Managing Patients With Sympathetic Crashing Acute Pulmonary Edema (SCAPE) Using the SCAPE Treatment Protocol: A Case Series

Abstract

Pulmonary edema refers to the accumulation of excessive fluid in the alveolar walls and alveolar spaces of the lungs. It is a life-threatening condition with a high mortality rate and requires immediate assessment and management. Use of intravenous nitroglycerin has been advocated for such cases. The authors present a case series of 3 patients who presented to the emergency department with sympathetic crashing acute pulmonary edema (SCAPE) and were managed with high-dose intravenous nitroglycerin and bilevel positive airway pressure support using the SCAPE treatment protocol, leading to early correction of blood pressure, avoidance of endotracheal intubation, and no episodes of hypotension or rebound hypertension. The authors recommend emergency physicians utilize the SCAPE treatment protocol while managing patients with SCAPE.

Introduction

Heart failure is prevalent worldwide, with high mortality and morbidity rates. Indian data suggests that the prevalence of heart failure ranges from 1.3 to 4.8 million, with an annual incidence of 491,600–1.8 million. ¹

Acute heart failure comprises a wide spectrum of clinical presentations with diverse pathophysiologies and triggering factors. Acute pulmonary edema is a potentially life-threatening presentation of heart failure that is mostly exacerbated by severely elevated blood pressure (BP). ² It is a complex clinical syndrome resulting from functional or structural heart disease that results in impaired ventricular filling or ejection of blood into the systemic circulation. Sympathetic crashing acute pulmonary edema (SCAPE) is a specific subset of acute heart failure in which patients present with acute onset of pulmonary congestion and severe dyspnea with severe systolic hypertension. ³ Clinical guidelines advise reducing BPs by 25% in the acute setting using nitroglycerin (NTG) within the first hour. ⁴ The authors present a case series of 3 patients, highlighting the use of the protocol-based SCAPE treatment protocol (STP) as first described by Matthew et al ⁵ using high-dose NTG and noninvasive positive pressure ventilation (NIPPV). The cases discussed here are those of the first 3 patients treated using the protocol, hence their selection for the case series. To date, the authors have had no patients with negative outcomes while being managed with the STP.

Case Presentations

Case presentation 1

A 43-year-old male with a previous history of coronary artery disease, left ventricular dysfunction with an ejection fraction (EF) of 35%, hypertension, and diabetes mellitus presented to the emergency department (ED) with sudden onset of breathing difficulty beginning 6 hours previous and which was aggravated upon lying down. On arrival to the ED, his BP was recorded as 230/120 mmHg with a heart rate of 115/min and a respiratory rate of 30/min with oxygen saturation (Spo2) at room air of 90% and a random blood sugar level of 214 mg/dL. On auscultation, the patient had reduced air entry and coarse crepitations bilaterally. Two-dimensional echocardiography (2D-echo) was done and was suggestive of global hypokinesia of the left ventricle with an EF of 25% to 30%. His initial N-terminal-pro B-type natriuretic peptide (N-terminal pro-brain natriuretic peptide) level was 6970 pg/mL (range: 0–450 pg/mL), and his troponin I (Trop I) level was 0.69 ng/mL (range: 0–0.04 ng/mL). A bedside chest x-ray was suggestive of pulmonary edema.

Treatment pathway

The patient was put on high-flow oxygen via a non-rebreather mask. The patient was further put on bilevel positive airway pressure (BPAP) support with a 12:6 (inspiratory:expiratory positive airway pressure) setting as per the STP. As per the STP, 1000 mcg of intravenous NTG was given as a bolus dose followed by a 100-mcg/min infusion. The infusion was tapered down every 10 minutes as the BP reduced. At 60 minutes, the BP of the patient had improved to 150/113 mmHg, and his heart rate was 89/min, his respiratory rate was 20/min, and his Spo2 was 95% on room air. He had improved air entry with significant reduction in the crepitations. BPAP was removed about 1 hour after initiation. At the time of transferring the patient to the cardiac care unit, the patient’s BP was 110/80 mmHg. The patient also underwent coronary angiography, which revealed a 90% mid-left anterior descending coronary artery stenosis, and he underwent further percutaneous coronary intervention.

