The document discusses methods for predicting fluid responsiveness in critically ill patients. It describes how static parameters like central venous pressure and pulmonary artery occlusion pressure are poor predictors on their own. Dynamic parameters that measure stroke volume variation with respiration are better predictors if the patient is mechanically ventilated. The ability to predict fluid responsiveness is important to optimize fluid administration and prevent under- or over-hydration in critically ill patients.

1. FLUID RESPONSIVENESS IN
CRITICAL CARE
‘‘will my patient’s cardiac output increase
following volume expansion?’’
‘‘is my patient preload dependent / not?’’

2. DR ISHA DESHMUKH

3.  The ability to identify patients who would
respond to fluid administration by
increasing stroke volume and hence
cardiac output is of vital importance.
 The recent increase of research interest in
this field reflects the evidence that early
fluid optimization of critically ill patients
improves outcome.

4.  The current internationally recommended
first line therapy for hypotensive critically
ill patients is a “fluid challenge”
 Hypotension in this setting can be due to
various causes like cardiac failure, actual
or relative hypovolemia, vasoplegia etc
occurring either in isolation or in
combination.

5. Clinical indices of the adequacy of tissue/organ
perfusion
 • Mean arterial pressure
 Cerebral and abdominal perfusion pressures
 • Urine output
 • Mentation
 • Capillary refill
 • Skin perfusion/mottling
 • Cold extremities (and cold knees)
 • Blood lactate
 • Arterial pH, BE, and HCO3
 • Mixed venous oxygen saturation SmvO2 (or ScvO2)
 • Mixed venous pCO2
 • Tissue pCO2
 • Skeletal muscle tissue oxygenation (StO2)

6. Concept……………………………
…
 Too little fluid may result in tissue
hypoperfusion and worsen organ
dysfunction
 Over-prescription of fluid also appears to
impede oxygen delivery and compromise
patient outcome.

7. If we are giving fluids we should
have a cardiovascular response.
SV and CO should rise

8. Clinical studies have, however, demonstrated
that only approximately 50% of
hemodynamically unstable critically ill
patients are volume-responsive
Marik PE, Cavallazzi R, Vasu T, Hirani A:
Dynamic changes in arterial waveform derived
variables and fluid responsiveness in
mechanically ventilated patients.
A systematic review of the literature.
Crit Care Med 2009, 37:2642-2647

9. MICHARD F, TEBOUL JL.
PREDICTING FLUID RESPONSIVENESS IN ICU
PATIENTS. A CRITICAL
ANALYSIS OF THE EVIDENCE.
CHEST 2002;121:2000E8.
Marik PE, Baram M, Vahid B.
Does central venous pressure predict fluid
responsiveness? A systematic review of the
literature and the tale of seven
mares.
Chest 2008;134:172e8.

10. Frank-Starling relationship
 Describes the intrinsic ability of the heart to
adapt to increasing volumes
 Normal cardiac physiology –
‘the energy of contraction is proportional to the
initial length of the cardiac muscle fibre’.
.

11. Stroke volume
Preload
Fluid responsiveness
Fluid unresponsiveness
Fluid responsiveness is related to cardiac responsive

12.  In physiological terms, predicting fluid
responsiveness seeks to identify patients
who are on the steep part of the Frank
Starling curve, who would increase their
SV and hence CO in response to a fluid
challenge.

13. Stroke volume
Preload
Fluid responsiveness is related to cardiac res
Normal heart
Failing heart
Fluid responsiveness
Fluid
unresponsiveness

14. Frank-Starling relationship
 Once the ventricle is functioning on the steep
part of the Frank-Starling curve, there is a
preload reserve.
 Volume expansion (VE) induces a significant
increase in stroke volume.
 The pulse pressure (PPV) and stroke volume
(SVV) variations are marked and the passive leg
raising (PLR) and end-expiratory occlusion (EEO)
tests are positive.
 By contrast, once the ventricle is operating near
the flat part of the curve, there is no preload
reserve and fluid infusion has little effect on the
stroke volume.
 There is a family of Frank-Starling curves
depending upon the ventricular contractility

15. Pressure Parameters Volume Parameters
Right ventricular
filling pressures
can be
obtained from CVP.
Left Ventricular filling
pressures –
indirectly from
PCWP - PAC
Left ventricular
EDV.
Left ventricular
End diastolic area
using
Echocardiography.

