Cases & Commentaries

Eptifibatide Epilogue

Commentary By William W. Churchill, MS, RPh; Karen Fiumara, PharmD

The Case

A 62-year-old man was admitted at 11:00 PM on a
Saturday night with the provisional diagnosis of acute coronary
syndrome. Serial testing for markers of cardiac injury was begun,
and he was treated with a beta-blocker, enoxaparin, and a statin.
At 6:00 AM Sunday, the patient's troponin was elevated and the
diagnosis was upgraded to NSTEMI (non-ST segment elevation
myocardial infarction). The intern entered an order for intravenous
eptifibatide (a powerful anticlotting agent given by intravenous
drip) into the computerized order entry system in anticipation of
expedited coronary intervention on Monday morning. The intern
entered the correct weight-based dosage of eptifibatide (a loading
dose, followed by a maintenance infusion of 2 µg/kg/min) into
the order template. Because of a forcing function in the template,
he also had to enter a maintenance infusion rate in milliliters per
hour (mL/hr). He was unsure of the proper infusion rate, so he
arbitrarily chose 0.5 mL/hr. He expected the pharmacist on duty to
make adjustments to the order as needed.

The eptifibatide order was electronically
transferred to the pharmacy for processing. The pharmacist
processed the order as entered, and eptifibatide was sent to the
floor for administration. The nurse on duty was harried because he
was caring for six patients instead of the usual four. He correctly
administered the loading dose and ran the maintenance infusion at
0.5 mL/hr, under-dosing the patient by a factor of 40. The night
shift nurse continued the infusion at this rate, as did the nurse
on the following day shift. The day shift nurse was curious about
the low dose and queried the intern, but the nurse was distracted
by her additional charge nurse duties. The patient was taken to the
percutaneous cardiac intervention (PCI) lab at 2:00 PM on Monday,
by which time his troponin values had peaked and were trending
down. In the PCI lab, the eptifibatide infusion error was
immediately noted. The patient subsequently underwent coronary
angioplasty with stenting. It is impossible to say whether the
underdose of the blood thinner led to more cardiac

The Commentary

The Institute of
Medicine report "To Err Is Human" estimated that more than a
million injuries and nearly 100,000 deaths are caused by medical
errors every year.(1)
Mistakes involving medications are often preventable and are
associated with significant clinical and financial
consequences.(2) An
analysis of serious medication errors determined that 39% of these
errors occurred during medication ordering.(3) Fortunately, computerized prescriber order entry
(CPOE) systems have been found to decrease medication order entry
errors by 55%–80%, thereby significantly improving patient
safety and health care performance.(4-6)
However, this case highlights the shortcomings and unintended
consequences inherent to many CPOE systems.

Clinical Decision

CPOE systems are most effective when they are
integrated into a comprehensive medication use process designed to
decrease medication errors and improve prescribing practices.
Unfortunately, many institutions have implemented CPOE as a
stand-alone, nonintegrated function where it serves as a very
expensive typewriter. These CPOE systems require prescribers to
enter medication orders into the computer, often without providing
critical feedback on therapy appropriateness or other pertinent
clinical decision support. These types of CPOE systems may be
effective at preventing some medication errors, such as those
resulting from illegible handwriting, but they are not as effective
at reducing prescribing errors associated with drug–drug
interactions, drug allergy alerts, or dosing errors. The efficient
and effective integration of evidence-based decision support
systems within CPOE is a necessary component to improve prescribing
practices. Every effort needs to be made to ensure that critical
alerts are shown to prescribers to alert them to potential safety
issues, while at the same time preventing an excessive frequency of
alerts and resultant alert fatigue. When this happens,
clinical decision support systems are rendered

Similarly, some CPOE systems may actually
facilitate medication errors. One recent study identified 22
situations in which CPOE increased the probability of prescribing
errors.(8) The
error in the case above is a classic example of how a forcing
function of a CPOE system can introduce error. During the ordering
of complex medications such as eptifibatide, which require
calculation of a weight-based loading dose, maintenance dose, and
calculation of infusion rate, the potential for order entry error
is high. Ideal CPOE systems should be designed with clinical
decision support to calculate infusion rates based on a maintenance
dose and standardized drug concentration. The system software
should alert the prescriber to any calculation discrepancies or
orders that are outside of the normal range.

Care—Importance of Communication at

Medication errors can also be prevented using
nontechnological solutions. Recent data suggest that adding
clinical pharmacists to the medical team can reduce
medication-related problems and prescribing errors by
66%.(9) In
a study evaluating the effects of pharmacists in the emergency
department (ED) setting, researchers determined that pharmacist
participation on rounds improved processes for managing
high-risk/high-alert medications, enhanced continuity of care, and
increased monitoring for adverse effects of medication
Many patients admitted to the hospital for evolving acute coronary
syndromes are admitted through the ED. The acuity of care and the
fast-paced nature of most ED settings often result in high error
rates. In the case above, if the patient was admitted via the ED
and there was a clinical pharmacist in the unit with experience in
dosing of emergency medications and reconciling dosages with
appropriate infusion rates, the dosing error may have been noted
and communicated to the ordering clinician.

