The Case

A 48-year-old woman with insulin-dependent diabetes mellitus presents to the emergency department with right upper quadrant pain, fever, and leukocytosis, prompting admission for presumed cholangitis. Overnight, the patient was made NPO (nothing by mouth) in anticipation of an endoscopic retrograde cholangiopancreatography (ERCP) the following morning. The admitting medical team ordered an insulin sliding scale for the patient, and her blood glucose levels became very difficult to control in the ensuing hours. In the morning, the patient developed an anion gap and evidence of mild diabetic ketoacidosis. The physician evaluating the patient in the morning realized that no basal insulin was ordered and instituted a more appropriate regimen of insulin, and the patient underwent an uneventful ERCP and hospitalization.

The Commentary

This case is about a near miss, a tragic outcome narrowly averted by an alert physician who promptly corrected a series of earlier misjudgments that led to an inappropriate plan for insulin administration. The errant plan resulted in the development of diabetic ketoacidosis (DKA) in a seriously ill, infected patient who was NPO and awaiting an ERCP. If not recognized or anticipated, DKA carries the potential for lethal consequences.(1,2) A key error by the admitting team was not providing for a greatly increased basal insulin requirement, opting instead for a less effective insulin sliding scale algorithm. This decision making represented the wrong approach in this setting, an example of a rule-based error. Reason characterizes such situations as "strong but wrong" rule-based errors—the rule is strong in general but was inappropriate or misapplied in this situation.(3)

Metabolic stressors such as myocardial ischemia, surgery, cardiovascular collapse, and severe infections greatly increase insulin requirements. Both hyperglycemia and ketosis reduce immune defenses to infective agents.(4) During metabolic stress, the degree of ensuing insulin resistance is often hard to predict.(5) An insulin-dependent (Type 1) patient with an initial basal requirement of 0.6 units/hr may develop insulin requirements of 3–20 units/hr or more, rapidly resulting in marked hyperglycemia. This same patient will then develop severe insulin deficiency leading to ketoacidosis. Since the cardiovascular compensatory response to DKA requires significantly increased cardiac output, any underlying cardiac compromise will greatly increase the risk of death. Aggressive management of hyperglycemia in critically ill patients can greatly improve outcomes.(6) In this case, the admitting providers delivered an initial care plan that did not take into account the increased basal insulin requirements and the cascade of clinical events that may have ultimately led to an adverse outcome—one that was entirely preventable with better strategies for glycemic management.

Supplemental subcutaneous insulin algorithms alone, as ordered in this case, are ineffective and often inadequate to protect against the development of in-hospital DKA, which carries an increased risk of death.(2,7) A better strategy would involve initial assessment of insulin requirements and institution of a variable-rate insulin infusion with frequent glucose monitoring. An accompanying algorithm would still be required to adjust the insulin doses over time. The recommendation is to reach a goal and maintain glucose levels in the target range of 80–110 mg/dL during both the perioperative period and through the active infection.(2,5,8) During a variable-rate insulin infusion, any initial assumptions about insulin requirements are constantly revised based on both the actual glucose level and the magnitude of change during the observed time intervals. Barriers to the use of insulin infusions in acute care settings stem from the fact that, without key changes in the system of care, insulin infusion utilization is fraught with difficulty.(1)

System Changes to Improve Glycemic Control

A well-studied and well-designed, uniform algorithm for insulin administration should be implemented in all acute care settings. All providers (e.g., nurses, physicians, and clinical pharmacists) who care for diabetic patients need to be familiar with the details of the algorithm. Although many excellent insulin algorithms exist in the public domain, the algorithm alone is seldom enough to improve patient outcomes.(2,5,8) Education and focused training for all providers are essential, since those experienced in using a specific insulin algorithm do so more effectively than those who understand neither the context nor the orders.(1,2,9) The Figure shows an example algorithm; these orders have been field tested over many years in six major hospitals and have been used safely in diverse clinical settings.

Another essential aspect of implementing an insulin algorithm is relying on interdisciplinary involvement. Many efforts to improve glycemic control focus on either nurses or physicians when in reality, a patient relies on both to safely order, monitor, and administer appropriate amounts of insulin. Often, a lack of improvement in glycemic control when using a well-designed algorithm may be due to an important new or previously unnoted clinical problem—perhaps a nursing error in the use of the algorithm, an incorrect insulin amount in the delivery system, or an increase in insulin resistance from early cardiovascular collapse or sepsis (with inappropriate adjustments to insulin delivery). Since timely physician input may be life-saving, the algorithm must include criteria as to when the physician must be consulted.

