|Year : 2014 | Volume
| Issue : 3 | Page : 269-273
Euglycemic control: does it affect the incidence of chest infection in ICU patients?
Hesham M Elazzazi, Mahmoud M Okasha
Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt
|Date of Submission||30-May-2013|
|Date of Acceptance||10-Dec-2013|
|Date of Web Publication||27-Aug-2014|
Hesham M Elazzazi
Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain Shams University, 11646 Cairo
Source of Support: None, Conflict of Interest: None
Acute hyperglycemia in ICU patients is associated with increased risk for nosocomial infections by raising plasma levels of proinflammatory cytokines, stimulating muscle-protein degradation, and inhibiting protein synthesis, which could contribute to muscle wasting. Euglycemic control with insulin reduced septicemia and the need for prolonged antibiotic therapy, prevented nosocomial infection, accelerated resolution of inflammation, and reduced muscle catabolism .
Patients and methods
A total of 200 patients of both sex, diabetic or nondiabetic, aged 20-70 years admitted to ICU of Ain Shams University Hospitals for more than 2 days who gave written and informed consent were enrolled in the study. Age, sex, clinical assessment for chest infection, C-reactive protein, chest radiograph, random blood sugar, HbA1C, and serum potassium were recorded at the time of ICU admission. Patients were divided into two groups. Group I was the euglycemic control group (n = 100 patients) in which blood sugar was kept between 100 and 120 mg/dl using regular insulin infusion and group II (n = 100 patients) received the standard care using an intravenous insulin infusion titrated to maintain blood glucose between 120 and 180 mg/dl. Blood sugar was measured every 1 h in both groups; indicator of chest infection (clinical signs, C-reactive protein, and chest radiography) was performed daily.
Regarding all demographic data (age and sex), there were no statistically significant differences between the studied groups (P = 0.744 and 0.730, respectively). Regarding duration of ICU stay, there was a significantly higher rate of ICU stay for more than 7 days among patients of group II (P < 0.001). Comparing the incidence of chest infection in group I and group II, there was low incidence of chest infection in four patients (4%) of group I , whereas 18 patients (18%) of group II (22 of 200 patients) showed chest infection (P 0.003).
Euglycemic control reduces the incidence of chest infection in ICU patients.
Keywords: chest infection, euglycemic control, hyperglycemia, ICU patients
|How to cite this article:|
Elazzazi HM, Okasha MM. Euglycemic control: does it affect the incidence of chest infection in ICU patients?. Ain-Shams J Anaesthesiol 2014;7:269-73
|How to cite this URL:|
Elazzazi HM, Okasha MM. Euglycemic control: does it affect the incidence of chest infection in ICU patients?. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2021 Dec 1];7:269-73. Available from: http://www.asja.eg.net/text.asp?2014/7/3/269/139541
| Introduction|| |
It is vital to recognize and understand the impact of nosocomial infections on ICU patients, as ICU-related infections increase morbidity, mortality, the cost of hospitalization, and hospital length of stay. In all, 23% of nosocomial infections in the ICU are urinary tract infections  and ventilator-associated pneumonia occurs in 9-27% of all intubated, with a crude mortality rate that may exceed 20% or greater if a high-risk pathogen is involved . Infection prevention measures can help improve these outcomes by limiting the incidence and spread of nosocomial infections [3,4].
ICU patients have numerous risk factors that increase risk for infection, such as compromised skin integrity by peripheral and central venous access devices or postoperative wounds, immunosuppressive medications that decrease the ability of humoral and cell-mediated immunity defenses, uncontrolled blood sugar, mechanical ventilation, malnutrition, and hospital environment .
Factors causing hyperglycemia in ICU patients include the release of stress hormones (e.g. epinephrine and cortisol), the release of mediators in cases of sepsis or surgical trauma, intravenous dextrose, and the use of medications such as exogenous glucocorticoids and catecholamines, all of which inhibit insulin release and action, thereby enhancing gluconeogenesis, inhibiting glycogen synthesis, and impairing insulin-mediated glucose uptake by tissues .
Acute hyperglycemia is associated with increased risk for nosocomial infections by raising plasma levels of proinflammatory cytokines, including interleukin-6, tumor necrosis factor-a, and interleukin-18, stimulating muscle-protein degradation, and inhibiting protein synthesis, which could contribute to muscle wasting . Intensive insulin therapy for controlling blood sugar reduced septicemia and the need for prolonged antibiotic therapy, prevented nosocomial infection, accelerated resolution of inflammation, and reduced muscle catabolism [7,8]. There is no universal agreement existing on an optimal range of blood glucose (BG) values in ICU patients because of the lack of evidence from randomized trials. All the trials in which the targeted glucose concentration ranged between 80 and 110 mg/dl (tight glycemic control) showed increased rates of hypoglycemia .
