(+)-Naltrexone is neuroprotective and promotes alternative activation in the mouse hippocampus after cardiac arrest/cardiopulmonary resuscitation.
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ABSTRACT:
SUBMITTER: Grace PM
PROVIDER: S-EPMC5548128 | biostudies-other | 2015 Aug
REPOSITORIES: biostudies-other
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Project description:To investigate the effects of the combination of extracorporeal cardiopulmonary resuscitation and thrombolytic therapy on the recovery of vital organ function after prolonged cardiac arrest.Laboratory investigation.University laboratory.Pigs.Animals underwent 30-minute untreated ventricular fibrillation cardiac arrest followed by extracorporeal cardiopulmonary resuscitation for 6 hours. Animals were allocated into two experimental groups: t-extracorporeal cardiopulmonary resuscitation (t-ECPR) group, which received streptokinase 1 million units, and control extracorporeal cardiopulmonary resuscitation (c-ECPR), which did not receive streptokinase. In both groups, the resuscitation protocol included the following physiologic targets: mean arterial pressure greater than 70 mm Hg, cerebral perfusion pressure greater than 50 mm Hg, PaO2 150 ± 50 torr (20 ± 7 kPa), PaCO2 40 ± 5 torr (5 ± 1 kPa), and core temperature 33°C ± 1°C. Defibrillation was attempted after 30 minutes of extracorporeal cardiopulmonary resuscitation.A cardiac resuscitability score was assessed on the basis of success of defibrillation, return of spontaneous heart beat, weanability from extracorporeal cardiopulmonary resuscitation, and left ventricular systolic function after weaning. The addition of thrombolytic to extracorporeal cardiopulmonary resuscitation significantly improved cardiac resuscitability (3.7 ± 1.6 in t-ECPR vs 1.0 ± 1.5 in c-ECPR). Arterial lactate clearance was higher in t-ECPR than in c-ECPR (40% ± 15% vs 18% ± 21%). At the end of the experiment, the intracranial pressure was significantly higher in c-ECPR than in t-ECPR. Recovery of brain electrical activity, as assessed by quantitative analysis of electroencephalogram signal, and ischemic neuronal injury on histopathologic examination did not differ between groups. Animals in t-ECPR group did not have increased bleeding complications, including intracerebral hemorrhages.In a porcine model of prolonged cardiac arrest, t-ECPR improved cardiac resuscitability and reduced brain edema, without increasing bleeding complications. However, early electroencephalogram recovery and ischemic neuronal injury were not improved.
| S-EPMC4948940 | biostudies-literature
Project description:AimTo assess the use of extracorporeal cardiopulmonary resuscitation (ECPR), compared with manual or mechanical cardiopulmonary resuscitation (CPR), for out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) in adults and children.MethodsThe PRISMA guidelines were followed. We searched Medline, Embase, and Evidence-Based Medicine Reviews for randomized clinical trials and observational studies published before May 22, 2018. The population included adult and pediatric patients with OHCA and IHCA of any origin. Two investigators reviewed studies for relevance, extracted data, and assessed risk of bias using the ROBINS-I tool. Outcomes included short-term and long-term survival and favorable neurological outcome.ResultsWe included 25 observational studies, of which 15 studies were in adult OHCA, 7 studies were in adult IHCA, and 3 studies were in pediatric IHCA. There were no studies in pediatric OHCA. No randomized trials were included. Results from individual studies were largely inconsistent, although several studies in adult and pediatric IHCA were in favor of ECPR. The risk of bias for individual studies was overall assessed to be critical, with confounding being the primary source of bias. The overall quality of evidence was assessed to be very low. Heterogeneity across studies precluded any meaningful meta-analyses.ConclusionsThere is inconclusive evidence to either support or refute the use of ECPR for OHCA and IHCA in adults and children. The quality of evidence across studies is very low.
