Abstract
Aim
We evaluated the prognostic value of serum- and cerebrospinal fluid (CSF)-ubiquitin
carboxyl-terminal esterase L1 protein (UCHL1) measurements in post- post-out of hospital
cardiac arrest (OHCA) patients treated with target temperature management (TTM), to
predict neurologic outcome.
Methods
This was a prospective single-centre observational cohort study, conducted from April
2018 to September 2019. Serum- and CSF-UCHL1 were obtained immediately (UCHL1initial), 24 h (UCHL124), 48 h (UCHL148), and 72 h (UCHL172) after return of spontaneous circulation (ROSC). The area under the receiver operating
characteristic curves (AUROC) and Delong method were used to identify cut-off values
of serum- and CSF-UCHL1initial, UCHL124, UCHL148, UCHL172 for predicting neurologic outcomes.
Results
Of 38 patients enrolled, 16 comprised the poor outcome group. The AUROCs for serum-
and CSF-UCHL1initial were 0.71 and 0.93 in predicting poor neurological outcomes, respectively (p = 0.01). The AUROCs for serum- and CSF-UCHL124 were 0.85 and 0.91 (p = 0.24). The AUROCs for serum- and CSF-UCHL148 were 0.90 and 0.97 (p = 0.07). The AUROCs for serum- and CSF-UCHL172 were 0.94 and 0.98 (p = 0.25).
Conclusion
Findings of this study demonstrate that CSF-UCHL1 measured immediately, 24, 48, and
72 h after ROSC is a valuable predictor for evaluating neurologic outcomes, whereas
serum-UCHL1 measured at 24, 48, and 72 h after ROSC showed a significant performance
in the prognostication of poor outcomes in post-OHCA patients treated with TTM.
Abbreviations:
CSF (cerebrospinal fluid), UCHL1 (ubiquitin carboxyl-terminal esterase L1 protein), TTM (targeted temperature management), CA (cardiac arrest), OHCA (out-of-hospital cardiac arrest), SOFA (sequential organ failure assessment), TBI (traumatic brain injury), BBB (blood–brain barrier), ROSC (return of spontaneous circulation), CPC (Cerebral Performance Categories), GCS (Glasgow Coma Scale), LP (lumbar puncture), ICP (intracranial pressure), Qa (serum and cerebrospinal fluid albumin quotient), CPR (cardiopulmonary resuscitation), IQR (interquartile range), SD (standard deviation), AUROC (area under the ROC curve), ECMO (extracorporeal membrane oxygenation), MI (myocardial infarction), PEA (pulseless electrical activity), VF (ventricular fibrillation), VT (ventricular tachycardia), CI (confidence interval), PPV (positive predict value), NPV (negative predict value)Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to ResuscitationAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Assessment of quality of life and cognitive function after out-of-hospital cardiac arrest with successful resuscitation.Am J Cardiol. 2004; 93: 131-135
- Long-term neurological outcome after cardiac arrest and therapeutic hypothermia.Resuscitation. 2009; 80: 1119-1123
- Part 9: post cardiac arrest care. 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care.Circulation. 2010; 122: S768-S786
- Prognosis of coma after therapeutic hypothermia: a prospective cohort study.Ann Neurol. 2012; 71: 206-212
- Early prognosis in coma after cardiac arrest: a prospective clinical, electrophysiological, and biochemical study of 60 patients.J Neurol Neurosurg Psychiatry. 1996; 61: 610-615
- Predicting outcome from hypoxic-ischemic coma.JAMA. 1985; 253: 1420-1426
- Limitations of the Glasgow Coma Scale in predicting outcome in children with traumatic brain injury.J Pediatr. 1992; 120: 195-199
- Predicting outcome in children with hypoxic ischemic encephalopathy.Pediatr Crit Care Med. 2008; 9: 32-39
- Predictors of neurologic outcome in hypothermia after cardiac arrest.Ann Neurol. 2010; 68: 907-914
- Serum neuron-specific enolase and S-100B protein in cardiac arrest patients treated with hypothermia.Stroke. 2003; 34: 2881-3286
- Serum biomarkers after traumatic and hypoxemic brain injuries: insight into the biochemical response of the pediatric brain to inflicted brain injury.Dev Neurosci. 2006; 28: 327-335
- Brain injury biomarkers may improve the predictive power of the IMPACT outcome calculator.J Neurotrauma. 2012; 29: 1770-1778
- Serum neuron-specific enolase as a predictor of short-term outcome and its correlation with Glasgow Coma Scale in traumatic brain injury.Neurosurg Rev. 2008; 31: 439-445
- Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury.Neurology. 2004; 62: 1303-1310
- Serum neuron-specific enolase S100B, and myelin basic protein concentrations after inflicted and noninflicted traumatic brain injury in children.J Neurosurg. 2005; 103: 61-68
- Tau proteins in serum predict outcome after severe traumatic brain injury.J Surg Res. 2010; 160: 302-307
- Update on protein biomarkers in traumatic brain injury with emphasis on clinical use in adults and pediatrics.Acta Neurochir. 2010; 152: 1-17
- Assessment of serum biomarkers and coagulation/fibrinolysis markers for prediction of neurological outcomes of out of cardiac arrest patients treated with therapeutic hypothermia.Clin Exp Emerg Med. 2019; 6: 9-18
- Raised serum S100B levels after acute bone fractures without cerebral injury.J Trauma. 2005; 58: 59-61
- UCHL1 (PGP 9.5): neuronal biomarker and ubiquitin system protein.Prog Neurobiol. 2010; 90: 327-362
- Serum concentrations of ubiquitin C-terminal hydrolase-L1 and alpha II-spectrin breakdown product 145 kDa correlate with outcome after pediatric TBI.J Neurotrauma. 2012; 29: 162-167
- Serum levels of neuron-specific ubiquitin carboxyl-terminal esterase-L1 predict brain injury in a canine model of hypothermic circulatory arrest.J Thorac Cardiovasc Surg. 2011; 142: 902-910
- Two simple questions to assess neurologic outcomes at 3 months after out-of-hospital cardiac arrest: experience from the public access defibrillation trial.Resuscitation. 2010; 81: 530-533
- Consensus guidelines for lumbar puncture in patients with neurological diseases.Alzheimers Dement (Amst). 2017; 8: 111-126
- Mean arterial pressure of 65 mmHg versus 85–100 mmHg in comatose survivors after cardiac arrest: Rationale and study design of the Neuroprotect post-cardiac arrest trial.Am Heart J. 2017; 191: 91-98
- Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations.Nat Biotechnol. 2010; 28: 595-599
- Elevated serum ubiquitin carboxy-terminal hydrolase L1 is associated with abnormal blood–brain barrier function after traumatic brain injury.J Neurotrauma. 2011; 28: 2453-2462
- UCH-L1 C-terminus plays a key role in protein stability but its farnesylation is not required for membrane association in primary neurons.J Biol Chem. 2014; 289: 36140-36149
- The demonstration of new human brain-specific proteins by high resolution two-dimensional polyacrylamide gel electrophoresis.J Neurol Sci. 1981; 49: 429-438
- Identification and preliminary characterization of ubiquitin C terminal hydrolase 1 (UCHL1) as a biomarker of neuronal loss in aneurysmal subarachnoid hemorrhage.J Neurosci Res. 2010; 88: 1475-1484
- A pilot study of novel biomarkers in neonates with hypoxic-ischemic encephalopathy.Pediatr Res. 2010; 68: 531-536
- Biokinetic analysis of ubiquitin C-terminal hydrolase-L1 (UCH-L1) in severe traumatic brain injury patient biofluids.J Neurotrauma. 2011; 28: 861-870
- Serum levels of ubiquitin C-terminal hydrolase distinguish mild traumatic brain injury from trauma controls and are elevated in mild and moderate traumatic brain injury patients with intracranial lesions and neurosurgical intervention.J Trauma Acute Care Surg. 2012; 72: 1335-1344
- Looking at the blood–brain barrier: molecular anatomy and possible investigation approaches.Brain Res Rev. 2010; 64: 328-363
- Development, maintenance and disruption of the bloodbrain barrier.Nat Med. 2013; 19: 1584-1596
- Drug delivery to the brain.J Cereb Blood Flow Metab. 1997; 17: 713-731
- Blood based diagnostics of traumatic brain injuries.Expert Rev Mol Diagn. 2011; 11: 65-78
- Therapy of malignant intracranial hypertension by controlled lumbar cerebrospinal fluid drainage.Crit Care Med. 2001; 29: 976-981
- Using external lumbar CSF drainage to treat communicating external hydrocephalus in adult patients after acute traumatic or non-traumatic brain injury.Acta Neurochir (Wien). 2017; 159: 2003-2009
- Lumbar puncture and brain herniation in acute bacterial meningitis: a review.J Intensive Care Med. 2007; 22: 194-207
Article info
Publication history
Published online: April 06, 2020
Accepted:
March 30,
2020
Received in revised form:
March 13,
2020
Received:
February 10,
2020
Identification
Copyright
© 2020 Elsevier B.V. All rights reserved.
