A “Wiring Surge” Contributing to Respiratory Failure?

The Problem

A middle-aged female with no significant past medical history was a passenger in car when she had a sudden onset of a severe headache in the back of her head. She subsequently vomited and became unresponsive. The driver pulled over to side of road and called 911. EMS arrived within 15 minutes and found the patient lethargic but answering simple questions and continuing to c/o headache. Her presentation to a local Emergency Department (ED) was clinically unchanged until shortly after arrival when she then seized, which was treated with Ativan and Keppra. She patient was intubated for airway protection and taken to head CT revealing the presence of a large subarachnoid hemorrhage.

A critical care transport team was called to transfer the patient by air to the nearest tertiary care center for neurosurgical intervention. On arrival of the team to the referring ED, the patient was tachycardic and hypertensive, with an SpO₂ of 99% on mechanical ventilation; sedated with Propofol and Fentanyl infusions, and unresponsive to painful stimuli. Additionally, the transport team observed high-pressure alarms on the ventilator with copious amounts of frothy secretions oscillating within the endotracheal tube and having saturated the inline filter and requiring continuous inline suction. It was suspected that the cause of this was a neurogenic pulmonary edema.

Background

Neurogenic pulmonary edema (NPE) is a clinical syndrome that as a result of an acute central nervous system (CNS) injury, presents with a rapid or delayed onset of respiratory distress due to increased pulmonary interstitial and alveolar fluid. As the name implies NPE is non-cardiogenic in nature, however, both NPE and cardiogenic pulmonary edema manifest, at least in part, as a consequence of increased hydrostatic pressure in the pulmonary capillary bed. Moreover, there is believed to be a component of increased pulmonary capillary permeability as seen in acute respiratory distress syndrome (ARDS) pulmonary edema.² Therefore, the diagnosis of NPE requires one to rule out both the likely cardiogenic and non-cardiogenic causes of pulmonary edema.

Any acute CNS injury may foment NPE. NPE has been described in patients suffering from traumatic brain injury, intracranial or subarachnoid hemorrhages, seizures, tumors, hydrocephalus, spinal cord injury, or neurosurgical procedures,^2,3 and ranging in presentation from mild shortness of breath to acute fulminating pulmonary edema. The severity of the CNS insult generally correlates with the severity of pulmonary edema. Time of onset can fall into one of two categories: 1. Early onset–symptoms present within minutes to hours; or 2. Delayed onset–symptoms seen 12-24 h post CNS insult.²

Several mechanisms have been proposed to explain the various aspects of NPE, yet the exact pathology and pathophysiology remain opaque. There is a consensus that NPE starts with a spike in intracranial pressure (ICP) due to any of the previously described neurological insults. The parenchymal compression and/or ischemia that is inseparable from elevated ICPs produces an increased sympathetic discharge and surge of endogenous catecholamines. The catecholamine surge/storm/tsunami/insert preferred atmospheric or geologic phenomenon, then invokes elevations in SVR & PVR, decreased left ventricular compliance that raises left atrial pressures, and increased venous return which collectively culminates in a deluge of blood volume into the pulmonary circulation rapidly raising pulmonary capillary bed hydrostatic pressure. As alluded to earlier, capillary leak in the pulmonary circulation contributes to NPE. Interestingly, NPE contains both protein and red blood cells (RBCs)–hence its pink frothy nature.¹ However, the presence of this cellular and proteinaceous exudate indicates the occurrence of damage to the capillary bed.^1,2 Exactly how the capillary bed is damaged is still up for debate with competing theories ranging from direct endothelial injury as a result of catecholamine surge to damage caused by rapid fluid shifts from the systemic to pulmonary circulation.^1,2,3

Management Options

Management of a patient presenting with NPE is geared towards management of the CNS insult with treatment of NPE via supportive therapies; the determining factor in patient outcome often follows the course of CNS insult, not the NPE.³ Hypoxemic patients will undoubtedly require supplemental oxygen with the most severe requiring intubation and mechanical ventilation. The nuances to mechanical ventilation in NPE are: 1. Increasing PEEP may lessen the pulmonary edema but at the expense of potentially worsening intracranial hypertension due to reduction in cerebral venous return; 2. Hypercapnia should be avoided because of the cerebral vasodilatory properties of carbon dioxide and the increased cerebral blood flow potentially elevating ICPs.³ Hemodynamic management requires the clinician to finely balance reducing pressure in pulmonary vasculature while preserving CPP. Although its effectiveness is in question, Dobutamine is mentioned in the literature as a first line drug for supporting cardiac output (CO) and dropping cardiac filling pressures without driving SVR higher.¹ Careful consideration of diuretics and intravenous fluid restriction can be undertaken if CPP will not be compromised.³ Ultimate treatment of NPE being the resolution of underlying CNS insult as NPE generally resolves within 48-72 h with stable physiologic ICPs.^1,2

Take Home Points

In closing, the presence of pulmonary edema gives minimal insight into its origins or appropriate clinical course of action. A diagnosis of NPE requires the exclusion of cardiogenic and non-cardiogenic causes in the presence of an array of neurologic catastrophes. The mechanism(s) behind the genesis of NPE remain “squishy” and leave the possibility of subsets within NPE. While there are no specific therapies available to treat NPE, the foundation of treatment for this cohort of patients is supportive care to prevent hypoxia while maintaining CPP until control of ICPs is achieved.

References

1. Bidkar, P., & H. Prabhakar. (2016). Neurogenic pulmonary edema. In H. Prabhakar (Ed.), Complications in neuroanesthesia (pp. 181-188). San Diego, CA: Elsevier.
2. Finsterer, J. (2019). Neurological perspectives of neurogenic pulmonary edema. European Neurology, 81:94–101. doi:10.1159/000500139
3. Wemple, M., Hallman, M., & Luks, A. (2019). Neurogenic pulmonary edema. In P. Parsons (Ed.), UpToDate, Retrieved July 5, 2019, from https://www.uptodate.com/contents/neurogenic-pulmonary-edema