Intrapulmonary concentrations of meropenem administered by continuous infusion in critically ill patients with nosocomial pneumonia: a randomized pharmacokinetic trial.

BACKGROUND: Optimal antimicrobial drug exposure in the lung is required for successful treatment outcomes for nosocomial pneumonia. Little is known about the intrapulmonary pharmacokinetics (PK) of meropenem when administered by continuous infusion (CI). The aim of this study was to evaluate the PK of two dosages of meropenem (3 g vs 6 g/day by CI) in the plasma and epithelial lining fluid (ELF) in critically ill patients with nosocomial pneumonia. METHODS: Thirty-one patients (81% male, median (IQR) age 72 (22) years) were enrolled in a prospective, randomized, clinical trial. Sixteen patients received 1 g/8 h and 15 2 g/8 h by CI (8 h infusion). Plasma and ELF meropenem concentrations were modeled using a population methodology, and Monte Carlo simulations were performed to estimate the probability of attaining (PTA) a free ELF concentration of 50% of time above MIC (50% fT>MIC), which results in logarithmic killing and the suppression of resistance in experimental models of pneumonia. RESULTS: The median (IQR) of meropenem AUC0-24 h in the plasma and ELF was 287.6 (190.2) and 84.1 (78.8) mg h/L in the 1 g/8 h group vs 448.1 (231.8) and 163.0 (201.8) mg h/L in the 2 g/8 h group, respectively. The penetration ratio was approximately 30% and was comparable between the dosage groups. In the Monte Carlo simulations, only the highest approved dose of meropenem of 2 g/8 h by CI allowed to achieve an optimal PTA for all isolates with a MIC < 4 mg/L. CONCLUSIONS: An increase in the dose of meropenem administered by CI achieved a higher exposure in the plasma and ELF. The use of the highest licensed dose of 6 g/day may be necessary to achieve an optimal coverage in ELF for all susceptible isolates (MIC ≤ 2 mg/L) in patients with conserved renal function. An alternative therapy should be considered when the presence of microorganisms with a MIC greater than 2 mg/L is suspected. TRIAL REGISTRATION: The trial was registered in the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT-no. 2016-002796-10). Registered on 27 December 2016.

Systemic pharmacokinetics and safety of high doses of nebulized colistimethate sodium in critically ill patients with hospital-acquired and ventilator-associated pneumonia.

OBJECTIVES: To assess the pharmacokinetics of formed colistin in plasma and the safety of two different high doses of colistimethate sodium administered via nebulization in critically ill surgical patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). PATIENTS AND METHODS: Formed colistin plasma concentrations were measured in critically ill surgical patients with pneumonia treated with two different doses of nebulized colistimethate sodium (3 MIU/8 h versus 5 MIU/8 h). Adverse events possibly related to nebulized colistimethate sodium were recorded. RESULTS: Twenty-seven patients (15 in the 3 MIU/8 h group and 12 in the 5 MIU/8 h group) were included. Colistin plasma concentrations were unquantifiable (<0.1 mg/L) in eight (53.3%) patients in the 3 MIU/8 h group and in seven patients (58.3%) in the 5 MIU/8 h group. Median (IQR) quantifiable colistin plasma concentrations before nebulization and at 1, 4 and 8 h were 0.17 (0.12-0.33), 0.20 (0.11-0.24), 0.17 (0.12-0.23) and 0.17 (0.11-0.32) mg/L, respectively, in the 3 MIU/8 h group and 0.20 (0.11-0.35), 0.24 (0.12-0.44), 0.24 (0.10-0.49) and 0.23 (0.11-0.44) mg/L, respectively, in the 5 MIU/8 h group, with no differences between the two groups at any time. Renal impairment during nebulized treatment was observed in three patients in each group, but was unlikely to be related to colistimethate sodium treatment. Nebulized colistimethate sodium therapy was well tolerated and no bronchospasms or neurotoxicity events were observed. CONCLUSIONS: In this limited observational case series of critically ill patients with HAP or VAP treated with high doses of nebulized colistimethate sodium, systemic exposure was minimal and the treatment was well tolerated.

Almitrine fails to improve oxygenation during one-lung ventilation with sevoflurane anesthesia.

