Recent estimates suggest that up to 34% of frontline workers in healthcare (FLWs) at the forefront of the COVID-19 pandemic response are reporting elevated symptoms of psychological distress due to resource constraints, ineffective treatments, and concerns about self-contamination. However, little systematic research has been carried out to assess the mental health needs of FLWs in Europe, or the extent of psychological suffering in FLWs within different European countries of varying outbreak severity. Accordingly, this project will employ a mixed-methods approach over three work packages to develop best-practice guidelines for alleviating psychological distress in FLWs during the different phases of the pandemic. Work package 1 will identify the point and long-term prevalence of psychological distress symptoms in a sample of Irish and Italian FLWs, and the predictors of these symptoms. Work package 2 will perform a qualitative needs assessment on a sample of Irish and Italian FLWs to identify sources of stress and resilience, barriers to psychological care, and optimal strategies for alleviating psychological distress in relation to the COVID-19 pandemic. Work package 3 will synthesise the findings from the preceding work packages to draft best practice guidelines, which will be co-created by a multidisciplinary panel of experts using the Delphi method. The guidelines will provide clinicians with a framework for alleviating psychological distress in FLWs, with particular relevance to the COVID-19 pandemic, but may also have relevance for future pandemics and other public health emergencies.

Recent estimates suggest that up to 34% of frontline workers in healthcare (FLWs) at the forefront of the COVID-19 pandemic response are reporting elevated symptoms of psychological distress due to resource constraints, ineffective treatments, and concerns about self-contamination. However, little systematic research has been carried out to assess the mental health needs of FLWs in Europe, or the extent of psychological suffering in FLWs within different European countries of varying outbreak severity. Accordingly, this project will employ a mixed-methods approach over three work packages to develop best-practice guidelines for alleviating psychological distress in FLWs during the different phases of the pandemic. Work package 1 will identify the point and long-term prevalence of psychological distress symptoms in a sample of Irish and Italian FLWs, and the predictors of these symptoms. Work package 2 will perform a qualitative needs assessment on a sample of Irish and Italian FLWs to identify sources of stress and resilience, barriers to psychological care, and optimal strategies for alleviating psychological distress in relation to the COVID-19 pandemic. Work package 3 will synthesise the findings from the preceding work packages to draft best practice guidelines, which will be co-created by a multidisciplinary panel of experts using the Delphi method. The guidelines will provide clinicians with a framework for alleviating psychological distress in FLWs, with particular relevance to the COVID-19 pandemic, but may also have relevance for future pandemics and other public health emergencies.

Grooming is often related to dearousal following stressors. Interestingly, electrical and chemical stimulation of the paraventricular nucleus of the hypothalamus (PVH), at levels that are known to activate the hypothalamus-pituitary adrenal axis (HPA), also elicits grooming. At the level of the PVH, the neuroendocrine stress response is apparently still linked to the behavioural response to stressors. However the precise nature of this relation is not fully understood. Here we report on grooming in rats following exposure to different stressors which are known to activate the HPA axis. Stressors such as handling, restraint, novelty, encounters with aggressive or non-aggressive conspecifics, or moistening the fur, change the amount and time course of grooming upon return in the home cage, as compared with controls that are just handled. However, the amount of grooming is not directly related to the strength of the stressor. Defeated intruders groom less upon return in their home cage. Novelty and non-aggressive encounters with conspecifics reduce the variation in the amount of grooming between rats. The time course of grooming over the 20-min observation period also differs between treatments. Following restraint, or exposure to non-aggressive conspecifics, grooming first increases and then decreases. Moistened rats immediately start grooming which subsequently decreases. Rats used as intruders in the territory of another rat maintain a constant low level of grooming. Rats placed in a novel cage steadily increase grooming during the 20-min observation period. These results suggest that grooming cannot be simply understood as an immediate response necessary to reduce arousal following stressors. Following exposure to a stressor, grooming rather seems temporary suppressed. If grooming has a restorative function, it is a delayed function, which is not directly related to the strength of the stressor.

