Kathleen Schmidt

CONVERSION OF INTRAVENOUS INSULIN INFUSIONS TO SUBCUTANEOUSLY ADMINISTERED INSULIN GLARGINE IN PATIENTS WITH HYPERGLYCEMIA

OBJECTIVE To determine the optimal dose of insulin glargine needed to maintain glycemic control in patients undergoing conversion from intravenous regular insulin infusions to a subcutaneous insulin regimen. METHODS Seventy-five hospitalized patients receiving continuous insulin infusions were randomized to receive 40%, 60%, or 80% of their total daily insulin requirement, calculated from the rate during the final 6 hours of the infusion, as insulin glargine at the time of conversion to a subcutaneous regimen. Prandial insulin aspart was added to the subcutaneous regimen when patients began oral intake, and the dosage was left to clinical judgment. Capillary blood glucose monitoring (CBGM) was performed before every meal and at bedtime. All CBGM values for the 24-hour period after conversion were collected. RESULTS Three hundred ninety-two CBGM values were recorded and analyzed. The mean for all CBGM values during the 24-hour period after conversion to the subcutaneous insulin regimen was 151.9 +/- 42.5 mg/dL in the 40% group, 164.0 +/- 41.6 mg/dL in the 60% group, and 153.2 +/- 66.2 mg/dL in the 80% group (P = 0.66). The percentage of CBGM values in the predefined study target range (80 to 140 mg/dL) was 43.2%, 34.8%, and 48% in the 40%, 60%, and 80% groups, respectively (P = 0.09). Secondary analysis with use of a glycemic target of 80 to 150 mg/dL and removal of outliers resulted in CBGM values within that range in 58.7%, 44.4%, and 67.6% for the 40%, 60%, and 80% groups, respectively (overall, P = 0.001; 40% group versus the 60% group, P = 0.03; 60% group versus the 80% group, P = 0.0004; and 40% group versus the 80% group, P = 0.18). CONCLUSION Conversion from continuous insulin infusion to subcutaneously administered insulin glargine at a dose equal to 80% of the total daily insulin requirements resulted in the highest percentage of CBGM values in the glycemic target range of 80 to 150 mg/dL within the first 24 hours after regimen conversion in comparison with conversion at 40% and 60%, albeit the difference between the 40% and 80% groups was not statistically significant.

INPATIENT MANAGEMENT OF HYPERGLYCEMIA: THE NORTHWESTERN EXPERIENCE

OBJECTIVE To describe a novel method of safe and effective intensive management of inpatient hyperglycemia with use of cost-effective protocols directed by a glucose management service (GMS). METHODS An intravenous insulin protocol was designed to achieve a glycemic target of 80 to 110 mg/dL. When stable inpatients were transferred from the intravenous protocol to a subcutaneous insulin protocol, which consisted of basal long-acting and prandial and supplemental rapid-acting insulins, the blood glucose target was 80 to 150 mg/dL. Glucose levels were reviewed by the GMS at least daily for protocol adjustments, when necessary. RESULTS The intravenous insulin protocol was used in 276 patients, and 4,058 capillary blood glucose levels were recorded. Glycemic target levels (80 to 110 mg/dL) were achieved, on average, 10.6 +/- 5.2 hours after initiation of insulin drip therapy. The mean capillary blood glucose level during the study interval was 135.3 +/- 49.9 mg/dL. Hypoglycemia (< or = 60 mg/dL) was recorded in 1.5% of glucose values, and hyperglycemia (> or = 400 mg/dL) was recorded in only 0.06%. The subcutaneous insulin protocol was used in 922 patients, and 18,067 capillary glucose levels were documented. The mean blood glucose level was 145.6 +/- 55.8 mg/dL during the study period. The blood glucose target of 80 to 150 mg/dL was achieved in 58.6%, whereas 74.3% of glycemic values were in the clinically acceptable range (80 to 180 mg/dL). Hypoglycemia (< or = 60 mg/dL) occurred in 1.3% of capillary blood glucose values, and hyperglycemia (> or = 400 mg/dL) occurred in 0.4% of values. CONCLUSION Validated protocols dedicated to the achievement of strict glycemic goals were implemented by a GMS and resulted in substantial improvements in glycemic control on the surgical inpatient services, with a reduced frequency of hypoglycemia. The protocols and the GMS have been well received by the inpatient nursing and surgical staff members, and all of this has been done in a cost-effective manner.

