Cardiac Dysfunction Due to Thiamine Deficiency after Hemodialysis for Biguanide-related Lactic Acidosis.

Biguanide is an ideal drug for the treatment of type 2 diabetes mellitus. When used appropriately, the incidence of lactic acidosis is reported to be very low. Risk factors associated with biguanide-related lactic acidosis include chronic kidney disease, congestive heart failure, alcohol use, severe dehydration, shock, hypoxic states, sepsis, and advanced age. We herein report a case of cardiac dysfunction due to thiamine deficiency after hemodialysis in a patient with suspected biguanide-related lactic acidosis. Patients who develop severe lactic acidosis while taking biguanides should be given a large dose of thiamine without delay, given the possibility of thiamine deficiency as a complication.

Review of Biguanide (Metformin) Toxicity.

In the 1920s, guanidine, the active component of Galega officinalis, was shown to lower glucose levels and used to synthesize several antidiabetic compounds. Metformin (1,1 dimethylbiguanide) is the most well-known and currently the only marketed biguanide in the United States, United Kingdom, Canada, and Australia for the treatment of non-insulin-dependent diabetes mellitus. Although phenformin was removed from the US market in the 1970s, it is still available around the world and can be found in unregulated herbal supplements. Adverse events associated with therapeutic use of biguanides include gastrointestinal upset, vitamin B12 deficiency, and hemolytic anemia. Although the incidence is low, metformin toxicity can lead to hyperlactatemia and metabolic acidosis. Since metformin is predominantly eliminated from the body by the kidneys, toxicity can occur when metformin accumulates due to poor clearance from renal insufficiency or in the overdose setting. The dominant source of metabolic acidosis associated with hyperlactatemia in metformin toxicity is the rapid cytosolic adenosine triphosphate (ATP) turnover when complex I is inhibited and oxidative phosphorylation cannot adequately recycle the vast quantity of H+ from ATP hydrolysis. Although metabolic acidosis and hyperlactatemia are markers of metformin toxicity, the degree of hyperlactatemia and severity of acidemia have not been shown to be of prognostic value. Regardless of the etiology of toxicity, treatment should include supportive care and consideration for adjunct therapies such as gastrointestinal decontamination, glucose and insulin, alkalinization, extracorporeal techniques to reduce metformin body burden, and metabolic rescue.

The Dramatic Recovery of a Patient with Biguanide-associated Severe Lactic Acidosis Following Thiamine Supplementation.

Biguanides are a drug of choice for the treatment of type 2 diabetes mellitus. Although they can cause lactic acidosis in susceptible patients with predisposing risk factors, the incidence of lactic acidosis is reported to be very low when they are used properly. We herein present a case of biguanide-associated severe lactic acidosis complicated with thiamine deficiency that was provoked without predisposing factors for thiamine deficiency. Diabetic patients taking biguanide may be predisposed to thiamine deficiency, even when there is no evidence of risk factors, and the high-dose administration of thiamine may be essential in the treatment of this otherwise under-recognized disorder.

[Recommendations for the use of polyhexanide-containing products for the treatment of wounds]. / Konsensus-Empfehlungen zum Einsatz polyhexanidhaltiger Produkte in der Behandlung von Wunden.

Polihexanide-containing wound products are often used for the treatment of acute and chronic wounds. Although information pertaining to the use of polihexanide can be found in the literature, the appropriate use of these products in clinical practice is not always clear. The goal of this short review is to provide clinically relevant recommendations to physicians and nurses treating patients with acute and chronic wounds. This review describes the clinically relevant characteristics of polihexanide and gives recommendations for the prophylaxis and treatment of wound infections.

Impact of a rub and rinse on solution-induced corneal staining.

