Case Of Metformin-associated Lactic Acidosis Research Articles

Lactic acidosis with metformin accumulation in the intensive care units of the Nord Pas de Calais region: A known serious adverse event that can be better prevented.

Metformin-associated lactic acidosis (MALA) is a rare but serious adverse drug reaction (ADR). The aim of the study was to identify clinical situations associated with the onset of MALA in patients hospitalised in the Nord Pas de Calais regional intensive care units (ICUs), and to assess its preventability. We included all cases of MALA, identified by metformin accumulation >2.3mg/dL and lactate >2.2mmol/L, reported by the regional ICU physicians to the Regional Centre of Pharmacovigilance and registered in the French Pharmacovigilance Database between 1 January 2017 and 30 December 2018. One hundred and ninety-eight (198) cases of MALA were included. 38 patients died in direct association with MALA (19.2%). There was a correlation between metformin plasma accumulation and acute renal failure and with the severity of MALA (P<0.0001). All patients presented an acute intercurrent event favouring MALA, dehydration for 87 (43.9%) patients, severe infection for 65 (32.8%) patients. For 172 patients (86.7%), the prescription was not adapted to the intercurrent medical situation as recommended. Seventy (40.5%) patients consulted their general practitioner for the acute intercurrent event, 1 temporarily stopped metformin and 34.3% had been referred directly to hospital. The remaining 65.7% presented to the hospital around 4 days later due to worsening symptoms. MALA was identified as preventable in 160 patients (80.8%). MALA in ICUs often follow acute dehydration or infection, and these high-risk situations must be signals to prevent this serious ADR. Specific education programmes for physicians and patients could also reduce this risk.

Metformin-Associated Lactic Acidosis: Which Elimination Therapy to Use in Case of Haemodynamic Instability? A Retrospective Cohort Study

Introduction: Metformin, a commonly used oral antihyperglycemic drug, poses a rare risk related to the development of metformin-associated lactic acidosis (MALA). The Extracorporeal Treatments in Poisoning (EXTRIP) group recommended intermittent haemodialysis (IHD) as a primary elimination therapy in case of severe metformin poisoning. However, in haemodynamically unstable patients, our previous observations suggested that continuous venovenous haemofiltration (CVVH) might be more effective. This retrospective cohort study aimed to contribute evidence on the use of IHD and CVVH in patients with severe MALA, particularly in haemodynamically unstable patients. Methods: Data from January 2015 to December 2020 were collected from the Leuven University Hospital. Two separate search methods, based on hospital activity records and laboratory criteria, were used to identify patients with MALA. Patients diagnosed with MALA, receiving extracorporeal treatment within 24 h of admission, were included. Patients were categorized into the IHD and CVVH groups. Patient characteristics, treatment details, and outcomes were analysed. Results: Among 358,148 patient records, 35 MALA cases were identified. IHD was chosen as the initial elimination technique in 13 cases, whereas 22 patients were first commenced on CVVH. Patients treated with CVVH were sicker, had more comorbidities and had higher ventilation and vasopressor requirements. CVVH group had longer vasopressor use, longer ICU stays, and higher in-hospital mortality. Discussion: CVVH rather than IHD seems to be the preferred elimination technique in the more critically ill patients with MALA. Due to its retrospective design, this study failed to identify the superior elimination technique in terms of efficacy. Poorer outcomes in the CVVH group are likely attributed to the severity of illness rather than the inferiority of the elimination therapy. We acknowledge the diagnostic challenges regarding MALA. Using metformin assays could be beneficial in managing these patients. Conclusions: This study suggests clinicians’ preference for CVVH in severe cases of MALA with haemodynamic instability.

