Presentation: unconscious on the street
Emergency medical personnel bring Mr. M, age 66, to the ER after passers-by find him supine on the sidewalk. On arrival, he is comatose as confirmed by a Glasgow Coma Scale score of 8 (eye opening 3, verbal response 2, motor response 3). Systolic blood pressure is 108 mm Hg on palpation, pulse is 135 beats per minute, and temperature is 105 °F. Minor abrasions cover his face and arms, and his hands and feet are rigid.
Mr. M has lived at a board-and-care facility for 30 years. The facility’s operator tells us that Mr. M has had schizophrenia for 40 years and has been taking:
- olanzapine, 7.5 mg each morning and 10 mg at bedtime
- chlorpromazine, 50 mg nightly
- lithium carbonate, 300 mg tid
- and benztropine, 2 mg bid.
Three weeks ago, Mr. M was hospitalized for 6 days with pneumonia. In 3 months, he will undergo surgery for prostate cancer. He is taking no medication for the prostate cancer.
Creatine phosphokinase (CPK) is 2,939 IU/L, indicating neuroleptic malignant syndrome (NMS). Other laboratory test results suggest diabetes or renal failure (Table 1). Lumbar puncture shows protein at 91 mg/dL, glucose at 74 mg/dL, and red- and white-blood-cell counts at 0 and 1, respectively. CSF Gram’s stain and brain CT are unremarkable. ECG is normal except for sinus tachycardia. Serum lithium is normal (1.1 mmol/L).
Mr. M undergoes tracheal intubation and receives ceftazidime, dose unknown, because chest radiograph shows lower lung opacities, suggesting aspiration. He receives morphine, 2 to 4 mg hourly as needed, to calm him during intubation. He is then transferred to the intensive care unit.
Table 1
Diabetes, renal failure, or NMS? The story behind Mr. M’s laboratory values
Mr. M’s reading | Normal range | Might suggest | |
---|---|---|---|
CPK | 2,939 IU/L | 8-150 IU/L | NMS |
Serum creatinine | 1.9 mg/dL | 0.6-1.5 mg/dL | Renal failure, a complication from elevated CPK |
Serum glucose | 143 mg/dL | 66-99 mg/dL | Diabetes mellitus |
NMS: Neuroleptic malignant syndrome | |||
CPK: Creatine phosphokinase |
The authors’ observations
NMS, a potentially fatal side effect of antipsychotics, is characterized by rigidity, hyperthermia, and autonomic instability1—as seen with Mr. M.
The patient’s rigidity, elevated creatine kinase, and face and arm abrasions could suggest a seizure. Mr. M’s EEG is negative, however, and he has no history of seizures or head trauma, so seizure is ruled out.
Researchers have associated bupropion with a small risk of developing seizures. Richmond and Zwar2 reported a 0.1% risk with bupropion, ≥300 mg/d, but Mr. M was taking 150 mg/d. Dunner et al3 estimated the risk of developing seizure while taking standard-release bupropion—the form Mr. M used—at 0.06%, but patients in this study who developed seizures typically had a past seizure disorder or head trauma.
The combination of hyperthermia, tachycardia, altered mental status, and positive chest X-ray suggest pneumonia, which was addressed with antibiotics. Pneumonia, however, does not solely account for Mr. M’s fever, rigidity, and profoundly increased CPK. These findings suggest NMS.
The Glasgow Coma Scale (GCS) is used to quantitatively rate degree of responsiveness in critically ill or injured patients (Table 2). Total scores range from 3 to 15 based on the patient’s best eye, motor, and verbal responses. Total score ≤8 indicates a probable coma. Serial GCS scores can measure clinical course in comatose patients.
Table 2
Using Glasgow Coma Scale to determine level of consciousness
Component | Response | Score |
---|---|---|
Best eye response | No eye opening | 1 |
Eye opening to pain | 2 | |
Eye opening to verbal command | 3 | |
Eyes open spontaneously | 4 | |
Best verbal response | No verbal response | 1 |
Incomprehensible sounds | 2 | |
Inappropriate words | 3 | |
Confused | 4 | |
Oriented | 5 | |
Best motor response | No motor response | 1 |
Extension to pain | 2 | |
Flexion to pain | 3 | |
Withdrawal from pain | 4 | |
Localizing pain | 5 | |
Obeys commands | 6 | |
Total score ≤8 is severe, and 90% of patients with scores ≤8 are in a coma). Coma is defined as not opening eyes, not obeying commands, and not saying understandable words. Composite scores listing eye, verbal, and motor responses (such as E3V3M5) are clinically more useful than totals. | ||
Source: Reprinted from Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974;304(7872):81-4, with permission from Elsevier. |
Treatment: slow progress
In the ICU, we diagnose NMS and stop all psychotropics, fearing that interactions between any of them might be causing NMS. We give midazolam, 1 to 2 mg hourly as needed for agitation, and continue morphine, 2 to 4 mg hourly as needed for pain. We stop ceftazidime after ruling out aspiration risk.