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Glycemic Control in Academic Hospitals
Hyperglycemia is a common occurrence in hospitalized patients, with and without a prior diagnosis of diabetes mellitus.13 Estimates of prevalence of diabetes mellitus in hospitalized adult patients range from 12% to 25%.4 Hyperglycemia is a strong predictor of adverse clinical outcome in a range of diseases such as acute stroke, congestive heart failure, community‐acquired pneumonia, and acute myocardial infarction.58 Hyperglycemia is also a risk factor for surgical infection in patients undergoing cardiac surgery.9, 10 A landmark prospective randomized controlled clinical trial by van den Berghe et al.11 demonstrated that tight glucose control (target blood glucose level 80110 mg/dL) with intravenous insulin in critically ill surgical patients led to dramatic reductions in acute renal failure, critical illness polyneuropathy, hospital mortality, and bloodstream infection. Other clinical studies have demonstrated that glycemic control with intravenous insulin improves clinical outcomes and reduces length of stay in patients with diabetes undergoing cardiac surgery.12, 13
Based upon these findings, the American College of Endocrinology (ACE) published recommendations in 2004 for hospital diabetes and metabolic control.14 Similar recommendations for hospital glycemic control have been included in the American Diabetes Association (ADA) guidelines since 2005.15 There is now emerging consensus that use of continuous insulin infusion given through a standardized protocol is the standard of care to control hyperglycemia in critically ill patients.1618 Likewise, use of specific hospital insulin regimens that include basal and short‐acting insulin with appropriate bedside glucose monitoring and avoiding use of sliding scale short‐acting insulin alone has become recognized as the most effective approach for glucose management in hospitalized patients not requiring intravenous insulin.4, 1921
The University HealthSystem Consortium (UHC) is an alliance of 97 academic health centers and 153 of their associated hospitals that conducts benchmarking studies on clinical and operational topics with member academic medical centers and develops new programs to improve quality of care, patient safety, and operational, clinical, and financial performance. In late 2004, UHC launched the Glycemic Control Benchmarking Project to determine the current status of glycemic control in adult patients admitted to academic medical centers, types of treatment employed to control glucose, and operational measures and practices of care for glycemic control in the hospital setting. The goal of the project was to describe contemporary glucose management for the purpose of identifying best practices. The information was later shared with each participating medical center to allow them to better align care delivery with ADA and ACE guidelines. Thirty‐seven academic medical centers agreed to participate and submit patient level data as well as an operational survey of current policies and practices for hospital glycemic control. This report summarizes the key findings from retrospective analyses of hospital and patient‐level data and describes contemporary management of hyperglycemia in academic medical centers.
PATIENTS AND METHODS
To be eligible for the study, hospital patients at each participating medical center had to be 18 years of age, have a 72‐hour or longer length of stay, and be admitted with 1 or more of the following Diagnostic‐related group (DRG) codes: 89 (simple pneumonia/ pleurisy), 109 (coronary artery bypass grafting without catheterization), 127 (heart failure and shock), 143 (chest pain), 209 (joint/limb procedure), 316 (renal failure), 478 (other vascular procedures), or 527 (percutaneous intervention with drug eluting stent without acute myocardial infarction). The DRG codes were selected from analysis of the UHC Clinical Data Base because they were the most common adult medical and surgical admission codes that included diabetes as a secondary diagnosis for academic medical centers and were believed to best represent the majority of hospital admissions. Each participating medical center received a secure electronic listing of their eligible patients discharged between July 1, 2004 and September 30, 2004 from the UHC Clinical Data Base. Each center identified data extractors who were trained via teleconference and received technical and content support by UHC staff. The data were collected by chart review and submitted electronically to UHC from February to April 2005.
For each medical center, patients were screened in reverse chronological order proceeding back in time until the minimum number of 50 eligible cases was obtained or until all potential cases were screened. Although 50 cases was the recommended minimum sample size per site, each medical center was encouraged to submit as many eligible cases as possible. The median number of cases submitted by site was 50 (interquartile range [IQR], 4251). Cases were entered into the study if they met the eligibility criteria and at least one of the following inclusion criteria: (1) two consecutive blood glucose readings >180 mg/dL within a 24hour period, or (2) insulin treatment at any time during the hospitalization. Exclusion criteria included history of pancreatic transplant, pregnancy at time of admission, hospice or palliative care during hospital admission, and patients who received insulin for a reason other than blood glucose control (ie, hyperkalemia). Early in the data collection, DRG 209 was dropped from potential screening due to the low yield of meeting screening criteria for blood glucose readings. Of the 315 cases screened for DRG 209 only 44 met all inclusion criteria and remain in the study population.
A maximum of 3 consecutive days of blood glucose (BG) readings were collected for each patient, referred to as measurement day 1, measurement day 2, and measurement day 3. Measurement day 1 is defined as the day the first of 2 consecutive blood glucose levels >180 mg/dL occurred during the hospitalization or as the first day insulin was administered during the hospitalization, whichever came first; 40.6% of patients had the day of admission as their first measurement day. Glucose measurements were recorded by hour for each measurement day as available, and if more than 1 glucose value was available within a particular hour, only the first result was recorded. Both bedside and laboratory serum glucose values were utilized, and glycosylated hemoglobin (A1C) values were included if they were recorded during the hospitalization or within 30 days prior to admission;22 95.7% of patients had BG results reported for all 3 measurement days. We defined estimated 6 AM glucose for each subject as: the 6 AM glucose if it was available; otherwise the average of the 5 AM and 7 AM glucose values if at least 1 of them was available; otherwise the average of the 4 AM and 8 AM glucose values if at least 1 of them was available. Relevant demographics, medical history, hospitalization details, type and route of insulin administration, and discharge data were also collected. For subcutaneous insulin administration, use of regular, lispro, or aspart insulin was classified as short‐acting insulin; use of neutral protamine Hagedorn (NPH), ultralente, or glargine insulin was classified as long‐acting insulin. For analysis of glycemic control measures, patient‐days in which location or glucose data were not recorded were excluded from analysis. For the analysis comparing subcutaneous versus intravenous insulin treatment on glucose control, patients who received a combination of therapy with subcutaneous and intravenous insulin on the same measurement day were excluded from the analysis (44 patients on day 1, 96 on day 2, and 47 on day 3). For this retrospective analysis, UHC provided a deidentified data set to the authors. The study protocol was reviewed by the Vanderbilt University Institutional Review Board and deemed to be nonhuman subject research since the data set contained no personal or institutional identifiers. Therefore, no informed consent of subjects was required.
Measures of glucose control (median glucose and estimated 6 AM glucose) were analyzed by patient‐day,23 and were compared by a Wilcoxon rank sum test or an analysis of variance, as indicated. P values <0.05 were considered significant. To compare effects of intravenous (IV) insulin, subcutaneous long‐acting short‐acting insulin, and subcutaneous short‐acting insulin use alone on glycemic control, mixed effects linear regression modeling for median glucose and mixed effects logistic regression modeling for hyperglycemia and hypoglycemia were used to adjust for fixed effects of age, gender, diabetes status, all patient refined diagnosis related groups (APR‐DRG) severity of illness score, outpatient diabetes treatment, patient location, admission diagnosis, and random effect of hospital site. Separate regression models were performed for measurement days 2 and 3. Statistical analyses were performed with Stata version 8 (Stata Corporation, College Station, TX), R version 2.1.0 (R Foundation for Statistical Computing, Vienna, Austria;
RESULTS
Thirty‐seven US academic medical centers from 24 states contributed to the analysis. A total of 4,367 cases meeting age, length of stay, and DRG criteria were screened for inclusion in the study; 2,649 (60.7%) screened cases were excluded due to failure to meet inclusion criteria (51%) or presence of exclusionary conditions (9.7%); 1,718 (39.3%) screened cases met all criteria and were included in this analysis. Patient characteristics are summarized in Table 1. A majority of patients (79%) had a documented history of diabetes, and most of these were classified as type 2 diabetes in the hospital record. Of the patients who were classified as having diabetes on admission, 50.8% were on some form of outpatient insulin therapy with or without oral diabetes agents. Patients with a diagnosis of diabetes had a median admission glucose of 158 mg/dL (IQR, 118221), which was significantly higher than the median admission glucose of 119 mg/dL (IQR, 100160) for patients without diabetes (P < 0.001, rank‐sum test).
| |
n | 1718 |
Age (years), median (IQR) | 65 (5674) |
Male | 928 (54) |
Female | 790 (46) |
Admission glucose (mg/dL) | 149 (111207) |
Race/Ethnicity | |
White | 1048 (61.0) |
Black | 480 (27.9) |
Hispanic | 67 (3.9) |
Other | 123 (7.2) |
Diabetes history | 1358 (79.0) |
Type 2 diabetes mellitus | 996 (58.0) |
Type 1 diabetes mellitus | 128 (7.5) |
Unspecified/other diabetes mellitus | 234 (13.6) |
No history of diabetes mellitus | 360 (21.0) |
Outpatient diabetes treatment | |
Insulin only | 522 (30.4) |
Oral agents only | 505 (29.4) |
Insulin and oral agents | 168 (9.8) |
No drug therapy | 137 (8.0) |
Not documented | 26 (1.5) |
Hospitalization DRG | |
127 Heart failure | 443 (25.8) |
109 Coronary artery bypass grafting | 389 (22.6) |
316 Renal failure | 251 (14.6) |
478 Other vascular procedure | 195 (11.4) |
89 Pneumonia | 186 (10.8) |
527 Percutaneous intervention with stent | 136 (7.9) |
143 Chest pain | 74 (4.3) |
209 Joint/limb procedure | 44 (2.6) |
Primary insurer | |
Medicare | 961 (56.0) |
Private/commercial | 392 (22.8) |
Medicaid | 200 (11.6) |
Government | 88 (5.1) |
Self‐pay | 67 (3.9) |
Other/unknown | 10 (0.6) |
To determine overall glycemic control for the cohort, median glucose was calculated for each patient, stratified by diabetes status and location for each measurement day (Table 2). Patient‐days with a location of emergency department (96 patients on day 1, 6 on day 2, and 2 on day 3) and two patients whose location was not defined were excluded from the analysis. Overall, median glucose declined from measurement day 1 to day 3. For patients with diabetes, median glucose was significantly lower in the intensive care unit (ICU) compared to the general ward or intermediate care for measurement days 1 and 2, but not day 3. This difference was more pronounced in patients without diabetes, with median glucose significantly lower in the ICU for all 3 measurement days compared to other locations. As expected, median glucose was lower for patients without diabetes compared to patients with diabetes for all measurement days and locations. Hyperglycemia was common; 867 of 1,718 (50%) patients had at least 1 glucose measurement 180 mg/dL on both days 2 and 3; 18% of all patients had a median glucose 180 mg/dL on all 3 measurement days. Daily 6 AM glucose was the summary glycemic control measure in the clinical trial by van den Berghe et al.,11 with goal glucose of 80 to 110 mg/dL in the intensive treatment group. Since the glycemic target of the American College of Endocrinology Position Statement is <110 mg/dL (based largely on van den Berghe et al.11) we also calculated estimated 6 AM glucose for ICU patient‐days to determine the proportion of patients attaining this target.14 Estimated 6 AM glucose was lower in ICU patients without diabetes compared to those with diabetes. For patients with diabetes, only 20% of patients in the ICU had an estimated 6 AM glucose 110 mg/dL on measurement day 2, and only 24% on day 3. For patients without diabetes, 27% and 25% had an estimated 6 AM glucose 110 mg/dL on days 2 and 3, respectively.
Measurement by Location | |||
---|---|---|---|
Day 1 | Day 2 | Day 3 | |
| |||
Patients with diabetes | |||
Estimated 6 AM glucose (mg/dL) | |||
Intensive care unit | 153.0 (119.0204.0) | 148.0 (118.0183.0) | 144.0 (113.0191.0) |
n | 167 | 231 | 161 |
Median glucose (mg/dL) | |||
General floor | 186.0 (151.0229.0) | 163.0 (131.0210.0) | 161.0 (127.0203.4) |
n | 681 | 757 | 758 |
Intermediate care | 193.0 (155.3233.8) | 170.0 (137.0215.5) | 169.0 (137.9215.6) |
n | 291 | 333 | 348 |
Intensive care unit | 177.5 (149.6213.6) | 152.5 (128.3187.0) | 156.5 (124.5194.3) |
n | 294 | 247 | 175 |
P value* | 0.038 | <0.001 | 0.068 |
Patients without diabetes | |||
Estimated 6 AM glucose (mg/dL) | |||
Intensive care unit | 133.0 (104.5174.0) | 134.0 (109.0169.0) | 128.0 (111.5151.3) |
n | 98 | 157 | 80 |
Median glucose (mg/dL) | |||
General floor | 179.0 (149.5209.5) | 161.3 (131.4188.3) | 143.5 (122.0170.0) |
n | 91 | 96 | 133 |
Intermediate care | 168.3 (138.1193.8) | 137.0 (119.8161.5) | 129.3 (116.3145.5) |
n | 46 | 71 | 86 |
Intensive care unit | 153.8 (132.9188.8) | 136.5 (120.0157.0) | 129.0 (116.0143.8) |
n | 218 | 186 | 106 |
P value* | <0.001 | <0.001 | <0.001 |
For the overall cohort, insulin was the most common treatment for hyperglycemia, with 84.6% of all patients receiving some form of insulin therapy on the second measurement day. On the second day, 30.8% received short‐acting subcutaneous insulin only, 8.2% received intravenous insulin infusion, 22.5% received both short‐acting and long‐acting subcutaneous insulin, 3.9% received oral agents, 23% received some combination of insulin therapies and/or oral agents, and 11.9% received no treatment. To determine the effect of intravenous versus subcutaneous insulin treatment on glycemic control, we compared patients by insulin treatment and location for each measurement day (Table 3). Intravenous insulin was used predominantly in the ICU, and was associated with significantly lower median glucose compared to subcutaneous insulin in both locations for all 3 measurement days. As expected, the average number of glucose measures per patient was significantly higher for those receiving intravenous insulin. Intravenous insulin use in the ICU was associated with a significantly lower number of patients with hyperglycemia, defined as the number who had 1 or more glucose values 180 mg/dL during a given measurement day. Of note, intravenous insulin use in the ICU was associated with a significantly higher proportion of patients who had hypoglycemia (defined as the number of patients who had one or more glucose values <70 mg/dL) compared to subcutaneous insulin only on measurement day 1 (8.1% versus 2.9%; P = 0.021), but not on days 2 (12.7% versus 8.0%; P > 0.05) or 3 (12.7% versus 7.8%; P > 0.05). Severe hypoglycemia, defined as a blood glucose recording <50 mg/dL,24 was rare, and occurred in only 2.8% of all patient days. On measurement day 1, 34 patients had a total of 49 severe hypoglycemic events; on day 2, 54 patients had 68 severe hypoglycemic events; on day 3, 54 patients had 68 severe hypoglycemic events. Only 3 patients had severe hypoglycemic events on all 3 measurement days. Analysis of severe hypoglycemia events stratified by intravenous versus subcutaneous insulin did not show any significant differences for any of the 3 measurement days (data not shown).
Location/Day | Outcome | Intravenous Insulin | Subcutaneous Insulin | P Value* |
---|---|---|---|---|
| ||||
Intensive Care Unit, Day 1 | Patient's glucose, median (mg/dL) | 148.0 | 183.0 | <0.001 |
Interquartile range | 128.0178.0 | 154.8211.0 | ||
Hypoglycemic patients, n (%) | 16 (8.1) | 6 (2.9) | 0.021 | |
Hyperglycemic patients, n (%) | 130 (66.0) | 175 (85.0) | <0.001 | |
Average glucose measures/patient | 8.4 | 4.8 | <0.001 | |
Patients, n | 197 | 206 | ||
Intermediate/General Ward, Day 1 | Patient's glucose, median (mg/dL) | 152.0 | 186.5 | <0.001 |
Interquartile range | 131.0164.5 | 150.0230.0 | ||
Hypoglycemic patients, n (%) | 1 (4.1) | 71 (7.4) | ns | |
Hyperglycemic patients, n (%) | 18 (78.3) | 808 (83.9) | ns | |
Average glucose measures/patient | 9.7 | 3.8 | <0.001 | |
Patients, n | 23 | 962 | ||
Intensive Care Unit, Day 2 | Patient's glucose, median (mg/dL) | 124.8 | 159.8 | <0.001 |
Interquartile range | 110.4140.5 | 138.6197.4 | ||
Hypoglycemic patients, n (%) | 15 (12.7) | 14 (8.0) | ns | |
Hyperglycemic patients, n (%) | 53 (44.9) | 135 (76.7) | <0.001 | |
Average glucose measures/patient | 12.5 | 5.3 | <0.001 | |
Patients, n | 118 | 176 | ||
Intermediate/General Ward, Day 2 | Patient's glucose, median (mg/dL) | 136.0 | 168.8 | <0.001 |
Interquartile range | 116.0168.0 | 136.1215.5 | ||
Hypoglycemic patients, n (%) | 2 (6.7) | 113 (11.3) | ns | |
Hyperglycemic patients, n (%) | 18 (60.0) | 784 (78.6) | 0.015 | |
Average glucose measures/patient | 11.0 | 4.6 | <0.001 | |
Patients, n | 30 | 996 | ||
Intensive Care Unit, Day 3 | Patient's glucose, median (mg/dL) | 123.5 | 171.0 | <0.001 |
Interquartile range | 110.0137.1 | 137.3198.5 | ||
Hypoglycemic patients, n (%) | 7 (12.7) | 11 (7.8) | ns | |
Hyperglycemic patients, n (%) | 24 (43.6) | 101 (71.1) | <0.001 | |
Average glucose measures/patient | 11.4 | 4.8 | <0.001 | |
Patients, n | 54 | 141 | ||
Intermediate/General Ward, Day 3 | Patient's glucose, median (mg/dL) | 129.8 | 166.0 | <0.001 |
Interquartile range | 120.5142.3 | 131.5208.0 | ||
Hypoglycemic patients, n (%) | 3 (13.6) | 104 (9.8) | ns | |
Hyperglycemic patients, n (%) | 13 (59.1) | 773 (72.7) | ns | |
Average glucose measures/patient | 10.3 | 4.3 | <0.001 | |
Patients, n | 22 | 1,055 |
We hypothesized that use of subcutaneous long‐acting (basal) insulin (with or without short‐acting insulin) would be associated with superior glucose control compared to use of subcutaneous short‐acting insulin (sliding scale and/or scheduled prandial insulin) alone. We performed an exploratory multivariate regression analysis to compare the effect of IV insulin, long acting subcutaneous insulin short acting insulin, or short acting subcutaneous insulin alone on median glucose, hyperglycemic events (glucose 180 mg/dL), and hypoglycemic events (glucose <70 mg/dL) for days 2 and 3 (Table 4). Compared to short‐acting subcutaneous insulin alone, use of IV insulin but not long‐acting subcutaneous insulin was predictive of lower median glucose for days 2 and 3. Use of long‐acting subcutaneous insulin was not associated with significantly lower odds of hyperglycemic events for days 2 and 3, but was associated with higher odds of hypoglycemic events on day 2 (odds ratio [OR], 1.8; P = 0.01) when compared to short‐acting subcutaneous insulin alone.
Glucose Control Measure | Intravenous Insulin Infusion | Long‐Acting Subcutaneous Insulin |
---|---|---|
| ||
Median glucose | ||
Day 2, n = 1,297 | 32.0 (45.4 to 18.5); P < 0.001* | 5.1 (13.8 to 3.6); P = 0.25* |
Day 3, n = 1,251 | 33.0 (48.9 to 17); P < 0.001* | 3.4 (5.2 to 11.9); P = 0.44* |
Patient has 1 hyperglycemic event | ||
Day 2, n = 1,298 | 0.4 (0.20.6); P < 0.001 | 0.7 (0.51.1); P = 0.11 |
Day 3, n = 1,261 | 0.6 (0.31.1); P = 0.11 | 0.8 (0.61.1); P = 0.24 |
Patient has 1 hypoglycemic event | ||
Day 2, n = 1,298 | 2.1 (1.04.7); P = 0.07 | 1.8 (1.22.9); P = 0.010 |
Day 3, n = 1,261 | 4.0 (1.69.8); P = 0.003 | 1.4 (0.92.3); P = 0.13 |
We measured the performance of recommended hospital diabetes care practices (A1C assessment, documentation of diabetes history in the hospital record, admission laboratory glucose assessment, bedside glucose monitoring, recommended insulin therapy)14, 15 for all study patients, and also stratified performance by hospital (Table 5); 98.6% of all patients with a diagnosis of diabetes had physician documentation of their diabetes status recorded in the hospital record, and there was consistently high performance of this by hospital (Table 5); 77% of all patients with a history of diabetes had a laboratory blood glucose result recorded within 8 hours of hospital admission, and 81.3% of patients with a history of diabetes had blood glucose monitored at least 4 times on measurement day 2. Performance by hospital (Table 5) varied widely for glucose monitoring (range, 56.5%95.5% of patients by hospital) and admission laboratory glucose assessment (range, 39.0%97.1% of patients by hospital).
Diabetes Care Measure | Mean Hospital Performance (%) | Standard Deviation (%) | Range (%) |
---|---|---|---|
| |||
Physician documentation of diabetes history in medical record | 98.8 | 2.1 | 91.5100 |
A1C assessment documented for diabetes patients (measured during hospitalization or within 30 days prior to admission) | 33.7 | 15.4 | 3.162.9 |
Laboratory glucose assessment within 8 hours of hospital presentation for diabetes patients | 77.0 | 13.4 | 39.097.1 |
Blood glucose monitoring at least 4 times on second measurement day for diabetes patients | 81.6 | 10.8 | 56.595.5 |
Percentage of patients receiving insulin therapy who were given short and long‐acting insulin OR IV insulin infusion OR insulin pump therapy on second measurement day | 44.9 | 14.3 | 12.176.5 |
Of all patients, 31% had A1C measurement recorded during their hospitalization or within 30 days prior to admission. There was wide variation in hospital performance of A1C assessment in patients with diabetes (Table 5). Patients with a diagnosis of diabetes had a median A1C of 7.4% (IQR, 6.4%8.9%; n = 473), and those without a diagnosis of diabetes had a median A1C of 5.9% (IQR, 5.6%6.4%; n = 70). Of the patients with a history of diabetes who had A1C recorded, 59% had a value >7%. Of the patients without a history of diabetes who had A1C recorded, 43% had a value >6.0%, suggesting previously undiagnosed diabetes.25
We found wide variation among hospitals (range, 12.1%76.5%) in use of recommended regimens of insulin therapy, defined as short‐acting and long‐acting subcutaneous insulin or IV insulin infusion or insulin pump therapy on second measurement day. Endocrine/diabetes consultation was infrequent, only 9% of all patients were evaluated by an endocrinologist or diabetologist at any time during the hospitalization.
