During the early posttraumatic phase, longstanding ­volume deficit and the hypovolemic-hemorrhagic shock are the most deleterious alterations that ­determine ­subsequent development and incidence of potentially ­devastating consequences. The most prominent pathophysiologic consequence is microcirculatory impairment, resulting from hypovolemia and subsequent sympathic-adrenergic precapillary vasoconstriction. These changes are accompanied by nitric oxide-­induced vasodilation that in turn causes shunts and impairs nutritive capillary perfusion, explaining heterogenous capillary perfusion. As a consequence, impaired organ perfusion with evolving tissue acidosis and lactate production with sustained increase in endothelial permeability will aggravate the underlying condition as a result of progressive edema formation. In case of persisting ischemia, degradation of energetically rich phosphates in conjunction with free oxygen radical induced mitochondrial damage will result in irreversible structural and functional cell injury. The degree of the damage strongly depends on the extent and duration of the underlying hypovolemia. Reperfusion injury resulting from restored perfusion is feared for its generation of highly toxic free oxygen radicals. These, in turn, are known to damage cell membranes by peroxidation of cell membrane lipids, accounting for resulting vasoplegia and swelling.

The criteria defining diagnosis of hemorrhagic shock have been refined over the years. The early definition of hemorrhagic shock consisting of a lost blood volume of 1–2 l [15] was substituted by the systolic blood pressure <90 mmHg [16] and the vital parameters were used to estimate prognosis [17]. Based on the observation that the cardiovascular system is able to maintain an adequate systolic pressure by a compensatory increase in heart rate despite a progressive volume loss, the so-called shock index was introduced [18]. The shock index consists of an easy-to-calculate formula dividing systolic blood pressure by heart rate. A shock index <1 is highly suggestive of hemodynamic instability resulting from hypovolemia. In addition to the absolute values, duration of shock is also of crucial importance. In this context, a threshold of 70 min appears to be clinically relevant [19, 20]. Additional predictive factors are heart and breathing frequency upon admission to the hospital [21–23]. Especially in younger patients with well preserved compensation mechanisms macrocirculation (blood pressure, heart frequency, filling pressures) may appear “normal” although microcirculation still is impaired (i.e. serum lactate concentrations 12 hours after admission). This condition is referred to as “occult” hypoperfusion and is accompanied by an increase in infectious and other complications [24–25].

Diuresis can also be used as a parameter to estimate volume depletion, provided urine production and urine release are not hampered by pre-existing renal disease and injuries to the urinary tract system.

The overall accepted goal is to swiftly restore sufficient circulation, maintain hemodynamic stability by improving organ perfusion and microcirculation using volume administration via large bore catheters, and by reducing further temperature loss. The primary goal is quantitative restoration guided by hemodynamic parameters, restoration of peripheral perfusion, restitution of sufficient diuresis (0.5–1 ml/kg body weight, >2 ml/kg body weight in case of rhabdomyolysis, that is, creatin kinase (CK) >5,000 IU/ml), and reduction or normalization of arterial lactate, pH, and base excess values. In this context, lactate >2.5 mmol/l and ­negative base excess that has a higher negativity than – 8 mmol/l represent important threshold values of acidosis (pH  <  7.2), and negative base excess values were shown to significantly predict outcome in traumatized patients [26].

Because low pH values did not unanimously correlate with the outcome, pH alone should not be used as a basis to limit therapeutic interventions. Predictive sensitivity is increased by the presence of other factors such as blood loss, hypothermia, increased lactate levels with negative base excess, and coagulopathy.

Perhaps more important than the absolute values is how long it takes to normalize lactacidosis and negative base excess during adequate treatment consisting of volume management, hemodynamic support, and rewarming. Persisting negative base excess and lactacidosis exceeding 24 h is clearly associated with significantly increased morbidity and mortality [24, 27]. Lactate-guided volume management was associated with significant reduction in mortality despite absence of improved signs of vasopressor-driven hemodynamic stabilization determined by measurements using the pulmonary artery catheter [24, 28].

Qualitative volume replacement consists of substituting oxygen carriers (hemoglobin), factors of hemostasis (plasmatic coagulation factors, platelets), and correcting existing intravascular volume depletion. While a hemoglobin target of 9–10 g/dl had been targeted for many years, a lower hemoglobin count of approximately 7 g/dl was shown to improve outcome [29]. In this context, bedside point of care analysis of hemoglobin as well as glucose and lactate have significantly influenced morbidity and mortality and have reduced the number of resources consumed [30].

