Fluid balance and clinically relevant outcomes Rui Moreno, MD, PhD, Professor UCINC, Hospital de São José Centro Hospitalar de Lisboa Central, E.P.E.
INSULT PRIMARY MODS SIRS SECONDARY MODS OUTCOME RECOVERY DEATH
MORTALITY DETERMINANTS - HOST Genetic background (inflammatory response) Age Prior diseases 45% of prognosis Imune response Cardiovascular reserve Acute disease (Bug) Time of intervention (Doctor) 20% of prognosis Acute physiological dysfunction 35% of prognosis Outcome Moreno R. SAPS 3 Score: Sepsis Model
Early Antimicrobials Early Haemodinamic Resusciatation
Too wet
Too dry
Review and Discuss Phases of Fluid Therapy Impact of Fluid Accumulation Fluid Removal (i.e. De-Resuscitation)
The Fluid Balance Paradigm F L U I D B A L A N C E I II III R E S U C I T A T I O N Maintenance/ Homeostasis TIME Removal/ Recovery
PHASE I OF THE FLUID PARADIGM Identification/diagnosis Therapeutic Monitoring Individualized Early/Aggressive Initially Resuscitation Hemodynamic stabilization Shock reversal Then: REASSESS!!
PHASE II OF THE FLUID PARADIGM Maintenance of fluid balance homeostasis and/or prevention of worsening (+/- unnecessary) fluid overload Assess need for all fluids (i.e. nutrition, medications, blood products) Assess ability to maintain fluid balance Assess patient s current fluid accumulation status Define the amount of fluids that the patient is still needing
Emmanuel Rivers and the EGDT trials: Rivers EGDT ARISE ProCESS PROMISe
Early Goal-Directed Therapy (EGDT)
Early Goal-Directed Therapy (EGDT): Design Single center, parallel-group, randomized, controlled trial N=263 patients with severe sepsis or septic shock Early-goal directed therapy (n=130) Standard therapy (n=133) Setting: Single, tertiary center in Detroit Enrollment: 1997-2000 Analysis: Intention-to-treat Primary outcome: In-hospital mortality Inclusion Criteria Patients presenting to the ED with signs of sepsis, severe sepsis, or septic shock (SIRS plus SBP <90mmHg despite 20-30ml/kg crystalloid challenge over 300 minutes or blood lactate >4mmol/L)
Early Goal-Directed Therapy (EGDT): Interventions Randomized to EGDT vs. standard therapy EGDT protocol consisted of several sequential goals started in the ER 6 hrs prior to ICU admission: CVP 8-12mmHg, achieved with fluid boluses MAP >65mmHg, achieved with vasopressors or vasodilators if necessary ScvO2 >70%, achieved with packed RBC transfusions to maintain Hct >30%, then dobutamine started at 2.5 mcg/kg/min (max 20 mcg/kg/min, HR<120bpm) until ScvO2 >70% if necessary UOP >0.5 ml/kg/hr Standard therapy maintained: CVP 8-12 mmhg UOP >0.5 ml/kg/hr MAP 65-90 mmhg with either vasopressors or vasodilators
Rivers, 2001 NEJM 9. Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock. Emanuel Rivers, M.D., M.P.H., et. Al. N Engl J Med 2001; 345:1368-1377November 8, 2001DOI: 10.1056/NEJMoa010307.
Early Goal-Directed Therapy (EGDT): Additional Analysis Additional Analyses Total fluids 0-6 hours: 4.9 L vs. 3.5 L (P<0.001) 7-72 hours: 8.6 L vs. 10.6 L (P=0.01) 0-72 hours: 13.4 L vs. 13.4 L (P=0.73) RBC transfusion 0-6 hours: 64.1% vs. 18.5% (P<0.001) 7-72 hours: 11.1% vs. 32.8% (P<0.001) 0-72 hours: 68.4% vs. 44.5% (P<0.001) Vasopressors 0-6 hours: 27.4% v.s 30.3% (P=0.62) 7-72 hours: 29.1% vs. 42.9% (P=0.03) 0-72 hours: 36.8% vs. 51.3% (P=0.02)
SHALL WE CONTINUE WITH EGDT?
ARISE trial Goal-Directed Resuscitation for Patients with Early Septic Shock 51 centers Australia/New Zealand 1600 enrolled patients assigned to EGDT or usual-care. 22. Goal-Directed Resuscitation for Patients with Early Septic Shock. The ARISE Investigators and the ANZICS Clinical Trials Group. N Engl J Med 2014;371:1496-506.
ARISE
ProCESS trial A Randomized Trial of Protocol-Based Care for Early Septic Shock 31 tertiary US emergency departments 1341 enrolled patients assigned to EGDT, protocol based standard therapy, or usual-care. 23. A Randomized Trial of Protocol-Based Care for Early Septic Shock. The ProCESS Investigators. N Engl J Med. 2014;370:1683-93.
PROMISE trial 23. A Randomized Trial of Protocol-Based Care for Early Septic Shock. The ProCESS Investigators. N Engl J Med. 2014;370:1683-93.
PROMISe trial A Pragmatic Randomized Trial of Protocol-Based Care for Early Septic Shock 56 hospitals in England; 630 patients assigned to EGDT and 630 to usual care. By 90 days, 184 of 623 patients (29.5%) in the EGDT group and 181 of 620 patients (29.2%) in the usual-care group had died (relative risk in the EGDT group, 1.01 (95% confidence interval [CI], 0.85 to 1.20); P = 0.90), for an absolute risk reduction. Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids, vasoactive drugs, and red-cell transfusions and reflected by significantly Worse organ-failure scores, more days receiving advanced cardiovascular support, and longer stays in the intensive care unit.
Table 3. Fluid resuscitation volumes at various time points in the study (mls). George E Evetts, and Kristina Birch Journal of the Intensive Care Society 2015;16:164-168 Copyright by The Intensive Care Society
SHALL WE CONTINUE WITH EGDT?
Did the last EGDT trials change my practice?
Summary Fluid is a Drug: considering its toxic cumulative effects to guide optimal dosing may improve outcome Volume and Timing of Fluid are critical (Excessive) Fluid accumulation is bad predictor of less favorable outcome Need to better understand ideal strategies to (safely) mitigate and/or remove excess extravascular fluid
PHASE IIII OF THE FLUID PARADIGM: DILEMMNA What if the critically ill patient (with AKI) cannot tolerate the needed fluid volumes without developing worsening fluid accumulation? A.Fluid restrict B. Loop Diuretic C. Early initiation of RRT renal replacement to maintain fluid homeostasis
r.moreno@mail.telepac.pt