Emergent Management of Hypoxic-Ischemic Brain Injury.

OBJECTIVE: This article outlines interventions used to improve outcomes for patients with hypoxic-ischemic brain injury after cardiac arrest. LATEST DEVELOPMENTS: Emergent management of patients after cardiac arrest requires prevention and treatment of primary and secondary brain injury. Primary brain injury is minimized by excellent initial resuscitative efforts. Secondary brain injury prevention requires the detection and correction of many pathophysiologic processes that may develop in the hours to days after the initial arrest. Key physiologic parameters important to secondary brain injury prevention include optimization of mean arterial pressure, cerebral perfusion, oxygenation and ventilation, intracranial pressure, temperature, and cortical hyperexcitability. This article outlines recent data regarding the treatment and prevention of secondary brain injury. Different patients likely benefit from different treatment strategies, so an individualized approach to treatment and prevention of secondary brain injury is advisable. Clinicians must use multimodal sources of data to prognosticate outcomes after cardiac arrest while recognizing that all prognostic tools have shortcomings. ESSENTIAL POINTS: Neurologists should be involved in the postarrest care of patients with hypoxic-ischemic brain injury to improve their outcomes. Postarrest care requires nuanced and patient-centered approaches to the prevention and treatment of primary and secondary brain injury and neuroprognostication.

"Decompression illness" on extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly being used for critically ill patients with cardiopulmonary failure. Air in the ECMO circuit is an emergency, a rare but fatal complication. CASE PRESENTATION: We introduce a case of a 76-year-old female who suffered from cardiac arrest complicated with severe trauma and was administered veno-arterial extracorporeal membrane oxygenation. In managing the patient with ECMO, air entered the ECMO circuit, which had not come out nor was folded or broken. Although the ECMO flow was quickly re-established, the patient died 6 h after initiating ECMO therapy. CONCLUSIONS: In this case report, the reason for the complication is drainage insufficiency. This phenomenon is similar to decompression sickness. Understanding this complication is very helpful for educating the ECMO team for preventing this rare but devastating complication of fatal decompression sickness in patients on ECMO.

The Bezold-Jarisch reflex and anaesthesia.

Spinal anaesthesia is considered an effective and safe method for providing pain relief during procedures below the waist. However, in a small subset of patients, life-threatening vasovagal reactions may develop leading to severe bradycardia and hypotension or ultimately asystole and complete circulatory collapse. Early recognition and prompt treatment of this condition can be lifesaving as illustrated in this case report where the patient developed asystole for ten seconds shortly after placing the spinal anaesthetic.

Multiple Causes of Death Associated with Pediatric Cardiopulmonary Arrest from 1996 to 2019 in Brazil. / Causas Múltiplas de Morte Associadas à Parada Cardiorrespiratória Pediátrica de 1996 a 2019 no Brasil.

BACKGROUND: In pediatrics, cardiopulmonary arrest (CPA) is associated with high mortality and severe neurologic sequelae. Information on the causes and mechanisms of death below the age of 20 years could provide theoretical support for health improvement among children and adolescents. OBJECTIVES: To conduct a population analysis of mortality rates due to primary and multiple causes of death below the age of 20 years in both sexes from 1996 to 2019 in Brazil, and identify the frequency in which CPA was recorded in the death certificates (DCs) of these individuals and the locations where the deaths occurred, in order to promote strategies to improve the prevention of deaths. METHOD: Ecological time-series study of deaths below the age of 20 years from 1996 to 2019, evaluating the mortality rates (MRs) and proportional mortality (PM) by primary cause of death. We analyzed the percentages of CPA recorded in any line of the DC and the location where the deaths occurred. We calculated the MRs per 100,000 inhabitants and the PM by primary cause of death under the age of 20 years according to sex and age group, the percentages of death from primary causes by age group when CPA was described in any line of Parts I and II of the DC, and the percentage of deaths from primary causes according to their location of occurrence. We retrieved the data from DATASUS, IBGE, and SINASC. RESULTS: From 1996 to 2019, there were 2,151,716 deaths below the age of 20 years in Brazil, yielding a mortality rate of 134.38 per 100,000 inhabitants. The death rate was highest among male neonates. Of all deaths, 249,334 (11.6%) had CPA recorded in any line of the DC. Specifically, CPA was recorded in 49,178 DCs between the ages of 1 and 4 years and in 88,116 of those between the ages of 29 and 365 days, corresponding, respectively, to 26% and 22% of the deaths in these age groups. These two age groups had the highest rates of CPA recorded in any line of the DC. The main primary causes of death when CPA was recorded in the sequence of death were respiratory, hematologic, and neoplastic diseases. CONCLUSION: Perinatal and external causes were the primary causes of death, with highest MRs under the age of 20 years in Brazil from 1996 to 2019. When multiple causes of death were considered, the main primary causes associated with CPA were respiratory, hematologic, and neoplastic diseases. Most deaths occurred in the hospital environment. Better understanding of the sequence of events in these deaths and improvements in teaching strategies in pediatric cardiopulmonary resuscitation are needed.

