Purpose
The purpose of this study was to describe inhaled colistin pharmacokinetics in patients with ventilator-associated tracheobronchitis (VAT) due to polymyxin-only susceptible Gram-negative ...bacteria (GNB).
Methods
Inhaled colistimethate sodium (CMS) was administered at a dose of 80 mg every 8 h for 7 days. Mini bronchoalveolar lavage (BAL) was performed before and at 1, 4 and 8 h, while blood samples were collected before and at 0.16, 0.5, 1, 2, 4 and 8 h after the first dose. Colistin concentrations in BAL and serum were determined by high-performance liquid chromatography.
Results
Our study population included 20 patients. At the end of treatment, cure was achieved in 16 patients and favorable microbiological response in 12 patients. Median (25–75 % interquartile range) colistin concentrations in epithelial lining fluid (ELF) were 6.7 (4.8–10.1), 3.9 (2.5–6.0) and 2.0 (1.0–3.8) μg/ml at 1, 4 and 8 h, respectively, and fivefold higher than those achieved in serum. Median ELF concentrations at 1 and 4 h were above the minimum inhibitory concentrations of all isolated pathogens; however, the 4-h median was below the European Committee on Antimicrobial Susceptibility Guidelines (EUCAST) breakpoints for
Pseudomonas aeruginosa
and the 8-h median was low relative to EUCAST breakpoints for all GNB. Colistin pharmacokinetic/pharmacodynamic parameters in ELF were associated with favorable microbiological response at the end of treatment.
Conclusion
Inhaled colistin may achieve high drug concentrations in the lung. However, a dose of 80 mg of inhaled CMS every 8 h may not be adequate for the treatment of lower respiratory tract infections due to multi-drug resistant GNB.
In patients with acute respiratory failure, gas exchange is impaired due to the accumulation of fluid in the lung airspaces. This life-threatening syndrome is treated with mechanical ventilation, ...which is adjusted to maintain gas exchange, but can be associated with the accumulation of carbon dioxide in the lung. Carbon dioxide (CO2) is a by-product of cellular energy utilization and its elimination is affected via alveolar epithelial cells. Signaling pathways sensitive to changes in CO2 levels were described in plants and neuronal mammalian cells. However, it has not been fully elucidated whether non-neuronal cells sense and respond to CO2. The Na,K-ATPase consumes approximately 40% of the cellular metabolism to maintain cell homeostasis. Our study examines the effects of increased pCO2 on the epithelial Na,K-ATPase a major contributor to alveolar fluid reabsorption which is a marker of alveolar epithelial function.
We found that short-term increases in pCO2 impaired alveolar fluid reabsorption in rats. Also, we provide evidence that non-excitable, alveolar epithelial cells sense and respond to high levels of CO2, independently of extracellular and intracellular pH, by inhibiting Na,K-ATPase function, via activation of PKCzeta which phosphorylates the Na,K-ATPase, causing it to endocytose from the plasma membrane into intracellular pools.
Our data suggest that alveolar epithelial cells, through which CO2 is eliminated in mammals, are highly sensitive to hypercapnia. Elevated CO2 levels impair alveolar epithelial function, independently of pH, which is relevant in patients with lung diseases and altered alveolar gas exchange.
Being able to accurately predict probability of death is important for the intensivist. Serum cytokine levels parallel physiological derangements observed in critically ill patients and are used in ...commonly applied scoring systems and prediction models. Thus, serum cytokine based prediction models of outcome seem to be reasonable and of great interest. In this issue of Critical Care, Gauglitz and colleagues present their prediction equation for paediatric burn patients with concomitant inhalation injury. They found that IL-10 on admission, or IL-6 and IL-7 five to seven days later, may predict outcome in an excellent way. Increased mortality is observed as serum IL-6 and IL-10 levels increase and serum IL-7 levels decrease. However, the complexity of cytokine kinetics in critically ill patients and the variety of factors capable to affect circulating cytokines even in a subgroup of critically ill patients may affect the validity of the results. Also, serum cytokine based prediction models need to be compared to commonly applied prediction models based on clinical parameters. This will enable identification of the most suitable, accurate, cheapest, and easiest to use model to predict outcome.
We present a case of a 67-year-old Caucasian female who was admitted to the pulmonary clinic of a general hospital in Athens with fever and respiratory symptoms. A lung biopsy was ordered because a ...clinical diagnosis of interstitial lung disease was suspected. The patient was then hospitalized in the intensive care unit. Because of the fact that peripheral catheterization was impossible and the prospect of further long-term hospitalization, the patient was referred to a vascular access nursing team composed of perianesthesia nurses to advance a peripherally inserted central catheter and support the line during treatment. The peripherally inserted central catheter line was advanced with no complications, and the position of the catheter was checked using the electrocardiography method.
