HES

Improving Perioperative Patient
Managment and Outcome
April 9, 2015 – Triemli City Hospital
IV Fluids: Is there still a place for colloids ?
Michael Ganter, MD
Institute of Anesthesiology and Pain Medicine
Kantonsspital Winterthur, Switzerland
Outline
 Rational for discussion, ideal IV colloid
 Body compartments
 Water; Fluid distribution; Crystalloid:Colloid ratio
 Types of IV colloids
 Albumin; Starches, Gelatins, Dextrans
 Adverse effects
 Studies out there
 Landmark studies; Most recent network meta-analysis
 Summary and what happend at my institution
2
Ideal IV colloid
 Optimize circulating blood volume w/o edema formation
 remain strict intravascular
 maintain intravascular colloid-osmotic pressure permanently
 Maintain electrolyte homeostasis
 if solved in physiological electrolyte solution (balanced)
 Minimal side effects, no harm
 no organ dysfunction (e.g. renal), acquired coagulopathy,
infection, retention (e.g. pruritus), and allergies
 Cost effective
 added costs justified by improved patient outcome
3
Harm of fluid excess
Stratified meta-anaylsis on perioperative fluid therapy – 12 RCT liberal vs restrictive; 1,160 patients
Pneumonia
Pulmonary
edema
First bowel
movement (days)
First flatus (days)
Length of stay
(days)
Mortality
4
Corcoran
T, et al. Anesth Analg 2012; 114:640-51)
Harm of fluid excess
Crystalloids and Outcome in blunt trauma patients, adjusted odds ratios
5
Kaotakis
G, et al. J Trauma Acute Care Surg 2013;74: 1215-22
Water, Distribution, Cristalloid:Colloid ratio
BODY COMPARTMENTS
6
Body water, compartments
Ganter MT, Hofer CK, Pittet JF; Postoperative intravascular fluid therapy
in Miller’s Anesthesia. 7th Edition. Churchill Livingstone 2009
7
75 kg man  TBW 60% = 45L
¼
¾
Plasma
Colloids
Cristalloids,
Cristalloids,
Cristalloids
interstitial
intravasal
Free Water, Free Water, Free Water, Free Water, Free Water, Free Water, Free Water, Free Water, Free Water, Free Water, Free Water, Free Water
ECR 15L
8
ICR 30L
Crystalloid : Colloid ratio
 Amount of fluid (crystalloids, colloids) required to achieve similar
hemodynamic end points
 calculation of crystalloid:colloid ratio
 Systematic search up to December 2013, to retrieve all studies
comparing (any) crystalloid with (any) colloid in all types of
patients
 From 976 studies, 48 were retained for the final analysis; 24 of
the studies had sufficient data for meta-analysis
9
Orbegozo
Cortés D, et al. Anesth Analg 2015; 120:389-402
Crystalloid : Colloid ratio
Ratio 1.55
Ratio 1.50
Ratio 1.36
10
Orbegozo
Cortés D, et al. Anesth Analg 2015; 120:389-402
Crystalloid : Colloid ratio
11
Orbegozo
Cortés D, et al. Anesth Analg 2015; 120:389-402
Albumin; Starches, Gelatins, Dextrans
TYPES OF IV COLLOIDS
12
IV Colloids
Concentration
(g/L)
MW / MS
(kDa)
Net volume
effect
Volume effect
(h)
(4)-5 / 20
66
0.7 / 2-3
3-4
6
70 / 0.5
0.7
3-4
6
130 / 0.4
1.0
4
6 / 10
200 / 0.5
1.3
4-6
6
450 / 0.7
1.0
6-8
Gelatins
3.5
30-35
0.8
2-3
Dextrans
10
6
40
60-75
2.0
1.2
2-4
6-8
Artificial Colloids
Human Albumin
13
Hydroxyethyl
Starch (HES)
6
4 5
1
3
2
6
4 5
1
3
2
HYDROXYETHYLSTARCH
14
HES solutions
 Concentration  initial volume effect (6% = iso-oncotic)
 Origin (waxy maize, potato starch)
 Solvent  carrier solution
 Molecular weight (MW)  polydispersity; if <45-60 kDa rapidly excreted
 Molar Substitution (MS)  physicochemical properties, metabolism, excretion
 C2/C6 ratio high  amylase breakdown slower
15
Westphal
M, et al. Anesthesiology 2009; 111:187-202
GELATINS
16
Adverse effects of IV Colloids
Origin;
Anaphylaxis
Coags
Human
plasma;
+(+)
-
-
- (+?)
$$$$$$$$$$
$$$$$$$$$$
(~10 fold)
Starch from
maize or
potato;
+
↓↓ - ↓↓↓
+
++ (+++)
$$
Gelatins
Bovine
collagen;
++
↓
-
+ (++?)