DISCUSSION
In this retrospective analysis of hospitalized patients who had 2 consecutive blood glucose values 180 mg/dL and/or received insulin therapy, hyperglycemia was common and hypoglycemia was infrequent. Use of intravenous insulin was associated with better glucose control, and did not increase the frequency of severe hypoglycemic events (glucose <50 mg/dL). The majority of patients with a history of diabetes had physician documentation in the hospital chart, laboratory serum glucose obtained within 8 hours of hospital admission, and at least 4 blood glucose determinations on the second measurement day.
Only 35% of patients with diabetes had an A1C measurement and of these almost 60% had an A1C level >7%. Though the A1C may not greatly affect acute glucose management in the hospital setting, it does identify patients that may require intensification of diabetes therapy at hospital discharge and coordination of outpatient follow‐up. A report of a UHC clinical benchmarking project of ambulatory diabetes care in academic medical centers demonstrated high rates of diagnostic testing, but only 34% of patients were at the A1C goal, and only 40% of patients above the A1C goal had adjustment of their diabetes regimen at their last clinic visit.26 In a retrospective study of patients with diabetes mellitus admitted to an academic teaching hospital, only 20% of discharges indicated a plan for diabetes follow‐up.27 Thus, intensification of antihyperglycemic therapy and formulation of a diabetes follow‐up plan on hospital discharge in those patients with A1C >7% represents an opportunity to improve glycemic control in the ambulatory setting. Also, measurement of A1C can be used for diabetes case‐finding in hospitalized patients with hyperglycemia.25 Previously unrecognized diabetes is a common finding in patients admitted with cardiovascular disease. In a study of patients admitted with myocardial infarction, 25% were found to have previously undiagnosed diabetes.28 Hospital patients with hyperglycemia but without a prior diagnosis of diabetes who have an elevation of A1C >6.0% can be identified as at‐risk for diabetes and postdischarge glucose evaluation can be arranged.
The target of maintaining all glucose values 180 mg/dL recommended in the 20052007 American Diabetes Association guidelines for hospital diabetes management was not commonly achieved, with over 70% of patients who received subcutaneous insulin therapy having 1 or more glucose values >180 on all 3 measurement days, regardless of patient location.15 The target of maintaining critically ill patients as close to 110 mg/dL as possible was also difficult to achieve, with only 25% of ICU patients having an estimated 6 AM glucose <110 mg/dL on measurement day 3. A prospective cohort study of 107 inpatients with diabetes at Brigham and Women's Hospital showed a 76% prevalence of patients with at least one BG >180 mg/dL.29 In that study, 90% of patients had a sliding‐scale order, 36% received an oral diabetes agent, and 43% received basal insulin at some time during hospitalization. A recently published analysis by Wexler et al.30 compiled data of hospitalized patients with diabetes from an earlier 2003 UHC Diabetes Benchmarking Project (n = 274) and patients from 15 not‐for‐profit member hospitals of VHA, Incorporated (n = 725) to examine the prevalence of hyperglycemia and hypoglycemia. Hyperglycemia (defined as a single BG value >200 mg/dL) was common, occurring in 77% of patients in the UHC cohort and 76% in the VHA, Inc. cohort. This was comparable to our findings that 76.7% of ICU patients and 78.6% of ward patients treated with subcutaneous insulin had 1 or more BG values 180 mg/dL on measurement day 2. Wexler et al.30 also determined that use of basal insulin was associated with a higher prevalence of hyperglycemia and hypoglycemia in their study. Our regression analysis finding that long‐acting (basal) insulin use was not associated with improvement in glycemic control is consistent with the findings of the aforementioned study. There are a number of potential explanations for this: (1) underdosing of basal insulin or lack of adequate prandial insulin coverage for nutritional intake; (2) lack of effective titration in response to hyperglycemia; and (3) variation in the ordering and administration of basal insulin at different hospital sites.
Use of both manual and computerized IV insulin protocols has been shown to provide effective glucose control in critically ill patients.1618 Though intravenous insulin use was associated with better overall glucose control in our study; only about 50% of ICU patients received it on measurement day 1. A recent prospective randomized clinical trial demonstrated superior glycemic control in noncritically ill hospitalized patients with type 2 diabetes with basal/bolus insulin therapy compared to sliding scale insulin alone.31 Use of basal/bolus insulin regimens as part of a comprehensive hospital diabetes management program has been shown to improve glycemic control in an academic medical center.20 Therefore, we do not believe that our regression analysis findings invalidate the concept of basal/bolus insulin for inpatients with hyperglycemia, but rather indicate the need for more research into subcutaneous insulin regimens and hospital care practices that lead to improved glucose control. We found wide variation in hospital use of basal/bolus insulin regimens. Overall only 22.5% of all patients on the second measurement day received both short‐acting and long‐acting subcutaneous insulin, compared to 30.8% who received short‐acting subcutaneous insulin only. A recent consensus statement on inpatient glycemic control by the American College of Endocrinology and American Diabetes Association highlighted the systematic barriers to improved glycemic control in hospitals, such as inadequate knowledge of diabetes management techniques, fear of hypoglycemia, and skepticism about benefits of tighter glucose control.32
There are some important limitations to this study. The data are retrospective and only a limited number of hospital days and clinical variables could be assessed for each patient. As indicated in Table 3, there were significant differences in the frequency of glucose measurement depending on treatment, which can potentially bias estimated prevalence of hyperglycemia and hypoglycemia. We did not have a practical method to assess nutritional status or the adequacy of insulin dosing over time for each patient. We also could not assess the association of glycemic control on clinical outcomes such as hospital mortality or infection rates. Since this study was exclusively in academic medical centers, the generalization of findings to community‐based medical centers may be limited. The risk‐benefit of tight glycemic control in medical ICU patients based on clinical trial evidence has been unclear, and there is not broad agreement among clinicians on the recommended target for glycemic control in this group.3335 When we analyzed glycemic control in ICU patients we did not have a practical method to control for type of ICU and variations in individual ICU glycemic control targets. We recognize that the 2004 American College of Endocrinology recommendation of maintaining glucose 110 mg/dL may not be appropriate for all critically ill patients.14 Finally, clinical trial data are lacking on the effect of tight glucose control on major clinical outcomes for noncritically ill hospital patients. This has led to significant controversy regarding glycemic targets for different subgroups of hospitalized patients.34, 36
In summary, we found a high prevalence of persistent hyperglycemia in this large cohort of hospitalized patients, and hypoglycemia was infrequent. Use of IV insulin was associated with improvement in glycemic control, but was used in less than half of ICU patients. There was wide variation in hospital performance of recommended diabetes care measures. Opportunities to improve care in academic medical centers include expanded use of intravenous and subcutaneous basal/bolus insulin protocols and increased frequency of A1C testing.
- Effects of admission hyperglycemia on mortality and costs in acute ischemic stroke.Neurology.2002;59:67–71. , , , et al.
- Hyperglycemia: an independent marker of in‐hospital mortality in patients with undiagnosed diabetes.J Clin Endocrinol Metab.2002;87:978–982. , , , , , .
- Unrecognized diabetes among hospitalized patients.Diabetes Care.1998;21:246–249. , , , , .
- Management of diabetes and hyperglycemia in hospitals.Diabetes Care.2004;27:553–591. , , , et al.
- Admission plasma glucose. Independent risk factor for long‐term prognosis after myocardial infarction even in nondiabetic patients.Diabetes Care.1999;22:1827–1831. , , .
- Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview.Stroke.2001;32:2426–2432. , , , , .
- Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview.Lancet.2000;355:773–778. , , , .
- The relation between hyperglycemia and outcomes in 2,471 patients admitted to the hospital with community‐acquired pneumonia.Diabetes Care.2005;28:810–815. , , , , , .
- Modifiable risk factors associated with deep sternal site infection after coronary artery bypass grafting.J Thorac Cardiovasc Surg.2000;119:108–114. , , , et al.
- The association of diabetes and glucose control with surgical‐site infections among cardiothoracic surgery patients.Infect Control Hosp Epidemiol.2001;22:607–612. , , , , .
- Intensive insulin therapy in the critically ill patients.N Engl J Med.2001;345:1359–1367. , , , et al.
- Tight glycemic control in diabetic coronary artery bypass graft patients improves perioperative outcomes and decreases recurrent ischemic events.Circulation.2004;109:1497–1502. , , , , , .
- Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland Diabetic Project.Endocr Pract.2004;10(Suppl 2):21–33. , , .
- American College of Endocrinology position statement on inpatient diabetes and metabolic control.Endocr Pract.2004;10(Suppl 2):4–9. , , , et al.
- American Diabetes Association.Standards of medical care in diabetes.Diabetes Care.2005;28(Suppl 1):S4–S36.
- Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit.Diabetes Care.2004;27:461–467. , , , et al.
- Use of a computerized guideline for glucose regulation in the intensive care unit improved both guideline adherence and glucose regulation.J Am Med Inform Assoc.2005;12:172–180. , , , , .
- Computer‐based insulin infusion protocol improves glycemia control over manual protocol.J Am Med Inform Assoc.2007;14:278–287. , , , et al.
- Management of diabetes mellitus in hospitalized patients: efficiency and effectiveness of sliding‐scale insulin therapy.Pharmacotherapy.2006;26:1421–1432. , , , , .
- Eliminating inpatient sliding‐scale insulin: a reeducation project with medical house staff.Diabetes Care.2005;28:1008–1011. , , , .
- 70/30 insulin algorithm versus sliding scale insulin.Ann Pharmacother.2005;39:1606–1610. , , .
- Glucose measurement: confounding issues in setting targets for inpatient management.Diabetes Care.2007;30:403–409. , , , .
- “Glucometrics”—assessing the quality of inpatient glucose management.Diabetes Technol Ther.2006;8:560–569. , , , et al.
- American Diabetes Association.Hospital admission guidelines for diabetes.Diabetes Care.2004;27(Suppl 1):S103.
- Utility of HbA(1c) levels for diabetes case finding in hospitalized patients with hyperglycemia.Diabetes Care.2003;26:1064–1068. , , , , , , .
- Quality of diabetes care in U.S. academic medical centers: low rates of medical regimen change.Diabetes Care.2005;28:337–442. , , .
- Diabetes care in the hospital: is there clinical inertia?J Hosp Med.2006;1:151–160. , , , et al.
- Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study.Lancet.2002;359:2140–2144. , , , et al.
- Inpatient management of diabetes and hyperglycemia among general medicine patients at a large teaching hospital.J Hosp Med.2006;1:145–150. , , , , .
- Prevalence of hyper‐ and hypoglycemia among inpatients with diabetes: a national survey of 44 U.S. hospitals.Diabetes Care.2007;30:367–369. , , , , .
- Randomized study of basal‐bolus insulin therapy in the inpatient management of patients with type 2 diabetes (RABBIT 2 trial).Diabetes Care.2007;30:2181–2186. , , , et al.
- The ACE/ADA Task Force on Inpatient Diabetes.American College of Endocrinology and American Diabetes Association Consensus Statement on Inpatient Diabetes and Glycemic Control: a call to action.Diabetes Care.2006;29:1955–1962.
- Intensive insulin therapy in the medical ICU.N Engl J Med.2006;354:449–461. , , , et al.
- Tight blood glucose control with insulin in the ICU: facts and controversies.Chest.2007;132:268–278. , , .
- Intensive insulin therapy and pentastarch resuscitation in severe sepsis.NEngl J Med.2008;358:125–139. , , , et al.
- Counterpoint: Inpatient glucose management: a premature call to arms?Diabetes Care.2005;28:976–979. , .
Hyperglycemia is a common occurrence in hospitalized patients, with and without a prior diagnosis of diabetes mellitus.13 Estimates of prevalence of diabetes mellitus in hospitalized adult patients range from 12% to 25%.4 Hyperglycemia is a strong predictor of adverse clinical outcome in a range of diseases such as acute stroke, congestive heart failure, community‐acquired pneumonia, and acute myocardial infarction.58 Hyperglycemia is also a risk factor for surgical infection in patients undergoing cardiac surgery.9, 10 A landmark prospective randomized controlled clinical trial by van den Berghe et al.11 demonstrated that tight glucose control (target blood glucose level 80110 mg/dL) with intravenous insulin in critically ill surgical patients led to dramatic reductions in acute renal failure, critical illness polyneuropathy, hospital mortality, and bloodstream infection. Other clinical studies have demonstrated that glycemic control with intravenous insulin improves clinical outcomes and reduces length of stay in patients with diabetes undergoing cardiac surgery.12, 13
Based upon these findings, the American College of Endocrinology (ACE) published recommendations in 2004 for hospital diabetes and metabolic control.14 Similar recommendations for hospital glycemic control have been included in the American Diabetes Association (ADA) guidelines since 2005.15 There is now emerging consensus that use of continuous insulin infusion given through a standardized protocol is the standard of care to control hyperglycemia in critically ill patients.1618 Likewise, use of specific hospital insulin regimens that include basal and short‐acting insulin with appropriate bedside glucose monitoring and avoiding use of sliding scale short‐acting insulin alone has become recognized as the most effective approach for glucose management in hospitalized patients not requiring intravenous insulin.4, 1921
The University HealthSystem Consortium (UHC) is an alliance of 97 academic health centers and 153 of their associated hospitals that conducts benchmarking studies on clinical and operational topics with member academic medical centers and develops new programs to improve quality of care, patient safety, and operational, clinical, and financial performance. In late 2004, UHC launched the Glycemic Control Benchmarking Project to determine the current status of glycemic control in adult patients admitted to academic medical centers, types of treatment employed to control glucose, and operational measures and practices of care for glycemic control in the hospital setting. The goal of the project was to describe contemporary glucose management for the purpose of identifying best practices. The information was later shared with each participating medical center to allow them to better align care delivery with ADA and ACE guidelines. Thirty‐seven academic medical centers agreed to participate and submit patient level data as well as an operational survey of current policies and practices for hospital glycemic control. This report summarizes the key findings from retrospective analyses of hospital and patient‐level data and describes contemporary management of hyperglycemia in academic medical centers.
PATIENTS AND METHODS
To be eligible for the study, hospital patients at each participating medical center had to be 18 years of age, have a 72‐hour or longer length of stay, and be admitted with 1 or more of the following Diagnostic‐related group (DRG) codes: 89 (simple pneumonia/ pleurisy), 109 (coronary artery bypass grafting without catheterization), 127 (heart failure and shock), 143 (chest pain), 209 (joint/limb procedure), 316 (renal failure), 478 (other vascular procedures), or 527 (percutaneous intervention with drug eluting stent without acute myocardial infarction). The DRG codes were selected from analysis of the UHC Clinical Data Base because they were the most common adult medical and surgical admission codes that included diabetes as a secondary diagnosis for academic medical centers and were believed to best represent the majority of hospital admissions. Each participating medical center received a secure electronic listing of their eligible patients discharged between July 1, 2004 and September 30, 2004 from the UHC Clinical Data Base. Each center identified data extractors who were trained via teleconference and received technical and content support by UHC staff. The data were collected by chart review and submitted electronically to UHC from February to April 2005.
For each medical center, patients were screened in reverse chronological order proceeding back in time until the minimum number of 50 eligible cases was obtained or until all potential cases were screened. Although 50 cases was the recommended minimum sample size per site, each medical center was encouraged to submit as many eligible cases as possible. The median number of cases submitted by site was 50 (interquartile range [IQR], 4251). Cases were entered into the study if they met the eligibility criteria and at least one of the following inclusion criteria: (1) two consecutive blood glucose readings >180 mg/dL within a 24hour period, or (2) insulin treatment at any time during the hospitalization. Exclusion criteria included history of pancreatic transplant, pregnancy at time of admission, hospice or palliative care during hospital admission, and patients who received insulin for a reason other than blood glucose control (ie, hyperkalemia). Early in the data collection, DRG 209 was dropped from potential screening due to the low yield of meeting screening criteria for blood glucose readings. Of the 315 cases screened for DRG 209 only 44 met all inclusion criteria and remain in the study population.
A maximum of 3 consecutive days of blood glucose (BG) readings were collected for each patient, referred to as measurement day 1, measurement day 2, and measurement day 3. Measurement day 1 is defined as the day the first of 2 consecutive blood glucose levels >180 mg/dL occurred during the hospitalization or as the first day insulin was administered during the hospitalization, whichever came first; 40.6% of patients had the day of admission as their first measurement day. Glucose measurements were recorded by hour for each measurement day as available, and if more than 1 glucose value was available within a particular hour, only the first result was recorded. Both bedside and laboratory serum glucose values were utilized, and glycosylated hemoglobin (A1C) values were included if they were recorded during the hospitalization or within 30 days prior to admission;22 95.7% of patients had BG results reported for all 3 measurement days. We defined estimated 6 AM glucose for each subject as: the 6 AM glucose if it was available; otherwise the average of the 5 AM and 7 AM glucose values if at least 1 of them was available; otherwise the average of the 4 AM and 8 AM glucose values if at least 1 of them was available. Relevant demographics, medical history, hospitalization details, type and route of insulin administration, and discharge data were also collected. For subcutaneous insulin administration, use of regular, lispro, or aspart insulin was classified as short‐acting insulin; use of neutral protamine Hagedorn (NPH), ultralente, or glargine insulin was classified as long‐acting insulin. For analysis of glycemic control measures, patient‐days in which location or glucose data were not recorded were excluded from analysis. For the analysis comparing subcutaneous versus intravenous insulin treatment on glucose control, patients who received a combination of therapy with subcutaneous and intravenous insulin on the same measurement day were excluded from the analysis (44 patients on day 1, 96 on day 2, and 47 on day 3). For this retrospective analysis, UHC provided a deidentified data set to the authors. The study protocol was reviewed by the Vanderbilt University Institutional Review Board and deemed to be nonhuman subject research since the data set contained no personal or institutional identifiers. Therefore, no informed consent of subjects was required.
Measures of glucose control (median glucose and estimated 6 AM glucose) were analyzed by patient‐day,23 and were compared by a Wilcoxon rank sum test or an analysis of variance, as indicated. P values <0.05 were considered significant. To compare effects of intravenous (IV) insulin, subcutaneous long‐acting short‐acting insulin, and subcutaneous short‐acting insulin use alone on glycemic control, mixed effects linear regression modeling for median glucose and mixed effects logistic regression modeling for hyperglycemia and hypoglycemia were used to adjust for fixed effects of age, gender, diabetes status, all patient refined diagnosis related groups (APR‐DRG) severity of illness score, outpatient diabetes treatment, patient location, admission diagnosis, and random effect of hospital site. Separate regression models were performed for measurement days 2 and 3. Statistical analyses were performed with Stata version 8 (Stata Corporation, College Station, TX), R version 2.1.0 (R Foundation for Statistical Computing, Vienna, Austria;
RESULTS
Thirty‐seven US academic medical centers from 24 states contributed to the analysis. A total of 4,367 cases meeting age, length of stay, and DRG criteria were screened for inclusion in the study; 2,649 (60.7%) screened cases were excluded due to failure to meet inclusion criteria (51%) or presence of exclusionary conditions (9.7%); 1,718 (39.3%) screened cases met all criteria and were included in this analysis. Patient characteristics are summarized in Table 1. A majority of patients (79%) had a documented history of diabetes, and most of these were classified as type 2 diabetes in the hospital record. Of the patients who were classified as having diabetes on admission, 50.8% were on some form of outpatient insulin therapy with or without oral diabetes agents. Patients with a diagnosis of diabetes had a median admission glucose of 158 mg/dL (IQR, 118221), which was significantly higher than the median admission glucose of 119 mg/dL (IQR, 100160) for patients without diabetes (P < 0.001, rank‐sum test).
| |
n | 1718 |
Age (years), median (IQR) | 65 (5674) |
Male | 928 (54) |
Female | 790 (46) |
Admission glucose (mg/dL) | 149 (111207) |
Race/Ethnicity | |
White | 1048 (61.0) |
Black | 480 (27.9) |
Hispanic | 67 (3.9) |
Other | 123 (7.2) |
Diabetes history | 1358 (79.0) |
Type 2 diabetes mellitus | 996 (58.0) |
Type 1 diabetes mellitus | 128 (7.5) |
Unspecified/other diabetes mellitus | 234 (13.6) |
No history of diabetes mellitus | 360 (21.0) |
Outpatient diabetes treatment | |
Insulin only | 522 (30.4) |
Oral agents only | 505 (29.4) |
Insulin and oral agents | 168 (9.8) |
No drug therapy | 137 (8.0) |
Not documented | 26 (1.5) |
Hospitalization DRG | |
127 Heart failure | 443 (25.8) |
109 Coronary artery bypass grafting | 389 (22.6) |
316 Renal failure | 251 (14.6) |
478 Other vascular procedure | 195 (11.4) |
89 Pneumonia | 186 (10.8) |
527 Percutaneous intervention with stent | 136 (7.9) |
143 Chest pain | 74 (4.3) |
209 Joint/limb procedure | 44 (2.6) |
Primary insurer | |
Medicare | 961 (56.0) |
Private/commercial | 392 (22.8) |
Medicaid | 200 (11.6) |
Government | 88 (5.1) |
Self‐pay | 67 (3.9) |
Other/unknown | 10 (0.6) |
To determine overall glycemic control for the cohort, median glucose was calculated for each patient, stratified by diabetes status and location for each measurement day (Table 2). Patient‐days with a location of emergency department (96 patients on day 1, 6 on day 2, and 2 on day 3) and two patients whose location was not defined were excluded from the analysis. Overall, median glucose declined from measurement day 1 to day 3. For patients with diabetes, median glucose was significantly lower in the intensive care unit (ICU) compared to the general ward or intermediate care for measurement days 1 and 2, but not day 3. This difference was more pronounced in patients without diabetes, with median glucose significantly lower in the ICU for all 3 measurement days compared to other locations. As expected, median glucose was lower for patients without diabetes compared to patients with diabetes for all measurement days and locations. Hyperglycemia was common; 867 of 1,718 (50%) patients had at least 1 glucose measurement 180 mg/dL on both days 2 and 3; 18% of all patients had a median glucose 180 mg/dL on all 3 measurement days. Daily 6 AM glucose was the summary glycemic control measure in the clinical trial by van den Berghe et al.,11 with goal glucose of 80 to 110 mg/dL in the intensive treatment group. Since the glycemic target of the American College of Endocrinology Position Statement is <110 mg/dL (based largely on van den Berghe et al.11) we also calculated estimated 6 AM glucose for ICU patient‐days to determine the proportion of patients attaining this target.14 Estimated 6 AM glucose was lower in ICU patients without diabetes compared to those with diabetes. For patients with diabetes, only 20% of patients in the ICU had an estimated 6 AM glucose 110 mg/dL on measurement day 2, and only 24% on day 3. For patients without diabetes, 27% and 25% had an estimated 6 AM glucose 110 mg/dL on days 2 and 3, respectively.
