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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with diabetes mellitus are at a higher risk to undergo surgical intervention compared with the non-diabetic population, and additionally, they have an increased perioperative morbidity and mortality. Insulin deficiency and insulin resistance are aggravated by surgery and anaesthesia. The consequences of hyperglycemia are glycosuria, volume depletion from osmotic diuresis, impairment of wound healing and leucocyte function and exacerbation of ischemic brain damage. Depending on the extent of hypoinsulinemia, lipolysis and ketogenesis are enhanced which may result in metabolic acidosis with subsequent electrolyte disturbances. Protein catabolism is increased because of increased breakdown and decreased synthesis. Insulin administration reverts or overcomes most of these disturbances. The preoperative assessment includes the diagnoses of the long-term complications to judge the intraoperative risks. Long-acting insulins, such as ultralente of animal origin should be stopped preoperatively and substituted by protamine and lente insulins. In type-2-diabetic patients, long-acting sulfonylurea drugs such as chlorpropamide should be stopped and substituted by short-acting agents. Metformin must always be stopped. Type-2-diabetic patients with marked hyperglycemia under oral treatment should be switched to insulin before operation. The insulin requirements in diabetic patients during surgery vary from 0.25-0.40 U per gram glucose in normal weight patients, 0.4-0.8 U per gram glucose in case of obesity, liver disease, steroid therapy or sepsis, to 0.8-1.2 U per gram glucose in patients undergoing cardiopulmonary bypass surgery. Therefore, the appropriate dose has to be determined individually. The regimen nowadays preferred by most authors is based on variable rate insulin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Perioperative management of the diabetic patient. 758 26

Metformin is a biguanide that can used alone or in combination with sulfonylureas or insulin in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). Since biguanides do not increase pancreatic insulin secretion, they are referred to as antihyperglycemic agents, as opposed to hypoglycemic agents. Biguanides reduce hyperglycemia by increasing, insulin sensitivity, decreasing glucose absorption, and inhibiting hepatic gluconeogenesis. Advantages of metformin include achieving glycemic control without exacerbating weight gain or hyperinsulinemia and beneficially affecting serum cholesterol concentrations. Although metformin has the potential to cause lactic acidosis, the incidence is significantly lower compared with phenformin. Risk factors for lactic acidosis include renal serum creatinine > 1.5 mg/dL and cardiovascular, pulmonary, and hepatic disease. Metformin should be temporarily discontinued prior to surgery and before administration of radiologic intravenous contrast, and in patients with sepsis, severe gastrointestinal disease, trauma, and acute cardiovascular events.
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PMID:Metformin: a new treatment option for non-insulin-dependent diabetes mellitus. 865 73

Metformin [2-(N,N-dimethylcarbamimidoyl)guanidine] is a drug used in the treatment of type 2 diabetes. Recent studies have suggested that metformin may have effects in addition to lowering serum glucose concentrations (e.g., anti-inflammatory). The aim of the present study was to determine whether metformin prevents the inflammatory reaction and liver damage in a model of postsurgical sepsis. Accordingly, rats underwent 2/3 partial hepatectomy (PH; or sham surgery); 48 h after surgery, animals were administered endotoxin (LPS; 1.5 mg/kg i.v.). Both PH and LPS alone caused some minor liver damage. However, their combined effect (PH/LPS) was synergistic, leading to robust hepatic damage, as indicated by plasma enzymes and histological assessment. Although metformin treatment did not alter changes caused by PH alone, it almost completely blunted the effects of LPS in the PH/LPS group. Increases in biomarkers of inflammation (e.g., interleukin 6, interferon gamma, and neutrophil number) were also blunted by metformin treatment. Furthermore, PH/LPS caused a >200x increase in hepatic plasminogen activator inhibitor 1 (PAI-1) mRNA expression and plasma PAI-1 protein. These increases were associated with inhibition of hepatic urokinase plasminogen activator activity and an increase in fibrin deposition, indicative of local thrombosis. These effects were markedly reduced by metformin treatment. In conclusion, these data demonstrate that metformin prevents liver damage in a model of postsurgical sepsis in rats by decreasing proinflammatory and hemostatic responses.
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PMID:Metformin prevents endotoxin-induced liver injury after partial hepatectomy. 1632 56

