591057
research-article2015
NCPXXX10.1177/0884533615591057Nutrition in Clinical PracticeDavidson et al
Invited Review
Management of Hyperglycemia and Enteral Nutrition in the Hospitalized Patient
Nutrition in Clinical Practice Volume XX Number X Month 201X 1–9 © 2015 American Society for Parenteral and Enteral Nutrition DOI: 10.1177/0884533615591057 ncp.sagepub.com hosted at online.sagepub.com
Patricia Davidson, DCN, RDN, CDE, LDN1; Cynthia Ann Kwiatkowski, MS, RD, CNSC, FAND2,3; and Michelle Wien, DrPH, RD, CDE4
Abstract There has been increased attention on the importance of identifying and distinguishing the differences between stress-induced hyperglycemia (SH), newly diagnosed hyperglycemia (NDH), and hyperglycemia in persons with established diabetes mellitus (DM). Inpatient blood glucose control is now being recognized as not only a cost issue for hospitals but also a concern for patient safety and care. The reasons for the increased incidence of hyperglycemia in hospitalized patients include preexisting DM, undiagnosed DM or prediabetes, SH, and medication-induced hyperglycemia with resulting transient blood glucose variability. It is clear that identifying and documenting hyperglycemia in hospitalized patients with and without a previous diagnosis of DM and initiating prompt insulin treatment are important. Agreement on the optimum treatment goals for hyperglycemia remains quite controversial, and the benefits of intensive glucose management may be lost at the cost of hypoglycemia in intensive care unit patients. Nutrition support in the form of enteral nutrition (EN) increases the risk of hyperglycemia in both critical and non–critically ill hospitalized patients. Reasons for beginning a tube feeding are the same whether a person has NDH or DM. What differs is how to incorporate EN into the established insulin management protocols. The risk for hyperglycemia with the addition of EN is even higher in those without a previous diagnosis of DM. This review discusses the incidence of hyperglycemia, the pathogenesis of hyperglycemia, factors contributing to hyperglycemia in the hospitalized patient, glycemic management goals, current glycemic management recommendations, and considerations for EN formula selection, administration, and treatment. (Nutr Clin Pract.XXXX;xx:xx-xx)
Keywords hyperglycemia; enteral nutrition; diabetes mellitus; prediabetic state; nutritional support; critical illness
Over the past decade, research has established the importance of blood glucose control in the management of critically ill hospitalized patients with hyperglycemia, with or without established diabetes mellitus (DM).1–3 There has been increased attention on the importance of identifying and distinguishing the differences between stress-induced hyperglycemia (SH), newly diagnosed hyperglycemia (NDH), and hyperglycemia in persons with established DM.4,5 It is well documented that clinical outcomes such as length of stay in the hospital and intensive care unit (ICU), mortality, and morbidity-related diseases are increased by persistent hyperglycemia and glucose variability in patients having a previous diagnosis of DM.4 Since the landmark studies in early 2000s, recommendations have moved from intensive insulin glucose management to less intensive insulin glucose management, and individualized protocols have been developed with consideration of the pathogenesis of hyperglycemia, risk for hypoglycemia, and nutrition support.6–9 Inpatient blood glucose control is now being recognized as not only a cost issue for hospitals but also a concern for patient safety and care.10,11 This review discusses the incidence of hyperglycemia, the pathogenesis of hyperglycemia, factors contributing to hyperglycemia in the hospitalized patient, glycemic management
goals, current glycemic management recommendations, and enteral nutrition (EN) formula selection, administration, and treatment considerations.
