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Plasma proenkephalin A 119-159 and dipeptidyl peptidase 3 on admission after cardiac arrest help predict long-term neurological outcome

Thorgeirsdóttir, Bergthóra LU orcid ; Levin, Helena LU ; Spångfors, Martin LU orcid ; Annborn, Martin LU ; Cronberg, Tobias LU ; Nielsen, Niklas LU ; Lybeck, Anna LU orcid ; Friberg, Hans LU and Frigyesi, Attila LU (2021) In Resuscitation 163. p.108-115
Abstract

BACKGROUND: A large proportion of adult survivors of cardiac arrest have a poor neurological outcome. Guidelines recommend multimodal neuro-prognostication no earlier than 72-96 hours after cardiac arrest. There is great interest in earlier prognostic markers, including very early markers at admission. The novel blood biomarkers proenkephalin A 119-159 (penKid), bioactive adrenomedullin (bio-ADM) and circulating dipeptidyl peptidase 3 (cDPP3) have not been previously investigated for the early prognosis of cardiac arrest survivors.

METHODS: This multicentre observational study included adult survivors of cardiac arrest admitted to intensive care at four Swedish intensive care units (ICUs) during 2016. Blood samples were collected... (More)

BACKGROUND: A large proportion of adult survivors of cardiac arrest have a poor neurological outcome. Guidelines recommend multimodal neuro-prognostication no earlier than 72-96 hours after cardiac arrest. There is great interest in earlier prognostic markers, including very early markers at admission. The novel blood biomarkers proenkephalin A 119-159 (penKid), bioactive adrenomedullin (bio-ADM) and circulating dipeptidyl peptidase 3 (cDPP3) have not been previously investigated for the early prognosis of cardiac arrest survivors.

METHODS: This multicentre observational study included adult survivors of cardiac arrest admitted to intensive care at four Swedish intensive care units (ICUs) during 2016. Blood samples were collected at ICU admission and batch analysed. The association between admission plasma penKid, bio-ADM and cDPP3 and poor long-term neurological outcome, according to the Cerebral Performance Category (CPC) scale, was assessed by binary logistic regression. Their prognostic performance was assessed using the area under the receiver operating characteristic curve (AUC).

RESULTS: A total of 190 patients were included, of which 136 patients had suffered out-of-hospital and 54 patients in-hospital cardiac arrest. Poor long-term neurological outcome was associated with elevated admission plasma concentrations of penKid and cDPP3, but not with bio-ADM. The association for penKid, but not for cDPP3, remained after adjusting for clinical cardiac arrest variables with prognostic value (time to return of spontaneous circulation (ROSC), initial rhythm, admission Glasgow Coma Scale (GCS) motor score and absence of pupillary reflexes). The prognostic performance of above mentioned clinical cardiac arrest variables alone was very good with an AUC of 0.90 (95% confidence interval, CI, 0.86-0.95), but improved further with the addition of penKid resulting in an AUC of 0.93 (95% CI 0.89-0.97, p < 0.026). Plasma penKid and cDPP3 alone provided moderate long-term prognostic information with AUCs of 0.70 and 0.71, respectively.

CONCLUSION: After cardiac arrest, admission plasma levels of penKid and cDPP3, but not bio-ADM, predicted long-term neurological outcome. When added to clinical cardiac arrest variables, penKid further improved prognostic performance.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Resuscitation
volume
163
pages
8 pages
publisher
Elsevier
external identifiers
  • scopus:85105302411
  • pmid:33930500
ISSN
1873-1570
DOI
10.1016/j.resuscitation.2021.04.021
project
SweCrit, a critical care biobank
language
English
LU publication?
yes
id
21fe233b-e88b-43b3-8463-dfa7cb104868
date added to LUP
2021-05-03 19:30:01
date last changed
2025-01-13 07:46:00
@article{21fe233b-e88b-43b3-8463-dfa7cb104868,
  abstract     = {{<p>BACKGROUND: A large proportion of adult survivors of cardiac arrest have a poor neurological outcome. Guidelines recommend multimodal neuro-prognostication no earlier than 72-96 hours after cardiac arrest. There is great interest in earlier prognostic markers, including very early markers at admission. The novel blood biomarkers proenkephalin A 119-159 (penKid), bioactive adrenomedullin (bio-ADM) and circulating dipeptidyl peptidase 3 (cDPP3) have not been previously investigated for the early prognosis of cardiac arrest survivors.</p><p>METHODS: This multicentre observational study included adult survivors of cardiac arrest admitted to intensive care at four Swedish intensive care units (ICUs) during 2016. Blood samples were collected at ICU admission and batch analysed. The association between admission plasma penKid, bio-ADM and cDPP3 and poor long-term neurological outcome, according to the Cerebral Performance Category (CPC) scale, was assessed by binary logistic regression. Their prognostic performance was assessed using the area under the receiver operating characteristic curve (AUC).</p><p>RESULTS: A total of 190 patients were included, of which 136 patients had suffered out-of-hospital and 54 patients in-hospital cardiac arrest. Poor long-term neurological outcome was associated with elevated admission plasma concentrations of penKid and cDPP3, but not with bio-ADM. The association for penKid, but not for cDPP3, remained after adjusting for clinical cardiac arrest variables with prognostic value (time to return of spontaneous circulation (ROSC), initial rhythm, admission Glasgow Coma Scale (GCS) motor score and absence of pupillary reflexes). The prognostic performance of above mentioned clinical cardiac arrest variables alone was very good with an AUC of 0.90 (95% confidence interval, CI, 0.86-0.95), but improved further with the addition of penKid resulting in an AUC of 0.93 (95% CI 0.89-0.97, p &lt; 0.026). Plasma penKid and cDPP3 alone provided moderate long-term prognostic information with AUCs of 0.70 and 0.71, respectively.</p><p>CONCLUSION: After cardiac arrest, admission plasma levels of penKid and cDPP3, but not bio-ADM, predicted long-term neurological outcome. When added to clinical cardiac arrest variables, penKid further improved prognostic performance.</p>}},
  author       = {{Thorgeirsdóttir, Bergthóra and Levin, Helena and Spångfors, Martin and Annborn, Martin and Cronberg, Tobias and Nielsen, Niklas and Lybeck, Anna and Friberg, Hans and Frigyesi, Attila}},
  issn         = {{1873-1570}},
  language     = {{eng}},
  month        = {{06}},
  pages        = {{108--115}},
  publisher    = {{Elsevier}},
  series       = {{Resuscitation}},
  title        = {{Plasma proenkephalin A 119-159 and dipeptidyl peptidase 3 on admission after cardiac arrest help predict long-term neurological outcome}},
  url          = {{http://dx.doi.org/10.1016/j.resuscitation.2021.04.021}},
  doi          = {{10.1016/j.resuscitation.2021.04.021}},
  volume       = {{163}},
  year         = {{2021}},
}