Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Bro-Jeppesen J, Kjaergaard J, Stammet P, Wise MP, Hovdenes J, Åneman A, Horn J, Devaux Y, Erlinge D, Gasche Y, Wanscher M, Cronberg T, Friberg H, Wetterslev J, Pellis T, Kuiper M, Nielsen N, Hassager C. Predictive value of interleukin-6 in post-cardiac arrest patients treated with targeted temperature management at 33 °C or 36 °C. Resuscitation 2015;98:1-8. [PMID: 26525271 DOI: 10.1016/j.resuscitation.2015.10.009] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Revised: 09/28/2015] [Accepted: 10/10/2015] [Indexed: 12/12/2022]

For:	Bro-Jeppesen J, Kjaergaard J, Stammet P, Wise MP, Hovdenes J, Åneman A, Horn J, Devaux Y, Erlinge D, Gasche Y, Wanscher M, Cronberg T, Friberg H, Wetterslev J, Pellis T, Kuiper M, Nielsen N, Hassager C. Predictive value of interleukin-6 in post-cardiac arrest patients treated with targeted temperature management at 33 °C or 36 °C. Resuscitation 2015;98:1-8. [PMID: 26525271 DOI: 10.1016/j.resuscitation.2015.10.009] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Revised: 09/28/2015] [Accepted: 10/10/2015] [Indexed: 12/12/2022]

Number

Cited by Other Article(s)

Berg-Hansen K, Wiggers H, Møller N, Johannsen M, Johansson PI, Meyer MAS, Kjærgaard J, Hassager C, Bro-Jeppesen J. Metabolic profiles associate with mortality and neurological outcomes in out-of-hospital cardiac arrest patients. Resuscitation 2025;209:110583. [PMID: 40090610 DOI: 10.1016/j.resuscitation.2025.110583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Revised: 03/02/2025] [Accepted: 03/06/2025] [Indexed: 03/18/2025]

Abstract

BACKGROUND

Out-of-hospital cardiac arrest (OHCA) is associated with high mortality and poor neurological outcome, with significant metabolic changes upon return of spontaneous circulation (ROSC). This study aimed to investigate the association of metabolic derangements with outcomes in patients resuscitated from OHCA.

METHODS

Blood samples from 156 consecutive unconscious OHCA patients in the Targeted Temperature Management trial were analyzed at hospital admission. Metabolic parameters including free fatty acids (FFAs), glucose, lactate, 3-hydroxybutyrate (3-OHB), and insulin were measured. Hierarchical clustering categorized patients based on metabolic response patterns. Thirty-day mortality and neurological outcomes were compared across these clusters.

RESULTS

The median age was 62 years (IQR 54-68) and 87% were male. Hierarchical clustering identified three distinct metabolic profiles. Cluster A showed severe metabolic distress with elevated lactate, high insulin resistance, and modest FFA/3-OHB levels. Cluster B had low FFA/3-OHB levels while Cluster C showed high FFA/3-OHB levels; both were associated with lower lactate and insulin resistance compared with Cluster A. Cluster A was linked to greater cardiac arrest severity, including longer time to ROSC, increased defibrillations, and higher adrenaline use. Thirty-day mortality rates were: Cluster A, 68%; B, 33%; C, 21% (log-rank P < 0.001). Neurological deaths were lowest in Clusters C. Baseline FFA levels were independently associated with neurological death.

CONCLUSION

This study identifies distinct metabolic profiles associated with neurological recovery after cardiac arrest, suggesting a potential link between metabolic states and outcomes that may reflect adaptive brain resilience. These findings highlight the need for further research to explore whether metabolic-targeted interventions could enhance recovery.

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Choi Y, Park S. Impact of Extreme Temperature and Particulate Matter 2.5 on Outcomes of Out-of-Hospital Cardiac Arrest. J Emerg Med 2025;69:32-42. [PMID: 39904640 DOI: 10.1016/j.jemermed.2024.10.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Revised: 10/08/2024] [Accepted: 10/27/2024] [Indexed: 02/06/2025]

Wang YD, Lin JF, Cao ZL, Zhang SY, Han XD. ECPR combined with CRRT successfully rescues a patient who experienced sudden cardiac arrest for 152 minutes: A case report. Medicine (Baltimore) 2025;104:e41298. [PMID: 39889195 PMCID: PMC11789887 DOI: 10.1097/md.0000000000041298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 12/23/2024] [Accepted: 01/03/2025] [Indexed: 02/02/2025] Open

Abstract

RATIONALE

Cardiac arrest (CA) is a life-threatening event with a high mortality rate, and neurological injury following cardiopulmonary resuscitation (CPR) is a leading cause of death and disability in survivors. While prolonged CPR is often associated with poor neurological outcomes, there is limited evidence of successful recovery following extended resuscitation efforts. This study aims to highlight the potential for recovery after prolonged CPR by reporting a case of a patient who underwent 152 minutes of CPR, regained consciousness, and made a full recovery. The purpose is to explore whether advanced life-support techniques, such as extracorporeal CPR (ECPR), can improve survival and neurological outcomes even after prolonged CA.

PATIENT CONCERNS

A 53-year-old man with no prior health issues experienced sudden CA while exercising and underwent prolonged CPR.

DIAGNOSES

Restoration of spontaneous circulation following CA and ventricular fibrillation.

INTERVENTIONS

ECPR, target temperature management, continuous renal replacement therapy, and intracranial pressure management.

OUTCOMES

Immediate recovery: following the restoration of spontaneous circulation, the patient was immediately transferred to the intensive care unit for further treatment. Despite the prolonged CPR duration, the patient remained hemodynamically stable and was able to tolerate the intensive interventions. Neurological recovery: after 1 week of intensive therapy, the patient regained consciousness. Initially, there was some confusion and disorientation, but he gradually became fully alert, oriented, and communicative. Neurological assessments indicated no significant long-term deficits, and brain imaging showed no signs of irreversible damage. Cardiological and renal recovery: cardiac function was closely monitored, with no evidence of significant ischemic damage to the myocardium. The patient's renal function improved with continuous renal replacement therapy, and kidney function returned to normal following the discontinuation of dialysis. Discharge: after 2 weeks of treatment in the intensive care unit and a transfer to the cardiology department for rehabilitation, the patient was discharged from the hospital. He had fully recovered both neurologically and physiologically, with no residual deficits.

LESSONS

This case demonstrates that prolonged CPR, when combined with advanced interventions such as ECPR, can result in favorable outcomes, including survival and neurological recovery. The findings suggest that with timely and appropriate treatment, even patients with extended resuscitation efforts may achieve full recovery, thus underscoring the potential of ECPR as a critical life-saving intervention in cases of prolonged CA.

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Bro-Jeppesen J, Grejs AM, Andersen O, Jeppesen AN, Duez C, Kirkegaard H. Soluble Urokinase-Type Plasminogen Activator Receptor in Comatose Survivors After Out-of-Hospital Cardiac Arrest Treated with Targeted Temperature Management. Ther Hypothermia Temp Manag 2024;14:243-251. [PMID: 37910781 PMCID: PMC11665269 DOI: 10.1089/ther.2023.0039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2023] Open

Abstract

Exposure to whole-body ischemia/reperfusion after out-of-hospital cardiac arrest (OHCA) triggers a systemic inflammatory response where soluble urokinase plasminogen activator receptor (suPAR) is released. This study investigated serial levels of suPAR in differentiated target temperature management and the associations with mortality and 6-month neurological outcome. This is a single-center substudy of the randomized Targeted Temperature Management (TTM) for 24-hour versus 48-hour trial. In this analysis, we included 82 patients and measured serial levels of suPAR at 24, 48, and 72 hours after achievement of target temperature (32-34°C). We assessed all-cause mortality and neurological function evaluated by the Cerebral Performance Categories (CPC) at 6 months after OHCA. Levels of suPAR between TTH groups were evaluated in repeated measures mixed models. Mortality was assessed by the Kaplan-Meier method and serial measurements of suPAR (log2 transformed) were investigated by Cox proportional-hazards models. Good neurological outcome at 6 months was assessed by logistic regression analyses. Levels of suPAR were significantly different between TTH groups (pinteraction = 0.04) with the highest difference at 48 hours, 4.7 ng/mL (95% CI: 4.1-5.4 ng/mL) in the TTH24 group compared to 2.8 ng/mL (95% CI: 2.2-3.5 ng/mL) in the TTH48 group, p < 0.0001. Levels of suPAR above the median value were significantly associated with increased all-cause mortality at any time point (plog-rank<0.05). The interaction of suPAR levels and TTH group was not significant (pinteraction = NS). A twofold increase in levels of suPAR was significantly associated with a decreased odds ratio of a good neurological outcome in both unadjusted and adjusted analyses without interaction of TTH group (pinteraction = NS). Prolonged TTM of 48 hours versus 24 hours was associated with lower levels of suPAR. High levels of suPAR were associated with increased mortality and lower odds for good neurological outcome at 6 months with no significant interaction of TTH group.

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Chen D, Lin Y, Ko P, Lin J, Huang C, Wang G, Chang KC. Effect of targeted temperature management on systemic inflammatory responses after out-of-hospital cardiac arrest: A prospective cohort study. Medicine (Baltimore) 2024;103:e39780. [PMID: 39312301 PMCID: PMC11419506 DOI: 10.1097/md.0000000000039780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Accepted: 08/30/2024] [Indexed: 09/25/2024] Open

Affiliation(s)

Dalong Chen Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung, Taiwan
Yukai Lin Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung, Taiwan Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
Poyen Ko Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung, Taiwan Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan
Jenjyh Lin Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung, Taiwan Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan
Chihyang Huang Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan
Gueijane Wang Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan Department of Medical Research, China Medical University Hospital, Taichung, Taiwan Pharmacy Department, Wizcare Medical Corporation Aggregate, Taichung, Taiwan School of Medicine, Weifang University of Science and Technology, Weifang, Shandong, China
Kuan-Cheng Chang Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung, Taiwan Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan

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Lascarrou JB, Geri G. Inflammatory response and post-cardiac arrest syndrome: Insights from the STEROHCA trial and implications for the future of resuscitation. Resuscitation 2024;202:110371. [PMID: 39168234 DOI: 10.1016/j.resuscitation.2024.110371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 08/16/2024] [Indexed: 08/23/2024]

Yoon JA, You Y, Park JS, Min JH, Jeong W, Ahn HJ, Jeon SY, Kim D, Kang C. Checkpoint for Considering Interleukin-6 as a Potential Target to Mitigate Secondary Brain Injury after Cardiac Arrest. Brain Sci 2024;14:779. [PMID: 39199472 PMCID: PMC11353038 DOI: 10.3390/brainsci14080779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 07/19/2024] [Accepted: 07/26/2024] [Indexed: 09/01/2024] Open