THU382 It’s Not What It Seems - Metformin Induced Severe Lactic Acidosis Mimicking Euglycemic Diabetic Ketoacidosis

Abstract Disclosure: M. Shaukat: None. R. Memon: None. M. Mack: None. E. Galarza: None. R. Saeed: None. Diabetic Ketoacidosis (DKA) is a life-threatening complication and, occasionally, the initial presentation of Diabetes Mellitus (DM). DKA can rarely present without elevated blood glucose levels, known as Euglycemic DKA, now typically associated with SGLT-2 inhibitors. Metformin is known to cause lactic acidosis but has not been reliably associated with euglycemic DKA. We present a case of metformin-associated lactic acidosis with renal failure and ketosis mimicking euglycemic DKA. Case: 82-year-old female with a history of DM type 2 on metformin and hypertension presented to the Emergency Department (ED) with complaints of presyncope, vomiting and generalized weakness for two weeks. In the ED, her temp. was 90.3 F and BP was 66/28 mmHg. Her labs revealed a potassium of 5.4mmol/L, bicarbonate 5 mmol/L, Creatinine 3.68 mg/dL (baseline 0.7mg/dL), Anion gap (AG) 45mmol/L, Lactate 25.1 mmol/L and Beta-hydroxybutyrate of 21.4 mg/dL. CT Scan of the chest and abdomen showed a 2 cm liver mass and pancreatitis. She was taken to the ICU and started on antibiotics, IV fluids, and vasopressors. The following day, her lactate was 13.5mg/dL, AG was 37mmol/L and Beta-hydroxybutyrate increased to 53.5mg/dL. Her blood sugars remained between 140-180mg/dL and her hemoglobin A1c was in the prediabetic range at 6.1%. She was thought to be in metformin induced euglycemic diabetic ketoacidosis and was started on an insulin drip with 5% Dextrose and 0.45% Normal Saline. Nephrology was consulted and she underwent hemodialysis for metformin toxicity. She remained on the insulin drip for 48 hours after which she was successfully weaned off. She currently remains off on any antidiabetic medication and is doing well. Discussion: DKA is a life-threatening complication of DM that presents as hyperglycemia, ketonemia, and AGMA. Euglycemic DKA is distinguished by blood glucose levels less than 250mg/dL and is usually seen with pregnancy, fasting states and use of SGLT-2 inhibitors. Previous cases of metformin-associated lactic acidosis (MALA) and concurrent euglycemic DKA have been reported, out of which several patients were concurrently on SGLT-2 inhibitors. After a thorough literature review, we were unable to determine a causal mechanism linking metformin and euglycemic DKA. In the reported cases, we believe that renal failure from various causes precipitated MALA due to decrease metformin clearance, with ketosis caused by starvation and exacerbated by metformin-induced inhibition of hepatic gluconeogenesis, further aggravated by an increase in stress hormones resulting in increased insulin resistance and ultimately leading to the development of the severe ketoacidosis. Even though this phenomenon has previously been referred to as “Metformin-induced euglycemic DKA”, we believe that this is more akin to a mimic, rather than true DKA. Presentation: Thursday, June 15, 2023

THE DARK SIDE OF BIGUANIDES: A CASE REPORT ON METFORMIN-ASSOCIATED LACTIC ACIDOSIS (MALA)

Metformin-associated lactic acidosis (MALA) is a rare but potentially fatal complication that can occur in a patient on metformin, who had a sudden reduction in the renal function resulting in a raised serum metformin level. We describe a case of MALA who survived with prompt haemodialysis. An elderly female with diabetes on metformin presented with gastrointestinal losses, lethargy and confusion. She was in circulatory shock and despite an aggressive fluid regime, she remained acidotic with an increasing lactate level of &gt; 15 mmol/L. After endotracheal intubation, she was referred to tertiary centre for haemodialysis. Her serum lactate level rapidly fell to a satisfactory range and a progressive recovery followed. We are highlighting this case for its rarity and to serve as a guidance on the early recognition of MALA for fellow clinicians. Despite the high mortality rate, MALA is reversible, and we urge clinicians to expedite haemodialysis as definitive treatment.

MALA: Lactic acidosis associated with the use of metformin, review of clinical cases

Metformin is the preferred medication for the initial management of type 2 diabetes mellitus (T2DM). Although its use is widely recommended, caution should be exercised when prescribing it to populations susceptible to systemic hypoperfusion conditions, as it can lead to accumulation in the body and metabolic disturbances that may result in metformin-associated lactic acidosis. This severe complication is often underdiagnosed. To promote a better understanding of this topic, the present review focuses on the analysis of the clinical, pathophysiological, diagnostic, and management aspects of metformin-associated lactic acidosis, with particular attention to management through renal replacement therapies. The analysis will be based on the experience of a series of cases of metformin-associated lactic acidosis treated at a hospital clinical center in Chile.