Background Simulation-based training is an excellent modality to practice complex airway emergencies while avoiding any harm to patients and can be used to improve the technical and non- technical skills required for difficult airway management. It is most effective when used to train teams that include all disciplines involved in the care of these patients as human factors issues, including poor communication and teamwork, contribute to adverse outcomes in up to 40% of difficult airway cases.1 Summary of work A collaborative multidisciplinary airway simulation programme was developed by a multidisciplinary team that included ENT, Anaesthesia, Perioperative Nursing Departments and the Irish Centre for Applied Patient Safety and Simulation (ICAPSS). A two-part programme was developed that focused on addressing the learning needs of all disciplines. The first part was three complex airway scenarios completed by teams of four learners comprised of ENT and anaesthesia doctors and nurses. The second part was a technical skills workshop supported by subject matter expert feedback. Skills included were cricothyroidotomy, percutaneous tracheostomy, fibreoptic intubation, high-flow nasal oxygen therapy and rigid bronchoscopy. All disciplines attended and participated in both parts of the programme. Summary of results Post-workshop evaluation was overwhelmingly positive. All participants (n = 17) agreed or strongly agreed that the workshop improved their ability to use skills related to the topic and that the knowledge and skills that they learned will be useful to them in their job. All participants agreed that the workshop was enjoyable and that it addressed their learning needs. Discussion The multidisciplinary team simulation programme specifically highlighted individual team member roles in managing difficult airways by including members for each discipline in every part of the programme. The inclusion of both medical and nursing staff to the practical workshop equally upskilled all members in respect to airway management to ensure a better understanding of equipment and procedures and ultimately benefiting all in the event of a challenging scenario. Conclusion Using multidisciplinary team simulation programmes is a well-received method to teach collaborative management of complex airway scenarios in a team setting. Recommendations The success of the programme highlights the need and the acceptability of this type of high impact training and how involving a multidisciplinary team at the development stage ensures buy-in and participation. The developers plan to deliver the programme more frequently to maintain team skills in managing difficult airway cases in a collaborative team setting. Reference Cook T, et al. 4th National Audit Project of The Royal College of Anaesthetists and The Difficult Airway Society. Major complications of airway management in the United Kingdom, Report and Findings. Royal College of Anaesthetists. London, 2011

Administration of blood is a complex process requiring vigilance and effective teamwork. Despite strict policies and training on blood administration, errors still occur and can lead to mistransfusion with adverse patient outcomes. We used an in situ simulated scenario within an operating room (OR) to identify weaknesses in the current process and hazards that could contribute to mistransfusion.

Purpose of review Hypercapnia is a central component of diverse respiratory disorders, while 'permissive hypercapnia' is frequently used in ventilatory strategies for patients with severe respiratory failure. This review will present data from recent studies relating to hypercapnia, focusing on issues that are of importance to anesthesiologists caring for the surgical and/or critically ill patient. Recent findings Protective ventilatory strategies involving permissive hypercapnia are widely used in patients with severe respiratory failure, particularly in acute respiratory distress syndrome, status asthmaticus, chronic obstructive pulmonary disease and neonatal respiratory failure. The physiologic effects of hypercapnia are increasingly well understood, and important recent insights have emerged regarding the cellular and molecular mechanisms of action of hypercapnia and acidosis. Acute hypercapnic acidosis is protective in multiple models of nonseptic lung injury. These effects are mediated in part through inhibition of the NF-kappa B pathway. Hypercapnia-mediated NF-kappa B inhibition may also explain several deleterious effects, including delayed epithelial wound healing and decreased bacterial killing, which has been demonstrated to cause worse lung injury in prolonged untreated pneumonia models. Summary The mechanisms of action of hypercapnia and acidosis continue to be elucidated, and this knowledge is central to determining the safety and therapeutic utility of hypercapnia in protective lung ventilatory strategies.

