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Background: The need to determine physical compatibility of intravenous admixtures is directly related to patient safety and patient outcomes. While the provision of multi-modal analgesic strategies has increased over the past decade, a paucity of data exists regarding physical compatibility of select medications. Objectives: To evaluate the physical compatibility of methocarbamol in Lactated Ringer's (LR), 0.45% normal saline (0.45% NaCl), and Plasma-Lyte A (PLA) at concentrations of 4, 10, and 20 mg/mL. Methods: Admixtures were prepared and evaluated using previously validated methods under a laminar flow hood using aseptic technique. Samples were prepared in a triplicate manner, 3 mL aliquots were placed into polymethyl methacrylate cuvettes for evaluation at time points 0, 1, 5, 8, and 24 hours. Visual inspection of samples included assignment of a number: 0—no precipitation, 1—trace evidence of precipitation, 2—slight haze, 3—medium haze, and 4—heavy precipitation. Any evidence of precipitation was considered significant. A variable wavelength spectrophotometer set at 547 nanometers was used to measure absorbance. A change in absorbance of ±0.010 was considered significant. A change in pH of ±0.1 was considered significant. Results: No significant changes occurred relating to visual inspection or absorbance across all concentrations and time points for LR; however, there was a significant change in pH across all concentrations at hour 5. In 0.45% NaCl and PLA, no remarkable changes occurred across all concentrations and time points regarding visual observation, spectrophotometric absorbance, and pH analysis. Conclusions: Methocarbamol at concentrations of 4, 10, and 20 mg/mL is physically compatible for up to 1 hour in LR. Methocarbamol is physically compatible in 0.45% NaCl and PLA for up to 24 hours. Chemical stability tests are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Background. In 2006, there were 16 796 toxic exposures attributed to valproic acid (VPA), carbamazepine (CBZ) and phenytoin (PHT) reported to the US Toxic Exposure Surveillance System. Of these, 30% (5046) were treated in a health care facility with 12 cases resulting in death. These drugs are highly protein bound and poorly dialyzable; however, it has been suggested that albumin-supplemented dialysate may enhance dialytic clearance. We investigated whether the addition of albumin to dialysate affects dialytic clearance of VPA, CBZ and PHT. Methods. VPA, CBZ and PHT were added to a bovine blood-based in vitro continuous hemodialysis circuit, which included a polysulfone or an AN69 hemodialyzer. VPA, CBZ and PHT clearances were calculated from spent dialysate and pre-dialyzer plasma concentrations. VPA, CBZ and PHT clearances with control (albumin-free) dialysate were compared to clearances achieved with 2.5% or 5% human albumin-containing dialysate. The influences of blood flow (180 and 270 mL/min) and dialysate flow (1, 2 and 4 L/h) on dialysis clearance were also assessed. Results. The addition of 2.5% albumin to dialysate significantly enhanced dialytic clearance of VPA and CBZ, but not PHT. Use of 5% albumin dialysate further increased VPA and CBZ clearance. Overall, drug clearance was related directly to dialysate flow but independent of blood flow. Conclusion. Continuous hemodialysis with albumin-supplemented dialysate significantly enhanced VPA and CBZ, but not PHT, clearance compared to control dialysate. Continuous hemodialysis with albumin-supplemented dialysate may be a promising therapy to enhance dialytic clearance of selected highly protein-bound drugs. [ABSTRACT FROM AUTHOR]

