Obligatory joke. The case for why it matters. Sepsis: More is more. Goal-Directed Fluid Resuscitation 6/1/2013

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1 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

2 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 Sepsis + CVP = Death Outcomes: Quartile x 28 d mortality Early (12 hrs) and Late (4 d) dry-ness saved lives: HR 0.57 and 0.47, respectively Dry Quartile Wet Quartile 12 hours +0.7L +8.2L 4 days +1.6L +20.5L Survival Dry Quartile Wet Quartile 12 hours 81% 58% 4 days 83% 65% Boyd, JH, et al CCM. 39(2) Boyd, JH, et al 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) Vent-Free days ICU-Free days Dialysis CNS failure free days 2

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

4 So how do we do it? It matters Murphry, CV, et al 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

5 Hemodynamic Goals Blood pressure CVP Dynamic respiratory indices: Pulse pressure/systolic pressure/perfusion index variation Blood pressure A proxy for flow, end organ perfusion Flow = pressure/resistance Do we ever really KNOW resistance? 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 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

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

8 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 Chest. 134(1) 8

9 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 Chest. 134(1) CVP Necessary? Certainly not sufficient Potentially misleading Blood pressure CVP/wedge Hemodynamic Dynamic respiratory indices: Pulse pressure/systolic pressure/perfusion index variation 9

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

11 29 studies, 685 patients 9 ICU 20 OR (15 in cardiac surgery) All included correlation/roc between SPV, PPV, or SVV and ΔSVI/CI after a fluid challenge. Measure r AUC for ROC Threshold PPV % SVV % SPV CVP 0.56 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

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

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

14 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 How did they do it? The underpinnings Jones, et al (JAMA) Jansen et al (AJRCCM) Monitoring interval 2 2 Goal 10% clearance 20% clearance Fluid totals (L) Control: 4.3 Intervention: 4.5 ns Control: 2.2 Intervention: 2.7 * Outcome Non-inferiority to EGDT Decreased time on vent, in ICU 14

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

16 DOGS Metabolic goals Changes in SvO2 and ScvO2 Humans w/ shock Humans w/ sepsis Lactate and ScvO 2 Base deficit? A-V (CO 2 ) gradient? A-V (CO 2 ) cer gradient? Physiological rationale meets objective data. Putting it all together: Volume isn t easy Volume is important Common conditions; competing goals Stepwise plan Hemodynamic Metabolic The End The end 16

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