Glycemic Control by a Glucose Management Service and Infection Rates After Liver Transplantation

OBJECTIVE To present an analysis of glycemic control before and after introduction of a dedicated glucose management service (GMS) and outcomes within 1 year after liver transplantation (LT). METHODS We conducted a retrospective review of patients undergoing LT, who were treated with insulin infusions after LT, before and after introduction of a GMS. Outcome measures within 1 year after LT included graft rejection, infection, prolonged ventilation (>48 hours on a ventilator), and graft survival. A multiple logistic regression was used to examine the relationship between GMS use and outcomes. RESULTS This study consisted of 73 (35 GMS and 38 non-GMS) organ transplant recipients. The mean perioperative blood glucose level in the GMS group was lower than in the non-GMS group: unadjusted, by 31.1 mg/dL (P = .001); adjusted for pre-insulin drip glucose, age, sex, Model for End-Stage Liver Disease (MELD) score, and type of transplant, by 23.4 mg/dL (P = .020). There were 27 rejection episodes, 48 infections, 26 episodes of prolonged ventilation, and 64 patients with graft survival at 1 year. The infection rate was lower in the GMS group than in the non-GMS group: the unadjusted odds ratio was 0.28 (P = .015); when adjustments were made for pre-insulin drip glucose, pretransplant glucose, age, sex, MELD score, type of transplant, and diabetes status before transplantation, the odds ratio was 0.24 (95% confidence interval, 0.06 to 0.97; P = .045). No significant associations were noted between GMS group and rejection rates, prolonged ventilation, or graft survival. CONCLUSION In this study of LT patients, a GMS was associated with improved glycemic control and reduced postoperative infections. Further studies investigating effects of strict glycemic control after LT are warranted.

Intensive glycemic control after heart transplantation is safe and effective for diabetic and non-diabetic patients.

Some studies have shown increased mortality, infection, and rejection rates among diabetic (DM) compared to non‐diabetic (non‐DM) patients undergoing heart transplant (HT). This is a retrospective chart review of adult patients (DM, n = 26; non‐DM, n = 66) undergoing HT between June 1, 2005, and July 31, 2009. Glycemic control used intravenous (IV) and subcutaneous (SQ) insulin protocols with a glucose target of 80–110 mg/dL. There were no significant differences between DM and non‐DM patients in mean glucose levels on the IV and SQ insulin protocols. Severe hypoglycemia (glucose <40 mg/dL) did not occur on the IV protocol and was experienced by only 3 non‐DM patients on the SQ protocol. Moderate hypoglycemia (glucose >40 and <60 mg/dL) occurred in 17 (19%) patients on the IV protocol and 24 (27%) on the SQ protocol. There were no significant differences between DM and non‐DM patients within 30 d of surgery in all‐cause mortality, treated HT rejection episodes, reoperation, prolonged ventilation, 30‐d readmissions, ICU readmission, number of ICU hours, hospitalization days after HT, or infections. This study demonstrates that DM and non‐DM patients can achieve excellent glycemic control post‐HT with IV and SQ insulin protocols with similar surgical outcomes and low hypoglycemia rates.

Comparison of Glycemic and Surgical Outcomes After Change in Glycemic Targets in Cardiac Surgery Patients

OBJECTIVE To compare perioperative glycemic and long-term surgical outcomes in patients undergoing cardiac surgery before and after the recommended 2009 changes in inpatient glycemic targets. RESEARCH DESIGN AND METHODS We performed a retrospective review of patients who underwent cardiac surgery between 4 September 2007 and 30 April 2011. Comparison was made of blood glucose (BG) outcomes 3 days after surgery, and 30-day cardiac outcomes before and after a change in insulin protocol that took place on 1 September 2009, which consisted of raising the glycemic targets during intravenous insulin infusions from 80–110 mg/dL (80–110 group) to 110–140 mg/dL (110–140 group). RESULTS When compared with the 80–110 group (n = 667), the 110–140 group (n = 658) had higher mean postoperative BG levels during the intravenous insulin infusion (141 ± 15 vs. 121 ± 15 mg/dL, P < 0.001) and the subcutaneous insulin period (134 ± 24 vs. 130 ± 23 mg/dL, P < 0.001), and for 3 days postoperatively (141 ± 17 vs. 127 ± 15 mg/dL, P < 0.001). Fewer patients in the 110–140 mg/dL group experienced moderate hypoglycemia (BG <70 mg/dL) (177 vs. 73, P = 0.04). Severe hypoglycemia (BG <40 mg/dL) occurred in only one patient in the 80–110 group and three patients in the 110–140 group. There were no significant differences in mortality or surgical complication rates (with the exception of reintubation) between the groups. CONCLUSIONS The higher glycemic target of 110–140 mg/dL resulted in similar mean glucose values, with significantly less hypoglycemia and no significant differences in mortality/morbidity compared with the more strict target of 80–110 mg/dL.

Examination of implementation of intravenous and subcutaneous insulin protocols and glycemic control in heart transplant patients.