OBJECTIVE: Almitrine enhances hypoxic pulmonary vasoconstriction (HPV) and can improve hypoxemia related to one-lung ventilation (OLV). Studies using almitrine have been conducted without inhaled anesthetics because they could inhibit HPV, counteracting the effect of almitrine. This hypothesis, however, has not been confirmed. This study's aim was to evaluate whether almitrine could improve oxygenation when administered during OLV with sevoflurane anesthesia. DESIGN: A prospective, randomized, double-blind, placebo-controlled trial. SETTING: A tertiary care, university teaching hospital. PARTICIPANTS: Thirty adult patients undergoing open-chest thoracic surgery. INTERVENTIONS: Patients were assigned randomly to receive almitrine or placebo during OLV. Respiratory and hemodynamic variables were recorded continuously. Anesthesia was maintained with sevoflurane and remifentanil. Intraoperative techniques and medical teams were the same all over the study. MEASUREMENTS AND MAIN RESULTS: Respiratory and hemodynamic variables were measured during two-lung ventilation and during open-chest OLV. Two-way repeated-measures analysis of variance was used to compare the effects of almitrine and placebo. During OLV, PaO2 and shunt fraction worsened in all patients without significant differences between groups. At 30-minutes of OLV, PaO2 was 184±67 mmHg in the almitrine group and 145±56 mmHg in the placebo group, while shunt fraction were 31%±6% and 36%±13%, respectively. Mean pulmonary artery pressure was higher in the almitrine group (31±5 v 24±5 mmHg, p<0.001). CONCLUSIONS: During anesthesia with sevoflurane for open-chest OLV, almitrine failed to improve oxygenation and increased pulmonary artery pressure. The combination of sevoflurane and almitrine should, therefore, be avoided.

Collaborative intervention to improve airway assessment and safety in management for anaesthesia: the Qualitat & Via Aèria (QUAVA) study.

BACKGROUND: Airway assessment and management are cornerstones of anaesthesia, yet airway complications remain an important source of morbidity. OBJECTIVE: We performed a before-and-after evaluation of a collaborative intervention to improve adherence to airway assessment and management guidelines in patients scheduled for surgery under general anaesthesia. DESIGN: A prospective, multicentre before-and-after evaluation of a collaborative intervention. SETTING: Collaborative intervention to improve adherence to airway assessment and management guidelines in patients scheduled for surgery under general anaesthesia. Data were collected on 21 consecutive days before and after the intervention. PARTICIPANTS: Anaesthetists with staff or residency positions at 22 hospitals. Patients aged 18 years or older undergoing nonemergency surgery were recruited. INTERVENTION: Establishing a learning network that included local leaders, meetings to share experiences and knowledge, interactive sessions and provision of printed materials on airway assessment and management. Clinical airway management for general anaesthesia was provided by the anaesthetists participating in the study. MAIN OUTCOME MEASURES: Outcomes were the completion of airway assessment at the preanaesthetic visit, rates of unanticipated difficult airway, algorithm adherence and related airway complications. RESULTS: The study included 3753 patients (1947 preintervention and 1806 postintervention). The percentage of patients with a complete airway assessment increased from 25.1% preintervention to 48.4% postintervention (P <0.001). The incidences of unanticipated difficult airway were 4.1% before the intervention and 3% after it (P = 0.433). Rates of adherence to the algorithms for anticipated and unanticipated difficult airway management were similar in the two periods. The incidences of related adverse events were also similar. CONCLUSION: The collaborative intervention was effective in improving airway assessment but not in changing difficult airway management practices.

Clinical, Microbiological and Treatment Characteristics of Severe Postoperative Respiratory Infections: An Observational Cohort Study.

