Neuroleptic Malignant Syndrome Symptoms Following Haloperidol Injection in an Acute Setting: A Case Report
Alexandria DeFabio
Ohio University Heritage College of Osteopathic Medicine. 845 Fairfield Drive. Boardman, OH 44512. Ad254215@ohio.edu.
Abstract
Neuroleptic malignant syndrome (NMS) is a rare and life-threatening adverse reaction to neuroleptic medications. Neuroleptic medications, such as Haloperidol, are often given in acute settings for agitation and delirium. It is very rare and there are few documented cases of NMS after an acute dose of Haloperidol. In this case report, I discuss a gentleman that acquired NMS after a one-time dose of an atypical antipsychotic.
Key Words: Seizure, Haloperidol, Neuroleptic malignant syndrome, B52, Sedation
Introduction
Neuroleptic malignant syndrome (NMS) is a life-threatening reaction to neuroleptic medications that presents with altered mentation, muscular rigidity, and autonomic dysfunction.1 The use of neuroleptics, particularly Haloperidol (Haldol), is very common to sedate agitated and/or delirious patients in the emergency department. Atypical and typical antipsychotics are associated with NMS, with the typical antipsychotics being more common due to their higher potency at the dopamine receptors.1 The incidence of NMS is 0.02% in patients repetitively exposed to neuroleptics, while the incidence of one time dose has not been calculated. These agents are usually given with an antihistamine such as Benadryl to offset the anticholinergic and extrapyramidal effects of the neuroleptic medication.2 Dopamine receptor blockade is considered the main physiologic change responsible for initiation of this syndrome.2 In this report, I discuss the case of a man that acquired muscle spasm, altered mental status, tachycardia and fever after receiving a dose of Haloperidol for sedation. These findings were unexplained by any other pathology or laboratory abnormalities.
Case Report
62 year old male with a history of seizures, bipolar, hepatitis C, cocaine and heroin abuse presents to the emergency room after having 3 seizures at home. The first seizure was unwitnessed, and he was found down. The next two seizures were witnessed. Wife states that he didn’t hit his head and he has been “groggy and confused” for the past hour or so since he started seizing. Wife mentions that he was acting normally with no complaints prior to the first episode this morning. After getting to the emergency room the patient is altered and combative and unwilling to speak with staff. The patient then seized while in his room. The patient was given Benadryl, Ativan and Haldol for seizure prophylaxis and sedation while in the emergency department. The patient initially arrived afebrile and upon recheck after medication administration, had a temperature of 102.9 and his limbs were found in a contracted position. The patient was sedated, therefore an appropriate mental status exam was not obtainable. Upon examination the patient did not display blatant rigidity, more so muscle spasms, and no other significant exam findings were apparent. Due to the inability to assess his mental status appropriately and his newfound fever, we did a number of exams. A non-contrast CT displayed no acute pathology and no mass-occupying lesions as we were concerned for a brain bleed or hydrocephalus displayed by dilated ventricles. A spinal tap with culture was within normal limits with no growth after 3 days. Blood cultures displayed no growth. Urinalysis, CBC, BMP and chest x-ray were within normal limits. Creatinine kinase was elevated at 593 U/L and lactic acid of 4 mmol/L. About 15 minutes after the initiation of a fever, the sedation wore off and he became responsive but confused and disoriented to person, place and time. His muscle spasms got worse and now included both his upper and lower extremities.
The patient was admitted and during his inpatient course was worked up for seizures and possible neuroleptic malignant syndrome. His EEGs displayed seizure activity and neuroleptics were discontinued while Benadryl and Benztropine were given to counteract the extrapyramidal effects of the previous Haloperidol treatment. The patient’s fever and muscle spasm resolved after two days inpatient. The patient was discharged with seizure prophylaxis.
Given his presentation and clinical course during his stay in the emergency department seizure-induced fever, medication adverse effect, and infections from urinary, pulmonary, hematologic or cerebral sources were considered. Since his symptoms improved after the discontinuation of the neuroleptic medication and addition of benztropine are most suggestive of NMS symptomology.
Discussion
According to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), neuroleptic malignant syndrome needs two criteria to be diagnosed.3 Among those criteria are fever, muscular rigidity, sweating, tachycardia, altered or generally elevated arterial tension, elevated white blood cell count, altered consciousness, tremor, urinary-fecal incontinence, and elevated CPK. The other important diagnostic tool in identifying NMS is the Nierenberg diagnostic criteria which are displayed in table 1 (below).4 As mentioned during the case report, our patient met the following criteria: fever, sweating, tachycardia, altered consciousness and elevated CPK. These would add NMS to his diagnosis if we focused on the DSM-IV criteria. He would also meet appropriate criteria under the Nierenberg system.
Table 1. Diagnostic Criteria of NMS (Nierenberg)
Essential Criteria Recently received neuroleptic medication, dopamine antagonist, or recent discontinuation of a dopamine agonist
Major Criteria Fever >38 Degrees Celsius without other cause
Muscular rigidity
Elevated CK > 3x normal limit
Autonomic instability
Altered mental status
Minor Criteria Respiratory compromise
Other extrapyramidal effects
Leukocytosis
Diagnostic Criteria 4 Major
3 Major + 3 Minor
Our patient did not have the characteristic muscular rigidity found in the majority of NMS cases which made us second guess the diagnosis. However there have been NMS cases noted in the literature that do not include muscular rigidity.6 Literature shows that 20-40% of NMS cases in the setting of atypical antipsychotic use only one, either fever or rigidity, were present.7
Another important factor to take into consideration that is commonly overlooked in the acute setting is illicit drug use. Street drugs, like cocaine, keep dopamine levels increased in the brain. Abrupt discontinuation of these can lead to an increased risk of NMS when given an antipsychotic.8 As you can see our patient has a history of cocaine and heroin use that could have placed him at an increased risk of developing NMS when the haloperidol was administered. This is something to keep in mind and possible an area of further study.
In terms of treatment, discontinuing the offending agent is the first step, the patient’s fever should be lowered, and rehydration therapy should be started to reduce renal involvement from the sequelae of muscular insult. As far as medical treatment, the use of dantrolene, bromocriptine, Benadryl, and/or benzodiazepines have been shown to have better outcomes.1,9
Our patient was taking to the ICU for aggressive rehydration and possible respiratory support. His fever, CPK, tachycardia and mental status returned to his baseline. It was suggested to have osteopathic follow-up to aid in the neutralization of his musculature tone as he was experiencing cramping and decreased range of motion following his stay in the emergency department and ICU. OMT has been found to be helpful in the treatment of muscular straining and return to normal functionality.10
NMS needs immediate intervention and identification due to its high mortality, making it extremely important to consider in all patients given antipsychotics in both the long term and acute settings.
Conclusion
NMS is a very rare and potentially fatal condition and considering it in patients that do not meet the stereotypical presentation, especially in acute settings where previous history and medical records may be lacking is extremely important. In addition, Taking into account the effect of illicit drugs on the dopaminergic pathways and choosing appropriate sedation could help avoid cases of NMS in emergency department patients treated for sedation.
As mentioned earlier, an area of further study would be to look into the effects and incidence of NMS cases where illicit drug use predispositioned the patient to this condition.
Acknowledgements: Thank you to the Akron General Emergency Department for allowing me to write this case and assistance in writing it.
References
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