scholarly journals The post-cardiac arrest syndrome: A case for lung–brain coupling and opportunities for neuroprotection

2019 ◽  
Vol 39 (6) ◽  
pp. 939-958 ◽  
Author(s):  
Nguyen Mai ◽  
Kathleen Miller-Rhodes ◽  
Sara Knowlden ◽  
Marc W Halterman

Systemic inflammation and multi-organ failure represent hallmarks of the post-cardiac arrest syndrome (PCAS) and predict severe neurological injury and often fatal outcomes. Current interventions for cardiac arrest focus on the reversal of precipitating cardiac pathologies and the implementation of supportive measures with the goal of limiting damage to at-risk tissue. Despite the widespread use of targeted temperature management, there remain no proven approaches to manage reperfusion injury in the period following the return of spontaneous circulation. Recent evidence has implicated the lung as a moderator of systemic inflammation following remote somatic injury in part through effects on innate immune priming. In this review, we explore concepts related to lung-dependent innate immune priming and its potential role in PCAS. Specifically, we propose and investigate the conceptual model of lung–brain coupling drawing from the broader literature connecting tissue damage and acute lung injury with cerebral reperfusion injury. Subsequently, we consider the role that interventions designed to short-circuit lung-dependent immune priming might play in improving patient outcomes following cardiac arrest and possibly other acute neurological injuries.

Author(s):  
Jerry P Nolan

Cardiac arrest is the most extreme of medical emergencies. If the victim is to have any chance of high-quality neurological recovery, cardiac arrest must be diagnosed quickly, followed by summoning for help as basic life support (chest compressions and ventilations) is started. In most cases, the initial rhythm will be shockable, but this will have often deteriorated to a non-shockable rhythm by the time a monitor and/or defibrillator is applied. While basic life support will sustain some oxygen delivery to the heart and brain and will help to slow the rate of deterioration in these vital organs, it is important to achieve restoration of a spontaneous circulation as soon as possible (by defibrillation if the rhythm is shockable). Once return of spontaneous circulation is achieved, the quality of post-cardiac arrest management will influence the patient’s final neurological outcome. These interventions aim to restore myocardial function and minimize neurological injury.


2018 ◽  
Author(s):  
Patrick Hughes ◽  
Oren Mechanic ◽  
Shamai A. Grossman

Most patients who achieve return of spontaneous circulation (ROSC) do not survive to hospital discharge. Focus on postarrest care is critical to maximize outcomes. In the post-ROSC phase, patients are frequently hemodynamically unstable, electrophysiologically vulnerable, and in need of airway management and/or ventilatory support. While focusing on further stabilizing the patient, attention should also be placed on identifying the etiology of arrest and minimizing postischemic injury to the brain and other organs. Goal-directed therapy can provide optimal care and outcomes. Neurologic prognostication should wait until 72 hours after ROSC or return to normothermia. If a patient remains is recognized as brain dead, tissue and organ donation should be considered. Debriefing after cardiopulmonary resuscitation improves objective measures in future resuscitation and allows a chance for closure after a stressful event. This review contains 4 figures, 4 tables and 42 references Key words: cardiac arrest, postarrest care, post–cardiac arrest syndrome, postresuscitation management, target temperature management, therapeutic hypothermia


Author(s):  
Jerry P Nolan

Cardiac arrest is the most extreme of medical emergencies. If the victim is to have any chance of high-quality neurological recovery, cardiac arrest must be diagnosed quickly, followed by summoning for help as basic life support (chest compressions and ventilations) is started. In most cases, the initial rhythm will be shockable, but this will have often deteriorated to a non-shockable rhythm by the time a monitor and/or defibrillator is applied. While basic life support will sustain some oxygen delivery to the heart and brain and will help to slow the rate of deterioration in these vital organs, it is important to achieve restoration of a spontaneous circulation as soon as possible (by defibrillation if the rhythm is shockable). Once return of spontaneous circulation is achieved, the quality of post-cardiac arrest management will influence the patient’s final neurological outcome. These interventions aim to restore myocardial function and minimize neurological injury.


