Avances en trauma

Effectsoftranexamicacidondeath,vascularocclusiveevents,
and blood transfusion in trauma patients with significant
haemorrhage (CRASH2): a randomised, placebocontrolled
trial
Background
Tranexamicacidcanreducebleedinginpatientsundergoingelective
surgery.Weassessedtheeffectsofearlyadministrationofashort
courseoftranexamicacidondeath,vascularocclusiveevents,and
thereceiptofbloodtransfusionintraumapatients.

Methods
Thisrandomisedcontrolledtrialwasundertakenin274hospitalsin
40 countries. 20211 adult trauma patients with, or at risk of,
significantbleedingwererandomlyassignedwithin8hofinjuryto
eithertranexamicacid(loadingdose1gover10mintheninfusion
of1gover8h)ormatchingplacebo.Randomisationwasbalanced
bycentre,withanallocationsequencebasedonablocksizeofeight,
generated with a computer random number generator. Both
participantsandstudystaff(siteinvestigatorsandtrialcoordinating
centre staff) were masked to treatment allocation. The primary
outcomewasdeathinhospitalwithin4weeksofinjury,andwas
describedwiththefollowingcategories:bleeding,vascularocclusion
(myocardialinfarction,strokeandpulmonaryembolism),multiorgan
failure, head injury, and other. All analyses were by intention to
treat. This study is registered as ISRCTN86750102,
Clinicaltrials.gov NCT00375258,andSouthAfricanClinicalTrial
RegisterDOH2706071919.

Findings
10096 patients were allocated to tranexamic acid and 10115 to
placebo,ofwhom10060and10067,respectively,wereanalysed.
Allcausemortalitywassignificantlyreducedwithtranexamicacid
(1463 [145%] tranexamic acid group vs 1613 [160%] placebo
group;relativerisk091,95%CI085097;p=00035).Theriskof
deathduetobleedingwassignificantlyreduced(489[49%]vs574

[57%];relativerisk085,95%CI076096;p=00077).

Interpretation
Tranexamicacidsafelyreducedtheriskofdeathinbleedingtrauma
patientsinthisstudy.Onthebasisoftheseresults,tranexamicacid
shouldbeconsideredforuseinbleedingtraumapatients.

Funding
UK NIHR Health Technology Assessment programme, Pfizer,
BUPAFoundation,andJPMoultonCharitableFoundation.
JumptoSectionIntroductionMethodsResultsDiscussionWebExtraMaterial

Introduction

Injuriesaremajorcausesofdeathworldwide. 1, 2 Everyyear,more
thanamillionpeopledieasaresultofroadtrafficinjuriesaround
theworld.Roadtrafficinjuriesaretheninthleadingcauseofdeath
globally,andsuchinjuriesarepredictedtobecomethethirdleading
causeofdeathanddisabilityby2020.About16millionpeopledie
asa result of intentional acts ofinterpersonal, collective, orself
directedviolenceeveryyear.Morethan90%oftraumadeathsoccur
in lowincome and middleincome countries. 2 Haemorrhage is
responsibleforaboutathirdofinhospitaltraumadeathsandcan
alsocontributetodeathsfrommultiorganfailure.3
Thehaemostaticsystemhelpstomaintaincirculationaftersevere
vascular injury, whether traumatic or surgical in origin. 4 Major
surgery and trauma trigger similar haemostatic responses, and in
bothsituationsseverebloodlosspresentsanextremechallengeto
thecoagulationsystem.Partoftheresponsetosurgeryandtraumais
stimulationofclotbreakdown(fibrinolysis),whichmightbecome
pathological(hyperfibrinolysis)insomecases.4

Results
Figure 1 shows the trial profile. 20211 patients were randomly
assignedtotranexamicacidorplacebo(figure1),ofwhom20116
were randomly assigned through the local pack system and 95
throughtelephonerandomisation.Thedatafromfourpatientswere
removedfromthetrialbecausetheirconsentwaswithdrawnafter
randomisation.Fivepatientsenrolledinthestudywerelaterfoundto
beyoungerthan16years.Agewasunknownforfourpatients.23
patients were enrolled more than 8 h after their injury. Time of
injurywasnotknownfor11patients.Ninepatientshadhaemorrhage

fromnontraumaticconditions.Threepatientsweregivenapackthat
differedfromthatallocated.Theplannedconsentprocedureswere
not fully followed in 34 patients. The relevant ethics committees
wereinformedandapprovalforuseofdatawasobtained.Allthe
patients,apartfromthefourinwhomconsentwaswithdrawn,were
includedintheanalysis.

