Case Study Medication Sleuth: An Important Role for Pharmacists in Determining the Etiology of Delirium
A 65-year-old female, brought into the emergencydepartment by her husband, presented with altered
mental status and increasingly aggressive behavior. Herhusband reported that she had been having trouble sleep-ing and had taken approximately five zolpidem 5-mgtablets to try to alleviate her insomnia. In the emergencydepartment, the patient was becoming increasingly com-
Delirium is characterized by disturbances of consciousness,
bative and was given multiple doses of haloperidol (a
attention, cognition, and perception and is the most com-
total of 15 mg intravenously [IV]) and lorazepam (a total
mon reason for acute cognitive dysfunction in hospitalized
of 6 mg IV) to try to calm her down. She was placed in
elderly patients. Causes of delirium can be multifactorial,
leather restraints and was transferred to the critical care
and a careful medical and medication history can help
unit for one-on-one care. She was started on ceftriaxone
determine the underlying cause of behavioral disturbances.
2 g IV every 12 hours and acyclovir 1 g IV every eight
A 65-year-old patient with a history of chronic pain,
hours for potential encephalopathy, and KCl 10 mEq IV,
insomnia, and multiple medical problems, who presented
with altered mental status and aggressive behavior, is
Her medical history included: diabetes mellitus with
described. The patient had taken an overdose of zolpidem
peripheral neuropathy, hypertension, migraines, anxiety,
prior to admission, and she required chemical and physical
hypercholesterolemia, hypokalemia, and chronic neck
restraints and one-on-one care for safety. With time and
pain. Her husband also reported a surgical history that
washout of the zolpidem, the patient’s behavior did not
included a total abdominal hysterectomy and a tonsillec-
improve. On the second day of admission, medication
tomy. Her outpatient medication regimen, as reported
reconciliation of this patient’s medication profile helped
to reveal a medication cause for this patient’s delirium.
A pharmacist should be included early in the process of
Orlistat 120 mg three times a day with meals
obtaining a medication history. Recommendations for the
Avandamet 2 mg/500 mg one tablet twice daily
management of chronic pain and insomnia in the elderly
KCl 40 mEq dailyHydrochlorothiazide 25 mg dailyPropranolol LA 80 mg dailyParoxetine 30 mg dailyEsomeprazole 40 mg daily
Almotriptan 12.5 mg as needed for migraine
This patient’s allergies/drug intolerances consisted
of nausea with codeine and rash with sulfa-containingmedications. Rebeccah J. Collins, PharmD, BCPS, is Assistant Professor,Virginia Commonwealth University, School of Pharmacy, Geriatric Pharmacotherapy Program, Richmond,Virginia. For Correspondence: Rebeccah J. Collins, PharmD, BCPS,Virginia Commonwealth University, School of Pharmacy, 410 North 12th Street, P.O. Box 980533, Richmond,VA 23298-0533; Phone: 804-828-2296; Fax: 804-828-8359; E-mail: rjcollins@vcu.edu.
2006 American Society of Consultant Pharmacists, Inc. All rights reserved.
VOL. 21. NO. 4 APRIL 2006 THE CONSULTANT PHARMACIST
Case Study: Medication Sleuth—Determining the Etiology of Delirium
Abnormal laboratory values on admission were serum
was no prescription for zolpidem in her medication profile
potassium 3.4 mmol/L and serum glucose of 204 mg/dL.
at the pharmacy.This list was reconciled with the list pro-
All other chemistry and blood count values were within
vided by the patient’s husband.The husband was not aware
normal limits. A toxicology screen revealed the following
that his wife had been taking Oxycontin and did not know
results: negative for salicylate, ethanol, PCP, ampheta-
where she could have gotten the zolpidem tablets.The
mine, cannabinoids, opiates, barbiturates, and tricyclics;
electronic record at her primary care physician’s office
acetaminophen < 10 mcg/mL; and positive for benzodi-
revealed that she was given zolpidem 5 mg tablet samples
azepine. Urinalysis suggested a urinary tract infection
(#15) at her last visit about one month prior to admis-
(UTI), and a urine culture was pending. Blood culture
sion. She was scheduled for a follow-up to reevaluate her
results were negative. No acute findings were revealed
neck and back pain and the effectiveness of Oxycontin and
on a head CT. However, the patient was uncooperative,
had missed her appointment one week prior.
