Stability of cefepime in peritoneal dialysis solution.

OBJECTIVE: To determine the stability of cefepime in peritoneal dialysis solution. DESIGN: Cefepime HCl was added to premade bags of Delflex peritoneal dialysis solution with 1.5% dextrose to produce a cefepime concentration of approximately 100 microg/mL. Peritoneal dialysis solution bags were stored at 4, 25, and 37 degrees C to simulate refrigeration, room temperature, and body temperature, respectively. Samples were drawn at scheduled times up to 336, 168, and 48 hours, respectively, after the addition of cefepime HCl. Cefepime concentrations were measured by HPLC. SETTING: This study was performed at a university-affiliated tertiary care hospital. OUTCOME MEASURE: If the mean concentration of the samples at a given time and condition was >90% of the initial concentration, cefepime was considered stable at that time and condition. RESULTS: The mean HPLC results for samples drawn at each time and condition were all >90%. CONCLUSIONS: Cefepime is stable in peritoneal dialysis solution with dextrose 1.5% for 14 days refrigerated, seven days at room temperature, and 48 hours at 37 degrees C.

Pharmacokinetic considerations.

Limited studies of the pharmacokinetics of pain medication suggest altered serum elimination when the liver is hypoperfused or affected by severe cirrhosis. Drugs that are eliminated by Phase I oxidation reactions are sensitive to changes in hepatic blood flow, while drugs eliminated by Phase II glucuronidation are more affected by diseased hepatocytes. Additionally, alterations in renal function decrease elimination of both parent drugs and metabolites, resulting in toxicity for selected opioids such as meperidine and morphine. Caution is suggested in drawing general conclusions from pharmacokinetic patterns of opioid elimination discussed in this review. Practitioners should be aware that drugs with short duration of action may have long half-lives and accumulate in end-stage liver and renal disease. While pharmacokinetic differences have been described in various populations, the clinical effects and adverse outcomes are greatly influenced by numerous independent physiologic alterations seen in critical care patients. Patients with severe alterations in liver and renal function should be administered pain medications judiciously because these patients are predisposed to metabolic disarrays. These patients should not be denied pain care, but they may benefit from smaller, less frequently administered doses, rather than continuous infusion of opioid drugs. Titration of doses to clinical effects with careful patient assessment for adverse effects is crucial for achieving desired therapeutic outcomes with analgesic agents in the ICU.

Establishing an institution-specific therapeutic range for heparin.

The relationship between heparin concentration and activated partial thromboplastin time (aPTT) in pooled plasma was compared with that in patient samples to assess the feasibility of using heparin-spiked pooled plasma in determining a therapeutic range for aPTT. Blood samples were taken from 32 patients who had been receiving intravenous unfractionated heparin sodium for more than 24 hours. The samples were stored at -70 degrees C until anti-Xa assay within three months of collection. Pooled normal plasma was spiked with unfractionated heparin sodium to produce nominal anti-Xa concentrations of 0, 0.05, 0.1, 0.2, and 0.5 unit/mL. Heparin concentrations and a aPTT values were measured, and the relationship between the two was determined by linear regression. For the ex vivo samples, the range of aPTT values corresponding to therapeutic heparin concentrations of 0.3-0.7 anti-Xa unit/mL was 64-106 seconds, which corresponds to an aPTT range of 2.3-3.9 times the mean of the normal range (compared with the traditionally defined therapeutic range of 1.5-2.5 times the control value). For the in vitro samples, the aPTT range corresponding to heparin concentrations of 0.3-0.7 unit/mL was 121-256 seconds, which corresponds to an aPTT range of 4.4-9.4 times the mean of the normal range. Each institution should establish a therapeutic aPTT range by calibrating aPTT values against heparin concentrations from blood samples of patients receiving intravenous heparin.

Analytic and clinical performance of two compact cholesterol-testing devices.

Several relatively inexpensive compact analyzers for measuring cholesterol are available for use outside of the clinical laboratory. We evaluated the analytic and clinical performance of total cholesterol assayed with the AccuMeter (ChemTrak) and the LDX (Cholestech). Accuracy of both devices was evaluated by collecting capillary and venous whole blood from 100 subjects and assaying for total cholesterol. Results were compared with the Centers for Disease Control standardized reference laboratory method. Mean percent bias, mean absolute percent bias, and percentage of subjects with total error above +/- 8.9% were calculated and results were compared with recommendations from National Cholesterol Education Program (NCEP) for total cholesterol measurements. Precision was evaluated by assay of three pooled serum samples with both devices in duplicate in two runs/day for 20 days. The CV for each serum pool for each device was calculated and compared with NCEP recommendations for precision for total cholesterol measurements. Results with the two devices were compared. The total cholesterol mean percent bias for capillary samples was 2.1% for the LDX and -1.0% for the AccuMeter (p<0.01), and for venous samples 1.6 and -2.0%, respectively (p<0.001). The mean absolute percent bias for capillary samples was 5.4 and 5.2%, respectively (p=0.29), and for venous samples was 5.0 and 5.7% (p=0.79). Each device had an excessive number (12-22%) of individual results that exceeded NCEP recommended total error for a single cholesterol measurement (+/- 8.9%). In the precision analysis the average CV from all three serum pools was 4.0% and 5.3% for the LDX and AccuMeter, respectively (p<0.05). Thus both devices failed to meet the NCEP recommendation for precision of 3% CV. They both provided total cholesterol results that correctly classified individual patients into appropriate risk groups 95% of the time or better if values within +/- 8.9% of NCEP cut points for risk classification were ignored. Both devices met the NCEP +/- 3% requirement for total cholesterol mean percent bias but did not meet the +/- 3% requirement for CV as a measure of precision. Because of the variability in results, both devices had excessive numbers of individual subjects with total cholesterol results greater than the recommended total error limit of +/- 8.9% difference from the standardized method. Despite variability in some individual results, the rate of clinical misclassifications for coronary heart disease risk was relatively low for both devices if results near the NCEP cut points were repeated.