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Emergent hemodialysis for acyclovir toxicity

Article in The American journal of emergency medicine · November 2005

DOI: 10.1016/j.ajcm.2005.04.012

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Wan-Ching Lien Cheng-Chung Fang

National Taiwan University Hospital National Taiwan University
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American Journal of Emergency Medicine (2005) 23, 899 – 900
Case Reports
Emergent hemodialysis for acyclovir toxicity
Chia-Chun Hsu MD, Ting-I Lai MD, Wan-Ching Lien MD,
Wen-Jone Chen MD, Cheng-Chung Fang MD*
Department of Emergency Medicine, National Taiwan University Hospital, and National Taiwan University,
College of Medicine, Taipei 100, Taiwan
Accepted 15 April 2005
Acyclovir (ACV) is an effective antiviral agent for
remedying herpes simplex virus and varicella-zoster virus
infection. Nephrotoxicity, caused by crystallization of ACV
and intratubular obstruction, was a well-known toxicity of
ACV. In contrast, neurotoxicity, presented as confusion,
hallucinations, seizures, and coma, is rarely encountered.
Clinically, these neurological symptoms have been mis-
interpreted as symptoms of herpes encephalitis [1]. Under
this circumstance, physicians tend to increase ACV dosage
in fear of disease progression. We report a case who
received treatment of ACV then developed concurrent acute
renal failure and neurotoxicity. Her neurological symptoms
dramatically improved after emergent hemodialysis received
in the emergency department (ED). We emphasize the dual
role of emergent hemodialysis as a diagnostic tool in the
differential diagnosis between ACV-induced neurotoxicity
and herpes encephalitis, as well as a fast and reliable
treatment of drug-induced neurotoxicity.
A previously healthy 59-year-old woman had right eye
pain for 3 days after vesicle formation at the forehead.
Under the impression of right herpes zoster involving the
first branch of trigeminal nerve and eye, she received
intravenous ACV, 250 mg every 8 hours, at a local hospital.
Her initial laboratory data revealed normal complete blood
counts. Her blood urea nitrogen (BUN) was 6 mg/dL, serum
* Corresponding author. Tel.: +886 2 2312 3456x5629; fax: +886 2
2322 3150.
E-mail address: cchsu@ha.mc.ntu.edu.tw (C.-C. Fang).
0735-6757/$ – see front matter D 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.ajem.2005.04.012
www.elsevier.com/locate/ajem
creatinine (SCr) was 0.6 mg/dL, and sodium level was
135 mEq/L. Unfortunately, 2 days later, she became drowsy
and lethargic, with incoherent speech and hallucinations.
She was immediately transferred to our ED. Upon arrival,
her blood pressure was 181/117 mm Hg, body temperature
was 37.18C, heart rate was 128 beats per minute, and
respiratory rate was 18 breaths per minute. Although
oriented to places and persons, she was still drowsy and
agitated. Her pupil size was 3 mm symmetrically with
prompt light reflex. Neurological examinations revealed that
muscle strength of the extremities was more than grade
4 symmetrically, and the deep tendon reflex was grade 2 to
3 with negative Babinski reflex bilaterally. Laboratory
studies found that BUN was 45.1 mg/dL (4.5-24 mg/dL),
SCr was 5.0 mg/dL (0.6-1.3 mg/dL), and sodium level was
121 mmol/L (135-148 mmol/L). Magnetic resonance
imaging (MRI) of the head was normal. Lumbar puncture
was refused by the family. Electroencephalography (EEG)
showed mild diffuse cortical dysfunction with more
emphasis in the right hemisphere and regional epileptiform
activities in the bilateral frontal and the right parietal region.
Because of deterioration of renal function and debilitating
nature of neurological symptoms suspected due to
ACV intoxication, hemodialysis was initiated. The pre-
hemodialysis plasma ACV concentration at trough level was
18 mg/L. The therapeutic peak and trough concentrations
ranged from 5.5 to 13.8 mg/L and 0.2 to 1 mg/L, respec-
tively, in adults who received 5 mg/kg of ACV [2]. The
patient underwent two sessions of 4-hour hemodialysis in
2 days. The post-hemodialysis plasma ACV level was
900
decreased to 3 mg/L. Her consciousness became clear and
BUN and SCr were 17.1 and 1.6 mg/dL, respectively. She
was discharged on the fifth day after visiting ED.
There had been various reports on the common side
effects such as nephrotoxicity and neurotoxicity in patients
receiving ACV [3]. Clinically, ACV-induced neurotoxicity
is often similar with herpes-associated encephalitis. Often,
emergency physicians may face challenges in differentiating
these diseases and the dilemma of whether to continue the
medication. Clinically, both herpes-associated encephalitis
and ACV-induced neurotoxicity can be presented as subtle
change of conscious level, ranging from delirium to coma
[4]. Sudden onset in symptoms, absence of fever and
headache, and lack of focal neurological finding are more
frequently encountered in ACV toxicity [4]. Unfortunately,
these clinical findings are not specific. Lumbar puncture,
neurological images, and EEG sometimes can aid us during
differential diagnosis. Although lumbar puncture is an
important test to diagnose herpes encephalitis, about 5% of
patients with viral encephalitis have a normal CSF profile,
which is likely to be confused with ACV neurotoxicity [5].
Brain computed tomography (CT) may be normal in viral
encephalitis, especially early in the illness. Brain MRI is
sensitive in the early stages of viral encephalitis, although,
rarely, it may be normal in this condition [6]. In cases of
ACV neurotoxicity, both CT and MRI are normal. Electro-
encephalography is particularly useful in the diagnosis of
encephalitis showing various forms of discharges that are
not specific to the disease and can be seen in cases of ACV
neurotoxicity [5]. Therefore, these examinations are useful
but not specific to differentiate between the two diseases.
Discontinuation of ACV and removal of the drug by
hemodialysis have proven to be the most effective treatment
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C.-C. Hsu et al.
for neurotoxicity [7]. Furthermore, emergent hemodialysis
can be a rapid way to differentiate between symptoms of
encephalitis and ACV toxicity [8]. By lowering the plasma
ACV level, hemodialysis can restore the renal function and
consciousness level within hours.
In conclusion, the dilemma of rapidly diagnosing cases
of ACV neurotoxicity lies on the need for a specific
diagnostic tool that is readily available in all EDs. Emergent
hemodialysis is a valuable tool for the early diagnosis and
treatment of ACV neurotoxicity.
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