1. COMBINED USE OF TRANSPULMONARY THERMODILUTION (TPTD) TECHNIQUE IN FLUID MANAGEMENT FOR SEPSIS PATIENTS 1 St. Marianna University School of Medicine, Kanagawa, Japan Department of Emergency and Critical Care Medicine 2 Tokyobay UrayasuIchikawa Medical Center, Chiba, Japan K. Morisawa 1, M. Yanai 1, Y. Takamatsu 1, M. Takita 1, S. Fujiwara 1 B. Lohman 1, J. Matsumoto 1, S. Fujitani 2, Y. Taira 1

2. INTRODUCTION Treatment for sepsis requires proper fluid transfusion and monitoring of hemodynamic changes. The mainstay guidelines recommend CVP for fluid management. Fluid management with CVP monitoring may lead to excessive transfusion resulting in the following adverse reactions. TPTD is a technique that can estimate the global end-diastolic volume (GEDV) from the thermodilution curve. CV catheter Bolus cold saline TPTD catheter at femoral artery Pulmonary circulation GEDV = Blood volume in the 4 chambers of the heart TPTD monitoring Blood temperature Time Thermodilution curve Bolus cold saline TPTD catheter measures the downstream temperature changes. CVP, central vein pressure; MV, mechanical ventilation; TPTD, transpulmonary thermodilution; GEDV, global end-diastolic volume Systemic circulation

3. Adequate volume resuscitation ? Further treatment Goal ? Adequate volume resuscitation Intubation and oxygenation for SpO 2 ≥ 92 % ScvO 2 ≥ 70 % ? Dobutamine RBC transfusion Hct > 30 % ? MAP 65 - 90 mmHg ? Norepinephrine or Nitroglycerin CVP group CVP 12 – 15 mmHg ? Volume infusion or reduction TPTD group GEDI 650 – 850 ? SVV < 15 % ? Hct > 30 % ScvO 2 ≥ 70 % Lactate < 4 mmol/L SpO 2 ≥ 92 % MAP 65 - 90 mmHg YESNO PROTOCOL TPTD group : using GEDI and SVV CVP group : based on the original EGDT TPTD group : using GEDI and SVV CVP group : based on the original EGDT We assessed and compared the clinical outcome and total fluid balance between 2 groups of sepsis patients that were managed with TPTD and CVP respectively within 72 hours of admission to the ICU. Primary outcome : 28-day mortality Secondary outcome : ICU stay days : Mechanical ventilation days : Total volume balance Primary outcome : 28-day mortality Secondary outcome : ICU stay days : Mechanical ventilation days : Total volume balance GEDI, global end-diastolic volume index calculated by the body surface area (mL/㎡) TPTD, transpulmonary thermodilution; CVP, central vein pressure; EGDT, early-goal directed therapy; GEDV, global end-diastolic volume; SVV, stroke volume variation

4. TPTD group (n = 11) CVP group (n = 12) P value Age73 (10)74 (9)ns Male [n(%)]8 (73%)6 (50%)ns SAPS II53 (13)56 (16)ns SOFA11 (3)10 (4)ns Pneumonia45 Peritonitis32 UTI22 Others23 Lactate [mmol/L] 3.5 (2.9)2.5 (1.8)ns PARTICIPANTS (Mean ± SD) 23 severe sepsis and septic shock patients in the ICU Vasopressors and Mechanical ventilation September 2012 to August 2013 43 sepsis patients in study 20 patients excluded No vasopressors (n=3) Protocol deviation (n=9) No infection (n=4) Data deficiency (n=3) DNAR order (n=1) TPTD group (n = 11) CVP group (n = 12) Flow diagram TPTD, transpulmonary thermodilution; CVP, central vein pressure; SAPS II, simplified acute physiology score II SOFA, sequential organ assessment score; UTI, urinary tract infection

5. TPTD group (n = 11) CVP group (n = 12) P value 28-day mortality [n(%)]2 (18)4 (33)ns ICU stay days6.3 (5.3)8.8 (3.4)0.01 MV days4.2 (2.3)5.6 (2.3)ns Volume balance[ml] 0-24hr2666 (1798)5014 (3351)0.02 24-48hr69 (1095)1889 (2120)0.01 48-72hr59 (648)171 (1446)ns Total in 3 days2885 (2678)7074 (5248)0.01 RESULTS (Mean ± SD) TPTD, transpulmonary thermodilution; CVP, central vein pressure; MV, mechanical ventilation

6. CONCLUSIONS TPTD monitoring may help reduce any excess fluid transfusion. TPTD monitoring method may help shorten ICU hospitalization in patients with severe sepsis and septic shock. RCT is needing to validate our result. Multicenter RCT for this question is in process. (UMIN000011493)