Definition: CRS is an acute systemic inflammatory syndrome characterized by fever and organ dysfunction Symptoms: fever (required) with possible hypoxia, hypotension, tachypnea, nausea, headache, fatigue, myalgias, or malaise Workup and evaluation: Pertinent history and physical examination including vital sign evaluation and evaluation of respiratory symptoms Review medications including BsAb received, last dose of antipyretic therapy, steroids, or anticytokine administration Assess for concurrent symptoms of neurotoxicity Assess for alternate diagnosis including infection (including neutropenic fever), venous thromboembolism, respiratory infection (including COVID-19 and influenza), volume overload or dehydration, and exacerbation of underlying cardiopulmonary condition. Treat as appropriate. For duration of symptoms over 1 week, consider excluding HLH/MAS12
Monitoring: consider monitoring patient for 1-2 h after infusion if outpatient administration of BsAb on day of step-up dosing
Next dose: follow prescribing label |
| Grade and definition | Management |
Grade 1:
Fever∗ of ≥100.4°F with/without constitutional symptoms requiring symptomatic treatment, no hypotension or hypoxia | Home:A/P 650-1000 mg orally, can repeat, if recurrent fever, ≥6-8 h later if clinically stable Recommend aggressive oral hydration Continue to check temperature every 1-2 h and other vitals if able. Patients should recontact the clinic urgently or present to ED if BP goes <10 mm Hg below baseline AND <90 mm Hg systolic, new orthostatic symptoms, weakness, confusion, dizziness, or new hypoxia (<90%).
Home vs outpatient/ED evaluation:If refractory or recurrent fever (<6-8 h) consider dexamethasone 10 mg once. Home management may be appropriate if vital signs remain stable and no other concerning symptoms. Otherwise, patients should be evaluated in a health care facility. Consider earlier administration of steroids and immediate in-person evaluation for patients with multiple disease risk factors or comorbidities (see text) Consider daily dexamethasone with persistent symptoms
Additional management:Consider anticytokine therapy (eg, tocilizumab) in cases of protracted fever (eg, >48 h despite corticosteroids) Early tocilizumab after trial of dexamethasone should be considered for patients with multiple medical risk factors (eg, comorbidities)
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Grade 2:
Fever of ≥100.4°F with either hypotension not requiring pressors and/or hypoxia managed with low-flow nasal canula or blow-by. | All patients should be urgently evaluated in person. Recommend inpatient management for most cases of grade 2 CRS unless qualified outpatient day hospital/infusion center and no hypoxia. If after hours without access to appropriate outpatient treatment area or if clinical scenario dictates, recommend ED evaluation A/P 650-1000 mg as needed, up to 3-4 times daily Dexamethasone 10 mg every 12 h Administer IV fluids/supplemental oxygen as appropriate Administer tocilizumab† if symptoms persist despite IV fluids and dexamethasone (∼4-6 h after dosing) or if clinically unstable. Consider alternative agent (eg, anakinra or siltuximab) if persistent symptoms despite maximal dosing.
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Grade 3:
Fever of ≥100.4°F with either hypotension (BP <90/60 or <10 mmHg below, not responsive to fluids and/or hypoxia requiring high-flow nasal canula, face mask, or venturi mask) | Emergent inpatient admission (floor or ICU) for hemodynamic monitoring, IV fluids, oxygen therapy, and vasopressors A/P 1000 mg IV as needed up to 3-4 times daily when safe Dexamethasone (eg, 10 mg IV Q 6 h), until resolution to grade ≤1, followed by dexamethasone taper Evaluate for sepsis and consider empiric antibiotics Administer tocilizumab† and consider alternative agent (eg, anakinra or siltuximab) if persistent grade 3 CRS despite maximal dosing If refractory hypotension/hypoxia, admit to ICU
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Grade 4:
Fever of ≥100.4°F with any of the following:
Life-threatening consequences, urgent intervention required; requiring multiple pressors and/or positive pressure respiratory support or mechanical intubation. | Inpatient admission to ICU for hemodynamic monitoring, IV fluids, oxygen therapy, and vasopressors A/P 1000 mg IV as needed up to 3-4 times daily when safe Dexamethasone (eg, 20 mg IV every 6 h), until resolution to grade ≤1, followed by dexamethasone taper Administer tocilizumab and if repeated doses of tocilizumab have been used, consider alternative agent (eg, anakinra or siltuximab) if persistent grade 4 CRS despite maximal dosing of first agent
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