Purpose: To compare dexmedetomidine (DEX) with standard care (SC, either propofol or midazolam) for long-term sedation in terms of maintaining target sedation and length of intensive care unit (ICU) stay. Methods: A pilot, phase III, double-blind multicenter study in randomized medical and surgical patients (n = 85) within the first 72 h of ICU stay with an expected ICU stay of C48 h and sedation need for C24 h after randomization. Patients were assigned to either DEX (B1.4 lg kg -1 h -1; n = 41) or SC (n = 44), with daily sedation stops.Results: Non-inferiority of DEX versus SC was not confirmed. Target Richmond agitation-sedation score (RASS) was reached a median of 64% (DEX) and 63% (SC) of the sedation time (ns). The length of ICU stay was similar in DEX and SC. Patients with RASS target 0-3 (DEX 78%, SC 80%) were at target sedation 74% (DEX) and 64% (SC) of the time (ns), whereas those with RASS target -4 or less reached the target 42% (DEX) and 62% (SC) of the time (P = .006). Post hoc analyses suggested shorter duration of mechanical ventilation for DEX (P = 0.025). Conclusions: This pilot study suggests that in long-term sedation, DEX is comparable to SC in maintaining sedation targets of RASS 0 to -3 but not suitable for deep sedation (RASS -4 or less). DEX had no effect on length of ICU stay. Its effects on other relevant clinical outcomes, such as duration of mechanical ventilation, should be tested further.

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.

The outcome of ARDS is unpredictable at the time of onset and also at the time of the worst oxygenation. Keeping the inspiratory pressures low (30-35 cm H2O [2.94 to 3.43 kPa]) reduces the frequency of pneumothorax, and might lower the mortality. Most patients are young, and therefore the costs per saved year of life are low.

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PEEP by itself does not have a consistent effect on splanchnic blood flow and metabolism when cardiac index is stable and patients are ventilated within the linear part of the pv curve.