Metformin is nowadays the first-line drug of choice for the treatment of adults with type 2 diabetes [ 2 ]. In particular, no cases of lactic acidosis a relatively common side effect of other biguanide compounds were reported in trials with 70, patient-years of metformin use [ 5 ].
Real life can differ from research settings, however, and lactic acidosis has been repeatedly, although rarely, observed in patients treated with metformin. The number of inquiries to the Swedish Poison Information Centre for metformin intoxication has increased 10 times during the past decade, with 25 cases of severe lactic acidosis reported in and [ 6 ].
Forty-nine cases of lactic acidosis and accidental metformin accumulation were reported to the Poison Control Centre of Pavia Italy from January to August , resulting in 11 deaths.
The term metformin- associated lactic acidosis refers to any case of lactic acidosis that develops in a patient treated with metformin, with no further mechanistic insight. In most of the cases, however, lactic acidosis cannot be directly attributed to metformin use but rather depends on concomitant low cardiac output, anemia, hypoxemia or liver failure. The term metformin- induced lactic acidosis specifically refers to cases that cannot be explained by any major risk factor other than metformin overdose [ 8 ].
The distinction between these two entities is sometimes very subtle and metformin accumulation may coexist with other risk factors, all contributing to the pathogenesis of lactic acidosis.
The present case series includes 10 patients admitted to intensive care with lactic acidosis and metformin accumulation due to renal failure [ 1 ]. At admission, arterial pH was 6. Treatment consisted of vital function support and renal replacement therapy. Conversely, there were no survivors out of 31 patients with similarly severe lactic acidosis from other causes mainly cardiogenic, septic or hemorrhagic shock who were admitted to the same institution during the same period of time.
This finding is in line with previous observations. We have recently reviewed the data for 24 critically ill patients with lactic acidosis and proven or probable metformin intoxication. Even patients with initial arterial pH down to 6. That lactic acidosis carries a poor prognosis has been known for decades [ 11 ].
Lactic acid per se , however, is unlikely to be the explanation for this association. Lactate production is indeed an adaptive response to impending energy failure. This response provides some energy and a chance for cells to survive, even when oxygen availability or utilization are defective [ 12 ]. Cancer cells in a way provide the best evidence for lactate overproduction being an efficient response to hypoxia. By mainly relying on anaerobic metabolism, malignant cells can not only survive but even proliferate in a hypoxic environment, so that tumor growth can exceed angiogenesis [ 13 ].
According to the theory of lactate shuttles proposed by Brooks, lactate may act as an oxidative substrate exchanged between cells and tissues [ 14 ].
Acidosis itself may arise as an adaptive response to inadequate energy provision and may extend cellular viability [ 15 ]. The prognosis of lactic acidosis primarily depends on the underlying mechanism and on its reversibility. When lactic acidosis is due to metformin accumulation, then renal replacement therapy can efficiently remove the toxic substance that is, metformin and not lactate! The situation can be much more complex and less easily reversible when lactic acidosis is primarily due to severe hypoxia or tissue hypoperfusion.
Based on present and past observations, one may conclude that the decision to treat or not to treat a patient with suspected metformin-induced lactic acidosis cannot be based only on the severity of clinical presentation.
You may also be instructed to curb your activity level in the hours leading up to the test. During the test, your doctor may tell you not to clench your fist, as this may artificially spike acid levels. Tying an elastic band around the arm may also have this result. For these reasons, the lactic acidosis blood test is sometimes done by finding a vein on the back of the hand instead of the arm.
The best way to treat lactic acidosis is by treating its root cause. For that reason, treatments vary. Lactic acidosis sometimes represents a medical emergency. This requires treating symptoms, regardless of their root cause. Increasing oxygen to the tissues and giving IV fluids are often used to reduce lactic acid levels.
Lactic acidosis caused by exercising can be treated at home. Electrolyte-replacement sports drinks, such as Gatorade, help with hydration, but water is usually best. Based on the root cause, treatments for lactic acidosis often result in full recovery, particularly if treatment is immediate.
Sometimes, kidney failure or respiratory failure may result. When left untreated, lactic acidosis can be fatal. Lactic acidosis prevention is also determined by its potential cause. If you have diabetes, HIV, or cancer, discuss your condition and the medications you need with your doctor.
Lactic acidosis from exercise can be prevented by remaining hydrated and providing yourself with long resting periods between exercise sessions. Discuss rehabilitation and step program options with your doctor or counselor.
When your body fluids contain too much acid, it's known as acidosis. Is it safe to drink alcohol while taking metformin for your diabetes? Learn about the specific risks of mixing alcohol with metformin and find out…. Metformin can cause side effects in some people. Metformin treats the symptoms of type 2 diabetes. Learn more about how this medication works and what you need to know if you want to stop taking….
The jejunum is one of three sections that make up the small intestine. Learn about its function and anatomy, as well as the conditions that can affect…. At-home microbiome testing kits can be a first step.
We look at these and give our recommendations for your overall gut health questions. Cholangitis is inflammation swelling in the bile duct. Treatment depends on your symptoms and whether you have chronic or acute cholangitis. Gastroparesis is a condition in which your stomach empties into your small intestine too slowly.
Learn about the best diet for gastroparesis and what…. There are no specific signs indicating lactic acidosis but its aetiology may be determined through careful examination. Lactic acidosis is suggested by the presence of metabolic acidosis without an obvious cause, such as ketosis or the presence of other acidic toxins. The anion gap should be calculated as below:. Any other cause of metabolic acidosis , particularly those due to diabetic ketoacidosis , other organic acidosis, chronic kidney disease, alcoholic ketoacidosis, hyperosmolar hyperglycaemic non-ketotic coma HONK , poisoning or drug toxicity.
Luft FC ; Lactic acidosis update for critical care clinicians. J Am Soc Nephrol. Suistomaa M, Ruokonen E, Kari A, et al ; Time-pattern of lactate and lactate to pyruvate ratio in the first 24 hours of intensive care emergency admissions.
Cochrane Database Syst Rev. Diabet Med. Kruse O, Grunnet N, Barfod C ; Blood lactate as a predictor for in-hospital mortality in patients admitted acutely to hospital: a systematic review. Bai Z, Zhu X, Li M, et al ; Effectiveness of predicting in-hospital mortality in critically ill children by assessing blood lactate levels at admission. BMC Pediatr. Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. Egton Medical Information Systems Limited has used all reasonable care in compiling the information but make no warranty as to its accuracy.
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