Perioperative use of metformin in cardiac surgery.
ABSTRACT Metformin is an oral antidiabetic agent, used to reduce blood glucose concentration in patients with non-insulin-dependent diabetes mellitus. Metformin was approved in Europe in 1957, and it is used for the treatment of non-insulin-dependent diabetes mellitus for more than 50 years. One of the most serious complications of the treatment with this drug is metformin-induced lactic acidosis. It is a rare but dangerous metabolic complication with a mortality rate of up to 50% that can result from the accumulation of lactates. Lactic acidosis is also associated with conditions such as diabetes mellitus, significant tissue hypoperfusion, and hypoxemia caused by lactic acid overproduction or underutilization. It is characterized by an increased serum lactate level (>5 mmol/L or >45 mg/dL), decreased blood pH (<7.35), and electrolyte imbalance with an increased anion gap. The rate of lactic acidosis in patients receiving metformin is not precisely known. The estimated incidence of this syndrome is 2-9 cases per 100 000 patients. However, in the majority of cases, lactic acidosis is diagnosed in patients with severe acute renal failure, which itself can cause lactic acidosis. Currently, there are no standardized guidelines for metformin administration during the perioperative period, and published data remain controversial. According to some investigators, metformin should be withdrawn before major surgery. Concerns have been raised for the use of metformin in patients with cardiovascular, renal, hepatic, and respiratory failure. The aim of the article is to overview the frequency of metformin-caused lactic acidosis and the latest recommendations for the use of metformin in the perioperative period proposed in recent years.
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ABSTRACT: Chronic pain is a critical medical problem afflicting hundreds of millions of people worldwide with costly effects on society and health care systems. Novel therapeutic avenues for the treatment of pain are needed that are directly targeted to the molecular mechanisms that promote and maintain chronic pain states. Recent evidence suggests that peripheral pain plasticity is promoted and potentially maintained via changes in translation control that are mediated by mTORC1 and MAPK pathways. While these pathways can be targeted individually, stimulating the AMPK pathway with direct or indirect activators achieves inhibition of these pathways via engagement of a single kinase. Here we review the form, function and pharmacology of AMPK with special attention to its emerging role as a potential target for pain therapeutics. We present the existing evidence supporting a role of AMPK activation in alleviating symptoms of peripheral nerve injury- and incision-induced pain plasticity and the blockade of the development of chronic pain following surgery. We argue that these preclinical findings support a strong rationale for clinical trials of currently available AMPK activators and further development of novel pharmacological strategies for more potent and efficacious manipulation of AMPK in the clinical setting. Finally, we posit that AMPK represents a unique opportunity for drug development in the kinase area for pain because it is pharmacologically manipulated via activation rather than inhibition potentially offering a wider therapeutic window with interesting additional pharmacological opportunities. Altogether, the physiology, pharmacology and therapeutic opportunities surrounding AMPK make it an attractive target for novel intervention for chronic pain and its prevention.Neuroscience Letters 07/2013; DOI:10.1016/j.neulet.2013.06.060 · 2.06 Impact Factor