Predicting Fluid Responsiveness in ICU patients: A Critical Analysis of the Evidence

1. Predicting Fluid Responsiveness in ICU patients: A Critical Analysis of the Evidence Fre�de�ric Michard, MD, PhD; and Jean-Louis Teboul, MD, PhD CHEST 2002; 121:2000�2008 critical care review ???

2. Volume expansion - critically ill patients to improve hemodynamics. Positive relationship : ventricular enddiastolic volume and stroke volume Depends on ventricular function Expected hemodynamic response to volume expansion increase Right ventricular end-diastolic volume (RVEDV) Left ventricular end-diastolic volume Stroke volume Cardiac output. Depends on fluid into the different cardiovascular compliances organized 40 to 72% of critically ill patients - respond to volume expansion by increase stroke volume or cardiac output

3. Predictive factors : Benefit from volume expansion Avoid ineffective or deleterious volume expansion Worsening in gas exchange, hemodilution Inotropic and/or vasopressor support should preferentially Guide fluid therapy in Germany Right atrial pressure (RAP) Pulmonary artery occlusion pressure (PAOP) Cardiac filling pressures Indicators of ventricular preload - predictors of fluid responsiveness RVEDV Left ventricular end-diastolic area (LVEDA) Respiratory - pleural pressure - RAP, arterial pressure, and aortic blood velocity - preload Analyze - predictive factors of fluid responsiveness in critically ill patients

4. Materials and Methods Selection of Studies To Be Evaluated Search in MEDLINE (from 1966). Studies Predictive factors of fluid responsiveness in critically ill patients Volume expansion performed in critically ill patients 12 included studies (Table 1) Volume expansion on stroke volume or on cardiac output Patients characteristics before volume expansion Classified in two groups Responders Nonresponders

5. Parameters Tested as Predictors of Fluid Responsiveness Ventricular preload indicators in predicting fluid responsiveness (Table 1) RAP in 5 studies PAOP in 9 studies RAP and PAOP : measured at end-expiration without ventilator disconnection or removal PEEP RVEDV in 6 studies RVEDV = (cardiac output/heart rate)/ right ventricular ejection fraction � 4 studies Fast-response thermistor pulmonary artery Catheter RVEDV - evaluated by cardiac scintigraphy � 2 studies LVEDA in 3 studies Transesophageal echocardiography

6. The value of dynamic parameters in predicting fluid responsiveness - 5 studies (Table 1) Inspiratory decrease in RAP (?RAP) - 2 studies ?RAP - the difference between the expiratory and the inspiratory RAP Expiratory decrease in arterial systolic pressure (?down) - 1 study ?down - the difference between the value of the systolic pressure during an end-expiratory pause and the minimal value of systolic pressure over a single respiratory cycle Respiratory changes in arterial pulse pressure (?PP) - 1 study ?PP - the difference between the maximal and the minimal value of pulse pressure over a single respiratory cycle Respiratory changes in aortic blood velocity(?Vpeak) - 1 study ?Vpeak - the difference between the maximal and minimal peak velocity of aortic blood flow over a single respiratory cycle Aortic blood flow - measured by a pulsed-wave Doppler echocardiographic beam at the level of the aortic valve.

7. Results 334 patients - 406 fluid challenges (Table 1). Septic (55%) Receiving mechanical ventilation (84%) The decision of volume expansion - based on criteria listed Table 2. Fluid administration Colloid solutions (albumin, fresh frozen plasma, or hydroxyethylstarch) - 253 instances Crystalloid solutions (serum saline solution or Ringer�s lactate) - 153 instances 250 to 500 mL colloids and 300 to 500 mL crystalloids - 9 studies Volume infusion performed until a rise in RAP = 2 mmHg � 2 studies The volume of serum saline solution infused varied from 100 to 950 mL Fluid administered until a rise in PAOP = 3 mm Hg � 1 study 938 � 480 mL for serum saline solution 574 � 187 mL for 5% albumin or fresh frozen plasma. Hemodynamic response Increase in stroke volume - 5 studies Cardiac output - 7 studies

