Dados do Resumo

Título

Cytokine Release Syndrome and Sepsis: Clinical Overlaps and Distinct Management Challenges

Introdução

Cytokine release syndrome (CRS) and sepsis exhibit considerable clinical overlap and a broad range of manifestations. CRS is defined as "organ dysfunction with life-threatening risk due to a dysregulated host response," and while neither term has a completely consensual definition, there is significant overlap between them. Furthermore, underlying disorders and treatments that predispose to CRS often lead to profound immunosuppression, which increases the risk of infection and sepsis. Both conditions may present with fever, hypotension, vasodilatory shock, and multi-organ failure.

Objetivo

Distinguishing between CRS and sepsis can be challenging but is crucial for initiating appropriate therapy. In the absence of a clear distinction, it is essential to address both conditions simultaneously, focusing on maintaining organ perfusion, adequate oxygenation, hemodynamic support, and frequent monitoring of inflammatory markers. Supportive treatment should also include management of coagulopathies and symptom relief.

Métodos

literature review

Resultados

Treatment:

-Tocilizumab and Corticosteroids: Tocilizumab, an anti-IL-6 monoclonal antibody, has demonstrated efficacy in mitigating CRS and is being investigated for sepsis treatment, with results yet to be determined. In severe cases of CRS or macrophage activation syndrome (MAS), early use of corticosteroids is recommended due to their cytolytic and anti-inflammatory effects and ability to cross the blood-brain barrier. However, a recent single-center study revealed that corticosteroid administration can be detrimental. Higher doses and early corticosteroid use in CAR-T treated patients were associated with reduced overall survival. The impact of corticosteroids on septic shock remains controversial, although large studies suggest they may accelerate recovery and improve mortality, leading most guidelines to recommend their use in refractory septic shock.

-Fluid Resuscitation Strategy: Unlike sepsis, CRS requires cautious fluid management due to the risk of pulmonary congestion. Institutional guidelines generally recommend early use of vasopressors following a modest fluid challenge to minimize third-space fluid leakage.

-Antimicrobial Therapy: Early antibiotic administration in septic shock has been shown to improve mortality. Patients with CRS following CAR-T therapy are at high risk for concomitant infections, and most guidelines recommend early initiation of antibiotics upon the onset of fever. Most CRS patients also experience neutropenia following conditioning therapy, necessitating immediate administration of broad-spectrum antibacterial agents.

Conclusões

Since CRS and sepsis are clinical syndromes rather than distinct diseases, accurately identifying and classifying patients with either or both conditions remains a challenge. Effective management of CRS and sepsis relies on robust supportive care, with a critical emphasis on swiftly differentiating between the conditions to enable the application of appropriate targeted therapies.

Palavras Chave

Sepsis; Cytokine Release Syndrome; CAR-T Cell