Affiliation(s)

Jung A Yoon Department of Emergency Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea; (J.A.Y.); (Y.Y.); (J.S.P.); (W.J.); (H.J.A.); (S.Y.J.)
Yeonho You Department of Emergency Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea; (J.A.Y.); (Y.Y.); (J.S.P.); (W.J.); (H.J.A.); (S.Y.J.) Department of Emergency Medicine, College of Medicine, Chungnam National University, 282 Mokdong-ro, Jung-gu, Daejeon 35015, Republic of Korea;
Jung Soo Park Department of Emergency Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea; (J.A.Y.); (Y.Y.); (J.S.P.); (W.J.); (H.J.A.); (S.Y.J.) Department of Emergency Medicine, College of Medicine, Chungnam National University, 282 Mokdong-ro, Jung-gu, Daejeon 35015, Republic of Korea;
Jin Hong Min Department of Emergency Medicine, College of Medicine, Chungnam National University, 282 Mokdong-ro, Jung-gu, Daejeon 35015, Republic of Korea; Department of Emergency Medicine, Chungnam National University Sejong Hospital, 20, Bodeum 7-ro, Sejong 30099, Republic of Korea
Wonjoon Jeong Department of Emergency Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea; (J.A.Y.); (Y.Y.); (J.S.P.); (W.J.); (H.J.A.); (S.Y.J.) Department of Emergency Medicine, College of Medicine, Chungnam National University, 282 Mokdong-ro, Jung-gu, Daejeon 35015, Republic of Korea;
Hong Joon Ahn Department of Emergency Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea; (J.A.Y.); (Y.Y.); (J.S.P.); (W.J.); (H.J.A.); (S.Y.J.) Department of Emergency Medicine, College of Medicine, Chungnam National University, 282 Mokdong-ro, Jung-gu, Daejeon 35015, Republic of Korea;
So Young Jeon Department of Emergency Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea; (J.A.Y.); (Y.Y.); (J.S.P.); (W.J.); (H.J.A.); (S.Y.J.) Department of Emergency Medicine, College of Medicine, Chungnam National University, 282 Mokdong-ro, Jung-gu, Daejeon 35015, Republic of Korea;
Dongha Kim Department of Statistics, Sungshin Women’s University, 2, Bomun-ro, Seongbuk-gu, Seoul 02844, Republic of Korea;
Changshin Kang Department of Emergency Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea; (J.A.Y.); (Y.Y.); (J.S.P.); (W.J.); (H.J.A.); (S.Y.J.) Department of Emergency Medicine, College of Medicine, Chungnam National University, 282 Mokdong-ro, Jung-gu, Daejeon 35015, Republic of Korea;

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Ju F, Abbott GW, Li J, Wang Q, Liu T, Liu Q, Hu Z. Canagliflozin Pretreatment Attenuates Myocardial Dysfunction and Improves Postcardiac Arrest Outcomes After Cardiac Arrest and Cardiopulmonary Resuscitation in Mice. Cardiovasc Drugs Ther 2024;38:279-295. [PMID: 36609949 DOI: 10.1007/s10557-022-07419-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/21/2022] [Indexed: 01/09/2023]

Abstract

OBJECTIVE

The SGLT2 inhibitor, canagliflozin, not only reduces glycemia in patients with type 2 diabetes but also exerts cardioprotective effects in individuals without diabetes. However, its potential beneficial effects in cardiac arrest have not been characterized. The purpose of this study was to examine the protective effect of canagliflozin pretreatment on postresuscitation-induced cardiac dysfunction in vivo.

METHODS

Male C57/BL6 mice were randomized to vehicle (sham and control) or canagliflozin treatment groups. All mice except for the sham-operated mice were subjected to potassium chloride-induced cardiac arrest followed by chest compressions and intravenous epinephrine for resuscitation. Canagliflozin therapy efficacies were evaluated by electrocardiogram, echocardiography, histological analysis, inflammatory response, serum markers of myocardial injury, protein phosphorylation analysis, and immunohistological assessment.

RESULTS

Canagliflozin-pretreated mice exhibited a higher survival rate (P < 0.05), a shorter return of spontaneous circulation (ROSC) time (P < 0.01) and a higher neurological score (P < 0.01 or P < 0.001) than control mice after resuscitation. Canagliflozin was effective at improving cardiac arrest and resuscitation-associated cardiac dysfunction, indicated by increased left ventricular ejection fraction and fractional shortening (P < 0.001). Canagliflozin reduced serum levels of LDH, CK-MB and α-HBDH, ameliorated systemic inflammatory response, and diminished the incidence of early resuscitation-induced arrhythmia. Notably, canagliflozin promoted phosphorylation of cardiac STAT-3 postresuscitation. Furthermore, pharmacological inhibition of STAT-3 by Ag490 blunted STAT-3 phosphorylation and abolished the cardioprotective actions of canagliflozin.

CONCLUSIONS

Canagliflozin offered a strong cardioprotective effect against cardiac arrest and resuscitation-induced cardiac dysfunction. This canagliflozin-induced cardioprotection is mediated by the STAT-3-dependent cell-survival signaling pathway.

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Bréchot N, Rutault A, Marangon I, Germain S. Blood endothelium transition and phenotypic plasticity: A key regulator of integrity/permeability in response to ischemia. Semin Cell Dev Biol 2024;155:16-22. [PMID: 37479554 DOI: 10.1016/j.semcdb.2023.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 07/05/2023] [Accepted: 07/09/2023] [Indexed: 07/23/2023]

Hirsch KG, Tamura T, Ristagno G, Sekhon MS. Wolf Creek XVII Part 8: Neuroprotection. Resusc Plus 2024;17:100556. [PMID: 38328750 PMCID: PMC10847936 DOI: 10.1016/j.resplu.2024.100556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2024] Open

Abstract

Introduction

Post-cardiac arrest brain injury (PCABI) is the primary determinant of clinical outcomes for patients who achieve return of spontaneous circulation after cardiac arrest (CA). There are limited neuroprotective therapies available to mitigate the acute pathophysiology of PCABI.

Methods

Neuroprotection was one of six focus topics for the Wolf Creek XVII Conference held on June 14-17, 2023 in Ann Arbor, Michigan, USA. Conference invitees included international thought leaders and scientists in the field of CA resuscitation from academia and industry. Participants submitted via online survey knowledge gaps, barriers to translation, and research priorities for each focus topic. Expert panels used the survey results and their own perspectives and insights to create and present a preliminary unranked list for each category that was debated, revised and ranked by all attendees to identify the top 5 for each category.

Results

Top 5 knowledge gaps included developing therapies for neuroprotection; improving understanding of the pathophysiology, mechanisms, and natural history of PCABI; deploying precision medicine approaches; optimizing resuscitation and CPR quality; and determining optimal timing for and duration of interventions. Top 5 barriers to translation included patient heterogeneity; nihilism & lack of knowledge about cardiac arrest; challenges with the translational pipeline; absence of mechanistic biomarkers; and inaccurate neuro-triage and neuroprognostication. Top 5 research priorities focused on translational research and trial optimization; addressing patient heterogeneity and individualized interventions; improving understanding of pathophysiology and mechanisms; developing mechanistic and outcome biomarkers across post-CA time course; and improving implementation of science and technology.

Conclusion

This overview can serve as a guide to transform the care and outcome of patients with PCABI. Addressing these topics has the potential to improve both research and clinical care in the field of neuroprotection for PCABI.

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Nikolovski SS, Lazic AD, Fiser ZZ, Obradovic IA, Tijanic JZ, Raffay V. Recovery and Survival of Patients After Out-of-Hospital Cardiac Arrest: A Literature Review Showcasing the Big Picture of Intensive Care Unit-Related Factors. Cureus 2024;16:e54827. [PMID: 38529434 PMCID: PMC10962929 DOI: 10.7759/cureus.54827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/23/2024] [Indexed: 03/27/2024] Open

Heymann M, Schorer R, Putzu A. The Effect of CytoSorb on Inflammatory Markers in Critically Ill Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Crit Care Med 2023;51:1659-1673. [PMID: 37607074 PMCID: PMC10645103 DOI: 10.1097/ccm.0000000000006007] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/24/2023]

Abstract

OBJECTIVES

The effectiveness of CytoSorb at removing inflammatory mediators in critically ill patients is controversial.

DATA SOURCES

Electronic databases were searched from inception to May 2023.

STUDY SELECTION

Randomized controlled trials reporting the effects of CytoSorb therapy on inflammatory parameters in critically ill patients with hyperinflammatory conditions were included.

DATA EXTRACTION

Two authors screened articles for eligibility, extracted data, and assessed the risk of bias, conflicts of interest, and certainty of evidence (CoE). The primary outcome was interleukin (IL)-6 at 1 day after initiation of the therapy. Secondary outcomes included various inflammatory markers at 1, 2, 3, and 5 days and mortality. Data were pooled if at least three trials reported the outcome of interest. We conducted meta-analyses of the data using a random-effects model.

DATA SYNTHESIS

Seventeen trials ( n = 855) were included. Fourteen trials were judged to have notable concern about conflicts of interest. Seven trials were performed in medical ICU patients with hyperinflammatory conditions and 10 in complex cardiovascular surgery under cardiopulmonary bypass. Hemoadsorption with CytoSorb was not associated with lower IL-6 at 1 day (mean difference -5.98 [95% CI, -30.44 to 18.48] pg/mL), 2 days, 3 days, or 5 days after initiation of the treatment, as well as the concentration of procalcitionin. The levels of C-reactive protein were not lower with CytoSorb at 1, 2, and 3 days. The use of CytoSorb was associated with higher mortality at latest follow-up (relative risk = 1.22 [95% CI, 1.02-1.45]) and at 30 days. CoE ranged from low to very low.

CONCLUSIONS

The use of CytoSorb hemoadsorption in a mixed population of critically ill patients with hyperinflammatory conditions does not exhibit a consistent decrease in IL-6 and other inflammatory parameters within the first 5 days of treatment. The significant uncertainty surrounding these findings highlights the need for further investigations.