Outcome

The patient was conservatively managed with diuretics and other cardio supportive drugs and was discharged after 4 days on oral beta blockers and nitrates. The patient did not require repeat NTG infusions during admission.

Case presentation 2

A 71-year-old female with a known history of dilated cardiomyopathy, diabetes mellitus, and left ventricular dysfunction (EF: 20%) presented to the ED with sudden onset breathing difficulty at rest and dizziness. Her BP measured on arrival was 190/120 mmHg with a heart rate of 120/min and significant tachypnea of 34/min with an Spo2 of 89% on room air and a random blood sugar level of 191 mg/dL. On auscultation, coarse crepitations were present bilaterally. The patient’s 2D-echo was suggestive of hypokinetic posterior and inferior walls, with an EF of 30%. Her initial NT-proBNP level was 7400 pg/mL, with a normal Trop I level of 0.01 ng/mL.

Treatment pathway

The patient was immediately put on BPAP, as per the STP, and was administered a bolus of 800 mcg of NTG followed by a 100-mcg/min infusion (tapered every 10 minutes). After 1 hour in the ED, the patient showed significant improvement in her vitals as her BP reduced to 140/90 mmHg, heart rate to 99/min, respiratory rate to 22/min, and Spo2 to 92% on room air. BPAP was removed about 1 hour after initiation. At the time of transferring the patient to the cardiac care unit, the patient’s BP was 140/80 mmHg. Repeat NTG infusion during the stay was not required.

Outcome

The patient was discharged on diuretics and oral NTG after 4 days of stay in the cardiac care unit. She followed-up at 10 days, 4 months, and 6 months. She was stable and was continued on antihypertensives, diuretics, antiplatelets, and diabetic medications.

Case presentation 3

A 70-year-old female with a known history of diabetes, hypertension, and coronary artery disease presented to the ED with acute onset of breathing difficulty and chest uneasiness. Her BP on arrival was 190/90 mmHg, with a heart rate of 100/min, and a respiratory rate of 32/min with an Spo2 of 85% on room air. On auscultation of the chest, creptitations were heard bilaterally. A bedside ultrasound was performed, and the results were suggestive of massive pulmonary edema. 2D-echo results were suggestive of akinetic anteroseptum and hypokinetic lateral wall, with an EF of 35%. Her initial NT-proBNP level was 15,500 pg/mL, and her Trop I level was 0.02 ng/mL.

Treatment pathway

The patient was immediately put on BPAP (12:6) support and an NTG bolus of 800 mcg was administered as per the STP. Following the bolus, an infusion of 100 mcg/min was started for the patient followed by 120 mcg/min after 10 minutes while her BP remained unchanged. It was then tapered down over the next hour. After 1 hour, the patient showed significant improvement as her BP improved to 140/80 mmHg, heart rate to 80/min, respiratory rate to 16/min, and Spo2 to 96% on BPAP. NTG infusion was stopped after 1 hour.

Outcome

The patient remained in the ED due to the unavailability of intensive care beds. The BPAP support was tapered down, and the patient was discharged from the ED itself after 2 days. NTG infusions were not required again, and at discharge the patient had a BP of 140/80 mmHg.

None of the patients had any episodes of hypotension or rebound hypertension during their hospital stay. Table 1 lists the comorbid conditions and medications that the patients were on at the time of presentation. Length of stay, NTG dose, and BPs of all 3 cases are shown in Table 2.

Table 1:

Comorbid conditions and medications of the patients at presentation

Patient	Comorbid conditions	Previous medications
1	Coronary artery disease, hypertension, diabetes mellitus, left ventricular dysfunction (EF: 35%)	Aspirin, atorvastatin, atenolol, metformin, sacubitril-valsartan
2	Dilated cardiomyopathy, diabetes mellitus, left ventricular dysfunction (EF: 20%)	Sacubitril-valsartan, human insulin, enalapril
3	Diabetes mellitus, hypertension, coronary artery disease	Sitagliptin, amlodipine, aspirin, rosuvastatin

EF, ejection fraction.

Table 2:

Length of stay, NTG dose, and BPs of all 3 cases

Case report	Total length of stay	NTG bolus	Initial BP	BP @ 60 min	BP at transfer to cardiac care unit
	days	mcg	mmHg	mmHg	mmHg
1	6	1000	230/120	150/113	110/80
2	4	800	190/120	140/90	140/80
3	3	800	190/90	140/80	140/80

BP: blood pressure; NTG: nitroglycerin.