and the study was of poor quality as a result of motion. Vital signs on admission were: pulse 99 bpm, respiratory
Medication-Related Problems of Highest Priority
rate 22, blood pressure 130/79 mmHg, and a tempera-
Differential diagnosis of this patient’s combative behav-
ior consisted of the following: zolpidem overdose,
encephalopathy—viral versus bacterial, cerebral vascular
The hospital family medicine team, which consisted
of an attending physician, a third-year family medicine
Zolpidem Overdose
resident, and a clinical pharmacist, saw the patient dur-
Sedative-hypnotic agents commonly are used by older
ing rounds. She was still restrained and combative, and
people to promote sleep.These agents put older patients
a nurse was providing one-on-one care.The patient was
at risk for falls and hip fractures and can lead to changes
also tearful and did not seem to understand that she
in mental status.1 Zolpidem has been shown to offer no
was in the hospital.The clinical pharmacist called the
benefit in risk profile compared with other sedative
patient’s pharmacy and obtained the following medica-
agents such as benzodiazepines, antidepressants, and anti-
convulsants.2 Doses should not exceed 5 mg in older
patients.3 Our patient took approximately 25 mg in an
effort to promote sleep and overcome withdrawal symp-
Avandamet 2 mg/500 mg one tablet twice daily
toms. Respiratory failure has been reported as a result of
Orlistat 120 mg three times/day before meals
zolpidem overdose.4 Other signs of zolpidem overdose
include drowsiness, coma, and vomiting. Fortunately, our
patient maintained adequate oxygen saturation and stable
vital signs throughout her hospitalization.
Albuterol MDI two puffs every four hours as needed
Medication History Discrepancies
A medication history was obtained from this patient’s
husband without reconciliation from other sources.The
clinical pharmacist was able to identify several discrepan-
cies by contacting the patient’s pharmacy and physician’s
office.Through compilation of the patient’s medication
history, we identified the patient’s risk of opiate with-
According to the pharmacy, she had missed a refill on
drawal and allowed the medical team to treat the patient
the atorvastatin and gabapentin, and she had been with-
appropriately.The patient was given an immediate dose
out her Oxycontin for approximately one week.There
of morphine with subsequent improvement in behavior
THE CONSULTANT PHARMACIST APRIL 2006 VOL. 21. NO. 4
Case Study: Medication Sleuth—Determining the Etiology of Delirium
and symptoms of psychosis.The patient was back to
easily as in this case.Typically the symptoms of delirium
baseline the next day, after receiving a standing order of
resolve within 10 to 12 days; however, up to 15% of
morphine, and was discharged on a taper of oral oxy-
patients will have symptoms that persist up to 30 days
codone/acetaminophen.The patient was scheduled for
close follow-up with her primary care physician. Oxycontin Withdrawal and Chronic Pain Delirium and Combative Behavior Management
Between 20% and 40% of elderly patients will experi-
Opioid addiction rates among patients with chronic,
ence delirium during hospitalization.5 The American
noncancer pain range from 3.2% to 18.9%. Addiction is
Psychiatric Association’s Diagnostic and Statistical Manual,
more common in patients with a history of drug or alco-
4th edition (DSM-IV), characterizes delirium by the
hol abuse.9 While our patient did not have a history of
abuse, she had been taking opioid agents for a number of
There is a disturbance of consciousness, with reduced
years for the management of her chronic neck and back
ability to focus, sustain, or shift attention.
pain, and she had received a recent prescription for a
There is a change in cognition or the development
longer-acting formulation, Oxycontin. Her combative
of a perceptual disturbance that is not better accounted
behavior and altered mental status were likely a result
for by a preexisting, established, or evolving dementia.
