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Catherine Juillard, MD MPH

May 29, 2014

Trauma: Year in Review

Overview

• Hemorrhage control

• Traumatic Neurologic Injury

• Shifting of practice patterns for specific injuries

– Rib Fractures

– Major Vascular Injuries

Hemorrhage Control

• Major advances

– 1:1 RBC:FFP resuscitation

• PROMMTT

• PROPPR

– Prothrombin Complex

• Minor advances

– CRASH-2 trial

Coagulopathy of Trauma

• 20%-30% of severely injured patients are coagulopathic upon arrival to ED.

• Causes – Consumption of factors (active hemorrhage)

– Dilution of factors (resuscitation)

– Prescription medications • Plavix, Coumadin, Aspirin, and new anticoagulants

increasingly common in trauma patients

• Cornerstone of “Lethal Triad” – Acidosis, hypothermia, coagulopathy

Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma. 2003 Jun;54(6):1127-30. Bellal J, Amini A, Friese RS, et al. Factor IX complex for the correction of coagulopathy. J Trauma. 2011 Dec;72(4):828-834.

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“Bloody Vicious Cycle”

Bleeding

Acidosis Hypothermia

Coagulopathy

“Damage Control”

• Permissive hypotension

• Minimization of crystalloid

• Liberal use of blood products

• Drugs to combat coagulopathy

Damage Control Resuscitation Prothrombin Complex

1:1 Resuscitation

• “Damage Controlled Resuscitation”

– >100 publications in last 24 months

• Avoid crystalloid in favor of balanced RBC:FFP in severely injured

• Significant mortality benefit

• Studies retrospective or non-randomized in civilian literature until 2013

Civilian Literature (2008)

2746 pts needing operative intervention

135 pts needing >10 units PRBC

4yr retrospective study

Closer to 1:1 = BETTER

>=8 units PRBC N = 415 Gluegrant data

J Trauma. 2008 Nov;65(5):986-93. J Trauma. 2008;65:272-278.

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Could these become a simple score?

But…in need of prospective data…

• Prospective, observational, cohort study • 10 Level 1 trauma centers • July 2009-October 2010 • Primary objective:

– Investigate in-hospital mortality in all patients surviving at least 30 minutes after ED admission

• Minute to minute tracking until resuscitation complete

• Followed until hospital discharge

Prospective Observational Multicenter Major Trauma Transfusion study

• Inclusion criteria: • Major trauma activation

• At least 16 years old

• Arrival from scene

• Received at least 1 unit of RBCs in first 6 hours of care

• 1245 patients • 905 Received 3 or more units of blood products

• 297 Massive transfusions (10+ RBC in 24 hours)

Prospective Observational Multicenter Major Trauma Transfusion study

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Methods: Trigger Selection

CITT Study

• Adapted from military

• SBP <90 mm Hg

• Hemoglobin <11 g/dL

• Temperature <35.5 C

• INR >1.5

• BD >=6

ABC Study

• Civilian Score

• SBP<90 mmHg

• HR >=120 bpm

• FAST exam positive

• Penetrating trauma

• Entire cohort (1245 patients)

• 1st ED Value utilized for each trigger

• As numbers of triggers positive increased, highly predictive of increasing risk for need for MT

plasma 2:1 1:1 1:2 pRBCs

Ev

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plasma 2:1 1:1 1:2 pRBCs

Ev

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Colon Evan’s Blue Lung Evan’s Blue

Figure 4:. Evan’s blue levels in the colon after resuscitation.

P<0.05 vs plasma alone

* *

Figure 5:. Evan’s blue levels after resuscitation in the lung.

P<0.05 vs pRBCs alone

Is 1:1 the correct ratio?

plasma 2:1 1:1 1:2 pRBCs

Co

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(p

g/m

L)

0

200

400

600

800

1000

1200

1400 MIP-2

Figure 1:. MIP-2 Levels after resuscitation. P<0.05 vs all other groups

*plasma 2:1 1:1 1:2 pRBCs

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(p

g/m

L)

0

200

400

600

800MIP-1α

Figure 2:. MIP-1α Levels after resuscitation. P<0.05 vs plasma

and pRBCs alone

*

Makley et al,

manuscript

2011

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• Phase III clinical trial

• Investigating 1:1:1 plasma:platelet:RBC vs. 1:1:2

• 12 US trauma centers

• Enroll 580 MT patients prospectively

• Outcome 24 hr & 30 d mortality

Prothrombin Complex

• Factor VII (rFVIIa) – Expensive, lacks optimal dosing regimen

• PCC (Prothrombin Complex Concentration) • Factor IX complex

– Vitamin K dependent factors (II, VII, IX, X) – Has to be generally given with 1 or 2 units FFP – Relatively inexpensive ($500-1000)

• Standard dose – 25 units per kg • Factor VII – very expensive ($3k to 12K per patient)

– To date, used for rapid Coumadin reversal

“PCC therapy leads to a significant correction of INR in ALL trauma patients, regardless of coumadin use…”

Reduction in RBC & FFP needs

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CRASH-2

• “Aim to assess effect of Transexamic acid on death in trauma patients with significant hemorrhage.”