Hyperglycemia Incidence The incidence of hyperglycemia in hospitalized patients is difficult to determine because it varies by patient population, disease state, and classification. Hyperglycemia unrelated to DM is a common occurrence in critically ill patients with as high as 90% of ICU patients experiencing impaired glucose From 1West Chester University of Pennsylvania, West Chester, Pennsylvania; 2Monmouth Medical Center, Long Branch, New Jersey; 3 Rutgers University, School of Health Related Professions, Scotch Plains, New Jersey; and 4Human Nutrition and Food Science Department, California State Polytechnic University, Pomona, California. Financial disclosure: None declared. Corresponding Author: Patricia Davidson, DCN, RDN, CDE, LDN, Assistant Professor of Nutrition, 855 South New Street, Sturzebecker Health Science Center, Room 307, West Chester University of Pennsylvania, West Chester, PA 19383. Email: [email protected]
Downloaded from ncp.sagepub.com at Uni of Southern Queensland on June 21, 2015
2
Nutrition in Clinical Practice XX(X)
INTERVENTIONS Exogenous glucocorticoids Enteral nutrition (EN) Parenteral nutrition (PN) Vasopressors
SYSTEMIC CHANGES ADIPOSE TISSUE Lipolysis LIVER Glycogenolysis Gluconeogenesis
PREDISPOSING FACTORS Insulin resistance Pancreatic reserve ANTAGONISTIC FACTORS
HYPERGLYCEMIA OUTCOME
MUSCLE Insulin resistance
Lipotoxicity Catecholamines Inflammatory cytokines
RESPONSE
STRESSORS
Figure 1. Mechanisms of stress-induced hyperglycemia.
tolerance and/or insulin resistance.10 In community-based hospitals, the incidence of documented hyperglycemia has been reported to be as high as 38%.10 The exact prevalence of SH or hospital-related hyperglycemia is unknown; however, approximately 1 in 4 hospitalization admissions includes a history of documented DM.4,10 The incidence varies based on the medical condition, and up to 50% of patients in cardiac units have been found to be classified as having DM or impaired glucose tolerance.12 The reasons for the increased incidence of hyperglycemia in hospitalized patients include preexisting DM, undiagnosed DM or prediabetes, SH, and medication-induced hyperglycemia and/or transient blood glucose variability.10,13
Pathogenesis of Hyperglycemia Glucose regulation involves 2 primary hormones (eg, insulin and glucagon). Insulin is required for the transport of glucose into cells by stimulating glucose transporters, glycogenesis, and fatty acid synthesis. Glucagon, a counterregulatory hormone to insulin, stimulates glucose production from liver glycogen stores through glycogenolysis and facilitates gluconeogenesis from non–carbohydrate (CHO) sources to prevent hypoglycemia. In addition, glucagon stimulates lipolysis and the production of ketones. In addition to glucagon’s role in glycogenolysis, other counterregulatory hormones, including the catecholamines, epinephrine, and norepinephrine, initiate the release of glucose from muscle glycogen for energy to be used primarily by the muscle.
Hyperglycemia in a person with DM occurs from an absolute or relative state of insulin deficiency, delayed insulin release, a lack of glucagon suppression, or postprandial hepatic/muscle insulin resistance. In persons with type 2 DM (T2DM), one or a combination of these conditions leads to the inability of cells to use glucose, an overproduction of insulin, and an exacerbation of insulin resistance.