BACKGROUND:Activation of the nuclear factor-κB (NF-κB) pathway is central to the pathogenesis of lung injury and inflammation. We determined whether targeted overexpression of inhibitor-κBα (IκBα) in the lung could decrease the severity of ventilator-induced lung injury (VILI).METHODS:Anaesthetized adult male Sprague-Dawley rats were randomly allocated to undergo intratracheal instillation of: (i) vehicle alone (surfactant, n=10); (ii) 1×10(10) adeno-associated virus encoding IκBα (AAV-IκBα, n=10); (iii) 5×10(10) AAV-IκBα (n=10); and (iv) 1×10(10) AAV-Null (n=5). This was followed by 4 h of injurious mechanical ventilation. Subsequent experiments examined the effect of IκBα overexpression in animals undergoing 'protective' mechanical ventilation.RESULTS:IκBα overexpression increased survival duration at both the lower [3.8 h (0.4)] and higher [3.6 h (0.7)] doses compared with vehicle [2.7 h (1.0)] or the null transgene [2.2 h (0.8)]. IκBα overexpression reduced the alveolar-arterial oxygen gradient (kPa) at both the lower [53 (21)] and higher [52 (19)] doses compared with vehicle [75 (8.5)] or the null transgene [70 (15)], decreased alveolar neutrophil infiltration, and reduced alveolar concentrations of interleukin (IL)-1β and IL-10. The lower IκBα dose was as effective as the higher dose. IκBα overexpression had no effect in the setting of protective lung ventilation.CONCLUSIONS:Inhibition of pulmonary NF-κB activity by IκBα overexpression reduced the severity of VILI in a rat model.

Objectives: Hypercapnic acidosis protects against ventilation-induced lung injury. We wished to determine whether the beneficial effects of hypercapnic acidosis in reducing stretch-induced injury were mediated via inhibition of nuclear factor-kappa B, a key transcriptional regulator in inflammation, injury, and repair.Design: Prospective randomized animal study.Setting: University research laboratory.Subjects: Adult male Sprague-Dawley rats.Interventions: In separate experimental series, the potential for hypercapnic acidosis to attenuate moderate and severe ventilation-induced lung injury was determined. In each series, following induction of anesthesia and tracheostomy, Sprague-Dawley rats were randomized to (normocapnia; Fico(2) 0.00) or (hypercapnic acidosis; Fico(2) 0.05), subjected to high stretch ventilation, and the severity of lung injury and indices of activation of the nuclear factor-kappa B pathway were assessed. Subsequent in vitro experiments examined the potential for hypercapnic acidosis to reduce pulmonary epithelial inflammation and injury induced by cyclic mechanical stretch. The role of the nuclear factor-kappa B pathway in hypercapnic acidosis mediated protection from stretch injury was then determined.Measurements and Main Results: Hypercapnic acidosis attenuated moderate and severe ventilation-induced lung injury, as evidenced by improved oxygenation, compliance, and reduced histologic injury compared to normocapnic conditions. Hypercapnic acidosis reduced indices of inflammation such as interleukin-6 and bronchoalveolar lavage neutrophil infiltration. Hypercapnic acidosis reduced the decrement of the nuclear factor-kappa B inhibitor I kappa B alpha and reduced the generation of cytokine-induced neutrophil chemoattractant-1. Hypercapnic acidosis reduced cyclic mechanical stretch-induced nuclear factor-kappa B activation, reduced interleukin-8 production, and decreased epithelial injury and cell death compared to normocapnia.Conclusions: Hypercapnic acidosis attenuated ventilation-induced lung injury independent of injury severity and decreased mechanical stretch-induced epithelial injury and death, via a nuclear factor-kappa B dependent mechanism. (Crit Care Med 2012; 40:2622-2630)

Purpose: Superoxide is produced by activated neutrophils during the inflammatory response to stimuli such as endotoxin, can directly or indirectly injure host cells, and has been implicated in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). We wished to determine the potential for pulmonary overexpression of the extracellular isoform of superoxide dismutase (EC-SOD) to reduce the severity of endotoxin-induced lung injury. Methods: Animals were randomly allocated to undergo intratracheal instillation of (1) surfactant alone (vehicle); (2) adeno-associated virus (AAV) vectors containing a null transgene (AAV-null); and (3) adeno-associated virus vectors containing the EC-SOD transgene (AAV-EC-SOD) and endotoxin was subsequently administered intratracheally. Two additional groups were randomized to receive (1) vehicle or (2) AAV-EC-SOD, and to undergo sham (vehicle) injury. The severity of the lung injury was assessed in all animals 24 h later. Results: Endotoxin produced a severe lung injury compared to sham injury. The AAV vector encoding EC-SOD increased lung EC-SOD concentrations, and enhanced the antioxidant capacity of the lung. EC-SOD overexpression decreased the severity of endotoxin-induced ALI, reducing the decrement in systemic oxygenation and lung compliance, decreasing lung permeability and decreasing histologic injury. EC-SOD attenuated pulmonary inflammation, decreased bronchoalveolar lavage neutrophil counts, and reduced interleukin-6 and CINC-1 concentrations. The AAV vector itself did not contribute to inflammation or to lung injury. Conclusions: Pulmonary overexpression of EC-SOD protects the lung against endotoxin-induced ALI.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) confer substantial morbidity and mortality, and have no specific therapy. The accessibility of the distal lung epithelium via the airway route, and the relatively transient nature of ALI/ARDS, suggest that the disease may be amenable to gene-based therapies. Ongoing advances in our understanding of the pathophysiology of ALI/ARDS have revealed multiple therapeutic targets for gene-based approaches. Strategies to enhance or restore lung epithelial and/or endothelial cell function, to strengthen lung defense mechanisms against injury, to speed clearance of infection and to enhance the repair process following ALI/ARDS have all demonstrated promise in preclinical models. Despite three decades of gene therapy research, however, the clinical potential for gene-based approaches to lung diseases including ALI/ARDS remains to be realized. Multiple barriers to effective pulmonary gene therapy exist, including the pulmonary architecture, pulmonary defense mechanisms against inhaled particles, the immunogenicity of viral vectors and the poor transfection efficiency of nonviral delivery methods. Deficits remain in our knowledge regarding the optimal molecular targets for gene-based approaches. Encouragingly, recent progress in overcoming these barriers offers hope for the successful translation of gene-based approaches for ALI/ARDS to the clinical setting.

