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Research shows that good control of blood glucose in postoperative patients improves outcomes.

Over the past five years, there has been much new information concerning the role of blood glucose control and outcomes in hospitalized patients. In the past, it was thought that blood glucose levels were acceptable “as long as blood glucose was under 200 to 220 milligrams per deciliter.” In 2001, Van den Berghe et al published landmark research indicating that “tight” blood glucose control led to a significant improvement in outcomes in postoperative patients in the surgical intensive care unit (SICU).1

This research led to the development and implementation of protocols and guidelines for managing blood glucose in hospitalized patients. This article reviews some research showing the relationship of blood glucose levels to outcome, recent studies supporting maintaining blood glucose levels close to normal, and provides some suggestions for RDs wanting to become more involved in managing blood glucose levels in hospitalized patients.

Diabetes Mellitus — A Primer
It’s estimated that more than 14 million individuals in the United States have been diagnosed with either type 1 or type 2 diabetes mellitus (DM). Additionally, another 6 million individuals have undiagnosed diabetes. The vast majority (approximately 90%) have type 2 DM, while approximately 10% have type 1 DM. Other subgroups are those who have gestational DM or pancreatic abnormalities that lead to blood glucose control problems.

Type 1 DM is typically diagnosed in younger individuals, although the disease can appear at any age and is marked by destruction of the insulin-producing beta cells of the pancreas. Most individuals with type 1 DM present with the “classic” symptoms: weight loss, increased thirst, and increased hunger. Onset of diabetic ketoacidosis (DKA) may also require ICU admission to stabilize fluid, electrolyte, and glucose levels. RDs must remember that individuals with type 1 DM require exogenous insulin for immediate survival. Type 1 DM is always treated with insulin; the type, timing, and dosage of insulin will vary. If adequate insulin is not provided, individuals with type 1 DM are at risk for potentially life-threatening DKA. RDs who care for patients or clients using insulin must be aware of the different types of insulin now available. Rapid-acting insulins (Humalog or Novolog) have a rapid onset of action, peak around one hour after injection, and have a duration of action of approximately three to four hours.

Regular insulin begins working approximately 30 minutes following injection, peaks at around three to four hours, and has a six- to eight-hour duration of action. Intermediate-acting insulins (NPH, Lente) have an onset of action of roughly one hour. NPH tends to peak at four to eight hours and lasts approximately 12 to 16 hours, while Lente peaks at nine to 12 hours with a slightly longer duration than NPH.

Long-acting insulin (Lantus) starts to work at roughly one hour after injection. There is either a small peak or no peak at all, with a duration of action of approximately 22 to 24 hours. Management of type 1 DM requires careful balancing of intake, insulin, and activity. Many individuals with type 1 manage their disease with insulin pumps. Insulin pump therapy is beyond the scope of this article.

Type 2 DM was once thought to be a disease of older, overweight adults. As the incidence of obesity has increased across all age ranges in industrialized countries, so has the incidence of type 2 DM. Type 2 DM is characterized by either suboptimal insulin secretion or altered insulin action at the cellular level. In some cases, there is a period of increased insulin secretion as the pancreas attempts to manage the altered insulin action and resulting hyperglycemia. Type 2 DM can be managed with diet, exercise, and/or medication. Medications used to treat type 2 DM include oral hypoglycemic agents, insulin, or a combination of medications. Oral agents used to treat type 2 DM have different mechanisms for action and can act to increase insulin secretion, potentiate the action of insulin at the periphery, or modify carbohydrate absorption.

Blood Glucose Abnormalities in Hospitalized Patients
It is common to see elevated blood glucose levels in hospitalized patients. There can be several reasons for hyperglycemia in the hospital beyond the presence of type 1 or type 2 DM. Hormones and cytokines released during stress, illness, or injury orchestrate the acute phase response (APR). The APR is marked by insulin resistance as well as increased gluconeogenesis often in excess of the body’s capacity to increase insulin secretion, leading to hyperglycemia. Prescribed medications, most commonly steroid medications, can also be associated with hyperglycemia in hospitalized patients. Some immunosuppressive medications used in transplant patients can also be associated with hyperglycemia development. For these reasons, not only are acutely ill patients at higher risk for hyperglycemia, but patients with preexisting DM may have higher insulin requirements than usual. Dietetics professionals need to be alert to these changes and ready to explain the rationale for increased insulin requirements to patients and their families.

