Neurofilament light compared to neuron-specific enolase as a predictor of unfavourable outcome after out-of-hospital cardiac arrest

Wihersaari, Lauri; Reinikainen, Matti; Furlan, Roberto; Mandelli, Alessandra; Vaahersalo, Jukka; Kurola, Jouni; Tiainen, Marjaana; Pettilä, Ville; Bendel, Stepani; Varpula, Tero; Latini, Roberto; Ristagno, Giuseppe; Skrifvars, MB

doi:10.1016/j.resuscitation.2022.02.024

Cited by 26 publications

(16 citation statements)

References 30 publications

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“…After CA, we found a rapid increase of plasmatic GFAP levels, consistent with observations in patients [25]. Of note, a significant reduction in plasmatic GFAP was observed in HSL groups at 6 and 12 h post CA.…”

Section: Discussionsupporting

confidence: 91%

Hypertonic lactate infusion reduces vasopressor requirement and biomarkers of brain and cardiac injury after experimental cardiac arrest

Annoni

Peluso

et al. 2023

Preprint

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Introduction: Prognosis after resuscitated cardiac arrest (CA) remains poor with high morbidity and mortality due to extensive cardiac and brain injuries and the lack of effective treatments. Hypertonic sodium lactate (HSL) could be beneficial after CA by buffering severe metabolic acidosis, increasing brain perfusion and cardiac performance, reducing cerebral swelling, and serving as alternative energetic cellular substrate. The aim of this study was therefore to test the effects of HSL infusion on brain and cardiac injury in an experimental model of CA. Methods: After a 10-min electrically induced CA followed by 5 min of cardiopulmonary resuscitation maneuvers, adult swine (n=35) were randomly assigned to receive either balanced crystalloids (controls, n=11) or HSL infusion, either starting during cardiopulmonary resuscitation (CPR, Intra-arrest, n=12) or after return of spontaneous circulation (Post-ROSC, n=11) for the following 12 hours. In all animals, extensive multimodal neurological and cardiovascular monitoring was implemented. All animals were treated with target temperature management at 34{degree sign}C. Results: 34 out of 35 (97.1%) animals achieved ROSC and one animal in the Intra-arrest group deceased before completing the observation period. Arterial pH, lactate, sodium concentrations and plasma osmolarity were higher in treated animals then in controls (p<0.001), while potassium concentrations were lower (p=0.004). HSL infusion either Intra-arrest or Post-ROSC improved hemodynamic compared to controls, as shown by reduced vasopressors need to maintain mean arterial pressure target above 65 mmHg (p=0.005 for interaction; p=0.01 for groups). Moreover, plasmatic troponin-I levels and glial fibrillary acid protein (GFAP) concentrations were lower in treated groups at several time-points than in controls. Conclusions: In this experimental CA model, HSL infusion was associated with reduced vasopressor requirements and decreased plasmatic levels of biomarkers of cardiac and cerebral injury.

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Section: Discussionsupporting

confidence: 91%

Hypertonic lactate infusion reduces vasopressor requirement and biomarkers of brain and cardiac injury after experimental cardiac arrest

Annoni

Peluso

et al. 2023

Preprint

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“…The prognostic performance of NfL at 12 h after OHCA in this study was similar to the accuracy of NfL at 24 and 48 h in two previous studies [ 2 , 4 ]. One study included an unselected OHCA cohort [ 4 ], and the other investigated a selected group of OHCA patients of a presumed cardiac cause [ 2 , 16 ]. The performance was slightly higher in the COMACARE trial [ 3 , 17 ], which included a more selected patient group with initial shockable rhythm.…”

Section: Discussionsupporting

confidence: 90%

“…Neurofilament light chain protein (NfL) is a novel biomarker of neuroaxonal injury. Elevated circulating NfL at 24–72 h is highly predictive of poor neurological outcome after out-of-hospital cardiac arrest (OHCA) [ 2 – 4 ]. Additionally, low levels of NfL at 24–72 h have been reported to accurately identify patients with good outcome [ 3 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Plasma neurofilament light is a predictor of neurological outcome 12 h after cardiac arrest

