Background:The antibiotic meropenem is commonly administered in patients with severe sepsis and septic shock. We compared the pharmacokinetic, clinical, and bacteriological efficacies of continuous infusion of meropenem versus intermittent administration in such patients.Methods:Patients admitted to the Intensive Care Unit (ICU) with severe sepsis or septic shock who received meropenem were randomly assigned to either the continuous (n = 25) or intermittent groups (n = 25). The continuous group received a loading dose of 0.5 g of meropenem followed by a continuous infusion of 3 g/day; the intermittent group received an initial dose of 1.5 g followed by 1 g for every 8 h. Clinical success, microbiological eradication, superinfection, ICU mortality, length of ICU stay, and duration of meropenem treatment were assessed. Serial plasma meropenem concentrations for the first and third dosing periods (steady state) were also measured.Results:Clinical success was similar in both the continuous (64%) and intermittent (56%) groups (P = 0.564); the rates of microbiological eradication and superinfection (81.8% vs. 66.7% [P = 0.255] and 4% vs. 16% [P = 0.157], respectively) showed improvement in the continuous group. The duration of meropenem treatment was significantly shorter in the continuous group (7.6 vs. 9.4 days; P = 0.035), where a better steady-state concentration was also achieved. Peak and trough concentrations were significantly different between the continuous and intermittent groups both in the first (Cmax: 19.8 mg/L vs. 51.8 mg/L, P = 0.000; Cmin: 11.2 mg/L vs. 0.5 mg/L, P = 0.000) and third dosing periods (Cmax: 12.5 mg/L vs. 46.4 mg/L, P = 0.000; Cmin: 11.4 mg/L vs. 0.6 mg/L, P = 0.000). For medium-susceptibility pathogens, continuous infusion concentrations above the minimal inhibitory concentration were 100%, which was better than that in the intermittent group.Conclusions:Continuous infusion of meropenem provides significantly shorter treatment duration and a tendency for superior bacteriological efficacy than intermittent administration. Continuous infusion may be more optimal against intermediate-susceptibility pathogens.

ObjectiveTo investigate the influence of analgesic-based midazolam sedation on delirium and outcomes in critically ill patients and to analyze the risk factors of delirium.DesignSingle center, prospective randomized controlled trial.SettingA surgical intensive care unit (ICU) in a tertiary care hospital in China.PatientsMechanically ventilated patients requiring sedation.Measurements and main resultsPatients admitted to the surgical intensive care unit who required sedation and were undergoing mechanical ventilation for longer than 24 hours were randomly divided into three groups: 1) the remifentanil group received remifentanil and midazolam, 2) the fentanyl group received fentanyl and midazolam, and 3) the control group received only midazolam. The analgesic effect, sedation depth, and presence of delirium were evaluated. To compare the effect of different therapies on the occurrence of delirium, days of mechanical ventilation, length of the ICU stay, and 28-day mortality were measured along with the risk factors for delirium. A total of 105 patients were enrolled, and 35 patients were included in each group. Compared to the control group, patients who received remifentanil and fentanyl required less midazolam each day (P = 0.038 and <0.001, respectively). Remifentanil has a significant effect on reducing the occurrence of delirium (P = 0.007). The logistic regression analysis of delirium demonstrated that remifentanil (OR 0.230, 95%Cl 0.074–0.711, P = 0.011) is independent protective factors for delirium, and high APACHE II score (OR 1.103, 95%Cl 1.007–1.208, P = 0.036) is the independent risk factor for delirium.ConclusionRemifentanil and fentanyl can reduce the amount of midazolam required, and remifentanil could further reduce the occurrence of delirium.

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OBJECTIVES: To determine the effectiveness and safety of ciprofol for sedating patients in ICUs who required mechanical ventilation (MV). DESIGN: A multicenter, single-blind, randomized, noninferiority trial. SETTING: Twenty-one centers across China from December 2020 to June 2021. PATIENTS: A total of 135 ICU patients 18 to 80 years old with endotracheal intubation and undergoing MV, who were expected to require sedation for 6–24 hours. INTERVENTIONS: One hundred thirty-five ICU patients were randomly allocated into ciprofol (n = 90) and propofol (n = 45) groups in a 2:1 ratio. Ciprofol or propofol were IV infused at loading doses of 0.1 mg/kg or 0.5 mg/kg, respectively, over 4 minutes ± 30 seconds depending on the physical condition of each patient. Ciprofol or propofol were then immediately administered at an initial maintenance dose of 0.3 mg/kg/hr or 1.5 mg/kg/hr, to achieve the target sedation range of Richmond Agitation-Sedation Scale (+1 to –2). Besides, continuous IV remifentanil analgesia was administered (loading dose: 0.5–1 μg/kg, maintenance dose: 0.02–0.15 μg/kg/min). MEASUREMENTS AND MAIN RESULTS: Of the 135 patients enrolled, 129 completed the study. The primary endpoint-sedation success rates of ciprofol and propofol groups were 97.7% versus 97.8% in the full analysis set (FAS) and were both 100% in per-protocol set (PPS). The noninferiority margin was set as 8% and confirmed with a lower limit of two-sided 95% CI for the inter-group difference of –5.98% and –4.32% in the FAS and PPS groups. Patients who received ciprofol had a longer recovery time (p = 0.003), but there were no differences in the remaining secondary endpoints (all p > 0.05). The occurrence rates of treatment-emergent adverse events (TEAEs) or drug-related TEAEs were not significantly different between the groups (all p > 0.05). CONCLUSIONS: Ciprofol was well tolerated, with a noninferior sedation profile to propofol in Chinese ICU patients undergoing MV for a period of 6–24 hours.