Background The time course and mechanisms of resolution and repair, and the potential for fibrosis following ventilation-induced lung injury (VILI), are unclear. We sought to examine the pattern of inflammation, injury, repair, and fibrosis following VILI. Methods Sixty anesthetized rats were subject to high-stretch; low-stretch, or sham ventilation, and randomly allocated to undergo periods of recovery of 6, 24, 48, and 96 h, and 7 and 14 days. Animals were then reanesthetized, and the extent of lung injury, inflammation, and repair determined. Results No injury was seen following low-stretch or sham ventilation. VILI caused severe lung injury, maximal at 24 h, but largely resolved by 96 h. Arterial oxygen tension decreased from a mean (SD) of 144.8 (4.1) mmHg to 96.2 (10.3) mmHg 6 h after VILI, before gradually recovering to 131.2 (14.3) mmHg at 96 h. VILI induced an early neutrophilic alveolitis and a later lymphocytic alveolitis, followed by a monocyte/macrophage infiltration. Alveolar tumor necrosis factor-α, interleukin-1β, and transforming growth factor-β1 concentrations peaked at 6 h and returned to baseline within 24 h, while interleukin-10 remained increased for 48 h. VILI generated a marked but transient fibroproliferative response, which restored normal lung architecture. There was no evidence of fibrosis at 7 and 14 days. Conclusions High-stretch ventilation caused severe lung injury, activating a transient inflammatory and fibroproliferative repair response, which restored normal lung architecture without evidence of fibrosis.

Acute respiratory distress syndrome is a devastating disease that causes substantial morbidity and mortality. Mechanical ventilation can worsen lung injury, whereas ventilatory strategies that reduce lung stretch, resulting in a "permissive" hypercapnic acidosis (HCA), improve outcome. HCA directly reduces nonsepsis-induced lung injury in preclinical models and, therefore, has therapeutic potential in these patients. These beneficial effects are mediated via inhibition of the host immune response, particularly cytokine signaling, phagocyte function, and the adaptive immune response. Of concern, these immunosuppressive effects of HCA may hinder the host response to microbial infection. Recent studies suggest that HCA is protective in the earlier phases of bacterial pneumonia-induced sepsis but may worsen injury in the setting of prolonged lung sepsis. In contrast, HCA is protective in preclinical models of early and prolonged systemic sepsis. Buffering of the HCA is not beneficial and may worsen pneumonia-induced injury.

Acute lung injury (ALI), and its more severe subset acute respiratory distress syndrome (ARDS), are a major cause of mortality in the ICU [1]. Mechanical ventilation, a supportive therapy necessary to sustain life in many cases, may contribute to and worsen ALI, termed ventilator-induced lung injury (VILI). Fibroproliferation is an early response to lung injury [2]. Indeed, dysregulated repair resulting in pulmonary fibrosis may be at the heart of ventilator dependence in ARDS. Characterising the role of excessive lung stretch in contributing to aberrant repair mechanisms would assist in developing strategies to hasten recovery from ARDS.