Glycemic Control: A Literature Review with Implications for Perioperative Nursing Practice

Article Outline

• ABSTRACT
• Importance of Perioperative Glycemic Control
• Clinical History and Policy Implications of Glycemic Control
• Review of the Literature
  • Perioperative hyperglycemia and infection
  • Perioperative hyperglycemia and morbidity and mortality
  • Perioperative glycemic control interventions and tight glycemic control
    • The Portland Protocol
    • Other interventional studies
  • Perioperative glycemic control in noncardiovascular surgeries
  • Nursing research and quality improvement (QI) projects
  • Safety and efficacy concerns of tight glycemic control
  • NICE-SUGAR study
  • Intensive insulin therapy meta-analysis including NICE-SUGAR results
• Summary of Studies
• Recommendations for Research
• Implications for Perioperative Nursing Practice
  • Preoperative phase
  • Intraoperative phase
  • Postoperative phase
• Conclusion
• Examination
  • Glycemic Control: A Literature Review with Implications for Perioperative Nursing Practice
    • Purpose/Goal
    • Behavioral Objectives
    • Questions
• Answer Sheet
  • Glycemic Control: A Literature Review with Implications for Perioperative Nursing Practice
• Learner Evaluation
  • Glycemic Control: A Literature Review with Implications for Perioperative Nursing Practice
    • Purpose/Goal
    • Objectives
    • Content
    • Test Questions/Answers
    • Learner Input
• References
• Copyright

ABSTRACT 

Surgical patients have an increased risk for hyperglycemia and its subsequent complications, such as increased risk of infection, morbidity and mortality, and length of stay.

Interventional studies indicate that tight glycemic control with intensive insulin therapy improves outcomes. More recent randomized controlled trials, however, provide conflicting results, indicating that hypoglycemia and death may result from tight glycemic control. This calls into question the safety and efficacy of tight glycemic control.

Perioperative nurses must be prepared to implement measures to control hyperglycemia for patients with and without diabetes throughout the perioperative process. Perioperative nurses should participate in multidisciplinary efforts to develop evidenced-based glycemic control protocols. AORN J 90 (November 2009) 714–726. © AORN, Inc, 2009.

Key words:  perioperative hyperglycemia , glycemic control , intensive insulin therapy , continuous insulin infusion

Perioperative glycemic control is the management of a patient's blood glucose levels (BGLs) throughout the surgical process. According to the American College of Endocrinology (ACE) and the American Diabetes Association (ADA) Task Force on Inpatient Diabetes, glycemic control in hospitalized patients has not been a major therapeutic focus until recently.¹ Contributing to this was a lack of published glucose targets and guidelines.

Recent research has demonstrated that preventing hyperglycemia with tight glycemic control via IV insulin infusions results in improved patient outcomes, so specific glucose targets are now being recommended.¹, ² Specific glucose targets are a topic of interest in the surgical arena because of controversial evidence about

All patients, whether or not they have diabetes, are at risk for altered blood glucose levels during surgery and also are at risk for adverse outcomes as a result.¹, ², ³, ⁴ Tight glycemic control protocols are being implemented across the country and glucose control targets are being recommended in national quality and patient safety initiatives. However, the available evidence does not support routine use of this practice in the OR.²

Evidenced-based practice, which results in improved patient outcomes, is a crucial element of perioperative nurses' commitment to provide quality care. Perioperative nurses must examine the evidence and collaborate with other perioperative team members to develop appropriate glycemic control protocols in their practice setting. This article discusses the importance of perioperative glycemic control, examines the clinical history of implementing perioperative glycemic control and relevant policy implications, and presents a review of the literature addressing perioperative glycemic control including implications for perioperative nursing practice.

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Importance of Perioperative Glycemic Control 

The prevalence of diabetes in the United States is increasing every year. It is estimated that 23.6 million US children and adults have diabetes.⁵ This estimate includes 17.9 million people with diagnosed diabetes and 5.7 million people with undiagnosed diabetes but not the 57 million people with prediabetes.⁵ Diabetes mellitus is associated with a number of preoperative comorbidities, such as obesity, small vessel coronary artery disease, and hypertension.⁶ Thus, patients with diabetes are more likely to need surgery than patients who do not have diabetes.⁷

In 2006, 46 million inpatient surgeries were performed in the United States.⁸ Because of the increased prevalence of diabetes, many patients with this diagnosis will be admitted to the hospital for surgery and will need blood glucose management.

Hyperglycemia is a common response to critical illness and metabolic stress and is associated with increased inflammation, susceptibility to infection, and multiorgan dysfunction.² Hyperglycemia is defined as a fasting BGL of 126 mg/dL or higher or two or more random BGLs of 200 mg/dL or higher.⁷, ¹⁰ Inpatient hyperglycemia can occur in patients with or without diabetes, particularly in surgical and critically ill populations.³, ⁴, ⁹ Levetan et al¹¹ found that 37.5% of all hyperglycemic medical patients and 33% of hyperglycemic surgical patients did not have a diagnosis of diabetes at the time of admission.