Metformin Use and Long-term Clinical Outcomes in Kidney Transplant Recipients

Metformin has been recommended for some patients with advanced chronic kidney disease. However, the value of metformin in kidney transplant recipients (KTRs) with pre-transplant diabetes mellitus (DM) or post-transplant diabetes mellitus (PTDM) is uncertain. We investigated the clinical effects of metformin in KTRs. Retrospective cohort study. A total of 1,995 KTRs with diabetes from six tertiary referral centers in the Republic of Korea. Metformin usage was defined as the use of metformin for >90 days after kidney transplantation; 1,193 KTRs were metformin users, and 802 KTRs did not use metformin. Changing usage of metformin among those exposed for >90 days was also characterized. Primary outcomes were all-cause mortality and death-censored graft failure (DCGF). Secondary outcomes were biopsy-proven acute rejection (BPAR) and lactic acidosis events. Survival analyses were conducted using multivariable Cox regression and competing risk analyses using Fine and Gray models. Changes in metformin use over time were modeled using a time-varying covariate. Metformin usage, mean daily dose, and HbA1c changes were considered in the landmark analysis to address time-varying confounding. Metformin use was associated with a lower risk of DCGF (adjusted hazard ratio [aHR] 0.47, 95% confidence interval [CI] 0.23-0.96, P = 0.038); there was no significant association with all-cause mortality (aHR 0.94, 95% CI 0.32-2.76, P = 0.915) or BPAR: (aHR 0.98, 95% CI 0.62-1.54, P = 0.942). In the subgroup analysis, metformin usage was associated with a reduced risk of all-cause mortality and a lower risk of DCGF for both the pre-transplantation DM and PTDM groups. Metformin usage was associated with a lower risk of BPAR in the PTDM group, although it was less effective in the pre-transplantation DM group. There was no confirmed case of metformin-associated lactic acidosis (MALA) in the present cohort. A higher dose of metformin was correlated with lower risks of DCGF and BPAR. Data on newer antidiabetic drugs such as SGLT2 inhibitors are limited; potential limited generalizability to other populations. Metformin usage may benefit KTRs, as evidenced by its association with a reduced risk of DCGF and the absence of MALA events. Randomized controlled trials are needed to validate these observational findings.

Safety of metformin continuation in diabetic patients undergoing invasive coronary angiography: the NO-STOP single arm trial

BackgroundDespite paucity of data, it is common practice to discontinue metformin before invasive coronary angiography due to an alleged risk of Metformin-Associated Lactic Acidosis (M-ALA). We aimed at assessing the safety of metformin continuation in diabetic patients undergoing coronary angiography in terms of significant increase in lactate levels.MethodsIn this open-label, prospective, multicentre, single-arm trial, all diabetic patients undergoing coronary angiography with or without percutaneous coronary intervention at 3 European centers were screened for enrolment. The primary endpoint was the increase in lactate levels from preprocedural levels at 72-h after the procedure. Secondary endpoints included contrast associated-acute kidney injury (CA-AKI), M-ALA, and all-cause mortality.Results142 diabetic patients on metformin therapy were included. Median preprocedural lactate level was 1.8 mmol/l [interquartile range (IQR) 1.3–2.3]. Lactate levels at 72 h after coronary angiography were 1.7 mmol/l (IQR 1.3–2.3), with no significant differences as compared to preprocedural levels (p = 0.91; median difference = 0; IQR − 0.5 to 0.4 mmol/l). One patient had 72-h levels ≥ 5 mmol/l (5.3 mmol/l), but no cases of M-ALA were reported. CA-AKI occurred in 9 patients (6.1%) and median serum creatinine and estimated glomerular filtration rate remained similar throughout the periprocedural period. At a median follow-up of 90 days (43–150), no patients required hemodialysis and 2 patients died due to non-cardiac causes.ConclusionsIn diabetic patients undergoing invasive coronary angiography, metformin continuation throughout the periprocedural period does not increase lactate levels and was not associated with any decline in renal function.Trial registration: The study was registered at Clinicaltrials.gov (NCT04766008).Graphical

Quality and Characteristics of 4241 Case Reports of Lactic Acidosis in Metformin Users Reported to a Large Pharmacovigilance Database.

