Investigations
1st investigations to order
serum creatine kinase (CK)
Test
NMS is associated with a significant increase in serum CK (at least 4 times the upper limit of normal range, and typically >1000 units/L) which indicates muscle damage.[35][38][43]
If rhabdomyolysis is present (CK >5 times the upper limit of normal range), the patient is at risk of myoglobinuric acute kidney injury, particularly if the CK activity is >5000 units/L.[35] See Rhabdomyolysis.
Rhabdomyolysis requires urgent treatment with intravenous fluids.[35] See Management recommendations.
If the initial CK is normal but you have clinical concern about muscle damage, consider a repeat measurement.[35]
Monitor CK daily until the patient’s CK levels and symptoms have resolved.
CK is a highly sensitive but non-specific marker of muscle tissue injury, and may be elevated in many other conditions (e.g., acute alcohol intoxication, acute psychosis).
The higher the level, the more likely that NMS is present (if there is no history of muscle trauma, e.g., seizure, prolonged immobility).
Result
high levels (at least 4 times the upper limit of normal, and typically >1000 units/L)[35]
CK >5 times the upper limit of normal range indicates rhabdomyolysis
levels above 180,000 units/L have been reported
blood gas
Test
To check for respiratory failure and metabolic acidosis.[46]
Result
may show respiratory failure or metabolic acidosis
blood glucose
urea, electrolytes, and creatinine
Test
Used to evaluate the presence of complications (e.g., acute kidney injury), determine hydration status, and identify any electrolyte disturbances such as hyperkalaemia, hyponatraemia, or hypernatraemia.[35]
Result
may show myoglobinuric acute kidney injury, hyperkalaemia, hyponatraemia, or hypernatraemia[35]
FBC
Test
Leukocytosis may be present due to NMS-specific immune activation (although bear in mind this is non-specific).[36]
Leukocytosis can also indicate a differential diagnosis (e.g., an infection that might progress or has progressed to sepsis).
Result
leukocytosis
liver function tests
Test
To exclude liver failure.[46]
Result
raised if liver failure is present.
clotting screen
Test
To exclude liver failure and disseminated intravascular coagulation (DIC).
Result
abnormal if liver failure or DIC present
ECG
Test
Perform a 12-lead ECG for any patient with suspected NMS.[35]
Check the patient’s cardiac rhythm, QT interval, and QRS duration.[35]
Be aware that further ECGs may be required depending on the clinical situation, even if the initial ECG is normal.
In particular, consider repeating the ECG if:[35]
The initial ECG is abnormal
The patient has ongoing symptoms of NMS.
ECG changes can occur at any time in patients with NMS, owing to the dynamic nature of the condition; abnormalities may result from direct cardiac effects and/or metabolic changes.
Result
may show prolonged PR, QRS, and QT intervals as well as ST and T-wave abnormalities[52]
myoglobin levels and urinalysis
Test
Myoglobinuria is a poor prognostic sign because it may herald multi-organ failure.
Haemolysed blood on urinalysis suggests myoglobinuria.[35]
Result
myoglobin may be present in urine and/or blood
Investigations to consider
brain CT scan
Test
Order if you suspect brain infection, mass, or bleed as differential diagnoses.[6]
Result
usually normal in NMS; may reveal potential structural brain abnormality
urine culture
Test
To exclude an infection.
Result
usually normal in NMS
blood culture
Test
To exclude an infection.
Result
usually normal in NMS
chest x-ray
Test
To exclude pneumonia. Some patients with NMS are at increased risk for aspiration.
Result
usually normal in NMS
toxicology screen
Test
Order if you suspect drug misuse/overdose/withdrawal of a drug that isn’t an antipsychotic (including prescription and illicit drugs).
Result
usually normal in NMS
lumbar puncture
Test
Key test in differential diagnosis. Cloudy cerebrospinal fluid and/or increased WBC count may indicate central nervous system infection (e.g., meningitis, encephalitis).
Result
usually normal in NMS
serum iron
Test
In practice, this is not ordered routinely. Acute, transient low levels have been described.[32] In some cases, transient low serum iron appears to signal imminent worsening of the patient’s condition.
Result
low levels
EEG
Test
Rarely used in practice but may be considered if hyperthermia and tachycardia are not responding to treatment or if the diagnosis is unclear. Non-convulsive status epilepticus can have similar clinical features to NMS; this can be a differential diagnosis or a consequence of NMS. See Status epilepticus.
Result
intermittent or continuous focal or generalised ictal discharges
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