Background. Continuous renal replacement therapy (CRRT) increasingly is being used to treat critically ill patients with renal disease. CRRT removes waste products but also nutrients. Our understanding of trace element CRRT clearance has been limited by poor assay sensitivity. The development of inductively coupled plasma mass spectrometry (ICP–MS) allows for the measurement of CRRT trace element removal. Methods. Continuous venovenous haemodialysis (CVVHD) transmembrane clearances of trace elements and urea were assessed using a bovine blood-based in vitro model using two different haemodialyser types. These findings were validated in 10 critically ill adult patients receiving continuous venovenous haemodiafiltration (CVVHDF). Calculated daily trace element loss was compared with a typical dose of daily trace element supplementation. Results. The mean ± SD in vitro CVVHD transmembrane clearances (ml/min) for the polysulfone haemodialyser were chromium 0.97 ± 0.23, copper 0.47 ± 0.18, manganese 4.6 ± 3.6, selenium 1.2 ± 0.63 and zinc 2.3 ± 0.32 and for the cellulose diacetate haemodialyser chromium 1.54 ± 0.91, copper 0.21 ± 0.07, manganese 7.8 ± 4.1, selenium 0.76 ± 0.39 and zinc 2.7 ± 0.37. The in vivo CVVHDF transmembrane clearances (ml/min) were chromium 5.4 ± 2.4, copper 0.45 ± 0.33, manganese 1.9 ± 4.6, selenium 1.6 ± 1.2, and zinc 4.0 ± 1.3. Conclusion. ICP–MS assays detected the five trace elements in the effluent of CVVHDF patients. Trace element CVVHD transmembrane clearance estimates for our in vitro model were supported by the in vivo CVVHDF findings. Calculated daily trace element loss attributed to CVVHD and CVVHDF with dialysate flow rates of 33.3 ml/min is less than what is provided in a daily dose of a trace element supplementation product. [ABSTRACT FROM AUTHOR]

Background: Catheters provide vascular access for patients requiring intravenous treatments, but frequently are a source of infection and/or thrombosis. Instilling a solution of an antimicrobial agent with an anticoagulant into the catheter lumen may salvage-infected catheters. Objective: The aim is to evaluate the physical compatibility, antibacterial activity, and stability of varying combinations of cefazolin (10 mg/mL), 40% ethanol, 4% sodium citrate with or without gentamicin (1 mg/mL) as a catheter lock solution over 48 h. Methods: Admixtures were prepared using aseptic technique and stored under four conditions with or without light at 25°C or 37°C. Prepared admixtures were assessed for physical compatibility, antimicrobial susceptibility, and chemical stability in triplicate at 0, 24 and 48 h. Admixture physical compatibility was determined by visual clarity, pH, and ultraviolet (UV) spectroscopy. Antibacterial activity was determined using the Kirby-Bauer disk diffusion method. The chemical stability of cefazolin and gentamicin were assessed using high performance liquid chromatography and UV spectroscopy, respectively. Results: All admixtures maintained clarity for 48 h. All admixtures stored at 25°C and the admixture containing 10 mg/mL cefazolin-4% sodium citrate stored at 37°C sustained antimicrobial activity and were chemically stable. A significant change in pH, antimicrobial activity, cefazolin concentration (<95% of baseline), were observed in admixtures containing ethanol stored at 37°C after 24 h. Gentamicin concentrations remained stable throughout the study. Conclusion: The admixture of 10 mg/mL cefazolin-4% sodium citrate sustained antimicrobial activity over 48 h and was chemically stable. However, admixtures containing ethanol stored at 37°C showed incompatibility with decreased antibacterial activity and cefazolin degradation after 24 h. [ABSTRACT FROM AUTHOR]

Background: Indwelling catheters deliver lifesaving medical treatments for many chronically ill patients but are frequently a source of infection. Treatment may include an antimicrobial agent(s) and anticoagulant solution dwelling within the catheter. In vitro determinations of solution compatibility and stability are necessary prior to use in patients. Objective: The aim of this study was to determine the physical compatibility, chemical stability, and antimicrobial activity of vancomycin (5 or 10 mg/mL) with gentamicin (1 mg/mL) or 40% ethanol in 4% sodium citrate lock solution over 72 hours. Methods: All solutions were prepared per manufacturer's instructions. Samples were studied under 4 conditions: (1) 25°C with light, (2) 25°C without light, (3) 37°C with light, and (4) 37°C without light. Physical compatibility and chemical stability were assessed at 0, 24, 48, and 72 hours. Antimicrobial susceptibility testing was conducted at 0 and 72 hours. All studies were carried out in triplicate. Results: All solution combinations under each condition remained patent from baseline to 48 hours. One solution combination of vancomycin (5 mg/mL) and ethanol (40% v/v) in 4% sodium citrate revealed a slight turbidity at 72 hours. Clarity and pH remained stable in all other solutions during the entire study period. Chemical compatibility and antibiotic activity ranged from 95% to 105% and 95% to 106% of initial baseline values, respectively, for all solutions under 4 storage conditions. Conclusions: All antibiotic-anticoagulant lock solutions were found to be physically, chemically, and microbiologically stable during the 72-hour study period except vancomycin (5 mg/mL) and ethanol (40% v/v) in 4% sodium citrate solution which showed slight turbidity at 72 hours. [ABSTRACT FROM AUTHOR]

