Treatment of severe metformin-associated lactic acidosis with renal replacement therapy and tris-hydroxymethyl aminomethane: a case report.

BACKGROUND: Type B lactic acidosis is a rare but serious side effect of metformin use. The risk of metformin-associated lactic acidosis is elevated in renal or liver impairment, heart failure and in metformin overdose. Metformin-associated lactic acidosis is treated with renal replacement therapy although this can be limited by metformin's large volume of distribution and a patient's hemodynamic instability. Tris-hydroxymethyl aminomethane is a buffer that rapidly equilibrates in liver cells and increases the intracellular pH of hepatocytes. Intracellular alkalosis increases lactate uptake by the liver and can promote gluconeogenesis which results in increased lactate metabolism and decreased lactate production. Unlike intravenous bicarbonate which can worsen acidosis due to carbon dioxide retention and hypocalcemia, tris-hydroxymethyl aminomethane does not generate large amounts of carbon dioxide and can improve cardiac contractility in experimental models. CASE PRESENTATION: We present a case of a 43-year-old African American male who intentionally ingested 480,000 g of metformin. He developed severe metformin-associated lactic acidosis that was refractory to 21 hours of high flux hemodialysis. This was followed by an additional 12 hours of high flux hemodialysis augmented by continuous intravenous infusion of tris-hydroxymethyl aminomethane. After initiating tris-hydroxymethyl aminomethane, the patient had rapid reversal of lactic acidosis and was weaned off vasopressors and mechanical ventilation. CONCLUSIONS: While metformin-associated lactic acidosis can be treated with renal replacement therapy, severe cases of lactic acidosis may not be amenable to renal replacement therapy alone. Through its unique buffer mechanisms, tris-hydroxymethyl aminomethane can be used in conjunction with dialysis to rapidly improve acidosis associated with metformin.

Derivation and validation of a prognostic model to predict mortality in patients with advanced chronic kidney disease.

BACKGROUND: Guiding patients with advanced chronic kidney disease (CKD) through advance care planning about future treatment obliges an assessment of prognosis. A patient-specific integrated model to predict mortality could inform shared decision-making for patients with CKD. METHODS: Patients with Stages 4 and 5 CKD from Massachusetts (749) and West Virginia (437) were prospectively evaluated for clinical parameters, functional status [Karnofsky Performance Score (KPS)] and their provider's response to the Surprise Question (SQ). A predictive model for 12-month mortality was derived with the Massachusetts cohort and then validated externally on the West Virginia cohort. Logistic regression was used to create the model, and the c-statistic and Hosmer-Lemeshow statistic were used to assess model discrimination and calibration, respectively. RESULTS: In the derivation cohort, the SQ, KPS and age were most predictive of 12-month mortality with odds ratios (ORs) [95% confidence interval (CI)] of 3.29 (1.87-5.78) for a 'No' response to the SQ, 2.09 (95% CI 1.19-3.66) for fair KPS and 1.41 (95% CI 1.15-1.74) per 10-year increase in age. The c-statistic for the 12-month mortality model for the derivation cohort was 0.80 (95% CI 0.75-0.84) and for the validation cohort was 0.74 (95% CI 0.66-0.83). CONCLUSIONS: Our integrated prognostic model for 12-month mortality in patients with advanced CKD had good discrimination and calibration. This model provides prognostic information to aid nephrologists in identifying and counseling advanced CKD patients with poor prognosis who are facing the decision to initiate dialysis or pursue medical management without dialysis.

Continuous cefazolin infusion versus cefazolin plus probenecid for the ambulatory treatment of uncomplicated cellulitis: A retrospective cohort study.

Background: The preferred ambulatory IV therapy for cellulitis is often once-daily cefazolin combined with once-daily oral probenecid (C+P). However, due to a national probenecid drug shortage in 2011, our centre developed a replacement protocol for the administration of cefazolin continuous infusion (CCI) using elastomeric infusers. Our goal was to compare treatment efficacy, duration of IV therapy, and recurrence associated with CCI and C+P using retrospective data from our centre. Methods: We conducted a non-inferiority single-centre retrospective cohort study of emergency department medical records. Patients received either C+P (cefazolin 2 g IV once daily plus probenecid 1 g PO once daily) or CCI (cefazolin 2 g IV loading dose, followed by cefazolin 6 g IV via continuous infusion over 24 hours, via an elastomeric infuser). We compared treatment efficacy, duration of IV therapy, and recurrence rates. Results:  total of 203 patients were analyzed, with 107 included in the CCI arm and 96 in the C+P arm. Overall, CCI users and C+P users were comparable in their sociodemographic and clinical variables measured at admission. We observed increased odds of achieving successful treatment among the CCI group, however it did not reach statistical significance (odds ratio [OR] 2.25; 95% CI 0.84 to 6.07). Recurrence rates were similar between both groups (OR 1.91; 95% CI 0.32 to 11.31). The average duration of IV therapy was similar between groups (p = 0.6). Conclusions: ith results suggesting that CCI was non-inferior to C+P, and that both approaches required similar treatment durations, CCI could represent an acceptable alternative to C+P for the ambulatory IV treatment of cellulitis.

