9/22/2012 Obligatory joke • Keep your eye on the food. Goal-Directed Fluid Resuscitation Christopher G. Choukalas, MD, MS Department of Anesthesia and Perioperative Care University of California, San Francisco The case for why it matters • • • • Fluid balance a common concern Sepsis ALI/ARDS Sepsis PLUS ARDS! Sepsis: More is more • Some impressive fluid totals Study Control Intervention Jansen (8 hrs) 2.2L 2.7L Jones (6 hrs) 4.5L 4.3L Rivers (6 hrs) 3.5L 5L 1 9/22/2012 Sepsis + CVP = Death Or is it? • Retrospective analysis of VASST trial – 778 pts w/ septic shock on NE • Divided into quartiles based on total fluid in at 12 hrs, 4 days Dry Quartile Wet Quartile 12 hours +0.7L +8.2L 4 days +1.6L +20.5L Boyd, JH, et al. 2011. CCM. 39(2) • Outcomes: Quartile x 28 d mortality • Early (12 hrs) and Late (4 d) “dry-ness” saved lives: – HR 0.57 and 0.47, respectively Survival Dry Quartile 12 hours 81% Wet Quartile 58% 4 days 83% 65% Boyd, JH, et al. 2011. CCM. 39(2) Just the FACTTs • 1001 w/ ALI randomized to liberal or conservative fluid algorithms • Varying amounts of fluid, furosemide, dobutamine Outcome Fluid total (day 7; mL) Conservative Liberal -136 +6990 Vent-Free days ICU-Free days Dialysis CNS failure free days 2 9/22/2012 Outcome Conservative Liberal Mortality (60d) 25.5% 28.4% (ns) Vent-Free days Vent-Free days +++ ICU-Free days ICU-Free days +++ Dialysis Dialysis CNS failure free days CNS failure free days Mortality (60d) Conservative Liberal 25.5% 28.4% (ns) Outcome • Patients with Sepsis who developed ALI • 4 groups: Outcome Conservative Liberal Mortality (60d) 25.5% 28.4% (ns) Vent-Free days +++ ICU-Free days +++ Dialysis Less CNS failure free days +++ More (ns) – Adequate initial + Conservative late fluids – Adequate initial only – Conservative late only – Neither 3 9/22/2012 It matters • So how do we do it? Murphry, CV, et al. 2009. Chest. 136(1) I would posit two factors: • Hemodynamic: – Is the circulation adequate? • Metabolic – Are oxygen delivery and utilization adequate? • Both have their own goals. Hemodynamic Goals • Blood pressure • CVP • Dynamic respiratory indices: – Pulse pressure/systolic pressure/perfusion index variation 4 9/22/2012 Hemodynamic Goals • Blood pressure • CVP • Dynamic respiratory indices: Blood pressure • A proxy for flow, end organ perfusion • Flow = pressure/resistance • Do we ever really KNOW resistance? – Pulse pressure/systolic pressure/perfusion index variation Wax, et al. • Non-cardiac cases with both ABP and NIBP. • Compared SBP, DBP, and MAP btwn technologies: – A-line alone vs A-line + cuff 5 9/22/2012 Randomized trials Interesting review • Reviewed 2 trials and 1 meta-analysis (13 studies) – Target BP – Actual BP • Dissociation – BPs invariably higher than goal – Higher goal ranges permitted higher actual ranges: pressors 6 9/22/2012 Blood pressure • Necessary but not sufficient • Goals are nebulous • Supra-normal levels common, not helpful Hemodynamic • Blood pressure • CVP • Dynamic respiratory indices: Concept: assumptions Normal CVP Optimal actin-myosin match – Pulse pressure/systolic pressure/perfusion index variation Adequate contractility Adequate DO2 7 9/22/2012 The data • Critical target in EGDT for sepsis • Incorporated into SSC guidelines Fluid responsiveness and total blood volume • Prong one: – Volume responsiveness – Cardiac output before and after fluid challenge – 19 evaluated CVP and volume responsiveness Marik, PE, et al. 2008. Chest. 