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Comment on Organ allocation waiting time during extracorporeal bridge to lung transplant affects outcomes. [Chest. 2013] Prolonged extracorporeal membrane oxygenation use as a bridge to lung transplantation: it is time for a national registry. [Chest. 2014

Steady-state pharmacokinetics and BAL concentration of colistin in critically III patients after IV colistin methanesulphonate administration

Background: Infections caused by multidrug-resistant gram-negative bacteria have caused a resurgence of interest in colistin. To date, information about pharmacokinetics of colistin is very limited in critically ill patients, and no attempts have been made to evaluate its concentration in BAL. Methods: In this prospective, open-label study, 13 adult patients with ventilator-associated pneumonia caused by gram-negative bacteria were treated with colistin methanesulfonate (CMS) IV, 2 million International Units (174 mg) q8h, a usually recommended dose, for at least 2 days. Blood samples were collected from each patient at time intervals after the end of infusion. BAL was performed at 2 h. Colistin was measured by a selective, sensitive high-performance liquid chromatography-based method. Pharmacokinetic parameters were determined by noncompartmental analysis. Results: Patients received 2.19 6 0.38 mg/kg (range, 1.58-3.16) of CMS per dose. At steady state, mean 6 SD plasma colistin maximum (Cmax) and trough (Ctrough) concentrations were 2.21 6 1.08 and 1.03 6 0.69 m g/mL, respectively. Mean 6 SD area under the plasma concentration-time curve from 0 to 8 h (AUC 0-8 ), apparent elimination half-life, and apparent volume of distribution were 11.5 6 6.2 m g 3 h/mL, 5.9 6 2.6 h, and 1.5 6 1.1 L/kg, espectively. Cmax/minimum inhibitory concentration (MIC) ratio and AUC 0-24 /MIC ratio (MIC 5 2 m g/mL) were 1.1 6 0.5 and 17.3 6 9.3, respectively. Colistin was undetectable in BAL. Nephrotoxicity was not observed. Conclusions: Although the pharmacodynamic parameters that better predict the effi cacy of colistin are not known in humans, in critically ill adult patients the IV administration of CMS 2 million International Units (174 mg) q8h results in apparently suboptimal plasma concentrations of colistin, which is undetectable in BAL. A better understanding of the pharmacokinetic-pharmacodynamic relationship of colistin is urgently needed to determine the optimal dosing regime

The organ allocation waiting time during extracorporeal bridge to lung transplantation affects outcomes

ABSTRACT BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation (LTX) is still debated. METHODS: We performed a retrospective two-center analysis on the relationship between ECMO bridging duration and survival in twenty-five patients. Further survival analysis was obtained by dividing the patients according to waiting time on ECMO: up to 14 days (Early) or longer (Late). We also analyzed the impact of the ventilation strategy during ECMO bridging, i.e. spontaneous breathing and non-invasive ventilation (NIV) or intubation and invasive mechanical ventilation (IMV). RESULTS: 17 out of 25 patients were transplanted (with 76% 1-year survival) while 8 patients died on bridge. In the 17 transplanted patients, mortality was positively related to waiting days until LTX (HR 1.12 per day, 95%CI 1.02-1.23, p=0.02) and the group Early showed better Kaplan-Meier curves (p=0.02), higher 1-year survival rates (100% versus 50% p=0.03) and lower morbidity (days on IMV, length of stay in ICU and hospital). During bridge to transplantation, mortality steadily increased with time. Considering the overall outcome of the bridging program (25 patients), bridge duration adversely affected survival (HR 1.06 per day, 95%CI 1.01-1.11, p=0.015) and 1-year survival (Early group 82 % versus Late 29%, p=0.015). Morbidity indices were lower in patients treated with NIV during bridge. CONCLUSIONS: The duration of bridge on ECMO is a relevant co-factor for mortality and morbidity of critically ill patients awaiting organ allocation. The NIV strategy was associated with a less complicated clinical course after LTX