Neuroleptic Malignant Syndrome

Elevated

1

It's a bright, warm Sunday. You're in the process of choosing between a jog in the park and a relaxed stroll down the street for some ice cream, before heading to the ER for your night shift .... ... only to be interrupted by the sudden ringing of your phone.


2

"I need your help!" says Jane, an old friend, sounding breathless and panicked. "My son, Tierre, has run away." You recall that Tierre, now 20 years old, was diagnosed with schizophrenia around four years ago. Despite proper medical care, and a supportive family enviroment, he has experienced no less than three relapses since the time of diagnosis.


3

Jane's family had recently moved to the city and Tierre seemed to be having a hard time adjusting to his new life. Jane tells you that he has been looking especially upset these last few days. Yesterday, he barely ate, saying that he was unable to swallow. This morning the parents noticed him muttering incoherently, although he has been taking his antipsychotic medication quite regularly. Jane and her husband Mark realized from experience that he may be hallucinating, but before they could calm him down or seek help, he became agitated and ran out the front door screaming "They're out to get me!"


4

"Let's split up and search along the routes familiar to him," you suggest helpfully. Your conversation is interrupted as Jane receives a call on her other line. Mark answers. It's the local police. The police found Tierre sitting on a nearby street corner, holding his head and looking terrified. Thankfully, they quickly figured that he may require medical attention and managed to reassure him and bring him to the nearby hospital, where you work.


5

You tell Jane you'll meet them at the hospital and quickly hang up the phone, grab your keys and leave. You arrive at the ER to find Tierre looking weak but alert and quite agitated. You request his parents to wait outside, and gently ask him what's wrong. "I don't feel well at all. They're out to get me," he says, somewhat effortfully. You reassure him, saying that you can help, and request to examine him, to which he agrees. His temperature is 39˚C (102.2˚F), with a pulse of 130 beats per minute, a blood pressure of 80/50 mmHg, and respirations of 32 cycles per minute. You notice that he is barefoot with small shards of glass sticking out from several cuts on his sole. He is perspiring despite the air conditioning of the ER; he speaks through a clenched jaw with an unemotive countenance, although he is evidently agitated and overly alert to his surroundings.


6

You request for his wounds to be cleaned and dressed and begin fluid replacement with a crystalloid infusion, administering acetaminophen (paracetamol) for his fever. As a catheter is inserted to monitor his output, you notice a dark red discoloration of the outflowing urine. Blood and urine samples are sent to the lab for analysis. Mark looks uneasy. "He still seems quite agitated doctor, and he hasn't been sleeping well these last couple of days. Can we give him haloperidol or something to get him to sleep?"


8

You choose to inject haloperidol but then realize that the test results will arrive shortly and that you may as well wait before making a hasty decision.


9

The labs read as follows: Leukocyte count: 15000 cells/mm3 (3,500-10,500) Creatine phosphokinase (CK): 2100 U/L (15-130) Aspartate aminotransferase (AST): 173 U/L (0-37) Alanine aminotransferase (ALT): 70 U/L (20-60) The urinalysis shows no red blood cells, leukocytes, crystals, or casts.


11

Determined that reducing the agitation will benefit the patient, you inject haloperidol. You then pen in an order for cefotaxime 1000 mg QID to treat his possible sepsis. However, after a while, you notice that Tierre's condition is not improving. He has now developed severe rigidity.


12

You suddenly recall that he has been having difficulty swallowing and that his jaw was clenched during the examination; this along with the ongoing antipsychotic medication makes you revise your diagnosis.


13

You think that Tierre is in septic shock and order cefotaxime 1000 mg QID with vasopressin. However, while rechecking his labs, the lack of RBCs in his urine and elevated CK levels catch your eye. You quickly reconsider your diagnosis and revise the treatment plan.


14

You are now quite sure that Tierre has developed neuroleptic malignant syndrome (NMS). His presentation fulfills the triad of fever, muscle rigidity, and altered mental status. He also has myoglobinuria, elevated CK, blood pressure disturbances, an increased leukocyte count, and raised AST and ALT, the less specific signs of NMS. You manage his agitation with diazepam, knowing that is will also serve as a muscle relaxant. Further, dantrolene and bromocriptine are proven to be useful for the management of NMS; you decide to add them to the therapy. You explain the serious nature of Tierre's condition and the urgent need to withhold neuroleptics to his parents. You reassure the understandably distressed couple, telling them that he is receiving the best possible care, and admit him to the ICU for further management.


15

The next morning, you find that Tierre's condition has not improved. His blood pressure is still labile; he is currently hypertensive at 170/100mm of Hg. Jane looks at you pleadingly, "Is he going to be all right? What needs to be done now?"


17

You're about to suggest increasing the dosages when you recall that these treatments all have narrow therapeutic windows. "We may want to consider electroconvulsive therapy," you say instead. "I'll guide you through the process and answer all your questions. It has been used safely for decades, and the benefits far outweigh the risks in Tierre's case." The couple thanks you and promises to consider your suggestion.


18

You consider a wait-and-watch approach but it strikes you that there is a safe, second line of management that can be employed instead. "We may want to consider electroconvulsive therapy," you say. "I'll guide you through the process and answer all your questions. It has been used quite safely for decades, and the benefits far outweigh the risks in Tierre's case." The couple thanks you and promises to consider your suggestion.


19

"We may want to consider electroconvulsive therapy," you say. "I'll guide you through the process and answer all your questions. It has been used quite safely for decades, and the benefits far outweigh the risks in Tierre's case." The couple thanks you and promises to consider your suggestion.


20

Tierre and his family consent to electroconvulsive therapy and schedule sessions with the psychiatrist. Five sessions later, his condition has improved significantly, and it possible to shift him from the ICU to the psychiatric inpatient unit. A few days later, Jane asks you about restarting Tierre's antipsychotic medication as she is worried he may have a relapse of schizophrenia.


22

As you're about to answer Jane, you recall that the shorter the time to rechallenge, the more likely it is that NMS will recur. It's best to wait at least two to four weeks. "We need to wait for a few weeks before he can start taking the antipsychotics again", you tell her.


23

You're aware that the shorter the time to rechallenge, the more likely it is that NMS will recur. However, Tierre must restart his antipsychotic medication eventually, to prevent a relapse of schizophrenia, especially given the history of three relapses in the four years since diagnosis. "We need to wait for a few weeks and then he can start taking his medication, in order to prevent a relapse of NMS" you tell Jane, who nods in understanding.


24

Tierre recovers uneventfully and the drug rechallenge does not trigger a relapse. A few months later, you get a rare free day and decide to pay a visit to their house, to catch up with Jane and to see how her son is faring. You meet Tierre in the kitchen and are glad to see the once terrified and severely ill boy looking healthy and functioning well. Well done!