PURPOSE: To investigate whether the inclusion of a rub and rinse step before contact lens disinfection has an impact on solution-induced corneal staining. METHODS: This was a prospective, double-masked, single investigator study. Twenty participants were recruited for two visits, where balafilcon-A lenses were worn bilaterally for 2 h. Each pair of lenses was prepared using two different methodologies. The "control" lens was transferred from the blister pack directly into a storage case containing polyhexamethylene biguanide-based lens care solution. The contralateral "test" lens was rubbed and simultaneously rinsed using the same polyhexamethylene biguanide-based care solution, for either 60 s (visit 1) or 20 s (visit 2). Both lenses were then soaked in the solution overnight. After baseline corneal staining assessments, the lenses were inserted following a randomized contralateral model. After 2 h, lenses were removed, corneal staining was regraded, and comfort scores were obtained. RESULTS: Rubbed and rinsed test lenses induced significantly less corneal staining than control lenses for all participants during visit 1 (mean ± SD: 516 ± 843 vs. 2170 ± 902; p < 0.001) and visit 2 (522 ± 417 vs. 2091 ± 965; p < 0.001). There was no significant difference between the test lenses during visits 1 and 2 (p = 0.72) or controls (p = 0.50). Comfort scores did not differ between eyes (p > 0.05). CONCLUSIONS: Corneal staining induced after 2 h of lens wear with the combination of balafilcon-A and polyhexamethylene biguanide-based lens care solution can be significantly reduced by including a rub and rinse step before overnight soaking. Further work is required to establish the longevity of this effect during the monthly wearing cycle.

Oral antihyperglycemic therapy for type 2 diabetes mellitus.

Diabetes mellitus is a chronic disease that is growing in prevalence worldwide. Pharmacologic therapy is often necessary to achieve optimal glycemic control in the management of diabetes. Orally administered antihyperglycemic agents (OHAs) can be used either alone or in combination with other OHAs or insulin. The number of available OHAs has increased significantly in the last decade, which translates into more therapeutic options and complex decision-making for physicians. This review article is designed to help with these decisions. We review the mechanism of action, efficacy and side effects of the different classes of OHAs (alpha-glucosidase inhibitors, biguanides, insulin secretagogues, insulin sensitizers and intestinal lipase inhibitor) and discuss the current recommendations for their use.

Pharmacotherapy of type 2 diabetes mellitus.

OBJECTIVE: To review the drug treatments and some of the popular, nontraditional remedies now available for type 2 diabetes mellitus, as well as selected investigational agents; to describe each medication's place in the overall approach to treatment. DATA SOURCES: English-language journals, abstracts, review articles, and newspaper accounts. DATA SYNTHESIS: In the past five years, there has been tremendous progress in the pharmacotherapy of diabetes, particularly type 2 diabetes. Several new agents have entered the clinical arena, and many more are in the late stages of investigation leading to approval. Sulfonylureas stimulate the production and release of insulin; these drugs must be used in patients with an intact pancreas. The meglitinides are nonsulfonylurea agents that are also insulin secretagogues. Unlike the sulfonylureas, repaglinide appears to require the presence of glucose to close the adenosine triphosphate-sensitive potassium channels and induce calcium influx. Metformin reduces hepatic glucose production in some patients and increases peripheral glucose utilization, but its use is hampered by a high percentage of adverse reactions. Disaccharidase inhibitors effectively compensate for the defective early-phase insulin release by slowing the production of sugars from carbohydrates. Thiazolidinediones appear to activate peroxisome proliferator-activated receptor gamma, which is involved in the metabolism of lipids. Short-acting insulin and the role of weight-loss agents are also discussed. CONCLUSIONS: The availability of new options for diabetes therapy provides a chance for successful therapy in a larger number of patients. However, it is important to consider how much true benefit these new forms of treatment will have on the diabetic community. The best choice for a patient remains controversial.

[Pitfalls in treatment with oral antidiabetic agents]. / Uskalí lécby perorálními antidiabetiky.

