Download Poster 1

.
Crazy for Cefepime?
Tinsley Harrison
Internal Medicine
Residency Program
Cefepime neurotoxicity in an ICU patient with normal renal function.
Allison Rogers MD, Jeremey Walker MD, Vera Bittner MD
Learning Objectives
• Recognize cefepime as a cause of delirium even in
patients with preserved renal function.
Cefepime
Treatment
Disease Course
Vancomycin
Admitted to
Cardiac Care
unit
Following
commands,
paranoid
Mute with
myoclonus
and spasticity
Disoriented,
agitated on exam
Back to
baseline
• Describe the clinical manifestations and management
of cefepime induced neurotoxicity.
Day 1
Patient Presentation
IV inotropes
and diuresis
initiated
Day 3
Day 6
Broad spectrum
antibiotics started
for suspected
sepsis
CT head negative
Sedating meds
discontinued
69 year old white female with advanced heart failure
admitted for inotropic support and diuresis. Broad
spectrum antibiotics initiated for suspected sepsis.
Day 11
EEG findings
ICU Delirium
Supportive Measures
• Cefepime encephalopathy is an under-recognized
cause of ICU delirium
Identify Underlying
Causes
Manage Agitation
Electroencephalogram showing generalized
sharp and slow wave discharges.
http://dx.doi.org/10.1016/j.yebeh.2005.09.010
Cefepime Encephalopathy
Drug Induced
Metabolic
Electrolytes
• Neurotoxicity is a known, but rare complication of
cephalosporins due to competitive binding of GABA
receptors causing increased excitatory
neurotransmission.
• Symptoms include confusion, hallucinations,
myoclonus, seizure, and coma.
• Recent observational study reported 15% of exposed
patients within a critically ill population developed
cefepime-induced neurotoxicity.
EEG
performed
Cefepime
discontinued
Day 10
Take Home Points
• After 72 hours of antimicrobials, patient developed
acute mental status changes.
• Physical exam notable only for mental status changes.
• Vital signs stable.
• Atypical antipsychotics administered without
improvement.
Introduction
Day 8
Day 7
• Discontinuation of cefepime
• Supportive measures
- Consensus favors benzodiazepine use for
agitation as neurotoxicity GABA mediated
- Avoid over-sedation
• Antipsychotics or antiepileptics
- No proven benefit
- Literature suggests conservative approach
136
99
15
112
3.9
24
0.6
Common causes
excluded:
- Hyper/hyponatremi
a
- Hypoglycemia
- Acidosis
- Uremia
Infectious
9.4
8.9
252
30
Blood cultures/UA/
CXR all negative
Common causes
excluded:
- Bacteremia
- Pneumonia
- Urinary tract
infection
Organ failure
Albumin 4.5, Tbili 1.0
Ammonia 26
Alk phos 99
ALT/AST 22
ABG 7.46/36/83/26
CT head negative
Common causes
excluded:
- AKI
- Hepatic injury
- Stroke
Common drugs causing
delirium:
-
Digoxin (level 1.3)
Anticholinergics
Anticonvulsants
Benzos
Opioids
Corticosteroids
Antibiotics
• Almost all patients initially
exhibit confusion and
disorientation
• One-third progress to
myoclonus
• One-tenth epileptiform activity
• Onset seen on antibiotic
day 1-10
• Typically seen in patients:
- older than 50
- with underlying renal
dysfunction
• Long-term prognosis unclear
• In patients with acute mental status changes,
consider cefepime when reviewing medications.
Consider EEG if uncertain etiology.
• Treatment of cefepime encephalopathy is
discontinuation of cefepime and supportive care.
References
•
•
•
•
•
•
Qingping S, Feng D, Ran S, Yan L, HaoYu Y, Meiling Y. Drug use evaluation of cefepime in the first
affiliated hospital of Bengbu medical college: a retrospective and prospective analysis. BMC
Infectious Diseases. 2013;13:160. doi:10.1186/1471-2334-13-160.
Cephalosporin-induced neurotoxicity: clinical manifestations, potential pathogenic mechanisms,
and the role of electroencephalographic monitoring. Marie Francisca Grill, Rama Maganti Ann
Pharmacother. 2008 December; 42(12): 1843–1850. Published online 2008 November 25. doi:
10.1345/aph.1L307.
Fugate et al.: Cefepime neurotoxicity in the intensive care unit: a cause of severe,
underappreciated encephalopathy. Critical Care 2013 17:R264.
Chow KM, Szeto CC, Hul AC, et al. Retrospective review of neurotoxicity induced by cefepime and
ceftazidime. Pharmacotherapy 2003;23: 369-73.
FDA Drug Safety Communication: Cefepime and risk of seizure in patients not receiving dosage
adjustments for kidney impairment. <http://www.fda.gov/Drugs/DrugSafety/ucm309661.htm>.
Accessed 1/28/16.
Gaspard, N. et. al. Nonconvulsive Status Epilepticus. In: UpToDate, Eichler A. (Ed),
UpToDate, Waltham, MA. (Accessed on January 28, 2016).