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Journal of the Neurological Sciences 264 (2008) 163 – 165
Endovascular cooling in a patient with neuroleptic malignant syndrome
Jennifer Diedler a,⁎, Patricio Mellado a,b, Roland Veltkamp a
a Department of Neurology, University of Heidelberg, Germany
b Department of Neurology, Pontificia Universidad Catolica de Chile, Chile
Received 11 April 2007; received in revised form 20 June 2007; accepted 28 June 2007
We report a case of severe neuroleptic malignant syndrome with hyperthermia, rhabdomyolysis and hepatic failure where we applied
endovascular cooling in order to reverse hyperthermia. After rapid normalization of core temperature at 37.5 °C, the patient's conditionimproved and CK levels dropped. However, upon withdrawl of endovascular temperature control there was a relapse. This is the first casewhere endovascular cooling was applied successfully in neuroleptic malignant syndrome.
2007 Elsevier B.V. All rights reserved.
Keywords: Endovascular cooling; Neuroleptic malignant syndrome
served. Except for detoxification with enteral carbon, notherapy was administered. Since the patient had a psychiatric
Neuroleptic malignant syndrome (NMS) is a rare but
history with a known severe depression she was transferred
potentially life-threatening condition. A crucial therapeutic
to a psychiatric hospital, where she received 20 mg of i.v.
issue is to control hyperthermia . However, standard
haloperidol because of a ‘delirious state’. Soon after
approaches including antipyretic medication such as para-
receiving haloperidol, the patient started shivering and
cetamol or metamizole or external cooling are frequently
hyperventilating, became comatose and developed muscular
ineffective . We report a case of NMS where endovascular
rigidity. After injection of 10 mg of diazepam for suspected
cooling was successfully applied in order to control
status epilepticus, she was transferred to our neurocritical
care unit. Upon admission, her core temperature was 40.4 °C(bladder temperature), she was comatose and had to be
rapidly intubated and mechanically ventilated because ofacute respiratory insufficiency. A cerebral CT scan as well as
A 59 year old woman was admitted to an outside hospital
analysis of cerebrospinal fluid was normal. EEG intermit-
after attempted suicide with 7.5 g of promethazine. Initially,
tently showed generalized slowing, but no epileptic activity.
she was confused but not febrile and there was no muscular
The diagnosis of neuroleptic malignant syndrome was based
rigidity. Intermittent choreatiform movements were ob-
on preceding exposure to promethazine and haloperidol,hyperthermia and severe rhabdomyolsis with substantiallyelevated serum creatinine kinase (CK) levels (CK on
Abbreviations: NMS, neuroleptic malignant syndrome; CT, computed
admission 3515 U/l, CK max 17433 U/l) and myoglobinuria
tomography; EEG, electroencephalogram; CK, creatinine kinase; GOT,glutamic-oxaloacetic transaminase; GPT, glutamic-pyruvic transaminase;
(on admission 17450 ug/l). Other laboratory findings on
PTT, partial thromboplastin time; INR, international normalized ratio; AT
admission included elevated transaminases (glutamic–oxa-
III, antithrombin III; NSAID, non-steroidal anti-inflammatory drugs.
loacetic transaminase (GOT) 731 U/l, glutamic–pyruvic
⁎ Corresponding author. Department of Neurology, University of Heidel-
transaminase (GPT) 159 U/l), leukocytosis (14.29/nl),
berg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. Tel.: +49
elevated CRP (41.1 mg/l), low platelets, low ATIII levels
6221 56 37557; fax: +49 6221 56 4671.
and elevated D-dimers. Upon admission there were no signs
0022-510X/$ - see front matter 2007 Elsevier B.V. All rights reserved.
J. Diedler et al. / Journal of the Neurological Sciences 264 (2008) 163–165
Fig. 1. Temperature, CK, GOT and GPT: The endovascular cool catheter was removed after 6 days. Note the simultaneous rise of temperature and serumcreatinine levels around day 12.
of an infectious focus, the chest X-ray was normal, liquor
sedated and mechanically ventilated. Shivering, a frequent
and blood cultures remained sterile.
side effect of endovascular cooling, was not observed. The
Intravenous metamizole (1 × 1000 mg) and physical
patient’s general condition stabilized over the next two
external cooling with cooling blankets did not lower temper-
weeks and liver function recovered. Due to prolonged
ature. Paracetamol was not administered because of potential
weaning, she underwent tracheotomy. After 21 days she was
hepatotoxicity. Instead an endovascular heat-exchange
transferred to a rehabilitation clinic. At that time, she was
catheter (CoolLine®) was placed into the right femoral vein
awake, followed simple verbal commands and showed no
and connected to the ALSIUS® CoolGard® system. Endo-
vascular cooling was initialized 4.5 h after arrival at our
Upon follow-up three months later, the patient had no
hospital. The temperature was gradually lowered to 37.7 °C
(bladder temperature) over 5.5 h and then held around thetarget temperature of 37.5 °C. Additionally, dantrolene
(40 mg q 6 h) and amantadine (100 mg q 12 h) wereadministered. Further treatment included high-dose cate-
The most urgent therapeutic issue in neuroleptic malig-
cholamine infusion due to cardio-circulatory insufficiency,
nant syndrome, after immediate withdrawal of neuroleptic
forced diuresis and antibiotic therapy with tazobactam and
medication, is reversal of hyperthermia . Commonly
clindamycin for suspected aspiration during emergency
accepted treatments include external physical cooling (e.g.