The aim of our study was to assess the efficacy and safety of euglycemic control (blood sugar between 100 and 120 mg/dl) in reducing the incidence of chest infection in ICU patients.
| Patients and methods|| |
A total of 200 patients of both sex, diabetic or nondiabetic patients, aged between 20 and 70 years admitted to ICU of Ain Shams University Hospitals for more than 2 days who gave written and informed consent were enrolled in the randomized, controlled, and single-blinded study (the researcher was aware of what belonged to the studied groups but the participants were not) after the approval of the Ethical Medical Committee and obtaining written informed consent from each patient. Patients with the following criteria were excluded from the study: increased risk for hypoglycemia (e.g. renal or hepatic failure), reduced awareness of potential hypoglycemia (treatment with β-blockers), pregnancy, patients with chest infection [proved by clinical signs, C-reactive protein (CRP), and chest radiography], and ICU patients admitted for less than 2 days.
Assessment at ICU admission
Demographic information was collected for all participants (age, sex), in addition to clinical assessment for chest infection [fever (temperature ≥ 38°C), cough, and purulent sputum], CRP, chest radiography, random blood sugar, HbA1C (to assess blood sugar control over the last 3 months), and serum potassium (K + ).
Patients were randomly divided into two groups. The patients were assigned to one of the two groups using a computer-generated random number table.
The euglycemic control group (n = 100 patients): The aim was to control blood sugar between 100 and 120 mg/dl using regular insulin infusion (50 IU actrapid insulin in 50 ml NaCl 0.9%); blood sugar values were measured every 1 h. The rate of infusion was adjusted according to BG measurement. We followed the protocol by Gandhi and colleagues  shown in [Table 1].
If glucose level is less than 60 mg/dl, intravenous insulin infusions are ceased immediately and treatment of hypoglycemia protocol is initiated.
The conventional group (n = 100 patients): Group II received the standard of care using an intravenous insulin infusion titrated to maintain BG between 120 and 180 mg/dl. Preparation of this insulin infusion was the same as in group I.
The regimen was applied as follows:
If baseline BG level is greater than 180 mg/dl, a bolus of 2 U was initiated followed by insulin infusion at 2 U/h. BG measurement was performed every 1 h. The regimen is demonstrated in [Table 2].
Blood sugar measurements
Blood was obtained by fingerprick and analyzed using a bedside glucometer (glucosemeters; Accu-check Go, Roche, Mannheim, Germany) every 1 h. The same device was used for all measurements in the study and was calibrated weekly. Assessment for chest infection: clinical signs for chest infection [fever (temperature ≥ 38°C), cough, and purulent sputum], CRP and chest radiography (for presence of new or progressive radiological finding) were performed daily. Once chest infection was diagnosed, treatment was initiated according to the protocol for chest infection. Antipseudomonal carbepenem (imipenem or meropenem); β-lactam/β-lactamase inhibitor (cefoperazon-sulbactam, piperacillin-tazobactam) +aminoglycoside (amikacin, gentamicin, or tobramycin); or antipseudomonal fluoroquinolone (ciprofloxacin or levofloxacin)+vancomycin were used. If there was no clinical improvement in the next 48-72 h, adjust antibiotic if the culture is positive.
Hypoglycemia was considered if BG was less than or equal to 60 mg/dl or if neuroglycopenic symptoms (agitation, drowsiness, confusion, and ataxia) and autonomic symptoms (sweating, tremor, palpitations, and tachycardia) occurred. On detection of hypoglycemia, intravenous insulin infusions were ceased immediately and participants were given intravenous glucose [50 ml glucose (10%]. Glucose is then rechecked every 30 min until glucose level is greater than 60 mg/dl and/or until symptoms had resolved then dextrose 10% was discontinued and insulin infusion was always resumed in column 1 . BG was greater than 60 mg/dl on detection of hypoglycemia and was restarted at half the previous infusion rate once the BG was greater than 120 mg/dl. Serum K + : if K + concentrations were less than 3.5 mmol/l at study entry, participants received oral or intravenous replacement to ensure a K + concentration of at least 3.5 mmol/l before insulin administration. When insulin treatment was initiated, K + was checked at 2, 4, and 6 h, then 6-h intervals during intravenous insulin. K + of less than 3.5 mmol/l during insulin treatment was treated with K + replacement .
