Chapter 11

Neuroleptic Malignant Syndrome and Hyperpyrexia


Dr. Vasanthi Vidyasagaran*

Department of Anaesthesiology, Kauvery Hospital, Chennai, Tamilnadu, India


Case 1

Young man with severe burns was posted for wound debridement under general anaesthesia. History suggested antipsychotic drug treatment. The patient and the relatives could not give any relevant details. This was an emergency and the patient had to be taken up.

Patient had mild pyrexia – 38.4℃, tachycardia – pulse rate of 110/min. He was induced with Propofol 100 mg and Fentanyl 100 mcg. Anaesthesia was given with Bag and mask ventilation using 1% Sevoflurane/Oxygen/Nitrous Oxide. Haemodynamics was maintained. Bolus of crystalloids 1L and colloids 500 ml were given. BP remained 90/50, HR between 100-120/min. His temperature began to rise despite IV Paracetamol and tepid sponging. Central line was then introduced, as a precautionary step for administration of vasopressors and bolus intravenous fluids, if a situation were to arise, and for CVP monitoring.

Procedure was completed in about 30 min. Anaesthesia was stopped and recovery was attempted. He did not recover smoothly. He was very agitated and confused. He had tachycardia 130-140/min, BP was fluctuating between 100/60-110/60 mm Hg. Temperature was still rising 38-39℃. Tepid sponging continued in the post-operative ward. Few intermittent ventricular ectopics were noted.

Patient developed severe rigidity of the body and was difficult to manage in the postoperative ward. At this point, considering the history, sepsis, neuroleptic syndrome or malignant hyperthermia was the differential diagnosis. Dantrolene sodium was not available in spite of trying hard to procure it.

The plan was to provide supportive management to the patient and shift to ICU. Blood sample was sent to check for creatinine kinase levels. He still had tachycardia and blood pressure maintained at 100/60 mm Hg. Midazolam infusion was started. Ventilatory support was given. On day two, he developed ventricular arrhythmias and succumbed to it despite appropriate treatment and resuscitation.

Case 2

A 28-year- young and fit woman was posted for emergency appendectomy. She preferred general anaesthesia. Rapid sequence induction and intubation was done using thiopentone and suxamethonium. She had mild jaw rigidity while attempting to intubate. Trachea was intubated and ventilation uneventful, GA maintained with Sevoflurane, Oxygen and Nitrous Oxide.

It was noticed that despite analgesia and muscle relaxation patient continued to have tachycardia, and end tidal carbon dioxide values were slowly increasing. Suspecting malignant hyperthermia, temperature was checked and it was 39℃. Cooling methods were applied, Dantrolene was requested for immediately, but was available only after 1 h during which time she continued to receive supportive measures. Injection Dantrolene 1.5 mg/kg was given. Control of cardiovascular events was achieved. Patient was kept intubated for further 24 h, sedated on supportive care. She was extubated after 24 h when clinically stable. She was discharged with a note regarding her condition for future reference.


Both clinical scenarios were interesting and challenging to manage. In the first patient, while we were paying attention to managing a patient with severe burns, unexpected change of clinical events posed a challenge. Diagnosis was tricky. This was probably a case of neuroleptic malignant syndrome in a patient on antipsychotics triggered by stress and surgery. None of the drugs given have been postulated to trigger such an event. Severe burns and stress itself can trigger such situations.

In the second patient, it was quickly suspected to be malignant hyperthermia. The clinical triad of hyperthermia, autonomic instability and rigidity was diagnostic of neuroleptic pathophysiology, either malignant hyperthermia or NMS.

Neuroleptic malignant syndrome (NMS) is a relatively rare but potentially fatal complication of neuroleptic drugs. All classes of anti-psycotics have been associated with NMS and it is common in patients on haloperidol and chlorpromazine. NMS is caused by dopamine depletion or dopamine D2 receptor blockade, which results in abnormal central thermoregulation and muscle rigidity. There is sympatho-adrenal hyper activity and dysregulation which leads to autonomic dysfunction. No laboratory test is diagnostic of NMS.

The molecular basis for NMS is unclear, but studies suggest that genetic factors are involved in its pathogenesis. Involvement of the serotonergic system in NMS has been suggested. Clinical features and elevated creatinine kinase are common for both the conditions of NMS and MH.

Medication associated with NMS are highly potent drugs like Haloperidol. Fluphenazine, Chlorpromazine, atypical antipsychotics like Clozapine, Risperidone, Olanxepine, antiemetic like Metoclopramide and Promethazine.

Drugs to be avoided include Droperidol, Succinylcholine, Prochlorperazine, Promethazine and Metoclopramide. Studies have shown that Isoflurane or Sevoflurane is not associated with hypotension, arrhythmias or seizures, and is safe.


Adnet P, et al. Neuroleptic malignant syndrome Br. J. Anaesth. 2000;85(1):129-35.

Asakura Y, et al. The WHO analgesic ladder and neuroleptic malignant syndrome. Acta Anaesthesiologica Scandinavica 2006;50(10):1311-2.

Silva HCA, et al. Malignant hyperthermia susceptibility in three patients with malignant neuroleptic syndrome. Arquivos de Neuro-Psiquiatria 2000;58(3):713-9.


Chapter 12

No Blood Transfusion – Even if it means Death – Jehovah’s Witness

A 45-year-old man with renal cell carcinoma was admitted to undergo radical nephrectomy. He was very emaciated and undernourished. He was a known smoker. Investigations showed haemoglobin of 7 gm%, renal functions and liver functions were within normal limits. Chest x-ray showed emphysematous changes, ECG and ECHO were within normal limits. He was assessed under ASA III.