Loss of coagulation factors and platelets as a result of uncontrolled hemorrhage, as well as dilution of coagulation factors and platelets resulting from excessive fluid replacement and reduced ionized calcium concentrations, hypothermia, and acidosis, in conjunction with the type and extent of injury (e.g., brain) all contribute to disturbed hemostatic mechanisms [31]. Contrary to the diffuse intravascular coagulopathy which includes thrombus formation we are confronted with traumatic intravascular coagulopathy (TIC) in which coagulation is hampered. In this context, the clinical picture of coagulopathy is not always reflected by laboratory values in a timely fashion. It is critical to base the subsequent administration of various coagulation factors on clinical judgment that, in turn, is strongly influenced by individual experience. Obvious bleeding requires immediate correction during the process of obtaining laboratory values that can take up to 60 min before results of plasmatic coagulation can be integrated into the fine-tuning of correcting TIC. Bedside analysis using thrombelastography may aid in faster and differentiated decision making. It is important to keep in mind that other elements apart from the concentration of coagulation factors and platelets are responsible for hemostatic failure [32]. An important devastating factor is underlying hypothermia that will disturb the entire coagulation cascade [33]. Inhibition of enzymatic reactions is reflected by prolonged prothrombin- and thromboplastin time during hypothermia even when the measured coagulation factors are normal. Another important technical detail is that functional coagulation tests are performed at 37 °C and not corrected for the actual temperature of the injured patients. This, in turn, will underestimate the extent of disturbed coagulation [34]. In addition, platelet function is impaired by hypothermia via reversible, temperature-dependent disturbance of thromboxane B2 production that will prolong the hemorrhage time [35]. Additional changes of the enzyme kinetics will delay initiation and propagation of platelet aggregation despite adequate platelet substitution [36]. This, in turn, explains the often seen poor correlation between platelet count and progressive bleeding in patients receiving massive transfusions and can be seen as an indication for platelet transfusion despite normal platelet count [37].

The following additional and preexisting coagulation disorders can aggravate the acute coagulation disorder: Release of tissue factors because of severe TBI, pharmacologic anticoagulation, functional disturbance of platelet functions due to pharmacological and endogenous (hepatic and renal insufficiency) influences, hemophilia and deficit in von Willebrand factor. Moreover, consumption of factors due to massive transfusions (MT) and underlying hemorrhage resulting in low 2,3-DPG concentrations, low activity of factors IV (ionized calcium), V, VIII, and XIII, low fibrinogen levels, dilution thrombocytopenia, functional platelet disturbance, hypothermia, and acidosis have to be taken into consideration. Massive transfusion is thought to increase citrate concentration which chelates calcium that in turn will impair the coagulation cascade and is also believed to increase protein C that can inhibit plasminogen activator inhibitor, thereby resulting in sustained activation of plasminogen; which can generate hyperfibrinolysis, and in turn, promote the development of microvascular hemorrhages at the mucosa, injuries, puncture sites, and sutures. Microvascular hemorrhages generally result from dilution coagulopathy and an increased consumption of hemostatic factors that can lead to diffuse bleeding that cannot be managed surgically. Consequently, the diagnosis of such a hemostatic disturbance must be made early to allow timely correction and prevention of aggravated complications. The diagnosis of such a hemostatic disturbance strongly depends on the vigilance and experience of the treating physicians in all involved disciplines.

Contrary to dilution coagulopathy, the combination of consumption and dilution coagulopathy will result in more severe disturbances seen in laboratory parameters reflected by a larger decrease in platelets, international normalized ratio, and fibrogen, as well as a pronounced prolongation of the activated ­prothrombine time (aPTT). Therefore, in patients requiring massive transfusion use of fresh frozen plasma (FFP) in order to provide a balanced set of activating and inhibitory coagulation factors (including Factor V) still may be indicated particularly because blood donors carrying a higher risk for induction of transfusion-related lung injury have been identified and excluded from FFP donation. This procedure is supported by a meta-analysis published in 2010 reporting that plasma infusion at high plasma: RBC ratios in patients undergoing MT was associated with a significant reduction in the risk of death [odds ratio (OR), 0.38; 95 % confidence interval (CI), 0.24–0.60] and multiorgan failure (OR, 0.40; 95 % CI, 0.26–0.60) [38]

