Faculty Bibliography

CONTEXT/BACKGROUND:Despite the risk of aluminum (Al) toxicity in dialysis patients, little is known about its toxicokinetics (TK) in this population. A national contamination of dialysate solutions with Al provided the opportunity to study Al TK in peritoneal dialysis (PD) patients and to better understand the influence of covariates on its disposition. METHODS:Al levels in serum and dialysate as well as other laboratory values were collected prospectively from 83 PD patients after correction of Al contamination. Population TK analyses were conducted with NONMEM VI using standard model discrimination criteria. Covariate analyses were also performed using stepwise forward regression followed by backward deletion. RESULTS:After correction of Al exposure, serum levels declined in a biphasic manner, which was captured by the TK model. The TK of Al were best described by a 2-compartment model with linear elimination. Total creatinine clearance was a significant covariate for total clearance (CL). Mean parameter estimates for volume of central compartment (V1), CL, volume of peripheral compartment (V2), volume of distribution at steady-state (Vss), and intercompartmental clearance (Q) were 168 L, 8.99 L/day, 12 000 L, 12 168 L, and 4.93 L/day, respectively. Inter-individual variability for CL and V2 were 22.6 and 51.1%, respectively. Al distributional half-life was 8.5 days, while the terminal elimination half-life was 7.2 years. This model confirms that the large Vss reflects the widespread distribution of Al in bone, lungs, liver, and other tissues. CONCLUSION/CONCLUSIONS:This study describes the first population Al TK model in a large group of PD patients, which includes a covariate effect. The model confirms the extensive half-life and tissue distribution of Al in a dialysis-dependent population.

Contrary to popular opinion, application of extracorporeal therapies for poisonings predates their use for ESRD. Despite this observation, the science of blood purification in toxicology remains desperately stagnant today. In fact, much of our current knowledge is derived from George Schreiner's 1958 review. Original publications are almost exclusively composed of case reports and case series, from which good inference is impossible. Until randomized controlled trials become available, the medical community would be well served by a group mandated to systematically review available literature, extract relevant information, provide recommendations based on current evidence, and propose research initiatives. The EXtracorporeal TReatments In Poisoning workgroup, formed by several international experts in different medical fields and represented by over 20 societies, now has this mission

We describe the case of a 42-year-old female who presented to our care 1 hour after ingesting 3.6 g of phenytoin. She was stuporous 48 hours after admission despite supportive therapy. She was treated with hemodialysis (HD) for nearly 6 hours in order to remove phenytoin. Her level of consciousness improved markedly during the procedure. During HD, phenytoin levels decreased by 47% and measured half-life was 6.8 hours as compared to 116 hours when not on HD. Finally, we were able to remove 547 mg of phenytoin (directly measured from the dialysate), representing approximately a third of estimated body stores. The use of extracorporeal therapy in phenytoin overdose is reviewed here. We believe that in severe cases of phenytoin intoxication, hemodialysis can be used to accelerate total body burden of the drug, even if protein binding is significant.

CONTEXT/BACKGROUND:Lithium (Li) is a first-line treatment for bipolar disorder but has a narrow therapeutic index. Treatment of Li toxicity includes supportive measures and hemodialysis in severe cases, but this modality is not always immediately available. Sodium polystyrene sulfonate (SPS, Kayexalate), a cation exchanger, has been promising in animal models and human reports to reduce absorption and enhance elimination of Li. MATERIAL AND METHODS/METHODS:A retrospective cohort study was conducted. All cases of chronic Li intoxication were reviewed in two adult-care hospitals from 2000 to 2009. A group comparison and a within-patient comparison were performed to compare the effect of SPS on the median Li half-life (T(1/2)). For this study, at least three serum Li levels were required for T(1/2) calculations. RESULTS:Forty-eight patients met inclusion requirements, 12 of whom had taken SPS. Median Li T(1/2) in the treated and control groups was 20.5 and 43.2 hours, respectively (p = 0.0006). In the 12 treated patients, Li T(1/2) during SPS was on average 48.9% shorter than without SPS. Furthermore, in one subject in whom urinary Li data were available, Li clearance with SPS was superior to Li renal clearance. Prolonged constipation was noted in one patient whereas mild hypokalemia was noted in six patients treated with SPS. CONCLUSION/CONCLUSIONS:This study shows that SPS reduced Li T(1/2) and suggests that SPS is capable of promoting Li elimination in chronic intoxications. These results warrant a prospective trial looking at the use of SPS in the treatment of Li overdose as an adjunct to supportive measures and hemodialysis.

