IntroductionSeveral reports have shown marked heterogeneity of antibiotic pharmacokinetics (PK) in patients admitted to ICUs, which might potentially affect outcomes. Therefore, the pharmacodynamic (PD) parameter of the efficacy of β-lactam antibiotics, that is, the time that its concentration is above the bacteria minimal inhibitory concentration (T > MIC), cannot be safely extrapolated from data derived from the PK of healthy volunteers.MethodsWe performed a full review of published studies addressing the PK of intravenous β-lactam antibiotics given to infected ICU patients. Study selection comprised a comprehensive bibliographic search of the PubMed database and bibliographic references in relevant reviews from January 1966 to December 2010. We selected only English-language articles reporting studies addressing β-lactam antibiotics that had been described in at least five previously published studies. Studies of the PK of patients undergoing renal replacement therapy were excluded.ResultsA total of 57 studies addressing six different β-lactam antibiotics (meropenem, imipenem, piperacillin, cefpirome, cefepime and ceftazidime) were selected. Significant PK heterogeneity was noted, with a broad, more than twofold variation both of volume of distribution and of drug clearance (Cl). The correlation of antibiotic Cl with creatinine clearance was usually reported. Consequently, in ICU patients, β-lactam antibiotic half-life and T > MIC were virtually unpredictable, especially in those patients with normal renal function. A better PD profile was usually obtained by prolonged or even continuous infusion. Tissue penetration was also found to be compromised in critically ill patients with septic shock.ConclusionsThe PK of β-lactam antibiotics are heterogeneous and largely unpredictable in ICU patients. Consequently, the dosing of antibiotics should be supported by PK concepts, including data derived from studies of the PK of ICU patients and therapeutic drug monitoring.

No abstract

ObjectiveWe aimed to compare patient’s and physician’s ratings of inhaled medication adherence and to identify predictors of patient-physician discordance.DesignBaseline data from two prospective multicentre observational studies.Setting29 allergy, pulmonology and paediatric secondary care outpatient clinics in Portugal.Participants395 patients (≥13 years old) with persistent asthma.MeasuresData on demographics, patient-physician relationship, upper airway control, asthma control, asthma treatment, forced expiratory volume in one second (FEV1) and healthcare use were collected. Patients and physicians independently assessed adherence to inhaled controller medication during the previous week using a 100 mm Visual Analogue Scale (VAS). Discordance was defined as classification in distinct VAS categories (low 0–50; medium 51–80; high 81–100) or as an absolute difference in VAS scores ≥10 mm. Correlation between patients’ and physicians’ VAS scores/categories was explored. A multinomial logistic regression identified the predictors of physician overestimation and underestimation.ResultsHigh inhaler adherence was reported both by patients (median (percentile 25 to percentile 75) 85 (65–95) mm; 53% VAS>80) and by physicians (84 (68–95) mm; 53% VAS>80). Correlation between patient and physician VAS scores was moderate (rs=0.580; p<0.001). Discordance occurred in 56% of cases: in 28% physicians overestimated adherence and in 27% underestimated. Low adherence as assessed by the physician (OR=27.35 (9.85 to 75.95)), FEV1 ≥80% (OR=2.59 (1.08 to 6.20)) and a first appointment (OR=5.63 (1.24 to 25.56)) were predictors of underestimation. An uncontrolled asthma (OR=2.33 (1.25 to 4.34)), uncontrolled upper airway disease (OR=2.86 (1.35 to 6.04)) and prescription of short-acting beta-agonists alone (OR=3.05 (1.15 to 8.08)) were associated with overestimation. Medium adherence as assessed by the physician was significantly associated with higher risk of discordance, both for overestimation and underestimation of adherence (OR=14.50 (6.04 to 34.81); OR=2.21 (1.07 to 4.58)), while having a written action plan decreased the likelihood of discordance (OR=0.25 (0.12 to 0.52); OR=0.41 (0.22 to 0.78)) (R2=44%).ConclusionAlthough both patients and physicians report high inhaler adherence, discordance occurred in half of cases. Implementation of objective adherence measures and effective communication are needed to improve patient-physician agreement.

