Cardiac arrest – prognostic biomarkers and aspects of shock

Martin Annborn

Research output: ThesisDoctoral Thesis (compilation)

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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 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.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Anesthesiology and Intensive Care
Supervisors/Advisors
  • Friberg, Hans, Supervisor
  • Erlinge, David, Supervisor
  • Nielsen, Niklas, Supervisor
Award date2014 Dec 11
Publisher
ISBN (Print)978-91-7619-069-2
Publication statusPublished - 2014

Bibliographical note

Defence details

Date: 2014-12-11
Time: 09:00
Place: Segerfalkssalen, BMC, Sölvegatan 17, Lund.

External reviewer(s)

Name: Cariou, Alain
Title: Prof.
Affiliation: Paris Descarets University, Paris, France

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Subject classification (UKÄ)

  • Anesthesiology and Intensive Care

Keywords

  • Cardiac arrest
  • shock
  • outcome
  • prognostication
  • post cardiac arrest syndrome
  • hypothermia

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