DCR in trauma differs from traditional approaches by attempting an earlier and more aggressive correction of coagulopathy and metabolic derangements and prioritising haemorrhage control.
Each of these is examined below. It is reasonable to apply individual aspects of this approach initially and escalate or step back as more information regarding injuries and response becomes apparent. For example, in a multiply injured patient with suspected abdominal and pelvic injury, but without initial indicators of massive blood loss, it is reasonable to rewarm the patient as required whilst adopting restrictive fluid resuscitation until more information is available. It should be ensured that blood products are available should they be required. Any deterioration should prompt the use of a Haemostatic resuscitation regime potentially with permissive hypotension whilst arrangements are made for surgical or endovascular haemorrhage arrest.
Permissive hypotension and restrictive fluid administration
Traditional fluid resuscitation in the polytrauma patient involved rapid infusion of large volumes of clear fluids in an attempt to rapidly restore circulating blood volume and blood pressure. It has become apparent that this approach has several potentially detrimental consequences. The premise of permissive hypotension is to keep the blood pressure low enough to avoid exacerbating haemorrhage by hydrostatic clot disruption whilst maintaining adequate end organ perfusion. Permissive hypotension and restrictive fluid administration are therefore reciprocal components of this approach; initial fluid administration is delayed or minimised and less aggressive resuscitative end points are used. In practical terms this means targeting systolic blood pressures of 70–90 or 50 mmHg mean arterial. This approximately equates to aiming for the restoration of a palpable radial pulse [
2,
11]. Such an approach decreases both the severity and incidence of dilutional coagulopathy, and as such compliments a strategy of haemostatic resuscitation [
11]. Second, this reduces fluctuations in, and elevation of, systolic blood pressure which may disrupt the premature blood clot forming in areas of injury causing further bleeding.
The concept of delayed fluid administration in trauma is not new. In the early 1990s a randomised controlled trial of immediate (pre-hospital) versus delayed fluid administration in patients with penetrating truncal injuries demonstrated decreased morbidity (including systemic inflammatory response syndrome, pulmonary oedema and thrombocytopaenia) and mortality in the delayed resuscitation group as well as a shorter hospital stay [
27]. The delayed administration group, who received no IV fluid prior to entering the operating room, had lower recorded blood pressures pre-hospital and in the emergency room. Further analysis of this data showed that such an approach might only be advantageous in those with specific injuries, particularly penetrating cardiac trauma, this subgroup benefited most from delayed fluid resuscitation. This study stimulated changes to resuscitative protocols, with consideration given to the timing of fluid administration and resuscitative end points [
2,
11].
Whilst having theoretical and practical merits, clear evidence to support permissive hypotension has not been entirely forthcoming. Animal studies appear to support this approach in models of simple exsanguinating haemorrhage and clinical work in other situations, particularly ruptured aortic aneurysm, has demonstrated advantages. Whilst this situation is likely analogous to simple vascular or visceral injury, the situation in trauma is often more complex, particularly in patients with head injury and multiple blunt trauma. In the head injured, the competing interests of maintaining cerebral perfusion pressure whilst keeping the patient from exsanguination can be extremely challenging, hypotension in such patients is generally poorly tolerated. Current advice is to avoid this approach in head injured patients. Further work is necessary to clearly delineate in what situations permissive hypotension should be rigorously applied but as with much of DCR decision making should be individualised [
11,
28,
29]. New technologies are allowing novel end points in resuscitation to be investigated which may prove more appropriate than blood pressure in the severely injured. These include near-infrared spectroscopy, measurement of skeletal muscle acid–base status and more sophisticated measures of global acid–base balance [
7].
In conclusion therefore, it would appear that restricting initial IV fluid administration in the severely injured should have advantages and the infusion of large volumes of crystalloid is no longer appropriate. In specific situations, permissive hypotension may also be of benefit, particularly in patients with severe haemorrhage from an arterial source. Great caution should be taken in those with concomitant head injury and further work is required to clearly delineate which patients might benefit the most from this approach [
11].
Haemostatic resuscitation and massive transfusion protocols
Better understanding of the mechanisms underlying coagulopathy in trauma has lead to a paradigm shift in management. Recent protocols attempt to prevent such states occurring in the first place or correct them very rapidly. In terms of restoring circulating volume alone, the type of fluid administered appears to have little consequence. Some advantages to the use of hypertonic saline exist in patients with traumatic brain injury [
11,
30,
31]. In general however, there are good reasons to avoid clear fluids and early administration of blood and blood products is generally recommended to replace all the constituents of whole blood from the outset. Recent evidence suggests that timely transfusion, can reduce blood product use overall [
7,
32]. The concept centres around the assumption that coagulopathy is present very early after severe injury and rapidly corrective interventions can improve outcomes [
2,
33]. This requires us to rethink our concept of massive transfusion and massive transfusion protocols. Massive transfusion has traditionally been defined as those patients requiring more than 10 units of red cells in 24 h. Management of coagulopathy was almost exclusively reactive and only instituted once the patient had received large volumes of blood. Clearly a DCR approach requires the recognition of patients with the potential to require large volume transfusion, this is discussed above [
11,
34].