The family mentioned that they belonged to Jehovah’s Witness group and would not accept any blood or blood products in any form. The procedure involved high risk of blood loss with requirement for blood transfusion. The team of surgeons and anaesthetists, discussed the pros and cons with them. However, they were very strong in their belief and would not agree on any blood transfusion even in the event of impending death. This was documented and high risk surgical and anaesthesia consent was obtained.

The patient was prepared preoperatively. Haematologist consultation was obtained. It was decided to give him parenteral haematinics and post for surgery a week later, as the surgery could not be delayed further. Vitamin B12 and zinc supplementation and erythropoietin were given.

Surgical team was prepared with the best of equipment and skills. The plan to give general anaesthesia and epidural analgesia was discussed. Post-operative care in intensive care unit was also arranged.

An epidural catheter was placed preoperatively with tip at T8. General anaesthesia was induced using Propofol 100 mg, Fentanyl 100 µg, and muscle relaxant Atracurium 30 mg. Intubated with 8 size cuffed endotracheal tube. Isoflurane, Oxygen and Nitrous Oxide for maintenance of anaesthesia. 0.125% Bupivacaine 8ml with Fentanyl 50 µg was administered in the epidural. His fluid status over 3 hours was maintained with 3 units of colloid (HES) and 3 units of RL. Urine output was maintained at 40 ml/hr during the procedure.

The surgery was smooth sailing, until a tear in a large blood vessel resulting in sudden massive blood loss of about 1 litre. The surgeon managed to achieve haemostasis promptly. However, patient’s BP dropped to 90/40 mm Hg and the heart rate went up to 130 beats/min.

ECG changes were noted with rising tachycardia up to 140 beats/min. ST depression greater than 2mm was noted. Dopamine 8 µg/kg/min was initiated for stabilising BP. Blood or blood products could not be transfused at this stage. Inotrope requirement increased. Noradrenaline was added, and Dopamine was tapered off. Surgery was completed and patient shifted to ICU.

Now we had an ASA 3 patient post major surgery, major blood loss, haem diluted, with haemoglobin 4 gm/dl, ABG showing metabolic acidosis, BE of -5.5, raising levels of lactate and creatinine, high metabolic rate, maintained on inotropic and ventilator support, with 80% Oxygen, and high oxygen consumption.

That night patient suffered further cardiac ischemia and an infarction, which was picked up by changes in the ECG. A bed side echo revealed global hypokinesia. His clinical condition was discussed with the family again and asked for consent for blood transfusion, without which there will be increased chances of morbidity and mortality. However, the family remained very strong in their belief and refused transfusion.

He remained anaemic with a Hb of 4 gms % and continued to have tachycardia for 24 hours. His urine output reduced gradually to less than 20 ml/hour and renal function deteriorated. He eventually suffered cardio-respiratory arrest on the 3rd post-operative day, from which he could not be revived.


Jehovah’s Witness are a group of people who live worldwide, and believe that blood is representation of an individual’s life. Prohibition of blood transfusion is a deeply held core value and is a sign of respect for the sanctity of life. There are no absolute rules regarding blood products. Some Witnesses are willing to accept the use of plasma protein fraction (PPF) or components such as albumin, immunoglobulins and haemophilic preparations, when asked individually.

Given the refusal of blood products in this case, our aim was to conduct ‘blood less surgery’. In preparation for this, our plans included:

1. Haemodilution and hypotensive anaesthesia

2. Tranexamic acid 1 gm followed by another 1 gm after one hour

3. Preoperative administration of haematinics, erythropoietin and Factor VII a – Widespread availability and cost effectiveness of this option is yet to be explored in our country.

4. Damage limiting surgery – meticulous procedure, using fine equipment like the harmonic scalpel, and performed by expert hands

5. Goal directed fluid therapy

6. Early use of vasopressor

7. Cerebral, cardiac and renal protection

8. Postoperative care including ventilator and cardiovascular support to manage oxygen supply demand mismatch due to potential blood loss and low haemoglobin

Any competent adult is entitled to accept surgery and also refuse treatment such as blood transfusion. Hence clear discussion and documentation is required for medico legal implications. Counselling and informed consent is essential. The situation is more complex in paediatric patients.

Management of blood less surgery and anaesthesia has been learnt well and performed successfully. However, they become ‘no win situations’ if there is a major blood loss and patient succumbs to it for want of transfusion. When there is severe anaemia there is gross oxygen supply demand mismatch and patients suffer hypoxia leading to operative mortality and morbidity.

The team involved may be affected due to the ethical dilemma of providing care to this group of patients particularly in an event of death. They may also need to be counselled. This should also be a topic for major discussion and decision making, since we do not feel ethically clear about allowing a patient to die. This may have been a ‘preventable death’ had the patient been given blood at the appropriate time as clinically warranted.

This is a war of ethical dilemma for doctors versus religious beliefs of patient groups.

This leaves us wondering if anyone has the right to give up their life…


Management of Anaesthesia for Jehovah’s Witnesses 2nd edition Published by The Association of Anaesthetists of Great Britain and Ireland, 2005.

Lisa J Milligan et al. Anaesthesia and critical care of Jehovah’s Witnesses. Continuing Education in Anaesthesia, Critical Care & Pain | Volume 4 Number 2 2004 British Journal of Anaesthesia

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