8. RAP Not significantly lower in 3/5 studies Lower RAP baseline in responders, significant (r2 = 0.20) � 2/5 studies (Wagner and Leatherman)

9. PAOP 6/9 studies - not significantly lower 3/9 studies - significant difference 1/3 study, mean value significantly higher in responder patients (14 � 7 mmHg vs 7 � 2 mmHg, p < 0.01) 2/3 studies, significantly lower (r2 = 0.33) in responders (Wagner and Leatherman)

10. RVEDV Not significantly lower in 4/6 studies Lower RVEDV at baseline of responders in 2/6 studies (Diebel et al) RVEDV index < 90 mL/m2 - high rate of response (100% and 64%) RVEDV index > 138 mL/m2 - lack of response to volume expansion One of not significantly lower study (Wagner and Leatherman ) Positive response in 4/9 patients with a RVEDV index > 138 mL/m2 Lack of response in 3/9 patients despite a RVEDV < 90 mL/m2 Significant but weak relationship between the baseline RVEDV index (r2 = 0.19)

12. LVEDA Significantly lower in 2 studies Tavernier et al - significant and negative relationship (r2 = 0.4, p = 0.01) Tousignant et al. - marked overlap of baseline - could not be used to predict the response Another study (Feissel et al ) Not different (10 � 4 cm2/m2 vs 10 � 2 cm2/m2) No significant relationship (r2 = 0.11, p = 0.17)

13. ?RAP Spontaneous breathing activity, 2 studies (Magder et al) Inspiratory decrease in RAP = 1 mm Hg Predicted positive response to volume expansion Positive predictive values of 77% and 84% Negative predictive values of 81% and 93%

14. ?down Sedated patients receiving mechanical ventilation with sepsis-induced hypotension � 1 study ?down was significantly greater (11 � 4 mm Hg vs 4 � 2 mm Hg, p = 0.0001) in responders ?down threshold value - 5 mm Hg Positive predictive value of 95% Negative predictive value of 93% Positive and good relationship (r2 = 0.58, p = 0.001)

15. ?PP Sedated patients receiving mechanical ventilation with acute circulatory failure related to sepsis � 1 study ?PP was significantly greater (24 � 9% vs 7 � 3%, p = 0.001) in responders ?PP threshold value - 13% Positive predictive value of 94% Negative predictive value of 96% Significantly and closely correlated (r2 = 0.85, p = 0.001) with the volume expansion-induced changes in cardiac output

16. ?Vpeak Sedated patients receiving mechanical ventilation with septic shock � 1 study ?Vpeak was significantly greater (20 � 6% vs 10 � 3%, p = 0.01) in responder ?Vpeak threshold value - 12% Positive predictive value of 91% Negative predictive value of 100% Positive and tight linear correlation (r2 = 0.83, p = 0.001) between the ?Vpeak before volume expansion and the volume expansion induced changes in cardiac output.

17. Discussion Volume expansion cannot be expected of beneficial hemodynamic effect RAP > 12 mm Hg PAOP > 12 mm Hg or > 15 mm Hg. RAP and PAOP - lower in responders patients in 2 studies by Wagner and Leatherman (Fig 1, Table 3). The lower RAP or PAOP before volume expansion, the greater the increase in response to fluid infusion. These relationships were weak No difference in all other clinical studies (Fig 1, Table 3) No relationship reported between cardiac filling pressures and hemodynamic response Fluid infusion shown significantly increase cardiac output with CVP > 15 mm Hg.

18. Lower RVEDV index suggested a beneficial hemodynamic effect of volume expansion in 2 studies (Diebel et al ) RVEDV index < 90 mL/m2 - high rate of response (100% and 64%) RVEDV index > 138 mL/m2 - lack of response to volume expansion (rate of response of 0%) RVEDV index ranged from 90 to 138 mL/m2 - no cutoff value Wagner and Leatherman reported Positive response with a RVEDV index > 138 mL/m2 Lack of response despite a RVEDV < 90 mL/m2 4/6 studies - RVEDV could not predict fluid responsiveness (Fig 2).