$$
Dextrans
Sugar,
bacteria;
+++
↓↓↓ - ↓↓↓↓
-
+ (++)
$$
Human
Albumin
Hydroxyethyl
Starch
(HES)
17
Retention End organ
(RES,
dysfunction
Pruritus)
(kidney)
Price
18
http://www.ema.europa.eu
Landmark studies; Most recent network meta-analysis
STUDIES OUT THERE
19
Landmark RCT’s
Study
Population
Fluids
Outcomes
Critiques
VISEP
N = 537, blinded
Sepsis
HES 10% 200/0.5
vs R-lac
‘old’ HES
Excessive doses
N = 196, blinded
Sepsis
HES 6% 130/0.4
vs NS
Mortality (dosedependent) ⬆
ARF ⬆, RRT ⬆
Transf. (bleeding) ⬆
N = 798, blinded
Sepsis
HES 6% 130/0.42
vs R-Ac
N = 7,000, blinded
Mixed ICU pts
(Sepsis 29%)
HES 6% 130/0.4
vs NS
N = 2,857
Mixed ICU pts in
hypovolemic shock
(Sepsis 54%)
Any Colloid
(G,H,D,A)
vs any Crystalloid
(NS,HS,R-lac)
Brunkhorst FM et al
NEJM 2008; 358
CRYSTMAS
Guidet B et al
Crit Care 2012; 16
6S
Perner A et al
NEJM 2012; 367
CHEST
Myburgh JA et al
NEJM 2012; 367
CRISTAL
Annane D et al
JAMA 2013; 310
20
Hemodynamic
stabilization ⬆
(-2.5h, ns; -0.3L, s)
other Outcomes =
NS as reference
crystalloid
(hyperchloremia)
Mortality 90d =
RIFLE-R/I ⬇, RRT ⬆
Pruritus, rash ⬆
NS as reference
crystalloid
(hyperchloremia)
Mortality 90d ⬆
ARF ⬆, RRT ⬆
Transf. (bleeding) ⬆
Inclusion after
hemodynamic
stabilization
Mortality 28d =
Mortality 90d ⬇
RRT =
net Fluid balance ⬇
9 year period
(2003-2012)
Unblinded
Any fluids
Gelatin – an alternative to HES ?
Sequential analysis of different fluid regimens (HES, Gelatin,
Crystalloids only) in cardiac surgical patients
Outcomes:
Renal failure / RRT (1°),
hemodynamic normalization, fluid intake and balance, mortality (2°)
HES
Period
GEL
Period
• 2004-2006, n=2,137
• 6% HES (130/0.4; Voluven®)
• 2006-2008, n=2,324
• 4% Gelatin (succinylated; Gelafusal®)
CRYST • 2008-2010, n=2,017
Period
• Balanced crystalloid (R-Ac, Jonosteril®)
21
Bayer
O, et al. Crit Care Med 2013; 41:2532-42
Gelatin – an alternative to HES ?
Total fluid balance
Crystalloid:HES ratio = 1.4
Crystalloid:Gelatin ratio = 1.1
22
Bayer
O, et al. Crit Care Med 2013; 41:2532-42
Gelatin – an alternative to HES ?
Fluids and blood products, RRT and hospital mortality
23
Bayer
O, et al. Crit Care Med 2013; 41:2532-42
Network meta-analysis in sepsis
Effect of resuscitation fluids (in hemodynamic instability) on mortality
Forest plot
Direct comparison (crude analysis) of all crystalloids vs. all colloids
24
Rochwerg
B, … Annane D. Ann Intern Med 2014; 161:347-55
Network meta-analysis in sepsis
4-Nodes
Effect of resuscitation fluids (in hemodynamic instability) on mortality
 14 studies (18,916 pts) with 15 direct comparisons
2
A
4
2
10
H
1
G
S
23
H A2H
1 1
2
L
6-Nodes
C
H
B G
Saline (S)
Bal. Cryst (B)
Albumin
L-HES, H-HES
Gelatin
25
Rochwerg
B, … Annane D. Ann Intern Med 2014; 161:347-55
Current IV colloids; My institution
SUMMARY
26
Current IV colloids
 Optimize circulating blood volume w/o edema formation
 remain strict intravascular
 maintain intravascular colloid-osmotic pressure permanently
 Maintain electrolyte homeostasis
 if solved in physiological electrolyte solution (balanced)
 Minimal side effects, no harm
 no organ dysfunction (e.g. renal), acquired coagulopathy,
infection, retention (e.g. pruritus), allergies
 Cost effective
 added costs justified by improved patient outcome
27
What happened at my institution
Costs for 1L (2014): CHF 3.3 (Ringerfundin) vs CHF 22.4 (Voluven)
 Routine use of any colloid stopped end of 2012
 Ringer: Ringerlactat® BBraun to Ringerfundin® BBraun in 2013

28
Voluven: 6% Voluven balanced® Fresenius
OR / ANESTHESIA activity (minutes): 3-5% increase per year
THANK YOU
Michael Ganter, MD
Institute of Anesthesiology and Pain Medicine
Kantonsspital Winterthur, Switzerland