Pyruvate dehydrogenase complex deficiency masked by septic shock-induced lactic acidosis: a case report.

Pyruvate dehydrogenase complex (PDHC) deficiency is a common genetic disorder leading to lactic acidosis, which can also result from several nongenetic conditions, such as septic shock. The present study reports a case of PDHC deficiency masked by septic shock-induced lactic acidosis. This case involved a 16-year-old adolescent with poor exercise tolerance compared with his peers, and no underlying diseases. The disease onset was characterized by cough, fever, and dyspnea, with hypotension and elevated lactate levels, which indicated septic shock. However, severe hypoglycemia and lactic acidosis persisted despite resolution of a pulmonary infection and correction of septic shock, requiring continuous intravenous infusion of 50% glucose. Although the patient did not experience acute kidney injury and had normal urine output, continuous renal replacement therapy was used to regulate the internal environment owing to the severity of the acidosis. The diagnosis of PDHC deficiency was considered on the basis of the persistent hypoglycemia and hyperlactatemia, before genetic mutation testing was completed. The clinical thinking process required a rich accumulation of pathophysiological knowledge. This article reports a case of PDHC deficiency masked by septic shock-induced lactic acidosis to raise awareness of the disease and avoid misdiagnosis and missed diagnosis.

Factors associated with D-lactic acidosis in pediatric intestinal failure: A case-control study.

BACKGROUND: D-lactic acidosis (DLA) is a serious complication of short bowel syndrome (SBS) in children with intestinal failure (IF). Malabsorbed carbohydrates are metabolized by bacteria in the intestine to D-lactate which can lead to metabolic acidosis and neurologic symptoms. METHODS: A retrospective chart review was performed in children ≤18 years old with SBS who had one of the following criteria: unexplained metabolic acidosis, neurologic signs or symptoms, history of antibiotic therapy for small bowel bacterial overgrowth, or high clinical suspicion of DLA. Cases had serum D-lactate concentration >0.25 mmol/L; controls with concentrations ≤0.25 mmol/L. RESULTS: Of forty-six children, median age was 3.16 (interquartile range (IQR): 1.98, 5.82) years, and median residual bowel length was 40 (IQR: 25, 59) cm. There were 23 cases and 23 controls. Univariate analysis showed that cases had significantly lower median bicarbonate (19 vs. 24 mEq/L, p = 0.001), higher anion gap (17 vs. 14 mEq/L, p < 0.001) and were less likely to be receiving parenteral nutrition, compared with children without DLA. Multivariable analysis identified midgut volvulus, history of intestinal lengthening procedure, and anion gap as significant independent risk factors. Midgut volvulus was the strongest independent factor associated with DLA (adjusted odds ratio = 17.1, 95% CI: 2.21, 133, p = 0.007). CONCLUSION: DLA is an important complication of pediatric IF due to SBS. Patients with IF, particularly those with history of midgut volvulus, having undergone intestinal lengthening, or with anion gap acidosis, should be closely monitored for DLA.

Malignancy Associated Type B Lactic Acidosis: A Rare, yet Fascinating Oncological Emergency.

Type B lactic acidosis has been described infrequently in hematologic malignancies, but even less often in solid tumors. Since 1978, there have been only 58 cases of solid tumor associated Type B lactic acidosis described in the literature. Lung cancer (neuroendocrine) is the most common tumor; others frequently have a poorly/undifferentiated histology. The prognosis is dismal. Malignancy associated type B lactic acidosis is not associated with hypoxemia. The most highlighted pathogenetic mechanism is the Warburg effect (aerobic glycolysis of tumor cells causing excess lactate). We describe a patient with metastatic GI neuroendocrine carcinoma with profound lactic acidosis, who died within 24 hours. When extremely ill cancer patients present with lactic acidosis, sepsis is usually a primary concern. This case highlights the need for providers to consider malignancy associated lactic acidosis (MA-LA) in the differential diagnosis, particularly in patients with advanced malignancies, of lung origin, of neuroendocrine or poorly/undifferentiated histologic subtypes. The implications and approach are distinct from Type A/D lactic acidosis, and would involve treatment of the underlying malignancy at the earliest.

B-cell hepatosplenic lymphoma presenting in adult patient after spontaneous splenic rupture followed by severe persistent hypoglycaemia: type B lactic acidosis and acute liver failure.

