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Paul Marik - The Myths of Fluids in Severe Sepsis

EMCrit
November 08, 2013

Paul Marik - The Myths of Fluids in Severe Sepsis

From the GNYHA STOP Sepsis Meeting
11-8-13

EMCrit

November 08, 2013
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  1. Scientific Disclosures  Three Great Myths in the management of

    sepsis  Sepsis is associated with tissue hypoxia  Protocols to “optimize” CI or DO2 improve outcome  Sepsis is “volume depleted” state
  2. From: Effect of Heart Rate Control With Esmolol on Hemodynamic

    and Clinical Outcomes in Patients With Septic Shock: A Randomized Clinical Trial JAMA. 2013;():-. doi:10.1001/jama.2013.278477 0 100 200 300 400 500 600 BL 24 hr 48 hr 72 hr DO2 Esmolol Control
  3. From: Effect of Heart Rate Control With Esmolol on Hemodynamic

    and Clinical Outcomes in Patients With Septic Shock: A Randomized Clinical Trial JAMA. 2013;():-. doi:10.1001/jama.2013.278477 Time Hrs 0 20 40 60 80 100 120 0 100 200 400 500 600 Lactate 1.0 1.5 2.0 2.5 3.0 Time vs Lactate - E Time vs Lactate - C DO2/VO2 DO2
  4. From: Effect of Heart Rate Control With Esmolol on Hemodynamic

    and Clinical Outcomes in Patients With Septic Shock: A Randomized Clinical Trial JAMA. 2013;():-. doi:10.1001/jama.2013.278477
  5. Oxygen kinetics in sepsis  Oxygen requirement are not increased

    in patients with sepsis  An oxygen debt does not exist in patients with sepsis  Lactate is produced aerobically as part of the stress response  Attempts to increase DO2 in response to an elevated lactate is  Illogical and devoid of scientific evidence  Likely to be harmful
  6. His first patient was an elderly women who had reached

    the last moments of her earthly existence. “Having no precedent to guide me I proceeded with much caution”
  7. His first patient was an elderly women who had reached

    the last moments of her earthly existence. “Having no precedent to guide me I proceeded with much caution” Latta inserted a tube into the basilic vein and injected ounce after ounce of fluid, closely observing the patient.
  8. His first patient was an elderly women who had reached

    the last moments of her earthly existence. “Having no precedent to guide me I proceeded with much caution” Latta inserted a tube into the basilic vein and injected ounce after ounce of fluid, closely observing the patient. “the sunken eyes and fallen jaw, pale and cold extremities bearing the manifest imprint of deaths signet, began to glow with returning animation; the pulse returned to the wrist”
  9. Goals of Hemodynamic Resuscitation  Achieve an adequate perfusion pressure

     MAP > 65 mmHg  Improve microcirculatory flow  Limit tissue edema
  10. The Hemodynamic derangements of sepsis  Vasoplegic shock/vasodilatory shock 

    Nitric oxide  ANP  KATP  Vasopressin  Leaky capillaries  Glycocalyx  Endothelial junctions  Myocardial depression  Nitric Oxide
  11. Starling Principle  Starling (1896) states fluid exchange is governed

    by high vascular COP and low interstitial COP  Recently it is proved that intravascular COP is almost identical to extravascular one Jacob M. et al Cardiovascular Research 2007; 73:
  12.  EG consists of membrane-bound proteoglycans and glycoproteins network in

    which plasma or endothelial proteins are retained - forms the endothelial surface layer (ESL)  ESL thickness is 1μm Jacob M. et al Cardiovascular Research 2007; 73: Endothelial Glycocalyx
  13. Crit Care Med 2008; 36:1701 Norepi 0.8 ug/kg/min Norepi 0.4

    ug/kg/min Dobutamine 5 ug/kg/min LVFAC= left ventricular fractional area contraction
  14. The Hemodynamic derangements of sepsis  FLUIDS INCREASE Vasoplegic shock/vasodilatory

    shock  Nitric oxide  BNP  KATP  Vasopressin  FLUIDS INCREASE Leaky capillaries  Glycocalyx  Endothelial junctions  FLUIDS INCREASE Myocardial depression  Nitric Oxide  Myocardial edema
  15. BNP damages glycocalyx  Inc atrial pressure leads to a

    release of natriuretic peptides  ANP/BNP shed off the glycocalyx components (syndecan -1) into the circulation  This is accompanied by significant rapid shifts of intravascular fluid into interstitial space Bruegger D. et al Am J Physiol 2005; 289: H1993
  16. Ueda S, et al. Shock 2006;26:123 Resuscitated according to EGDRx