• RCT double blind placebo controlled

• 20,211 pts in 274 hospitals in 40 countries

• Adult patients with or at risk of major hemorrhage

– 1 gm over 10 minute loading dose

– 1 gm infusion over 8 hours Lancet 377(9771): 1096-101; 2011

CRASH-2 Criticisms

• Only 5% of patients had bleeding as a cause of death

• Patients randomized on clinician gestalt (not evidence of fibrinolysis)

• Injury severity not measured

• TXA not found to reduce blood transfusions

• Patient follow up reported as 100% (!?)

• Effect size small (0.8% absolute reduction in death caused by bleeding)

Traumatic Neurologic Injury

• ProTECT trial – role of progesterone

• Vasopressor therapy/targets

• Spinal Cord Injury

• Amantadine role in recovery once rehab stage is reached.

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ProTECT (Phase III)

• Progesterone for Traumatic Brain Injury: Experimental Clinical Treatment (ProTECT)

• 2008 – Two completed Phase II RCTs that showed benefit

• Progesterone – acts as a neurosteroid

– Protecting damaged cells

• Multi-center, NIH, randomized, placebo controlled, Phase III trial begun

ProTECT (Phase III)

• Progesterone felt to have several neuroprotective effects:

– Decreases cerebral edema

– Rebuilding of Blood-brain barrier

– Downregulating inflammatory cascade

– Limiting cellular necrosis/apoptosis

VERY PRELIMINARY – “Vasopressin safe and effective for

maintenance of CPP after TBI”

• Multi-center, prospective cohort study

• 360 patients, 14 centers, 2005-2009

• 43% of C-spine had attempt at extubation – 89% were successful

• High C-spine 35% attempt

– 88% successful

• 72% no MV @ d/c

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Amantadine Hydrochloride

• Aimed at those with severe TBI in a minimally conscious state or vegetative state

• Vegetative state: • 50% regain consciousness at 1 year

• Minimally conscious state • 50% severely disabled at 1 year

• Mechanism of action unknown • Acts as an indirect dopamine agonist

• 184 patients, 11 sites, 3 countries

• Vegetative or minimally conscious state for 4-16 wks after TBI

• 4 week course of drug or placebo

• No difference in adverse effects

Injury Specific

• Rib fracture stabilization

• Vascular trauma

– Shunts

– Balloon occlusion control of major injury

– Stent injuries

Rib Fractures

Kaewlai R et al. Radiographics 2008;28:1555-1570

©2008 by Radiological Society of North America

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Rib Fixation

• >20 studies

• Indications debated

– ?Pain

– ?Flail chest

– ?non-union at what time point

• Markov analysis

• Showed ORIF is cost-effective

Vascular Injuries

• Shunts • Extremity injury

• Balloon Occlusion • Venous Injuries

• Covered Stents • Subclavian Artery

• Aorta

• Vena Cava

Shunts

Tourniquets, vascular shunts, and endovascular technologies: Esoteric or essential? A report from the 2011 AAST Military Liaison Panel.

J Trauma Acute Care Surg. 2012 Jul;73(1):282-285.

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Gaining Control IVC

Traditional

• Manual tamponade • Sponge stick

• Hard to maintain while repairing

• Flatten IVC • Complicated repair

• Urinary/Fogarty balloons • Still have to disrupt

hematoma

• Ligation • High amputation rate

• Very morbid

Cattell Maneuver

Gaining Control IVC

Traditional

• Manual tamponade • Sponge stick

• Hard to maintain while repairing

• Flatten IVC • Complicated repair

• Urinary/Fogarty balloons • Still have to disrupt

hematoma

• Ligation • High amputation rate

• Very morbid

Cattell Maneuver

GB Duodenum and pancreas

Ao

rta

Cava

Gaining Control IVC

Angiogram Balloon Occlusion

• Percutaneously delivered

• Can be done before opening

• Theoretically reduces blood loss

• Avoids entering hematoma without proximal control

• Reduces operative time

• Allows potential stent options

• Resuscitative endovascular balloon occlusion of the aorta (REBOA)

• Emergence of training courses (ESTARS, BEST)

