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Background: Limiting tidal volume (V T ), plateau pressure, and driving pressure is essential during the acute respiratory distress syndrome (ARDS), but may be challenging when brain injury coexists due to the risk of hypercapnia. Because lowering dead space enhances CO 2 clearance, we conducted a study to determine whether and to what extent replacing heat and moisture exchangers (HME) with heated humidifiers (HH) facilitate safe V T lowering in brain-injured patients with ARDS., Methods: Brain-injured patients (head trauma or spontaneous cerebral hemorrhage with Glasgow Coma Scale at admission < 9) with mild and moderate ARDS received three ventilatory strategies in a sequential order during continuous paralysis: (1) HME with V T to obtain a PaCO 2 within 30-35 mmHg (HME1); (2) HH with V T titrated to obtain the same PaCO 2 (HH); and (3) HME1 settings resumed (HME2). Arterial blood gases, static and quasi-static respiratory mechanics, alveolar recruitment by multiple pressure-volume curves, intracranial pressure, cerebral perfusion pressure, mean arterial pressure, and mean flow velocity in the middle cerebral artery by transcranial Doppler were recorded. Dead space was measured and partitioned by volumetric capnography., Results: Eighteen brain-injured patients were studied: 7 (39%) had mild and 11 (61%) had moderate ARDS. At inclusion, median [interquartile range] PaO 2 /FiO 2 was 173 [146-213] and median PEEP was 8 cmH 2 O [5-9]. HH allowed to reduce V T by 120 ml [95% CI: 98-144], V T /kg predicted body weight by 1.8 ml/kg [95% CI: 1.5-2.1], plateau pressure and driving pressure by 3.7 cmH 2 O [2.9-4.3], without affecting PaCO 2 , alveolar recruitment, and oxygenation. This was permitted by lower airway (- 84 ml [95% CI: - 79 to - 89]) and total dead space (- 86 ml [95% CI: - 73 to - 98]). Sixteen patients (89%) showed driving pressure equal or lower than 14 cmH 2 O while on HH, as compared to 7 (39%) and 8 (44%) during HME1 and HME2 (p < 0.001). No changes in mean arterial pressure, cerebral perfusion pressure, intracranial pressure, and middle cerebral artery mean flow velocity were documented during HH., Conclusion: The dead space reduction provided by HH allows to safely reduce V T without modifying PaCO 2 nor cerebral perfusion. This permits to provide a wider proportion of brain-injured ARDS patients with less injurious ventilation.

The rising frequency of multidrug-resistant and extensively drug-resistant (MDR/XDR) pathogens is making more frequent the inappropriate empirical antimicrobial therapy (IEAT) in nosocomial pneumonia, which is associated with increased mortality. We aim to determine the short-term benefits of appropriate empirical antimicrobial treatment (AEAT) with ceftolozane/tazobactam (C/T) compared with IEAT with piperacillin/tazobactam (TZP) in MDR Pseudomonas aeruginosa pneumonia. Twenty-one pigs with pneumonia caused by an XDR P. aeruginosa strain (susceptible to C/T but resistant to TZP) were ventilated for up to 72 h. Twenty-four hours after bacterial challenge, animals were randomized to receive 2-day treatment with either intravenous saline (untreated) or 25 to 50 mg of C/T per kg body weight (AEAT) or 200 to 225 mg of TZP per kg (IEAT) every 8 h. The primary outcome was the P. aeruginosa burden in lung tissue and the histopathology injury. P. aeruginosa burden in tracheal secretions and bronchoalveolar lavage (BAL) fluid, the development of antibiotic resistance, and inflammatory markers were secondary outcomes. Overall, P. aeruginosa lung burden was 5.30 (range, 4.00 to 6.30), 4.04 (3.64 to 4.51), and 4.04 (3.05 to 4.88) log 10 CFU/g in the untreated, AEAT, and IEAT groups, respectively ( P  = 0.299), without histopathological differences ( P  = 0.556). In contrast, in tracheal secretions ( P  < 0.001) and BAL fluid ( P  = 0.002), bactericidal efficacy was higher in the AEAT group. An increased MIC to TZP was found in 3 animals, while resistance to C/T did not develop. Interleukin-1β (IL-1β) was significantly downregulated by AEAT in comparison to other groups ( P  = 0.031). In a mechanically ventilated swine model of XDR P. aeruginosa pneumonia, appropriate initial treatment with C/T decreased respiratory secretions' bacterial burden, prevented development of resistance, achieved the pharmacodynamic target, and may have reduced systemic inflammation. However, after only 2 days of treatment, P. aeruginosa tissue concentrations were moderately affected., (Copyright © 2021 American Society for Microbiology.)