FUNDAMENTO: Em pediatria, a parada cardiorrespiratória (PCR) está associada a alta mortalidade e graves sequelas neurológicas. Informações sobre as causas e mecanismos de morte abaixo de 20 anos poderiam fornecer subsídios teóricos para a melhoria da saúde de crianças e adolescentes. OBJETIVOS: Realizar uma análise populacional das taxas de mortalidade por causas primárias e múltiplas de morte abaixo de 20 anos, em ambos os sexos, no período de 1996 a 2019, no Brasil, e identificar a frequência com que a PCR foi registrada nas declarações de óbito (DOs) desses indivíduos e os locais de ocorrência dos óbitos, a fim de promover estratégias para melhorar a prevenção de mortes. MÉTODO: Estudo ecológico de séries temporais de óbitos em indivíduos menores de 20 anos, no período de 1996 a 2019, avaliando as taxas de mortalidade (TMs) e a mortalidade proporcional (MP) por causa básica de morte. Foram analisados os percentuais de PCR registrados em qualquer linha da DO e o local de ocorrência dos óbitos. Foram calculadas as TMs por 100 mil habitantes e a MP por causa básica de morte nos menores de 20 anos segundo sexo e faixa etária, os percentuais de óbito por causas básicas por faixa etária quando a PCR foi descrita em qualquer linha das Partes I e II da DO, e o percentual de óbitos por causas básicas segundo o local de ocorrência. Os dados foram retirados do DATASUS, IBGE e SINASC. RESULTADOS: De 1996 a 2019, ocorreram 2.151.716 óbitos de menores de 20 anos, no Brasil, gerando uma taxa de mortalidade de 134,38 por 100 mil habitantes. A taxa de óbito foi maior entre os recém-nascidos do sexo masculino. Do total de óbitos, 249.334 (11,6%) tiveram PCR registrada em qualquer linha da DO. Especificamente, a PCR foi registrada 49.178 vezes na DO na faixa etária entre 1 e 4 anos e em 88.116 vezes entre 29 e 365 dias, correspondendo, respectivamente, a 26% e 22% dos óbitos nessas faixas etárias. Essas duas faixas etárias apresentaram as maiores taxas de PCR registradas em qualquer linha da DO. As principais causas básicas de óbito quando a PCR foi registrada na sequência de óbitos foram doenças respiratórias, hematológicas e neoplásicas. CONCLUSÃO: As causas perinatais e externas foram as principais causas de morte, com maior TM nos menores de 20 anos no Brasil de 1996 a 2019. Quando consideradas as causas múltiplas de morte, as principais causas primárias associadas à PCR foram as doenças respiratórias, hematológicas e neoplásicas. A maioria dos óbitos ocorreu no ambiente hospitalar. Melhor compreensão da sequência de eventos nesses óbitos e melhorias nas estratégias de ensino em ressuscitação cardiopulmonar pediátrica são necessárias.

Post-intensive care syndrome and health-related quality of life in long-term survivors of cardiac arrest: a prospective cohort study.

