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

Philippe Van der Linden MD, PhDCHU Brugmann-HUDERF, Free University of Brussels

Fees for lectures, advisory board and consultancy: Fresenius Kabi GmbHB Braun Medical SA

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

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

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 !

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

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

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)

* 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

Perioperative Fluid Management in Cardiac Surgery

TissueFluid

accumulation

TissueO2 deliveryoptimization

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/dlWhite circle: survival with with Δcreat < 0.6 mg/dlBlack square: non survival with Δcreat ≥ 0.6 mg/dlWhite square: survival with with Δcreat ≥ 0.6 mg/dl

17 patients died during their ICU stay

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

Perioperative Fluid Management in Cardiac Surgery

Pre-bypass

On-bypass

Post-bypass

Physiopathology of Cardiopulmonary Bypass

Interstitial fluid accumulation

Complementactivation

Capillarpermeability

HYPOVOLEMIA

Catecholaminerelease

HypothermiaVasoconstriction Venous

capacitance

Hemodilution Plasma COP

Interstitial COPTranslocationof interstitial

albumin

Interstitial Volume (ISFV) During Cardiac SurgeryOlthof CG et al. Acta Anaesthesiol Scand 39:508-12, 1995.

Start CPB10 min CPB

End CPBEnd 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 CPB10 min CPB

End CPBEnd Operation

0

1,000

2,000

3,000

4,000

5,000

Changes compared to pre-op values

Fluid balance (ml)

*

*

**

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

Albumin vs Crystalloids for Pump Primingin Cardiac Surgery

Meta-analysis of controlled trials (adult & pediatric patients): 21 studies, 1346 patients

Albumin prime reduces:The on-bypass drop in platelet countpooled WMD: -23,8 10 /L [-42,8 to -4,7 10 /L]

The colloid oncotic pressure declinepooled WMD: -3,6 mmHg [-4,8 to -2,3 mmHg]

The on-bypass positive fluid balancepooled WMD: -584 ml [-819 to -348 ml]

The postoperative weight gainpooled 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.

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.

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)

* p<0.05 vs gelatins

* **

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

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.

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

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

Plasmavolume

Cardiac index

0,9% saline Colloids

%

p<0.001p<0.005

From Verheij J et al. Intensive Care Med 32: 1030-8, 2006.

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

Prospective randomized single-blind study Intermittent thermodilution cardiac output measurementsNo difference in HR, MAP and CVP between the groups

Stroke volume Index (mL/beat.m²)

Pre-in

fusi

on

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-in

fusi

on

7 m

l/kg

14 m

l/kg

21 m

l/kg

28 m

l/kg

0

1

2

3

4

5HES (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.

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

From Van der Linden P et al. Anesth Analg 101: 629-34, 2005.

Gelatin vs HES 130/0.4 in Cardiac Surgery

perop postop total0

10

20

30

40

50

60

Synthetic colloids (ml/kg)

perop postop total0

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.

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)

From Van der Linden P et al. Anesth Analg 101: 629-34, 2005.

Gelatin vs HES 130/0.4 in Cardiac Surgery

Gelatin vs HES 130/0.4 in Cardiac Surgery

From Van der Linden P et al. Anesth Analg 101: 629-34, 2005.

p<0.05

p<0.01

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 witha combination of crystalloids AND colloids

Choice between the different solutionsPhysiological compartment that needs to be restored

(intravascular, interstitial, intracellular)

Characteristics of the solutions• Pharmacokinetic and pharmacodynamic properties• Side effects• Costs

Thank you very much for your attention

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

bal

ance

end C

PB

Postop b

lood d

rain

age

0

500

1000

1500

2000RingerHES

p=0.0001 p=0.0001

No difference in creatinine clearance at 72 hours

No difference in ICU and hospital length of stay

Perioperative colloids to maximize stroke volume (guided by oesophageal doppler)

6% HES 200/0.62:

Control (N= 30): 0-1800 mLProtocol (N= 30): 800-2400 mL

Gut mucosal hypoperfusion:56% vs 7% (p<0.001)

Perioperative Volume ExpansionDuring 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:1-111-1

range:5-485-9