5
Table 1. Cytokine Release Syndrome Recommendations
Workup/Evaluation and supportive care recommendations (all grades):
• CBC, CMP, magnesium, phosphorus, CRP, LDH, uric acid, fibrinogen, PT/PTT,
and ferritin.
• Assess for infection with blood and urine cultures, and a chest radiograph if fever
present.
• If patient is neutropenic, follow institutional neutropenic fever guidelines.
• Patients who experience Grade 2 or higher CRS (e.g., hypotension, not responsive
to fluids, or hypoxia requiring supplemental oxygenation) should be monitored with
continuous cardiac telemetry and pulse oximetry. For patients experiencing severe
CRS, consider performing an echocardiogram to assess cardiac function.
• Perform cardiac monitoring in patients who experience at least G2 CRS, clinically
significant arrhythmia, and additionally as clinically indicated.
• Consider screening for CMV and EBV.
• Consider chest/abdominal CT imaging, brain MRI, and/or lumbar puncture.
Grading (based on ASTCT
consensus grading )
Management
G1:
Fever:* temperature ≥38°C not
attributable to any other cause
Hypotension: none
Hypoxia: none
• Offer supportive care with antipyretics, IV
hydration, and symptomatic management of
organ toxicities and constitutional symptoms.
• May consider empiric broad-spectrum
antibiotics and granulocyte colony-stimulating
factor (G-CSF) if neutropenic.
Note: GM-CSF is not recommended.
• In patients with persistent (>3 days) or
refractory fever, consider managing as per G2.
G2:
Fever:* temperature ≥38°C not
attributable to any other cause
Plus
Hypotension: not requiring
vasopressors
And/or
Hypoxia: Requiring low-flow
nasal cannula (i.e., oxygen
delivered at ≤6 L/min) or
blow-by
• Continue supportive care as per G1 and include
IV fluid bolus and/or supplemental oxygen as
needed.
• Administer tocilizumab 8 mg/kg IV over 1 hour
(not to exceed 800 mg/dose). Repeat every 8
hours if no improvement in signs and symptoms
of CRS; limit to a maximum of 3 doses in a 24–
hour period, with a maximum of 4 doses total.
• In patients with hypotension that persists after 2
fluid boluses and after 1–2 doses of tocilizumab,
may consider dexamethasone 10 mg IV (or
equivalent) every 12 hours for 1–2 doses, then
reassess.
• Manage per G3 if no improvement within 24
hours of starting tocilizumab.