There is increasing evidence that hyperglycemia during an acute surgical or medical illness in patients with diabetes and patients with undiagnosed diabetes is associated with increased morbidity and mortality as well as increased health care costs.¹, ², ³, ⁴ Krinsley¹² reported that hospital mortality was 42.5% among patients with mean BGLs exceeding 300 mg/dL. Umpierrez et al¹³ found that patients with new hyperglycemia have an 18.3-fold increase in mortality rate compared with a 2.7-fold increase in patients with known diabetes, and patients with new hyperglycemia have worse functional outcomes and increased lengths of hospital stay (LOS). The total annual economic cost of diabetes care in 2007 was estimated to be $174 billion.⁵ Of this amount, inpatient hospital costs were $58.3 billion.³

Patients who undergo surgery are at an increased risk for hyperglycemia as a result of the surgical procedure and the effects of anesthesia. The stress of surgery and anesthesia results in the release of counter-regulatory hormones and inflammatory cytokines, which cause alterations in carbohydrate metabolism, including

General anesthesia is associated with higher blood glucose concentrations than local or epidural anesthesia because of higher circulating concentrations of catecholamines, cortisol, and glucagon.⁷, ⁹, ¹⁴

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Clinical History and Policy Implications of Glycemic Control 

For more than 10 years, the relationship between hyperglycemia and outcomes has been investigated in surgical patients, the critically ill, and other patient populations.², ³ In surgical patients, particularly those undergoing cardiovascular surgery, hyperglycemia has been shown to increase infection as well as morbidity and mortality.⁷, ¹⁶ Patients with diabetes undergoing surgery are at an even greater risk for adverse outcomes; this is often referred to as the “diabetic disadvantage.”⁷, ¹⁶, ¹⁷ Elevated glucose levels are a predictor of congestive heart failure and mortality in patients with and without diabetes who experience an acute myocardial infarction (MI).³, ⁴, ¹⁸ Hyperglycemia after ischemic stroke is associated with worse functional outcomes, and after trauma, patients who do not have diabetes but who have hyperglycemia are at increased risk for longer hospital stays, infections, and death.³, ⁴, ¹⁸

More recently, interventional studies have emerged that link glycemic control to improved outcomes in medical and surgical patients, particularly in the areas of acute MI, critical illness, and cardiac surgical procedures.¹, ², ³ In 1999, the first randomized multicenter Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study showed that IV insulin therapy to control glucose levels significantly reduced morbidity and mortality rates in patients with acute MI.¹, ³, ¹⁶ However, the landmark study that provided evidence and set a new standard for controlling BGLs in hospitalized patients was performed in Leuven, Belgium.¹⁹ In 2001, van den Berghe et al¹⁹ published the first Leuven study, a prospective randomized controlled trial (RCT) involving 1,548 adults admitted to the surgical intensive care unit (ICU) who were being mechanically ventilated. Patients were randomly assigned to receive intensive insulin therapy (IIT) to maintain a BGL between 80 mg/dL and 110 mg/dL or conventional infusion treatment to maintain a BGL between 180 mg/dL and 200 mg/dL if the BGL exceeded 215 mg/dL. In the group receiving IIT, an insulin infusion was started if the patient's BGL exceeded 110 mg/dL. The results showed that IIT reduced inhospital mortality by 34% compared to conventional therapy.¹⁹ Intensive insulin therapy also was shown to significantly decrease morbidity including bloodstream infections, acute renal failure, red blood cell transfusions, and critical illness polyneuropathy.¹⁹

According to Lipshutz and Gropper, “Widespread implementation of IIT in the perioperative period ensued on the basis of these data.”^2(p408) In addition, the Joint Commission has included controlled postoperative BGLs in cardiac surgical patients in its core measurement set based on the Surgical Care Improvement Project (SCIP) standard.²⁰ The SCIP, a national quality partnership of leading public and private health care organizations, calls for cardiac surgery patients to have a controlled BGL of less than 200 mg/dL by 6 AM on postoperative day (POD) one.², ²⁰ In their effort to encourage improved quality of care, the Centers for Medicare & Medicaid Services has included glycemic control in its Hospital-Acquired Conditions in Acute Inpatient Prospective Payment System and Medicare's Pay-for-Performance initiatives.²¹ The Centers for Medicare & Medicaid Services policy states that hospitals will not receive reimbursement for manifestations of poor glycemic control. The ACE developed a consensus report recommending a target BGL of 110 mg/dL in ICU patients. They also recommend a non-ICU preprandial BGL target of 110 mg/dL with a maximum BGL of 180 mg/dL.²² Additionally, the American Association of Clinical Endocrinologists (AACE) recommends IIT as the standard of care with a target blood glucose level of 80 mg/dL to 110 mg/dL for critically ill patients.²³ In noncritically ill patients, the AACE recommends a preprandial level of less than 110 mg/dL and a peak postprandial level of less than 180 mg/dL.

