[No abstract available]

Nebulised antibiotics are frequently used for the prevention or treatment of ventilator-associated pneumonia. Many factors may influence pulmonary drug concentrations with inaccurate dosing schedules potentially leading to therapeutic failure and/or the emergence of antibiotic resistance. We describe a research pathway for studying the pharmacokinetics of a nebulised antibiotic during mechanical ventilation using in vitro methods and ovine models, using tobramycin as the study antibiotic.

Microdialysis is a technique used to measure the unbound antibiotic concentration in the interstitial spaces, the target site of action. In vitro recovery studies are essential to calibrating the microdialysis system for in vivo studies. The effect of a combination of antibiotics on recovery into microdialysate requires investigation. In vitro microdialysis recovery studies were conducted on a combination of vancomycin and tobramycin, in a simulated in vivo model. Comparison was made between recoveries for three different concentrations and three different perfusate flow rates. The overall relative recovery for vancomycin was lower than that of tobramycin. For tobramycin, a concentration of 20µg/mL and flow rate of 1.0µL/min had the best recovery. A concentration of 5.0µg/mL and flow rate of 1.0µL/min yielded maximal recovery for vancomycin. Large molecular size and higher protein binding resulted in lower relative recoveries for vancomycin. Perfusate flow rates and drug concentrations affected the relative recovery when a combination of vancomycin and tobramycin was tested. Low perfusate flow rates were associated with higher recovery rates. For combination antibiotic measurement which includes agents that are highly protein bound, in vitro studies performed prior to in vivo studies may ensure the reliable measurement of unbound concentrations.

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Background: Adrenomedullin and endothelin-1 are hormones with opposing effects on the cardiovascular system. Adrenomedullin acts as a vasodilator and seems to be important for the initiation and continuation of the hyperdynamic circulatory response in sepsis. Endothelin-1 is a vasoconstrictor and has been linked to decreased cardiac performance. Few studies have studied the relationship between adrenomedullin and endothelin-1, and morbidity and mortality in septic shock patients. High-sensitivity troponin T (hsTNT) is normally used to diagnose acute cardiac injury but is also prognostic for outcome in intensive care. We investigated the relationship between mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), and myocardial injury, measured using transthoracic echocardiography and hsTNT in septic shock patients. We were also interested in the development of different biomarkers throughout the ICU stay, and how early measurements were related to mortality. Further, we assessed if a positive biomarker panel, consisting of MR-proADM, CT-proET-1, and hsTNT changed the odds for mortality. Methods: A cohort of 53 consecutive patients with septic shock had their levels of MR-proADM, CT-proET-1, hsTNT, and left ventricular systolic functions prospectively measured over 7 days. The relationship between day 1 levels of MR-proADM/CT-proET-1 and myocardial injury was studied. We also investigated the relationship between biomarkers and early (7-day) and later (28-day) mortality. Likelihood ratios, and pretest and posttest odds for mortality were calculated. Results: Levels of MR-proADM and CT-proET-1 were significantly higher among patients with myocardial injury and were correlated with left ventricular systolic dysfunction. MR-proADM and hsTNT were significantly higher among 7-day and 28-day non-survivors. CT-proET-1 was also significantly higher among 28-day but not 7-day non-survivors. A positive biomarker panel consisting of the three biomarkers increased the odds for mortality 13-fold to 20-fold. Conclusions: MR-proADM and CT-proET-1 are associated with myocardial injury. A biomarker panel combining MR-proADM, CT-proET-1, and hsTNT increases the odds ratio for death, and may improve currently available scoring systems in critical care.

BACKGROUND: Abnormal serum sodium concentrations are common in patients presenting for surgery. It remains unclear whether these abnormalities are independent risk factors for postoperative mortality.

METHODS: This is a secondary analysis of the European Surgical Outcome Study (EuSOS) that provided data describing 46 539 patients undergoing inpatient non-cardiac surgery. Patients were included in this study if they had a recorded value of preoperative serum sodium within the 28 days immediately before surgery. Data describing preoperative risk factors and serum sodium concentrations were analysed to investigate the relationship with in-hospital mortality using univariate and multivariate logistic regression techniques.

RESULTS: Of 35 816 (77.0%) patients from the EuSOS database, 21 943 (61.3%) had normal values of serum sodium (138-142 mmol litre(-1)) before surgery, 8538 (23.8%) had hyponatraemia (serum sodium ≤137 mmol litre(-1)) and 5335 (14.9%) had hypernatraemia (serum sodium ≥143 mmol litre(-1)). After adjustment for potential confounding factors, moderate to severe hypernatraemia (serum sodium concentration ≥150 mmol litre(-1)) was independently associated with mortality [odds ratio 3.4 (95% confidence interval 2.0-6.0), P<0.0001]. Hyponatraemia was not associated with mortality.

