Multiple limb compartment syndrome as a manifestation of capillary leak syndrome secondary to metformin and dipeptidyl peptidase IV inhibitor overdose: A case report.

RATIONALE: Capillary leak syndrome is a condition that increases systemic capillary permeability and causes characteristic manifestations such as recurrent hypovolemia, systemic edema, and hemoconcentration. Acute limb compartment syndrome is a possible complication of severe capillary leak syndrome. However, timely diagnosis and prompt treatment are challenging because of atypical presentation. PATIENT CONCERNS: An 18-year-old woman with a history of clinical depression was admitted to our intensive care unit (ICU) because of metformin and vildagliptin overdose. She developed marked vasodilatory shock with recurrent severe hypovolemia and disseminated intravascular coagulation. After urgent hemodialysis and plasma exchange, she started to stabilize hemodynamically. However, her limbs became stone-hard with massive edema. Her serum creatinine kinase level increased to an extremely high level. DIAGNOSIS: Extremities were distended, and her skin developed pallor with blistering. Intramuscular pressure in both forearms and lower legs was significantly elevated. INTERVENTIONS: Decompressive fasciotomy was performed. Hemodialysis was continued because of rhabdomyolyses-induced acute kidney injury. OUTCOMES: The patient was finally able to walk by herself at the time of hospital discharge on day 109. LESSONS: The possibility of acute compartment syndrome should be considered in patients with marked capillary leakage, especially after aggressive fluid resuscitation. It is important to be aware of the compartment syndrome in an ICU setting because communication barriers often mask typical symptoms and make diagnosis difficult.

In vitro toxic evaluation of two gliptins and their main impurities of synthesis.

BACKGROUND: The presence of impurities in some drugs may compromise the safety and efficacy of the patient's treatment. Therefore, establishing of the biological safety of the impurities is essential. Diabetic patients are predisposed to tissue damage due to an increased oxidative stress process; and drug impurities may contribute to these toxic effects. In this context, the aim of this work was to study the toxicity, in 3 T3 cells, of the antidiabetic agents sitagliptin, vildagliptin, and their two main impurities of synthesis (S1 and S2; V1 and V2, respectively). METHODS: MTT reduction and neutral red uptake assays were performed in cytotoxicity tests. In addition, DNA damage (measured by comet assay), intracellular free radicals (by DCF), NO production, and mitochondrial membrane potential (ΔψM) were evaluated. RESULTS: Cytotoxicity was observed for impurity V2. Free radicals generation was found at 1000 µM of sitagliptin and 10 µM of both vildagliptin impurities (V1 and V2). A decrease in NO production was observed for all vildagliptin concentrations. No alterations were observed in ΔψM or DNA damage at the tested concentrations. CONCLUSIONS: This study demonstrated that the presence of impurities might increase the cytotoxicity and oxidative stress of the pharmaceutical formulations at the concentrations studied.