Prehospital blood glucose concentrations significantly improved the prediction of traumatic shock necessitating fluid resuscitation and administration of catecholamines (Integrated Discrimination Improvement P < 0.0001) compared with prediction by GCS, HR, respiratory rate and blood pressure alone (Table 3).
This retrospective, multicentre analysis demonstrates that prehospital deranged blood glucose concentration is common in trauma patients. Hypo- and hyperglycaemia were associated with traumatic shock in our study. Hyperglycaemia was especially common in young polytraumatised patients with traumatic shock. Hypoglycaemia was more frequently observed in older patients (>65 years) with traumatic shock (Fig. 2). In our study, blood glucose concentration showed predictive value for patients with traumatic shock in addition to common vital parameters concordant with a recent investigation.13 Thus, we recommend blood glucose concentration measurement in all trauma patients to get further information on the severity of trauma in the prehospital setting.
Hyperglycaemia may be a consequence of the hypothalamic–pituitary–adrenal stress response following trauma as levels of stress hormones correlate with injury severity and shock.19,20 In animal studies, severe haemorrhage and haemorrhagic shock are among the strongest stressors leading to the highest catecholamine concentrations.20–22 High catecholamine concentrations lead to massive release of pro-inflammatoric cytokines in the liver23,24 and trigger glycogenolysis and gluconeogenesis by degradation of muscle lactate and glucoplastic amino acids25 and lipolysis.26 In severe trauma and shock, renal gluconeogenesis produces up to 40% of blood glucose by renal degradation of lactate and glycerol.27,28 In parallel, tumor necrosis factor alpha mediates a peripheral insulin resistance mainly in muscles producing glucose from muscle glycogen.29–31 In addition, the stress response has impacts on immune defence and wound healing.32–34. Furthermore, hyperglycaemia facilitates glucose uptake because of a higher concentration gradient in tissue with disturbed microcirculation and increased need especially in the brain following injury,34–36 and improves cardiac function and resistance during stress.37–39
Hypoglycaemia in trauma patients may result from antihyperglycaemic drug overdose from insulin, antidiabetic drugs or glucagon. In some cases, hypoglycaemia may even be the cause of the accident and not a consequence. Other causes of hypoglycaemia may be from shivering because of hypothermia,40,41 chronic liver disease with limited functional reserves and organ failure of liver and kidney in patients with traumatic shock.13,42–44
Up to now, blood glucose concentration measurements are not advocated as routine investigation in Prehospital Trauma Care, Advanced Trauma Care and in German guidelines for the treatment of multiple-injured patients.45 In addition to standard vital parameters, blood glucose concentrations may provide advanced information on the volume state of patients, depending on age and injury pattern. (Table 1, Figs. 2 and 3) The large number of patients treated during a 9-year observation period in a nationwide study permits reliable interpretation of study results. However, there is no colinearity between blood glucose concentrations and arterial blood gas sample results.10,11,13 Furthermore, blood glucose concentrations seem to be independent of the volume administered on-site, but may be influenced by impaired circulation.13 The results of our study underline that there is a marked relation between blood glucose concentration and outcome in patients with trauma of varying severity.5–13
Although excessive hyperglycaemia and hypoglycaemia were predictive for traumatic shock in our study, we have no information on the impact that glucose infusion has on survival in trauma patients with proven hypoglycaemia.