Patients discharged from intensive care are at risk for post-intensive care syndrome (PICS), which consists of physical, psychological, and/or neurological impairments. This study aimed to analyze PICS at 24 months follow-up, to identify potential risk factors for PICS, and to assess health-related quality of life in a long-term cohort of adult cardiac arrest survivors. This prospective cohort study included adult cardiac arrest survivors admitted to the intensive care unit of a Swiss tertiary academic medical center. The primary endpoint was the prevalence of PICS at 24 months follow-up, defined as impairments in physical (measured through the European Quality of Life 5-Dimensions-3-Levels instrument [EQ-5D-3L]), neurological (defined as Cerebral Performance Category Score > 2 or Modified Rankin Score > 3), and psychological (based on the Hospital Anxiety and Depression Scale and the Impact of Event Scale-Revised) domains. Among 107 cardiac arrest survivors that completed the 2-year follow-up, 46 patients (43.0%) had symptoms of PICS, with 41 patients (38.7%) experiencing symptoms in the physical domain, 16 patients (15.4%) in the psychological domain, and 3 patients (2.8%) in the neurological domain. Key predictors for PICS in multivariate analyses were female sex (adjusted odds ratio [aOR] 3.17, 95% CI 1.08 to 9.3), duration of no-flow interval during cardiac arrest (minutes) (aOR 1.17, 95% CI 1.02 to 1.33), post-discharge job-loss (aOR 31.25, 95% CI 3.63 to 268.83), need for ongoing psychological support (aOR 3.64, 95% CI 1.29 to 10.29) or psychopharmacologic treatment (aOR 9.49, 95% CI 1.9 to 47.3), and EQ-visual analogue scale (points) (aOR 0.88, 95% CI 0.84 to 0.93). More than one-third of cardiac arrest survivors experience symptoms of PICS 2 years after resuscitation, with the highest impairment observed in the physical and psychological domains. However, long-term survivors of cardiac arrest report intact health-related quality of life when compared to the general population. Future research should focus on appropriate prevention, screening, and treatment strategies for PICS in cardiac arrest patients.

The Role of Phospholipid Alterations in Mitochondrial and Brain Dysfunction after Cardiac Arrest.

The human brain possesses three predominate phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS), which account for approximately 35-40%, 35-40%, and 20% of the brain's phospholipids, respectively. Mitochondrial membranes are relatively diverse, containing the aforementioned PC, PE, and PS, as well as phosphatidylinositol (PI) and phosphatidic acid (PA); however, cardiolipin (CL) and phosphatidylglycerol (PG) are exclusively present in mitochondrial membranes. These phospholipid interactions play an essential role in mitochondrial fusion and fission dynamics, leading to the maintenance of mitochondrial structural and signaling pathways. The essential nature of these phospholipids is demonstrated through the inability of mitochondria to tolerate alteration in these specific phospholipids, with changes leading to mitochondrial damage resulting in neural degeneration. This review will emphasize how the structure of phospholipids relates to their physiologic function, how their metabolism facilitates signaling, and the role of organ- and mitochondria-specific phospholipid compositions. Finally, we will discuss the effects of global ischemia and reperfusion on organ- and mitochondria-specific phospholipids alongside the novel therapeutics that may protect against injury.

Benefits of cardiopulmonary resuscitation in cancer patients.

PURPOSE: According to meta-analytic data, the prognosis of a cancer patient post-cardiopulmonary resuscitation (CPR) is relatively similar to the general population. However, preselection of patients, the details of CPR, patient-specific characteristics, and post-CPR care are poorly described. The aim of this study is to identify prognostic factors in order to recognize cancer patient profiles more likely to benefit from CPR. METHODS: This is a retrospective study on a series of patients with solid or hematological malignancies who received CPR between January 2010 and December 2020 in a cancer institute. RESULTS: Sixty-eight patients were included. The ratio of solid to hematological malignancy was 44/24, of which 32 were metastatic solid tumors. Median age was 61 years. Hypoxemia (29%) was the primary factor for cardiac arrest, followed by septic shock (21%). ICU mortality and hospital mortality were 87% and 88% respectively. Younger age, the presence of hematological malignancy, or a metastatic solid tumor were poor predictors for in-hospital mortality. Similarly, cardiac arrest in the ICU, as the final consequence of a pathological process, and a resuscitation time of more than 10 min have a negative influence on prognosis. CONCLUSIONS: This study shows that CPR is a useful intervention in cancer patients, even in the elderly patient, especially in non-metastatic solid tumors where cardiac arrest is the consequence of an acute event and not a terminal process.

