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Author(s): Jayesh Dhanani [sup.1] [sup.2], Leandro U. Taniguchi [sup.3] [sup.4], Otavio T. Ranzani [sup.5] [sup.6] Author Affiliations: (1) grid.1003.2, 0000 0000 9320 7537, UQ Centre for Clinical Research, Faculty of [...]

Unfractionated heparin is a widely used anticoagulant in critically ill patients. It has a well-established safety profile and remains an attractive option for clinicians due to its short half-life and reversibility. Heparin has a unique pharmacokinetic profile, which contributes to significant inter-patient and intra-patient variability in effect. The variability in anticoagulant effect combined with heparin's short half-life mean close monitoring is required for clinical efficacy and preventing adverse effects. To optimize heparin use in critically ill patients, effective monitoring assays and dose adjustment strategies are needed. This paper explores the use of heparin as an anticoagulant and optimal approaches to monitoring in critically ill patients. Conventional monitoring assays for heparin dosing have significant limitations. Emerging data appear to favor using anti-Xa assay monitoring for heparin anticoagulation, which many centers have successfully adopted as the standard. The anti-Xa assay appears have important benefits relative to the aPTT for heparin monitoring in critically ill patients, and should be considered for broader use. [ABSTRACT FROM AUTHOR]

Pulmonary infection is one of the main complications occurring in patients suffering from acute respiratory distress syndrome (ARDS). Besides traditional risk factors, dysregulation of lung immune defenses and microbiota may play an important role in ARDS patients. Prone positioning does not seem to be associated with a higher risk of pulmonary infection. Although bacteria associated with ventilator-associated pneumonia (VAP) in ARDS patients are similar to those in patients without ARDS, atypical pathogens (Aspergillus, herpes simplex virus and cytomegalovirus) may also be responsible for infection in ARDS patients. Diagnosing pulmonary infection in ARDS patients is challenging, and requires a combination of clinical, biological and microbiological criteria. The role of modern tools (e.g., molecular methods, metagenomic sequencing, etc.) remains to be evaluated in this setting. One of the challenges of antimicrobial treatment is antibiotics diffusion into the lungs. Although targeted delivery of antibiotics using nebulization may be interesting, their place in ARDS patients remains to be explored. The use of extracorporeal membrane oxygenation in the most severe patients is associated with a high rate of infection and raises several challenges, diagnostic issues and pharmacokinetics/pharmacodynamics changes being at the top. Prevention of pulmonary infection is a key issue in ARDS patients, but there is no specific measure for these high-risk patients. Reinforcing preventive measures using bundles seems to be the best option., Author(s): Charles-Edouard Luyt [sup.1] [sup.2], Lila Bouadma [sup.3] [sup.4], Andrew Conway Morris [sup.5] [sup.6], Jayesh A. Dhanani [sup.7] [sup.8], Marin Kollef [sup.9], Jeffrey Lipman [sup.7] [sup.8], Ignacio Martin-Loeches [sup.10] [sup.11], [...]

Summary: Extracorporeal cardiopulmonary resuscitation (ECPR) in patients with prolonged or refractory out‐of‐hospital cardiac arrest (OHCA) is likely to be beneficial when used as part of a well developed emergency service system.ECPR is technically challenging to initiate and resource‐intensive, but it has been found to be cost‐effective in hospital‐based ECPR programs.ECPR expansion within Australia has thus far been reactive and does not provide broad coverage or equity of access for patients.Newer delivery strategies that improve access to ECPR for patients with OHCA are being trialled, including networked hospital‐based ECPR and pre‐hospital ECPR programs. The efficacy, scalability, sustainability and cost‐effectiveness of these programs need to be assessed.There is a need for national collaboration to determine the most cost‐effective delivery strategies for ECPR provision along with its place in the OHCA survival chain. [ABSTRACT FROM AUTHOR]