Metformin-associated lactic acidosis (MaLA) occurs rarely and is thus difficult to study. We analysed 4241 individual case safety reports of lactic acidosis (LA) that implicated metformin as a suspected drug reported to the pharmacovigilance database of Merck KGaA, Darmstadt, Germany. The primary objective was to review reports for quality and completeness of data to support diagnoses of MaLA. We also explored the correlations between reported biomarkers, and associations between biomarkers and outcomes. Records were analysed for completeness in supporting diagnoses of LA or metformin-associated LA (MaLA), against commonly used diagnostic criteria. Correlations between indices of exposure to metformin and biomarkers of LA and mortality were investigated. Missing data was common, especially for plasma metformin. Clinical/biomarker evidence supported a diagnosis of LA in only 33% of cases (LA subpopulation) and of MaLA in only 9% (MaLA subpopulation). The metformin plasma level correlated weakly with plasma lactate (positive) and pH (negative). About one-fifth (21.9%) of cases reported a fatal outcome. Metformin exposure (plasma level or dose) was not associated with increased mortality risk (there was a suggestion of decreased risk at higher levels of exposure to metformin). Plasma lactate was the only variable associated with increased risk of mortality. Examination of concomitant risk factors for MaLA identified renal dysfunction (including of iatrogenic origin) as a potential driver of mortality in this population. Despite the high frequency of missing data, this is the largest analysis of cases of MaLA supported by measurements of circulating metformin, and lactate, and pH, to date. Plasma lactate, and not metformin dose or plasma level, appeared to be the main driver of mortality in the setting of LA or MaLA. Further research with more complete case reports is required.

Achieving High Dialysis Dose via Continuous Renal Replacement Therapy in the Setting of Metformin Associated Lactic Acidosis. A Case Series.

Severe and life-threatening cases of metformin-associated lactic acidosis (MALA) are treated with renal replacement therapy. Intermittent hemodialysis is recommended, as it achieves rapid more elimination of metformin compared to continuous renal replacement therapy (CRRT). This case series describes 4 patients, 2 with acute metformin intoxications and 2 with insidious metformin toxicity. All were treated using a novel approach with dual CRRT to achieve rapid elimination of metformin. Three of the 4 patients survived to hospital discharge. Dual CRRT may be an effective alternative when dialysis is not readily available.

Metformin-associated lactic acidosis exacerbated by acute kidney injury in an overseas traveler

We report the case of metformin-associated lactic acidosis (MALA) exacerbated by acute kidney injury (AKI) in a 65-year-old Asian American woman who was an overseas traveler. She had vomiting and diarrhea before arriving in Osaka, Japan, from the Philippines. She suffered from worsening respiratory distress, consciousness loss and anuria the day after coming to Japan. When she arrived at our emergency room via ambulance, she appeared to be in a state shock. Arterial blood gas analysis revealed severe lactic acidosis (pH 6.681, PO2 302 Torr under O2 supplementation, PCO2 15 Torr, HCO3−1.7 mmol/L, and lactate 17.00 mmol/L). She also had renal failure (BUN 108 mg/dL and serum creatinine 8.68 mg/dL) with hyperkalemia (6.1 mEq/L). We collected medical information from family members, and found her prescription medicines including metformin, diuretics and angiotensin-converting enzyme inhibitor (ACEI). We diagnosed her with MALA due to an unintended overdose of metformin resulting from acute kidney injury that can be induced by ACEI and diuretics in the volume-depleted condition. We immediately started hemodialysis therapy. Although she had a temporary cardiopulmonary arrest at the beginning of the treatment, her physical status was gradually improved and the severe acidemia resolved. On hospital day 4, she had urine and no longer needed hemodialysis therapy. On day 14, she was discharged and returned to the United States without noticeable sequelae. This is a case report of an overseas traveler who was successfully rescued through the collection of accurate medical information and understanding of the pathological condition.

