CASE REPORT
Effectively Managing Intractable Central Hyperthermia in a Stroke Patient by
Bromocriptine: a Case Report
Kuo-Wei Yu1, Yu-Hui Huang2,3, Chien-Lin Lin1,4, Chang-Zern Hong, MD5, Li-Wei Chou1,4
¹Department of Physical Medicine and Rehabilitation, China Medical University Hospital,
Taichung 40447, Taiwan; 2School of Medicine, Chung Shan Medical University, Taichung
40201, Taiwan; 3Department of Physical Medicine and Rehabilitation, Chung Shan Medical
University Hospital, Taichung 40201, Taiwan; 4School of Chinese Medicine, College of
Chinese Medicine, China Medical University, Taichung 40402, Taiwan; 5Department of
Physical Therapy, Hungkuang University, Taichung 43302, Taiwan
* Chien-Lin Lin and Kuo-Wei Yu contributed equally to this work.
Correspondence to: Li-Wei Chou, M.D., MS
Department of Physical Medicine and Rehabilitation, China Medical University Hospital
Address: No 2 Yuh-Der Road, Taichung, 404, Taiwan, ROC.
TEL: 886-4-22052121 Extn 2381
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Fax: 886-4-22026041
E-mail address: chouliwe@gmail.com
Disclosures:
No commercial party having a direct financial interest in the results of the research
supporting this article has or will confer a benefit upon the authors or upon any organization
with which the authors are associated.
Running Head: Bromocriptine for Intractable Stroke Central Hyperthermia
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Abstract:
Objective: The characteristics of central hyperthermia included rapid onset, higher
temperature, marked temperature fluctuation. The central hyperthermia had poor response to
the antipyretics and the antibiotics. Although the central hyperthermia post stroke was not
uncommon, the long-term central hyperthermia was rare. We report a case of prolonged
central fever after intracranial hemorrhage. Before an accurate diagnosis and management of
central fever were made, the patient received long-term antibiotic use and which led to
pseudomembranous colitis.
Method: The Bromocriptine was a dopamine agonist and acted at the level of the
hypothalamus and the corpus striatum. The dysfunction of hypothalamus could lead to wide
fluctuations in core body temperature. Thus, the bromocriptine could be used to control the
central hyperthermia. The administration of bromocriptine for this patient was prescribed
with 2.5mg/day for 3 days and then increased to 5mg/day for one month.
Results: The fever didn’t exceed 39° C after the administration of bromocriptine. One week
later, the body temperature baseline was 37° C and only sometimes low grade fever with
minor temperature fluctuation. After discharge to the nursing home, we followed up the
patient and there was no fever one month later.
Implications/Impact on Rehabilitation: Bromocriptine as the first choice to treat the
prolonged central hyperthermia due to the effect of modification of autonomic dysfunction
3
without side effect of baclofen including general weakness and lethargy. After the fever
subsided, the patient could receive aggressive rehabilitation program.
Key words: Bromocriptine; Central Hyperthermia; Fever; Stroke
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Introduction
Fever is a frequent complication of stroke, which is associated with worsened prognosis.
[1, 2] In general, fever is associated with infection. [3] Because of the individual with stroke
is susceptible to various complications including aspiration pneumonia, urinary tract infection
or atelectasis. [4] The fever without documented infection (probably fever of central origin or
the term of “central hyperthermia’’) is 33% in stroke patients in a prospective study. [5] It is
important to differentiate fever of central origin from fever due to infection because of the
treatment strategies were totally different.
Patients with central hyperthermia may have rapid onset, higher temperature, marked
temperature fluctuation and higher mortality. [5, 6] Intracranial hemorrhage especially in
brainstem is more predisposed to central fever than cerebral infarction. Most of stroke
patients with central fever developed fever up to 39°C within one day. Central fever is not
persistent and 90% of stroke patients with central fever abated within 96 hours. It rarely
occurred in the subacute stage of stroke. [7] Besides, the antipyretics have no effect on
central hyperthermia. [8] We reported a patient who suffered from prolonged central fever
after intracranial hemorrhage involved cerebellar, putaminal and brainstem hemorrhagic
stroke. The fever was difficulty to control until the administration of bromocriptine.
