You are in: eMedicine Specialties >
Pulmonology > Altitude Edema and Lung Diseases
Pulmonary Edema, Neurogenic
Article Last Updated: May 30, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Sat Sharma, MD, FRCPC, FACP, FCCP, DABSM, Program Director, Associate Professor, Department of Internal Medicine, Divisions of Pulmonary and Critical Care Medicine, University of Manitoba; Site Director of Respiratory Medicine, St Boniface General Hospital
Sat Sharma is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, and World Medical Association
Editors: Cory Franklin, MD, Professor, Department of Medicine, Rosalind Franklin University of Medicine and Science; Director, Division of Critical Care Medicine, Cook County Hospital; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Harold L Manning, MD, Associate Professor, Departments of Medicine, Anesthesiology and Physiology, Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School; Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine; Zab Mosenifar, MD, Professor of Medicine, University of California at Los Angeles School of Medicine; Director, Division of Pulmonary/Critical Care Medicine, Executive Vice Chair, Department of Medicine, Cedars-Sinai Medical Center
Author and Editor Disclosure
Synonyms and related keywords:
neurogenic pulmonary edema, NPE, pulmonary edema, epileptic seizures, epilepsy, seizures, cerebral hemorrhage, head trauma, cerebral bleeding, head injury, multiple sclerosis with medullary involvement, medullary multiple sclerosis, nonhemorrhagic stroke, non-hemorrhagic stroke, bulbar poliomyelitis, poliomyelitis, air embolism, air emboli, brain tumor, electroconvulsive therapy, ECT, bacterial meningitis, cervical spinal cord injury, spine injury
Background
Neurogenic pulmonary edema (NPE) is a relatively rare form of pulmonary edema caused by an increase in pulmonary interstitial and alveolar fluid. It develops within a few hours of a well-defined neurologic insult.
Pathophysiology
General The pathogenesis of NPE is not completely understood. Because the most common neurological events are associated with increased intracranial pressure, intracranial hypertension is considered a key etiologic factor. Within the central nervous system, the sites responsible for the development of NPE are not fully established. Animal studies suggest that the hypothalamus, the medulla, elevated intracranial pressure, and activation of the sympathetic system have potential roles. Both hypothalamic lesions and stimulation of the vasomotor centers of the medulla (A1 and A5, nuclei of solitary tract, and area postrema) can increase output along the sympathetic trunk. Neuroanatomic structures The medulla is believed to activate sympathetic components of the autonomic nervous system. Experimentally, bilateral lesions of the nuclei in the medulla produce profound pulmonary and systemic hypertension and pulmonary edema. Alpha-adrenergic blockade (with phentolamine) and spinal cord transection at the C7 level prevent the formation of NPE, suggesting an important role for sympathetic activation. An acute neurological crisis, accompanied by a marked increase in intracranial pressure, may stimulate the hypothalamus and the vasomotor centers of the medulla. This, in turn, initiates a massive autonomic discharge mediated by preganglionic centers within the cervical spine. Mechanism of edema formation A central nervous system event produces a dramatic change in Starling forces, which govern the movement of fluid between capillaries and the interstitium. Both hemodynamic (cardiogenic) and nonhemodynamic (noncardiogenic) components contribute to edema formation. Changes in capillary hydrostatic pressure Alterations in pulmonary vascular pressures appear to be the most likely Starling force to influence the formation of NPE. Experimental observations suggest the following mechanisms by which pulmonary capillary hydrostatic pressures can be increased acutely:
- An increase in left atrial pressure may occur because of increases in sympathetic tone and venous return. Left ventricular performance may deteriorate secondary to the direct effects of catecholamines and other mediators, as well as transient systemic hypertension.
- Pulmonary venoconstriction occurs with sympathetic stimulation, which may increase the capillary hydrostatic pressure and produce pulmonary edema without affecting left atrial or pulmonary capillary wedge pressures.
