Hydrogen gas with extracorporeal cardiopulmonary resuscitation improves survival after prolonged cardiac arrest in rats

Abstract Background Despite the benefits of extracorporeal cardiopulmonary resuscitation (ECPR) in cohorts of selected patients with cardiac arrest (CA), extracorporeal membrane oxygenation (ECMO) includes an artificial oxygenation membrane and circuits that contact the circulating blood and induce excessive oxidative stress and inflammatory responses, resulting in coagulopathy and endothelial cell damage. There is currently no pharmacological treatment that has been proven to improve outcomes after CA/ECPR. We aimed to test the hypothesis that administration of hydrogen gas (H2) combined with ECPR could improve outcomes after CA/ECPR in rats. Methods Rats were subjected to 20 min of asphyxial CA and were resuscitated by ECPR. Mechanical ventilation (MV) was initiated at the beginning of ECPR. Animals were randomly assigned to the placebo or H2 gas treatment groups. The supplement gas was administered with O2 through the ECMO membrane and MV. Survival time, electroencephalography (EEG), brain functional status, and brain tissue oxygenation were measured. Changes in the plasma levels of syndecan-1 (a marker of endothelial damage), multiple cytokines, chemokines, and metabolites were also evaluated. Results The survival rate at 4 h was 77.8% (7 out of 9) in the H2 group and 22.2% (2 out of 9) in the placebo group. The Kaplan–Meier analysis showed that H2 significantly improved the 4 h-survival endpoint (log-rank P = 0.025 vs. placebo). All animals treated with H2 regained EEG activity, whereas no recovery was observed in animals treated with placebo. H2 therapy markedly improved intra-resuscitation brain tissue oxygenation and prevented an increase in central venous pressure after ECPR. H2 attenuated an increase in syndecan-1 levels and enhanced an increase in interleukin-10, vascular endothelial growth factor, and leptin levels after ECPR. Metabolomics analysis identified significant changes at 2 h after CA/ECPR between the two groups, particularly in d-glutamine and d-glutamate metabolism. Conclusions H2 therapy improved mortality in highly lethal CA rats rescued by ECPR and helped recover brain electrical activity. The underlying mechanism might be linked to protective effects against endothelial damage. Further studies are warranted to elucidate the mechanisms responsible for the beneficial effects of H2 on ischemia–reperfusion injury in critically ill patients who require ECMO support.

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Quantitative assessment of brain tissue oxygenation in porcine models of cardiac arrest and cardiopulmonary resuscitation using hyperspectral near-infrared spectroscopy

10.1117/12.2039620 ◽

2014 ◽

Author(s):

Shahin S. Lotfabadi ◽

Vladislav Toronov ◽

Andrew Ramadeen ◽

Xudong Hu ◽

Siwook Kim ◽

...

Keyword(s):

Cardiac Arrest ◽

Infrared Spectroscopy ◽

Cardiopulmonary Resuscitation ◽

Brain Tissue ◽

Near Infrared Spectroscopy ◽

Quantitative Assessment ◽

Near Infrared ◽

Tissue Oxygenation ◽

Brain Tissue Oxygenation

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Xenon Attenuates Cerebral Damage after Ischemia in Pigs

Anesthesiology ◽

10.1097/00000542-200505000-00011 ◽

2005 ◽

Vol 102 (5) ◽

pp. 929-936 ◽

Cited By ~ 46

Author(s):

Michael Schmidt ◽

Thomas Marx ◽

Egon Glöggl ◽

Helmut Reinelt ◽

Uwe Schirmer

Keyword(s):

Cardiac Arrest ◽

Brain Tissue ◽

Tissue Oxygenation ◽

Cell Damage ◽

Total Intravenous Anesthesia ◽

Cerebral Microdialysis ◽

Intravenous Anesthesia ◽

Brain Tissue Oxygenation ◽

Ischemic Lesion

Background Cerebral blood flow may be compromised in a variety of anesthetic procedures, and ischemic cerebral complications represent the leading cause of morbidity after cardiac operations. With the growing importance of neuroprotective strategies, the current study was designed to determine whether xenon would attenuate cardiac arrest-induced brain injury in pigs. Methods Twenty-four pigs (aged 12-16 weeks) were investigated in a randomized design. General hemodynamics, intracranial pressure, brain tissue oxygenation, and cerebral microdialysis parameters were investigated. The animals were assigned to two groups to receive anesthesia with either xenon (75%) in oxygen (25%) or total intravenous anesthesia combined with air in oxygen (25%) ventilation 15 min before cardiac arrest. After induction (t0) of cardiac arrest of 4 min, cardiopulmonary resuscitation was performed for 1 min, and the induced ventricular fibrillation was terminated by electrical defibrillation. The investigation time was 240 min. Results Approximately 60 s after cardiac arrest, brain tissue oxygenation decreased to a critical level of less than 5 mmHg, paralleled by a decrease in electroencephalographic activity. Glycerol as a damage marker increased significantly (> 200 m; P < 0.05), with a peak 90 min after cardiac arrest in both groups. Glycerol concentrations during reperfusion were significantly lower and normalized faster in the xenon group as compared with the total intravenous anesthesia group. Conclusion Although the primary ischemic lesion in this model was similar in both groups, the cerebral microdialysis data show that xenon induces a differential neurochemical benefit in cerebral cell damage and metabolism as compared with total intravenous anesthesia in vivo during cerebral reperfusion after cardiac arrest in a pig model.