CONCLUSIONS: Preoperative abnormalities in serum sodium concentrations are common, and hypernatraemia is associated with increased mortality after surgery. Abnormalities of serum sodium concentration may be an important biomarker of perioperative risk resulting from co-morbid disease.

BackgroundShock is common in intensive care units, and treatment includes fluids, vasopressor and/or inotropic drugs, guided by hemodynamic monitoring. The aim of this study was to identify current practice for treatment of shock in Scandinavian intensive care units. MethodsSeven-day inception cohort study in 43 intensive care units in Scandinavia. Patients 15years old receiving more than 4h of cardiovascular acting drug infusion were included. The use of fluids, vasopressor and inotropic drugs, type of monitoring, and target values were recorded. ResultsOne hundred and seventy-one patients were included. At inclusion, 136/168 (81%) had received vasopressor and/or inotropic drug therapy for less than 24h, and 143/171 (84%) had received volume loading before the onset of vasoactive drug treatment. Ringers solution was given to 129/143 (90%) of patients and starches in 3/143 (2%) patients. Noradrenaline was the most commonly used cardiovascular acting drug, given in 168/171 (98%) of cases while dopamine was rarely used. Mean arterial pressure was considered the most important variable for hemodynamic monitoring. Invasive arterial blood pressure was monitored in 166/171 (97%) of patients, arterial pulse wave analysis in 11/171 (7%), and echocardiography in 50/171 (29%). ConclusionIn this survey, Ringers solution and noradrenaline were the most common first-line treatments in shock. The use of starches and dopamine were rare. Almost all patients were monitored with invasive arterial blood pressure, but comprehensive hemodynamic monitoring was used only in a minority of patients.

BACKGROUND: The European Surgical Outcomes Study (EuSOS) revealed large variations in outcomes among countries. In-hospital mortality and ICU admission rates in Sweden were low, going against the assumption that access to ICU improves outcome. Long-term mortality was not reported in EuSOS and is generally poorly described in the current literature.

OBJECTIVE: To describe the characteristics of the Swedish subset of EuSOS and identify predictors of short and long-term mortality after surgery.

DESIGN: An observational cohort study.

SETTING: Six universities and two regional hospitals in Sweden.

PATIENTS: A cohort of 1314 adult patients scheduled for surgery between 4 April and 11 April 2011.

MAIN OUTCOME MEASURES: 30-day and 1-year mortality.

RESULTS: A total of 303 patients were lost to follow-up, leaving 1011 for analysis; 69% of patients were classified as American Society of Anesthesiologists' physical status 1 or 2, and 68% of surgical procedures were elective. The median length of stay in postanaesthesia care units (PACUs) was 175 min (interquartile range 110-270); 6.6% of patients had PACU length of stay of more than 12 h and 3.6% of patients were admitted to the ICU postoperatively. Thirty-day mortality rate was 1.8% [95% confidence interval (CI) 1.0-2.6] and 8.5% (CI 6.8-10.2) at 1 year (n = 18 and 86). The risk of death was higher than in an age and sex-matched population after 30 days (standardised mortality ratio 10.0, CI 5.9-15.8), and remained high after 1 year (standardised mortality ratio 3.9, CI 3.1-4.8). Factors predictive of 30-day mortality were age, American Society of Anesthesiologists' physical status, number of comorbidities, urgency of surgery and ICU admission. For 1-year mortality, age, number of comorbidities and urgency of surgery were independently predictive. ICU admission and long stay in PACU were not significant predictors of long-term mortality.

CONCLUSION: Mortality rate increased almost five-fold at 1 year compared with 30-day mortality after surgery, demonstrating a significantly sustained long-term risk of death in this surgical population. In Sweden, factors associated with long-term postoperative mortality were age, number of comorbidities and surgical urgency.

There is a need for large trials that test the clinical effectiveness of interventions in the field of perioperative medicine. Clinical outcome measures used in such trials must be robust, clearly defined and patient-relevant. Our objective was to develop standards for the use of clinical outcome measures to strengthen the methodological quality of perioperative medicine research. A literature search was conducted using PubMed and opinion leaders worldwide were invited to nominate papers that they believed the group should consider. The full texts of relevant articles were reviewed by the taskforce members and then discussed to reach a consensus on the required standards. The report was then circulated to opinion leaders for comment and review. This report describes definitions for 22 individual adverse events with a system of severity grading for each. In addition, four composite outcome measures were identified, which were designed to evaluate postoperative outcomes. The group also agreed on standards for four outcome measures for the evaluation of healthcare resource use and quality of life. Guidance for use of these outcome measures is provided, with particular emphasis on appropriate duration of follow-up. This report provides clearly defined and patient-relevant outcome measures for large clinical trials in perioperative medicine. These outcome measures may also be of use in clinical audit. This report is intended to complement and not replace other related work to improve assessment of clinical outcomes following specific surgical procedures.