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Aim There are few assessments of sedatives during the acute phase under sedation protocols for patients with sepsis. We aimed to compare the influence of different sedation strategies using midazolam and propofol under light sedation on clinical outcomes of ventilated patients with sepsis. Methods This study was a post‐hoc analysis of data from the dexmedetomidine for sepsis in the ICU Randomized Evaluation (DESIRE) trial. Patients were divided into propofol and midazolam groups based on continuously used drug, and sedation control between groups compared on day three. We assessed the incidence of delirium, length of ICU stay, number of ventilator‐free days within the first 28 days, and mortality after 28 days. Results The midazolam and propofol groups consisted of 51 and 66 patients, respectively. Both groups had similar characteristics, except for age and emergency surgery. The number of well‐controlled sedation patients in the propofol group on day three was significantly higher than that in the midazolam group (odds ratio [OR] 3.9, 95% CI [1.30, 11.7]). The incidence of daily coma and delirium within the initial week was different between groups and increased with midazolam administration (P = 0.0138). The number of Confusion Assessment Method for ICU‐positive patients was significantly higher in the midazolam group than in the propofol group (OR 5.71, 95% CI [2.30, 14.2]). Conclusion In patients with sepsis required mechanical ventilation, sedation with midazolam based on a light sedation protocol may be associated with inappropriate sedation during the acute phase, with increased coma and delirium as compared to propofol.

Abstract Background Dexmedetomidine has been reported to improve organ dysfunction in critically ill patients. In a recent randomized controlled trial (Dexmedetomidine for Sepsis in Intensive Care Unit (ICU) Randomized Evolution [DESIRE]), we demonstrated that dexmedetomidine was associated with reduced mortality risk among patients with severe sepsis. We performed this exploratory sub-analysis to examine the mechanism underlying improved survival in patients sedated with dexmedetomidine. Methods The DESIRE trial compared a sedation strategy with and without dexmedetomidine among 201 mechanically ventilated adult patients with sepsis across eight ICUs in Japan. In the present study, we included 104 patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of ≥ 23 (54 in the dexmedetomidine [DEX] group and 50 in the non-dexmedetomidine [non-DEX] group). Initially, we compared the changes in the sequential organ failure assessment (SOFA) scores from the baseline within 6 days after randomization between groups. Subsequently, we evaluated the variables comprising the organ component of the SOFA score that showed relevant improvement in the initial comparison. Results The mean patient age was 71.0 ± 14.1 years. There was no difference in the median APACHE II score between the two groups (29 [interquartile range (IQR), 25–31] vs. 30 [IQR, 25–33]; p = 0.35). The median SOFA score at the baseline was lower in the DEX group (9 [IQR, 7–11] vs. 11 [IQR, 9–13]; p = 0.01). While the renal SOFA subscore at the baseline was similar for both groups, it significantly decreased in the DEX group on day 4 (p = 0.02). During the first 6 days, the urinary output was not significantly different (p = 0.09), but serum creatinine levels were significantly lower (p = 0.04) in the DEX group. The 28-day and in-hospital mortality rates were significantly lower in the DEX group (22% vs. 42%; p = 0.03, 28% vs. 52%; p = 0.01, respectively). Conclusion A sedation strategy with dexmedetomidine is associated with improved renal function and decrease mortality rates among patients with severe sepsis. Trial registration This trial was registered on ClinicalTrials.gov (NCT01760967) on January 1, 2013.