| S-EPMC6441971 | biostudies-literature
Project description:BackgroundVeno-arterial extracorporeal membrane oxygenation has increasingly emerged as a feasible treatment to mitigate the progressive multiorgan dysfunction that occurs during cardiac arrest, in support of further resuscitation efforts.ObjectivesBecause the recent systematic review commissioned in 2018 by the International Liaison Committee on Resuscitation Advanced Life Support task did not include studies without a control group, our objective was to conduct a review incorporating these studies to increase available evidence supporting the use of extracorporeal cardiopulmonary resuscitation (ECPR) for cardiac arrest patients, while waiting for high-quality evidence from randomized controlled trials (RCTs).MethodsMEDLINE, Embase, and Science Citation Index (Web of Science) were searched for eligible studies from database inception to July 20, 2020. The population of interest was adult patients who had suffered cardiac arrest in any setting. We included all cohort studies with 1 exposure/1 group and descriptive studies (ie, case series studies). We excluded RCTs, non-RCTs, and observational analytic studies with a control group. Outcomes included short-term survival and favorable neurological outcome. Short-term outcomes (ie, hospital discharge, 30 days, and 1 month) were combined into a single category.ResultsOur searches of databases and other sources yielded a total of 4302 citations. Sixty-two eligible studies were included (including a combined total of 3638 participants). Six studies were of in-hospital cardiac arrest, 34 studies were of out-of-hospital cardiac arrest, and 22 studies included both in-hospital and out-of-hospital cardiac arrest. Seven hundred and sixty-eight patients of 3352 (23%) had short-term survival; whereas, 602 of 3366 (18%) survived with favorable neurological outcome, defined as a cerebral performance category score of 1 or 2.ConclusionsCurrent clinical evidence is mostly drawn from observational studies, with their potential for confounding selection bias. Although studies without controls cannot supplant case-control or cohort studies, several ECPR studies without a control group show successful resuscitation with impressive results that may provide valuable information to inform a comparison.
| S-EPMC7813516 | biostudies-literature
Project description:BackgroundExtracorporeal cardiopulmonary resuscitation (ECPR) is an emerging concept in cardiac arrest and cardiopulmonary resuscitation. Recent research has documented a significant improvement in favorable outcomes, notable survival to discharge, and neurologically intact survival.ObjectivesThe present study undertakes a scoping review to summarize the available evidence by assessing the use of ECPR, compared with no ECPR or the standard of care, for adult patients who sustain cardiac arrest in any setting, in studies which record survival and neurologic outcomes.MethodsThis review followed the PRISMA extension for scoping reviews (PRISMA-ScR) guidelines. Four online databases were used to identify papers published from database inception to July 12, 2020. We selected 23 observational studies from Asia, Europe, and North America that used survival to discharge or neurologically intact survival as a primary or secondary endpoint variable in patients with cardiac arrest refractory to standard treatment.ResultsTwenty-three observational studies were included in the review. Eleven studies were of out-of-hospital cardiac arrest, 7 studies were of in-hospital cardiac arrest, and 5 studies included mixed populations. Ten studies reported long-term favorable neurological outcomes (ie, Cerebral Performance Category score of 1 - 2 at 3 months [n = 3], 6 months [n = 3], and 1 year [n = 4]), of which only 4 had statistical significance at 5% significance levels. Current knowledge is mostly drawn from single-center observations, with most of the evidence coming from case series and cohort studies, hence is prone to publication bias. No randomized control trials were included.ConclusionsThis scoping review highlights the need for high-quality studies to increase the level of evidence and reduce knowledge gaps to change the paradigm of care for patients with shock-refractory cardiac arrest.
| S-EPMC7880165 | biostudies-literature
Project description:Cardiac arrest (CA) causes hippocampal neuronal death that frequently leads to severe loss of memory function in survivors. No specific treatment is available to reduce neuronal death and improve functional outcome. The brain's inflammatory response to ischemia can exacerbate injury and provides a potential treatment target. We hypothesized that microglia are activated by CA and contribute to neuronal loss. We used a mouse model to determine whether pharmacologic inhibition of the proinflammatory microglial enzyme soluble epoxide hydrolase (sEH) after CA alters microglial activation and neuronal death. The sEH inhibitor 4-phenylchalcone oxide (4-PCO) was administered after successful cardiopulmonary resuscitation (CPR). The 4-PCO treatment significantly reduced neuronal death and improved memory function after CA/CPR. We found early activation of microglia and increased expression of inflammatory tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the hippocampus after CA/CPR, which was unchanged after 4-PCO treatment, while expression of antiinflammatory IL-10 increased significantly. We conclude that sEH inhibition after CA/CPR can alter the transcription profile in activated microglia to selectively induce antiinflammatory and neuroprotective IL-10 and reduce subsequent neuronal death. Switching microglial gene expression toward a neuroprotective phenotype is a promising new therapeutic approach for ischemic brain injury.