Hyperglycemia in the Hospitalized Patient Due to the body’s intricate glucose regulatory system, SH that developed in response to illness or trauma was considered a normal occurrence and a benign condition for many decades. It is well documented that in parallel to hepatic gluconeogenesis persisting during critical illness, there is selective glucose uptake by body tissues. Similar to what occurs in DM, SH causes increased glucose production in the presence of hyperglycemia and hyperinsulinemia. The selective uptake of glucose spares the skeletal and heart muscles from glucose toxicity but simultaneously increases glucose uptake by other tissues. Acute hyperglycemia or SH is caused by a concomitant relationship between 2 metabolic systems responses to illness and involves both cytokines and counterregulatory hormones (Figure 1). These counterregulatory hormones (eg, epinephrine, norepinephrine, cortisol, glucagon, and growth hormone) are released to oppose the effects of insulin and other anabolic hormones. These counterregulatory hormones are responsible for increasing gluconeogenesis and protein catabolism.14 During metabolic stress (eg, acute illness, critical illness, surgery, and
Downloaded from ncp.sagepub.com at Uni of Southern Queensland on June 21, 2015
Davidson et al
3
trauma), circulating insulin is elevated, but the responsiveness of tissues to insulin, particularly within muscle, is blunted. The interrelationship between these 2 systems leads to insulin resistance, alterations in carbohydrate metabolism, and hyperglycemia. Ljungqvist et al15 have observed a 7-fold increase of insulin resistance in surgical patients. It is well accepted that chronic hyperglycemia in persons with DM leads to both microvascular and macrovascular complications in addition to poor wound healing.16 What is unclear are the effects of transient hyperglycemia that occur during episodes of acute or critical illness. Patients with SH or NDH have a higher rate of mortality, increased length of stay, and greater need for transitional care in a rehabilitation or long-term care facility.4 Baker et al17 found that for every 18-mg/dL increase in hospital admission fasting glucose level, a 33% increase in mortality occurred in persons not previously diagnosed with DM. It has become evident over the past decade that hyperglycemia in the hospital setting due to SH, NDH, or DM has a significant impact on clinical outcomes, including lengths of stay in the hospital and ICU, mortality, and morbidity-related diseases. Hyperglycemia in the hospital setting is now being recognized as not only a cost issue but also a concern for patient safety and care. Further research is needed to determine how to manage this condition when it is related to the acute response to injury/illness vs preexisting DM. In some disease states, SH is beneficial, but in others, it is associated with an increased risk of complications and mortality, especially in patients receiving nutrition support.6–9 It has been documented that patients with SH have a higher mortality rate (16%) compared with patients with preexisting DM (3%) or normal glucose levels (1.7%).4,5 It is important for clinicians to remember that both insulin resistance and hyperglycemia are directly related to and represent the severity of the disease and inflammatory response, as well as being strong pathologic stimuli to increased rates of morbidity, mortality, renal insufficiency, and infection.18,19 Factors contributing to these complications include increased osmotic diuresis, decreased glomerular filtration rate, increased inflammatory response, and decreased immune response associated with compromised leukocyte function, natural killer cells, and chemotaxis.
Glycemic Management Goals There is consistent evidence from numerous population-based observational studies that optimization of blood glucose levels improves clinical outcomes in hospitalized patients. However, agreement on the optimal treatment goals for hyperglycemia remains quite controversial. Krinsley20 observed that even slight elevations in blood glucose levels in both surgical and medical patients in an ICU markedly compromised patient recovery and increased both the risk of infection and length of stay. Kosiborod et al21 reported that mortality increased exponentially for every 10-mg/dL increase in the glucose level above 120 mg/dL among patients hospitalized with an acute
