Cytokine Release Syndrome

(C.R.S.)

Systemic Inflammatory Response Syndrome (SIRS) that can be triggered by different factors:

-        a viral infection: Spanish flu, Ebola fever, H5N1 avian flu, hantavirus pulmonary syndrome, COVID-19

-        certain drugs: monoclonal antibodies such as rituximab

-        as part of lymphohystiocytic hemophagocytosis (see this term).


The syndrome develops when a large quantity of leukocytes, including B, T, NK lymphocytes, macrophages, dendritic cells and monocytes, are activated and release uncontrolled and massive amounts of cytokines that in turn activate more lymphocytes. These leukocytes are activated by infected cells  that die by apoptosis or necrosis. This can happen when the immune system fights infectious agents, when the cytokines send a signal to the immune cells to go to the site of infection. Interleukin 6, a multifunctional cytokine, is a key player in the syndrome.


Symptoms: fever, fatigue, muscle and joint pain, headache, nausea, vomiting, diarrhea, rash, hypoxemic dyspnea (ARDS), tachycardia, hypotension, confusion, delirium, hallucinations, etc.


Biological signs:

-        cytopenia affecting at least two cell lines

-        hypertriglyceridemia (inhibition of lipoprotein lipase)

-        low level of fibrinogen (increased level of plasminogen)

-        high ferritin (> 500 µg/l)

-        high levels of soluble CD25 (part of the 2Ra-interleukin) (> 2400 U/ml)

-        no hemophagocytosis (bone marrow aspiration)


A particular form of the disease has recently been observed during the COVID-19 pandemic: it involved children generally over 5 years of age: they present with fever lasting for a few days with diarrhea and abdominal pain, evolving into a hyperinflammatory state (cytokinic storm) intermediate between typical Kawasaki syndrome and toxin shock. Most of these cases were infected with COVID 19.


Treatment: symptomatic of the respiratory and other organs involvement (myocarditis ?), IL-6 receptor (tocilizumab) or Janus kinase (JAK) inhibitors, colchicin (?)



Anesthetic implications:

shock, sepsis, ARDS, risk of contagion if of infectious origin, avoid a continuous infusion of propofol that can aggravate hypertriglyceridemia (pancreatitis)


References :

-        Zhang C, Wu Z, Li J-W et al.
The cytokine release syndrome (CRS) of severe COVID-19 and interleukin 6 receptor (IL6-R) antagonist Tocilizumab may be the key to reduce mortality.
Int J Antimicrobial Agents, 2020, in press

-        Riphagen S, Gomez J, Gonzalez-Martinez  C, Wilkinson N, Theocharis P.
Hyperinflammatory shock in children during COVID-19 pandemic.
The Lancet doi.org/10.1016/S0140-6736(20)31094-1 (May 6, 2020)


Updated: April 2020