Metformin-associated lactic acidosis and factors associated with 30-day mortality.

BACKGROUND: Metformin-associated lactic acidosis (MALA) is a rare event but underrecognition may lead to unfavorable outcomes in type 2 diabetes patients. While many risk factors of MALA have been identified, how to reduce mortality from MALA is a matter of debate. This study aimed to explore the factors associated with 30-day mortality amongst MALA patients. METHODS: An observational study enrolled patients diagnosed with MALA between January 2014 and December 2017. MALA was defined by a history of metformin administration, metabolic acidosis (arterial blood gas pH <7.35 or HCO3 <15 mmol/L), and elevated plasma lactate level (>5 mmol/L). We examined risk factors including age, sex, underlying diseases, current medications, blood tests, disease severity, and dialysis data. Mortality status was identified from medical records or report on telephone. RESULTS: We included 105 MALA patients. Most patients (95.2%) were diagnosed acute kidney injury stage 3 according to KDIGO 2012 definition. The 30-day mortality rate was 36.2% and dialysis rate was 85.7%. The survivors had higher proportions of underlying chronic kidney disease, presence of metabolic acidosis, receiving renal replacement therapy within 6 hours, and haemodialysis, whereas the non-survivors had higher percentage of hypertension and disease severity. Lower APACHE II score (HR = 0.95; 95%CI, 0.91-0.99; p = 0.038), time to dialysis < 6 hours (0.31; 0.14-0.69; 0.004), and haemodialysis (0.20;0.06-0.67; 0.010) were associated with lower 30-day mortality, using multivariate Cox-regression analysis. CONCLUSIONS: Mortality rate amongst patients with MALA was high. Early dialysis treatment within 6 hours after admission and haemodialysis were independently associated with lower 30-day mortality. The large scale, well-designed studies need to confirm these encouraging results.

Efficacy of Potassium Supplementation in Hypokalemic Patients Receiving Peritoneal Dialysis: A Randomized Controlled Trial.

RATIONALE & OBJECTIVE: Hypokalemia is a common electrolyte abnormality in patients on peritoneal dialysis (PD) and has been associated with increased risks of peritonitis and death. Whether correction of hypokalemia improves these outcomes is unknown. STUDY DESIGN: Multicenter, open-label, prospective, randomized controlled trial. SETTING & PARTICIPANTS: Adult (aged ≥18 years) PD patients with hypokalemia (defined as at least 3 values or an average value <3.5 mEq/L in the past 6 months). Randomization was stratified according to center and residual urine output (≤100 or >100 mL/day). INTERVENTIONS: Random assignment to either protocol-based potassium supplementation (titratable dose of oral potassium chloride to maintain serum potassium of 4-5 mEq/L) or conventional potassium supplementation (reactive supplementation when serum potassium is <3.5 mEq/L) over 52 weeks. Treatment groups were compared using intention-to-treat analyses implemented using Cox proportional hazards regression. OUTCOME: The primary outcome was time from randomization to first peritonitis episode (any organism). Secondary outcomes were all-cause mortality, cardiovascular mortality, hospitalization, and conversion to hemodialysis. RESULTS: A total of 167 patients with time-averaged serum potassium concentrations of 3.33 ± 0.28 mEq/L were enrolled from 6 PD centers: 85 were assigned to receive protocol-based treatment, and 82 were assigned to conventional treatment. The median follow-up time was 401 (IQR, 315-417) days. During the study period, serum potassium levels in the protocol-based treatment group increased to 4.36 ± 0.70 mEq/L compared with 3.57 ± 0.65 mEq/L in the group treated conventionally (mean difference, 0.66 [95% CI, 0.53-0.79] mEq/L; P < 0.001). The median time to first peritonitis episode was significantly longer in the protocol-based group (223 [IQR, 147-247] vs 133 [IQR, 41-197] days, P = 0.03). Compared with conventional treatment, the protocol-based group had a significantly lower hazard of peritonitis (HR, 0.47 [95% CI, 0.24-0.93]) but did not differ significantly with respect to any of the secondary outcomes. Asymptomatic hyperkalemia (>6 mEq/L) without characteristic electrocardiographic changes occurred in 3 patients (4%) in the protocol-based treatment group. LIMITATIONS: Not double-masked. CONCLUSIONS: Compared with reactive potassium supplementation when the serum potassium level falls below 3.5 mEq/L, protocol-based oral potassium treatment to maintain a serum potassium concentration in the range of 4-5 mEq/L may reduce the risk of peritonitis in patients receiving PD who have hypokalemia. TRIAL REGISTRATION: Registered at the Thai Clinical Trials Registry with study number TCTR20190725004.