Effect of Remote Ischaemic Conditioning on the inflammatory cytokine cascade of COVID-19 (RIC in COVID-19): a Randomized Controlled Trial

Kishal Lukhna, Helison R. P. do Carmo, Alejandro Rossell Castillo, Sean M. Davidson, Hayli Geffen, Sara Giesz, Pelin Golforoush, Ticiane Gonçalez Bovi, Diana Gorog, Alan Salama, Aqeela Imamdin, Siavash Kalkhoran, Sandrine Lecour, Mauricio W. Perroud Jr., Mpiko Ntsekhe, Andrei C. Sposito, Derek M. Yellon

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Abstract

Purpose
Patients hospitalized with COVID-19 may develop a hyperinflammatory, dysregulated cytokine “storm” that rapidly progresses to acute respiratory distress syndrome, multiple organ dysfunction, and even death. Remote ischaemic conditioning (RIC) has elicited anti-inflammatory and cytoprotective benefits by reducing cytokines following sepsis in animal studies. Therefore, we investigated whether RIC would mitigate the inflammatory cytokine cascade induced by COVID-19.

Methods
We conducted a prospective, multicentre, randomized, sham-controlled, single-blind trial in Brazil and South Africa. Non-critically ill adult patients with COVID-19 pneumonia were randomly allocated (1:1) to receive either RIC (intermittent ischaemia/reperfusion applied through four 5-min cycles of inflation (20 mmHg above systolic blood pressure) and deflation of an automated blood-pressure cuff) or sham for approximately 15 days. Serum was collected following RIC/sham administration and analyzed for inflammatory cytokines using flow cytometry. The endpoint was the change in serum cytokine concentrations. Participants were followed for 30 days.

Results
Eighty randomized participants (40 RIC and 40 sham) completed the trial. Baseline characteristics according to trial intervention were overall balanced. Despite downward trajectories of all cytokines across hospitalization, we observed no substantial changes in cytokine concentrations after successive days of RIC. Time to clinical improvement was similar in both groups (HR 1.66; 95% CI, 0.938–2.948, p 0.08). Overall RIC did not demonstrate a significant impact on the composite outcome of all-cause death or clinical deterioration (HR 1.19; 95% CI, 0.616–2.295, p = 0.61).

Conclusion
RIC did not reduce the hypercytokinaemia induced by COVID-19 or prevent clinical deterioration to critical care.
Original languageEnglish
Number of pages13
JournalCardiovascular Drugs and Therapy
DOIs
Publication statusPublished - 29 Nov 2022

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