CONTENTS

• Rapid Reference 🚀
• SCAPE vs subacute pulmonary edema
• Diagnosis
• Triggers of SCAPE
• Principles of treatment
  • CPAP or BiPAP
  • Nitroglycerine
  • Oral vasodilators
  • Volume management & diuresis
  • Opioid
• Podcast
• Questions & discussion
• Pitfalls

---

rapid reference

(back to contents)

---

SCAPE dx & rx checklist ✅

central clinical findings of SCAPE (more)

1. Rapid onset of severe dyspnea.
2. Hypoxemia.
3. Hypertension (SBP >160 mm and/or MAP > 120 mm).
4. Diffuse rales (sometimes with pink frothy sputum).
5. POCUS shows diffuse B-lines.

rx #1: CPAP/BiPAP (more)

• Either works fine (the key is a high expiratory pressure).
• Rapidly uptitrate pressures, to target:
  • CPAP of ~15-18 cm.
  • BiPAP of ~18/15 cm.
• If not tolerated, consider IV midazolam.

rx #2: nitroglycerine (more)

• (1) Bolus of 1,000-2,000 mcg over ~2 minutes (e.g., 400-800 mcg/min for 2.5 min).
• (2) Start infusion at ~100-300 mcg/min.
• (3) Aggressively uptitrate to 800 mcg/min if needed, targeting Bp reduction (SBP <~140 mm).
• (4) After SCAPE episode breaks, aggressively wean down nitroglycerine to avoid hypotension.

rx #3: if refractory hypertension (more)

• Rapid reduction in Bp is essential (e.g., SBP <~140).
• CPAP/BiPAP plus nitroglycerine infusion are usually adequate. If not, then consider:
• (#1) Clevidipine gtt (preferably) or nicardipine gtt.
• (#2) Enalaprilat, 1.25 mg IV (may repeat q15 minutes to a maximal dose of 5 mg).

---

SCAPE vs subacute pulmonary edema

(back to contents)

---

physiology of sympathetic crashing acute pulmonary edema (SCAPE)

• SCAPE occurs due to a vicious spiral involving increasing sympathetic outflow, excessive afterload, and progressively worsening heart failure. Since SCAPE is a vicious spiral, this may develop very rapidly (hence the terminology “flash pulmonary edema”). With aggressive therapy, it may resolve very rapidly as well.
• The central, defining pathophysiological feature of SCAPE is pathologically elevated afterload due to systemic vasoconstriction and hypertension.
• SCAPE patients may be euvolemic or hypovolemic. The problem is a shift of fluid into the lungs, rather than hypervolemia.

fluid overload subacute pulmonary edema (FOSPE)

• FOSPE occurs in patients who develop gradual volume overload. This is compared with SCAPE in the table above.
• SCAPE and FOSPE aren't mutually exclusive. For example, some patients can have SCAPE superimposed upon FOSPE (i.e., gradual volume accumulation over time, which eventually reaches a tipping point and triggers an acute episode of SCAPE). Some authors have proposed that SCAPE and FOSPE represent two extreme forms of pulmonary edema, with some patients lying in between.(29478124)
• Differentiating SCAPE vs. FOSPE is clinically important, because the treatment is different.

nomenclature

• SCAPE is known by a variety of different terms throughout the scientific literature, most notably:
  • Flash pulmonary edema (this is becoming less popular).
  • Hypertensive acute heart failure (preferred terminology in hypertension journals).
  • SCAPE (increasingly utilized in emergency medicine and critical care journals).
• SCAPE is currently the preferred terminology, since it is clear and unique.
• SCAPE patients often meet the criteria for “hypertensive emergency” (i.e., severe hypertension plus target organ dysfunction). However, SCAPE represents a unique entity which requires uniquely tailored therapy. For example, SCAPE develops very rapidly so patients can be promptly lowered to their baseline blood pressure (unlike many patients with hypertensive emergency, who have more gradual elevation of blood pressure and consequently require a more gradual therapeutic reduction). More on hypertensive emergency here.

