Fluid responsiveness and extravascular lung water Prof. Jean-Louis TEBOUL Medical ICU Bicetre hospital University Paris-South France
Conflicts of interest Member of the Medical Advisory Board of Maquet/Pulsion
Critically ill patients often experience hemodynamic instability Clinicians are tempted to give fluid to restore adequate hemodynamic conditions However, often, patients were already fluid-resuscitated for hours or days potential fluid overload with subsequent risks of pulmonary edema especially in conditions of increased lung permeability positive cumulative fluid balance: independent predictor of death
Highest positive fluid balance
Critically ill patients often experience hemodynamic instability Clinicians are tempted to give fluid to restore adequate hemodynamic conditions However, often, patients were already fluid-resuscitated for hours or days potential fluid overload with subsequent risks of pulmonary edema especially in conditions of increased lung permeability positive cumulative fluid balance: independent predictor of death no certainty of fluid responsiveness
CHEST 2002, 121:2000-8 Only 52% of patients responded to fluid administration in terms of CO increase
Critically ill patients often experience hemodynamic instability However, Clinicians are tempted to give fluid to restore adequate hemodynamic conditions Fluid infusion benefit / risk ratio? often, patients were already fluid-resuscitated for hours or days potential fluid overload with subsequent risks of pulmonary edema especially in this condition of increased lung permeability Predictors of fluid responsiveness are required positive cumulative fluid balance: independent predictor of death no certainty of fluid responsiveness Markers of lung edema are required
SSC «static» approach «dynamic» approach
SSC approach: Stop IV fluids when a certain level of CVP has been reached Stroke Volume preload unresponsiveness CVP
Initial resuscitation 1. Protocolized, quantitative resuscitation of patients with sepsis-induced hypoperfusion (defined as hypotension persisting after initial fluid challenge or blood lactate 4 mmol/l). Goals during the first 6h of resuscitation: (a) pressure 8-12 mmhg Central venous pressure 8-12 mmhg (b) Mean arterial pressure (MAP) 65 mmhg (c) Urine output 0.5 ml.kg -1 h (d) Central venous or mixed venous oxygen saturation 70 or 65%, respectively (grade 1C) Central venous pressure 12-15 mmhg if MV
normal heart preload responsiveness Stroke volume failing heart preload unresponsiveness. CVP
Responders Nonresponders
Crit Care Med 2013; 41:1774-81 1802 pts Summary AUC 0.56 Predicting fluid responsiveness with CVP is like
SSC «static» approach «dynamic» approach No. Statement/recommendation GRADE level of recommendation; quality of evidence 30. We recommend not to target any absolute value of ventricular filling pressure or volume 31. We recommend using dynamic over static variables to predict fluid responsiveness, when applicable Level 1; QoE moderate (B) Level 1; QoE moderate (B)
Dynamic indices of preload responsiveness normal heart Stroke volume preload responsiveness failing heart. preload unresponsiveness Ventricular preload
Stroke volume preload responsiveness preload unresponsiveness A B Ventricular preload
Sensitivity PPV CVP PAOP 1 - Specificity
Anesth Analg 2011; 113:523-8 Chest 2005;128;848-854 Chest 2004, 126:1563-1568 PPV Crit Care Med 2005;33:2534-9 M. Cannesson, J. Slieker, O. Desebbe, F. Fahdi,O. Bastien, JJ. Lehot X. Monnet 1,2*,L. Guerin 1,2,M. Jozwiak 1,2,A. Bataille 1,2,F. Julien 1,2,C. Richard 1,2,J-L. Teboul 1,2
Pulse Pressure Variation Calculated automatically and displayed in real-time by usual hemodynamic monitors
Threshold: 12% AUC: 0.94
