Acute Lung Injury after Cardiopulmonary Resuscitation: A Narrative Review.

Although cardiopulmonary resuscitation (CPR) includes lifesaving maneuvers, it might be associated with a wide spectrum of iatrogenic injuries. Among these, acute lung injury (ALI) is frequent and yields significant challenges to post-cardiac arrest recovery. Understanding the relationship between CPR and ALI is determinant for refining resuscitation techniques and improving patient outcomes. This review aims to analyze the existing literature on ALI following CPR, emphasizing prevalence, clinical implications, and contributing factors. The review seeks to elucidate the pathogenesis of ALI in the context of CPR, assess the efficacy of CPR techniques and ventilation strategies, and explore their impact on post-cardiac arrest outcomes. CPR-related injuries, ranging from skeletal fractures to severe internal organ damage, underscore the complexity of managing post-cardiac arrest patients. Chest compression, particularly when prolonged and vigorous, i.e., mechanical compression, appears to be a crucial factor contributing to ALI, with the concept of cardiopulmonary resuscitation-associated lung edema (CRALE) gaining prominence. Ventilation strategies during CPR and post-cardiac arrest syndrome also play pivotal roles in ALI development. The recognition of CPR-related lung injuries, especially CRALE and ALI, highlights the need for research on optimizing CPR techniques and tailoring ventilation strategies during and after resuscitation.

Treatment with inhaled Argon: a systematic review of pre-clinical and clinical studies with meta-analysis on neuroprotective effect.

BACKGROUND: Argon (Ar) has been proposed as a potential therapeutic agent in multiple clinical conditions, specifically in organ protection. However, conflicting data on pre-clinical models, together with a great variability in Ar administration protocols and outcome assessments, have been reported. The aim of this study was to review evidence on treatment with Ar, with an extensive investigation on its neuroprotective effect, and to summarise all tested administration protocols. METHODS: Using the PubMed database, all existing pre-clinical and clinical studies on the treatment with Ar were systematically reviewed (registration: https://doi.org/10.17605/OSF.IO/7983D). Study titles and abstracts were screened, extracting data from relevant studies post full-text review. Exclusion criteria included absence of full text and non-English language. Furthermore, meta-analysis was also performed to assess Ar potential as neuroprotectant agent in different clinical conditions: cardiac arrest, traumatic brain injury, ischemic stroke, perinatal hypoxic-ischemic encephalopathy, subarachnoid haemorrhage. Standardised mean differences for neurological, cognitive and locomotor, histological, and physiological measures were evaluated, through appropriate tests, clinical, and laboratory variables. In vivo studies were evaluated for risk of bias using the Systematic Review Center for Laboratory Animal Experimentation tool, while in vitro studies underwent assessment with a tool developed by the Office of Health Assessment and Translation. FINDINGS: The systematic review detected 60 experimental studies (16 in vitro, 7 ex vivo, 31 in vivo, 6 with both in vitro and in vivo) investigating the role of Ar. Only one clinical study was found. Data from six in vitro and nineteen in vivo studies were included in the meta-analyses. In pre-clinical models, Ar administration resulted in improved neurological, cognitive and locomotor, and histological outcomes without any change in physiological parameters (i.e., absence of adverse events). INTERPRETATION: This systematic review and meta-analysis based on experimental studies supports the neuroprotective effect of Ar, thus providing a rationale for potential translation of Ar treatment in humans. Despite adherence to established guidelines and methodologies, limitations in data availability prevented further analyses to investigate potential sources of heterogeneity due to study design. FUNDING: This study was funded in part by Italian Ministry of Health-Current researchIRCCS and by Ministero della Salute Italiano, Ricerca Finalizzata, project no. RF 2019-12371416.

Evolution of brain injury and neurological dysfunction after cardiac arrest in the rat - A multimodal and comprehensive model.

