IFAD 2013

1. High Fluid Need During Cardiac Surgery:
Can We Do Without HES?
Philippe Van der Linden MD, PhD
CHU Brugmann-HUDERF, Free University of Brussels

2. Fees for lectures, advisory
board and consultancy:
Fresenius Kabi GmbH
B Braun Medical SA

3. High Fluid Need During Cardiac Surgery:
Can We Do Without HES?

4. Effects of Hydroxyethyl Starch on Bleeding
After Cardiopulmonary Bypass
From Navickis R et al. J Thorac Cardiovasc Surg 144:223-230e5, 2012.
 Meta-analysis including 18 trials (N=970)
 Compared to albumin, HES:
•  postop blood loss by 33% (18.2-48.3%)
•  risk of reoperation RR:2.24 (1.14-4.40)
•  risk of RBC transfusion by 28.4% (12.2-44.6%)
•  risk of FFP transfusion by 30.6% (8.0-53.1%)
•  risk of platelet transfusion by 29.8% (3.4-56.2%)
No difference between HES 450/0.7 and HES 200/0.5…
but mix of 6% and 10% solutions
Insufficient data available for HES 130/0.4 versus albumin

5. HES Solutions For Cardiovascular Surgery:
A Systematic Review of Randomized Trials
From Shi XY et al. Eur J Clin Pharmacol 67:767-82, 2011.
Quantitative and qualitative analysis of all pertinent
randomized controlled trials (up to December 2010)
52 randomized trials; 3234 patients (23 trials with HES130/0.4)
Blood loss N Std mean diff
(95% CI)
HES 130/0.4 vs
albumin
7 -0.61 (-0.82, -0.40)
HES 130/0.4 vs
gelatin
10 -0.02 (-0.16, 0.12)
HES 130/0.4 vs
crystalloids
3 -0.19 (-0.45, 0.08)
Transfusion N RR
(95% CI)
p
HES 130/0.4 vs
albumin
4 0.77 (0.62, 0.94) 0.01
HES 130/0.4 vs
gelatin
4 1.03 (0.86, 1.24) 0.74
HES 130/0.4 vs
crystalloids
1 0.67 (0.13, 3.44) 0.63
Boldt’ studies not retrieved !

6. Perioperative Fluid Therapy in Cardiac Surgery
From Bayer O et al. Crit Care Med 41:2532-42, 2013.
 Observational cohort study: fluid therapy in the operating
room and on the ICU directed at preset hemodynamic goals
• HES (predominantly 130/0.4) in 2004-2006 (N=2137)
• 4% Gelatin in 2006-2008 (N=2324)
• Only crystalloids in 2008-2010 (N=2017)
 Clinical outcomes
• RRT more common with HES and gelatins than crystalloids
• Hospital mortality: HES = crystalloids, but higher with gelatin
• ICU length of stay longer for HES than for gelatin and crystalloids

7. Perioperative Fluid Therapy in Cardiac Surgery
From Bayer O et al. Crit Care Med 41:2532-42, 2013.
 Observational cohort study: fluid therapy in the operating
room and on the ICU directed at preset hemodynamic goals
• HES (predominantly 130/0.4) in 2004-2006 (N=2137)
• 4% Gelatin in 2006-2008 (N=2324)
• Only crystalloids in 2008-2010 (N=2017)
 Clinical outcomes
• RRT more common with HES and gelatin than crystalloids… in
patients who already had an intermediate or high risk for RRT
• Mean SOFA score higher with crystalloids than with HES or gelatin
• Duration of mechanical ventilation shorter with HES

8. Perioperative Fluid Therapy in Cardiac Surgery
From Bayer O et al. Crit
Care Med 41:2532-42,
2013.
 Observational cohort study: fluid therapy in the operating
room and on the ICU directed at preset hemodynamic goals
• HES (predominantly 130/0.4) in 2004-2006 (N=2137)
• 4% Gelatin in 2006-2008 (N=2324)
• Only crystalloids in 2008-2010 (N=2017)
D
ay
0
D
ay
1
D
ay
2
D
ay
3
Total
0
100
200
300
400
Fluid volume (ml/kg)
HES 130/0.4
Gelatin
Crystalloids
* p<0.01 vs colloids
*
*
*
“Colloid” period “Crystalloid” period
6% HES 130/0.4 500 ml 1000 ml
Ringer’s lactate 750 ml 250 ml
15% mannitol 250 ml 250 ml

