Neurocrit Care DOI 10.1007/s12028-014-9973-z
ORIGINAL ARTICLE
Effect of Triple-H Prophylaxis on Global End-Diastolic Volume and Clinical Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage Takashi Tagami • Kentaro Kuwamoto • Akihiro Watanabe Kyoko Unemoto • Shoji Yokobori • Gaku Matsumoto • Yutaka Igarashi • Hiroyuki Yokota
•
Ó Springer Science+Business Media New York 2014
Abstract Background 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. Methods 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. Results 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). Conclusions 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.
Takashi Tagami and Kentaro Kuwamoto contributed equally to this work.
Keywords Cardiac output Delayed cerebral ischemia Goal-directed therapy Cerebral vasospasm Transpulmonary thermodilution method
This study was conducted on behalf of the SAH PiCCO Study Group. T. Tagami (&) A. Watanabe S. Yokobori G. Matsumoto Y. Igarashi H. Yokota Department of Emergency and Critical Care Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan e-mail: [email protected] T. Tagami Department of Clinical Epidemiology and Health Economics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan K. Kuwamoto K. Unemoto Department of Emergency and Critical Care Medicine, Nippon Medical School Tamanagayama Hospital, Tokyo, Japan
Introduction Subarachnoid hemorrhage (SAH) is a common and devastating condition resulting in high morbidity, mortality, and healthcare burden [1–3]. The occurrence of delayed cerebral ischemia (DCI) increases poor outcomes following SAH [4, 5], and the presence of hypovolemia significantly increases the risk of DCI [6, 7]. Prophylactic triple-H therapy (i.e., the combination of hypertensive, hypervolemic, and hemodilution therapies) has been suggested to decrease the frequency and severity of symptomatic vasospasms and subsequently reduce the incidence of DCI [1,
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Neurocrit Care
6, 8]. However, there is limited evidence from clinical trials to support the efficacy of prophylactic triple-H therapy [9–11]. Moreover, few studies have investigated the effect of triple-H therapy on the hemodynamic variables that represent hypovolemia [12, 13]. Previous studies used central venous pressure (CVP) as an indicator for cardiac preload and to guide fluid therapy in the treatment groups [12, 13]. However, CVP does not represent intravascular volume status and is currently considered a poor indicator for fluid therapy [14, 15]. Recent evidence suggests that the quantitative assessment of hemodynamic variables by the single-indicator transpulmonary thermodilution method, the PiCCOÒ monitoring system (Pulsion Medical Systems, Munich, Germany), is useful for fluid management after SAH [16– 19]. In addition to monitoring continuous cardiac output, the system provides accurate and quantitative volumetric variables for direct measurement of cardiac preload in the form of the global end-diastolic volume index (GEDI), which represents the combined end-diastolic volumes of the four cardiac chambers [20]. Previous studies have suggested an association between low GEDI and DCI onset in SAH patients [18, 21]. However, the effect of triple-H prophylaxis on GEDI remains unknown. We hypothesized that triple-H prophylaxis increases GEDI and prevents the onset of DCI following SAH. In the present prospective multicenter study (SAH PiCCO study), we, therefore, aimed to assess the effects of triple-H prophylaxis on GEDI, measured using the PiCCO system.
Materials and Methods Patients and Management The SAH PiCCO study was a multicenter prospective cohort study that examined aneurysmal SAH patients admitted to 9 participating Japanese university hospitals [15, 22]. The current study reports the main outcome results of the SAH PiCCO study, which was registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN-CTR ID UMIN000003794 (http://apps.who.int/ trialsearch/trial.aspx?trialid=JPRN-UMIN000003794). This study was approved by the ethics committees of all 9 institutions, and written informed consent was obtained from all patients or their next of kin. Patients with aneurysmal SAH who were admitted to any of the 9 participating institutions from October 2008 to March 2012 and were monitored with the PiCCOÒ system during the perioperative period (i.e., patients treated with surgical aneurysmal clipping or intravascular coil embolization) were included in the study. The exclusion criteria were as follows: (1) aged
ORIGINAL ARTICLE
Effect of Triple-H Prophylaxis on Global End-Diastolic Volume and Clinical Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage Takashi Tagami • Kentaro Kuwamoto • Akihiro Watanabe Kyoko Unemoto • Shoji Yokobori • Gaku Matsumoto • Yutaka Igarashi • Hiroyuki Yokota
•
Ó Springer Science+Business Media New York 2014
Abstract Background 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. Methods 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. Results 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). Conclusions 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.