In some cases, the diagnosis of DM is made during an admission for non–diabetes-related issues. Acute illness and some medications can lead to isolated elevated blood glucose levels in some individuals. One study found that 38% of patients admitted to a community teaching hospital had hyperglycemia on admission (defined as an admission or in-hospital fasting glucose greater than 126 milligrams per deciliter or a random blood glucose level greater than 200 milligrams per deciliter). Of these individuals, only 26% had a prior history of DM. Patients who had hyperglycemia had a longer hospital stay, were more likely to be admitted to the ICU, and were less likely to be discharged to home.2

Hyperglycemia and Outcomes
It has long been known that hospitalized patients with abnormal blood glucose control have an increased risk for complications, increased length of hospital stay, and increased costs associated with hospitalization. Patients with DM are at increased risk for infectious complications.3 Hyperglycemia—defined as at least one blood glucose level greater than 220 milligrams per deciliter—on the first postoperative day was associated with a significantly increased risk for infections in a series of patients who had DM and underwent elective surgery.4 Patients with DM who underwent cardiovascular surgery were at significantly higher risk for infectious complications if they had a mean postoperative blood glucose (average of six readings) greater than 200 milligrams per deciliter.5 Early hyperglycemia was also associated with poor outcomes in a series of trauma patients, further demonstrating the importance of glucose control early in hospitalization.6

Does Glucose Control Affect Outcome?
The link between hyperglycemia and infectious complications is well known, as discussed above. Until recently, there was little consensus concerning the blood glucose level at which risk for complications increased. Initiation of a protocol to maintain blood glucose levels less than 200 milligrams per deciliter in the postoperative period led to a significant decrease in deep wound infections following open heart operations.7 In 2001, Van den Berghe et al published the results of a study that demonstrated the distinct benefits of tight glycemic control in SICU patients.1 More than 1,500 patients admitted to the SICU following surgery were randomized to usual care or tight control consisting of use of insulin infusion to maintain blood glucose levels between 80 and 110 milligrams per deciliter. Patients in the “usual care” group received insulin only if blood glucose levels were greater than 215 milligrams per deciliter; treatment goals in this group were blood glucose between 180 and 200 milligrams per deciliter. Insulin infusion was initiated in the treatment group if blood glucose levels exceeded 110 milligrams per deciliter. Enteral, parenteral, or combination enteral/parenteral feedings were started the postoperative day.1 Results showed a significant benefit to tighter blood glucose control in postoperative patients who had a significant decrease in risk for mortality and significantly fewer episodes of septicemia in treatment patients.

Van den Berghe’s work showed the benefits of maintaining blood glucose levels as close to normal as possible in the SICU. Questions remaining to be answered following publication included investigation of the impact of blood glucose levels between 120 and 200 milligrams per deciliter and whether tight blood glucose control would be associated with a decrease in complications in other patient populations. Further research done in a heterogeneous group of critically ill medical and surgical patients found a 29.3% decrease in mortality (p = 0.002) and 10.8% decrease in ICU length of stay (p = 0.01) when an insulin infusion protocol was used to maintain blood glucose levels lower than 140 milligrams per deciliter.8 Thus, it appears that previous goals of less than 200 milligrams per deciliter for glucose control in hospitalized patients should be lowered somewhat.

Achieving Blood Glucose Control in Hospitalized Patients
Given the growing body of evidence supporting achieving normoglycemia in hospitalized patients, RDs should be involved in developing protocols for glycemic management. Intravenous (IV) insulin infusions are often used in ICU settings and are sometimes used outside the ICU if staffing allows for closer blood glucose monitoring. Other options for blood glucose management include insulin algorithms using sliding scale regular insulin and use of some combination of shorter and longer-acting insulins. The traditional sliding scale insulin order is no longer appropriate unless accompanied by a mechanism to proactively adjust insulin dosing based on the sliding scale. Regular insulin can also be added to parenteral nutrition solutions for those patients requiring IV feeding.