2021 ◽  
Author(s):  
Ryuichiro Kakizaki ◽  
Naofumi Bunya ◽  
Shuji Uemura ◽  
Takehiko Kasai ◽  
Keigo Sawamoto ◽  
...  

Abstract Background: Targeted temperature management (TTM) is recommended for unconscious patients after a cardiac arrest. However, its effectiveness in patients with post-cardiac arrest syndrome (PCAS) by hanging remains unclear. Therefore, this study aimed to investigate the relationship between TTM and favorable neurological outcomes in patients with PCAS by hanging.Methods: This study was a retrospective analysis of the Japanese Association for Acute Medicine out-of-hospital cardiac arrest (OHCA) registry between June 2014 and December 2017 among patients with PCAS admitted to the hospitals after an OHCA caused by hanging. A multivariate logistic regression analysis was performed to estimate the propensity score and to predict whether patients with PCAS by hanging receive TTM. We compared patients with PCAS by hanging who received TTM (TTM group) and those who did not (non-TTM group) using propensity score analysis.Results: A total of 199 patients with PCAS by hanging were enrolled in this study. Among them, 43 were assigned to the TTM group and 156 to the non-TTM group. Logistic regression model adjusted for propensity score revealed that TTM was not associated with favorable neurological outcome at 1-month (adjusted odds ratio [OR]: 1.38, 95% confidence interval [CI]: 0.27–6.96). Moreover, no difference was observed in the propensity score-matched cohort (adjusted OR: 0, 73, 95% CI: 0.10–4.71) and in the inverse probability of treatment weighting-matched cohort (adjusted OR: 0.63, 95% CI: 0.15–2.69).Conclusions: TTM was not associated with increased favorable neurological outcomes at 1-month in patients with PCAS after OHCA by hanging.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ian R Drennan ◽  
Steve Lin ◽  
Kevin E Thorpe ◽  
Jason E Buick ◽  
Sheldon Cheskes ◽  
...  

Introduction: Targeted temperature management (TTM) reduces neurologic injury from out-of-hospital cardiac arrest (OHCA). As the risk of neurologic injury increases with prolonged cardiac arrests, the benefit of TTM may depend upon cardiac arrest duration. We hypothesized that there is a time-dependent effect of TTM on neurologic outcomes from OHCA. Methods: Retrospective, observational study of the Toronto RescuNET Epistry-Cardiac Arrest database from 2007 to 2014. We included adult (>18) OHCA of presumed cardiac etiology that remained comatose (GCS<10) after a return of spontaneous circulation. We used multivariable logistic regression to determine the effect of TTM and the duration of cardiac arrest on good neurologic outcome (Modified Rankin Scale (mRS) 0-3) and survival to hospital discharge while controlling for other known predictors. Results: There were 1496 patients who met our inclusion criteria, of whom 981 (66%) received TTM. Of the patients who received TTM, 59% had a good neurologic outcome compared to 39% of patients who did not receive TTM (p< 0.001). After adjusting for the Utstein variables, use of TTM was associated with improved neurologic outcome (OR 1.60, 95% CI 1.10-2.32; p = 0.01) but not with survival to discharge (OR 1.23, 95% CI 0.90-1.67; p = 0.19). The impact of TTM on neurologic outcome was dependent on the duration of cardiac arrest (p<0.05) (Fig 1). Other significant predictors of good neurologic outcome were younger age, public location, initial shockable rhythm, and shorter duration of cardiac arrest (all p values < 0.05). A subgroup analysis found the use of TTM to be associated with neurologic outcome in both shockable (p = 0.01) and non-shockable rhythms (p = 0.04) but was not associated with survival to discharge in either group (p = 0.12 and p = 0.14 respectively). Conclusion: The use of TTM was associated with improved neurologic outcome at hospital discharge. Patients with prolonged durations of cardiac arrest benefited more from TTM.


Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Alexandra Weissman ◽  
Jacob S Puyana ◽  
David Spencer ◽  
Melissa Repine ◽  
Jon C Rittenberger ◽  
...  

Introduction: Post cardiac arrest syndrome, therapeutic hypothermia, and CPR confound the clinical diagnosis of pneumonia. Accurate pneumonia diagnosis is required to improve targeted antibiotic allocation and prevent sequelae of untargeted antibiotic therapy. Hypothesis: We can rigorously define pneumonia after cardiac arrest (CA) using accepted clinical parameters adapted from existing guidelines and innate immune system biomarkers Interleukin-17A (IL-17A), integrin α9β1, and CD11b specific to the response to pulmonary infection. Methods: A prospective cohort of consecutive OHCA patients surviving at least 72 hours from arrival was enrolled. IL-17A, integrin α9β1, and CD11b were measured daily at 4 timepoints from time 0 (arrival) through 72 hours. Chest radiography, pulmonary microbiology, temperature, and white blood cell count were recorded concurrently from the medical record. Pneumonia was defined narrowly (pna_narrow) by the presence of at least 2 of the following criteria in the initial 72 hours of presentation: fever ≥38°C; persistent infiltrate on chest radiography; positive sputum or bronchoalveolar lavage per the hospital microbiology laboratory. Broad criteria (pna_broad) also incorporated persistent leukocytosis ≥15,000 or leukopenia <3,000. Results: Of the 56 subjects with all data, 23% (13 of 56) met pna_narrow criteria while 43% (24 of 56) met pna_broad criteria. Positive clinical pulmonary microbiology was present in 62% (8 of 13) subjects meeting pna_narrow and 46% (11 of 24) subjects meeting pna_broad criteria. Antibiotics were given to 65% (28 of 43) subjects without pna_narrow and 63% (20 of 32) without pna_broad. Overall, 70% (39 of 56) subjects received antibiotics regardless of pneumonia status. Integrin α9β1 at Time 28 hours and Time 72 hours was associated with pna_narrow (p = 0.010, p = 0.049). CD11b at Time 0 and 72 hours was associated with pna_narrow (p = 0.03, p = 0.049). IL-17 at Time 28 and Time 72 was associated with pna_narrow (p = 0.04, p = 0.01). Conclusions: Pneumonia was rigorously defined in 23 to 43% of our sample, yet 70% of subjects received antibiotics. More rigorous definitions for pneumonia after CA, combined with pulmonary infection biomarkers, could be used to improve diagnosis and antibiotic allocation.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Changshin Kang

Aim: In a previous study, low and high-normal arterial carbon dioxide tension (PaCO 2 ) were not associated with serum neuron specific enolase (NSE) in cardiac arrest survivors. We assessed the effect of PaCO 2 on NSE in cerebrospinal fluid (CSF) and serum. Methods: This was a retrospective study. PaCO 2 for the first 24 h was analysed in four means, qualitative exposure state (qES), time-weighted average (TWA), median, and minimum-maximum (Min-Max). These subgroups were divided into low (LCO 2 ) and high PaCO 2 (HCO 2 ) groups defined as PaCO 2 ≤35.3 and PaCO 2 >43.5 mmHg, respectively. NSE was measured at 24, 48, and 72 h (sNSE 24,48,72 and cNSE 24,48,72 ) from return of spontaneous circulation (ROSC). The primary outcome was the association between PaCO 2 and the NSE measured at 24 h after ROSC. Results: Forty-two subjects (male, 33; 78.6%) were included in total cohort. PaCO 2 in TWA subgroup was associated with cNSE 24,48,72 , while PaCO 2 in the other subgroup were only associated with cNSE 24 . PaCO 2 and cNSE in qES subgroup showed good correlation (r= -0.61; p< 0.01), and in TWA, Median, and Min-Max subgroup showed moderate correlations (r= -0.57, r= -0.48, and r= -0.60; p< 0.01). Contrastively, sNSE was not associated and correlated with PaCO 2 in all analysis. Poor neurological outcome in LCO 2 was significantly higher than HCO 2 in qES, TWA, and Median subgroups ( p< 0.01, p< 0.01, and p= 0.02). Conclusion: Association was found between NSE and PaCO 2 using CSF, despite including normocapnic ranges; TWA of PaCO 2 may be most strongly associated with CSF NSE levels. A prospective, multi-centre study is required to confirm our results.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Hiromichi Naito ◽  
Takashi Yorifuji ◽  
Tetsuya Yumoto ◽  
Tsuyoshi Nojima ◽  
Noritomo Fujisaki ◽  
...  