Measurement by Location | |||
---|---|---|---|
Day 1 | Day 2 | Day 3 | |
| |||
Patients with diabetes | |||
Estimated 6 AM glucose (mg/dL) | |||
Intensive care unit | 153.0 (119.0204.0) | 148.0 (118.0183.0) | 144.0 (113.0191.0) |
n | 167 | 231 | 161 |
Median glucose (mg/dL) | |||
General floor | 186.0 (151.0229.0) | 163.0 (131.0210.0) | 161.0 (127.0203.4) |
n | 681 | 757 | 758 |
Intermediate care | 193.0 (155.3233.8) | 170.0 (137.0215.5) | 169.0 (137.9215.6) |
n | 291 | 333 | 348 |
Intensive care unit | 177.5 (149.6213.6) | 152.5 (128.3187.0) | 156.5 (124.5194.3) |
n | 294 | 247 | 175 |
P value* | 0.038 | <0.001 | 0.068 |
Patients without diabetes | |||
Estimated 6 AM glucose (mg/dL) | |||
Intensive care unit | 133.0 (104.5174.0) | 134.0 (109.0169.0) | 128.0 (111.5151.3) |
n | 98 | 157 | 80 |
Median glucose (mg/dL) | |||
General floor | 179.0 (149.5209.5) | 161.3 (131.4188.3) | 143.5 (122.0170.0) |
n | 91 | 96 | 133 |
Intermediate care | 168.3 (138.1193.8) | 137.0 (119.8161.5) | 129.3 (116.3145.5) |
n | 46 | 71 | 86 |
Intensive care unit | 153.8 (132.9188.8) | 136.5 (120.0157.0) | 129.0 (116.0143.8) |
n | 218 | 186 | 106 |
P value* | <0.001 | <0.001 | <0.001 |
For the overall cohort, insulin was the most common treatment for hyperglycemia, with 84.6% of all patients receiving some form of insulin therapy on the second measurement day. On the second day, 30.8% received short‐acting subcutaneous insulin only, 8.2% received intravenous insulin infusion, 22.5% received both short‐acting and long‐acting subcutaneous insulin, 3.9% received oral agents, 23% received some combination of insulin therapies and/or oral agents, and 11.9% received no treatment. To determine the effect of intravenous versus subcutaneous insulin treatment on glycemic control, we compared patients by insulin treatment and location for each measurement day (Table 3). Intravenous insulin was used predominantly in the ICU, and was associated with significantly lower median glucose compared to subcutaneous insulin in both locations for all 3 measurement days. As expected, the average number of glucose measures per patient was significantly higher for those receiving intravenous insulin. Intravenous insulin use in the ICU was associated with a significantly lower number of patients with hyperglycemia, defined as the number who had 1 or more glucose values 180 mg/dL during a given measurement day. Of note, intravenous insulin use in the ICU was associated with a significantly higher proportion of patients who had hypoglycemia (defined as the number of patients who had one or more glucose values <70 mg/dL) compared to subcutaneous insulin only on measurement day 1 (8.1% versus 2.9%; P = 0.021), but not on days 2 (12.7% versus 8.0%; P > 0.05) or 3 (12.7% versus 7.8%; P > 0.05). Severe hypoglycemia, defined as a blood glucose recording <50 mg/dL,24 was rare, and occurred in only 2.8% of all patient days. On measurement day 1, 34 patients had a total of 49 severe hypoglycemic events; on day 2, 54 patients had 68 severe hypoglycemic events; on day 3, 54 patients had 68 severe hypoglycemic events. Only 3 patients had severe hypoglycemic events on all 3 measurement days. Analysis of severe hypoglycemia events stratified by intravenous versus subcutaneous insulin did not show any significant differences for any of the 3 measurement days (data not shown).
Location/Day | Outcome | Intravenous Insulin | Subcutaneous Insulin | P Value* |
---|---|---|---|---|
| ||||
Intensive Care Unit, Day 1 | Patient's glucose, median (mg/dL) | 148.0 | 183.0 | <0.001 |
Interquartile range | 128.0178.0 | 154.8211.0 | ||
Hypoglycemic patients, n (%) | 16 (8.1) | 6 (2.9) | 0.021 | |
Hyperglycemic patients, n (%) | 130 (66.0) | 175 (85.0) | <0.001 | |
Average glucose measures/patient | 8.4 | 4.8 | <0.001 | |
Patients, n | 197 | 206 | ||
Intermediate/General Ward, Day 1 | Patient's glucose, median (mg/dL) | 152.0 | 186.5 | <0.001 |
Interquartile range | 131.0164.5 | 150.0230.0 | ||
Hypoglycemic patients, n (%) | 1 (4.1) | 71 (7.4) | ns | |
Hyperglycemic patients, n (%) | 18 (78.3) | 808 (83.9) | ns | |
Average glucose measures/patient | 9.7 | 3.8 | <0.001 | |
Patients, n | 23 | 962 | ||
Intensive Care Unit, Day 2 | Patient's glucose, median (mg/dL) | 124.8 | 159.8 | <0.001 |
Interquartile range | 110.4140.5 | 138.6197.4 | ||
Hypoglycemic patients, n (%) | 15 (12.7) | 14 (8.0) | ns | |
Hyperglycemic patients, n (%) | 53 (44.9) | 135 (76.7) | <0.001 | |
Average glucose measures/patient | 12.5 | 5.3 | <0.001 | |
Patients, n | 118 | 176 | ||
Intermediate/General Ward, Day 2 | Patient's glucose, median (mg/dL) | 136.0 | 168.8 | <0.001 |
Interquartile range | 116.0168.0 | 136.1215.5 | ||
Hypoglycemic patients, n (%) | 2 (6.7) | 113 (11.3) | ns | |
Hyperglycemic patients, n (%) | 18 (60.0) | 784 (78.6) | 0.015 | |
Average glucose measures/patient | 11.0 | 4.6 | <0.001 | |
Patients, n | 30 | 996 | ||
Intensive Care Unit, Day 3 | Patient's glucose, median (mg/dL) | 123.5 | 171.0 | <0.001 |
Interquartile range | 110.0137.1 | 137.3198.5 | ||
Hypoglycemic patients, n (%) | 7 (12.7) | 11 (7.8) | ns | |
Hyperglycemic patients, n (%) | 24 (43.6) | 101 (71.1) | <0.001 | |
Average glucose measures/patient | 11.4 | 4.8 | <0.001 | |
Patients, n | 54 | 141 | ||
Intermediate/General Ward, Day 3 | Patient's glucose, median (mg/dL) | 129.8 | 166.0 | <0.001 |
Interquartile range | 120.5142.3 | 131.5208.0 | ||
Hypoglycemic patients, n (%) | 3 (13.6) | 104 (9.8) | ns | |
Hyperglycemic patients, n (%) | 13 (59.1) | 773 (72.7) | ns | |
Average glucose measures/patient | 10.3 | 4.3 | <0.001 | |
Patients, n | 22 | 1,055 |
We hypothesized that use of subcutaneous long‐acting (basal) insulin (with or without short‐acting insulin) would be associated with superior glucose control compared to use of subcutaneous short‐acting insulin (sliding scale and/or scheduled prandial insulin) alone. We performed an exploratory multivariate regression analysis to compare the effect of IV insulin, long acting subcutaneous insulin short acting insulin, or short acting subcutaneous insulin alone on median glucose, hyperglycemic events (glucose 180 mg/dL), and hypoglycemic events (glucose <70 mg/dL) for days 2 and 3 (Table 4). Compared to short‐acting subcutaneous insulin alone, use of IV insulin but not long‐acting subcutaneous insulin was predictive of lower median glucose for days 2 and 3. Use of long‐acting subcutaneous insulin was not associated with significantly lower odds of hyperglycemic events for days 2 and 3, but was associated with higher odds of hypoglycemic events on day 2 (odds ratio [OR], 1.8; P = 0.01) when compared to short‐acting subcutaneous insulin alone.
Glucose Control Measure | Intravenous Insulin Infusion | Long‐Acting Subcutaneous Insulin |
---|---|---|
| ||
Median glucose | ||
Day 2, n = 1,297 | 32.0 (45.4 to 18.5); P < 0.001* | 5.1 (13.8 to 3.6); P = 0.25* |
Day 3, n = 1,251 | 33.0 (48.9 to 17); P < 0.001* | 3.4 (5.2 to 11.9); P = 0.44* |
Patient has 1 hyperglycemic event | ||
Day 2, n = 1,298 | 0.4 (0.20.6); P < 0.001 | 0.7 (0.51.1); P = 0.11 |
Day 3, n = 1,261 | 0.6 (0.31.1); P = 0.11 | 0.8 (0.61.1); P = 0.24 |
Patient has 1 hypoglycemic event | ||
Day 2, n = 1,298 | 2.1 (1.04.7); P = 0.07 | 1.8 (1.22.9); P = 0.010 |
Day 3, n = 1,261 | 4.0 (1.69.8); P = 0.003 | 1.4 (0.92.3); P = 0.13 |
We measured the performance of recommended hospital diabetes care practices (A1C assessment, documentation of diabetes history in the hospital record, admission laboratory glucose assessment, bedside glucose monitoring, recommended insulin therapy)14, 15 for all study patients, and also stratified performance by hospital (Table 5); 98.6% of all patients with a diagnosis of diabetes had physician documentation of their diabetes status recorded in the hospital record, and there was consistently high performance of this by hospital (Table 5); 77% of all patients with a history of diabetes had a laboratory blood glucose result recorded within 8 hours of hospital admission, and 81.3% of patients with a history of diabetes had blood glucose monitored at least 4 times on measurement day 2. Performance by hospital (Table 5) varied widely for glucose monitoring (range, 56.5%95.5% of patients by hospital) and admission laboratory glucose assessment (range, 39.0%97.1% of patients by hospital).
Diabetes Care Measure | Mean Hospital Performance (%) | Standard Deviation (%) | Range (%) |
---|---|---|---|
| |||
Physician documentation of diabetes history in medical record | 98.8 | 2.1 | 91.5100 |
A1C assessment documented for diabetes patients (measured during hospitalization or within 30 days prior to admission) | 33.7 | 15.4 | 3.162.9 |
Laboratory glucose assessment within 8 hours of hospital presentation for diabetes patients | 77.0 | 13.4 | 39.097.1 |
Blood glucose monitoring at least 4 times on second measurement day for diabetes patients | 81.6 | 10.8 | 56.595.5 |
Percentage of patients receiving insulin therapy who were given short and long‐acting insulin OR IV insulin infusion OR insulin pump therapy on second measurement day | 44.9 | 14.3 | 12.176.5 |
Of all patients, 31% had A1C measurement recorded during their hospitalization or within 30 days prior to admission. There was wide variation in hospital performance of A1C assessment in patients with diabetes (Table 5). Patients with a diagnosis of diabetes had a median A1C of 7.4% (IQR, 6.4%8.9%; n = 473), and those without a diagnosis of diabetes had a median A1C of 5.9% (IQR, 5.6%6.4%; n = 70). Of the patients with a history of diabetes who had A1C recorded, 59% had a value >7%. Of the patients without a history of diabetes who had A1C recorded, 43% had a value >6.0%, suggesting previously undiagnosed diabetes.25
We found wide variation among hospitals (range, 12.1%76.5%) in use of recommended regimens of insulin therapy, defined as short‐acting and long‐acting subcutaneous insulin or IV insulin infusion or insulin pump therapy on second measurement day. Endocrine/diabetes consultation was infrequent, only 9% of all patients were evaluated by an endocrinologist or diabetologist at any time during the hospitalization.
DISCUSSION
In this retrospective analysis of hospitalized patients who had 2 consecutive blood glucose values 180 mg/dL and/or received insulin therapy, hyperglycemia was common and hypoglycemia was infrequent. Use of intravenous insulin was associated with better glucose control, and did not increase the frequency of severe hypoglycemic events (glucose <50 mg/dL). The majority of patients with a history of diabetes had physician documentation in the hospital chart, laboratory serum glucose obtained within 8 hours of hospital admission, and at least 4 blood glucose determinations on the second measurement day.
Only 35% of patients with diabetes had an A1C measurement and of these almost 60% had an A1C level >7%. Though the A1C may not greatly affect acute glucose management in the hospital setting, it does identify patients that may require intensification of diabetes therapy at hospital discharge and coordination of outpatient follow‐up. A report of a UHC clinical benchmarking project of ambulatory diabetes care in academic medical centers demonstrated high rates of diagnostic testing, but only 34% of patients were at the A1C goal, and only 40% of patients above the A1C goal had adjustment of their diabetes regimen at their last clinic visit.26 In a retrospective study of patients with diabetes mellitus admitted to an academic teaching hospital, only 20% of discharges indicated a plan for diabetes follow‐up.27 Thus, intensification of antihyperglycemic therapy and formulation of a diabetes follow‐up plan on hospital discharge in those patients with A1C >7% represents an opportunity to improve glycemic control in the ambulatory setting. Also, measurement of A1C can be used for diabetes case‐finding in hospitalized patients with hyperglycemia.25 Previously unrecognized diabetes is a common finding in patients admitted with cardiovascular disease. In a study of patients admitted with myocardial infarction, 25% were found to have previously undiagnosed diabetes.28 Hospital patients with hyperglycemia but without a prior diagnosis of diabetes who have an elevation of A1C >6.0% can be identified as at‐risk for diabetes and postdischarge glucose evaluation can be arranged.
The target of maintaining all glucose values 180 mg/dL recommended in the 20052007 American Diabetes Association guidelines for hospital diabetes management was not commonly achieved, with over 70% of patients who received subcutaneous insulin therapy having 1 or more glucose values >180 on all 3 measurement days, regardless of patient location.15 The target of maintaining critically ill patients as close to 110 mg/dL as possible was also difficult to achieve, with only 25% of ICU patients having an estimated 6 AM glucose <110 mg/dL on measurement day 3. A prospective cohort study of 107 inpatients with diabetes at Brigham and Women's Hospital showed a 76% prevalence of patients with at least one BG >180 mg/dL.29 In that study, 90% of patients had a sliding‐scale order, 36% received an oral diabetes agent, and 43% received basal insulin at some time during hospitalization. A recently published analysis by Wexler et al.30 compiled data of hospitalized patients with diabetes from an earlier 2003 UHC Diabetes Benchmarking Project (n = 274) and patients from 15 not‐for‐profit member hospitals of VHA, Incorporated (n = 725) to examine the prevalence of hyperglycemia and hypoglycemia. Hyperglycemia (defined as a single BG value >200 mg/dL) was common, occurring in 77% of patients in the UHC cohort and 76% in the VHA, Inc. cohort. This was comparable to our findings that 76.7% of ICU patients and 78.6% of ward patients treated with subcutaneous insulin had 1 or more BG values 180 mg/dL on measurement day 2. Wexler et al.30 also determined that use of basal insulin was associated with a higher prevalence of hyperglycemia and hypoglycemia in their study. Our regression analysis finding that long‐acting (basal) insulin use was not associated with improvement in glycemic control is consistent with the findings of the aforementioned study. There are a number of potential explanations for this: (1) underdosing of basal insulin or lack of adequate prandial insulin coverage for nutritional intake; (2) lack of effective titration in response to hyperglycemia; and (3) variation in the ordering and administration of basal insulin at different hospital sites.
Use of both manual and computerized IV insulin protocols has been shown to provide effective glucose control in critically ill patients.1618 Though intravenous insulin use was associated with better overall glucose control in our study; only about 50% of ICU patients received it on measurement day 1. A recent prospective randomized clinical trial demonstrated superior glycemic control in noncritically ill hospitalized patients with type 2 diabetes with basal/bolus insulin therapy compared to sliding scale insulin alone.31 Use of basal/bolus insulin regimens as part of a comprehensive hospital diabetes management program has been shown to improve glycemic control in an academic medical center.20 Therefore, we do not believe that our regression analysis findings invalidate the concept of basal/bolus insulin for inpatients with hyperglycemia, but rather indicate the need for more research into subcutaneous insulin regimens and hospital care practices that lead to improved glucose control. We found wide variation in hospital use of basal/bolus insulin regimens. Overall only 22.5% of all patients on the second measurement day received both short‐acting and long‐acting subcutaneous insulin, compared to 30.8% who received short‐acting subcutaneous insulin only. A recent consensus statement on inpatient glycemic control by the American College of Endocrinology and American Diabetes Association highlighted the systematic barriers to improved glycemic control in hospitals, such as inadequate knowledge of diabetes management techniques, fear of hypoglycemia, and skepticism about benefits of tighter glucose control.32
There are some important limitations to this study. The data are retrospective and only a limited number of hospital days and clinical variables could be assessed for each patient. As indicated in Table 3, there were significant differences in the frequency of glucose measurement depending on treatment, which can potentially bias estimated prevalence of hyperglycemia and hypoglycemia. We did not have a practical method to assess nutritional status or the adequacy of insulin dosing over time for each patient. We also could not assess the association of glycemic control on clinical outcomes such as hospital mortality or infection rates. Since this study was exclusively in academic medical centers, the generalization of findings to community‐based medical centers may be limited. The risk‐benefit of tight glycemic control in medical ICU patients based on clinical trial evidence has been unclear, and there is not broad agreement among clinicians on the recommended target for glycemic control in this group.3335 When we analyzed glycemic control in ICU patients we did not have a practical method to control for type of ICU and variations in individual ICU glycemic control targets. We recognize that the 2004 American College of Endocrinology recommendation of maintaining glucose 110 mg/dL may not be appropriate for all critically ill patients.14 Finally, clinical trial data are lacking on the effect of tight glucose control on major clinical outcomes for noncritically ill hospital patients. This has led to significant controversy regarding glycemic targets for different subgroups of hospitalized patients.34, 36
In summary, we found a high prevalence of persistent hyperglycemia in this large cohort of hospitalized patients, and hypoglycemia was infrequent. Use of IV insulin was associated with improvement in glycemic control, but was used in less than half of ICU patients. There was wide variation in hospital performance of recommended diabetes care measures. Opportunities to improve care in academic medical centers include expanded use of intravenous and subcutaneous basal/bolus insulin protocols and increased frequency of A1C testing.
Hyperglycemia is a common occurrence in hospitalized patients, with and without a prior diagnosis of diabetes mellitus.13 Estimates of prevalence of diabetes mellitus in hospitalized adult patients range from 12% to 25%.4 Hyperglycemia is a strong predictor of adverse clinical outcome in a range of diseases such as acute stroke, congestive heart failure, community‐acquired pneumonia, and acute myocardial infarction.58 Hyperglycemia is also a risk factor for surgical infection in patients undergoing cardiac surgery.9, 10 A landmark prospective randomized controlled clinical trial by van den Berghe et al.11 demonstrated that tight glucose control (target blood glucose level 80110 mg/dL) with intravenous insulin in critically ill surgical patients led to dramatic reductions in acute renal failure, critical illness polyneuropathy, hospital mortality, and bloodstream infection. Other clinical studies have demonstrated that glycemic control with intravenous insulin improves clinical outcomes and reduces length of stay in patients with diabetes undergoing cardiac surgery.12, 13
Based upon these findings, the American College of Endocrinology (ACE) published recommendations in 2004 for hospital diabetes and metabolic control.14 Similar recommendations for hospital glycemic control have been included in the American Diabetes Association (ADA) guidelines since 2005.15 There is now emerging consensus that use of continuous insulin infusion given through a standardized protocol is the standard of care to control hyperglycemia in critically ill patients.1618 Likewise, use of specific hospital insulin regimens that include basal and short‐acting insulin with appropriate bedside glucose monitoring and avoiding use of sliding scale short‐acting insulin alone has become recognized as the most effective approach for glucose management in hospitalized patients not requiring intravenous insulin.4, 1921
The University HealthSystem Consortium (UHC) is an alliance of 97 academic health centers and 153 of their associated hospitals that conducts benchmarking studies on clinical and operational topics with member academic medical centers and develops new programs to improve quality of care, patient safety, and operational, clinical, and financial performance. In late 2004, UHC launched the Glycemic Control Benchmarking Project to determine the current status of glycemic control in adult patients admitted to academic medical centers, types of treatment employed to control glucose, and operational measures and practices of care for glycemic control in the hospital setting. The goal of the project was to describe contemporary glucose management for the purpose of identifying best practices. The information was later shared with each participating medical center to allow them to better align care delivery with ADA and ACE guidelines. Thirty‐seven academic medical centers agreed to participate and submit patient level data as well as an operational survey of current policies and practices for hospital glycemic control. This report summarizes the key findings from retrospective analyses of hospital and patient‐level data and describes contemporary management of hyperglycemia in academic medical centers.