Continuous Insulin Infusion Management
Insulin infusions are often used in ICU patients to maintain blood glucose levels as near normal as possible. Several protocols for use of continuous infusion have been published and many facilities have developed their own protocols.9-11 Insulin infusions have the benefit of rapid titration due to the short half-life of IV insulin. Typically, insulin infusions are initiated immediately on admission to the ICU for patients with preexisting type 1 or type 2 diabetes or when blood glucose levels are abnormal in other patients. It is also recommended that a dextrose infusion be given along with the insulin so there is metabolic substrate for the infused insulin.

Tight glucose control can lead to a significantly increased risk for hypoglycemia. While patients in the Van den Berghe study did not experience adverse sequelae of hypoglycemia, 39 patients in the tight control group did experience hypoglycemia (defined as blood glucose less than 40 milligrams per deciliter), which, in two patients, was marked by sweating and agitation.1 Severe hypoglycemia can be immediately life threatening, so close monitoring, including up to hourly blood glucose checks, is imperative when using IV insulin infusions. Healthcare facilities should develop protocols for management of hypoglycemic events.12

Subcutaneous Insulin Management
Many institutions are unable to manage IV insulin infusions in non-critical care areas and, thus, rely on subcutaneous insulin management. Most healthcare providers are familiar with the concept of sliding scale insulin (SSI). Traditional SSI requires that insulin dosage be modified based on current blood glucose levels rather than management of patterns of blood glucose response to diet, activity, and clinical condition. There is no provision to prevent future excursions in glycemic control. In fact, most sliding scales do not require physician involvement unless severe hyperglycemia or hypoglycemia occurs. Individuals with type 1 DM should never be managed with SSI alone because there is no provision for basal insulin requirements. A more proactive management protocol would be to modify the SSI orders daily based on previous blood glucose levels and insulin requirements with a goal of developing known daily insulin dosing.

Nutrition Management and Glycemic Control
The dietetics professional plays a vital role in caring for patients with abnormal glycemic control or DM. Hospital admission is associated with changes in meal schedules, foods eaten, and appetite that can all lead to difficulty with glycemic control. One study found that changes in diet without concurrent changes in medication orders was the most common cause of hypoglycemia in hospitalized patients.13 The dietetics professional should be well prepared to coordinate and communicate with others in the healthcare team to ensure that nutrition needs are met and glycemic control optimized.

Oral Diets
In the past, it was common for American Diabetes Association (ADA) diets with specified calorie levels—eg, an 1,800-kilocalorie ADA diet—to be ordered for hospitalized patients with abnormal glycemic control or DM. Most would agree that such diet orders are no longer considered necessary or appropriate. Newer guidelines from the ADA state that such restricted diets are no longer necessary nor are they currently endorsed by the ADA.14 Other diet orders such as “No concentrated sweets” or “No simple sugars” should be eliminated. Many healthcare facilities are adopting menus that allow for consistent carbohydrate intake, thus meeting the needs for flexibility in meal planning based on medical therapy and clinical condition.15

Enteral Nutrition
Enteral nutrition support is indicated for patients unable to meet nutrient needs through voluntary oral intake. Preadmission and current therapy for DM should be reviewed when initiating enteral feedings. Formula choice has been controversial with the advent of special formulas for patients with abnormal glycemic control. While nutrient composition of formulas varies, most have lower carbohydrate content when compared with standard formulas as well as differences in the types of carbohydrate. Formulas should also be compared for types and amounts of other nutrients.

The dietetics professional responsible for development of enteral formularies should review the need for these special formulas with a critical eye. Most of these formulas are more expensive than standard formulas and have not been shown to have a significant clinical benefit when compared with standard formulas in hospitalized patients. Use of standard formulas along with close monitoring and adjustment of insulin based on the preceding day’s requirements led to acceptable glycemic control in patients with DM who were admitted to an acute stroke unit.16

One study reported improved glycemic control in critically ill patients fed a specialized diet. However, this did not translate into improvement in length of stay or other outcomes measures. Neither the treatment nor control groups in this study achieved tight control.17 While a recent meta-analysis of specialized formulas used in glycemic control suggested some benefit from these formulas, the studies included in the meta-analysis had poor methodology, thus limiting interpretation.18 Until there is more evidence to support use of specialized formulas in critically ill patients, enteral formula choice should be based on clinical condition, not blood glucose levels.

