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Seventy-two hours of mild hypothermia after cardiac arrest is associated with a lowered inflammatory response during rewarming in a prospective observational study.

Bisschops LL, van der Hoeven JG, Mollnes TE, Hoedemaekers CW - Crit Care (2014)

Bottom Line: In general, the cytokines and chemokines remained stable during hypothermia and decreased during rewarming, whereas complement activation was suppressed during the whole hypothermia period and increased modestly during rewarming.Complement activation was low during the whole hypothermia period, indicating that complement activation is also highly temperature-sensitive in vivo.Because inflammation is a strong mediator of secondary brain injury, a blunted proinflammatory response after rewarming may be beneficial.

View Article: PubMed Central - PubMed

Affiliation: Department of Intensive Care, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen, 6500 HB, The Netherlands. laurens.bisschops@radboudumc.nl.

ABSTRACT

Introduction: Whole-body ischemia and reperfusion trigger a systemic inflammatory response. In this study, we analyzed the effect of temperature on the inflammatory response in patients treated with prolonged mild hypothermia after cardiac arrest.

Methods: Ten comatose patients with return of spontaneous circulation after pulseless electrical activity/asystole or prolonged ventricular fibrillation were treated with mild therapeutic hypothermia for 72 hours after admission to a tertiary care university hospital. At admission and at 12, 24, 36, 48, 72, 96 and 114 hours, the patients' temperature was measured and blood samples were taken from the arterial catheter. Proinflammatory interleukin 6 (IL-6) and anti-inflammatory (IL-10) cytokines and chemokines (IL-8 and monocyte chemotactic protein 1), intercellular adhesion molecule 1 and complement activation products (C1r-C1s-C1inhibitor, C4bc, C3bPBb, C3bc and terminal complement complex) were measured. Changes over time were analyzed with the repeated measures test for nonparametric data. Dunn's multiple comparisons test was used for comparison of individual time points.

Results: The median temperature at the start of the study was 34.3°C (33.4°C to 35.2°C) and was maintained between 32°C and 34°C for 72 hours. All patients were passively rewarmed after 72 hours, from (median (IQR)) 33.7°C (33.1°C to 33.9°C) at 72 hours to 38.0°C (37.5°C to 38.1°C) at 114 hours (P <0.001). In general, the cytokines and chemokines remained stable during hypothermia and decreased during rewarming, whereas complement activation was suppressed during the whole hypothermia period and increased modestly during rewarming.

Conclusions: Prolonged hypothermia may blunt the inflammatory response after rewarming in patients after cardiac arrest. Complement activation was low during the whole hypothermia period, indicating that complement activation is also highly temperature-sensitive in vivo. Because inflammation is a strong mediator of secondary brain injury, a blunted proinflammatory response after rewarming may be beneficial.

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Terminal complement complex during hypothermia (0 to 72 hours) and after rewarming (72 to 114 hours) in ten patients after cardiac arrest. The medians (black lines in boxes), 25th and 75 interquartile ranges (boxes) and minimums and maximums (whiskers) are depicted for arterial samples. *Statistically significant difference compared to time 0. #Statistically significant difference compared to 72 hours. TCC: Terminal complement complex (terminal pathway).
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Fig5: Terminal complement complex during hypothermia (0 to 72 hours) and after rewarming (72 to 114 hours) in ten patients after cardiac arrest. The medians (black lines in boxes), 25th and 75 interquartile ranges (boxes) and minimums and maximums (whiskers) are depicted for arterial samples. *Statistically significant difference compared to time 0. #Statistically significant difference compared to 72 hours. TCC: Terminal complement complex (terminal pathway).

Mentions: The median C1rs-C1inh concentration was 9.8 AU/ml (7.0 to 11) upon admission and decreased to 7.2 AU/ml (5.0 to 12) at 72 hours, followed by a significant increase during rewarming to 9.4 AU/ml (7.4 to 17) at 114 hours (P = 0.0283). The median C4bc concentration decreased from 14 AU/ml (9.3 to 66) at the start of the study to 8.5 AU/ml (7.1 to 19) at 72 hours, followed by a nonsignificant increase to 11 AU/ml (8.4 to 20) (P = 0.6361). The median C3bPBb concentration decreased significantly from 97 AU/ml (32 to 136) upon admission to 23 AU/ml (15 to 94) at 72 hours and 17 AU/ml at 114 hours (15 to 39) (P = 0.0179). The median C3bc concentration decreased by a trend from 36 AU/ml (11 to 89) upon admission to 9.1 AU/ml at 72 hours (5.0 to 51) and 8.3 AU/ml (6.3 to 15) at 114 hours (P = 0.0619). The median end product TCC concentration was 1.3 AU/ml (0.9 to 5.1) at admission, decreased significantly during hypothermia to 0.5 AU/ml (0.4 to 0.7) at 72 hours and increased significantly during rewarming to 1.1 AU/ml (0.7 to 1.6) at 114 hours (P <0.001) (Figure 5). There were no differences in concentrations of the complement products between survivors and nonsurvivors (data not shown).Figure 5


Seventy-two hours of mild hypothermia after cardiac arrest is associated with a lowered inflammatory response during rewarming in a prospective observational study.