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Obling LER, Beske RP, Meyer MAS, Grand J, Wiberg S, Nyholm B, Josiassen J, Søndergaard FT, Mohr T, Damm-Hejmdal A, Bjerre M, Frikke-Schmidt R, Folke F, Møller JE, Kjaergaard J, Hassager C. Prehospital high-dose methylprednisolone in resuscitated out-of-hospital cardiac arrest patients (STEROHCA): a randomized clinical trial. Intensive Care Med 2023;49:1467-1478. [PMID: 37943300 PMCID: PMC10709228 DOI: 10.1007/s00134-023-07247-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 10/04/2023] [Indexed: 11/10/2023]

Affiliation(s)

Laust E R Obling Department of Cardiology, Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark.
Rasmus P Beske Department of Cardiology, Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark
Martin A S Meyer Department of Cardiology, Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark
Johannes Grand Department of Cardiology, Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark
Sebastian Wiberg Department of Cardiology, Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark Department of Thoracic Anesthesiology, Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark
Benjamin Nyholm Department of Cardiology, Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark
Jakob Josiassen Department of Cardiology, Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark
Frederik T Søndergaard Department of Cardiology, Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark
Thomas Mohr Department of Intensive Care, Herlev-Gentofte Hospital - Copenhagen University Hospital, Copenhagen, Denmark
Anders Damm-Hejmdal Copenhagen Emergency Services, University of Copenhagen, Copenhagen, Denmark
Mette Bjerre Department of Clinical Medicine, Medical/Steno, Aarhus Research Laboratory, Aarhus University, Aarhus, Denmark
Ruth Frikke-Schmidt Department of Clinical Biochemistry, Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Fredrik Folke Copenhagen Emergency Services, University of Copenhagen, Copenhagen, Denmark Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark Department of Cardiology, Herlev-Gentofte Hospital - University of Copenhagen, Copenhagen, Denmark
Jacob E Møller Department of Cardiology, Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark Department of Cardiology, Odense University Hospital, Odense, Denmark
Jesper Kjaergaard Department of Cardiology, Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Christian Hassager Department of Cardiology, Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Seppä AMJ, Skrifvars MB, Pekkarinen PT. Inflammatory response after out-of-hospital cardiac arrest-Impact on outcome and organ failure development. Acta Anaesthesiol Scand 2023;67:1273-1287. [PMID: 37337696 DOI: 10.1111/aas.14291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 05/21/2023] [Accepted: 05/24/2023] [Indexed: 06/21/2023]

Abstract

BACKGROUND

Post-cardiac arrest syndrome that occurs in out-of-hospital cardiac arrest (OHCA) patients is characterized by inflammatory response. We conducted a scoping review of current evidence regarding several inflammatory markers' usefulness for assessment of patient outcome and illness severity. We also discuss the proposed underlying mechanisms leading to inflammatory response after OHCA.

METHODS

We searched the MEDLINE, PubMed Central, Cochrane CENTRAL and Web of Science Core Collection databases with the following search terms: ("inflammation" OR "cytokines") AND "out-of-hospital cardiac arrest." Each inflammatory marker found was combined with "out-of-hospital cardiac arrest" using "AND" to find further relevant studies. We included original studies measuring inflammatory markers in adult OHCA patients that assessed their prognostic capabilities for mortality, neurological outcome, or organ failure severity.

RESULTS

Fifty-nine studies met the inclusion criteria, covering in total 65 different markers. Interleukin-6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP) were the most studied markers, and they were associated with poor outcomes in 13/15, 13/14 and 11/17 studies, respectively. Based on area under the receiver operating characteristic curve (AUC) value, the time point of best discriminatory capacity for poor outcome was ICU admission for IL-6 (median AUC 0.78, range 0.71-0.98) and day one after OHCA for PCT (median AUC 0.84, range 0.61-0.98). Seven studies reported AUCs for CRP (range 0.52-0.76) with no measurement time point being superior to others. The association of IL-6 and PCT with outcome appeared stronger in studies with more severely ill patients. Studies reported conflicting results regarding each marker's association with organ failure severity.

CONCLUSION

Inflammatory markers are potentially useful for early risk stratification after OHCA. PCT and IL-6 have moderate prognostic value during the first 24 h of the ICU stay. Predictive accuracy appears to be associated with the study overall event rate.

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Grand J, Hassager C. State of the art post-cardiac arrest care: evolution and future of post cardiac arrest care. EUROPEAN HEART JOURNAL. ACUTE CARDIOVASCULAR CARE 2023;12:559-570. [PMID: 37329248 DOI: 10.1093/ehjacc/zuad067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/12/2023] [Accepted: 06/15/2023] [Indexed: 06/18/2023]

Lesbekov T, Nurmykhametova Z, Kaliyev R, Kuanyshbek A, Faizov L, Bekishev B, Jabayeva N, Samalavicius R, Pya Y. Hemadsorption in patients requiring V-A ECMO support: Comparison of Cytosorb versus Jafron HA330. Artif Organs 2023;47:721-730. [PMID: 36398369 DOI: 10.1111/aor.14457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 10/13/2022] [Accepted: 11/04/2022] [Indexed: 11/19/2022]

Meyer MAS, Bjerre M, Wiberg S, Grand J, Obling LER, Meyer ASP, Josiassen J, Frydland M, Thomsen JH, Frikke-Schmidt R, Kjaergaard J, Hassager C. Modulation of inflammation by treatment with tocilizumab after out-of-hospital cardiac arrest and associations with clinical status, myocardial- and brain injury. Resuscitation 2023;184:109676. [PMID: 36572373 DOI: 10.1016/j.resuscitation.2022.109676] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 12/15/2022] [Accepted: 12/15/2022] [Indexed: 12/25/2022]

Monard C, Bianchi N, Poli E, Altarelli M, Debonneville A, Oddo M, Liaudet L, Schneider A. Cytokine hemoadsorption with CytoSorb^® in post-cardiac arrest syndrome, a pilot randomized controlled trial. Crit Care 2023;27:36. [PMID: 36691082 PMCID: PMC9869834 DOI: 10.1186/s13054-023-04323-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 01/14/2023] [Indexed: 01/25/2023] Open

Abstract

BACKGROUND

Hemoadsorption (HA) might mitigate the systemic inflammatory response associated with post-cardiac arrest syndrome (PCAS) and improve outcomes. Here, we investigated the feasibility, safety and efficacy of HA with CytoSorb® in cardiac arrest (CA) survivors at risk of PCAS.

METHODS

In this pilot randomized controlled trial, we included patients admitted to our intensive care unit following CA and likely to develop PCAS: required norepinephrine (> 0.2 µg/kg/min), and/or had serum lactate > 6 mmol/l and/or a time-to-return of spontaneous circulation (ROSC) > 25 min. Those requiring ECMO or renal replacement therapy were excluded. Eligible patients were randomly allocated to either receive standard of care (SOC) or SOC plus HA. Hemoadsorption was performed as stand-alone therapy for 24 h, using CytoSorb® and regional heparin-protamine anticoagulation. We collected feasibility, safety and clinical data as well as serial plasma cytokines levels within 72 h of randomization.

RESULTS

We enrolled 21 patients, of whom 16 (76%) had out-of-hospital CA. Median (IQR) time-to-ROSC was 30 (20, 45) minutes. Ten were assigned to the HA group and 11 to the SOC group. Hemoadsorption was initiated in all patients allocated to the HA group within 18 (11, 23) h of ICU admission and conducted for a median duration of 21 (14, 24) h. The intervention was well tolerated except for a trend for a higher rate of aPTT elevation (5 (50%) vs 2 (18%) p = 0.18) and mild (100-150 G/L) thrombocytopenia at day 1 (5 (50%) vs 2 (18%) p = 0.18). Interleukin (IL)-6 plasma levels at randomization were low (< 100 pg/mL) in 10 (48%) patients and elevated (> 1000 pg/mL) in 6 (29%). The median relative reduction in IL-6 at 48 h was 75% (60, 94) in the HA group versus 5% (- 47, 70) in the SOC group (p = 0.06).

CONCLUSIONS

In CA survivors at risk of PCAS, HA was feasible, safe and was associated with a nonsignificant reduction in cytokine plasma levels. Future trials are needed to further define the role of HA after CA. Those studies should include cytokine assessment to enrich the study population.

TRIAL REGISTRATION

NCT03523039, registered 14 May 2018.

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Zipperle J, Ziegler B, Schöchl H, Voelckel W, Dungel P, Cadamuro J, Osuchowski M, Schlimp CJ, Oberladstätter D. Conventional and Pro-Inflammatory Pathways of Fibrinolytic Activation in Non-Traumatic Hyperfibrinolysis. J Clin Med 2022;11:7305. [PMID: 36555922 PMCID: PMC9787796 DOI: 10.3390/jcm11247305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 11/29/2022] [Accepted: 12/01/2022] [Indexed: 12/14/2022] Open

Abstract

Hyperfibrinolysis (HF) frequently occurs after severe systemic hypoperfusion during major trauma and out-of-hospital cardiac arrest (OHCA). In trauma-induced HF, hypoperfusion, the activation of protein C (APC), and the release of tissue plasminogen activator (t-PA) have been identified as the driving elements of premature clot breakdown. The APC pathway also plays a role in inflammatory responses such as neutrophil extracellular trap formation (NETosis), which might contribute to lysis through cleavage of fibrin by neutrophil elastases. We investigated whether the APC and the plasminogen pathway were general drivers of HF, even in the absence of a traumatic incident. Additionally, we were interested in inflammatory activation such as the presence of NETs as potential contributing factors to HF. A total of 41 patients with OHCA were assigned to a HF and a non-HF group based on maximum lysis (ML) in thromboelastometry. Thrombin-antithrombin (TAT)-complex, soluble thrombomodulin (sTM), APC-PC inhibitor complex, t-PA, PAI-1, t-PA-PAI-1 complex, plasmin-antiplasmin (PAP), d-dimers, neutrophil elastase, histonylated DNA (hDNA) fragments, and interleukin-6 were assessed via immunoassays in the HF group vs. non-HF. APC-PC inhibitor complex is significantly higher in HF patients. Antigen levels of t-PA and PAI-1 do not differ between groups. However, t-PA activity is significantly higher and t-PA-PAI-1 complex significantly lower in the HF group. Consistent with these results, PAP and d-dimers are significantly elevated in HF. HDNA fragments and neutrophil elastase are not elevated in HF patients, but show a high level of correlation, suggesting NETosis occurs in OHCA as part of inflammatory activation and cellular decay. Just as in trauma, hypoperfusion, the activation of protein C, and the initiation of the plasminogen pathway of fibrinolysis manifest themselves in the HF of cardiac arrest. Despite features of NETosis being detectable in OHCA patients, early pro-inflammatory responses do not appear be associated with HF in cardiac arrest.

