Treatment of Metformin Intoxication Complicated by Lactic Acidosis and Acute Kidney Injury: The Role of Prolonged Intermittent Hemodialysis

Metformin intoxication with lactic acidosis, a potentially lethal condition, may develop in diabetic patients when the drug dose is inappropriate and/or its clearance is reduced. Diagnosis and therapy may be delayed due to nonspecific symptoms at presentation, with severe anion gap metabolic acidosis and elevated serum creatinine values being the most prominent laboratory findings. Confirmation requires measurement of serum metformin by high-performance liquid chromatographyâ\u80\u93tandem mass spectrometry, but this technique is available only at specialized institutions and cannot be relied on as a guide to immediate treatment. Thus, based on strong clinical suspicion, renal replacement therapy must be started promptly to achieve efficient drug clearance and correct the metabolic acidosis. However, because metformin accumulates in the intracellular compartment with prolonged treatment, a rebound in serum concentrations due to redistribution is expected at the end of dialysis. We report a case of metformin intoxication, severe lactic acidosis, and acute kidney injury in a diabetic patient with pre-existing chronic kidney disease stage 3, treated effectively with sustained low-efficiency dialysis. We discuss the pathophysiology, differential diagnosis, and treatment options and highlight specific pharmacokinetic issues that should be considered in selecting the appropriate modality of renal replacement therapy

Effects of continuous renal replacement therapy on linezolid pharmacokinetic/pharmacodynamics: a systematic review

BACKGROUND: Major alterations in linezolid pharmacokinetic/pharmacodynamic (PK/PD) parameters might be expected in critically ill septic patients with acute kidney injury (AKI) who are undergoing continuous renal replacement therapy (CRRT). The present review is aimed at describing extracorporeal removal of linezolid and the main PK-PD parameter changes observed in critically ill septic patients with AKI, who are on CRRT. METHOD: Citations published on PubMed up to January 2016 were systematically reviewed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. All authors assessed the methodological quality of the studies and consensus was used to ensure studies met inclusion criteria. In-vivo studies in adult patients with AKI treated with linezolid and on CRRT were considered eligible for the analysis only if operational settings of the CRRT machine, membrane type, linezolid blood concentrations and main PK-PD parameters were all clearly reported. RESULTS: Among 68 potentially relevant articles, only 9 were considered eligible for the analysis. Across these, 53 treatments were identified among the 49 patients included (46 treated with high-flux and 3 with high cut-off membranes). Continuous veno-venous hemofiltration (CVVH) was the most frequent treatment performed amongst the studies. The extracorporeal clearance values of linezolid across the different modalities were 1.2–2.3 L/h for CVVH, 0.9–2.2 L/h for hemodiafiltration and 2.3 L/h for hemodialysis, and large variability in PK/PD parameters was reported. The optimal area under the curve/minimum inhibitory concentration (AUC/MIC) ratio was reached for pathogens with an MIC of 4 mg/L in one study only. CONCLUSIONS: Wide variability in linezolid PK/PD parameters has been observed across critically ill septic patients with AKI treated with CRRT. Particular attention should be paid to linezolid therapy in order to avoid antibiotic failure in these patients. Strategies to improve the effectiveness of this antimicrobial therapy (such as routine use of target drug monitoring, increased posology or extended infusion) should be carefully evaluated, both in clinical and research settings

Reliability of bedside ultrasound for measurement of quadriceps muscle thickness in critically ill patients with acute kidney injury

Main problem: In patients with Acute Kidney Injury there is a lack of nutritional variables that can assess nutritional status, more specifically lean body mass (LBM) and skeletal muscle mass, at the individual level. In this clinical setting, ultrasound (US)) of the quadriceps femoris could represent a widely available, non-invasive, affordable, and reliable tool to evaluate skeletal muscle. Methods: We performed a cross-sectional observational study in adult critically ill patients with KDIGO stage 3 AKI on dialysis. Quadriceps rectus femoris and vastus intermedius thickness were measured by two assessors. Intra- and interobserver reliability was evaluated using the intraclass correlation coefficient (ICC). The same US measures were obtained before and after dialysis. Results: We enrolled 34 patients, 22 (65%) were male and the mean APACHE II score was 22.7 (±5.6). In the intraobserver reliability study, assessor 1 performed 288 paired measurements and assessor 2 performed 430 paired measurements in 34 patients, with an ICC equal to 0.99 and 1.00, respectively. There were 238 paired measurements (34 patients) in the interobserver reliability study, with an ICC = 0.92. No difference was found in the measurements obtained before and after dialysis (11.5 (4.2) vs 11.4 (4.1) mm, P = 0.2498), independently from acute body weight changes due to fluid removal. Conclusion: In patients with AKI, US of quadriceps femoris could represent a simple, accurate, and non-invasive method to evaluate quantitative changes in skeletal muscle