Discussion

This case series of 3 patients highlights the beneficial effects of high-dose NTG and BPAP administration in a protocol-based manner, as recommended in the STP. None of the patients with SCAPE required invasive airway support and all showed significant improvement before being transferred to cardiac care. None of the patients experienced hypotensive episodes as is commonly feared with the administration of high-dose NTG.

SCAPE, a severe form of acute heart failure, is sympathetically induced as a result of reduced perfusion, leading to pulmonary edema. ⁶ Catecholamine release during this sympathetic surge leads to an increase in arterial tone and redistribution of fluid, causing flash pulmonary edema, even in euvolemic patients. ⁷ The shift of fluids in the lungs is the major problem rather than hypervolemia. ⁵ Activation of the renin–angiotensin–aldosterone system leads to an increase in the peripheral vascular resistance and sodium and water reabsorption, which worsens the cardiac function and decreases pulmonary venous return. Hypoxia, dyspnea, and further sympathetic surge ensue as the intravascular fluid shifts into the pulmonary interstitium and alveoli. ⁵ Loop diuretics used to be a regular choice of drug, but they have fallen out of popularity as evidence regarding their benefit in SCAPE patients is scarce. ⁸ Loop diuretics responses peak at 30 minutes to 2 hours and are unlikely to provide immediate relief to patients presenting with SCAPE. Also, as mentioned earlier, redistribution of fluid is the issue, not hypervolemia. Management strategies are now aimed at rapid initiation to reduce arterial tone and hence the elevated afterload. The mainstay of treatment for hypertensive acute heart failure has been vasodilators for reducing preload and afterload. ⁹ Conventional low-dose NTG ( < 100 mcg/min) has not been shown to reduce the arterial tone and hence is not an effective therapy. ¹⁰ NTG is converted to nitric oxide while activating cyclic guanosine monophosphate. This further relaxes smooth muscles, thereby reducing the preload due to venodilatation and, at higher doses, reduces afterload by causing arterial dilatation. ¹¹ Much higher doses (up to 250 mcg/min) have shown beneficial reduction in arterial tones and better patient outcomes. High-dose NTG has also been shown to reduce intubation rates and Intensive Care Unit admissions as compared to low-dose NTG. ¹² High-dose NTG, when compared with low-dose NTG, has been shown to be superior in achieving timely control of BP in acute pulmonary edema. ¹³ Studies have further reported favorable outcomes, including improved BP, shorter length of hospital stay, and decreased mortality when incorporating high-dose NTG. ^3,14 Adding NIPPV to the initial management strategy along with the high-dose NTG further helps in redistributing fluid from the pulmonary spaces, thereby improving ventilation. All the patients in this study had significant improvements in their ventilation and were weaned off the BPAP.

This study’s patients received a maximum NTG infusion rate of 120 mcg/min with no adverse events. Higher doses of up to 400 mcg/min have been given to patients by Stemple et al in their case series with no adverse events noted. ⁶ Hsieh et al gave 1000-mcg boluses every 2 minutes to their patients with SCAPE, who showed even rapid reduction of BP without any adverse effects. Two of those patients had end-stage renal disease. ¹⁵ Brandon et al in their retrospective chart review of 67 patients showcased the use of high-dose NTG (100- to 1000-mcg bolus) for patients with SCAPE. Hypotension was reported in only 3 patients. Fifty-one percent of patients had heart failure as a comorbid condition, while 36% had end-stage renal disease. ¹⁶ Siddiqua et al treated their patient with SCAPE with a bolus dose of 9 mg and a 76-mg infusion over 12 hours. Their patient did not have any episodes of hypotension. It may also be proposed that administration of high-dose NTG seem to be beneficial for both nephrogenic and cardiogenic pulmonary edema.

Conclusion

The STP ⁵ can provide relief to patients within an hour, as seen in the cases presented here. It would be prudent for emergency physicians to use the STP for managing patients with SCAPE presenting to their EDs. Randomized controlled studies need to be performed to further validate the algorithm-based management strategy.