A fatal autopsy case of metformin-associated lactic acidosis and respiratory failure with proven high plasma metformin concentration

A fatal autopsy case of metformin-associated lactic acidosis and respiratory failure with proven high plasma metformin concentration

A Rare Case of Metformin Associated Lactic Acidosis in a Type 2 Diabetic Patient With No Known Contraindications for Metformin Prescription - a Diagnostic Conundrum!

Introduction: Metformin is a biguanide drug primarily inhibits hepatic gluconeogenesis and improves insulin sensitivity. Lactic acidosis is a rare complication of metformin. The incidence of Metformin-associated lactic acidosis (MALA) is 6.3 per 100,000 patient-years. Metformin raises lactate levels by inhibiting the conversion of lactate and pyruvate into glucose, shunting towards anaerobic glycolysis. Although, MALA is a reported side effect, metformin is still identified as the drug of choice for Type 2 DM. Here we present a case of MALA in a Type 2 Diabetic patient to shed light on this controversial dilemma. Case Presentation: A 56-year-old African-American male with Type 2 DM and diabetic retinopathy presented after a fall and generalized weakness. Upon arrival, his blood sugar was 22 mg/dL. Patient was vitally stable with signs of dehydration. Home medications includes Metformin 1000 mg twice daily and Glipizide. Laboratory results showed an anion gap metabolic acidosis of 18 mmol/L, Lactic acid was 6.5 mmol/L with repeat of 7.6 mmol/L. Creatinine was 6.0 mg/dL with a BUN of 89 mg/dL. Baseline creatinine from 1 year prior was 1.3–1.5 mg/dL with GFR of 52 mL/min. Hemoglobin A1c was 5.9%. Sodium bicarbonate infusion in 5% dextrose in water. The patient clinically improved with closure of the anion gap and resolution of the metabolic acidosis. Metformin level was 10 mcg/mL. He was discharged on basal insulin and discontinued Metformin and Glipizide. Discussion: Metformin is the first line treatment of Type 2 DM due to its safety. The most common adverse events of Metformin include nausea, bloating, and diarrhea. MALA is a rare, yet serious side effect with a reported mortality of 45%. Higher mortality was associated with increased age, lower arterial pH, and need for mechanical ventilation and vasopressor medicationsThe following criteria should raise concern for MALA in patients with history of Metformin use; elevated lactate level, high anion gap, severe acidosis, low serum bicarbonate level and a history of renal insufficiency. Our patient met the above criteria. The treatment approach for MALA includes adequate supportive measures and correction of acidosis with the acceleration of lactic acid metabolism. Ultimately, if there is no improvement with the aforementioned strategies, then the next step is elimination of the offending agent by renal excretion or dialysis. Fortunately our patient improved with intravenous hydration and did not require advanced intervention. This case highlights the importance of the early recognition of MALA in a patient with unexplained anion gap acidosis and history of Metformin use as even with no risk factors, an episode of gastroenteritis can be enough to impair renal function which increases the risk of MALA. More importantly, it is crucial to educate patients to withhold Metformin in the setting of acute illness and volume contraction to prevent MALA.

Do Patients Die with or from Metformin-Associated Lactic Acidosis (MALA)? Systematic Review and Meta-analysis of pH and Lactate as Predictors of Mortality in MALA.

