Lactic Acidosis and Rhabdomyolysis are Rare Complications of Metformin Toxicity, a Case Report.

Dialysis Dosing in Critically Ill Patients With Acute Kidney Injury

Metformin has been recommended as the first-line therapeutic option for diabetes mellitus. Lactic acidosis is a rare but life-threatening side effect of metformin. In previously reported cases, the occurrence of metformin -associated lactic acidosis (MALA) was usually accompanied by acute kidney injury (AKI). Among these risk factors for AKI, concurrent use of nephrotoxic agent, such as contrast medium, is common but often ignored in clinical practice. We present an elderly diabetic patient who was initially hospitalized due to complete AV block associated with AKI. After supportive therapy and temporary pacemaker implantation, the renal function recovered 5 days later. Metformin was prescribed again for better glucose control; CT angiography of bilateral lower limbs was then performed to prepare for revascularization. Four days later, acute renal failure with high anion gap metabolic acidosis manifesting as bradycardia with conscious change was noted. After exclusion of other etiologies, the diagnosis of MALA following contrast medium-induced nephropathy (CIN) was made. In view of hypotension and increased respiratory distress, vasopressors and ventilator support were instituted immediately. To correct acidosis and remove lactate as well as metformin, emergent hemodialysis was also initiated within 2 hours. However, despite intensive support of cardiovascular, respiratory and renal system, the patient died of sepsis with multiple organ failure 6 days later. We present this case to remind clinicians that metformin should be discontinued in diabetic patients receiving intravascular contrast study. For hospitalized patients, metformin should only be reused if reassessed renal function 48 hours after contrast medium administration has not deteriorated.

Metformin-associated lactic acidosis following contrast media-induced nephrotoxicity V. Jain;D. Sharma;H. Prabhakar;H. Dash; European Journal of Anaesthesiology

The prevalence of type 2 diabetes mellitus has surged globally. Metformin is recommended as the first-line oral treatment. However, metformin-associated lactic acidosis (MALA) is recognized as a rare but potentially dangerous complication. The pathogenesis of MALA is multifactorial, primarily resulting from the interference of metformin with mitochondrial function and hepatic gluconeogenesis, leading to lactate accumulation. Risk of MALA escalates with impaired kidney function, poorly controlled diabetes, fasting, and liver dysfunction. A 57-year-old woman with diabetes and hypertension presented with prolonged gastrointestinal symptoms. During this episode she continued using metformin. She had severe metabolic acidosis and acute kidney injury. Continuous venovenous hemodiafiltration was initiated, resulting in significant clinical improvement and normalized arterial blood gas parameters within 16 hours. The pharmacokinetic properties of metformin facilitate efficient elimination via hemodialysis and/or hemofiltration. Continuous venovenous hemodiafiltration emerges as effective for MALA treatment. In the case described the calculated metformin clearance during continuous venovenous hemodiafiltration was notably higher than reported values, possibly due to residual renal clearance. Clinical improvement occurred despite elevated metformin levels, suggesting a lack of correlation between metformin levels and patient outcomes. Comorbidities rather than metformin levels guide treatment decisions in MALA. This case underscores the efficacy of continuous venovenous hemodiafiltration in the treatment of MALA, suggesting its potential as a standard therapeutic approach. However, further research is needed to elucidate the complex interplay between metformin levels, clinical presentation, (extracorporeal) treatment modalities and outcome in MALA. Continuous venovenous hemodiafiltration seems to be an efficient and effective treatment to eliminate metformin in patients with metformin-associated lactic acidosis.The metformin level does not seem to correlate with the clinical condition of the patient.For a comparison between the effectiveness of different renal replacement therapies in metformin-associated lactic acidosis, more research is needed.

Metformin-associated lactic acidosis (MALA) is a rare but life-threatening complication of metformin therapy. We present a case of a 63-year-old female with type 2 diabetes mellitus (on metformin and insulin) who developed severe lactic acidosis, euglycemic diabetic ketoacidosis (DKA), and acute kidney injury (AKI) following a three-day history of gastrointestinal symptoms. Despite initial stabilization efforts, the patient deteriorated into refractory shock and cardiac arrest, requiring intensive care unit (ICU) admission, continuous venovenous hemodiafiltration (CVVHD), vasopressor support, and mechanical ventilation. Serial arterial blood gas (ABG) analyses demonstrated profound metabolic acidosis (pH 6.77, lactate 20 mmol/L) with gradual normalization following CVVHD. The patient recovered fully, highlighting the importance of early recognition and aggressive management of MALA, including renal replacement therapy (RRT), in critically ill patients.

