Argon Attenuates Multiorgan Failure in Relation with HMGB1 Inhibition.

Argon inhalation attenuates multiorgan failure (MOF) after experimental ischemic injury. We hypothesized that this protection could involve decreased High Mobility Group Box 1 (HMGB1) systemic release. We investigated this issue in an animal model of MOF induced by aortic cross-clamping. Anesthetized rabbits were submitted to supra-coeliac aortic cross-clamping for 30 min, followed by 300 min of reperfusion. They were randomly divided into three groups (n = 7/group). The Control group inhaled nitrogen (70%) and oxygen (30%). The Argon group was exposed to a mixture of argon (70%) and oxygen (30%). The last group inhaled nitrogen/oxygen (70/30%) with an administration of the HMGB1 inhibitor glycyrrhizin (4 mg/kg i.v.) 5 min before aortic unclamping. At the end of follow-up, cardiac output was significantly higher in Argon and Glycyrrhizin vs. Control (60 ± 4 and 49 ± 4 vs. 33 ± 8 mL/kg/min, respectively). Metabolic acidosis was attenuated in Argon and Glycyrrhizin vs. Control, along with reduced amount of norepinephrine to reverse arterial hypotension. This was associated with reduced interleukin-6 and HMGB1 plasma concentration in Argon and Glycyrrhizin vs. Control. End-organ damages were also attenuated in the liver and kidney in Argon and Glycyrrhizin vs. Control, respectively. Argon inhalation reduced HMGB1 blood level after experimental aortic cross-clamping and provided similar benefits to direct HMGB1 inhibition.

Population Pharmacokinetics of Amikacin in Patients on Veno-Arterial Extracorporeal Membrane Oxygenation.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) support leads to complex pharmacokinetic alterations, whereas adequate drug dosing is paramount for efficacy and absence of toxicity in critically ill patients. Amikacin is a major antibiotic used in nosocomial sepsis, especially for these patients. We aimed to describe amikacin pharmacokinetics on V-A ECMO support and to determine relevant variables to improve its dosing. All critically ill patients requiring empirical antimicrobial therapy, including amikacin for nosocomial sepsis supported or not by V-A ECMO, were included in a prospective population pharmacokinetic study. This population pharmacokinetic analysis was built with a dedicated software, and Monte Carlo simulations were performed to identify doses achieving therapeutic plasma concentrations. Thirty-nine patients were included (control n = 15, V-A ECMO n = 24); 215 plasma assays were performed and used for the modeling process. Patients received 29 (24-33) and 32 (30-35) mg/kg of amikacin in control and ECMO groups, respectively. Data were best described by a two-compartment model with first-order elimination. Inter-individual variabilities were observed on clearance, central compartment volume (V1), and peripherical compartment volume (V2). Three significant covariates explained these variabilities: Kidney Disease Improving Global Outcomes (KDIGO) stage on amikacin clearance, total body weight on V1, and ECMO support on V2. Our simulations showed that the adequate dosage of amikacin was 40 mg/kg in KDIGO stage 0 patients, while 25 mg/kg in KDIGO stage 3 patients was relevant. V-A ECMO support had only a secondary impact on amikacin pharmacokinetics, as compared to acute kidney injury.

Effect of Noninvasive Ventilation After Unplanned Extubation.

BACKGROUND: Our study set out to test the effect of noninvasive ventilation (NIV) performed after unplanned extubation. METHODS: Retrospective analysis of prospectively collected data in a university-affiliated mixed ICU of 12 beds during a 5-y period (January 2013 to December 2017). Unplanned extubation was defined as the occurrence of an unplanned removal of the endotracheal tube, whether deliberate or accidental. NIV after an unplanned extubation was not protocolized and was decided by the physician in charge on an individual basis. RESULTS: A total of 121 subjects (median [25th-75th percentile] age, 62.1 [43.3-73.6] y; median [25th-75th percentile] Simplified Acute Physiology Score II, 45 [36-54]) experienced 131 unplanned extubation episodes. Re-intubation was deemed necessary in 35 subjects (28.9%). NIV was used in 24 subjects (19.8%) (prophylactic NIV, n = 10; rescue NIV, n = 14). The re-intubation rates were 25.8%, 10%, and 64.3% in the no NIV, prophylactic, and rescue NIV subgroups, respectively. The median (25th-75th percentile) time to re-intubation was longer for subjects on NIV (9.1 [3.5-49.2] vs 0.46 [0.25-1] h, P = .001). The median (25th-75th percentile) ICU length of stay and duration of mechanical ventilation were longer in the subjects who underwent NIV (14.5 [7-24.5] vs 6 [3-14] d, respectively, P = .004; and 9 [3-22] vs 3 [1-7.3] d, respectively, P = .003). CONCLUSIONS: NIV after unplanned extubation had uncertain efficacy, especially when provided as rescue management of postextubation respiratory failure.