et al. 2023

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Background Previous studies have reported high prognostic accuracy of circulating neurofilament light (NfL) at 24–72 h after out-of-hospital cardiac arrest (OHCA), but performance at earlier time points and after in-hospital cardiac arrest (IHCA) is less investigated. We aimed to assess plasma NfL during the first 48 h after OHCA and IHCA to predict long-term outcomes. Methods Observational multicentre cohort study in adults admitted to intensive care after cardiac arrest. NfL was retrospectively analysed in plasma collected on admission to intensive care, 12 and 48 h after cardiac arrest. The outcome was assessed at two to six months using the Cerebral Performance Category (CPC) scale, where CPC 1–2 was considered a good outcome and CPC 3–5 a poor outcome. Predictive performance was measured with the area under the receiver operating characteristic curve (AUROC). Results Of 428 patients, 328 (77%) suffered OHCA and 100 (23%) IHCA. Poor outcome was found in 68% of OHCA and 55% of IHCA patients. The overall prognostic performance of NfL was excellent at 12 and 48 h after OHCA, with AUROCs of 0.93 and 0.97, respectively. The predictive ability was lower after IHCA than OHCA at 12 and 48 h, with AUROCs of 0.81 and 0.86 (p ≤ 0.03). AUROCs on admission were 0.77 and 0.67 after OHCA and IHCA, respectively. At 12 and 48 h after OHCA, high NfL levels predicted poor outcome at 95% specificity with 70 and 89% sensitivity, while low NfL levels predicted good outcome at 95% sensitivity with 71 and 74% specificity and negative predictive values of 86 and 88%. Conclusions The prognostic accuracy of NfL for predicting good and poor outcomes is excellent as early as 12 h after OHCA. NfL is less reliable for the prediction of outcome after IHCA.

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“…After CA, there was a rapid increase in plasma GFAP levels, consistent with observations in patients [ 26 ]. Of note, there was a significant reduction in plasma GFAP in HSL groups at 6 and 12 h post CA.…”

Section: Discussionsupporting

confidence: 89%

Hypertonic sodium lactate infusion reduces vasopressor requirements and biomarkers of brain and cardiac injury after experimental cardiac arrest

Annoni

Peluso

et al. 2023

Crit Care

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Introduction Prognosis after resuscitation from cardiac arrest (CA) remains poor, with high morbidity and mortality as a result of extensive cardiac and brain injury and lack of effective treatments. Hypertonic sodium lactate (HSL) may be beneficial after CA by buffering severe metabolic acidosis, increasing brain perfusion and cardiac performance, reducing cerebral swelling, and serving as an alternative energetic cellular substrate. The aim of this study was to test the effects of HSL infusion on brain and cardiac injury in an experimental model of CA. Methods After a 10-min electrically induced CA followed by 5 min of cardiopulmonary resuscitation maneuvers, adult swine (n = 35) were randomly assigned to receive either balanced crystalloid (controls, n = 11) or HSL infusion started during cardiopulmonary resuscitation (CPR, Intra-arrest, n = 12) or after return of spontaneous circulation (Post-ROSC, n = 11) for the subsequent 12 h. In all animals, extensive multimodal neurological and cardiovascular monitoring was implemented. All animals were treated with targeted temperature management at 34 °C. Results Thirty-four of the 35 (97.1%) animals achieved ROSC; one animal in the Intra-arrest group died before completing the observation period. Arterial pH, lactate and sodium concentrations, and plasma osmolarity were higher in HSL-treated animals than in controls (p < 0.001), whereas potassium concentrations were lower (p = 0.004). Intra-arrest and Post-ROSC HSL infusion improved hemodynamic status compared to controls, as shown by reduced vasopressor requirements to maintain a mean arterial pressure target > 65 mmHg (p = 0.005 for interaction; p = 0.01 for groups). Moreover, plasma troponin I and glial fibrillary acid protein (GFAP) concentrations were lower in HSL-treated groups at several time-points than in controls. Conclusions In this experimental CA model, HSL infusion was associated with reduced vasopressor requirements and decreased plasma concentrations of measured biomarkers of cardiac and cerebral injury.

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Neurofilament light compared to neuron-specific enolase as a predictor of unfavourable outcome after out-of-hospital cardiac arrest

Cited by 26 publications

References 30 publications

Hypertonic lactate infusion reduces vasopressor requirement and biomarkers of brain and cardiac injury after experimental cardiac arrest

Hypertonic lactate infusion reduces vasopressor requirement and biomarkers of brain and cardiac injury after experimental cardiac arrest

Plasma neurofilament light is a predictor of neurological outcome 12 h after cardiac arrest

Hypertonic sodium lactate infusion reduces vasopressor requirements and biomarkers of brain and cardiac injury after experimental cardiac arrest

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