|Year : 2017 | Volume
| Issue : 3 | Page : 160-164
Prognostic significance of glycemic control in burn injury patients: A study in Tertiary Care Hospital of Odisha
Srikanta Panda1, Amit Bagur Lokesh1, Anshuman Sarangi2
1 Department of Surgery, S.C.B. Medical College and Hospital, Cuttack, Bhubaneswar, Odisha, India
2 KIIT-Technology Business Incubator, KIIT School of Biotechnology, KIIT University, Bhubaneswar, Odisha, India
|Date of Web Publication||27-Oct-2017|
KIIT-TBI, KIIT School of Biotechnology, Campus - 11, Kiit University, Patia, Bhubaneswar, Odisha
Source of Support: None, Conflict of Interest: None
Background: Thermal injury is associated with anatomic, physiologic, endocrinologic, and immunologic alterations, which require specialized care. Advances in medical care have changed the principal cause of death in burn patients from burn shock to wound sepsis. An intervention that has drastically changed this outlook is early excision and primary closure of wounds. We used insulin for glycemic control and attenuating systemic inflammation. Materials and Methods: Patients admitted to S. C. B Medical College hospital were divided into 2 groups of 34 each: control group (n = 34) which did not receive insulin and study group (n = 34) which received insulin. Serum C-reactive protein (CRP), fibrinogen, albumin white blood cell, and blood cultures were done every 7th day. Results: Albumin levels decreased over 7 days followed by gradual recovery which was faster in the study group. CRP levels rose and attained its peak by day 14, then declined. CRP peak in the study group was found to be lower than control. Fibrinogen levels showed identical trend as CRP. Leukocytosis was higher in control compared to study group. Blood culture positive was higher in control compared to study group; Pseudomonas and Candida were most common organisms, but study group patients were resistant to Candida. Out of 29 deceased patients, 55% were from control group. Conclusions: Insulin administration in severely burned patients has demonstrated benefits among various parameters. In critically ill burn injury patients, obtaining tight glycemic control with intensive insulin therapy was shown to reduce morbidity and mortality.
Keywords: Albumin, burn injury, C-reactive protein, fibrinogen, glycemic control, insulin
|How to cite this article:|
Panda S, Lokesh AB, Sarangi A. Prognostic significance of glycemic control in burn injury patients: A study in Tertiary Care Hospital of Odisha. Apollo Med 2017;14:160-4
|How to cite this URL:|
Panda S, Lokesh AB, Sarangi A. Prognostic significance of glycemic control in burn injury patients: A study in Tertiary Care Hospital of Odisha. Apollo Med [serial online] 2017 [cited 2020 Jul 7];14:160-4. Available from: http://www.apollomedicine.org/text.asp?2017/14/3/160/217368
| Introduction|| |
Thermal injury is associated with anatomic, physiologic, endocrinologic, and immunologic alterations, which require specialized care. Cutaneous injury results in significant fluid loss as well as the release of multiple inflammatory mediators. When disseminated by the circulation to central organs, bacteria and inflammatory mediators can cause cardiovascular compromise, a breakdown of gastrointestinal mucosal integrity, and ultimately, multiple organ failure. Inhalation injury can further accelerate these responses. Specialized burn care centers and research institutions emphasize a multidisciplinary team approach that strives to preserve organ function while promoting rapid wound closure and eventual rehabilitation.
Advances in medical care have changed the principal cause of death in burn patients from burn shock to wound sepsis. In the 1940s and 1950s, inadequate fluid resuscitation during the immediate hours after a burn injury resulted in 20%–40% of deaths among burn patients. With the advent of vigorous fluid resuscitation in the 1960s and 1970s, irreversible burn shock has been replaced by wound sepsis as the leading cause of death in the burn population. The development of topical and systemic antimicrobial agents, advances in nutritional support for the hypermetabolic response, and the use of surgical techniques for early burn wound excision have now changed the primary cause of death from wound sepsis to pulmonary sepsis, which often follows an inhalation injury.,, Overall, advances in the treatment of initial injuries and their complications as well as new surgical techniques for closing wounds and reducing scar tissue have increased burn patients' chances not only of survival but also of recovery and readjustment into society.
