Review Article

Pathophysiology and Management of Neurogenic Pulmonary Edema in Patients with Acute Severe Brain Injury

Authors: Matthew A. Maslonka, MD, Kristin N. Sheehan, MD, Sudhir V. Datar, MD, Vidula Vachharajani, MD, Andrew Namen, MD

Abstract

Acute brain injury (ABI) consists of any acquired insult to the brain and is a significant cause of morbidity and mortality worldwide. Approximately 20% to 30% of patients with ABI develop a lung injury called neurogenic pulmonary edema (NPE), and its development often results in poor outcomes. This article provides a narrative review of the evidence regarding proposed mechanisms of injury, diagnosis, and treatment of NPE in the critical care setting. PubMed and Ovid databases were searched for observational or prospective studies relevant to the diagnosis and treatment of NPE. Overall, studies showed that although the specific mechanisms responsible for NPE remain uncertain, putative mechanisms include vaso- and venoconstriction, catecholamine release with resultant pulmonary vasoconstriction called the “blast injury theory,” increased vagal tone, and increased capillary permeability. Diagnosis involves identifying signs of pulmonary edema in patients who experienced a neurologic insult. Management strategies aim to address both brain and lung injury, and treatment modalities appear to work best when balanced toward maintaining a normal physiologic state. In summary, NPE is an often underdiagnosed but important sequela of ABI, which may result in additional long-term morbidity. It is therefore an important entity for providers to recognize and tailor their clinical approach toward.

 
Posted in: Acute Respiratory Distress Syndrome (Ards)1

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. McKee AC, Daneshvar DH. The neuropathology of traumatic brain injury. Handb Clin Neurol 2015;127:45–66. .
 
2. Hoyt DB, Simons RK, Winchell RJ, et al. A risk analysis of pulmonary complications following major trauma. J Trauma 1993;35:524–531.
 
3. Holland MC, Mackersie RC, Morabito D, et al. The development of acute lung injury is associated with worse neurologic outcome in patients with severe traumatic brain injury. J Trauma 2003;55:106-111.
 
4. Maramattom BV, Weigand S, Reinalda M, et al. Pulmonary complications after intracerebral hemorrhage. Neurocrit Care 2006;5:115-119.
 
5. Kahn JM, Caldwell EC, Deem S, et al. Acute lung injury in patients with subarachnoid hemorrhage: incidence, risk factors, and outcome. Crit Care Med 2006;34:196-202.
 
6. Contant CF, Valadka AB, Gopinath SP, et al. Adult respiratory distress syndrome: a complication of induced hypertension after severe head injury. J Neurosurg 2001;95:560-568.
 
7. Mascia L. Acute lung injury in patients with severe brain injury: a double hit model. Neurocrit Care 2009;11:417-426.
 
8. Zygun DA, Kortbeek JB, Fick GH, et al. Non-neurologic organ dysfunction in severe traumatic brain injury. Crit Care Med 2005;33:654–660.
 
9. O’Leary MP, Keeley JA, Yule A, et al. Clinical predictors of early acute respiratory distress syndrome in trauma patients. Am J Surg 2016;212: 1096–1100.
 
10. Weisman S. Edema and congestion of the lungs resulting from intracranial hemorrhage. Surgery 1939;6:722-729.
 
11. Muroi C, Keller M, Pangalu A, et al. Neurogenic pulmonary edema in patients with subarachnoid hemorrhage. J Neurosurg Anesthesiol 2008;20: 188–192.
 
12. Obata Y, Takeda J, Sato Y, et al. A multicenter prospective cohort study of volume management after subarachnoid hemorrhage: circulatory characteristics of pulmonary edema after subarachnoid hemorrhage. J Neurosurg 2016;125:254–263.
 
13. Sarnoff SJ, Sarnoff LC. Neurohemodynamics of pulmonary edema. II. The role of sympathetic pathways in the elevation of pulmonary and stemic vascular pressures following the intracisternal injection of fibrin. Circulation 1952;6:51-62.
 
14. Paine R, Smith JR, Butcher HR, et al. Heart failure and pulmonary edema produced by certain neurologic stimuli. Circulation 1952;5:759-765.
 
15. Campbell GS, Visscher MB. Pulmonary lesions in guinea pigs with increased intracranial pressure, and the effect of bilateral cervical vagotomy. Am J Physiol 1949;157:130-134.
 
16. Pelliccia F, Kaski JC, Crea F, et al. Pathophysiology of Takotsubo syndrome. Circulation 2017;135:2426-2441.
 
17. de Leeuw PW, Waltman FL, Birkenhager WH. Noncardiogenic pulmonary edema as the sole manifestation of pheochromocytoma. Hypertension 1986;8:810-812.
 