OBJECTIVE Perioperative glycemic management is particularly challenging in heart transplant (HT) patients who are on high-dose steroids and subject to surgical stress. The objective of the study was to examine the efficacy and safety of perioperative insulin administration in HT patients with and without diabetes. METHODS Medical records of 71 HT patients from June 1, 2005 to July 31, 2009 whose hyperglycemia was managed by our Glucose Management Service (GMS) were analyzed for up to 1 year after HT. Their daily blood glucose (BG) averages on intravenous (i.v.) insulin drips and subcutaneous (s.q.) insulin, hypoglycemia rates, reasons for hypoglycemia, and deviations from insulin protocols were analyzed. RESULTS Daily BG averages between diabetic (DM) and nondiabetic (nonDM) patients were not significantly different while on the drip but were significantly different for first 5 days on s.q. (P<.05). The daily insulin glargine doses were similar. No patients developed severe hypoglycemia (BG ≤40 mg/dL) while on drip, and only 2.8% experienced hypoglycemia on s.q. Among 40 episodes of moderate hypoglycemia while on drip, 15 had nurse deviations from protocol prior to the episode. Posttransition day fasting glucose was at goal (mean 124.7 ± 35.4 mg/dL); however 39.4% (28/71) of patients received a transition insulin glargine dose that was different from the amount indicated by protocol. The likelihood of developing moderate hypoglycemia on s.q. was associated with the glargine dose used at the time of transition (odds ratio [OR] 1.03, P = .034). CONCLUSION Inpatient insulin protocols implemented by a GMS are successful in obtaining glycemic control with minimal side effects in patients with and without diabetes, even when they are on a high-dose steroid regimen.

Insulin resistance following cardiothoracic surgery in patients with and without a preoperative diagnosis of type 2 diabetes during treatment with intravenous insulin therapy for postoperative hyperglycemia

OBJECTIVE To assess insulin resistance postoperatively in patients with (DM) and without (nonDM) a prior diagnosis of diabetes. RESEARCH DESIGN AND METHODS Following cardiac surgery, 122 nonDM and 33 DM were treated with insulin infusions to obtain glucose levels <110 mg dl(-1). Glucose levels, insulin infusion rates, and insulin infusion rate/glucose ratios were calculated to assess insulin resistance. RESULTS The average blood glucose at insulin drip initiation (209 vs. 173 mg dl(-1); P<.001) and during the first 12 h (146 vs. 135 mg dl(-1); P<.05) was higher in DM, but during Hours 12-24 glucose levels were not different. The peak (5.7 vs. 4.1 U h(-1); P<.001) and average insulin drip rates (3.7 vs. 2.9 U h(-1); P<.01) were higher in DM. Insulin resistance (insulin drip rate/glucose ratio) was higher in DM during Hours 1-12 (0.029 vs. 0.022 U h(-1) mg(-1) dl(-1); P<.001), but not during Hours 12-24 (P=.57). To eliminate glucotoxicity as a cause of the insulin resistance, 23 DM patients were pair matched with 23 nonDM patients based first on glucose levels at drip initiation then by body mass index (BMI) and then catecholamine use to maintain blood pressure. The average blood glucose levels, insulin drip rates, and insulin resistance ratios were not significantly different between the pair-matched groups at all time points. CONCLUSIONS When matched for initial glucose levels, insulin resistance is not different between DM and nonDM following cardiac surgery, likely due to the overwhelming stress response. Insulin drip protocols used postoperatively do not have to be modified for those with a prior diagnosis of diabetes.

Glycemic Control Reduces Infections in Post-Liver Transplant Patients: Results of a Prospective, Randomized Study

Context: Previous studies have shown a relationship between glycemic control and posttransplant morbidity. Objective: We conducted a prospective randomized controlled trial in postliver transplant patients to evaluate intensive inpatient glycemic control and effects on outcomes to 1 year. Research Design and Intervention: A total of 164 patients [blood glucose (BG) >180 mg/dL] were randomized into 2 target groups: 82 with a BG of 140 mg/dL and 82 with a BG of 180 mg/dL. Continuous insulin infusions were initiated and then converted to subcutaneous basal bolus insulin therapy by our glucose management service. Results: The inpatient mean BG level was significantly different (140 group, 151.4 ± 19.5 mg/dL vs 180 group, 172.6 ± 27.9 mg/dL; P < 0.001). Any infection within 1 year occurred in 35 of the 82 patients (42.7%) in the 140 group and 54 of 82 (65.9%) in the 180 group (P = 0.0046). In a time-to-first infection analysis, being in the 140 group resulted in a hazard ratio of 0.54 (95% confidence interval, 0.35 to 0.83; P = 0.004); the difference between the 2 groups was statistically significant at 1 month (P = 0.008). The number with adjudicated transplant rejection was similar between the 2 groups [17 of 82 (20.7%) and 20 of 82 (24.3%) in the 140 and 180 groups, respectively; P = not significant]. Severe hypoglycemia (BG ⩽40 mg/dL) occurred in 3 patients (2 in the 140 group and 1 in the 180 group). However, more patients had moderate hypoglycemia (BG, 41 to 70 mg/dL) in the 140 group [27 of 82 (32.9%) vs 10 of 82 (12.2%) in the 180 group; P = 0.003]. Insulin-related hypoglycemia was not associated with the incidence of severe adverse outcomes. Conclusions: Glycemic control of 140 mg/dL safely resulted in a reduced incidence of infection after transplantation compared with 180 mg/dL, but with an increase in moderate hypoglycemia.

