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Cardiac arrest – prognostic biomarkers and aspects of shock

Annborn, Martin LU (2014) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2014:140.
Abstract
Background:

Some improvement has been seen in survival after cardiac arrest but the outcome is still poor and 50-70% of patients do not survive despite successful return of spontaneous circulation (ROSC). The cause of death is multifactorial. The majority of patients die from brain injury, but up to 35% die as a result of circulatory failure.



Purpose:

First, to investigate the release profiles of an array of biomarkers in patients treated with mild induced hypothermia after cardiac arrest and study their correlation to the post-cardiac arrest syndrome (PCAS) and long-term outcome; Second, to investigate the effect of two different target temperatures (33°C and 36°C) on hemodynamics and vasopressor... (More)
Background:

Some improvement has been seen in survival after cardiac arrest but the outcome is still poor and 50-70% of patients do not survive despite successful return of spontaneous circulation (ROSC). The cause of death is multifactorial. The majority of patients die from brain injury, but up to 35% die as a result of circulatory failure.



Purpose:

First, to investigate the release profiles of an array of biomarkers in patients treated with mild induced hypothermia after cardiac arrest and study their correlation to the post-cardiac arrest syndrome (PCAS) and long-term outcome; Second, to investigate the effect of two different target temperatures (33°C and 36°C) on hemodynamics and vasopressor requirement in cardiac arrest patients and; Third, to investigate the association of target temperature with outcome in patients with shock in admission.



Methods:

The biomarkers were collected serially at 8 time points during the first 72 hours following cardiac arrest in 84 still comatose post-resuscitation cardiac arrest patients treated with mild induced hypothermia. We analysed markers of inflammation; procalcitonin (PCT) and c-reactive protein (CRP), oxidation; peroxiredoxin 4 (prx4), cardiac stress; MR-proANP, cardiac injury; Troponin T (TnT), brain injury; Neuron specific enlolase (NSE), and the stress hormone; CT-proAVP (copeptin). Outcome was assessed at 6 months with the cerebral performance category scale (CPC) where CPC 1-2 was considered a good outcome. The cardiovascular sequential organ failure assessment score (SOFA-score) and the time to ROSC were used as surrogate markers for the PCAS. Three different definitions of infection were used to assess occurrence of infection.

The effect of a target temperature of 33°C or 36°C on hemodynamics was investigated in all patients with available vasopressor data (n=920) in the ‘Targeted temperature management at 33°C versus 36°C after cardiac arrest’ trial and in patients with shock on admission (n=139). Primary outcome was mortality. Secondary outcomes were vasopressor requirements as assessed by the cardiovascular SOFA-score, serum lactate concentrations, mean arterial pressure, and heart rate.



Results:

PCT, CT-proAVP and MR-proANP were all significantly higher in patients with poor outcome and correlated to surrogate markers of the PCAS. No specific cut-off levels were identified. PCT release was not associated to infection. Combinations of biomarkers may be a promising concept to improve prognostication. A targeted temperature of 33°C was associated with increased vasopressor requirements and increased lactate levels in both our investigated cohorts. A low MAP during the intervention (0-36 hours) was associated with poor outcome after adjustment for baseline characteristics.



Conclusion:

Biomarkers from other sources than the brain are associated to the PCAS and may be promising biomarkers to prognosticate outcome, alone or in combination. Targeted temperature management at 33°C is associated with increased vasopressor requirements and severity of shock and does not improve outcome as compared to 36°C. (Less)
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author
supervisor
opponent
  • Prof. Cariou, Alain, Paris Descarets University, Paris, France
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Cardiac arrest, shock, outcome, prognostication, post cardiac arrest syndrome, hypothermia
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2014:140
pages
91 pages
publisher
Anaesthesiology and Intensive Care
defense location
Segerfalkssalen, BMC, Sölvegatan 17, Lund.
defense date
2014-12-11 09:00
ISSN
1652-8220
ISBN
978-91-7619-069-2
language
English
LU publication?
yes
id
cb829585-5632-4d3e-aac1-f38309a8ef99 (old id 4812666)
date added to LUP
2014-11-25 13:59:28
date last changed
2016-09-19 08:44:47
@phdthesis{cb829585-5632-4d3e-aac1-f38309a8ef99,
  abstract     = {Background: <br/><br>
Some improvement has been seen in survival after cardiac arrest but the outcome is still poor and 50-70% of patients do not survive despite successful return of spontaneous circulation (ROSC). The cause of death is multifactorial. The majority of patients die from brain injury, but up to 35% die as a result of circulatory failure.<br/><br>
<br/><br>
Purpose: <br/><br>
First, to investigate the release profiles of an array of biomarkers in patients treated with mild induced hypothermia after cardiac arrest and study their correlation to the post-cardiac arrest syndrome (PCAS) and long-term outcome; Second, to investigate the effect of two different target temperatures (33°C and 36°C) on hemodynamics and vasopressor requirement in cardiac arrest patients and; Third, to investigate the association of target temperature with outcome in patients with shock in admission.<br/><br>
<br/><br>
Methods: <br/><br>
The biomarkers were collected serially at 8 time points during the first 72 hours following cardiac arrest in 84 still comatose post-resuscitation cardiac arrest patients treated with mild induced hypothermia. We analysed markers of inflammation; procalcitonin (PCT) and c-reactive protein (CRP), oxidation; peroxiredoxin 4 (prx4), cardiac stress; MR-proANP, cardiac injury; Troponin T (TnT), brain injury; Neuron specific enlolase (NSE), and the stress hormone; CT-proAVP (copeptin). Outcome was assessed at 6 months with the cerebral performance category scale (CPC) where CPC 1-2 was considered a good outcome. The cardiovascular sequential organ failure assessment score (SOFA-score) and the time to ROSC were used as surrogate markers for the PCAS. Three different definitions of infection were used to assess occurrence of infection.<br/><br>
The effect of a target temperature of 33°C or 36°C on hemodynamics was investigated in all patients with available vasopressor data (n=920) in the ‘Targeted temperature management at 33°C versus 36°C after cardiac arrest’ trial and in patients with shock on admission (n=139). Primary outcome was mortality. Secondary outcomes were vasopressor requirements as assessed by the cardiovascular SOFA-score, serum lactate concentrations, mean arterial pressure, and heart rate.<br/><br>
<br/><br>
Results: <br/><br>
PCT, CT-proAVP and MR-proANP were all significantly higher in patients with poor outcome and correlated to surrogate markers of the PCAS. No specific cut-off levels were identified. PCT release was not associated to infection. Combinations of biomarkers may be a promising concept to improve prognostication. A targeted temperature of 33°C was associated with increased vasopressor requirements and increased lactate levels in both our investigated cohorts. A low MAP during the intervention (0-36 hours) was associated with poor outcome after adjustment for baseline characteristics.<br/><br>
<br/><br>
Conclusion: <br/><br>
Biomarkers from other sources than the brain are associated to the PCAS and may be promising biomarkers to prognosticate outcome, alone or in combination. Targeted temperature management at 33°C is associated with increased vasopressor requirements and severity of shock and does not improve outcome as compared to 36°C.},
  author       = {Annborn, Martin},
  isbn         = {978-91-7619-069-2},
  issn         = {1652-8220},
  keyword      = {Cardiac arrest,shock,outcome,prognostication,post cardiac arrest syndrome,hypothermia},
  language     = {eng},
  pages        = {91},
  publisher    = {Anaesthesiology and Intensive Care},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Cardiac arrest – prognostic biomarkers and aspects of shock},
  volume       = {2014:140},
  year         = {2014},
}