Introduction

Trauma is a frequent cause of Acute Brain Injury (ABI) worldwide and although less frequent, Subdural Hemorrhage (SDH), Subarachnoid Hemorrhage (SAH), Intra-Parenchymal Hemorrhage (IPH), meningitis, stroke, status epilepticus and others have also been attributed to brain injury [1]. An often under-recognized unique complication of ABI is Neurogenic Pulmonary Edema (NPE). Overall, the incidence of NPE is estimated to be around 20-30% of patients with ABI [2-9]. Approximately 15% of patients with either Hunt and Hess grade III-V or Fisher grade III-IV Subarachnoid Hemorrhage (SAH) develop neurogenic pulmonary edema [10,11].

This review aims to describe the proposed pathophysiologic mechanisms with an additional focus on the management of pulmonary complications in patients with NPE.

Methodology

Pathophysiology

Although the exact cause is unknown, several theories have been proposed to explain the pathophysiology of pulmonary edema in the setting of ABI. We will discuss the proposed mechanisms involving multiple cascading events that concomitantly occur during the development of NPE.

Catecholamine induced peripheral vasoconstriction: A wealth of knowledge was gained from the early observations in animal experiments using noxious stimulation of the Central Nervous System (CNS) to study its effects on the cardio-pulmonary system. It was observed that lesions of the CNS produced in this way resulted in an elevation of pulmonary and systemic arterial pressures [13-15]. Moreover, bilateral upper thoracic sympathetectomy or even total lung denervation did not prevent the elevation of these pressures [13]. It was thus concluded that severe peripheral vasoconstriction induced by catecholamines released as a consequence of CNS injury results in severe systemic hypertension causing strain on the Left Ventricle (LV), similarly seen in Takotsubo cardiomyopathy [16]. This leads to secondary LV dysfunction causing elevation of left atrial and pulmonary venous pressures, and subsequently pulmonary edema. Pulmonary edema has been seen as the sole presentation in patients with pheochromocytoma, presumably from the catecholamine surge [17].

Pulmonary venoconstriction: Maron MB and Dawson CA [18] showed that in an experimental model with increased cerebrospinal fluid pressure in dogs caused catecholamine induced pulmonary venoconstriction in a denervated lobe of the lung. Indirect observations in humans using initial alveolar edema fluid to plasma protein concentration ratio in patients without heart failure or volume overload points towards a hydrostatic mechanism for the development of NPE. Smith WS and Matthay MA [19] concluded either pulmonary venoconstriction or transient elevation in left-sided cardiovascular pressures as the contributing causes to the development of human neurogenic pulmonary edema.

In addition to the catecholamine mediated pulmonary venoconstriction, centrally mediated reflex neural mechanisms have also been proposed. Moss G, et al. [20] demonstrated that changes of ARDS can occur following cerebral hypoxemia without any increase in systemic blood pressure. They proposed a centrally mediated pulmonary venous spasm triggered by hypothalamic hypoxia resulting into pulmonary hypertension and ARDS, suggesting an alternative reflex neural mechanism independent of systemic hypertension. Other studies demonstrated by Gamble JE and Patton HD [21] and Maire FW and Patton HD [22], that selective bilateral lesions of the preoptic regions of the hypothalamus resulted into hemorrhagic pulmonary edema in rats. However, the effects of these lesions on the cardiovascular system were not studied in these experiments. Schraufnagel DE and Patel KR [23] studied the effects on neural stimulation after a blunt force to the brain in a rat model. They found that pulmonary veins have sphincters that are strategically placed to influence blood flow which respond to neural stimuli initiated by a sharp head blow and could potentiate the degree of neurogenic pulmonary edema.