CONTENTS
- Pathophysiology
- Causes
- Clinical presentation
- Differential diagnosis
- Investigations to consider
- Treatment
- Podcast
- Questions & discussion
- Pitfalls
general mechanisms of neurogenic pulmonary edema
- (1) The primary mechanism appears to be increased sympathetic outflow from the central nervous system.
- Increased sympathetic tone may cause vasoconstriction of the pulmonary veins, which increases the pulmonary capillary wedge pressure.
- Increased sympathetic tone may cause vasoconstriction of systemic capacitance veins, increasing venous return to the heart (shifting blood volume from the systemic circulation into the pulmonary circulation).
- Increased sympathetic output may cause hypertension (which increases the afterload of the left ventricle), increasing the pulmonary capillary wedge pressure.
- (2) Another potential mechanism may be increased pulmonary capillary permeability. This could be caused by various factors:
- The “blast theory” suggests that a transient increase in transcapillary pressure (due to factors described above) may cause pulmonary microvascular injury, leading to a prolonged increase in pulmonary capillary permeability. Essentially, the pulmonary capillary endothelium gets “blasted” open.(22429697) Endothelial injury may help explain why pulmonary edema may persist, even after a transient sympathetic surge has passed.
- Central nervous system injury may cause systemic inflammation, which increases the permeability of alveolar capillaries.
neurological causes of neurogenic pulmonary edema
- Involvement of specific brain areas may be especially likely to cause a sympathetic surge which initiates neurogenic pulmonary edema (“neurogenic pulmonary edema trigger zones”). These include:
- Hypothalamus.
- Medulla (especially the caudal medulla, area postrema, and the nucleus tractus solitarius).
- Insular cortex. The left insular cortex often modulates parasympathetic tone, whereas the right insular cortex modulates sympathetic tone.(32659457) This could explain why ischemic strokes involving the left insular cortex may precipitate neurogenic pulmonary edema.(32739737)
- Decreased perfusion of the medulla may serve as a trigger for increased sympathetic outflow (as an autoregulatory mechanism to re-establish adequate perfusion). Various mechanisms of impaired perfusion might include globally elevated intracranial pressure, or focal hypoperfusion due to stroke.(31117074)
- Elevated intracranial pressure (ICP) may be the most common physiological trigger of neurogenic pulmonary edema.(22429697) Thus, neurogenic pulmonary edema should always prompt consideration regarding whether the patient requires therapies to reduce the intracranial pressure.
more common causes
- Intracranial hemorrhage, especially:
- Traumatic brain injury (neurogenic pulmonary edema is common among patients with severe traumatic brain injury, especially patients with elevated intracranial pressure).(28187807)
- Status epilepticus (neurogenic pulmonary edema may occur in ~1/3 of patients).(22429697)
- CNS infection (especially brainstem encephalitis, as due to enterovirus-71).(31117074)
- Brain death with ongoing ventilatory support, pending organ donation (~15%).
less common causes
- Acute hydrocephalus.
- Ischemic stroke, including vertebral artery dissection (especially posterior strokes involving the medulla, or anterior strokes involving the insular cortex).(31117074)
- Neurosurgical procedures and complications thereof.
- Guillain-Barre syndrome (GBS) with dysautonomia. 📖
- Acute demyelination involving the nucleus tractus solitarius in the medulla. 📖
- Electroconvulsive therapy (ECT).
- High spinal cord injury may rarely cause neurogenic pulmonary edema as a delayed consequence of autonomic dysreflexia.(19139757) Autonomic dysreflexia isn't an acute complication of trauma, but rather a subacute/chronic process (more on autonomic dysreflexia here 📖). Pulmonary edema occurring soon after traumatic spinal cord injury therefore suggests an alternative explanation (e.g., neurogenic pulmonary edema due to concomitant traumatic brain injury).
timing
- An early form of neurogenic pulmonary edema is most common, beginning within minutes to hours (usually within <60 minutes) of acute brain injury. A delayed form may occur ~12-24 hours after brain injury.(26066018)
- Resolution usually occurs within 48-72 hours, but pulmonary edema may persist among patients with ongoing brain injury.(26066018)
signs & symptoms
- Patients may have abrupt onset of dyspnea. This is generally accompanied by tachypnea, tachycardia, and hypoxemia.
- Pink frothy sputum or “hemoptysis” is common (figure below).
- This may be a clinical correlate with the presence of diffuse alveolar hemorrhage.
- Hypertension is classically present, but blood pressure can also normalize prior to presentation.
