Authors Scott Mayer, MD - HCA HealthONE, Denver, CO Daniel Kissau, MD – HCA HealthONE, Denver, CO Aakash Ghai, DO – HCA HealthONE, Denver, CO Nikhilesh Srinivasan, MD – HCA Healthcare, Denver, CO James Hunt, MD – Pulmonary and Critical Care Consultants Dmitriy Scherbak, MD – HCA Healthcare, Denver, CO
Case
A 46-year-old female with a past medical history of hypertension and
paroxysmal atrial fibrillation on warfarin presented as a transfer from
an outside hospital with altered mental status.
Upon initial evaluation, patient was obtunded and was unable to
answer questions or follow commands. Her family reported that her mental
status deteriorated from fully alert and oriented over just a few
hours. Her vitals on presentation included a temperature of 36.4° C, HR
of 115 bpm, BP of 198/93 mmHg, RR of 16 /min and a SpO2 of 95% on room
air. Other notable labs included a WBC 17.1 K/uL. The patient’s other
laboratory values were unremarkable including a high-sensitivity
troponin, complete metabolic panel, and international normalized ratio.
Chest XRay demonstrated bibasilar atelectasis. Blood cultures were
obtained, and a urinary analysis was bland. Electrocardiogram
demonstrated sinus tachycardia without evidence of ischemic changes. On
physical exam, the patient had no focal neurologic deficits and her
cranial nerves and brainstem reflexes were intact.
MRI imaging was performed with image shown below.
Question
Administration of which medication is the next best step?
A. Intravenous nicardipine B. Tissue plasminogen activator C. Prothrombin complex concentrate D. Amlodipine
Answer
A. Intravenous nicardipine
Discussion
This patient presented with posterior reversible encephalopathy
syndrome (PRES), also known as reversible posterior leukoencephalopathy
syndrome, secondary to her severely elevated blood pressure. PRES is
characterized by bilateral vasogenic edema in the posterior lobes on
imaging as demonstrated below. The most prudent next step in management
is a rapid reduction in blood pressure using titratable IV
anti-hypertensives such as intravenous nicardipine.
Patients may present with a range of neurologic symptoms including
encephalopathy, seizures, and visual disturbances from involvement of
the occipital lobes. Focal neurologic deficits are also possible due to
complicating ischemic and hemorrhagic strokes.
Neuroimaging is required for diagnosis of PRES. Most cases are
initially detected on CT scan and further characterized on MRI. Imaging
will typically reveal vasogenic edema with a bihemispheric pattern. The
parietal and occipital lobes are most commonly involved, although
extension to the frontal lobes and spinal cord are possible. Lumbar
puncture is not required but is often performed to exclude meningeal
involvement and encephalitis.
The treatment of PRES is aimed at the correction of the underlying
etiology. Consistent with other forms of hypertensive emergency, a rapid
20% reduction of blood pressure in the first hour is recommended
followed by a gradual reduction to a normal range. IV antihypertensives
such as nicardipine are the treatment of choice for the rapid reduction
and titration of blood pressure. Oral anti-hypertensives such as
amlodipine would be inappropriate to achieve a rapid reduction in blood
pressure as they have a longer onset of action, nor can their effects be
titrated in case of over-correction. (Answer D is incorrect).
Correction of the blood pressure most commonly results in the resolution
of clinical symptoms and regression of imaging findings. Potential
complications of PRES include seizures and ischemic or hemorrhagic
strokes. This patient has no evidence of an infarct on imaging and no
focal neurologic deficits on exam, thereby making a diagnosis of a
stroke unlikely. Tissue plasminogen activator would be appropriate
treatment for an ischemic stroke within the first 3-4.5 hours of symptom
onset, however this is not evident by history, exam, or imaging (Answer
B is incorrect). Prothrombic complex concentrate would be an
appropriate treatment for warfarin reversal in a severe hypertensive
hemorrhagic stroke. However, they are not typically seen in the
posterior lobes and are not bilateral. (Answer C is incorrect).
Anti-epileptic drugs may be required if PRES is complicated by seizures.
PRES is a consequence of the breakdown in the blood-brain barrier.
Although a majority of PRES is associated with high blood pressure, up
to 30% of presentations do not feature elevations in blood pressure.
There are several proposed mechanisms for the pathophysiology of PRES
which account for this observed clinical discrepancy in blood pressure.
The first mechanism addresses hypertensive patients; it features
elevated systolic blood pressure causing impaired cerebral
autoregulation and consequential cerebral hyperperfusion leading to
breakdown of the blood-brain barrier. In normotensive patients, however,
the major mechanism is likely endothelial dysfunction resulting in
capillary leakage into the surrounding parenchyma and subsequent edema.
Etiologies of normotensive PRES include cytotoxic medications,
electrolyte derangements such as hypercalcemia, Guillain-Barre syndrome,
and autoimmune disorders, among others. Although these theories
disagree on the degree of cerebral blood flow, both hypotheses have a
common final pathway of cerebral perfusion abnormalities via blood brain
barrier dysfunction with subsequent cerebral vasogenic edema. The edema
creates in the characteristic bihemispheric pattern demonstrated on the
imaging above. Intensivists should be familiar with the
different mechanisms, typical presentation, and imaging findings of
PRES, as prognosis is typically good with early recognition and reversal
of the inciting factor.
References
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