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Review of the Literature 

The vast majority of perioperative glycemic control research has been quantitative research conducted in the intraoperative and postoperative phases of surgery, particularly in the area of cardiovascular surgery. Outcomes research has focused on infection, morbidity, and mortality. Interventional research has largely examined the effects of IIT or continuous insulin infusion (CII). Research studies on perioperative glucose control in noncardiovascular surgery and nursing research studies also have been conducted.

Perioperative hyperglycemia and infection 

Early studies in perioperative glycemic control focused on hyperglycemia and its associated risk for adverse outcomes (eg, infection). In a prospective study, Pomposelli et al²⁴ studied 100 patients with diabetes undergoing elective abdominal and cardiovascular surgery who initially did not have an infection. The researchers monitored the patients for perioperative glucose control and postoperative nosocomial infections. Monitored infections included bacteremia, pneumonia, and wound infection. Patients were stratified into “good” perioperative glucose control (220 mg/dL) or “poor” perioperative glucose control (at least one value > 220 mg/dL). Serum glucose greater than 220 mg/dL on POD one was sensitive (87.5%) for later development of postoperative nosocomial infection. In patients with hyperglycemia (> 220 mg/dL) on POD one, the infection rate was 2.7 times that observed in patients with diabetes whose serum glucose values were all less than or equal to 220 mg/dL (31.3% versus 11.5%, P < .05).²⁴ When minor urinary tract infections were excluded, there was a 5.8-fold increase in the rate of infection (24.6% versus 4.2%, P < .03). Hyperglycemia on POD two did not show the same risk for infection.

In a nonconcurrent prospective cohort study of 411 adults with diabetes who underwent coronary artery surgery from 1990 to 1995, Golden et al²⁵ assessed the relationship of perioperative glycemic control to the subsequent risk of infections including leg and chest wounds, pneumonia, and urinary tract infection. Their measurement consisted of a mean of six capillary glucose measurements taken during the initial 36-hour interval after surgery. Mean postoperative BGLs were divided into quartiles ([1] 121 mg/dL to 216 mg/dL, [2] 217 mg/dL to 229 mg/dL, [3] 230 mg/dL to 252 mg/dL, [4] 253 mg/dL to 352 mg/dL). The researchers determined that patients in quartiles 2 (relative odds of infection 1.17, 95% confidence interval [CI] 0.57–2.40), 3 (1.86, 95% CI 0.94–3.68), and 4 (1.78, 95% CI 0.86–3.47, P = .05 for trend) had a progressively higher risk for infection compared to patients in quartile 1.

In a prospective cohort and case-controlled study, Latham et al²⁶ assessed the importance of diabetes, diabetes control, hyperglycemia, and previously undiagnosed diabetes in the development of surgical site infections (SSIs) among patients undergoing cardiothoracic surgery. Between November 1998 and September 1999, 1,000 patients who underwent cardiothoracic surgery had glycated hemoglobin (HgA1c) determinations (ie, a form of hemoglobin used primarily to identify the average plasma glucose concentration over prolonged periods of time). The researchers found that diabetes (odds ratio [OR] 2.76, P < .001) and postoperative hyperglycemia (OR 2.02, P = .007) were independently associated with the development of SSIs. Among patients with known diabetes, elevated HgA1c values were not associated with a significant increase in risk of infection (P = .09).²⁶ Six percent of the 700 patients without prior diabetes history had evidence of undiagnosed diabetes. Their infection rate was comparable to patients with known diabetes (7% versus 6%, P = .72). The rate of SSIs directly correlated with the degree of hyperglycemia encountered during the postoperative period. Compared to patients with BGLs greater than 200 mg/dL, the odds ratio of SSIs increased as BGLs increased:

Perioperative hyperglycemia and morbidity and mortality 

Several studies address the effect of perioperative hyperglycemia on morbidity and mortality. In one of the few studies comparing people with and without diabetes, Doenst et al²⁷ used a retrospective chart review to assess the influence of hyperglycemia during cardiopulmonary bypass on morbidity and mortality in 1,579 patients with diabetes and 4,701 patients without diabetes undergoing cardiac surgery between 1999 and 2001. Boluses of insulin were given during cardiopulmonary bypass when BGLs exceeded 270 mg/dL (15 millimole [mmol]/L), when the serum potassium level exceeded 6.0 mmol/L, or both.²⁷ They found that a high BGL during cardiopulmonary bypass was an independent predictor for mortality per mmol/L increase in both patients with diabetes (P =.0005) and patients without diabetes (P < .0001).²⁷ A high glucose level during bypass was also an independent predictor of all major adverse events (eg, stroke, infection, MI, low output syndrome, death) in patients with diabetes (P = .0378) and those without diabetes (P < .0001).²⁷ For adverse cardiac events only, however, the odds ratios reached significance in patients without diabetes only (P = .0031).²⁷ Mortality was less than 2% when the peak glucose level remained < 360 mg/dL (20 mmol/L); however, the incidence of mortality tripled when the peak glucose level exceeded 360 mg/dL (20 mmol/L) for both groups. The relationship for mortality was identical for patients with and without diabetes (2.1% and 1.7%, respectively; P > .4). Because of this lack of difference between patients with and without diabetes, the authors hypothesized that insulin resistance rather than hyperglycemia might be the cause of these adverse outcomes.²⁷