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The monoacylglycerol lipase inhibitor, JZL184, has comparable effects to therapeutic hypothermia, attenuating global cerebral injury in a rat model of cardiac arrest. Biomed Pharmacother 2022;156:113847. [DOI: 10.1016/j.biopha.2022.113847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 09/24/2022] [Accepted: 10/06/2022] [Indexed: 11/18/2022] Open

Vallabhajosyula S, Verghese D, Henry TD, Katz JN, Nicholson WJ, Jaber WA, Jentzer JC. Contemporary Management of Concomitant Cardiac Arrest and Cardiogenic Shock Complicating Myocardial Infarction. Mayo Clin Proc 2022;97:2333-2354. [PMID: 36464466 DOI: 10.1016/j.mayocp.2022.06.027] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 06/08/2022] [Accepted: 06/24/2022] [Indexed: 12/03/2022]

Obling LER, Beske RP, Wiberg S, Folke F, Moeller JE, Kjaergaard J, Hassager C. Steroid treatment as anti-inflammatory and neuroprotective agent following out-of-hospital cardiac arrest: a randomized clinical trial. Trials 2022;23:952. [PMID: 36414975 PMCID: PMC9682762 DOI: 10.1186/s13063-022-06838-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 10/11/2022] [Indexed: 11/24/2022] Open

Abstract

BACKGROUND

Patients resuscitated from out-of-hospital cardiac arrest (OHCA) have a high morbidity and mortality risk and often develop post-cardiac arrest syndrome (PCAS) involving systemic inflammation. The severity of the inflammatory response is associated with adverse outcome, with anoxic irreversible brain injury as the leading cause of death following resuscitated OHCA. The study aimed to investigate the anti-inflammatory and neuroprotective effect of pre-hospital administration of a high-dose glucocorticoid following OHCA.

METHODS

The study is an investigator-initiated, randomized, multicenter, single-blinded, placebo-controlled, clinical trial. Inclusion will continue until one hundred twenty unconscious OHCA patients surviving a minimum of 72 h are randomized. Intervention is a 1:1 randomization to an infusion of methylprednisolone 250 mg following a minimum of 5 min of sustained return of spontaneous circulation in the pre-hospital setting. Methylprednisolone will be given as a bolus infusion of 1 × 250 mg (1 × 4 mL) over a period of 5 min. Patients allocated to placebo will receive 4 mL of isotonic saline (NaCl 0.9%). Main eligibility criteria are OHCA of presumed cardiac cause, age ≥ 18 years, Glasgow Coma Scale ≤ 8, and sustained ROSC for at least 5 min. Co-primary endpoint: Reduction of interleukin-6 and neuron-specific-enolase. Secondary endpoints: Markers of inflammation, brain, cardiac, kidney and liver damage, hemodynamic and hemostatic function, safety, neurological function at follow-up, and mortality. A research biobank is set up with blood samples taken daily during the first 72 h from hospitalization to evaluate primary and secondary endpoints.

DISCUSSION

We hypothesize that early anti-inflammatory steroid treatment in the pre-hospital setting can mitigate the progression of PCAS following resuscitated OHCA. Primary endpoints will be assessed through analyses of biomarkers for inflammation and neurological damage taken during the first 72 h of admission.

TRIAL REGISTRATION

EudraCT number: 2020-000855-11 ; submitted March 30, 2020 ClinicalTrials.gov Identifier: NCT04624776; submitted October 12, 2020, first posted November 10, 2020.

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Wang C, Bischof E, Xu J, Guo Q, Zheng G, Ge W, Hu J, Georgescu Margarint EL, Bradley JL, Peberdy MA, Ornato JP, Zhu C, Tang W. Effects of Methylprednisolone on Myocardial Function and Microcirculation in Post-resuscitation: A Rat Model. Front Cardiovasc Med 2022;9:894004. [PMID: 35872886 PMCID: PMC9301050 DOI: 10.3389/fcvm.2022.894004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 06/20/2022] [Indexed: 11/13/2022] Open

Affiliation(s)

Changsheng Wang Department of Emergency Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, United States
Evelyne Bischof Department of Basic and Clinical Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, China Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Jing Xu Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, United States
Qinyue Guo Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, United States
Guanghui Zheng Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, United States
Weiwei Ge Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, United States
Juntao Hu Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, United States
Elena Laura Georgescu Margarint Shanghai East International Medical Center, Shanghai, China
Jennifer L. Bradley Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, United States
Mary Ann Peberdy Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, United States Department of Internal Medicine and Emergency Medicine, Virginia Commonwealth University Health System, Richmond, VA, United States
Joseph P. Ornato Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, United States Department of Internal Medicine and Emergency Medicine, Virginia Commonwealth University Health System, Richmond, VA, United States
Changqing Zhu Department of Emergency Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China *Correspondence: Changqing Zhu,
Wanchun Tang Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, United States Department of Emergency Medicine, Virginia Commonwealth University Health System, Richmond, VA, United States Wanchun Tang,

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Mentzelopoulos SD, Pappa E, Malachias S, Vrettou CS, Giannopoulos A, Karlis G, Adamos G, Pantazopoulos I, Megalou A, Louvaris Z, Karavana V, Aggelopoulos E, Agaliotis G, Papadaki M, Baladima A, Lasithiotaki I, Lagiou F, Temperikidis P, Louka A, Asimakos A, Kougias M, Makris D, Zakynthinos E, Xintara M, Papadonta ME, Koutsothymiou A, Zakynthinos SG, Ischaki E. Physiologic effects of stress dose corticosteroids in in-hospital cardiac arrest (CORTICA): A randomized clinical trial. Resusc Plus 2022;10:100252. [PMID: 35652112 PMCID: PMC9149191 DOI: 10.1016/j.resplu.2022.100252] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 05/09/2022] [Accepted: 05/11/2022] [Indexed: 01/15/2023] Open

Abstract

Aim

Postresuscitation hemodynamics are associated with hospital mortality/functional outcome. We sought to determine whether low-dose steroids started during and continued after cardiopulmonary resuscitation (CPR) affect postresuscitation hemodynamics and other physiological variables in vasopressor-requiring, in-hospital cardiac arrest.

Methods

We conducted a two-center, randomized, double-blind trial of patients with adrenaline (epinephrine)-requiring cardiac arrest. Patients were randomized to receive either methylprednisolone 40 mg (steroids group) or normal saline-placebo (control group) during the first CPR cycle post-enrollment. Postresuscitation shock was treated with hydrocortisone 240 mg daily for 7 days maximum and gradual taper (steroids group), or saline-placebo (control group). Primary outcomes were arterial pressure and central-venous oxygen saturation (ScvO₂) within 72 hours post-ROSC.

Results

Eighty nine of 98 controls and 80 of 86 steroids group patients with ROSC were treated as randomized. Primary outcome data were collected from 100 patients with ROSC (control, n = 54; steroids, n = 46). In intention-to-treat mixed-model analyses, there was no significant effect of group on arterial pressure, marginal mean (95% confidence interval) for mean arterial pressure, steroids vs. control: 74 (68–80) vs. 72 (66–79) mmHg] and ScvO₂ [71 (68–75)% vs. 69 (65–73)%], cardiac index [2.8 (2.5–3.1) vs. 2.9 (2.5–3.2) L/min/m²], and serum cytokine concentrations [e.g. interleukin-6, 89.1 (42.8–133.9) vs. 75.7 (52.1–152.3) pg/mL] determined within 72 hours post-ROSC (P = 0.12–0.86). There was no between-group difference in body temperature, echocardiographic variables, prefrontal blood flow index/cerebral autoregulation, organ failure-free days, and hazard for poor in-hospital/functional outcome, and adverse events (P = 0.08–>0.99).

Conclusions

Our results do not support the use of low-dose corticosteroids in in-hospital cardiac arrest.

Trial Registration:ClinicalTrials.gov number: NCT02790788 (https://www.clinicaltrials.gov).

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Affiliation(s)

Spyros D. Mentzelopoulos First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece Corresponding author at: Department of Intensive Care Medicine, Evaggelismos General Hospital, 45-47 Ipsilandou Street, GR-10675 Athens, Greece.
Evanthia Pappa First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece
Sotirios Malachias First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece
Charikleia S. Vrettou First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece
Achilleas Giannopoulos First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece
George Karlis First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece
George Adamos First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece
Ioannis Pantazopoulos First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece
Aikaterini Megalou First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece
Zafeiris Louvaris Faculty of Movement and Rehabilitation Sciences, Department of Rehabilitation Sciences, Research Group for Rehabilitation in Internal Disorders, KU Leuven, Belgium University Hospitals Leuven, Department of Intensive Care Medicine, Leuven, Belgium
Vassiliki Karavana First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece
Epameinondas Aggelopoulos First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece
Gerasimos Agaliotis First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece
Marielen Papadaki First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece
Aggeliki Baladima First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece
Ismini Lasithiotaki Department of Anesthesiology, Evaggelismos General Hospital, Athens, Greece
Fotini Lagiou First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece
Prodromos Temperikidis First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece
Aggeliki Louka Department of Anesthesiology, Evaggelismos General Hospital, Athens, Greece
Andreas Asimakos First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece
Marios Kougias First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece
Demosthenes Makris Department of Intensive Care Medicine, University of Thessaly Medical School, Larissa, Greece
Epameinondas Zakynthinos Department of Intensive Care Medicine, University of Thessaly Medical School, Larissa, Greece
Maria Xintara Department of Intensive Care Medicine, University of Thessaly Medical School, Larissa, Greece
Maria-Eirini Papadonta Department of Anesthesiology, University of Thessaly Medical School, Larissa, Greece
Aikaterini Koutsothymiou Department of Anesthesiology, University of Thessaly Medical School, Larissa, Greece
Spyros G. Zakynthinos First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece
Eleni Ischaki First Department of Intensive Care Medicine, National and Kapodistrian University of Athens Medical School, Evaggelismos General Hospital, Athens, Greece

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Toftgaard Pedersen A, Kjaergaard J, Hassager C, Frydland M, Hartvig Thomsen J, Klein A, Schmidt H, Møller JE, Wiberg S. Association between inflammatory markers and survival in comatose, resuscitated out-of-hospital cardiac arrest patients. SCAND CARDIOVASC J 2022;56:85-90. [PMID: 35546563 DOI: 10.1080/14017431.2022.2074093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]

Cytokine adsorption in patients with post-cardiac arrest syndrome after extracorporeal cardiopulmonary resuscitation (CYTER) – a single-centre, open-label, randomised, controlled trial. Resuscitation 2022;173:169-178. [DOI: 10.1016/j.resuscitation.2022.02.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 01/31/2022] [Accepted: 02/01/2022] [Indexed: 01/19/2023]

Supady A, Zahn T, Rieder M, Benk C, Lother A, Bode C, Wengenmayer T, Staudacher D, Kellum JA, Duerschmied D. Effect of Cytokine Adsorption on Survival and Circulatory Stabilization in Patients Receiving Extracorporeal Cardiopulmonary Resuscitation. ASAIO J 2022;68:64-72. [PMID: 33883508 DOI: 10.1097/mat.0000000000001441] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open

Affiliation(s)

