1. Fluid Resuscitation in Critical Care Patients
2013/05/19
佛教慈濟醫院台北分院
外科加護病房 周志道

2. Outlines
1. Basics
2. Crystalloid vs. Colloid update
3. Albumin update
4. Standard vs. Delayed fluid resuscitation update
5. Hemodynamic parameters to guide fluid therapy
6. Fluid therapy of severe sepsis 2012
7. Blood substitutes
8. FVII

3. Hemoconcentration
L. Zgraggen et al. Thrombosis Research (2005) 115, 175—183

4. Hemorrhagic Shock
J Obstet Gynaecol Can 2002;24(6):504-11

5. Hypothetical Capillary Endothelial Barriers
Peripheral Capillary Brain Blood Barrier
65A
7A
Vascular lumen Vascular lumenInterstitial space Interstitial space
H2OH2O H2OH2O
Na+
Small ion
Na+
Small ion Na+
Small ion
Na+
Small ion
Protein Protein
Protein Protein
C. Tommasino. Anesthesiology Clin N Am 20 (2002):329-346

6. Effect of Different Solutions on Plasma
Volume Expansion
Rizoli: J Trauma, Volume 54(5) Supplement.May 2003.S82-S88

7. Fluid resuscitation with colloid or crystalloid solutions in
critically ill patients (II)
Gill Schierhout; Ian Roberts. BMJ 1998; 316:7136

8. Colloids versus crystalloids for fluid
resuscitation in critically
ill patients ( 2009 Review)
Perel P, Roberts I, Pearson M. Cochrane Database
of Systematic Reviews 2007, Issue 4..
PPF: Plasma protein fraction is the portion of the plasma remaining after fibrinogen
and globulin have been removed

9. 9
Effect of HES Solutions on Hemostasis
Sibylle A. Anesthesiology.2005;103: 654-60

10. Hydroxyethyl Starch 130/0.42 versus
Ringer’s Acetate in Severe Sepsis
Perner et al. N Engl J Med 2012;367:124-34.

11. Hydroxyethyl Starch or Saline for fluid resuscitation in
Intensive Care
Mybergh et. N EJ M
2012;367:1901-11

12. Association of Hydroxyethyl Starch Administration With Mortality and Acute
Kidney Injury in Critically Ill Patients Requiring Volume Resuscitation
A Systematic Review and Meta-analysis
JAMA. 2013;309(7):678-688

13. Association of Hydroxyethyl Starch Administration With Mortality and Acute
Kidney Injury in Critically Ill Patients Requiring Volume Resuscitation
A Systematic Review and Meta-analysis
JAMA. 2013;309(7):678-688

14. A Comparison of Albumin and Saline for Fluid
Resuscitation in the Intensive Care Unit
The SAFE Study Investigators, . N Engl J Med 2004;350:2247-2256

15. Effect of baseline serum albumin concentration on outcome of
resuscitation with albumin or saline in patients in ICU
The SAFE Study Investigators ; BMJ Nov 2006; 333: 1044;

16. Saline or Albumin for Fluid Resuscitation
in Patients with Traumatic Brain Injury
The SAFE Study Investigators* NEJM 2007; 357;9

17. Saline or Albumin for Fluid Resuscitation
in Patients with Traumatic Brain Injury
The SAFE Study Investigators* NEJM 2007; 357;9

18. Albumin Administration in Patients with Severe
Sepsis due to Secondary Peritonitis
C.D. Chou J Chin Med Assoc 2009;5:243-250
Baseline albumin concentration more than 20
g/l.
Baseline albumin concentration of 20 g/l or less

19. Impact of albumin compared to saline
on organ function and mortality of patients
with severe sepsis- The SAFE Study Investigators
Administration of albumin compared
to saline did not impair renal or other
organ function and may have
decreased the risk of death.
Intensive Care Med. 2011 Jan;37(1):86-96

20. Impact of albumin compared to saline
on organ function and mortality of patients
with severe sepsis- The SAFE Study Investigators
Intensive Care Med. 2011 Jan;37(1):86-96

