1. The Hemodynamic Puzzle
ScvO2
Heart Rate
Urine Output
Mental Status
The
missing
link
SVV
P(cv-a)CO2
SvO2
GEDV SV
NIRS
OPSI
O2ER
Lactate

2. Oxygen Debt: To Pay or Not to Pay?
Full Recovery Possible
Delayed Repayment of O2 Debt
Oxygen
Deficit
Oxygen Deficit
The principle task of acute care is to avoid or correct oxygen debt by optimization of the oxygen supply and consumption.
(Oxygen Consumption)
Energy Metabolism
(Ml/min/m2)
Oxygen Deficit
Time
Excessive O2 Deficit Produces Lethal Cell Injury with Non-recovery Recovery Possible

3. Providing the right amount of fluid is vital in a critically ill patient, as both too little and too much can result in poor outcomes
Under Resuscitation
Over Resuscitation
It is just as important to recognize that DO2 and tissue perfusion has normalized, therefore any further measures to increase DO2 may do harm by unnecessary over resuscitation

4. HR and BP as Resuscitation EndpointSV
Heart Rate
The
missing
link
SVV
SvO2
ScvO2
O2ER
Lactate
GEDV
NIRS
P(cv-a)CO2
OPSI
CVP
Urine Output
Mental Status

6. Correlation Between Arterial Pressure And Oxygen Delivery
100
300
500
700
900
1100
n= 1232 30 60 90
120
150
180
MAP mmHg
DO2 ml*m-2*min-1

7. Correlation Between Heart Rate And Oxygen Delivery
100
300
500
700
900
1100
n= 1236 30 60 90
120
150
180
HR b/min
DO2 ml*m-2*min-1

8. CVP as a Resuscitation EndpointSV
Heart Rate
The
missing
link
SVV
SvO2
ScvO2
O2ER
Lactate
GEDV
P(cv-a)CO2
NIRS
OPSI
CVP
Urine Output
Mental Status

9. Passive leg raising (PLR)
Volume of blood transferred (usually mL) to the heart during PLR is sufficient to increase the left cardiac preload and thus challenge the Frank-Starling curve. Maximal effect occurs at seconds and assess for a 10% increase in stroke volume (cardiac output monitor) or using a surrogate such as pulse pressure (using an arterial line)
approximately 200 mL of blood from the lower extremities toward the central circulatory compartment

10. Diagnostic Accuracy of Passive Leg Raising for Prediction of Fluid Responsiveness in Adults: Systematic Review and Meta-analysis of Clinical Studies.
Meta-analysis 9 studies
PLR changes in CO predicts fluid responsiveness
Regardless of ventilation mode and cardiac rhythm
Difference in CO of 18% distinguished responder from NR
AUC= 0.96
To systematically review the published evidence on the ability of passive leg raising-induced changes in cardiac output (PLR-cCO) and in arterial pulse pressure (PLR-cPP) to predict fluid responsiveness.
PLR changes in PP are less reliable
The pooled sensitivity and specificity of PLR-cCO were 89.4% ( %) and 91.4% ( %) respectively
Cavallaro, F. et al. Intensive Care Med. 2010 Sep;36(9):

11. CVP as a Resuscitation EndpointSV
Heart Rate
CVP
The
missing
link
SVV
SvO2
ScvO2
O2ER
Lactate
GEDV
NIRS
P(cv-a)CO2
OPSI
Urine Output
Mental Status

12. European survey:
More the 90% of intensivist or anesthesiologists used the CVP to guide fluid management.
Canadian survey:
90% of intensivists used the CVP to monitor fluid resuscitation in patients with septic shock.

13. Crit Care Med 2013; 41:1774–1781)

14. Does Central Venous Pressure Predict Fluid Responsiveness
Does Central Venous Pressure Predict Fluid Responsiveness?: A Systematic Review of the Literature and the Tale of Seven Mares
Paul E. Marik, MD, FCCP; Michael Baram, MD, FCCP; Bobbak Vahid, MD Chest. 2008;134(1):

15. Cardiac Filling Pressures are Not  Appropriate to Predict Hemodynamic Response to Volume Challenge
The study demonstrates that cardiac filling pressures are poor predictors of fluid responsiveness in septic patients. Therefore, their use as targets for volume resuscitation must be discouraged, at least after the early phase of sepsis has concluded
Osman D1, Ridel C, Ray P, Monnet X, Anguel N, Richard C, Teboul JL. Crit Care Med. 2007 Jan;35(1):64-8.