Alexander Supady From the Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Germany Heidelberg Institute of Global Health, University of Heidelberg, Heidelberg, Germany
Timm Zahn From the Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Germany
Marina Rieder From the Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Germany
Christoph Benk Department of Cardiovascular Surgery, Heart Center Freiburg University, University of Freiburg, Freiburg, Germany
Achim Lother From the Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Germany Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Christoph Bode From the Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Germany
Tobias Wengenmayer From the Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Germany
Dawid Staudacher From the Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Germany
John A Kellum Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, USA
Daniel Duerschmied From the Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Germany

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Takegawa R, Hayashida K, Yin T, Choudhary RC, Miyara SJ, Khalili H, Shoaib M, Endo Y, Molmenti EP, Becker LB. Real-Time Brain Monitoring by Near-Infrared Spectroscopy Predicts Neurological Outcome after Cardiac Arrest and Resuscitation in Rats: A Proof of Concept Study of a Novel Prognostic Measure after Cardiac Arrest. J Clin Med 2021;11:jcm11010131. [PMID: 35011872 PMCID: PMC8745661 DOI: 10.3390/jcm11010131] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 12/21/2021] [Accepted: 12/23/2021] [Indexed: 12/03/2022] Open

Affiliation(s)

Ryosuke Takegawa Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA; (R.T.); (T.Y.); (R.C.C.); (S.J.M.); (H.K.); (M.S.); (Y.E.); (L.B.B.) Department of Emergency Medicine, North Shore University Hospital, Northwell Health System, Manhasset, NY 11030, USA Department of Traumatology and Acute Critical Medicine, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
Kei Hayashida Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA; (R.T.); (T.Y.); (R.C.C.); (S.J.M.); (H.K.); (M.S.); (Y.E.); (L.B.B.) Department of Emergency Medicine, North Shore University Hospital, Northwell Health System, Manhasset, NY 11030, USA Correspondence:
Tai Yin Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA; (R.T.); (T.Y.); (R.C.C.); (S.J.M.); (H.K.); (M.S.); (Y.E.); (L.B.B.) Department of Emergency Medicine, North Shore University Hospital, Northwell Health System, Manhasset, NY 11030, USA
Rishabh C. Choudhary Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA; (R.T.); (T.Y.); (R.C.C.); (S.J.M.); (H.K.); (M.S.); (Y.E.); (L.B.B.) Department of Emergency Medicine, North Shore University Hospital, Northwell Health System, Manhasset, NY 11030, USA
Santiago J. Miyara Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA; (R.T.); (T.Y.); (R.C.C.); (S.J.M.); (H.K.); (M.S.); (Y.E.); (L.B.B.) Department of Emergency Medicine, North Shore University Hospital, Northwell Health System, Manhasset, NY 11030, USA
Houman Khalili Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA; (R.T.); (T.Y.); (R.C.C.); (S.J.M.); (H.K.); (M.S.); (Y.E.); (L.B.B.)
Muhammad Shoaib Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA; (R.T.); (T.Y.); (R.C.C.); (S.J.M.); (H.K.); (M.S.); (Y.E.); (L.B.B.) Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA;
Yusuke Endo Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA; (R.T.); (T.Y.); (R.C.C.); (S.J.M.); (H.K.); (M.S.); (Y.E.); (L.B.B.) Department of Emergency Medicine, North Shore University Hospital, Northwell Health System, Manhasset, NY 11030, USA
Emesto P. Molmenti Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA; Department of Surgery, North Shore University Hospital, Northwell Health, Manhasset, NY 11030, USA
Lance B. Becker Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA; (R.T.); (T.Y.); (R.C.C.); (S.J.M.); (H.K.); (M.S.); (Y.E.); (L.B.B.) Department of Emergency Medicine, North Shore University Hospital, Northwell Health System, Manhasset, NY 11030, USA Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA;

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Lascarrou JB, Guichard E, Reignier J, Le Gouge A, Pouplet C, Martin S, Lacherade JC, Colin G. Impact of rewarming rate on interleukin-6 levels in patients with shockable cardiac arrest receiving targeted temperature management at 33 °C: the ISOCRATE pilot randomized controlled trial. Crit Care 2021;25:434. [PMID: 34920723 PMCID: PMC8680374 DOI: 10.1186/s13054-021-03842-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 11/24/2021] [Indexed: 02/06/2023] Open

Abstract

Purpose

While targeted temperature management (TTM) has been recommended in patients with shockable cardiac arrest (CA) and suggested in patients with non-shockable rhythms, few data exist regarding the impact of the rewarming rate on systemic inflammation. We compared serum levels of the proinflammatory cytokine interleukin-6 (IL6) measured with two rewarming rates after TTM at 33 °C in patients with shockable out-of-hospital cardiac arrest (OHCA).

Methods

ISOCRATE was a single-center randomized controlled trial comparing rewarming at 0.50 °C/h versus 0.25 °C/h in patients coma after shockable OHCA in 2016–2020. The primary outcome was serum IL6 level 24–48 h after reaching 33 °C. Secondary outcomes included the day-90 Cerebral Performance Category (CPC) and the 48-h serum neurofilament light-chain (NF-L) level.

Results

We randomized 50 patients. The median IL6 area-under-the-curve was similar between the two groups (12,389 [7256–37,200] vs. 8859 [6825–18,088] pg/mL h; P = 0.55). No significant difference was noted in proportions of patients with favorable day-90 CPC scores (13/25 patients at 0.25 °C/h (52.0%; 95% CI 31.3–72.2%) and 13/25 patients at 0.50 °C/h (52.0%; 95% CI 31.3–72.2%; P = 0.99)). Median NF-L levels were not significantly different between the 0.25 °C/h and 0.50 °C/h groups (76.0 pg mL, [25.5–3074.0] vs. 192 pg mL, [33.6–4199.0]; P = 0.43; respectively).

Conclusion

In our RCT, rewarming from 33 °C at 0.25 °C/h, compared to 0.50 °C/h, did not decrease the serum IL6 level after shockable CA. Further RCTs are needed to better define the optimal TTM strategy for patients with CA.

Trial registration ClinicalTrials.gov, NCT02555254. Registered September 14, 2015.

Take-Home Message: Rewarming at a rate of 0.25 °C/h, compared to 0.50 °C, did not result in lower serum IL6 levels after achievement of hypothermia at 33 °C in patients who remained comatose after shockable cardiac arrest. No associations were found between the slower rewarming rate and day-90 functional outcomes or mortality.

140-character Tweet: Rewarming at 0.25 °C versus 0.50 °C did not decrease serum IL6 levels after hypothermia at 33 °C in patients comatose after shockable cardiac arrest.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13054-021-03842-9.

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Kernan KF, Kochanek PM. Black swans or red herrings - inflammatory derangement after cardiac arrest. Resuscitation 2021;171:100-102. [PMID: 34920016 DOI: 10.1016/j.resuscitation.2021.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 12/06/2021] [Indexed: 11/28/2022]

Langeland H, Damås JK, Mollnes TE, Ludviksen JK, Ueland T, Michelsen AE, Løberg M, Bergum D, Nordseth T, Skjærvold NK, Klepstad P. The inflammatory response is related to circulatory failure after out-of-hospital cardiac arrest: A prospective cohort study. Resuscitation 2021;170:115-125. [PMID: 34838662 DOI: 10.1016/j.resuscitation.2021.11.026] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 10/31/2021] [Accepted: 11/17/2021] [Indexed: 12/12/2022]

Abstract

BACKGROUND

Whole body ischemia and reperfusion injury after cardiac arrest leads to the massive inflammation clinically manifested in the post-cardiac arrest syndrome. Previous studies on the inflammatory effect on circulatory failure after cardiac arrest have either investigated a selected patient group or a limited part of the inflammatory mechanisms. We examined the association between cardiac arrest characteristics and inflammatory biomarkers, and between inflammatory biomarkers and circulatory failure after cardiac arrest, in an unselected patient cohort.

METHODS

This was a prospective study of 50 consecutive patients with out-of-hospital cardiac arrest. Circulation was invasively monitored from admission until day five, whereas inflammatory biomarkers, i.e. complement activation, cytokines and endothelial injury, were measured daily. We identified predictors for an increased inflammatory response, and associations between the inflammatory response and circulatory failure.

RESULTS

We found a marked and broad inflammatory response in patients after cardiac arrest, which was associated with clinical outcome. Long time to return of spontaneous circulation and high lactate level at admission were associated with increased complement activation (TCC and C3bc), pro-inflammatory cytokines (IL-6, IL-8) and endothelial injury (syndecan-1) at admission. These biomarkers were in turn significantly associated with lower mean arterial blood pressure, lower cardiac output and lower systemic vascular resistance, and increased need of circulatory support in the initial phase. High levels of TCC and IL-6 at admission were significantly associated with increased 30-days mortality.

CONCLUSION

Inflammatory biomarkers, including complement activation, cytokines and endothelial injury, were associated with increased circulatory failure in the initial period after cardiac arrest.

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Affiliation(s)

Halvor Langeland Department of Anaesthesiology and Intensive Care Medicine, St. Olav's University Hospital, Trondheim, Norway; Institute of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Jan Kristian Damås Gemini Center for Sepsis Research, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Centre of Molecular Inflammation Research, Institute for Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Infectious Diseases, St. Olav's University Hospital, Trondheim, Norway
Tom Eirik Mollnes Centre of Molecular Inflammation Research, Institute for Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway; Research Laboratory, Nordland Hospital, Bodø, Norway; K. G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway
Judith Krey Ludviksen Research Laboratory, Nordland Hospital, Bodø, Norway
Thor Ueland K. G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital (Rikshospitalet), Oslo, Norway
Annika E Michelsen Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital (Rikshospitalet), Oslo, Norway
Magnus Løberg Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo, Norway; Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
Daniel Bergum Department of Anaesthesiology and Intensive Care Medicine, St. Olav's University Hospital, Trondheim, Norway
Trond Nordseth Department of Anaesthesiology and Intensive Care Medicine, St. Olav's University Hospital, Trondheim, Norway; Institute of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Anaesthesia, Molde Hospital, Molde, Norway
Nils Kristian Skjærvold Department of Anaesthesiology and Intensive Care Medicine, St. Olav's University Hospital, Trondheim, Norway; Institute of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
Pål Klepstad Department of Anaesthesiology and Intensive Care Medicine, St. Olav's University Hospital, Trondheim, Norway; Institute of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

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Editorial on: "Complement Activation is associated with poor outcome after out-of-hospital Cardiac Arrest". Resuscitation 2021;166:142-143. [PMID: 34363858 DOI: 10.1016/j.resuscitation.2021.07.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 07/23/2021] [Indexed: 11/22/2022]

