Genesis of NPE.

In order to explain the presence of both
Genesis of NPE. In order to explain the presence of both hydrostatic factors and vascular leak, Theodore and Robin introducedDavison et al. Critical Care 2012, 16:212 http://ccforum.com/content/16/2/Page 4 ofthe "blast theory" of NPE [39]. Similar to the neurohemodynamic model, the "blast theory" posits that the severe abrupt increases in systemic and pulmonary pressures following the catecholamine surge result in a net shift of blood volume from the systemic circulation (R)-1-(3-Chlorophenyl)ethan-1-ol to the low resistance pulmonary circulation. This increase in pulmonary Cyclohept-2-enone venous pressure leads to the development of transudative pulmonary edema. The "blast theory" further posits that the acute rise in capillary pressure induces a degree of barotrauma capable of damaging the capillary-alveolar membrane. The structural damage to the pulmonary endothelium ultimately leads to vascular leak and persistent protein-rich pulmonary edema [39]. The pulmonary edema according to the "blast theory" is thus the result of two mechanisms which act synergistically: A high-pressure hydrostatic influence and pulmonary endothelial injury. Several pre-clinical models support this mechanism [40,41]. Maron showed that barotrauma and vascular permeability occurred when pulmonary pressures exceeded 70 torr following CNS injury in dogs [40]. In another study, EVLW was observed when pulmonary artery pressures reached 25 torr or greater in rabbits [41]. The authors concluded that some degree of pulmonary hypertension is required for the development of pulmonary edema, and that the degree of permeability is "pressure dependent" [41]. Theodore and Robin in the "blast theory" acknowledged that it is rare to document elevated systemic and pulmonary pressures in human cases of NPE. According to their theory, this can be explained by the fact that the sympathetic surge and subsequent hemodynamic instability occurs at the time of the inciting event when hemodynamic monitoring is rare [39]. During the later stages of NPE, systemic and pulmonary pressures can return to normal, whereas the endothelial injury and vascular leak may persist [39]. A few case reports have been able to document this sequence of events in human subjects, lending credence to the "blast theory". One case study described a patient who had hemodynamic monitoring at the time of a seizure that led to NPE. Within minutes of the seizure, marked increases in systemic, pulmonary and pulmonary artery occlusion pressures were recorded. The hemodynamics quickly normalized PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/20460822 and two hours later, pulmonary edema developed, which was determined to be high in protein content [37]. In another case report of a patient with an intracranial hemorrhage, extreme increases in systemic and mean pulmonary pressures (410/200 mmHg and 48 mmHg, respectively) lasted 4 minutes. This was followed by a dramatic decrease in the patient's oxygen levels. The patient's pulmonary edema did not clear on radiograph for 72 hours following the last PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/22993420 episode of transient systemic and pulmonary hypertension. The authors concluded that persistent vascular leak was the basis for these findings [42].Pulmonary venule adrenergic hypersensitivityMany reports of NPE fail to consistently demonstrate the hypertensive surges and changes in left atrial pressures as described in the theories above. This suggests that systemic hypertension and its effect on cardiac contractility may not always contribute to the development of NPE. An alternative hypothesis is that the massive sympathet.