Obligatory joke Keep your eye on the food. Goal-Directed Fluid - PDF document

6/1/2013 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 Sepsis: More is more • Fluid balance a common concern • Some impressive fluid totals • Sepsis • ALI/ARDS Study Control Intervention Jansen (8 hrs) 2.2L 2.7L • Sepsis PLUS ARDS! Jones (6 hrs) 4.5L 4.3L Rivers (6 hrs) 3.5L 5L 1

6/1/2013 Sepsis +  CVP = Death Or is it? • Retrospective analysis of VASST trial • Outcomes: Quartile x 28 d mortality – 778 pts w/ septic shock on NE • Early (12 hrs) and Late (4 d) “dry - ness” • Divided into quartiles based on total fluid saved lives: – HR 0.57 and 0.47, respectively in at 12 hrs, 4 days Dry Quartile Wet Quartile Survival Dry Quartile Wet Quartile 12 hours +0.7L +8.2L 12 hours 81% 58% 4 days +1.6L +20.5L 4 days 83% 65% Boyd, JH, et al. 2011. CCM. 39(2) 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 Conservative Liberal Fluid total (day 7; mL) -136 +6990 Vent-Free days ICU-Free days Dialysis CNS failure free days 2

6/1/2013 Outcome Conservative Liberal Outcome Conservative Liberal Mortality (60d) 25.5% 28.4% (ns) 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 • Patients with Sepsis who developed ALI • 4 groups: – Adequate initial + Conservative late fluids Outcome Conservative Liberal – Adequate initial only Mortality (60d) 25.5% 28.4% (ns) – Conservative late only Vent-Free days +++ – Neither ICU-Free days +++ Dialysis Less More (ns) CNS failure free days +++ 3

6/1/2013 It matters • So how do we do it? Murphry, CV, et al. 2009. Chest. 136(1) I would posit two factors: Hemodynamic Goals • Hemodynamic: • Blood pressure – Is the circulation adequate? • CVP • Metabolic • Dynamic respiratory indices: – Are oxygen delivery and utilization adequate? – Pulse pressure/systolic pressure/perfusion • Both have their own goals. index variation 4

6/1/2013 Hemodynamic Goals Blood pressure • Blood pressure • A proxy for flow, end organ perfusion • CVP • Flow = pressure/resistance • Dynamic respiratory indices: • 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

6/1/2013 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

6/1/2013 Blood pressure • Necessary but not sufficient • Goals are nebulous • Supra-normal levels common, not helpful Hemodynamic Concept: assumptions • Blood pressure Normal CVP • CVP • Dynamic respiratory indices: Optimal actin-myosin match – Pulse pressure/systolic pressure/perfusion index variation Adequate contractility Adequate DO 2 7

6/1/2013 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

6/1/2013 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 Hemodynamic • Necessary? • Blood pressure • Certainly not sufficient • CVP/wedge • Potentially misleading • Dynamic respiratory indices: – Pulse pressure/systolic pressure/perfusion index variation 9

6/1/2013 The Principles Applies to lots of measures • Systolic pressure variation • Pulse pressure variation • Plethysmogram variation • Outcome is “fluid responsiveness”  LV Preload  LV SV Decreased RV SV  RV Preload  RV Afterload Variations on a theme… The data • A waveform… • Small studies • A peak and trough… • Mostly OR • And a proprietary algorithm: SVV, Vigileo PVI, Masimo 40% MORE fluid 1/3 LESS fluid Lower lactate Lower lactate Fewer “complications” 10

6/1/2013 • 29 studies, 685 patients – 9 ICU Measure r AUC for ROC Threshold – 20 OR (15 in cardiac surgery) PPV 0.78 0.94 12.5% • All included correlation/ROC between SVV 0.72 0.84 15.3% SPV, PPV, or SVV and ΔSVI/CI after a SPV 0.72 0.86 CVP 0.56 fluid challenge. ECOM ECOM • ETT-based electrodes • Current generated by flow in ascending aorta • Current + Nomogram = SV • SV  CO, SVV • R 2 = 0.63 Wallace, AW, et al. Under Review. 11

6/1/2013 Now, keep in mind… PVI + NE = NEB • Regular HR • Sedated, mechanically ventilated • Vt = 8 mL/kg • Pressors? Monnet, et al Monnet, et al Biais, et al Population Population 35 ICU patients on NE 35 ICU patients on NE 35 ICU patients on NE Gold Standard Gold Standard TD TD PPV > 13% Sensitivity FR Sensitivity FR 43 43 58 100 Specificity FR Specificity FR 90 90 61 72 AUC ROC AUC ROC 0.68 0.68 0.69 0.93 Hemodynamic goals Metabolic • Numerous • Mental status, urine output • State of the art: Dynamic indices • Lactate – PPV • S(c)vO2 – SPV – PVI – VTI and esophageal doppler • Necessary but not sufficient 12

6/1/2013 Metabolic Physical exam • Mental status, urine output • Evidence of end-organ perfusion and function • Lactate • Slow to change • S(c)vO2 • Numerous confounders • Summarily dismissed Metabolic Lactate • Mental status, urine output • The product of anaerobic respiration • Lactate • Presence implies inadequate oxygen utilization, shock • S(c)vO2 • Easily, quickly measured in arterial blood 13

6/1/2013 Lactate: the data Two trials: • 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 The underpinnings… How did they do it? 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: 4.5 ns Intervention: 2.7 * Outcome Non-inferiority to EGDT Decreased time on vent, in ICU 14

6/1/2013 Metabolic • Mental status, urine output • Lactate • S(c)vO2 How it’s used: ScvO 2  ScvO 2 attributed to: • The cornerstone of Early Goal-Directed Therapy.  Supply (cardiac output)  Demand (hypermetabolism) • And we know that targeting SvO 2  • In either case, treat by increasing DO 2 mortality. – Septic, cardiogenic shock in humans, dogs – Volume, inotropes, RBCs – ScvO 2 = SvO 2 ? • But does it work? SvO 2 ScvO 2 15

6/1/2013 Metabolic goals DOGS • Lactate and ScvO 2 – Base deficit? – A-V (CO 2 ) gradient? Changes in SvO2 and ScvO2 – A-V (CO 2 ) cer gradient? Humans w/ shock • Physiological rationale meets objective Humans w/ sepsis data. Putting it all together: The end • Volume isn’t easy The End • Volume is important • Common conditions; competing goals • Stepwise plan – Hemodynamic – Metabolic 16