16. Does the Central Venous Pressure Predict Fluid Responsiveness
Does the Central Venous Pressure Predict Fluid Responsiveness? An Updated Meta-Analysis and a Plea for Some Common Sense
There are no data to support the widespread practice of using central venous pressure to guide fluid therapy. This approach to fluid resuscitation should be abandoned.
Marik PE, Cavallazzi R . Crit Care Med. 2013 Jul;41(7):

17. IVC Diameter and Collapsibility as End Point
The
missing
link
Heart Rate
CVP
SVV
SvO2
OPSI
P(cv-a)CO2
NIRS
ScvO2 SV
O2ER
Lactate
GEDV
Urine Output
Mental Status

18. Simultaneous measurements of the central venous pressure (CVP) and IVC diameter at the end of expiration in 108 mechanically ventilated patients
Wide variation and the absolute measurements are not applicable with positive pressure ventilation.
IVC size is an indicator of volume status and not volume responsiveness - these two are not the same.
Completely collapsed IVC means severe hypovolemia in the absence of raised intra-abdominal pressure.

19. Collapsibility Index = 𝑰𝑽𝑪𝒎𝒂𝒙 −𝑰𝑽𝑪𝒎𝒊𝒏 𝑰𝑽𝑪𝒎𝒂𝒙
>12% = responders
(PPV 93% and NPV92%).
Marked variation

20. <12% = non-responders
Collapsibility Index = 𝑰𝑽𝑪𝒎𝒂𝒙 −𝑰𝑽𝑪𝒎𝒊𝒏 𝑰𝑽𝑪𝒎𝒂𝒙
<12% = non-responders
(PPV 93% and NPV92%).
Insignificant variation

21. Ultrasonographic Measurement of the Respiratory Variation in the Inferior Vena Cava Diameter is Predictive of Fluid Responsiveness in Critically Ill Patients: Systematic Review and Meta-analysis
Total of 8 studies/235 Pts
ΔIVC measured is of great value in predicting fluid responsiveness, particularly in patients on controlled mechanical ventilation
Forest plot indicating the area under the receiver operating characteristic curve (AUROC) and 95% confidence interval (CI) for individual studies and the combined results.
Zhongheng Zhang, Xiao Xu, Sheng Ye, Lei Xu. Ultrasound in Medicine and Biology. Volume 40, Issue 5, Pages 845–853, May 2014

22. Schematic diagrams of different volumes that can be measured (dark shaded areas) with the transpulmonary thermodilution technique. ITTV, intrathoracic thermal volume; PTV, pulmonary thermal volume; GEDV, global end-diastolic volume; ITBV, intrathoracic blood volume; EVLW, extravascular lung water

23. CO/SV as a Resuscitation Endpoint
The
missing
link
Heart Rate
CVP
SV/CO
SVV
SvO2
ScvO2
O2ER
Lactate
NIRS
GEDV
P(cv-a)CO2
OPSI
Urine Output
Mental Status

24. Review of 21 randomized controlled trials with various approaches to treatment revealed statistically significant mortality reductions, with hemodynamic optimization, when patients with acute critical illness were treated early to achieve optimal goals before the development of organ failure, when there were control group mortalities of >20% and when therapy produced differences in oxygen delivery between the control and protocol groups