Zimmermann GS, Palm J, Lahmann AL, Peltz F, Okrojek R, Weis F, Müller A, Ziegler T, Steger A, Haller B, Hoppmann P, Laugwitz KL, Hautmann H. Early Bronchoscopy Improves Extubation Rates after Out-of-Hospital Cardiac Arrest: A Retrospective Cohort Analysis. J Clin Med 2021;10:jcm10143055. [PMID: 34300221 PMCID: PMC8306153 DOI: 10.3390/jcm10143055] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/05/2021] [Accepted: 07/08/2021] [Indexed: 11/16/2022] Open

Affiliation(s)

Gregor S. Zimmermann Department of Internal Medicine I, School of Medicine & Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (J.P.); (F.P.); (R.O.); (F.W.); (A.M.); (T.Z.); (A.S.); (P.H.); (K.-L.L.); (H.H.) Correspondence:
Jana Palm Department of Internal Medicine I, School of Medicine & Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (J.P.); (F.P.); (R.O.); (F.W.); (A.M.); (T.Z.); (A.S.); (P.H.); (K.-L.L.); (H.H.)
Anna Lena Lahmann Department of Cardiology, German Heart Center Munich, Technical University of Munich, 80636 Munich, Germany;
Friedhelm Peltz Department of Internal Medicine I, School of Medicine & Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (J.P.); (F.P.); (R.O.); (F.W.); (A.M.); (T.Z.); (A.S.); (P.H.); (K.-L.L.); (H.H.)
Rainer Okrojek Department of Internal Medicine I, School of Medicine & Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (J.P.); (F.P.); (R.O.); (F.W.); (A.M.); (T.Z.); (A.S.); (P.H.); (K.-L.L.); (H.H.)
Florian Weis Department of Internal Medicine I, School of Medicine & Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (J.P.); (F.P.); (R.O.); (F.W.); (A.M.); (T.Z.); (A.S.); (P.H.); (K.-L.L.); (H.H.)
Arne Müller Department of Internal Medicine I, School of Medicine & Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (J.P.); (F.P.); (R.O.); (F.W.); (A.M.); (T.Z.); (A.S.); (P.H.); (K.-L.L.); (H.H.)
Tilman Ziegler Department of Internal Medicine I, School of Medicine & Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (J.P.); (F.P.); (R.O.); (F.W.); (A.M.); (T.Z.); (A.S.); (P.H.); (K.-L.L.); (H.H.)
Alexander Steger Department of Internal Medicine I, School of Medicine & Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (J.P.); (F.P.); (R.O.); (F.W.); (A.M.); (T.Z.); (A.S.); (P.H.); (K.-L.L.); (H.H.)
Bernhard Haller Institute of Medical Informatics, Statistics and Epidemiology, Technical University of Munich, 81675 Munich, Germany;
Petra Hoppmann Department of Internal Medicine I, School of Medicine & Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (J.P.); (F.P.); (R.O.); (F.W.); (A.M.); (T.Z.); (A.S.); (P.H.); (K.-L.L.); (H.H.)
Karl-Ludwig Laugwitz Department of Internal Medicine I, School of Medicine & Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (J.P.); (F.P.); (R.O.); (F.W.); (A.M.); (T.Z.); (A.S.); (P.H.); (K.-L.L.); (H.H.)
Hubert Hautmann Department of Internal Medicine I, School of Medicine & Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (J.P.); (F.P.); (R.O.); (F.W.); (A.M.); (T.Z.); (A.S.); (P.H.); (K.-L.L.); (H.H.) Department of Internal Medicine, Klinik Ottobeuren, 87724 Ottobeuren, Germany

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Kutkut I, Uceda D, Kumar A, Wong J, Li X, Wright KC, Straka S, Adams D, Deckard M, Kovacs R, Chen PS, Everett TH. Skin sympathetic nerve activity as a biomarker for neurologic recovery during therapeutic hypothermia for cardiac arrest. Heart Rhythm 2021;18:1162-1170. [PMID: 33689908 PMCID: PMC8254741 DOI: 10.1016/j.hrthm.2021.03.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 03/02/2021] [Accepted: 03/03/2021] [Indexed: 01/01/2023]

Napp LC, Lebreton G, De Somer F, Supady A, Pappalardo F. Opportunities, controversies, and challenges of extracorporeal hemoadsorption with CytoSorb during ECMO. Artif Organs 2021;45:1240-1249. [PMID: 34152637 DOI: 10.1111/aor.14025] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 06/07/2021] [Accepted: 06/09/2021] [Indexed: 11/28/2022]

Gaestel M, Nebreda AR, Yaffe MB. Cytokine Storm. N Engl J Med 2021;384:e59. [PMID: 33882214 DOI: 10.1056/nejmc2036236] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]

Andersson P, Johnsson J, Björnsson O, Cronberg T, Hassager C, Zetterberg H, Stammet P, Undén J, Kjaergaard J, Friberg H, Blennow K, Lilja G, Wise MP, Dankiewicz J, Nielsen N, Frigyesi A. Predicting neurological outcome after out-of-hospital cardiac arrest with cumulative information; development and internal validation of an artificial neural network algorithm. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2021;25:83. [PMID: 33632280 PMCID: PMC7905905 DOI: 10.1186/s13054-021-03505-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 02/10/2021] [Indexed: 12/16/2022]

Abstract

Background

Prognostication of neurological outcome in patients who remain comatose after cardiac arrest resuscitation is complex. Clinical variables, as well as biomarkers of brain injury, cardiac injury, and systemic inflammation, all yield some prognostic value. We hypothesised that cumulative information obtained during the first three days of intensive care could produce a reliable model for predicting neurological outcome following out-of-hospital cardiac arrest (OHCA) using artificial neural network (ANN) with and without biomarkers.

Methods

We performed a post hoc analysis of 932 patients from the Target Temperature Management trial. We focused on comatose patients at 24, 48, and 72 h post-cardiac arrest and excluded patients who were awake or deceased at these time points. 80% of the patients were allocated for model development (training set) and 20% for internal validation (test set). To investigate the prognostic potential of different levels of biomarkers (clinically available and research-grade), patients’ background information, and intensive care observation and treatment, we created three models for each time point: (1) clinical variables, (2) adding clinically accessible biomarkers, e.g., neuron-specific enolase (NSE) and (3) adding research-grade biomarkers, e.g., neurofilament light (NFL). Patient outcome was the dichotomised Cerebral Performance Category (CPC) at six months; a good outcome was defined as CPC 1–2 whilst a poor outcome was defined as CPC 3–5. The area under the receiver operating characteristic curve (AUROC) was calculated for all test sets.

Results

AUROC remained below 90% when using only clinical variables throughout the first three days in the ICU. Adding clinically accessible biomarkers such as NSE, AUROC increased from 82 to 94% (p < 0.01). The prognostic accuracy remained excellent from day 1 to day 3 with an AUROC at approximately 95% when adding research-grade biomarkers. The models which included NSE after 72 h and NFL on any of the three days had a low risk of false-positive predictions while retaining a low number of false-negative predictions.

Conclusions

In this exploratory study, ANNs provided good to excellent prognostic accuracy in predicting neurological outcome in comatose patients post OHCA. The models which included NSE after 72 h and NFL on all days showed promising prognostic performance.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13054-021-03505-9.

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Affiliation(s)

Peder Andersson Department of Clinical Sciences Lund, Anaesthesia and Intensive Care, Lund University, Skåne University Hospital, Lund, Sweden. .,Department of Intensive and Perioperative Care, Skåne University Hospital, Getingevägen 4, 222 41, LundLund, Sweden.
Jesper Johnsson Department of Clinical Sciences Lund, Anesthesia and Intensive Care, Lund University, Helsingborg Hospital, Lund, Sweden
Ola Björnsson Department of Energy Sciences, Faculty of Engineering, Lund University, Lund, Sweden.,Centre for Mathematical Sciences, Mathematical Statistics, Lund University, Lund, Sweden
Tobias Cronberg Department of Clinical Sciences Lund, Neurology, Lund University, Skåne University Hospital, Lund, Sweden
Christian Hassager Department of Cardiology, Rigshospitalet and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Henrik Zetterberg Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy At the University of Gothenburg, Mölndal, Sweden.,Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.,Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.,UK Dementia Research Institute At UCL, London, UK
Pascal Stammet Medical and Health Directorate, National Fire and Rescue Corps, 1, rue Robert Stumper, 2557, Luxembourg, Luxembourg
Johan Undén Department of Clinical Sciences Malmö, Anaesthesia and Intensive Care, Lund University, Hallands Hospital Halmstad, Halland, Sweden
Jesper Kjaergaard Department of Cardiology, Rigshospitalet and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Hans Friberg Department of Clinical Sciences Lund, Anaesthesia and Intensive Care, Lund University, Skåne University Hospital, Malmö, Sweden
Kaj Blennow Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy At the University of Gothenburg, Mölndal, Sweden.,Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Gisela Lilja Department of Clinical Sciences Lund, Neurology, Lund University, Skåne University Hospital, Lund, Sweden
Matt P Wise Adult Critical Care, University Hospital of Wales, Cardiff, UK
Josef Dankiewicz Department of Clinical Sciences Lund, Cardiology, Lund University, Skåne University Hospital, Lund, Sweden
Niklas Nielsen Department of Clinical Sciences Lund, Anesthesia and Intensive Care, Lund University, Helsingborg Hospital, Lund, Sweden
Attila Frigyesi Department of Clinical Sciences Lund, Anaesthesia and Intensive Care, Lund University, Skåne University Hospital, Lund, Sweden.,Centre for Mathematical Sciences, Mathematical Statistics, Lund University, Lund, Sweden

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Wang L, Li RF, Guan XL, Liang SS, Gong P. The Value of Extracellular Cold-Inducible RNA-Binding Protein (eCIRP) in Predicting the Severity and Prognosis of Patients After Cardiac Arrest: A Preliminary Observational Study. Shock 2020;56:229-236. [PMID: 34276038 DOI: 10.1097/shk.0000000000001702] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]

Abstract

BACKGROUND

Extracellular cold-inducible RNA-binding protein (eCIRP) acting as a novel damage-associated molecular pattern molecule promotes systemic inflammatory responses, including neuroinflammation in cerebral ischemia. We aimed to observe the changes of serum eCIRP and evaluate whether the increased serum eCIRP was associated with the severity and prognosis in patients with restoration of spontaneous circulation (ROSC).

METHODS

A total of 73 patients after ROSC were divided into non-survivor (n = 48) and survivor (n = 25) groups based on 28-day survival. Healthy volunteers (n = 25) were enrolled as controls. Serum eCIRP, procalcitonin (PCT), the pro-inflammatory mediators tumor necrosis factor (TNF)-α, interleukin-6 (IL)-6 and high mobility group protein (HMGB1), the neurological damage biomarkers neuron-specific enolase (NSE), and soluble protein 100β (S100β) were measured on days 1, 3, and 7 after ROSC. Clinical data and laboratory findings were collected, and the Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE II) were calculated concurrently. Cerebral performance category scores on day 28 after ROSC were recorded.