---

diagnosis

(back to contents)

---

defining clinical features of SCAPE (34215472)

• Rapid onset of respiratory distress (e.g., usually within <6 hours).
• Marked tachypnea and dyspnea.
• Hypoxemia.
• Hypertension (generally SBP>160 mm and/or MAP>120 mm).(31327485, 29776826)
• Diffuse rales on auscultation.
• Pink, frothy sputum may be seen.
• Clinical features of sympathetic activation:
  • Diaphoresis, pallor, appearing extremely unwell.
  • Tachycardia.
  • Agitation.
• Patients may have a history of recurrent episodes of SCAPE.

POCUS

• Aside from history and examination, POCUS is the most powerful tool for the diagnosis of SCAPE.
• Lung sonography:
  • Cardiogenic pulmonary edema generates a pattern of diffuse B-lines throughout the chest, with a thin pleural interface (unlike non-cardiogenic pulmonary edema, which often causes a patchy distribution of B-lines and a thickened pleural interface including patches of subpleural consolidation). Small bilateral pleural effusions may further support the diagnosis of cardiogenic pulmonary edema.
  • Ultrasonography is extremely sensitive for cardiogenic pulmonary edema. If a diffuse pattern of B-lines is not seen in a patient with acute dyspnea, cardiogenic pulmonary edema may be immediately and confidently excluded as the cause of the patient's dyspnea.
• Cardiac ultrasonography should generally reveal some form of heart failure, for example:
  • Systolic heart failure, with reduced left ventricular ejection fraction.
  • Diastolic heart failure may be suggested by left ventricular hypertrophy and a dilated left atrium.
• ⚠️ Note that SCAPE patients may be hypovolemic, hypervolemic, or euvolemic. Therefore, the IVC will not necessarily be distended (nor will the patient necessarily have distended jugular veins).

chest X-ray

• Chest X-ray may also be used as a diagnostic tool. However, X-ray is less sensitive for acute pulmonary edema compared to thoracic ultrasonography. Some patients with SCAPE may not have an unequivocally abnormal chest X-ray.
• Chest x-ray findings may include:
  • Bilateral, fluffy infiltrates centered in the hila (“bat wing pulmonary edema”).
  • Kerley B lines (fluid in the interlobular septa causing fine lines perpendicular to the pleura).
  • Pleural effusion(s).
  • Lack of an alternative diagnosis (e.g., absence of pneumothorax or lobar pneumonia).

⚠️ diagnostic pitfall: other forms of respiratory distress cause hypertension

• Any form of severe respiratory failure may lead to distress and hypertension. Therefore, don't assume that the combination of respiratory failure plus hypertension necessarily implies a diagnosis of SCAPE.
• In uncertain situations, it is reasonable to initiate treatment for SCAPE while simultaneously investigating for other problems.
• One of the hallmarks of SCAPE is rapid improvement with therapy. For patients who aren't turning around rapidly, evaluate carefully for alternative or additional problems, for example:
  • Wrong diagnosis (patient has ARDS, not cardiogenic pulmonary edema).
  • Underlying problem (cardiogenic edema is due to acute STEMI or valvular regurgitation)

brain natriuretic peptide (BNP)

• There is no evidence that BNP testing adds clinical information above and beyond the combination of clinical judgement and POCUS for patients with heart failure.(29887195) This is particularly true of SCAPE patients, wherein the diagnosis is generally not subtle.
• Pragmatically, the turn-around time of the BNP test is too long to be clinically useful for the immediate bedside management of SCAPE.
  • 💡 SCAPE is a bedside clinical diagnosis which must be reached within minutes (on the basis of history, examination, and POCUS).

---

triggers of SCAPE

(back to contents)

---

SCAPE usually results from the combination of an underlying substrate plus an acute trigger. Even after a diagnosis of SCAPE is clear, an acute process causing SCAPE should be considered as well (e.g., myocardial infarction or acute valve dysfunction).

there is usually an underlying substrate of SCAPE:

• Chronic left ventricular failure (especially diastolic heart failure).
  • On the contrary, preserved right ventricular function might also predispose patients to have SCAPE (if the right ventricle is outperforming the left ventricle, this will cause fluid to accumulate in the lungs).
• History of hypertension in ~90% of patients (especially labile hypertension).(27825693)
  • Renal artery stenosis in particular predisposes to SCAPE (a combination known as Pickering syndrome).(33563668)

acute triggers of SCAPE may include:

• Nonadherence with antihypertensives (especially vasodilators such as ACE inhibitors or angiotensin receptor blockers).
• Volume overload (e.g., missed hemodialysis sessions, nonadherence with diuretics).
• Sympathomimetic intoxication.
• Withdrawal (e.g., from clonidine).
• Acute MI.
• Exertion, stress, or anxiety.(31472891)
• Rare causes of acute heart failure (e.g., acute valve dehiscence or viral cardiomyopathy).

