Susan S. Braithwaite

American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus.

Acknowledgments We would like to recognize Elliot Sternthal, MD, FACE, and Joseph Vassalotti, MD, for their review of these guidelines and thoughtful comments.

Guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients.

Objective:To evaluate the literature and identify important aspects of insulin therapy that facilitate safe and effective infusion therapy for a defined glycemic end point. Methods:Where available, the literature was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology to assess the impact of insulin infusions on outcome for general intensive care unit patients and those in specific subsets of neurologic injury, traumatic injury, and cardiovascular surgery. Elements that contribute to safe and effective insulin infusion therapy were determined through literature review and expert opinion. The majority of the literature supporting the use of insulin infusion therapy for critically ill patients lacks adequate strength to support more than weak recommendations, termed suggestions, such that the difference between desirable and undesirable effect of a given intervention is not always clear. Recommendations:The article is focused on a suggested glycemic control end point such that a blood glucose ≥150 mg/dL triggers interventions to maintain blood glucose below that level and absolutely <180 mg/dL. There is a slight reduction in mortality with this treatment end point for general intensive care unit patients and reductions in morbidity for perioperative patients, postoperative cardiac surgery patients, post-traumatic injury patients, and neurologic injury patients. We suggest that the insulin regimen and monitoring system be designed to avoid and detect hypoglycemia (blood glucose ⩽70 mg/dL) and to minimize glycemic variability.Important processes of care for insulin therapy include use of a reliable insulin infusion protocol, frequent blood glucose monitoring, and avoidance of finger-stick glucose testing through the use of arterial or venous glucose samples. The essential components of an insulin infusion system include use of a validated insulin titration program, availability of appropriate staffing resources, accurate monitoring technology, and standardized approaches to infusion preparation, provision of consistent carbohydrate calories and nutritional support, and dextrose replacement for hypoglycemia prevention and treatment. Quality improvement of glycemic management programs should include analysis of hypoglycemia rates, run charts of glucose values <150 and 180 mg/dL. The literature is inadequate to support recommendations regarding glycemic control in pediatric patients. Conclusions:While the benefits of tight glycemic control have not been definitive, there are patients who will receive insulin infusion therapy, and the suggestions in this article provide the structure for safe and effective use of this therapy.

Intravenous insulin infusion therapy: indications, methods, and transition to subcutaneous insulin therapy.

OBJECTIVE To describe indications for intravenous (IV) insulin infusion therapy and glycemic thresholds, discuss methods and protocols, and promote use of and access to IV insulin infusion therapy for all appropriate patients in the hospital setting. RESULTS Randomized, prospectively designed trials support the use of IV insulin infusion therapy for patients in the surgical intensive-care unit, including postoperative cardiac patients and patients having myocardial infarction. Among patients in the surgical intensive-care unit, reanalysis of the data suggested no threshold at which benefit occurred above the blood glucose level of 110 mg/dL. In another study, retrospective analysis of data among critically ill medical and surgical patients suggested a target blood glucose level of 145 mg/dL or less. In other populations, the threshold or ideal target blood glucose range has not been determined. Three protocols for IV insulin infusion are described that maintain blood glucose levels safely below the upper limit of their respective target ranges without substantial risk of hypoglycemia. CONCLUSION The threshold for initiation of IV insulin infusion is 110 mg/dL for critically ill surgical patients, 140 mg/dL for other medical or surgical patients, 180 mg/dL for patients in whom subcutaneous insulin regimens fail, and 100 mg/dL for pregnant women. The blood glucose target range is 80 to 110 mg/dL for selected critically ill surgical patients, 70 to 100 mg/dL for pregnant women, and 90 to 140 mg/dL for all other patients. Hospitals should develop procedures to make IV insulin infusion therapy available to all appropriate patients.

HOSPITAL HYPOGLYCEMIA: NOT ONLY TREATMENT BUT ALSO PREVENTION

OBJECTIVE To propose a strategy, applicable on general hospital wards, for prevention of hypoglycemia in hospitalized patients. RESULTS Although the mortality rate among hospitalized patients with hypoglycemia has been shown to be 22.2 to 27% in series that included patients with diabetes, some investigators have shown that hypoglycemia is not an independent predictor of mortality. Outside the critical care setting, the comparative risks of hyperglycemia and hypoglycemia and the relationship of hospital hypoglycemia to intensification of glycemic control have not been determined. The reported incidence of hospital hypoglycemia ranges from 1.2% for hospitalized adults to 20% for nonpregnant patients with diabetes admitted without a metabolic emergency. Among patients receiving antihyperglycemic therapy, the literature describes precipitating events--usually a sudden change of caloric exposure-- and predisposing conditions for hypoglycemic episodes. CONCLUSION Hospital hypoglycemia is predictable, and it is preventable by measures other than undertreatment of hyperglycemia. Physician orders for antihyperglycemic therapy should be written and, if necessary, be revised so as to respond to the presence of predisposing conditions for hypoglycemia. A ward-based protocol or hospital-wide policy should establish the appropriate response to triggering events. Within the time frame of action of previously administered antihyperglycemic drugs (after abrupt interruption of caloric exposure), the threshold for preventive intravenous administration of dextrose is a glucose concentration of 120 mg/dL.

Evaluation of hospital glycemic control at US academic medical centers.