Bisschops LL, van der Hoeven JG, Mollnes TE, Hoedemaekers CW - Crit Care (2014)

Terminal complement complex during hypothermia (0 to 72 hours) and after rewarming (72 to 114 hours) in ten patients after cardiac arrest. The medians (black lines in boxes), 25th and 75 interquartile ranges (boxes) and minimums and maximums (whiskers) are depicted for arterial samples. *Statistically significant difference compared to time 0. #Statistically significant difference compared to 72 hours. TCC: Terminal complement complex (terminal pathway).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4209077&req=5

Fig5: Terminal complement complex during hypothermia (0 to 72 hours) and after rewarming (72 to 114 hours) in ten patients after cardiac arrest. The medians (black lines in boxes), 25th and 75 interquartile ranges (boxes) and minimums and maximums (whiskers) are depicted for arterial samples. *Statistically significant difference compared to time 0. #Statistically significant difference compared to 72 hours. TCC: Terminal complement complex (terminal pathway).
Mentions: The median C1rs-C1inh concentration was 9.8 AU/ml (7.0 to 11) upon admission and decreased to 7.2 AU/ml (5.0 to 12) at 72 hours, followed by a significant increase during rewarming to 9.4 AU/ml (7.4 to 17) at 114 hours (P = 0.0283). The median C4bc concentration decreased from 14 AU/ml (9.3 to 66) at the start of the study to 8.5 AU/ml (7.1 to 19) at 72 hours, followed by a nonsignificant increase to 11 AU/ml (8.4 to 20) (P = 0.6361). The median C3bPBb concentration decreased significantly from 97 AU/ml (32 to 136) upon admission to 23 AU/ml (15 to 94) at 72 hours and 17 AU/ml at 114 hours (15 to 39) (P = 0.0179). The median C3bc concentration decreased by a trend from 36 AU/ml (11 to 89) upon admission to 9.1 AU/ml at 72 hours (5.0 to 51) and 8.3 AU/ml (6.3 to 15) at 114 hours (P = 0.0619). The median end product TCC concentration was 1.3 AU/ml (0.9 to 5.1) at admission, decreased significantly during hypothermia to 0.5 AU/ml (0.4 to 0.7) at 72 hours and increased significantly during rewarming to 1.1 AU/ml (0.7 to 1.6) at 114 hours (P <0.001) (Figure 5). There were no differences in concentrations of the complement products between survivors and nonsurvivors (data not shown).Figure 5

Bottom Line: In general, the cytokines and chemokines remained stable during hypothermia and decreased during rewarming, whereas complement activation was suppressed during the whole hypothermia period and increased modestly during rewarming.Complement activation was low during the whole hypothermia period, indicating that complement activation is also highly temperature-sensitive in vivo.Because inflammation is a strong mediator of secondary brain injury, a blunted proinflammatory response after rewarming may be beneficial.

View Article: PubMed Central - PubMed

Affiliation: Department of Intensive Care, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen, 6500 HB, The Netherlands. laurens.bisschops@radboudumc.nl.

ABSTRACT

Introduction: Whole-body ischemia and reperfusion trigger a systemic inflammatory response. In this study, we analyzed the effect of temperature on the inflammatory response in patients treated with prolonged mild hypothermia after cardiac arrest.

Methods: Ten comatose patients with return of spontaneous circulation after pulseless electrical activity/asystole or prolonged ventricular fibrillation were treated with mild therapeutic hypothermia for 72 hours after admission to a tertiary care university hospital. At admission and at 12, 24, 36, 48, 72, 96 and 114 hours, the patients' temperature was measured and blood samples were taken from the arterial catheter. Proinflammatory interleukin 6 (IL-6) and anti-inflammatory (IL-10) cytokines and chemokines (IL-8 and monocyte chemotactic protein 1), intercellular adhesion molecule 1 and complement activation products (C1r-C1s-C1inhibitor, C4bc, C3bPBb, C3bc and terminal complement complex) were measured. Changes over time were analyzed with the repeated measures test for nonparametric data. Dunn's multiple comparisons test was used for comparison of individual time points.

Results: The median temperature at the start of the study was 34.3°C (33.4°C to 35.2°C) and was maintained between 32°C and 34°C for 72 hours. All patients were passively rewarmed after 72 hours, from (median (IQR)) 33.7°C (33.1°C to 33.9°C) at 72 hours to 38.0°C (37.5°C to 38.1°C) at 114 hours (P <0.001). In general, the cytokines and chemokines remained stable during hypothermia and decreased during rewarming, whereas complement activation was suppressed during the whole hypothermia period and increased modestly during rewarming.

Conclusions: Prolonged hypothermia may blunt the inflammatory response after rewarming in patients after cardiac arrest. Complement activation was low during the whole hypothermia period, indicating that complement activation is also highly temperature-sensitive in vivo. Because inflammation is a strong mediator of secondary brain injury, a blunted proinflammatory response after rewarming may be beneficial.

Show MeSH
Related in: MedlinePlus