Sepsis and septic shock
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1 Sepsis and septic shock Practical hemodynamic consequences Intensive Care Training Program Radboud University Medical Centre Nijmegen
2 Septic cardiomyopathy Present in > 50% and often masked by low vascular resistance - unmasked by NE Acute and reversible (in a few days) Accompanied by low filling pressures due to concomitant RV function and small increase in LV compliance Veillard-Baron A. Ann Int Care 2011;1:6
3 Veillard-Baron A. Ann Int Care 2011;1:6
4 Day 1 Day 2 Veillard-Baron A. Ann Int Care 2011;1:6
5 Veillard-Baron A. Ann Int Care 2011;1:6
6 Small increase in compliance Veillard-Baron A. Ann Int Care 2011;1:6
7 Size of balloon is LV volume Highest mortality Lowest mortality Intermediate mortality Veillard-Baron A. Ann Int Care 2011;1:6
8 LVEF and CI in sepsis Veillard-Baron A. Ann Int Care 2011;1:6
9 Mitochondrial dysfunction Microcirculatory shunting Systolic myocardial dysfunction Diastolic myocardial dysfunction Excessive vasodilation Venous pooling Increased endothelial permeability
10 Septic shock with lactate acidosis ino synthase ATP, H +, Lactate vascular smooth Vasopressin secretion NO Open KCa Open KATP Vasopressin stores cgmp Cytoplasmic Calcium Vasopressin plasma Phosphorylated myosin Vasodilatation
11
12 IFN-Υ ± IL-10 IDO activity Tryptophan & kynurenine Lymphocyte apoptosis Increased KT ratio plasma Microvascul ar reactivity IL-6 e NO N = 80 Darcey CJ. PLOSone 2011;6:e21185
13 INOTROPIC DOSE IDO ACTIVITY N = 16 Changsirivathanathamrong D. Crit Care Med 2011;39:
14 Changsirivathanathamrong D. Crit Care Med 2011;39:
15 Microcirculation Measured by Sidestream Darkfield Imaging or NIRS Decrease in capillary density with increased heterogeneous perfusion Evidence accumulating that changes in perfusion induce tissue hypoxia (in contrast to the adaptive theory)
16 De Backer D. Ann Intensive Care 2011;1:27
17 Microcirculation in sepsis Control Normal Acetylcholine Sepsis De Backer D. Am J Respir Crit Care Med 2002;166:98-104
18 N = 70 Nitroglycerin and microcirculation in sepsis Patients with severe sepsis/septic shock treated with EGDT Boerma EC. Crit Care Med 2010;38:93-100
19 Boerma EC. Crit Care Med 2010;38:93-100
20 Mitochondrial
21 XXX XXX Sepsis Peroxynitrite ONOO- PARP + Caspase activation Apoptosi s Necrosis
22 Treatment Volume loading Inotropic agents Increasing afterload with NE / vasopressin Vasodilator (experimental)
23 HES 130/0.4 versus NaCl 0.9% - CRYSTMAS Prospective MC (N=24), DB RCT Age 18, severe sepsis Primary endpoint: amount of fluid for achieving hemodynamic stability Guidet B. Crit Care 2012;16:R94
24 HES 130/0.4 versus NaCl 0.9% - CRYSTMAS 88 vs 86 patients reached hemodynamic stability (NS) Amount of fluid < with HES: 1379 ± 886 vs 1709 ± 1164 ml (p = ) Cumulative volume over 4 days similar Time to reach HDS 11.8 ± 10.1 vs 14.3 ± 11.1 hours (NS) No differences in LOS, morbidity, mortality Guidet B. Crit Care 2012;16:R94
25 HES 130/0.4 versus NaCl 0.9% - CRYSTMAS HES 130/0.4 NaCl 0.9% 40 NS NS NS 30 (%) Mortality 28D Mortality 90D ARF after screening Guidet B. Crit Care 2012;16:R94
26 Guidet B. Crit Care 2012;16:R94
27 HES 130/0.42 versus Ringer s acetate Adult patients with severe sepsis MC (N = 26), blinded, stratified clinical trial HES 130/042 vs Ringer s acetate Daily maximum dose 33 ml/kg IBW Primary outcome composite death/dialysis dependence at D90 Perner A. N Engl J Med 2012;367:
28 HES 130/0.42 versus Ringer s acetate Ringer s HES 130/04 60 P = 0.03 P = 0.03 P = 0.09 P = Death/DD Day 90 Death Day 90 Severe bleeding RRT No differences in total amount of fluid needed Perner A. N Engl J Med 2012;367:
29 HES 130/0.4 versus Ringer s acetate Perner A. N Engl J Med 2012;.../...
30 % 15% BJA 2012 Durairaj L. Chest 2008;133:
31 Fluid therapy and microcirculation Proportion perfused small vessels Baseline Early septic shock Late septic shock Fluids Despite similar changes in CI Ospina-Tascon G. Intensive Care Med 2010;36:
32 Lactate driven therapy Control Lactate driven P = ,5 N = 348 After correction for risk factors mortality lower in lactate group (HR 0.61, p = 0.006) Mortality (%) ,9 Duration MV, duration ICU stay, lower SOFA score 0 Admission lactate 3 mmol/l Goal: lactate 20% in 2 hrs Jansen TC. Am J Respir Crit Care Med 2010, 182:
33
34 Lactate driven therapy Gu WJ. Intensive Care Med 2015;41:
35 Patient with septic shock Observation Hypotension - Lactate - Low UP Inference Inadequate vital organ perfusion Inference Cardiac output must be low Consequence Rapid fluid bolus resuscitation Often repeated Therapy is necessary and life-saving and better than moderate fluid therapy + early vasopressors Hilton AK. Crit Care 2012;16:302
36 SmvO2 Fick Equation Cardiac Output = VO2 CaO2 - CmvO2 CaO2 = (Hb (mmol/l) 2.16 SaO2) + (0.003 PaO2 (mm Hg)) CmvO2 = (Hb (mmol/l) 2.16 SmvO2) + (0.003 PmvO2 (mm Hg)) The amount of dissolved oxygen in plasma is negligible
37 Normally ScvO2<SmvO2 due to the higher oxygen extraction of the brain Oxygen extraction in the heart almost maximal Low cardiac output may decrease perfusion of the GI tract, lowering oxygen saturation in the VCI and changing the relationship between ScvO2 - SmvO2
38 General remarks SmvO2 is a surrogate for cardiac output only if Hb, SaO2 and VO2 remain constant If SaO2 is low, the difference between A-V saturation is a better surrogate for cardiac output The relation between cardiac output and SmvO2 is non-lineair (next slide)
39 Cardiac Index (% of normal) 50% 70% Mixed Venous Oxygen Saturation (%)
40 Initial lactate clearance and mortality % Lactate clearance Lactate non-clearance N = 166 Lactate Nonclearance Lactate clearance ScvO2 < 70% ScvO2 70% P = N = 128 In-Hosptal mortality N = 38 No relation between ScvO2 > 70 and lactate clearance Non-clearance is decrease in lactate < 10% Arnold RC. Shock 2009;32:35-39
41 ScvO 2 and cardiac output in sepsis Perner A. Acta Anaesthesiol Scand 2010;54:98-102
42 Arterial waveform derived variables PPV 29 full-text articles 685 patients P < SPV SVV LVEDAI P < GEDVI CVP 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1 AUC Marik PE. Crit Care Med 2009;37:
43 PPV SPV SVV Lansdorp B. BJA 2012: Epub ahead of print
44 Predictive value of PLR test 9 full-text articles 353 patients PLR-cCO P < PLR-cPP Controlled ventilation Partial support Sinus rhythm Arrhythmias Supine starting Semirecumbent starting 0,6 0,80 1 Area Under Curve Cavallaro F. Intensive Care Med 2010;36:
45 Venous Return Cardiac Output (l/min) Increase in CVP Increase in CVP CVP (mm Hg) PEEP increase
46 Venous Return Cardiac Output (l/min) CVP (mm Hg)
47 Dopamine or Norepi in patients with shock 26 Norepenephrine Dopamine 21,667 17,333 % 13 8,667 4,333 0 Arrhythmic events De Backer D. N Engl J Med 2010;362:
48 Dopamine or Norepinephrine in patients with shock 25 24,1 Dopa NE 20 20,5 15 * % 10 12,4 11, ,4 1,0 1,2 Arrhythmias A. fib VT VF 0,5 De Backer D. N Engl J Med 2010;362;
49 Dopamine or Norepi in patients with shock De Backer D. N Engl J Med 2010;362:
50 Norepinephrine and preload Septic shock N = 105 Before After CI (l/min/m 2 ) 3.2 ± ± 1.1 GEDVI (ml/m 2 ) 694 ± ± 168 Decreased SVV from13 ± 6 to 9 ± 5% Only patients with a low EF (< 45%) and an increase in MAP > 75 mm Hg had no increase in CI Hamzaoui O. Crit Care 2010;14:R142
51 Vasodilatory shock - N = 21 NE 0.20 ± 0.18 μg/kg/min. NE 0.29 ± 0.18 μg/kg/min. NE 0.42 ± 0.31 μg/kg/min. Nygren A. Acta Anaesthesiol Scand 2010;54:
52 Vasopressin after cardiac surgery Laser Doppler flowmetry Tonometry Jejunal mucosal perfusion (U) Control VP 1.2 U/h VP 2.4 U/h VP 4.8 U/h Post-control Vasopressin dose (U/h) A-G CO2 gradient (mm Hg) Control VP 1.2 U/h VP 2.4 U/h VP 4.8 U/h Post-control Vasopressin dose (U/h) 8 patients with postoperative vasodilatory shock after cardiac surgery Nygren A. Acta Anaesthesiol Scand 2009;53:
53 Levosimendan and myocardial depression Dobu (5 μg/kg/min) + Norepinephrine (MAP 70) Levosimendan (0.2) or dobutamine (5 μg/kg/min) N = hours 24 hours Enrolment Screening LVEF > 45% Start Screening LVEF < 45% Stop Echo Hemodynamics Gastric perfusion Echo Hemodynamics Gastric perfusion Morelli A. Intensive Care Med 2005;31:
54 Levosimendan and myocardial depression Levosimendan Dobutamine Baseline 24 h Baseline 24 h EDVI (ml/m 2 ) 75.8 ± ± 24.6 ** 84.2 ± ± 26.4 ESVI (ml/m 2 ) 46.7 ± ± 19.4 ** 52.4 ± ± 25.3 LVEF (%) 37.1 ± ± 8.4 ** 37.3 ± ± Before After ** ** SVI LVSWI SVI LVSWI Levosimendan Dobutamine Morelli A. Intensive Care Med 2005;31:
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