- Pulmonary auscultation may reveal bilateral crackles.(28187807)
investigations
- Chest X-ray and/or CT scan show bilateral pulmonary infiltrates that appear similar to cardiogenic pulmonary edema.
cardiogenic pulmonary edema
- Takotsubo cardiomyopathy 📖 (although this may frequently coexist with neurogenic pulmonary edema).
- Acute myocardial ischemia causing cardiogenic pulmonary edema.
- Iatrogenic volume overload.
- Sympathetic Crashing Acute Pulmonary Edema 📖 (SCAPE).
- SCAPE generally occurs in the context of chronic heart failure, whereas neurogenic pulmonary edema may occur in patients with normal baseline cardiac function.
- SCAPE and neurogenic pulmonary edema are not mutually exclusive, but rather they share many physiological similarities. Thus, it is entirely possible that a patient could have a combination of these two pathologies simultaneously, as an overlap between SCAPE and neurogenic pulmonary edema.
noncardiogenic pulmonary edema
- Aspiration pneumonitis.
- Pneumonia (including aspiration pneumonia).
- Fat emboli syndrome.
- Pulmonary contusion.
- Transfusion related acute lung injury (TRALI).
- Negative pressure pulmonary edema (could result from airway obstruction due to a neurological/traumatic event).
- Other etiologies of noncardiogenic pulmonary edema (a more exhaustive differential diagnosis of noncardiogenic pulmonary edema is here: 📖)
- Cardiopulmonary ultrasonography:
- Cardiac ultrasonography to assess left ventricular function, volume status, and valvular function.
- Pulmonary ultrasonography might be expected to show a bilateral B-line pattern. This examination could be used to exclude alternative diagnoses (such as bilateral effusions or tension pneumothorax).
- ⚠️ There is no high-quality evidence regarding the performance of POCUS in neurogenic pulmonary edema. Caution and clinical correlation are warranted.
- EKG (evaluate for occlusive myocardial infarction as the etiology of cardiopulmonary failure).
- Chest X-ray (useful for assessment of the global distribution of infiltrates, as well as for trending progression over time).
- Chest CT scan:
- CT scan is often unnecessary, but it is the definitive thoracic imaging study. In more complex scenarios, CT scan may help sort out competing diagnoses.
- Especially consider obtaining a chest CT scan if the patient is being transported to the CT scanner for a head CT. The patient may deteriorate later, at which point transportation for a CT scan may not be possible.
overall comments
- ⚠️ There is no high-quality evidence regarding the management of neurogenic pulmonary edema. Given its rarity, it's dubious that any will emerge.
- Neurogenic pulmonary edema is generally self-limiting, with spontaneous resolution over a few days. Observation and supportive care are generally the primary therapies (especially for more mild cases).
- The following are some general comments that might help guide management, but treatment must be tailored to the individual patient.
1) management of the underlying neurologic disorder
- The primary focus should generally be on addressing the acute neurologic disorder. The underlying neurological disorder is usually the main determinant of the overall clinical outcome.
- In many patients, increased intracranial pressure (ICP) may be a driver of elevated sympathetic tone, which in turn is causing neurogenic pulmonary edema. Management of elevated intracranial pressure may be extremely important in this context (more on this here 📖).(33308892)
- For patients with underlying status epilepticus, definitive seizure control is of paramount importance.📖
- For patients with ischemic stroke, immediate re-establishment of perfusion is critical.
2) respiratory support
- Patients will generally require some form of oxygenation support (e.g., nasal cannula, high-flow nasal cannula, or intubation with mechanical ventilation). The selection of support mode is a clinical decision (e.g., depending on disease severity and anticipated clinical course).
- BiPAP or CPAP via full-face interface are generally inadvisable, as patients often have altered mental status, with an increased risk of aspiration. However, BiPAP or CPAP applied via a nasal interface could be a reasonable alternative to high-flow nasal cannula.
- Establishment of normoxia and normocarbia are important to minimize secondary neurologic injury.(26066018)
3) hemodynamic management
- Any hemodynamic strategy must take into account the needs of the injured brain. For example, patients with acute stroke may require an elevated blood pressure to perfuse the penumbra. However, in other contexts, precise hemodynamic targets may be less important (e.g., resolved seizure in a patient with epilepsy).
- Dobutamine could be considered in the context of severe pulmonary edema with a markedly reduced ejection fraction. However, dobutamine may tend to reduce the systemic blood pressure, which could be problematic in some patients.
- If the patient is markedly hypertensive and such hypertension is not deemed to be beneficial to the brain injury, then cautious institution of an antihypertensive agent could be useful. Reduction of the systemic pressure will reduce the afterload on the left ventricle, potentially improving pulmonary edema.