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Case report
The 44-year-old male had been well before the onset of stroke. He didn’t have the past
history of autoimmune disease or hepatitis and didn’t have recent travel history. He was sent
to the nearest emergency department of the community hospital because of dizziness and
nausea with occasional vomiting. He was noted to be initially alert and followed by a rapid
decline in mental status.
The patient underwent rapid sequence intubation and was transferred to the emergency
department of the medical center. His blood pressure was 170/117 mmHg. The left pupil
dilatation (6 mm) without light reflex was noted. A head computed tomography (CT) scan
showed a big acute hematoma in left cerebellum (48 mm X 46 mm) with ruptured into the 4th
ventricle causing intraventricular hemorrhage (IVH) and an another acute hematoma in the
pons and midbrain (20 mm X 20 mm) (Figure 1A). Emergency operation of bilateral
suboccipital craniectomy for removal of hamatoma and IVH with external ventricular drain
insertion was performed (Figure 1B). One week later, the conversion of external ventricular
drain to ventriculoperitoneal shunt was done. Because of extubation failure, the patient
received tracheostomy. After condition became stable, he was transferred to the regular ward.
Consciousness improvement with the Glasgow Coma Scale from E1VtM1 to E4VtM5 was
noted. But the intermittent fever was noted since this admission. (Figure 2) The temperature
was characterized by spike fever up to 41°C with marked temperature fluctuations ranged
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from 37°C to 41°C. The neurosurgeon prescribed the Unasyn (Ampicillin and Sulbactam)
empirically for two weeks. The antibiotics were shifted to Tazocin due to the existence of the
Pseudomonas in one set of sputum culture. Because of the intermittent high fever was still
noted, the antibiotics was shifted to Tienam.
Despite the full course of antibiotics treatment and a normal white blood cell count
(WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and negative blood
cultures, the fever persisted. Then he was transferred to the rehabilitation ward. The complete
fever workup was done but no definitely infection source was noted. The autoimmune profile
blood test including antinuclear antibody (ANA) and rheumatoid factor (RF) were all
negative. The tumor markers including carcinoembryonic antigen (CEA), alpha-fetoprotein
and carbohydrate antigen 19-9 (CA19-9) were also negative too. The electroencephalograms
showed no epileptic activity. Because of long-term use of the antibiotics, we check the stool
toxin for clostridium difficile, which showed positive. The pseudomembranous colitis was
diagnosed and the patient received the full course of metronidazole. But the fever with
marked temperature fluctuations and poor response to antipyretics was still noted.
Due to unsolved fluctuated high fever, the inflammation scan was arranged to found out
if anywhere infection or inflammatory, but revealed no occult infections. The physical
cooling including sponging, wet towel and removing clothing were employed to reduce
temperature. But the hyperthermia rose again when ceasing the physical cooling procedure.
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Under the impression of central hyperthermia, the Bromocriptine 2.5 mg/day was prescribed
for 3 days and then increased to 5mg/day. In the following one week, the fever didn’t exceed
39° C. One week later, the body temperature baseline was 37° C and only sometimes low
grade fever with minor temperature fluctuation. (Figure 2) After discharge to the nursing
home, we followed up the patient and there was no fever one month later.
Table 1 showed the fever pattern, impression/diagnosis and management during this
clinical course. After solving the fever problem, the improvement of endurance and
motivation were noted and the patient could receive more aggressive rehabilitation programs.