Introduction: Mid/long-term outcomes of out-of-hospital cardiac arrest (OHCA) survivors have not been extensively studied. Targeted temperature management (TTM) after return of spontaneous circulation is one known therapeutic approach to ameliorate short-term neurological improvement of OHCA patients; however, the prognostic significance of TTM in the mid/long-term clinical setting have not been defined. Hypothesis: TTM would confer additional improvement of OHCA patients’ mid-term neurological outcomes. Methods: Retrospective study using the Japanese Association for Acute Medicine OHCA Registry (Jun 2014 - Dec 2017): a nationwide multicenter registry. Patients who did not survive 30 days after OHCA, those with missing 30-day Cerebral Performance Category (CPC) scores, and those < 18 years old were excluded. Primary endpoint was alteration of neurological function evaluated with 30-day and 90-day CPC. Association between application of TTM (33-36°C) and mid-term CPC alteration was evaluated. Multivariable logistic regression analysis was used for the primary outcome; results are expressed with odds ratio (OR) and 95% confidence interval (CI). Results: We included 2,905 in the analysis. Patient characteristics were: age: 67 [57 - 78] years old, male gender: 70.8%, witnessed collapse: 81.4%, dispatcher instruction for CPR: 51.6%, initial shockable rhythm: 67.0%, and estimated cardiac origin: 76.5%. TTM was applied to 1,352/2,905 (46.5%) patients. Thirty-day CPC values in surviving patients were: CPC 1: 1,155/2,905 (39.8%), CPC 2: 321/2,905 (11.1%), CPC 3: 497/2,905 (17.1%), and CPC 4: 932/2,905 (32.1%), respectively. Ninety-day CPC values were: CPC 1: 866/1,868 (46.4%), CPC 2: 154/1,868 (8.2%), CPC 3: 224/1,868 (12.0%), CPC 4: 392/1,868 (20.1%), and CPC 5: 232/1,868 (12.4%), respectively. Of 1,636 patients with 90-day survival, 28 (1.7%) demonstrated improved CPC at 90 days, whereas, 133 (8.1%) showed worsened CPC at 90 days compared with 30-day CPC, respectively. Multivariable logistic regression analysis revealed TTM did not result in favorable mid-term neurological changes (adjusted OR: 1.44, 95% CI: 0.48 - 4.31). Conclusions: TTM may not contribute to the beneficial effect on OHCA patients’ mid-term neurological changes.


2020 ◽  
Vol 31 (4) ◽  
pp. 383-393
Author(s):  
Linda Dalessio

More than 356 000 out-of-hospital cardiac arrests occur in the United States annually. Complications involving post–cardiac arrest syndrome occur because of ischemic-reperfusion injury to the brain, lungs, heart, and kidneys. Post–cardiac arrest syndrome is a clinical state that involves global brain injury, myocardial dysfunction, macrocirculatory dysfunction, increased vulnerability to infection, and persistent precipitating pathology (ie, the cause of the arrest). The severity of outcomes varies and depends on precipitating factors, patient health before cardiac arrest, duration of time to return of spontaneous circulation, and underlying comorbidities. In this article, the pathophysiology and treatment of post–cardiac arrest syndrome are reviewed and potential novel therapies are described.


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