---

principles of treatment

(back to contents)

---

The hallmark of SCAPE is rapid deterioration, but aggressive treatment can rapidly reverse this process. Four core principles may be helpful to guide the overall management strategy.

principle #1: the primacy of positive pressure

• The most important intervention is BiPAP or CPAP (which have equivalent efficacy). From an evidentiary standpoint, these interventions are superior to any other intervention for SCAPE.
  • These therapies have been demonstrated in multiple RCTs and meta-analyses to avoid intubation and mortality (table below).
• All possible efforts should be made to use CPAP/BiPAP, for example:
  • Coaching the patient to encourage adherence.
  • Initially gently holding the mask on the patient's face.
  • Medication use to reduce air hunger and improve CPAP/BiPAP tolerance.

principle #2: blood pressure (afterload) control

• Excessively high blood pressure increases the afterload on the left ventricle, promoting fluid backup into the lungs. This is fundamental to the pathophysiology of SCAPE. Therefore, one of the essential goals of treatment is to rapidly reduce the blood pressure.
• There is no well-defined blood pressure goal, but a common target may be to reduce the systolic Bp to <~140 mm rapidly.(28149030, 27262665, 30165588) However, the MAP or diastolic Bp may actually be superior targets, since they are more closely correlated with systemic vascular resistance.(33611627, 32278569)
• Frontline therapies to control hypertension are to maximize BiPAP/CPAP pressure and to maximize the nitroglycerine infusion dose. The vast majority of SCAPE patients can be rendered normotensive with optimization of these two therapies.
• Nicardipine or clevidipine are useful in refractory hypertension:
  • These vasodilators are more potent arterial vasodilators than nitroglycerine, so they may work in patients who are failing to respond to nitroglycerine.(33358327) They may also be useful options in patients on phosphodiesterase type-5 inhibitors (e.g., sildenafil), who have contraindications to nitroglycerine.
  • Clevidipine is ideal, due to its shorter half-life and stronger evidentiary basis in acute heart failure.(20412469, 24655702)
  • Nicardipine has a longer half-life, so there is a risk of causing overshoot hypotension (especially when the underlying SCAPE abates).
• IV Enalaprilat (1.25 mg, may repeat q15 minutes to a maximal dose of 5 mg) is another option for refractory hypertension, but it would be uncommon to actually need this.(28032307, 8822986, 27262665) Oral captopril is less desirable, since it would require removal of the BiPAP or CPAP mask.

principle #3: beta-blockers are contraindicated

• Beta-blockers will impair pump function, so they are generally contraindicated in the context of acute decompensated cardiogenic pulmonary edema (which includes SCAPE). Reduced contractility could cause the ventricle to fail even more, leading to worsening pulmonary edema.
• Beta-blockers should not be administered in efforts to control blood pressure in SCAPE patients.
  • The key pathophysiologic problem in SCAPE is excessive afterload, which requires treatment with vasodilators.
• 💡 Remember that positive inotropes (e.g., dobutamine) are sometimes used for the management of cardiogenic pulmonary edema! Inotropes are used for patients with lower blood pressure than SCAPE patients (such patients usually have more of a pump problem, rather than an afterload problem). Nonetheless, this should underscore the concept that beta-blockers aren't beneficial in decompensated cardiogenic pulmonary edema (including SCAPE).

principle #4: watch for when the SCAPE breaks

• If treated appropriately, the SCAPE will break rapidly – the vicious spiral will stop and the patient will improve. The most obvious way to tell this is happening is often when the blood pressure starts to drop precipitously. Management involves:
  • (1) Rapidly down-titrate the nitroglycerine infusion and CPAP/BiPAP pressures (while watching for recurrent SCAPE).
  • (2) Consider any triggers of SCAPE and treat them (e.g., nonadherence to antihypertensives, volume overload).
• (Further discussion of this phenomenon here.)