This study is one of a kind, wherein we have applied one of the recent advances into actual practice in our hospital. Managing hypermetabolic response has been quite challenging for doctors over many years. An intervention that has drastically changed this outlook is early excision and primary closure of wounds. Apart from surgical intervention, there have been attempts of pharmacological intervention in achieving the same, and most of them have been quite successful. Propranolol, metformin, growth hormone analogs, and testosterone analogs have been tried out. A simpler drug that is equally efficacious, cost-effective, and widely available is insulin. We have elucidated three main objectives in our study: (1) to correlate stress-induced hyperglycemia with outcome of burn patients, (2) to correlate acute phase proteins with the severity of burn injury and predictability on patients' outcome, and (3) role of Intensive Insulin Therapy (IIT) on glycemic control and attenuating systemic inflammation.
| Materials and Methods|| |
Study area and patients
Patients admitted to S. C. B Medical College and Hospital, Cuttack, from October 2011 to September 2013 were considered into the study. The patients were randomly allocated to control group who did not receive insulin (n = 34) and study group who received insulin (n = 34). Effectively, 34 patients in each group completed the study (n = 34).
Selection of cases
- Patients sustaining burn injury for not more than 12 h, presenting to emergency department of SCB Medical College, Cuttack
- Injuries caused by fire alone
- Age 10–60 years
- Burns extent 21%–60% total body surface area (TBSA); burn depth of second degree or higher.
- Burn associated with other major traumatic injuries
- Patients who succumbed on the day of admission
- Patients with documented diabetes mellitus, hypertension, active tuberculosis, myocardial infarction, stroke, and other chronic systemic inflammatory illness.
Permission was obtained from the Institutional Ethics Committee. Patients who met the eligibility criteria were explained regarding the risks and benefits of the study. The patients who met the eligibility criteria were pooled in. Their consent was obtained in written form.
Airway was secured; patients suspected of inhalational injury were put of corticosteroids with support of mechanical ventilation. Fluid resuscitation was done as per Parkland formula. Urine output was maintained >50 ml/h. First day values of blood glucose, C-reactive protein (CRP), serum fibrinogen, serum albumin, and white cell counts were obtained.
Protocol for insulin infusion is based on guideline, “intravenous insulin infusion protocol for critically-ill adult patients in the intensive care unit (ICU) setting” laid out by the Texas Diabetes Council.
Target blood glucose was set at 80–120 mg/dL. Insulin infusion was started on all patients in the study group irrespective of their glycemic status. The algorithm for insulin administration was based on the protocol laid out by the University of Texas. Infusion began with solution of 25 units regular insulin in 500 ml 0.9% saline [Table 1]. Based on the initial venous blood glucose level, infusion drip rate was started as per algorithm 1. Capillary blood glucose levels were serially monitored every 2 h. Drip rate continued if the patient achieved euglycemia. On failure to reach target blood glucose range, drip rate was increased so as to move up the algorithm by one scale. If blood glucose fell <70 mg/dL, drip rate was moved down the algorithm scale. Patients with prior euglycemic status, as with all the other patients, received insulin along with high dextrose fluids and carbohydrate-rich enteral nutrition. Subsequently, capillary blood glucose levels (finger stick) were serially monitored every 6 h if euglycemic. Hypoglycemia was defined as <60 mg/dL. Hypoglycemia was managed by withholding insulin drip and infusion of 50% dextrose fluid (1/2 amp if glucose 40–60 mg/dL, 1 amp if glucose <40 mg/dL). Glucose estimated every 15–30 min till >80 mg/dL for two consecutive assays. Further, insulin drip resumed at a lower algorithm than before. Among the patients in control group, insulin administered only if blood glucose levels exceeded >220 mg/dL. Serum potassium estimated on a daily basis. Any episode of hypokalemia defined as <3.5 mg/dL was documented. Such patients were administered with oral preparation of potassium chloride.
Serial estimates of CRP, serum fibrinogen, serum albumin, white cell count estimates, and blood culture were done every 7th day. General burn management was followed as per standard protocol. Early excision (within 7 days) of wound and primary autologous skin grafting was done among patients with burn size <40%. Beyond 40% burn TBSA, they were managed by regular dressing with silver sulfadiazine. Nutrition was maintained with high carbohydrate-rich and protein-rich diet. Enteral nutrition was calculated by means of Curreri formula to provide 25 kCal/kg/day + 40 kCal per % burn area TBSA and 1–2 g/Kg of proteins per day.
| Results|| |
Among the study population, the majority (46.9%) of burn injuries were found between adults between the age group of 21 and 30 years. A female preponderance was noticed among both the control and the study groups. Twenty-two patients (64.7%) in control group and 19 patients (55.9%) in the study group were females [Graph 1].
