Full Disclosure. The case for why it matters. Goal-directed Fluid Resuscitation

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1 Goal-directed Fluid Resuscitation Christopher G. Choukalas, MD, MS Department of Anesthesia and Perioperative Care University of California, San Francisco I own no stocks Full Disclosure The case for why it matters Fluid balance a common concern Sepsis ALI/ARDS Sepsis PLUS ARDS!

2 Some impressive fluid totals Study Control Intervention Jansen (8 hrs) 2.2L 2.7L Jones (6 hrs) Rivers (6 hrs) 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 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 Sepsis + CVP = Death 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 CCM. 39(2) 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 Survival Dry Quartile Wet Quartile 12 hours 81% 58% 4 days 83% 65% Boyd, JH, et al CCM. 39(2)

4 Just the FACTTs 1001 w/ ALI randomized to liberal or conservative fluid algorithms Varying amounts of fluid, furosemide, dobutamine Catheter type, shock, UOP, and effectiveness of circulation Outcome Conservative Liberal Fluid total (day 7; ml) 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 +++

5 Adequate initial: W/in 6 hours, CVP > 8, fluid intake > 20 ml/kg. Conservative late: W/in 7 days, at least 2 consecutive negative days. Patients with Sepsis who developed ALI 4 groups: Adequate initial + Conservative late fluids Adequate initial only Conservative late only Neither Murphry, CV, et al Chest. 136(1)

6 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 Hemodynamic Goals Blood pressure CVP Dynamic respiratory indices: Pulse pressure/systolic pressure/perfusion index variation

7 Blood pressure A proxy for flow, end organ perfusion Flow = pressure/resistance Do we ever really KNOW resistance? Auscultation Kortikoff sounds: Hz Human hearing as low as 16 Hz when we re young Stethoscope heads w/o Bell Low flow (hypotensive) states associated with invasive-kortikoff difference Cohn JN JAMA Oscillometric: Basically replaces your ear with a pressure sensor Still prone to error (kinked tubing, vascular disease, zero drift) Demonstrated invasive-oscillometric differences Cardiac surgery patients prior to bypass Gravlee, GP, et al. J Clin Monitor

8 Guidelines Critical part of EGDT (MAP > 65 mmhg) Surviving Sepsis Campaign guidelines Expert opinion Based on EGDT guidelines Premise that 85 was not superior to 65 Randomized trials

9 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 In the Rivers paper, at hour 6, avg MAPs: Control: 81 Rx: 95!

10 Dissociation MAPs kept higher than recommended More pressor exposure Outcomes? Post-hoc analysis of a NOS-antagonist Above MAP 70, no association w/ mortality pressor = mortality Dusner, MW, et al. Crit Care :181 Blood pressure Necessary but not sufficient Goals are nebulous Supra-normal levels common, not helpful Hemodynamic Blood pressure CVP Dynamic respiratory indices: Pulse pressure/systolic pressure/perfusion index variation

11 Concept: assumptions The data Critical target in EGDT for sepsis Incorporated into SSC guidelines

12 Marik, PE, et al Chest. 134(1) Fluid responsiveness and total blood volume Two prongs: Volume responsiveness Total blood volume 24 studies, 803 patients 19 evaluated CVP and volume responsiveness 5 studies evaluated CVP and total blood volume Fluid 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

13 Volume responsiveness Marik, PE, et al Chest. 134(1) Used CVP to predict changes in SV, CO, CI w/ volume loading ROC Curve Coefficient: 0.56 Pearson s r = 0.18 Barely better than a coin-flip Blood volume Five studies, < 200 patients Radio-labeled albumin, mostly Created pearson s correlation of blood volume x CVP.

