Review Article Recent Advances of Hemorrhage Management …downloads.hindawi.com/journals/emi/2014/638956.pdf · Review Article Recent Advances of Hemorrhage Management in Severe

Review ArticleRecent Advances of Hemorrhage Management in Severe Trauma

Mohamed El Sayad1 and Hussein Noureddine2

1 Trauma and Orthopaedics, Wishaw General Hospital, Wishaw, UK2 Trauma and Orthopaedics, Ninewells Hospital, Dundee, UK

Correspondence should be addressed to Mohamed El Sayad; [email protected]

Received 3 May 2013; Revised 14 September 2013; Accepted 31 October 2013; Published 30 January 2014

Academic Editor: Chak W. Kam

Copyright 2014 M. El Sayad and H. Noureddine. This is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

Trauma is one of the most common causes of mortality worldwide with a substantial percentage of deaths resulting secondary tohaemorrhages, which are preventable and treatable when adequately managed. This paper offers a review of the current literatureon how to successfully resuscitate patients with major haemorrhage.

1. Introduction

Trauma is the third most common cause of mortality world-wide and is the leading cause of death in the age group rang-ing between 1 and 44 years [1]. Among those trauma patients,major haemorrhage is responsible for 30 to 40% of mortality,with up to half of them dying prior to their arrival to hospital[1]. Whilst injuries to the central nervous system are theleading cause of mortality, haemorrhagic shock ranks seconddespite the fact that it could be preventable and reversible.Within hospital settings, it accounts for more than 80% of themortality in operating theatres and 50% of the overall mortal-ity in the first 24 hours of admission [1]. Major haemorrhageis defined as the loss of 100% of total blood volume within 24hours, loss of 50% within four hours, or the loss of 150mLper minute. Given the above, the importance of successfulresuscitation of major haemorrhage becomes paramount [2].

2. Early Identification

Early identification of patients with major haemorrhage is anecessity and the diagnosis should be established promptly.Suffering from hypovolemia due to haemorrhage presentswith a variety of clinical features. The American College ofSurgeons through their ATLS protocols have traditionallyprovided a classification for haemorrhagic shock that isdivided according to the amount of blood loss; see Table 1[3]. However, there are limitations to this classification. For

example, the clinical signs might be masked in young fitindividuals with larger physiological reserves, as well aselderly patients on medications such as beta-blockers thatmanipulate normal physiological responses.

Introduction of new methods of shock assessment hasshown to be more sensitive compared to conventional mon-itoring of vital signs. The shock index is the ratio of heartrate to systolic blood pressure. Birkhahn et al. proved thatthe shock index was a more useful tool in diagnosing earlyhaemorrhage. They performed an observational study thatincluded 46 healthy blood-donating individuals; each patienthad 450mLs of blood taken over 20 minutes. Their vitalsigns were measured before donation, immediately afterdonation while lying down, and after one and five minutesof standing. The results showed a significant increase in themean shock index, whilst the vital signs remained within thenormal limits despite revealing some extent of variation frompredonation readings [4].

Cannon et al. performed a retrospective review of 2445trauma patients to examine the correlation between shockindex and mortality rates. Results showed that patients witha shock index ratio of more than 0.9 had a higher mortalityrate of 15.9% compared to a rate of 6.9% in those witha normal shock index. Furthermore, patients whose shockindices measured in the emergency department were higherthan those measured in the field had a mortality rate of 9.3%compared to only 5.7% in those who had unchanged shockindices [5].

Hindawi Publishing CorporationEmergency Medicine InternationalVolume 2014, Article ID 638956, 5 pageshttp://dx.doi.org/10.1155/2014/638956

2 Emergency Medicine International

Table 1: Classification of haemorrhagic shock (ATLS manual American College of Surgeons).

