Current concepts, which effect outcome following major hemorrhage.

There are a multitude of factors, which effect outcome following major trauma. The recent conflict in the middle-east has advanced our knowledge and developed clinical practice, here within the UK. This article reviews the current and emerging concepts, which effect the outcome of patients sustaining major hemorrage in trauma.

INTRODUCTION

Major hemorrhage as defined as “the loss of a patients total body volume in less than 24 h,” is a condition which, if allowed to continue, will inevitably result in death. Second to neurological injury, it is the largest cause of death in the trauma patient.[1]"Successful resuscitation" may have several different meanings in this circumstance. It can be defined as “stabilized within given physiological parameters;” however, it is understood that there is a delayed insult following the trauma, which caused the major hemorrhage. As I will discuss, although this “second wave” insult doesn't occur until around the 3rd day following initial insult, resuscitation should not be considered successful until after this phase has passed.

A multitude of factors will influence the overall outcome, which can be broadly divided into three categories: Circumstances prior to the trauma sustained, events at the time of injury and factors following injury.

Pre-injury

These are the factors put in place by society and optimize chances of a successful outcome.

With the consideration of trauma as a disease entity, it carries a public health and epidemiological component and thus we can influence, not only the prevention of major hemorrhage, but in improving our ability to impede its natural progression. It has been argued that the biggest intervention is to prevent the injury itself as the majority of deaths from trauma are due to irreparable causes;[1] however, this is out with the context of this article.

Many of the factors, which will influence our success in the resuscitation of patients with major hemorrhage, rely on environmental and pre-existing infrastructure. In the environment of the developed world, key factors such as extrication and retrieval, having the public first aid trained, all serve to minimize the severity of bleeding and optimize transfer times to hospital services.

From retrospective analyzes,[123] we know that areas, which we persistently fall short in preventable causes of death, are failure to recognize sick patients, airway issues and hemorrhagic shock. Therefore, the implementation of trauma networks, with major trauma centers and “spoke” trauma units, with rapid access to specialist services from any presenting hospital, should further see patients having definitive treatment for their major hemorrhage.[3]

It is futile to have the resources to successfully manage all major hemorrhage in a trauma center if prompt recognition and adequate initial impedance or cessation of bleeding cannot be achieved out with this setting. The successful initiation of ambulatory care ensures hemorrhaging casualties access definitive care.

Peri-injury

These are the factors, which although largely cannot be influenced, do ultimately determine the outcome.

The premorbid condition of patient plays a significant role in the outcome. Patients with multiple co-morbidities, specific medications and gender all influence the prognosis of the bleeding patient. Although the severity of co-morbidities in the form of acute physiological and chronic health evaluation II (APACHE II) scores have been associated with higher mortality in both trauma[4] and gastrointestinal hemorrhage,[5] there is no available evidence for traumatic hemorrhage. Patients on beta blockers prior to injury will ultimately have a poor outcome[6] as they fail to mount a sympathetic response to blood loss. The female phenotype is one factor, in which we cannot not change and is associated with a favorable outcome.[78]

The mechanism of injury, energy expended and thus severity of injury understandably plays a large part in the outcome of injury. “Major hemorrhage” may have a defined diagnosis, but there remains a spectrum of the severity of injuries which are causative. The advanced trauma life support (ATLS) manual teaches that death from injuries fall into primary, secondary and tertiary phases, where primary injuries are essentially an insurmountable insult where patients exsanguinate within the moments, for example, transection of the great vessels from a sudden deceleration injury. However, a major hemorrhage where a patient sustains a much slower arterial bleed, for example, an avulsed mesenteric artery may be an occult injury still meets the above definition. Both of these circumstances meet the criteria for “major hemorrhage,” but it is the mode of injury, which allows time to intervene and thus the chance to succeed in the act of resuscitation.

Along with major hemorrhage itself, there are frequently associated injuries, albeit of a lower “resuscitative hierarchy,” which will impede overall success in casualty resuscitation. Of the 753 patients who died in one retrospective series,[1] 21% had both shock and central nervous system damage.

The environment in which the injury occurs has an overall predictive factor in the outcome. A low body temperature on presentation is associated with higher rates of mortality, for any given injury severity score, independent of hypotension.[9] The negative impact of ongoing hypothermia will be discussed later.

Post-injury

The events following injury are those, which we have most influence over and as thus are the interventions most easily studied.