Continuous insulin infusions provide the best coverage for patients receiving continuous enteral feedings. However, insulin infusion is often not feasible in non-ICU settings. Subcutaneous insulin can be used successfully with appropriate monitoring. Insulin glargine provides continuous coverage for stable patients receiving enteral feedings, although these patients may require an additional source of carbohydrate intake if feedings are held or stopped. Regular insulin given at scheduled times can also be used to maintain glycemic control with continuous feedings.

When initiating enteral feedings, previous insulin requirements as well as feeding rate and schedule should be noted. Due to the variability of intake of enteral feedings during the initiation phase, only a percentage of usual insulin requirements should be scheduled with supplemental regular insulin used to manage blood glucose abnormalities. A percentage of the additional insulin should then be added to the next day’s orders. For example, enteral feedings are to be initiated in a patient who had been requiring a total daily dose of 68 units insulin. The initial continuous enteral feeding order is to provide 25% of the patient’s usual intake. The dietetics professional requests that 3 units of regular insulin be given every six hours with glucose monitoring every six hours. Additional insulin will be given based on blood glucose levels throughout the day. If an additional 12 units of insulin are given on day one, then 3 units are added to the scheduled insulin order for the next day. If the feeding is increased, then an additional amount of insulin is added to cover the additional feedings.

Parenteral Nutrition
Parenteral nutrition (PN) support is a potentially life-saving therapy for patients who cannot be fed orally or enterally. Glycemic control can be more difficult in patients who are fed intravenously, as the presence of carbohydrate in the gastrointestinal tract signals early insulin release, which blunts hyperglycemia in patients who are fed orally or enterally. Regular insulin can be added to PN solutions or continuous insulin infusions can be used to maintain glycemic control. There are benefits and drawbacks to either method.

If a continuous insulin infusion is used and PN is stopped or held for any reason, then the insulin infusion will also need to be decreased or stopped to prevent hypoglycemia. (Remember that patients with type 1 DM will always require a basal insulin source before stopping insulin infusion.) If insulin is added to the PN solution, hypoglycemia can occur if changes in clinical condition improve glucose tolerance. When adding insulin to PN, a quick rule of thumb is to start with 1 unit of insulin for every 10 to 15 grams of dextrose.19,20 As with enteral feedings, supplemental subcutaneous insulin can be given based on blood glucose monitoring with adjustment of the next day’s PN insulin dose based on the amount of supplemental insulin given.

Transitional Feedings
Transitional feedings present a challenge to the dietetics professional managing patients with DM or abnormal glucose control. When transitioning from PN to enteral feedings and insulin is added to the PN solution, a quick rule of thumb is that insulin in PN should cover the PN with subcutaneous insulin given to cover enteral feedings. The transition from enteral feeding to oral diets can present unique challenges in glycemic management. Insulin dosage for enteral feedings should be decreased proportionately to the decrease in enteral feeding rate. Bolus doses of rapid-acting insulin can then be given for meal intake.

Conclusion
Given the prevalence of DM in the United States, it is likely that dietetics professionals working in acute care settings will be managing nutrition care for patients with type 1 or type 2 DM or other abnormalities of glycemic control. Dietetics professionals must understand the underlying pathophysiology of different types of diabetes as well as management strategies. Patients with type 1 DM require basal insulin even when not eating. If nil per os, these patients will require basal insulin plus some sort of carbohydrate source, usually in the form of a dextrose infusion. Patients with type 2 DM who were managed with diet alone or with diet plus oral hypoglycemic agents prior to admission will often need insulin to maintain glycemic control. As these individuals often have insulin resistance at baseline and illness can exacerbate insulin resistance insulin requirements can be much higher than thought based on outpatient management.