Local protocols will vary but Haemostatic resuscitation aims to deliver a mixture of red blood cells (RBCs), fresh frozen plasma (FFP) and platelets in approximately a 1:1:1 ratio [
1]. This is known as balanced transfusion, administration of packed red blood cells being balanced with coagulation factor delivery. Without this, dilution of coagulation factors will exacerbate consumptive loss, this has the potential to rapidly result in a spiral of coagulopathy and worsening blood loss [
11]. Whilst such protocols have been found to reduce morbidity and mortality, [
35] the requirement for such large amounts of clotting products and the exact composition of this transfusion regime does remain controversial [
36]. An observational study recently demonstrated the early survival benefits of delivering clotting product to red cell ratios above 0.5:1 in patients with severe haemorrhage [
37]. Conversely, recent military evidence suggests that ratios of a low as 0.35:1 may be preferable [
38]. Clearly further work is needed to clarify the situation and it may be that patients with different injury patterns benefit from different regimes. Most major trauma centres have developed their own protocols based upon availability of blood products and local experience [
11].
The documented detrimental effects of red blood cell transfusion should also be considered in this context. Blood transfusion has been shown to induce derangements in the immune-inflammatory system with both systemic pro-inflammatory effects and increased infection reported. Volume of blood transfused has been demonstrated to be an independent risk factor for overall morbidity and mortality in trauma patients. Degradation of stored red blood cells during storage has been implicated with decreased red blood cell aggregation and increased release of inflammatory mediators [
9]. Further concern comes from the aggressive use of blood products in cases that initially appear to warrant a DCR approach but are subsequently found to be less severely injured than was thought. These patients may receive blood and blood products that were not required at all. The effect of these small volume transfusions is less clear and needs further investigation if the consequences of unnecessary use of blood products are to be understood [
39]. Currently therefore, a careful balance must be struck to avoid over zealous use of blood products. Recent evidence would suggest that massive transfusion is still associated with poor outcome and overall use of red blood cells has decreased over time, whilst that of clotting products has increased. This has been associated with a fall in overall mortality [
40]. It is important to consider that other factors might explain the observed improvements in outcome.
Advances in laboratory methods mean that when patients do suffer derangement to their clotting mechanism this can now be assessed more rapidly and accurately. Thromboelastography (TEG) provides users with a holistic overview of coagulation through the analysis of platelet function, clotting strength and fibrinolysis. With results available within 20 min, TEG can measure the function of the entire coagulation cascade including platelets, hence simplifying the diagnosis of coagulopathy and guiding further management [
2,
19]. Its speed and ability to simultaneously measure multiple aspects of coagulation offer major advantages over standard laboratory methods. It can be used to guide appropriate use of rFVIIa, identify hypercoagulable states and can identify patients at risk for thrombotic events, even when these patients are receiving deep vein thrombosis prophylaxis and have therapeutic concentrations of anti factor Xa [
20,
32]. However, TEG is still not widely available and some reliance on traditional methods of assessing clotting function remains [
11].
Rewarming
Though hypothermia is associated with poor outcome including mortality in multiple trauma patients, the benefits of rewarming remain unclear. Laboratory work has suggested that permissive hypothermia may be beneficial in certain situations, but this has not been demonstrable in clinical practice and early rewarming is still advocated [
41‐
43]. Where hypothermia has not been prevented, it should therefore be reversed. Rewarming may increase vasodilation of peripheral vascular beds, hence improving tissue perfusion, it is recommended that the torso is rewarmed before the extremities to prevent progressive hypotension as a result of this vasodilation. Rewarming can be carried out in the following ways:
1.
Passive external rewarming—achieved by warm blankets or increasing room temperature.
2.
Active external rewarming—through the use of forced air-warming devices and other heaters.
3.
Active internal core rewarming—warming administered fluids and potentially the use of heated oxygen. Warmed bladder and peritoneal irrigation, arteriovenous rewarming and even haemodialysis have all been successfully used in extreme circumstances. Such extracorporeal rewarming techniques are the most efficient, increasing body temperature at a rate of 4–5 °C per hour (compared to only 2 °C by the other aforementioned techniques) [
19].
No specific guidelines exist regarding techniques to employ in specific situations, it is important to take steps to prevent hypothermia worsening and identify such states when they occur. Where patients fail to respond to simple measures consideration should be given to more aggressive techniques. When hypothermia is persistent or relapsing, further investigations should be carried out to look for occult on-going haemorrhage [
11,
44].