25. Effects of Cardiac Output and Stroke Volume Guided Hemorrhage and Fluid Resuscitation
21 animal subjects were bled until CI (n=9) or SVI (n=12) decreased by 50% then resuscitated during 60 minutes with LR till target is achieved
CI-group
SVI-group
Tbsl T0
tend
Tend
SVI (ml/m2)
33.6 ± 6.2
14.6 ± 10.1
23.4 ± 7.9
26.8 ± 4.7
13.4 ± 2.3
26.6 ± 4.1
CI (l/min/m2)
2.88 ± 0.42
1.79 ± 0.53
2.73 ± 0.35
2.6 ± 0.4
1.8 ± 0.3
2.9 ± 0.5
MAP (mmHg)
127 ± 13.07
75 ± 25
85 ± 22
112 ± 23
74 ± 18
91 ± 19
Heart rate (beats/min)
87 ± 16
140 ± 40
124 ± 37
95 ± 12
131 ± 27
107 ± 16
Central venous oxygen saturation (%)
81 ± 8
58 ± 18
64 ± 15
78 ± 7
61 ± 5
73 ± 9
Venous to arterial carbon dioxide gap (mm Hg)
3.3 ± 3.1
8.9 ± 3.3
7.8 ± 4.8
5.3 ± 2
9.6 ± 2.3
5.1 ± 2.6
GEDV (ml/m2)
317 ± 36
198 ± 57
249 ± 46
309 ± 57
231 ± 61
287 ± 49
Stroke volume variation (%)
10.8 ± 5.5
17.3 ± 5.1
16.4 ± 8.2
13.6 ± 4.3
22.6 ± 5.6
12.2 ± 4.3
Nemeth, M. et al. Acta Anaesthesiol Scand (2014). doi: /aas.12312

26. SVV & PPV as End Point CVP ScvO2 SvO2 SVV SV OPSI P(cv-a)CO2 O2ER GEDV
Heart Rate
CVP SV
SVV
ScvO2
OPSI
P(cv-a)CO2
O2ER
SvO2
The
missing
link
GEDV
NIRS
Urine Output
Mental Status

27. Hemodynamics During Positive Pressure Ventilation: SVV and PPV

28. Hemodynamics During Positive Pressure Ventilation: SVV and PPV
↑ RV Afterload
↓ RV Preload
Positive Pressure Ventilation
↑ LV Preload
Increased Blood Pressure in Inspiration

29. PVI to Help Clinicians Optimize Preload / Cardiac Output
Stroke Volume
Lower PVI = Less likely to respond
to fluid administration
10 %
24 %
Increasing preload can have a significant or minimal impact on SV depending on where the patient is at in the Starling curve
Higher PVI = More likely to respond to fluid administration
Preload
Frank-Starling Relationship
Maxime Cannesson, MD, PhD

30. Determine success of fluid by the response in stroke volume/index and SvO2
Fluid Non-Responders
Fluid Responders
End-Diastolic Volume

31. Dynamic parameters should be used preferentially to static parameters to predict fluid responsiveness in ICU patients

32. Limited to patients on controlled ventilation
Dynamic Changes in Arterial Waveform Derived Variables and Fluid Responsiveness in Mechanically Ventilated Patients: A Systematic Review of Literature
Dynamic changes of arterial waveform-derived variables during MV are highly accurate in predicting volume responsiveness in critically ill patients
Limited to patients on controlled ventilation
Sens. 0.89
Spec. 0.88
AUC= 0.94
Standardized receiver operating characteristic (SROC) curve with confidence and predictive ellipses for the 14 studies that allowed abstraction of the true/false positive/negative values for the ability of the pulse pressure variation to predict volume responsiveness. SENS, sensitivity; SPEC, specificity; AUC, area under the curve.
Marik, PE et al. (2009). Citi Care Med. 37:

33. Lactic Acid as Endpoint Resuscitation
The
missing
link
OPSI
Heart Rate
CVP SV
SVV
P(cv-a)CO2
NIRS
O2ER
ScvO2
SvO2
GEDV
Lactate
Urine Output
Mental Status

34. A nice theory… Critical DO2 DO2 dependent in septic patients
Oxygen consumption
VO2 mls/min
Critical DO2
DO2 dependent in
septic patients
Oxygen Debt
DO2 independent in
normal patients
Remember we said that in normal people and beagles..we run along at a certain oxygen consumption which is independent of our oxygen delivery because we have lots of spare oxygen. But at a point we begin to use less oxygen because we are not getting enough at this point here. But the critically ill patient has a higher baseline oxygen consumption, a bigger engine, runs out of petrol sooner and builds up lactate..at this point…so perhaps he needs more petrol delivery from the outset?..
It’s a good theory and perhps ok for the high risk surgical patient..but when Micheele Hays and then gattinoi applied the same supra normal goals to septic patients they found several things
Firstly more petrol delivery didn’t mean more survivors, it meant less.
Secondly too much petrol 20 mics Dobutamine killed patients
Thirdly driving Do2 did not bring down lactate.
Lactate
Oxygen delivery
DO2 mls/min
300mls/min

