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Effect of Triple-H Prophylaxis on Global End-Diastolic Volume and Clinical Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage

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Although prophylactic triple-H therapy has been used in a number of institutions globally to prevent delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH), limited evidence is available for the effectiveness of triple-H therapy on hemodynamic variables. Recent studies have suggested an association between low global end-diastolic volume index (GEDI), measured using a transpulmonary thermodilution method, and DCI onset. The current study aimed at assessing the effects of prophylactic triple-H therapy on GEDI.


This prospective multicenter study included aneurysmal SAH patients admitted to 9 hospitals in Japan. The decision to administer prophylactic triple-H therapy and the management protocols were left to the physician in charge (physician-directed therapy) of each participating institution. The primary endpoints were the changes in the hemodynamic variables as analyzed using a generalized linear mixed model.


Of 178 patients, 62 (34.8 %) received prophylactic triple-H therapy and 116 (65.2 %) did not. DCI was observed in 35 patients (19.7 %), with no significant difference between the two groups [15 (24.2 %) vs. 20 (17.2 %), p = 0.27]. Although a greater amount of fluid (p < 0.001) and a higher mean arterial pressure (p = 0.005) were observed in the triple-H group, no significant difference was observed between the groups in GEDI (p = 0.81) or cardiac output (p = 0.62).


Physician-directed prophylactic triple-H administration was not associated with improved clinical outcomes or quantitative hemodynamic indicators for intravascular volume. Further, GEDI-directed intervention studies are warranted to better define management algorithms for SAH patients with the aim of preventing DCI.

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We would like to acknowledge all the institutions and their staff who participated in the SAH PiCCO study, especially Prof. Eiji Isotani, MD, PhD (Department of Emergency and Critical Care Medicine, Tokyo Women’s Medical University Medical Center East) who is the director of the study. We are grateful to Prof. Hideo Yasunaga, MD, PhD (Department of and Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo) for assistance during the statistical review of the manuscript. Takashi Tagami received speaker honoraria from Tokibo Co., Ltd. (import trader of the PiCCO system) for educational lectures at Japanese scientific meetings. This study was not funded or sponsored by any organization.

Conflicts of interest

Kentaro Kuwamoto, Akihiro Watanabe, Kyoko Unemoto, Shoji Yokobori, Gaku Matsumoto, Yutaka Igarashi, and Hiroyuki Yokota declare that they have no conflicts of interest.

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Correspondence to Takashi Tagami.

Additional information

Takashi Tagami and Kentaro Kuwamoto contributed equally to this work.

This study was conducted on behalf of the SAH PiCCO Study Group.

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Tagami, T., Kuwamoto, K., Watanabe, A. et al. Effect of Triple-H Prophylaxis on Global End-Diastolic Volume and Clinical Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care 21, 462–469 (2014).

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