Changes in pulmonary capillary permeability An increase in capillary permeability can result in NPE without elevation of pulmonary capillary hydrostatic pressure, since causative hemodynamic alteration is inconsistent. However, evidence shows that alpha-adrenergic blockade can protect against NPE. Epinephrine, norepinephrine, and even a release of secondary mediators may directly increase pulmonary vascular permeability. Whether the capillary leak is produced by pressure-induced mechanical injury because of the elevated capillary hydrostatic pressure or because of some direct nervous system control over the pulmonary capillary permeability remains uncertain. An initial and rapid rise in pulmonary vascular pressure due to pulmonary vasoconstriction or pulmonary blood flow can lead to pulmonary microvascular injury. Consequently, an increase in vascular permeability results in edema formation, as suggested by the frequent observation of pulmonary hemorrhage in NPE (ie, blast theory).
Frequency
United States
As many as one third of patients with status epilepticus have evidence of NPE. Over one half of patients with severe, blunt, or penetrating head injury have associated NPE. Approximately 71% of fatal cases of subarachnoid hemorrhage are complicated by NPE. NPE may complicate subarachnoid and intercerebral hemorrhage in 30-70% of patients and may recur after initial resolution. A series of 457 patients with subarachnoid hemorrhage reported a 6% incidence of severe NPE. Solenski et al reported in 1995 that increased age and a worse clinical grade of subarachnoid hemorrhage were associated with NPE.
Mortality/Morbidity
The mortality rates following NPE have not been well documented in the literature. The outcome usually is determined by the course of the neurological insult that produced NPE.
History
- NPE characteristically presents within minutes to hours of a severe central nervous system insult.
-
- Sudden onset of dyspnea is the most common symptom; mild hemoptysis may occur as well.
-
Physical
- Tachypnea
-
- Tachycardia
-
- Bibasilar crackles
-
- Respiratory distress
-
- Pulmonary edema with normal jugular venous pressure and the absence of cardiac gallop
-
- Fever - May occur secondary to the neurological disturbance (eg, subarachnoid hemorrhage)
-
Causes
- Major causes
-
- Epileptic seizures
-
- Cerebral hemorrhage
-
- Head injury
-
- Minor causes
-
- Multiple sclerosis with medullary involvement
-
- Nonhemorrhagic strokes
-
- Bulbar poliomyelitis
-
- Air embolism
-
- Brain tumors
-
- Electroconvulsive therapy
-
- Bacterial meningitis
-
- Cervical spinal cord injury
-
Pneumonia, Aspiration
Pneumonia, Bacterial
Pulmonary Edema, Cardiogenic
Other Problems to be Considered
Adult respiratory distress syndrome Aspiration pneumonia: This condition also occurs in the setting of altered consciousness. NPE tends to develop more rapidly than aspiration pneumonia. Although NPE does not cause fever, the neurological insults that result in NPE (eg, subarachnoid hemorrhage) may be associated with fever. Aspiration pneumonia may take 1-2 weeks to resolve, whereas NPE resolves within hours to several days.
Lab Studies
- Laboratory studies are not helpful in making a diagnosis.
-
Imaging Studies
- The chest radiograph shows a bilateral alveolar filling process and a normal-sized heart (see Media File 1). This may mimic congestive heart failure with cephalization of blood flow, although other features of heart failure, such as septal lines, are usually not evident.
Procedures
- Hemodynamic measurements with right heart catheterization (ie, Swan-Ganz catheter) may be necessary to differentiate NPE from hydrostatic or cardiogenic pulmonary edema. Systemic blood pressure, cardiac output, and pulmonary capillary wedge pressure are usually normal by the time NPE is diagnosed clinically.
-
Medical Care
- General
- Focus treatment on the underlying disorder.
- Manage NPE in a supportive and conservative fashion.
- NPE resolves within 48-72 hours in the majority of affected patients.
- General supportive care
- Supplemental oxygen is required in most patients to correct hypoxemia.
