Cases & Commentaries

Too Tight Control

Spotlight Case
Commentary By Haya R. Rubin, MD, PhD; Vera T. Fajtova, MD

Case Objectives

  • Appreciate the advantages and potential
    complications of intensive insulin therapy in the hospitalized
  • List hospital-based safeguards available
    to prevent insulin-related hypoglycemia
  • Understand the difference between
    efficacy and effectiveness with regards to results of clinical

Case & Commentary: Part 1

A 28-year-old man with insulin-dependent
diabetes mellitus was admitted with hyperglycemia and an infected
foot ulcer. Due to new hospital initiatives aimed at tighter
glucose control, he was started on an insulin drip rather than
subcutaneous insulin. The patient eventually required 8 units of
regular insulin per hour to maintain a fingerstick glucose in the
180-220 mg/dL range.

Traditionally, only patients hospitalized for
acute decompensation of diabetes were treated with intravenous (IV)
insulin drips. More recently, intensive IV insulin therapy is being
used in post-surgical patients for whom diabetes or hyperglycemia
is a co-morbid, rather than a primary, condition. Emerging
literature supports this new approach. In one study, the wound
infection rate was reduced from 3% to 1% using a nurse-managed IV
insulin protocol targeted to keep blood glucose less than 200 mg/dL
for 72 hours after heart surgery.(1) In another,
1500 critically ill surgical patients were randomized to intensive
(IV drip for blood glucose > 110 mg/dL, goal 80-110 mg/dL) and
traditional (IV insulin reserved for blood glucose > 215 mg/dL)
treatment of hyperglycemia.(2) The
intensively treated group had about 50% lower ICU and hospital
mortality rates, shorter hospital stays, and less morbidity.
Although a few episodes of hypoglycemia were noted in the
intensively managed group, there were no serious complications.
These studies have generated a new consensus regarding the benefits
of tighter glucose control in surgical ICU patients.

Given these results, and other studies
demonstrating that hyperglycemia greater than 200 mg/dL is
associated with more infections in patients undergoing "clean"
surgery and in outpatients (and in vitro studies that show that
ambient glucose over 200 mg/dL reduces macrophage migration and
phagocytosis [3,4]), it is tempting to extrapolate that tight
control will benefit medical, and not just surgical, inpatients.
However, there are no data to support this extrapolation. Without
demonstrated benefit in these broader populations, any efforts to
improve glycemic control in such patients (including the one
presented here) must place a premium on safety.

In non-critically ill hospitalized patients with
hyperglycemia, subcutaneous insulin may be safer than an IV insulin
drip. Physiologic insulin replacement requires a basal (delayed or
extended absorption) form of insulin, especially for
insulin-dependent (type 1) diabetes. This basal insulin is
supplemented before meals with fast-acting insulin. New insulin
analogues (such as insulin glargine [Lantus], insulin aspart
[Novolog] and insulin lispro [Humalog]) meet both basal and
mealtime insulin needs. For example, a once-daily dose of insulin
glargine will meet the basal requirement and need not be held or
adjusted for NPO status; whereas, doses of insulin aspart or
insulin lispro will meet mealtime requirements and are easily
adjusted for the patient's nutritional intake. Since the
physiologic attractiveness of using subcutaneous insulin in the
non-ICU patient now conflicts with the potentially generalizable
benefits of IV insulin drips seen in the ICU, we believe that we
are at equipoise, and thus the two methods should be compared in
randomized trials.

Case & Commentary: Part 2

On hospital day 2, the patient was evaluated
by an orthopedic surgeon, who decided the wound needed surgical
debridement. The orthopedic resident notified the cross-covering
medicine resident that the patient would be taken to the operating
room (OR) the following day. In preparation for the operation, the
orthopedic service made the patient "NPO after midnight." At 2 am,
when the nurse came to measure the hourly fingerstick, she found
the patient somnolent, tremulous, and diaphoretic. His fingerstick
glucose was 20 mg/dL.

Hypoglycemia is the most common complication of
any insulin therapy and is an extremely frequent adverse event in
hospitals worldwide.(5) In the
perioperative population, oral intake is highly variable; patients
receiving insulin therapy are at particularly high risk for
hypoglycemia in this period. Broader use of insulin drips outside
the ICU requires that safeguards be put in place to prevent a
potential increase in the frequency of hypoglycemia. The clinical
trials cited used strict protocols (1,2); most
hospitals do not have such guidelines in place (H.R.R., unpublished
data, 2004). Protocols for insulin drips should be created, which
clearly outline proper adjustment of the drip at specific glucose
levels, alterations in rate and IV fluid type if the patient is
NPO, and frequency of glucose monitoring.(6,7)
Automated orders and preprinted order sheets have been effective in
reducing chemotherapy-dosing errors and in ensuring appropriate
therapy for myocardial infarction in the emergency
department.(8,9) Such
interventions could be instituted for insulin dosing. Where
computerized physician order entry (CPOE) and computerized
medication administration records are available, standard orders
could be brought to the screen whenever a patient with diabetes is
admitted or an insulin drip is ordered or begun.