| S-EPMC3790926 | biostudies-literature
Project description:Extracorporeal cardiopulmonary resuscitation (ECPR) followed by targeted temperature management has been demonstrated to significantly improve the outcomes of out-of-hospital cardiac arrest (OHCA) in adult patients. Although recent narrative and systematic reviews on extracorporeal life support in the emergency department are available in the literature, they are focused on the efficacy of ECPR, and no comprehensively summarized review on ECPR for OHCA in adult patients is available. In this review, we aimed to clarify the prevalence, pathophysiology, predictors, management, and details of the complications of ECPR for OHCA, all of which have not been reviewed in previous literature, with the aim of facilitating understanding among acute care physicians. The leading countries in the field of ECPR are those in East Asia followed by those in Europe and the United States. ECPR may reduce the risks of reperfusion injury and deterioration to secondary brain injury. Unlike conventional cardiopulmonary resuscitation, however, no clear prognostic markers have been identified for ECPR for OHCA. Bleeding was identified as the most common complication of ECPR in patients with OHCA. Future studies should combine ECPR with intra-aortic balloon pump, extracorporeal membrane oxygenation flow, target blood pressure, and seizure management in ECPR.
| S-EPMC7428656 | biostudies-literature
Project description:The use of extracorporeal cardiopulmonary resuscitation (E-CPR) for the treatment of patients with out-of-hospital cardiac arrest who do not respond to conventional cardiopulmonary resuscitation CPR) has increased significantly in the past 10 years, in response to case reports and observational studies reporting encouraging results. However, no randomized controlled trials comparing E-CPR with conventional CPR have been published to date. The evidence from systematic reviews of the available observational studies is conflicting. The inclusion criteria for published E-CPR studies are variable, but most commonly include witnessed arrest, immediate bystander CPR, an initial shockable rhythm, and an estimated time from CPR start to establishment of E-CPR (low-flow time) of <60 minutes. A shorter low-flow time has been consistently associated with improved survival. In an effort to reduce low-flow times, commencement of E-CPR in the prehospital setting has been reported and is currently under investigation. The provision of an E-CPR service, whether hospital based or prehospital, carries considerable cost and technical challenges. Despite increased adoption, many questions remain as to which patients will derive the most benefit from E-CPR, when and where to implement E-CPR, optimal post-arrest E-CPR care, and whether this complex invasive intervention is cost-effective. Results of ongoing trials are awaited to determine whether E-CPR improves survival when compared with conventional CPR.
| S-EPMC7660839 | biostudies-literature
Project description:Precise criteria for extracorporeal cardiopulmonary resuscitation (ECPR) are still lacking in patients with out-of-hospital cardiac arrest (OHCA). We aimed to investigate whether adopting our hypothesized criteria for ECPR to patients with refractory OHCA could benefit. This before-after study compared 4.5 years after implementation of ECPR for refractory OHCA patients who met our criteria (Jan, 2015 to May, 2019) and 4 years of undergoing conventional CPR (CCPR) prior to ECPR with patients who met the criteria (Jan, 2011 to Jan, 2014) in the emergency department. The primary and secondary outcomes were good neurologic outcome at 6-months and 1-month respectively, defined as 1 or 2 on the Cerebral Performance Category score. A total of 70 patients (40 with CCPR and 30 with ECPR) were included. For a good neurologic status at 6-months and 1-month, patients with ECPR (33.3%, 26.7%) were superior to those with CCPR (5.0%, 5.0%) (all Ps < 0.05). Among patients with ECPR, a group with a good neurologic status showed shorter low-flow time, longer extracorporeal membrane oxygenation duration and hospital stays, and lower epinephrine doses used (all Ps < 0.05). The application of the detailed indication before initiating ECPR appears to increase a good neurologic outcome rate.
