The role of catecholamines in the pathogenesis of neurogenic pulmonary edema associated with subarachnoid hemorrhage

Abstract

Neurogenic pulmonary edema (NPE) occurs frequently after aneurysmal subarachnoid hemorrhage (SAH), and excessive release of catecholamines (epinephrine/norepinephrine) has been suggested as its principal cause. The objective of this retrospective study is to evaluate the relative contribution of each catecholamine in the pathogenesis of NPE associated with SAH. Records of 63 SAH patients (20 men/43 women) whose plasma catecholamine levels were measured within 48 h of SAH onset were reviewed, and the clinical characteristics and laboratory data of those who developed early-onset NPE were analyzed thoroughly. Seven patients (11 %) were diagnosed with NPE on admission. Demographic comparison revealed that the NPE+ group sustained more severe SAH than the NPE- group. Cardiac dysfunction was also significantly more profound in the former, and the great majority of the NPE+ group sustained concomitant cardiac wall motion abnormality. There was no significant difference in the plasma epinephrine levels between NPE+ and NPE- group (324.6 ± 172.8 vs 163.1 ± 257.2 pg/ml, p = 0.11). By contrast, plasma norepinephrine levels were significantly higher in the NPE+ group (2977.6 ± 2034.5 vs 847.9 ± 535.6 pg/ml, p < 0.001). Multivariate regression analysis revealed that increased norepinephrine levels were associated with NPE (OR, 1.003; 95 % CI, 1.002-1.007). Plasma epinephrine and norepinephrine levels were positively correlated (R = 0.48, p < 0.001). According to receiver operating characteristic curve analysis, the threshold value for plasma norepinephrine predictive of NPE was 2,000 pg/ml, with an area under the curve value of 0.85. Elevated plasma norepinephrine may have more active role in the pathogenesis of SAH-induced NPE compared with epinephrine, although both catecholamines may be involved via multiple signaling pathways.