of withdrawal from this medication. She had failed to
The disturbance develops over a short period of time
follow up with her primary care physician and therefore
(usually hours to days) and tends to fluctuate during the
ran out of her medication.With reinstitution of an opioid
agent, the patient’s behavior returned to normal. Close
There is evidence from the history, physical examina-
follow up and careful selection of pain medication for
tion, or laboratory findings that the disturbance is
caused by a medical condition, substance intoxication,or medication side effect. Discussion
Impaired sleep may also accompany delirium and con-
Delirium is characterized by disturbances of conscious-
fusion.This patient displayed a disturbance of conscious-
ness, attention, cognition, and perception. It is the most
ness and a change in cognition that had developed over
common reason for acute cognitive dysfunction in hospi-
the period of a single day. Infection, including UTI, can
talized elderly patients. Risk factors for delirium include
be a risk factor for the development of confusion and
dementia, medical illness, alcohol abuse, and increased
altered mental status in the elderly.5 This patient was
blood urea nitrogen level. Benzodiazepines and opioids
given high-dose ceftriaxone for a presumed encephalopa-
are also commonly associated with delirium.5 A pharma-
thy, which also covered her UTI. Upon review of her
cist’s review of a medication profile can detect possible
medication history, we determined that she had taken an
medication-related causes of delirium.Treatment of
overdose of a sedative hypnotic and had been without a
the underlying conditions causing delirium should be
narcotic prescription for several days. She also had been
priority; however, for the patient’s safety, a chemical or
having sleep disturbances as is evidenced by the recent
addition of zolpidem to her medication regimen. Her
The Joint Commission on Accreditation of Healthcare
combative behavior was treated by both chemical and
Organizations (JCAHO), in its 2006 National Patient
mechanical restraints. She had not improved with time as
Safety Goals, requires an accurate and completely recon-
would be expected if her behavior were entirely a result
ciled medication list to be used across the continuum of
of the overdose of zolpidem.The reinitiation of narcotic
care.10 This initiative was established to try to reduce the
therapy successfully brought the patient back to baseline,
number of medication errors in the inpatient setting. A list
and she was able to go home with close supervision.
should be compiled upon admission or at least within the
The ceftriaxone and acyclovir were discontinued, and
first 24 hours and should be maintained throughout the
levofloxacin was ordered to cover the UTI.
patient’s hospital stay. Upon discharge, the list should be
It is important to note that delirium may not resolve as
communicated to the next health care provider. In our
VOL. 21. NO. 4 APRIL 2006 THE CONSULTANT PHARMACIST
Case Study: Medication Sleuth—Determining the Etiology of Delirium
patient case, a list was obtained from a family member.
be assessed for medical/psychiatric reasons for insomnia,
The goal of medication reconciliation is to obtain patient
such as uncontrolled pain, depression, anxiety, or med-
medication information from multiple sources to ensure
ication-related sleep disturbance. Pharmacists can edu-
that an accurate and complete list is compiled. Refill histo-
cate patients regarding nonpharmacological sleep mea-
ries, physician office medical records, family members,
sures and help detect medical/medication reasons for
prescription vials, and previous admission data are all good
sleep disturbances. Pharmacological agents, such as seda-
resources for clarifying medication conflicts. Pharmacists
tive-hypnotics, may be necessary for the treatment of
are the obvious choice for making sure that patients are
sleep disturbances.These agents put older patients at risk
taking the appropriate medications. A 51% reduction in
for falls and hip fractures and can lead to changes in
medication errors has been observed when pharmacists
mental status.1 Benzodiazepines are commonly used for
were involved in obtaining medication histories.11
insomnia; however, these agents can impair sleep quality
However, at most hospitals, pharmacists are not directly
and cause many adverse effects.14 Nonbenzodiazepines,
involved in obtaining medication-history information.12 A
such as zolpidem and zopiclone, are also commonly used
pharmacist should be on the hospital team that prepares a
for sleep. Use of zolpidem in older people has been asso-
standardized medication-reconciliation process.This prin-
ciated with nearly twice the risk of hip fracture and
ciple crosses all patient care settings. Communication
therefore may not be a safe alternative for sleep.1 Long-
between outpatient and inpatient pharmacists would
term use of zopiclone may lead to dependence, but its
greatly aid the medication reconciliation effort.