---

CPAP or BiPAP

(back to contents)

---

basics

• Positive airway pressure achieves an immediate and titratable reduction in both cardiac preload and afterload.
• Either CPAP or BiPAP may be used – the key intervention is an increase in the mean airway pressure (the time average of pressure in the airway).
  • CPAP: Mean airway pressure is equal to the pressure setting of the CPAP.
  • BiPAP: Mean airway pressure is a bit over the expiratory pressure (ePAP). For example, with BiPAP set at 15 cm/10 cm, the mean airway pressure might be somewhere around ~12 cm.
• BiPAP is often used as this gives the patient a bit of mechanical support, which may improve comfort (patients perceive the machine as giving them support). However, either BiPAP or CPAP are equally effective.

nuts and bolts

• CPAP: Start at a low pressure (e.g., 5-8 cm), up-titrate rapidly as tolerated to a maximal pressure of ~15-18 cm.
• BiPAP: Start at a low pressure (e.g., 12 cm/6 cm). Up-titrate rapidly as tolerated, with a goal of increasing the expiratory pressure (e.g., titrate up to ~18 cm/15 cm).
• The maximal safe pressure is not precisely defined, but pressures above ~20 cm may increase the risk of gastric insufflation.(24317204)

make sure to optimize the CPAP or BiPAP

• CPAP or BiPAP is the most important, evidence-based therapy for SCAPE – so the first priority should be utilizing this treatment and optimizing it.
• Higher airway pressure will more effectively reduce preload and afterload in a dose-dependent fashion.
• Airway pressures should generally be rapidly up-titrated, while monitoring patient comfort and hemodynamics (higher pressures may cause a reduction in blood pressure – which is generally a welcome effect).
• ⚠️ Perhaps the most common pitfall in management of SCAPE is failure to up-titrate CPAP or BiPAP settings. Up-titrating the airway pressure will cause an instantaneous reduction in preload and afterload, which might be faster and more reliably effective than any medication.

if the patient can't tolerate the usual mask

• (1) Basic techniques:
  • Start by holding the mask gently to the patient's face.
  • Start with lower pressures, then ramp up the pressure as the patient adapts to it.
• (2) Medication:
  • IV benzodiazepine (e.g., midazolam) works in many patients. However, paradoxical agitation can occur – in which case a different agent is needed.
  • IV haloperidol or IV droperidol may also be a reasonable choice here.
• (3) Other interfaces:
  • Helmets and nasal interfaces are both potentially effective. Some patients may tolerate these better than the usual orofacial mask. Both of these interfaces may be safer among patients who are at risk of emesis and subsequent aspiration.

---

nitroglycerine

(back to contents)

---

It is essential to rapidly reduce the blood pressure, perhaps targeting a systolic blood pressure <140 mm (as explored further above). Nitroglycerine is the key intervention used to achieve this.

some key points about nitroglycerine in SCAPE

• The dose of nitroglycerine required to achieve arterial vasodilation in SCAPE is about an order of magnitude greater than the usual doses of nitroglycerine required for management of anginal chest pain. This is because higher doses of nitroglycerine are required to achieve arterial vasodilation (whereas lower doses are sufficient to achieve venodilation).
• Patients vary widely in their individual sensitivity to nitroglycerine, which underscores the importance of aggressive, empiric dose-titration.(33358327)

step #1) loading dose of nitroglycerine

• Start with an initial loading dose of IV nitroglycerine of ~1,000-2,000 micrograms.(29887195, 31327485) This may be provided in one of two ways:
  • (a) Pushing a bolus of 1,000-2,000 mcg nitroglycerine over ~2 minutes.
  • (b) Nitroglycerine infusion at 400-800 mcg/min for 2.5 minutes.
• Both approaches are equivalent, with the choice depending on logistics.
• The main risk of nitroglycerine boluses is hypotension. However, this is unlikely if the diagnosis of SCAPE is secure (since these patients are profoundly vasoconstricted). Several studies have found nitroglycerine boluses to be safe in the context of SCAPE. Occasional patients who have SCAPE along with underlying hypovolemia may develop hypotension that usually responds to observation or administration of small volumes of crystalloid – since the nitroglycerine levels will naturally fall within minutes.(34215472)
• IV nitroglycerine boluses have been shown to be safe, even when administered by paramedics in the field.(33023684, 31900011) Consequently, resuscitationists working within the critical care arena should feel quite comfortable with this as well.