myocardial infarction. Furthermore, similar increases in mortality have been observed in hospitalized patients with hypoglycemia (blood glucose ≤70 mg/dL).22,23
Historical Perspective on Glycemic Control The controversy surrounding the optimal target blood glucose range for hospitalized patients stems from research in which intensive insulin protocols were used to achieve blood glucose levels of 80–110 mg/dL.22,23 These studies demonstrated an improvement on clinical outcomes but at the cost of an increased incidence of severe hypoglycemic events involving blood glucose levels of ≤40 mg/dL. A landmark study in 2001, the Leuven study, was conducted to evaluate the effects of intensive insulin therapy using continuous infusion protocols in critically ill hospitalized patients and to determine the relationship between glycemic control and clinical outcomes (eg, mortality).1 The results demonstrated the importance of normalizing blood glucose in ICU patients to decrease hospital and ICU mortality, sepsis, and need for mechanical ventilation, as well as improve renal function. Based on the Leuven study findings, a consensus was reached by the American College of Endocrinology recommending tight blood glucose control, more specifically, maintaining blood glucose levels below 110 mg/dL (6.1 mmol/L).24 This same team of investigators applied the same continuous insulin infusion protocol on medical patients in the ICU and demonstrated similar beneficial outcomes but only if the ICU length of stay was >3 days.1 Comparable results were demonstrated by Vlasselaers et al25 in the first randomized clinical trial involving intensive insulin therapy in pediatric ICU patients, which found a decreased length in stay and mortality rate compared with the conventional treatment group. Similar studies in varying patient populations since the landmark Leuven study have not been able to replicate the results and in fact have demonstrated conflicting and detrimental outcomes.22,23 Several issues to consider when developing glucose management protocols in the hospital setting have not been completely delineated. For example, there may be different treatment goals for patients in the ICU vs the medical/surgical units vs persons with preexisting DM. Another concern is which has more impact on patient outcomes, the glucose variability or persistent elevation of blood glucose levels? A number of studies, including the Normoglycaemia Evaluation and Survival Using Glucose Algorithm Regulation (NICESUGAR) trial, have demonstrated that hypoglycemia caused by intensive insulin treatment is an independent risk factor for increased mortality in critical care patients.22,26,27 A meta-analysis including research conducted in surgical, medical, and mixed ICUs demonstrated that the mortality risk at 90 and 180 days was not different between the intensive insulin management groups and the control group.28 In contrast to these findings, a meta-analysis of randomized controlled trials by Ling
Downloaded from ncp.sagepub.com at Uni of Southern Queensland on June 21, 2015
4
Nutrition in Clinical Practice XX(X)
Table 1. Guidelines on the Management of Glucose Levels for Hyperglycemia: Critically Ill vs Non–Critically Ill.24 Target Blood Glucose Levels Target threshold initiation, mg/dL Fasting and premeal, mg/dL Random, mg/dL Hypoglycemia defined
Critical Illness
Non–Critical Illness
180 140 140–180 70 mg/dL (reassess treatment if 180
research-article2015
NCPXXX10.1177/0884533615591057Nutrition in Clinical PracticeDavidson et al
Invited Review
Management of Hyperglycemia and Enteral Nutrition in the Hospitalized Patient
Nutrition in Clinical Practice Volume XX Number X Month 201X 1–9 © 2015 American Society for Parenteral and Enteral Nutrition DOI: 10.1177/0884533615591057 ncp.sagepub.com hosted at online.sagepub.com
Patricia Davidson, DCN, RDN, CDE, LDN1; Cynthia Ann Kwiatkowski, MS, RD, CNSC, FAND2,3; and Michelle Wien, DrPH, RD, CDE4