Limitations of this study are because of its retrospective nature. No information on laboratory examination results after hospitalisation is available, including course of the disease, confirmed diagnoses, trauma scores and outcome at hospital discharge. No information on previous illnesses, especially diabetes mellitus, was obtainable. According to the German Diabetes Report,46 the prevalence of diabetes mellitus among adults averaged about 7 to 8% with increasing prevalence depending on age. Approximately, 1500 patients in that study population may have had diabetes mellitus in addition to the known increase in insulin resistance with age.47 This could in part explain why the age-dependent increase in initial blood glucose concentration did not depend on injury severity in our study (Fig. 4). No information on chronic medication, especially antidiabetic drugs and insulin, was obtainable. Blood glucose concentration may vary individually depending on the time of drug ingestion/administration, the extent of recent oral carbohydrate intake and the individual stress response after trauma. In addition, blood glucose concentrations in traumatised patients may increase during initial care with ongoing stress response and development of traumatic shock until hospital admission, especially in polytraumatised patients. The incidence of polytraumatised patients with blood glucose concentration exceeding 10.0 mmol l−1 increased from 376/2790 (13.5%) in the prehospital population to 195/834 (23.4%) on hospital admission (P
The number of patients in the included and excluded study population was similar and both populations were clinically comparable. (Table 4) However, those excluded because of missing documented blood glucose concentration contained nine-fold more patients who were declared dead or did not survive resuscitation on scene (NACA 7) [220/20 177 patients (1.1%) vs. 1970/20 479 patients (9.6%), P < 0.0001] compared with the study group. Consequently, this population differed in initial vital signs, state of consciousness and initial GCS, and included more severely injured patients. (Table 4) When excluding these NACA 7 patients, the study population and the sample lacking blood glucose concentration documentation were even more comparable. Nevertheless, a biased selection of patients in both groups cannot be excluded. In more severe cases, HEMS physicians focus on vital functions and cardiorespiratory support rather than on laboratory investigations. As blood glucose concentration can provide further information on severity and prognostic outcome, we recommend that on-site blood glucose concentration measurement should become a standard investigation in trauma patients.
In our study, blood glucose concentration was measured before intravenous treatment was started. In patients with haemodynamic shock it may be more difficult to obtain venous blood for glucose concentration measurement. In venous blood, measured blood glucose concentration may be lower than in capillary blood,48–50 but Ramachandran et al.51 did not find significant differences between venous and capillary blood glucose concentrations in children with shock. In contrast, Pulzi Júnior et al.52 found higher blood glucose concentrations in capillary blood from patients in shock who received noradrenaline (norepinephrine) or had diminished tissue perfusion. Furthermore, we do not know about the accuracy of glucose concentration measurements in different point-of-care devices53–55 used during the study phase. However, a study testing reflectometer analysis of venous blood from venous access in prehospital emergency patients found a very high congruence of the results with laboratory analysis.56 Nevertheless, especially when glucose concentrations are extremely low or high, repeated measurements are recommended.
Owing to rather short arrival intervals of the HEMS emergency physician, cases with delayed onset of shock may have been missed. Furthermore, the need for catecholamine administration during on-site treatment of critically injured patients is not always associated with bleeding and haemorrhagic shock. Patients with severe traumatic brain injury, for instance, may have received catecholamines to maintain cerebral perfusion pressure. However, in traumatic brain injury without clinical signs of hypovolaemia deranged blood glucose concentration is associated with poor outcome too.8,9
In conclusion, blood glucose concentration measurements in addition to common vital parameters (GCS, HR, blood pressure, breathing frequency) may help identify patients at risk of traumatic shock in adult trauma patients.
Assistance with the study: the authors wish to thank all emergency physicians and emergency medical technicians of the German HEMS of ADAC for their devoted work and for collecting these important and valuable data over years. The authors also thank Ms Beatrice Möller for her demanding work in data editing and PD Martin Dünser, MD for critical reviewing of the manuscript.
Financial support and sponsorship: none.
Conflicts of interest: none.
