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Doi:10.1016/j.jns.2007.06.052

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 [1] Pelonero AL, Levenson JL, Pandurangi AK. Neuroleptic malignant lowering and controlling body temperature (Bladder syndrome: a review. Psychiatr Serv 1998;49(9):1163–72.
[2] Halloran LL, Bernard DW. Management of drug-induced hyperthermia.
temperature fell from 40.4 °C to 37.7 °C 5.5 h after initial- Curr Opin Pediatr 2004;16(2):211–5.
ization. Temperature was held stable around 37.5 °C until [3] Utili R, Boitnott JK, Zimmerman HJ. Dantrolene-associated hepatic injury.
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- [4] Hadad E, Weinbroum AA, Ben-Abraham R. Drug-induced hyperther- 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 [5] Syverud SA, Barker WJ, Amsterdam JT, Bills GL, Goltra DD, Armao 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 [6] 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 [7] 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 [8] Georgiadis D, Schwarz S, Kollmar R, Schwab S. Endovascular cooling 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 [9] 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.
[10] De Georgia MA, Krieger DW, Abou-Chebl A, Devlin TG, Jauss 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 [11] 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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