Allcausemortalitywassignificantlyreducedwithtranexamicacid
(table2).TheRRofdeathwithtranexamicacidwas091(95%CI
085097,p=00035;table2).Theriskofdeathduetobleedingwas
significantly reduced (table 2). This effect was also apparent for
deaths due to bleeding on the day of randomisation (282 [28%]
tranexamicacidgroupvs355[35%]placebogroup;RR080,95%
CI 068093, p=00036). There were 33 (03%) deaths in the
tranexamicacidgroupversus48(05%)intheplacebogroupfrom
vascularocclusion(table2),includingsevenversus22deathsfrom
myocardialinfarction,eightversusfivefromstroke,and18versus
21frompulmonaryembolism,respectively.Deathsfrommultiorgan
failure, from head injury, or due to other causes did not differ
significantlyinthetranexamicacidgroupversustheplacebogroup

Artificialoxygencarriers
Artificialoxygencarriersarenotbloodsubstitutes.They
servetocarryoxygentotissuesandareeitherhemoglobin
basedorperfluorocarbonbased.Drivingthedevelopment
ofartificialoxygencarriersareconcernsinvolvingboththe
safetyandquantityofthebloodsupply.Noartificialoxygen
carriersarecurrentlyapprovedforclinicaluseintheUnited
States.HemopurehasbeenapprovedforuseinSouth
Africa.ThecompaniesproducingHemopureandPolyHeme,
bothofwhicharehemoglobinbasedoxygencarriers,have
filedaBiologicLicenseApplicationintheUnitedStates.
PhaseIIItrialshavebeencompletedforHemopure,while
PolyHemeiscurrentlyundergoingphaseIIItrialsinthe
PolyHemeUrbanAmbulanceTrial.NoNorthAmericantrials
areunderwayforperfluorocarbons.

Use
Context
Restorationoffluidvolumestatusand
oxygencarryingcapacity,bridgeoxygenator
Reversaloflocaltissueischemia
Gasadsorber(emulsifiedPFCsonly)
Reductionoftumorhypoxia
Partialliquidventilation(emulsifiedPFCsonly)
Organpreservation
Cellculturemedium
NOscavenging
Radiology(PFCsonly)
Perioperativehemodilution
Table1.Potentialusesofartificialoxygencarriers*
*PFCsindicateperfluorocarbons;NO,nitricoxide.
Avoid,reduce,ordelaybloodtransfusion
Resuscitationfluidforprehospitaluse,forbattlefielduse,orin
theeventofmassivecasualties
Rarebloodtypesorrefusalofallogeneictransfusion
Surgicalhemorrhage
Percutaneoustransluminalcoronaryangioplasty
Necrotizingenterocolitis(intraluminalgastrointestinaltract)
Myocardialorcerebralischemia
Cardiopulmonarybypass
Decompressionsickness
Increasedeffectivenessofradiotherapyandchemotherapy
Acuterespiratorydistresssyndrome(ARDS)
Transplantationmedicine
Treatmentofhypotensioninsepsis
Medicalimaging
Elective,urgent,oremergencysurgery

Estrogen hormone reveals protective

ability after traumatic brain injury
Date:
April 22, 2012
Source:
Federation of American Societies for Experimental Biology (FASEB)
Summary:
With more than 1.7 million people sustaining a traumatic brain injury
each year, the need to identify processes to limit inflammation and
subsequent damage is critical. New research demonstrates that estrone
provides anti-inflammatory and antioxidant capabilities that are
important after traumatic brain injury.
Dr. Joshua Gatson, Assistant Professor of Surgery at the University of
Texas Southwestern Medical Center in Dallas, investigates biomarkers
and novel therapies for traumatic brain injury. His previous work has
shown that estrone, one of the three naturally occurring estrogen
hormones in the body, has shown some promise in reducing
inflammation and cell death in the brain. His latest study is the first to
demonstrate estrone provides those anti-inflammatory and antioxidant
capabilities after traumatic brain injury. It is likewise the first to reveal the
cellular pathways that are involved. His findings were presented April
22, 2012 during Experimental Biology 2012 in San Diego, CA
The study, conducted in male rats, compared 0.5 mg of estrone to a
placebo, both given 30 minutes after the injury. It demonstrated that
estrone is involved in promoting brain-derived neurotrophic factor
(BDNF), which promotes cell survival. "BDNF, one of the main growth
factors that regulates repair following injury, is actually increased
following treatment with estrone after brain injury," said Gatson, who

administered the injections within 30 minutes of the injury. "So if you

give this drug shortly after injury, it is thought to increase repair
mechanisms."
Most research involving protective capabilities of estrogen have focused
instead on estradiol, one of the other two types of estrogen hormones,
Dr. Gatson noted, so this finding indicates a fresh avenue for future
study.