| S-EPMC7746692 | biostudies-literature
Project description:BACKGROUND:The prognosis in refractory out-of-hospital cardiac arrest (OHCA) with ongoing cardiopulmonary resuscitation (CPR) at hospital arrival is often considered dismal. The use of extracorporeal cardiopulmonary resuscitation (eCPR) for perfusion enhancement during resuscitation has shown variable results. We aimed to investigate outcome in refractory OHCA patients managed conservatively without use of eCPR. METHODS:We included consecutive OHCA patients with refractory arrest or prehospital return of spontaneous circulation (ROSC) in the Copenhagen area in 2002-2011. RESULTS:A total of 3992 OHCA patients with resuscitation attempts were included; in 2599, treatment was terminated prehospital, and 1393 (35%) were brought to the hospital either with ROSC (n?=?1285, 92%) or with refractory OHCA (n?=?108, 8%). Of patients brought in with refractory OHCA, 56 (52%) achieved ROSC in the emergency department. There were no differences between patients with refractory OHCA or prehospital ROSC with regard to age, sex, comorbidities, or etiology of OHCA. Time to emergency medical services (EMS) arrival was similar, whereas time to ROSC (when ROSC was achieved) was longer in refractory OHCA patients (EMS, 6 (5-9] vs. 7 [5-10] min, p?=?0.8; ROSC, 15 [9-22] vs. 27 [20-41] min, p?<?0.001). Independent factors associated with transport with refractory OHCA instead of prehospital termination of therapy were OHCA in public (OR, 3.6 [95% CI, 2.2-5.8]; p?<?0.001), witnessed OHCA (OR, 3.7 [2.0-7.1]; p?<?0.001), shockable rhythm (OR, 3.0 [1.9-4.7]; p?<?0.001), younger age (OR, 1.2 [1.1-1.2]; p?<?0.001), and later calendar year (OR, 1.4 [1.2-1.6]; p?<?0.001). Thirty-day survival was 20% in patients with refractory OHCA compared with 42% in patients with prehospital ROSC (p?<?0.001). Four of 28 refractory OHCA patients with duration of resuscitation >?60 min achieved ROSC. No difference in favorable neurological outcome in patients surviving to discharge was found (prehospital ROSC 84% vs. refractory OHCA 86%; p?=?0.7). CONCLUSIONS:Survival after refractory OHCA with ongoing CPR at hospital arrival was significantly lower than among patients with prehospital ROSC. Despite a lower survival, the majority of survivors with both refractory OHCA and prehospital ROSC were discharged with a similar degree of favorable neurological outcome, indicating that continued efforts in spite of refractory OHCA are not in vain and may still lead to favorable outcome even without eCPR.
| S-EPMC6162879 | biostudies-other
Project description:We performed a meta-analysis to compare the impact of extracorporeal cardiopulmonary resuscitation (ECPR) to that of conventional cardiopulmonary resuscitation (CCPR) in adult patients who experience cardiac arrest of cardiac origin. A literature search was performed using criteria set forth in a predefined protocol. Report inclusion criteria were that ECPR was compared to CCPR in adult patients with cardiac arrest of cardiac origin, and that survival and neurological outcome data were available. Exclusion criteria were reports describing non-cardiac origin arrest, review articles, editorials, and nonhuman studies. The efficacies of ECPR and CCPR were compared in terms of survival and neurological outcome. A total of 38,160 patients from 7 studies were ultimately included. ECPR showed similar survival (odds ratio [OR] 2.26, 95% confidence interval [CI] 0.45-11.20) and neurologic outcomes (OR 3.14, 95% CI 0.66-14.85) to CCPR in out-of-hospital cardiac arrest patients. For in-hospital cardiac arrest (IHCA) patients, however, ECPR was associated with significantly better survival (OR 2.40, 95% CI 1.44-3.98) and neurologic outcomes (OR 2.63, 95% CI 1.38-5.02) than CCPR. Hence, ECPR may be more effective than CCPR as an adjuvant therapy for survival and neurologic outcome in cardiac-origin IHCA patients.
| S-EPMC5034223 | biostudies-literature