16. Pulse pressure variation
 The dynamic parameters of fluid responsiveness are
related to cardiopulmonary interactions in patients
under general anesthesia with mechanical ventilation.
 Far superior to static indicators (such as central
venous pressure)
 Single arterial pressure waveform [systolic pressure
variations (SPV), and pulse pressure variations
(PPV)].
 These new monitoring parameters can more readily
predict the need for fluid administration to improve
cardiac output and perfusion as compared to more
invasive cardiac output monitoring.

17. FROM KUSSMAUL’S PULSUS PARADOXUS TO
RESPIRATORY
VARIATIONS IN THE PULSE OXIMETER
PLETHYSMOGRAPHIC
WAVEFORM AMPLITUDE
 Pulsus paradoxus - Spontaneously breathing
volunteers presenting with conditions which
cause right ventricular dysfunction, impaired
right ventricular filling, and raised atrial pressure.

19.  Inspiration – increase in negative intrathoracic
pressure
increase in venous return to the
right heart
Exaggerated ventricular
interdependence displacement of the
septum into the left ventricle
reducing its size & volume
Increase pulmonary vascular filling,
decrease in left ventricular filling
& stroke volume.

20. Patients with mechanical ventilation and no
spontaneous breathing activity

21. Heart-lung interactions
Hemodynamic effects of mechanical ventilation.
The cyclic changes in left ventricular (LV) stroke volume are
mainly related to the expiratory decrease in LV preload due to the
inspiratory decrease in right ventricular (RV) filling

24. In patients under general anesthesia
 Intermittent positive-pressure ventilation
 cyclic changes in the loading conditions of the left and right
ventricles.
 cyclic changes in vena cava blood flow, pulmonary artery
flow, and aortic blood flow
During inspiration, vena cava blood flow decreases
(venous return decreases)
according to the Frank-Starling relationship
pulmonary artery flow decreases
 Approximately three beats later,  this decrease in
pulmonary artery flow is transmitted to the left ventricle
inducing a decrease in aortic stroke volume.
 Consequently, mechanically ventilated patients
under general anesthesia have cyclic changes in
left ventricular stroke volume due to changes in
intrathoracic pressure.

25.  The reduction in RV preload and increase
in RV afterload both lead to a decrease in
RV stroke volume, which is at a minimum
at the end of the inspiratory period.
 The LV preload reduction may induce a
decrease in LV stroke volume, which is at
its minimum during the expiratory period
when conventional mechanical ventilation
is used.
 The cyclic changes in RV and LV stroke
volume are greater when the ventricles
operate on the steep rather than the flat
portion of the Frank-Starling curve.

27. Fluid responsiveness
 ‘Fluid
responsiveness’ is
defined as the
ability of SV to
increase in
response to a fluid
infusion or a “fluid
challenge”.
 Weil and Henning
introduced the
concept of a “fluid
challenge”.
 Weil MH, Henning RJ.
New concepts in the
diagnosis and fluid
treatment of circulatory
shock.
 Anesth Analg
1979;58:124e32.

28. Parameters involved in a fluid challenge.
 Choice of fluid - Colloid (usually)
 Amount to be infused - 250 ml or 3 ml/kg
 Duration of infusion - 5-10 min
 Adequacy of challenge - Change in CVP of
2 cm H2O
 Target parameter - MAP, SV, CO
 Assessment time frame - Variable
depending on CO monitor used
 Positive response -Increment of SV/CO by
10-15%

29.  Advantages of a resuscitation strategy
involving fluid challenges include:
1. Testing preload reserve and quantification
of the cardiovascular response to fluid
administration.
2. Prompt correction of fluid deficit.
3. Minimising the risk of fluid overload and
its subsequent complications.

30.  An ideal method to predict fluid responsiveness
would be a cheap, direct, easy to perform,
minimally invasive and continuous measurement
with a high specificity and sensitivity.
 The fact that a multitude of methods is used to
predict fluid responsiveness is a reflection of the
lack of an ideal method.
 Currently used methods either use static or
dynamic measurements.