Statistical presentation and analysis of data of the present study were conducted using the mean, SE, the Student t-test, and the χ2 -test using SPSS version 13.0 statistical software packages (IBM Corporation, Endicott, New York, USA). Description of quantitative variables was in the form of mean, SD, and range. Description of qualitative variables was in the form of frequency and percentages. Unpaired Student's t-test was used to compare between two groups in quantitative data. The χ2 -test was used to compare qualitative variables. The differences were considered significant at P value of less than or equal to 0.05.
| Results|| |
Analysis of data
A total of 200 patients completed this study, 100 in each group, 98 (49%) women and 102 (51%) men. The age ranged from 22 to 70 years in group I and group II. In all, 52 patients were admitted for more than 7 days (38 in group II and 14 in group I) and 148 patients were admitted from 2 to 7 days (62 in group II and 86 in group I).
In group I, 75% of patients were admitted due to surgical cause (colectomy 19%, craniotomy 29%, dynamic hip screw 9%, esophagectomy 7%, gastrectomy 4%, and radical cystectomy 7%) and 25% were admitted due to medical cause [CVS 9%, intracerebral hemorrhage (ICH) 1%, respiratory failure (RF) 9%, sepsis 4%, and postcardiac arrest 2%]. However, in group II, 71% of patients were admitted due to surgical cause (colectomy 17%, craniotomy 26%, dynamic hip screw 7%, esophagectomy 9%, gastrectomy 5%, and radical cystectomy 7%) and 29% were admitted due to medical cause (cerebral vascular stroke (CVS) 7%, ICH 9%, RF 9%, sepsis 2%, and postcardiac arrest 2%). Regarding the surgical causes for ICU admission, there was no statistically significant difference between the two groups (P = 0.979) and for the medical causes for ICU admission, there was no statistically significant difference between the two groups (P = 0.133). There was no statistically significant difference between the two groups regarding the surgical and medical causes for ICU admission (P = 0.633) [Table 3].
Of all blood sugar measurements, there were no episodes of hypoglycemia. Of all admitted patients, 10 patients were ventilated (eight patients on day 1: four patients following cardiac arrest and four patients due to disturbed conscious level; two on day 3 due to RF). Four patients died (two patients died from multiorgan failure at day 10 and day 15, one patient died at day 9 due to massive ICH, and one patient died at day 8 due to severe septic shock).
Regarding all demographic data (age and sex), there were no statistically significant differences between the studied groups (P = 0.44 and 0.730, respectively). Regarding duration of ICU stay, there was a statistically significant higher rate of ICU stay for more than 7 days among patients of group II (P < 0.001) [Table 4].
Chest infection in the two groups
Comparing between the incidence of chest infection in the euglycemic and conventional groups (group I and group II, respectively), there was low incidence of chest infection in four patients (4%) of group I, whereas 18 patients (18%) of group II (22 of 200 patients) showed chest infection; hence, there was a high statistical significant difference between the two groups (P = 0.003) [Table 5].
Regarding the CRP, of all participating patients, 56 patients of both groups showed positive CRP value (23 in group I and 33 in group II) with no statistically significant difference between the two groups (P = 0.156) [Table 6]. Of positive CRP value patients, only 22 patients showed chest infection as CRP may be positive in other conditions - for example, cancer, old age, and autoimmune diseases.
| Discussion|| |
Glucose homeostasis is dysregulated in critically ill patients, resulting in hyperglycemia, irrespective of previously diagnosed diabetes . This condition has been labeled stress diabetes or diabetes of injury . Strict glycemic control by insulin infusion was found to significantly reduce chest infection among the ICU admitted patients . Nonetheless, no universal agreement exists on an optimal range of BG values in ICU patients because of the lack of evidence from randomized trials. Evidence is only provided from observational studies that propose that euglycemic control may reduce chest infection in ICU patients. Tight glycemic control (BG 80-110 mg/dl) is associated with a high incidence of hypoglycemia and an increased risk of death especially in patients not receiving parenteral nutrition ; therefore, in our study we chose to keep blood sugar between 100 and 120 mg/dl and tried to detect its effect. Consequently, the results provided by the above study and several other studies have led the professional organizations to implement euglycemic control in ICU patients and to determine the benefits of euglycemic control in ICU patients.
