Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia.

BACKGROUND: Whether preventive inhaled antibiotics may reduce the incidence of ventilator-associated pneumonia is unclear. METHODS: In this investigator-initiated, multicenter, double-blind, randomized, controlled, superiority trial, we assigned critically ill adults who had been undergoing invasive mechanical ventilation for at least 72 hours to receive inhaled amikacin at a dose of 20 mg per kilogram of ideal body weight once daily or to receive placebo for 3 days. The primary outcome was a first episode of ventilator-associated pneumonia during 28 days of follow-up. Safety was assessed. RESULTS: A total of 850 patients underwent randomization, and 847 were included in the analyses (417 assigned to the amikacin group and 430 to the placebo group). All three daily nebulizations were received by 337 patients (81%) in the amikacin group and 355 patients (83%) in the placebo group. At 28 days, ventilator-associated pneumonia had developed in 62 patients (15%) in the amikacin group and in 95 patients (22%) in the placebo group (difference in restricted mean survival time to ventilator-associated pneumonia, 1.5 days; 95% confidence interval [CI], 0.6 to 2.5; P = 0.004). An infection-related ventilator-associated complication occurred in 74 patients (18%) in the amikacin group and in 111 patients (26%) in the placebo group (hazard ratio, 0.66; 95% CI, 0.50 to 0.89). Trial-related serious adverse effects were seen in 7 patients (1.7%) in the amikacin group and in 4 patients (0.9%) in the placebo group. CONCLUSIONS: Among patients who had undergone mechanical ventilation for at least 3 days, a subsequent 3-day course of inhaled amikacin reduced the burden of ventilator-associated pneumonia during 28 days of follow-up. (Funded by the French Ministry of Health; AMIKINHAL ClinicalTrials.gov number, NCT03149640; EUDRA Clinical Trials number, 2016-001054-17.).

Does Chloride Intake at the Early Phase of Septic Shock Resuscitation Impact on Renal Outcome?

INTRODUCTION: Fluid administration is one of the first lines of treatment for hemodynamic management of sepsis and septic shock. Studies investigating the effects of chloride-rich fluids including normal saline on renal function report controversial findings. METHODS: This is a prospective, observational, multicenter study. Patients with septic shock, defined according to Sepsis-2 definition, were eligible. A "high-dose" of chloride was defined as a chloride intake greater than 18 g administrated within the first 48 h of septic shock management. The purpose of this study was to investigate the impact of cumulative chloride infusion within the first 48 h of septic shock resuscitation on acute kidney injury (AKI). RESULTS: Two hundred thirty-nine patients with septic shock were included. Patients who received a "high-dose" of chloride had significantly higher Sequential Organ Failure Assessment score at the time of enrolment (P < 0.001). Cumulative chloride load was higher in patients requiring renal replacement therapy (RRT) (31.1 vs. 25.2 g/48 h; P < 0.005). Propensity score-weighted regression did not find any association between "high-dose" of chloride and AKI requiring RRT (OR: 0.97 [0.88-1.1]; P = 0.69). There was no association between "high-dose" of chloride and worsening kidney function at H48 (OR: 0.94 [0.83-1.1]; P = 0.42). There was also no association between "high-dose" of chloride and ICU length of stay (P = 0.61), 28-day mortality (P = 0.83), or hospital mortality (P = 0.89). CONCLUSION: At the early stage of resuscitation of critically ill patients with septic shock, administration of "high-dose" of chloride (> 18 g/48 h) was not associated with renal prognosis.

Prevalence and impact of frailty on mortality in elderly ICU patients: a prospective, multicenter, observational study.

PURPOSE: Frailty is a recent concept used for evaluating elderly individuals. Our study determined the prevalence of frailty in intensive care unit (ICU) patients and its impact on the rate of mortality. METHODS: A multicenter, prospective, observational study performed in four ICUs in France included 196 patients aged ≥65 years hospitalized for >24 h during a 6-month study period. Frailty was determined using the frailty phenotype (FP) and the clinical frailty score (CFS). The patients were separated as follows: FP score <3 or ≥3 and CFS <5 or ≥5. RESULTS: Frailty was observed in 41 and 23% of patients on the basis of an FP score ≥3 and a CFS ≥5, respectively. At admission to the ICU, the Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) scores did not differ between the frail and nonfrail patients. In the multivariate analysis, the risk factors for ICU mortality were FP score ≥3 [hazard ratio (HR), 3.3; 95% confidence interval (CI), 1.6-6.6; p < 0.001], male gender (HR, 2.4; 95% CI, 1.1-5.3; p = 0.026), cardiac arrest before admission (HR, 2.8; 95% CI, 1.1-7.4; p = 0.036), SAPS II score ≥46 (HR, 2.6; 95% CI, 1.2-5.3; p = 0.011), and brain injury before admission (HR, 3.5; 95% CI, 1.6-7.7; p = 0.002). The risk factors for 6-month mortality were a CFS ≥5 (HR, 2.4; 95% CI, 1.49-3.87; p < 0.001) and a SOFA score ≥7 (HR, 2.2; 95% CI, 1.35-3.64; p = 0.002). An increased CFS was associated with significant incremental hospital and 6-month mortalities. CONCLUSIONS: Frailty is a frequent occurrence and is independently associated with increased ICU and 6-month mortalities. Notably, the CFS predicts outcomes more effectively than the commonly used ICU illness scores.