Correction of acidosis
The ultimate treatment to reverse metabolic acidosis in the severely injured is the restoration of organ perfusion through volume replacement, permitting acid-base balance to normalise by homeostatic mechanisms. This may be difficult to achieve until haemorrhage is controlled, indeed such measures provide good endpoints to guide resuscitation and persisting abnormalities of acid-base balance should prompt investigation for on-going occult bleeding and hypoperfusion. Whilst it is possible to correct acid-base disturbances pharmacologically, this has more relevance where the cause includes base losses such as in diabetic ketoacidosis. Administration of sodium bicarbonate has been shown to cause the production of carbon dioxide, paradoxically lowering intra cellular pH and leading to a fall in the ionised calcium concentration which has implications for coagulation and cardiac function. Tris(hydroxymethyl)aminomethane leads to a similar effect by accepting hydrogen ions and it’s use has been reported in trauma patients [
23]. However, it is widely accepted that correction of metabolic acidosis in these patients is best achieved through aggressive blood and blood product administration alongside appropriate use of vasopressors until the other components of the lethal triad can be addressed [
11]. No studies have shown any advantage to pharmacologic management of acidosis in the trauma setting and there are currently no specific guidelines to address the specific reversal of acidosis in the trauma patient [
11].
Early haemorrhage control
Experience dealing with patients suffering from haemorrhagic shock has demonstrated it is often not possible to restore normal physiology until haemorrhage has been arrested. Indeed, until that point many patients continue to deteriorate despite resuscitative efforts [
15]. The speed with which haemorrhage control is achieved is therefore critical. The focus of major trauma protocols on rapid delivery of patients to facilities that allow this are not misplaced [
45,
46].
Simple interventions that reduce bleeding before definitive care is available should form part of trauma care resuscitative protocols. Examples of this include the use of pelvic binders, application of compressive dressings to actively bleeding wounds and the use of tourniquets in more severe injuries where this is not effective [
47]. These measures should be taken as soon as possible, increasingly in the pre-hospital setting. Tourniquets render the limb ischaemic and may lead to nerve injury, these should therefore be employed with caution. It is important that everything possible is done after application to deliver the patient expediently to appropriate definitive care facilitates. In cases of devastating limb injury, the arrest of life threatening haemorrhage must outweigh any concerns about limb salvage [
48]. Temporary aortic balloon catheter tamponade is seeing a resurgence in use [
53]. This can be used as a temporising measure in patients with catastrophic abdominal, pelvic and lower limb haemorrhage. Whilst there are significant potential complications and consequences, when simple interventions fail or are not possible, this provides a valid alternative [
1]. Many such interventions have been adapted from military practice and further developments are still being seen [
49].
The use of tranexamic acid (TXA) in the major trauma setting has been found through multiple studies to reduce the mortality associated with blood loss when administered during resuscitation [
27]. TXA functions by blocking the lysine-binding sites on plasminogen and hence inhibiting fibrinolysis, resulting in inhibition of clot degradation [
50]. The CRASH-2 trial, showed that the use of TXA could reduce mortality rates associated with exsanguinating haemorrhage by 15 % with few complications. To have such an effect it must be given within 3 h of injury as an immediate intravenous dose of one gram followed by a further 1 g infusion over 8 h. It therefore should form part of early resuscitative protocols. The use of other pro-coagulant therapies remains controversial. Early administration of rFVIIa has been associated with decreased red blood cell use in bleeding patients [
32,
51]. Other research has shown a decrease in the transfusion requirements associated with its early use as an adjunct to massive transfusion. However, clinical application remains debatable, with questions remaining regarding the appropriate timing of delivery, selection of patients and the simultaneous use of additional blood components to enhance its effect [
32]. The drug appears to be less effective in acidotic patients but remains effective in all but the most severely hypothermic. Recent evidence has suggested an increased risk of subsequent thromboembolic complication following its use [
9].
Surgical haemorrhage control is still regarded as the gold standard for the majority of patients and should be rapidly available where required. Open surgery comes with a cost in terms of physiologic derangement however and modern alternatives are increasingly being employed. Endovascular management by interventional radiology allows selective embolisation of bleeding vessels and organs and stent grafting of major and peripheral vessel injuries without many of the specific risks of open procedures [
52]. It is often definitive in nature. Temporary intravascular shunts can be life and limb saving by bridging damaged vessels and maintaining blood flow, hence reducing acute haemorrhage and critical warm ischaemia times of distal organs and limbs [
1]. As timing of interventions is so critical, interventional radiology facilitates need to be rapidly available 24 h a day to be effective and, this requires organisational development and investment in major trauma centres [
54]. It is important to balance decision making and remember that not all bleeding can be controlled non-operatively in a timely manner [
55]. Multidisciplinary input is critical and the application of some of these techniques remains controversial [
24,
56].