[Pathophysiology of Acute Kidney Injury in sepsis]

Sepsis is a serious medical condition often complicated by multiorgan failure, especially in the intensive care unit setting. Acute renal failure is a frequent complication of sepsis, leading to increased hospital mortality risk and worsening of patient outcome. Despite recent advances in the treatment of sepsis and acute renal failure, the pathophysiological mechanisms of acute renal failure in sepsis is still not fully ascertained. The aim of this review is to illustrate the pathophysiological mechanisms that are involved in the development of acute renal failure in sepsis, with special regard to the systemic hemodynamic alterations, renal microvascular and inflammatory/immunological mechanisms

[Pathophysiology of Acute Kidney Injury in sepsis]

Sepsis is a serious medical condition often complicated by multiorgan failure, especially in the intensive care unit setting. Acute renal failure is a frequent complication of sepsis, leading to increased hospital mortality risk and worsening of patient outcome. Despite recent advances in the treatment of sepsis and acute renal failure, the pathophysiological mechanisms of acute renal failure in sepsis is still not fully ascertained. The aim of this review is to illustrate the pathophysiological mechanisms that are involved in the development of acute renal failure in sepsis, with special regard to the systemic hemodynamic alterations, renal microvascular and inflammatory/immunological mechanisms

[Metabolic acidosis]

Metabolic acidosis is frequently observed in clinical practice, especially among critically ill patients and/or in the course of renal failure. Complex mechanisms are involved, in most cases identifiable by medical history, pathophysiology-based diagnostic reasoning and measure of some key acid-base parameters that are easily available or calculable. On this basis the bedside differential diagnosis of metabolic acidosis should be started from the identification of the two main subtypes of metabolic acidosis: the high anion gap metabolic acidosis and the normal anion gap (or hyperchloremic) metabolic acidosis. Metabolic acidosis, especially in its acute forms with elevated anion gap such as is the case of lactic acidosis, diabetic and acute intoxications, may significantly affect metabolic body homeostasis and patients hemodynamic status, setting the stage for true medical emergencies. The therapeutic approach should be first aimed at early correction of concurrent clinical problems (e.g. fluids and hemodynamic optimization in case of shock, mechanical ventilation in case of concomitant respiratory failure, hemodialysis for acute intoxications etc.), in parallel to the formulation of a diagnosis. In case of severe acidosis, the administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need of renal replacement therapy

A Novel Transcatheter Device for the Edge-to-Edge Treatment of Tricuspid Regurgitation: A Preliminary Evaluation

Tricuspid regurgitation (TR) is the most common pathology of the tricuspid valve (TV), with significant mortality in severe cases. A well-established strategy to treat TR is represented by the clover surgical technique, which consists of stitching together the free edges of TV leaflets, producing a clover-shaped valvular orifice. Transcatheter treatments for TR constitute a valuable alternative for high-risk patients. In this work we investigated haemodynamic performances and safety of a novel device (StarTric device (STD)) aiming to perform the clover technique via percutaneous access. To assess haemodynamic performances, STD and clover were applied on porcine pathological TVs and tested. Fluid dynamic indexes of both strategies were compared to the pathological model. To evaluate device safety, forces exchanged between device and leaflets were compared to the extraction force (EF) required to STD to completely pass through the leaflet. Clover technique and STD induced a comparable TV backflow reduction (48% and 47%, respectively), with associated increase of TV flow in all tested conditions. Diastolic transvalvular pressure similarly increased indicating a reduction, though not significant, of the valvular orifice. Forces ranged from 1N to 1.71N, compared to an EF of 22.16 +/- 8.6N. Force varied significantly amongst different working conditions (normotensive, mild, and severe hypertensive) for each leaflet, whilst no significative variation was found on different leaflets in the same working condition. In the adopted experimental scenario, STD demonstrated comparable efficacy to the surgical strategy in restoring TV haemodynamic. The forces acting on the leaflets following STD implantation were far lower when compared to EFs

Multifocal phaeohyphomycosis caused by Exophiala xenobiotica in a kidney transplant recipient

In recent years, black fungi have been increasingly reported as causing opportunistic infections after solid organ transplantation. Here, we report a case of insidious, relentless, and multifocal Exophiala xenobiotica infection in a kidney transplant recipient that eventually required multiple surgical excisions along with oral and intravenous antifungal combination therapy using liposomal amphotericin B and posaconazole. We compare the present case with all previously reported cases of Exophiala infection after kidney transplantation