Anidulafungin dosing in critically ill patients with continuous venovenous haemodiafiltration.

BACKGROUND: Anidulafungin is indicated as a first-line treatment for invasive candidiasis in critically ill patients. In the intensive care unit, sepsis is the main cause of acute renal failure, and treatment with continuous renal replacement therapy (CRRT) has increased in recent years. Antimicrobial pharmacokinetics is affected by CRRT, but few studies have addressed the optimal dosage for anidulafungin during CRRT. PATIENTS AND METHODS: We included 12 critically ill patients who received continuous venovenous haemodiafiltration to treat acute renal failure. Anidulafungin was infused on 3 consecutive days, starting with a loading dose (200 mg) on Day 1, and doses of 100 mg on Days 2 and 3. Blood and ultradiafiltrate samples were collected on Day 3 (during steady-state) before, and at regular intervals after, the infusion had started. Anidulafungin concentrations were determined with HPLC. RESULTS: On Day 3, peak plasma concentrations with the 100 mg dose were 6.2 ±â€Š1.7 mg/L and 7.1 ±â€Š1.9 mg/L in the arterial and venous samples, respectively. The mean, pre-filter trough concentration was 3.0 ±â€Š0.6 mg/L. The mean AUC0-24 values for plasma anidulafungin were 93.9 ±â€Š19.4 and 104.1 ±â€Š20.3mg·h/L in the arterial and venous samples, respectively. There was no adsorption to synthetic surfaces, and the anidulafungin concentration in the ultradiafiltrate was below the limit of detection. CONCLUSION: The influence of CRRT on anidulafungin elimination appeared to be negligible. Therefore, we recommend no adjustments to the anidulafungin dose for patients receiving CRRT.

Cardioprotective effect of sevoflurane and propofol during anaesthesia and the postoperative period in coronary bypass graft surgery: a double-blind randomised study.

CONTEXT: Volatile anaesthetics may have direct cardioprotective properties due to effects similar to ischaemic preconditioning and postconditioning. Clinical results in cardiac surgery patients are controversial and may be related to the timing of administration of anaesthetics intraoperatively. OBJECTIVE: We hypothesised that the cardioprotective effect of sevoflurane in coronary bypass graft surgical patients would be greater if administration during anaesthesia continued in the ICU for at least 4 h postoperatively until weaning from mechanical ventilation. DESIGN: Double-blind, double-dummy, prospective, randomised and controlled clinical trial. SETTING: In a single centre between June 2006 and June 2007. PATIENTS: Seventy-five adult patients were assigned randomly to receive anaesthesia and postoperative sedation either with propofol (control, n = 37) or sevoflurane (n = 36). INTERVENTIONS: Myocardial biomarkers were measured before surgery, at the time of admission to the intensive care unit and at 6, 24, 48 and 72 h. The need for inotropic support, and lengths of stay in the intensive care unit and hospital were also recorded. MAIN OUTCOME MEASURES: Elevation of myocardial biomarkers was the primary endpoint. The secondary endpoints were haemodynamic events and lengths of stay in the intensive care unit and hospital. RESULTS: Necrosis biomarkers increased significantly in the postoperative period in both groups with no significant differences at any time. Inotropic support was needed in 72.7 and 54.3% of patients in the propofol and sevoflurane groups, respectively (P = 0.086). There were no significant differences in haemodynamic variables, incidence of arrhythmias, myocardial ischaemia or and lengths of stay in the ICU and hospital between the two groups. CONCLUSION: In patients undergoing coronary bypass graft surgery, continuous administration of sevoflurane as a sedative in the ICU for at least 4 h postoperatively did not yield significant improvements in the extent and time course of myocardial damage biomarkers compared to propofol.

The accuracy of the anesthetic conserving device (AnaConDa©) as an alternative to the classical vaporizer in anesthesia.

BACKGROUND: The Anesthetic Conserving Device--AnaConDa® (ACD)--has been compared with a conventional vaporizer. However, the accuracy of the administered concentration of volatile anesthetics was not examined. In the present study we measured the accuracy of the ACD when used as a portable vaporizer. METHODS: This prospective study included 30 ASA I-III patients scheduled for elective surgery under general anesthesia. The patients were randomly organized into 3 groups of 10 patients per group. In each group, the sevoflurane infusion rate was adjusted to deliver 1.0 vol%, 1.5 vol%, and 2.0 vol% alveolar concentration. Hemodynamic data, bispectral index, and end-tidal sevoflurane concentrations were recorded every 2 minutes. RESULTS: We analyzed 801 data points from 30 patients. The mean difference between the end-tidal sevoflurane concentration and the target concentration was -11.0 ± 9.3% of the target when the target was 1.0 vol%, -5.4 ± 6.4% when the target was 1.5 vol%, and -4.0 ± 7.4% when the target was 2.0 vol%. No significant differences were found in the error at the different target concentrations. CONCLUSIONS: We found that the ACD may be a valid alternative to the conventional vaporizer. The ACD is very simple to use, delivery rate needs to be adjusted only once per hour, and the anesthetic savings are independent of the circuit characteristics and fresh gas flow rate.

The predictive performance of a pharmacokinetic model for manually adjusted infusion of liquid sevofluorane for use with the Anesthetic-Conserving Device (AnaConDa): a clinical study.

BACKGROUND: The Anesthetic-Conserving Device (AnaConDa) can be used to administer inhaled anesthetics using an intensive care unit (ICU) ventilator. We evaluated the predictive performance of a simple manually adjusted pump infusion scheme, for infusion of liquid sevoflurane to the AnaConDa. METHODS: We studied 50 ICU patients who received sevoflurane via the AnaConDa. They were randomly divided into three groups. A 6-h infusion of liquid anesthetic was adjusted according to the infusion scheme to a target end-tidal sevoflurane concentration of 1% (Group 1%, n = 15) and 1.5% (Group 1.5%, n = 15). The initial rate was adjusted to reach the target concentration in 10 min and then the infusion was reduced to the first hour maintenance rate and readjusted once each hour afterwards. The actual concentrations were measured in the breathing circuit and compared with the target values. In the third group (n = 20) we used the model to increase and decrease the target concentration (+/-0.3%) for 3 h and evaluated the actual change in concentration achieved. The ability of the infusion scheme to provide the target concentration was quantified by calculating the performance error (PE). Infusion scheme performance was evaluated in terms of accuracy (median absolute PE, MDAPE) and bias (median PE, MDPE). RESULTS: Performance parameters (mean +/- SD, %) were for 1%, 1.5%, increase of concentration by 0.3% and decrease of concentration by 0.3% groups, respectively: MDAPE 5.3 +/- 5.5, 2.6 +/- 4.0, 5.0 +/- 5.6, 5.5 +/- 5.4; MDPE -5.3 +/- 5.5, -2.3 +/- 4.1, -0.1 +/- 7.1, 0.2 +/- 5.4. No significant differences were found between means of all performance parameters when the 1% and 1.5% groups were compared. CONCLUSIONS: There is an excellent 6-h predictive performance of a simplified pharmacokinetic model for manually adjusted infusion of liquid sevoflurane when using the AnaConDa to deliver sevoflurane to ICU patients.