Dietitians must understand how different types of insulin affect care management in an acute setting. It is no longer acceptable to simply order a sliding scale insulin schedule.

— Pam Charney, MS, RD, LD, CNSD, is a PhD candidate at the University of Medicine and Dentistry of New Jersey. She has more than 20 years of experience as a nutrition support dietitian and clinical nutrition manager. She is now a consultant in nutrition management issues and will soon be defending her dissertation.

References
1. Van Den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. New Engl J Med. 2001;345(19):1359-1367.

2. Umpierrez GE, Isaacs SD, Bazargan N, et al. Hyperglycemia: An independent marker of in-hospital mortality in patients with undiagnosed diabetes. J Clin Endocrin Metab. 2002;87(3):978-982.

3. Rayfield EJ, Ault MJ, Keusch GT, et al. Infection and diabetes: The case for glucose control. Am J Med. 1982;72(3):439-450.

4. Pomposelli JJ, Baxter JK 3rd, Babineau TJ, et al. Early postoperative glucose control predicts nosocomial infection rate in diabetic patients. Journal of Parenteral & Enteral Nutrition. 1998;22(2):77-81.

5. Golden SH, Peart-Vigilance C, Kao WH, et al. Perioperative glycemic control and the risk of infectious complications in a cohort of adults with diabetes. Diabetes Care. 1999;22(9):1408-1414.

6. Laird AM, Miller PR, Kilgo PD, et al. Relationship of early hyperglycemia to mortality in trauma patients. J Trauma Inj Infec Crit Care. 2004;56(5):1058-1062.

7. Zerr KJ, Furnary AP, Grunkemeier GL, et al. Glucose control lowers the risk for wound infection in diabetics after open heart operations. Ann Thorac Surg. 1997;63(2):356-361.

8. Krinsley JS. Effect of an intensive glucose management protocol on the mortality of critically ill patients. Mayo Clin Proceedings. 2004;79(8):992-1000.

9. Brown G, Dodek P. Intravenous insulin nomogram improves blood glucose control in the critically ill. Critical Care Medicine. 2001;29(9):1714-1719.

10. Furnary AP, Zerr KJ, Grunkemeier GL, et al. Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures [comment]. Annals of Thoracic Surgery. 1999;67(2):352-360; discussion 360-362.

11. Moghissi E. Hospital management of diabetes: Beyond the sliding scale. Cleve Clin J Med. 2004;71(10):801-808.

12. Braithwaite SS, Buie MM, Thompson DC, et al. Hospital hypoglycemia: Not only treatment but prevention. Endocr Prac. 2004;10(Suppl 2):89-99.

13. Smith WD, Winterstein AG, Johns T, et al. Causes of hyperglycemia and hypoglycemia in adult inpatients. Am J Health Syst Pharm. 2005;62(7):714-719.

14. American Diabetes Association. Translation of the diabetes nutrition recommendations for health care institutions. Diabetes Care. 2003;26(Suppl 1):S70-S72.

15. Swift CS, Boucher JL. Nutrition care for hospitalized individuals with diabetes. Diabetes Spectrum. 2005;18(1):34-38.

16. Kerr D, Hamilton P, Cavan DA. Preventing glycaemic excursions in diabetic patients requiring percutaneous endoscopic gastrostomy (PEG) feeding after a stroke. Diabetic Medicine. 2002;19(12):1006-1008.

17. Mesejo A, Acosta JA, Ortega C, et al. Comparison of a high-protein disease-specific enteral formula with a high-protein enteral formula in hypergycemic critically ill patients. Clin Nutr. 2003;22(3):295-305.

18. Elia M, Ceriello A, Laube H, et al. Enteral nutritional support and use of diabetes-specific formulas for patients with diabetes: A systematic review and meta-analysis. Diabetes Care. 2005;28(9):2267-2279.

19. Boord JB, Graber AL, Christman JW, et al. Practical management of diabetes in critically ill patients. Am J Respir Crit Care Med. 2001;164:1763-1767.

20. DiNardo MM, Korytkowski MT, Siminerio LS. The importance of normoglycemia in critically ill patients. Crit Care Nurs Q. 2004;27(2):126-134.