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Faculty Opinions recommendation of Effects of cerebrovascular pressure reactivity-guided optimization of cerebral perfusion pressure on brain tissue oxygenation after traumatic brain injury.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.2082971.2577054 ◽

2010 ◽

Author(s):

Jonathan Rhodes

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Brain Tissue ◽

Cerebral Perfusion Pressure ◽

Cerebral Perfusion ◽

Tissue Oxygenation ◽

Perfusion Pressure ◽

Brain Tissue Oxygenation ◽

Pressure Reactivity ◽

Cerebrovascular Pressure Reactivity

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Faculty Opinions recommendation of Effects of cerebrovascular pressure reactivity-guided optimization of cerebral perfusion pressure on brain tissue oxygenation after traumatic brain injury.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.2082971.1671069 ◽

2010 ◽

Author(s):

Nicolas Bruder

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Brain Tissue ◽

Cerebral Perfusion Pressure ◽

Cerebral Perfusion ◽

Tissue Oxygenation ◽

Perfusion Pressure ◽

Brain Tissue Oxygenation ◽

Pressure Reactivity ◽

Cerebrovascular Pressure Reactivity

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Management of out-of hospital cardiac arrest patients with extracorporeal cardiopulmonary resuscitation in 2021

Expert Review of Medical Devices ◽

10.1080/17434440.2021.1886076 ◽

2021 ◽

pp. 1-10

Author(s):

Christopher Gaisendrees ◽

Matias Vollmer ◽

Sebastian G Walter ◽

Ilija Djordjevic ◽

Kaveh Eghbalzadeh ◽

...

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Extracorporeal Cardiopulmonary Resuscitation ◽

Hospital Cardiac Arrest

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Does Targeted Temperature Management Improve Neurological Outcome in Extracorporeal Cardiopulmonary Resuscitation (ECPR)?

Journal of Intensive Care Medicine ◽

10.1177/08850666211018982 ◽

2021 ◽

pp. 088506662110189

Author(s):

Merry Huang ◽

Aaron Shoskes ◽

Migdady Ibrahim ◽

Moein Amin ◽

Leen Hasan ◽

...

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Neurological Outcome ◽

Targeted Temperature Management ◽

Temperature Management ◽

Survival Outcomes ◽

Pool Data ◽

Good Neurological Outcome ◽

Extracorporeal Cardiopulmonary Resuscitation ◽

Over Time

Purpose: Targeted temperature management (TTM) is a standard of care in patients after cardiac arrest for neuroprotection. Currently, the effectiveness and efficacy of TTM after extracorporeal cardiopulmonary resuscitation (ECPR) is unknown. We aimed to compare neurological and survival outcomes between TTM vs non-TTM in patients undergoing ECPR for refractory cardiac arrest. Methods: We searched PubMed and 5 other databases for randomized controlled trials and observational studies reporting neurological outcomes or survival in adult patients undergoing ECPR with or without TTM. Good neurological outcome was defined as cerebral performance category <3. Two independent reviewers extracted the data. Random-effects meta-analyses were used to pool data. Results: We included 35 studies (n = 2,643) with the median age of 56 years (interquartile range [IQR]: 52-59). The median time from collapse to ECMO cannulation was 58 minutes (IQR: 49-82) and the median ECMO duration was 3 days (IQR: 2.0-4.1). Of 2,643, 1,329 (50.3%) patients received TTM and 1,314 (49.7%) did not. There was no difference in the frequency of good neurological outcome at any time between TTM (29%, 95% confidence interval [CI]: 23%-36%) vs. without TTM (19%, 95% CI: 9%-31%) in patients with ECPR ( P = 0.09). Similarly, there was no difference in overall survival between patients with TTM (30%, 95% CI: 22%-39%) vs. without TTM (24%, 95% CI: 14%-34%) ( P = 0.31). A cumulative meta-analysis by publication year showed improved neurological and survival outcomes over time. Conclusions: Among ECPR patients, survival and neurological outcome were not different between those with TTM vs. without TTM. Our study suggests that neurological and survival outcome are improving over time as ECPR therapy is more widely used. Our results were limited by the heterogeneity of included studies and further research with granular temperature data is necessary to assess the benefit and risk of TTM in ECPR population.

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