Cytokine Release Syndrome (CRS) Grading

CRS Grading Calculator

Cytokine Release Syndrome Grade

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Assesses severity of CRS in patients on immunotherapy.

Why Use

Helps guide interventions for patients receiving immunological therapies for cancer.

When to Use

Patients receiving immunotherapy for cancer with signs of cytokine-mediated immunological reactions and multi-organ dysfunction.

Formula

Selection of the appropriate symptoms/signs: Toxicity Grade Symptoms not life-threatening; only symptomatic treatment required (fever, nausea, fatigue, headache, myalgias, malaise) 1 Moderate intervention required for response: oxygen requirement <40%, hypotension responsive to fluids, low dose of one pressor, or grade 2 organ toxicity 2 Aggressive intervention required for response: oxygen requirement ≥40%, hypotension requiring high dose/multiple pressors*, grade 3 organ toxicity, or grade 4 transaminitis 3 Life-threatening symptoms: ventilator required, or grade 4 organ toxicity (excluding transaminitis) 4 Death 5 Grade organ toxicity by Common Terminology Criteria for Adverse Events (CTCAE) v4.0 . *High dose pressors defined as any of the following for ≥3 hours: Pressor Dose** Monotherapy NorEPINEPHrine ≥20 μg/kg/min DOPamine ≥10 μg/kg/min Phenylephrine ≥200 μg/kg/min EPINEPHrine ≥10 μg/kg/min If on vasopressin Vasopressin + norEPINEPHrine equivalent of ≥10 μg/kg/min If on combination pressors (excluding vasopressin) NorEPINEPHrine equivalent of ≥20 μg/kg/min **VASST Trial vasopressor equivalent equation: norEPINEPHrine equivalent dose = [norEPINEPHrine (μg/min)] + [DOPamine (μg/kg/min) / 2] + [EPINEPHrine (μg/min)] + [phenylephrine (μg/min) / 10].

Pearls / Pitfalls

Do not forget coagulopathy as organ dysfunction. High-dose vasopressors need to be on board for ≥3 hours in order to be assigned grade 3. Consider corticosteroids at 24 hours if no improvement. Most patients receiving immunological therapies have complicated ongoing processes and require specialized care. Clinical expertise, vigilance, and frequent follow-up are key to recognizing CRS and not attributing signs and symptoms to an alternate cause (e.g. infection).

Management

Monitoring and aggressive supportive care should be considered in order to prevent irreversible end-organ damage. Consider ICU setting (1:1 nursing care). Consider involving expert consultative services.

Critical Actions

Always investigate for alternate causes such as infection, tumor lysis syndrome, or organ dysfunction. Always evaluate for end-organ damage.

Advice

Clinical judgment should be exercised at all times regarding the observed time course of symptoms and the patient's functional reserve. Tailoring interventions and moving to second-line agents, ruling out other causes, and follow-up are key.

More Information

Interpretation: CRS Grade Treatment Grade 1 CRS Vigilant supportive care, assess for infection (treat fever and neutropenia if present; monitor fluid balance; give antipyretics/analgesics as needed) Grade 2 CRS, no extensive comorbidities or older age Vigilant supportive care (monitor cardiac and other organ function closely) Grade 2 CRS with extensive comorbidities or older age Vigilant supportive care, tocilizumab ± corticosteroids Grade 3-4 CRS Grade 5 Not applicable From Lee 2014 .