Evaluation of the Fast Prior Authorization Technology Highway.

BACKGROUND: Prior authorization (PA) is a utilization management tool used by health plans and pharmacy benefit managers where the payer requires additional documentation from health care providers before authorization of payment for a medication or procedure. PA processes are hypothesized to be more efficient if electronic transmission is utilized instead of manual submission. OBJECTIVE: To evaluate the impact of electronic PA (ePA) on approval rate and time to decision and to assess health care provider perception of using ePA. METHODS: America's Health Insurance Plans selected 2 technology companies, Availity and Surescripts, and used an independent research organization (Research Triangle Institute [RTI]) to conduct a provider survey and analyze over 40,000 PA transactions from participating health plans. RTI examined processing time, provider experience, and other measures for PAs both before and after provider implementation of ePA. RESULTS: Providers used these tools for roughly 62% of PAs in the 6 months after implementation. The median time from PA request to decision fell from 18.7 hours to 5.7 hours. Providers using ePA reported observing some benefits relative to the number of phone calls and faxes required after ePA implementation. CONCLUSION: The primary benefit of ePA implementation was reduced time to decision. Additional benefits may occur with greater adoption since 38% of PAs were still manual after implementation of ePA.

Vibration enhances clearance of solutes with varying molecular weights during in vitro hemodialysis.

This proof of concept pilot study was performed to determine whether vibration can increase solute clearance when applied to an in vitro dialysis model. Urea, creatinine, gentamicin, and vancomycin transmembrane clearances were calculated at a blood flow rate of 200 ml/min, dialysate flow rates of 2 and 8 L/hr, and no concurrent ultrafiltration at various vibration intensities. Dialyzer integrity was determined by measuring transmembrane pressure, filter drop pressure, and albumin clearance, and by visually inspecting the dialysate. Comparing the highest vibration modality with no vibration, the median percentage increase in urea, creatinine, gentamicin, and vancomycin clearance was 18% (all p < 0.005). The transmembrane clearance of albumin was negligible for all experiments. When measuring transmembrane pressure and filter drop pressure, no significant differences were found between nonvibration and vibration dialysis. The addition of vibration during dialysis increased transmembrane clearance for solutes with molecular weights of 60-1450 Daltons.

Drug dosing consideration in patients with acute and chronic kidney disease-a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO).

Drug dosage adjustment for patients with acute or chronic kidney disease is an accepted standard of practice. The challenge is how to accurately estimate a patient's kidney function in both acute and chronic kidney disease and determine the influence of renal replacement therapies on drug disposition. Kidney Disease: Improving Global Outcomes (KDIGO) held a conference to investigate these issues and propose recommendations for practitioners, researchers, and those involved in the drug development and regulatory arenas. The conference attendees discussed the major challenges facing drug dosage adjustment for patients with kidney disease. In particular, although glomerular filtration rate is the metric used to guide dose adjustment, kidney disease does affect nonrenal clearances, and this is not adequately considered in most pharmacokinetic studies. There are also inadequate studies in patients receiving all forms of renal replacement therapy and in the pediatric population. The conference generated 37 recommendations for clinical practice, 32 recommendations for future research directions, and 24 recommendations for regulatory agencies (US Food and Drug Administration and European Medicines Agency) to enhance the quality of pharmacokinetic and pharmacodynamic information available to clinicians. The KDIGO Conference highlighted the gaps and focused on crafting paths to the future that will stimulate research and improve the global outcomes of patients with acute and chronic kidney disease.

Longitudinal hemodiafilter performance in modeled continuous renal replacement therapy.

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.

Continuous venovenous hemodiafiltration trace element clearance in pediatric patients: a case series.

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 m(2) body surface area per minute. The calculated CVVHDF losses were substantially smaller than the daily parenteral supplementation for all trace elements.

Enhanced clearance of highly protein-bound drugs by albumin-supplemented dialysate during modeled continuous hemodialysis.

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.

The epidemiology of drug-induced disorders: the kidney.

The epidemiology of drug-induced renal disorders is a complex topic. Drug-associated nephrotoxicity accounts for 18 - 27% of all acute kidney injury cases in US hospitals. Medications can affect all aspects of the kidney, and drugs that are associated with renal dysfunction are used commonly in clinical practice. The article reviews six major mechanisms of drug-induced renal dysfunction as well as lists the major medications involved. NSAIDs, aminoglycosides, amphotericin B and calcineurin inhibitors are just some examples of drugs that contribute to renal dysfunction. The medical community must be aware of patient risk factors for nephrotoxicity, as well as the drug's inherent nephrotoxic potential, when prescribing and administering medications.