RESULTS

Serum eCIRP, IL-6, TNF-α, PCT, and HMGB1, NSE and S100β were significantly increased within the first week after ROSC. The increased levels of eCIRP were positively correlated with IL-6, TNF-α, lactate, NSE, S100β, CPR time, SOFA score, APACHE II score, and HMGB1 after ROSC. Serum eCIRP on days 1, 3, and 7 after ROSC could predict 28-day mortality and neurological prognosis. Serum eCIRP on day 3 after ROSC had a biggest AUC [0.862 (95% CI: 0.741-0.941)] for 28-day mortality and a biggest AUC [0.807 (95% CI: 0.630-0.981)] for neurological prognosis.

CONCLUSIONS

Systemic inflammatory response with increased serum eCIRP occurred in patients after ROSC. Increased eCIRP level was positively correlated with the aggravation of systemic inflammatory response and the severity after ROSC. Serum eCIRP serves as a potential predictor for 28-day mortality and poor neurological prognosis after ROSC.

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Boissady E, Kohlhauer M, Lidouren F, Hocini H, Lefebvre C, Chateau‐Jouber S, Mongardon N, Deye N, Cariou A, Micheau P, Ghaleh B, Tissier R. Ultrafast Hypothermia Selectively Mitigates the Early Humoral Response After Cardiac Arrest. J Am Heart Assoc 2020;9:e017413. [PMID: 33198571 PMCID: PMC7763769 DOI: 10.1161/jaha.120.017413] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 09/18/2020] [Indexed: 12/17/2022]

Abstract

Background Total liquid ventilation (TLV) has been shown to prevent neurological damage though ultrafast cooling in animal models of cardiac arrest. We investigated whether its neuroprotective effect could be explained by mitigation of early inflammatory events. Methods and Results Rabbits were submitted to 10 minutes of ventricular fibrillation. After resuscitation, they underwent normothermic follow-up (control) or ultrafast cooling by TLV and hypothermia maintenance for 3 hours (TLV). Immune response, survival, and neurological dysfunction were assessed for 3 days. TLV improved neurological recovery and reduced cerebral lesions and leukocyte infiltration as compared with control (eg, neurological dysfunction score=34±6 versus 66±6% at day 1, respectively). TLV also significantly reduced interleukin-6 blood levels during the hypothermic episode (298±303 versus 991±471 pg/mL in TLV versus control at 3 hours after resuscitation, respectively), but not after rewarming (752±563 versus 741±219 pg/mL in TLV versus control at 6 hours after resuscitation, respectively). In vitro assays confirmed the high temperature sensitivity of interleukin-6 secretion. Conversely, TLV did not modify circulating high-mobility group box 1 levels or immune cell recruitment into the peripheral circulation. The link between interleukin-6 early transcripts (<8 hours) and neurological outcome in a subpopulation of the previously described Epo-ACR-02 (High Dose of Erythropoietin Analogue After Cardiac Arrest) trial confirmed the importance of this cytokine at the early stages as compared with delayed stages (>8 hours). Conclusions The neuroprotective effect of hypothermic TLV was associated with a mitigation of humoral interleukin-6 response. A temperature-dependent attenuation of immune cell reactivity during the early phase of the post-cardiac arrest syndrome could explain the potent effect of rapid hypothermia. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00999583.

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High plasma levels of pro-inflammatory factors interleukin-17 and interleukin-23 are associated with poor outcome of cardiac-arrest patients: a single center experience. BMC Cardiovasc Disord 2020;20:170. [PMID: 32293300 PMCID: PMC7158084 DOI: 10.1186/s12872-020-01451-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Accepted: 03/29/2020] [Indexed: 12/12/2022] Open

Abstract

Background

Systemic inflammation is an important feature of post-cardiac arrest syndrome (PCAS). This study was designed to determine whether the plasma concentrations of some circulating pro-inflammatory cytokines (interleukin-17 [IL-8], IL-22, IL-23 and IL-33) are of value in predicting the outcome of patients after return of spontaneous circulation (ROSC) during the post–cardiac arrest period.

Methods

This was a prospective observational clinical study. In total, 21 patients (survivors, n = 10; non-survivors, n = 11) who experienced cardiac arrest and successful ROSC with expected survival of at least 7 days were consecutively enrolled from January 2016 to December 2017. Of the 21 enrolled patients, ten survived were designated “survivors”. The other eleven patients died between 2 days and 1 months post ROSC. Venous blood was drawn at three time-points: baseline (< 1 h post ROSC), 2 days post ROSC and 7 days post ROSC. Plasma IL-8, IL-22, IL-23 and IL-33 were determined using commercial enzyme-linked immunosorbent assays.

Results

Plasma creatinine levels, but aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, were elevated in non-survivors compared with survivors. Plasma levels of IL-17, IL-22, IL-23 and IL-33 of the 21 total patients did not change at 2 or 7 days post ROSC compared to baseline. In survivors, the plasma levels of IL-17 and IL-23 at 2 or 7 days post ROSC were lower than baseline. In non-survivors, plasma levels of IL-17 increased compared with baseline. Receiver operating characteristic curve analysis showed that the plasma levels of IL-17 and IL-23 at 2 or 7 days post ROSC were able to predict the mortality of PCAS patients, and positively correlated with Acute Physiology and Chronic Health Evaluation (APACHE)-II score and time to ROSC.

Conclusion

These results provide the first evidence that the elevated plasma IL-17 and IL-23 levels are associated with poor outcome in PCAS patients. The role of IL-17/IL-23 axis post ROSC is worth paying attention to in PCAS patients.

Trial registration

Clinicaltrial.govNCT02297776, 2014-11-21.

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Tamura T, Suzuki M, Hayashida K, Kobayashi Y, Yoshizawa J, Shibusawa T, Sano M, Hori S, Sasaki J. Hydrogen gas inhalation alleviates oxidative stress in patients with post-cardiac arrest syndrome. J Clin Biochem Nutr 2020;67:214-221. [PMID: 33041520 PMCID: PMC7533855 DOI: 10.3164/jcbn.19-101] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 01/07/2020] [Indexed: 12/27/2022] Open

Liu H, Luo Z, Liu L, Yang X, Zhuang Y, Tu G, Ma G, Zhang Y, Zheng J, Zhu D, Wang C. Inflammatory biomarkers to predict adverse outcomes in postoperative patients with acute type A aortic dissection. SCAND CARDIOVASC J 2020;54:37-46. [PMID: 31738077 DOI: 10.1080/14017431.2019.1689289] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Grand J, Bro-Jeppesen J, Hassager C, Rundgren M, Winther-Jensen M, Thomsen JH, Nielsen N, Wanscher M, Kjærgaard J. Cardiac output during targeted temperature management and renal function after out-of-hospital cardiac arrest. J Crit Care 2019;54:65-73. [DOI: 10.1016/j.jcrc.2019.07.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 07/11/2019] [Accepted: 07/12/2019] [Indexed: 01/20/2023]

Rueda F, Cediel G, García-García C, Aranyó J, González-Lopera M, Aranda Nevado MC, Serra Gregori J, Oliveras T, Labata C, Ferrer M, El Ouaddi N, Bayés-Genís A. Growth differentiation factor 15 and early prognosis after out-of-hospital cardiac arrest. Ann Intensive Care 2019;9:119. [PMID: 31624933 PMCID: PMC6797678 DOI: 10.1186/s13613-019-0593-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Accepted: 10/05/2019] [Indexed: 12/20/2022] Open

Abstract

BACKGROUND

Growth differentiation factor 15 (GDF-15) is an inflammatory cytokine released in response to tissue injury. It has prognostic value in cardiovascular diseases and other acute and chronic conditions. Here, we explored the value of GDF-15 as an early predictor of neurologic outcome after an out-of-hospital cardiac arrest (OHCA).

METHODS

Prospective registry study of patients in coma after an OHCA, admitted in the intensive cardiac care unit from a single university center. Serum levels of GDF-15 were measured on admission. Neurologic status was evaluated according to the cerebral performance category (CPC) scale. The relationship between GDF-15 levels and poor neurologic outcome at 6 months was analyzed.

RESULTS

Among 62 patients included, 32 (51.6%) presented poor outcome (CPC 3-5). Patients with CPC 3-5 exhibited significantly higher GDF-15 levels (median, 17.1 [IQR, 11.1-20.4] ng/mL) compared to those with CPC 1-2 (7.6 [IQR, 4.1-13.1] ng/mL; p = 0.004). Multivariable logistic regression analyses showed that age (OR, 1.09; 95% CI 1.01-1.17; p = 0.020), home setting arrest (OR, 8.07; 95% CI 1.61-40.42; p = 0.011), no bystander cardiopulmonary resuscitation (OR, 7.91; 95% CI 1.84-34.01; p = 0.005), and GDF-15 levels (OR, 3.74; 95% CI 1.32-10.60; p = 0.013) were independent predictors of poor outcome. The addition of GDF-15 in a dichotomous manner (≥ 10.8 vs. < 10.8 ng/mL) to the resulting clinical model improved discrimination; it increased the area under the curve from 0.867 to 0.917, and the associated continuous net reclassification improvement was 0.90 (95% CI 0.48-1.44), which allowed reclassification of 37.1% of patients.

CONCLUSIONS

After an OHCA, increased GDF-15 levels were an independent, early predictor of poor neurologic outcome. Furthermore, when added to the most common clinical factors, GDF-15 improved discrimination and allowed patient reclassification.

