Severe trauma induces massive changes of the physiological state by alteration of metabolic pathways and activation of the innate immune system [
1‐
5]. The posttraumatic metabolic changes are characterized by hypermetabolism with increased energy expenditure, enhanced protein catabolism, insulin resistance associated with hyperglycemia, failure to tolerate glucose load, and high plasma insulin levels ("traumatic diabetes") [
1,
2,
6‐
11]. The alterations of the physiological metabolic pathways leads to the development of hyperglycemia and metabolic acidosis with hyperlactatemia [
10,
12]. The increased oxygen demands of the polytraumatized patient further aggravate the hypermetabolic state by enhanced mitochondrial oxygen utilization [
1,
10,
13,
14].
Metabolic changes after trauma were described more than six decades ago by Cuthbertson (
Lancet 1942, 1:433–437) and characterized as occurring in two different phases, termed the
"ebb" phase and the
"flow" phase (table
1). The
"ebb" phase is initiated within minutes after trauma and persists for several hours after the initial insult. It is characterized by a decline in body temperature and oxygen consumption, aimed at reducing posttraumatic energy depletion. However, the brief duration of this phase limits its clinical relevance. The
"flow" phase, which occurs after compensation of the state of traumatic-hemorrhagic shock, is associated with an increased metabolic turnover, activation of the innate immune system and induction of the hepatic acute-phase response [
2,
3]. This results in an increase of the catabolic state with a significantly increased consumption of energy and oxygen [
2,
10,
13,
14]. The amount of oxygen consumption and demand in patients with traumatic-hemorrhagic shock can be calculated using a formula described by Nunn and Freeman in 1964 (table
2) [
15].
Table 1
Metabolic changes after major trauma.
Decreased body temperature | Increased body temperature |
Decreased oxygen consumption | Increased oxygen consumption |
Lactate acidosis | Negative nitrogen balance |
Increased stress hormone levels | Increased stress hormone levels |
Decreased insulin levels | Normal to increased insulin levels |
Hyperglycaemia, insulin resistance | Hyperglycaemia, insulin resistance |
Gluconeogenesis | Gluconeogenesis |
Increased substrate consumption | Proteinolysis ("autocannibalism") |
Hepatic acute-phase response | Lipolysis |
Immune activation | Immunosuppression |
Table 2
Calculation of available oxygen (O2av in ml/min) in bleeding polytrauma patients according to the formula described by Nunn and Freeman in 1964 [15].
O2av= CO × SaO2 × Hb × 1.34 |
In addition to the acute hypermetabolic state, the systemic inflammatory cascade is initiated as a consequence of trauma, as characterized by the release of pro-inflammatory cytokines and activation of the complement system [
4,
5,
16,
17]. The bacterial translocation caused by the traumatic-hemorrhagic shock may further aggravate these metabolic sequelae and inflammatory response [
5,
10,
17‐
19], but this issue remains controversial [
20]. Additionally, the frequent use of vasoactive drug therapy for hemodynamic resuscitation in traumatic-hemorrhagic shock has a profound impact on metabolism and organ energy status of the injured patient [
1,
10]. Most severely injured patients require inotropic support to promote hemodynamic stability. For example dopamine, a commonly used epinephrine precursor, leads to depression of pituitary function and inhibition of prolactin and growth hormone production [
21]. Thus, the use of vasoactive drugs further promotes catabolism by reducing serum levels of anabolic hormones. In contrast, endogenous catecholamines, cortisol and glucagon levels are highly elevated after trauma, leading to increased energy substrate mobilization [
3,
6]. Interestingly, studies in severe burn patients have shown that exogenous insulin administration can attentuate protein catabolism as indicated by an increase in protein synthesis [
11,
22,
23]. Proteinolysis of skeletal muscle and glycolysis are increased with the aim to provide the substrates for the hepatic gluconeogenesis and the hepatic biosynthesis of acute-phase proteins [
2,
24]. The metabolic state is reoriented towards supporting the organism's immune response and wound healing at the cost of enhanced proteinolysis of skeletal muscle [
1,
2]. In addition, the physical and psychological stimulation of the neuroendocrine axis through fear, stress, pain, inflammation and shock increases the caloric turnover significantly above the baseline situation in healthy individuals [
6,
10]. This leads to increased serum levels of catabolic hormones, such as cortisol, glucagon and catecholamines, and decreased levels of insulin causing the posttraumatic catabolic diabetic phase [
10,
11,
25]. In contrast, the phenomenon of "occult adrenal insufficiency" has been demonstrated to occur in severely injured patients in the ICU, as defined by a serum cortisol below 18 mg/dL [
26] or below 25 mg/dL [
27] in different publications. However, up to present the clinical implication of posttraumatic adrenal failure with regard to patient outcome remains controversial [
26‐
29].