In the treatment of type 2 diabetes (NIDDM) we possess three groups of oral hypoglycaemic drugs: sulfonyl urea derivatives, biguanides (metformin) and alpha-glucosidase (acarbose) inhibitors. Oral treatment of diabetes has a favourable impact on the patients metabolic deviations but it involves also certain dangers and pitfalls. The side-effects of oral antidiabetics can be reduced to a minimum by respecting consequentially contraindications of administration of different preparations, knowledge of their mechanism of action and individual selection of a suitable antidiabetic for every patient.

Comparative tolerability profiles of oral antidiabetic agents.

The sulphonylureas and the biguanides are widely used as adjuncts to dietary measures in the treatment of non-insulin-dependent (type 2) diabetes mellitus (NIDDM). Adverse effect profiles differ markedly between the sulphonylureas and biguanides, reflecting differences in chemical structure and mode of action. Sulphonylureas are generally well tolerated, although pharmacokinetic differences between these agents have important clinical implications. The main adverse effect associated with sulphonylureas is hypoglycaemia. This effect is a predictable consequence of the principal pharmacological effect of these drugs, i.e. sensitisation of the islet beta-cell to glucose, resulting in enhanced endogenous insulin secretion. Sulphonylurea-induced suppression of hepatic glucose production may cause profound and protracted hypoglycaemia, especially in elderly patients, in individuals with intercurrent illnesses and reduced caloric intake, or when taken in combination with other compounds with hypoglycaemic potential, e.g. alcohol (ethanol). Sulphonylureas with a longer duration of action, notably chlorpropamide and glibenclamide (glyburide), are more liable to induce serious hypoglycaemia, particularly when drug elimination is reduced by renal impairment. Other drugs such as salicylates may potentiate the actions of sulphonylureas, thereby increasing the risk of hypoglycaemia. Biguanide therapy is associated with alterations in lactate homeostasis which under certain clinical circumstances may result in fatal lactic acidosis. Phenformin is associated with a markedly greater risk of lactic acidosis than metformin. Phenformin has been withdrawn in many countries for this reason. All biguanides must be avoided in patients with renal impairment, hepatic dysfunction and cardiac failure--conditions where drug accumulation or disordered lactate metabolism may predispose to lactic acidosis. Phenformin should not be given to individuals who exhibit a severe, genetically conferred hepatic defect of hydroxylation which impedes metabolism of this drug. Less seriously, the biguanides are associated with a relatively high incidence of gastrointestinal adverse effects which limit compliance. Acarbose, a competitive inhibitor of intestinal alpha-glucosidases, has recently been introduced. In contrast to the sulphonylureas and biguanides, acarbose has not been associated with life-threatening adverse effects. This reflects the low systemic absorption of the drug and, predictably, its principal unwanted effects are gastrointestinal disturbances resulting from iatrogenic carbohydrate malabsorption.

[Local antiseptics in surgery--rebirth and advances]. / Lokale Antiseptika in der Chirurgie--Wiedergeburt und Weiterentwicklung.

The history of antisepsis is marked by names such as Pringle, Lister, Billroth, Koch, Kocher, von Volkmann, von Nussbaum, Schloffer and Carrel. The revolutionary initial success of Lister's method was followed by severe setbacks because persisting biological intolerance of the chemical and physical antiseptics prevented the main purpose of application: killing bacteria without damaging cells. Until the discovery of penicillin the predominantly used antiseptics were perubalsam (balsamum peruvianum), azo-dyes (Rivanol), and sulphonamides (Cibazol). The dawn of the "antibiotic age" demonstrated once more the limits of locally applied therapeutic effectiveness of these substances (antiseptics, antibiotics) and was often outweighed by the damage caused. For the same reason systemicly applied substances frequently lack satisfactory effectiveness in the area of tissue damage. Experiences with intraoperative and postoperative wound lavage have shown that favourable results achieved by this surgical procedure are more likely due to the mechanical cleaning process than to the effectiveness of the locally applied substances being limited by the restricted duration of influence and the restricted depth of tissue penetration. Taking into account earlier studies and long-term experiences, antiseptic solutions were tested in view of their tissue compatibility, their biologic availability, and their effectiveness in close cooperation of clinic, bacteriology and laboratory medicine. The coordinated investigations resulted in a solution of biguanid (Lavasept) which is free from iodine, quicksilver, PVP and aldehyde. It can be applied for local treatment of wounds liable to infection, as an adjuvant for wound treatment in cases of acute tissue infections, as well as in the surgival practise to take care of acute and chronic infections of soft tissue. Sofar locally applied antiseptics in surgery have proved to be less satisfactory than considered in the course of their history due to side effects, e.g. tissue damage. Coordinated investigations now present an antiseptic solution of biguanid which can be used in various cases of wound treatment to prevent or counteract infections.