Success step 1: Recognize the bleeding

In order to successfully treat a patient with hemorrhage, it is logical that recognition of ongoing bleeding is the priority. However, multiple retrospective case series have identified that this is an area which is persistently underappreciated.[23] As thus, the clinician should always have a low threshold for further investigation to exclude ongoing hemorrhage. The five sources to be considered in major hemorrhage are chest, abdomen, pelvis, long bones and external.[10]

Success step 2: Stop the bleeding

Once the sources of major bleeding have been identified, prompt cessation of catastrophic hemorrhage is accepted as the first priority as part of a “battlefield resuscitation” hierarchy.[111213] The particular method of cessation of hemorrhage will depend on the source of the bleeding, the experience of the clinician and the tools available in that setting. Fast and effective methods should be available in any resuscitation area and include tourniquets, pelvic binder apparatus and long bone splinting.

Should timely arrest of catastrophic hemorrhage not be possible, “damage control surgery” should be arranged. This is the rapid surgical cessation of bleeding, which may coincide with diagnostic surgery, e.g., laparotomy. It is not necessarily, definitive management and should be used to stop life-threatening hemorrhage. Ongoing diagnostic uncertainties can be addressed by radiological interventions, e.g., computed tomography scans.

Success step 3: Supportive measures

Whilst cessation of catastrophic hemorrhage is underway, a policy of damage control resuscitation should then be adopted. This can be seen as an adjunct to the follow through assessment using the ATLS approach. It has two distinct features; permissive hypotension and hemostatic resuscitation.

Permissive hypotension is a technique, where in circumstance of major hemorrhage (with the exception of coexisting head injury), resuscitation of blood pressure should be carefully tailored to aim for a systolic pressure of 90 mmHg. This can also be crudely estimated as the pressure required for maintaining a radial pulse. The purpose of this is to protect any crucial clots, which may have been formed and not let an increased systolic pressure compromise this. The technique has been criticized as to its effect on end organ perfusion; however, a recent albeit animal study would indicate otherwise.[14] Clinical trials have shown early survival benefits, when control of hemorrhage is sought, prior to commencing aggressive fluid resuscitation with a target of physiological blood pressures.[1516]

Hemostatic resuscitation refers to the type of intravenous fluid therapies we use to maintain the above blood pressures. The principle of resuscitation of patients with ongoing hemorrhage is firstly to maintain any clots possible and minimize ongoing bleeding due to consumption coagulopathy and secondly to maintain end organ perfusion. The value of “non-physiological” fluids (i.e., crystalloids and colloids) is therefore very limited. The best fluid as indicated primarily from military studies and reviews, is blood products.[171819] If blood products are used in a 1:1:1 ratio of packed red cells:fresh frozen plasma: Platelets, the oxygen carrying capacity of the blood reaching the end organs is maximized. The use of blood products also addresses issues with arising “consumption” and dilutional coagulopathies. The recognition of requirements for prompt availability of blood products[20] has led to the widespread uptake of major hemorrhage protocols or massive transfusion protocols.[21]

Both of these techniques complement the present ATLS approach standard, which serves to maintain ventilation, oxygenation and end organ perfusion; however, these processes will ultimately fail, should rapid cessation of hemorrhage not occur.

This cautious resuscitation, during or following the control of catastrophic hemorrhage, will lead toward an initial success. However, I would argue that this alone is not “successful” resuscitation. This initial battle will see the patient through the early minutes to hours, but will be short lived if the impending second insult is not prevented; this is known as the lethal triad.

Success step 4: Prevent the lethal triad

The lethal triad consists of:

Hypothermia

Acidosis and hypoperfusion

Coagulopathy of trauma

These will be discussed in turn, but the essence of management of all three critical responses, are to restore normal core temperature, tissue perfusion and coagulation. Where all three are present, the prognosis is poor.[2223]

Hypothermia

The role of hypothermia as a predictor of mortality in trauma patients has been repeatedly observed.[92425] The environment plays a large role in the initial core temperature is not entirely accountable. Hypothermia, if allowed to persist, has significant consequences primarily due to its effects on coagulation. Secondarily, it has a global effect on other enzymatic activities, including drug metabolism[26] and cardiac stability.[27] As such, the resuscitation method used needs to include active warming of the cold patient (e.g., warm blankets and mattresses) and not iatrogenically cooling them (e.g., warm blood products, minimal surgical exposures). One recent study indicated that during the massive transfusion, a temperature below 34° was the most important predictor for mortality, even when adjusting for coagulopathy.[28] It must be clear then that in order to successfully prevent hypothermia and the associated mortality, these techniques must be adopted.

