Paul Marik - The Myths of Fluids in Severe Sepsis

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November 08, 2013

Paul Marik - The Myths of Fluids in Severe Sepsis

From the GNYHA STOP Sepsis Meeting
11-8-13

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EMCrit

November 08, 2013
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Transcript

  1. Fluid in Sepsis: A New Paradigm Paul Marik, MD, FCCP,

    FCCM
  2. Disclosures  Stocks  Advisory boards  Grants  Speakers

    Bureau None
  3. 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
  4. JAMA 1992;267:1503

  5. Ronco JJ, et al. JAMA 1993;270:1724 4ml/kg/min

  6. None
  7. N Engl J Med 1994; 330:1717

  8. 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
  9. 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
  10. 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
  11. None
  12. None
  13. 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
  14. Historical Perspective

  15. Lancet, Feb 4 1882

  16. None
  17. None
  18. 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”
  19. 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.
  20. 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”
  21. From this to …. The “Rivers” Protocol

  22. Goals of Hemodynamic Resuscitation  Achieve an adequate perfusion pressure

     MAP > 65 mmHg  Improve microcirculatory flow  Limit tissue edema
  23. None
  24. Crit Care Med 2013; 41:34

  25. The Hemodynamic derangements of sepsis  Vasoplegic shock/vasodilatory shock 

    Nitric oxide  ANP  KATP  Vasopressin  Leaky capillaries  Glycocalyx  Endothelial junctions  Myocardial depression  Nitric Oxide
  26. None
  27. 1. NO/ANP

  28. 2. Activation of KATP

  29. 3. Vasopressin deficiency

  30. VGEF Angiopoeitin 2

  31. 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:
  32.  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
  33. None
  34. The Glycocalyx Denuded in Sepsis

  35. None
  36. 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
  37. 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
  38. Fluid may not be the most efficient method to increase

    MAP in septic shock
  39. Crit Care Med 2007;35:477 % change in cardiac Index

  40. Eur J Pharmacology 2009;621:67

  41. 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
  42. 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)
  43. None
  44. None
  45. Bark BP, et al. Crit Care Med 2013;41 CLP

  46. Excess fluid Increases mortality in patients with sepsis

  47. The Evidence: Experimental Models

  48. 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
  49. Crit Care 2009; 13:R186

  50. None
  51. None
  52. The Evidence: Clinical Studies

  53. Alsous F et al. Chest 2000;117:1749

  54. The Soap Study Crit Care Med 2006; 34:34

  55. Crit Care Med 2011;39:256-2

  56. Crit Care Med 2011;39:256-2 Optimal survival occurred with a positive

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

    lowest mortality. Crit Care Med 2011;39:256-2
  58. None
  59. Days

  60. Association of cumulative fluid balance on outcome in ALI: A

    review of the ARDSnet cohort J Intens Care Med 2009;24:35
  61. 2009; 136:102-109 Non-survivors Survivors

  62. Resp Med 2008;102:956

  63. Mortality 48 hrs Mortality 4 weeks Maitland K, et al.

    NEJM 2011; 364:2483
  64. None
  65. None
  66. None
  67. Fluid resuscitation in sepsis “Give them as much as they

    need and not a drop more”….
  68. Where's the Blood Volume?

  69. None
  70. 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
  71. 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
  72. Geleon A, et al. Crit Care Med 2014 (ePu

  73. Normal adrenal function Impaired adrenal function Before HC After HC

    Annane, British Journal of Clinical Pharmacology, 19 Effect of Hydrocortisone on Sepsis-Induced Hypotension
  74. 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
  75. Techniques to Assess Fluid Responsiveness

  76. Excellent Fair-Good Worthless ROC Curves & Diagnostic Accuracy

  77. 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 &
  78. Assessment of fluid responsiveness Technique PLR Volume Challenge Technology Esophageal

    Doppler Calibrated pulse contour NICOM - Bioreactance
  79. 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
  80. Which Fluid?  Crystalloids  Balanced Salt Solutions (BSS) 

    Ringers  Plasmalyte  Un-physiologic Salt Solutions (USS)  NaCl  Colloids  Albumin (USS)  Starches (USS)
  81. None
  82. Chloride liberal vs. Chloride Restrictive Strategy

  83. Anesth Analg 2013:117:412

  84. “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
  85. NEJM 2008;358:125

  86. None
  87. 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:
  88. Kozar R, et al. Anesth Analg

  89. 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
  90. 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
  91. None
  92. None
  93. Marik PE. Chest 2014 (in press)

  94. None
  95. None