Background
In-hospital hypo- and hyperglycaemia are known to be predictive for outcome in several acute and critical diseases [
1‐
3], but especially trauma patients seem to be more prone to poor outcome than are other critically ill patients due to both hyperglycaemia and hypoglycaemia [
4‐
6]. Survival of trauma patients with out-of-hospital cardiac arrest is still low [
7].
There is little data about the association between pre-hospital blood glucose concentration and dysrhythmias or cardiac arrest in trauma patients. The aim of this trial was to analyse the association between pre-hospital blood glucose concentrations and documented cardiac rhythms in trauma patients following arrival of the emergency physician. We particularly focused on the association between cardiac arrest and return of spontaneous circulation (ROSC) among pre-defined blood glucose levels. This information, in addition to vital parameters, could be helpful since measurement of blood glucose is simple, rapid, and inexpensive and may complement clinical assessment of patients at increased risk at the accident site.
The primary outcome of this study was the level of blood glucose observed during various cardiac rhythms in adult trauma patients. Secondary outcome parameter was blood glucose and its association with the rate of cardiac arrest and ROSC on scene. In addition, we also evaluated the predictive value of blood glucose in trauma patients who suffered cardiac arrest during emergency treatment.
Discussion
In this retrospective analysis of 18,879 trauma patients we demonstrate that prehospital dysrhythmia was associated with significantly deranged blood glucose concentrations. Patients with cardiac arrest presented with blood glucose concentrations in a U-shaped manner. This was especially evident in polytraumatised patients ≤40 years with either hypoglycaemia (32%) or hyperglycaemia (15%). Furthermore, the rate of ROSC correlated positively with initial blood glucose levels.
In cardiac arrest patients with high-frequency rhythms such as tachycardia or ventricular fibrillation we observed significantly higher blood glucose levels than in patients with pulseless electrical activity and asystole. To put it another way, 77.4% of cardiac arrest patients with hypoglycaemia (≤4.2 mmol/L) presented with asystole or pulseless electrical activity, whereas only one patient presented with ventricular fibrillation. The heart relies primarily on augmented glucose utilisation to meet energetic needs for force generation. Increased heart work, usually elicited by catecholamines, increases carbohydrate oxidation because of activation of the pyruvate dehydrogenase complex [
21]. Amazingly, administration of i.v. glucose was recorded in only half of the patients with severe hypoglycaemia and in only one-quarter of the patients with moderate hypoglycaemia.
Except in patients with diabetes mellitus, acute hyperglycaemia following trauma is mainly a consequence of distress causing a hypothalamic-hypophysic-adrenal stress response modulated by trauma severity, incidence of shock, and age [
22‐
24]. Haemorrhagic shock and hypoxaemia belong to the strongest stressors in mammals, triggering highest levels of cortisol and catecholamines [
24‐
26]. They lead to release of pro-inflammatory cytokines in the liver [
27,
28], trigger glycogenolysis, and gluconeogenesis by degradation of muscle lactate, glucoplastic amino acids, and glycerol in liver and kidneys, and lipolysis [
29‐
31]. Simultaneously, tumor necrosis factor α induces a peripheral insulin resistance [
32]. This stress response-induced hyperglycaemia supports initial steps of immune defense and wound healing. In addition, hyperglycaemia leads to a higher concentration gradient to tissues with disturbed microcirculation and increased need, especially in the brain following injury [
33‐
35], which eases glucose uptake. Over and above this, hyperglycaemia may improve cardiac function and resistance during stress and osmotic effects counteract blood loss [
36‐
39].
In severely injured patients who were found to be hyperglycaemic on arrival of the emergency physician, circulation presumably lasted long enough to develop a stress response. In contrast, patients with asystole or pulseless electrical activity had less time for a physical stress response. This assumption is supported by the fact that 80% of the patients with asystole or pulseless electrical activity were polytraumatised, whereas patients with ventricular fibrillation or ventricular tachycardia had suffered a single injury in 60% of the cases in our study.
The potentially positive effects of hyperglycaemia in the acute post-traumatic situation are accompanied by negative sequelae from prolonged hyperglycaemia known as “diabetes of injury” [
40,
41], which seems to be more pronounced than diabetes mellitus-induced hyperglycaemia. [
42,
43].
The high frequency of hypoglycaemic patients in cardiac arrest needs further investigation. The prevalence of diabetes mellitus among adults in the German population averages about 7–8%, with increasing prevalence depending on age [
44]. Theoretically, in some of the diabetic trauma patients hypoglycaemia may have been a consequence of anti-hyperglycaemic drug overdose from insulin or anti-diabetic drugs. In addition, hypoglycaemia in non-diabetic patients could have resulted from extensive shivering due to hypothermia, due to exposure to cold and wet environment, but also from chronic liver disease, intoxication, or severe liver and kidney trauma [
22,
23,
45‐
48].