Correction of disturbed coagulation occurs by supplementing the different components. To date there has been considerable controversy regarding correction strategies of impaired coagulation in trauma patients. Whereas in slight or moderate bleeding, targeted supplementation of coagulation factors monitored by means of thrombelastography or preferably thrombelastomety (i.e. ROTEM) as point of care testing (POCT) might be feasible, in severe and life-threatening bleeding this approach might fail because of the time lag between sample drawing and availability of the results. Therefore, as mentioned above use of fresh frozen plasma (FFP) in severe bleeding still is an important option in order to achieve hemostasis. However, certain factors, frequently fibrinogen and sometimes factor XIII must be additionally supplemented because provision by FFP alone might be insufficient. Factor XIII is a protein responsible for stabilizing the formation of a blood clot. In the absence of Factor XIII, a clot will still develop but it will remain unstable. If Factor XIII is deficient, the tenuously formed clot will eventually break down and cause recurrent bleeds. Suspicion in Factor XIII deficiency should be raised if in a patient with clinical relevant bleeding (i.e. diffuse micro vascular bleeding without clearly identifiable bleeding source if FXIII-activity is below 60 %). In such circumstances administration of FXIII in a dose of 30 IE/kg BW may be indicated. Furthermore, in trauma patients a positive influence on the development of the systemic inflammatory response syndrome (SIRS) could be demonstrated [39, 40, 41].

Apart from possibilities of uncontrolled bleeding, trauma patients are exposed to a considerably elevated risk of thromboembolic complications in part because of an imbalance of pro- and anticoagulating factors and an increase in pro-coagulant factors (i.e., fibrinogen) resulting from a post-traumatic acute phase reaction.

Venous thromboembolic complications lead to a significant increase in morbidity and mortality and present in two forms:

A prophylaxis in trauma patients is important because clinical investigations for establishing a diagnosis are not sensitive enough. In a meta-analysis of 73 studies, however, it was found that none of the prophylaxis used was superior to another, even compared with no prophylaxis. Moreover, spinal injuries, spinal cord injuries, and age were identified as major risk factors for thromboembolic complications [42]. A prophylactic placement of caval filters may reduce the incidence of lung embolism [43, 44]. Our own experience demonstrates that cava filters can temporarily be inserted and removed in a high percentage of patients, and that they provide reliable protection against clinically relevant lung embolism [45–47].

The choice of the type as well as of the amount of volume substitutes is still a matter of controversy. Young, healthy, trauma patients generally tolerate large amounts of intravenous fluids. In elderly patients, on the other hand, fluid and sodium overload may induce congestive heart failure, impaired blood–gas exchange, and hypoxia leading to the classic day 3 myocardial infarction and increased mortality, particularly if they are already suffering from a preexisting heart condition or renal insufficiency [48, 49].

It must be stressed that the classic 0.9 % sodium chloride solution is somehow toxic because it leads to hyperchloremic and dilution acidosis that exacerbates the existing acidosis in patients [48, 50, 51]. If the situation goes unrecognized, the attempt to correct the acidosis with additional fluid replacement will lead to a volume overload, with all its consequences [44, 52]. Additional unwanted effects of pure crystalloid fluid replacement are the decrease of cardiac output [53] and stroke volume by as much as 20 % even if adequate end diastolic pressure is achieved [44]. Furthermore, it has been shown that after pure crystalloid infusion – as opposed to higher concentration hydroxy ethyl starch – higher concentrations of pro-inflammatory cytokines, a depression of peritoneal macrophage function, and a higher expression of adhesion molecules can be found [54].

Patient’s microcirculation is very vulnerable to become compromised during the acute phase. Once a SIRS is induced, fluid overload and edema potentiate capillary leak leading to a local loss of control of inflammatory mediators and an increase of edema [55]. Furthermore, volume substitution with crystalloids alone leads to a reduced colloidosmotic pressure by up to 50 % with a consecutive fourfold increase of pulmonary transendothelial flux. Corrective administration of colloid fluids will consecutively reduce inflammation and edema [56–58].

In summary, volume expansion will improve cardiac output to a certain point via the Starling mechanism. Beyond that point it will, however, worsen cardiac function and promote edema formation, particularly if based solely on crystalloids [59]. Therefore, monitoring of stroke volume and cardiac output before and after fluid challenge is a more reliable alternative than assessing heart frequency and blood pressure alone [60–62].