The burden of diabetes mellitus type 2 (DM2) is increasing worldwide. The combination of DM2 and hypertension (HT) is frequently encountered. Concurrent use of drugs blocking the renin angiotensin system (angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB)) and metformin have become frequent in this group of patients. That combination can become life-threatening under certain circumstances. We present 5 patients with DM2 and HT who developed severe metformin-associated lactic acidosis in a setting with acute renal failure, precipitated by dehydration and aggravated by the use of ACEI or ARB. None of the patients had reduced renal function before the acute illness. They were admitted to the hospital in critical condition with severe metabolic acidosis (pH 6.60 6.94), high S-lactate (14 - 23 mmol/l) and S-creatinine 796 1,621 micromol/l. They were all hypothermic and 3 were hypoglycemic. All developed circulatory and respiratory collapse. They were treated with either intermittent bicarbonate hemodialysis (HD) or with continuous venovenous hemodiafiltration (CVVHDF) and bicarbonate buffering. All patients recovered without renal sequela. We believe that the incidence of metformin-associated lactic acidosis in Norway may become more frequent due to increased use of metformin and drugs blocking the renin angiotensin system. The awareness of lactic acidosis as a complication to the use ofmetformin in predisposed individuals is important. General advice should be given to patients regarding reduction of dosage or withdrawal of the drugs during acute intercurrent illness with dehydration. Early diagnosis and treatment of metformin-associated lactic acidosis are crucial for the patient outcome. Hemodialysis can be life-saving and should be started without delay.

Background: Metformin-associated lactic acidosis (MALA) and metformin-induced lactic acidosis (MILA) remain controversial entities. Metformin toxic effect depends on accumulation to lead to lactic acidosis (LA), particularly during an episode of acute kidney injury (AKI). In MILA, no other condition contributing to LA is found. The aims of this study were to describe the characteristics and prognosis of AKI associated with LA in metformin users and to clarify the role of this drug in the different types of LA.Methods: We performed a French multicenter retrospective study in diabetic patients treated by metformin presenting with LA in a context of AKI in 2015. 126 nephrology units (NU) and 23 intensive care units (ICU) were contacted. We individualized MILA and MALA patients in order to illustrate the role of metformin.Results: We included 173 patients (109 MILA, 64 MALA). 103 patients presented without hemodynamic instability (82 MILA and 21 MALA) whereas 70 patients were shocked including 27 MILA. The shock was associated with death with an odds ratio (OR) of 12.92 (p < .001). Digestive disorders (DD) were strongly associated with MILA (p = .0001). MALA was significantly associated with shock (p < .0001). The mortality rate was higher in MALA (26%) when compared with MILA (7%). Dialysis performed in 133 patients was significantly associated with shock, kalemia, lactate and serum creatinine levels. In multivariate analysis, metformin level was independently associated with pH or lactate level only in MILA patients.Conclusions: MILA is associated with DD and death is due to severe refractory acidosis leading to cardiovascular collapse attributed to metformin accumulation mainly via AKI. MALA patients are more frequently shocked and death is related to their underlying condition, metformin accumulation increasing LA.

Objective: Lactic acidosis, a rare but serious complication of metformin treatment, is always a major concern of clinicians. This study aimed to describe the clinical profile of metformin-associated lactic acidosis (MALA) and the impact of acute kidney injury.Methods: We conducted a retrospective study, excluding other causes of hyperlactatemia, to identify patients with MALA in a regional hospital during a 5-year period. The pre-morbid conditions, clinical presentation, biochemical data, therapeutic strategies and outcomes were recorded for analysis.Results: A total of 10 cases were diagnosed as MALA. All were elderly type 2 diabetic patients accompanied with acute kidney injury at presentation. All patients had more than one vascular comorbidity. Most patients had acute intercurrent illness or took medications that might compromise renal function. Gastrointestinal symptoms, hypoglycemia, hypothermia and hypotension were predominant clinical features. Among them, two patients were ventilated, four patients required vasoactive support and seven patients received urgent hemodialysis to clear the acidosis and treat the renal failure. All but one of these patients survived. A combination of contrast medium and metformin led to the only mortality case. Recovery of renal function was the general rule in survivors.Conclusions: MALA is usually associated with acute kidney injury. Despite the severity of this illness, lactic acidosis solely related to metformin use seems to have a favorable outcome with intensive support of cardiovascular, respiratory and renal system.