35. Prolonged lactate clearance is associated with increased mortality in the surgical intensive care unit
J. McNelis et al. The American Journal of Surgery 182 (2001) 481–485

36. Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial.
Jansen TC,van Bommel J, Schoonderbeek FJ,Sleeswijk Visser SJ, vander Klooster JM, Lima AP, et al. Am J Respir Crit Care Med (2010) 182:752–61.doi: /rccm OC

37. Effects of Cardiac Output and Stroke Volume Guided Hemorrhage and Fluid Resuscitation
CI-group
SVI-group
Tbsl T0
tend
Tend
Oxygen delivery (ml/min/m2)
335 ± 63
158 ± 62
284 ± 52
419 ± 62
272 ± 56
341 ± 62
VO2 (ml/min/m2)
44 ± 25
62 ± 38
76 ± 34
77 ± 26
96 ± 19
82 ± 27
Oxygen extraction (VO2/DO2)
0.13 ± 0.08
0.38 ± 0.19
0.32 ± 0.14
0.20 ± 0.07
0.36 ± 0.05
0.24 ± 0.09
Central venous oxygen saturation (%)
81 ± 8
58 ± 18
64 ± 15
78 ± 7
61 ± 5
73 ± 9
Venous to arterial carbon dioxide gap (mm Hg)
3.3 ± 3.1
8.9 ± 3.3
7.8 ± 4.8
5.3 ± 2
9.6 ± 2.3
5.1 ± 2.6
Lactate (mmol/L)
3.6 ± 1.1
5.0 ± 1.6
4.6 ± 2.0
1.62 ± 0.43
3.86 ± 1.49
3.54 ± 1.9
Hemoglobin (g/L)
9.0 ± 0.7
8.0 ± 2.7
6.9 ± 1.3
12.05 ± 1.37
11.22 ± 1.39
8.45 ± 1.1
Nemeth, M. et al. Acta Anaesthesiol Scand (2014). doi: /aas.12312

38. Oxygen Extraction-based Resuscitation
P(cv-a)CO2
OPSI
NIRS
The
missing
link
Oxygen Extraction-based Resuscitation
Heart Rate
CVP SV
SVV
SVV
SvO2
O2ER
GEDV
ScvO2
Urine Output
Mental Status

39. Oxygen Extraction-based Resuscitation
ScVO2
The main factors, which influence ScvO2, are hemoglobin, arterial oxygen saturation of hemoglobin, CO, and oxygen consumption.
Theoretically if three of these factors are kept constant, the value of ScvO2 reflects the changes of the latter.
There are multiple physiologic, pathologic, and therapeutic factors, which influence venous oxygen saturation, such as anemia, hypovolemia, contractility, bleeding, sedation, fever, and pain
CaO2= [Hb X 1.34 x SaO2] x PaO2
O2ER =𝟏𝟎𝟎 𝐗 VO2 DO2
DO2= CO x [CaO2]
VO2= CO x [CaO2-CvO2]

40. Effects of Cardiac Output and Stroke Volume Guided Hemorrhage and Fluid Resuscitation
CI-group
SVI-group
Tbsl T0
tend
Tend
Oxygen delivery (ml/min/m2)
335 ± 63
158 ± 62
284 ± 52
419 ± 62
272 ± 56
341 ± 62
VO2 (ml/min/m2)
44 ± 25
62 ± 38
76 ± 34
77 ± 26
96 ± 19
82 ± 27
Oxygen extraction (VO2/DO2)
0.13 ± 0.08
0.38 ± 0.19
0.32 ± 0.14
0.20 ± 0.07
0.36 ± 0.05
0.24 ± 0.09
Central venous oxygen saturation (%)
81 ± 8
58 ± 18
64 ± 15
78 ± 7
61 ± 5
73 ± 9
Venous to arterial carbon dioxide gap (mm Hg)
3.3 ± 3.1
8.9 ± 3.3
7.8 ± 4.8
5.3 ± 2
9.6 ± 2.3
5.1 ± 2.6
Lactate (mmol/L)
3.6 ± 1.1
5.0 ± 1.6
4.6 ± 2.0
1.62 ± 0.43
3.86 ± 1.49
3.54 ± 1.9
Hemoglobin (g/L)
9.0 ± 0.7
8.0 ± 2.7
6.9 ± 1.3
12.05 ± 1.37
11.22 ± 1.39
8.45 ± 1.1
Nemeth, M. et al. Acta Anaesthesiol Scand (2014). doi: /aas.12312