Abstract There has been increased attention on the importance of identifying and distinguishing the differences between stress-induced hyperglycemia (SH), newly diagnosed hyperglycemia (NDH), and hyperglycemia in persons with established diabetes mellitus (DM). Inpatient blood glucose control is now being recognized as not only a cost issue for hospitals but also a concern for patient safety and care. The reasons for the increased incidence of hyperglycemia in hospitalized patients include preexisting DM, undiagnosed DM or prediabetes, SH, and medication-induced hyperglycemia with resulting transient blood glucose variability. It is clear that identifying and documenting hyperglycemia in hospitalized patients with and without a previous diagnosis of DM and initiating prompt insulin treatment are important. Agreement on the optimum treatment goals for hyperglycemia remains quite controversial, and the benefits of intensive glucose management may be lost at the cost of hypoglycemia in intensive care unit patients. Nutrition support in the form of enteral nutrition (EN) increases the risk of hyperglycemia in both critical and non–critically ill hospitalized patients. Reasons for beginning a tube feeding are the same whether a person has NDH or DM. What differs is how to incorporate EN into the established insulin management protocols. The risk for hyperglycemia with the addition of EN is even higher in those without a previous diagnosis of DM. This review discusses the incidence of hyperglycemia, the pathogenesis of hyperglycemia, factors contributing to hyperglycemia in the hospitalized patient, glycemic management goals, current glycemic management recommendations, and considerations for EN formula selection, administration, and treatment. (Nutr Clin Pract.XXXX;xx:xx-xx)
Keywords hyperglycemia; enteral nutrition; diabetes mellitus; prediabetic state; nutritional support; critical illness
Over the past decade, research has established the importance of blood glucose control in the management of critically ill hospitalized patients with hyperglycemia, with or without established diabetes mellitus (DM).1–3 There has been increased attention on the importance of identifying and distinguishing the differences between stress-induced hyperglycemia (SH), newly diagnosed hyperglycemia (NDH), and hyperglycemia in persons with established DM.4,5 It is well documented that clinical outcomes such as length of stay in the hospital and intensive care unit (ICU), mortality, and morbidity-related diseases are increased by persistent hyperglycemia and glucose variability in patients having a previous diagnosis of DM.4 Since the landmark studies in early 2000s, recommendations have moved from intensive insulin glucose management to less intensive insulin glucose management, and individualized protocols have been developed with consideration of the pathogenesis of hyperglycemia, risk for hypoglycemia, and nutrition support.6–9 Inpatient blood glucose control is now being recognized as not only a cost issue for hospitals but also a concern for patient safety and care.10,11 This review discusses the incidence of hyperglycemia, the pathogenesis of hyperglycemia, factors contributing to hyperglycemia in the hospitalized patient, glycemic management
goals, current glycemic management recommendations, and enteral nutrition (EN) formula selection, administration, and treatment considerations.
Hyperglycemia Incidence The incidence of hyperglycemia in hospitalized patients is difficult to determine because it varies by patient population, disease state, and classification. Hyperglycemia unrelated to DM is a common occurrence in critically ill patients with as high as 90% of ICU patients experiencing impaired glucose From 1West Chester University of Pennsylvania, West Chester, Pennsylvania; 2Monmouth Medical Center, Long Branch, New Jersey; 3 Rutgers University, School of Health Related Professions, Scotch Plains, New Jersey; and 4Human Nutrition and Food Science Department, California State Polytechnic University, Pomona, California. Financial disclosure: None declared. Corresponding Author: Patricia Davidson, DCN, RDN, CDE, LDN, Assistant Professor of Nutrition, 855 South New Street, Sturzebecker Health Science Center, Room 307, West Chester University of Pennsylvania, West Chester, PA 19383. Email: [email protected]
Downloaded from ncp.sagepub.com at Uni of Southern Queensland on June 21, 2015
2
Nutrition in Clinical Practice XX(X)
INTERVENTIONS Exogenous glucocorticoids Enteral nutrition (EN) Parenteral nutrition (PN) Vasopressors
SYSTEMIC CHANGES ADIPOSE TISSUE Lipolysis LIVER Glycogenolysis Gluconeogenesis
PREDISPOSING FACTORS Insulin resistance Pancreatic reserve ANTAGONISTIC FACTORS
HYPERGLYCEMIA OUTCOME
MUSCLE Insulin resistance
Lipotoxicity Catecholamines Inflammatory cytokines
RESPONSE
STRESSORS
Figure 1. Mechanisms of stress-induced hyperglycemia.