Failures in communication and
ineffective teamwork are leading causes of patient harm. A Joint
Commission analysis of more than 2400 sentinel events indicated
that the root cause of error was communication failure in 70% of
the events.(11)
Often, clinicians who provide care have different perceptions of a
patient's clinical course. Also, the hierarchal nature of medical
practice frequently inhibits team members from speaking up. In
recent years, much effort and research have been dedicated to
improving communication between clinicians (e.g., nurse to
physician) and to improving communication during handoffs. The use
of standardized checklists and simple communication tools such as
SBAR (situation, background, assessment, and recommendation) during
interdisciplinary communication can reduce the potential for
medical errors.(12)

In 2005, the Joint Commission issued a National
Patient Safety Goal requiring hospitals to standardize
communication processes to reduce the potential for errors during
handoffs. Many hospitals have implemented systems designed to
comply with the Joint Commission requirement, such as standardizing
the handoff process, ensuring that handoff information is
communicated in both verbal and written formats, and implementing a
team approach to patient care that allows and encourages all
members of the clinical team to exchange ideas and concerns. The
error described in the present case may have been prevented with
the use of a standardized checklist requiring that infusion rates
be checked during the handoff process. The National Quality Forum
also recommends that hospitals establish organization-wide
approaches to team care as a safe practice for better health


Medications that
have a high risk of causing significant patient harm when misused
are known as high-alert medications. Errors aren't necessarily more
common with high-alert medications, but the consequences of error
are potentially more severe. The Institute for Safe Medicine
Practices (ISMP) has classified 19 medications or medication
classes (including eptifibatide) as high risk.(14) Many institutions have implemented universal
protocols for managing high-alert or high-risk
Some recommended precautions include: implementation of
double-check processes for calculations and pump programming;
barcode verification of all medications during preparation,
dispensing, and administration; use of intelligent infusion
technology; standardization of dilution guidelines and drug
administration guidelines; and use of tall man lettering for
look-alike, sound-alike medications (e.g., HYDROmorphone).
Implementation of some of these precautions, including an
independent double-check process during pharmacy order review and
medication administration, may help to prevent the type of error
described in this case.

Smart Pump

Including smart
infusion pump technology as part of a comprehensive medication
safety system can further help to improve medication safety. Smart
pumps are intravenous infusion devices equipped with
dose-error–reduction software (DERS). The software contains a
customizable list of parenteral medications, standardized admixture
concentrations, and approved dose ranges. If users program an
infusion rate that falls outside of approved ranges (i.e.,
over-doses or under-doses the patient), an alert sounds and must be
acknowledged prior to the start of the infusion. In the case above,
the nurse programming the pump was caring for a larger number of
patients than usual. In situations of stress, the use of alerting
systems may function as a double check. In one study, Fanikos and
colleagues demonstrated a 73% reduction in the frequency of
reported infusion rate programming errors 16 months following
implementation of smart pump technology.(16) The use of smart infusion technology could have
alerted the pump programmer to a potential error.


is also important to ensure that CPOE, pharmacy, electronic
medication administration record (eMAR), and smart pump systems all
share key information with each other in real time. System
connectivity via wireless networks will help to maximize the value
of electronic system double checks in the pharmacy and at the
bedside, improve the synergy between CPOE clinical decision support
and pharmacy systems, and provide real-time information about
medication administration for all care providers including drug,
dose, route, rate, and time of administration.

Take-Home Points

  • CPOE systems (with clinical decision
    support) are one type of technology solution designed to reduce
    medication errors. Additional medication error reduction strategies
    include robust clinical pharmacy information systems, barcode
    verification of medication dispensing and administration, and smart
    pump technology—with all systems connected to each other in
    real time.
  • Clinical decision support tools need to
    be carefully evaluated and designed to ensure that key alerts are
    received and acted upon and do not result in clinician alert
  • Specific processes for high-alert,
    high-risk medications, such as process double-check protocols, can
    help to draw attention to medications associated with significant
    clinical sequelae when used in error.
  • Smart pump technology should be used to
    alert pump programmers of potential overdoses and under-doses.
  • Team training should be a key step in
    educating care providers about the roles and responsibilities for
    each discipline in caring for acutely ill patients.

William W.
Churchill, MS, RPh

Executive Director of Pharmacy

and Women's Hospital

Boston, Massachusetts

Karen Fiumara,

Medication Safety Officer

and Women's Hospital

Boston, Massachusetts


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