19. The echocardiographic measurement of LVEDA Left ventricular preload Detect changes in left ventricular function caused by acute blood loss In 9 anesthetized mongrel dogs, Swenson et al reported Significant relationship between baseline LVEDA and changes in cardiac output induced by IV fluid therapy LVEDA could be an indicator of fluid responsiveness. Significantly lower LVEDA in responders in 2 studies A significant relationship between the baseline LVEDA index and the changes in stroke volume induced by volume expansion has also been reported.

20. Tavernier et al Patients with sepsis-induced hypotension Receiver operating characteristic curve analysis Minimal value of LVEDA index value to discriminate responders and nonresponders before fluid was administered. Tousignant et al Including medical-surgical ICU patients Considerable overlap of baseline individual values of LVEDA Cannot reliably predict fluid responsiveness in an individual patient. Feissel et al Septic shock patients No any difference of the mean baseline value of LVEDA index No any relationship between the baseline value of LVEDA index and the percentage of change in cardiac index in response to volume expansion. Lack of value of ventricular preload indicators as predictors of fluid responsiveness

21. First, RAP, PAOP, RVEDV, and LVEDA are not always accurate indicators of ventricular preload. RAP and PAOP - overestimate transmural pressures with external or intrinsic PEEP. PAOP : highly dependent on left ventricular compliance (sepsis, ischemic, hypertrophic cardiopathy). RAP and PAOP - related to end-diastolic volumes via the chamber compliance Pulmonary hypertension (ARDS, mechanical ventilation with PEEP) - tricuspid regurgitation The LVEDA by echocardiography - not accurately reflect left ventricular enddiastolic volume and LV preload. Second - right ventricular dysfunction Beneficial hemodynamic effect of volume expansion cannot be expected even in the case of low left ventricular preload

22. Third, diastolic chamber compliance Hypovolemia associated with a normal or high LVEDA value with dilated cardiopathy. Finally, two matters must be stressed: (1) The partitioning of the fluid into the different cardiovascular compliances organized (2) Ventricular function - decrease in ventricular contractility decreases the relationship between end-diastolic volume and stroke volume. Nonresponder to a fluid challenge High venous compliance Low ventricular compliance Ventricular dysfunction

23. Respiratory changes in pleural pressure - decrease in RAP when inspiratory (Magder et al) Inspiratory decrease in RAP = 1 mm Hg - Predicted positive response to volume expansion Unable to produce an inspiratory decrease in ICU Sedated patients receiving mechanical ventilation Sedated patients receiving mechanical ventilation with acute circulatory failure related to sepsis Respiratory changes in left ventricular stroke volume - predict fluid responsiveness Arterial pulse pressure (systolic minus diastolic pressure) Proportional to left ventricular stroke volume Respiratory changes in systolic pressure Less specific indicator of changes in left ventricular stroke volume

24. Septic patients with hypotension -?down predictor (Tavernier et al) Cardiac arrhythmias, shock states - ?down and ?PP requires invasive arterial pressure catheterization (A-line). Doppler echocardiographic imaging of aortic blood velocity - noninvasively (Feissel et al) Predictors of fluid responsiveness in sedated patients receiving mechanical ventilation with sepsis ?down ?PP ?Vpeak In the studies analyzed (Table 1) Various types and volumes of fluid Speeds of fluid infusion Definitions of responders to volume expansion

25. The hemodynamic effects Hypertonic colloid infusion are expected to more dramatic than isotonic crystalloid infusion Intravascular- extravascular equilibration Speed of volume infusion Systemic capillary leakness Different definitions of responders from study Individual data were not available Predictive value of dynamic parameters tested only few studies. Further studies are required to confirm the high value of dynamic parameters Our analysis emphasizes the minimal value of static ventricular preload parameters Strongly supports the use of the dynamic parameters in the decision-making process concerning volume expansion in critically ill patients.

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