Global emergence of multidrug-resistant and extensive drug-resistant gram-negative bacteria has increased the risk of treatment failure, especially for healthcare- or ventilator-associated pneumonia (HAP/VAP). Nebulization of antibiotics, by providing high intrapulmonary antibiotic concentrations, represents a promising approach to optimize the treatment of HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria, while limiting systemic antibiotic exposure. Aminoglycosides and colistin methanesulfonate are the most common nebulized antibiotics. Although optimal nebulized drug dosing regimen is not clearly established, high antibiotic doses should be administered using vibrating-mesh nebulizer with optimized ventilator settings to ensure safe and effective intrapulmonary concentrations. When used preventively, nebulized antibiotics reduced the incidence of VAP without any effect on mortality. This approach is not yet recommended and large randomized controlled trials should be conducted to confirm its benefit and explore the impact on antibiotic selection pressure. Compared with high-dose intravenous administration, high-dose nebulized colistin methanesulfonate seems to be more effective and safer in the treatment of ventilator-associated tracheobronchitis and VAP caused by multidrug resistant and extensive-drug resistant gram-negative bacteria. Adjunctive nebulized aminoglycosides could increase the clinical cure rate and bacteriological eradication in patients suffering from HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria. As nebulized aminoglycosides broadly diffuse in the systemic circulation of patients with extensive bronchopneumonia, monitoring of plasma trough concentrations is recommended during the period of nebulization. Large randomized controlled trials comparing high dose of nebulized colistin methanesulfonate to high dose of intravenous colistin methanesulfonate or to intravenous new β-lactams in HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria are urgently needed. [ABSTRACT FROM AUTHOR]

The Royal Brisbane and Women's Hospital has introduced an extracorporeal membrane oxygenation (ECMO) cardiopulmonary resuscitation (E-CPR) service with collaboration between ED and ICU teams for refractory cardiac arrest patients. E-CPR is potentially beneficial to patients who do not gain return of spontaneous circulation after conventional advanced cardiac life support treatments, provided specific demographic and biochemical inclusion criteria are met. A joint ICU and ED decision is reached to commence ECMO flow. We discuss our rationale to use the ED and the emergency physician role in leading the multidisciplinary team, with ICU leading the cannulation team. The development of ED processes and the increased availability of this intervention can significantly impact the survivability of refractory cardiac arrest with good neurological outcomes. [ABSTRACT FROM AUTHOR]

Why and when to administer nebulized aminoglycosides and colistin in VAP The main reason for nebulizing aminoglycosides and colistin in VAP is to bypass the alveolar-capillary barrier which offers a severe obstacle to lung penetration following intravenous administration. In comparison to intravenous route, nebulized aminoglycosides and colistin can achieve significantly higher lung tissue concentrations necessary for the effective treatment of VAP due to MDR GNB [[1]]. In 2018, the French Society of Anaesthesia and Intensive Care Medicine (FSAICM) and the French Intensive Care Society (FICS) published guidelines regarding hospital-acquired pneumonia (HAP) in the intensive care unit [[11]], and recommended nebulized colistin and/or aminoglycosides alone in HAP due to MDR GNB susceptible to colistin and/or aminoglycosides, when no other antibiotics can be used. [Extracted from the article]

Background: The aim of our work was to develop and validate a hydrophilic interaction liquid chromatography-electrospray ionization-tandem mass spectrometry (HILIC-ESI-MS/MS) methods for the quantification of tobramycin (TMC) and lincomycin (LMC)in plasma, microdialysis fluid and urine. Methods: Protein precipitation was used to extract TMC and LMC from plasma, while microdialysis fluid and urine sample were diluted prior to instrumental analysis. Mobile phase A consisted of 2 mM ammonium acetate in 10% acetonitrile with 0.2% formic acid (v/v) and mobile phase B consisted of 2 mM ammonium acetate in 90% acetonitrile with 0.2% formic acid (v/v). Gradient separation (80%–10% of mobile phase B) for TMC was done using a SeQuant zic-HILIC analytical guard column. While separation of LMC was performed using gradient elution (100%–40% of mobile phase B) on a SeQuant zic-HILIC analytical column equipped with a SeQuant zic-HILIC guard column. Vancomycin (VCM) was used as an internal standard. A quadratic calibration was obtained over the concentration range for plasma of 0.1–20 mg/L for TMC and 0.05–20 mg/L for LMC, for microdialysis fluid of 0.1–20 mg/L for both TMC and LMC, and 1–100 mg/L for urine for both TMC and LMC. Results: For TMS and LMC, validation testing for matrix effects, precision and accuracy, specificity and stability were all within acceptance criteria of ±15%. Conclusions: The methods described here meet validation acceptance criteria and were suitable for application in a pilot pharmacokinetic research study performed in a sheep model. [ABSTRACT FROM AUTHOR]

The original version of this article unfortunately contained a mistake. There was a typographical error in Figure 1: "Nebulization time ≤ 30 min" (first light blue square) should be replaced by "Nebulization time ≤ 90 min". The authors apologize for the mistake. [ABSTRACT FROM AUTHOR]