Noninvasive Positive Pressure Ventilation Use and In-Hospital Cardiac Arrest in Bronchiolitis.

IMPORTANCE: A recent study showed an association between high hospital-level noninvasive positive pressure ventilation (NIPPV) use and in-hospital cardiac arrest (IHCA) in children with bronchiolitis. OBJECTIVES: We aimed to determine if patient-level exposure to NIPPV in children with bronchiolitis was associated with IHCA. DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort study at a single-center quaternary PICU in North America including children with International Classification of Diseases primary or secondary diagnoses of bronchiolitis in the Virtual Pediatric Systems database. MAIN OUTCOMES AND MEASURES: The primary exposure was NIPPV and the primary outcome was IHCA. MEASUREMENTS AND MAIN RESULTS: Of 4698 eligible ICU admissions with bronchiolitis diagnoses, IHCA occurred in 1.2% (57/4698). At IHCA onset, invasive mechanical ventilation (IMV) was the most frequent level of respiratory support (65%, 37/57), with 12% (7/57) receiving NIPPV. Patients with IHCA had higher Pediatric Risk of Mortality-III scores (3 [0-8] vs. 0 [0-2]; p < 0.001), more frequently had a complex chronic condition (94.7% vs. 46.2%; p < 0.001), and had higher mortality (21.1% vs. 1.0%; p < 0.001) compared with patients without IHCA. Return of spontaneous circulation (ROSC) was achieved in 93% (53/57) of IHCAs; 79% (45/57) survived to hospital discharge. All seven children without chronic medical conditions and with active bronchiolitis symptoms at the time of IHCA achieved ROSC, and 86% (6/7) survived to discharge. In multivariable analysis restricted to patients receiving NIPPV or IMV, NIPPV exposure was associated with lower odds of IHCA (adjusted odds ratio [aOR], 0.07; 95% CI, 0.03-0.18) compared with IMV. In secondary analysis evaluating categorical respiratory support in all patients, compared with IMV, NIPPV was associated with lower odds of IHCA (aOR, 0.35; 95% CI, 0.14-0.87), whereas no difference was found for minimal respiratory support (none/nasal cannula/humidified high-flow nasal cannula [aOR, 0.56; 95% CI, 0.23-1.36]). CONCLUSIONS AND RELEVANCE: Cardiac arrest in children with bronchiolitis is uncommon, occurring in 1.2% of bronchiolitis ICU admissions. NIPPV use in children with bronchiolitis was associated with lower odds of IHCA.

Carbon monoxide as a cellular protective agent in a swine model of cardiac arrest protocol.

Out-of-hospital cardiac arrest (OHCA) affects over 360,000 adults in the United States each year with a 50-80% mortality prior to reaching medical care. Despite aggressive supportive care and targeted temperature management (TTM), half of adults do not live to hospital discharge and nearly one-third of survivors have significant neurologic injury. The current treatment approach following cardiac arrest resuscitation consists primarily of supportive care and possible TTM. While these current treatments are commonly used, mortality remains high, and survivors often develop lasting neurologic and cardiac sequela well after resuscitation. Hence, there is a critical need for further therapeutic development of adjunctive therapies. While select therapeutics have been experimentally investigated, one promising agent that has shown benefit is CO. While CO has traditionally been thought of as a cellular poison, there is both experimental and clinical evidence that demonstrate benefit and safety in ischemia with lower doses related to improved cardiac/neurologic outcomes. While CO is well known for its poisonous effects, CO is a generated physiologically in cells through the breakdown of heme oxygenase (HO) enzymes and has potent antioxidant and anti-inflammatory activities. While CO has been studied in myocardial infarction itself, the role of CO in cardiac arrest and post-arrest care as a therapeutic is less defined. Currently, the standard of care for post-arrest patients consists primarily of supportive care and TTM. Despite current standard of care, the neurological prognosis following cardiac arrest and return of spontaneous circulation (ROSC) remains poor with patients often left with severe disability due to brain injury primarily affecting the cortex and hippocampus. Thus, investigations of novel therapies to mitigate post-arrest injury are clearly warranted. The primary objective of this proposed study is to combine our expertise in swine models of CO and cardiac arrest for future investigations on the cellular protective effects of low dose CO. We will combine our innovative multi-modal diagnostic platform to assess cerebral metabolism and changes in mitochondrial function in swine that undergo cardiac arrest with therapeutic application of CO.