tolerance and/or insulin resistance.10 In community-based hospitals, the incidence of documented hyperglycemia has been reported to be as high as 38%.10 The exact prevalence of SH or hospital-related hyperglycemia is unknown; however, approximately 1 in 4 hospitalization admissions includes a history of documented DM.4,10 The incidence varies based on the medical condition, and up to 50% of patients in cardiac units have been found to be classified as having DM or impaired glucose tolerance.12 The reasons for the increased incidence of hyperglycemia in hospitalized patients include preexisting DM, undiagnosed DM or prediabetes, SH, and medication-induced hyperglycemia and/or transient blood glucose variability.10,13
Pathogenesis of Hyperglycemia Glucose regulation involves 2 primary hormones (eg, insulin and glucagon). Insulin is required for the transport of glucose into cells by stimulating glucose transporters, glycogenesis, and fatty acid synthesis. Glucagon, a counterregulatory hormone to insulin, stimulates glucose production from liver glycogen stores through glycogenolysis and facilitates gluconeogenesis from non–carbohydrate (CHO) sources to prevent hypoglycemia. In addition, glucagon stimulates lipolysis and the production of ketones. In addition to glucagon’s role in glycogenolysis, other counterregulatory hormones, including the catecholamines, epinephrine, and norepinephrine, initiate the release of glucose from muscle glycogen for energy to be used primarily by the muscle.
Hyperglycemia in a person with DM occurs from an absolute or relative state of insulin deficiency, delayed insulin release, a lack of glucagon suppression, or postprandial hepatic/muscle insulin resistance. In persons with type 2 DM (T2DM), one or a combination of these conditions leads to the inability of cells to use glucose, an overproduction of insulin, and an exacerbation of insulin resistance.
Hyperglycemia in the Hospitalized Patient Due to the body’s intricate glucose regulatory system, SH that developed in response to illness or trauma was considered a normal occurrence and a benign condition for many decades. It is well documented that in parallel to hepatic gluconeogenesis persisting during critical illness, there is selective glucose uptake by body tissues. Similar to what occurs in DM, SH causes increased glucose production in the presence of hyperglycemia and hyperinsulinemia. The selective uptake of glucose spares the skeletal and heart muscles from glucose toxicity but simultaneously increases glucose uptake by other tissues. Acute hyperglycemia or SH is caused by a concomitant relationship between 2 metabolic systems responses to illness and involves both cytokines and counterregulatory hormones (Figure 1). These counterregulatory hormones (eg, epinephrine, norepinephrine, cortisol, glucagon, and growth hormone) are released to oppose the effects of insulin and other anabolic hormones. These counterregulatory hormones are responsible for increasing gluconeogenesis and protein catabolism.14 During metabolic stress (eg, acute illness, critical illness, surgery, and
Downloaded from ncp.sagepub.com at Uni of Southern Queensland on June 21, 2015
Davidson et al
3
trauma), circulating insulin is elevated, but the responsiveness of tissues to insulin, particularly within muscle, is blunted. The interrelationship between these 2 systems leads to insulin resistance, alterations in carbohydrate metabolism, and hyperglycemia. Ljungqvist et al15 have observed a 7-fold increase of insulin resistance in surgical patients. It is well accepted that chronic hyperglycemia in persons with DM leads to both microvascular and macrovascular complications in addition to poor wound healing.16 What is unclear are the effects of transient hyperglycemia that occur during episodes of acute or critical illness. Patients with SH or NDH have a higher rate of mortality, increased length of stay, and greater need for transitional care in a rehabilitation or long-term care facility.4 Baker et al17 found that for every 18-mg/dL increase in hospital admission fasting glucose level, a 33% increase in mortality occurred in persons not previously diagnosed with DM. It has become evident over the past decade that hyperglycemia in the hospital setting due to SH, NDH, or DM has a significant impact on clinical outcomes, including lengths of stay in the hospital and ICU, mortality, and morbidity-related diseases. Hyperglycemia in the hospital setting is now being recognized as not only a cost issue but also a concern for patient safety and care. Further research is needed to determine how to manage this condition when it is related to the acute response to injury/illness vs preexisting DM. In some disease states, SH is beneficial, but in others, it is associated with an increased risk of complications and mortality, especially in patients receiving nutrition support.6–9 It has been documented that patients with SH have a higher mortality rate (16%) compared with patients with preexisting DM (3%) or normal glucose levels (1.7%).4,5 It is important for clinicians to remember that both insulin resistance and hyperglycemia are directly related to and represent the severity of the disease and inflammatory response, as well as being strong pathologic stimuli to increased rates of morbidity, mortality, renal insufficiency, and infection.18,19 Factors contributing to these complications include increased osmotic diuresis, decreased glomerular filtration rate, increased inflammatory response, and decreased immune response associated with compromised leukocyte function, natural killer cells, and chemotaxis.