INPATIENT HYPOGLYCEMIC EVENTS IN A COMPARATIVE EFFECTIVENESS TRIAL FOR GLYCEMIC CONTROL IN A HIGH-RISK POPULATION.

OBJECTIVE Inpatient hypoglycemia (glucose ≤70 mg/dL) is a limitation of intensive control with insulin. Causes of hypoglycemia were evaluated in a randomized controlled trial examining intensive glycemic control (IG, target 140 mg/dL) versus moderate glycemic control (MG, target 180 mg/dL) on post-liver transplant outcomes. METHODS Hypoglycemic episodes were reviewed by a multidisciplinary team to calculate and identify contributing pathophysiologic and operational factors. A subsequent subgroup case control (1:1) analysis (with/without) hypoglycemia was completed to further delineate factors. A total of 164 participants were enrolled, and 155 patients were examined in depth. RESULTS Overall, insulin-related hypoglycemia was experienced in 24 of 82 patients in IG (episodes: 20 drip, 36 subcutaneous [SQ]) and 4 of 82 in MG (episodes: 2 drip, 2 SQ). Most episodes occurred at night (41 of 60), with high insulin amounts (44 of 60), and during a protocol deviation (51 of 60). Compared to those without hypoglycemia (n = 127 vs. n = 28), hypoglycemic patients had significantly longer hospital stays (13.6 ± 12.6 days vs. 7.4 ± 6.1 days; P = .002), higher peak insulin drip rates (17.4 ± 10.3 U/h vs. 13.1 ± 9.9 U/h; P = .044), and higher peak insulin glargine doses (36.8 ± 21.4 U vs. 26.2 ± 24.3 U; P = .035). In the case-matched analysis (24 cases, 24 controls), those with insulin-related hypoglycemia had higher median peak insulin drip rates (17 U/h vs. 11 U/h; P = .04) and protocol deviations (92% vs. 50%; P = .004). CONCLUSION Peak insulin requirements and protocol deviations were correlated with hypoglycemia. ABBREVIATIONS DM = diabetes mellitus ICU = intensive care unit IG = intensive glycemic control MELD = Model for End-stage Liver Disease MG = moderate glycemic control SQ = subcutaneous.

EVALUATION OF OUTCOMES AND COMPLICATIONS IN PATIENTS WHO EXPERIENCE HYPOGLYCEMIA AFTER CARDIAC SURGERY.

OBJECTIVE The objective of the study was to elucidate 30-day and long-term outcomes in patients experiencing postoperative hypoglycemia. METHODS We conducted a retrospective review of patients who underwent cardiac surgery between September 4, 2007, and April 30, 2011, at Northwestern Memorial Hospital who had intensive treatment of hyperglycemia postoperatively. Of 1,325 patients, 215 experienced a hypoglycemic episode (blood glucose <70 mg/dL) within the first 3 postoperative days. A total of 198 were propensity-score (PS) matched to 363 patients without hypoglycemia. The analysis consisted of a comparison of 30-day cardiac outcomes and long-term mortality between those who experienced a hypoglycemic event and those who did not. RESULTS Between patients who experienced hypoglycemia compared to those that did not, there were no significant differences in mean glucose values while on insulin drips (119.8 ± 33.5 mg/dL vs. 120.9 ± 30.5 mg/dL; P = .69) or subcutaneous insulin (122.0 ± 38.0 mg/dL vs. 127.2 ± 35.5 mg/dL; P = .11) or postoperative surgical complication rates (30-day mortality: 3.5% vs. 1.7%; complications (any): 40% vs. 42%; 30-day re-admissions: 13% vs. 13%; all cardiac complications: 35% vs. 31%; and all infections: 8% vs. 5%). Over an average of 5.1 ± 2.2 years following index surgery, there was higher all-cause mortality among those PS-matched who had experienced hypoglycemia compared to those who had not (log-rank P = .031), primarily due to those (n = 32) experiencing more than one episode of hypoglycemia. CONCLUSION Postoperative hypoglycemia did not negatively impact immediate surgical complication rates but was associated with a significant risk of increased postoperative morbidity and long-term all-cause mortality in patients experiencing multiple episodes of hypoglycemia. ABBREVIATIONS BG = blood glucose BMI = body mass index CARD = Cardiovascular Research Database HR = hazard rate PS = propensity score.