Daily Ards Research Analysis

INTRODUCTION: Inhaled anaesthetics can be used in mechanically ventilated critically ill patients to provide sedation. This approach to sedation potentially improves patient and health system outcomes, but further supportive evidence is needed. The objective of the SAVE-ICU clinical trial is to compare the effectiveness of inhaled versus intravenous sedation in ventilated adults with acute hypoxaemic respiratory failure. METHODS AND ANALYSIS: SAVE-ICU is a multicentre, open-label, pragmatic, randomised controlled trial conducted in 15 intensive care units (ICUs) in Canada and the USA. Eligible patients include mechanically ventilated and sedated adults with acute hypoxemic respiratory failure from COVID-19 or non-COVID causes with PaO ETHICS AND DISSEMINATION: The protocol was approved by all hospital ethics committees and by Health Canada. Informed consent will be obtained from substitute decision makers or deferred consent (as permitted by site ethics board). Trial findings will be shared at the end of the study using peer-review publications, conference presentations and social media as part of the trial knowledge translation plan. TRIAL REGISTRATION NUMBER: NCT04415060.

The increasing prevalence of multidrug-resistant pathogens such as Klebsiella pneumoniae, which causes pneumonia and acute respiratory distress syndrome (ARDS) with high mortality rates, poses a significant clinical challenge. Fourth-generation antibiotics, such as cefepime, are often considered the last line of defense against these pathogens. The emergence of cefepime-resistant K. pneumoniae (CRKP) compromises the efficacy of available antibiotics and highlights the importance of new alternative therapies. This study directed the phyto-synthesis of copper oxide (CuO) nanoparticles using Melia azedarach leaf extract and evaluated their antibacterial efficacy, both individually and synergistically with cefepime, against multidrug-resistant Klebsiella pneumoniae through in vitro and in vivo models. The phyto-synthesized copper oxide nanoparticles were characterized using UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FESEM), and energy-dispersive X-ray analysis (EDAX). The antimicrobial efficacy of phyto-synthesized CuONPs, both alone and in combination with the antibiotic cefepime, was assessed through disk diffusion, minimum inhibitory concentration (MIC) assays, and in vivo experimentation. The phyto-synthesized CuONPs were characterized as crystalline, hexagonal in shape, and less than 30 nm in size. The antimicrobial efficacy was confirmed by inhibition zones ranging from 12 to 14 mm against multidrug-resistant Klebsiella pneumoniae. The CuONPs showed strong antimicrobial activity, with a minimum inhibitory concentration (MIC) of 2.25 µg/mL against the pathogenic strain. In comparison, cefepime alone showed no antimicrobial activity. Notably, when CuONPs were combined with cefepime, a synergistic effect was observed, lowering the MIC to 1.92 µg/mL. This study addresses the in vitro and in vivo analysis of CuONPs, with cefepime exerting a potent synergistic effect against the multidrug-resistant strain Klebsiella pneumoniae. This combined treatment resulted in an 82% inhibition rate, a significant reduction in bacterial burden, improved histopathological profiles, faster wound healing, and a regulated immune response.

Pneumothorax under positive-pressure ventilation can present within hours of intubation, particularly when a small, non-recruitable "baby lung" bears most of the mechanical load. We report a 67-year-old man with hypertrophic cardiomyopathy, hypertension, diabetes, and hypothyroidism who arrived obtunded (Glasgow Coma Scale 6) with severe hypoxaemia. He was intubated and initially ventilated in volume control; because saturations remained low with high airway pressures, he was switched to pressure control with higher positive end-expiratory pressure (PEEP). After a brief improvement, he acutely deteriorated with desaturation, hypotension, tachycardia, reduced minute ventilation, and rising airway pressures. Bedside lung ultrasound showed absent sliding with a barcode/stratosphere pattern and a lung point on the right; high-resolution computed tomography (HRCT) confirmed a large right pneumothorax with near-complete right-lung collapse and extensive ipsilateral consolidation. A right intercostal drain produced rapid physiological improvement. Initial studies showed neutrophilic leucocytosis, mild acute kidney injury, a cholestatic-predominant liver profile, markedly elevated NT-proBNP with normal high-sensitivity troponin, and near-normal coagulation; cultures remained negative, and bronchoalveolar lavage GeneXpert and cytology were negative. Endotracheal bleeding with anaemia and thrombocytopenia prompted bronchoscopy, which removed a lower-lobe endobronchial clot. Despite stabilisation, he sustained two intensive care unit (ICU) cardiac arrests with the return of spontaneous circulation; echocardiography demonstrated a dilated left atrium, asymmetric septal hypertrophy with paradoxical septal motion, grade-I diastolic dysfunction, and pulmonary hypertension. Weaning to pressure support occurred on days 4 and 5; he was extubated on day 6, stepped down from ICU on day 7, the chest drain was removed on day 10, and he was discharged home on day 12 on oral antibiotics. At two-week follow-up, he remained stable with no recurrent pneumothorax. This case emphasises three practical points: pneumothorax may occur immediately post-intubation in severely consolidated, low-compliance lungs; ultrasound outperforms supine radiography for rapid bedside diagnosis and should guide timely decompression when physiology is unstable; and power-aware ventilation - limiting driving pressure and avoiding injudicious PEEP escalation in non-recruitable lungs - helps prevent a transient oxygenation "win" from tipping into structural failure.