RESUMEN
OBJECTIVES: To explore the relationship between real-time therapeutic drug monitoring (TDM)-guided pharmacodynamic target attainment of continuous infusion (CI) beta-lactam monotherapy and microbiological outcome in the treatment of critically ill children with severe documented Gram-negative infections. METHODS: Observational, monocentric, retrospective study of critically ill patients receiving CI piperacillin-tazobactam, ceftazidime, or meropenem in monotherapy for documented Gram-negative infections optimized by means of a real-time TDM-guided strategy. Average steady-state beta-lactam concentrations (C ss ) were calculated for each patient, and the beta-lactam C ss /minimum inhibitory concentration (MIC) ratio was selected as a pharmacodynamic parameter of efficacy. The C ss /MIC ratio was defined as optimal if ≥4, quasi-optimal if between 1 and 4, and suboptimal if <1. The relationship between C ss /MIC and microbiological outcome was assessed. RESULTS: Forty-six TDM assessments were carried out in 21 patients [median age 2 (interquartile range: 1-8) years]. C ss /MIC ratios were optimal in 76.2% of cases. Patients with optimal C ss /MIC ratios had both a significantly higher microbiological eradication rate (75.0% vs. 0.0%; P = 0.006) and lower resistance development rate (25.0% vs. 80.0%; P = 0.047) than those with quasi-optimal or suboptimal C ss /MIC ratios. Quasi-optimal/suboptimal C ss /MIC ratio occurred more frequently when patients had infections caused by pathogens with MIC values above the European Committee on Antimicrobial Susceptibility Testing clinical breakpoint (100.0% vs. 6.3%; P < 0.001). CONCLUSIONS: Real-time TDM-guided pharmacodynamic target attainment of CI beta-lactam monotherapy allowed to maximize treatment efficacy in most critically ill children with severe Gram-negative infections. Attaining early optimal C ss /MIC ratios of CI beta-lactams could be a key determinant associated with microbiologic eradication during the treatment of Gram-negative infections. Larger prospective studies are warranted for confirming our findings.
RESUMEN
BACKGROUND: Positive end-expiratory pressure (PEEP) is a key element of mechanical ventilation. It should optimize recruitment, without causing excessive overdistension, but controversy exists on the best method to set it. The purpose of the study was to test the feasibility of setting PEEP with electrical impedance tomography in order to prevent lung de-recruitment following a recruitment maneuver. We enrolled 16 patients undergoing mechanical ventilation with PaO2/FiO2 <300 mmHg. In all patients, under constant tidal volume (6-8 ml/kg) PEEP was set based on the PEEP/FiO2 table proposed by the ARDS network (PEEPARDSnet). We performed a recruitment maneuver and monitored the end-expiratory lung impedance (EELI) over 10 min. If the EELI signal decreased during this period, the recruitment maneuver was repeated and PEEP increased by 2 cmH2O. This procedure was repeated until the EELI maintained a stability over time (PEEPEIT). RESULTS: The procedure was feasible in 87% patients. PEEPEIT was higher than PEEPARDSnet (13 ± 3 vs. 9 ± 2 cmH2O, p < 0.001). PaO2/FiO2 improved during PEEPEIT and driving pressure decreased. Recruited volume correlated with the decrease in driving pressure but not with oxygenation improvement. Finally, regional alveolar hyperdistention and collapse was reduced in dependent lung layers and increased in non-dependent lung layers. CONCLUSIONS: In hypoxemic patients, a PEEP selection strategy aimed at stabilizing alveolar recruitment guided by EIT at the bedside was feasible and safe. This strategy led, in comparison with the ARDSnet table, to higher PEEP, improved oxygenation and reduced driving pressure, allowing to estimate the relative weight of overdistension and recruitment.