In a retrospective observational study, Gandhi et al²⁸ estimated the magnitude of association between intraoperative hyperglycemia and perioperative outcomes in 409 consecutive adult patients who underwent cardiac surgery between June 10, 2002, and August 30, 2002. The primary endpoint was a composite of death and infectious, neurologic, renal, cardiac, or pulmonary complications developing within 30 days after surgery. They found that patients with at least one of these outcomes had significantly higher mean glucose levels than those who did not (P < .01). This was true whether or not the patients had diabetes. The initial (122 versus 114 mg/dL, P < .01); the mean (141 versus 127 mg/dL, P < .01); and the maximal (172 versus 151 mg/dL, P < .01) intraoperative glucose concentrations were significantly higher in patients experiencing any event. When variables such as age, gender, diagnosis of diabetes mellitus, and body mass index were considered, the initial glucose level was not a significant predictor of outcome (P = .47); however, the mean (P < .01) and the maximal (P < .01) glucose levels were significant. The researchers determined that a 20 mg/dL increase in the mean intraoperative glucose level was associated with a 30% increase in adverse outcomes. Their analysis showed a positive linear relationship between the mean glucose level and the likelihood of experiencing a postoperative event, with the lowest likelihood corresponding to a mean glucose level < 100 mg/dL (35%) and the highest occurring in patients with a mean glucose level of 200 mg/dL or more (76%).²⁸

In a prospective observational cohort study, Quattara et al¹⁷ sought to determine whether poor intraoperative glycemic control was associated with increased inhospital morbidity among 200 patients with diabetes undergoing on-pump heart surgery. Poor intraoperative glycemic control was defined as four consecutive BGLs > 200 mg/dL without any decrease despite insulin therapy. The main endpoints were severe cardiovascular, respiratory, infectious, neurologic, and renal inhospital morbidity. Their results showed an adjusted odds ratio of 7.2 (95% CI 2.7–19.0) for severe postoperative morbidity among patients with poor intraoperative glycemic control.¹⁷

Perioperative glycemic control interventions and tight glycemic control 

Interventional studies emphasizing tight glycemic control with IIT or CII therapy began to be conducted based on the research results indicating that perioperative hyperglycemia is associated with adverse outcomes. In the early 1990s, Anthony P. Furnary, MD, and colleagues began to question what they called the conventional wisdom of the “diabetic disadvantage.” This refers to the disadvantage that diabetic cardiac surgery patient have because they are more likely to acquire cardiac disease and they have worse short- and long-term outcomes. To determine whether the diabetic disadvantage was a result of the acute effects of hyperglycemia on outcomes, they started the Portland Diabetic Project, an ongoing, 19-year, prospective, nonrandomized interventional study of hyperglycemia and its pharmacologic reduction with CII, which has pioneered research in this area.

The Portland Protocol 

The goal of the Portland Diabetic Project was to clarify the effects of perioperative hyperglycemia and its subsequent reduction with CII on inhospital outcomes.¹⁶ The study included 5,534 patients with diabetes undergoing cardiac surgery:

Surgeries included coronary artery bypass graft (CABG) surgery, valve surgery with CABG, isolated valve replacements or repairs, and other surgeries such as replacement of the ascending aorta. The independent variable was an average of all glucose values on the first three days after surgery (ie, 3-BG) consisting of no less than 24 and as many as 72 glucose measurements.¹⁶

The researchers examined the CABG subpopulation to assess the relationship between hyperglycemia and mortality and found that increasing 3-BG significantly and independently affects mortality (OR 2.6 for 50 mg/dL increase in 3-BG, P < .001). Blood glucose levels on the day of surgery and on the first and second POD (P < .001 for all) were found to be independently associated with inhospital mortality. The researchers found that inhospital mortality was greater for the subcutaneous insulin group than the CII group (5.3% versus 2.1%, P < .001). Their analysis revealed that CII independently conferred a 65% reduction in mortality in the diabetic CABG population (OR 0.35, P < .001). Mortality was found to be independent of the use of epinephrine (P < .001).¹⁶

Their results also suggest a significant and independent association between hyperglycemia and postoperative deep sternal wound infection (DSWI). A 3-BG greater than 175 mg/dL was associated with DSWI (1.3% versus 0.6%, P = .02), and the risk of DSWI increased more than two-fold for every 50 mg/dL increase in 3-BG (OR 2.1, P < .0001). They reported a 63% reduction in DSWI with the use of CII (1.6% versus 0.7%, P < .01). The LOS was examined in the CABG population and was found to independently increase by one day for every 64 mg/dL increase in 3-BG (P < .0001). Use of CII was found to reduce LOS by 2.0 days (P < .0001) compared to use of subcutaneous insulin. Interestingly, the study showed no significant effect of HgAlc and the 3-BG on mortality, DSWI, or LOS on POD three.¹⁶