Takashi Tagami and Kentaro Kuwamoto contributed equally to this work.
Keywords Cardiac output Delayed cerebral ischemia Goal-directed therapy Cerebral vasospasm Transpulmonary thermodilution method
This study was conducted on behalf of the SAH PiCCO Study Group. T. Tagami (&) A. Watanabe S. Yokobori G. Matsumoto Y. Igarashi H. Yokota Department of Emergency and Critical Care Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan e-mail: [email protected] T. Tagami Department of Clinical Epidemiology and Health Economics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan K. Kuwamoto K. Unemoto Department of Emergency and Critical Care Medicine, Nippon Medical School Tamanagayama Hospital, Tokyo, Japan
Introduction Subarachnoid hemorrhage (SAH) is a common and devastating condition resulting in high morbidity, mortality, and healthcare burden [1–3]. The occurrence of delayed cerebral ischemia (DCI) increases poor outcomes following SAH [4, 5], and the presence of hypovolemia significantly increases the risk of DCI [6, 7]. Prophylactic triple-H therapy (i.e., the combination of hypertensive, hypervolemic, and hemodilution therapies) has been suggested to decrease the frequency and severity of symptomatic vasospasms and subsequently reduce the incidence of DCI [1,
123
Neurocrit Care
6, 8]. However, there is limited evidence from clinical trials to support the efficacy of prophylactic triple-H therapy [9–11]. Moreover, few studies have investigated the effect of triple-H therapy on the hemodynamic variables that represent hypovolemia [12, 13]. Previous studies used central venous pressure (CVP) as an indicator for cardiac preload and to guide fluid therapy in the treatment groups [12, 13]. However, CVP does not represent intravascular volume status and is currently considered a poor indicator for fluid therapy [14, 15]. Recent evidence suggests that the quantitative assessment of hemodynamic variables by the single-indicator transpulmonary thermodilution method, the PiCCOÒ monitoring system (Pulsion Medical Systems, Munich, Germany), is useful for fluid management after SAH [16– 19]. In addition to monitoring continuous cardiac output, the system provides accurate and quantitative volumetric variables for direct measurement of cardiac preload in the form of the global end-diastolic volume index (GEDI), which represents the combined end-diastolic volumes of the four cardiac chambers [20]. Previous studies have suggested an association between low GEDI and DCI onset in SAH patients [18, 21]. However, the effect of triple-H prophylaxis on GEDI remains unknown. We hypothesized that triple-H prophylaxis increases GEDI and prevents the onset of DCI following SAH. In the present prospective multicenter study (SAH PiCCO study), we, therefore, aimed to assess the effects of triple-H prophylaxis on GEDI, measured using the PiCCO system.
Materials and Methods Patients and Management The SAH PiCCO study was a multicenter prospective cohort study that examined aneurysmal SAH patients admitted to 9 participating Japanese university hospitals [15, 22]. The current study reports the main outcome results of the SAH PiCCO study, which was registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN-CTR ID UMIN000003794 (http://apps.who.int/ trialsearch/trial.aspx?trialid=JPRN-UMIN000003794). This study was approved by the ethics committees of all 9 institutions, and written informed consent was obtained from all patients or their next of kin. Patients with aneurysmal SAH who were admitted to any of the 9 participating institutions from October 2008 to March 2012 and were monitored with the PiCCOÒ system during the perioperative period (i.e., patients treated with surgical aneurysmal clipping or intravascular coil embolization) were included in the study. The exclusion criteria were as follows: (1) aged