9. Perioperative Fluid Management
in Cardiac Surgery
Tissue
Fluid
accumulation
Tissue
O2 delivery
optimization

10. Fluid Overload Predicts Mortality
after Cardiac Surgery
From Stein A et al. Crit Care 16:R99, 2012.
 Prospective cohort study
(N=502)
 Fluid overload and
creatinine levels recorded
daily in ICU
Black circle: non survival with Δcreat < 0.6 mg/dl
White circle: survival with with Δcreat < 0.6 mg/dl
Black square: non survival with Δcreat ≥ 0.6 mg/dl
White square: survival with with Δcreat ≥ 0.6 mg/dl
Black circle: non survival with Δcreat < 0.6 mg/dl
White circle: survival with with Δcreat < 0.6 mg/dl
Black square: non survival with Δcreat ≥ 0.6 mg/dl
White square: survival with with Δcreat ≥ 0.6 mg/dl
17 patients died during their ICU stay17 patients died during their ICU stay

11. Optimization of Circulatory Status After
Cardiac Surgery
From McKendry M et al. BMJ 329:258-62, 2004.
 Randomized controlled trial
• Conventional hemodynamic management (N=85)
• Protocol (N=89): stroke index > 35 ml/m2
(esophageal doppler)
 Primary outcome: hospital length of stay

12. Perioperative Fluid Management
in Cardiac Surgery
Pre-bypass
On-bypass
Post-bypass

13. Physiopathology of Cardiopulmonary Bypass
Interstitial fluid accumulation
Complement
activation
Capillar
permeability
HYPOVOLEMIA
Catecholamine
release
Hypothermia
Vasoconstriction Venous
capacitance
Hemodilution Plasma COP
Interstitial COPTranslocation
of interstitial
albumin

14. Interstitial Volume (ISFV) During Cardiac Surgery
Olthof CG et al. Acta Anaesthesiol Scand 39:508-12, 1995.
Start CPB
10 min CPB
End CPB
End Operation
0
20
40
60
80
100
120
Changes compared to pre-op values (%)
COP (%) ISFV (%)
ISFV: measured by a non-invasive conductivity technique * p<0.05 vs pre-op
*
*
*
*
*
*
Start CPB
10 min CPB
End CPB
End Operation
0
1,000
2,000
3,000
4,000
5,000
Changes compared to pre-op values
Fluid balance (ml)
*
*
*
*

15. Fluid Management in Pediatric Cardiac Surgery:
On-bypass
Albumin in the prime: precoats the CPB circuit surface
To delay the absorption of circulating fibrinogen
To reduce surface activation and adhesion of platelets

16. Albumin vs Crystalloids for Pump Priming
in Cardiac Surgery
Meta-analysis of controlled trials (adult & pediatric patients):
 21 studies, 1346 patients
Albumin prime reduces:
The on-bypass drop in platelet count
pooled WMD: -23,8 10 /L [-42,8 to -4,7 10 /L]
The colloid oncotic pressure decline
pooled WMD: -3,6 mmHg [-4,8 to -2,3 mmHg]
The on-bypass positive fluid balance
pooled WMD: -584 ml [-819 to -348 ml]
The postoperative weight gain
pooled WMD: -1,0 kg [-0,6 to -1,3 kg]
9 9
From Russel JA et al. J Cardiothorac Vasc Anesth 18:429-437, 2004.

17. Colloids Vs. Crystalloids as Priming Solutions
for Cardiopulmonary Bypass
From Himpe D. Acta Anaesthesiol Belg 54:20-15, 2003.
 Meta-analysis of prospective randomized trials: N=17 (997
patients). Wide variations in priming fluid regimens
 Colloids in the prime resulted in higher COP and lower
positive fluid balance. No difference between albumin-
based priming and synthetic-based priming
 No difference in postoperative bleeding between crystalloids
and colloids-based priming. No difference between albumin-
based priming and synthetic-based priming.

