Background Little information is available about the geo-economic variations in demographics, management, and outcomes of patients with acute respiratory distress syndrome (ARDS). We aimed to characterise the effect of these geo-economic variations in patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE). Methods LUNG SAFE was done during 4 consecutive weeks in winter, 2014, in a convenience sample of 459 intensivecare units in 50 countries across six continents. Inclusion criteria were admission to a participating intensive-care unit (including transfers) within the enrolment window and receipt of invasive or non-invasive ventilation. One of the trial's secondary aims was to characterise variations in the demographics, management, and outcome of patients with ARDS. We used the 2016 World Bank countries classification to define three major geo-economic groupings, namely European high-income countries (Europe-High), high-income countries in the rest of the world (rWORLD-High), and middle-income countries (Middle). We compared patient outcomes across these three groupings. LUNG SAFE is registered with ClinicalTrials.gov, number NCT02010073. Findings Of the 2813 patients enrolled in LUNG SAFE who fulfilled ARDS criteria on day 1 or 2, 1521 (54%) were recruited from Europe-High, 746 (27%) from rWORLD-High, and 546 (19%) from Middle countries. We noted significant geographical variations in demographics, risk factors for ARDS, and comorbid diseases. The proportion of patients with severe ARDS or with ratios of the partial pressure of arterial oxygen (PaO 2) to the fractional concentration of oxygen in inspired air (F I O 2) less than 150 was significantly lower in rWORLD-High countries than in the two other regions. Use of prone positioning and neuromuscular blockade was significantly more common in Europe-High countries than in the other two regions. Adjusted duration of invasive mechanical ventilation and length of stay in the intensive-care unit were significantly shorter in patients in rWORLD-High countries than in Europe-High or Middle countries. High gross national income per person was associated with increased survival in ARDS; hospital survival was significantly lower in Middle countries than in Europe-High or rWORLD-High countries. Interpretation Important geo-economic differences exist in the severity, clinician recognition, and management of ARDS, and in patients' outcomes. Income per person and outcomes in ARDS are independently associated.

No abstract

ImportanceMeropenem is a widely prescribed β-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes.ObjectiveTo determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis.Design, Setting, and ParticipantsA double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022.InterventionsPatients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304).Main Outcomes and MeasuresThe primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events.ResultsAll 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients).Conclusions and RelevanceIn critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28.Trial RegistrationClinicalTrials.gov Identifier: NCT03452839

The detection of epidural space is usually performed by the technique of loss of resistance (LOR) without technological support, although there are few commercial options. We sought to design and develop a new noninvasive system able to detect the LOR without any changes to the conventional procedure. It allows detecting the LOR by a custom made algorithm. The system provides a visual and acoustic feedback when the LOR is detected. We optimized the detection algorithm and investigated the performance of the system during experiments on a custom simulator. During the experiments performed by 10 anesthetists and 10 trainees, the pressure exerted on the syringe plunger was monitored using the custom-made system. Each participant performed four experiments using the system on the simulator. The performance of the system in LOR detection was evaluated comparing the feedback activation and the breaches of the last layer of the simulator. Moreover, each participant filled out a questionnaire to assess how the procedure with the simulator mimics the clinical scenario. A higher questionnaire score corresponds to a more realistic condition (0 = not real, 5 = extremely real). Results showed that the LOR was detected in 74 of the 80 trials (92.5% of the cases); the anesthetists obtained better results than trainees: 97.5 versus 87.5%. The questionnaires showed that all the participants found the trial realistic (score ≥3); anesthetists found it more realistic than trainees (4.2 ± 0.78 vs. 3.8 ± 0.78, mean ± SD). In summary, the proposed system successfully detected the LOR in the large part of the trials. The participants found the trials realistic. A higher success rate was observed in the anesthetists group.

Colistin is a last resort antibiotic to treat multidrug-resistant Gram-negative bacteria infections. Colistin is administered intravenously in the form of its inactive prodrug colistin methanesulfonate (CMS). For patients with acute kidney impairment and continuous renal replacement therapy high extracorporeal clearance may cause a substantial removal of active colistin from the bloodstream, eventually decreasing its antibacterial efficacy. Currently recommended doses of CMS may therefore be inadequate for these patients. We report on the potential value of a modified regimen that adopts a loading dose of CMS (bolus of 9 MU vs. conventional 3 MU every 8 h), followed by maintenance (3 MU every 8 h). Preliminary pharmacokinetic evidence for the feasibility and efficacy of this regimen is described for 2 patients.