Paul Marik - The Myths of Fluids in Severe Sepsis

From the GNYHA STOP Sepsis Meeting
11-8-13

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
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
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
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
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
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
34. The Glycocalyx Denuded in Sepsis
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)
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
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
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
67. Fluid resuscitation in sepsis “Give them as much as they need and not a drop more”….
68. Where's the Blood Volume?
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)
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
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
93. Marik PE. Chest 2014 (in press)