An increasing number of critically ill patients are immunocompromised. Acute hypoxemic respiratory failure (ARF), chiefly due to pulmonary infection, is the leading reason for ICU admission. ...Identifying the cause of ARF increases the chances of survival, but may be extremely challenging, as the underlying disease, treatments, and infection combine to create complex clinical pictures. In addition, there may be more than one infectious agent, and the pulmonary manifestations may be related to both infectious and non-infectious insults. Clinically or microbiologically documented bacterial pneumonia accounts for one-third of cases of ARF in immunocompromised patients. Early antibiotic therapy is recommended but decreases the chances of identifying the causative organism(s) to about 50%. Viruses are the second most common cause of severe respiratory infections. Positive tests for a virus in respiratory samples do not necessarily indicate a role for the virus in the current acute illness. Invasive fungal infections (
Aspergillus
,
Mucorales
, and
Pneumocystis jirovecii
) account for about 15% of severe respiratory infections, whereas parasites rarely cause severe acute infections in immunocompromised patients. This review focuses on the diagnosis of severe respiratory infections in immunocompromised patients. Special attention is given to newly validated diagnostic tests designed to be used on non-invasive samples or bronchoalveolar lavage fluid and capable of increasing the likelihood of an early etiological diagnosis.
Background
Antimicrobial de-escalation (ADE) is a strategy of antimicrobial stewardship, aiming at preventing the emergence of antimicrobial resistance (AMR) by decreasing the exposure to ...broad-spectrum antimicrobials. There is no high-quality research on ADE and its effects on AMR. Its definition varies and there is little evidence-based guidance for clinicians to use ADE in the intensive care unit (ICU).
Methods
A task force of 16 international experts was formed in November 2016 to provide with guidelines for clinical practice to develop questions targeted at defining ADE, its effects on the ICU population and to provide clinical guidance. Groups of 2 experts were assigned 1–2 questions each within their field of expertise to provide draft statements and rationale. A Delphi method, with 3 rounds and an agreement threshold of 70% was required to reach consensus.
Results
We present a comprehensive document with 13 statements, reviewing the evidence on the definition of ADE, its effects in the ICU population and providing guidance for clinicians in subsets of clinical scenarios where ADE may be considered.
Conclusion
ADE remains a topic of controversy due to the complexity of clinical scenarios where it may be applied and the absence of evidence to the effects it may have on antimicrobial resistance.
Electrical impedance tomography measures changes in lung impedance, which are mainly related to changes in lung volume. We used electrical impedance tomography to investigate the effects of high-flow ...nasal cannula (HFNC) and body position on global and regional end-expiratory lung impedance variation (ΔEELI).
Prospective study with 20 healthy adults. Two periods were defined: the first in supine position and the second in prone position. Each period was divided into 3 phases. In the first and the third phases the subjects were breathing ambient air, and in the second HFNC was implemented. Four regions of interest were defined: 2 ventral and 2 dorsal. For each respiratory cycle, global and regional ΔEELI were measured by electrical impedance tomography and were expressed as a function of the tidal variation of the first stable respiratory cycle (units).
HFNC increased global EELI by 1.26 units (95% CI 1.20-1.31, P < .001) in supine position, and by 0.87 units (95% CI 0.82-0.91, P < .001) in prone position. The distribution of ΔEELI was homogeneous in prone position, with no difference between ventral and dorsal lung regions (-0.01 units, 95% CI -0.01 to 0, P = .18), while in supine position a significant difference was found (0.22 units, 95% CI 0.21-0.23, P < .001) with increased EELI in ventral areas.
HFNC increased global EELI in our population, regardless of body position, suggesting an increase in functional residual capacity. Prone positioning was related to a more homogeneous distribution of ΔEELI, while in supine position ΔEELI was higher in the ventral lung regions.
