness of breath while watching the Cardinals game earlier in the evening. He arrives very dyspneic, in severe distress, with a blood pressure of 220/145, O2 saturation 93% on a non-rebreather, and a HR of 113. He has diffuse rales on your exam, denies chest pain, denies recent lower extremity swelling, and reports adherence with his anti-hypertensives and diuretics.

You are concerned for SCAPE (sympathetic crashing acute pulmonary edema) and immediately place the patient on BiPAP and request a nitroglycerin drip, which you start a 100 mcg/min with a plan to uptitrate to achieve blood pressure control and improvement in symptoms. Your attending asks if you would consider an IV bolus of nitroglycerin (which you have never given before) and if you’re sure you don’t want to start the drip at a significantly higher rate.

You continue managing the patient, who improves significantly with BiPAP and the nitroglycerin drip, but continue to ponder your attending’s questions. When your shift ends, you decide to look further into the literature to see what the evidence shows…

PICO Question

Adult patients presenting to the ED with sympathetic crashing acute
pulmonary edema (SCAPE)
Intervention: IV bolus nitroglycerin + other standard care
Comparison: Standard care with continuous IV nitroglycerin infusion
Outcome: Need for intubation, mortality, ICU admission, ICU and hospital length of
stay, clinically significant hypotension, stroke, myocardial infarction

Search Strategy

PubMed was searched using the term “nitroglycerin bolus” which resulted in 413
citations (https://tinyurl.com/rvyz5mua). From these, 4 relevant articles were

Article 1: Levy P, Compton S, Welch R, Delgado G, Jennett A, Penugonda N, Dunne R, Zalenski R. Treatment of severe decompensated heart failure with high-dose intravenous nitroglycerin: a feasibility and outcome analysis. Ann Emerg Med. 2007 Aug;50(2):144-52. doi: 10.1016/j.annemergmed.2007.02.022. Epub 2007 May 23. PMID: 17509731. Answer Key.

Article 2: Wilson SS, Kwiatkowski GM, Millis SR, Purakal JD, Mahajan AP, Levy PD. Use of nitroglycerin by bolus prevents intensive care unit admission in patients with acute hypertensive heart failure. Am J Emerg Med. 2017 Jan;35(1):126-131. doi: 10.1016/j.ajem.2016.10.038. Epub 2016 Oct 18. PMID: 27825693. Answer Key.

Article 3: Nashed AH, Allegra JR. Intravenous nitroglycerin boluses in treating
patients with cardiogenic pulmonary edema. Am J Emerg Med. 1995
Sep;13(5):612-3. Answer Key.

Article 4: Mathew R, Kumar A, Sahu A, Wali S, Aggarwal P. High-Dose Nitroglycerin Bolus for Sympathetic Crashing Acute Pulmonary Edema: A Prospective Observational Pilot Study. J Emerg Med. 2021 Sep;61(3):271-277. doi: 10.1016/j.jemermed.2021.05.011. Epub 2021 Jun 30. PMID: 34215472. Answer Key.

Bottom Line:

Sympathetic crashing acute pulmonary edema (SCAPE)—formerly referred to as flash pulmonary edema—is characterized by a sudden rise in blood pressure resulting in the rapid development of pulmonary edema leading to dyspnea, hypoxia, and respiratory distress. The primary management includes the use of positive pressure ventilation, either by continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP), combined with nitroglycerin. Nitroglycerin leads to both venodilation, thereby decreasing preload to the heart, and arterial dilation, which decreases afterload. The doses required to affect the arterial system are typically much higher than those used for ischemic chest pain, leading to the frequent use of high-dose IV nitroglycerin in patients with SCAPE, with rates often as high as 200-300 mcg/minute. Some institutions also use bolus doses of IV nitroglycerin, often as high 1-2 mg over 2 minutes, in the initial phase of management.

Literature supporting bolus doses of IV nitroglycerin in the management of SCAPE is limited, but does suggest utility and safety with this approach. Two cases series published over two decades apart (Nashed 1995, Mathew 2021) using bolus doses as high as 0.4 mg and 1 mg, respectively, in addition to continuous nitroglycerin infusions found that symptom resolution occurred in 83.3% of patients within 30 minutes in the former study and 96% of patients within 6 hours in the latter. No incidents of clinically relevant hypotension occurred in either series.

A retrospective observational study from Detroit Receiving Hospital (Wilson 2017) found that patients receiving bolus IV nitroglycerin without continuous infusion were significantly less likely to require ICU admission (48.4%) than those receiving a continuous infusion alone (68.7%) or a combination of bolus and continuous infusion (83%; p = 0.0001). They also had lower total hospital LOS (bolus = median 3.7 days; infusion = 4.7 days; and combination = 5.0 days; P = .02). In-hospital mortality, hypotension, myocardial injury, or worsening renal function occurred with similar frequency in the groups. It should be noted that the primary outcome (need for ICU admission) was likely influenced by hospital policy dictating that all patients on a continuous nitroglycerin infusion require ICU admission.

A prospective, case-control study, also from Detroit Receiving and its sister hospital (Sinai-Grace) compared patients who patients who received an initial 2 mg bolus of IV nitroglycerin, following an infusion at a rate of 0.3 to 0.5 mcg/kg/min, with a control group treated without bolus dosing (Levy 2007). Endotracheal intubation within 6 hours occurred in 13.8% of patients treated with bolus nitroglycerin and 26.7% of the control group (relative risk 0.52; 95% CI 0.18 to 1.45). Cardiovascular complications (hypotension requiring intervention or acute MI) occurred in 20.7% (95% CI 9.1% to 37.8%) of bolus patients and 28.9% (95% CI 17.3% to 43.1%) of the control group. Patients receiving IV bolus nitroglycerin were much less likely to require ICU admission compared to the control group (37.9% vs. 80%), but again this may have been influenced by hospital policy regarding continuous nitroglycerin infusions. The mean initial intravenous nitroglycerin infusion rate for the nonintervention group was 31.7 mcg/minute, much lower than the higher doses typically required to achieve afterload reduction (100-300 mcg/min).

While limited, the data suggest that boluses of IV nitroglycerin for the management of SCAPE, up to 1 to 2 mg given over 2 minutes, are safe and effective. There is no evidence that bolus dosing is superior (or even noninferior) to high-dose continuous nitroglycerin infusions.