Metformin-associated lactic acidosis (MALA) may occur after acute metformin overdose, or from therapeutic use in patients with renal compromise. The mortality is high, historically 50% and more recently 25%. In many disease states, lactate concentration is strongly associated with mortality. The aim of this systematic review and meta-analysis is to investigate the utility of pH and lactate concentration in predicting mortality in patients with MALA. We searched PubMed, EMBASE, and Web of Science from their inception to April 2019 for case reports, case series, prospective, and retrospective studies investigating mortality in patients with MALA. Cases and studies were reviewed by all authors and included if they reported data on pH, lactate, and outcome. Where necessary, authors of studies were contacted for patient-level data. Receiver operating characteristic (ROC) curves were generated for pH and lactate for predicting mortality in patients with MALA. Forty-four studies were included encompassing 170 cases of MALA with median age of 68.5years old. Median pH and lactate were 7.02mmol/L and 14.45mmol/L, respectively. Overall mortality was 36.2% (95% CI 29.6-43.94). Neither lactate nor pH was a good predictor of mortality among patients with MALA. The area under the ROC curve for lactate and pH were 0.59 (0.51-0.68) and 0.43 (0.34-0.52), respectively. Our review found higher mortality from MALA than seen in recent studies. This may be due to variation in standard medical practice both geographically and across the study interval, sample size, misidentification of MALA for another disease process and vice versa, confounding by selection and reporting biases, and treatment intensity (e.g., hemodialysis) influenced by degree of pH and lactate derangement. The ROC curves showed poor predictive power of either lactate or pH for mortality in MALA. With the exception of patients with acute metformin overdose, patients with MALA usually have coexisting precipitating illnesses such as sepsis or renal failure, though lactate from MALA is generally higher than would be considered survivable for those disease states on their own. It is possible that mortality is more related to that coexisting illness than MALA itself, and many patients die with MALA rather than from MALA. Additional work looking solely at MALA in healthy patients with acute metformin overdose may show a closer relationship between lactate, pH, and mortality.

Metformin-associated lactic acidosis: A case reporting a serious complication in the perioperative period

The worldwide prevalence of diabetes mellitus (DM) has risen dramatically over the past two decades and this affects 10-15% of the surgical population1. Metformin represents the mainstay of anti-hyperglycaemic therapy for type 2 DM, providing numerous beneficial effects. However, a rare but severe adverse effect is the development of metformin-associated lactic acidosis (MALA) with high mortality rate. We describe a severe case of MALA in the postoperative period that culminated in cardiac arrest. Whereby anaesthetists should be knowledgeable and skilled in the care of patients with diabetes being imperative to focus on preoperative assessment, optimisation, management of pre-existing treatment during the starvation period and identification of patients medicated with metformin at risk of developing MALA.

TheAssociation between Metformin Therapy and Lactic Acidosis.

There is increasing evidence to suggest that therapeutic doses of metformin are unlikely to cause lactic acidosis. The aims of this research were (1) to formally evaluate the association between metformin therapy and lactic acidosis in published case reports using two causality scoring systems, (2) to determine the frequency of pre-existing independent risk factors in published metformin-associated lactic acidosis cases, (3) to investigate the association between risk factors and mortality in metformin-associated lactic acidosis cases, and (4) to explore the relationship between prescribed metformin doses, elevated metformin plasma concentrations and the development of lactic acidosis in cases with chronic renal impairment. A systematic review was conducted to identify metformin-associated lactic acidosis cases. Causality was assessed using the World Health Organisation-Uppsala Monitoring Centre system and the Naranjo adverse drugreaction probability scale. Compliance to dosing guidelines was investigated for cases with chronic renal impairment as well as the association between steady-state plasma metformin concentrations prior to admission. We identified 559 metformin-associated lactic acidosis cases. Almost all cases reviewed (97%) presented with independent risk factors for lactic acidosis. The prescribed metformin dose exceeded published guidelines in 60% of cases in patients with impaired kidney function. Metformin steady-state plasma concentrations prior to admission were predicted to be below the proposed upper limit of the therapeutic range of 5mg/L. Almost all cases of metformin-associated lactic acidosis reviewed presented with independent risk factors for lactic acidosis, supporting the suggestion that metformin plays a contributory role. The prescribed metformin dose, on average, exceeded the dosing recommendations by 1000mg/day in patients with varying degrees of renal impairment but the predicted pre-admission plasma concentrations did not exceed the therapeutic range.

A case of metformin-associated lactic acidosis successfully treated by continuous renal replacement therapy

A case of metformin-associated lactic acidosis successfully treated by continuous renal replacement therapy

Development, implementation and outcome analysis of semi-automated alerts for metformin dose adjustment in hospitalized patients with renal impairment.