PATIENTS AND METHODS
To be eligible for the study, hospital patients at each participating medical center had to be 18 years of age, have a 72‐hour or longer length of stay, and be admitted with 1 or more of the following Diagnostic‐related group (DRG) codes: 89 (simple pneumonia/ pleurisy), 109 (coronary artery bypass grafting without catheterization), 127 (heart failure and shock), 143 (chest pain), 209 (joint/limb procedure), 316 (renal failure), 478 (other vascular procedures), or 527 (percutaneous intervention with drug eluting stent without acute myocardial infarction). The DRG codes were selected from analysis of the UHC Clinical Data Base because they were the most common adult medical and surgical admission codes that included diabetes as a secondary diagnosis for academic medical centers and were believed to best represent the majority of hospital admissions. Each participating medical center received a secure electronic listing of their eligible patients discharged between July 1, 2004 and September 30, 2004 from the UHC Clinical Data Base. Each center identified data extractors who were trained via teleconference and received technical and content support by UHC staff. The data were collected by chart review and submitted electronically to UHC from February to April 2005.
For each medical center, patients were screened in reverse chronological order proceeding back in time until the minimum number of 50 eligible cases was obtained or until all potential cases were screened. Although 50 cases was the recommended minimum sample size per site, each medical center was encouraged to submit as many eligible cases as possible. The median number of cases submitted by site was 50 (interquartile range [IQR], 4251). Cases were entered into the study if they met the eligibility criteria and at least one of the following inclusion criteria: (1) two consecutive blood glucose readings >180 mg/dL within a 24hour period, or (2) insulin treatment at any time during the hospitalization. Exclusion criteria included history of pancreatic transplant, pregnancy at time of admission, hospice or palliative care during hospital admission, and patients who received insulin for a reason other than blood glucose control (ie, hyperkalemia). Early in the data collection, DRG 209 was dropped from potential screening due to the low yield of meeting screening criteria for blood glucose readings. Of the 315 cases screened for DRG 209 only 44 met all inclusion criteria and remain in the study population.
A maximum of 3 consecutive days of blood glucose (BG) readings were collected for each patient, referred to as measurement day 1, measurement day 2, and measurement day 3. Measurement day 1 is defined as the day the first of 2 consecutive blood glucose levels >180 mg/dL occurred during the hospitalization or as the first day insulin was administered during the hospitalization, whichever came first; 40.6% of patients had the day of admission as their first measurement day. Glucose measurements were recorded by hour for each measurement day as available, and if more than 1 glucose value was available within a particular hour, only the first result was recorded. Both bedside and laboratory serum glucose values were utilized, and glycosylated hemoglobin (A1C) values were included if they were recorded during the hospitalization or within 30 days prior to admission;22 95.7% of patients had BG results reported for all 3 measurement days. We defined estimated 6 AM glucose for each subject as: the 6 AM glucose if it was available; otherwise the average of the 5 AM and 7 AM glucose values if at least 1 of them was available; otherwise the average of the 4 AM and 8 AM glucose values if at least 1 of them was available. Relevant demographics, medical history, hospitalization details, type and route of insulin administration, and discharge data were also collected. For subcutaneous insulin administration, use of regular, lispro, or aspart insulin was classified as short‐acting insulin; use of neutral protamine Hagedorn (NPH), ultralente, or glargine insulin was classified as long‐acting insulin. For analysis of glycemic control measures, patient‐days in which location or glucose data were not recorded were excluded from analysis. For the analysis comparing subcutaneous versus intravenous insulin treatment on glucose control, patients who received a combination of therapy with subcutaneous and intravenous insulin on the same measurement day were excluded from the analysis (44 patients on day 1, 96 on day 2, and 47 on day 3). For this retrospective analysis, UHC provided a deidentified data set to the authors. The study protocol was reviewed by the Vanderbilt University Institutional Review Board and deemed to be nonhuman subject research since the data set contained no personal or institutional identifiers. Therefore, no informed consent of subjects was required.
Measures of glucose control (median glucose and estimated 6 AM glucose) were analyzed by patient‐day,23 and were compared by a Wilcoxon rank sum test or an analysis of variance, as indicated. P values <0.05 were considered significant. To compare effects of intravenous (IV) insulin, subcutaneous long‐acting short‐acting insulin, and subcutaneous short‐acting insulin use alone on glycemic control, mixed effects linear regression modeling for median glucose and mixed effects logistic regression modeling for hyperglycemia and hypoglycemia were used to adjust for fixed effects of age, gender, diabetes status, all patient refined diagnosis related groups (APR‐DRG) severity of illness score, outpatient diabetes treatment, patient location, admission diagnosis, and random effect of hospital site. Separate regression models were performed for measurement days 2 and 3. Statistical analyses were performed with Stata version 8 (Stata Corporation, College Station, TX), R version 2.1.0 (R Foundation for Statistical Computing, Vienna, Austria;
RESULTS
Thirty‐seven US academic medical centers from 24 states contributed to the analysis. A total of 4,367 cases meeting age, length of stay, and DRG criteria were screened for inclusion in the study; 2,649 (60.7%) screened cases were excluded due to failure to meet inclusion criteria (51%) or presence of exclusionary conditions (9.7%); 1,718 (39.3%) screened cases met all criteria and were included in this analysis. Patient characteristics are summarized in Table 1. A majority of patients (79%) had a documented history of diabetes, and most of these were classified as type 2 diabetes in the hospital record. Of the patients who were classified as having diabetes on admission, 50.8% were on some form of outpatient insulin therapy with or without oral diabetes agents. Patients with a diagnosis of diabetes had a median admission glucose of 158 mg/dL (IQR, 118221), which was significantly higher than the median admission glucose of 119 mg/dL (IQR, 100160) for patients without diabetes (P < 0.001, rank‐sum test).
| |
n | 1718 |
Age (years), median (IQR) | 65 (5674) |
Male | 928 (54) |
Female | 790 (46) |
Admission glucose (mg/dL) | 149 (111207) |
Race/Ethnicity | |
White | 1048 (61.0) |
Black | 480 (27.9) |
Hispanic | 67 (3.9) |
Other | 123 (7.2) |
Diabetes history | 1358 (79.0) |
Type 2 diabetes mellitus | 996 (58.0) |
Type 1 diabetes mellitus | 128 (7.5) |
Unspecified/other diabetes mellitus | 234 (13.6) |
No history of diabetes mellitus | 360 (21.0) |
Outpatient diabetes treatment | |
Insulin only | 522 (30.4) |
Oral agents only | 505 (29.4) |
Insulin and oral agents | 168 (9.8) |
No drug therapy | 137 (8.0) |
Not documented | 26 (1.5) |
Hospitalization DRG | |
127 Heart failure | 443 (25.8) |
109 Coronary artery bypass grafting | 389 (22.6) |
316 Renal failure | 251 (14.6) |
478 Other vascular procedure | 195 (11.4) |
89 Pneumonia | 186 (10.8) |
527 Percutaneous intervention with stent | 136 (7.9) |
143 Chest pain | 74 (4.3) |
209 Joint/limb procedure | 44 (2.6) |
Primary insurer | |
Medicare | 961 (56.0) |
Private/commercial | 392 (22.8) |
Medicaid | 200 (11.6) |
Government | 88 (5.1) |
Self‐pay | 67 (3.9) |
Other/unknown | 10 (0.6) |
To determine overall glycemic control for the cohort, median glucose was calculated for each patient, stratified by diabetes status and location for each measurement day (Table 2). Patient‐days with a location of emergency department (96 patients on day 1, 6 on day 2, and 2 on day 3) and two patients whose location was not defined were excluded from the analysis. Overall, median glucose declined from measurement day 1 to day 3. For patients with diabetes, median glucose was significantly lower in the intensive care unit (ICU) compared to the general ward or intermediate care for measurement days 1 and 2, but not day 3. This difference was more pronounced in patients without diabetes, with median glucose significantly lower in the ICU for all 3 measurement days compared to other locations. As expected, median glucose was lower for patients without diabetes compared to patients with diabetes for all measurement days and locations. Hyperglycemia was common; 867 of 1,718 (50%) patients had at least 1 glucose measurement 180 mg/dL on both days 2 and 3; 18% of all patients had a median glucose 180 mg/dL on all 3 measurement days. Daily 6 AM glucose was the summary glycemic control measure in the clinical trial by van den Berghe et al.,11 with goal glucose of 80 to 110 mg/dL in the intensive treatment group. Since the glycemic target of the American College of Endocrinology Position Statement is <110 mg/dL (based largely on van den Berghe et al.11) we also calculated estimated 6 AM glucose for ICU patient‐days to determine the proportion of patients attaining this target.14 Estimated 6 AM glucose was lower in ICU patients without diabetes compared to those with diabetes. For patients with diabetes, only 20% of patients in the ICU had an estimated 6 AM glucose 110 mg/dL on measurement day 2, and only 24% on day 3. For patients without diabetes, 27% and 25% had an estimated 6 AM glucose 110 mg/dL on days 2 and 3, respectively.
Measurement by Location | |||
---|---|---|---|
Day 1 | Day 2 | Day 3 | |
| |||
Patients with diabetes | |||
Estimated 6 AM glucose (mg/dL) | |||
Intensive care unit | 153.0 (119.0204.0) | 148.0 (118.0183.0) | 144.0 (113.0191.0) |
n | 167 | 231 | 161 |
Median glucose (mg/dL) | |||
General floor | 186.0 (151.0229.0) | 163.0 (131.0210.0) | 161.0 (127.0203.4) |
n | 681 | 757 | 758 |
Intermediate care | 193.0 (155.3233.8) | 170.0 (137.0215.5) | 169.0 (137.9215.6) |
n | 291 | 333 | 348 |
Intensive care unit | 177.5 (149.6213.6) | 152.5 (128.3187.0) | 156.5 (124.5194.3) |
n | 294 | 247 | 175 |
P value* | 0.038 | <0.001 | 0.068 |
Patients without diabetes | |||
Estimated 6 AM glucose (mg/dL) | |||
Intensive care unit | 133.0 (104.5174.0) | 134.0 (109.0169.0) | 128.0 (111.5151.3) |
n | 98 | 157 | 80 |
Median glucose (mg/dL) | |||
General floor | 179.0 (149.5209.5) | 161.3 (131.4188.3) | 143.5 (122.0170.0) |
n | 91 | 96 | 133 |
Intermediate care | 168.3 (138.1193.8) | 137.0 (119.8161.5) | 129.3 (116.3145.5) |
n | 46 | 71 | 86 |
Intensive care unit | 153.8 (132.9188.8) | 136.5 (120.0157.0) | 129.0 (116.0143.8) |
n | 218 | 186 | 106 |
P value* | <0.001 | <0.001 | <0.001 |
For the overall cohort, insulin was the most common treatment for hyperglycemia, with 84.6% of all patients receiving some form of insulin therapy on the second measurement day. On the second day, 30.8% received short‐acting subcutaneous insulin only, 8.2% received intravenous insulin infusion, 22.5% received both short‐acting and long‐acting subcutaneous insulin, 3.9% received oral agents, 23% received some combination of insulin therapies and/or oral agents, and 11.9% received no treatment. To determine the effect of intravenous versus subcutaneous insulin treatment on glycemic control, we compared patients by insulin treatment and location for each measurement day (Table 3). Intravenous insulin was used predominantly in the ICU, and was associated with significantly lower median glucose compared to subcutaneous insulin in both locations for all 3 measurement days. As expected, the average number of glucose measures per patient was significantly higher for those receiving intravenous insulin. Intravenous insulin use in the ICU was associated with a significantly lower number of patients with hyperglycemia, defined as the number who had 1 or more glucose values 180 mg/dL during a given measurement day. Of note, intravenous insulin use in the ICU was associated with a significantly higher proportion of patients who had hypoglycemia (defined as the number of patients who had one or more glucose values <70 mg/dL) compared to subcutaneous insulin only on measurement day 1 (8.1% versus 2.9%; P = 0.021), but not on days 2 (12.7% versus 8.0%; P > 0.05) or 3 (12.7% versus 7.8%; P > 0.05). Severe hypoglycemia, defined as a blood glucose recording <50 mg/dL,24 was rare, and occurred in only 2.8% of all patient days. On measurement day 1, 34 patients had a total of 49 severe hypoglycemic events; on day 2, 54 patients had 68 severe hypoglycemic events; on day 3, 54 patients had 68 severe hypoglycemic events. Only 3 patients had severe hypoglycemic events on all 3 measurement days. Analysis of severe hypoglycemia events stratified by intravenous versus subcutaneous insulin did not show any significant differences for any of the 3 measurement days (data not shown).
Location/Day | Outcome | Intravenous Insulin | Subcutaneous Insulin | P Value* |
---|---|---|---|---|
| ||||
Intensive Care Unit, Day 1 | Patient's glucose, median (mg/dL) | 148.0 | 183.0 | <0.001 |
Interquartile range | 128.0178.0 | 154.8211.0 | ||
Hypoglycemic patients, n (%) | 16 (8.1) | 6 (2.9) | 0.021 | |
Hyperglycemic patients, n (%) | 130 (66.0) | 175 (85.0) | <0.001 | |
Average glucose measures/patient | 8.4 | 4.8 | <0.001 | |
Patients, n | 197 | 206 | ||
Intermediate/General Ward, Day 1 | Patient's glucose, median (mg/dL) | 152.0 | 186.5 | <0.001 |
Interquartile range | 131.0164.5 | 150.0230.0 | ||
Hypoglycemic patients, n (%) | 1 (4.1) | 71 (7.4) | ns | |
Hyperglycemic patients, n (%) | 18 (78.3) | 808 (83.9) | ns | |
Average glucose measures/patient | 9.7 | 3.8 | <0.001 | |
Patients, n | 23 | 962 | ||
Intensive Care Unit, Day 2 | Patient's glucose, median (mg/dL) | 124.8 | 159.8 | <0.001 |
Interquartile range | 110.4140.5 | 138.6197.4 | ||
Hypoglycemic patients, n (%) | 15 (12.7) | 14 (8.0) | ns | |
Hyperglycemic patients, n (%) | 53 (44.9) | 135 (76.7) | <0.001 | |
Average glucose measures/patient | 12.5 | 5.3 | <0.001 | |
Patients, n | 118 | 176 | ||
Intermediate/General Ward, Day 2 | Patient's glucose, median (mg/dL) | 136.0 | 168.8 | <0.001 |
Interquartile range | 116.0168.0 | 136.1215.5 | ||
Hypoglycemic patients, n (%) | 2 (6.7) | 113 (11.3) | ns | |
Hyperglycemic patients, n (%) | 18 (60.0) | 784 (78.6) | 0.015 | |
Average glucose measures/patient | 11.0 | 4.6 | <0.001 | |
Patients, n | 30 | 996 | ||
Intensive Care Unit, Day 3 | Patient's glucose, median (mg/dL) | 123.5 | 171.0 | <0.001 |
Interquartile range | 110.0137.1 | 137.3198.5 | ||
Hypoglycemic patients, n (%) | 7 (12.7) | 11 (7.8) | ns | |
Hyperglycemic patients, n (%) | 24 (43.6) | 101 (71.1) | <0.001 | |
Average glucose measures/patient | 11.4 | 4.8 | <0.001 | |
Patients, n | 54 | 141 | ||
Intermediate/General Ward, Day 3 | Patient's glucose, median (mg/dL) | 129.8 | 166.0 | <0.001 |
Interquartile range | 120.5142.3 | 131.5208.0 | ||
Hypoglycemic patients, n (%) | 3 (13.6) | 104 (9.8) | ns | |
Hyperglycemic patients, n (%) | 13 (59.1) | 773 (72.7) | ns | |
Average glucose measures/patient | 10.3 | 4.3 | <0.001 | |
Patients, n | 22 | 1,055 |
We hypothesized that use of subcutaneous long‐acting (basal) insulin (with or without short‐acting insulin) would be associated with superior glucose control compared to use of subcutaneous short‐acting insulin (sliding scale and/or scheduled prandial insulin) alone. We performed an exploratory multivariate regression analysis to compare the effect of IV insulin, long acting subcutaneous insulin short acting insulin, or short acting subcutaneous insulin alone on median glucose, hyperglycemic events (glucose 180 mg/dL), and hypoglycemic events (glucose <70 mg/dL) for days 2 and 3 (Table 4). Compared to short‐acting subcutaneous insulin alone, use of IV insulin but not long‐acting subcutaneous insulin was predictive of lower median glucose for days 2 and 3. Use of long‐acting subcutaneous insulin was not associated with significantly lower odds of hyperglycemic events for days 2 and 3, but was associated with higher odds of hypoglycemic events on day 2 (odds ratio [OR], 1.8; P = 0.01) when compared to short‐acting subcutaneous insulin alone.
Glucose Control Measure | Intravenous Insulin Infusion | Long‐Acting Subcutaneous Insulin |
---|---|---|
| ||
Median glucose | ||
Day 2, n = 1,297 | 32.0 (45.4 to 18.5); P < 0.001* | 5.1 (13.8 to 3.6); P = 0.25* |
Day 3, n = 1,251 | 33.0 (48.9 to 17); P < 0.001* | 3.4 (5.2 to 11.9); P = 0.44* |
Patient has 1 hyperglycemic event | ||
Day 2, n = 1,298 | 0.4 (0.20.6); P < 0.001 | 0.7 (0.51.1); P = 0.11 |
Day 3, n = 1,261 | 0.6 (0.31.1); P = 0.11 | 0.8 (0.61.1); P = 0.24 |
Patient has 1 hypoglycemic event | ||
Day 2, n = 1,298 | 2.1 (1.04.7); P = 0.07 | 1.8 (1.22.9); P = 0.010 |
Day 3, n = 1,261 | 4.0 (1.69.8); P = 0.003 | 1.4 (0.92.3); P = 0.13 |
We measured the performance of recommended hospital diabetes care practices (A1C assessment, documentation of diabetes history in the hospital record, admission laboratory glucose assessment, bedside glucose monitoring, recommended insulin therapy)14, 15 for all study patients, and also stratified performance by hospital (Table 5); 98.6% of all patients with a diagnosis of diabetes had physician documentation of their diabetes status recorded in the hospital record, and there was consistently high performance of this by hospital (Table 5); 77% of all patients with a history of diabetes had a laboratory blood glucose result recorded within 8 hours of hospital admission, and 81.3% of patients with a history of diabetes had blood glucose monitored at least 4 times on measurement day 2. Performance by hospital (Table 5) varied widely for glucose monitoring (range, 56.5%95.5% of patients by hospital) and admission laboratory glucose assessment (range, 39.0%97.1% of patients by hospital).
Diabetes Care Measure | Mean Hospital Performance (%) | Standard Deviation (%) | Range (%) |
---|---|---|---|
| |||
Physician documentation of diabetes history in medical record | 98.8 | 2.1 | 91.5100 |
A1C assessment documented for diabetes patients (measured during hospitalization or within 30 days prior to admission) | 33.7 | 15.4 | 3.162.9 |
Laboratory glucose assessment within 8 hours of hospital presentation for diabetes patients | 77.0 | 13.4 | 39.097.1 |
Blood glucose monitoring at least 4 times on second measurement day for diabetes patients | 81.6 | 10.8 | 56.595.5 |
Percentage of patients receiving insulin therapy who were given short and long‐acting insulin OR IV insulin infusion OR insulin pump therapy on second measurement day | 44.9 | 14.3 | 12.176.5 |
Of all patients, 31% had A1C measurement recorded during their hospitalization or within 30 days prior to admission. There was wide variation in hospital performance of A1C assessment in patients with diabetes (Table 5). Patients with a diagnosis of diabetes had a median A1C of 7.4% (IQR, 6.4%8.9%; n = 473), and those without a diagnosis of diabetes had a median A1C of 5.9% (IQR, 5.6%6.4%; n = 70). Of the patients with a history of diabetes who had A1C recorded, 59% had a value >7%. Of the patients without a history of diabetes who had A1C recorded, 43% had a value >6.0%, suggesting previously undiagnosed diabetes.25
We found wide variation among hospitals (range, 12.1%76.5%) in use of recommended regimens of insulin therapy, defined as short‐acting and long‐acting subcutaneous insulin or IV insulin infusion or insulin pump therapy on second measurement day. Endocrine/diabetes consultation was infrequent, only 9% of all patients were evaluated by an endocrinologist or diabetologist at any time during the hospitalization.
DISCUSSION
In this retrospective analysis of hospitalized patients who had 2 consecutive blood glucose values 180 mg/dL and/or received insulin therapy, hyperglycemia was common and hypoglycemia was infrequent. Use of intravenous insulin was associated with better glucose control, and did not increase the frequency of severe hypoglycemic events (glucose <50 mg/dL). The majority of patients with a history of diabetes had physician documentation in the hospital chart, laboratory serum glucose obtained within 8 hours of hospital admission, and at least 4 blood glucose determinations on the second measurement day.
Only 35% of patients with diabetes had an A1C measurement and of these almost 60% had an A1C level >7%. Though the A1C may not greatly affect acute glucose management in the hospital setting, it does identify patients that may require intensification of diabetes therapy at hospital discharge and coordination of outpatient follow‐up. A report of a UHC clinical benchmarking project of ambulatory diabetes care in academic medical centers demonstrated high rates of diagnostic testing, but only 34% of patients were at the A1C goal, and only 40% of patients above the A1C goal had adjustment of their diabetes regimen at their last clinic visit.26 In a retrospective study of patients with diabetes mellitus admitted to an academic teaching hospital, only 20% of discharges indicated a plan for diabetes follow‐up.27 Thus, intensification of antihyperglycemic therapy and formulation of a diabetes follow‐up plan on hospital discharge in those patients with A1C >7% represents an opportunity to improve glycemic control in the ambulatory setting. Also, measurement of A1C can be used for diabetes case‐finding in hospitalized patients with hyperglycemia.25 Previously unrecognized diabetes is a common finding in patients admitted with cardiovascular disease. In a study of patients admitted with myocardial infarction, 25% were found to have previously undiagnosed diabetes.28 Hospital patients with hyperglycemia but without a prior diagnosis of diabetes who have an elevation of A1C >6.0% can be identified as at‐risk for diabetes and postdischarge glucose evaluation can be arranged.
