Fluid Resuscitation in Trauma presented at 2014 Singapore Trauma Conference - 12.4.14 Review and update on transfusion trends.

1. Tan Hon Liang
SingaporeGeneral Hospital
Anaesthesiology and Critical Care

2. Fluid Resuscitation inTrauma
 What is aTrauma Conference without a talk on Fluid
Resuscitation?
……….To Death

3. No conflicts of interest to
disclose

4. Nothing good comes out
of war ….

5. …except trauma research.

6. Fluid Resuscitation inTrauma
 WorldWar 1: Preoperative resuscitation uncommon.
 WorldWar 2: Resuscitation with fluids and blood.
 VietnamWar: 3 crystalloid : 1 RBC ratio.
 1980s: Advent of damage control surgery.
 Middle East Conflict : United States Armed Forces
added plasma as a resuscitation fluid.

7. So what should we give?

8. What are we trying to
achieve?

9. Goals ofTrauma Resuscitation
 Vital organ perfusion while avoiding the “bloody” vicious
cycle:
1. Continued bleeding
2. Hypothermia
3. Acidosis
4. Coagulopathy

10. Minimizing Continued Bleeding
 Nothing to do with what fluid or ratios.
 “Restrained resuscitation”. “Permissive hypotension”.
 Generally target systolic blood pressure 80-90 mmHg if
no traumatic brain injury (TBI).
 But mean arterial pressure of 80 mmHg ifTBI present.

11. Minimizing Hypothermia
 Nothing to do with what fluid or ratios.
 But about how you give it and temperature/environment
management.
 “Active warming”, “warmed fluids”, “climate control”.
 Admission hypothermia was independently associated
with increased odds of death 3.03. (95% CI 2.62-3.51)

12. Acidosis and Coagulopathy
 When fluid type and ratios may matter.
 What is available?
 Crystalloids
 Colloids
 What is less available?
 Blood

13. Let’s start with crystalloids

14. Normal Saline?

15. Crystalloids
 0.9% Sodium Chloride
 Nothing normal about “normal saline”: pH 7.0.
 NS associated with lower systemic vascular resistance, worse
acidosis and coagulopathy in animal hemorrhage models.
 Need to give quite a bit.
 Little doubt that it is NOTideal.

16. Hypertonic Saline then?

17. Crystalloids
 Hypertonic saline
 ICP decreased by a mean of 8.3 mm Hg (P < 0.0001)
 PbtO2 improved by 3.1 mm Hg (P < 0.01).
 ICP of more than 31 mm Hg decreased by 14.2 mm Hg.
 CPP values of less than 70 mm Hg increased by a mean of
6 mm Hg (P < 0.0001).
 Sounds great!

18. Crystalloids
 Hypertonic Saline
 No difference in neurological function at six months
 No difference in 28 day mortality

19. Hypertonic Saline doesn’t
quite work.
Is it because of Chloride?

20. The Problem of Chloride

21. Chloride
 Chloride and metabolic acidosis/strong ion acidosis
 Chloride and coagulopathy
 Chloride and kidney injury
 Chloride and reduced splanchnic perfusion

22. Crystalloids
 Before (760 patients) vs After (773 patients)
Study, Australia.
 ~200 mmol of chloride less.
 Hyperchloridemia associated with double the odds
of RIFLE-defined kidney injury (p = .004).
Before After P
Serum Cr Rise (umol/L) 22.6 14.8 0.03
AKI incidence 14% 8.4% 0.001
Use of RRT 10% 6.3% 0.005

23. So chloride laden
crystalloids are not good…

24. Let’s remove Chloride
then!
Lactated solution better?

25. Lactated solutions
Hypotonicity TBI

26. Crystalloids
 Severe (MAP: 25 to 30 mmHg) vs Moderate (MAP: 40 to
45 mmHg)
 Resuscitated with RS or RL.
 Observed for 150 min.
 Moderate shock: 100% survived and improved.
 Severe shock group:
 25% of RS rats survived.
 100% of RL rats died before the end of the study period with
worsened acid-base and metabolic parameters.

27. So Lactated solution may
not be better.
How about replacing lactate?

28. Crystalloids
 Plasma-Lyte A: acetate and gluconate instead.
 46 patients.
 Better acid base and biochemistry with Plasma-lyte A, but
no difference in urine output and mortality.
 Small numbers.Too early to say.

29. Hmm… crystalloids
CMI, how about colloids?

30. Colloids
 Hydroxyethyl starch
 Bad press: increase renal failure and mortality
 115 patients. SouthAfrica. Blunt and Penetrating injury.
 Found better lactate clearance and less renal failure In
penetrating trauma.
 No firm conclusions drawn for blunt trauma.

31. Colloids
 Did not emphasize:
 Transfusion needs in HES130/0.4 blunt trauma patients.
 RBC 2x more, FFP 3x more, Platelets 5x more (All P < 0.005)!
 Renal injury and lactate clearance were post hoc and not pre-
specified end points!
 Baseline characteristics were not equal!
 HES 130/0.4 group: 5 years younger, 5kg lighter with 20% lower
baseline lactate than comparator.

