Cases & Commentaries

Is the Admission Drug Dose Too Low?

Commentary By Rainu Kaushal, MD, MPH; Erika Abramson, MD

The Case

A 72-year-old man with a long history of chronic
obstructive pulmonary disease (COPD) was admitted to the hospital
with increasing shortness of breath. His admitting diagnoses were
COPD exacerbation and pneumonia. Among his preadmission
medications, the patient was taking Theo-Dur (extended-release
theophylline), 300 mg three times daily. A theophylline blood
level, drawn on admission, was 1.2 mg/L (therapeutic range: 10-20
mg/L). The admitting physician ordered Theo-Dur, 600 mg TID. A
nurse questioned the order since this was double the patient's
usual dosage, but the physician stated that he needed to get the
patient's blood level up. The patient received Theo-Dur, 600 mg, at
12:00 AM, 5:56 AM, 11:43 AM, and 11:00 PM.

A theophylline blood
level, drawn at 3:22 AM the following day, was 28.7 mg/L. The lab
called the "critical result" to the floor at 6:55 AM. The
night-shift nurse, a recent hire, had not checked to see if the
blood level result was back before giving the patient his next dose
of Theo-Dur at 6:05 AM. Later that day, the patient developed
atrial flutter with a rapid ventricular response (heart rate in the
range of 140 bpm), chest pain, and increased shortness of breath. A
repeat theophylline blood level, drawn at 7:08 PM, was 38.1 mg/L, a
very dangerous level. The patient was given oral activated
charcoal, intravenous digoxin, and a continuous infusion of
diltiazem. The patient's heart rate remained elevated for 3 days
but ultimately returned to normal.

The Commentary

Medication errors are the most common type of
medical error and occur frequently in the inpatient
setting.(1)
This elderly man with long-standing chronic obstructive pulmonary
disease (COPD) suffered a serious cardiac arrhythmia as a result of
a series of errors in dosing theophylline, monitoring for side
effects, and responding to critical information in a timely
fashion.

After presenting with a low theophylline
level, the admitting physician could have verified the patient's
dose and medication compliance, rather than doubling his reported
dose immediately. In addition, when questioned by a nurse, the
admitting physician should have performed additional investigative
steps, such as comparing the admission theophylline level with
previous values obtained during ambulatory care visits. Although
the physician did obtain an admission blood level, many factors
might cause this level to be an inaccurate reflection of the
patient's current medication history. These include inaccurate
recollection by the patient, nonadherence, incorrect administration
(such as crushing the Theo-Dur tablet), and drug–drug or
drug–disease state interactions.

In the inpatient setting, there is often a
mismatch between a patient's preadmission dosage and the dosage
ordered by the admitting physician. This is the focus of medication
reconciliation—a critical safeguard in preventing medication
errors. Medication reconciliation is the process of comparing a
patient's medication orders to all of the medications that the
patient has been taking.(2)
This should be done at every transition of care in which new
medications are ordered or existing orders are rewritten. A study
by Pippins and colleagues found 1.4 unintentional and potentially
harmful medication discrepancies per admitted general medical
patient in a large tertiary hospital.(3) Of these discrepancies, 72% were due to errors in
history-taking, suggesting the importance of verifying patient
histories with pharmacists, primary care providers, or electronic
health information when available. Apparently, none of these
actions were taken in this case. In 2005, The Joint Commission made
inpatient medication reconciliation a National Patient Safety Goal,
focusing nationwide attention on the issue of inpatient medication
errors as patients transition between health care
settings.(2)

Within hospitals, ordering errors are the most
common type of medication errors. A study of adult inpatients found
5.3 errors per 100 orders, with 6.6% being near misses and 0.9%
resulting in actual patient harm.(4)
Medications with a narrow therapeutic index, such as theophylline,
require a heightened level of attention when prescribed. A study by
Aitken and Marten, for example, showed that 65% of toxic
theophylline levels received by their toxicology laboratory
occurred in patients whose levels were not in the toxic range at
admission.(5) In
this case, the admitting physician failed to follow appropriate
guidelines for dosing and monitoring theophylline. For patients
presenting with low theophylline levels, doses should be increased
by 25% and then monitored with serum levels.(6) It is also necessary to verify that all doses have
been taken for 60 hours prior to blood sampling to ensure that
steady state has been achieved and that the level is an accurate
reflection of the chronic dosing regimen. If this is not possible,
comparing the present blood level to past levels (on the same
regimen) may provide a clue as to medication adherence. This
elderly patient had additional risk factors for theophylline
toxicity that should have resulted in an even more cautious
approach to theophylline dosing. Reduced theophylline clearance has
been documented in patients older than 55 years, particularly in
males and those with chronic lung disease.(6)