The target of maintaining all glucose values 180 mg/dL recommended in the 20052007 American Diabetes Association guidelines for hospital diabetes management was not commonly achieved, with over 70% of patients who received subcutaneous insulin therapy having 1 or more glucose values >180 on all 3 measurement days, regardless of patient location.15 The target of maintaining critically ill patients as close to 110 mg/dL as possible was also difficult to achieve, with only 25% of ICU patients having an estimated 6 AM glucose <110 mg/dL on measurement day 3. A prospective cohort study of 107 inpatients with diabetes at Brigham and Women's Hospital showed a 76% prevalence of patients with at least one BG >180 mg/dL.29 In that study, 90% of patients had a sliding‐scale order, 36% received an oral diabetes agent, and 43% received basal insulin at some time during hospitalization. A recently published analysis by Wexler et al.30 compiled data of hospitalized patients with diabetes from an earlier 2003 UHC Diabetes Benchmarking Project (n = 274) and patients from 15 not‐for‐profit member hospitals of VHA, Incorporated (n = 725) to examine the prevalence of hyperglycemia and hypoglycemia. Hyperglycemia (defined as a single BG value >200 mg/dL) was common, occurring in 77% of patients in the UHC cohort and 76% in the VHA, Inc. cohort. This was comparable to our findings that 76.7% of ICU patients and 78.6% of ward patients treated with subcutaneous insulin had 1 or more BG values 180 mg/dL on measurement day 2. Wexler et al.30 also determined that use of basal insulin was associated with a higher prevalence of hyperglycemia and hypoglycemia in their study. Our regression analysis finding that long‐acting (basal) insulin use was not associated with improvement in glycemic control is consistent with the findings of the aforementioned study. There are a number of potential explanations for this: (1) underdosing of basal insulin or lack of adequate prandial insulin coverage for nutritional intake; (2) lack of effective titration in response to hyperglycemia; and (3) variation in the ordering and administration of basal insulin at different hospital sites.
Use of both manual and computerized IV insulin protocols has been shown to provide effective glucose control in critically ill patients.1618 Though intravenous insulin use was associated with better overall glucose control in our study; only about 50% of ICU patients received it on measurement day 1. A recent prospective randomized clinical trial demonstrated superior glycemic control in noncritically ill hospitalized patients with type 2 diabetes with basal/bolus insulin therapy compared to sliding scale insulin alone.31 Use of basal/bolus insulin regimens as part of a comprehensive hospital diabetes management program has been shown to improve glycemic control in an academic medical center.20 Therefore, we do not believe that our regression analysis findings invalidate the concept of basal/bolus insulin for inpatients with hyperglycemia, but rather indicate the need for more research into subcutaneous insulin regimens and hospital care practices that lead to improved glucose control. We found wide variation in hospital use of basal/bolus insulin regimens. Overall only 22.5% of all patients on the second measurement day received both short‐acting and long‐acting subcutaneous insulin, compared to 30.8% who received short‐acting subcutaneous insulin only. A recent consensus statement on inpatient glycemic control by the American College of Endocrinology and American Diabetes Association highlighted the systematic barriers to improved glycemic control in hospitals, such as inadequate knowledge of diabetes management techniques, fear of hypoglycemia, and skepticism about benefits of tighter glucose control.32
There are some important limitations to this study. The data are retrospective and only a limited number of hospital days and clinical variables could be assessed for each patient. As indicated in Table 3, there were significant differences in the frequency of glucose measurement depending on treatment, which can potentially bias estimated prevalence of hyperglycemia and hypoglycemia. We did not have a practical method to assess nutritional status or the adequacy of insulin dosing over time for each patient. We also could not assess the association of glycemic control on clinical outcomes such as hospital mortality or infection rates. Since this study was exclusively in academic medical centers, the generalization of findings to community‐based medical centers may be limited. The risk‐benefit of tight glycemic control in medical ICU patients based on clinical trial evidence has been unclear, and there is not broad agreement among clinicians on the recommended target for glycemic control in this group.3335 When we analyzed glycemic control in ICU patients we did not have a practical method to control for type of ICU and variations in individual ICU glycemic control targets. We recognize that the 2004 American College of Endocrinology recommendation of maintaining glucose 110 mg/dL may not be appropriate for all critically ill patients.14 Finally, clinical trial data are lacking on the effect of tight glucose control on major clinical outcomes for noncritically ill hospital patients. This has led to significant controversy regarding glycemic targets for different subgroups of hospitalized patients.34, 36
In summary, we found a high prevalence of persistent hyperglycemia in this large cohort of hospitalized patients, and hypoglycemia was infrequent. Use of IV insulin was associated with improvement in glycemic control, but was used in less than half of ICU patients. There was wide variation in hospital performance of recommended diabetes care measures. Opportunities to improve care in academic medical centers include expanded use of intravenous and subcutaneous basal/bolus insulin protocols and increased frequency of A1C testing.
- Effects of admission hyperglycemia on mortality and costs in acute ischemic stroke.Neurology.2002;59:67–71. , , , et al.
- Hyperglycemia: an independent marker of in‐hospital mortality in patients with undiagnosed diabetes.J Clin Endocrinol Metab.2002;87:978–982. , , , , , .
- Unrecognized diabetes among hospitalized patients.Diabetes Care.1998;21:246–249. , , , , .
- Management of diabetes and hyperglycemia in hospitals.Diabetes Care.2004;27:553–591. , , , et al.
- Admission plasma glucose. Independent risk factor for long‐term prognosis after myocardial infarction even in nondiabetic patients.Diabetes Care.1999;22:1827–1831. , , .
- Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview.Stroke.2001;32:2426–2432. , , , , .
- Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview.Lancet.2000;355:773–778. , , , .
- The relation between hyperglycemia and outcomes in 2,471 patients admitted to the hospital with community‐acquired pneumonia.Diabetes Care.2005;28:810–815. , , , , , .
- Modifiable risk factors associated with deep sternal site infection after coronary artery bypass grafting.J Thorac Cardiovasc Surg.2000;119:108–114. , , , et al.
- The association of diabetes and glucose control with surgical‐site infections among cardiothoracic surgery patients.Infect Control Hosp Epidemiol.2001;22:607–612. , , , , .
- Intensive insulin therapy in the critically ill patients.N Engl J Med.2001;345:1359–1367. , , , et al.
- Tight glycemic control in diabetic coronary artery bypass graft patients improves perioperative outcomes and decreases recurrent ischemic events.Circulation.2004;109:1497–1502. , , , , , .
- Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland Diabetic Project.Endocr Pract.2004;10(Suppl 2):21–33. , , .
- American College of Endocrinology position statement on inpatient diabetes and metabolic control.Endocr Pract.2004;10(Suppl 2):4–9. , , , et al.
- American Diabetes Association.Standards of medical care in diabetes.Diabetes Care.2005;28(Suppl 1):S4–S36.
- Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit.Diabetes Care.2004;27:461–467. , , , et al.
- Use of a computerized guideline for glucose regulation in the intensive care unit improved both guideline adherence and glucose regulation.J Am Med Inform Assoc.2005;12:172–180. , , , , .
- Computer‐based insulin infusion protocol improves glycemia control over manual protocol.J Am Med Inform Assoc.2007;14:278–287. , , , et al.
- Management of diabetes mellitus in hospitalized patients: efficiency and effectiveness of sliding‐scale insulin therapy.Pharmacotherapy.2006;26:1421–1432. , , , , .
- Eliminating inpatient sliding‐scale insulin: a reeducation project with medical house staff.Diabetes Care.2005;28:1008–1011. , , , .
- 70/30 insulin algorithm versus sliding scale insulin.Ann Pharmacother.2005;39:1606–1610. , , .
- Glucose measurement: confounding issues in setting targets for inpatient management.Diabetes Care.2007;30:403–409. , , , .
- “Glucometrics”—assessing the quality of inpatient glucose management.Diabetes Technol Ther.2006;8:560–569. , , , et al.
- American Diabetes Association.Hospital admission guidelines for diabetes.Diabetes Care.2004;27(Suppl 1):S103.
- Utility of HbA(1c) levels for diabetes case finding in hospitalized patients with hyperglycemia.Diabetes Care.2003;26:1064–1068. , , , , , , .
- Quality of diabetes care in U.S. academic medical centers: low rates of medical regimen change.Diabetes Care.2005;28:337–442. , , .
- Diabetes care in the hospital: is there clinical inertia?J Hosp Med.2006;1:151–160. , , , et al.
- Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study.Lancet.2002;359:2140–2144. , , , et al.
- Inpatient management of diabetes and hyperglycemia among general medicine patients at a large teaching hospital.J Hosp Med.2006;1:145–150. , , , , .
- Prevalence of hyper‐ and hypoglycemia among inpatients with diabetes: a national survey of 44 U.S. hospitals.Diabetes Care.2007;30:367–369. , , , , .
- Randomized study of basal‐bolus insulin therapy in the inpatient management of patients with type 2 diabetes (RABBIT 2 trial).Diabetes Care.2007;30:2181–2186. , , , et al.
- The ACE/ADA Task Force on Inpatient Diabetes.American College of Endocrinology and American Diabetes Association Consensus Statement on Inpatient Diabetes and Glycemic Control: a call to action.Diabetes Care.2006;29:1955–1962.
- Intensive insulin therapy in the medical ICU.N Engl J Med.2006;354:449–461. , , , et al.
- Tight blood glucose control with insulin in the ICU: facts and controversies.Chest.2007;132:268–278. , , .
- Intensive insulin therapy and pentastarch resuscitation in severe sepsis.NEngl J Med.2008;358:125–139. , , , et al.
- Counterpoint: Inpatient glucose management: a premature call to arms?Diabetes Care.2005;28:976–979. , .
- Effects of admission hyperglycemia on mortality and costs in acute ischemic stroke.Neurology.2002;59:67–71. , , , et al.
- Hyperglycemia: an independent marker of in‐hospital mortality in patients with undiagnosed diabetes.J Clin Endocrinol Metab.2002;87:978–982. , , , , , .
- Unrecognized diabetes among hospitalized patients.Diabetes Care.1998;21:246–249. , , , , .
- Management of diabetes and hyperglycemia in hospitals.Diabetes Care.2004;27:553–591. , , , et al.
- Admission plasma glucose. Independent risk factor for long‐term prognosis after myocardial infarction even in nondiabetic patients.Diabetes Care.1999;22:1827–1831. , , .
- Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview.Stroke.2001;32:2426–2432. , , , , .
- Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview.Lancet.2000;355:773–778. , , , .
- The relation between hyperglycemia and outcomes in 2,471 patients admitted to the hospital with community‐acquired pneumonia.Diabetes Care.2005;28:810–815. , , , , , .
- Modifiable risk factors associated with deep sternal site infection after coronary artery bypass grafting.J Thorac Cardiovasc Surg.2000;119:108–114. , , , et al.
- The association of diabetes and glucose control with surgical‐site infections among cardiothoracic surgery patients.Infect Control Hosp Epidemiol.2001;22:607–612. , , , , .
- Intensive insulin therapy in the critically ill patients.N Engl J Med.2001;345:1359–1367. , , , et al.
- Tight glycemic control in diabetic coronary artery bypass graft patients improves perioperative outcomes and decreases recurrent ischemic events.Circulation.2004;109:1497–1502. , , , , , .
- Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland Diabetic Project.Endocr Pract.2004;10(Suppl 2):21–33. , , .
- American College of Endocrinology position statement on inpatient diabetes and metabolic control.Endocr Pract.2004;10(Suppl 2):4–9. , , , et al.
- American Diabetes Association.Standards of medical care in diabetes.Diabetes Care.2005;28(Suppl 1):S4–S36.
- Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit.Diabetes Care.2004;27:461–467. , , , et al.
- Use of a computerized guideline for glucose regulation in the intensive care unit improved both guideline adherence and glucose regulation.J Am Med Inform Assoc.2005;12:172–180. , , , , .
- Computer‐based insulin infusion protocol improves glycemia control over manual protocol.J Am Med Inform Assoc.2007;14:278–287. , , , et al.
- Management of diabetes mellitus in hospitalized patients: efficiency and effectiveness of sliding‐scale insulin therapy.Pharmacotherapy.2006;26:1421–1432. , , , , .
- Eliminating inpatient sliding‐scale insulin: a reeducation project with medical house staff.Diabetes Care.2005;28:1008–1011. , , , .
- 70/30 insulin algorithm versus sliding scale insulin.Ann Pharmacother.2005;39:1606–1610. , , .
- Glucose measurement: confounding issues in setting targets for inpatient management.Diabetes Care.2007;30:403–409. , , , .
- “Glucometrics”—assessing the quality of inpatient glucose management.Diabetes Technol Ther.2006;8:560–569. , , , et al.
- American Diabetes Association.Hospital admission guidelines for diabetes.Diabetes Care.2004;27(Suppl 1):S103.
- Utility of HbA(1c) levels for diabetes case finding in hospitalized patients with hyperglycemia.Diabetes Care.2003;26:1064–1068. , , , , , , .
- Quality of diabetes care in U.S. academic medical centers: low rates of medical regimen change.Diabetes Care.2005;28:337–442. , , .
- Diabetes care in the hospital: is there clinical inertia?J Hosp Med.2006;1:151–160. , , , et al.
- Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study.Lancet.2002;359:2140–2144. , , , et al.
- Inpatient management of diabetes and hyperglycemia among general medicine patients at a large teaching hospital.J Hosp Med.2006;1:145–150. , , , , .
- Prevalence of hyper‐ and hypoglycemia among inpatients with diabetes: a national survey of 44 U.S. hospitals.Diabetes Care.2007;30:367–369. , , , , .
- Randomized study of basal‐bolus insulin therapy in the inpatient management of patients with type 2 diabetes (RABBIT 2 trial).Diabetes Care.2007;30:2181–2186. , , , et al.
- The ACE/ADA Task Force on Inpatient Diabetes.American College of Endocrinology and American Diabetes Association Consensus Statement on Inpatient Diabetes and Glycemic Control: a call to action.Diabetes Care.2006;29:1955–1962.
- Intensive insulin therapy in the medical ICU.N Engl J Med.2006;354:449–461. , , , et al.
- Tight blood glucose control with insulin in the ICU: facts and controversies.Chest.2007;132:268–278. , , .
- Intensive insulin therapy and pentastarch resuscitation in severe sepsis.NEngl J Med.2008;358:125–139. , , , et al.
- Counterpoint: Inpatient glucose management: a premature call to arms?Diabetes Care.2005;28:976–979. , .
Copyright © 2009 Society of Hospital Medicine
Tight Glycemic Control / Michota and Braithwaite
Hyperglycemia is common in the hospital among patients with diabetes and those without. The exact overall prevalence of diabetes in the hospital is unknown; however, in 2000, 12.4% of U.S. hospital discharges listed diabetes as a diagnosis. Among cardiac surgery patients, the prevalence of diabetes is as high as 29%.2 Another study reported a 26% prevalence of diabetes in a community teaching hospital, with an additional 12% of patients having unrecognized diabetes or hospital‐related hyperglycemia.3 Levetan et al. found laboratory‐documented hyperglycemia in 13% of 1034 consecutively hospitalized patients.4 A subsequent chart review found that more than one‐third of patients with hyperglycemia identified by laboratory testing remained unrecognized as having diabetes documented in the discharge summary, although diabetes or hyperglycemia was noted in the progress notes. In a retrospective chart review study, Umpierrez et al. similarly found 38% of 1886 consecutively hospitalized patients who had glucose measurements on admission were hyperglycemic.3 One‐third of these patients were not previously known to have diabetes, and compared to patients with diagnosed diabetes, they were more likely to require admission to the intensive care unit, had longer hospital stays, and were less likely to be discharged straight home.
Until recently, most clinicians viewed tight glucose control in the hospitalized patient as an intervention with little immediate benefit and significant potential for harm. The goal was simply to prevent excessive hyperglycemia and avoid ketoacidosis or significant fluid derangements while minimizing the risk for hypoglycemia. Today, a growing body of evidence suggests a close correlation between tight glucose control and improved clinical outcomes. Among those who have had a myocardial infarction and those in the surgical intensive care unit, it is known that intensive glycemic control reduces mortality.5, 6 Maintaining normoglycemia in patients in the surgical intensive care unit through intravenous insulin infusion also reduces the incidence of comorbidities such as transfusion requirements, renal failure, sepsis, and neuropathy and reduces the duration of ventilator dependence.6 Although trials using glucose‐insulin‐potassium infusions (GIK), when conducted such that lowering of blood glucose occurred, have shown benefit in the settings of myocardial infarction5, 7 and cardiac surgery,8 not all studies of GIK therapy have yielded positive results. The negative results of the CREATE‐ECLA study suggest that GIK therapy per se is not beneficial unless it reduces blood glucose.9 An abundance of additional observational data and comparisons with historical control data suggest that favorable outcomes might be causally dependent on euglycemia. The outcomes studied include hospital or critical care unit mortality and nosocomial infection,1014 specifically outcomes of strokes,1522 trauma,2325 renal transplantation,2628 myocardial infarction,2936 endocarditis,37 acute lymphocytic leukemia,38 community‐acquired pneumonia,39 infectious complications in the hospital,4046 and cardiac surgery,9, 44, 45, 4751 as well as length of stay and costs.11, 25, 5156
It is important for each hospital to consider the methodology used for blood glucose measurement, realizing that measurements in the Leuven Belgium studies were performed on arterial whole blood using a blood gas analyzer. With recognition that the normal range for blood glucose is method dependent, the data presented above form the basis for the recommended glycemic targets for hospitalized patients:
Target range blood glucose (AACE et al., 2004)
-
Preprandial: < 110 mg/dL
-
Peak postprandial: < 180 mg/dL
-
Critically ill surgical patients: 80‐110 mg/dL Target range blood glucose (ADA, 2006)
-
Critically ill: Blood glucose as close to 110 mg/dL as possible and generally < 180 mg/dL. These patients generally will require IV insulin.
-
Noncritically ill: Premeal blood glucose as close to 90‐130 mg/dL as possible (midpoint 110 mg/dL). Postprandial blood glucose < 180 mg/dL.
This supplement, Avoiding Complications in the Hospitalized Patient: The Case for Tight Glycemic Control, reviews several aspects of hyperglycemia in the hospital setting. Evidence that supports more intensive glucose control is reviewed, along with a real‐world success story that demonstrates how to apply the new glycemic targets in a multidisciplinary performance improvement project. In addition, the standard insulin sliding scale is examined in terms of efficacy, safety, and potential for meeting the new recommended glycemic targets.
- Tierney E: Data from the national hospital discharge survey database 2000.Centers for Disease Control and Prevention, Division of Diabetes translation,Atlanta, GA,2003.
- Moghissi E: Hospital management of diabetes: beyond the sliding scale.Clev Clin J Med.2004;71:801–808.
- Hyperglycemia: an independent marker of in‐hospital mortality in patients with undiagnosed diabetes.J Clin Endocrinol Metab.2002;87:978–982. , , , , , .
- Ratner RE: Unrecognized diabetes among hospitalized patients.Diabetes Care.1998;21:246–249. , , , ,
- DIGAMI study group.Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus.BMJ.1997;314:1512–1515. , for the
- Intensive insulin therapy in critically ill patients.N Engl J Med.2001;345:1359–1367. , , , et al.
- Randomized trial of insulin‐glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year.J Am Coll Cardiol.1995;26:57–65. , , , et al.
- Tight glycemic control in diabetic coronary artery bypass graft patients improves perioperative outcomes and decreases recurrent ischemic events.Circulation.2004;109:1497–1502. , , , , , .
- CREATE‐ECLA Trial Group Investigators.Effect of glucose‐insulin‐potassium infusion on mortality in patients with acute st‐segment elevation myocardial infarction: the CREATE‐ECLA randomized controlled trial.JAMA.2005;293:437–446.
- Intensive insulin therapy in the medical ICU.N Engl J Med.2006;354:449–461. , , , et al.
- Reduction of nosocomial infections in the surgical intensive‐care unit by strict glycemic control.Endocr Pract.2004;10(suppl 2):46–52. , .
- Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting.J Thorac Cardiovasc Surg.2003;125:1007–1021. , , , et al.
- Mortalilty in hospitalized patients with hypoglycemia and severe hyperglycemia.Mt Sinai J Med.1995;62:422–426. , , , , , .
- Hyperglycemia: an independent marker of in‐hospital mortality in patients with undiagnosed diabetes.J Clin Endocrinol Metab.2002;87:978–982. , , , , , .
- Glucose control and mortality in critically ill patients.JAMA.2003;290:2041–2047. , , , .
- Effect of an intensive glucose management protocol on the mortality of critically ill adult patients.Mayo Clin Proc.2004:79:992–1000. .
- Insulin therapy for critically ill hospitalized patients: a meta‐analysis of randomized controlled trials.Arch Intern Med.2004;164:2005–2011. , , .
- Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome.Stroke.2003;34:2208–2214. , , , et al.
- Stress hyperglycemia and prognosis of stroke in nodiabetic and diabetic patients: a systematic overview.Stroke.2001;32:2426–2432. , , , , .
- Admission glucose level and clinical outcomes in the NINDS rt‐PA Stroke Trial.Neurology.2002;59:669–674. , , , et al.
- Effect of hyperglycemia on stroke outcomes.Endocr Pract.2004;10(suppl 2):34–39. .
- Predictors of hyperacute clinical worsening in ischemic stroke patients receiving thrombolytic therapy.Stroke.2004;35:1903–1907. , , , et al.
- Hyperglycemia in acute stroke.Stroke.2004;35:363–364. , .
- Decreased mortality by normalizing blood glucose after acute ischemic stroke.Acad Emerg Med.2006;13:174–180. , , , , .
- Blood glucose control after acute stroke: a retrospective study.Acad Emerg Med.2003;10:432. , , .
- Relationship of early hyperglycemia to mortality in trauma patients.J Trauma.2004;56:1058–1062. , , , , .
- Admission hyperglycemia is predictive of outcome in critically ill trauma patients.J Trauma.2005;59:80–83. , , , , , .
- Effects of admission hyperglycemia on mortality and costs in acute ischemic stroke.Neurology.2002;59(1):67–71. , , , et al.