Cardiac arrest (CA) is one of the leading causes of death worldwide. Due to hypoxic ischemic brain injury, CA survivors may experience variable degrees of neurological dysfunction. This study, for the first time, describes the progression of CA-induced neuropathology in the rat. CA rats displayed neurological and exploratory deficits. Brain MRI revealed cortical and striatal edema at 3 days (d), white matter (WM) damage in corpus callosum (CC), external capsule (EC), internal capsule (IC) at d7 and d14. At d3 a brain edema significantly correlated with neurological score. Parallel neuropathological studies showed neurodegeneration, reduced neuronal density in CA1 and hilus of hippocampus at d7 and d14, with cells dying at d3 in hilus. Microgliosis increased in cortex (Cx), caudate putamen (Cpu), CA1, CC, and EC up to d14. Astrogliosis increased earlier (d3 to d7) in Cx, Cpu, CC and EC compared to CA1 (d7 to d14). Plasma levels of neurofilament light (NfL) increased at d3 and remained elevated up to d14. NfL levels at d7 correlated with WM damage. The study shows the consequences up to 14d after CA in rats, introducing clinically relevant parameters such as advanced neuroimaging and blood biomarker useful to test therapeutic interventions in this model.

Transthoracic impedance variability to assess quality of chest compression in out-of-hospital cardiac arrest.

BACKGROUND: Chest compression is a lifesaving intervention in out-of-hospital cardiac arrest (OHCA), but the optimal metrics to assess its quality have yet to be identified. The objective of this study was to investigate whether a new parameter, that is, the variability of the chest compression-generated transthoracic impedance (TTI), namely ImpCC , which measures the consistency of the chest compression maneuver, relates to resuscitation outcome. METHODS: This multicenter observational, retrospective study included OHCAs with shockable rhythm. ImpCC variability was evaluated with the power spectral density analysis of the TTI. Multivariate regression model was used to examine the impact of ImpCC variability on defibrillation success. Secondary outcome measures were return of spontaneous circulation and survival. RESULTS: Among 835 treated OHCAs, 680 met inclusion criteria and 565 matched long-term outcomes. ImpCC was significantly higher in patients with unsuccessful defibrillation compared to those with successful defibrillation (p = .0002). Lower ImpCC variability was associated with successful defibrillation with an odds ratio (OR) of 0.993 (95% confidence interval [95% CI], 0.989-0.998, p = .003), while the standard chest compression fraction (CCF) was not associated (OR 1.008 [95 % CI, 0.992-1.026, p = .33]). Neither ImpCC nor CCF was associated with long-term outcomes. CONCLUSIONS: In this population, consistency of chest compression maneuver, measured by variability in TTI, was an independent predictor of defibrillation outcome. ImpCC may be a useful novel metrics for improving quality of care in OHCA.

Concomitant hypokalemia and hypocalcemia: a very rare but life-threating combination of reversible causes of cardiac arrest - an unusual first manifestation of coeliac disease.

The causes of cardiac arrest are extremely heterogeneous. Among these, both hypokalemia and hypocalcemia are known reversible factors that can lead to cardiac arrest. In this report, we present a unique case report of a patient with previously undiagnosed coeliac disease who experienced cardiac arrest due a combination of hypokalemia and hypocalcemia resulting from malabsorption. A 66-year-old male presented to the emergency department with symptoms of malaise, weakness, weight loss, and persistent diarrhea. The patient exhibited characteristic signs of hypokalemia and hypocalcemia, including fasciculations, weakness, and swelling. An electrocardiogram showed a normal rhythm, and blood tests confirmed the electrolyte imbalances. Despite initial treatment, the patient experienced sudden cardiac arrest. Prompt resuscitation efforts were successful in restoring spontaneous circulation. However, recurrent episodes of ventricular arrhythmias and cardiac arrest occurred. Large doses of intravenous potassium chloride, in conjunction with magnesium, were needed prior to restore electrolyte balance. The concomitant severe hypocalcemia required caution calcium supplementation, to avoid further decreases in serum potassium levels. Appropriate ion replacements ultimately led to successful resuscitation with good functional recovery. During the hospital stay, the patient was diagnosed with coeliac disease. This case is noteworthy for its uniqueness, as there are no documented instances in the scientific literature linking cardiac arrest directly to coeliac disease. It is important to emphasize the need for investigating potential reversible causes of cardiac arrest, such as hypokalemia and hypocalcemia, and implementing appropriate interventions to address these factors.

Amplitude spectrum area measured in real-time during cardiopulmonary resuscitation - How does this technology work?

