We Shall Not Bleed to Death Crystalloid: Colloid: Blood

Fluid Resuscitation in Trauma

12 April 2014

Tan Hon LiangSingapore General HospitalAnaesthesiology and Critical Care

Fluid Resuscitation in Trauma

What is a Trauma Conference without a talk on Fluid Resuscitation?

………. To Death

No conflicts of interest to disclose

Nothing good comes out of war ….

…except trauma research.

Fluid Resuscitation in Trauma

World War 1: Preoperative resuscitation uncommon.

World War 2: Resuscitation with fluids and blood.

Vietnam War: 3 crystalloid : 1 RBC ratio.

1980s: Advent of damage control surgery.

Middle East Conflict : United States Armed Forces added plasma as a resuscitation fluid.

So what should we give?

What are we trying to achieve?

Goals of Trauma Resuscitation

Vital organ perfusion while avoiding the “bloody” vicious cycle:1. Continued bleeding

2. Hypothermia

3. Acidosis

4. Coagulopathy

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 if TBI present.

Minimizing HypothermiaNothing 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)

Acidosis and Coagulopathy

When fluid type and ratios may matter.

What is available? Crystalloids Colloids

What is less available? Blood

Let’s start with crystalloids

Normal Saline?

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 NOT ideal.

Hypertonic Saline then?

CrystalloidsHypertonic 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!

Crystalloids Hypertonic Saline

No difference in neurological function at six months

No difference in 28 day mortality

Hypertonic Saline doesn’t quite work.

Is it because of Chloride?

The Problem of Chloride

Chloride

Chloride and metabolic acidosis/strong ion acidosis

Chloride and coagulopathy

Chloride and kidney injury

Chloride and reduced splanchnic perfusion

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

So chloride laden crystalloids are not

good…

Let’s remove Chloride then!

Lactated solution better?

Lactated solutionsHypotonicity

TBI

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.

So Lactated solution may not be better.

How about replacing lactate?

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.

Hmm… crystalloids CMI, how about

colloids?

Colloids Hydroxyethyl starch

Bad press: increase renal failure and mortality

115 patients. South Africa. Blunt and Penetrating injury.

Found better lactate clearance and less renal failure In penetrating trauma.

No firm conclusions drawn for blunt trauma.

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.

Colloids

Not published

So semi-synthetic colloid is also not the

answer…

How about a human derived colloid?

Albumin?

Colloids Albumin

SAFE Study: post hoc: higher mortality with albumin in TBI.

No benefit in burn patients given 14 days of 5% albumin.

Expensive, no distinct advantage during initial presentation.

Hidden chloride.

Crystalloid vs ColloidRock and a hard place

Colloid vs Crystalloid

Colloid No. of Trials

Patients Pooled RR

95% CI

Albumin/plasma 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

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.”

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.”

Crystalloid and Colloid stalemate

None proven better. Avoid HES if you can.

Blood is thicker than water, but is it

better?

Blood ProductsRed Blood Cells Transfusion

Temperature Acid-base electrolyte – K, Ca, TRALI Massive Transfusion Coagulopathy

Multifactorial •Add:• Plasma

• TRALI• Platelets• Cryoprecipitate

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%

Blood Product RatiosCivilian 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.

Platelet : Red Cell ratios?

Does it matter?

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.

So is 1:1:1 the answer?

Blood Products

So how?

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)

Warm fresh blood is the answer?

Pragmatically speaking…

Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR)

Phase III trial (680 patients), USA and Canada.

http://clinicaltrials.gov/show/NCT01545232

Started August 2012 Completed recruitment December 2013

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

And so we wait…

Ideal Trauma Resuscitation Fluid – Will we get there?

NO

Why Not?What Trauma?

Penetrating Blunt Head injury Burns Combinations

Who gets TraumaPaediatricsAdultElderlyPremorbids

Different Resuscitation Goals

ConclusionWe 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.

ConclusionUntil then… we shall not:

Give cold fluidsGive excessive chloride Give too little/much blood products(Forget Tranexamic acid)Forget the context of the patient, injury and

individualized resuscitation goals.

Thank You.tan.hon.liang@sgh.com.sg