- Early peri‐operative glycaemic control and allograft rejection in patients with diabetes mellitus: a pilot study.Transplantation.2001;72:1321–1324. , , , , .
- Early peri‐operative hyperglycaemia and renal allograft rejection in patients without diabetes.BMC Nephrol.2000;1:1. , , , , .
- Protective effect of insulin on ischemic renal injury in diabetes mellitus.Kidney Int.2002;61:1383–1392. , , , , .
- Impaired glucose metabolism predicts mortality after a myocardial infarction.Int J Cardiol.2001;79 (2–3):207–214. , , , , , .
- Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview.Lancet.2000;355:773–778. , , , .
- A single serum glucose measurement predicts adverse outcomes across the whole range of acute coronary syndromes.Heart.2003;89:512–516. , , , et al.
- Intensification of therapeutic approaches reduces mortality in diabetic patients with acute myocardial infarction: the Munich registry.Diabetes Care.2004;27:455–460. , , , , , .
- Admission blood glucose level as risk indicator of death after myocardial infarction in patients with and without diabetes mellitus.Arch Intern Med.2004;164:982–988. , , , et al.
- Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long‐term results from the diabetes and insulin‐glucose infusion in acute myocardial infarction (DIGAMI) study.Circulation.1999;99:2626–2632. , , , .
- Plasma glucose at hospital admission and previous metabolic control determine myocardial infarct size and survival in patients with and without type 2 diabetes: the Langendreer Myocardial Infarction and Blood Glucose in Diabetic Patients Assessment (LAMBDA).Diabetes Care.2005;28:2551–2553. , , , , , .
- Admission glucose and mortality in elderly patients hospitalized with acute myocardial infarction: implications for patients with and without recognized diabetes.Circulation.2005;111:3078–3086. , , , et al.
- Early predictors of in‐hospital death in infective endocarditis.Circulation.2004;109:1745–1749. , , , et al.
- Relation between the duration of remission and hyperglycemia in induction chemotherapy for acute lymphocytic leukemia.Cancer.2004;100:1179–1185. .
- Etiology and outcome of community‐acquired pneumonia in patients with diabetes mellitus.Chest.2005;128:3233–3239. , , , , .
- Perioperative glycemic control and the risk of infectious complications in a cohort of adults with diabetes.Diabetes Care.1999;22:1408–1414. , , , .
- Early postoperative glucose control predicts nosocomial infection rate in diabetic patients.J Parenter Enteral Nutr.1998;22(2):77–81. , , , et al.
- The association of diabetes and glucose control with surgical‐site infections among cardiothoracic surgery patients.Infect Control Hosp Epidemiol.2001;22:607–612. , , , , .
- Early post‐operative glucose levels are an independent risk factor for infection after peripheral vascular surgery. A retrospective study.Eur J Vasc Endovasc Surg.2004;5:520–525. , , , , .
- Glucose control lowers the risk of wound infection in diabetics after open heart operations.Ann Thorac Surg.1997;63:356–61. , , .
- Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures.Ann Thorac Surg.1999;67:352–362. , , , .
- Improving outcomes for diabetic patients undergoing vascular surgery.Diabetes Spectr.2005;18(1):53–60. , , , et al.
- Early postoperative outcome and medium‐term survival in 540 diabetic and 2239 nondiabetic patients undergoing coronary artery bypass grafting.Ann Thorac Surg.2002;74:712–719. , , .
- Diabetes and coronary artery bypass surgery: an examination of perioperative glycemic control and outcomes.Diabetes Care.2003;26:1518–1524. , , , , .
- Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland diabetic project.Endocr Pract.2004;10(suppl 2):21–33. , , .
- Glucose‐insulin‐potassium solutions improve outcomes in diabetics who have coronary artery operations.Ann Thorac Surg.2000;70:145–150. , , , , .
- Intraoperative hyperglycemia and perioperative outcomes in cardiac surgery patients.Mayo Clin Proc.2005;80:862–866. , , , et al.
- Postoperative hyperglycemia prolongs length of stay in diabetic CABG patients.Circulation. II2000;102(II):556 (abstract). , , , .
- Reduction of hospital costs and length of stay by good control of blood glucose levels.Endocr Pract.2004;10(suppl 2):53–56. .
Hyperglycemia is common in the hospital among patients with diabetes and those without. The exact overall prevalence of diabetes in the hospital is unknown; however, in 2000, 12.4% of U.S. hospital discharges listed diabetes as a diagnosis. Among cardiac surgery patients, the prevalence of diabetes is as high as 29%.2 Another study reported a 26% prevalence of diabetes in a community teaching hospital, with an additional 12% of patients having unrecognized diabetes or hospital‐related hyperglycemia.3 Levetan et al. found laboratory‐documented hyperglycemia in 13% of 1034 consecutively hospitalized patients.4 A subsequent chart review found that more than one‐third of patients with hyperglycemia identified by laboratory testing remained unrecognized as having diabetes documented in the discharge summary, although diabetes or hyperglycemia was noted in the progress notes. In a retrospective chart review study, Umpierrez et al. similarly found 38% of 1886 consecutively hospitalized patients who had glucose measurements on admission were hyperglycemic.3 One‐third of these patients were not previously known to have diabetes, and compared to patients with diagnosed diabetes, they were more likely to require admission to the intensive care unit, had longer hospital stays, and were less likely to be discharged straight home.
Until recently, most clinicians viewed tight glucose control in the hospitalized patient as an intervention with little immediate benefit and significant potential for harm. The goal was simply to prevent excessive hyperglycemia and avoid ketoacidosis or significant fluid derangements while minimizing the risk for hypoglycemia. Today, a growing body of evidence suggests a close correlation between tight glucose control and improved clinical outcomes. Among those who have had a myocardial infarction and those in the surgical intensive care unit, it is known that intensive glycemic control reduces mortality.5, 6 Maintaining normoglycemia in patients in the surgical intensive care unit through intravenous insulin infusion also reduces the incidence of comorbidities such as transfusion requirements, renal failure, sepsis, and neuropathy and reduces the duration of ventilator dependence.6 Although trials using glucose‐insulin‐potassium infusions (GIK), when conducted such that lowering of blood glucose occurred, have shown benefit in the settings of myocardial infarction5, 7 and cardiac surgery,8 not all studies of GIK therapy have yielded positive results. The negative results of the CREATE‐ECLA study suggest that GIK therapy per se is not beneficial unless it reduces blood glucose.9 An abundance of additional observational data and comparisons with historical control data suggest that favorable outcomes might be causally dependent on euglycemia. The outcomes studied include hospital or critical care unit mortality and nosocomial infection,1014 specifically outcomes of strokes,1522 trauma,2325 renal transplantation,2628 myocardial infarction,2936 endocarditis,37 acute lymphocytic leukemia,38 community‐acquired pneumonia,39 infectious complications in the hospital,4046 and cardiac surgery,9, 44, 45, 4751 as well as length of stay and costs.11, 25, 5156
It is important for each hospital to consider the methodology used for blood glucose measurement, realizing that measurements in the Leuven Belgium studies were performed on arterial whole blood using a blood gas analyzer. With recognition that the normal range for blood glucose is method dependent, the data presented above form the basis for the recommended glycemic targets for hospitalized patients:
Target range blood glucose (AACE et al., 2004)
-
Preprandial: < 110 mg/dL
-
Peak postprandial: < 180 mg/dL
-
Critically ill surgical patients: 80‐110 mg/dL Target range blood glucose (ADA, 2006)
-
Critically ill: Blood glucose as close to 110 mg/dL as possible and generally < 180 mg/dL. These patients generally will require IV insulin.
-
Noncritically ill: Premeal blood glucose as close to 90‐130 mg/dL as possible (midpoint 110 mg/dL). Postprandial blood glucose < 180 mg/dL.
This supplement, Avoiding Complications in the Hospitalized Patient: The Case for Tight Glycemic Control, reviews several aspects of hyperglycemia in the hospital setting. Evidence that supports more intensive glucose control is reviewed, along with a real‐world success story that demonstrates how to apply the new glycemic targets in a multidisciplinary performance improvement project. In addition, the standard insulin sliding scale is examined in terms of efficacy, safety, and potential for meeting the new recommended glycemic targets.
Hyperglycemia is common in the hospital among patients with diabetes and those without. The exact overall prevalence of diabetes in the hospital is unknown; however, in 2000, 12.4% of U.S. hospital discharges listed diabetes as a diagnosis. Among cardiac surgery patients, the prevalence of diabetes is as high as 29%.2 Another study reported a 26% prevalence of diabetes in a community teaching hospital, with an additional 12% of patients having unrecognized diabetes or hospital‐related hyperglycemia.3 Levetan et al. found laboratory‐documented hyperglycemia in 13% of 1034 consecutively hospitalized patients.4 A subsequent chart review found that more than one‐third of patients with hyperglycemia identified by laboratory testing remained unrecognized as having diabetes documented in the discharge summary, although diabetes or hyperglycemia was noted in the progress notes. In a retrospective chart review study, Umpierrez et al. similarly found 38% of 1886 consecutively hospitalized patients who had glucose measurements on admission were hyperglycemic.3 One‐third of these patients were not previously known to have diabetes, and compared to patients with diagnosed diabetes, they were more likely to require admission to the intensive care unit, had longer hospital stays, and were less likely to be discharged straight home.
Until recently, most clinicians viewed tight glucose control in the hospitalized patient as an intervention with little immediate benefit and significant potential for harm. The goal was simply to prevent excessive hyperglycemia and avoid ketoacidosis or significant fluid derangements while minimizing the risk for hypoglycemia. Today, a growing body of evidence suggests a close correlation between tight glucose control and improved clinical outcomes. Among those who have had a myocardial infarction and those in the surgical intensive care unit, it is known that intensive glycemic control reduces mortality.5, 6 Maintaining normoglycemia in patients in the surgical intensive care unit through intravenous insulin infusion also reduces the incidence of comorbidities such as transfusion requirements, renal failure, sepsis, and neuropathy and reduces the duration of ventilator dependence.6 Although trials using glucose‐insulin‐potassium infusions (GIK), when conducted such that lowering of blood glucose occurred, have shown benefit in the settings of myocardial infarction5, 7 and cardiac surgery,8 not all studies of GIK therapy have yielded positive results. The negative results of the CREATE‐ECLA study suggest that GIK therapy per se is not beneficial unless it reduces blood glucose.9 An abundance of additional observational data and comparisons with historical control data suggest that favorable outcomes might be causally dependent on euglycemia. The outcomes studied include hospital or critical care unit mortality and nosocomial infection,1014 specifically outcomes of strokes,1522 trauma,2325 renal transplantation,2628 myocardial infarction,2936 endocarditis,37 acute lymphocytic leukemia,38 community‐acquired pneumonia,39 infectious complications in the hospital,4046 and cardiac surgery,9, 44, 45, 4751 as well as length of stay and costs.11, 25, 5156
It is important for each hospital to consider the methodology used for blood glucose measurement, realizing that measurements in the Leuven Belgium studies were performed on arterial whole blood using a blood gas analyzer. With recognition that the normal range for blood glucose is method dependent, the data presented above form the basis for the recommended glycemic targets for hospitalized patients:
Target range blood glucose (AACE et al., 2004)
-
Preprandial: < 110 mg/dL
-
Peak postprandial: < 180 mg/dL
-
Critically ill surgical patients: 80‐110 mg/dL Target range blood glucose (ADA, 2006)
-
Critically ill: Blood glucose as close to 110 mg/dL as possible and generally < 180 mg/dL. These patients generally will require IV insulin.
-
Noncritically ill: Premeal blood glucose as close to 90‐130 mg/dL as possible (midpoint 110 mg/dL). Postprandial blood glucose < 180 mg/dL.
This supplement, Avoiding Complications in the Hospitalized Patient: The Case for Tight Glycemic Control, reviews several aspects of hyperglycemia in the hospital setting. Evidence that supports more intensive glucose control is reviewed, along with a real‐world success story that demonstrates how to apply the new glycemic targets in a multidisciplinary performance improvement project. In addition, the standard insulin sliding scale is examined in terms of efficacy, safety, and potential for meeting the new recommended glycemic targets.
- Tierney E: Data from the national hospital discharge survey database 2000.Centers for Disease Control and Prevention, Division of Diabetes translation,Atlanta, GA,2003.
- Moghissi E: Hospital management of diabetes: beyond the sliding scale.Clev Clin J Med.2004;71:801–808.
- Hyperglycemia: an independent marker of in‐hospital mortality in patients with undiagnosed diabetes.J Clin Endocrinol Metab.2002;87:978–982. , , , , , .
- Ratner RE: Unrecognized diabetes among hospitalized patients.Diabetes Care.1998;21:246–249. , , , ,
- DIGAMI study group.Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus.BMJ.1997;314:1512–1515. , for the
- Intensive insulin therapy in critically ill patients.N Engl J Med.2001;345:1359–1367. , , , et al.
- Randomized trial of insulin‐glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year.J Am Coll Cardiol.1995;26:57–65. , , , et al.
- Tight glycemic control in diabetic coronary artery bypass graft patients improves perioperative outcomes and decreases recurrent ischemic events.Circulation.2004;109:1497–1502. , , , , , .
- CREATE‐ECLA Trial Group Investigators.Effect of glucose‐insulin‐potassium infusion on mortality in patients with acute st‐segment elevation myocardial infarction: the CREATE‐ECLA randomized controlled trial.JAMA.2005;293:437–446.
- Intensive insulin therapy in the medical ICU.N Engl J Med.2006;354:449–461. , , , et al.
- Reduction of nosocomial infections in the surgical intensive‐care unit by strict glycemic control.Endocr Pract.2004;10(suppl 2):46–52. , .
- Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting.J Thorac Cardiovasc Surg.2003;125:1007–1021. , , , et al.
- Mortalilty in hospitalized patients with hypoglycemia and severe hyperglycemia.Mt Sinai J Med.1995;62:422–426. , , , , , .
- Hyperglycemia: an independent marker of in‐hospital mortality in patients with undiagnosed diabetes.J Clin Endocrinol Metab.2002;87:978–982. , , , , , .
- Glucose control and mortality in critically ill patients.JAMA.2003;290:2041–2047. , , , .
- Effect of an intensive glucose management protocol on the mortality of critically ill adult patients.Mayo Clin Proc.2004:79:992–1000. .
- Insulin therapy for critically ill hospitalized patients: a meta‐analysis of randomized controlled trials.Arch Intern Med.2004;164:2005–2011. , , .
- Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome.Stroke.2003;34:2208–2214. , , , et al.
- Stress hyperglycemia and prognosis of stroke in nodiabetic and diabetic patients: a systematic overview.Stroke.2001;32:2426–2432. , , , , .
- Admission glucose level and clinical outcomes in the NINDS rt‐PA Stroke Trial.Neurology.2002;59:669–674. , , , et al.
- Effect of hyperglycemia on stroke outcomes.Endocr Pract.2004;10(suppl 2):34–39. .
- Predictors of hyperacute clinical worsening in ischemic stroke patients receiving thrombolytic therapy.Stroke.2004;35:1903–1907. , , , et al.
- Hyperglycemia in acute stroke.Stroke.2004;35:363–364. , .
- Decreased mortality by normalizing blood glucose after acute ischemic stroke.Acad Emerg Med.2006;13:174–180. , , , , .
- Blood glucose control after acute stroke: a retrospective study.Acad Emerg Med.2003;10:432. , , .
- Relationship of early hyperglycemia to mortality in trauma patients.J Trauma.2004;56:1058–1062. , , , , .
- Admission hyperglycemia is predictive of outcome in critically ill trauma patients.J Trauma.2005;59:80–83. , , , , , .
- Effects of admission hyperglycemia on mortality and costs in acute ischemic stroke.Neurology.2002;59(1):67–71. , , , et al.
- Early peri‐operative glycaemic control and allograft rejection in patients with diabetes mellitus: a pilot study.Transplantation.2001;72:1321–1324. , , , , .
- Early peri‐operative hyperglycaemia and renal allograft rejection in patients without diabetes.BMC Nephrol.2000;1:1. , , , , .
- Protective effect of insulin on ischemic renal injury in diabetes mellitus.Kidney Int.2002;61:1383–1392. , , , , .
- Impaired glucose metabolism predicts mortality after a myocardial infarction.Int J Cardiol.2001;79 (2–3):207–214. , , , , , .
- Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview.Lancet.2000;355:773–778. , , , .
- A single serum glucose measurement predicts adverse outcomes across the whole range of acute coronary syndromes.Heart.2003;89:512–516. , , , et al.
- Intensification of therapeutic approaches reduces mortality in diabetic patients with acute myocardial infarction: the Munich registry.Diabetes Care.2004;27:455–460. , , , , , .
- Admission blood glucose level as risk indicator of death after myocardial infarction in patients with and without diabetes mellitus.Arch Intern Med.2004;164:982–988. , , , et al.
- Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long‐term results from the diabetes and insulin‐glucose infusion in acute myocardial infarction (DIGAMI) study.Circulation.1999;99:2626–2632. , , , .
- Plasma glucose at hospital admission and previous metabolic control determine myocardial infarct size and survival in patients with and without type 2 diabetes: the Langendreer Myocardial Infarction and Blood Glucose in Diabetic Patients Assessment (LAMBDA).Diabetes Care.2005;28:2551–2553. , , , , , .
- Admission glucose and mortality in elderly patients hospitalized with acute myocardial infarction: implications for patients with and without recognized diabetes.Circulation.2005;111:3078–3086. , , , et al.
- Early predictors of in‐hospital death in infective endocarditis.Circulation.2004;109:1745–1749. , , , et al.
- Relation between the duration of remission and hyperglycemia in induction chemotherapy for acute lymphocytic leukemia.Cancer.2004;100:1179–1185. .
- Etiology and outcome of community‐acquired pneumonia in patients with diabetes mellitus.Chest.2005;128:3233–3239. , , , , .
- Perioperative glycemic control and the risk of infectious complications in a cohort of adults with diabetes.Diabetes Care.1999;22:1408–1414. , , , .
- Early postoperative glucose control predicts nosocomial infection rate in diabetic patients.J Parenter Enteral Nutr.1998;22(2):77–81. , , , et al.
- The association of diabetes and glucose control with surgical‐site infections among cardiothoracic surgery patients.Infect Control Hosp Epidemiol.2001;22:607–612. , , , , .
- Early post‐operative glucose levels are an independent risk factor for infection after peripheral vascular surgery. A retrospective study.Eur J Vasc Endovasc Surg.2004;5:520–525. , , , , .
- Glucose control lowers the risk of wound infection in diabetics after open heart operations.Ann Thorac Surg.1997;63:356–61. , , .
- Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures.Ann Thorac Surg.1999;67:352–362. , , , .
- Improving outcomes for diabetic patients undergoing vascular surgery.Diabetes Spectr.2005;18(1):53–60. , , , et al.
- Early postoperative outcome and medium‐term survival in 540 diabetic and 2239 nondiabetic patients undergoing coronary artery bypass grafting.Ann Thorac Surg.2002;74:712–719. , , .
- Diabetes and coronary artery bypass surgery: an examination of perioperative glycemic control and outcomes.Diabetes Care.2003;26:1518–1524. , , , , .
- Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland diabetic project.Endocr Pract.2004;10(suppl 2):21–33. , , .
- Glucose‐insulin‐potassium solutions improve outcomes in diabetics who have coronary artery operations.Ann Thorac Surg.2000;70:145–150. , , , , .
- Intraoperative hyperglycemia and perioperative outcomes in cardiac surgery patients.Mayo Clin Proc.2005;80:862–866. , , , et al.
- Postoperative hyperglycemia prolongs length of stay in diabetic CABG patients.Circulation. II2000;102(II):556 (abstract). , , , .
- Reduction of hospital costs and length of stay by good control of blood glucose levels.Endocr Pract.2004;10(suppl 2):53–56. .
- Tierney E: Data from the national hospital discharge survey database 2000.Centers for Disease Control and Prevention, Division of Diabetes translation,Atlanta, GA,2003.
- Moghissi E: Hospital management of diabetes: beyond the sliding scale.Clev Clin J Med.2004;71:801–808.
- Hyperglycemia: an independent marker of in‐hospital mortality in patients with undiagnosed diabetes.J Clin Endocrinol Metab.2002;87:978–982. , , , , , .
- Ratner RE: Unrecognized diabetes among hospitalized patients.Diabetes Care.1998;21:246–249. , , , ,
- DIGAMI study group.Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus.BMJ.1997;314:1512–1515. , for the
- Intensive insulin therapy in critically ill patients.N Engl J Med.2001;345:1359–1367. , , , et al.
- Randomized trial of insulin‐glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year.J Am Coll Cardiol.1995;26:57–65. , , , et al.
- Tight glycemic control in diabetic coronary artery bypass graft patients improves perioperative outcomes and decreases recurrent ischemic events.Circulation.2004;109:1497–1502. , , , , , .
- CREATE‐ECLA Trial Group Investigators.Effect of glucose‐insulin‐potassium infusion on mortality in patients with acute st‐segment elevation myocardial infarction: the CREATE‐ECLA randomized controlled trial.JAMA.2005;293:437–446.
- Intensive insulin therapy in the medical ICU.N Engl J Med.2006;354:449–461. , , , et al.
- Reduction of nosocomial infections in the surgical intensive‐care unit by strict glycemic control.Endocr Pract.2004;10(suppl 2):46–52. , .
- Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting.J Thorac Cardiovasc Surg.2003;125:1007–1021. , , , et al.
- Mortalilty in hospitalized patients with hypoglycemia and severe hyperglycemia.Mt Sinai J Med.1995;62:422–426. , , , , , .
- Hyperglycemia: an independent marker of in‐hospital mortality in patients with undiagnosed diabetes.J Clin Endocrinol Metab.2002;87:978–982. , , , , , .
- Glucose control and mortality in critically ill patients.JAMA.2003;290:2041–2047. , , , .
- Effect of an intensive glucose management protocol on the mortality of critically ill adult patients.Mayo Clin Proc.2004:79:992–1000. .
- Insulin therapy for critically ill hospitalized patients: a meta‐analysis of randomized controlled trials.Arch Intern Med.2004;164:2005–2011. , , .
- Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome.Stroke.2003;34:2208–2214. , , , et al.