The current study aimed at evaluation of the safety of euglycemic control and its efficacy in reducing the incidence of chest infection in ICU patients. In the current study, all demographic data (age and sex) and causes of ICU admission were not statistically significant between the two groups, whereas there was a statistically significant difference between the two groups regarding duration of ICU stay as there was a statistically significant higher rate of ICU stay for more than 7 days among patients of group II (the conventional group) (P < 0.001) and the incidence of chest infection as the incidence of chest infection among group II (the conventional group) was 18% and was 4% in group I (euglycemic control). Of all blood sugar measurements, there were no episodes of hypoglycemia, emphasizing the safety of euglycemic control.
Supporting the results of our study, Lepper et al.  studied the impact of serum glucose on the severity of chest infection and the effect of serum glucose levels for predicting death in patients admitted to hospital for community-acquired pneumonia. They concluded that serum glucose levels on admission to hospital can predict death in patients with community-acquired pneumonia without pre-existing diabetes. Acute hyperglycemia may therefore identify patients in need for intensified care to reduce the risk of death from community-acquired pneumonia. Other studies emphasized that tight glycemic control is hazardous for ICU patients. A meta-analysis conducted by Wiener et al. , who studied the benefits and risks of tight glycemic control in critically ill adults, concluded that tight glucose control is not associated with significantly reduced hospital mortality but is associated with an increased risk for hypoglycemia. Another meta-analysis study conducted by Marik and Preiser  concluded that tight glucose control is associated with a high incidence of hypoglycemia and an increased risk of death especially in patients not receiving parenteral nutrition. In contrast, Agus et al.  studied the effect of tight glycemic control on postcardiac surgery pediatric patients, and they concluded that tight glycemic control can be achieved with a low hypoglycemia rate after cardiac surgery, but it does not significantly change the infection rate, mortality, length of stay, or measures of organ failure, as compared with standard care.
| Conclusion|| |
Euglycemic control (blood sugar between 100 and 120 mg/dl) reduces the incidence of chest infection in ICU patients.
| Acknowledgements|| |
| References|| |
|1.||Edwards JR, Peterson KD, Andrus ML, et al. National healthcare safety network (NHSN) report, data summary for 2006 through 2007. Am J Infect Control 2008; 36:609-626. |
|2.||Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med 2002; 165:867-903. |
|3.||Safdar N, Dezfulian C, Collard HR, et al. Clinical and economic consequences of ventilator associated pneumonia: a systematic review. Crit Care Med 2005; 33:2184-2193. |
|4.||Barsanti MC, Woeltje KF. Infection prevention in the intensive care unit. Infect Dis Clin N Am 2009; 23:703-725. |
|5.||Brian P, Kavanagh, MB, Karen CM. Glycemic Control in the ICU. N Engl J 2010; 363:2540-2546. |
|6.||Archer JRH, Misra S, Simmgen M, et al. Phase II study of tight glycemic control in COPD patients with exacerbations admitted to the acute medical unit. BMJ Open 2011; 1:e000210. |
|7.||Ellger B, Richir MC, van Leeuwen PA, et al. Glycemic control modulates arginine and asymmetrical-dimethylarginine levels during critical illness by preserving dimethylarginine-dimethylaminohydrolase activity. Endocrinology 2008; 149:3148-3157. |
|8.||Biolo G, De Cicco M, Lorenzon S, et al. Treating hyperglycemia improves skeletal muscle protein metabolism in cancer patients after major surgery. Crit Care Med 2008; 36:1768-1775. |
|9.||Albacker T, Carvalho G, Schricker T, Lachapelle K. High-dose insulin therapy attenuates systemic inflammatory response in coronary artery bypass grafting patients. Ann Thorac Surg 2008; 86:20-27. |
|10.||Gandhi GY, Nuttall GA, Abel MD, et al. Intensive intraoperative insulin therapy versus conventional glucose management during cardiac surgery: a randomized trial. Ann Intern Med 2007; 146:233-243. |
|11.||American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171:388-416. |
|12.||Vanhorebeek I, Langouche L, Van den Berghe G. Tight blood glucose control with insulin in the ICU: facts and controversies. Chest 2007; 132:268-278. |
|13.||McCowen KC, Malhotra A, Bistrian BR. Stress-induced hyperglycaemia. Crit Care Clin 2001; 17:107-124. |
|14.||Marik PE, Preiser JC. Toward understanding tight glycemic control in the ICU: a systematic review and metaanalysis. Chest 2010; 137:544-551. |
|15.||Lepper PM, Ott S, Nüesch E, et al. Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia. BMJ 2012; 344:e3397. |
|16.||Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults. JAMA 2008; 300:933-944. |
|17.||Agus MS, Steil GM, Wypij D, et al. Tight glycemic control versus standard care after pediatric cardiac. N Engl J Med 2012; 367:1208-1219. |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]