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.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Bederson JB, Connolly ES Jr, Batjer HH, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke. 2009;40:994–1025.
Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012;43:1711–37.
van den Berg R, Foumani M, Schroder RD, et al. Predictors of outcome in World Federation of Neurologic Surgeons grade V aneurysmal subarachnoid hemorrhage patients. Crit Care Med. 2011;39:2722–7.
Frontera JA, Fernandez A, Schmidt JM, et al. Defining vasospasm after subarachnoid hemorrhage: what is the most clinically relevant definition? Stroke. 2009;40:1963–8.
Vergouwen MD, Vermeulen M, van Gijn J, et al. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke. 2010;41:2391–5.
Hoff R, Rinkel G, Verweij B, Algra A, Kalkman C. Blood volume measurement to guide fluid therapy after aneurysmal subarachnoid hemorrhage: a prospective controlled study. Stroke. 2009;40:2575–7.
Kasuya H, Onda H, Yoneyama T, Sasaki T, Hori T. Bedside monitoring of circulating blood volume after subarachnoid hemorrhage. Stroke. 2003;34:956–60.
Meyer R, Deem S, David Yanez N, Souter M, Lam A, Treggiari MM. Current practices of triple-H prophylaxis and therapy in patients with subarachnoid hemorrhage. Neurocrit Care. 2010;14:24–36.
Rinkel GJ, Feigin VL, Algra A, van Gijn J. Circulatory volume expansion therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 2004:CD000483.
Diringer MN, Bleck TP, Claude Hemphill J III, et al. Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference. Neurocrit Care. 2011;15:211–40.
Treggiari MM, Walder B, Suter PM, Romand JA. Systematic review of the prevention of delayed ischemic neurological deficits with hypertension, hypervolemia, and hemodilution therapy following subarachnoid hemorrhage. J Neurosurg. 2003;98:978–84.
Egge A, Waterloo K, Sjoholm H, Solberg T, Ingebrigtsen T, Romner B. Prophylactic hyperdynamic postoperative fluid therapy after aneurysmal subarachnoid hemorrhage: a clinical, prospective, randomized, controlled study. Neurosurgery. 2001;49:593–605 discussion 605-596.
Lennihan L, Mayer SA, Fink ME, et al. Effect of hypervolemic therapy on cerebral blood flow after subarachnoid hemorrhage: a randomized controlled trial. Stroke. 2000;31:383–91.
Marik PE, Cavallazzi R. Does the central venous pressure predict fluid responsiveness? An updated meta-analysis and a plea for some common sense. Crit Care Med. 2013;41:1774–81.
Tagami T, Kuwamoto K, Watanabe A, et al. Optimal range of global end-diastolic volume for fluid management after aneurysmal subarachnoid hemorrhage: a multicenter prospective cohort study. Crit Care Med. 2014.
Lazaridis C. Advanced hemodynamic monitoring: principles and practice in neurocritical care. Neurocrit Care. 2012;16:163–9.
Mutoh T, Kazumata K, Ajiki M, Ushikoshi S, Terasaka S. Goal-directed fluid management by bedside transpulmonary hemodynamic monitoring after subarachnoid hemorrhage. Stroke. 2007;38:3218–24.
Mutoh T, Kazumata K, Ishikawa T, Terasaka S. Performance of bedside transpulmonary thermodilution monitoring for goal-directed hemodynamic management after subarachnoid hemorrhage. Stroke. 2009;40:2368–74.
Segal E, Greenlee JD, Hata SJ, Perel A. Monitoring intravascular volumes to direct hypertensive, hypervolemic therapy in a patient with vasospasm. J Neurosurg Anesthesiol. 2004;16:296–8.
Michard F, Alaya S, Zarka V, Bahloul M, Richard C, Teboul JL. Global end-diastolic volume as an indicator of cardiac preload in patients with septic shock. Chest. 2003;124:1900–8.
Watanabe A, Tagami T, Yokobori S, et al. Global end-diastolic volume is associated with the occurrence of delayed cerebral ischemia and pulmonary edema after subarachnoid hemorrhage. Shock. 2012;38:480–5.