- Mechanical ventilation may be necessary, either noninvasive with a face mask or via endotracheal tube. The goals of mechanical ventilation are to assure adequate oxygenation and ventilation and to prevent iatrogenic lung injury. To avoid excessively high inflation pressures, tidal volumes between 5 and 8 mL/kg are used. With the use of low inflation volumes, positive end-expiratory pressure (PEEP) is added to prevent compression atelectasis. The peak inspiratory (plateau) pressure should be kept below 30-35 cm water, and eucapnia should be maintained to avoid further increases in intracranial pressure.
- In a prospective randomized clinical trial, the Acute Respiratory Distress Syndrome Network demonstrated a striking reduction in hospital mortality in patients with acute respiratory distress syndrome ventilated with 6 mL/kg of predicted body weight compared with 12 mL/kg. More ventilator-free and organ failure-free days occurred in patients who received the lower tidal volume strategy. In the lower tidal volume group, the target tidal volume was 6 mL/kg of predicted body weight. This strategy may lead to respiratory acidosis, which requires either high respiratory rates and/or sodium bicarbonate infusion.
- High levels of PEEP may be required to treat severe hypoxemia. Caution is advised, however, since PEEP can inhibit cerebral venous return and increase intracranial hypertension.
- Diuretic therapy may reduce lung water by decreasing capillary hydrostatic pressure and increasing colloid osmotic pressure, but the strategies to reduce lung water are not uniformly successful. The use of diuretics to minimize or reduce fluid overload seems a more reasonable approach, but adequate cardiac output and cerebral perfusion pressure must be maintained.
- The goal of management in respiratory failure is to achieve an adequate level of oxygenation in the vital organs. Swan-Ganz catheterization may be helpful in guiding fluid and hemodynamic management, particularly if diuretics are used. To maintain adequate tissue oxygenation, sufficient cardiac output (cardiac index >2.2 L/min/m2) and hemoglobin (>10 g/L) are required to ensure optimal oxygen delivery. Since cardiac output depends upon cardiac filling pressures (central venous pressure and wedge pressure), meticulous monitoring of intravascular volume is mandatory.
- Pharmacological therapy
- Pharmacological agents are not used routinely in treatment of NPE.
- Several agents such as alpha-adrenergic antagonists, beta-adrenergic blockers, dobutamine, and chlorpromazine are advocated by some authors, but assessment of their effectiveness is difficult because NPE is usually a self-limited condition that ameliorates spontaneously.
- Alpha-adrenergic antagonists
- These antagonists (eg, phentolamine) can prevent NPE or hasten its resolution in experimental models. However, no human trials have established the safety and efficacy of these agents.
- These agents may be used to treat concomitant systemic hypertension, if present, but care must be taken to avoid significant hypotension that can diminish cerebral perfusion.
Consultations
- Consult a critical-care medicine specialist for ongoing intensive care.
-
- Consult a neurosurgeon or neurologist for evaluation and management of any underlying precipitating event.
-
Further Inpatient Care
- The combination of NPE and a neurological insult severe enough to cause NPE always warrants admission to hospital.
-
- Intensive care admission may be required if patients develop increasingly severe hypoxemia or respiratory distress, or if invasive monitoring is required.
-
Prognosis
- NPE usually is well tolerated by the patient, and the process usually resolves within 48-72 hours.
-
- Prognosis is determined by the course of underlying neurological problems.
-
Patient Education
- For excellent patient education resources, visit eMedicine's Stroke Center. Also, see eMedicine's patient education article Stroke.
-
Medical/Legal Pitfalls
- Diagnosis of NPE is difficult because of the nonspecific nature of clinical signs and findings on routine diagnostic tests.
-
- Consider NPE when pulmonary edema occurs in an appropriate setting.
-
- The characteristic features of NPE are dyspnea, hypoxemia, and radiographic pulmonary infiltrates developing within a few hours of the neurological event.
