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

Düring, Joachim LU orcid (2022) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Harris, Tim, Queen Mary University Hospital of London
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Cardiac Arrest, Out-of hospital cardiac arrest, Circulatory failure, Survival, Copeptin, Lactate, Temperature management
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2022:85
pages
88 pages
publisher
Lund University, Faculty of Medicine
defense location
Aulan, CRC, Jan Waldenströms gata 35, Skånes Universitetssjukhus i Malmö
defense date
2022-06-13 09:00:00
ISSN
1652-8220
ISBN
978-91-8021-246-5
language
English
LU publication?
yes
id
a628a147-1bdb-4046-885a-4233b26497e8
date added to LUP
2022-05-20 11:25:52
date last changed
2023-02-22 15:55:25
@phdthesis{a628a147-1bdb-4046-885a-4233b26497e8,
  abstract     = {{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.<br/>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.<br/>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.<br/>Paper III: In this retrospective registry study of 4004 adult, unconscious patients resuscitated from OHCA, a composite definition of circulatory shock (systolic blood pressure &lt; 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.<br/>Paper IV: Patients with moderate vasopressor support (defined as mean arterial pressure &lt; 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.<br/>Conclusion: Circulatory failure after OHCA is associated with outcome, however, the mechanism is complex and probably contains multiple pathways.}},
  author       = {{Düring, Joachim}},
  isbn         = {{978-91-8021-246-5}},
  issn         = {{1652-8220}},
  keywords     = {{Cardiac Arrest; Out-of hospital cardiac arrest; Circulatory failure; Survival; Copeptin; Lactate; Temperature management}},
  language     = {{eng}},
  number       = {{2022:85}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Circulatory Failure and Outcome in Out-of-Hospital Cardiac Arrest}},
  url          = {{https://lup.lub.lu.se/search/files/118738661/Thesis_JD_wo_papers.pdf}},
  year         = {{2022}},
}