Comparison of the bisbiguanide antiseptics alexidine and chlorhexidine. II. Clinical and in vitro staining properties.

A blind cross-over trial was carried out to compare the tooth and tongue staining associated with the use of a 0.035% alexidine and a 0.2% chlorhexidine mouthrinse. Twenty-two volunteers were divided into two groups termed "tea drinkers" and "non-tea drinkers". All volunteers were requested to refrain from oral hygiene measures throughout two 10-day periods when they rinsed twice a day with the preparation randomly allocated for the respective period. During both periods the members of the groups excluded coffee, red wine and port from their diet. The tea drinking group consumed seven cups of tea per day. Tooth and tongue staining was recorded for extent and severity at the end of each period. The amount of stain accumulating in the two groups was similar following the use of chlorhexidine and alexidine. However, for both chlorhexidine and alexidine the extent and severity of tooth and tongue staining were significantly increased in the tea drinking group. An in vitro study of tea staining of perspex blocks exposed twice a day to 0.035% solutions of alexidine or chlorhexidine throughout a 5-day period demonstrated significantly more staining with alexidine when measured spectrophotometrically. Visually however, the differences in the specimens were minimal. Saliva treatment of the perspex did not significantly alter the staining by alexidine or chlorhexidine. The results provide further evidence for a dietary aetiology to the staining associated with cationic antiseptics. However, alexidine at the concentration used offered no advantage in reducing the side effect of staining when compared with chlorhexidine.

Tooth staining effects of an alexidine mouthwash.

The primary purpose of this study was to determine the amount of tooth staining produced by an alexidine mouthrinse. One hundred and eighty subjects rinsed twice daily for 1 month with either 15 ml of alexidine (0.035%) or a placebo solution. Prior to the study, the subjects were classified according to their smoking, coffee and tea drinking habits and these factors were subsequently considered in the analysis of the stain scores. Additionally, the effects on staining of a prior prophylaxis and the use of a fluoridated toothpaste during the study were determined. Upon termination of the study, subjects utilizing the active mouthrinse manifested a greater degree of staining than placebo users. The amount and intensity of the stain due to alexidine were not influenced (increased) by smoking, tea or coffee drinking habits. A prior prophylaxis did not reduce the staining propensity of alexidine users. The method of scoring developed can be used to assess the degree of tooth staining induced by antiplaque agents.

Treament of biguanide-induced lactic acidosis with dichloroacetate. 3 case histories.

The administration of dichloroacetate (DCA) in cases of biguanide-induced lactic acidosis (LA) improves pyruvate oxidation and therefore increases energy production from glucose. Preliminary results of treatment of LA in humans are reported. A continuous fall in pyruvate was observed in all 3 cases after administration of at least 20 g of DCA (4 g i.v. bolus, then continuously 12 g/h). In Case 1, in which no supplementary measures for controlling the acidosis were applied, the acidosis did not improve and the patient died. In Case 2, despite administration of tris-buffer and dialysis, pH-values could not be raised sufficiently. The production of hydrogen ions persisted and lactate continued to rise. This patient also died. Case 3 was admitted in the beginning stages of a phenformin-induced LA, and in this case therapy was successful. The decline in pyruvate was accompanied by a slow fall in lactate, and a further fall in pH was averted. The clinical condition of the patient improved markedly after i.v. administration of a total of 34 g of DCA.