18. Maron MB, Dawson CA. Pulmonary venoconstriction caused by elevated cerebrospinal fluid pressure in the dog. J Appl Physiol 1980;49:73-78.
 
19. Smith WS, Matthay MA. Evidence for a hydrostatic mechanism in human neurogenic pulmonary edema. Chest 1997;111:1326-1333.
 
20. Moss G, Staunton C, Stein AA. Cerebral etiology of the “shock lung syndrome”. J Trauma 1972;12:885-890.
 
21. Gamble JE, Patton HD. Pulmonary edema and hemorrhage from preoptic lesions in rats. Am J Physiol 1953;172:623-631.
 
22. Maire FW, Patton HD. Neural structures involved in the genesis of preoptic pulmonary edema, gastric erosions and behavior changes. Am J Physiol 1956;184:345–350.
 
23. Schraufnagel DE, Patel KR. Sphincters in pulmonary veins. An anatomic study in rats. Am Rev Respir Dis 1990;141:721–726.
 
24. Chen HI, Chai CY. Pulmonary adema and hemorrhage as a consequence of systemic vasoconstriction. Am J Physiol 1974;227:144-151.
 
25. Theodore J, Robin ED. Speculations on neurogenic pulmonary edema (NPE). Am Rev Respir Dis 1976;113:405-411.
 
26. McClellan MD, Dauber IM, Weil JV. Elevated intracranial pressure increases pulmonary vascular permeability to protein. J Appl Physiol 1989; 67:1185-1191.
 
27. Maron MB. Effect of elevated vascular pressure transients on protein permeability in the lung. J Appl Physiol 1989;67:305-310.
 
28. Ducker TB. Increased intracranial pressure and pulmonary edema. 1. Clinical study of 11 patients. J Neurosurg 1968;28:112-117.
 
29. Blanco E, Martins-Pinge M, Oliveira-Sales E, et al. Involvement of nitric oxide pathways in neurogenic pulmonary edema induced by vagotomy. Clinics (Sao Paulo) 2011;66:1061-1066.
 
30. Touho H, Karasawa J, Shishido H, et al. Neurogenic pulmonary edema in the acute stage of hemorrhagic cerebrovascular disease. Neurosurgery 1989;25: 762-768.
 
31. Avlonitis VS, Wigfield CH, Kirby JA, et al. Treatment of the brain-dead lung donor with aprotinin and nitric oxide. J Heart Lung Transplant 2010;29: 1177-1184.
 
32. Tanabe M, Crago EA, Suffoletto MS, et al. Relation of elevation in cardiac troponin I to clinical severity, cardiac dysfunction, and pulmonary congestion in patients with subarachnoid hemorrhage. Am J Cardiol 2008;102: 1545-1550.
 
33. Junttila E, Ala-Kokko T, Ohtonen P, et al. Neurogenic pulmonary edema in patients with nontraumatic intracerebral hemorrhage: predictors and association with outcome. Anesth Analg 2013;116:855-861.
 
34. Nastasovic T, Milakovic B, Marinkovic JE, et al. Could cardiac biomarkers predict neurogenic pulmonary edema in aneurysmal subarachnoid hemorrhage? Acta Neurochir (Wien) 2017;159:705-712.
 
35. Burchiel KJ, Steege TD, Wyler AR. Intracranial pressure changes in brain-injured patients requiring positive end-expiratory pressure ventilation. Neurosurgery 1981;8:443-449.
 
36. Shapiro HM, Marshall LF. Intracranial pressure responses to PEEP in head-injured patients. J Trauma 1978;18:254-256.
 
37. Cooper KR, Boswell PA, Choi SC. Safe use of PEEP in patients with severe head injury. J Neurosurg 1985;63:552-555.
 
38. Frost EA. Effects of positive end-expiratory pressure on intracranial pressure and compliance in brain-injured patients. J Neurosurg 1977;47:195-200.
 
39. Georgiadis D, Schwarz S, Baumgartner RW, et al. Influence of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure in patients with acute stroke. Stroke 2001;32:2088-2092.
 
40. McGuire G, Crossley D, Richards J, et al. Effects of varying levels of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure. Crit Care Med 1997;25:1059-1062.
 
41. Caricato A, Conti G, Della Corte F, et al. Effects of PEEP on the intracranial system of patients with head injury and subarachnoid hemorrhage: the role of respiratory system compliance. J Trauma 2005;58:571-576.
 
42. Permutt S, Riley RL. Hemodynamics of collapsible vessels with tone: the vascular waterfall. J Appl Physiol 1963;18:924-932.
 
43. Chen H, Menon DK, Kavanagh BP. Impact of altered airway pressure on intracranial pressure, perfusion, and oxygenation: a narrative review. Crit Care Med 2019;47:254-263.
 