Association between the triglyceride-glucose index and in-hospital major adverse cardiovascular events in patients with acute coronary syndrome: results from the Improving Care for Cardiovascular Disease in China (CCC)-Acute Coronary Syndrome project.

OBJECTIVE: Although the TyG index is a reliable predictor of insulin resistance (IR) and cardiovascular disease, its effectiveness in predicting major adverse cardiac events in hospitalized acute coronary syndrome (ACS) patients has not been validated in large-scale studies. In this study, we aimed to explore the association between the TyG index and the occurrence of MACEs during hospitalization. METHODS: We recruited ACS patients from the CCC-ACS (Improving Cardiovascular Care in China-ACS) database and calculated the TyG index using the formula ln(fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). These patients were classified into four groups based on quartiles of the TyG index. The primary endpoint was the occurrence of MACEs during hospitalization, encompassing all-cause mortality, cardiac arrest, myocardial infarction (MI), and stroke. We performed Cox proportional hazards regression analysis to clarify the correlation between the TyG index and the risk of in-hospital MACEs among patients diagnosed with ACS. Additionally, we explored this relationship across various subgroups. RESULTS: A total of 101,113 patients were ultimately included, and 2759 in-hospital MACEs were recorded, with 1554 (49.1%) cases of all-cause mortality, 601 (21.8%) cases of cardiac arrest, 251 (9.1%) cases of MI, and 353 (12.8%) cases of stroke. After adjusting for confounders, patients in TyG index quartile groups 3 and 4 showed increased risks of in-hospital MACEs compared to those in quartile group 1 [HR = 1.253, 95% CI 1.121-1.400 and HR = 1.604, 95% CI 1.437-1.791, respectively; p value for trend < 0.001], especially in patients with STEMI or renal insufficiency. Moreover, we found interactions between the TyG index and age, sex, diabetes status, renal insufficiency status, and previous PCI (all p values for interactions < 0.05). CONCLUSIONS: In patients with ACS, the TyG index was an independent predictor of in-hospital MACEs. Special vigilance should be exercised in females, elderly individuals, and patients with renal insufficiency.

Evaluation of the factors affecting mortality after cardiac arrest - do lactate and procalcitonin concentrations have any implications?

OBJECTIVE: Mortality and morbidity rates are very high in patients admitted to the Intensive Care Unit (ICU) after cardiac arrest. In this study, we aimed to determine the mortality rates, risk factors, and predictive factors for mortality in post-cardiac arrest patients admitted to the ICU. PATIENTS AND METHODS: Following approval from the Ethics Committee, we conducted a retrospective review of patient files for individuals over the age of 18 who received treatment for cardiac arrest in the ICU from January 2017 to June 2020. Demographic data of the patients, comorbidities, arrest location, etiology of arrest, duration of hospitalization, CPR duration, APACHE 2 scores, pH and HCO3 measurements in initial blood gases, lactate levels (1st, 6th, 12th, 24th hour), change in lactate levels (24-1), rate of lactate change, procalcitonin (PRC) levels (1st and 24th hour), change in PRC levels (24-1), rate of PRC change, and blood glucose levels were recorded. The patients were divided into two groups (survivors and non-survivors groups). RESULTS: 151 patients were included in the study. pH and HCO3 levels were lower in the non-survivors group than in the survivors group. Initial PRC levels were similar in both groups, but the 24th-hour PRC levels were higher, and the changes in PRC levels in the first 24 hours were greater in the non-survivors group. The lactate changes in the first 24 hours were higher in the non-survivors group. The receiver operating characteristic (ROC) curve showed that the HCO3 levels, 1st-, 6th-, 12th-, and 24th-hour lactate levels, and changes in lactate levels had predictability for mortality. In logistic regression analysis, we found that high 24th-hour lactate levels and changes in lactate levels were independent risk factors for mortality. CONCLUSIONS: Considering PRC and lactate levels, along with clinical examination and laboratory findings, may improve the accuracy of determining the prognosis of patients experiencing cardiac arrest.

