Circulatory Failure and Outcome in Out-of-Hospital Cardiac Arrest

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Circulatory failure is considered one of the entities of the post cardiac arrest syndrome contributing to poor outcome. It is reported at 15-70% of all patients successfully resuscitated from out-of-hospital cardiac arrest (OHCA). The pathophysiologic mechanism is attributed to limitation of cell metabolism due to inadequate supply of oxygen, caused by pump or conduction failure within the cardiovascular system. The term, however, remains poorly defined and no general consensus on definition exists. Due to the heterogeneity in definition and mechanism, the association with outcome for circulatory failure in cardiac arrest varies, and is partly conflicting. In this thesis we investigate four different surrogate measures of circulatory failure and their association with outcome after out-of-hospital cardiac arrest.
Paper I: We conducted a post hoc analysis of adult, unconscious survivors of out-of-hospital included in the TTM- 1 trial, to investigate lactate, a marker of anaerobic metabolism, as a predictor of short-term survival. 877 patients had admission lactate sampled and were included in analyses. Lactate at admission and 12 hours were independently associated with 30-day survival in a model adjusted for known predictors of survival after out-of- hospital cardiac arrest. Estimations of area under the receiver operator curve indicate a poor precision for predicting short time survival, limiting the clinical utility for lactate metrics as a sole predictor of outcome.
Paper II: Copeptin, physiologically associated with vasoregulatory status, was analyzed as a marker of severity of circulatory failure, in this post hoc analysis of 690 patients included in the TTM-1 biobank sub study. Copeptin measured at 24 hours was found to be independently associated with 30-day survival, circulatory etiology of death and cardiovascular deterioration.
Paper III: In this retrospective registry study of 4004 adult, unconscious patients resuscitated from OHCA, a composite definition of circulatory shock (systolic blood pressure < 90 mmHg, or use of inotropes/vasoactive agents, or clinical signs of hypoperfusion), compared to no circulatory shock on admission was associated with worse odds of good neurological outcome at hospital discharge in an analysis adjusted for baseline comorbidity and predictors of outcome.
Paper IV: Patients with moderate vasopressor support (defined as mean arterial pressure < 70 mmHg and/or adrenalin/noradrenaline dose ≤ 0.25 μg/kg/min) treated with target temperature management at 33oC had higher incidence of 6-month mortality compared to patients treated with normothermia, in a post hoc analysis of 1861 OHCA patients included in the TTM-2 trial. No difference in mortality was detected with temperature intervention in patients with no- or high vasopressor support. The increase in mortality seems to be driven by an increase in 30- day incidence of non-neurological death in patients treated at 33oC, compared to normothermia, in the moderate vasopressor support group, while no difference in etiology of death was detected for intervention in the no-, and high vasopressor support group.
Conclusion: Circulatory failure after OHCA is associated with outcome, however, the mechanism is complex and probably contains multiple pathways.
Original languageEnglish
Awarding Institution
  • Department of Clinical Sciences, Lund
  • Nielsen, Niklas, Supervisor
  • Friberg, Hans, Assistant supervisor
  • Dankiewicz, Josef, Assistant supervisor
  • Annborn, Martin, Assistant supervisor
Award date2022 Jun 13
Place of PublicationLund
ISBN (Print)978-91-8021-246-5
Publication statusPublished - 2022

Bibliographical note

Defence details
Date: 2022-06-13
Time: 09:00
Place: Aulan, CRC, Jan Waldenströms gata 35, Skånes Universitetssjukhus i Malmö
External reviewer(s)
Name: Harris, Tim
Title: Professor
Affiliation: Queen Mary University Hospital of London

Subject classification (UKÄ)

  • Anesthesiology and Intensive Care
  • Cardiac and Cardiovascular Systems

Free keywords

  • Cardiac Arrest
  • Out-of hospital cardiac arrest
  • Circulatory failure
  • Survival
  • Copeptin
  • Lactate
  • Temperature management


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