Temperature management after cardiac arrest, postanoxic injury and neurological recovery

Abstract

In patients admitted alive to hospital after cardiac arrest the most common mode of death is withdrawal of life sustaining therapy due to brain injury. This decicion is preceeed by multimodal neuroprognostication, which includes clinical examination, neurophysiological tests, imagning and serum markers of braininjury. The search for methods to ameliorate the brain injury after cardiac arrest is ongoing. Target temperature manegemnt (TTM) is a neuroprotective stratery recommended by guidelines.
This thesis investigates the characteristics of and neuroprognostic value of time until awakening (I) and clinical seizures (II) at two levels of TTM (33°C vs 36°C). It also investigates the potential bed-side use of simplified continuous electroencephalogram (cEEG) in the ICU (III) and whether electrographic status epilepticus diagnosed on cEEG results in additional brain injury (IV). The thesis is designed to reflect the collaboration between anesthesiologists, neurologists and neurophysiologists in this area of medicine.
Data were collected during the TTM-trial, an international, randomized, parallel group, assessor-blinded trial designed to evaluate outcome in comatose survivors of cardiac arrest after TTM at 33°C or 36°C with no difference in long-term neurological outcome between intervention arms.
Late awakening is common and patients often has a good long-term neurological outcome. Time to awakening was longer in TTM at 33°C than at 36°C. The difference could not be attributed to sedative drugs administered during the first 48 h after cardiac arrest or severity of brain injury. Independent predictors of late awakening were: TTM at 33°C, level of consciousness on admission and clinical seizures. Results may be explained by the effect of body temperature on pharmacokinetics of sedative drugs.
Clinical seizures are common after cardiac arrest and associated with a poor outcome. There were no differences in outcome between early and late onset clinical seizures. Level of TTM did not affect the prevalence or prognostic significance of clinical seizures Good outcomes occur, even in early status myoclonus.
After cardiac arrest, preliminary bedside interpretations of simplified cEEGs by trained ICU physicians may allow earlier detection of clinically relevant cEEG changes and prompt evaluation by an EEG-expert. Bedside interpretation of cEEG by ICU physicians requires awareness of limitations of both the simplified electrode montage and the cEEG interpretations performed by ICU physicians.
After cardiac arrest, ESE is associated with higher levels of serum neurofilament light chain suggesting more severe neuronal injury possibly caused by ESE, which can potentially be mitigated by treatment with antiepileptic drugs. Associations with glial fibrillary acidic protein and glial injury are less clear.

Abstract (Swedish)

In patients admitted alive to hospital after cardiac arrest the most common mode of death is withdrawal of life sustaining therapy due to brain injury. This decicion is preceeed by multimodal neuroprognostication, which includes clinical examination, neurophysiological tests, imagning and serum markers of braininjury. The search for methods to ameliorate the brain injury after cardiac arrest is ongoing. Target temperature manegemnt (TTM) is a neuroprotective stratery recommended by guidelines.
This thesis investigates the characteristics of and neuroprognostic value of time until awakening (I) and clinical seizures (II) at two levels of TTM (33°C vs 36°C). It also investigates the potential bed-side use of simplified continuous electroencephalogram (cEEG) in the ICU (III) and whether electrographic status epilepticus diagnosed on cEEG results in additional brain injury (IV). The thesis is designed to reflect the collaboration between anesthesiologists, neurologists and neurophysiologists in this area of medicine.
Data were collected during the TTM-trial, an international, randomized, parallel group, assessor-blinded trial designed to evaluate outcome in comatose survivors of cardiac arrest after TTM at 33°C or 36°C with no difference in long-term neurological outcome between intervention arms.
Late awakening is common and patients often has a good long-term neurological outcome. Time to awakening was longer in TTM at 33°C than at 36°C. The difference could not be attributed to sedative drugs administered during the first 48 h after cardiac arrest or severity of brain injury. Independent predictors of late awakening were: TTM at 33°C, level of consciousness on admission and clinical seizures. Results may be explained by the effect of body temperature on pharmacokinetics of sedative drugs.
Clinical seizures are common after cardiac arrest and associated with a poor outcome. There were no differences in outcome between early and late onset clinical seizures. Level of TTM did not affect the prevalence or prognostic significance of clinical seizures Good outcomes occur, even in early status myoclonus.
After cardiac arrest, preliminary bedside interpretations of simplified cEEGs by trained ICU physicians may allow earlier detection of clinically relevant cEEG changes and prompt evaluation by an EEG-expert. Bedside interpretation of cEEG by ICU physicians requires awareness of limitations of both the simplified electrode montage and the cEEG interpretations performed by ICU physicians.
After cardiac arrest, ESE is associated with higher levels of serum neurofilament light chain suggesting more severe neuronal injury possibly caused by ESE, which can potentially be mitigated by treatment with antiepileptic drugs. Associations with glial fibrillary acidic protein and glial injury are less clear.

• author: Lybeck, Anna
• supervisor: Hans Friberg; Tobias Cronberg; Erik Westhall; Malin Rundgren
• opponent: professor Naredi, Silvana, Göteborgs universitet
• organization: Anesthesiology and Intensive Care; Center for cardiac arrest (research group)
• publishing date: 2020
• type: Thesis
• publication status: published
• subject: Cardiac and Cardiovascular Systems
• keywords: Cardiac arrest, target temperature mangement, outcome, neuroprognostication, seizures, EEG, Cardiac arrest, target temperature mangement, outcome, neuroprognostication, seizures, EEG
• in: Lund University, Faculty of Medicine Doctoral Dissertation Series
• issue: 2020:8
• pages: 71 pages
• defense location: Segerfalksalen, BMC A10, Sölvegatan 17 i Lund
• defense date: 2020-01-30 09:00:00
• ISSN: 1652-8220
• ISBN: 978-91-7619-868-1
• language: English
• LU publication?: yes
• id: ff4a05b9-9192-4ae9-b01f-d41ab3f6e023
• date added to LUP: 2019-12-17 08:09:00
• date last changed: 2020-12-04 07:59:33