Respiratory infections are frequent and life-threatening complications of surgery. This study aimed to evaluate the clinical, microbiological and treatment characteristics of severe postoperative pneumonia (POP) and tracheobronchitis (POT) in a large series of patients. This single-center, prospective observational cohort study included patients with POP or POT requiring intensive care unit admission in the past 10 years. We recorded demographic, clinical, microbiological and therapeutic data. A total of 207 patients were included, and 152 (73%) were men. The mean (SD) age was 70 (13) years and the mean (SD) ARISCAT score was 46 (19). Ventilator-associated pneumonia was reported in 21 patients (10%), hospital-acquired pneumonia was reported in 132 (64%) and tracheobronchitis was reported in 54 (26%). The mean (SD) number of days from surgery to POP/POT diagnosis was 6 (4). The mean (SD) SOFA score was 5 (3). Respiratory microbiological sampling was performed in 201 patients (97%). A total of 177 organisms were cultured in 130 (63%) patients, with a high proportion of Gram-negative and multi-drug resistant (MDR) bacteria (20%). The most common empirical antibiotic therapy was a triple-drug regimen covering MDR Gram-negative bacteria and MRSA. In conclusion, surgical patients are a high-risk population with a high proportion of early onset severe POP/POT and nosocomial bacteria isolation.

Moderate sedation with dexmedetomidine-remifentanil is safer than deep sedation with propofol-remifentanil for endobronchial ultrasound while providing comparable quality: a randomized double-blind trial.

OBJECTIVE: We compared dexmedetomidine-remifentanil vs. propofol-remifentanil in terms of safety and quality during sedation for Endobronchial ultrasonography (EBUS). METHODS: A randomized, double-blind trial. Outpatients undergoing EBUS randomly received 1 µg/kg/hour dexmedetomidine or a target concentration of 2.5 µg/mL propofol, both combined with remifentanil initially targeted at 1.5 ng/mL and subsequently titrated. Additional sedatives were restricted. The primary outcome was the need for airway rescue interventions to treat oxygen desaturation. RESULTS: Twenty-eight patients received dexmedetomidine-remifentanil and 27 received propofol-remifentanil. Airway rescue interventions were fewer in the dexmedetomidine group vs. the propofol one (23 vs. 76% patients, relative risk 3.21 (95% CI 1.55-6.64, P < 0.002)). Desaturation in the dexmedetomidine group was always resolved by increasing nasal oxygen flow, whereas additional interventions were needed in 60% of patients receiving propofol. Hypotension was more frequent in the propofol group, while hypertension, bradycardia and coughing were similar in both. Bronchoscopists' and patients' satisfaction were similar, although in the dexmedetomidine group two patients needed additional sedatives and two patients would not repeat the sedation technique. CONCLUSION: Moderate sedation with dexmedetomidine-remifentanil for EBUS is safer than deep sedation with propofol-remifentanil but it would occasionally need additional sedatives to ensure patient satisfaction.

Relationship of abdominal obesity with alcohol consumption at population scale.

BACKGROUND: The high energy content of alcohol makes its consumption a potential contributor to the obesity epidemic. AIM OF THE STUDY: To determine whether alcohol consumption is a risk factor for abdominal obesity, taking into account energy underreporting. METHODS: The subjects were Spanish men (n = 1491) and women (n = 1563) aged 25-74 years who were examined in 1999-2000, in a population-based cross-sectional survey in northeastern Spain (Girona). Dietary intake, including alcohol consumption, was assessed using a food frequency questionnaire. Anthropometric variables were measured. RESULTS: The mean consumption of alcohol was 18.1 +/- 20.7 g/d in men and 5.3 +/- 10.4 g/d in women. 19.3% of men and 2.3% of women reported alcohol consumption of more than 3 drinks per day. The consumption of alcohol was directly associated with total energy intake in men (P < 0.001) and women (P = 0.001). The proportion of energy underreporting significantly (P < 0.001) decreased with higher amounts of alcohol drinking in both genders. Multiple logistic regression analysis, controlled for energy underreporting, smoking, educational level, leisure-time physical activity, energy, and diet quality, revealed that consuming more than 3 drinks of alcohol (>30 g ethanol) was significantly associated with the risk of abdominal obesity (Odds ratio 1.80; 1.05, 3.09) and exceeding recommended energy consumption (Odds ratio 1.97; 1.32, 2.93) in men. A very small number (2.13%) of women in this population reported high levels of alcohol consumption. CONCLUSIONS: Alcohol consumption in elevated amounts was associated with risk of abdominal obesity in men, independent of energy underreporting.