use has been associated with improvements in sleep pat-
Chronic pain management in the elderly can be a chal-
terns.15 Newer agents may prove to be more safe and
lenge. Opioids are the current standard of care for the
effective; however, actual risks associated with these
treatment of chronic nociceptive pain.9 Longer-acting
agents are unknown. Pharmacists should counsel patients
agents are preferred for continuous, chronic-pain manage-
and their family members on possible adverse effects and
ment because they minimize the occurrence of withdraw-
al and opioid-induced euphoria.13 Therefore, Oxycontinwas an appropriate choice for this patient’s chronic pain. However, it is important to maintain close follow-up and
Take-Home Points
monitor for adverse events. Community pharmacists can
Acute delirium in the newly admitted older
detect changes in a patient’s pain regimen and help moni-
patient can be a result of multiple causes.
tor for effectiveness, as well as toxicity.
Chronic pain and insomnia management require
The prevalence of sleep disturbances increases with
appropriate drug selection and careful monitoring
age.3 Nonpharmacological management should be
exhausted before adding a pharmacological agent forsleep. Nonpharmacological tools for sleep include stimu-
Medication history reconciliation is key in reducing
lus control, sleep restriction, sleep hygiene, cognitive
medication errors and decreasing health care costs.
therapy, and relaxation therapy. Also, the patient should
THE CONSULTANT PHARMACIST APRIL 2006 VOL. 21. NO. 4
Case Study: Medication Sleuth—Determining the Etiology of Delirium References
9. Nicholson B. Responsible prescribing of opioids for the management of
1.Wang PS, Bohn RL, Glynn RJ et al. Zolpidem use and hip fractures in older
people. J Am Geriatr Soc 2001;49:1685-90.
10. Joint Commission on Accreditation of Healthcare Organizations. 2006
2. Rush CR, Baker RW,Wright K. Acute behavioral effects and abuse potential
national patient safety goals. http://www.jcaho.org/accredited+organiza-
of trazodone, zolpidem, and triazolam in humans. Psychopharmacology
11. Bond CA, Raehl CL, Franke T. Clinical pharmacy services, hospital phar-
3.Wortelboer U, Cohrs S, Rodenbeck A et al.Tolerability of hypnosedatives in
macy staffing and medication errors in United States hospitals.
older patients. Drugs Aging 2002;19:529-39.
4. Hamad A, Sharma N. Acute zolpidem overdose leading to coma and respira-
12. Gleason KM, Groszek JM, Sullivan C et al. Reconciliation of discrepancies
tory failure. Intensive Care Med 2001;27:1239.
in medication histories and admission orders of newly hospitalized patients.
5. Korevaar JC, van Munster BC, de Rooij SE. Risk factors for delirium in
Am J Health Syst Pharm 2004;61:1689-95.
acutely admitted elderly patients: a prospective cohort study. BMC Geriatrics
13. Adriaensen H,Vissers K, Noorduin H et al. Opioid tolerance and depen-
dence: an inevitable consequence of chronic treatment? Acta Anaesthesiol Belg
6. American Psychiatric Association. Diagnostic and statistical manual, 4th ed.
14. Petit L, Azad N, Byszewski A et al. Non-pharmacological management of
7. Rockwood K.The occurrence and duration of symptoms in elderly patients
primary and secondary insomnia among older people: review of assessment
with delirium. J Gerontol 1993;48:M162-M166.
tools and treatments. Age Ageing 2003;32:19-25.
8. Sirois F. Delirium: 100 cases. Can J Psychiatry 1988;33:375-8.
VOL. 21. NO. 4 APRIL 2006 THE CONSULTANT PHARMACIST
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