step #2) maintenance infusion of nitroglycerine

• The nitroglycerine infusion may be initiated at a rate of ~100-300 mcg/min (depending on the baseline blood pressure and illness severity).(34215472) A high dose of nitroglycerine is required to achieve arterial vasodilation, possibly at least ~150 mcg/min.(14715359) Based on the vicious-spiral physiology of SCAPE, it's generally better to start at a high dose, control the blood pressure promptly, and then back down.
• If blood pressure isn't controlled promptly, up-titrate the nitroglycerine aggressively. Very high doses (e.g., 800 mcg/min) may be required for limited periods of time, to break the cycle of progressive hypertension.(32278569)
  • Re-bolusing nitroglycerine is unnecessary, since a high-dose infusion will provide the same amount (e.g., 800 mcg/min for five minutes is roughly equal to a 4,000 mcg bolus every 5 minutes).
• If hypertension is refractory to 800 mcg/min nitroglycerine, then:
  • Make sure the CPAP/BiPAP pressures are maximized.
  • Consider the addition of nicardipine, clevidipine, IV enalaprilat, and/or captopril. (More on this above.)

step #3) wean off nitroglycerine as SCAPE resolves

• Generally the SCAPE will start resolving rapidly (within minutes to a couple of hours), causing the blood pressure to decrease. As quickly as the storm began, it quietly abates.
• Nitroglycerine can usually be titrated off rapidly as SCAPE resolves. In some cases, ongoing hypertension control may require the addition of an oral vasodilator (e.g., ACE inhibitor) – but in many cases this isn't required. (More on oral vasodilators below.)
• 💡 Watch the blood pressure very carefully and down-titrate the nitroglycerine infusion accordingly, to avoid hypotension.

contraindications to nitroglycerine?

• Nitroglycerine is contraindicated among patients who recently received phosphodiesterase type-5 inhibitors (e.g., sildenafil, tadalafil, vardenafil). Nicardipine or clevidipine might be considered in such patients.
• Aortic stenosis isn't a contraindication to nitroglycerine in the context of SCAPE. However, some caution is required (with perhaps somewhat lower doses and more gradual dose titration than usual).(26002298)
• Nitroglycerine may increase ICP (intracranial pressure) and has been reported to worsen PRES (posterior reversible encephalopathy syndrome).

sublingual nitroglycerine

• This may be utilized if a patient experiences SCAPE in a location unable to provide IV nitroglycerine (e.g., a medicine ward).
• The goal of sublingual nitroglycerine is solely to bridge the patient until they are able to receive IV nitroglycerine – not as an alternative or replacement for IV nitroglycerine. Patients should be transported immediately to a location capable of administering definitive therapy (IV nitroglycerine and noninvasive ventilation).
• The optimal dose is unclear, but 3-5 sublingual 400-mcg tablets q5 minutes might be reasonable. (Note that the bioavailability of sublingual nitroglycerine is only ~40%.)

---

oral vasodilators

(back to contents)

---

⚠️ caution with oral vasodilators

• The hallmark of SCAPE is labile blood pressure.  Initially patients are profoundly hypertensive, but with resolution of SCAPE they often transition to being normotensive (without requiring any medication).
• Be careful about starting long-acting antihypertensives during the acute phase of SCAPE, because this may eventually lead to rebound hypotension after SCAPE has resolved.

when to use oral vasodilators

• The best time to initiate oral vasodilators is if the following situation occurs – which is actually infrequent:
  • (1) Pulmonary edema resolves following treatment with an IV nitroglycerine infusion (e.g., resolution of dyspnea and hypoxemia).
  • (2) There is a persistent requirement for IV nitroglycerine in order to control the blood pressure.
  • (3) The nitroglycerine requirement has been relatively stable for a couple of hours.
• In this situation, oral vasodilators may be used to wean off the IV nitroglycerine.  Continued use of oral vasodilators may also help prevent the recurrence of SCAPE episodes.
• 💡 In most cases of SCAPE, clinical resolution will allow the IV nitroglycerine to be weaned off without the use of any oral antihypertensive agents.