14 Marik, PE, et al Chest. 134(1) The peanut gallery Perhaps the single # is inaccurate, but surely the trend is meaningful A logical fallacy Perhaps the CVP IS inaccurate, but surely very high and very low levels are useful

15 CVP Necessary? Certainly not sufficient Potentially misleading Hemodynamic Blood pressure CVP/wedge Dynamic respiratory indices: Pulse pressure/systolic pressure/perfusion index variation The Principles

16 Applies to lots of measures Systolic pressure variation Pulse pressure variation Plethysmogram variation Outcome is fluid responsiveness Pleth Variability Index Essentially systolic pressure variation from pleth

17 Stroke Volume Variability Proprietary algorithm: Invasive BP -> SV Pulse pressure Systolic pressure Physiologic rationale Different manifestations of the same physiology But what about the data? Pleth variability index Stroke volume variability Meta-analysis of several techniques

18 The data Small studies Mostly OR 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

19 Now, keep in mind Regular HR Sedated, mechanically ventilated Vt = 8 ml/kg Hemodynamic goals Numerous Necessary but not sufficient State of the art: Dynamic indices PPV SPV PVI Metabolic Mental status, urine output Lactate S(c)vO2 Base deficit

20 Metabolic Mental status, urine output Lactate S(c)vO2 Base deficit 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 Base deficit

21 Lactate The product of anaerobic respiration Presence implies inadequate oxygen utilization, shock Easily, quickly measured in arterial blood Lactate: the data ScvO 2 vs lactate: JAMA 300 patients randomized, all got an Edwards catheter 150 to CVP, MAP, and ScvO 2 goals 150 to CVP, MAP, and lactate reduction 10% drop from pre-resuscitation level RBCs and/or dobutamine Jones, et al. JAMA, 2010

22 Outcome Lactate Control Baseline lactate 4 4 Goal attained? >90% >90% RBCs? 7% 3% (ns) Mortality 17% 23% (ns) AJRCCM 348 ICU admits w/ lactate > 3 Randomized to 8 hours of: Essentially EGDT EGDT + lactate Q2H More fluid (2.7L v 2.2L) Less time on vent Less time in ICU Less time on pressors

23 The underpinnings Metabolic Mental status, urine output Lactate S(c)vO2 Base deficit Venous oximetry In principle: Post-capillary oxygenation Reflects oxygen extraction ratio Should infer adequacy of oxygen delivery Mixed venous blood should reflect extraction/delivery of all organ beds.

24 In principle: Venous oximetry As oxygen demand approaches supply, extraction ratio. venous saturation. Measured in the mixed or central position to reflect total body extraction. How it s used: SvO 2 attributed to: Supply (cardiac output) Demand (hypermetabolism) In either case, treat by increasing DO 2 Volume, inotropes, RBCs But does it work?

25 Data for SvO 2 Associated with prognosis: Data in heart failure Sepsis Cardiogenic shock Post-cardiac surgery Reinhart and Bloos. Curr Opin Crit Care. 11 (2005) Enter: ScvO 2 Central line No PAC required A different degree of mixing? Is it the same? DOGS Humans w/ sepsis

26 Changes in SvO2 and ScvO2 ScvO 2 The cornerstone of Early Goal-Directed Therapy. And we know that targeting ScvO 2 mortality. Heavily researched, summarized as follows: SvO2 and ScvO2 are not interchangeable Following the trends seems to lead to the same outcome. Metabolic Mental status, urine output Lactate S(c)vO2 Base deficit

27 Base Deficit mmols of base required to titrate 1 L blood to ph 7.4 Derived from ABG by nomogram More deficit = more oxygen debt Stoichiometrically related to lactate Trauma BD correlated with degree of shock, req d transfusions 2 to -5: mild -6 to -14: moderate >-15: severe Numerous retrospective animal, human studies Prospective studies using BD as a target? Davis, JW, et al J Trauma. 28. In summary Supply/demand mismatch Detected by straightforward labs Various parameters No target-specific therapies: just get more oxygen to the cells

28 Putting it all together: Volume isn t easy Volume is important Lots of goals Stepwise plan Hemodynamic Metabolic