- Stress hyperglycemia and prognosis of stroke in nodiabetic and diabetic patients: a systematic overview.Stroke.2001;32:2426–2432. , , , , .
- Admission glucose level and clinical outcomes in the NINDS rt‐PA Stroke Trial.Neurology.2002;59:669–674. , , , et al.
- Effect of hyperglycemia on stroke outcomes.Endocr Pract.2004;10(suppl 2):34–39. .
- Predictors of hyperacute clinical worsening in ischemic stroke patients receiving thrombolytic therapy.Stroke.2004;35:1903–1907. , , , et al.
- Hyperglycemia in acute stroke.Stroke.2004;35:363–364. , .
- Decreased mortality by normalizing blood glucose after acute ischemic stroke.Acad Emerg Med.2006;13:174–180. , , , , .
- Blood glucose control after acute stroke: a retrospective study.Acad Emerg Med.2003;10:432. , , .
- Relationship of early hyperglycemia to mortality in trauma patients.J Trauma.2004;56:1058–1062. , , , , .
- Admission hyperglycemia is predictive of outcome in critically ill trauma patients.J Trauma.2005;59:80–83. , , , , , .
- Effects of admission hyperglycemia on mortality and costs in acute ischemic stroke.Neurology.2002;59(1):67–71. , , , et al.
- Early peri‐operative glycaemic control and allograft rejection in patients with diabetes mellitus: a pilot study.Transplantation.2001;72:1321–1324. , , , , .
- Early peri‐operative hyperglycaemia and renal allograft rejection in patients without diabetes.BMC Nephrol.2000;1:1. , , , , .
- Protective effect of insulin on ischemic renal injury in diabetes mellitus.Kidney Int.2002;61:1383–1392. , , , , .
- Impaired glucose metabolism predicts mortality after a myocardial infarction.Int J Cardiol.2001;79 (2–3):207–214. , , , , , .
- Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview.Lancet.2000;355:773–778. , , , .
- A single serum glucose measurement predicts adverse outcomes across the whole range of acute coronary syndromes.Heart.2003;89:512–516. , , , et al.
- Intensification of therapeutic approaches reduces mortality in diabetic patients with acute myocardial infarction: the Munich registry.Diabetes Care.2004;27:455–460. , , , , , .
- Admission blood glucose level as risk indicator of death after myocardial infarction in patients with and without diabetes mellitus.Arch Intern Med.2004;164:982–988. , , , et al.
- Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long‐term results from the diabetes and insulin‐glucose infusion in acute myocardial infarction (DIGAMI) study.Circulation.1999;99:2626–2632. , , , .
- Plasma glucose at hospital admission and previous metabolic control determine myocardial infarct size and survival in patients with and without type 2 diabetes: the Langendreer Myocardial Infarction and Blood Glucose in Diabetic Patients Assessment (LAMBDA).Diabetes Care.2005;28:2551–2553. , , , , , .
- Admission glucose and mortality in elderly patients hospitalized with acute myocardial infarction: implications for patients with and without recognized diabetes.Circulation.2005;111:3078–3086. , , , et al.
- Early predictors of in‐hospital death in infective endocarditis.Circulation.2004;109:1745–1749. , , , et al.
- Relation between the duration of remission and hyperglycemia in induction chemotherapy for acute lymphocytic leukemia.Cancer.2004;100:1179–1185. .
- Etiology and outcome of community‐acquired pneumonia in patients with diabetes mellitus.Chest.2005;128:3233–3239. , , , , .
- Perioperative glycemic control and the risk of infectious complications in a cohort of adults with diabetes.Diabetes Care.1999;22:1408–1414. , , , .
- Early postoperative glucose control predicts nosocomial infection rate in diabetic patients.J Parenter Enteral Nutr.1998;22(2):77–81. , , , et al.
- The association of diabetes and glucose control with surgical‐site infections among cardiothoracic surgery patients.Infect Control Hosp Epidemiol.2001;22:607–612. , , , , .
- Early post‐operative glucose levels are an independent risk factor for infection after peripheral vascular surgery. A retrospective study.Eur J Vasc Endovasc Surg.2004;5:520–525. , , , , .
- Glucose control lowers the risk of wound infection in diabetics after open heart operations.Ann Thorac Surg.1997;63:356–61. , , .
- Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures.Ann Thorac Surg.1999;67:352–362. , , , .
- Improving outcomes for diabetic patients undergoing vascular surgery.Diabetes Spectr.2005;18(1):53–60. , , , et al.
- Early postoperative outcome and medium‐term survival in 540 diabetic and 2239 nondiabetic patients undergoing coronary artery bypass grafting.Ann Thorac Surg.2002;74:712–719. , , .
- Diabetes and coronary artery bypass surgery: an examination of perioperative glycemic control and outcomes.Diabetes Care.2003;26:1518–1524. , , , , .
- Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland diabetic project.Endocr Pract.2004;10(suppl 2):21–33. , , .
- Glucose‐insulin‐potassium solutions improve outcomes in diabetics who have coronary artery operations.Ann Thorac Surg.2000;70:145–150. , , , , .
- Intraoperative hyperglycemia and perioperative outcomes in cardiac surgery patients.Mayo Clin Proc.2005;80:862–866. , , , et al.
- Postoperative hyperglycemia prolongs length of stay in diabetic CABG patients.Circulation. II2000;102(II):556 (abstract). , , , .
- Reduction of hospital costs and length of stay by good control of blood glucose levels.Endocr Pract.2004;10(suppl 2):53–56. .
Twilight of the Sliding Scale
An explosion of interest in managing hyperglycemia in the hospital has resulted from recent evidence that glycemic control can reduce mortality and other morbidities. Programs of intensification using historical controls for comparison and clinical trials demonstrating the ability of glycemic control to improve outcomes have mandated specific blood glucose thresholds for initiating intensive therapy in the ICU.1-12 These studies have convinced the world that in the ICU intravenous insulin infusion should supplant sliding scale.
A large body of observational data point to the likelihood that the benefits of glycemic control might extend to the general hospital ward.13,14 Although intravenous infusion of insulin might be more widely used in the future than it is now, the standard practice at most hospitals is to address glycemic control on general wards through the use of subcutaneous insulin.15,16
Two recent publications from Rush University Medical Center in Chicago and from St. Joseph’s/Candler Health System in Savannah, Ga., added weight to older literature and to a large body of long-held expert opinion that the anticipatory use of subcutaneous insulin in the hospital outperforms sliding scale.
Sliding Scale and Its Flaws
Throughout a half century of PubMed indexing, the medical literature has referred to sliding scale insulin.17 In its simplest form at a given blood glucose level, sliding scale delivers the same number of units of subcutaneous regular insulin to every patient. For example, it might require:
150-199 + 2
200-249 + 4
250-299 + 6
300-349 + 8
350-399 +10
400 and up Call physician
Protocols attempting to improve upon the scale offer differing amounts of insulin at several assumed degrees of insulin sensitivity.18,19 However, these protocols still retain a reactive approach to glycemic management such that hyperglycemia will recur given the absence of adequate basal and nutritional insulin coverage. Under sliding scale the risk of ketoacidosis in type-1 diabetes is not addressed. Overcompensation for hyperglycemia results in hypoglycemia for some patients. By writing sliding scale orders physicians may create the appearance of having designed a detailed and attentive care plan, while in reality they neglect to individualize care to meet the patient’s needs.20
Discussions about sliding scale and correction dose insulin are frequently misinterpreted because of differences in use of terminology. Practitioners who disagree with use of sliding scale monotherapy nevertheless recommend using correction doses or supplements of insulin for patients already receiving anticipatory insulin.21 Some practitioners may refer to correction doses used in addition to anticipatory insulin as sliding scale insulin.22,23 Patients themselves sometimes use the term sliding scale.
A patient may, for example, use glargine and aspart and, when asked how she determines the dose of aspart, she may say she uses “sliding scale.” What she means, though, may be one of several possible management styles. She may mean that she uses aspart only for correction of hyperglycemia. She may mean that she has a table with two columns, showing paired blood glucose ranges and premeal aspart doses, such that the prandial and correction components of the aspart doses are bundled. She may mean that she practices advanced carbohydrate counting, utilizes an insulin-to-carbohydrate ratio to determine aspart coverage for the meal, and additionally calculates a premeal correction dose of aspart for hyperglycemia (i.e., she may practice basal-prandial-correction therapy).24-26
For purposes of this discussion, by “sliding scale” insulin, I mean monotherapy with sliding scale without concomitant anticipatory use of insulin (scheduled, routine, standing, or programmed insulin) or sliding scale with its faults, as described by Saul Genuth, MD.27
Evidence Against Sliding Scale
Relying on sliding scale insulin sometimes causes hypoglycemic events, severe hyperglycemic events, patient relapse after treatment of ketoacidosis, and the in-house development of diabetic ketoacidosis. In the study by Kathleen and colleagues, using sliding scale doses too high for patients with renal insufficiency was identified as the cause of six episodes of hypoglycemia.28
In the quality improvement project by Roman and colleagues, the use of quality indicators of a) BG < 40 mg/dL, b) BG > 450 mg/dL on two occasions, or c) BG > 45 with acetone, revealed that five cases were caused by physician failure to respond appropriately to hyperglycemia, despite administration of large amounts of additional regular insulin as coverage for capillary blood glucose (one of which resulted in the in-house development of ketoacidosis).29
In a retrospective review of management following ketoacidosis Gearhart and colleagues showed a higher median glucose among the patients treated with sliding scale than those treated proactively with insulin (prospective or anticipatory insulin), or treated with a combination of proactive insulin and “sliding scale” (correction dose insulin).30 Queale and colleagues showed that the use of either a standing dose of insulin or an oral hypoglycemic agent was associated with a reduced risk of hyperglycemic episodes, whereas sliding scale insulin regimens (when used without a standing dose of intermediate-acting insulin) were associated with an increased rate of hyperglycemic episodes.31
Baldwin and colleagues at Rush University Medical Center in Chicago recently reported the superiority of glycemic control among 88 patients for whom sliding scale was not allowed, in comparison with 98 well-matched controls from a historical comparison period.32 In the study group, standing orders for insulin were not permitted. House staff reviewed the results of glucose monitoring performed four times daily, and they twice daily reordered anticipatory insulin if appropriate. Glargine and rapid-acting analog were continued only for those patients already using such therapy prior to admission. Premixed insulins were not used. Oral agents were not used in combination with insulin and sometimes were discontinued for medical reasons.
In the control group, the percentages of patients with specific orders were: 100% sliding scale as defined by the authors, 32% twice-daily dosing with NPH/regular insulin, 37% orals agents, and 15% combination oral agents with NPH/regular insulin. In the study group, the percentages were: 0% sliding scale, 68% twice-daily NPH/regular insulin, 30% orals, and 0% combination NPH/regular with oral agents. For the study patients versus the historical controls, the mean blood glucose was 150 ± 37 mg/dL mg/dL versus 200 ± 51 mg/dL (p<0.01). The frequency of hypoglycemia between the two groups did not differ.
Schoeffler and colleagues in the St. Joseph’s/Candler Health System in Savannah, Ga., recently conducted a randomized study of 20 patients that reported the use of a 70/30 dose titration algorithm is superior to sliding scale insulin in achieving glycemic control.33 Patients were identified for possible enrollment through discovery of orders for sliding scale insulin in the pharmacy. After exclusion of patients receiving tube feeds or TPN and patients having type-1 diabetes, those consenting to be randomized either received the sliding scale as written by their physician or titration of 70/30 insulin given twice daily under algorithm. Hypoglycemia did not occur in either group. Downward trend over time and lower mean blood glucose (151.3 versus 175.6 mg/dL, p = 0.042) were observed in the 70/30 insulin group.
Anticipatory Use of Insulin in the Hospital
The components of anticipatory subcutaneous insulin order-writing have been described according to preference of several authors (having basal, nutritional, and correction components). But in the hospital no style has been validated as superior to any other.34-37 The anticipatory delivery of nutritional insulin must match the expected pattern of exposure to carbohydrate. Specific standing orders should include additional nursing directions such as “do not withhold” or “hold if NPO.” For abrupt discontinuation of carbohydrate exposure, change of organ function, or decline of insulin resistance, protections must be in place to guard against hypoglycemia.38
An essential aspect of management is the frequent review of orders for subcutaneous insulin and patient response. At least once every day, the caregiver must reconsider “today’s insulin dose.”
How to Get Rid of Sliding Scale
Computerized order entry for managing hyperglycemia now is widespread among hospitals. Under a misdirected allocation of resources, motivated by concern for quality and safety, institutions have embraced the programming of order-entry options for standardized sliding scales. The sliding scale menu may provide a quick link to order entry for point-of-care blood capillary glucose monitoring, call parameters, and treatment of hypoglycemia. Nurses and doctors may come to believe that it is impossible even to order blood glucose monitoring without an accompanying sliding scale. Thus the sliding scale menu may possess all the accoutrements of glycemic management program except the one element most needed—a provision for anticipatory insulin.
One study by Achtmeyer and colleagues reduced utilization of a computerized sliding scale order by attaching a warning that the order was not approved by endocrinology.39 Emphasizing the importance of physician education to the successful abolition of sliding scale insulin, the study by Baldwin details an intensive house staff re-education program on how to write anticipatory insulin orders.32 The computerized order entry options used at Rush University Medical Center in Chicago (one of the two better performers in the recent benchmarking study of the University HealthSystem Consortium) were presented by Baldwin at the Aug. 19, 2005, “Glycemic Control Knowledge Transfer Meeting of the Consortium in Chicago.”
Why has use of the sliding scale persisted in practice? Is it for fear of hypoglycemia? Is it for lack of evidence on the importance of glycemic control? Even before computerization was sliding scale the path of least resistance? Is it because no clear superiority has been demonstrated among various styles of writing anticipatory insulin plans? Is it because physicians do not know how to write insulin orders? Or is it all in a name?
It just might seem that ordering sliding scale is the easy thing to call for or is the sophisticated thing to order. After all, sliding scale is an in-group term. A newly graduated physician is not likely to reject the suggestion of an experienced nurse that an order is needed for sliding scale.
For the next 50 years what is the call for, and what are the orders? Quite simply we have seen the twilight of the sliding scale—and “today’s insulin” dawning. TH
Dr. Braithwaite is clinical professor of medicine at the University of North Carolina, Diabetes Care Center, Durham.
References
- Zerr KJ, Furnary AP, Grunkemeier GL. Glucose control lowers the risk of wound infection in diabetics after open heart operations. Ann Thorac Surg. 1997;63:356-361.
- 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. Ann Thorac Surg. 1999;67:352-362.
- Furnary AP, Wu Y, Bookin SO. Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland diabetic project. Endocr Pract. 2004;10 (Suppl. 2):21-33.
- Furnary AP, Gao G, Grunkemeier GL, et al. Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2003;125(5):1007-1021.
- Malmberg K, Rydén L, Efendic S, et al. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol. 1995;26:57-65.
- Malmberg K, Norhammar A, Wedel H, et al. Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the diabetes and insulin-glucose infusion in acute myocardial infarction (DIGAMI) study. Circulation. 1999;99:2626-2632.
- Malmberg K. (for the DIGAMI study group) Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. BMJ. 1997;314:1512-1515.
- Van den Berghe G, Wouters PJ, Bouillon R, et al. Outcome benefit of intensive insulin therapy in the critically ill: insulin dose versus glycemic control. Crit Care Med. 2003;31(2):359-366.
- Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. November 8, 2001;345(19):1359-1367.
- Van den Berghe G, Schoonheydt K, Becx P, et al. Insulin therapy protects the central and peripheral nervous system of intensive care patients. Neurology. April 26, 2005;64(8):1348-1353.
- Krinsley JS. Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clin Proc. 2004:992-1000.
- Krinsley JS. Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients Mayo Clin Proc. 2003;78:1471-1478.
- Clement S, Braithwaite SS, Magee MF, et al. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27(2):553-591.
- American College of Endocrinology Position Statement on Inpatient Diabetes and Metabolic Control. Endocr Pract. 2004;10(1):77-82.
- Ku SY, Sayre CA, Hirsch IB, et al. New insulin infusion protocol improves blood glucose control in hospitalized patients without increasing hypoglycemia. Jt Comm J Qual Patient Saf. 2005;31(3):141-147.
- Davidson PC, Steed RD, Bode BW. Glucommander: a computer-directed intravenous insulin system shown to be safe, simple, and effective in 120,618 h of operation. Diabetes Care. 2005;28(10):2418-2423.
- Massie RW. Use of the sliding scale for determination of insulin dosage. J Tn State Med Assoc. 1958;51(10):423-425.
- Hanish LR. Standardizing regimens for sliding-scale insulin. Am J Health Syst Pharm. May 1, 1997;54(9):1046-1047.
- Raforth RJ. Standardizing sliding scale insulin orders. Am J Med Qual. 2002;17(5):169-170.
- Kletter GG. Sliding scale fallacy. Arch Intern Med. July 13, 1998;158(13):1472.
- Hirsch IB, Paauw DS, Brunzell J. Inpatient management of adults with diabetes. Diabetes Care. 1995;18(6):870-878.
- Bergenstal RM, Fish LH, List S. The insulin sliding scale is not dead. Arch Intern Med. February 9, 1998;158(3):298.
- Dickerson LM, Xiaobu Y, Sack JL. Glycemic control in medical inpatients with type 2 diabetes mellitus receiving sliding scale insulin regimens versus routine diabetes medications: a multicenter randomized controlled trial. Ann Fam Med. 2003;1(1):29-35.
- Hirsch IB. Insulin analogues. N Engl J Med. January 13, 2005 ;352(2):174-183.
- DeWitt DE, Hirsch IB. Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review. JAMA. May 7, 2003;289(17):2254-2264.
- DAFNE Study Group. Training in flexible, intensive insulin management to enable dietary freedom in people with type 1 diabetes: dose adjustment for normal eating (DAFNE) randomised controlled trial. BMJ. 2002;325(7367):746-752.
- Genuth S. The automatic (regular insulin) sliding scale, or 2, 4, 6, 8—call H.O. Clinical Diabetes. 1994:40-42.
- Fischer KF, Lees JA, Newman JH. Hypoglycemia in hospitalized patients. N Engl J Med. 1986;315:1245-1250.
- Roman SH, Linekin PL, Stagnaro-Green A. An inpatient diabetes QI program. Jt Comm J Qual Improv. 1995;21(2):693-699.
- Gearhart JG, Duncan JL, Replogle WH, et al. Efficacy of sliding-scale insulin therapy: a comparison with prospective regimens. Fam Pract Res J. 1994;14:313-322.
- Queale WS, Seidler AJ, Brancati FL. Glycemic control and sliding scale insulin use in medical inpatients with diabetes mellitus. Arch Intern Med. 1997;157(5):545-552.
- Baldwin D, Villanueva G, McNutt R, et al. Eliminating inpatient sliding-scale insulin: a reeducation project with medical house staff. Diabetes Care. 2005;28(5):1008-1011.
- Schoeffler JM, Rice DAK, Gresham DG. 70/30 insulin algorithm versus sliding scale insulin. Ann Pharmacother. 2005;39(10):1606-1609.
- Trence DL, Kelly JL, Hirsch IB. The rationale and management of hyperglycemia for in-patients with cardiovascular disease: time for change. J Clin Endocrinol Metab. 2003;88 2430-2437.
- Magee MR, Clement S. Subcutaneous insulin therapy in the hospital setting: issues, concerns, and implementation. Endocr Pract. 2004;10 (suppl 2):81-88.
- Thompson CL, Dunn KC, Menon MC, et al. Hyperglycemia in the hospital. Diabetes Spectr. 2005;18(1):20-27.
- Campbell KB, Braithwaite SS. Hospital management of hyperglycemia. Clinical Diabetes. April 2004;22(2):81-88.
- Braithwaite SS, Buie MM, Thompson CL, et al. Hospital hypoglycemia: not only treatment but also prevention. Endocr Pract. 2004;10 (Suppl 2):71-80.
- Achtmeyer CE, Payne TH, Anawalt BD. Computer order entry system decreased use of sliding scale insulin regimens. Methods Inf Med. 2002;41:277-281.
An explosion of interest in managing hyperglycemia in the hospital has resulted from recent evidence that glycemic control can reduce mortality and other morbidities. Programs of intensification using historical controls for comparison and clinical trials demonstrating the ability of glycemic control to improve outcomes have mandated specific blood glucose thresholds for initiating intensive therapy in the ICU.1-12 These studies have convinced the world that in the ICU intravenous insulin infusion should supplant sliding scale.
A large body of observational data point to the likelihood that the benefits of glycemic control might extend to the general hospital ward.13,14 Although intravenous infusion of insulin might be more widely used in the future than it is now, the standard practice at most hospitals is to address glycemic control on general wards through the use of subcutaneous insulin.15,16
Two recent publications from Rush University Medical Center in Chicago and from St. Joseph’s/Candler Health System in Savannah, Ga., added weight to older literature and to a large body of long-held expert opinion that the anticipatory use of subcutaneous insulin in the hospital outperforms sliding scale.
Sliding Scale and Its Flaws
Throughout a half century of PubMed indexing, the medical literature has referred to sliding scale insulin.17 In its simplest form at a given blood glucose level, sliding scale delivers the same number of units of subcutaneous regular insulin to every patient. For example, it might require:
150-199 + 2
200-249 + 4
250-299 + 6
300-349 + 8
350-399 +10
400 and up Call physician
Protocols attempting to improve upon the scale offer differing amounts of insulin at several assumed degrees of insulin sensitivity.18,19 However, these protocols still retain a reactive approach to glycemic management such that hyperglycemia will recur given the absence of adequate basal and nutritional insulin coverage. Under sliding scale the risk of ketoacidosis in type-1 diabetes is not addressed. Overcompensation for hyperglycemia results in hypoglycemia for some patients. By writing sliding scale orders physicians may create the appearance of having designed a detailed and attentive care plan, while in reality they neglect to individualize care to meet the patient’s needs.20
Discussions about sliding scale and correction dose insulin are frequently misinterpreted because of differences in use of terminology. Practitioners who disagree with use of sliding scale monotherapy nevertheless recommend using correction doses or supplements of insulin for patients already receiving anticipatory insulin.21 Some practitioners may refer to correction doses used in addition to anticipatory insulin as sliding scale insulin.22,23 Patients themselves sometimes use the term sliding scale.