Historique: Le traitement intraveineux (IV) ambulatoire favorisé pour la cellulite prend souvent la forme d'une injection quotidienne de céfazoline associée à une dose quotidienne de probénécide par voie orale (PO) (C+P). Cependant, à cause d'une pénurie nationale de probénécide en 2011, le centre des auteurs a mis au point un autre protocole de perfusion continue de céfazoline (PCC) à l'aide de perfuseurs élastomériques. Les auteurs ont comparé l'efficacité du traitement, la durée du traitement IV et la récurrence associée à la PCC et aux C+P à partir des données rétrospectives du centre. Méthodologie: Les auteurs ont réalisé une étude de cohorte rétrospective monocentrique de non-infériorité à partir des dossiers médicaux du département d'urgence. Les patients ont reçu soit des C+P (2 g de céfazoline IV une fois par jour associés à 1 g de probénécide PO une fois par jour), soit une PCC (dose de charge de 2 g de céfazoline IV, suivie d'une perfusion continue de 6 g de céfazoline IV par perfuseur élastomérique sur une période de 24 heures). Ils ont comparé l'efficacité thérapeutique, la durée du traitement IV et le taux de récurrence. Résultats: Au total, les auteurs ont analysé 203 patients, dont 107 faisaient partie du volet de PCC et 96, du volet de C+P. Dans l'ensemble, les utilisateurs de la PCC et des C+P présentaient des variables sociodémographiques et cliniques semblables à l'admission. Les auteurs ont observé que le traitement du groupe sous PCC avait tendance à être plus efficace, mais cette constatation n'était pas statistiquement significative (rapport de cotes [RC] 2,25; IC à 95 %, 0,84 à 6,07). Les taux de récurrence étaient semblables entre les deux groupes (RC 1,91; IC à 95 %, 0,32 à 11,31). La durée moyenne du traitement IV était semblable entre les groupes (p = 0,6). Conclusions: Puisque, selon les résultats, la PCC n'était pas inférieure aux C+P et que la durée du traitement était semblable dans les deux cas, il serait acceptable comme traitement de rechange acceptable de C+P pour le traitement IV ambulatoire de la cellulite.

Effects of prolonged ethanol lock exposure to carbothane- and silicone-based hemodialysis catheters: a 26-week study.

PURPOSE: Antibiotic locks in catheter-dependent chronic hemodialysis patients reduce the rate of catheter-related bloodstream infections (CRBSIs), but may be associated with the development of resistant bacteria. Ethanol-based catheter locks may provide a better alternative; however, there are limited data on the long-term integrity of dialysis catheters exposed to ethanol. METHODS: We performed in vitro testing of two types of hemodialysis catheters­silicone (SLC) and carbothane (CBT) based­with a 70% ethanol lock (EL) versus heparin lock (HL) for 26 weeks. Lock solutions were changed thrice weekly to mimic a conventional hemodialysis schedule. We tested mechanical properties of the catheters at 0, 13 and 26 weeks by examining stress/strain relationships (SS400%) and modulus of elasticity (ME). Electron microscopy was performed to examine catheter ultrastructure at 0 and 26 weeks. RESULTS: Catheter integrity for HL versus EL in SLC (SS400%: 4.5 vs. 4.5 MPa, p = NS; ME: 4.6 vs. 4.7 MPa, p = NS) or CBT-based catheters (SS400%: 7.6 vs. 8.9 MPa, p = NS; ME: 9.6 vs. 12.2 MPa, p = NS) were all similar at 13 and 26 weeks. Scanning electron microscopy revealed no structural changes in the central and luminal wall internal surfaces of EL- versus HL-treated catheters. CONCLUSIONS: There were no significant differences in catheter integrity between SLC or CBT catheters exposed to a 70% EL for 26 weeks. Given its low cost, potential to avoid antibiotic resistance and structural integrity after 6 months of high-dose ethanol, ELs should be studied prospectively against antibiotic locks to assess the efficacy and safety in hemodialysis patients.

Emergence of gentamicin-resistant bacteremia in hemodialysis patients receiving gentamicin lock catheter prophylaxis.

BACKGROUND AND OBJECTIVES: Antibiotic locks in catheter-dependent chronic hemodialysis patients reduce the rate of catheter-related blood stream infections (CRIs), but there are no data regarding the long-term consequences of this practice. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Over a 4-year period, from October 1, 2002, to September 30, 2006, we initiated a gentamicin and heparin lock (GHL) protocol in 1410 chronic hemodialysis patients receiving dialysis through a tunneled catheter in eight outpatient units. RESULTS: Within the first year of the GHL protocol, our CRI rate decreased from 17 to 0.83 events per 1000 catheter-days. Beginning 6 months after initiation of the GHL protocol, febrile episodes occurred in 13 patients with coagulase-negative Staphylococcus bacteremia resistant to gentamicin. Over the 4 years of GHL use, an additional 10 patients developed 11 episodes of gentamicin-resistant CRI (including 7 with Enterococcus faecalis), in which there were 4 deaths, 2 cases of septic shock requiring intensive care unit admission, and 4 cases of endocarditis. Because of these events, the GHL protocol was discontinued at the end of 2006. CONCLUSIONS: Although the use of GHL effectively lowered the CRI rate in our dialysis population, gentamicin-resistant CRIs emerged within 6 months. Gentamicin-resistant infections are a serious complication of the long-term use of GHLs. Alternative nonantibiotic catheter locks may be preferable to decrease the incidence of CRIs without inducing resistant pathogens.