Other factors in this case also contributed to
the adverse drug event experienced by this patient. Theo-Dur is
usually dosed twice daily, although this physician ordered the
medication three times a day. Despite the TID order, it was
administered at inconsistent intervals such that the patient
received four doses of the drug in less than 24 hours. A "critical
result" that was called to the floor was not appropriately acted
upon, perhaps secondary to nursing inexperience, a transition
between day and night teams, and maybe even a suboptimal critical
test reporting system. Finally, there was likely no urgent need to
achieve a theophylline blood level within the therapeutic range in
the setting of an acute COPD exacerbation. A position paper
published in 2001 by a Joint Expert Panel on Chronic Obstructive
Pulmonary Disease stated that methylxanthines are not beneficial
for treating an acute COPD exacerbation and in fact can be harmful
given their potential serious side effects.(7)

Preventing future similar errors
requires not just individual physician and nurse education, but
also systematic solutions to safeguard against potential harm.
Increasing the availability of medication history information at
the point of care through the use of multiple interventions,
including information technology (IT) applications, would be
helpful. In this case, as the patient had a long history of COPD, a
call to the patient's outpatient pharmacist or the primary care
physician might have confirmed the patient's previous theophylline
doses and levels as well as adherence history.(8) Pharmacy benefit manager data and/or electronic
ambulatory clinical data at the point of care could be of great
assistance in clarifying issues as well.(9) The implementation of interoperable electronic health
records, as stipulated by the American Recovery and Reinvestment
Act, may be very helpful in creating this type of access to medical
information across multiple settings.(10)

Optimizing the critical result
reporting system may also have proven useful in this
case.(11)
This might include a protocol for reporting the laboratory result
if the ordering physician cannot be reached, requiring a
"read-back" mechanism verifying the information, employing
laboratory-based surveillance by clinical pharmacists, and
monitoring internal and external laboratory turnaround
time.

This patient's experience helps to illustrate
several key lessons about improving medication safety for
hospitalized patients:

  • Check, then double-check the
    medication history prior to writing medication orders.
  • When a patient is admitted with a low
    or high dose (or blood level) of a medication, especially those
    with a narrow therapeutic index, consider a triple check.
  • Gather the medication history from
    multiple sources—patient report, other health professionals,
    primary care providers, visiting nurses, pharmacists, and health
    records.
  • Perform medication reconciliation at
    all transitions of care.
  • Employ systematic solutions to
    improve medication ordering, including information technology
    applications.

Rainu
Kaushal, MD, MPH
Chief, Division of Quality and Clinical Informatics

Weill
Cornell Medical College
Director of Pediatric Quality and Patient Safety

Komansky Center for Children's Health

New York-Presbyterian
Hospital

Erika Abramson, MD
Instructor, Division of Quality and Clinical
Informatics

Weill Cornell Medical
College

References

1. Kohn LT, Corrigan JM, Donaldson MS, eds. To
Err is Human: Building a Safer Health System. Committee on Quality
of Health Care in America, Institute of Medicine. Washington, DC:
National Academies Press; 2000. ISBN: 9780309068376.

2. The Joint Commission. Using medication
reconciliation to prevent errors. Sentinel Event Alert. January 25,
2006. [Available at]

3. Pippins JR, Gandhi TK, Hamann C, et al.
Classifying and predicting errors of inpatient medication
reconciliation. J Gen Intern Med. 2008;23:1414-1422. [go
to PubMed]

4. Bates DW, Boyle DL, Vander Vliet MB,
Schneider J, Leape L. Relationship between medication errors and
adverse drug events. J Gen Intern Med. 1995;10:199-205. [go to
PubMed]

5. Aitken ML, Martin TR. Life-threatening
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6. Theophylline (May 2009). In:
DrugPoints® System [Internet database]. Greenwood Village, CO:
Thomson Reuters (Healthcare) Inc. Updated periodically.

7. Snow V, Lascher S, Mottur-Pilson, C; Joint
Expert Panel on Chronic Obstructive Pulmonary Disease of the
American College of Chest Physicians and the American College of
Physicians-American Society of Internal Medicine. Evidence base for
management of acute exacerbations of chronic obstructive pulmonary
disease. Ann Intern Med. 2001;134:595-599. [go to
PubMed]

8. Ko Y, Malone DC, Skrepnek GH, et al.
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9. Kaushal R, Dhopeshwarker R, Gottlieb L, Jordan H. User experiences with pharmacy benefit manager data at point of care. J Eval Clin Pract. 2010;16:1076-1080. [go to
PubMed]

10. American Recovery and Reinvestment Act of
2009. Pub L No. 111-005. [Available at]

11. Kuperman GJ, Teich JM, Tanasijevic MJ, et
al. Improving response to critical laboratory results with
automation: results of a randomized controlled trial. J Am Med
Inform Assoc. 1999;6:512-522. [go to
PubMed]