134(1) 8 9/22/2012 Fluid responsiveness Volume responsiveness • Calculated a Receiver Operating Characteristic curve • Likelihood that at any given point (CVP level, score, etc) the true positives will exceed false positives. • Higher = better discrimination Marik, PE, et al. 2008. Chest. 134(1) CVP • Necessary? • Certainly not sufficient • Potentially misleading Hemodynamic • Blood pressure • CVP/wedge • Dynamic respiratory indices: – Pulse pressure/systolic pressure/perfusion index variation 9 9/22/2012 The Principles Applies to lots of measures • • • • LV Preload Systolic pressure variation Pulse pressure variation Plethysmogram variation Outcome is “fluid responsiveness” LV SV Decreased RV SV RV Preload RV Afterload Variations on a theme… • A waveform… • A peak and trough… • And a proprietary algorithm: The data • Small studies • Mostly OR SVV, Vigileo 40% MORE fluid Lower lactate Fewer “complications” PVI, Masimo 1/3 LESS fluid Lower lactate 10 9/22/2012 • 29 studies, 685 patients – 9 ICU – 20 OR (15 in cardiac surgery) • All included correlation/ROC between SPV, PPV, or SVV and ∆SVI/CI after a fluid challenge. Measure r AUC for ROC Threshold PPV 0.78 0.94 12.5% SVV 0.72 0.84 15.3% SPV 0.72 0.86 CVP ECOM 0.56 ECOM • ETT-based electrodes • Current generated by flow in ascending aorta • Current + Nomogram = SV • SV CO, SVV • R2 = 0.63 Wallace, AW, et al. Under Review. 11 9/22/2012 Now, keep in mind… • Regular HR • Sedated, mechanically ventilated • Vt = 8 mL/kg Hemodynamic goals • Numerous • State of the art: Dynamic indices – PPV – SPV – PVI – VTI and esophageal doppler • Necessary but not sufficient Metabolic Metabolic • Mental status, urine output • Lactate • S(c)vO2 • Mental status, urine output • Lactate • S(c)vO2 12 9/22/2012 Physical exam • Evidence of end-organ perfusion and function • Slow to change • Numerous confounders • Summarily dismissed Lactate Metabolic • Mental status, urine output • Lactate • S(c)vO2 Lactate: the data • The product of anaerobic respiration • Presence implies inadequate oxygen utilization, shock • Easily, quickly measured in arterial blood 13 9/22/2012 Two trials: How did they do it? • JAMA: 300 patients, EGDT vs lactate clearance – Non-inferiority • AJRCCM: 348 patients, EGDT vs lactate clearance – Improved mortality (multivariate) – Less time on vent, in ICU Jones, et al (JAMA) Jansen et al (AJRCCM) Monitoring interval 2 2 Goal 10% clearance 20% clearance Fluid totals (L) Control: 4.3 Control: 2.2 Intervention: 4.5ns Intervention: 2.7* Non-inferiority to EGDT Decreased time on vent, Outcome in ICU The underpinnings… Metabolic • Mental status, urine output • Lactate • S(c)vO2 14 9/22/2012 How it’s used: • ScvO2 attributed to: - Supply (cardiac output) - Demand (hypermetabolism) • In either case, treat by increasing DO2 - Volume, inotropes, RBCs • But does it work? ScvO2 • The cornerstone of Early Goal-Directed Therapy. • And we know that targeting SvO2 mortality. – Septic, cardiogenic shock in humans, dogs – ScvO2 = SvO2? DOGS Changes in SvO2 and ScvO2 Humans w/ shock Humans w/ sepsis 15 9/22/2012 Metabolic goals • Lactate and ScvO2 – Base deficit? – A-V CO2 gradient? • Physiological rationale meets objective data. Putting it all together: • • • • Volume isn’t easy Volume is important Common conditions; competing goals Stepwise plan In summary… • Supply/demand mismatch • Detected by straightforward labs • No target-specific therapies: just get more oxygen to the cells The end The End – Hemodynamic – Metabolic 16