Ketone Bodies after Cardiac Arrest: A Narrative Review and the Rationale for Use.

Cardiac arrest survivors suffer the repercussions of anoxic brain injury, a critical factor influencing long-term prognosis. This injury is characterised by profound and enduring metabolic impairment. Ketone bodies, an alternative energetic resource in physiological states such as exercise, fasting, and extended starvation, are avidly taken up and used by the brain. Both the ketogenic diet and exogenous ketone supplementation have been associated with neuroprotective effects across a spectrum of conditions. These include refractory epilepsy, neurodegenerative disorders, cognitive impairment, focal cerebral ischemia, and traumatic brain injuries. Beyond this, ketone bodies possess a plethora of attributes that appear to be particularly favourable after cardiac arrest. These encompass anti-inflammatory effects, the attenuation of oxidative stress, the improvement of mitochondrial function, a glucose-sparing effect, and the enhancement of cardiac function. The aim of this manuscript is to appraise pertinent scientific literature on the topic through a narrative review. We aim to encapsulate the existing evidence and underscore the potential therapeutic value of ketone bodies in the context of cardiac arrest to provide a rationale for their use in forthcoming translational research efforts.

Organ donation after extracorporeal cardiopulmonary resuscitation: a nationwide retrospective cohort study.

BACKGROUND: Limited data are available on organ donation practices and recipient outcomes, particularly when comparing donors who experienced cardiac arrest and received extracorporeal cardiopulmonary resuscitation (ECPR) followed by veno-arterial extracorporeal membrane oxygenation (ECMO) decannulation, versus those who experienced cardiac arrest without receiving ECPR. This study aims to explore organ donation practices and outcomes post-ECPR to enhance our understanding of the donation potential after cardiac arrest. METHODS: We conducted a nationwide retrospective cohort study using data from the Japan Organ Transplant Network database, covering all deceased organ donors between July 17, 2010, and August 31, 2022. We included donors who experienced at least one episode of cardiac arrest. During the study period, patients undergoing ECMO treatment were not eligible for a legal diagnosis of brain death. We compared the timeframes associated with each donor's management and the long-term graft outcomes of recipients between ECPR and non-ECPR groups. RESULTS: Among 370 brain death donors with an episode of cardiac arrest, 26 (7.0%) received ECPR and 344 (93.0%) did not; the majority were due to out-of-hospital cardiac arrests. The median duration of veno-arterial ECMO support after ECPR was 3 days. Patients in the ECPR group had significantly longer intervals from admission to organ procurement compared to those not receiving ECPR (13 vs. 9 days, P = 0.005). Lung graft survival rates were significantly lower in the ECPR group (log-rank test P = 0.009), with no significant differences in other organ graft survival rates. Of 160 circulatory death donors with an episode of cardiac arrest, 27 (16.9%) received ECPR and 133 (83.1%) did not. Time intervals from admission to organ procurement following circulatory death and graft survival showed no significant differences between ECPR and non-ECPR groups. The number of organs donated was similar between the ECPR and non-ECPR groups, regardless of brain or circulatory death. CONCLUSIONS: This nationwide study reveals that lung graft survival was lower in recipients from ECPR-treated donors, highlighting the need for targeted research and protocol adjustments in post-ECPR organ donation.