How to resuscitate the patient in early sepsis? A physiological approach. J.G. van der Hoeven, Nijmegen
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1 How to resuscitate the patient in early sepsis? A physiological approach J.G. van der Hoeven, Nijmegen
2 Disclosure interests speaker (potential) conflict of interest Potentially relevant relationships with companies Sponsorship or grant for research Fee or other (financial) compensation Shareholder Other relationship,.. None / See below Company names
3 Overall it must be simple Circulatory failure that results in inadequate cellular oxygen utilization Septic Shock Treatment goal Host response Restore tissue oxygenation
4 Unfortunately Inadequate O2 delivery on a macrocirculatory level Inadequate O2 delivery on a microcirculatory level Inadequate O2 utilization (mitochondrial dysfunction) Oxygen delivery (DO2) = CO Hb SaO2
5 Arterial and venous vasodilatation Increased capillary permeability Absolute/relative hypovolemia Cardiodepressant factors Microcirculatory disturbances Systolic/diastolic dysfunction Increased NO, vasopressin deficiency, IDO activation Vasodilatation Hypotension Insufficient perfusion pressure / low DO2
6 Change in P ra and P pericard after fluid challenge Cardiac surgery N = 9 FC op to 2.1 L Pra (mmhg) Pra = 0.99 Ppericard Ppericardium (mmhg) Taberg JV. Circulation 1986;3:
7 Normal RV works below its stressed volume FC 60 ml 0 75 ml 0 Conformational changes Increase in MSFP and venous return
8 Important consequence If increasing RV volume increases RV preload and thus RV distending pressure, the RV is either hypertrophied with diastolic dysfunction or over distended as in acute cor pulmonale Any increase in CVP is abnormal!
9 Hagen-Poisseuille equation Flow = P r 4 η L
10 Does CVP play a role in organ hypoperfusion? Slower loss of fluid from vasculature Normal Rapid vascular refilling with fluid removal Normal oncotic pressure Arterial Arteriolar constriction Venous MAP X Normal intersitium Fluid therapy Ultrafiltration CVP Interstitial oedema Low oncotic pressure Increased capillary permeability Plasma protein leak Hypoalbuminaemia Rapid loss of fluid from vasculature Systemic inflammation Slow vascular refilling with fluid removal
11 Septic patient CVP will increase due to Excessive fluid loading RV constraint due to increased pericardial pressure (MV) Diastolic and systolic RV dysfunction
12 CVP and septic AKI Sepsis (N = 137) - retrospective study design Relation systemic hemodynamics and AKI 20 No AKI AKI 15 CVP (mmhg) CVP (mean) CVP (LLR) CVP (ULR) Legrand M. Crit Care 2013;17:R278
13 Microcirculation Septic shock - N = 70 Microvascular flow index 2 1,5 1 0,5 0 MFI CVP P = CVP 12 CVP > CVP Percentage Perfused Vessels (%) PPV CVP P = CVP 12 CVP > CVP Increased CVP associated with microcirculatory perfusion Vellinga NAR. BMC Anesthesiology 2013;13:17
14 VIP treatment Increase systemic oxygen delivery Ensure sufficient oxygenation - no evidence that hyperoxia is harmful in circulatory shock Fluid therapy depending on resuscitation phase (SOSD) - salvage - optimization - stabilization - deescalation Restore a minimal tissue perfusion pressure
15 SOSD Salvage Optimization Stabilization De-escalation ml/kg No monitoring Based on Fluid responsiveness Neutral fluid balance Negative fluid balance
16 Passive leg raising (meta-analysis 1) Sensitivity Specificity AUC N = 23 Total 1013 patients 86% 92% 0.95 Unaffected by ventilation mode, fluid type, PLR starting position Abdominal hypertension? Measure between seconds after leg raising Cherpanath TGV. Crit Care Med 2016;44:
17 Passive leg raising (meta-analysis 2) Sensitivity Specificity AUC N = 21 Total 991 patients 85% 91% 0.95 In both studies AUC with CO changes >> PP changes Monnet X. Intensive Care Med 2016
18 Mini fluid challenge N = min 10 sec M1 VTI M2 VTI M3 VTI 50 cc 450 cc Wu Y. Crit Care 2014;18:R108
19 Transfusion in septic shock 80 Restrictive (4.3 mmol/l) Liberal (5.6 mmol/l) ,4 62,2 % ,9 16,1 7,2 8 Mortality D 90 Ischemic events Life support D 5 Life support D 28 N = 998 Holst LB. N Engl J Med 2014;371:
20 % N = 776 MAP in septic shock SEPSISPAM trial MAP mmhg 43,7 42,3 MAP mmhg P = 0.57 P = 0.74 P = 0.50 P = ,5 35, ,5 19,1 17,8 28 D Mortality 90 D Mortality RRT SAE Personalized medicine Less AKI/RRT in high MAP group with previous hypertension Asfar P. N Engl J Med 2014
21 When to start NE? When MAP is inadequate CO (l/min) Preload (mm Hg) Bai X. Crit Care 2014;18:R532 Beck V. Crit Care 2014;18:R97
22 N = VEs Dynamic arterial elastance = ratio PPV/SVV during single MV breath All fluid responders (increase CO 10%) Eadyn& 1,4" 1,2" 1" 0,8" 0,6" 0,4" 0,2" *** Ea#(mmHg/mL)# 3" 2,5" 2" 1,5" 1" 0,5" C"(mL/mmHg)" 2" 1,5" 1" 0,5" SVR$(dyn*s*cm-5)$ 2000" 1500" 1000" 500" 0" Responder" Non2Responder" 0" Responder" Non1Responder" 0" Responder" Non0Responder" 0" Responder" Non/Responder" MAP responders defined by increase MAP 10%) García MIM. Crit Care 2014;18:626
23 Norepinephrine optimal vasopressor? Stolk RF. Am J Respir Crit Care Med 2016;194:
24 Myocardial depression 30-50% Rapid increase in filling pressures without increase in cardiac output - cardiac ultrasound Highly susceptible for NE induced excessive afterload increase Milrinone/Enoximone or Dobutamine
25 Diastolic heart failure with tachycardia? Esmolol group Higher SVI Higher LVSWI Lower NE dose Less volume therapy Morelli A. JAMA 2013;310:
26 Potential therapies for the microcirculation Fluid therapy Vasopressors Proportion perfused vessels = < 24 hrs = > 48 hrs Variable effects Variable effects Improvement with severe derangements but worsening when nearly normal Ospina-Tascon G. Intensive Care Med 2010;36: Inotropes? Vasodilators? Experimental??? Dobutamine has no effect after resuscitation of macrocirculation Hernandez G. Intensive Care Med 2013;39: Nitroglycerine has no effect after resuscitation of macrocirculation Boerma EC. Crit Care Med 2010;38: NOS modulation Dexmedetomidine
27 Beyond hemodynamics - early metabolic therapy to improve mitochondrial function Thiamine (cofactor for PDH) Ascorbic acid, tocopherol, selenium and zinc Coenzyme Q10, L-carnitine, caffeine, melatonine No definite evidence yet
28 My recommendations Besides early fluid resuscitation early vasopressor therapy may be beneficial For a number of reasons the goals of resuscitation should be established with the lowest possible CVP Optimization of fluid therapy should probably be guided by tests of fluid responsiveness Resuscitate both the macro- and the microcirculation At least for the first 3 days make a daily echocardiogram and treat myocardial dysfunction accordingly
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