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

Crit Care. 2014 Jul 30;18(4):R162. doi: 10.1186/cc14002.


Introduction: Induced 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.

Methods: A 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.

Results: In 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.

Conclusions: Patients 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 registration: NCT01020916, registered 25 November 2009.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Body Temperature / immunology
  • Cytokines / blood
  • Cytokines / immunology
  • Female
  • Glasgow Coma Scale
  • Heart Arrest / immunology*
  • Heart Arrest / therapy
  • Humans
  • Hypothermia, Induced / adverse effects
  • Hypothermia, Induced / methods*
  • Inflammation / immunology*
  • Intensive Care Units
  • Leukocytes / immunology
  • Lipopolysaccharides / blood
  • Lipopolysaccharides / immunology
  • Male
  • Middle Aged
  • Netherlands
  • Prospective Studies
  • Toll-Like Receptors / blood
  • Toll-Like Receptors / immunology


  • Cytokines
  • Lipopolysaccharides
  • Toll-Like Receptors

Associated data