32. Colloids
Not published

33. So semi-synthetic colloid
is also not the answer…

34. How about a human
derived colloid?
Albumin?

35. Colloids
 Albumin
 SAFE Study: post hoc: higher mortality with albumin inTBI.
 No benefit in burn patients given 14 days of 5% albumin.
 Expensive, no distinct advantage during initial presentation.
 Hidden chloride.

36. Crystalloid vs Colloid
Rock and a hard place

37. Colloid vs Crystalloid
Colloid No. of
Trials
Patients Pooled RR 95% CI
Albumin/plasm
a Protein
24 9920 1.01 0.93 to 1.10
HES 25 9147 1.10 1.02 to 1.19
Modified
Gelatin
11 506 0.91 0.49 to 1.72
Dextran 9 834 1.24 0.94 to
1.65
Dextran in
hypertonic
crystalloid
9 1985 0.91 0.71 to 1.06

38. Colloid vs Crystalloid
“There is no evidence from randomized controlled trials that
resuscitation using colloids compared with crystalloids
reduces the risk of death in patients with trauma, burns or
following surgery.The use of hydroxyethyl starch might
even increase mortality.”

39. Colloid vs Crystalloid
 2857 patients in Europe. 57 centres.
 Multicenter, randomized clinical trial stratified by case mix
(sepsis, trauma, or hypovolemic shock without sepsis or
trauma).
 No difference in 28-day mortality.
 90-day mortality was lower (RR, 0.92 [95% CI, 0.86 to 0.99];
P = 0.03).
 “this finding should be considered exploratory and requires further
study before reaching conclusions about efficacy.”

40. Crystalloid and Colloid
stalemate
None proven better.
Avoid HES if you can.

41. Blood is thicker than
water, but is it better?

42. Blood Products
 Red Blood CellsTransfusion
 Temperature
 Acid-base
 electrolyte – K, Ca,
 TRALI
 MassiveTransfusion Coagulopathy
 Multifactorial :
•Plasma
•TRALI
•Platelets
•Cryoprecipitate

43. Blood Product Ratios
Military Data
 Retrospective. 246 MT patients. US combat support hospital.
 Logistic regression, plasma to RBC ratio independently
associated with survival (odds ratio 8.6, 95% confidence interval
2.1-35.2).
Plasma : RBC Overall mortality rate Hemorrhage mortality
rate
1:8 65% 92.5%
1:2.5 34% 78%
1:1.4 19% 37%

44. Blood Product Ratios
Civilian Data
 Prospective cohort study. 1245 patients. 10 US Level 1
Trauma Centre.
 Increased plasma : RBC and platelets : RBC ratios
independently associated with decreased early
mortality, due to hemorrhage.
 Patients with ratios less than 1:2 were 3 to 4 times more
likely to die than patients with ratios of 1:1 or higher.

45. Platelet : Red Cell ratios?
Does it matter?

46. Blood Product Ratios
 6,123 citations: no RCTs identified.
 Seven observational studies (4,230 patients):
Heterogeneity of studies precluded meta-analysis.
 5 studies involving only patients requiring massive
transfusions
 4 observed a lower mortality with higher ratios.
 2 studies involving non-massively bleeding patients
 observed no benefit of using higher ratios.

47. So is 1:1:1 the answer?

48. Blood Products

49. So how?

50. Blood Products
 24-hour survival
 96 of 100 (96%) versus 223 of 254 (88%), (p = 0.018)
 30-day survival
 95% to 82%, (p = 0.002)

51. Warm fresh blood is the
answer?

54. Pragmatically speaking…

55. Pragmatic, Randomized Optimal Platelets
and Plasma Ratios (PROPPR)
 Phase III trial (680 patients), USA and Canada.
 http://clinicaltrials.gov/show/NCT01545232
 StartedAugust 2012
 Completed recruitment December 2013

56. Pragmatic, Randomized Optimal Platelets
and Plasma Ratios (PROPPR)
 Intervention:
 Primary outcomes:
 24-hour
 30-day mortality among subjects predicted to receive
massive transfusion
Group 1 6 FFP : 6 Platelet (1 CSP) : 6 RBC 1:1:1
Group 2 Alternating
3 FFP : 0 Platelet : 6 RBC
3 FFP : 6 Platelet (1 CSP) : 6 RBC
1:1:2

57. And so we wait…

58. IdealTrauma Resuscitation
Fluid –Will we get there?

59. NO

60. Why Not?
 What Trauma?
 Penetrating
 Blunt
 Head injury
 Burns
 Combinations
 Who getsTrauma
 Paediatrics
 Adult
 Elderly
 Premorbids
Different Resuscitation Goals

61. Conclusion
 We shall not bleed to death
 if…
 Correct type of fluid for the
 Correct patient for the
 Correct injury in the
 Correct amounts or ratios for the
 Correct end points.

62. Conclusion
 Until then… we shall not:
 Give cold fluids
 Give excessive chloride
 Give too little/much blood products
 (ForgetTranexamic acid)
 Forget the context of the patient, injury and individualized
resuscitation goals.

64. ThankYou.
tan.hon.liang@sgh.com.sg