Glucose MetabolismFailure to achieve euglycemia despite aggressive insulin control signals abnormal physiologic response to trauma☆,☆☆
Introduction
Hyperglycemia at the time of admission has been used as a marker of mortality in the trauma population over the last several years [1], [2]. Authors have shown that untreated hyperglycemia that persists through the patient's admission leads to adverse outcomes [3]. Even before the most recent publications questioning the appropriate goal range [4], [5], [6], widespread institution of tight glycemic control (goal 80-110 mg/dL) has not been the standard of care in the trauma population because of concerns and fears of hypoglycemia. When instituted, protocols used more liberal goals (80-150 mg/dL), with mixed results of tight glycemic control's effect on outcome in the trauma population [7], [8]. Recent publications in nontrauma populations aimed at addressing the uncertainty of the best goal range have made appropriate goal selection even more challenging [4], [5], [6].
Although the question of whether hyperglycemia after trauma is an adaptive mechanism or a pathologic response to stress remains, there is evidence that aiming for euglycemia leads to improved outcomes in other populations [9], [10], [11], [12], [13]. Trauma practitioners have questioned the applicability of euglycemia protocols because their patients often represent a young, heterogeneous, critically ill population, which contrasts with the population seen in other studies.
As hyperglycemia protocols become more widespread and effective, traditional means of differentiating patients based on summary measures such as median blood glucose and the percentage of values within goal range become more difficult. The aggressive management of both hypoglycemia and hyperglycemia makes them poor predictors of differentiating survivors from nonsurvivors. Individuals' responses to the initiation of tight glucose control and their responses to insulin as a drug are methods of differentiating these patients. Basic science as well as clinical research supports that hyperglycemia is due to peripheral insulin resistance (IR) as well as increased hepatic glucose production [14], [15], [16], [17], [18], [19], [20]. This IR has been shown to be a predictor of poor outcomes in a more diverse critically ill surgical population [21].
Against the backdrop of this IR and hyperglycemia, we sought to further describe the prognostic ability of persistent hyperglycemia while attempting tight glucose control. We developed a computer-based order entry system to assist in the maintenance of euglycemia in critically ill patients that captures all glucose values, insulin doses, and a mathematical multiplier (M) used to determine the insulin dose for each patient. We hypothesize that a failure to normalize a patient's glucose on an automated euglycemia protocol signals an adverse response after trauma and that this response can identify patients with an increased mortality.
Section snippets
Study population
One thousand eight hundred eighty six patients were admitted to the Vanderbilt University trauma intensive care unit (ICU) from March 1, 2006, to April 26, 2008. There were 1709 patients treated with the tight glucose control protocol using the computer-based order entry system at Vanderbilt University Medical Center who met study criteria. Inclusion criteria for being placed on the protocol were all mechanically ventilated patients found to have blood glucose value greater than 110 mg/dL.
Results
A total of 1246 patients were enrolled with an overall mortality rate of 16.3% (n = 203). On admission, 137 (11.0%) of 1246 patients had a medical history of diabetes, with 123 (89.8%) of the 137 persons with diabetes being non–insulin-dependent diabetic persons and 14 (10.2%) having insulin-dependent diabetes. As a group, the mean age was 44 ± 19 years, the mean ISS was 26 ± 11, and the mean Revised Trauma Score was 7.8 ± 3.7. The mean glucose for the entire group was 122 ± 22 mg/dL. There
Discussion
As we attempt to control the hyperglycemia that results after trauma, the patients' individual responses to the therapy reveal important differences in their physiology. The ability to distinguish between patients based on their median blood glucose has been lost. The advancements in euglycemia protocols have driven patients artificially to a level where survivors and nonsurvivors have the same median blood glucose values. Despite these advances, patients are being identified, whose acute IR
Conclusions
In an era where avoiding unchecked hyperglycemia is considered standard, we continue to strive to further evaluate how a patient's response to glucose control can give clues about their physiologic status. We found that there is an increased mortality in patients with persistent hyperglycemia while on glucose control, irrespective of the goal range targeted. That these patients were on an aggressive glucose control protocol with similar injury severity patterns would suggest that these patients
References (43)
- et al.
Glucose metabolism in severely burned patients
Metabolism
(1979) - et al.
Computer-based insulin infusion protocol improves glycemia control over manual protocol
J Am Med Inform Assoc
(2007) - et al.
Blood glucose control in critically ill adults and children: a survey on stated practice
Chest
(2008) Effect of an intensive glucose management protocol on the mortality of critically ill adult patients
Mayo Clin Proc
(2004)- et al.