Enhanced photoemission spectroscopy for verification of high-risk i.v. medications.

PURPOSE: The sensitivity and specificity of enhanced photoemission spectroscopy (EPS) for performing an automated final check of compounded i.v. admixtures at a pediatric hospital pharmacy were studied. METHODS: A tabletop EPS device was used to test samples of seven high-risk drug-diluent combinations compounded in the pharmacy; the drugs were vancomycin, lorazepam, morphine, insulin, hydromorphone, gentamicin, and epinephrine. Ten sets of samples were prepared for each drug. Typically, a sample set consisted of dilutions ranging from 10-fold above to 10-fold below the targeted concentration. Testing was performed twice weekly between November 2005 and March 2006. RESULTS: The EPS device detected errors departing from the targeted concentration by 20% or more with a sensitivity of at least 95%. Specificity in distinguishing among test medications at targeted concentrations was 100%. The percentage of passing samples with intermediate concentrations varied among the drugs. CONCLUSION: A tabletop EPS device demonstrated acceptable sensitivity and specificity for validating the identity and concentrations of selected high-risk i.v. medications compounded for pediatric patients. The device may help prevent clinically important medication errors caused by inaccurate compounding.

Trace element removal during in vitro and in vivo continuous haemodialysis.

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.

Daptomycin clearance during modeled continuous renal replacement therapy.

BACKGROUND/AIMS: Pharmacotherapy in critically ill patients receiving continuous renal replacement therapies (CRRT) is challenging due to the lack of published information to base dosing regimens. METHODS: Daptomycin's transmembrane clearance during continuous hemofiltration and hemodialysis was assessed using an in vitro model with AN69 and polysulfone hemodiafilters at varying ultrafiltrate and dialysate flow rates (1, 2, 3 and 6 l/h). RESULTS: During continuous hemofiltration, mean daptomycin sieving coefficient ranged from 0.14 to 0.20. Transmembrane clearances were significantly different between filter types for ultrafiltration rates of 2, 3 and 6 l/h. For continuous hemodialysis, mean daptomycin saturation coefficient ranged from 0.05 to 0.15. AN69-based daptomycin clearances were significantly lower than polysulfone values at dialysate flow rates of 2, 3 and 6 l/h. CONCLUSION: The extent of daptomycin's transmembrane clearance is dependent on hemodiafilter type, dialysate and ultrafiltration rates. CRRT with high ultrafiltrate or dialysate rates may result in substantial daptomycin clearances.

Hyperosmolar solutions in continuous renal replacement therapy for hyperosmolar acute renal failure: a preliminary report.

OBJECTIVE: To demonstrate the efficacy of hyperosmolar dialysis and prefilter replacement fluid solutions for continuous renal replacement therapies in the correction of hyperosmolar disorders in acute renal failure. DATA SOURCE: An Institutional Review Board-approved pediatric acute renal failure database at the University of Michigan C. S. Mott Children's Hospital. STUDY SELECTION: Three patients were identified meeting the inclusion criteria. The mean serum sodium concentration and plasma osmolality were 158 mmol/L and 357 mOsm/kg, respectively, at the time of initiation of renal replacement therapy. The sodium and/or dextrose concentrations of the dialysate or replacement fluids initially were increased and subsequently decreased to affect the solutions' calculated osmolalities in an effort to control the rate of decline of the patients' measured plasma osmolalities. DATA EXTRACTION: The case patients' serum sodium concentrations and plasma osmolalities were measured. Additionally, the sodium and dextrose concentrations of the dialysate or replacement fluid were recorded and the solutions' osmolalities calculated. DATA SYNTHESIS: The three patients experienced a mean rate of reduction of their serum sodium concentration and plasma osmolality of 0.5 mmol/L/hr and 1.6 mOsm/kg/hr, respectively. CONCLUSIONS: Hyperosmolar dialysis or prefilter replacement fluid solutions can affect a slow decline in both the serum sodium and plasma osmolality in cases of hyperosmolar acute renal failure.

In vitro clearance of trace elements via continuous renal replacement therapy.