18. Albumin Vs. Gelatins as Priming Solutions for
Cardiopulmonary Bypass
From Himpe D et al. J
Cardiothorac Vasc Anesth
5:457-66, 1991
 Prospective randomized trial: elective CABG patients
 Randomization according to the priming volume (2200 ml)
• 3% albumin (N=35)
• 3.5% urea-linked gelatin (N=35)
• 3% balanced modified fluid gelatin (N=35)
B
efore
C
PB
O
N
C
PBC
PB
+
60
m
in
End
C
PBEnd
surgery
10
15
20
25
30
Colloid osmotic pressure (mmHg)
3% albumin
3.5% urea gelatin
3% MF gelatin
* p<0.05 vs gelatins
* *
*

19. Factors Influencing Fluid Distribution after CPB
Preoperative
Patient's characteristics (age, clinical status, blood volume...)
Intraoperative
Physiologic factors (capillary permeability, hydrostatic pressures...)
Mechanical factors (bypass circuit, T°, MAP, flow...)
Fluids (pre- post-CPB, priming, cardioplegia)
Clinical factors (surgery, CPB & Ao clamping times)
Postoperative
Fluids
Ventilatory modes
Vasoactive agents

20. Plasma Volume Expansion After Cardiac Surgery
Hemodynamic stability occurred faster after colloids (dextran
70), but ventilatory weaning somewhat easier with crystalloids
Karanko MS et al. Crit Care Med 15:559-566, 1987.
Volume effect of colloid solutions after CABG surgery patients
are comparable to those obtained in other elective surgical
patients
Immediate volume effect: dextran 70>gelatin>4% PPF (albumin)
Duration of volume effect: dextran 70> 4% PPF>gelatin
Karanko MS. Crit Care Med 15:1015-1022, 1987.

21. Fluid Loading in Cardiovascular
Hypovolemic Patients
From Verheij J et al. Intensive Care Med 32:1030-8, 2006.
Prospective randomized trial: treatment of hypovolemic
hypotension after cardiac and major vascular surgery (N=63)
Fluids administered < strict fluid challenge protocol

22. Cardiac Response to Fluid Loading After
Cardiac or Vascular Surgery
• Single-blinded RCT (N=67)
• 90 min filling pressure-guided
challenge
- 0.9% saline
- Colloids: 4%GEL, 6% HES, or 5% alb
• More saline than colloids infused
• Saline: ↓ COP; colloids: ↑ COP
• Colloids equally effective
0
5
10
15
20
25
Plasma
volume
Cardiac index
0,9% saline Colloids
%
p<0.001
p<0.005
From Verheij J et al. Intensive Care Med 32: 1030-8, 2006.

23.  Prospective randomized single-blind study
 Elective surgery – crystalloid-based pump prime; no TXA
Fluid administration immediately after ICU admission:
• 6% HES 130/ 0.4 (N=15)
• 4% Modified fluid gelatin (N=15)
• Ringer’s acetate (N=15)
Hemodynamic monitoring: PAC, thermodilution cardiac output
 Hemodynamics & blood transfusion guided by strict protocols
3 bolus of 7 mL/kg
+ 7 mL/kg over 12h
From Schramko A et al. Perfusion 25:283-91, 2010; Br J Anaesth 104:691-7, 2010.
Effects of 6% HES 130/0.4 & 4% Gelatin
On Hemodynamics After Cardiac Surgery

24.  Prospective randomized single-blind study
 Intermittent thermodilution cardiac output measurements
No difference in HR, MAP and CVP between the groups
Stroke volume Index (mL/beat.m²)
Pre-infusion
7
m
l/kg
14
m
l/kg
21
m
l/kg
28
m
l/kg
0
20
40
60
80
* * *#
Cardiac Index (L/min.m²)
Pre-infusion
7
m
l/kg
14
m
l/kg
21
m
l/kg
28
m
l/kg
0
1
2
3
4
5
HES (N=15)
Gelatin (N=14)
Ringer's acetate (N=13)
*p <0.05 Vs. Colloids
# p<0.05 Vs. HES
#
* * *
Effects of 6% HES 130/0.4 & 4% Gelatin
On Hemodynamics After Cardiac Surgery
From Schramko A et al. Perfusion 25:283-91, 2010; Br J Anaesth 104:691-7, 2010.