Glycemic Management Goals There is consistent evidence from numerous population-based observational studies that optimization of blood glucose levels improves clinical outcomes in hospitalized patients. However, agreement on the optimal treatment goals for hyperglycemia remains quite controversial. Krinsley20 observed that even slight elevations in blood glucose levels in both surgical and medical patients in an ICU markedly compromised patient recovery and increased both the risk of infection and length of stay. Kosiborod et al21 reported that mortality increased exponentially for every 10-mg/dL increase in the glucose level above 120 mg/dL among patients hospitalized with an acute
myocardial infarction. Furthermore, similar increases in mortality have been observed in hospitalized patients with hypoglycemia (blood glucose ≤70 mg/dL).22,23
Historical Perspective on Glycemic Control The controversy surrounding the optimal target blood glucose range for hospitalized patients stems from research in which intensive insulin protocols were used to achieve blood glucose levels of 80–110 mg/dL.22,23 These studies demonstrated an improvement on clinical outcomes but at the cost of an increased incidence of severe hypoglycemic events involving blood glucose levels of ≤40 mg/dL. A landmark study in 2001, the Leuven study, was conducted to evaluate the effects of intensive insulin therapy using continuous infusion protocols in critically ill hospitalized patients and to determine the relationship between glycemic control and clinical outcomes (eg, mortality).1 The results demonstrated the importance of normalizing blood glucose in ICU patients to decrease hospital and ICU mortality, sepsis, and need for mechanical ventilation, as well as improve renal function. Based on the Leuven study findings, a consensus was reached by the American College of Endocrinology recommending tight blood glucose control, more specifically, maintaining blood glucose levels below 110 mg/dL (6.1 mmol/L).24 This same team of investigators applied the same continuous insulin infusion protocol on medical patients in the ICU and demonstrated similar beneficial outcomes but only if the ICU length of stay was >3 days.1 Comparable results were demonstrated by Vlasselaers et al25 in the first randomized clinical trial involving intensive insulin therapy in pediatric ICU patients, which found a decreased length in stay and mortality rate compared with the conventional treatment group. Similar studies in varying patient populations since the landmark Leuven study have not been able to replicate the results and in fact have demonstrated conflicting and detrimental outcomes.22,23 Several issues to consider when developing glucose management protocols in the hospital setting have not been completely delineated. For example, there may be different treatment goals for patients in the ICU vs the medical/surgical units vs persons with preexisting DM. Another concern is which has more impact on patient outcomes, the glucose variability or persistent elevation of blood glucose levels? A number of studies, including the Normoglycaemia Evaluation and Survival Using Glucose Algorithm Regulation (NICESUGAR) trial, have demonstrated that hypoglycemia caused by intensive insulin treatment is an independent risk factor for increased mortality in critical care patients.22,26,27 A meta-analysis including research conducted in surgical, medical, and mixed ICUs demonstrated that the mortality risk at 90 and 180 days was not different between the intensive insulin management groups and the control group.28 In contrast to these findings, a meta-analysis of randomized controlled trials by Ling
Downloaded from ncp.sagepub.com at Uni of Southern Queensland on June 21, 2015
4
Nutrition in Clinical Practice XX(X)
Table 1. Guidelines on the Management of Glucose Levels for Hyperglycemia: Critically Ill vs Non–Critically Ill.24 Target Blood Glucose Levels Target threshold initiation, mg/dL Fasting and premeal, mg/dL Random, mg/dL Hypoglycemia defined
Critical Illness
Non–Critical Illness
180 140 140–180 70 mg/dL (reassess treatment if 180