Other interventional studies 

In addition to the Portland Diabetic Project, other interventional research has examined the efficacy of tight glycemic control. In an RCT, Lazar et al²⁹ prospectively randomized 141 patients with diabetes undergoing CABG to tight glycemic control (target BGL, 125 mg/dL to 200 mg/dL) with a modified glucose-insulin-potassium (GIK) therapy or standard therapy (target BGL < 250 mg/dL) using intermittent subcutaneous insulin beginning before anesthesia and continuing for 12 hours after surgery. The researchers determined that patients treated with GIK therapy had lower serum glucose levels (P < .0001), a lower incidence of atrial fibrillation (P = .0017), and a shorter LOS (P = .003). Better glycemic control resulted in lower incidence of pneumonia and wound infections (P = .01). Compared to the standard therapy group, patients treated with GIK therapy

Gandhi et al³⁰ conducted an RCT to compare outcomes of IIT with those of conventional intraoperative glucose management among 400 adults with and without diabetes undergoing on-pump cardiac surgery. The primary outcome measure was a composite of death and

within 30 days after surgery. The secondary outcome measure was LOS. One hundred ninety-nine patients were randomly assigned to receive IIT to maintain intraoperative glucose levels between 4.4 mmol/L (80 mg/dL) and 5.6 mmol/L (100 mg/dL), and 210 patients were assigned to receive conventional treatment where insulin was not administered during surgery unless glucose levels were greater than 11.1 mmol/L (200 mg/dL). There was no significant difference between groups in the composite endpoint (P = .71) but more deaths (4 versus 0, P = .061) and strokes (8 versus 1, P = .02) occurred in the IIT group. The authors concluded that IIT during cardiac surgery does not reduce perioperative death or morbidity and that the increased incidence of death and stroke in the IIT group raised concern about routine implementation of this intervention. The researchers acknowledged that study limitations included its single-center design using a composite endpoint and the inability to determine whether outcomes differed by diabetic status.³⁰

Gandhi et al³¹ conducted a systematic review and meta-analysis of 34 RCTs that evaluated the effect of perioperative insulin infusion during any type of surgery on outcomes important to patients. For each RCT, relative risks (RR) were calculated for outcomes for patients receiving a perioperative insulin infusion compared with patients receiving a control intervention. In the 14 trials that assessed mortality, there were 69 deaths among 2,192 patients randomized to receive insulin infusion compared with 98 deaths among 2,163 patients randomly assigned to receive control therapy. In all trials, hypoglycemia occurred more in the group receiving insulin infusions (RR 2.07, 95% CI 1.29–3.32). No significant effect was seen in any other outcomes. The authors concluded that perioperative insulin infusions might reduce mortality but increase hypoglycemia in patients who undergo surgery. They acknowledged that the available mortality data represented only 40% of the optimal information size required to reliably detect a plausible treatment effect. More RCTs were recommended.³¹

Perioperative glycemic control in noncardiovascular surgeries 

There is a growing body of evidence regarding perioperative glycemic control research in noncardiovascular surgical fields. In a retrospective study, Ramos et al³² evaluated the association of perioperative hyperglycemia and 30-day postoperative infections (POIs) in 995 patients who had undergone general and vascular surgery. Postoperative glucose (POG) was their primary predictor of interest. They found that POG increased the risk of POI by 30% with every 40 mg/dL increase from normoglycemia (< 110 mg/dL, P = .026).³² Patients with POI had significantly elevated POG (P < .001) compared to those without. Longer hospitalization also was observed for patients with POG greater than 110 mg/dL. Patients with BGLs of 110 mg/dL to 200 mg/dL had a 0.4-day longer hospital stay (P = .001) and those with BGLs greater than 200 mg/dL had a 0.8-day longer stay (P < .0001). The risk for POI was independent of preoperative BGLs and diabetic status.³²

In a retrospective, nonrandomized chart review, McConnell et al³³ investigated the relationship between postoperative glycemic control and SSI in 149 patients with diabetes mellitus undergoing colorectal resection between April 2001 and May 2006. They defined poor glycemic control as a mean 48-hour postoperative capillary glucose > 200 mg/dL (> 11.0 mmol/L). In their study, 24% of the cohort had poor glycemic control, and those patients developed SSIs at a significantly higher rate than patients with postoperative capillary glucose less than or equal to 200 mg/dL (29.7% versus 14.3%, OR 2.5, P = .03). A 48-hour capillary glucose greater than 200 mg/dL (> 11.0 mmol/L) was significantly associated with SSI (OR 3.6, P = .02), independent of treatment type.³³

Nursing research and quality improvement (QI) projects 

Although nurses were involved in many of these studies, nursing research in perioperative glycemic control has occurred mainly in the area of QI projects. Pennell et al³⁴ and Najarian et al³⁵ conducted before-and-after retrospective chart reviews to evaluate whether quality and performance improvement initiatives in hyperglycemic management resulted in substantiated practice changes and improved outcomes for patients. Pennell et al³⁴ examined 103 randomly selected patients hospitalized for CABG and Najarian et al³⁵ examined 90 preintervention and 144 postintervention patients who underwent vascular surgery. Both improvement protocols called for the use of sliding scale insulin and insulin infusions perioperatively.