Clinicians are faced with an expansive array of treatment choices when caring for patients with type 2 diabetes. Because patient compliance may be affected when media sensationalism about controversial findings is misunderstood, we sought to clarify the recent controversy surrounding the cardiovascular and bone-health risks of thiazolidinediones, the risk of lactic acidosis with metformin, and the risk of hypoglycemia with oral therapies. The side effect profile of thiazolidinediones includes fluid retention, heart failure; and an increased risk of fracture. A recent controversial meta-analysis suggested that rosiglitazone increases the risk of myocardial infarction, which is possibly related to thiazolidinedione-induced lipid changes, weight gain, congestive heart failure, and anemia. Metformin is restricted to patients with normal renal function because of concerns that metformin may cause lactic acidosis. However, few cases of metformin-associated lactic acidosis have been reported, and most have occurred in patients with other reasons for developing lactic acidosis, such as sepsis or renal failure. Although the use of metformin continues to increase, observational studies have not been able to demonstrate an increased incidence of lactic acidosis in metformin-treated patients, even when it is used in populations with relative contraindications. Some oral hypoglycemic medications can cause hypoglycemia. Hypoglycemia is especially common in older patients, alcoholics, and patients with liver or renal disease. Patients on sulfonylureas and meglitinides have the highest incidence of hypoglycemia because of their pharmacological action of increasing insulin secretion. Of the sulfonylureas, glyburide presents the highest risk of hypoglycemia. Combination therapies, especially those regimens containing a sulfonylurea, increase the risk of hypoglycemia.
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PMID:Balancing risk and benefit with oral hypoglycemic drugs. 1942 67

Metformin is the first-line oral agent in the treatment of type 2 diabetes and has many established benefits, including the reduction of macrovascular complications of diabetes. Its prescription in patients with renal impairment is limited by concerns relating to the theoretical risk of lactic acidosis, a fear which is perpetuated by numerous case reports in which it is implicated. Critical review of this literature calls into question the validity of these claims, with metformin usually acting as an 'innocent bystander' in acutely unwell patients with conditions well recognised to precipitate lactic acidosis such as sepsis or hypovolaemia. In fact, the evidence supports the safe use of appropriate doses of metformin in patients with chronic stable renal impairment, and highlights the important possible greater risks of the alternatives, most notably severe hypoglycaemia in patients taking sulphonylureas and/or insulin and fluid retention in patients taking a thiazolidinedione. Other traditional contraindications to metformin use such as heart failure are also being re-evaluated, as the benefits of metformin in these patients are increasingly recognised. Physicians should weigh this evidence carefully before deciding to withdraw metformin therapy in their patients with stable chronic kidney disease.
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PMID:Metformin: the safest hypoglycaemic agent in chronic kidney disease? 2132 70

Glucose-lowering treatment in patients with type 2 diabetes and heart failure is controversial. Metformin is clearly contraindicated when such diseases coexist. Conversely, no contraindications have been established for insulin in this subset of patients, even though several observational and retrospective studies have shown increased mortality and worsening heart failure. Data from the literature have demonstrated that in this patient population, which accounts for one third of all cases of heart failure, metformin reduces mortality by 14-35%. In patients with a glomerular filtration rate >30 ml/min who do not show dehydration, shock, sepsis, severe liver disease or hypoxemia, the administration of metformin doses <2 g/day was associated with a null risk of lactic acidosis. The positive effects of metformin are correlated with the reduction in insulin resistance, which is responsible for both the onset and development of heart failure in diabetic patients. Insulin can provoke severe hypoglycemia and fluid retention, resulting in negative effects. Further randomized and prospective studies are warranted to address these controversial issues in such a large population with high mortality and morbidity rates. Longitudinal studies would be crucial to the understanding of the optimal therapy and for stratification of patients according to the severity of heart failure.
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PMID:[Metformin and insulin in chronic heart failure: contraindications not contraindicated and indications not indicated]. 2215 50