44. Boone MD, Jinadasa SP, Mueller A, et al. The effect of positive endexpiratory pressure on intracranial pressure and cerebral hemodynamics. Neurocrit Care 2017;26:174-181.
 
45. Mascia L, Grasso S, Fiore T, et al. Cerebro-pulmonary interactions during the application of low levels of positive end-expiratory pressure. Intensive Care Med 2005;3:373-379.
 
46. Magnoni S, Ghisoni L, Locatelli M, et al. Lack of improvement in cerebral metabolism after hyperoxia in severe head injury: a microdialysis study. J Neurosurg 2003;98:952-958.
 
47. Reinert M, Barth A, Rothen HU, et al. Effects of cerebral perfusion pressure and increased fraction of inspired oxygen on brain tissue oxygen, lactate and glucose in patients with severe head injury. Acta Neurochir (Wien) 2003;145: 341-350.
 
48. Griffith DE, Garcia JG, James HL, et al. Hyperoxic exposure in humans. Effects of 50 percent oxygen on alveolar macrophage leukotriene B4 synthesis. Chest 1992;101:392-397.
 
49. Rockswold SB, Rockswold GL, Zaun DA, et al. A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury. J Neurosurg 2013;118:1317-1328.
 
50. Gupta AK, Menon DK, Czosnyka M, et al. Thresholds for hypoxic cerebral vasodilation in volunteers. Anesth Analg 1997;85:817-820.
 
51. Markwalder TM, Grolimund P, Seiler RW, et al. Dependency of blood flow velocity in the middle cerebral artery on end-tidal carbon dioxide partial pressure—a transcranial ultrasound Doppler study. J Cereb Blood Flow Metab 1984;4:368-372.
 
52. Huber P, Handa J. Effect of contrast material, hypercapnia, hyperventilation, hypertonic glucose and papaverine on the diameter of the cerebral arteries. Angiographic determination in man. Invest Radiol 1967;2:17-32.
 
53. Muizelaar JP, Marmarou A, Ward JD, et al. Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg 1991;75:731-739.
 
54. Paul RL, Polanco O, Turney SZ, et al. Intracranial pressure responses to alterations in arterial carbon dioxide pressure in patients with head injuries. J Neurosurg 1972;36:714–720.
 
55. Carney N, Totten AM, O’Reilly C, et al. Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery 2017;80:6-15.
 
56. 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 2000;342:1301–1308.
 
57. Mascia L, Zavala E, Bosma K, et al. High tidal volume is associated with the development of acute lung injury after severe brain injury: an international observational study. Crit Care Med 2007;35:1815-1820.
 
58. Elmer J, Hou P, Wilcox SR, et al. Acute respiratory distress syndrome after spontaneous intracerebral hemorrhage. Crit Care Med 2013;41:1992-2001.
 
59. Meduri GU, Headley AS, Golden E, et al. Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial. JAMA 1998;280:159-165.
 
60. Steinberg KP, Hudson LD, Goodman RB, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 2006;354:1671–1684.
 
61. Tang BM, Craig JC, Eslick GD, et al. Use of corticosteroids in acute lung injury and acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care Med 2009;37:1594–1603.
 
62. Peter JV, John P, Graham PL, et al. Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: metaanalysis. BMJ 2008;336:1006–1009.
 
63. Roberts I, Yates D, Sandercock P, et al. Effect of intravenous corticosteroids on death within 14 days in 10 008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet 2004;364:1321–1328.
 
64. Skolnick BE, Maas AI, Narayan RK, et al. A clinical trial of progesterone for severe traumatic brain injury. N Engl J Med 2014;371:2467–2476.
 
65. Durward QJ, Amacher AL, Del Maestro RF, et al. Cerebral and cardiovascular responses to changes in head elevation in patients with intracranial hypertension. J Neurosurg 1983;59:938–944.
 
66. Gattinoni L, Tognoni G, Pesenti A, et al. Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med 2001;345:568–573.
 
67. Thelandersson A, Cider A, Nellgard B. Prone position in mechanically ventilated patients with reduced intracranial compliance. Acta Anaesthesiol Scand 2006;50:937–941.
 
68. Beuret P, Carton M-J, Nourdine K, et al. Prone position as prevention of lung injury in comatose patients: a prospective, randomized, controlled study. Intensive Care Med 2002;28:564–569.
 
69. Reinprecht A, Greher M, Wolfsberger S, et al. Prone position in subarachnoid hemorrhage patients with acute respiratory distress syndrome: effects on cerebral tissue oxygenation and intracranial pressure. Crit Care Med 2003; 31:1831–1838.
 
70. Claure-Del Granado R, Mehta RL. Fluid overload in the ICU: evaluation and management. BMC Nephrol 2016;17:109.