Insulin infusions can be used safely throughout the hospital (i.e., they do not require admission to a step-down unit or intensive care unit) when the system of care allows for adequate training and supervision of those using the selected algorithms. Moreover, the use of hospital electronic health records (EHR) can make bedside glucose results available in real time throughout the hospital system and in remote locations, allowing timely oversight.(10) Computerized physician order entry systems (CPOE) can also be used with approved insulin algorithms to reduce errors in the implementation of medical orders.(10,11)

The Pitfalls of Sliding Scale Insulin Use

In closing, we should also note why the sliding scale–only approach led to near disaster in this patient. Nearly all of the published sliding scale approaches give inadequate amounts of insulin subcutaneously.(12) Subcutaneous absorption may be slow and erratic, particularly in critical illness, and when insulin is given subcutaneously every 4–6 hours, the insulin dosage is often "too little too late." Also, in many sliding scale algorithms, if the glucose level is under 150 mg/dL, there may be no insulin recommended at all, a potentially disastrous error in an insulin-dependent patient with high basal requirements. Insulin-dependent patients develop uncontrolled ketone production, even if fasting, within minutes of the onset of severe insulin deficiency. Dr. Stephen Clement presented two cases of patients with in-hospital deaths due to cardiovascular complications of new-onset ketoacidosis after the use of sliding scale insulin algorithms overnight.(13) Comments also have been published regarding catastrophic insulin errors stemming from inappropriate treatment approaches.(1,2)

Take-Home Points

• Metabolic stressors, such as infections, greatly increase basal insulin requirements, putting patients at risk for hyperglycemia and DKA.
• Sliding scale insulin algorithms alone are not useful for achieving normoglycemia, which is the standard of care for critically ill patients with diabetes.
• Variable-rate insulin infusions are extremely useful, but often underutilized, in treating hyperglycemia associated with severe infections. Implementing these algorithms requires adequate training and supervision of staff and close monitoring of patients.
• Information technology (e.g., EHR and CPOE) can serve as a useful tool to improve monitoring and ordering of insulin, resulting in fewer errors.

Richard Hellman, MD Clinical Professor of Medicine University of Missouri-Kansas City School of Medicine

References

1. Hellman R. A systems approach to reducing errors in insulin therapy in the inpatient setting. Endocr Pract. 2004;10(suppl 2):100-108. [go to PubMed]

2. Hellman R. Strategies to reduce medical errors in the management of diabetes. Updates: Harrison's Internal Medicine [AccessMedicine Web site]. October 9, 2002. Available at: http://www.accessmedicine.com/updatesContent.aspx?aid=395683. Accessed March 15, 2007.

3. Reason J. Human Error. Cambridge, UK: Cambridge University Press; 1990.

4. McManus LM, Bloodworth RC, Prihoda TJ, Blodgett JL, Pinckard RN. Agonist-dependent failure of neutrophil function in diabetes correlates with extent of hyperglycemia. J Leuk Biol. 2001;70:395-404. [go to PubMed]

5. van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345:1359-1367. [go to PubMed]

6. 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;31:359-366. [go to PubMed]

7. 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. [go to PubMed]

8. Goldberg PA, Siegel MD, Sherwin RS, et al. Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit. Diabetes Care. 2004;27:461-467. [go to PubMed]

9. Hellman R. Patient safety and inpatient glycemic control: translating concepts into action. Endocr Pract. 2006;12(suppl 3):49-55. [go to PubMed]

10. Bates D, Clark NG, Cook RI, Hellman R, et al. American College of Endocrinology and American Association of Clinical Endocrinologists position statement on patient safety and medical system errors in diabetes and endocrinology. Endocr Pract. 2005;11:197-202. [go to PubMed]

11. Bates DW, Gawande AA. Improving safety with information technology. N Engl J Med. 2003;348:2526-2534. [go to PubMed]

12. Clement S, Braithwaite SS, Magee MF, et al, for the Diabetes in Hospitals Writing Committee. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27:553-591. [go to PubMed]

13. Clement S. Inpatient diabetes care and insulin delivery. Presented at: Patient Safety and Medical System Errors in Diabetes and Endocrinology Consensus Conference; January 9, 2005; Washington, DC.

Figure

Figure. Example Insulin Protocol. (Reprinted with permission of Richard Hellman, MD.)