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Novel Therapeutic Targets to Improve Neurologic Outcome in Cardiac Arrest
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Novel Therapeutic Targets to Improve Neurologic Outcome in Cardiac Arrest

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Emergency Medicine".

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 19395

Special Issue Editor

Dr. Michael Schwameis

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Guest Editor
Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria
Interests: cardiac arrest; extracorporeal membrane oxygenation; disseminated intravascular coagulation; platelet disorders; hyperfibrinolysis; staphylococcal disease; vaccine- preventable diseases

Special Issue Information

Dear Colleagues,

Neurologic disability causes a high degree of morbidity in cardiac arrest survivors. Ischemic reperfusion is considered to trigger a complex cascade of pro-inflammatory and pro-thrombotic events, which impair microvascular perfusion and contribute to secondary neurologic damage. Lack of knowledge of the exact molecular mechanisms and pathways driving post-resuscitative neurologic damage, however, limit current post-resuscitation care to unselective targeted temperature management and no specific treatment strategies are available to diminish secondary organ damage. The potential of post-resuscitation care to improve neurologic outcome is yet to be realized. Timely targeted interventions could offer the opportunity to alleviate or even interrupt early organ damage cascades triggered by ischemia and/or reperfusion after or even during cardiac arrest. There is a pressing need to identify molecular structures, which have the potential to serve as future therapeutic targets in cardiac arrest survivors to prevent neurologic damage and improve outcome.

This Special Issue, “Novel therapeutic targets to improve neurologic outcome in cardiac arrest”, welcomes all basic and clinical research on molecular mechanisms and pathways involved in neurologic damage after cardiac arrest, which may serve as novel therapeutic targets in the future.

Dr. Michael Schwameis
Guest Editor

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Keywords

  • Out-of-hospital cardiac arrest
  • In-hospital cardiac arrest
  • Cerebral damage
  • Pathophysiologic mechanisms and pathways
  • Therapeutic target structures
  • Neurologic outcome

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Published Papers (3 papers)

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Research

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11 pages, 1087 KiB  
Article
Low PCSK-9 levels Are Associated with Favorable Neurologic Function after Resuscitation from out of Hospital Cardiac Arrest
by Anne Merrelaar, Nina Buchtele, Christoph Schriefl, Christian Clodi, Michael Poppe, Florian Ettl, Harald Herkner, Bernd Jilma, Michael Schwameis and Christian Schoergenhofer
J. Clin. Med. 2020, 9(8), 2606; https://doi.org/10.3390/jcm9082606 - 11 Aug 2020
Cited by 2 | Viewed by 1934
Abstract
Endotoxemia after cardiopulmonary resuscitation (CPR) is associated with unfavorable outcome. Proprotein convertase subtilisin/kexin type-9 (PCSK–9) regulates low-density lipoprotein receptors, which mediate the hepatic uptake of endotoxins. We hypothesized that PCSK–9 concentrations are associated with neurological outcome in patients after CPR. Successfully resuscitated out-of-hospital [...] Read more.
Endotoxemia after cardiopulmonary resuscitation (CPR) is associated with unfavorable outcome. Proprotein convertase subtilisin/kexin type-9 (PCSK–9) regulates low-density lipoprotein receptors, which mediate the hepatic uptake of endotoxins. We hypothesized that PCSK–9 concentrations are associated with neurological outcome in patients after CPR. Successfully resuscitated out-of-hospital cardiac arrest patients were included prospectively (n = 79). PCSK–9 levels were measured on admission, 12 h and 24 h thereafter, and after rewarming. The primary outcome was favorable neurologic function at day 30, defined by cerebral performance categories (CPC 1–2 = favorable vs. CPC 3–5 = unfavorable). Receiver operating characteristic curve analysis was used to identify the PCSK–9 level cut-off for optimal discrimination between favorable and unfavorable 30-day neurologic function. Logistic regression models were calculated to estimate the effect of PCSK–9 levels on the primary outcome, given as odds ratio (OR) and 95% confidence interval (95%CI). PCSK–9 levels on admission were significantly lower in patients with favorable 30-day neurologic function (median 158 ng/mL, (quartiles: 124–225) vs. 207 ng/mL (174–259); p = 0.019). The optimally discriminating PCSK–9 level cut-off was 165 ng/mL. In patients with PCSK–9 levels ≥ 165 ng/mL, the odds of unfavorable neurological outcome were 4.7-fold higher compared to those with PCSK–9 levels < 165 ng/mL. In conclusion, low PCSK–9 levels were associated with favorable neurologic function. Full article
(This article belongs to the Special Issue Novel Therapeutic Targets to Improve Neurologic Outcome in Cardiac Arrest)
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12 pages, 733 KiB  
Article
Association of Taurine with In-Hospital Mortality in Patients after Out-of-Hospital Cardiac Arrest: Results from the Prospective, Observational COMMUNICATE Study
by Naemi Herzog, Rahel Laager, Emanuel Thommen, Madlaina Widmer, Alessia M. Vincent, Annalena Keller, Christoph Becker, Katharina Beck, Sebastian Perrig, Luca Bernasconi, Peter Neyer, Stephan Marsch, Philipp Schuetz, Raoul Sutter, Kai Tisljar and Sabina Hunziker
J. Clin. Med. 2020, 9(5), 1405; https://doi.org/10.3390/jcm9051405 - 9 May 2020
Cited by 12 | Viewed by 2683
Abstract
Background: Studies have suggested that taurine may have neuro- and cardio-protective functions, but there is little research looking at taurine levels in patients after out-of-hospital cardiac arrest (OHCA). Our aim was to evaluate the association of taurine with mortality and neurological deficits in [...] Read more.
Background: Studies have suggested that taurine may have neuro- and cardio-protective functions, but there is little research looking at taurine levels in patients after out-of-hospital cardiac arrest (OHCA). Our aim was to evaluate the association of taurine with mortality and neurological deficits in a well-defined cohort of OHCA patients. Methods: We prospectively measured serum taurine concentration in OHCA patients upon admission to the intensive care unit (ICU) of the University Hospital Basel (Switzerland). We analyzed the association of taurine levels and in-hospital mortality (primary endpoint). We further evaluated neurological outcomes assessed by the cerebral performance category scale. We calculated logistic regression analyses and report odds ratios (OR) and 95% confidence intervals (CI). We calculated different predefined multivariable regression models including demographic variables, comorbidities, initial vital signs, initial blood markers and resuscitation measures. We assessed discrimination by means of area under the receiver operating curve (ROC). Results: Of 240 included patients, 130 (54.2%) survived until hospital discharge and 110 (45.8%) had a favorable neurological outcome. Taurine levels were significantly associated with higher in-hospital mortality (adjusted OR 4.12 (95%CI 1.22 to 13.91), p = 0.02). In addition, a significant association between taurine concentration and a poor neurological outcome was observed (adjusted OR of 3.71 (95%CI 1.13 to 12.25), p = 0.03). Area under the curve (AUC) suggested only low discrimination for both endpoints (0.57 and 0.57, respectively). Conclusion: Admission taurine levels are associated with mortality and neurological outcomes in OHCA patients and may help in the risk assessment of this vulnerable population. Further studies are needed to assess whether therapeutic modulation of taurine may improve clinical outcomes after cardiac arrest. Full article
(This article belongs to the Special Issue Novel Therapeutic Targets to Improve Neurologic Outcome in Cardiac Arrest)
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Review