Background: Anemia of inflammation (AI) is common in critically ill patients. Although this syndrome negatively impacts the outcome of critical illness, understanding of its pathophysiology is limited. Also, new therapies that increase iron availability for erythropoiesis during AI are upcoming. A model of AI induced by bacterial infections that are relevant for the critically ill is currently not available. This paper describes the development of an animal model for AI that is relevant for critical care research., Results: In experiments with rats, the rats were inoculated either repeatedly or with a slow release of Streptococcus pneumoniae or Pseudomonas aeruginosa. Rats became ill, but their hemoglobin levels remained stable. The use of a higher dose of bacteria resulted in a lethal model. Then, we turned to a model with longer disease duration, using pigs that were supported by mechanical ventilation after inoculation with P. aeruginosa. The pigs became septic 12 to 24 h after inoculation, with a statistically significant decrease in mean arterial pressure and base excess, while heart rate tended to increase. Pigs needed resuscitation and vasopressor therapy to maintain a mean arterial pressure > 60 mmHg. After 72 h, the pigs developed anemia (baseline 9.9 g/dl vs. 72 h, 7.6 g/dl, p = 0.01), characterized by statistically significant decreased iron levels, decreased transferrin saturation, and increased ferritin. Hepcidin levels tended to increase and transferrin levels tended to decrease., Conclusions: Using pathogens commonly involved in pulmonary sepsis, AI could not be induced in rats. Conversely, in pigs, P. aeruginosa induced pulmonary sepsis with concomitant AI. This AI model can be applied to study the pathophysiology of AI in the critically ill and to investigate the effectivity and toxicity of new therapies that aim to increase iron availability.

Purpose: Optimizing pressure support ventilation (PSV) can improve patient-ventilator interaction. We conducted a two-center, randomized cross-over study to determine whether automated PSV lowers asynchrony rate during difficult weaning from mechanical ventilation., Methods: Thirty patients failing the first weaning attempt were randomly ventilated for 2 three-hour consecutive periods with: 1)PSV managed by physicians (convPSV); 2)PSV managed by Smartcare® (autoPSV). These 2 periods were applied in the afternoon and overnight, for a 12-h total study time. Two independent clinicians offline analyzed ventilator waveforms to compute asynchrony index(AI)., Results: AI was lower during autoPSV than during convPSV (medians[interquartile ranges] 5.1[2.6-9.5]% vs. 7.3[2.3-13.4]%, p = 0.02), without changes in the proportion of patients with AI>10%(p = 0.31). Pressure support (PS) variability was higher during autoPSV (p < 0.001), but average PS did not vary. In patients with baseline PS > 12 cmH 2 O (n = 15), PS and tidal volume were lower with autoPSV (12 [10-15]cmH 2 O vs. 15 [14-18]cmH 2 O,p = 0.003; 7.2[6.2-8.3]ml/Kg vs. 8.2[7.1-9.1]ml/Kg, p = 0.02) and AI reduction was driven by lower tidal volume (p = 0.03). In patients with baseline PS ≤ 12 cmH 2 O, AI reduction during autoPSV was mediated by increased PS variability (p = 0.04)., Conclusion: During difficult weaning, autoPSV improves patient-ventilator interaction by lowering tidal volume and enhancing PS variability. In expert centres, however, the size effect of the intervention appears clinically small, likely because physicians themselves adequately limit PS and tidal volume., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Rationale: Oxygen is commonly administered after extubation. Although several devices are available, data about their clinical efficacy are scarce., Objectives: To compare the effects of the Venturi mask and the nasal high-flow (NHF) therapy on PaO2/FiO2SET ratio after extubation. Secondary endpoints were to assess effects on patient discomfort, adverse events, and clinical outcomes., Methods: Randomized, controlled, open-label trial on 105 patients with a PaO2/FiO2 ratio less than or equal to 300 immediately before extubation. The Venturi mask (n = 52) or NHF (n = 53) were applied for 48 hours postextubation., Measurements and Main Results: PaO2/FiO2SET, patient discomfort caused by the interface and by symptoms of airways dryness (on a 10-point numerical rating scale), interface displacements, oxygen desaturations, need for ventilator support, and reintubation were assessed up to 48 hours after extubation. From the 24th hour, PaO2/FiO2SET was higher with the NHF (287 ± 74 vs. 247 ± 81 at 24 h; P = 0.03). Discomfort related both to the interface and to airways dryness was better with NHF (respectively, 2.6 ± 2.2 vs. 5.1 ± 3.3 at 24 h, P = 0.006; 2.2 ± 1.8 vs. 3.7 ± 2.4 at 24 h, P = 0.002). Fewer patients had interface displacements (32% vs. 56%; P = 0.01), oxygen desaturations (40% vs. 75%; P < 0.001), required reintubation (4% vs. 21%; P = 0.01), or any form of ventilator support (7% vs. 35%; P < 0.001) in the NHF group., Conclusions: Compared with the Venturi mask, NHF results in better oxygenation for the same set FiO2 after extubation. Use of NHF is associated with better comfort, fewer desaturations and interface displacements, and a lower reintubation rate. Clinical trial registered with www.clinicaltrials.gov (NCT 01575353).