The distribution depicted in [Graph 2] clearly demonstrates that patients with higher myocardial blush grade levels carry higher risk of mortality. Eight patients (47%) among deceased had mean blood glucose levels >140 mg/dL, while only 2 patients (11.8%) with mean blood glucose >140 mg/dL survived.
On mapping mean serum albumin levels, there is a downward trend over the initial 7 days followed by gradual recovery. On comparing both the groups, patients on insulin had significantly faster recovery than controls. Although greater the extent of burn injury, lower is albumin levels; patients on insulin have significantly increased levels of serum albumin than controls.
On serial estimation of CRP levels over days, the levels begin to rise from the very beginning itself; the levels reach its peak by around day 14; further, it tends to decline slowly. In the group receiving insulin therapy, the peak attained is much lower than that of the control group. However, difference among them appears to be significant only day 14 onward. Greater the extent of burn injury, higher is the peak attained by CRP levels. Nevertheless, patients on insulin have significantly lower levels of serum CRP than controls for burn injuries 21%–50% TBSA.
On serial estimation of fibrinogen levels over days, the levels begin to rise from the very beginning itself; the levels reach its peak by around day 7; further, it tends to decline slowly.
In the group receiving insulin therapy, the peak of mean fibrinogen levels attained is slightly lower than that of the control group. Greater the extent of burn injury, higher is the peak attained by fibrinogen levels. Nevertheless, patients on insulin have significantly lower levels of serum CRP than controls for burn injuries 31%–60% TBSA.
Cultures that yielded growth about 31 (66%) of them were found to be from that of patients in control group, while the rest of 16 (34%) from the group receiving insulin. Pseudomonas and Candida were the most common organisms that grew. The numbers of positive cultures among all the organisms were less in the insulin group than that of the control group.
| Discussion|| |
Hyperglycemia plays an important role not only in influencing the cascade of inflammatory cytokines but also in increasing oxidative stress. Burn stimulates insulin production weeks after the occurrence of injury and produces insulin resistance in skeletal muscle, adipose tissue, and liver by processes that are associated with postreceptor alterations in the absence of changes in insulin receptor binding  [Graph 2].
The most important function of albumin is to maintain an oncotic pressure of at least 80% of the normal level. Its reduction could induce complications that predispose patients to malnutrition, the loss of immune responses, and an increased risk of infection  [Table 2]. Several studies have shown the deleterious effects of hypoalbuminemia in terms of hospital stay, morbidity, and mortality in patients with various conditions, including critically ill patients or those patients undergoing chronic renal replacement therapy and surgical patients.,, Among the control group of our study, mean of serum albumin levels was compared among the survivors and deceased. Patients who succumbed had mean albumin of 2.04 g/dL significantly reduced than those who survived with albumin levels of 2.9 g/dL. Patients whose albumin levels were <2 g/dL on the day of hospitalization had 80% mortality, while those with >2 g/dL had mortality of 33.33%, almost comparable with the study of Aguayo-Becerra et al.
|Table 2: Comparison of serum albumin levels over days and total burn surface area between control and study groups|
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Insulin administration in severely burned patients has demonstrated benefits among various parameters that are increasingly being studied than ever. Apart from its benefits on glycemic control, it is known to downregulate cell-mediating persistent systemic inflammation and bring about its immune-modulatory effects. Insulin is known to augment DNA replication, protein synthesis, fatty acid synthesis, and decreased proteolysis. IIT among critically ill patients managed in ICU has demonstrated far less frequent incidence of infections, faster weaning from mechanical ventilation, and faster recovery rates.
More importantly, insulin was found to decrease serum CRP levels [Table 3]. CRP increased immediately after trauma and approached normal levels in the insulin group but not in the control group. In this study of ours, we have involved comparison among serum levels of CRP and fibrinogen. An analysis of outcome among patients within the control was done with respect to different burn size. CRP levels among survived patients had significantly reduced levels (mean 14.3 mg/dL, standard deviation [SD] ±6.45) than deceased (mean 18.34 mg/dL, SD ± 9.8) [Table 2].
|Table 3: Comparison of C-reactive protein levels over days and total burn surface area between control and study groups|
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Fibrin, activated form of fibrinogen, interacts with inflammation by means of its action in coagulation cascade. However, raised serum levels of fibrinogen pose risk of thromboembolic manifestations. Fibrinogen levels in our study attained peak by around day 7, levels fall gradually over several months [Table 4].