31. Static measurements & Limitations
 CVP
 PAOP
 RV end-diastolic volume index (RVEDVI)
 LV end-diastolic area (LVEDA)

32. CVP
 Magder’s maxim ‘‘no left-sided success
without right-sided success.’’
 Only right heart pressures (RAP - as a
surrogate for right ventricular end-
diastolic pressure [RVEDP]) and, hence,
right ventricular preload (RVEDV) are
assessed.
 The basis - effective regulation of CO
through the right heart’s determination of
venous return, independent of the left
heart’s function.

33. External reference mark
 In practice- the midaxillary line intersects a
cross-sectional plane through the fourth
intercostal space.
 Magder’s group, is a point 5 cm vertically below
the sternal angle (at the junction of the sternum
and the second rib costal cartilage).
 Figg and Nemergut – recent study.
 The investigators concluded that hospital-wide
standardization of appropriate zero-point levels
and staff education are required to minimize
systematic errors in CVP measurement from
interprovider variability.

34. The Effects of the Respiratory
Cycle & Cardiac cycle
 At no point in the respiratory cycle (and
definitely not at end-expiration) will the
pleural pressure be close to zero.
 In such instances, which are common in
ventilated patients, an accurate
measurement of CVP cannot be made.
 Relationship of ventricular diastole and
systole should be considered when
interpreting CVP (and Ppao) pressure
tracings.

35. Physiologic and Anatomic Properties of the Heart
 heart failure or acute myocardial infarction
 hyperadrenergic states
 pulmonary hypertension
 tricuspid insufficiency- ‘‘ventricularize’’ the CVP
waveform  resulting in an elevated mean CVP.
 tricuspid stenosis elevates the mean CVP,
resulting in a gradient between the RAP and the
RVEDP

36. STUDY TRIALS
 In a prospective observational study of
 83 patients admitted to a medical-surgical ICU,
most of whom were nonseptic patients after
cardiac surgery and all of whom had a PA
catheter inserted, Magder and Bafaqeeh
investigated fluid responsiveness over a range of
CVP values in an attempt to identify a threshold
CVP above which volume expansion was unlikely
to increase cardiac output.

37.  66 pts 40- responders
26- non-responders.
 No patient responded when the CVP>13
 3 of 12 pts with an initial CVP >10 mm Hg
responded to fluids on their first trial.
 Nonresponders, however, were identified
at all initial CVP levels.
 Conclusion-CVP >10 mm Hg (measured
with a transducer leveled 5 cm below the
sternal angle) indicates a low likelihood of
improving CO in response to fluid
challenge, with the caveat that
nonresponders will still be found at CVPs
less than 10 mm Hg..

38. Conclusion:
 Hence,
CVP is best viewed as a negative
predictor of fluid responsiveness
 Magder S, Bafaqeeh F. The clinical role of
central venous pressure measurements.
 J Intensive Care Med 2007;22(1):44–51.

39. (CHEST 2008; 134:172–178)

40.  Meta-analysis of 24 studies incorporating 830
medical and surgical patients that examined both
CVP and changes in CVP as predictors of
intravascular blood volume and fluid
responsiveness.
 In none of the studies was CVP able to predict
either blood volume or fluid responsiveness.
 our results suggest that at any CVP the likelihood
that CVP can accurately predict fluid
responsiveness is only 56%.

42.  Fifteen hundred simultaneous
measurements of blood volume and CVP
in a heterogenous cohort of 188 ICU
patients demonstrating no association
between these two variables (r 0.27).
 The correlation between CVP and change
in blood volume was 0.1 (r2 0.01).
 This study demonstrates that patients with
a low CVP may have volume overload and
likewise patients with a high CVP may be
 volume depleted.

44.  Summary-
 CVP should no longer be routinely
measured in the ICU, operating room/ER.
 However, measurement of the CVP may
be useful in select circumstances, such as
in patients who have undergone heart
transplant/in those who have suffered a
RV infarction /acute PE.
 In these cases, CVP may be used as a
marker of right ventricular function rather
than an indicator of volume status.

45. Cardiac filling pressures are not appropriate to predict hemodynamic
response to volume challenge. Crit CareMed 2007;35:64–8.
 Osman and colleagues- retrospectively
analyzed prospective data on 150 fluid
challenges in 96 patients with severe
sepsis.
 Defining a response as a 15% or greater
increase in CI, responders and
nonresponders showed increases in Ppao
and CVP after fluid challenge, with a
baseline (preinfusion) Ppao difference that
was slightly but statistically significantly
lower in the responder group.

