Cardiac arrest patients have an impaired immune response, which is not influenced by induced hypothermia

Abstract

IntroductionInduced hypothermia is increasingly applied as a therapeutic intervention in ICUs. One of the underlying mechanisms of the beneficial effects of hypothermia is proposed to be reduction of the inflammatory response. However, a fear of reducing the inflammatory response is an increased infection risk. Therefore, we studied the effect of induced hypothermia on immune response after cardiac arrest.MethodsA prospective observational cohort study in a mixed surgical-medical ICU. Patients admitted at the ICU after surviving cardiac arrest were included and during 24 hours body temperature was strictly regulated at 33°C or 36°C. Blood was drawn at three time points: after reaching target temperature, at the end of the target temperature protocol and after rewarming to 37°C. Plasma cytokine levels and response of blood leucocytes to stimulation with toll-like receptor (TLR) ligands lipopolysaccharide (LPS) from Gram-negative bacteria and lipoteicoic acid (LTA) from Gram-positive bacteria were measured. Also, monocyte HLA-DR expression was determined.ResultsIn total, 20 patients were enrolled in the study. Compared to healthy controls, cardiac arrest patients kept at 36°C (n = 9) had increased plasma cytokines levels, which was not apparent in patients kept at 33°C (n = 11). Immune response to TLR ligands in patients after cardiac arrest was generally reduced and associated with lower HLA-DR expression. Patients kept at 33°C had preserved ability of immune cells to respond to LPS and LTA compared to patients kept at 36°C. These differences disappeared over time. HLA-DR expression did not differ between 33°C and 36°C.ConclusionsPatients after cardiac arrest have a modest systemic inflammatory response compared to healthy controls, associated with lower HLA-DR expression and attenuated immune response to Gram-negative and Gram-positive antigens, the latter indicative of an impaired immune response to bacteria. Patients with a body temperature of 33°C did not differ from patients with a body temperature of 36°C, suggesting induced hypothermia does not affect immune response in patients with cardiac arrest.Trial registrationClinicalTrials.gov NCT01020916, registered 25 November 2009

Patients with out‐of‐hospital cardiac arrest show decreased human leucocyte antigen‐DR expression on monocytes and B and T lymphocytes after return of spontaneous circulation

“…Our finding that HLA‐DR expression on monocytes decreased after ROSC is consistent with previous results . However, unlike in the previous reports, we did not find a significant difference in HLA‐DR expression on monocytes between survivors and non‐survivors on day 1.…”

“…Previous studies have shown that TNF‐α and IL‐6 levels decrease after whole blood stimulation with LPS, indicating the functional suppression of circulatory immune cells . The high rates of infections in patients with OHCA may be due to immune system suppression.…”

“…Human leucocyte antigen‐DR molecules are expressed on the surfaces of professional APCs, such as monocytes, B lymphocytes and dendritic cells, or non‐professional APCs, such as T lymphocytes . Only two studies with limited sample sizes have demonstrated changes in HLA‐DR expression on monocytes in patients with OHCA, and HLA‐DR expression levels on B and T lymphocytes have not been reported. In this study, we explored early alterations in the circulatory immune system in patients with OHCA after ROSC; in particular, we evaluated HLA‐DR expression on monocytes and B and T lymphocytes in circulation.…”

The Effect of Therapeutic Temperature Management on Cell Death and Apoptosis in Resuscitative Attempts

“…Post-arrest patients have a modest systemic inflammatory response compared to healthy controls, associated with lower HLA-DR expression and attenuated immune response to Gramnegative and Gram-positive antigens [23]. Inhibition of the exaggerated systemic inflammatory response syndrome is thought to be one of the mechanisms through which TTM can mitigate the harmful effects of ischemia-reperfusion.…”

“…Beurskens et al [23] conducted a cohort study to enlighten the impact of TTM on immune response after CA. They reported that CA patients maintained in mild hypothermia (at 36°C) had higher plasma cytokines levels than that of healthy controls, which was not apparent in patients kept at 33°C.…”