41. Mixed Venous Saturation in Critically Ill Patient
Oxygen Supply: DO2
Oxygen Demand: VO2
SvO2/ScvO2
Low
↓DO2
↑VO2
Anemia
Bleeding
Hypovolemia
Hypoxia
Heart faliure
Pain
Agitation
Shivering
Seizure
Fever
High
↑DO2
↓VO2 Hg
Oxygen
Fluids
Inotropics
Sedation
Analgesia
Hypothermia
Sepsis

42. Correlation of Oxygen - Supply to - Demand Ratio with Mixed Venous Oxygen Saturation25 70 55 40 85
100
1.0
2.8
4.6
6.4
8.2
10.0
r= 0.906
y= *x
n= 1149
DO2/ VO2
SvO2 %

43. Lee J et al. (1972) Anaesthesiology 36: 472
ScvO2 vs SvO2
100 80 60 40 20
r= 0.73
r= 0.88
Shock
Normal
% SsvO2
% SvO2
Lee J et al. (1972) Anaesthesiology 36: 472

44. ScvO2 % Sat SvO2 % Sat r= 0.9761 p< 0.001 n= 131 80 60 40 20 -20
-20
-40
-60
-80 r=
p< 0.001
n= 131
ScvO2 % Sat
SvO2 % Sat
Reinhart K et al, Chest, 1989; 95:

45. SvO2 closely correlates with ScvO280 60 40 20 30 90
120
150
180
210
240
Normoxia
Bleeding
Volume Therapy (HAES)
Hypoxia
Hyperoxia
Mixed venous
Central venous
% Sat
Time (min)
Reinhart K et al, Chest, 1989; 95:

46. Multi-Center Study of Central Venous Oxygen Saturation (ScvO2) as a Predictor of Mortality in Patients with Sepsis
ScvO2 of < 70%,
ScvO2 of > 90%,
Pope, J et al. Ann Emerg Med. 55:40-46

47. Oxygen Parameters as Endpoint
OPSI
NIRS
The
missing
link
Oxygen Parameters as Endpoint
Heart Rate
CVP SV
SVV
SVV
SvO2
O2ER
GEDV
ScvO2
P(cv-a)CO2
Urine Output
Mental Status

48. P(cv-a)CO2
∆PCO2= K X 𝑽𝑪𝑶𝟐 𝑪𝒂𝒓𝒅𝒊𝒂𝒄 𝑶𝒖𝒕𝒑𝒖𝒕
Normal is 2-5 mmHg. Is not a marker of tissue hypoxia but it is a marker of the adequacy of cardiac output
Under physiological conditions, DeltaPCO2 ranges from 2 to 5 mmHg. The DeltaPCO2 depends on carbon dioxide and cardiac output by a complex fashion. In this article, we detail the influence of these factors on DeltaPCO2 in normoxic conditions and in hypoxic conditions. We bring evidence that DeltaPCO2 cannot serve as a marker of tissue hypoxia contrary to what was initially thought. However, DeltaPCO2 can be considered as a marker of the adequacy of venous blood flow (i.e. cardiac output) to remove the total CO2 produced by the peripheral tissues. In this regard, the knowledge of DeltaPCO2 should help the clinicians for the decision of giving therapy aimed at increasing cardiac output.
B. Lamia et al. Minerva Anestesiol Jun; 72(6):

49. Persistently high venous-to-arterial carbon dioxide differences during early resuscitation are associated with poor outcomes in septic shock
The persistence of high Pv-aCO2 during the early resuscitation of septic shock was associated with more severe multi-organ dysfunction and worse outcomes at day-28
Survival probabilities at day 28 by the development of mixed venous-to-arterial carbon dioxide difference during the first 6 hours of resuscitation. Log-rank, Mantel–Cox: 19.21, P < H-H, mixed venous-to-arterial carbon dioxide difference (Pv-aCO2) high at Time 0 (T0) and 6 hours later (T6); L-H, Pv-aCO2 normal at T0 and high at T6; H-L, Pv-aCO2 high at T0 and normal at T6; and L-L, Pv-aCO2 normal at T0 and T6
H-H, mixed venous-to-arterial carbon dioxide difference (Pv- aCO2) high at Time 0 (T0) and 6 hours later (T6); L-H, Pv- aCO2 normal at T0 and high at T6; H-L, Pv-aCO2 high at T0 and normal at T6; and L-L, Pv-aCO2 normal at T0 and T6
Ospina-Tascón GA et al., Crit Care. 2013; 17(6)

