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Neuroleptic Malignant Syndrome: A Case Presentation Janel Liane Bernardo Cala PGY1 Pharmacy Resident September 8, 2017 Neuroleptic Malignant Syndrome Infrequent (0.02% 3% neuroleptic use), life threatening Most often associated with

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  1. Neuroleptic Malignant Syndrome: A Case Presentation Janel Liane Bernardo Cala PGY1 Pharmacy Resident September 8, 2017

  2. Neuroleptic Malignant Syndrome  Infrequent (0.02% – 3% neuroleptic use), life threatening  Most often associated with high potency neuroleptics, but all classes have been implicated  including atypical APs and antiemetics (metoclopramide, promethazine)  More likely to develop following initiation of neuroleptic therapy or an increase in the dose of drug  Decreased dopamine activity in CNS  D2 receptor Blockade  Decreased Dopamine availability Onset: can be hours, but mostly 4-14 days after initiation of therapy

  3. Antipsychotics Low Potency High Potency Newer Agents Chlorpromazine Haloperidol Clozapine Thioridazine Perphenazine Olanzapine Pimozide Quetiapine Fluphenazine Aripiprazole Risperidone Ziprasidone Less EPS More EPS More Anticholinergic Less Anticholinergic

  4. Clinical Features Motor Autonomic Hyperthermia Symptoms Instability Altered Elevated CK Mental Status

  5. Risk Factors  Higher doses of neuroleptics  Greater neuroleptic dose increments over short period (<5 days)  Simultaneous use of ≥2 neuroleptic drugs  Parenteral administration of neuroleptics (especially IM depot)  Male gender  Dehydration

  6. Complications  Dehydration  Electrolyte Imbalances  Acute renal failure 2/2 rhabdomyolysis  Cardiac arrhythmias  Respiratory failure 2/2 chest wall rigidity, aspiration  DVT  Seizures 2/2 hyperthermia, electrolyte disturbances

  7. Management  Supportive Care  Pharmacotherapy  Electroconvulsive Therapy

  8. Supportive Care  Discontinue neuroleptic agent or precipitating drug  Maintain cardiorespiratory stability  +/- Mechanical Ventilation  +/- Antiarrhythmics  IV hydration  +/- high volume fluids  Urine alkalinization (IV NaHCO3 )  Lower temperature  Lower BP (Clonidine)  DVT ppx  Control agitation (BZDs )

  9. Electroconvulsive Therapy  Done under general anesthesia  Small electric currents are passed through the brain  Triggers a brief seizure  changes in brain chemistry  reverse illness  Facilitates brain DA activity (?)  Improves  Fever  Sweating  Level of consciousness  For severe and refractory NMS (>48hr)

  10. CASE PRESENTATION

  11.  WK, 35M, presented to MCH ER for Fever, AMS  Per Mom: mental status worse this morning, “speaking like a crazy man”  PMH: Psychosis  Allergy: NKDA  Recent admission in MMH 2/2 Haldol overdose  Home Meds: ergocalciferol 8000 IU/mL; olanzapine 2.5mg qd

  12.  HR 128, RR 25, BP 189/101, Tmax 104  Na 166, K 3.4, Cl 128; CO2 21; BUN 27; SCr 1.5  Sugar 873, Lactate 4, WBC 11.6  AG 22, Osm 372, pH 7.38, HCO3 20  CXR suggestive of PNA  UA clean; (+) ketones, protein  LP not done, mother refused  Drug levels negative (salicylate, EtOH, BZD, opioid, APAP) Initial Diagnosis: DKA, Pneumonia (both managed accordingly), new onset DM (A1C 11.9) Home meds restarted

  13.  Over the course of a few days,  DKA resolved  electrolytes normalized  WBC trended down quickly  Cultures were unremarkable  Still spiking high grade fever despite being on adequate antibiotic therapy  Vitals were unstable  Patient would burst out nonsensical statements intermittently  Disoriented to time and place  Muscle stiffness is seen; Left hand contracture is noted  No facial droop seen

  14.  ID was consulted; Pancultures were sent  Per ID fever’s etiology is unclear; suggested to take CK levels  Olanzapine was discontinued  Bromocriptine 2.5 mg TID was started  Cooling Blanket, APAP prn  Pyrexia started resolving, CK started decreasing, muscle rigidity improving  Psych consult  Transfer out

  15. Olanzapine  Atypical antipsychotic  High affinity to 5HT2A/2C; Dopamine D1-D4, Muscarinic 11-6, Histamine H1 and Adrenergic 1  MOA: 5HT2 + D2 antagonism  T1/2: 21-54 hr (IR); 30 d (ER)  Vd: 1000 L  Adverse effects: orthostatic hypotension, EPS, hypertriglyceridemia, weight gain, hyperglycemia  5- 10 mg/d; titrate in increments of 5mg/day at intervals > 1 week; MAX: 20mg/day

  16. Discussion  Most cases resolve within 2 weeks, usually 7- 11 days  Cases of >6 months motor symptoms are reported  Risk factors for prolonged cause  IM depot antipsychotic injections  structural brain disease  Most patients recover without neurologic sequelae  Patient restarted on neuroleptic agents may or may not have NMS recurrence

  17. Restarting Neuroleptics  Risk factors for recurrence: To restart neuroleptic therapy, Wait at least 2 weeks  Early resumption of Use Low potency neuroleptic therapy Start with low doses and titrate slowly  Use of high potency drugs Avoid lithium Avoid dehydration  Parenteral neuroleptics Carefully monitor for NMS symptoms  Concomitant use of lithium

  18. References  Rajamani, B., Kumar, Y., & Rahman, S. M. F. (2016). Neuroleptic malignant syndrome. Journal of Family Medicine and Primary Care , 5 (1), 178 – 180. http://doi.org/10.4103/2249-4863.184660

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