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15 pages, 977 KiB  
Review
ECMO in Cardiac Arrest: A Narrative Review of the Literature
by Amandine De Charrière, Benjamin Assouline, Marc Scheen, Nathalie Mentha, Carlo Banfi, Karim Bendjelid and Raphaël Giraud
J. Clin. Med. 2021, 10(3), 534; https://doi.org/10.3390/jcm10030534 - 2 Feb 2021
Cited by 27 | Viewed by 14286
Abstract
Cardiac arrest (CA) is a frequent cause of death and a major public health issue. To date, conventional cardiopulmonary resuscitation (CPR) is the only efficient method of resuscitation available that positively impacts prognosis. Extracorporeal membrane oxygenation (ECMO) is a complex and costly technique [...] Read more.
Cardiac arrest (CA) is a frequent cause of death and a major public health issue. To date, conventional cardiopulmonary resuscitation (CPR) is the only efficient method of resuscitation available that positively impacts prognosis. Extracorporeal membrane oxygenation (ECMO) is a complex and costly technique that requires technical expertise. It is not considered standard of care in all hospitals and should be applied only in high-volume facilities. ECMO combined with CPR is known as ECPR (extracorporeal cardiopulmonary resuscitation) and permits hemodynamic and respiratory stabilization of patients with CA refractory to conventional CPR. This technique allows the parallel treatment of the underlying etiology of CA while maintaining organ perfusion. However, current evidence does not support the routine use of ECPR in all patients with refractory CA. Therefore, an appropriate selection of patients who may benefit from this procedure is key. Reducing the duration of low blood flow by means of performing high-quality CPR and promoting access to ECPR, may improve the survival rate of the patients presenting with refractory CA. Indeed, patients who benefit from ECPR seem to carry better neurological outcomes. The aim of this present narrative review is to present the most recent literature available on ECPR and to clarify its potential therapeutic role, as well as to provide an in-depth explanation of equipment and its set up, the patient selection process, and the patient management post-ECPR. Full article
(This article belongs to the Special Issue Novel Therapeutic Targets to Improve Neurologic Outcome in Cardiac Arrest)
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