Yoneda H, Nakamura T, Shirao S, et al. Multicenter prospective cohort study on volume management after subarachnoid hemorrhage: hemodynamic changes according to severity of subarachnoid hemorrhage and cerebral vasospasm. Stroke. 2013;44:2155–61.
Jordan LC, Johnston SC, Wu YW, Sidney S, Fullerton HJ. The importance of cerebral aneurysms in childhood hemorrhagic stroke: a population-based study. Stroke. 2009;40:400–5.
Sakowitz OW, Raabe A, Vucak D, Kiening KL, Unterberg AW. Contemporary management of aneurysmal subarachnoid hemorrhage in Germany: results of a survey among 100 neurosurgical departments. Neurosurgery. 2006;58:137–45.
Stevens RD, Naval NS, Mirski MA, Citerio G, Andrews PJ. Intensive care of aneurysmal subarachnoid hemorrhage: an international survey. Intensive Care Med. 2009;35:1556–66.
Meyer R, Deem S, Yanez ND, Souter M, Lam A, Treggiari MM. Current practices of triple-H prophylaxis and therapy in patients with subarachnoid hemorrhage. Neurocrit Care. 2011;14:24–36.
Kurtz P, Helbok R, Ko SB, et al. Fluid responsiveness and brain tissue oxygen augmentation after subarachnoid hemorrhage. Neurocrit Care. 2013.
Monnet X, Persichini R, Ktari M, Jozwiak M, Richard C, Teboul JL. Precision of the transpulmonary thermodilution measurements. Crit Care. 2011;15:R204.
Tagami T, Kushimoto S, Tosa R, et al. The precision of PiCCO measurements in hypothermic post-cardiac arrest patients. Anaesthesia. 2012;67:236–43.
Sakka SG, Reuter DA, Perel A. The transpulmonary thermodilution technique. J Clin Monit Comput. 2012;26:347–53.
Badjatia N, Carpenter A, Fernandez L, et al. Relationship between C-reactive protein, systemic oxygen consumption, and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Stroke. 2011;42:2436–42.
Sen J, Belli A, Albon H, Morgan L, Petzold A, Kitchen N. Triple-H therapy in the management of aneurysmal subarachnoid haemorrhage. Lancet Neurol. 2003;2:614–20.
Rondeau N, Cinotti R, Rozec B, et al. Dobutamine-induced high cardiac index did not prevent vasospasm in subarachnoid hemorrhage patients: a randomized controlled pilot study. Neurocrit Care. 2012;17:183–90.
Velat GJ, Kimball MM, Mocco JD, Hoh BL. Vasospasm after aneurysmal subarachnoid hemorrhage: review of randomized controlled trials and meta-analyses in the literature. World Neurosurg. 2011;76:446–54.
Ibrahim GM, Macdonald RL. The effects of fluid balance and colloid administration on outcomes in patients with aneurysmal subarachnoid hemorrhage: a propensity score-matched analysis. Neurocrit Care. 2013;19:140–9.
Lu N, Jackson D, Luke S, Festic E, Hanel RA, Freeman WD. Intraventricular nicardipine for aneurysmal subarachnoid hemorrhage related vasospasm: assessment of 90 days outcome. Neurocrit Care. 2012;16:368–75.
Ortega-Gutierrez S, Thomas J, Reccius A, et al. Effectiveness and safety of nicardipine and labetalol infusion for blood pressure management in patients with intracerebral and subarachnoid hemorrhage. Neurocrit Care. 2013;18:13–9.
Goepfert MS, Richter HP, Eulenburg CZ, et al. Individually optimized hemodynamic therapy reduces complications and length of stay in the intensive care unit: a prospective, randomized controlled trial. Anesthesiology. 2013;119:824–36.
Marik PE, Monnet X, Teboul JL. Hemodynamic parameters to guide fluid therapy. Ann Intensive Care. 2011;1:1.
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.
Takashi Tagami and Kentaro Kuwamoto contributed equally to this work.
This study was conducted on behalf of the SAH PiCCO Study Group.
About this article
Cite this article
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). https://doi.org/10.1007/s12028-014-9973-z