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Affiliation(s)

Ferran Rueda Heart Institute, Germans Trias i Pujol University Hospital, Carretera de Canyet s/n, Badalona, 08916, Barcelona, Spain.,Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain.,PhD Program in Internal Medicine, Autonomous University of Barcelona, Barcelona, Spain
Germán Cediel Heart Institute, Germans Trias i Pujol University Hospital, Carretera de Canyet s/n, Badalona, 08916, Barcelona, Spain.,Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain
Cosme García-García Heart Institute, Germans Trias i Pujol University Hospital, Carretera de Canyet s/n, Badalona, 08916, Barcelona, Spain.,Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain
Júlia Aranyó Heart Institute, Germans Trias i Pujol University Hospital, Carretera de Canyet s/n, Badalona, 08916, Barcelona, Spain.,Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain
Marta González-Lopera Heart Institute, Germans Trias i Pujol University Hospital, Carretera de Canyet s/n, Badalona, 08916, Barcelona, Spain.,Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain
M Cruz Aranda Nevado Heart Institute, Germans Trias i Pujol University Hospital, Carretera de Canyet s/n, Badalona, 08916, Barcelona, Spain.,Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain
Judith Serra Gregori Heart Institute, Germans Trias i Pujol University Hospital, Carretera de Canyet s/n, Badalona, 08916, Barcelona, Spain.,Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain
Teresa Oliveras Heart Institute, Germans Trias i Pujol University Hospital, Carretera de Canyet s/n, Badalona, 08916, Barcelona, Spain.,Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain
Carlos Labata Heart Institute, Germans Trias i Pujol University Hospital, Carretera de Canyet s/n, Badalona, 08916, Barcelona, Spain.,Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain
Marc Ferrer Heart Institute, Germans Trias i Pujol University Hospital, Carretera de Canyet s/n, Badalona, 08916, Barcelona, Spain.,Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain
Nabil El Ouaddi Heart Institute, Germans Trias i Pujol University Hospital, Carretera de Canyet s/n, Badalona, 08916, Barcelona, Spain.,Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain
Antoni Bayés-Genís Heart Institute, Germans Trias i Pujol University Hospital, Carretera de Canyet s/n, Badalona, 08916, Barcelona, Spain. .,Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain.

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Mauracher LM, Buchtele N, Schörgenhofer C, Weiser C, Herkner H, Merrelaar A, Spiel AO, Hell L, Ay C, Pabinger I, Jilma B, Schwameis M. Increased Citrullinated Histone H3 Levels in the Early Post-Resuscitative Period Are Associated with Poor Neurologic Function in Cardiac Arrest Survivors-A Prospective Observational Study. J Clin Med 2019;8:jcm8101568. [PMID: 31581493 PMCID: PMC6832426 DOI: 10.3390/jcm8101568] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 09/23/2019] [Accepted: 09/24/2019] [Indexed: 12/29/2022] Open

Abstract

The exact contribution of neutrophils to post-resuscitative brain damage is unknown. We aimed to investigate whether neutrophil extracellular trap (NET) formation in the early phase after return of spontaneous circulation (ROSC) may be associated with poor 30 day neurologic function in cardiac arrest survivors. This study prospectively included adult (≥18 years) out-of-hospital cardiac arrest (OHCA) survivors with cardiac origin, who were subjected to targeted temperature management. Plasma levels of specific (citrullinated histone H3, H3Cit) and putative (cell-free DNA (cfDNA) and nucleosomes) biomarkers of NET formation were assessed at 0 and 12 h after admission. The primary outcome was neurologic function on day 30 after admission, which was assessed using the five-point cerebral performance category (CPC) score, classifying patients into good (CPC 1–2) or poor (CPC 3–5) neurologic function. The main variable of interest was the effect of H3Cit level quintiles at 12 h on 30 day neurologic function, assessed by logistic regression. The first quintile was used as a baseline reference. Results are given as crude odds ratio (OR) with 95% confidence interval (95% CI). Sixty-two patients (79% male, median age: 57 years) were enrolled. The odds of poor neurologic function increased linearly, with 0 h levels of cfNDA (crude OR 1.8, 95% CI: 1.2–2.7, p = 0.007) and nucleosomes (crude OR 1.7, 95% CI: 1.0–2.2, p = 0.049), as well as with 12 h levels of cfDNA (crude OR 1.6, 95% CI: 1.1–2.4, p = 0.024), nucleosomes (crude OR 1.7, 95% CI: 1.1–2.5, p = 0.020), and H3Cit (crude OR 1.6, 95% CI: 1.1–2.3, p = 0.029). Patients in the fourth (7.9, 95% CI: 1.1–56, p = 0.039) and fifth (9.0, 95% CI: 1.3–63, p = 0.027) H3Cit quintile had significantly higher odds of poor 30 day neurologic function compared to patients in the first quintile. Increased plasma levels of H3Cit, 12 h after admission, are associated with poor 30 day neurologic function in adult OHCA survivors, which may suggest a contribution of NET formation to post-resuscitative brain damage and therefore provide a therapeutic target in the future.

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Eyileten C, Soplinska A, Pordzik J, Siller‐Matula JM, Postuła M. Effectiveness of Antiplatelet Drugs Under Therapeutic Hypothermia: A Comprehensive Review. Clin Pharmacol Ther 2019;106:993-1005. [DOI: 10.1002/cpt.1492] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Accepted: 04/12/2019] [Indexed: 12/13/2022]

Ryzhov S, May T, Dziodzio J, Emery IF, Lucas FL, Leclerc A, McCrum B, Lord C, Eldridge A, Robich MP, Ichinose F, Sawyer DB, Riker R, Seder DB. Number of Circulating CD 73-Expressing Lymphocytes Correlates With Survival After Cardiac Arrest. J Am Heart Assoc 2019;8:e010874. [PMID: 31237169 PMCID: PMC6662342 DOI: 10.1161/jaha.118.010874] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]

Abstract

Background

Patients resuscitated from cardiac arrest (CA) have highly variable neurological, circulatory, and systemic ischemia‐reperfusion injuries. After the initial hypoxic‐ischemic insult, a cascade of immune and inflammatory responses develops and is often fatal. The role of the immune response in pathophysiological characteristics and recovery is not well understood. We studied immune cell activity and its association with outcomes in a cohort of CA survivors.

Methods and Results

After informed consent, we collected blood samples at intervals over a week after resuscitation from CA. We examined the expression of CD39 and CD73 (alias 5′‐nucleotidase), production of tumor necrosis factor‐α, generation of reactive oxygen species, and secretion of vascular endothelial growth factor by circulating myeloid and lymphoid cells, in comparison to cells obtained from control subjects before coronary artery bypass grafting surgery. The number of circulating total and CD73‐expressing lymphocytes correlated with survival after CA. Incubation of immune cells, obtained from post‐CA subjects, with AMP, a substrate for CD73, resulted in inhibition of tumor necrosis factor‐α production and generation of reactive oxygen species. This effect was blocked by adenosine 5′‐(α, β‐methylene) diphosphate, a specific inhibitor of CD73 and ZM 241385, an A2 adenosine receptor antagonist. We also found that AMP‐dependent activation of CD73 induces production of vascular endothelial growth factor.

Conclusions

CD73‐expressing lymphocytes mediate cellular protection from inflammation after CA through inhibition of proinflammatory activation of myeloid cells and promotion of vascular endothelial growth factor secretion. The contribution of CD73 lymphocytes in the regulation of acute inflammation and tissue injury after CA warrants further study.

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Lother A, Benk C, Staudacher DL, Supady A, Bode C, Wengenmayer T, Duerschmied D. Cytokine Adsorption in Critically Ill Patients Requiring ECMO Support. Front Cardiovasc Med 2019;6:71. [PMID: 31275944 PMCID: PMC6593298 DOI: 10.3389/fcvm.2019.00071] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 05/13/2019] [Indexed: 12/12/2022] Open

Abstract

Systemic inflammation is a key characteristic of sepsis but also also in non-infectious conditions such as post-cardiac arrest syndrome. Cytokine adsorption and extracorporeal membrane oxygenation are emerging therapies applied in these critically ill patients, but the experience with their concurrent use is limited. We evaluated cytokine adsorption in critically ill patients requiring support with either veno-venous (vv) or veno-arterial (va) extracorporeal membrane oxygenation (ECMO) support and hypothesized that adsorber incorporation into the ECMO circuit was technically feasible and not associated with imminent risk. We analyzed data from the first six cases of a prospective single-center registry of patients undergoing veno-venous (vv) or veno-arterial (va) ECMO therapy. While in most published cases cytokine adsorbers were inserted into a hemofiltration circuit, we directly incorporated the adsorber into the ECMO circuit without interruption of continuous ECMO support. We observed no relevant side effects attributable to cytokine adsorption. Thirty-day mortality was 83% (predicted mortality 87%), indicating that the decision for adding cytokine adsorption may have been considered as an ultima ratio decision in severe cases with poor prognosis. Vasopressor or inotrope use, lactate level, and fluid balance did not change significantly when comparing pre- vs. post-cytokine adsorption values. Interestingly, the real-time course of the mentioned three surrogate parameters remained unaltered in all but two cases, regardless of cytokine removal. Beneficial effects of cytokine adsorption are plausible in two va-ECMO-treated patient, where increasing lactate began to drop after initiation of cytokine adsorption. Taken together, these data suggest that incorporation of cytokine adsorption into the management of critically ill patients requiring continued ECMO support is feasible and easy to handle. Whether cytokine removal improves clinical outcome in ECMO-treated patients should now be investigated in randomized controlled trials.

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Affiliation(s)

Achim Lother Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center Freiburg University, University of Freiburg, Freiburg, Germany.,Department of Medicine III (Interdisciplinary Medical Intensive Care), Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany.,Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Christoph Benk Department of Cardiovascular Surgery, Heart Center Freiburg University, University of Freiburg, Freiburg, Germany
Dawid L Staudacher Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center Freiburg University, University of Freiburg, Freiburg, Germany.,Department of Medicine III (Interdisciplinary Medical Intensive Care), Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany
Alexander Supady Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center Freiburg University, University of Freiburg, Freiburg, Germany.,Department of Medicine III (Interdisciplinary Medical Intensive Care), Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany
Christoph Bode Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center Freiburg University, University of Freiburg, Freiburg, Germany.,Department of Medicine III (Interdisciplinary Medical Intensive Care), Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany
Tobias Wengenmayer Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center Freiburg University, University of Freiburg, Freiburg, Germany.,Department of Medicine III (Interdisciplinary Medical Intensive Care), Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany
Daniel Duerschmied Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center Freiburg University, University of Freiburg, Freiburg, Germany.,Department of Medicine III (Interdisciplinary Medical Intensive Care), Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany

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Grand J, Kjaergaard J, Nielsen N, Friberg H, Cronberg T, Bro-Jeppesen J, Karsdal MA, Nielsen HB, Frydland M, Henriksen K, Mattsson N, Zetterberg H, Hassager C. Serum tau fragments as predictors of death or poor neurological outcome after out-of-hospital cardiac arrest. Biomarkers 2019;24:584-591. [PMID: 31017476 DOI: 10.1080/1354750x.2019.1609580] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]

Podolec J, Trąbka-Zawicki A, Badacz R, Siedliński M, Tomala M, Bartuś K, Legutko J, Przewłocki T, Żmudka K, Kabłak-Ziembicka A. Chemokine RANTES and IL-1β in mild therapeutic hypothermia-treated patients after out-of-hospital sudden cardiac arrest. ADVANCES IN INTERVENTIONAL CARDIOLOGY 2019;15:98-106. [PMID: 31043991 PMCID: PMC6488836 DOI: 10.5114/aic.2019.83653] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Accepted: 02/26/2019] [Indexed: 11/17/2022] Open