    0 200 400 600 800 1000 1200 1400 Admission Day 1 Day 2 Day 4 Survivors Non-survivors BNP (pg/ml)
  17. Crit Care 2009; 13:R186  48 pigs randomized to endotoxin

    infusion, fecal peritonitis or control  Each group randomized to Moderate (10ml/kg/hr) or High volume-EGDRx (20 ml/kg/hr) LR resuscitation for 24 hrs  High Volume-EGDRx Group  Higher CI  Higher MAP  Higher PCWP  Lower lactate  Higher SmvO2
  18. Crit Care Med 2011;39:256-2 Optimal survival occurred with a positive

    fluid balance of approximately 3 liters at 12 hours
  19. Patients with CVP <8 mmHg at 12 hrs had the

    lowest mortality. Crit Care Med 2011;39:256-2
  20. Association of cumulative fluid balance on outcome in ALI: A

    review of the ARDSnet cohort J Intens Care Med 2009;24:35
  21. Crit Care Med 2012;40:3146 Before After Dose norepinephrine (ug/kg/min) 0.3

    0.19 CI (l/min/M2) 3.47 3.28 CI change by PLR (%) 1 8 Mean systemic pressure (mmHg) 33 26 GEDVI (ml/m2) 819 774
  22. The lowest mortality was seen in patients with lower SOFA

    scores and early norepinephrine administration after admission. Conclusion: Both the time of starting norepinephrine after admission to the ICU and the degree of organ dysfunction have an important bearing on subsequent Outcome Crit Care Med 2000;28:947
  23. Normal adrenal function Impaired adrenal function Before HC After HC

    Annane, British Journal of Clinical Pharmacology, 19 Effect of Hydrocortisone on Sepsis-Induced Hypotension
  24. SV EVLW Preload Large increase in EVLW Small increase in

    CO The Frank-Starling & Marik-Phillips Curves Large increase in CO Small increase in EVLW Sepsis
  25. Assessment of fluid responsiveness Technique CVP/PAOP IVC/SVC diameter FTc (LVETc)

    RVEDV/LVEDA/GEDI IVC/SVC - respiratory variation PPV/SVV/PVI Aortic blood flow - respiratory variation Passive Leg Raising (PLR) Technology CVP/PAC Non calibrated pulse contour Bioimpedance Ultrasound (IVC/SVC) Ultrasound (IVC/SVC resp. variability) Pleth waveform (PVI) ECHO- Aortic Doppler (resp. variability) Calibrated pulse contour (PPV/SVV) Esophageal Doppler (PLR & volume) Calibrated pulse contour (PLR &
  26. Study name sample size AUC Monnet CCM 2006 71 0.96

    Lafanéchère CC 2006 22 0.95 Lamia ICM 2007 24 0.96 Maizel ICM 2007 34 0.89 Monnet CCM 2009 34 0.94 Thiel CC 2009 102 0.89 Biais CC 2009 30 0.96 Preau CCM 2010 34 0.94 351 0.95 Study name sample size AUC Monnet CCM 2006 71 0.75 Monnet CCM 2009 34 0.68 Preau CCM 2010 34 0.86 139 0.76 PLR-induced changes in PP
  27. Which Fluid?  Crystalloids  Balanced Salt Solutions (BSS) 

    Ringers  Plasmalyte  Un-physiologic Salt Solutions (USS)  NaCl  Colloids  Albumin (USS)  Starches (USS)
  28. “Ab-Normal” Saline vs. Balanced Salt Solution  Metabolic and dilutional

    acidosis  Decreased renal blood flow  Coagulopathy- more bleeding  Increased inflammation  Increased risk of renal failure  Increased risk of death
  29. 5% Albumin  Maintains endothelial glycocalyx and “endothelial function” 

    Anti-oxidant properties  Anti-inflammatory properties  May limit “third” space loss Albumin has a number of features that may be theoretically adv in patients with sepsis and SIRS including:
  30. Pts. with severe sepsis or septic shock (6-24 hr) Albumin

    Crystalloid s crystalloids Albumin: [300 ml at 20% in 3* hrs] + crystalloids Study design Randomization Volume replacement Study design
  31. from day 1 to day 28 Plasma albumin level <

    30 g/L ≥ 25 g/L ≥ 30 g/L No infusion of Albumin Infusion of Albumin: 200 ml at 20% in 3* hrs < 25 g/L Infusion of Albumin: 300 ml at 20% in 3* hrs Albumin