Neuroleptic Malignant Syndrome and Anaesthesia: A Case Report
Pramendra Agrawal1, Abha Agrawal2, Ishwar Singh3
1. DNB Resident Presently working as Senior Resident, JPNATC, AIIMS, New Delhi
2. Consultant, 3. Head of the Department
Department of Anaesthesiology and Intensive Care
Jaipur Golden Hospital, Rohini, New Delhi.
Correspondence: Pramendra Agrawal (pramendraagrawal@yahoo.com)
About the Author: Dr Pramendra Agrawal passed
DNB in Anaesthesiology in the year 2008. He is
presently working as Senior Resident in Jai Prakash
Narayan Apex Trauma Centre, All India Institute of
Medical Sciences [AIIMS], New Delhi, India. His field
of interests include trauma care, regional
interventional techniques and intensive care.
Neuroleptic Malignant Syndrome (NMS) is a life threatening, neurological disorder most
often caused by an adverse reaction to neuroleptic or anti psychotic drugs. We report a case
of Neuroleptic Malignant Syndrome who was posted for an incidental surgery and its
anaesthetic management.
Key Words: Neuroleptic Malignant Syndrome, anti psychotics, hyperthermia
Neuroleptic Malignant Syndrome (NMS) is a rare but potentially life threatening
idiosyncratic reaction to neuroleptic drugs. It causes hyperthermia, muscular rigidity, altered
mental status, elevated creatine phosphokinase (CPK) and autonomic dysfunction. The
underlying pathological abnormality is thought to be the central dopamine D2 receptor
blockade or dopamine depletion in the hypothalamus, nigrostriatal and spinal pathways.
The condition shares many features with the serotonin syndrome and malignant
hyperthermia. Anaesthesia for an incidental surgery in such a patient poses unique
challenges to an anaesthesiologist.
Case Report: An 18 year old male, a known case of Bipolar mood disorder on antipsychotics
was admitted to our Intensive Care Unit with complaints of high grade fever (1060F) for 2
days, agitation and involuntary movements for 8 days and vomiting with altered sensorium
for 1 day. Patient was immediately intubated to protect his airway, intensive measures to
bring down temperature commenced and investigations including haematological, biochemical,
brain imaging and cerebrospinal fluid sent for evaluation. Investigations revealed:
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Agrawal P,Agrawal A, Singh I: Neuroleptic Malignant Syndrome and Anaesthesia : A Case Report 2
leukocytosis (TLC 19,000/mm3), elevated liver enzymes (SGOT 477 IU/l, SGPT 190 IU/l);
progressively increasing Creatine Kinase (1004; 2040; 3270; 39794 U/l), Serum Creatinine
(1.3; 1.5; 1.8 mg/dl) and Serum K+ (4.8, 4.9, 5.5 meq/l). Computed tomography of brain and
cerebrospinal fluid examination were normal. So a diagnosis of neuroleptic malignant
syndrome was made. All antipsychotic medications were then stopped. Tab. Bromocriptine
1.25 mg thrice daily and Tab. Alprazolam 0.25 mg four times daily were started and other
intensive care measures continued. Patient was gradually weaned off ventilator support and
extubated on 6th day.
Unfortunately patient developed a bed sore on the buttock which needed a flap
cover He was posted for surgery on 15th day of admission. A pre-anaesthetic check up
revealed a responsive patient, hypertonia present in all limbs and restricted mouth opening
(just 2 fingers due to hypertonia). Investigations revealed elevated CPK 829 U/l, S. K+ 4.9
meq/l, INR = 1.54; rest of examination and investigations were within acceptable limits.
Anaesthetic management included avoidance of following drugs perioperatively: Inj.