Background: Dexmedetomidine has been reported to improve organ dysfunction in critically ill patients. In a recent randomized controlled trial (Dexmedetomidine for Sepsis in Intensive Care Unit (ICU) Randomized Evolution [DESIRE]), we demonstrated that dexmedetomidine was associated with reduced mortality risk among patients with severe sepsis. We performed this exploratory sub-analysis to examine the mechanism underlying improved survival in patients sedated with dexmedetomidine. Methods: The DESIRE trial compared a sedation strategy with and without dexmedetomidine among 201 mechanically ventilated adult patients with sepsis across eight ICUs in Japan. In the present study, we included 104 patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of ≥ 23 (54 in the dexmedetomidine [DEX] group and 50 in the non-dexmedetomidine [non-DEX] group). Initially, we compared the changes in the sequential organ failure assessment (SOFA) scores from the baseline within 6 days after randomization between groups. Subsequently, we evaluated the variables comprising the organ component of the SOFA score that showed relevant improvement in the initial comparison. Results: The mean patient age was 71.0 ± 14.1 years. There was no difference in the median APACHE II score between the two groups (29 [interquartile range (IQR), 25–31] vs. 30 [IQR, 25–33]; p = 0.35). The median SOFA score at the baseline was lower in the DEX group (9 [IQR, 7–11] vs. 11 [IQR, 9–13]; p = 0.01). While the renal SOFA subscore at the baseline was similar for both groups, it significantly decreased in the DEX group on day 4 (p = 0.02). During the first 6 days, the urinary output was not significantly different (p = 0.09), but serum creatinine levels were significantly lower (p = 0.04) in the DEX group. The 28-day and in-hospital mortality rates were significantly lower in the DEX group (22% vs. 42%; p = 0.03, 28% vs. 52%; p = 0.01, respectively). Conclusion: A sedation strategy with dexmedetomidine is associated with improved renal function and decrease mortality rates among patients with severe sepsis. Trial registration: This trial was registered on ClinicalTrials.gov (NCT01760967) on January 1, 2013. [ABSTRACT FROM AUTHOR]

Importance: Dexmedetomidine provides sedation for patients undergoing ventilation; however, its effects on mortality and ventilator-free days have not been well studied among patients with sepsis.Objectives: To examine whether a sedation strategy with dexmedetomidine can improve clinical outcomes in patients with sepsis undergoing ventilation.Design, Setting, and Participants: Open-label, multicenter randomized clinical trial conducted at 8 intensive care units in Japan from February 2013 until January 2016 among 201 consecutive adult patients with sepsis requiring mechanical ventilation for at least 24 hours.Interventions: Patients were randomized to receive either sedation with dexmedetomidine (n = 100) or sedation without dexmedetomidine (control group; n = 101). Other agents used in both groups were fentanyl, propofol, and midazolam.Main Outcomes and Measures: The co-primary outcomes were mortality and ventilator-free days (over a 28-day duration). Sequential Organ Failure Assessment score (days 1, 2, 4, 6, 8), sedation control, occurrence of delirium and coma, intensive care unit stay duration, renal function, inflammation, and nutrition state were assessed as secondary outcomes.Results: Of the 203 screened patients, 201 were randomized. The mean age was 69 years (SD, 14 years); 63% were male. Mortality at 28 days was not significantly different in the dexmedetomidine group vs the control group (19 patients [22.8%] vs 28 patients [30.8%]; hazard ratio, 0.69; 95% CI, 0.38-1.22; P = .20). Ventilator-free days over 28 days were not significantly different between groups (dexmedetomidine group: median, 20 [interquartile range, 5-24] days; control group: median, 18 [interquartile range, 0.5-23] days; P = .20). The dexmedetomidine group had a significantly higher rate of well-controlled sedation during mechanical ventilation (range, 17%-58% vs 20%-39%; P = .01); other outcomes were not significantly different between groups. Adverse events occurred in 8 (8%) and 3 (3%) patients in the dexmedetomidine and control groups, respectively.Conclusions and Relevance: Among patients requiring mechanical ventilation, the use of dexmedetomidine compared with no dexmedetomidine did not result in statistically significant improvement in mortality or ventilator-free days. However, the study may have been underpowered for mortality, and additional research may be needed to evaluate this further.Trial Registration: clinicaltrials.gov Identifier: NCT01760967. [ABSTRACT FROM AUTHOR]