A patient may, for example, use glargine and aspart and, when asked how she determines the dose of aspart, she may say she uses “sliding scale.” What she means, though, may be one of several possible management styles. She may mean that she uses aspart only for correction of hyperglycemia. She may mean that she has a table with two columns, showing paired blood glucose ranges and premeal aspart doses, such that the prandial and correction components of the aspart doses are bundled. She may mean that she practices advanced carbohydrate counting, utilizes an insulin-to-carbohydrate ratio to determine aspart coverage for the meal, and additionally calculates a premeal correction dose of aspart for hyperglycemia (i.e., she may practice basal-prandial-correction therapy).24-26
For purposes of this discussion, by “sliding scale” insulin, I mean monotherapy with sliding scale without concomitant anticipatory use of insulin (scheduled, routine, standing, or programmed insulin) or sliding scale with its faults, as described by Saul Genuth, MD.27
Evidence Against Sliding Scale
Relying on sliding scale insulin sometimes causes hypoglycemic events, severe hyperglycemic events, patient relapse after treatment of ketoacidosis, and the in-house development of diabetic ketoacidosis. In the study by Kathleen and colleagues, using sliding scale doses too high for patients with renal insufficiency was identified as the cause of six episodes of hypoglycemia.28
In the quality improvement project by Roman and colleagues, the use of quality indicators of a) BG < 40 mg/dL, b) BG > 450 mg/dL on two occasions, or c) BG > 45 with acetone, revealed that five cases were caused by physician failure to respond appropriately to hyperglycemia, despite administration of large amounts of additional regular insulin as coverage for capillary blood glucose (one of which resulted in the in-house development of ketoacidosis).29
In a retrospective review of management following ketoacidosis Gearhart and colleagues showed a higher median glucose among the patients treated with sliding scale than those treated proactively with insulin (prospective or anticipatory insulin), or treated with a combination of proactive insulin and “sliding scale” (correction dose insulin).30 Queale and colleagues showed that the use of either a standing dose of insulin or an oral hypoglycemic agent was associated with a reduced risk of hyperglycemic episodes, whereas sliding scale insulin regimens (when used without a standing dose of intermediate-acting insulin) were associated with an increased rate of hyperglycemic episodes.31
Baldwin and colleagues at Rush University Medical Center in Chicago recently reported the superiority of glycemic control among 88 patients for whom sliding scale was not allowed, in comparison with 98 well-matched controls from a historical comparison period.32 In the study group, standing orders for insulin were not permitted. House staff reviewed the results of glucose monitoring performed four times daily, and they twice daily reordered anticipatory insulin if appropriate. Glargine and rapid-acting analog were continued only for those patients already using such therapy prior to admission. Premixed insulins were not used. Oral agents were not used in combination with insulin and sometimes were discontinued for medical reasons.
In the control group, the percentages of patients with specific orders were: 100% sliding scale as defined by the authors, 32% twice-daily dosing with NPH/regular insulin, 37% orals agents, and 15% combination oral agents with NPH/regular insulin. In the study group, the percentages were: 0% sliding scale, 68% twice-daily NPH/regular insulin, 30% orals, and 0% combination NPH/regular with oral agents. For the study patients versus the historical controls, the mean blood glucose was 150 ± 37 mg/dL mg/dL versus 200 ± 51 mg/dL (p<0.01). The frequency of hypoglycemia between the two groups did not differ.
Schoeffler and colleagues in the St. Joseph’s/Candler Health System in Savannah, Ga., recently conducted a randomized study of 20 patients that reported the use of a 70/30 dose titration algorithm is superior to sliding scale insulin in achieving glycemic control.33 Patients were identified for possible enrollment through discovery of orders for sliding scale insulin in the pharmacy. After exclusion of patients receiving tube feeds or TPN and patients having type-1 diabetes, those consenting to be randomized either received the sliding scale as written by their physician or titration of 70/30 insulin given twice daily under algorithm. Hypoglycemia did not occur in either group. Downward trend over time and lower mean blood glucose (151.3 versus 175.6 mg/dL, p = 0.042) were observed in the 70/30 insulin group.
Anticipatory Use of Insulin in the Hospital
The components of anticipatory subcutaneous insulin order-writing have been described according to preference of several authors (having basal, nutritional, and correction components). But in the hospital no style has been validated as superior to any other.34-37 The anticipatory delivery of nutritional insulin must match the expected pattern of exposure to carbohydrate. Specific standing orders should include additional nursing directions such as “do not withhold” or “hold if NPO.” For abrupt discontinuation of carbohydrate exposure, change of organ function, or decline of insulin resistance, protections must be in place to guard against hypoglycemia.38
An essential aspect of management is the frequent review of orders for subcutaneous insulin and patient response. At least once every day, the caregiver must reconsider “today’s insulin dose.”
How to Get Rid of Sliding Scale
Computerized order entry for managing hyperglycemia now is widespread among hospitals. Under a misdirected allocation of resources, motivated by concern for quality and safety, institutions have embraced the programming of order-entry options for standardized sliding scales. The sliding scale menu may provide a quick link to order entry for point-of-care blood capillary glucose monitoring, call parameters, and treatment of hypoglycemia. Nurses and doctors may come to believe that it is impossible even to order blood glucose monitoring without an accompanying sliding scale. Thus the sliding scale menu may possess all the accoutrements of glycemic management program except the one element most needed—a provision for anticipatory insulin.
One study by Achtmeyer and colleagues reduced utilization of a computerized sliding scale order by attaching a warning that the order was not approved by endocrinology.39 Emphasizing the importance of physician education to the successful abolition of sliding scale insulin, the study by Baldwin details an intensive house staff re-education program on how to write anticipatory insulin orders.32 The computerized order entry options used at Rush University Medical Center in Chicago (one of the two better performers in the recent benchmarking study of the University HealthSystem Consortium) were presented by Baldwin at the Aug. 19, 2005, “Glycemic Control Knowledge Transfer Meeting of the Consortium in Chicago.”
Why has use of the sliding scale persisted in practice? Is it for fear of hypoglycemia? Is it for lack of evidence on the importance of glycemic control? Even before computerization was sliding scale the path of least resistance? Is it because no clear superiority has been demonstrated among various styles of writing anticipatory insulin plans? Is it because physicians do not know how to write insulin orders? Or is it all in a name?
It just might seem that ordering sliding scale is the easy thing to call for or is the sophisticated thing to order. After all, sliding scale is an in-group term. A newly graduated physician is not likely to reject the suggestion of an experienced nurse that an order is needed for sliding scale.
For the next 50 years what is the call for, and what are the orders? Quite simply we have seen the twilight of the sliding scale—and “today’s insulin” dawning. TH
Dr. Braithwaite is clinical professor of medicine at the University of North Carolina, Diabetes Care Center, Durham.
References
- Zerr KJ, Furnary AP, Grunkemeier GL. Glucose control lowers the risk of wound infection in diabetics after open heart operations. Ann Thorac Surg. 1997;63:356-361.
- 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. Ann Thorac Surg. 1999;67:352-362.
- Furnary AP, Wu Y, Bookin SO. Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland diabetic project. Endocr Pract. 2004;10 (Suppl. 2):21-33.
- Furnary AP, Gao G, Grunkemeier GL, et al. Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2003;125(5):1007-1021.
- Malmberg K, Rydén L, Efendic S, et al. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol. 1995;26:57-65.
- Malmberg K, Norhammar A, Wedel H, et al. Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the diabetes and insulin-glucose infusion in acute myocardial infarction (DIGAMI) study. Circulation. 1999;99:2626-2632.
- Malmberg K. (for the DIGAMI study group) Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. BMJ. 1997;314:1512-1515.
- Van den Berghe G, Wouters PJ, Bouillon R, et al. Outcome benefit of intensive insulin therapy in the critically ill: insulin dose versus glycemic control. Crit Care Med. 2003;31(2):359-366.
- Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. November 8, 2001;345(19):1359-1367.
- Van den Berghe G, Schoonheydt K, Becx P, et al. Insulin therapy protects the central and peripheral nervous system of intensive care patients. Neurology. April 26, 2005;64(8):1348-1353.
- Krinsley JS. Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clin Proc. 2004:992-1000.
- Krinsley JS. Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients Mayo Clin Proc. 2003;78:1471-1478.
- Clement S, Braithwaite SS, Magee MF, et al. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27(2):553-591.
- American College of Endocrinology Position Statement on Inpatient Diabetes and Metabolic Control. Endocr Pract. 2004;10(1):77-82.
- Ku SY, Sayre CA, Hirsch IB, et al. New insulin infusion protocol improves blood glucose control in hospitalized patients without increasing hypoglycemia. Jt Comm J Qual Patient Saf. 2005;31(3):141-147.
- Davidson PC, Steed RD, Bode BW. Glucommander: a computer-directed intravenous insulin system shown to be safe, simple, and effective in 120,618 h of operation. Diabetes Care. 2005;28(10):2418-2423.
- Massie RW. Use of the sliding scale for determination of insulin dosage. J Tn State Med Assoc. 1958;51(10):423-425.
- Hanish LR. Standardizing regimens for sliding-scale insulin. Am J Health Syst Pharm. May 1, 1997;54(9):1046-1047.
- Raforth RJ. Standardizing sliding scale insulin orders. Am J Med Qual. 2002;17(5):169-170.
- Kletter GG. Sliding scale fallacy. Arch Intern Med. July 13, 1998;158(13):1472.
- Hirsch IB, Paauw DS, Brunzell J. Inpatient management of adults with diabetes. Diabetes Care. 1995;18(6):870-878.
- Bergenstal RM, Fish LH, List S. The insulin sliding scale is not dead. Arch Intern Med. February 9, 1998;158(3):298.
- Dickerson LM, Xiaobu Y, Sack JL. Glycemic control in medical inpatients with type 2 diabetes mellitus receiving sliding scale insulin regimens versus routine diabetes medications: a multicenter randomized controlled trial. Ann Fam Med. 2003;1(1):29-35.
- Hirsch IB. Insulin analogues. N Engl J Med. January 13, 2005 ;352(2):174-183.
- DeWitt DE, Hirsch IB. Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review. JAMA. May 7, 2003;289(17):2254-2264.
- DAFNE Study Group. Training in flexible, intensive insulin management to enable dietary freedom in people with type 1 diabetes: dose adjustment for normal eating (DAFNE) randomised controlled trial. BMJ. 2002;325(7367):746-752.
- Genuth S. The automatic (regular insulin) sliding scale, or 2, 4, 6, 8—call H.O. Clinical Diabetes. 1994:40-42.
- Fischer KF, Lees JA, Newman JH. Hypoglycemia in hospitalized patients. N Engl J Med. 1986;315:1245-1250.
- Roman SH, Linekin PL, Stagnaro-Green A. An inpatient diabetes QI program. Jt Comm J Qual Improv. 1995;21(2):693-699.
- Gearhart JG, Duncan JL, Replogle WH, et al. Efficacy of sliding-scale insulin therapy: a comparison with prospective regimens. Fam Pract Res J. 1994;14:313-322.
- Queale WS, Seidler AJ, Brancati FL. Glycemic control and sliding scale insulin use in medical inpatients with diabetes mellitus. Arch Intern Med. 1997;157(5):545-552.
- Baldwin D, Villanueva G, McNutt R, et al. Eliminating inpatient sliding-scale insulin: a reeducation project with medical house staff. Diabetes Care. 2005;28(5):1008-1011.
- Schoeffler JM, Rice DAK, Gresham DG. 70/30 insulin algorithm versus sliding scale insulin. Ann Pharmacother. 2005;39(10):1606-1609.
- Trence DL, Kelly JL, Hirsch IB. The rationale and management of hyperglycemia for in-patients with cardiovascular disease: time for change. J Clin Endocrinol Metab. 2003;88 2430-2437.
- Magee MR, Clement S. Subcutaneous insulin therapy in the hospital setting: issues, concerns, and implementation. Endocr Pract. 2004;10 (suppl 2):81-88.
- Thompson CL, Dunn KC, Menon MC, et al. Hyperglycemia in the hospital. Diabetes Spectr. 2005;18(1):20-27.
- Campbell KB, Braithwaite SS. Hospital management of hyperglycemia. Clinical Diabetes. April 2004;22(2):81-88.
- Braithwaite SS, Buie MM, Thompson CL, et al. Hospital hypoglycemia: not only treatment but also prevention. Endocr Pract. 2004;10 (Suppl 2):71-80.
- Achtmeyer CE, Payne TH, Anawalt BD. Computer order entry system decreased use of sliding scale insulin regimens. Methods Inf Med. 2002;41:277-281.
An explosion of interest in managing hyperglycemia in the hospital has resulted from recent evidence that glycemic control can reduce mortality and other morbidities. Programs of intensification using historical controls for comparison and clinical trials demonstrating the ability of glycemic control to improve outcomes have mandated specific blood glucose thresholds for initiating intensive therapy in the ICU.1-12 These studies have convinced the world that in the ICU intravenous insulin infusion should supplant sliding scale.
A large body of observational data point to the likelihood that the benefits of glycemic control might extend to the general hospital ward.13,14 Although intravenous infusion of insulin might be more widely used in the future than it is now, the standard practice at most hospitals is to address glycemic control on general wards through the use of subcutaneous insulin.15,16
Two recent publications from Rush University Medical Center in Chicago and from St. Joseph’s/Candler Health System in Savannah, Ga., added weight to older literature and to a large body of long-held expert opinion that the anticipatory use of subcutaneous insulin in the hospital outperforms sliding scale.
Sliding Scale and Its Flaws
Throughout a half century of PubMed indexing, the medical literature has referred to sliding scale insulin.17 In its simplest form at a given blood glucose level, sliding scale delivers the same number of units of subcutaneous regular insulin to every patient. For example, it might require:
150-199 + 2
200-249 + 4
250-299 + 6
300-349 + 8
350-399 +10
400 and up Call physician
Protocols attempting to improve upon the scale offer differing amounts of insulin at several assumed degrees of insulin sensitivity.18,19 However, these protocols still retain a reactive approach to glycemic management such that hyperglycemia will recur given the absence of adequate basal and nutritional insulin coverage. Under sliding scale the risk of ketoacidosis in type-1 diabetes is not addressed. Overcompensation for hyperglycemia results in hypoglycemia for some patients. By writing sliding scale orders physicians may create the appearance of having designed a detailed and attentive care plan, while in reality they neglect to individualize care to meet the patient’s needs.20
Discussions about sliding scale and correction dose insulin are frequently misinterpreted because of differences in use of terminology. Practitioners who disagree with use of sliding scale monotherapy nevertheless recommend using correction doses or supplements of insulin for patients already receiving anticipatory insulin.21 Some practitioners may refer to correction doses used in addition to anticipatory insulin as sliding scale insulin.22,23 Patients themselves sometimes use the term sliding scale.
A patient may, for example, use glargine and aspart and, when asked how she determines the dose of aspart, she may say she uses “sliding scale.” What she means, though, may be one of several possible management styles. She may mean that she uses aspart only for correction of hyperglycemia. She may mean that she has a table with two columns, showing paired blood glucose ranges and premeal aspart doses, such that the prandial and correction components of the aspart doses are bundled. She may mean that she practices advanced carbohydrate counting, utilizes an insulin-to-carbohydrate ratio to determine aspart coverage for the meal, and additionally calculates a premeal correction dose of aspart for hyperglycemia (i.e., she may practice basal-prandial-correction therapy).24-26
For purposes of this discussion, by “sliding scale” insulin, I mean monotherapy with sliding scale without concomitant anticipatory use of insulin (scheduled, routine, standing, or programmed insulin) or sliding scale with its faults, as described by Saul Genuth, MD.27
Evidence Against Sliding Scale
Relying on sliding scale insulin sometimes causes hypoglycemic events, severe hyperglycemic events, patient relapse after treatment of ketoacidosis, and the in-house development of diabetic ketoacidosis. In the study by Kathleen and colleagues, using sliding scale doses too high for patients with renal insufficiency was identified as the cause of six episodes of hypoglycemia.28
In the quality improvement project by Roman and colleagues, the use of quality indicators of a) BG < 40 mg/dL, b) BG > 450 mg/dL on two occasions, or c) BG > 45 with acetone, revealed that five cases were caused by physician failure to respond appropriately to hyperglycemia, despite administration of large amounts of additional regular insulin as coverage for capillary blood glucose (one of which resulted in the in-house development of ketoacidosis).29
In a retrospective review of management following ketoacidosis Gearhart and colleagues showed a higher median glucose among the patients treated with sliding scale than those treated proactively with insulin (prospective or anticipatory insulin), or treated with a combination of proactive insulin and “sliding scale” (correction dose insulin).30 Queale and colleagues showed that the use of either a standing dose of insulin or an oral hypoglycemic agent was associated with a reduced risk of hyperglycemic episodes, whereas sliding scale insulin regimens (when used without a standing dose of intermediate-acting insulin) were associated with an increased rate of hyperglycemic episodes.31
Baldwin and colleagues at Rush University Medical Center in Chicago recently reported the superiority of glycemic control among 88 patients for whom sliding scale was not allowed, in comparison with 98 well-matched controls from a historical comparison period.32 In the study group, standing orders for insulin were not permitted. House staff reviewed the results of glucose monitoring performed four times daily, and they twice daily reordered anticipatory insulin if appropriate. Glargine and rapid-acting analog were continued only for those patients already using such therapy prior to admission. Premixed insulins were not used. Oral agents were not used in combination with insulin and sometimes were discontinued for medical reasons.
In the control group, the percentages of patients with specific orders were: 100% sliding scale as defined by the authors, 32% twice-daily dosing with NPH/regular insulin, 37% orals agents, and 15% combination oral agents with NPH/regular insulin. In the study group, the percentages were: 0% sliding scale, 68% twice-daily NPH/regular insulin, 30% orals, and 0% combination NPH/regular with oral agents. For the study patients versus the historical controls, the mean blood glucose was 150 ± 37 mg/dL mg/dL versus 200 ± 51 mg/dL (p<0.01). The frequency of hypoglycemia between the two groups did not differ.
Schoeffler and colleagues in the St. Joseph’s/Candler Health System in Savannah, Ga., recently conducted a randomized study of 20 patients that reported the use of a 70/30 dose titration algorithm is superior to sliding scale insulin in achieving glycemic control.33 Patients were identified for possible enrollment through discovery of orders for sliding scale insulin in the pharmacy. After exclusion of patients receiving tube feeds or TPN and patients having type-1 diabetes, those consenting to be randomized either received the sliding scale as written by their physician or titration of 70/30 insulin given twice daily under algorithm. Hypoglycemia did not occur in either group. Downward trend over time and lower mean blood glucose (151.3 versus 175.6 mg/dL, p = 0.042) were observed in the 70/30 insulin group.
Anticipatory Use of Insulin in the Hospital
The components of anticipatory subcutaneous insulin order-writing have been described according to preference of several authors (having basal, nutritional, and correction components). But in the hospital no style has been validated as superior to any other.34-37 The anticipatory delivery of nutritional insulin must match the expected pattern of exposure to carbohydrate. Specific standing orders should include additional nursing directions such as “do not withhold” or “hold if NPO.” For abrupt discontinuation of carbohydrate exposure, change of organ function, or decline of insulin resistance, protections must be in place to guard against hypoglycemia.38
An essential aspect of management is the frequent review of orders for subcutaneous insulin and patient response. At least once every day, the caregiver must reconsider “today’s insulin dose.”
How to Get Rid of Sliding Scale
Computerized order entry for managing hyperglycemia now is widespread among hospitals. Under a misdirected allocation of resources, motivated by concern for quality and safety, institutions have embraced the programming of order-entry options for standardized sliding scales. The sliding scale menu may provide a quick link to order entry for point-of-care blood capillary glucose monitoring, call parameters, and treatment of hypoglycemia. Nurses and doctors may come to believe that it is impossible even to order blood glucose monitoring without an accompanying sliding scale. Thus the sliding scale menu may possess all the accoutrements of glycemic management program except the one element most needed—a provision for anticipatory insulin.
One study by Achtmeyer and colleagues reduced utilization of a computerized sliding scale order by attaching a warning that the order was not approved by endocrinology.39 Emphasizing the importance of physician education to the successful abolition of sliding scale insulin, the study by Baldwin details an intensive house staff re-education program on how to write anticipatory insulin orders.32 The computerized order entry options used at Rush University Medical Center in Chicago (one of the two better performers in the recent benchmarking study of the University HealthSystem Consortium) were presented by Baldwin at the Aug. 19, 2005, “Glycemic Control Knowledge Transfer Meeting of the Consortium in Chicago.”
Why has use of the sliding scale persisted in practice? Is it for fear of hypoglycemia? Is it for lack of evidence on the importance of glycemic control? Even before computerization was sliding scale the path of least resistance? Is it because no clear superiority has been demonstrated among various styles of writing anticipatory insulin plans? Is it because physicians do not know how to write insulin orders? Or is it all in a name?
It just might seem that ordering sliding scale is the easy thing to call for or is the sophisticated thing to order. After all, sliding scale is an in-group term. A newly graduated physician is not likely to reject the suggestion of an experienced nurse that an order is needed for sliding scale.
For the next 50 years what is the call for, and what are the orders? Quite simply we have seen the twilight of the sliding scale—and “today’s insulin” dawning. TH
Dr. Braithwaite is clinical professor of medicine at the University of North Carolina, Diabetes Care Center, Durham.
References
- Zerr KJ, Furnary AP, Grunkemeier GL. Glucose control lowers the risk of wound infection in diabetics after open heart operations. Ann Thorac Surg. 1997;63:356-361.
- 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. Ann Thorac Surg. 1999;67:352-362.
- Furnary AP, Wu Y, Bookin SO. Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland diabetic project. Endocr Pract. 2004;10 (Suppl. 2):21-33.
- Furnary AP, Gao G, Grunkemeier GL, et al. Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2003;125(5):1007-1021.
- Malmberg K, Rydén L, Efendic S, et al. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol. 1995;26:57-65.
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