Cases & Commentaries

Vial Mistakes Involving Heparin

Commentary By Tim Vanderveen, PharmD, MS

The Case

A 65-year-old man was admitted to the hospital
for an elective left carotid endarterectomy. During the procedure,
the surgeon requested 5000 units of intravenous (IV) heparin prior
to clamping the carotid artery. The anesthesiologist administered 5
mL of heparin from what he believed was a 1000 units/mL
concentration vial. After 3 minutes, an activated clotting time
(ACT) was drawn while the surgeon clamped the carotid artery and
proceeded with the surgery. When the ACT returned normal rather
than prolonged (as it should have been after the heparin), the
anesthesiologist repeated the ACT to confirm the result.

The anesthesiologist then re-dosed and
administered what he thought was 7000 units of heparin as the
surgeon grew concerned about the cross clamp time without adequate
anticoagulation. When a repeat ACT once again returned normal, the
anesthesiologist requested a new batch of heparin vials while
reaching into the garbage and picking up the vial from which he had
drawn. He quickly realized that the heparin vial from the
garbage was a 10 units/mL
concentration rather than a 1000 units/mL as intended. The two
vials of heparin were designed to be color differentiated with
different shades of yellow, and the anesthesiologist had chosen the
wrong one from the cart. Another dose was administered from the
correct vial, and the patient's ACT time rapidly became
appropriately therapeutic. Luckily, the prolonged clamp time
without anticoagulation led to no obvious clinical harm, making
this a serious "near miss" event.

The Commentary

This heparin error is similar to two highly
publicized heparin concentration mix-ups involving neonates. At
Methodist Hospital (Indianapolis) in 2006,
three infants died and three were injured when nurses administered
heparin flushes prepared from 10,000 units/mL vials rather than
from similar-looking vials containing the 10 units/mL concentration
used to flush intravenous catheters.

The 10,000 units/mL vials had inadvertently
been loaded into the automated dispensing cabinet (ADC) drawer that
usually held 10 units/mL vials, and multiple nurses administered
the high-concentration heparin as catheter flushes. One year later
at Cedars-Sinai Hospital, Dennis Quaid's newborn
twins also were administered high-concentration heparin in place of
the heparin flush. In both cases, numerous system errors were
identified. These included storage issues in the pharmacy, an
omitted second manual check or bar code scan before dispensing,
confirmation bias on the part of nurses
selecting the vials, a 1000-fold difference in concentration
between similar-looking vials, and delay in recognizing the cause
of the sudden change in each infant's condition.

This operating room (OR) case also involved a
look-alike packaging issue (Figure). However, instead of inadvertent
substitution of high-concentration for low-concentration vials in
the ADC, apparently both high-concentration and low-concentration
vials were intentionally stocked on the anesthesia cart,
greatly increasing the potential for error. If similar practices
exist in other ORs, additional accidents are waiting to
happen.

Heparin Errors in the
OR

In 1984, medication errors were
reported as a leading cause of adverse events during
anesthesia.(1) In
2001, one drug administration error was reported for every 133
anesthetics administered.(2)
More recently, the United States Pharmacopeia's MEDMARX database
identified 3298 medication errors in the OR from 1998 to 2005.
Heparin was involved in 143 (3.9%); however, it was second among
the drugs most frequently associated with patient harm.(3) Of
particular interest, a past study reported that nurses found the
expected placement of a drug container in an ADC to be most
important in selecting a medication, while anesthesiologists found
the color of the container most important.(4) In the infant error cases highlighted, nurses pulled
the concentrated heparin from the expected location, while in the
OR error, a similar-color vial was selected.