Oxygen therapy can be delivered using low-flow, intermediate-flow (air entrainment mask), or high-flow devices. Low/intermediate-flow oxygen devices have several drawbacks that cause critically ill ...patients discomfort and translate into suboptimal clinical results. These include limitation of the FiO
2
(due to the high inspiratory flow often observed in patients with respiratory failure), and insufficient humidification and warming of the inspired gas. High-flow nasal cannula oxygenation (HFNCO) delivers oxygen flow rates of up to 60 L/min and over the last decade its effect on clinical outcomes has widely been evaluated, such as in the improvement of respiratory distress, the need for intubation, and mortality. Mechanisms of action of HFNCO are complex and not limited to the increased oxygen flow rate. The main aim of this review is to guide clinicians towards evidence-based clinical practice guidelines. It summarizes current knowledge about HFNCO use in ICU patients and the potential areas of uncertainties. For instance, it has been recently suggested that HFNCO could improve the outcome of patients with hypoxemic acute respiratory failure. In other settings, research is ongoing and additional evidence is needed. For instance, if intubation is required, studies suggest that HFNCO may help to improve preoxygenation and can be used after extubation. Likewise, HFNCO might be used in obese patients, or to prevent respiratory deterioration in hypoxemic patients requiring bronchoscopy, or for the delivery of aerosol therapy. However, areas for which conclusive data exist are limited and interventions using standardized HFNCO protocols, comparators, and relevant clinical outcomes are warranted.
Complications following lung transplantation (LTx) are diverse and range from immunologic reactions to cancerous malignancies. The correct identification of the causative pathology requires a ...purposive diagnostic strategy that considers all these possibilities (Fig. 1). Here, we present ten general tips for the intensive care management of post-LTx patients. However, case-by-case decisions on volume therapy and ventilator strategies should be obtained in a specialized center.
Low serum albumin levels are very common in critically ill patients, with reported incidences as high as 40-50%. This condition appears to be associated with alterations in the degree of protein ...binding of many highly protein-bound antibacterials, which lead to altered pharmacokinetics and pharmacodynamics, although this topic is infrequently considered in daily clinical practice. The effects of hypoalbuminaemia on pharmacokinetics are driven by the decrease in the extent of antibacterial bound to albumin, which increases the unbound fraction of the drug. Unlike the fraction bound to plasma proteins, the unbound fraction is the only fraction available for distribution and clearance from the plasma (central compartment). Hence, hypoalbuminaemia is likely to increase the apparent total volume of distribution (V(d)) and clearance (CL) of a drug, which would translate to lower antibacterial exposures that might compromise the attainment of pharmacodynamic targets, especially for time-dependent antibacterials. The effect of hypoalbuminaemia on unbound concentrations is also likely to have an important impact on pharmacodynamics, but there is very little information available on this area. The objectives of this review were to identify the original research papers that report variations in the highly protein-bound antibacterial pharmacokinetics (mainly V(d) and CL) in critically ill patients with hypoalbuminaemia and without renal failure, and subsequently to interpret the consequences for antibacterial dosing. All relevant articles that described the pharmacokinetics and/or pharmacodynamics of highly protein-bound antibacterials in critically ill patients with hypoalbuminaemia and conserved renal function were reviewed. We found that decreases in the protein binding of antibacterials in the presence of hypoalbuminaemia are frequently observed in critically ill patients. For example, the V(d) and CL of ceftriaxone (85-95% protein binding) in hypoalbuminaemic critically ill patients were increased 2-fold. A similar phenomenon was reported with ertapenem (85-95% protein binding), which led to failure to attain pharmacodynamic targets (40% time for which the concentration of unbound free antibacterial was maintained above the minimal inhibitory concentration fT>MIC of the bacteria throughout the dosing interval). The V(d) and CL of other highly protein-bound antibacterials such as teicoplanin, aztreonam, fusidic acid or daptomycin among others were significantly increased in critically ill patients with hypoalbuminaemia compared with healthy subjects. Increased antibacterial V(d) appeared to be the most significant pharmacokinetic effect of decreased albumin binding, together with increased CL. These pharmacokinetic changes may result in decreased achievement of pharmacodynamic targets especially for time-dependent antibacterials, resulting in sub-optimal treatment. The effects on concentration-dependent antibacterial pharmacodynamics are more controversial due to the lack of data on this topic. In conclusion, altered antibacterial-albumin binding in the presence of hypoalbuminaemia is likely to produce significant variations in the pharmacokinetics of many highly protein-bound antibacterials. Dose adjustments of these antibacterials in critically ill patients with hypoalbuminaemia should be regarded as another step for antibacterial dosing optimization. Moreover, some of the new antibacterials in development exhibit a high level of protein binding although hypoalbuminaemia is rarely considered in clinical trials in critically ill patients. Further research that defines dosing regimens that account for such altered pharmacokinetics is recommended.
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