Washington University Emergency Medicine Journal Club – May 2024
Hello all,
This month’s journal club will focus on ultra-high dose nitroglycerin and IV nitroglycerin bolus for SCAPE (sympathetic crashing acute pulmonary edema). Please see the attached articles and make every effort to attend.
The PGY-1 and PGY-2 articles will be reviewed using the Therapy form; the PGY-3 and PGY-4 articles will be reviewed using the Case Series form.
Vignette
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
Population: 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
chosen.
Article 1: Levy P, Compton S, Welch R, et al. 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. [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. [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. [AnswerKey]
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. [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.