COVID-19 does not influence functional status after ARDS therapy.

RATIONALE: Health-related quality of life after surviving acute respiratory distress syndrome has come into focus in recent years, especially during the coronavirus disease 2019 pandemic. OBJECTIVES: A total of 144 patients with acute respiratory distress syndrome caused by COVID-19 or of other origin were recruited in a randomized multicenter trial. METHODS: Clinical data during intensive care treatment and data up to 180 days after study inclusion were collected. Changes in the Sequential Organ Failure Assessment score were used to quantify disease severity. Disability was assessed using the Barthel index on days 1, 28, 90, and 180. MEASUREMENTS: Mortality rate and morbidity after 180 days were compared between patients with and without COVID-19. Independent risk factors associated with high disability were identified using a binary logistic regression. MAIN RESULTS: The SOFA score at day 5 was an independent risk factor for high disability in both groups, and score dynamic within the first 5 days significantly impacted disability in the non-COVID group. Mortality after 180 days and impairment measured by the Barthel index did not differ between patients with and without COVID-19. CONCLUSIONS: Resolution of organ dysfunction within the first 5 days significantly impacts long-term morbidity. Acute respiratory distress syndrome caused by COVID-19 was not associated with increased mortality or morbidity.

Needle-free connectors catheter-related bloodstream infections: a prospective randomized controlled trial.

BACKGROUND: In the critically ill, catheter-related bloodstream infection can result from bacterial contamination of infusion hubs of intravascular catheters. Needle-free connectors (NFC) have been suggested to reduce the rate of bacterial contamination and subsequent catheter-related bloodstream infection (CRBSI), but data remains ambiguous. Thus, we tested if a novel NFC would reduce bacterial contamination and subsequent CRBSI. RESULTS: In a prospective, randomized controlled trial, surgical ICU patients were randomized to three-way hubs closed by caps or Bionecteur® (Vygon, Inc.) of central venous catheters. Every 72 h, infusion lines were renewed and microbiological samples were taken. Bacterial growth was analyzed by blinded microbiologists. Incidence of bacterial contamination and CRSBI were assessed. Outcome parameters like length of stay on ICU and outcome were retrospectively assessed. Two thousand seven hundred patients were screened, 111 were randomized to the NFC, and 109 into the control group. Finally, 24 patients in the NFC and 23 control patients were analyzed. The majority of samples (NFC 77%; control 70%) found no bacterial growth. Coagulase-negative staphylococci were most commonly detected on CVC samples (NFC 17%; control 21%). We found CRBSI (defined as identical pathogens in blood culture and catheter line tip culture, and clinical manifestations of infection) in two control patients and one patient of the NFC group. Their length of ICU stay did not differ between groups (NFC 19 days; control 23 days). CONCLUSION: The use of NFC does not influence the rate of bacterial contamination of infusion hubs of central venous catheters. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02134769. Registered 09 May 2014.

Population pharmacokinetics and pharmacodynamic evaluation of intravenous and enteral moxifloxacin in surgical intensive care unit patients.

OBJECTIVES: To describe the plasma concentration-time profile of moxifloxacin after intravenous and enteral administration in intensive care unit (ICU) patients and to provide a pharmacodynamic (PD) evaluation with regard to pneumonia. PATIENTS AND METHODS: Twenty-five adult patients from a cardiothoracic/mixed surgical ICU were enrolled. Moxifloxacin was given as a standard dose (400 mg once daily). Therapy was successfully switched to enteral administration on day 5 in 16 patients. A rich data sampling schedule was performed after intravenous (day 4) and enteral (day 8) administration. Moxifloxacin concentrations were analysed by HPLC. A population pharmacokinetic (PK) model was developed using NONMEM VII. Simulated concentration-time profiles were evaluated for their probability of attaining PK/PD target values relevant for community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). RESULTS: A linear-elimination two-compartment model described the data adequately. Parameter estimates (coefficient of variation of inter-individual variability) were: absorption rate constant, 1.09/h (135%); enteral bioavailability, 76% (20.0%); central volume of distribution, 55.6 L; peripheral volume of distribution, 59.6 L (15.3%); inter-compartmental clearance, 47.7 L/h; and clearance, 11.3 L/h (23.7%). Both intravenously and enterally administered standard-dose moxifloxacin reliably attained the PK/PD target values for pathogens with MICs ≤ 0.25 mg/L for CAP and ≤ 0.125 mg/L for HAP. CONCLUSIONS: Drug exposure to moxifloxacin in ICU patients was more variable than in healthy volunteers. The standard dosing provides sufficient drug exposure for treatment of CAP but for HAP it does so only when a highly susceptible pathogen is present. Intravenous/enteral sequential therapy may be considered for cautiously selected cases in ICU patients.