After implementation of the QI project, Pennell et al³⁴ found that perioperative use of IV insulin infusion therapy increased in the total population (4.9% versus 24.2%, P = .01) and in the diabetic population (12.5% versus 44.8%, P = .03). Although the finding was not significant, they determined that the frequency of blood glucose tests ordered for undiagnosed patients increased from 2.8 per day to 4.3 per day (P = .38). Their results showed an increase in the number of patients with diabetes whose BGLs were in the range of 110 mg/dL to 139 mg/dL (13.2% versus 24.5%, P = .048).³⁴

Najarian et al³⁵ found that the difference in mean BGLs was significant between groups (186.9 versus 172.5, P < .0001) and that there was a 19% decrease (P < .001) in the total rate of infections. The authors of both projects concluded that the hospital QI project produced practice changes that improved clinical outcomes for patients.

Safety and efficacy concerns of tight glycemic control 

The recent study by Gandhi et al³⁰ and meta-analysis by Gandhi et al³¹ have questioned the safety and efficacy of tight glycemic control. In addition, two recent RCTs of IIT and conventional therapy were stopped early because of patient safety concerns and the high incidence of hypoglycemia. The European GLUCONTROL trial of mixed medical and surgical patients was stopped because of the increased incidence of hypoglycemia (BGL < 40 mg/dL) in the IIT group (target BGL 80 mg/dL to 110 mg/dL) compared to the conventional treatment group (target BGL 140 mg/dL to 180 mg/dL, 8.6% versus 2.4%) and the increase in mortality among patients with hypoglycemia in both treatment groups (32.6% versus 53.8%).², ³, ⁹, ³¹

The German multicenter Volume Substitution and Insulin Therapy in Severe Sepsis (VISEP) study was stopped at the first planned safety analysis. At 28 days, there was no difference in the rate of death between IIT (BGL target 80 mg/dL to 110 mg/dL) and conventional therapy (BGL target 180 mg/dL to 200 mg/dL) but the rate of severe hypoglycemia (BGL < 40 mg/dL) was significantly higher in the IIT group (12.1% versus 2.1%, P < .001).², ⁹, ³¹

In an RCT by van den Berghe et al³⁶ comparing IIT (target BGL 80 mg/dL to 100 mg/dL) and conventional therapy (insulin infusion administered for BGL > 215 mg/dL) in the medical ICU, IIT was not found to reduce mortality (P = .33). In addition, hypoglycemia occurred in 18.7% of patients in the IIT group compared to 3.1% in the conventional group.³⁶ Finally, in a retrospective database review of 102 critically ill patients with at least one episode of hypoglycemia, Krinsley and Grover³⁷ determined that a single episode of hypoglycemia was independently associated with increased risk of mortality (55.9% versus 39.5% among 306 controls).

NICE-SUGAR study 

Many researchers and practitioners are looking to the international, multicenter Normoglycemia in Intensive Care Evaluation—Survival Using Glucose Algorithm Regulation (NICE–SUGAR) study to provide answers.², ⁹, ³¹ This RCT, from which results were published on March 26, 2009, is the largest trial of IIT to date.³⁸, ³⁹ The NICE-SUGAR study was a collaborative effort between the Australian and New Zealand Intensive Care Society Clinical Trials Group, the George Institute for International Health (University of Sydney), the Canadian Critical Care Trials Group, and the Vancouver Costal Health Research Institute (University of British Columbia).³⁹ Because the optimal target range for BGLs in critically ill patients has not been clearly identified, the NICE–SUGAR trial was designed to test the hypothesis that intensive glucose control reduces mortality at 90 days.

The study, a parallel-group RCT, randomized 6,104 adult medical and surgical patients admitted to the ICUs of 42 hospitals: 3,054 received intensive glucose control and 3,050 received conventional glucose control.³⁹ The BGL target for the intensive glucose control group was 81 mg/dL to 108 mg/dL; the BGL target for the conventional glucose control group was 180 mg/dL or less. Blood glucose control was achieved by using IV infusions of insulin and saline. The primary outcome measure, death from any cause within 90 days, was also examined in six subgroups:

After 90 days, data for the primary outcome were available for 3,010 patients receiving intensive glucose control therapy and 3,012 patients receiving conventional glucose control therapy. In the intensive glucose control group, 829 patients died (27.5%) compared to 751 (24.9%) in the conventional glucose control group, a difference of 2.6%. The odds ratio for death in the intensive glucose control group was 1.14 (95% CI 1.02–1.28, P = .02). Causes of death were similar in both groups; however, cardiovascular causes were significantly more common in the intensive glucose control group (41.6% versus 35.8%, P = .02). Severe hypoglycemia (BGL ≤ 40 mg/dL) occurred in 206 of 3,016 patients (6.8%) receiving intensive glucose control therapy compared to 15 of 3,014 patients (0.5%) undergoing conventional glucose control therapy (OR 14.7, 95% CI 9.0–25.9, P < .001).³⁹

Their analysis of the six subgroups showed no significant difference in the treatment effect for any of the groups. However, the results showed a possible trend toward an intensive glucose control treatment effect benefiting patients with trauma compared to those without trauma (P = .07) and for patients receiving corticosteroids compared to those not receiving corticosteroids (P = .06). Other outcome measures included LOS in the ICU, days of mechanical ventilation, and duration of renal replacement therapy. The results showed no significant difference between the treatment groups for any of these outcomes (P = .84, P = .86, and P = .39, respectively).³⁹

The results of the study did not support the hypothesis that intensive glucose control reduces mortality at 90 days. Instead, the authors concluded that intensive glucose control increased mortality among adults in the ICU and that a blood glucose target of 180 mg/dL or less resulted in a lower mortality than did a target of 81 mg/dL to 108 mg/dL.

Intensive insulin therapy meta-analysis including NICE-SUGAR results 

Griesdale et al³⁸ recently updated a meta-analysis of IIT and mortality among critically ill patients to include the NICE–SUGAR trial results. Twenty-six trials were included in the analysis. The researchers found that IIT had no effect on the overall risk of death (RR 0.93%, 95% CI 0.83–1.04). Yet, when the researchers analyzed the effect of IIT by type of ICU, they found that patients in a surgical ICU benefited from IIT compared with those in the control group (P = .02).³⁸ Their analysis, however, showed a six-fold increase in the risk of severe hypoglycemia among patients given IIT compared to those given the control treatment.³⁸

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Summary of Studies 

Due to a believed disadvantage for patients with diabetes who are undergoing cardiovascular surgery, the vast majority of perioperative glycemic control studies have been conducted with this patient population. The Portland Diabetic Project concluded, however, that diabetes mellitus is not the true risk factor; rather, it is the presence of perioperative hyperglycemia. The results from these studies indicate that both diabetic and nondiabetic populations are at risk for adverse outcomes and that undiagnosed diabetes is an important consideration in perioperative glycemic control. Because of this, Doenst et al²⁷ suggested that adverse outcomes may result from insulin resistance rather than hyperglycemia. Evidence supports the theory that perioperative hyperglycemia, particularly from the intraoperative period through the second POD, is independently associated with increased infection, morbidity and mortality, and increased LOS.

Preoperative BGLs and HgAlc values have not been shown to affect outcomes. Research with ICU and critically ill populations suggest a strict BGL target of 80 mg/dL to 110 mg/dL to reduce morbidity and mortality. Although specific targets were not recommended in the research reviewed, most authors suggest maintaining perioperative BGL at less than or equal to 200 mg/dL. Research in other surgical areas shows similar results. Nursing QI projects have led to practice changes that improve clinical outcomes for patients.

Recent RCTs including the NICE-SUGAR study, two meta-analyses of RCTs using IIT, and two studies that were stopped early because of complications present conflicting results, suggesting that IIT does not reduce mortality and that the hypoglycemic risks posed by IIT may outweigh the benefits. These results warrant cautious use of this intervention until further research provides evidence showing which subpopulations, if any, will benefit from tight glycemic control. The appropriate perioperative glucose targets have yet to be determined.

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Recommendations for Research 

The majority of studies reviewed were nonrandomized and observational—either prospective or retrospective—and many authors cited the need for more RCTs. Most research on this topic has been done with patients undergoing cardiovascular surgery and with ICU and critically ill populations. Research in other surgical fields and with other patient groups is warranted, including patients with comorbidities such as hypermetabolic syndrome. Doenst et al²⁷ stated that conclusions from previous studies regarding the effect of hyperglycemia on outcomes after cardiac surgery have to be considered with caution for three reasons:

According to Garber et al,²² questions that need further research include the following:

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Implications for Perioperative Nursing Practice 

The current state of knowledge relating to glycemic control throughout the surgical process has many implications for perioperative nurses. Caring for patients at risk for hyperglycemia perioperatively is a collaborative process involving a multidisciplinary team that includes perioperative nurses, anesthesia care providers, surgeons, and advanced practice nurses. Perioperative nurses committed to providing quality care and improving patient outcomes through evidenced-based practice can promote practice changes in relation to perioperative glycemic control. This can be achieved by helping to formulate perioperative glycemic control standards of care (eg, policies, procedures, protocols) based on the best available evidence; developing QI projects based on these protocols; and collecting data to evaluate the care processes and patient outcomes. According to Newhouse et al,

Combining research, organizational experience (including QI data and financial data), clinical expertise, expert opinion, and patient preference ensures clinical decisions based on all the available evidence.^40(p4)

Perioperative nurses participate in caring for patients needing glycemic control in a variety of ways, including monitoring BGLs and administering treatments for hyperglycemia. This includes administering subcutaneous insulin based on a hospital-established sliding-scale protocol and implementing IV insulin protocols.