-
| Media file 1:
Chest radiograph showing bilateral alveolar opacities in a patient with subarachnoid hemorrhage who developed neurogenic pulmonary edema. |
 |  View Full Size Image | |
Media type: X-RAY
|
- Brewer RP, Borel CO. Neurogenic pulmonary edema during intracranial endovascular therapy. Neurocrit Care. 2004;1(4):423-7.
- Fletcher SJ, Atkinson JD. Use of prone ventilation in neurogenic pulmonary oedema. Br J Anaesth. Feb 2003;90(2):238-40. [Medline].
- Fontes RB, Aguiar PH, Zanetti MV, Andrade F, Mandel M, Teixeira MJ. Acute neurogenic pulmonary edema: case reports and literature review. J Neurosurg Anesthesiol. Apr 2003;15(2):144-50. [Medline].
- Gonçalves V, Silva-Carvalho L, Rocha I. Cerebellar haemorrhage as a cause of neurogenic pulmonary edema - case report. Cerebellum. 2005;4(4):246-9. [Medline].
- Hoff JT, Nishimura M, Garcia-Uria J, Miranda S. Experimental neurogenic pulmonary edema. Part 1: The role of systemic hypertension. J Neurosurg. May 1981;54(5):627-31. [Medline].
- Jain R, Deveikis J, Thompson BG. Management of patients with stunned myocardium associated with subarachnoid hemorrhage. AJNR Am J Neuroradiol. Jan 2004;25(1):126-9. [Medline].
- Knudsen F, Jensen HP, Petersen PL. Neurogenic pulmonary edema: treatment with dobutamine. Neurosurgery. Aug 1991;29(2):269-70. [Medline].
- Maron MB, Dawson CA. Pulmonary venoconstriction caused by elevated cerebrospinal fluid pressure in the dog. J Appl Physiol. Jul 1980;49(1):73-8. [Medline].
- Ohlmacher AP. Acute pulmonary edema as a terminal event in certain forms of epilepsy. Am J Med Sci. 1910;139:417.
- Qin SQ, Sun W, Wang HB, Zhang QL. Neurogenic pulmonary edema in head injuries: analysis of 5 cases. Chin J Traumatol. Jun 2005;8(3):172-4, 178.
- Rochester CL, Mohsenin V. Respiratory complications of stroke. Semin Respir Crit Care Med. Jun 2002;23(3):248-60.
- Schraufnagel DE, Thakkar MB. Pulmonary venous sphincter constriction is attenuated by alpha- adrenergic antagonism. Am Rev Respir Dis. Aug 1993;148(2):477-82. [Medline].
- Simmons RL, Heisterkamp CA 3rd, Collins JA, Bredenberg CE, Mills DE, Martin AM Jr. Respiratory insufficiency in combat casualties. IV. Hypoxemia during convalescence. Ann Surg. Jul 1969;170(1):53-62. [Medline].
- Simon RP, Gean-Marton AD, Sander JE. Medullary lesion inducing pulmonary edema: a magnetic resonance imaging study. Ann Neurol. Nov 1991;30(5):727-30. [Medline].
- Solenski NJ, Haley EC Jr, Kassell NF, Kongable G, Germanson T, Truskowski L, et al. Medical complications of aneurysmal subarachnoid hemorrhage: a report of the multicenter, cooperative aneurysm study. Participants of the Multicenter Cooperative Aneurysm Study. Crit Care Med. Jun 1995;23(6):1007-17. [Medline].
- The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. May 4 2000;342(18):1301-8. [Medline].
- Wartenberg KE, Mayer SA. Medical complications after subarachnoid hemorrhage: new strategies for prevention and management. Curr Opin Crit Care. Apr 2006;12(2):78-84.
- Wray NP, Nicotra MB. Pathogenesis of neurogenic pulmonary edema. Am Rev Respir Dis. Oct 1978;118(4):783-6. [Medline].
Pulmonary Edema, Neurogenic excerpt Article Last Updated: May 30, 2006
|