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Discussion
Fever appeared in 23% of stroke patients and a third of these fever were without
infection documented. [5] Either supratentorial or infratentorial, hemorrhagic or ischemic
might cause elevation in body temperature on the first day of stroke. [9, 10] Although the
central hyperthermia post stroke was not uncommon, the long-term central hyperthermia was
rare. About 90% patient with central hyperthermia exceeding 39° C subsided with 4 days.[7]
It is important to distinguish central hyperthermia from infection with fever due to
totally different treatment. In the present case, the diagnosis of central hyperthermia was
delayed for several weeks and long-term use of antibiotics also led to pseudomembranous
colitis. The overuse of the antibiotics may happen in the patient with central hyperthermia
and led to pseudomembranous colitis. [11]
Because of hyperthermia is detrimental for the recovery of the injured brain and the
duration of fever is associated with poor outcome. [6, 12] Thus, the timely and accurate
diagnosis of central hyperthermia is crucial and could prevent unnecessary antibiotic use. The
characteristics of central hyperthermia included rapid onset (76% developed 39° C within 12
hours after stroke), higher temperature, marked temperature fluctuation. [7] The central
hyperthermia had poor response to the antipyretics and the antibiotics.
The treatment of the central hyperthermia was based on the physical cooling. The
pharmacological management of prolonged central hyperthermia was difficult to study
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because of high mortality and poor prognosis of central hyperthermia. The baclofen was used
successfully to abolish the prolonged central hyperthermia in a case report. [13] But the side
effect of baclofen included drowsiness, tiredness and muscle weakness either on the affected
or unaffected limb. [14] These side effects may interfere with the rehabilitation program.
Some medications have been reported to lower the body temperature after traumatic brain
injury by regulating the sympathetic activity. [15] In another case report, the patient with
traumatic brain injury and high fever up to 40.5° C without documented infection received
the bromocriptine (0.025 mg/kg twice daily and gradually increase to 0.05 mg/kg three times
a day). Comparison of the mean daily temperatures before and after bromocriptine revealed a
significant effect of lowering the body temperatures (P = 0.003). The patient slowly weaned
from bromocriptine over the next 5 weeks. [16]
Bromocriptine was a dopamine agonist and acted at the level of the hypothalamus and
the corpus striatum. [17] The hypothalamus was the regulator of central autonomic activity
and has numerous connections with other parts of the central nervous system. [18] The
dysfunction of hypothalamus could lead to wide fluctuations in core body temperature. [19]
Thus, the bromocriptine could be used to control the central hyperthermia. [16, 17] The
stroke could be associated with autonomic dysfunction and the hemorrhagic stroke was more
commonly than ischemic stroke. [20, 21] On the basis of these reports, we choose the
bromocriptine as our first choice to treat the prolonged central hyperthermia due to the effect
10
of modification of autonomic dysfunction without side effect of baclofen including general
weakness and lethargy. After the fever subsided, the patient could receive aggressive
rehabilitation program.
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Conclusion
This case report describes a phenomenon of prolonged central hyperthermia managed
with bromocriptine. The central hyperthermia should be considered a possible diagnosis in
the stroke patient with fever to prevent unnecessary antibiotic use. The bromocriptine may be
an effective treatment for the central hyperthermia.
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Figure 1. Computed tomography (CT) findings of the brain. (A) Left cerebellar hemorrhage
and brainstem hemorrhage with
IVH showed in the pre-operational CT. (B)
Encephalomalacia change in left cerebellum and midbrain (30 days later after the emergent
operation).
A
B
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Figure 2. The high fever with marked temperature fluctuation was note during the hospital
course while the blood pressure, heart rate and respiratory rate were within normal range. The
body temperature became stable after the administration of the Bromocriptine.
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Table 1. The fever pattern, impression/diagnosis and management during this clinical course.
Days after operation
Fever pattern
Impression/ Diagnosis
Management
2~15
Marked fluctuation
Empirically
Unasyn
16~31
Marked fluctuation
Sputum Pseudomonas
Tazocin
32~42
Marked fluctuation
No obvious fever origin
Tienam
42~54
Marked fluctuation
Pseudomembranous colitis
Metronidazole
54~60
Subsided only in use
Central hyperthermia
Physical cooling
60
Subside
Central hyperthermia
Bromocriptine
18