Class of haemorrhagic shockI II III IV

Blood loss (mL) Up to 750 7501500 15002000 >2000Blood loss (% blood volume) Up to 15 1530 3040 >40Pulse rate (per minute) 140Blood pressure Normal Normal Decreased DecreasedPulse pressure (mmHg) Normal or increased Decreased Decreased DecreasedRespiratory rate (per minute) 1420 2030 3040 >35Urine output (mL/hour) >30 2030 515 NegligibleCentral nervous system/mental status Slightly anxious Mildly anxious Anxious/confused Confused/lethargic

ROPE is another method of assessment that has alsobeen described; it involves the division of pulse rate by pulsepressure (pulse rate/systolic blood pressure-diastolic bloodpressure). Ardagh et al. assessed ROPE as a mean to predictthe risk of decompensation in patients with compensatedhaemorrhagic shock, by undergoing a retrospective study ona cohort of 184 trauma victims. Their results showed thata ROPE value of less than 3.0 was predictive of patientsremaining stable while a ROPE value of more than 3.0was predictive of patients that may develop decompensatedhaemorrhagic shock [6].

Both methods were assessed by Campbell et al. [7] whocarried out a prospective observational study of one hundredand sixteen healthy individuals that donated one unit of blood(420mLs); both their heart rate and blood pressure weremeasured immediately before and after donating the blood.Their shock index and ROPE measurements were calculatedand the mean of both measurements increased significantlyby 12.2%. This study showed that the rope and shock indicescorrelated with blood loss better than conventional observa-tion monitoring and that they are suitable methods to detectearly blood loss.

Subsequent to diagnosing hypovolemia due to haemor-rhage, it becomes imperative to identify the source of bleed-ing. This can be achieved by clinical examination (reducedbreath sounds, abdominal or pelvic tenderness, deformedlimbs, etc.), bedside investigations in the emergency depart-ment (trauma series X-rays, fast scan), or radiological investi-gationmost notablywhole bodyCT scanwhich is very helpfulin rapid diagnosis after patient stabilization [8].

3. Damage Control Resuscitation (Preventionand Treatment of the Lethal Triad)

Our approach to major haemorrhage mainly stems fromexperiences accumulated during periods of war.The conflictsin both Afghanistan and Iraq have inspired us to implementchanges to current practice. The military has developeda trauma resuscitation protocol of their own similar tothe ATLS called Battlefield Advanced Trauma Life Support(BATLS). This is applied to the management of militarytrauma victims where the starting point is stopping catas-trophic haemorrhage, ensued by the conventional ABCDEATLS algorithm [9].

For appropriate resuscitation to be established, it is im-portant to understand the severe pathophysiological derange-ments of the exsanguinating patients, in terms of hypother-mia, coagulopathy, and acidosis also known as the lethaltriad. Bleeding patients with these findings have up to 90%mortality rate requiring massive transfusion [10]. We willdiscuss each of the elements of the lethal triad in turn.

3.1. Hypothermia. Hypothermia secondary to trauma is acommon occurrence; it is due to the inability of the bodyto generate heat, because of altered central thermoregulation,blocked shivering response, and reduction ofmetabolic activ-ity at the cellular level. Resuscitation is also a common reasonfor hypothermia. Cold intravenous fluid administration andpatient exposure during initial evaluation aswell as peritonealexposure during laparotomies in the operating theatres areall major contributors. Hypothermia is clinically significantwhen the core temperature is less than 36 degrees for morethan 4 hours.

Hypothermia exacerbates coagulopathy by affectingplatelet function; the imbalance of thromboxane and pros-tacyclin reduces the response of platelet activation. Hypo-thermia also reduces the enzyme activation pathway of thecoagulation cascade. At 35C, factors eleven and twelvewould only function at 65% of normal [11]. Trauma victimswith a core temperature below 35C have a poor prognosis,and those with a core temperature of 32C have a 100%mortality rate [11]. Recent data from the 31st Combat SupportHospital in Iraq showed that 18% of 2848 trauma patientswere hypothermic and that hypothermia is significantlycorrelated with admission GCS, tachycardia, hypotension,low hematocrit, and acidosis thus making it an independentcontributor to overall mortality [12].