OBJECTIVE To evaluate contemporary hospital glycemic management in US academic medical centers. DESIGN This retrospective cohort study was conducted on patients discharged from 37 academic medical centers between July 1 and September 30, 2004; 1,718 eligible adult patients met at least 1 of the inclusion criteria: 2 consecutive blood glucose readings >180 mg/dL within 24 hours, or insulin treatment at any time during hospitalization. We assessed 3 consecutive measurement days of glucose values, glycemic therapy, and additional clinical and laboratory characteristics. RESULTS In this diverse cohort, 79% of patients had a prior diagnosis of diabetes, and 84.6% received insulin on the second measurement day. There was wide variation in hospital performance of recommended hospital diabetes care measures such as glycosylated hemoglobin (A1C) assessment (range, 3%-63%) and timely admission laboratory glucose measurement (range, 39%-97%). Median glucose was significantly lower for patients in the intensive care unit (ICU) compared to ward/intermediate care. ICU patients treated with intravenous insulin had significantly lower median glucose when compared to subcutaneous insulin. Only 25% of ICU patients on day 3 had estimated 6 AM glucose <or=110 mg/dL. Hyperglycemia was common, 50% of all patients had >or=1 glucose measurement >or=180 mg/dL on measurement days 2 and 3. Severe hypoglycemia (<50 mg/dL) occurred in 2.8% of all patient days. CONCLUSIONS Despite frequent insulin use, glucose control was suboptimal. Academic medical centers have opportunities to improve care to meet current American Diabetes Association hospital diabetes care standards.

The case for supporting inpatient glycemic control programs now: The evidence and beyond

8 Department of Medicine, Division of Hospital Medicine, University of California San Diego, San Diego, California. M edical centers are faced with multiple competing priorities when deciding how to focus their improvement efforts and meet the ever expanding menu of publicly reported and regulatory issues. In this article we expand on the rationale for supporting inpatient glycemic control programs as a priority that should be moved near the top of the list. We review the evidence for establishing glycemic range targets, and also review the limitations of this evidence, acknowledging, as does the American Diabetes Association (ADA), that in ‘‘both the critical care and non-critical care venue, glycemic goals must take into account the individual patient’s situation as well as hospital system support for achieving these goals.’’ We emphasize that inpatient glycemic control programs are needed to address a wide variety of quality and safety issues surrounding the care of the inpatient with diabetes and hyperglycemia, and we wish to elevate the dialogue beyond arguments surrounding adoption of one glycemic target versus another. The Society of Hospital Medicine Glycemic Control Task Force members are not in unanimous agreement with the American Association of Clinical Endocrinologists (AACE)/ADA inpatient glycemic targets. However, we do agree on several other important points, which we will expand on in this article:

Procalcitonin: new insights on regulation and origin.

Procalcitonin (PCT) is a 116 amino acid protein, synthesized as part of the precursor molecule preprocalcitonin and containing within its midportion the 33amino acid sequence of calcitonin, a peptide that requires carboxyterminal amidation for full biological activity. The mature calcitonin molecule itself is a normal product of the C-cells of the thyroid, secreted in response to hypercalcemia and inhibitory to osteoclastic bone resorption. Expression of calcitonin receptors is a key event in the differentiation of osteoclasts from stem cell precursors (1). A human calcitonin receptor gene has been cloned from an ovarian carcinoma cell line (2).

No patient left behind: evaluation and design of intravenous insulin infusion algorithms.

OBJECTIVE To define the characteristics of performance evaluation, algorithm design, and regulation of insulin delivery by which professionals and the healthcare system might differentiate between methodologies for intravenous insulin infusion. METHODS Published performance criteria used in the assessment of intravenous insulin infusion algorithms are classified. The structure of intravenous insulin infusion formulae is reviewed, as are technologies that might lead to future improvement. RESULTS Among published reports, no standardization was discernable for description of algorithm characteristics or performance. Except for time-to-target and hypoglycemic episodes, measures using the patient as unit of observation are not employed consistently. CONCLUSION The healthcare system needs criteria for evaluation and minimal acceptable standards for assessing performance of any algorithm, decision support system, or closed-loop system for intravenous insulin infusion. Inclusion of patient-based measures is necessary to assess the ability of an algorithm to control variability between patients and within a given run. Standardization of performance reporting will help users to select appropriate methodologies.

Metformin-associated lactic acidosis in a burn patient.

Hyperglycemia commonly is observed as part of the hypermetabolic response to severe burn injury. In routine burn care, physicians use interventions to address and reduce the complications of this stress-induced hyperglycemia. Metformin (1,1-dimethylbiguanide), an orally administered hyperglycemic medication, has been used previously to modulate the stress-induced hyperglycemic response in nondiabetic burn patients. The use of this medication in nonburn diabetic patients has been associated with the development of lactic acidosis. We present an acute burn patient who developed lactic acidosis while receiving metformin for management of his diabetes.

Managing hyperglycemia in hospitalized patients.

Insulin infusion is used in the critical care setting for prevention of hyperglycemia and is administered most safely under a structured, dynamic, dose-defining algorithm. The ordering of basal-prandial-correction SC insulin therapy, appropriate for most hospitalized patients who are eating, is simplified and standardized to excellence by the development of institutional order sets or computerized order entry templates. Basal insulin therapy is prescribed as intermediate-acting insulin or long-acting insulin analogue. Prandial insulin therapy is delivered with meals to prevent excessive glycemic excursions from occurring after ingestion of meals and is prescribed as rapid-acting insulin analogue. Correction-dose insulin therapy is ordered as small doses of rapid-acting insulin analogue delivered to correct hyperglycemia and is prescribed with appropriate timing so as to avoid stacking with previously administered doses of rapid-acting insulin analogue. Patients knowledgeable in diabetes self-management will experience satisfaction under an institutional policy that allows self-management to continue under appropriate conditions during hospitalization. To craft appropriate institutional tools for patient care, the input and consensus of a multidisciplinary group of health care professionals, including primary care providers and hospitalists, as well as specialists in diabetes with backgrounds in endocrinology, nutrition and dietetics, nursing, pharmacy, laboratory sciences, and quality assurance, is required.