|Table 4: Comparison of serum fibrinogen levels over days and total burn surface area between control and study groups|
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In our study, data were analyzed within the control group. Nineteen patients (62.50%) with hyperglycemia had positive blood cultures, while only 12 patients (22.22%) with euglycemic patients had positive cultures [Table 5]. We came across a total of 34 samples of leukocytosis among control group over several days; of which, 55.88% of the samples were from patients who had persistent hyperglycemia. Seven out of 9 patients (77.78%) with persistent hyperglycemia died compared to 10 out of 25 patients (40%) with euglycemia.
Over the past years, there has been a significant decrease in mortality and morbidity in patients suffering from severe burns due to improved burn wound management and approaches in critical care. Survival is no longer the exception, but unfortunately, death still occurs.
There are some clear messages this study has offered us. One of the key elements concerning state-of-the-art burn care is blood glucose control and insulin therapy; it is well known that burn-induced hyperglycemia is associated with adverse clinical outcomes. Serum albumin and CRP can be relied upon in predicting prognosis of patients with burn injury. IIT apart from glycemic control creates positive nitrogen balance by improved protein synthesis. It downregulates inflammatory mediators and slows down systemic inflammation clearly indicated by fall in CRP levels, improves immunity as evidenced by reduced number of positive blood cultures and leukocytosis.
In critically ill burn injury patients, obtaining tight glycemic control with IIT was shown to reduce morbidity and mortality and has increasingly become the standard of care. In addition to its well-known antihyperglycemic action and reduction in infections, insulin promotes muscle anabolism and regulates the systemic inflammatory response.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Chen XL, Xia ZF, Wei HF. Escharectomy and allografting during shock stage reduces insulin resistance induced by major burn. J Burn Care Res 2011;32:e59-66.
Delgado-Rodríguez M, Medina-Cuadros M, Gómez-Ortega A, Martínez-Gallego G, Mariscal-Ortiz M, Martinez-Gonzalez MA, et al.
Cholesterol and serum albumin levels as predictors of cross infection, death, and length of hospital stay. Arch Surg 2002;137:805-12.
De Maio A, Mooney ML, Matesic LE, Paidas CN, Reeves RH. Genetic component in the inflammatory response induced by bacterial lipopolysaccharide. Shock 1998;10:319-23.
Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, et al
. Medical management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: A Consensus Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009;32:193-203.
Rybka J. Glycaemia control in critically ill patients is justified and effective. Vnitr Lek 2010;56:977-87.
Carter EA, Burks D, Fischman AJ, White M, Tompkins RG. Insulin resistance in thermally-injured rats is associated with post-receptor alterations in skeletal muscle, liver and adipose tissue. Int J Mol Med 2004;14:653-8.
Kumar P, D'Souza J, Bhaskara KG, Bharadwaj S. Serum protein level in conjunction with serum albumin/globulin ratio as an indicator of severity of changes in capillary permeability. Burns 2003;29:628-9.
Goldwasser P, Feldman J. Association of serum albumin and mortality risk. J Clin Epidemiol 1997;50:693-703.
Gibbs J, Cull W, Henderson W, Daley J, Hur K, Khuri SF, et al.
Preoperative serum albumin level as a predictor of operative mortality and morbidity: Results from the national VA surgical risk study. Arch Surg 1999;134:36-42.
Hsu CW, Sun SF, Lin SL, Huang HH, Wong KF. Moderate glucose control results in less negative nitrogen balances in medical Intensive Care Unit patients: A randomized, controlled study. Crit Care 2012;16:R56.
Aguayo-Becerra OA, Torres-Garibay C, Macías-Amezcua MD, Fuentes-Orozco C, Chávez-Tostado Mde G, Andalón-Dueñas E, et al.
Serum albumin level as a risk factor for mortality in burn patients. Clinics (Sao Paulo) 2013;68:940-5.
Deng HP, Chai JK. The effects and mechanisms of insulin on systemic inflammatory response and immune cells in severe trauma, burn injury, and sepsis. Int Immunopharmacol 2009;9:1251-9.
Pidcoke HF, Wade CE, Wolf SE. Insulin and the burned patient. Crit Care Med 2007;35:S524-30.
van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, et al.
Intensive insulin therapy in critically ill patients. N
Engl J Med 2001;345:1359-67.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]