Treatment of the hypothermic patient could be carriedout passively or actively. Passive warming entails preventingfurther heat loss, by means such as covering the patientsand warming the operating or resuscitation room. Activewarming involves covering the trauma victims with warmingblankets and administering warmed intravenous fluid orblood and warm body cavity lavage, aiming to keep coretemperature at 36 degrees.

3.2. Acidosis. Metabolic acidosis is due to the prolongedinadequate tissue perfusion.This leads to cellularmetabolism

Emergency Medicine International 3

converting from aerobic to anaerobic and the increased pro-duction of lactate causing a reduction in pH. This reductionin pH has a negative effect on cardiac contractility.

The effect of the acidosis on the coagulation cascadewas shown by Meng et al. They measured the activity ofrecombinant factor VIIa on phospholipids and platelets, andthe results showed that it was reduced by 90% when thepH was reduced from 7.4 to 7 [13]. Martini et al. showedthe effect of acidosis on coagulation by infusing 12 pigswith 0.2mol/L of hydrochloric acid until their pH was7.1. Ringer lactate was continually transfused to maintainthat pH. Blood samples were taken at baseline and at 15minutes after acidosis induction. Coagulation function wasassessed by measuring the prothrombin time (PT), partialthromboplastin time (PTT), and thrombin generation. Theyconcluded that acidosis reduced fibrinogen concentrationto 66% 2%, decreased platelet counts to 49% 4%, anddecreased thrombin generation to 60% 4%. Acidosis alsoprolonged PT and PTT by about 20% [14].

A sensitive means of assessing tissue oxygenation is bymeasuring the base deficit, which is a measure of the numberof millimoles of base required to correct the pH of one liter ofwhole blood to 7.4 and its normal value is3 to +3. Davis et al.demonstrated that measurement of the base deficit was moreaccurate in deciding the clearance of the acidosis after traumashock than PHmeasurement.They performed a retrospectiveanalysis of 674 trauma victims that had both their pH andbase deficitsmeasured during their admission to hospital.Thebase deficit was significantly different between the survivorsand the nonsurvivors at all of the time intervals at which itwas measured. However, the same differences were not notedwhen the pH was assessed making it a less reliable predictorof outcome [15].

Treatment of acidosis mainly constitutes restoration ofthe circulation to maintain tissue perfusion. Lier et al.provided a comprehensive review of the effect of aci-dosis on coagulation and recommended neutralization ofthe acidosis to improve the coagulopathy especially whenthe trauma victim is receiving a massive transfusion. Therecommendation was that buffering could be establishedby using either sodium bicarbonate or trishydroxymethy-laminomethane (THAM), with the latter recording superiorresults. This is due to its effect on coagulation, as it didnot inhibit thrombin formation when compared to sodiumbicarbonate, but they both had a negative effect on theconversion of fibrinogen to fibrin [16].

3.3. Coagulopathy. Hess et al. reviewed the reasons for thedevelopment of acute coagulopathy following trauma. Theyidentified 6 initiators: (1) tissue damage which leads tothe exposure of endothelium and initiates the coagulationcascade and fibrinolysis; (2) shock, which is dose dependentto the degree of coagulopathy; this mechanism is not clearlyunderstood; (3) haemodilution from the shift of cellular andinterstitial fluid that is deficient in clotting factors into theplasma, and the administration of intravenous fluid, whichalso interrupts clot formation and the transfusion of redblood cells, (4) inflammation which interferes in coagulationas it causes monocytes to adhere to platelets, activation of

the thrombomodulin-protein C pathway, and the binding ofC4b to protein S [17], finally the last 2 initiators which are (5)hypothermia and (6) acidosis as discussed previously.

Acute coagulopathies are found in one in four traumapatients as shown by Brohi et al.They underwent a retrospec-tive review of 1088 patients that were admitted to their traumacentre between the years of 1993 and 1998.These patients hadtheir coagulation profile measured on admission, includingPT, APTT, and thrombin time.The results showed that 24.4%of patients had a coagulopathy and that these patients hada mortality of 46%. This was significantly different to themortality of 10.9% for those with normal clotting [18].