21. Morbidity in hospitalized patients receiving
human albumin: Meta-analysis
Jean-Louis Vincent et al .Crit Care Med 2004; 32(10): 2029-2038

22. Transfusion practice in the
critically ill: Can we do better?
Restrictive transfusion strategy
– Transfusion threshold --- 7.0 g/dL
– Maintained between 7.0- 9.0 g/dL
Corwin, Howard L. Critical Care Medicine 2005 ;33(1):232
Canadian Critical Care Trials Group NEJM 1999;304:409-417

23. Is fresh frozen plasma clinically effective?
Stanworth, S. J et al. Br J Hematology 2004 ;126(1):139–152
Study Intervention
details
Comparator
details
Clinical group Main outcome as reported
Reed et al
(1986)
FFP 2 U every 12
U of blood
PLT 6 every 12
U of blood
Massive transfusion No differences in clinical
bleeding outcomes
Boldt (1989)
Trimble (1964)
FFP 2U
FFP 3U
No FFP Cardiac surgery with
bypass
No positive effect on blood loss
or transfusion requirement
Consten et al
(1996)
FFP 3U Gelufusion 750
ml
Cardiac surgery with
bypass
No significant difference in
blood loss or requirement
Kasper et al
(2001)
Autologous
FFP 15 ml/kg
Hetastarch 15
ml/kg
Coronary artery bypass
grafting
No significant reduction in
blood loss or requirement
Wilhelmi et al
(2001)
FFP 4U Hydroxy-
ethyl-starch
1000 ml
Coronary artery bypass
grafting
No significant reduction in
blood loss or requirement
Oliver et al
(2003)
FFP 1U Albumin 5%
200ml
Open heart surgery for
children < 10 kg
No significant differences in
blood loss or requirement
Bocanegra (1979) Plasma
(high volume)
Plasma
(low volume)
Burn (children) No significant difference in
mortality
Liu et al
(1994)
Autologous
plasma saver
No FFP Hysterectomy No clinical outcome difference
Leese et al
(1991)
FFP 8 U for 3 d Albumin sol
2000ml
Acute severe pancreatitis No significant difference in
clinical outcome/mortality
Boyed et al
(1996)
FFP 2U Conjugated
estrogen 50 mg
Renal disease and
transplantation
No clinical outcomes reported
( outcomes of coagulation
testing)
Menges et al Plasma with Allogenic red Orthopedic hip surgery No significant differences in

24. Limited fluid resuscitation
Bickell WH et al. N Engl J Med. 1994; 331: 1105–1109.
Immediate Delayed
Resuscitation Resuscitation P
Value
Survival to discharge 193/309 (62) 203/289 (70) 0.04
Blood Loss (ml) 3127 ± 4937 2555 ± 3546 0.11
LOS (hospital) (days) 14 ± 24 11 ± 19 0.006
LOS (ICU) (days) 8 ± 16 7 ± 11 0.30

25. Effects of Delaying Fluid Resuscitation on an Injury to
the Systemic Arterial Vasculature
JAMES F. HOLMES. Et al. ACADEMIC EMERGENCY
MEDICINE 2002; 9:267–274

26. Restrictive strategy of intraoperative fluid maintenance during
optimization of oxygen delivery decreases major complications after
high-risk surgery
Lobo at et. Critical Care 2011, 15:R226

27. Delaying Fluid Resuscitation in hemorrhage shock
Induce Pro-inflammatory Cytokine Response
失血性休克延遲輸液治療會引發發炎性細胞激素反應
陳石池 李建璋 顏瑞昇 許瓊元 陳世英 蘇展平 江文莒
台大醫院 急診醫學部
Chieng-Chang Lee. et al. Anal of EMERGENCY
MEDICINE 2007; 49:37-44
Delayed fluid resuscitation in hemorrhagic shock
induces increased production of pro-inflammatory
cytokines and the release of cytokine was correlated
with the time delayed for resuscitation.