Abstract Objectives We aimed to investigate the accuracy of certain laboratory examinations obtained by the ABG analyzer (ROCHE AVL OMNI S ) as compared to hospital central laboratory (CL). Methods ...We prospectively collected data obtained from the same arterial blood sample regarding hematocrit, hemoglobin, potassium, and sodium. Results ABG analyzer results were significantly lower ( p < 0.0001) compared to CL values thus values between the two methods are not interchangeable. The mean bias for Hb, Na+ and K+ were within accepted by US Clinical Laboratory Improvement Amendment (USCLIA) differences (cut-off points) but not for Ht. In 8.0%, 17.5%, 37.5% and 56.0% of Hb, Na+ , K+ and Ht measurements respectively and 29.75% in sum the differences were over the USCLIA accepted limits. ABG analyzer significantly underestimate the values of Hb, Ht, Na+ and K+ , compared to CL and almost 30% of all examined parameters were beyond USCLIA accepted biases. Conclusions ABG analyzer significantly underestimates the values of Hb, Ht, Na+ and K+ compared to CL and almost 30% for all examined parameters are beyond USCLIA accepted biases. These data do not support widespread or even careful use of POCT for making diagnostic and treatment decisions until technology improves and results in improved outcomes.
Acid-base disturbances, such as metabolic or respiratory alkalosis, are relatively common in critically ill patients. We examined the effects of alkalosis (hypocapnic or metabolic alkalosis) on ...alveolar fluid reabsorption in the isolated and continuously perfused rat lung model. We found that alveolar fluid reabsorption after 1 hour was impaired by low levels of CO2 partial pressure (PCO2; 10 and 20 mm Hg) independent of pH levels (7.7 or 7.4). In addition, PCO2 higher than 30 mm Hg or metabolic alkalosis did not have an effect on this process. The hypocapnia-mediated decrease of alveolar fluid reabsorption was associated with decreased Na,K-ATPase activity and protein abundance at the basolateral membranes of distal airspaces. The effect of low PCO2 on alveolar fluid reabsorption was reversible because clearance normalized after correcting the PCO2 back to normal levels. These data suggest that hypocapnic but not metabolic alkalosis impairs alveolar fluid reabsorption. Conceivably, correction of hypocapnic alkalosis in critically ill patients may contribute to the normalization of lung ability to clear edema.
Chronic heart failure (CHF) may be considered a state of immune activation and persistent inflammation expressed by increased circulating levels of pro- and anti-inflammatory cytokines. The purpose ...of the study was to investigate the immune status in patients with CHF compared to normal individuals. We measured serum cytokine levels as well as cytokine production after ex vivo LPS stimulation of whole blood taken from 14 patients with CHF and 14 healthy volunteers. We used 500
pg/ml of LPS for an incubation period of 4
h to stimulate 100
μL of whole blood. Patients with CHF had significantly higher levels of TNF-RI, and TNF-RII in serum compared to normal individuals. TNF-α, IL-6, and IL-10 did not differ significantly. After LPS stimulation, patients with CHF had significantly higher levels of TNF-α and IL-10, and significantly lower IL-6 levels compared to normal individuals. TNF-α receptors did not differ significantly. Patients with CHF may be found in a pro- as well as an anti-inflammatory state. They also do not develop endotoxin tolerance in an ex vivo laboratory model using whole blood stimulated with LPS. They may have increased TNF-α and IL-10 production after LPS stimulation of whole blood, which may contribute to a worsening of heart function, more severe disease presentation and a worse outcome during infections.
Nosocomial pneumonia (NP) is defined as pneumonia that develops within 48 hours or more of hospital admission and which was not developing at the time of admission. Nosocomial pneumonia, also known ...as hospital-acquired pneumonia (HAP), is the second most common hospital infection, while ventilator-associated pneumonia represents the most common intensive care unit (ICU) infection. Nosocomial pneumonia significantly contributes to morbidity, mortality, and escalating healthcare costs because of increases in antibiotic prescription and administration, length of ICU stay, and length of hospital stay. Aspiration and colonization of the upper respiratory tract seem to be the major pathogenetic mechanisms for the development of NP, either in intubated or spontaneously breathing patients. The microbiology of NP depends on the timing of onset. In early-onset NP, the responsible pathogens are generally endogenous community-acquired pathogens. In late-onset NP, the responsible microbes include potentially multi-drug-resistant nosocomial organisms residing in oropharyngeal or gastric contents. Important risk factors for development of NP include coma, intubation, prolonged mechanical ventilation, repeated intubations, supine positioning, and long-term antibiotic use. The most significant preventive measures include routine hand washing and avoidance of (1) the supine position, (2) inappropriate antibiotics, and (3) overuse of H2-antagonists for stress ulcer prophylaxis. Accurate diagnosis of NP is difficult and controversial, warranting consideration for the application of invasive quantitative culture techniques over tracheal aspirates. Empiric antibiotic treatment should be prompt, starting on clinical suspicion, and based on local ICU pathogen epidemiology and antibiotic resistance patterns and on a deescalating antibiotic strategy. Innovative antibiotic strategies, such as antibiotic rotation, to help prevent the emergence of multi-drug-resistant pathogens and improve survival should be considered.
PDF