1. Bilotta F, Caramia R, Paoloni FP, et al. Safety and efficacy of intensive insulin therapy in critical neurosurgical patients. Anesthesiology
2. Capes SE, Hunt D, Malmberg K, et al. Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet
3. Capes SE, Hunt D, Malmberg K, et al. Stress hyperglycaemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke
4. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med
5. Yendamuri S, Fulda GJ, Tinkoff GH. Admission hyperglycaemia as a prognostic indicator in trauma. J Trauma
6. Bochicchio GV, Sung J, Joshi M, et al. Persistent hyperglycaemia is predictive of outcome in critically ill trauma patients. J Trauma
7. Laird AM, Miller PR, Kilgo PD, et al. Relationship of early hyperglycaemia to mortality in trauma patients. J Trauma
8. Jeremitsky E, Omert LA, Dunham CM, et al. The impact of hyperglycaemia on patients with severe brain injury. J Trauma
9. Kinoshita K, Kraydieh S, Alonso O, et al. Effect of posttraumatic hyperglycaemia on contusion volume and neutrophil accumulation after moderate fluid-percussion brain injury in rats. J Neurotrauma
10. Kreutziger J, Wenzel V, Kurz A, et al. Admission blood glucose is an independent predictive factor for hospital mortality in polytraumatized patients. Intensive Care Med
11. Kreutziger J, Schlaepfer J, Wenzel V, et al. The role of admission blood glucose in outcome prediction of surviving patients with multiple injuries. J Trauma
12. Vogelzang M, Nijboer JM, van der Horst IC, et al. Hyperglycaemia has a stronger relation with outcome in trauma patients than in other critically ill patients. J Trauma
13. Kreutziger J, Rafetseder A, Mathis S, et al. Admission blood glucose predicts traumatic shock rather than in-hospital mortality in multiple injury patients. Injury
14. Messelken M, Schlechtriemen Th. Der minimale notarztdatensatz MIND2. Notf Rettungsmed
15. Hern HG, Kiefer M, Louie D, et al. D10 in the treatment of prehospital hypoglycemia: a 24 month observational cohort study. Prehosp Emerg Care
16. Bilhimer MH, Treu CN, Acquisto NM. Current practice of hypoglycemia management in the ED. Am Emerg Med
17. Youden WJ. Index for rating diagnostic tests. Cancer
18. Brunauer A, Koköfer A, Bataar O, et al. The arterial blood pressure associated with terminal cardiovascular collapse in critically ill patients: a retrospective cohort study. Crit Care
19. Marik PE, Bellomo R. Stress hyperglycemia: an essential survival response!. Critical Care
20. Chernow B, Rainey TG, Lake CR. Endogenous and exogenous catecholamines in critical care medicine. Crit Care Med
21. Hart BB, Stanford GG, Ziegler MG, et al. Catecholamines: study of interspecies variation. Crit Care Med
22. Woolf PD. Endocrinology of shock. Ann Emerg Med
23. Molina PE, Malek S, Lang CH, et al. Early organ-specific hemorrhage-induced increases in tissue cytokine content: associated neurohormonal and opioid alterations. Neuroimmunomodulation
24. Shimizu T, Yu HP, Hsieh YC, et al. Flutamide attenuates pro-inflammatory cytokine production and hepatic injury following trauma-hemorrhage via estrogen receptor-related pathway. Ann Surg
25. Blumberg D, Hochwald S, Burt M, et al. Tumor necrosis factor alpha stimulates gluconeogenesis from alanine in vivo. J Surg Oncol
26. Verbruggen SC, Coss-Bu J, Wu M, et al. Current recommended parenteral protein intakes do not support protein synthesis in critically ill septic, insulin-resistant adolescents with tight glucose control. Crit Care Med
27. Stumvoll M, Chintalapudi U, Perriello G, et al. Uptake and release of glucose by the human kidney. Postabsorptive rates and responses to epinephrine. J Clin Invest
28. Meyer C, Stumvoll M, Welle S, et al. Relative importance of liver, kidney, and substrates in epinephrine-induced increased gluconeogenesis in humans. Am J Physiol Endocrinol Metab
29. Dungan KM, Braithwaite SS, Preiser JC. Stress hyperglycaemia. Lancet