Heparin is unique in the wide range of doses used
clinically. When used to flush IV catheters, heparin concentrations
typically range from 1-10 units/mL. When continuous infusion is
used for systemic anticoagulation, the final concentration is
usually 50 or 100 units/mL. Complicating matters is that initial
loading or bolus doses prior to continuous infusion are typically
prepared from a concentration of 1000 units/mL. Most pharmacies
purchase heparin infusions in pre-mixed IV bags from IV fluid
manufacturers to comply with Joint Commission National Patient
Safety Goals (NPSGs).(5)
Current shortages may force hospitals to accept alternate
concentrations just to have heparin available. With available
concentrations ranging from 1-20,000 units/mL, substitutions with
infrequently used concentrations can lead to serious errors.

Adding to the challenges, heparin infusions
prepared in the OR or in procedure areas may not be the same
concentration used in inpatient treatment areas. This poses
significant risk if infusions are transferred with the patient from
an OR to an inpatient unit. Failure of nurses to recognize
concentration differences can lead to serious errors when dosages
are adjusted or heparin containers are changed to a different
concentration. The Joint Commission has mandated limiting the
number of available concentrations of high-risk IV medications.
Nonetheless, review of a 207-hospital sample identified 15
different concentrations in drug libraries intended for IV
infusions.(6)

Finally, there is significant variability in
prescribing doses of heparin and programming the infusion on
infusion pumps. For example, the surgeon may recommend a dose in
units/hr, with the anesthesiologist converting this dose to a rate
in mL/hr and programming the infusion pump. Then upon transfer of
the patient from the OR with the continuous infusion, the nurses
may reprogram the pumps using the dose, either in units/hr or
units/kg/hr. A review of 54 hospitals' practices showed that 48%
standardized units/hr for infusion pump programming, 23% used
units/kg/hr, and 29% used both weight- and non–weight-based
dosing. Hospitals using smart IV pumps (computerized IV infusion
pumps with dose-errorreduction software
[DERS]) with both weight- and non–weight-based heparin
selections had a four-fold higher incidence of averted programming
errors identified by the DERS than those that standardized on
units/kg/hr programming.(6)

Strategies to Reduce Heparin
Errors

With the incredible variability possible in
heparin use, and the related potential for patient harm,
identifying unsafe practices and opportunities for error prevention
must be a shared responsibility. Progress has been and continues to
be made to improve the safety of heparin therapy in inpatient
settings, including tight control or removal of concentrated
heparin floor stock; standardization on a single concentration of
"pre-mixed" heparin for continuous infusions; pharmacist review of
medication orders prior to administration; heparin dosing
protocols; and point-of-care technologies for nurses including bar
code medication administration, smart IV pumps, and electronic
medication administration records. However, these advances are much
more difficult to apply in the OR. For example, orders for heparin
are verbal, there is no pharmacist review, the heparin doses are
prepared by the same clinician administering the drug, and bar code
and other technology solutions are not easily adapted to this
environment. In addition, the transition of patients from the OR to
inpatient units may include continuation of heparin therapy.

The Joint Commission 2009 NPSGs
specifically address medication labeling in the OR (NPSG 03.04.01)
and set forth performance standards for the safe use of
anticoagulant therapy (NPSG 03.05.01) throughout the
hospital.(5)
Although this is a good start, there is no one "silver bullet" that
can address all safety risks for drugs such as heparin. Certainly,
widespread publicity about infant deaths did not prevent the same
error from happening again, and regulations typically set forth
minimum standards but leave the implementation specifics to each
institution. Ideally, a multidisciplinary assessment of heparin use
in the OR would include anesthesiologists, surgeons, pharmacists,
OR nurses, and nonprofessional OR staff. The goals of this
assessment should include identification of unnecessary variation;
agreement on how to standardize practices, procedures, and
products; shifting of responsibilities where appropriate; and
creation of an ongoing method of monitoring compliance with the
required changes. Applying aviation principles of crew resource
management to the OR is one example of an approach that can have
dramatic benefits.