Without seeing the specific insulin drip order in
this case, it is difficult to know how it might have been improved
to avoid the adverse event. However, carefully developed decision
support, to assist in adjusting insulin drips, and
standardization of glucose monitoring in patients on IV insulin
drips might have helped prevent this error. In an even more robust
system of decision support, both orders (NPO status and insulin
therapy) would have been entered into a CPOE system and adjustments
suggested automatically. A pop-up flag could have alerted the
surgeon to ensure the insulin drip was appropriate for the
situation, or that the primary care physician be notified. Finally,
one can even envision a "forcing
function," in which IV insulin is automatically discontinued,
or a dextrose drip started, when an NPO order is written (with the
physician immediately notified), further decreasing the chance of a
mistake harming a patient.(10)

Results obtained in clinical trials often achieve
rates of adverse events lower than those found in routine clinical
practice. There are several reasons for these differences. First,
patients in day-to-day practice are rarely monitored as closely as
those in trials. Secondly, clinicians may administer therapies to
patients who would have been excluded from trials.(11). This
broadening of inclusion criteria can lead to a lesser benefit in
actual practice, an issue known as the difference between the
"efficacy" vs. "effectiveness" of an intervention.(11-14) We
believe that it will be important for the safety literature to
distinguish between patient harm in a clinical trial vs. "practical
safety"—that which can be expected in real world

In this case, the orthopedic surgeon wrote the
NPO order, and did not notice the insulin drip. Allowing consulting
services to write orders on patients may lead to poor
communication, which can then result in errors and poor outcomes
(15): through
delays in diagnosis, unnecessary or duplicative diagnostic tests,
delays in needed treatment, or unnecessary treatment. In the
absence of "smart" information systems, it may be helpful to
provide a procedural forcing function. For example, a hospital
policy might require that the primary physician approve all new
orders (obviously, such a policy will raise important staffing
issues). The widely adopted hospitalist model (16)
may reduce the potential for error that results from multiple
physicians writing orders, as hospitalist services can be
designated to write all orders on inpatients.

Case & Commentary: Part 3

The patient was treated with 1 amp of D50 and
his insulin drip was held. He recovered completely from this

Increasingly, quality improvement efforts focus
on decreasing the extent of "underuse" of effective therapies.
However, even as we focus on ensuring that such therapies are
uniformly used, we must remember that harm can result if no
protocols or systems are in place to help monitor for and prevent
their common side effects. Quality improvement efforts, exemplified
by those of the Institute for Healthcare Improvement in its
"Breakthrough Collaboratives" (17), suggest
that a single, central outcome should be monitored to help make
quality improvement projects practical and do-able. Some refer to
this as "moving the dot," derived from the popular run chart illustrating
changes over time in a particular parameter.(18)

Assuming that "the dot" was the level of glucose
control, this case sounds a cautionary note regarding such an
approach. When our quality and safety improvement projects focus on
correcting underuse of particular medications or therapies, we must
carefully consider adverse events that may be increased by
promoting a particular treatment, and implement safeguards to avoid
them. Like physicians, quality improvement professionals will serve
patients best if we focus on the Hippocratic mantra of primum
non nocere
: first, do no harm.

Take-Home Points

  • Insulin, both intravenous and
    subcutaneous, can be a safe and effective means of controlling
    blood glucose levels in hospitalized patients when appropriate
    standard protocols are followed.
  • Recent data support the practice of tighter
    control (through the use of IV insulin drips) in the surgical ICU.
    The extent to which such data can be generalized to medical and
    surgical patients on the general medical-surgery ward is
  • Protocols for tighter
    glucose control must incorporate adequate monitoring frequency to
    avoid hypoglycemia.
  • Hospitals should implement hospital-wide standard
    insulin drip protocols that have been tested and shown to be
  • Various strategies,
    including standard order sets, decision support, and computerized
    forcing functions, can be used to help prevent adverse
  • Safety in clinical trials differs from safety in
  • Quality improvement
    efforts that focus on increasing use of medications and "tight
    control" of physiologic parameters must incorporate efforts to
    monitor and prevent the most common adverse events of
    over-treatment of those

Haya R. Rubin, MD, PhD
Professor of Medicine
Director, Quality of Care Research
The Johns Hopkins

Vera T. Fajtova,
Assistant Professor of Medicine, Harvard Medical School
Medical Director, Diabetes Management Service, Brigham and Women's

Disclosure: Drs. Rubin and Fajtova have declared that neither
they, nor any immediate member of their family, have a financial
arrangement or other relationship with the manufacturers of any
commercial products discussed in this continuing medical education
activity. In addition, their commentary does not include
information regarding investigational or off-label use of
pharmaceutical products or medical devices.


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