THE METFORMIN GAP

Objective To investigate the effect and outcome of critically illness with acute kidney injury (AKI) treated with continuous veno-venous hemodiafiltration (CVVHDF) in children.Methods Twenty-four cases of critically illness with AKI were treated with CVVHDF in our pediatric intensive care unit from Jan 2008 to Dec 2010.The levels of creatinine (Cr),blood urea nitrogen (BUN),K +,Na + and HCO3- were observed before CVVHDF and 6,12,24,48,72 h after CVVHDF.Results Catheter was successfully established for CVVHDF in 24 cases of AKI.The average duration of CVVHDF was 46 h ( 16 ～142 h).The blood levels of Cr and BUN were significantly decreased at 6 h after CVVHDF [ ( 196.3 ±112.4) μmol/L,( 13.3 ± 8.5 ) mmol/L] and 12 h after CVVHDF [ ( 106.1 ± 84.2) μ mol/L,( 10.2 ± 9.7 )mmol/L] as compared to those before treatment [ (340.6 ±298.2) μmol/L,(31.6 ± 11.3) mmol/L] (P ＜0.05,P ＜ 0.01 ).After 48 h of CVVHDF,the Cr,BUN returned to normal range.The imbalance of blood K +,Na +,and HCO3- improved at 6 h after CVVHDF and returned to nomal levels at 24 h.Total 28 d fatality rate was 29.2％ (7/24),and all death cases were complicated with multiple organ dysfunction syndrome.Conclusion CVVHDF therapy for AKI can quickly clear Cr,BUN and excess water,correct electrolyte disorders,improve kidney function in children. Key words: Continuous veno-venous hemodiafiltration; Acute kidney injury; Multiple organ dysfunction syndrome; Children

Metformin-associated lactic acidosis (MALA) carries a high mortality rate. It is seen in patients with type 2 diabetes on metformin or patients who attempt suicide with metformin overdose. We present...

Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial

Metabolic acidosis is a common disorder defined by an imbalance in the body’s acid-base balance. Identifying the cause of acidosis is critical for its management. We describe a case of acute renal failure with lactic acidosis in a 69-year-old man who was taking metformin for type 2 diabetes. The patient presented with decreased urine output after two weeks of intermittent nausea and vomiting. During this time, the patient had continued to take limited fluids and medication, including lisinopril and metformin. Physical exam on initial evaluation was remarkable only for hypertension and minimal abdominal tenderness. However, laboratory tests revealed a severe lactic acidosis and renal failure with hyperkalemia. The patient had normal renal function and a normal urine albumin level three weeks prior. Broad-spectrum antibiotics and sodium bicarbonate were administered, followed by hemodialysis. During hemodialysis, the patient became hemodynamically unstable, requiring vasopressors. Post-dialysis, the lactic acidosis worsened, prompting the initiation of additional prolonged dialysis during the first hospital day. After the second lengthy dialysis, the patient’s condition improved significantly and he was discharged on hospital day 12, with the diagnosis of metformin-associated lactic acidosis (MALA) in the setting of acute tubular necrosis from gastrointestinal fluid loss accompanied by the continued use of an angiotensin-converting enzyme inhibitor. After discharge, his renal function returned to normal.Severe lactic acidosis from metformin is relatively rare. Metformin has a large volume of distribution and accumulates in erythrocytes and intestinal cells, resulting in less efficient removal with dialysis and rebound lactic acidosis. Prolonged dialysis may be necessary for MALA to improve outcomes. Identifying metformin levels may help in diagnosis and management. However, the means to Identify metformin levels are not widely available. Patients receiving metformin should be counseled to stop metformin and seek medical care in the setting of illnesses. This is particularly important given the frequency of metformin prescription and the common use of renin-angiotensin system blockade in patients with type 2 diabetes, which increases the risk of kidney dysfunction.

Exertional Rhabdomyolysis

Metformin-associated lactic acidosis (MALA) is a rare but life-threatening complication of metformin therapy. We present a case of a 63-year-old female with type 2 diabetes mellitus (on metformin and insulin) who developed severe lactic acidosis, euglycemic diabetic ketoacidosis (DKA), and acute kidney injury (AKI) following a three-day history of gastrointestinal symptoms. Despite initial stabilization efforts, the patient deteriorated into refractory shock and cardiac arrest, requiring intensive care unit (ICU) admission, continuous venovenous hemodiafiltration (CVVHD), vasopressor support, and mechanical ventilation. Serial arterial blood gas (ABG) analyses demonstrated profound metabolic acidosis (pH 6.77, lactate 20 mmol/L) with gradual normalization following CVVHD. The patient recovered fully, highlighting the importance of early recognition and aggressive management of MALA, including renal replacement therapy (RRT), in critically ill patients.