The finding that the rate of successful resuscitation attempts correlated with blood glucose levels, especially in polytraumatised and young patients, raises the question whether blood glucose levels need to be increased during CPR in patients with traumatic cardiac arrest. Some studies support the hypothesis that hyperglycaemia could be beneficial during cardiac arrest: Nehme et al. observed that diabetes affects at least one in five patients who have had an out-of-hospital cardiac arrest and is associated with poorer survival and 12-month functional recovery. In contrast, a mild-to-moderate elevation of pre-hospital blood glucose level was associated with improved survival and functional recovery, which were independent of diabetes status [
49]. Mentzelopoulos found better outcome by administering – among others - blood glucose-increasing steroids for resuscitation of in-hospital cardiac arrest [
50]. In animal studies, hyperglycaemia during cardiac arrest led to greater cerebral oxygenation [
51], and blood glucose-increasing glucagon administration during cardiac arrest improved survival rate, cardiac function, and neurological outcome [
52,
53]. Hyperglycaemia was associated with reduced myocardial infarction size and improved systolic function during myocardial ischaemia [
37]. In traumatised patients and patients with sepsis, glucose uptake in macrophage-rich tissues is significantly increased [
54]. A substantial hyperglycaemia level may overcome local or general microcirculation disturbances (injuries, sepsis, ischaemia) by increasing the concentration gradient, which facilitates non-insulin-dependent glucose uptake. These positive findings are accompanied by a long list of publications with negative results regarding hyperglycaemia and outcome in several diseases and critical conditions [
2,
55‐
60]. Russo et al. retrospectively investigated clinical outcome in relation to mean blood glucose during the first 96 h after hospital admission in comatose survivors of out-of-hospital cardiac arrest with an initial shockable rhythm. They found that higher mean blood glucose levels during the first 96 h after admission were associated with increased rates of death and severe neurological dysfunction [
61]. However, initial blood glucose level could be a surrogate marker of ischaemic insult severity during cardiac arrest [
62].
After all, measuring blood glucose during pre-hospital care of trauma patients is easy, rapid, inexpensive and may yield additional information to estimate or complement clinical assessment of a patient’s pre-hospital situation as a whole.
Limitations
Limitations of this study are its retrospective design, although all data were collected prospectively.
In our study about 46% of the trauma patients were excluded mostly due to missing prehospital glucose measurement or ECG rhythm documentation (Fig.
1). Thus, we cannot exclude selection bias, especially in the more severe cases in which HEMS physicians focus on supporting vital functions rather than on lab investigations. Patients in category NACA 7 were more numerous in the excluded population than in study patients.
In addition, we have no in-hospital data. In particular, we lack information on the frequencies of confirmed diagnoses and injury patterns, the in-hospital course of blood glucose concentrations and the ultimate outcome. However, this does not affect the core parameters of our study, initial ECG and on-site blood glucose concentrations. Worse, there is no on-site information available about pre-existing diseases such as diabetes, which probably influenced the course. The prevalence of diabetes in the German population is quoted as being 7–8% [
44]. Accordingly, about 1500 patients in the study population may have been diagnosed with diabetes. We do not know the frequency of study patients with diabetes complicated by vascular and end-organ damage and we cannot tell how many of them were under anticoagulation therapy or had taken anti-diabetic drugs. Furthermore, our results regarding outcome of hypoglycaemic trauma patients do not consider administration of glucose in half of them. The extent to which oral anti-diabetic drugs or insulin may influence blood glucose concentrations during trauma and shock is not known and may vary individually with the time of drug ingestion/administration, the extent of oral carbohydrate intake, and the individual patient’s stress response. In recent studies it was reported that stress-induced hyperglycaemia rather than diabetic hyperglycaemia is associated with higher mortality in trauma [
42,
43].
Another problem may arise from differences in point-of-care devices and with either venous or capillary blood measurements when haemodynamic shock developed. Routinely, blood glucose concentrations in pre-hospital trauma patients were measured from blood drawn from venous access before any drug or volume administration. However, we cannot exclude that in selected cases capillary blood glucose was measured by ear or finger sticks. The literature shows contradictory conclusions regarding the impact of venous vs. capillary blood glucose measurements, the existence of shock or the administration of catecholamines. In addition, the limited precision of point-of-care devices is well-known, especially when blood glucose concentrations are extremely high or low [
63‐
65]. In this study, measurements of blood glucose concentration were conducted while establishing the initial iv access and before drug administration, for which reason the influence of external catecholamines (e.g. in the context of cardiopulmonary resuscitation) can be excluded as far as possible.