Currently, there are no accurate methods to assess acutetrauma coagulopathy. The traditional investigations of PT,PTT, fibrinogen, and platelet count are of limited value duringmassive hemorrhage as they do not provide enough informa-tion about clot formation. Additionally, the platelet count isusually normal during the initial stage of haemorrhage. Thecurrent treatment of coagulopathy is by the early empiricaltransfusion of blood and clotting factors [19].

3.4. Massive Transfusion and Fluid Resuscitation. Massivetransfusion is defined as transfusion of more than ten units ofpacked red cells over 24 hours or four units within one hour.Administering blood should be initiated at the scene of theaccident, thus avoiding the rapid administration of iv fluids(filler fluid) that has been traditionally promoted by the ATLSguidelines. This involves giving two liters of crystalloids andcontinuing with packed red blood cells (PRBCs) and fresh-frozen plasma (FFP) if there was transient or no response,with the aim of achieving normotension.

Duke et al. provided data from a retrospective analysisof 307 patients that were admitted to a level one-traumacentre between January 2007 and May 2011. The inclusioncriteria were patients with penetrating torso injuries anda systolic blood pressure less than 90mmHg who weremanaged by damage control resuscitation and surgery. 175patients received standard fluid resuscitation (SFR) whichwas 150mLs of crystalloid or more; 132 patients receivedrestricted fluid resuscitation (RFR) which was less than150mLs of crystalloid before damage control surgery. Theresults showed that the first group (SFR) received morepreoperative fluid then the (RFR) group (2,275mLs versus129mLs) and that they had a higher intraoperative mortalityrate (32% versus 9%) and overall mortality rate (37% versus21%). The higher mortality rate was attributed to the effectof large volume of fluids in diluting clotting factors andreducing blood viscosity and the increase of blood pressure.RFR was beneficial to these patients as it provided them withpermissive hypotension (systolic blood pressure of 90) untildamage control surgery was achieved [20].

Serious attempts at challenging the clinical validity of thewidely accepted concept of conventional fluid resuscitationfirst surfaced in the mid-1990s. In 1996, Dries published amini review of summaries in his paper hypotensive resus-citation suggesting that Limited attempts to restore bloodpressure improve cardiac output, tissue perfusion, and sur-vivalwhile attempts to restore normal tensionwith crystalloidresult in increased hemorrhage volume and highermortality

4 Emergency Medicine International

[21]. However, some of the earlier randomized controlledtrials did not concurwith those findings. For instance,Duttonet al. [22] underwent a study where a cohort of 110 patientspresenting in hemorrhagic shock, more than half of whichwere victims of penetrating trauma,was randomized to one oftwo fluid resuscitation protocols: target SBP > 100mmHg ortarget SBP of 70mmHg. And fluid therapywas titrated to thisendpoint until definitive hemostasis was achieved. His resultsshowed similar survival rates in both groups suggestingthat resorting to hypotensive resuscitation did not affectmortality [22]. Nevertheless, since then, more evidence hasemerged favoring the concept of hypotensive resuscitation.Morrison et al. performed a randomized controlled studyon 90 patients that required a laparotomy or thoracotomyfollowing trauma; they were divided into 2 groups; the firstgroup was resuscitated aiming for a mean arterial bloodpressure of 65mmHg with standard fluid protocol, whilethe second group was managed by hypotensive resuscitationto a mean blood pressure of 50mmHg. The results showedthat the second group had a lower requirement of fluid andblood product transfusion, lower postoperative mortality,and reduced postoperative bleeding. And in those of themwho did develop a coagulopathy, it was less severe comparedto coagulopathic patients of the first group as evidenced byINR measurements [23].

The ratio of packed RBC (PRBC) : fresh frozen plasma(FFP) : platelets (plt) should be 1 : 1 : 1. Two studies showedthat there was an increase in survival rate by increasing theratio of FFP to RBC [24] and platelets to RBC [25].This is thecurrent military guidelines in massive transfusion [9].