OBJECTIVE: Trace element loss during continuous renal replacement therapy in patients with acute renal failure has not been quantified sufficiently. DESIGN: Trace element loss was quantified using an in vitro model of continuous venovenous hemofiltration. Bovine blood was used for the experiment, and the plasma was analyzed for its chromium, copper, selenium, manganese, and zinc content. Two different polysulfone hemodiafilters, a low-flux F8 and high-flux F70 were used, and tested at two different ultrafiltrate flow rates of 1 L/hr and 2 L/hr, respectively. Trace element concentrations in the plasma and ultrafiltrate were analyzed using inductively coupled plasma mass spectrometry. The sieving coefficient and clearance of each trace element were calculated and compared between the two hemodiafilters. SETTING: In vitro bovine model of continuous venovenous hemofiltration. PATIENTS OR OTHER PARTICIPANTS: Not applicable. RESULTS: Mean sieving coefficients of both F8 and F70 hemodiafilters were similar for each trace element. Copper, chromium, manganese, selenium, and zinc all were detected in the ultrafiltrate. Estimated trace element loss using typical trace element blood concentrations and study-derived sieving coefficients suggest that daily losses of selenium are greater than what is replenished with a standard daily trace element supplement in total parenteral nutrition. CONCLUSION: These data suggest that the degree of continuous venovenous hemofiltration clearance chromium, copper, selenium, manganese, and zinc differ between elements and that selenium and copper might need to be replaced with doses that exceed typical supplementation guidelines.

Pre dialysis of blood prime in continuous hemodialysis normalizes pH and electrolytes.

In critically ill children weighing <10 kg, it is necessary to use blood as a priming solution for the extracorporeal continuous renal replacement therapy (CRRT) circuit before initiating CRRT to prevent hemodilution and maintain adequate oxygenation. However, blood bank blood usually contains supra-physiological electrolyte concentrations and a non-physiological acid-base balance that may exacerbate the patient's condition. The objective of this trial was to develop a simple protocol to pre-treat blood bank-derived blood to yield a more physiological blood priming solution. Expired human blood in a recirculating in vitro CRRT circuit was dialyzed prior to the initiation of CRRT using a physiological dialysate solution. Serial blood samples were assessed for electrolyte and pH content. Regimens using maximal blood flow rates (180-200 ml/min) and aggressive dialysate flow rates (33-42 ml/min) were able to correct severely hyperkalemic and acidemic blood within 7.5 min. Initially elevated blood potassium concentrations >20 mEq/l were normalized to below 5 mEq/l within 7.5 min of dialysis in all cases. Blood bank-derived blood can be "conditioned" quickly to physiological pH and electrolyte concentrations using these simple pre-dialysis regimens. Unlike some blood preparation regimens that have been published, the technique used in this trial requires no special equipment or added medications that are not already used in CRRT.

Higher renal replacement therapy dose delivery influences on drug therapy.

Higher doses of renal replacement therapy have profound effects on pharmacotherapy, yet little research has been conducted in this area. High-volume renal replacement therapies influence both the pharmacokinetic and the pharmacodynamic profiles of all drugs administered to these critically ill patients. Intermittent high-dose "hybrid" hemodialysis therapies remove drugs to a much different degree than standard thrice-weekly hemodialysis, yet pharmacokinetic studies have not been performed in patients receiving these therapies. High-volume continuous renal replacement therapies offer dosing challenges not seen with standard low-dose therapies. This article describes the pharmacokinetic and pharmacodynamic issues presented by high-volume renal replacement therapies. Given the importance that pharmacotherapy has on optimal patient outcomes, a better understanding of the influence that high-volume renal replacement therapy has on drugs is essential if these high volume therapies are to be used successfully in the intensive care unit.

Linezolid clearance during continuous venovenous hemodiafiltration: a case report.

OBJECTIVE: To determine the linezolid clearance and serum concentrations in a critically ill man receiving continuous venovenous hemodiafiltration (CVVHDF). METHODS: Intravenous linezolid 600 mg every 12 hours was administered to a critically ill, 85-year-old man with anuria who was receiving CVVHDF at a dialysate flow rate of 2000 ml/hour and a mean ultrafiltrate production rate of 775 ml/hour. Samples of blood and spent dialysate and ultrafiltrate were obtained at the time of linezolid peaks and troughs, and linezolid concentrations were determined. RESULTS: The CVVHDF yielded a mean linezolid clearance of 36.5 ml/minute and an elimination half-life of 7.5 hours. The linezolid saturation coefficient ranged from 0.77-0.81. Administration of intravenous linezolid 600 mg every 12 hours yielded suitable serum trough concentrations. CONCLUSION: Administration of intravenous linezolid 600 mg every 12 hours maintained therapeutic serum trough concentrations in this critically ill patient receiving CVVHDF.