Arterial pressure waveform analysis Stroke volume Arterial Pressure Stroke Volume Variation Calculated automatically and displayed in real-time by new hemodynamic monitors
Arterial pressure waveform analysis Stroke volume Arterial Pressure
X. Monnet 1,2* L., Guerin 1,2,M. Jozwiak 1,2,A. Bataille 1,2 F., Julien 1,2,C. Richard 1,2,J-L. Teboul 1,2 Assessing fluid responsiveness by stroke volume variation in mechanically ventilated patients with severe sepsis G. Marx, T. Cope, L. McCrossan, S. Swaraj, C. Cowan, SM. Mostafa, R. Wenstone, M. Leuwer European Journal of Anaesthesiology 2004; 21:132-138 Chest 2005;128;848-854
685 pts
In all these situations and in case of any doubt about interpretation other reliable dynamic tests are required and are now available
Stroke Volume PLR mimics fluid challenge preload responsiveness b' a' Unlike fluid challenge, no fluid is infused, preload unresponsiveness and, the effects are reversible and transient b a The hemodynamic response to PLR A PLR B Ventricular preload can predict the hemodynamic response to volume infusion
Crit Care 2015, 19:18
Real-time CO response to PLR 2012
PLR-induced changes in CO PLR-induced changes in AP Study name sample size AUC 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 Monnet CCM 2006 71 0.75 Monnet CCM 2009 34 0.68 Preau CCM 2010 34 0.86 139 0.76 351 0.95
n = 30 pts n = 30 pts
Preload dependence group Control group
Control Preload dependence
Critically ill patients often experience hemodynamic instability Fluid infusion benefit / risk ratio? Predictors of fluid responsiveness are required Markers of lung edema are required
How to assess the risk of pulmonary edema? PAOP?
Increased lung capillary permeability Increased inflammation volume of lung edema 12 Pcrit mmhg Pulmonary artery occlusion pressure
Increased inflammation Amount of pulmonary edema Increased lung capillary permeability 12 mmhg Pcrit Pulmonary artery occlusion pressure
EVLW ml/kg PAOP mmhg
How to assess the risk of pulmonary edema? PAOP? EVLW? cannot reliably assess the risk of pulmonary edema
Central Venous Catheter (cold bolus injection) Thermodilution femoral arterial catheter
200 pts D 28 mortality: 54% Odds Ratio ( CI 95%) p value Maximal blood lactate 1.29 (1.14-1.46) 0.0001 Mean PEEP 0.78 (0.67 0.91) 0.002 Minimal PaO 2 / FiO 2 0.98 (0.97-0.99) 0.006 SAPS II 1.03 (1.01-1.05) 0.02 EVLW max 1.07 (1.02-1.12) 0.007 Mean fluid balance 1.0004 (1.0001 1.0008) 0.02
Cumulative fluid balance (L) 7 5 * * * * PAOP group 3 1 EVLW group -1-3 -5 * p < 0.0001 vs time 0 0 12 24 36 48 60 72 Time (hours)
25 20 15 10 * * PAOP group EVLW group 5 0 MV days ICU days
PVPI = EVLW/Pulmonary blood volume PVPI marker of lung µvessels permeability
200 pts D 28 mortality: 54% Odds Ratio ( CI 95%) p value Maximal blood lactate 1.27 (1.12-1.45) 0.0002 Mean PEEP 0.78 (0.67 0.91) 0.002 Minimal PaO 2 / FiO 2 0.98 (0.97-0.99) 0.0009 SAPS II 1.03 (1.01-1.05) 0.008 PVPI max 1.07 (1.02-1.12) 0.03 Mean fluid balance 1.0004 (1.0000 1.0007) 0.03
Decision of starting fluid administration presence of hemodynamic instability/peripheral hypoperfusion (mottled skin, hypotension, oliguria, hyperlactatemia ) and presence of preload responsiveness and limited risks of fluid overload
Decision of stopping fluid administration disappearance of hemodynamic instability/peripheral hypoperfusion or appearance of preload unresponsiveness or appearance of fluid overload or marked increase in EVLW
Conclusion Before infusing fluids in critically ill patients, and especially in ARDS patients Fluid infusion benefit / risk ratio should be assessed patient per patient Predictors of fluid responsiveness are required Markers of lung edema are required