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Hypothermia After Cardiac Arrest in Large Animals (HACA-LA) : Study protocol of a randomized controlled experimental trial

Persson, Olof LU ; Valerianova, Anna ; Bělohlávek, Jan ; Cronberg, Tobias LU ; Nielsen, Niklas LU ; Englund, Elisabet LU orcid ; Mlček, Mikuláš and Friberg, Hans LU (2024) In Resuscitation Plus 19.
Abstract

Background: Induced hypothermia post-cardiac arrest is neuroprotective in animal experiments, but few high-quality studies have been performed in larger animals with human-like brains. The neuroprotective effect of postischemic hypothermia has recently been questioned in human trials. Our aim is to investigate whether hypothermia post-cardiac arrest confers a benefit compared to normothermia in large adult animals. Our hypothesis is that induced hypothermia post cardiac arrest is neuroprotective and that the effect diminishes when delayed two hours. Methods: Adult female pigs were anesthetized, mechanically ventilated and kept at baseline parameters including normothermia (38 °C). All animals were subjected to ten minutes of cardiac... (More)

Background: Induced hypothermia post-cardiac arrest is neuroprotective in animal experiments, but few high-quality studies have been performed in larger animals with human-like brains. The neuroprotective effect of postischemic hypothermia has recently been questioned in human trials. Our aim is to investigate whether hypothermia post-cardiac arrest confers a benefit compared to normothermia in large adult animals. Our hypothesis is that induced hypothermia post cardiac arrest is neuroprotective and that the effect diminishes when delayed two hours. Methods: Adult female pigs were anesthetized, mechanically ventilated and kept at baseline parameters including normothermia (38 °C). All animals were subjected to ten minutes of cardiac arrest (no-flow) by induced ventricular fibrillation, followed by four minutes of cardiopulmonary resuscitation with mechanical compressions, prior to the first countershock. Animals with sustained return of spontaneous circulation (systolic blood pressure >60 mmHg for ten minutes) within fifteen minutes from start of life support were included and randomized to three groups; immediate or delayed (2 h) intravenous cooling, both targeting 33 °C, or intravenously controlled normothermia (38 °C). Temperature control was applied for thirty hours including cooling time, temperature at target and controlled rewarming (0.5 °C/h). Animals were extubated and kept alive for seven days. The primary outcome measure is histological brain injury on day seven. Secondary outcomes include neurological and neurocognitive recovery, and the trajectory of biomarkers of brain injury. Conclusion: High-quality animal experiments in clinically relevant large animal models are necessary to close the gap of knowledge regarding neuroprotective effects of induced hypothermia after cardiac arrest. Trial registration: Preclinicaltrials.eu (PCTE0000272), published 2021-11-03.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cardiac arrest, Functional outcome, Hypothermia, Swine, Temperature control
in
Resuscitation Plus
volume
19
article number
100704
publisher
Elsevier
external identifiers
  • pmid:39040822
  • scopus:85197026662
ISSN
2666-5204
DOI
10.1016/j.resplu.2024.100704
language
English
LU publication?
yes
id
e6d0991a-de67-44df-8ced-0e3d328c3a37
date added to LUP
2024-09-09 16:08:30
date last changed
2024-09-10 14:17:18
@article{e6d0991a-de67-44df-8ced-0e3d328c3a37,
  abstract     = {{<p>Background: Induced hypothermia post-cardiac arrest is neuroprotective in animal experiments, but few high-quality studies have been performed in larger animals with human-like brains. The neuroprotective effect of postischemic hypothermia has recently been questioned in human trials. Our aim is to investigate whether hypothermia post-cardiac arrest confers a benefit compared to normothermia in large adult animals. Our hypothesis is that induced hypothermia post cardiac arrest is neuroprotective and that the effect diminishes when delayed two hours. Methods: Adult female pigs were anesthetized, mechanically ventilated and kept at baseline parameters including normothermia (38 °C). All animals were subjected to ten minutes of cardiac arrest (no-flow) by induced ventricular fibrillation, followed by four minutes of cardiopulmonary resuscitation with mechanical compressions, prior to the first countershock. Animals with sustained return of spontaneous circulation (systolic blood pressure &gt;60 mmHg for ten minutes) within fifteen minutes from start of life support were included and randomized to three groups; immediate or delayed (2 h) intravenous cooling, both targeting 33 °C, or intravenously controlled normothermia (38 °C). Temperature control was applied for thirty hours including cooling time, temperature at target and controlled rewarming (0.5 °C/h). Animals were extubated and kept alive for seven days. The primary outcome measure is histological brain injury on day seven. Secondary outcomes include neurological and neurocognitive recovery, and the trajectory of biomarkers of brain injury. Conclusion: High-quality animal experiments in clinically relevant large animal models are necessary to close the gap of knowledge regarding neuroprotective effects of induced hypothermia after cardiac arrest. Trial registration: Preclinicaltrials.eu (PCTE0000272), published 2021-11-03.</p>}},
  author       = {{Persson, Olof and Valerianova, Anna and Bělohlávek, Jan and Cronberg, Tobias and Nielsen, Niklas and Englund, Elisabet and Mlček, Mikuláš and Friberg, Hans}},
  issn         = {{2666-5204}},
  keywords     = {{Cardiac arrest; Functional outcome; Hypothermia; Swine; Temperature control}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Resuscitation Plus}},
  title        = {{Hypothermia After Cardiac Arrest in Large Animals (HACA-LA) : Study protocol of a randomized controlled experimental trial}},
  url          = {{http://dx.doi.org/10.1016/j.resplu.2024.100704}},
  doi          = {{10.1016/j.resplu.2024.100704}},
  volume       = {{19}},
  year         = {{2024}},
}