30. Grimble RF. Inflammatory status and insulin resistance. Curr Opin Clin Nutr Metab Care
31. Marette A. Mediators of cytokine-induced insulin resistance in obesity and other inflammatory settings. Curr Opin Clin Nutr Metab Care
32. Lang CH, Dobrescu C. Gram-negative infection increases noninsulin-mediated glucose disposal. Endocrinology
33. Meszaros K, Lang CH, Bagby GJ, et al. In vivo glucose utilization by individual tissues during nonlethal hypermetabolic sepsis. FASEB J
34. Hamlin GP, Cernak I, Wixey JA, et al. Increased expression of neuronal glucose transporter 3 but not glial glucose transporter 1 following severe diffuse traumatic brain injury in rats. J Neurotrauma
35. Losser MR, Damoisel C, Payen D. Bench-to-bedside review: glucose and stress conditions in the intensive care unit. Crit Care
36. Van Cromphaut SJ. Hyperglycaemia as part of the stress response: the underlying mechanisms. Best Pract Res Clin Anaesthesiol
37. Ma G, Al-Shabrawey M, Johnson JA, et al. Protection against myocardial ischemia/reperfusion injury by short-term diabetes: enhancement of VEGF formation, capillary density, and activation of cell survival signaling. Naunyn Schmiedebergs Arch Pharmacol
38. Malfitano C, Alba Loureiro TC, Rodrigues B, et al. Hyperglycaemia protects the heart after myocardial infarction: aspects of programmed cell survival and cell death. Eur J Heart Fail
39. Malfitano C, de Souza Junior AL, Irigoyen MC. Impact of conditioning hyperglycemic on myocardial infarction rats: Cardiac cell survival factors. World J Cardiol
40. Alfonsi P, Nourredine K, Adam F, et al. The effect of postoperative skin-surface warming on oxygen consumption and the shivering threshold. Anaesthesia
41. Frank SM, Fleisher LA, Olson KF, et al. Multivariate determinants of early postoperative oxygen consumption in elderly patients. Effects of shivering, body temperature, and gender. Anesthesiology
42. Chen JH, Michiue T, Inamori-Kawamoto O, et al. Comprehensive investigation of postmortem glucose levels in blood and body fluids with regard to the cause of death in forensic autopsy cases. Leg Med (Tokyo)
43. Strapazzon G, Nardin M, Zanon P, et al. Respiratory failure and spontaneous hypoglycemia during noninvasive rewarming from 24.7°C (76.5°F) core body temperature after prolonged avalanche burial. Ann Emerg Med
44. Wouters M, Posma RA, van der Weerd L, et al. Incidence, causes and consequences of early hypoglycaemia in severe trauma patients. Abstract presented at the ESICM Paris 2013
47. Fink RI, Kolterman OG, Griffin J, et al. Mechanisms of insulin resistance in aging. J Clin Invest
48. Holtkamp HC, Verhoef NJ, Leijnse B. The difference between the glucose concentrations in plasma and whole blood. Clin Chim Acta
49. Morrison B, Fleck A. Plasma or whole blood glucose? Clin Chim Acta
50. Pereira AJ, Corrêa TD, de Almeida FP, et al. Inaccuracy of venous point-of-care glucose measurements in critically ill patients: a cross-sectional study. PLoS One
51. Ramachandran B, Sethuraman R, Ravikumar KG, et al. Comparison of bedside and laboratory blood glucose estimations in critically ill children with shock. Ped Crit Care Med
52. Pulzi Júnior SA, Assunção MS, Mazza BF, et al. Accuracy of different methods for blood glucose measurement in critically ill patients. Sao Paulo Med J
53. Stiftung-Warentest. Bestechend genau. Blutzuckermessgeräte. Test
54. Aslan B, Stemp J, Yip P, et al. Method precision and frequent causes of errors observed in point-of-care glucose testing: a proficiency testing program perspective. Am J Clin Pathol
55. Gijzen K, Moolenaar DL, Weusten JJ, et al. Is there a suitable point-of-care glucose meter for tight glycemic control? Evaluation of one home-use and four hospital-use meters in an intensive care unit. Clin Chem Lab Med
56. Holstein A, Kühne D, Elsing HG, et al. Practicality and accuracy of prehospital rapid venous blood glucose determination. Am J Emerg Med