What is the work-up for a patient (Pt) with schizophrenia and fever, presenting with acute altered mental status and increased muscle tone?

From the Guidelines

For a patient with schizophrenia presenting with fever, acute altered mental status, and increased muscle tone, neuroleptic malignant syndrome (NMS) should be immediately considered, and initial management includes discontinuing all antipsychotic medications and providing supportive care. The clinical presentation of NMS, as described in 1, includes hyperthermia, altered mental status, muscle rigidity, and autonomic instability, which are all present in this patient. The treatment of NMS, as outlined in 1, involves primarily supportive care and removal of the initiating agent, which in this case would be the antipsychotic medication.

Key considerations in the work-up of this patient include:

• Discontinuing all antipsychotic medications and transferring the patient to an intensive care unit
• Initiating supportive care with IV fluids and cooling measures
• Laboratory workup, including complete blood count, comprehensive metabolic panel, creatine kinase, urinalysis, blood cultures, and toxicology screen
• Specific pharmacologic treatment, such as dantrolene sodium (1-2.5 mg/kg IV every 6 hours) to reduce muscle rigidity and bromocriptine (2.5-10 mg orally three times daily) to address dopamine blockade
• Alternative diagnoses to consider, including serotonin syndrome, malignant hyperthermia, malignant catatonia, and central nervous system infections
• Benzodiazepines, like lorazepam (1-2 mg IV every 4-6 hours), can help with agitation and muscle rigidity

According to 1, the American Psychiatric Association recommends that patients with schizophrenia be treated with an antipsychotic medication and monitored for effectiveness and side effects. However, in the case of NMS, the priority is to discontinue the antipsychotic medication and provide supportive care. Once the patient stabilizes, careful reintroduction of antipsychotics may be considered after 2 weeks, preferably using a different class than what precipitated the episode. NMS is a life-threatening emergency with mortality rates of 10-20%, caused by dopamine blockade from antipsychotics, resulting in autonomic instability, muscle rigidity, hyperthermia, and altered mental status.

From the FDA Drug Label

Dantrolene Sodium for Injection is indicated, along with appropriate supportive measures, for the management of the fulminant hypermetabolism of skeletal muscle characteristic of malignant hyperthermia crises in patients of all ages Dantrolene Sodium for Injection should be administered by continuous rapid intravenous push as soon as the malignant hyperthermia reaction is recognized (i.e., tachycardia, tachypnea, central venous desaturation, hypercarbia, metabolic acidosis, skeletal muscle rigidity, increased utilization of anesthesia circuit carbon dioxide absorber, cyanosis and mottling of the skin, and, in many cases, fever)

The patient's symptoms of fever, acute altered mental status, and increased muscle tone may be indicative of malignant hyperthermia, a condition for which dantrolene is indicated. Key considerations include:

• Rapid recognition of malignant hyperthermia reaction
• Prompt administration of dantrolene by continuous rapid intravenous push
• Supportive measures to manage the condition 2

From the Research

Clinical Presentation

• The patient presents with schizophrenia, fever, acute altered mental status, and increased muscle tone, which are characteristic symptoms of neuroleptic malignant syndrome (NMS) 3.
• NMS is a life-threatening idiosyncratic reaction to antipsychotic drugs, and its clinical features include fever, altered mental status, muscle rigidity, and autonomic dysfunction 3.

Diagnosis and Treatment

• The diagnosis of NMS requires prompt recognition to prevent significant morbidity and death, and treatment includes immediately stopping the offending agent and implementing supportive measures, as well as pharmacological interventions in more severe cases 3.
• Different therapies for NMS, such as dantrolene, bromocriptine, and electroconvulsive therapy (ECT), have been compared, and the results suggest that specific NMS therapy is advantageous over purely symptomatic therapy in severe NMS cases 4.
• The approach to the pharmacotherapy of NMS is based on the available evidence, and the importance of this case report is to highlight the lack of robust evidence-based treatment for this emergency 5.

Risk Factors and Outcomes

• The incidence of NMS is associated with antipsychotic treatment change, increased number of antipsychotics, higher antipsychotic dose, co-treatment with anticholinergics, lithium, benzodiazepines, and comorbid cardiovascular disease 6.
• The mortality rate for NMS associated with atypical antipsychotic drugs is lower than that with conventional antipsychotic drugs, and the mortality rate may simply be a reflection of physicians' awareness and ensuing early treatment 7.
• Long-acting injectable antipsychotics (LAIs) are not associated with worse outcomes if NMS occurs, and the results should further contribute to mitigate concerns about LAI safety regarding NMS onset or outcomes, including mortality 6.

Management Considerations

• The management of NMS requires a multidisciplinary approach, and the treatment should be individualized based on the severity of the symptoms and the patient's medical history 4, 5.
• The use of dantrolene, bromocriptine, and ECT may be considered in severe cases of NMS, and the treatment should be guided by the patient's response to therapy and the presence of any adverse effects 4, 5.