Background/Aims: With advanced anticoagulation, many institutions operate continuous renal replacement therapy (CRRT) circuits longer than manufacturers' recommendations. This extended use may change hemodiafilter performance and clearance properties. However, hemodiafilter performance over time has not been assessed. We investigated solute clearance over time in modeled CRRT. Methods: In vitro continuous hemofiltration (CH) and continuous hemodialysis (CD) were operated for 48 h using AN69 polyacrylonitrile, cellulose triacetate, F70 polysulfone, and Optiflux F160NR polysulfone hemodiafilters with citrated bovine blood. Urea, creatinine, gentamicin, vancomycin, and albumin clearances were assessed in CH (ultrafiltration rates = 1 and 3 l/h). Clearances of urea, creatinine, gentamicin, and albumin, were assessed in CD with dialysate flow rate of 2 l/h. Results: Solute CH clearances were significantly higher at 3 l/h. Only creatinine and gentamicin clearances were affected by time. Creatinine CD clearance significantly declined at 48 h for all hemodiafilters, especially polysulfone hemodiafilters. Conclusions: CRRT duration affects solute transmembrane clearance. Clinicians should consider hemodiafilter age when assessing hemodialysis dose or drug clearance. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Continuous renal replacement therapy (CRRT) is used to treat critically ill children with acute kidney injury. The effect of CRRT on trace element clearance is poorly characterized. The purpose of this study was to quantify the transmembrane clearance of chromium, copper, manganese, selenium and zinc during continuous venovenous hemodiafiltration (CVVHDF). The transmembrane clearance of trace elements was assessed prospectively in five critically ill children receiving CVVHDF at the pediatric intensive care unit of a tertiary care university hospital. Pre-filter blood and effluent samples were measured for trace element concentrations. Transmembrane clearance of trace elements was calculated, and daily loss of each trace element was determined. Daily trace element loss via CVVHDF was compared with daily standard supplementation of trace elements in pediatric parenteral nutrition. Five patients (age range 23 months to 15 years) with a body weight range of 10.5–53 kg completed the study. The median transmembrane clearance of chromium, copper, manganese, selenium and zinc during CVVHDF was calculated as 0 ml, 0.59 ml, 2.48 ml, 1.22 ml, and 1.90 ml, respectively, per 1.73 m2 body surface area per minute. The calculated CVVHDF losses were substantially smaller than the daily parenteral supplementation for all trace elements. [ABSTRACT FROM AUTHOR]

Continuous renal replacement therapy (CRRT) has given clinicians an important option in the care of critically ill patients. The slow and continuous dialysate and ultrafiltrate flow rates that are employed with CRRT can yield drug clearances similar to an analogous glomerular filtration rate of the native kidneys. Advantages such as superior volume control, excellent metabolic control, and hemodynamic tolerance by critically ill patients are well documented, but an understanding of drug dosing for CRRT is still a bit of a mystery. Although some pharmaceutical companies have dedicated postmarket research in this direction, many pharmaceutical companies have chosen not to pursue this information as it is not mandated and represents a relatively small part of their market. This lack of valuable information has created many challenges in the care of the critically ill patient as intermittent hemodialysis drug dosing recommendations cannot be extrapolated to CRRT. This drug dosing review will highlight factors that clinicians should consider when determining a pharmacotherapy regimen for a patient receiving CRRT. [ABSTRACT FROM AUTHOR]

Pharmacotherapy plays an important role in the care of a chronic kidney disease (CKD) patient but delivering this therapy can be challenging. Besides alterations in the pharmacokinetic parameters of absorption, distribution, metabolism and elimination, the average CKD patient must take multiple medications each day. The likelihood of an adverse drug reaction increases with each medication added to these patients' daily regimen. In this article we discuss selected pharmacokinetic issues unique to CKD patients. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]