50. Central Venous-to-Arterial  Gap Is a Useful Parameter in Monitoring Hypovolemia-Caused Altered Oxygen Balance: Animal Study
ScvO2 < 73% and CO2 gap >6 mmHg can be complementary tools in detecting hypovolemia-caused imbalance of oxygen extraction.
Kocsi S et al, Crit Care Res Pract. 2013;

51. The Hemodynamic Puzzle
missing
link
The Hemodynamic Puzzle
Heart Rate
CVP SV
SVV
SVV
SvO2
O2ER
GEDV
ScvO2
P(cv-a)CO2
OPSI
NIRS
Urine Output
Mental Status

52. Near-infrared spectroscopy (NIRS)

53. NIRS
StO2 (at 20 mm, skeletal muscle) is an index of profusion that tracks DO2 during active resuscitation
Shock resuscitation variables during shock resuscitation (first 24 hours) and the following 12 hours
StO at 20 mm tracked DO2
Lactate & Base Deficit tracked also but
SvO2 from PA cath & StO2 at 6 mm (subcutaneous) did not change significantly
Crit Care. 2009; 13(Suppl 5): S10.

54. NIRS
(NIRS) has recently been applied in a novel technology designed to measure skeletal muscle tissue perfusion in critically ill patients.
Peripheral circulation will be the first region to manifest tissue hypoperfusion and the last to show signs of reperfusion following resuscitation
Initial observational findings recommend cutoff StO2 value of less than 70% to 75% to represent a cause for concern.
More research is required to evaluate the clinical utility and its possible use in predicting complications and early identification of patients at risk for complications.
Shock resuscitation variables during shock resuscitation (first 24 hours) and the following 12 hours
StO at 20 mm tracked DO2
Lactate & Base Deficit tracked also but
SvO2 fro PA cath & StO2 at 6 mm (subcutaneous) did not change significantly

55. Orthogonal Polarization Spectral Imaging (OPS): Sublingual capillaroscopy.
Orthogonal polarization spectral (OPS) imaging is an optical imaging technique that uses a handheld microscope and green polarized light to visualize the red blood cells in the microcirculation of organ surfaces

56. Orthogonal Polarization Spectral Imaging (OPS): Sublingual capillaroscopy.
Red blood cells are visualised as black-grey points flowing along the vessels. Up-right and up-left: normal findings; bottom-left: septic shock; bottom-right: after cardiac arrest under therapeutic hypothermia

57. Hemodynamic monitoring - Pearls
Lactate can be slowly changing  over-resuscitation
Noncardiac conditions may increase BNP  unreliable in ICU.
A positive PLR predicts preload responsiveness (sensitivity of 97% and specificity of 94%.)
PAC remains useful when used for the appropriate indication
CVP could not predict fluid responsiveness across numerous studies.
Dynamic variables more accurate at predicting volume responsiveness
Many minimally invasive monitors are potential alternatives to invasive catheterization. Limitations should be understood.

58. Hemodynamic monitoring - Pearls
Measuring IVC diameter and ΔIVC can estimate RA pressure. Less reliable in spontaneous breathing.
Several hemodynamic parameters can be evaluated using the different modalities of echocardiography
Esophageal Doppler monitor is a minimally invasive, safe, and easy means to continuous monitoring
Pcv-aCO2 increase the specificity of ScvO2 to low perfusion when this is falsely elevated due to microcirculation and/or mitochondrial defect.
New technologies of NIRS, OPS may develop to have a place in the clinical use
A need for investigating the efficacy and outcome improvement using a combination of two modalities

60. The Hemodynamic Puzzle
Heart Rate
CVP SV
SVV
SvO2
O2ER
GEDV
The
missing
link
ScvO2
P(cv-a)CO2
OPSI
NIRS
Lactate
Urine Output
Mental Status