The influence of anaesthesia and surgery on plasma cortisol, insulin and free fatty acids
Br J Anaesth
(1970) - et al.
Effect of abdominal operation on glucose tolerance and serum levels of insulin, growth hormone, and hydrocortisone
Lancet
(1966) - et al.
Insulin resistance and elective surgery
Surgery
(2000) - et al.
Preoperative oral carbohydrate administration reduces postoperative insulin resistance
Clin Nutr
(1998) - et al.
Admission hyperglycemia is predictive of outcome in critically ill trauma patients
J Trauma
(2005) - et al.
Admission hyperglycemia as a prognostic indicator in trauma
J Trauma
(2003)
Persistent hyperglycemia is predictive of outcome in critically ill trauma patients
J Trauma
Intensive insulin therapy and pentastarch resuscitation in severe sepsis
N Engl J Med
Impact of tight glucose control by intensive insulin therapy on ICU mortality and the rate of hypoglycaemia: final results of the glucontrol study [European Society of Intensive Care Medicine 20th Annual Congress abstract 0735]
Intensive Care Med
Intensive versus conventional glucose control in critically ill patients
N Engl J Med
Poor glycemic control is associated with increased mortality in critically ill trauma patients
Am Surg
Tight glycemic control in critically injured trauma patients
Ann Surg
Complications of coronary artery surgery in diabetic patients
Am Surg
Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) study group
BMJ
Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study
Circulation
Stress hormone and blood glucose response following acute stroke in the elderly
Stroke
Glucose potassium insulin infusions in the treatment of acute stroke patients with mild to moderate hyperglycemia: the Glucose Insulin in Stroke Trial (GIST)
Stroke
Cited by (9)
Glycemic control in the intensive care unit: A control systems perspective
2019, Annual Reviews in ControlCitation Excerpt :This metric is critical as it is used to guide care, and inaccuracy will translate through to any control derived using its value with potential patient harm. Perhaps more importantly, such model-based SI (Blaha et al., 2016; Chase, Le Compte, Suhaimi, et al., 2011; Chase, Suhaimi, et al., 2010; Cobelli, Pacini, Toffolo, & Sacca, 1986; Dalla Man et al., 2002; Dalla Man et al., 2005; Docherty, Chase, Morenga, et al., 2011; Hann et al., 2005; Hovorka et al., 2008; Hovorka et al., 2002; Langouche et al., 2007; Le Compte et al., 2009; J. Lin et al., 2011; Lin et al., 2006; Lin et al., 2008; Mari, Pacini, Brazzale, & Ahren, 2005; Pielmeier, Andreassen, Nielsen, et al., 2010; Pillonetto et al., 2006; Wilinska et al., 2008) can be monitored and its level and/or variation assessed relative to condition (Blaha et al., 2016; Cueni-Villoz et al., 2011; Ferenci et al., 2013; Jamaludin, Docherty, Geoffrey Chase, & Shaw, 2015; Koch, Gressner, Sanson, Tacke, & Trautwein, 2009; Langouche et al., 2007; Laviano et al., 2011; Le Compte, Pretty, et al., 2011; J. Lin et al., 2011; Mowery et al., 2011; Pretty et al., 2011; Pretty et al., 2012; Sah Pri et al., 2014; Thomas et al., 2014). Thus, if accurate, this value offers not only the potential of good, personalised control, but also further insight into patient condition.
Time to reach target glucose level and outcome after cardiac arrest patients treated with therapeutic hypothermia
2015, Journal of Critical CareCitation Excerpt :To our knowledge, this study is the first report on the association between patient outcome and the time to reach target glucose level in patients after cardiac arrest treated with TH. In a previous study of trauma patients, patients who failed to reach euglycemia in the first 6 hours after admission had increased hospital mortality [35]. That study found that nonsurvivors with demographic factors similar to the survivors required more time to reach the blood glucose goal range and more insulin to stay within that range.
Elderly patients may benefit from tight glucose control
2012, Surgery (United States)Citation Excerpt :This is further supported by greater insulin requirements in nonsurvivors to achieve similar glucose levels compared to patients with more favorable outcomes. A recent study of critical trauma patients on computerized insulin protocols found that patients who did not normalize their glucose levels rapidly required significantly greater doses of insulin, also suggesting insulin resistance.23 This pattern of insulin resistance may be a marker of the severity of the postinjury inflammatory response.
- ☆
Work was completed at Vanderbilt University Medical Center.
- ☆☆
Sources of support: institution departmental funds; no conflicts of interest to declare.