Preoperative phase 

The perioperative nurse should preoperatively evaluate patients with diabetes or patients at risk for hyperglycemia. This evaluation should include an assessment of the patient's metabolic status and corresponding comorbidities such as cardiovascular disease, peripheral and autonomic neuropathy, and nephropathy.⁷, ¹⁴ This requires reviewing and interpreting the patient's laboratory results (eg, plasma glucose, pH, creatinine, blood urea nitrogen [BUN], electrolytes).¹⁴

Intraoperative phase 

Intraoperative management may involve frequent BGL monitoring to allow for early detection of metabolic changes.⁷ The perioperative nurse should ensure the availability of blood glucose monitoring equipment, appropriate insulin, and infusion pumps if needed. For example, when a patient has a preoperative BGL greater than 200 mg/dL, the anesthesia care provider may order preoperative insulin administration. Regular BGL measurements may be required intraoperatively depending on the patient's condition, preoperative BGL, and length of surgery.

Postoperative phase 

The perioperative nurse should anticipate the need to measure the BGL of patients who have hyperglycemia while in the postanesthesia care unit. Other patients, depending on their medical history and type of surgery, may require an intraoperative insulin infusion. Based on the results of the studies presented here, close monitoring of BGLs through POD two is necessary. When the patient is transferred to a room on the medical/surgical unit, regular BGL monitoring may be ordered through POD two.

The perioperative nurse also must be aware of potential complications for this patient population and management of these complications. For example, the stress of surgery in patients with diabetes may cause diabetic ketoacidosis or hyperosmolar hyperglycemic nonketotic syndrome.⁷ Patients with diabetes who require emergency surgery also are at risk for diabetic ketoacidosis. Hypoglycemia is a concern because of the altered nutrition experienced by the patient with diabetes in the perioperative period and as a potential complication of tight glycemic control when used.⁷ Perioperative nurses also must remember that patients with undiagnosed diabetes and patients without diabetes are also at risk for adverse outcomes as a result of hyperglycemia. Vigilance through all phases of surgery for all patients is required because perioperative nurses may not anticipate potential problems in patients who are not diagnosed with diabetes. Commitment to working as part of a multidisciplinary and collaborative perioperative team will ensure improved outcomes for all patients.

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Conclusion 

Hyperglycemia commonly occurs among hospitalized patients with and without diabetes and is associated with increased morbidity and mortality rates, LOS, and health care costs. Surgical patients have an increased risk of perioperative hyperglycemia, which also has been shown to increase infection rates, morbidity and mortality rates, and LOS. Perioperative glycemic control reduces these adverse outcomes; however, there is currently conflicting evidence from RCTs as to the safety and efficacy of tight glycemic control with IIT. According to Lipshutz and Gropper,

… there is currently insufficient evidence to support the routine use of tight glycemic control (target BGL 80 mg/dL to 110 mg/dL) in the OR or ICU….”^2(p419)

They also warn that including BGL targets as core measures in the SCIP program and using BGL targets in pay-for-performance initiatives before appropriate target values are defined may create more harm than good.²

More research, including nursing research, is needed to provide additional evidence regarding the mechanisms that contribute to hyperglycemia and the harm it causes, as well as to identify appropriate perioperative glucose targets and determine how to achieve these targets in the perioperative setting. Perioperative nurses who use evidenced-based practice will help to set the standards of care for perioperative glycemic control resulting in improved quality of care, improved outcomes for patients, and overall cost savings.

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Examination 

Glycemic Control: A Literature Review with Implications for Perioperative Nursing Practice 

Purpose/Goal 

To educate perioperative nurses about nursing implications of tight glycemic control for the surgical patient.

Behavioral Objectives 

After reading and studying the article on glycemic control, nurses will be able to

Questions 

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Answer Sheet 

Glycemic Control: A Literature Review with Implications for Perioperative Nursing Practice 

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Learner Evaluation 

Glycemic Control: A Literature Review with Implications for Perioperative Nursing Practice 

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This evaluation is used to determine the extent to which this continuing education program met your learning needs. Rate these items on a scale of 1 to 5.

Purpose/Goal 

To educate perioperative nurses about using biological tissue grafts to reconstruct abdominal wall defects.

Objectives 

To what extent were the following objectives of this continuing education program achieved?

Content 

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Test Questions/Answers 

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Learner Input 

What other topics would you like to see addressed in a future continuing education article? Would you be interested or do you know someone who would be interested in writing an article on this topic?

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References 

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