Cases & Commentaries

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Commentary By Richard Hellman, MD

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.)

Click on thumbnail for a larger view