Amplitude spectrum area (AMSA) is one of the most accurate predictors of defibrillation outcome. Details on functioning and use of the available technology to measure AMSA during cardiopulmonary resuscitation (CPR) in the real clinical scenario are described. During chest compression (CC) pauses for ventilations, AMSA is promptly calculated and values displayed through a modified defibrillator. In addition, real-time AMSA analysis has the additional promise to monitor CPR quality, being AMSA threshold values contingent on CC depth. Future larger studies employing this new technology are now needed to demonstrate the impact of AMSA on survival of cardiac arrest.

Indoleamine 2,3-Dioxygenase Deletion to Modulate Kynurenine Pathway and to Prevent Brain Injury after Cardiac Arrest in Mice.

BACKGROUND: The catabolism of the essential amino acid tryptophan to kynurenine is emerging as a potential key pathway involved in post-cardiac arrest brain injury. The aim of this study was to evaluate the effects of the modulation of kynurenine pathway on cardiac arrest outcome through genetic deletion of the rate-limiting enzyme of the pathway, indoleamine 2,3-dioxygenase. METHODS: Wild-type and indoleamine 2,3-dioxygenase-deleted (IDO-/-) mice were subjected to 8-min cardiac arrest. Survival, neurologic outcome, and locomotor activity were evaluated after resuscitation. Brain magnetic resonance imaging with diffusion tensor and diffusion-weighted imaging sequences was performed, together with microglia and macrophage activation and neurofilament light chain measurements. RESULTS: IDO-/- mice showed higher survival compared to wild-type mice (IDO-/- 11 of 16, wild-type 6 of 16, log-rank P = 0.036). Neurologic function was higher in IDO-/- mice than in wild-type mice after cardiac arrest (IDO-/- 9 ± 1, wild-type 7 ± 1, P = 0.012, n = 16). Indoleamine 2,3-dioxygenase deletion preserved locomotor function while maintaining physiologic circadian rhythm after cardiac arrest. Brain magnetic resonance imaging with diffusion tensor imaging showed an increase in mean fractional anisotropy in the corpus callosum (IDO-/- 0.68 ± 0.01, wild-type 0.65 ± 0.01, P = 0.010, n = 4 to 5) and in the external capsule (IDO-/- 0.47 ± 0.01, wild-type 0.45 ± 0.01, P = 0.006, n = 4 to 5) in IDO-/- mice compared with wild-type ones. Increased release of neurofilament light chain was observed in wild-type mice compared to IDO-/- (median concentrations [interquartile range], pg/mL: wild-type 1,138 [678 to 1,384]; IDO-/- 267 [157 to 550]; P < 0.001, n = 3 to 4). Brain magnetic resonance imaging with diffusion-weighted imaging revealed restriction of water diffusivity 24 h after cardiac arrest in wild-type mice; indoleamine 2,3-dioxygenase deletion prevented water diffusion abnormalities, which was reverted in IDO-/- mice receiving l-kynurenine (apparent diffusion coefficient, µm2/ms: wild-type, 0.48 ± 0.07; IDO-/-, 0.59 ± 0.02; IDO-/- and l-kynurenine, 0.47 ± 0.08; P = 0.007, n = 6). CONCLUSIONS: The kynurenine pathway represents a novel target to prevent post-cardiac arrest brain injury. The neuroprotective effects of indoleamine 2,3-dioxygenase deletion were associated with preservation of brain white matter microintegrity and with reduction of cerebral cytotoxic edema.

"De trop" meta-analyses and systematic reviews in cardiopulmonary resuscitation - A way to rapidly improve authors' citation index at a price of real science.

Meta-analyses and systematic reviews (MSR) have been conceived as tools to summarize evidence on a specific health question. However, in the last years, an exaggerated number of MSRs published by scientific journals has been observed, i.e. 286 MSRs in the field of Resuscitation Science over the last 3 years, i.e. approximately 95 per year. Thus, doubts on the real scientific need of such a high number of MSRs may arise, potentially being only a way to rapidly improve authors' citation index and fame and sometimes the journals' impact factor.

One-Year Review in Cardiac Arrest: The 2022 Randomized Controlled Trials.

