Role of dexmedetomidine in modifying immune paralysis in patients with septic shock: randomized controlled trial

Abstract

Background

Immune paralysis can be defined as a hypoinflammatory state associated with the incapacity of the immune system to release proinflammatory mediators despite the clearance of pathogens by antimicrobials. Persistent immune paralysis leads to failure to eradicate primary infections with a substantial increase in the risk of multiorgan dysfunction and mortality. The state of immune paralysis is caused mainly by the diminished ability of monocytes to release proinflammatory cytokines in response to endotoxin. This phenomenon is known as endotoxin tolerance. This study aimed to assess the role of dexmedetomidine in modifying immune paralysis in septic shock patients.

Methods

Twenty-four patients with septic shock were randomized into two groups of 12 patients. A continuous intravenous infusion of dexmedetomidine started at 0.15 µg kg⁻¹ hr⁻¹ and adjusted by 0.15 µg kg⁻¹ h⁻¹ to a maximum of 0.75 µg kg⁻¹ h⁻¹ (10 ml h⁻¹), while midazolam was started at 1 mg h⁻¹ (2 mL hr⁻¹) and adjusted by 1 mg h⁻¹ to a maximum of 5 mg h⁻¹ (10 mL h⁻¹). All infusions were adjusted by increments of 2 mL/hr⁻¹ to maintain blinding. Serum levels of CD42a+/CD14+, HLADR+/CD14+, CRP, IL-6, IL-10 and TNF-α were measured at baseline (T1), 12 h (T2), and 24 h (T3).

Results

Treatment with dexmedetomidine yielded no significant difference in CD42a+/CD14+, HLADR+/CD14, CD24b-MFI, HLADR-MFI, IL6 and TREM1 at all time points when compared with midazolam treatment. There was no significant difference in TLR levels between the two groups. Cardiac output in the dexmedetomidine group showed a significant decrease at 6, 12 and 24 h (P = 0.033, 0.021, and 0.005, respectively) compared with that in the midazolam group.

Conclusion

Our results indicated that dexmedetomidine did not affect CD42a+/CD14+ and HLA-DR+/CD14+ expression in septic patients. Furthermore, cytokine production and inflammatory biomarkers did not change with dexmedetomidine infusion.

Trial registration Clinical trial.gov registry (NCT03989609) on June 14, 2019, https://register.clinicaltrials.gov.