droperidol, succinylcholine, prochlorperazine, promethazine and metoclopramide. Patient
received premedication with alprazolam 0.25 mg at 10 p.m. before the day of operation and
at 6 a.m. on day of surgery. Consent taken and patient shifted to operation theatre. Drip
started with 16 G intravenous cannula and standard monitoring established. Fentanyl 1.5
μg/kg and midazolam 1 mg IV was administered. Anaesthesia induced by thiopentone
sodium 4 mg/kg IV slowly, after pre-oxygenation or 5 minutes and adequacy of mask
ventilation confirmed, muscle paralysis achieved with atracurium 0.5mg/kg. Airway secured
with 34Fr cuffed armoured endotracheal tube orally and anaesthesia maintained with 50%
of O2 + N2O + Isoflurane < 0.4%, fentaynl was used for analgesia and atracurium for muscle paralysis assisted by neuromuscular monitoring. Surgery was conducted in prone position; procedure lasted 2½ hours during which 2 units of whole blood, 2 units of FFP and 1.5 litres crystalloid were infused. Patient remained haemodynamically stable throughout procedure. At end of surgery, neuromuscular blockade was reversed with neostigmine and glycopyrrolate. Trachea was extubated in prone posture itself as requested by surgeons to avoid pressure on flap after patient was awake; Ondansteron 4mg IV was used as antiemetic. Post operatively patient was shifted to post anaesthesia care unit with O2 supplementation and then towards after 2 hrs. Patient was discharged from hospital on 7th post operative day with psychiatry referral. Discussion: Neuroleptic Malignant Syndrome (NMS) was first described by Delay et al during early trials of haloperidol1. The incidence is estimated to range from 0.02–2.4% with The Indian Anaesthetists’ Forum – (http://www.theiaforum.org) Online ISSN 0973-0311 January 2010(4) Agrawal P,Agrawal A, Singh I: Neuroleptic Malignant Syndrome and Anaesthesia : A Case Report 3 conventional anti-psychotics and a much lower incidence for atypical antipsychotics2 The Diagnostic criteria are: • Administration of neuroleptics • Hyperthermia (> 38oC)
• Muscle rigidity
• Five of following: mental status change, tremor, tachycardia, incontinence, labile
blood pressure, metabolic acidosis, tachypnoea/hypoxia, CPK elevation,
diaphoresis/sialorrhea, leukocytosis.
• Exclusion of other central and systemic causes of hyperthermia.
Although NMS has a variable onset and sometimes evolves rapidly, rigidity and
altered mental status usually occur early, followed by autonomic changes and
hyperthermia3. No laboratory tests are pathognomonic of diagnosis. Serum creatine kinase
is frequently elevated reflecting rhabdomyolysis, with resultant risk of myoglobinuric renal
failure. CT scan brain and cerebrospinal fluid examination and sepsis evaluation are negative
in NMS and allow for the exclusion of other causes of fever and neurological deterioration.
Other frequently described laboratory abnormalities include metabolic acidosis, hypoxia,
low serum iron, electrolyte abnormalities, elevated serum catecholamines and
coagulopathies
Differential Diagnosis of NMS: Infectious encephalitis4,5, structural lesion of brain, rare
cases of status epilepticus6, lethal catatonia7, heat stroke, endocrinopathies, drugs,
autoimmune disorders, thyrotoxicosis, phaeochromocytoma, malignant hyperthermia,
serotonin syndrome8. Volatile anaesthetics and succinylcholine are associated with
malignant hypertherma during surgery, which can be confused with NMS if neuroleptics are
administered9
The basic management of NMS remains risk reduction, early diagnosis, cessation of
neuroleptic medications and institution of Intensive, medical and nursing care10,11.
Benzodiazepines, bromocriptine, amantadine or other dopamine agonists may be a
reasonable next step in patients with moderate symptoms of NMS. Dantrolene may be
beneficial in cases of NMS with extreme rigidity and hyperthermia. Electro convulsion
therapy (ECT) is used if NMS is refractory to other measures or who remain psychotic after
NMS is resolved. Since a common pathophysiology has been suggested between NMS and
malignant hypertherima (MH)12,13 the possibility that patients with a history of NMS may be
vulnerable to developing MH is an important factor when considering general anaesthesia,
especially succinylcholine administration. To date, there is no report in the literature of
(MH) as a complication of ECT in NMS patients. However, until the association between
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January 2010(4)
Agrawal P,Agrawal A, Singh I: Neuroleptic Malignant Syndrome and Anaesthesia : A Case Report 4
NMS and MH is conclusively disproved, careful metabolic monitoring of general anaesthesia
is necessary.
Conclusion: Neuroleptics are highly effective medications that have achieved wide spread
use in medicine and psychiatry. However they have been associated with NMS in about 0.2
percent of patients. Awareness of diagnosis, cessation of medications, early medical
intervention and consideration of specific remedies can reduce morbidity and mortality
when NMS occurs.