46. Study methods-
 A total of 150 volume challenges in 96 patients
were reviewed. In 65 instances, the volume
challenge resulted in an increase in cardiac index of
>15% (responders).
 The pre-infusion central venous pressure was
similar in responders and nonresponders (8 4 vs. 9
4 mm Hg).
 The pre-infusion pulmonary artery occlusion
pressure was slightly lower in responders (10 4 vs.
11 4 mm Hg, p < .05).

47.  The significance of pulmonary artery occlusion
pressure to predict fluid responsiveness was poor
and similar to that of central venous pressure, as
indicated by low values of areas under the receiver
operating characteristic curves (0.58 and 0.63,
respectively).
 A CVP of <8 mm Hg and a PAOP of <12 mm Hg
predicted volume responsiveness with a positive
predictive value of only 47% and 54%, respectively.
 With the knowledge of a low stroke volume index
(<30 mL·m2), their PPV were still unsatisfactory:
61% and 69%
 When the combination of CVP and PAOP was
considered instead of either pressure alone, the
degree of prediction of volume responsiveness was
not improved.

48. Relationship between central venous pressure (CVP) and pulmonary
artery occlusion pressure (PAOP) before fluid loading in the overall
population.
Linear correlation: r .547, r .740, p .0001.

49. Summary
 Cardiac filling pressures are poor
predictors of fluid responsiveness in septic
patients.
 Their use as targets for volume
resuscitation must be discouraged, at
least after the early phase of sepsis has
concluded.

51. Conclusion
 Regardless of GEF, CVP may be useful for predicting
fluid responsiveness in patients after coronary &
major vascular surgery provided that PEEP is low.
 When GEF is low (<20%), PAOP is more useful than
GEDVI for predicting fluid responsiveness, but when
GEF is near-normal (≥20%) GEDVI is more useful
than PAOP.
 This favors predicting & monitoring fluid
responsiveness by PAC-derived filling pressures in
surgical patients with systolic LV dysfunction & by
trans pulmonary thermodilution derived GEDVI
when systolic LV function is relatively normal.

52. Why the difference ??
 Patients with similar cardiac filling
pressures may be on different parts of the
Franke Starling curve as regards to their
cardiac function.
 Hence, those in the steep part of the
curve may not demonstrate an increase in
filling pressure to a fluid challenge while
those on the flat part of the curve may do
so.

53.  It is the transmural pressure and not the
intracavitary pressure such as (RAP) and
PAOP that is related to EDV via the
chamber compliance.
 Ventricular compliance is frequently
altered in critically ill patients.
 The ventricular diastolic compliance curves
are non-linear. In patients with isolated
RV dysfunction, a fluid challenge may
increase the right heart filling pressure
even with low LV preload.

54.  RAP and PAOP have been shown to
overestimate transmural pressures in
patients with external or intrinsic positive
end expiratory pressure (PEEP).
 Filling pressures can paradoxically decline
after fluid repletion as a result of
decreased sympathetic stimulation.

55. Superior vena cava collapsibility index and inferior
vena cava distensibility index
 The changes in RAP during positive pressure
ventilation are reflected on to the vena cavae.
 The subsequent change in their diameter can be
measured using echocardiography.
 In mechanically ventilated patients, the SVC
collapsibility index is calculated as the max diameter
on expiration minus the min diameter on inspiration
divided by the max diameter on expiration.
 Vieillard-Baron et al. have demonstrated that a
threshold superior vena cava collapsibility index of
36% can reliably predict responders to fluid
challenge with 90% sensitivity and 100% specificity
in ventilated septic patients

56.  The inferior vena cava distensibility index
(dIVC) is calculated as follows: maximum
diameter (Dmax) minus minimum
diameter (Dmin) divided by Dmin.
 Barbier et al. found that a dIVC threshold
of 18% can reliably predict a responder
with 90% sensitivity and 90% specificity.