25. 1st objective: to compare the effects on total blood
losses of two synthetic colloids:
3% modified fluid gelatin (N=64) or
6% HES 130/0.4 (N=68)
in patients undergoing coronary artery surgery (up to 20 h postop)
Max dose 50 ml/kg
PAOP: 8-15 mmHg; CI > 2.5L/min.m²; diuresis > 0.5 ml/kg.h
Gelatin vs HES 130/0.4 in Cardiac Surgery
From Van der Linden P et al. Anesth Analg 101: 629-34, 2005.
Propspective randomized single-blind study
2nd objective: efficacy in maintaining hemodynamics

26. From Van der Linden P et al. Anesth Analg 101: 629-34, 2005.
Gelatin vs HES 130/0.4 in Cardiac Surgery

27. perop postop total
0
10
20
30
40
50
60
Synthetic colloids (ml/kg)
perop postop total
0
10
20
30
40
50
60
70
Crystalloids (ml/kg)
GEL - HES
Gelatin vs HES 130/0.4 in Cardiac Surgery
From Van der Linden P et al. Anesth Analg 101: 629-34, 2005.

28. From Van der Linden P et al. Anesth Analg 101: 629-34, 2005.
Gelatin vs HES 130/0.4 in Cardiac Surgery
Gel group: 21/64 were transfused (0 [0-6] units)
HES 130/0.4: 24/68 were transfused (0 [0-6] units)

29. From Van der Linden P et al. Anesth Analg 101: 629-34, 2005.
Gelatin vs HES 130/0.4 in Cardiac Surgery

30. Gelatin vs HES 130/0.4 in Cardiac Surgery
From Van der Linden P et al.
Anesth Analg 101: 629-34, 2005.
Total
0
200
400
600
800
US$
p<0.05
C
rystalloids
C
olloids
PR
B
C
FFP
Plts
0
100
200
300
400
US$
3% MF gelatin (N=64)
6% HES 130/0.4 (N=68)
p<0.01

31. Conclusions
Primary goal of fluid volume therapy:
To correct absolute or relative volume deficit in order
to optimize tissue oxygen delivery
The optimal amount at the right moment with
a combination of crystalloids AND colloids
Choice between the different solutions
Physiological compartment that needs to be restored
(intravascular, interstitial, intracellular)
Characteristics of the solutions
• Pharmacokinetic and pharmacodynamic properties
• Side effects
• Costs

32. Thank you very much for your attention

33. HES 130/0.4 Vs. Ringer Solution For
Cardiopulmonary Bypass Prime
From Tiryakioglu O et al. J Cardiothorac Surg 3:45, 2008.
Prospective randomized controlled trial (N=140)
Prime volume
-1500 ml Ringer solution (Ringer group: N=70)
- 1500 ml HES 130/0.4 (HES group: N=70)
mL
Fluid
added
to
C
PB
Fluid
balance
end
C
PB
Postop
blood
drainage
0
500
1000
1500
2000
Ringer
HES
p=0.0001 p=0.0001
No difference in creatinine
clearance at 72 hours
 No difference in ICU and
hospital length of stay

34. Perioperative colloids to
maximize stroke volume
(guided by oesophageal doppler)
6% HES 200/0.62:
Control (N= 30): 0-1800 mL
Protocol (N= 30): 800-2400 mL
Gut mucosal hypoperfusion:
56% vs 7% (p<0.001)
Perioperative Volume Expansion
During Cardiac Surgery
Morbidity (N)
ICU LOS (d)
Hospital LOS (d)
0
2
4
6
8
10
12
**
**
*
* p<0.05 ** p<0.01 vs controlFrom Mythen MG et al. Arch Surg 130:423-9, 1995.
range:
1-11
1-1
range:
5-48
5-9