We describe the case of a patient with severe lactic acidosis, as well as presenting some data on its incidence, diagnosis, prognostic factors, and the most appropriate treatment. A 76 year-old male patient with diabetes on treatment with metformin, hypertension, dyslipaemia, and with mild cognitive impairment, was admitted to the Intensive Care Unit in a state of circulatory shock, requiring aggressive treatment with vasopressors and volume. The patient had acute kidney injury with an anuria of 3 days, probably secondary to dehydration to vomiting and to NSAIDs. As a result of the acute renal damage, the patient suffered a severe metformin-associated lactic acidosis. The rest of the causes of metabolic acidosis with an increased anion gap were ruled out, as well as a possible sepsis or rhabdomyolysis. Metformin-associated lactic acidosis is an uncommon metabolic condition, but with a high mortality. To reduce the mortality of these patients, it is important to make an early diagnosis using the clinical records, physical examination, and laboratory tests, with an early resuscitation with volume, vasopressors, bicarbonate, and renal replacement therapy.
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PMID:[Metformin-associated lactic acidosis: incidence, diagnosis, prognostic factors and treatment]. 2260 63

A wide array of benefits has been attributed to metformin. These include attenuation of abnormal glucose metabolism (diabetes treatment and prevention), weight neutrality or weight loss, improvement in the pathophysiologic components of metabolic syndrome (insulin resistance, subclinical inflammation, and endothelial dysfunction), lipid-lowering properties, cardiovascular protection, and antineoplastic potential. Metformin itself is not a nephrotoxic drug. Initially appointed as the safest hypoglycemic agent in chronic kidney disease, its use has been limited in these patients because of the perceived risk of lactic acidosis. A fear perpetuated by numerous case reports in which it is implicated. Current guidelines stipulate that it must be used with caution in estimated glomerular filtration rates (eGFRs) of less than 60 mL/minute and not at all in eGFRs of less than 30 mL/minute. Identified risk factors for metformin-associated lactic acidosis include acute kidney injury, hypoxemia, sepsis, alcohol abuse, liver failure, myocardial infarction, and shock. Treatment may include supportive care and dialysis techniques. On the other hand, it is likely that the use of metformin would be beneficial in many with chronic kidney disease according to the advantages associated with attenuation of metabolic syndrome and cardiovascular protection. The reality of severe metformin-induced lactic acidosis in the absence of chronic renal impairment raises the question of limitation of its use in these patients.
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PMID:Metformin in patients with chronic kidney disease: strengths and weaknesses. 2264 82

Metformin is the first-line, widely used oral antidiabetic agent for the management of type 2 diabetes. There is increasing evidence that metformin use results in a reduction in cardiovascular morbidity and mortality, and might have anticancer activity. An extremely rare, but potentially life-threatening adverse effect of metformin is lactic acidosis, therefore, its use is traditionally contraindicated if the glomerular filtrate rate is below 60 mL/min. However, lactic acidosis is always associated with acute events, such as hypovolemia, acute cardiorespiratory illness, severe sepsis and acute renal or hepatic failure. Furthermore, administration of insulins and conventional antihyperglycemic agents increases the risk of severe hypoglycemic events when renal function is reduced. Therefore, the magnitude of the benefit of metformin use would outweigh potential risk of lactic acidosis in moderate chronic renal disease. After reviewing the literature, the authors give a proposal for the administration of metformin, according to the calculated glomerular filtrate rate.
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PMID:[Proposal for the modification of metformin use in patients with chronic kidney disease]. 2300 Apr 19

Metformin is a drug widely used in type 2 diabetic patients. Metformin-associated lactic acidosis (MALA) in diabetic patients is rare but can be serious. However, the relationship between metformin and lactic acidosis is under debate. We present seven cases of patients with MALA who came to our centre over a period of one year and who were treated early with haemodiafiltration. There are some risk factors that appear to predispose patients to this pathology, such as: acute renal failure, situations of hypoxemia and sepsis, cardiac or respiratory failure, previous history of lactic acidosis, liver disease and dehydration. As such, the use of metformin is discouraged in patients with GFR below 30 ml/min/1.73 m(2). All patients in our study were treated early with haemodiafiltration. The mortality in our study was 16.6%. We believe that MALA is a serious condition that requires prompt diagnosis and early treatment. Renal replacement therapy is not the solution for all patients, but can improve prognosis in more severe cases if started early. We should limit the use of metformin in diabetic patients with impaired renal function, although there is still controversy in the medical literature.
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PMID:The importance of early haemodiafiltration in the treatment of lactic acidosis associated with the administration of metformin. 2301 54


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