This document summarizes key information about neuroleptic malignant syndrome (NMS) published in 1968 by Delay and Dencker, including that NMS is characterized by fever and rigidity developing within 2 weeks of starting drugs like Serenace, progressing over a week to include hyperthermic dehydration, shock, and potentially myoglobinuric acute renal failure requiring ICU care for about a week. While NMS remained poorly understood even 40 years later, the syndrome typically involves fever and rigidity in the second week of initiating drugs like Serenace, progressing over the next week to include hyperthermic dehydration, shock and/or myoglobinuric acute renal failure, with about 3/4 of cases

1. Delay and Dencker 1968
Still few authentic studies

2. Neuroleptic
• Nonselective dopamine receptor blockers [D2B]
• Introduced in 1952
Malignant
• High mortality [>20 %] in pre-ICU era

3. Subacute evolution
• ~9 days
Autonomic dysfunction
• Hyperthermia
• Labile B.P.
Generalized rigidity
• With necrosis in skeletal muscles
Stupor

4. Major criteria
• 1.Fever 2.Rigidity 3.High CPK
Minor criteria
• 1.Tachycardia 2.Abnormal BP
3.Tachypnea 4.Altered consciousness
5.Profuse sweating 6.High TLC
All 3 major or 2 major +4 minor needed for
probable NMS

5. ~1-2% patients treated with neuroleptics
• Mostly Serenace
• Within 2 weeks of initiation
Risk factors
• Young males
• Affective disorder
• Dehydration
• Renal insufficiency

6. Dopamine deficiency hypothesis
• h/o D2B drugs, esp potent drugs
• Response to dopamine agonists [DA]
[antiparkinsonian drugs]
• Also in withdrawal of DA drugs in PD – called
parkinsonism-hyperpyrexia syndrome

7. Uncertain whether to ban D2B drugs in
future
• No data on relapse rate
• Whether atypical neuroleptics safe
 Olanzepine not safe
Role of co-prescription psychotropes
• Lithium
• Anticholinergics
Role of ECTs

8. Hyperthermia is the most dramatic and
decisive feature
• Dehydration, shock
Other features
• Labile blood pressure
• Tachycardia
• Profuse sweating

9. Common causes of hyperthermia
• Infections
 Malaria, septicemia, meningoencephalitis
• Heatstroke
Uncommon causes
• Malignant hyperthermia syndrome

10. Generalized ‘lead pipe’ rigidity all over
• Pacitane worsens rigidity!
Always subacute [d/d acute EPS]
Secondary muscle necrosis
• CPK and K+
• myoglobinuria Acute Renal Shutdown
ARF is 2nd decisive factor in outcome
SGPT and TLC is common

11. Common [3/4 cases] but insignificant
CT/MRI and CSF are always normal
EEG shows generalized slowing
d/d Lethal catatonia
• Rare encephalitic illness
• Starts as delirium progresses to coma with fever
• Irrespective of neuroleptics

12. Medicolegally difficult to prove as well as
disprove
Doubtful cases of
• Antiemetic D2B drugs use
• Single dose of D2B drug ~10 % cases
• Chronic stable D2B drug use

13. Undisclosed D2B drug use
Poor supervision by care takers with acute
presentations
Malignant hyperthermia
• Strong family history
• Scoline +halothane for surgical anesthesia
• stiff muscles, rhabdomyolysis and hyperthermia
acutely in 24 hrs

14. Hyperthermia, sweating – dehydration,
shock
Myoglobinuria – ARF
Rigidity – respiratory failure
Immobility – DVT, aspiration pneumonia

15. No real systematic studies
Rapid supportive measures
• Cooling
• Rehydration
• Blood pressure monitoring
• Ventilatory support
• Very high caloric needs
No intramuscular injections

16. Stop neuroleptics
Stop lithium and anticholinergics
Start dopamine agonists
• Bromocriptine 2.5 mg as test dose, 5-10 mg tds po
• Apomorphine sq [preceded by rectal domperidone]
Start benzodiazepines

17. Most specific is dantrolene 0.25-3 mg iv or
25 mg tds po
• Hepatotoxic
• Wait for 48 hours before starting
Pancuronium with ventilator
Dialysis for renal failure

18. Life
• Hyperthermia
• Shock and Acute renal shutdown
• DVT  PTE
• Pneumonia
Recovery
• Persistent parkinsonism or dementia in few
• Most recover in 8d-8wks completely

19. NMS exists
• even after 40 yrs
• with little consensus
Fever and rigidity
• in 2nd week of initiation of serenace
Progressing over next week to
• hyperthermic dehydration
• shock and/or
• myoglobinuric ARF

20. Needing
• ICU for about a week
• +/- dantrolene
¾ cases recover completely
Best managed with ECTs thereafter