3.5. Antifibrinolytics. Crash 2 was a randomized controlledtrial, that was performed in 274 hospitals in 40 differentcountries and involved 20,211 patients to assess the effect oftranexamic acid on death, vasoocclusive events, and bloodtransfusion in trauma patients. The patients had to be abovethe age of 16 years, exposed to trauma, and had to haveevidence of bleeding in the form of systolic blood pressureof less than 90mmHg or a pulse rate of 110 beats perminute. 10,060 patients received tranexamic acid and 10,067were randomized to the placebo group. The results yieldedthat tranexamic acid reduced the mortality rate to 14.5%compared to 16% in the placebo group.The conclusion of thistrial was that tranexamic acid reduced the risk of death intrauma patients that were at risk of hemorrhage [26].

This conclusion was also echoed by Morrison et al. inthe Military Application of Tranexamic Acid in TraumaEmergency Resuscitation study (MATTER) in 2012. Thestudy was designed as a retrospective observational studythat looked at a cohort of 896 patients admitted with combatinjuries; the cohort was primarily divided into two groupsthe first included 293 patients who received TXA, and thesecond included the rest of the cohort who did not receiveTXA. Both groups were further subdivided based onwhetherpatients received massive transfusion (identified as 10 ormore units of PRBCs within 24 hours). The outcomes thatwere measured were mortality at 24 hours, 48 hours, and30 days, as well as the influence of TXA administration on

postoperative coagulopathy and the rate of thromboemboliccomplications. The results showed an absolute reduction ofin-hospital mortality by 6.5% in the TXA group comparedto the non-TXA group and an absolute reduction of 49%in the TXA massive transfusion group compared to themassive transfusion non-TXAgroup.Thiswas not completelycost-free though, as the study established that there wasa higher rate of thromboembolic events in the TXA andTXA massive transfusion groups compared to their non-TXA counterparts, but it was noteworthy that there were noincreased fatalities due to those events.

4. Hemorrhage Control and DamageControl Surgery

Despite taking all the above measures, if hemorrhage controlis not achieved these resuscitation efforts would be futile.Hemorrhage control should be achieved in a timely fashion,initially by temporary measures such as direct compression,hemostatic dressings, tourniquets or the application of pelvicbinders, and finally by definitive surgical control of the sourceof bleeding.

Temporary measures like the tourniquet, is well recog-nized and was first documented in 1674. Bellamy believedthat 38% of the patients in the Vietnam War that died fromextremity hemorrhage could have been salvaged by appro-priate application of a tourniquet [27]. Pelvic binders helpstabilize exsanguinating patient with open pelvic fracturesby reducing their pelvic volume thus increasing intrapelvicpressure providing a tamponade effect to the catastrophicbleeding that is associated with these injuries. Extremecaution needs to be taken with both of these methods asthey are both associated with grave complications due toprolonged application; tourniquets can cause neuropraxia,limb ischemia muscle injury, and compartment syndrome.On the other hand, pelvic binders can lead to skin necrosis.

Damage control surgery is a concept that emergedbecause the physiological derangements of hemorrhagicshock are more important than definitive surgery. It wasdescribed by Feliciano et al. as a 3-stage procedure in whichthe first is to control the bleeding, the second stage is wherethe patient is transferred to ITU for correction of the lethaltriad and stabilization, and the 3rd stage is for definitivesurgical repair [28].

5. Conclusion

Whilst massive hemorrhage continues to be a major causeof mortality, it is often reversible, and it can be adequatelymanaged by early identification of these patients and thesource of their bleeding, approaching them with (CABC)protocol and prevention and treatment of the lethal triad anddamage control surgery to stop the bleeding.

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper.

Emergency Medicine International 5

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Review Article Recent Advances of Hemorrhage Management …downloads.hindawi.com/journals/emi/2014/638956.pdf · Review Article Recent Advances of Hemorrhage Management in Severe