- Nitroglycerine 💉 is often favored for management of cardiogenic pulmonary edema. However, nitroglycerine may increase the intracranial pressure, so this is relatively contraindicated among patients with known or suspected elevated intracranial pressure.
- Nicardipine 💉 or clevidipine 💉 infusions are effective, titratable antihypertensive agents which are often preferred for patients with possible elevation of intracranial pressure.
- An alpha-adrenergic inhibitor could theoretically be beneficial in the context of neurogenic pulmonary edema (e.g., prazosin or possibly even chlorpromazine). However, these agents are difficult to titrate and unfamiliar to most practitioners.
4) volume management
- The pathophysiology of neurogenic pulmonary edema involves predominantly fluid shifts into the lungs, rather than changes in total body volume. Therefore, aggressive diuresis is generally not indicated.
- Diuresis should be avoided in patients who don't have total body volume overload, as this could be detrimental to the brain (e.g., by reducing the cerebral perfusion, which might increase the risk of vasospasm among patients with subarachnoid hemorrhage).
- Gentle diuresis may be considered if there is clinical evidence of total body volume overload.
Follow us on iTunes
To keep this page small and fast, questions & discussion about this post can be found on another page here.
- Aggressive diuresis is generally misguided, since neurogenic pulmonary edema doesn't necessarily involve total body volume overload.
- Hemodynamic strategies which are typically employed for the management of Sympathetic Crashing Acute Pulmonary Edema (SCAPE), such as aggressive nitroglycerine infusion, could be detrimental to patients with some types of brain injury. In general, neuroprotection should be the primary consideration among patients with neurogenic pulmonary edema (because their long-term outcome will generally depend on the severity of brain injury).
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 open-access journal article.
- = Link to supplemental media.
References
- 19139757 Calder KB, Estores IM, Krassioukov A. Autonomic dysreflexia and associated acute neurogenic pulmonary edema in a patient with spinal cord injury: a case report and review of the literature. Spinal Cord. 2009 May;47(5):423-5. doi: 10.1038/sc.2008.152 [PubMed]
- 22429697 Davison DL, Terek M, Chawla LS. Neurogenic pulmonary edema. Crit Care. 2012 Dec 12;16(2):212. doi: 10.1186/cc11226 [PubMed]
- 26066018 Busl KM, Bleck TP. Neurogenic Pulmonary Edema. Crit Care Med. 2015 Aug;43(8):1710-5. doi: 10.1097/CCM.0000000000001101 [PubMed]
- 28187807 Balofsky A, George J, Papadakos P. Neuropulmonology. Handb Clin Neurol. 2017;140:33-48. doi: 10.1016/B978-0-444-63600-3.00003-9 [PubMed]
- 29692972 Romero Osorio OM, Abaunza Camacho JF, Sandoval Briceño D, Lasalvia P, Narino Gonzalez D. Postictal neurogenic pulmonary edema: Case report and brief literature review. Epilepsy Behav Case Rep. 2017 Sep 28;9:49-50. doi: 10.1016/j.ebcr.2017.09.003 [PubMed]
- 30955582 Connolly S, Hountras P. A 49-Year-Old Woman With Chest Pain, Cough, and Hypoxemia After a Seizure. Chest. 2019 Apr;155(4):e113-e116. doi: 10.1016/j.chest.2018.10.043 [PubMed]
- 31117074 Finsterer J. Neurological Perspectives of Neurogenic Pulmonary Edema. Eur Neurol. 2019;81(1-2):94-102. doi: 10.1159/000500139 [PubMed]
- 31687236 Suhail Najim M, Ali Mohammed Hammamy R, Sasi S. Neurogenic Pulmonary Edema Following a Seizure: A Case Report and Literature Review. Case Rep Neurol Med. 2019 Oct 9;2019:6867042. doi: 10.1155/2019/6867042 [PubMed]
- 32659457 Mrozek S, Gobin J, Constantin JM, Fourcade O, Geeraerts T. Crosstalk between brain, lung and heart in critical care. Anaesth Crit Care Pain Med. 2020 Aug;39(4):519-530. doi: 10.1016/j.accpm.2020.06.016 [PubMed]
- 32739737 Zhao J, Xuan NX, Cui W, Tian BP. Neurogenic pulmonary edema following acute stroke: The progress and perspective. Biomed Pharmacother. 2020 Oct;130:110478. doi: 10.1016/j.biopha.2020.110478 [PubMed]
- 33308892 Lo-Cao E, Hall S, Parsell R, Dandie G, Fahlström A. Neurogenic pulmonary edema. Am J Emerg Med. 2021 Jul;45:678.e3-678.e5. doi: 10.1016/j.ajem.2020.11.052 [PubMed]