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.

Background: Brain injury and neurological deficit are consequences of cardiac arrest (CA), leading to high morbidity and mortality. Peripheral activation of the kynurenine pathway (KP), the main catabolic route of tryptophan metabolized at first into kynurenine, predicts poor neurological outcome in patients resuscitated after out‐of‐hospital CA. Here, we investigated KP activation in hippocampus and plasma of rats resuscitated from CA, evaluating the effect of KP modulation in preventing CA‐induced neurological deficit. Methods and Results: Early KP activation was first demonstrated in 28 rats subjected to electrically induced CA followed by cardiopulmonary resuscitation. Hippocampal levels of the neuroactive metabolites kynurenine, 3‐hydroxy‐anthranilic acid, and kynurenic acid were higher 2 hours after CA, as in plasma. Further, 36 rats were randomized to receive the inhibitor of the first step of KP, 1‐methyl‐DL‐tryptophan, or vehicle, before CA. No differences were observed in hemodynamics and myocardial function. The CA‐induced KP activation, sustained up to 96 hours in hippocampus (and plasma) of vehicle‐treated rats, was counteracted by the inhibitor as indicated by lower hippocampal (and plasmatic) kynurenine/tryptophan ratio and kynurenine levels. 1‐Methyl‐DL‐tryptophan reduced the CA‐induced neurological deficits, with a significant correlation between the neurological score and the individual kynurenine levels, as well as the kynurenine/tryptophan ratio, in plasma and hippocampus. Conclusions: These data demonstrate the CA‐induced lasting activation of the first step of the KP in hippocampus, showing that this activation was involved in the evolving neurological deficit. The degree of peripheral activation of KP may predict neurological function after CA.

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. 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. 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). 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. 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.

Oxygen supplementation is widely used to enhance oxygen delivery and to treat or prevent hypoxia; however, it requires careful management to avoid the harmful effects of excessive oxygen exposure. Both hyperoxia (inspiratory oxygen fraction exceeding 0.21) and hyperoxemia (arterial oxygen tension oxygen partial pressure [PaO ₂ ] > 100 mmHg) can contribute to lung injury, promote systemic vasoconstriction, and increase the production of reactive oxygen species, which can impair macromolecular and cellular functions. Conversely, in certain situations, hyperoxemia may provide benefits, such as hemodynamic stabilization in hyperdynamic shock, immunomodulation, and bactericidal effects. The literature presents conflicting evidence regarding the impact of different oxygen targets (i.e., PaO ₂ and/or peripheral saturation of oxygen [SpO ₂ ]) on both short- and long-term outcomes in patients with acute critical conditions, such as acute respiratory distress syndrome, sepsis, cardiac arrest, and acute central nervous system injuries. These discrepancies may stem from the small differences between the oxygenation targets used in randomized trials, the physiological limitations of PaO ₂ and SpO ₂ targets, which reflect blood oxygen content rather than oxygen delivery, the lack of measurements of microvascular function or oxygen delivery, and the heterogeneity in treatment response. Furthermore, advanced analytical methods (e.g., machine learning) are emerging as promising tools to implement population enrichment strategies. By refining patient sub-group identification, these approaches can significantly optimize precision medicine, enabling more personalized oxygen therapy tailored to individual patient characteristics.