Overdosing of the oral antidiabetic metformin in impaired renal function is an important contributory cause to life-threatening lactic acidosis. The presented project aimed to quantify and prevent this avoidable medication error in clinical practice. We developed and implemented an algorithm into a hospital's clinical information system that prospectively identifies metformin prescriptions if the estimated glomerular filtration rate is below 60 mL/min. Resulting real-time electronic alerts are sent to clinical pharmacologists and pharmacists, who validate cases in electronic medical records and contact prescribing physicians with recommendations if necessary. The screening algorithm has been used in routine clinical practice for 3 years and generated 2145 automated alerts (about 2 per day). Validated expert recommendations regarding metformin therapy, i.e., dose reduction or stop, were issued for 381 patients (about 3 per week). Follow-up was available for 257 cases, and prescribers' compliance with recommendations was 79%. Furthermore, during 3 years, we identified eight local cases of lactic acidosis associated with metformin therapy in renal impairment that could not be prevented, e.g., because metformin overdosing had occurred before hospitalization. Automated sensitive screening followed by specific expert evaluation and personal recommendations can prevent metformin overdosing in renal impairment with high efficiency and efficacy. Repeated cases of metformin-associated lactic acidosis in renal impairment underline the clinical relevance of this medication error. Our locally developed and customized alert system is a successful proof of concept for a proactive clinical drug safety program that is now expanded to other clinically and economically relevant medication errors. Copyright © 2016 John Wiley & Sons, Ltd.

Metformin associated lactic acidosis in Auckland City Hospital 2005 to 2009.

To determine the incidence, clinical characteristics and outcomes of patients with metformin associated lactic acidosis (MALA). Auckland City Hospital drains a population of just over 400000 people. All cases presenting with metabolic acidosis between July 2005 and July 2009 were identified using clinical coding. A retrospective case notes review identified patients with MALA. Prescribing data for metformin was obtained from the national pharmaceutical prescribing scheme. There were 42 cases of metabolic lactic acidosis over 1718000 patient years. There were 51000 patient years of metformin prescribed to patients over the study period. There were thirty two cases of lactic acidosis due to sepsis, seven in patients treated with metformin. Ten cases of MALA were identified. The incidence of MALA was estimated at 19.46 per 100000 patient year exposure to metformin. The relative risk of lactic acidosis in patients on metformin was 13.53 (95%CI: 7.88-21.66) compared to the general population. The mean age of patients with MALA was 63 years, range 40-83 years. A baseline estimated glomerular filtration rate was obtained in all patients and ranged from 23-130 mL/min per 1.73 m(2). Only two patients had chronic kidney disease G4. Three patients required treatment with haemodialysis. Two patients died. Lactic acidosis is an uncommon but significant complication of use of metformin which carries a high risk of morbidity.

Monitoring of metformin-induced lactic acidosis in a diabetic patient with acute kidney failure and effect of hemodialysis

Metformin associated lactic acidosis (MALA) is a serious complication occurring especially in elderly patients given high doses of the drug. We report a non-fatal case of MALA with pronounced acidosis (pH 6.76, lactate 30.81 mmol/l) and high metformin concentrations (127 mg/l) in a patient who had developed acute renal failure after undergoing an operation. Multiple measurements of biological parameters and metformin blood concentrations showed the effectiveness of repeated hemodialysis sessions on metformin elimination. Cases previously reported with such a severe MALA were associated with a high mortality rate. We show that close monitoring in an intensive care unit together with prompt and repeated dialysis sessions can lead to a favorable outcome.

メトホルミンによる乳酸アシドーシスにたこつぼ心筋症を続発した1症例

症例は66歳，女性。2型糖尿病でメトホルミン内服中であった。酒石酸ゾルピデムの大量内服後に乳酸アシドーシスを発症しICU入室となった。入室後，輸液などによるアシドーシス補正中に胸痛を訴えた。超音波検査で心尖部の収縮低下を認め，たこつぼ心筋症が疑われた。第4病日には壁運動異常は著明に改善し，たこつぼ心筋症と診断した。経過良好で第9病日にICU退室となった。メトホルミンによる乳酸アシドーシスは，稀だが致死的な合併症である。本症例においては酒石酸ゾルピデムの大量内服による低酸素状態がメトホルミンによる乳酸アシドーシスを発症する契機の一つとなった可能性が考えられた。また，アシドーシスによる身体的ストレスや自殺企図にまで至った精神的ストレスによって，たこつぼ心筋症を続発したと考えられる。