• Hybrid ORs

• AORTA Study (AAST)

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Case 1

• 20 yo male single GSW to L scapula, no exit wound

• Decreased L Radial pulse

• Abnormal BP in L arm

• Initially HD stable

• CXR – no hemothorax

Case 1

• 20 yo male single GSW to L scapula, no exit wound

• Decreased L Radial pulse

• Abnormal BP in L arm

• Initially HD stable

• CXR – no hemothorax

Case 1

• 20 yo male single GSW to L scapula, no exit wound

• Decreased L Radial pulse

• Abnormal BP in L arm

• Initially HD stable

• CXR – no hemothorax

Case 1

• 20 yo male single GSW to L scapula, no exit wound

• Decreased L Radial pulse

• Abnormal BP in L arm

• Initially HD stable

• CXR – no hemothorax

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Case 1

• 20 yo male single GSW to L scapula, no exit wound

• Decreased L Radial pulse

• Abnormal BP in L arm

• Initially HD stable

• CXR – no hemothorax

Case 1

• 20 yo male single GSW to L scapula, no exit wound

• Decreased L Radial pulse

• Abnormal BP in L arm

• Initially HD stable

• CXR – no hemothorax

L subclavian artery injury

Proximal control – anterior thoracotomy through 3rd ICS Distal control – often need supraclavicular incision

Trap door

• Alternative for access for L subclavian /Common carotid

• Poor exposure

• Significant morbidity incision

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Considerations

• Pain

• Clavicular stability

• Not surgically that easy

• Takes time to expose

Subclavian Artery Repair

Dr. Paul Tahalele, Indonesia

Case 2

• 20 yo male multiple large caliber GSW to back, chest, LE

• Presented in extremis with hemoptysis

• Emergently intubated & resuscitated

• Injuries included: • L subclavian artery injury

• L IJ transection • Esophageal Injury x 2 • Mandible fracture • LE compartment syndrome • UE fractures

Case 2

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Case 2 Case 2

Case 2 Case 2

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Case 2 Case 2

Case 2 Case 2

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Subclavian Stent Considerations

• Hemodynamically stable

• Focal injury

• Endovascular-surgical hybrid suite

• Have to be able to traverse injury with guidewire

• Ready availability of trauma/vascular surgeon

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Subclavian Endovascular Repair

• >20 papers in last 12 months

• “Endovascular management of peripheral artery trauma in patients presenting in hemorrhagic shock.” (J Cardiovasc Surg Aug 2012) – 18 patients

– All were technical successes

• Experience is limited

Summary

• A number of important advances in last 12 months

• Exciting time

• More to come…

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References

• Bellal J, Amini A, Friese RS, et al. Factor IX complex for the correction of coagulopathy. J Trauma. 2011 Dec;72(4):828-834.

• Bhatnagar A, Mayberry J, Nirula R. Rib fracture fixation for flail chest: what is the benefit? J Am Coll Surg. 2012 Aug;215(2):201-5.

• Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma. 2003 Jun;54(6):1127-30. • Callcut RA, Cotton BA, Muskat P, et al. Defining when to initiate massive transfusion: A validation study of

individual massive transfusion triggers in PROMMTT patients. J Trauma Acute Care Surg. 2013 Jan;74(1):59-65. • CRASH-2 Trial Collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion

in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010 Jul 3;376(9734):23-32.

• CRASH-2 Trial Collaborators. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial .Lancet. 2011 Mar26;377(9771):1096-1101.

• Duchense JC, Hunt JP, Whal G, et al. Review of current blood transfusion strategies in a mature level I trauma center: were we wrong for the last 60 years? J Trauma. 2008;65:272-278.

• Giacino JT, White J, Bagiella E, et al. Placebo Controlled Trial of Amantadine for Severe Traumatic Brain Injury. N Engl J Med. 2012 Mar 1;366(9):819-26.

• Holcomb JB, Fox EE, Scalea TM, et al. Current opinion on catheter-based hemorrhage control in trauma patients. J Trauma Acute Care Surg. 2014 Mar;76(3):888-93

• Kornblith LZ, Kutcher ME, Callcut RA, et al. Mechanical ventilation weaning and extubation after spinal cord injury. J Trauma Acute Care Surg. 2013 Dec;75(6):1060-9.

• Sperry JL, Ochoa JB, Gunn SR, et al. An FFP:PRBC transfusion ratio >= 1:1.5 is associated with a lower risk of mortality after massive transfusion. J Trauma.2008 Nov;65(5):986-93.

• Wright DW, Kellerman AL, Hertzberg VS, et al. ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med. 2007 Apr;49(4):391-402