Lactic Acidosis Secondary to Thiamin Deficiency Following Autologous Stem Cell Transplantation.

A 22-month-old female with high-risk neuroblastoma completed 5 cycles of chemotherapy then underwent high-dose chemotherapy with autologous stem cell rescue (ASCR). Parenteral nutrition was administered from day +2 following ASCR, as she was unable to tolerate nasogastric feeds because of grade IV mucositis and vomiting. On day +12, she developed worsening metabolic acidosis with above reportable levels of lactic acid. Given the patient's well clinical appearance and paucity of evidence of end-organ dysfunction on physical examination and on laboratory studies, there was high suspicion that the patient's lactic acidosis did not result from tissue hypoxia and was, in fact, a type B lactic acidosis. Thiamin was empirically administered, with rapid improvement in lactic acidosis. Thiamin deficiency was later confirmed by laboratory studies drawn prior to thiamin administration.

Riboflavin responsive mitochondrial myopathy is a new phenotype of dihydrolipoamide dehydrogenase deficiency. The chaperon-like effect of vitamin B2.

Dihydrolipoamide dehydrogenase (DLD, E3) is a flavoprotein common to pyruvate, α-ketoglutarate and branched-chain α-keto acid dehydrogenases. We found two novel DLD mutations (p.I40Lfs*4; p.G461E) in a 19 year-old patient with lactic acidosis and a complex amino- and organic aciduria consistent with DLD deficiency, manifesting progressive exertional fatigue. Muscle biopsy showed mitochondrial proliferation and lack of DLD cross-reacting material. Riboflavin supplementation determined the complete resolution of exercise intolerance with the partial restoration of the DLD protein and disappearance of mitochondrial proliferation in the muscle. Morphological and functional studies support the riboflavin chaperon-like role in stabilizing DLD protein with rescue of its expression in the muscle.

Lactic acidosis following intentional overdose by inhalation of salmeterol and fluticasone.

Salmeterol, a long-acting ß2-adrenergic receptor agonist used for the treatment of asthma and chronic obstructive pulmonary disease, has an adverse effects profile that is similar to that of salbutamol and other ß2-agonists. We report a sympathomimetic syndrome with metabolic acidosis and hyperlactatemia after intentional inhalation of salmeterol in a suicide attempt. A 16-year-old female patient was admitted to the emergency department approximately 2 hours after having inhaled 60 puffs of a combination of salmeterol xinafoate 25 µg and fluticasone propionate 50 µg. She presented in an anxious state with complaints of palpitations and chest pain. The electrocardiogram demonstrated sinus tachycardia and ST-segment depression in the inferior and anterolateral leads. Laboratory findings showed hypokalemia, hypophosphatemia, and lactic acidosis. Cardiac troponin I and creatine kinase MB remained within the normal range. Treatment was supportive and included intravenous fluids and cautious potassium supplementation. The next day, electrocardiographic and laboratory findings returned to normal. We hypothesize that stimulation of ß2-adrenergic receptors by inhalation of salmeterol caused this patient's lactic acidosis. This observation is consistent with the hypothesis that the hyperlactatemia observed during asthma attacks is due in part to the administration of high doses of ß2-agonists. Salmeterol overdose by inhalation appears to be sufficient to cause lactic acidosis.

53-years-old with mental status changes.

D-lactic acidosis, a complication of short bowel syndrome, presents with a variety of neurological symptoms and metabolic acidosis. Treatment is hydration, replacement of nutritional deficiency replacement, and selective antibiotics. Prevention entails complex carbohydrate diet and vitamin and mineral supplements.

Severe lactic acidosis and thiamine deficiency during total parenteral nutrition--case report.

We encountered a case of total parenteral nutrition-associated lactic acidosis that did not respond to sodium bicarbonate or other conventional emergency treatments. He was characterized by minimal food intake before surgery, delayed gastric emptying after pylorus-preserving pancreatoduodenectomy due to pancreas head cancer and long-term total parenteral nutrition without food intake and vitamin supplements after surgery. After thiamine administration, the patient very quickly recovered with dramatic reestablishment of the acid-base balance. We emphasize the need to supplement total parenteral nutrition with thiamine-containing vitamins for the patients whose food intake does not meet nutritional requirements and to intravenously replenish using high-dose thiamine simultaneously with the manifestation of signs and symptoms of severe lactic acidosis with unknown cause. In conclusion, thiamine deficiency should be included in the differential diagnosis of lactic acidosis for the patients who received total parenteral nutrition without food intake and vitamin supplements.

[Severe lactic acidosis and thiamine deficiency during parenteral nutrition in a child]. / Acidose lactique sévère et déficit en thiamine au cours d'une nutrition parentérale chez un enfant.