ACE inhibitors & ARBs

• An ACE inhibitor or angiotensin receptor blocker (ARB) is probably the best antihypertensive for these patients, if renal function allows.
• Oral captopril may be preferred because it is fast-acting.  This allows for rapid assessment of its effects and prompt oral titration.  For example, a dose of 12.5-25 mg can be given and this can be repeated in ~2 hours if there is an inadequate effect.
• The main drawback of ACE inhibitors and ARBs is potential nephrotoxicity.  These agents may not be ideal for patients with acute kidney injury, or multimorbid patients with numerous active medical problems.

oral hydralazine/isosorbide dinitrate

• The combination of oral hydralazine plus isosorbide dinitrate produces similar hemodynamic effects compared to an ACE inhibitor, without a risk of nephrotoxicity.
• The usual starting dose is isosorbide dinitrate (ISORDIL) 20 mg PO q8hr plus hydralazine 37.5 mg PO q8hr.  The dose can be up-titrated to effect.
• This combination is useful for acute stabilization.  Once the patient has recovered from their acute illness and their volume status has been optimized, the combination will usually be transitioned to a different agent (e.g., an ACE inhibitor).

---

volume management & diuresis

(back to contents)

---

key concepts regarding fluid management

• Diuresis isn't a front-line intervention for SCAPE. The key pathophysiologic problem with SCAPE is uncontrolled sympathetic outpouring and increased afterload. Many patients with SCAPE may be euvolemic or even hypovolemic (merely experiencing a maldistribution of fluid that shifts into the lungs).

approach to fluid management in SCAPE

• The initial therapies are positive pressure ventilation and afterload control (usually with high-dose nitroglycerine). These should be instituted immediately, prior to consideration of diuretics.
• Assess the patient clinically after initiating nitrates and positive pressure ventilation (e.g., with echocardiography). If there is evidence of hypervolemia, then volume removal may be beneficial (either with diuresis or dialysis). A benefit from volume removal is particularly supported if there is a clinical history suggestive of volume overload (e.g., nonadherence with diuretics, or missed hemodialysis sessions).

---

opioid

(back to contents)

---

• Retrospective studies have correlated the use of morphine with worse outcomes among patients with pulmonary edema. This shouldn't be surprising. Sicker patients are more likely to be air hungry, prompting therapy with morphine. It's also conceivable that morphine could mask the symptoms of pulmonary edema, prompting providers to be less aggressive with other therapies (e.g., patient doesn't look sick enough to need CPAP).
• The MIMO prospective RCT compared morphine (up to 8 mg IV) with midazolam (up to 3 mg) among patients with acute pulmonary edema.(35780488) The study was stopped prematurely due to harm, with patients in the morphine group accruing higher rates of cardiovascular adverse events (including cardiac arrest and shock). This is only a single, relatively small trial – but it represents the highest quality data available. As such, opioids should arguably be avoided in the context of SCAPE (at least pending the availability of higher-quality evidence).

---

podcast

(back to contents)

---

Follow us on iTunes

---

questions & discussion

(back to contents)

---

To keep this page small and fast, questions & discussion about this post can be found on another page here.

• Know your patient's BiPAP pressures, and aggressively up-titrate them. Just starting BiPAP isn't enough; the pressures should be ramped up rapidly. BiPAP at 18cm/15 cm is going to do a lot more than at 10cm/5cm.
• DO NOT delay treatment with BiPAP and nitroglycerine while waiting to see if diuresis will work.
• DO NOT try to treat the hypertension of a SCAPE patient with beta-blockers. The pathophysiologic problem is excessive afterload, which a beta-blocker won't address. Beta-blockers may reduce pump function, thereby worsening the pulmonary edema.
• Try to avoid intubation if possible, because these patients will often improve dramatically and rapidly with BiPAP and high-dose nitroglycerine. Patients who look horrifically ill will often improve within minutes.

Guide to emoji hyperlinks

• = Link to online calculator.
• = Link to Medscape monograph about a drug.
• = Link to IBCC section about a drug.
• = Link to IBCC section covering that topic.
• = Link to FOAMed site with related information.
• = Link to supplemental media.

Going further

• EMCrit Podcast #1: Sympathetic crashing acute pulmonary edema
• When to wean the CPAP in SCAPE (EMCrit RACC, Scott Weingart)
• High-dose NTG and NIV for SCAPE (RebelEM by Salim Rezaie)

Imaging credits: Opening image includes figures from PMID 34215472, 32278569, and 29942881 (full references above).