28. Hemodynamic parameters to guide fluid therapy
Clinical indices of the adequacy organ/tissue perfusion

29. Hemodynamic parameters to guide fluid therapy

30. Hemodynamic parameters to guide fluid therapy

31. Fluid Therapy of Severe Sepsis
1. Crystalloids as the initial fluid of choice in the
resuscitation of severe sepsis and septic shock
(grade 1B).
2. Against the use of hydroxyethyl starches for fluid
resuscitation of severe sepsis and septic shock
(grade 1B).
3. Albumin in the fluid resuscitation of severe sepsis
and septic shock when patients require substantial
amounts of crystalloids
(grade 2C).
Surviving Sepsis Campaign 2012

32. Fluid Therapy of Severe Sepsis
4. Initial fluid challenge in patients with sepsis-induced tissue
hypoperfusion with suspicion of hypovolemia to achieve a
minimum of 30mL/kg of crystalloids (a portion of this may
be albumin equivalent). More rapid administration and
greater amounts of fluid may be needed in some patients
(grade 1C).
5. Fluid challenge technique be applied wherein fluid
administration is continued as long as there is
hemodynamic improvement either based on dynamic (eg,
change in pulse pressure, stroke volume variation) or static
(eg, arterial pressure, heart rate) variables (UG).
Surviving Sepsis Campaign 2012

33. 健保使用 Human Albumin 適應症 -
96/06/01
• 休克病人擴充有效循環血液量 :
.Ⅰ 休克病人至少已給生理鹽水或林格爾液等晶類溶液
1000 mL 後尚不能維持穩定血流動態，血比容
(hematocrit) ＞ 30 % ，或血色素 (hemoglobin) ＞ 10
gm/dL 須要繼續靜脈輸液時，宜優先使用合成膠類溶
液，如
dextran 、 hydroxyethylstarch 、 polyvinylpyrolidone 等。
若無上述合適製劑，可給白蛋白溶液，每一病人用量
限 50 gm (20% 50ml *5) 。
Crystalloid 1000 ml > Colloid (Dextran ) > Albunmin

34. Blood
Substitutes

35. •Blood shortages & donor recruitment
•Compatibility –need for cross-matching
•Cost of blood processing
•Shelf-life & storage
•Human error
•Unnecessary transfusions
•Risk of disease transmission
•Cultural & religious objection
Problems associated with blood
transfusion

36. Comparison of the Properties
Property Blood Blood substitutes Volume
expanders
Volume
expansion
Yes Yes Yes
Oxygen carrying
capacity
Yes Yes No
Other therapeutic
proteins
Yes No No
Therapeutic life 1-2 months 1-2 days Hours (varies with
dose and species)
Storage life 1 month 6-24 months 2 years
Changes during
storage
Yes No No
Type specific Yes No No
Viral inactivation No Yes Yes
Size Large Small Small
Viscosity High Low/moderate Low
Deanna J. Nelson Encyclopedia of Pharmaceutical Technology. 2002:236 - 262

37. • HBOC: hemoglobin-based oxygen carrier
• PFC: Perfluorocarbons

38. ADVERSE EFFECTS OF HBOCs
• Vasoactivity: Nitric oxide binds to free Hb,
– vasoconstricition occurs.
• Hemostasis : Reversal of the inhibition effect of nitric
oxide on platelet aggregation.
• Gastrointestinal side effects: such as nausea, vomiting,
diarrhea, and bloating.
– binding of nitrous oxide to gastrointestinal tissues is the proposed
cause.
• Interfere with laboratory assays.
Crit Care Clin 25 (2009) 279–301

39. Cell-Free Hemoglobin-Based
Blood Substitutes and Risk
of Myocardial Infarction and Death
JAMA. 2008;299(19):2304-2312

40. Crit Care Clin 25 (2009) 279–301

41. Mechanism of Action of Recombinant
Factor VIIa

42. Efficacy and Safety of Recombinant Activated
Factor VII for Acute Intracerebral Hemorrhage
N Engl J Med 2008;358:2127-37.

43. Efficacy and Safety of Recombinant Activated
Factor VII for Acute Intracerebral Hemorrhage
N Engl J Med 2008;358:2127-37.

44. Safety of Recombinant Activated Factor VII
in Randomized Clinical Trials
N Engl J Med 2010;363:1791-800.

45. Thanks