From my experience and consultation with several
medication safety experts, specific recommendations to prevent
heparin errors in the OR would include:

  • For single-dose, therapeutic
    anticoagulation, stock anesthesia carts or pharmacy-prepared
    medication trays with a single concentration of heparin.
  • Use a manual double-check or bar code
    verification system for items being dispensed by pharmacy.
  • For continuous infusions of heparin, use
    the same standard heparin concentration used in inpatient care
    areas. There is no need for anesthesiologists to admix heparin to
    IV containers since commercially pre-mixed containers are widely
    available.
  • Standardize all heparin loading and
    maintenance doses on either weight-based or non–weight-based
    dosing. Eliminate the use of multiple dosing units and switching
    between dosing units.
  • If smart IV pumps are in use, require
    anesthesiologists to use the safety features. Any continuous
    infusion transferred from the OR with a patient should be
    programmed using the dose and not the infusion rate.
  • Eliminate vials of heparin intended for
    flushing IV catheters and evaluate the need for heparin flushes,
    since their use is appropriately declining in favor of saline
    flushes.
  • If heparin flushes are to be used, use
    manufacturer- or pharmacy-prepared syringes; do not require
    anesthesiologists to prepare IV flushes from vials of concentrated
    heparin intended for therapeutic use.
  • If high-risk medications must be
    prepared in the OR, consider an independent double-check by a
    qualified, knowledgeable clinician.
  • Label medications removed from original
    containers immediately in accordance with Joint Commission
    requirements.(5)
  • Keep all original medication containers
    used during a case until the end of the case, and discard all
    opened containers at the conclusion of the case.(5)
  • Have pharmacy purchase with safety in
    mind. This incudes purchasing ready-to-use items whenever possible.
    Pharmacy must assess the risk of vial mix-ups due to similarly
    packaged containers, including vials of similar size and
    coloring.
  • Establish policies and procedures to
    immediately communicate any heparin product substitution involving
    a different concentration, through the use of emails, posters, and
    special auxiliary labels on the heparin container, etc.
  • Give special consideration to pediatric
    use of heparin since most drugs stocked in anesthesia are intended
    for adult use.

Take-Home Points

  • Heparin administration is fraught with
    risks for error, largely due to the tremendous variability in
    dosing usage and available concentrations.
  • For error prevention, only vials
    containing a single, standardized concentration of heparin should
    be stocked in the OR, and when patients are moved from an OR to an
    inpatient unit, the programming and choice of concentrations for
    use should remain consistent.
  • All aspects of the heparin
    administration process must be standardized.
  • Any variation from the use of the
    standardized products must be minimized or immediately communicated
    to all concerned.

Tim Vanderveen,
PharmD, MS
Vice President

Center
for Safety and Clinical Excellence

Cardinal
Health Center for Patient Safety and Clinical Improvement

San Diego,
California

References

1. Cooper JB, Newbower RS, Kitz RJ. An analysis
of major errors and equipment failures in anesthesia management:
considerations for prevention and detection. Anesthesiology.
1984;60:34-42. [go to PubMed]

2. Webster CS, Merry AF, Larson L, McGrath KA,
Weller J. The frequency and nature of drug administration errors
during anesthesia. Anaesth Intensive Care. 2001;29:494-500.
[go to
PubMed]

3. Hicks RW, Becker SC, Cousins DD. MEDMARX Data
Report: A Chartbook of Medication Error Findings from the
Perioperative Settings from 1998-2005. Rockville, MD: USP Center
for the Advancement of Patient Safety; 2006. [Available
at]

4. Smellie GD, Lees NM, Smith EM. Drug
recognition by nurses and anaesthetists. Anaesthesia.
1982;37:206-208. [go to PubMed]

5. The Joint Commission. Accreditation Program:
Hospital. Chapter: National Patient Safety Goals. The Joint
Commission on Accreditation of Healthcare Organizations; 2008.
[Available at]

6. Vanderveen TW, Crass
R, Lewis SR, et al. Impact of multiple dosing units on heparin
programming errors. Abstract presented at: Society of Critical Care
Medicine 37th Critical Care Congress; February 2-6, 2008; Honolulu,
HI.

Figure

Figure. Example of similar-looking heparin
vials. (Note: The vials pictured were not involved in the
presented case.)