57. •Because the AUC of the ROC curve for cIVC was 0.77
the present study shows that cIVC cannot reliably
predict fluid responsiveness in spontaneously breathing
patients with ACF.
•More precisely, a cIVC value below 40% cannot
exclude fluid responsiveness while patients with cIVC
above 40% are more likely to respond to fluid
challenge.
•The 40% cutoff value is in agreement with recent
studies

58. Pulse pressure variation
Marik PE, Cavallazzi R, Vasu T, Hirani A.
Dynamic changes in arterial waveform derived variables
and fluid responsiveness in mechanically ventilated
patients- a systematic review of the literature. Crit Care
Med 2009;37:2642e7.

59.  PPV is calculated as (PPmax PPmin)/ (Ppmax
PPmin)/2, and is expressed as a percentage.
 The sensitivity & specificity of PPV to predict
an increase in CO by 10-15% among
patients admitted to intensive care was 89%
and 88% .
 The area under the ROC curve was 0.94.
 The average threshold value for PPV
predicting fluid responsiveness including
different groups of patients is 12.5 1.6%.

60.  Systolic Pressure Variation (SPV) is the
difference between maximal and minimal
values of systolic blood pressure during
one positive pressure mechanical breath.
 The correlation coefficient of SPV to
predict fluid responsiveness in a mixed
population of surgical and intensive care
patients is 0.72 with an area under the
ROC curve of 0.86 .

62. Pulse oximeter plethysmograph
 A 9.5-15% respiratory variation in pulse oximeter
plethysmography waveform amplitude (ΔPOP) has
been shown to be a modest predictor of fluid
responsiveness in mechanically ventilated patients
 with a sensitivity of 81% and specificity of 78% and
an area under ROC 0.88.
 Plethysmographic variability index (PVI) is an
algorithm allowing for automated, non-invasive
continuous monitoring of ΔPOP, derived from the
perfusion index.
 PVI has shown a good ability to predict fluid
responsiveness both in the intra-operative &
intensive care patients with circulatory failure

63.  Loupec T, Nanadoumgar H, Frasca D,
Petitpas F, Laksiri L, Baudouin D, et al.
 Pleth variability index predicts fluid
responsiveness in critically ill patients.
 Crit Care Med 2011;39:294e9.

65. Limitations of Dynamic Measurements
 1.Controlled mechanical ventilation with no
spontaneous breathing and no active expiration
 2. Tidal volume of 8 ml/kg
 3. Sinus rhythm without frequent ventricular or
supraventricular ectopics
 4. Absence of cor pulmonale
 5. HR/RR >3.6
 6. No change in autonomic nervous system
activity (e.g. due to stimuli like pain, noise,
anxiety) during measurements

66. Passive Leg Raising - PLR
 PLR induces an ‘autotransfusion’ of blood from
the lower limbs & abdominal compartment into
the central circulation.
 The shifted volume is higher if the patient is
moved from a recumbent position into a supine
position with the legs elevated.
 Assessment of the haemodynamic response
induced by PLR requires a monitor which
calculates SV and CO almost real time, i.e., every
few seconds.

67. Study data -
 A recent meta-analysis by Carvallo et al.
showed that PLR induced changes in SV
and CO is a good predictor of fluid
responsiveness in critically ill patients.
 A PLR induced increase in SV and/or CO
was found to have a sensitivity &
specificity of 89% and 91% to predict fluid
responsiveness, respectively.
 The pooled area under the ROC was 0.95.

68. Ad-disadvantages:
 This manoeuvre, however, cannot be
performed in all critically ill patients,
especially those with spine, pelvic /limb
fractures.
 Elastic compression stockings and
elevated IAP can influence the volume
recruited by PLR.
 One specific advantage that PLR has over
other techniques is that PLR is a
‘reversible self volume challenge’.

69.  The ability of pulse pressure variation to predict
 fluid responsiveness was inversely related to
compliance of the respiratory system.
 If compliance of the respiratory system was <30
mL/cmH2O, then PPV became less accurate
 for predicting fluid responsiveness.
 However, the passive leg-raising and end-
expiratory occlusion tests remained valuable in
such cases.
 (Crit Care Med 2012; 40:000–000)

70. Critical Care 2009, 13:R195 (doi:10.1186/cc8195)
Conclusions
PLR-induced changes in SV-Flotrac are able
to predict the response to volume expansion
in spontaneously breathing patients without
vasoactive support.

71. The End…..