BACKGROUND/AIMS/OBJECTIVE:Vascular access-related bloodstream infection (BSI) is frequent among patients undergoing hemodialysis increasing their morbidity and mortality, but its occurrence across various dialysis centre types is not known. The aims of this study were to describe the incidence rates and assess the variability in BSI risk between dialysis centre types and other centre-level variables. METHODS:We conducted a retrospective cohort study of 621 patients initiating hemodialysis in 7 Canadian dialysis centres. Cox regression models, where access type was continuously updated, were used to identify predictors of BSI occurrence. RESULTS:During follow-up of the cohort (median age 68.1 years, 41.7% female, and 76.7% initiating with a central venous catheter, CVC), 73 patients had a BSI (rate: 0.21/1000 person-days). The BSI risk was not different in First Nation units (adjusted relative risk: 0.47, 95% confidence interval: 0.06-3.72) and teaching hospitals (1.33, 0.70-2.54) compared to community hospitals. No other centre-related variables were associated with the risk of BSI. CONCLUSION/CONCLUSIONS:We did not find differences in the BSI risk among dialysis unit types, or any other centre-related variables. The rates of BSI in our population were lower than those observed in other settings, but the high proportion of patients using CVCs is concerning.

Background. Controversy exists with volume resuscitation using crystalloids or colloids. Renal dysfunction has been reported with some colloids and osmotic agents, but remains poorly defined. Patient. We report the case of a 67-year-old male who had normal kidney function at baseline and who developed anuric ARF in relation to the administration of >10 litres of 10% pentastarch. A renal biopsy confirmed hydropic changes in tubular cells compatible with colloid-induced damage. Conclusion. This case demonstrates that hydroxyethyl starch preparations may be associated with acute kidney injury, and one should carefully consider their use, especially in patients with pre-existing renal dysfunction. Osmotic tubular cell lesions may be long lasting and irreversible.

OBJECTIVE:Hypophosphatemia often occurs during continuous renal replacement therapy (CRRT). The addition of phosphate to dialysate and replacement solutions facilitates phosphate handling, but the risk of precipitation with calcium within these solutions has not been addressed. DESIGN AND SETTING/METHODS:Experimental study with a retrospective observational study in a medico-surgical intensive care unit. METHODS AND PATIENTS/METHODS:We tested the addition of phosphate to calcium-rich lactate- and bicarbonate-based solutions (Hemosol LG2 and Hemosol B0) used in CRRT to see whether precipitation occurs. Two milliliters of potassium phosphate added to 5-l bags gives a physiological phosphate concentration of 1.2 mmol/l. In addition, calcium and phosphate homeostasis was retrospectively evaluated in 20 consecutive CRRT patients where potassium phosphate had been added to these solutions. MEASUREMENTS AND RESULTS/RESULTS:Total and ionized calcium, phosphate, pH, PCO(2) and bicarbonate remained essentially unchanged 5 h after the addition of 2 ml of potassium phosphate to 5-l Hemosol solutions. Visual inspection did not reveal any precipitate. Of the 20 patients studied, 14 received more than 24 h of phosphate supplementation to dialysate and replacement solutions. Phosphate remained stable throughout CRRT despite phosphate intake from nutrition in 11 cases. No adverse event was noted on potassium, calcium, pH and bicarbonate homeostasis. CONCLUSIONS:The addition of phosphate to Hemosol solutions does not precipitate with the calcium within these solutions. This practical method effectively prevents hypophosphatemia in CRRT patients.