Cardiac arrest, one of the leading causes of death, accounts for numerous clinical studies published each year. This review summarizes the findings of all the randomized controlled clinical trials (RCT) on cardiac arrest published in the year 2022. The RCTs are presented according to the following categories: out-of- and in-hospital cardiac arrest (OHCA, IHCA) and post-cardiac arrest care. Interestingly, more than 80% of the RCTs encompassed advanced life support and post-cardiac arrest care, while no studies focused on the treatment of IHCA, except for one that, however, explored the temperature control after resuscitation in this population. Surprisingly, 9 out of 11 RCTs led to neutral results demonstrating equivalency between the newly tested interventions compared to current practice. One trial was negative, showing that oxygen titration in the immediate pre-hospital post-resuscitation period decreased survival compared to a more liberal approach. One RCT was positive and introduced new defibrillation strategies for refractory cardiac arrest. Overall, data from the 2022 RCTs discussed here provide a solid basis to generate new hypotheses to be tested in future clinical studies.

Adrenalectomy for metastasis: long-term results and predictors of survival.

The purpose of this study was to analyze our experience with surgically treated isolated adrenal metastases in order to find those factors which can significantly affect survival. This method includes a retrospective single-center chart review. We evaluated how overall survival and disease-free survival (DFS) were influenced by demographic, tumor, and procedure-related variables. Thirty-seven adrenalectomies were performed in 34 patients. Procedures included 25 laparoscopic and 12 open adrenalectomies. Median follow-up was 49 months. Median overall survival was 63 months. Patients submitted to laparoscopic approach had a median survival of 57 months while it was 65 months for those who underwent open procedure (p = 0.67). DFS was 30 months, and these were 35 and 25 months after laparoscopic approach and open approach, respectively (p = 0.59). The concurrent resection of the adrenal metastasis with the primary tumor was the only factor influencing DFS (HR 6.8 95 % CI 1.2-37.3, p = 0.02). Patients with non-small cell lung cancer (n = 15) had a median survival of 63 months and DFS of 35 months. Our experience confirms that adrenalectomy, regardless of the surgical approach, can offer durable disease-free and overall survival outcomes for surgical candidates with isolated adrenal metastases.

Factors influencing outcomes in laparoscopic adrenal surgery.

PURPOSE: This study aims to recognize factors affecting operative and postoperative outcomes in patients undergoing unilateral laparoscopic adrenalectomy performed by using the transabdominal approach. METHODS: From a prospectively collected adrenal database, we performed a retrospective analysis of all patients undergoing unilateral adrenalectomy from July 2002 to December 2011. The outcome measures considered were the following: conversion rate, intra- and postoperative complications, duration of surgery, length of hospital stay, and return-to-work time. Demographic data, American Society of Anesthesiologists score, characteristics of adrenal tumor, and operative and postoperative variables were analyzed to assess their influence on the outcome variables. RESULTS: A total of 163 laparoscopic adrenalectomies were included. Intraoperative complications, conversion to laparotomy, and postoperative complications were observed in 6.7, 6.1, and 1.8 % of cases, respectively. Conversion to open surgery, intraoperative complications, metastasis, and pheochromocytoma were found to be predictive factors for operative time of >140 min. An operative duration of >140 min was associated with intraoperative complications. Tumor size, intraoperative complications, and adrenalectomy for metastasis significantly increased conversion rate. Hospital stay was extended by operative time of >140 min, conversion to laparotomy, and postoperative complications. CONCLUSION: Our study highlights that simple clinical variables, long procedures, and operative complications have a negative impact on procedural outcomes. Based on this, it may be possible to predict cases requiring collaboration with experienced surgeons in order to minimize perioperative morbidity.

Advanced sealing and dissecting devices in laparoscopic adrenal surgery.

OBJECTIVES: This study sought to analyze the impact of advanced sealing/dissecting devices on operative and postoperative outcomes in laparoscopic adrenalectomy. METHOD: Patients were divided into three groups according to the devices used during their procedures [electrothermal bipolar vessel system (EBVS), ultrasound shears (US), and monopolar electrocautery (ME)]. A comparison of the perioperative outcomes was performed. RESULTS: Conversion rates and intraoperative and postoperative complication rates did not differ among the three groups. Major blood loss that required transfusion was registered in only two cases, all of which were performed with ME. Procedures with EBVS were shorter than those with US or ME. For left adrenalectomies only, operative times were similar for US and EBVS. The use of EBVS was found to be an independent predictor of decreased operative time. CONCLUSION: The use of advanced sealing devices was associated with reduced operative time, with particular benefits in left adrenalectomy. EBVS and US may provide better hemostasis than ME.