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

  • Clinical Article
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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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Authors and Affiliations

  1. Department of Neurosurgery, Fujita Health University School of Medicine, 1-84 Kutsukake, Toyoake, 470-1192, Japan

    Joji Inamasu, Yasuhiro Yamada, Tsukasa Ganaha, Keisuke Ito, Takeya Watabe, Takuro Hayashi, Yoko Kato & Yuichi Hirose

  2. Department of Laboratory Medicine, Fujita Health University School of Medicine, Toyoake, Japan

    Keiko Sugimoto

  3. Department of Cardiology, Fujita Health University School of Medicine, Toyoake, Japan

    Yukio Ozaki

Authors
  1. Joji Inamasu
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  2. Keiko Sugimoto
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  3. Yasuhiro Yamada
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  4. Tsukasa Ganaha
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  5. Keisuke Ito
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  6. Takeya Watabe
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  7. Takuro Hayashi
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  8. Yoko Kato
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  9. Yukio Ozaki
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  10. Yuichi Hirose
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Corresponding author

Correspondence to Joji Inamasu.

Additional information

Comment

Inamasu and colleagues provide a retrospective study analysing the role of epinephrine and norepinephrine in the pathogenesis of pulmonary oedema after aneurysmal subarachnoid haemorrhage (SAH) in 63 patients.

Neurogenic pulmonary oedema presents a dangerous complication in the course of aneurysmal SAH and the pathogenesis of this kind of pulmonary oedema is still not completely understood. The presented study demonstrates the important role of norepinephrine in this disease and the less important role of epinephrine, even though a positive correlation between epinephrine and norepinephrine levels has been shown by the authors. Thus, this study may present a further little step in understanding neurogenic pulmonary oedema after aneurysmal SAH.

On the other hand, we have to keep in mind the retrospective design of this study with the well-known shortcomings of such a study design. Further, and in my opinion most important, haemodynamic parameters of the systemic and pulmonary circulation have not been acquired. Thus, pulmonary oedema due to an increased afterload following induced peripheral vasoconstriction and acute left ventricular failure as a consequence of increased levels of norepinephrine cannot be excluded by the study presented.

Further studies should be performed to clear these questions.

Marcus Reinges

Giessen, GERMANY

Neurogenic pulmonary edema (NPE) may complicate subarachnoid haemorrhage (SAH) in a significant percentage of patients, approximately 10 % according to the literature and the experience reported in this article. Nonetheless, it is has been shown that NPE occurs in more than 70 % of fatal cases of SAH [1]. This can be attributed to the severity of the bleeding, but it is possible and even likely that the relevance of NPE as a direct cause of death is underestimated.

The formation of edema has been alternatively attributed to an increase in capillary hydrostatic pressure secondary to a left ventricle performance deterioration due to the effects of catecholamines on peripheral circulation or to a direct, non-hydrostatic effect on the pulmonary capillary permeability induced by cathecolamines. This is an important issue with implications in the choice of medications that, however, is not addressed by this study. Nevertheless, in this clear and concise article Inamasu and co-workers demonstrated that the norepinephrine serum level represents an independent predictor of NPE. They also identified a cut-off value, thus providing a potential serum biomarker for the diagnosis of NPE. Further studies on this topic are necessary, but warranted by the importance of the question.

1. Muroi C, Keller M, Pangalu A, Fortunati M, Yonekawa Y, Keller E (2008) Neurogenic pulmonary edema in patients with subarachnoid hemorrhage. J Neurosurg Anesthesiol 20:188–192

Alfredo Conti

Messina, ITALY

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Inamasu, J., Sugimoto, K., Yamada, Y. et al. The role of catecholamines in the pathogenesis of neurogenic pulmonary edema associated with subarachnoid hemorrhage. Acta Neurochir 154, 2179–2185 (2012). https://doi.org/10.1007/s00701-012-1515-x

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  • DOI: https://doi.org/10.1007/s00701-012-1515-x

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