We report the case of a leukemic child treated with chemotherapy and parenteral nutrition for three weeks, who developed a severe lactic acidosis. Clinical features included both digestive and neurological disorders associated with a moderate cardiovascular collapse. After elimination of a toxic, a neoplastic or a septic cause, a thiamin (or vitamin B1) deficiency was suspected because of the lack of vitamin supply to parenteral nutrition. Intravenous administration of thiamin rapidly controlled lactic and clinical features. The diagnosis was confirmed by a low plasmatic concentration of thiamin. Thiamin deficiency must be suspected in case of severe lactic acidosis during parenteral nutrition and systematically prevented by supply of vitamins.

Phenformin-associated lactic acidosis due to imported phenformin.

OBJECTIVE: To emphasize the continued incidence of phenformin-associated lactic acidosis. CASE REPORT: We report a case of phenformin-associated lactic acidosis in a Chinese man who received phenformin while in China. Diagnosis was made; the patient was treated appropriately and survived. COMMENTS: Phenformin-associated lactic acidosis may still occur in the U.S.

Glutathione deficiency as a complication of methylmalonic acidemia: response to high doses of ascorbate.

A 7-year-old boy with deficient activity of methylmalonyl coenzyme A mutase (mut-methylmalonic acidemia) was seen in severe metabolic crisis. After hemodialysis and clearance of toxic metabolites, severe lactic acidosis persisted with multiorgan failure. Glutathione deficiency was noted and high-dose ascorbate therapy (120 mg/kg) commenced. Glutathione deficiency may contribute to the lactic acidosis observed during decompensation in patients with methylmalonic acidemia.

Diets enriched with N-3 fatty acids ameliorate lactic acidosis by improving endotoxin-induced tissue hypoperfusion in guinea pigs.

The effect of 6 weeks dietary lipid manipulation on the acute physiologic response to 7-hour continuous endotoxin infusion in guinea pigs was examined. One diet was enriched with N-3 fatty acids, whereas the other contained N-6 fatty acids, primarily linoleic acid. Animals fed N-6 fatty acids developed significant lactic acidemia, microvascular muscle hypoperfusion, and pulmonary infiltrates in response to endotoxin infusion. N-3 fatty acid-fed animals demonstrated improved lactate levels, microvascular muscle perfusion, and lung morphology compared to N-6 fatty acid-fed animals after endotoxin infusion. There was no significant change in cardiac output, PaO2, or mean arterial blood pressure at the end of the endotoxin infusion in either group. Pretreatment with indomethacin, or BM 13505, a specific thromboxane A2 receptor blocker, ameliorated the development of metabolic acidosis in N-6 fatty acid-fed animals, demonstrating a role for prostanoids in the sequelae of endotoxemia. The ability of dietary pretreatment with N-3 fatty acids to influence favorably the physiologic response to endotoxin represents a novel nutrient-metabolic interaction with potential therapeutic implications.

Severe lactic acidosis related to acute thiamine deficiency.

The authors report a case of severe lactic acidosis in a 3-year-old boy, after 20 days of total parenteral nutrition without vitamin supplementation. This child with acute lymphoblastic leukemia underwent a period of severe refractory lactic acidosis (pH between 6.81 and 7.00 and a serum lactate level up to 38 mmol/liter) leading to cardiac arrest. After the initial resuscitation and the subsequent treatment of shock and vitamin K deficiency, acute peritoneal dialysis was instituted to correct the severe lactic acidosis. Initial low plasma thiamine levels confirmed the diagnosis of thiamine deficiency. An associated transient pancreatic dysfunction was also noted. The patient's overall course with thiamine replacement therapy led to a complete recovery within 5 days and no sequelae were noted after 12 months.

Severe metabolic acidosis and "muti" (traditional herbal medicine) ingestion in young children.

Twenty infants and young children admitted with severe metabolic acidosis and a positive history of 'muti' ingestion were investigated. All had accompanying gastroenteritis and significant dehydration. Biochemical data was diagnostic of high anion/gap metabolic acidosis in the majority (70 per cent). Further biochemical data indicated that lactic acidosis and pre-renal azotaemia resulting from severe hypovolaemia were likely causes of the high anion GAP metabolic acidosis. There was no evidence to suggest that the ingested muti per se was associated directly with the acidosis or acute renal failure seen in these children.

Lactic acidosis in theophylline overdose.

An 18-year-old man with theophylline overdose developed an increased anion gap metabolic acidosis. Serum lactate levels were markedly elevated. A direct correlation was found between the increasing theophylline level, clinical hyperadrenergic state, and the worsening acidosis. Early hemoperfusion reversed the acidosis, the elevated serum theophylline level, and the hyperadrenergic state. This case substantiates the role of lactate accumulation in the metabolic acidosis associated with isolated theophylline toxicity.