Acidosis and hypoperfusion

With the insult of trauma, the subsequent inflammatory response drives a catabolic state. The co-contaminant presence of major hemorrhage, leads to hypoperfusion, forcing tissues into anaerobic respiration. This anaerobic respiration results in production of acidotic bi-products, consumption of acid-base buffers and systemic acidosis. This acidosis, particularly when prolonged is associated with a poor outcome,[2329] at least in part due to the enzymatic inhibition of clotting factors and platelet function. The most effective way to treat the acidosis is to address the hypoperfusion driving it and thus once again, the most important factor is the cessation of hemorrhage and supportive management (in particular with oxygen carrying resuscitation fluids).

Coagulopathy of trauma

The prevention of ongoing hemorrhage hinges on the rapid formation and adequacy of clot formation. “Coagulopathy of trauma” is a phenomenon, occurring due to several causative factors and results in decreased coagulation function. These factors have been revealed as but not limited to, dilution, acidosis, hypothermia,[30] hyper fibrinolysis,[31] and activation of protein C[32] (due to hypoperfusion and tissue trauma).[3334] Unfortunately, the coagulopathy forms a positive feedback loop, encouraging ongoing hemorrhage, further hypoperfusing tissues and exacerbating acidosis.

Diagnosis of this proves to be particularly troublesome, as routinely available laboratory “coagulation studies” (i.e., prothrombin time and partial thromboplastin times) do not detect such a coagulopathy. However, emerging tests such as thromboelastography may play a role.[32] Although international normalized ratio (INR) is an insensitive test, one retrospective case series describes 0% survival if INR is greater than 3.2 on presentation.[23]

In order to address this coagulopathy of trauma, although the tissue trauma cannot be reversed, we can aim primarily to stop hemorrhage. Whilst the most appropriate method of achieving this is underway, there are other temporary impeding factors which can be implemented. Tranexamic acid has been shown to have the benefit in significantly hemorrhaging patients, presumed to be due to its effect on fibrinolysis.[35] Other therapies have been hypothesized; however, remain to have sufficient evidence/economic viability to become implemented in mainstream practice; recombinant Factor VIIa,[36] calcium,[15] oestrogen.[737] These chemical therapies, along with the above-mentioned techniques in minimizing hypothermia and acidosis, which also exacerbate poor coagulation, should be implemented to minimize the ongoing effects of traumatic hemorrhage on systemic coagulation function. It is worth noting that the therapies mentioned here, do associate with the techniques of hemostatic resuscitation described previously.

Delayed success following injury

Attending physicians have a duty to think of the patient, not only in the acute resuscitation phase, where physiologically stable parameters are achieved, but in their continued care. The nature of sustaining major hemorrhage will often have associated complex injuries, which will require definitive surgical care. There is an increasing awareness of the systemic response to trauma and evidence continues to emerge indicating that a second insult, e.g., surgical intervention, between days 2 and 5 have significantly poorer outcomes, particularly due to systemic inflammatory response syndrome, acute lung injury, acquired respiratory distress syndrome and multi-organ dysfunction syndrome.[3839] It could be argued that we are not successful resuscitation from major hemorrhage is not complete until the patient is curatively managed and their risk of systemic inflammatory syndrome is minimized.

Finally and perhaps more anecdotally, efficient teamwork and communication are key in obtaining successful outcomes. The factors that have been mentioned are essential and well-evidenced, to achieve a successful resuscitation from major hemorrhage; however, that no individual can optimally implement all of the above alone. It therefore falls to a number of individuals, with a common goal, each with their own recognized role, to produce a successful outcome. These may be several individuals in a single resus room or a multitude of individuals communicating through a trauma network.

CONCLUSION

Although major hemorrhage may vary in severity and the definition of success can be debated, patients sustaining major hemorrhage will not be successfully resuscitated by any definition unless two broad factors are addressed; stopping the bleeding and supporting the bleeder. All the aforementioned factors are essentially refined techniques of prompt hemorrhage control, providing methods, in which catastrophic physiological manifestations can be minimized.

There are many factors, which have been set up in society to optimize outcome of trauma as a disease, which not only prevent trauma, but optimize recognition and transfer to areas of higher care. At the time of injury, there are several aspects, which will limit our ability to successfully resuscitate a bleeding patient. The main priority of resuscitation is to stop bleeding by first aid or surgical measures, whilst being aware of processes causing coagulopathy. Ongoing success will depend on the ability to prevent the lethal triad and delayed inflammatory insults.