A fundamental step in the successful management of sepsis and septic shock is early empiric antimicrobial therapy. However, for this to be effective, several decisions must be addressed simultaneously: (1) antimicrobial choices should be adequate, covering the most probable pathogens; (2) they should be administered in the appropriate dose, (3) by the correct route, and (4) using the correct mode of administration to achieve successful concentration at the infection site. In critically ill patients, antimicrobial dosing is a common challenge and a frequent source of errors, since these patients present deranged pharmacokinetics, namely increased volume of distribution and altered drug clearance, which either increased or decreased. Moreover, the clinical condition of these patients changes markedly over time, either improving or deteriorating. The consequent impact on drug pharmacokinetics further complicates the selection of correct drug schedules and dosing during the course of therapy. In recent years, the knowledge of pharmacokinetics and pharmacodynamics, drug dosing, therapeutic drug monitoring, and antimicrobial resistance in the critically ill patients has greatly improved, fostering strategies to optimize therapeutic efficacy and to reduce toxicity and adverse events. Nonetheless, delivering adequate and appropriate antimicrobial therapy is still a challenge, since pathogen resistance continues to rise, and new therapeutic agents remain scarce. We aim to review the available literature to assess the challenges, impact, and tools to optimize individualization of antimicrobial dosing to maximize exposure and effectiveness in critically ill patients.

BackgroundSkeletal-related events (SREs; pathologic fracture [PF], spinal cord compression and radiation or surgery to bone) are common complications of bone metastases or bone lesions and can impose a considerable burden on patients and healthcare systems. In this study, the healthcare resource utilisation (HRU) associated with PFs in patients with bone metastases or lesions secondary to solid tumours or multiple myeloma was estimated in eight European countries.MethodsEligible patients were identified in Austria, the Czech Republic, Finland, Greece, Poland, Portugal, Sweden and Switzerland. HRU data were extracted from hospital charts from 3.5 months before the index PF (defined as a PF preceded by a 6.5-month period without a SRE) until 3 months after the last SRE during the study period. Changes from baseline in the number and duration of inpatient stays, number of outpatient visits and number of procedures provided were recorded.ResultsOverall, 118 patients with PFs of long bones (those longer than they are wide, e.g. the femur) and 241 patients with PFs of other bones were included. Overall, HRU was greater in patients with long bone PFs than in those with PFs of other bones. A higher proportion of patients with long bone PFs had multiple SREs (79.7%), and more of their SREs were considered to be linked (73.4%) compared with patients with PFs of other bones (51.0% and 47.2%, respectively).ConclusionThe increased number and duration of inpatient stays for PFs of long bones compared with those for PFs of other bones may be due in part to the requirement for complicated and lengthy rehabilitation in patients with long bone PFs. Implementing strategies to delay or reduce the number of PFs experienced by patients with bone metastases or lesions may therefore reduce the associated HRU and patient burden.

SUMMARY BACKGROUND AND OBJECTIVES:Out-of-hospital cardiac arrest is a major cause of death with survival rates as low as 5% to 35%. A large number of patients who survive resuscitation will face significant neurological damage, as a result of the ischemia that occurs both during cardiac arrest and reperfusion. However understanding of the mechanisms responsible for brain damage has not resulted in prognostic improvement. Therapeutic hypothermia after resuscitation may be a valid option associated to reduction of neurological damage. The purpose of this study was to review scientific evidence related to a therapy for patients resuscitated from cardiac arrest. CONTENTS: Description and analysis of the main risk factors associated with neurological damage after resuscitation from cardiac arrest as well as prognostic criteria was carried out. A non-systematic search was conducted in the PubMed data base for papers on a therapeutic approach for patients resuscitated from cardiac arrest. Bibliographic references of reviewed papers were also analyzed. Practical rules were drafted for such an approach.

No abstract

No abstract