cooling blankets or ice-packs) and intravenous application of
Despite massively elevated serum CK levels as high as
non-steroidal anti-inflammatory drugs (NSAIDs). Some
17344 U/l and myoglobinuria of 17,450 μg/l our patient did
hospitals perform gastric lavage with cool fluids
not develop acute renal failure (highest creatinine level
Additional general pharmaceutical approaches include
0.61 mg/dl). Instead, elevated transaminases indicated
dantrolene for muscle relaxation and dopaminergic drugs
hepatic failure (GOTmax 13675./l, GPTmax 3655 U/l).
which are aimed at antagonizing the effect of neuroleptic
Furthermore, thrombocytes fell to 53/nl and had to be
drugs at dopaminerg receptors. Dopamine antagonism of
substituted. PTT and INR spontaneously rose and ATIII fell
neuroleptics is the suspected mechanism for induction of
to 36% either as sign of hepatic failure or disseminated
intravascular coagulation. Hepatic ultrasound showed dif-
In our case, NSAIDs and physical cooling were not
fuse parenchymal hyperechoic signals as seen in chronic
successful and both, paracatamol and dantrolene, were
alcohol abuse. Elevation of transaminases is a common
relatively contraindicated because of their potential hepato-
finding in neuroleptic malignant syndrome, however differ-
toxic side effects Therefore we placed an endovascular
ential diagnosis of severe hepatic failure in this case included
heat-exchange catheter (CoolLine®) in the right femoral vein
toxic side effects of dantrolene superimposed on a previously
and started endovascular cooling with the ALSIUS Cool-
Gard® system. The CoolLine® heat-exchange catheter has
The CoolLine® catheter was removed 158 h after
two balloons at the distal end which are connected to a closed
placement. Interestingly, in the days following removal of
loop system. Inside the loop system cooled saline is
the CoolGard® system the patient's body temperature
circulating from the external temperature control unit into
climbed again up to maximum 39 °C which was accompa-
the catheter and back to the control unit. Cooling rates can be
nied by rising CK levels (see During the entire
chosen between maximum power and controlled rate (from
episode of endovascular cooling our patient remained
0.05 °C/h to 0.65 °C/h). Compared to standard methods,
J. Diedler et al. / Journal of the Neurological Sciences 264 (2008) 163–165
endovascular cooling is relatively invasive since it requires
placement of a central line. However, most intensive carepatients will need a central venous catheter and the CoolLine®
The authors declare that they have no competing interests.
catheter provides a triple lumen central line. In addition to
We thank Dr. André Rupp for his kind help revising the
being highly effective, the main advantages of the CoolGard®
system compared to standard treatments are that cooling ratescan easily be controlled and temperature can be held stable at
In our patient, the system proved to be highly effective in
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lowering and controlling body temperature (Bladder
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ization. Temperature was held stable around 37.5 °C until
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day 6. At that time we had to remove the cooling device since
Incidence and character. Gastroenterology 1977;72(4 Pt 1):610–6.
it was needed for another patient. Remarkably, therapeuti-
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cally induced normothermia preceded partial remission of
mia and muscle rigidity: a practical approach. Eur J Emerg Med2003;10(2):149–54.
rhabdomyolysis parameters, and secondary worsening of
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rhabdomyolysis was observed when endovascular cooling
JC, et al. Iced gastric lavage for treatment of heatstroke: efficacy in a
canine model. Ann Emerg Med 1985;14(5):424–32.
Until now endovascular cooling has been performed in
 Al-Senani FM, Graffagnino C, Grotta JC, Saiki R, Wood D, Chung W,
patients undergoing therapeutic moderate hypothermia in
et al. A prospective, multicenter pilot study to evaluate the feasibilityand safety of using the CoolGard System and Icy catheter following
acute stroke or after cardiopulmonal resuscitation
cardiac arrest. Resuscitation 2004;62(2):143–50.
There have also been single case reports of the successful
 Diringer MN. Treatment of fever in the neurologic intensive care
application of endovascular cooling in patients suffering
unit with a catheter-based heat exchange system. Crit Care Med
from heat stroke . To our knowledge, controlled
endovascular cooling has not been previously studied in
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for moderate hypothermia in patients with acute stroke: first results of a
novel approach. Stroke 2001;32(11):2550–3.
Our experience suggests that it is an effective option to
 Keller E, Imhof HG, Gasser S, Terzic A, Yonekawa Y. Endovascular
lower body temperature and reduce rhabdomyolysis.
cooling with heat exchange catheters: a new method to induce andmaintain hypothermia. Intensive Care Med 2003;29(6):939–43.
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M, Davis SM, et al. Cooling for Acute Ischemic Brain Damage(COOL AID): a feasibility trial of endovascular cooling. Neurology
Severe hyperthermia in NMS is a life-threatening compli-
cation of neuroleptic medication. In our case, endovascular
 Broessner G, Beer R, Franz G, Lackner P, Engelhardt K, Brenneis C, et al.
cooling was a comfortable, safe and effective option to cope
Case report: severe heat stroke with multiple organ dysfunction— a novel
with hyperthermia. This technique should be considered in
intravascular treatment approach. Crit Care 2005;9(5):R498–501.
severe cases of NMS when conventional treatment ofhyperthermia fails. Further studies are warranted to evaluateefficacy and influence on prognosis of endovascular cooling inNMS.
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