A patient was admitted to hospital with splenic rupture, four 4 days after colonoscopy was performed following one month's intermittent and aggravating abdominal pain. During recovery from splenectomy, the patient developed sudden tachycardic and tachypnoea. A blood sample revealed a very low blood glucose, high lactate and acidaemia.The patient required high-dose continuous intravenous glucose, while the lactate remained elevated. Decreasing consciousness with signs of acute liver failure necessitated transfer to an advanced intensive care unit. The patient's clinical status rapidly deteriorated despite therapeutic intervention. The patient died of multiorgan failure eleven days post-splenectomy. Based on the pathology of the spleen and a post-mortem liver specimen, the patient was diagnosed with a primary extra-nodal B-cell hepatosplenic lymphoma (BCHSL) - an extremely rare form of non-Hodgkin lymphomanon.Splenic rupture followed by lactic acidosis and hypoglycaemia should lead to suspicion of a cancer-mediated Warburg effect, and prompt urgent chemotherapy.

An Elusive Diagnosis: Diffuse Large B-Cell Lymphoma Masquerading as Acute Liver Failure with Persistent Lactic Acidosis.

BACKGROUND Acute liver failure (ALF) associated with malignant lymphoma is a rare condition with non-specific clinical and radiological features. Here, we describe an unusual case of ALF due to DLBCL with an image negative on presentation posing diagnostic difficulty. CASE REPORT A 74-year-old man was admitted to our hospital with abdominal pain. Radiological and laboratory investigations revealed lymphadenopathy with mildly elevated transaminitis and alkaline phosphates levels. A right upper-quadrant ultrasound showed heterogeneous hepatic parenchyma. Eight days later, he had worsening abdominal pain. He was found to have altered mental status and asterixis. His liver function was worsened with ALT 101, AST 328, lactic acid 4.2, total bilirubin 2.5, INR 6.35, and ammonia level 117 µmol/L. He continued to deteriorate with worsening lactic acidosis, coagulopathy, severe anemia, elevated liver enzymes, and thrombocytopenia. Unfortunately, the patient died of multi-organ failure on the 14th day of hospitalization. The autopsy findings revealed DLBCL involving multiple organs, including the liver, lung, bone marrow, and multiple lymph nodes. Despite an extensive diagnostic workup, an underlying diagnosis was unable to be established antemortem. CONCLUSIONS We describe a case of ALF linked to DLBCL discovered at autopsy. The non-specific clinical and radiological features of this condition make diagnosis challenging, and the prognosis is often poor. Further research and awareness are needed to improve the early detection and management of ALF associated with malignant lymphoma. By expanding the literature on this topic, we aim to improve outcomes and optimize patient care in similar clinical scenarios.

Clinical presentation of Warburg effect in aggressive lymphoma: a case report.

BACKGROUND: The Warburg effect is a rare condition in tumor biology, illustrated by significant lactate production in the presence of oxygen. The Warburg effect is associated with very poor prognosis in patients with malignancy. CASE PRESENTATION: We report a 76-year-old Caucasian woman with double-expressor diffuse large B cell lymphoma who presented with severe lactic acidosis and extreme hypoglycemia with normal mentation. Her lactic acidosis was initially controlled with a bicarbonate infusion, and the patient was started promptly on steroids, followed by chemotherapy, but her clinical course was complicated by tumor lysis syndrome, acute renal failure requiring hemodialysis, and progressive liver failure. She manifested a temporary clinical response to chemotherapy but eventually died of complications. CONCLUSIONS: This case demonstrates the importance of prompt recognition of the Warburg effect, aggressive supportive measures, and early initiation of chemotherapy. Future studies are needed to characterize the role of hemodialysis in this setting.

A Review of Bicarbonate Use in Common Clinical Scenarios.

BACKGROUND: The use of sodium bicarbonate to treat metabolic acidosis is intuitive, yet data suggest that not all patients benefit from this therapy. OBJECTIVE: In this narrative review, we describe the physiology behind commonly encountered nontoxicologic causes of metabolic acidosis, highlight potential harm from the indiscriminate administration of sodium bicarbonate in certain scenarios, and provide evidence-based recommendations to assist emergency physicians in the rational use of sodium bicarbonate. DISCUSSION: Sodium bicarbonate can be administered as a hypertonic push, as a resuscitation fluid, or as an infusion. Lactic acidosis and cardiac arrest are two common scenarios where there is limited benefit to routine use of sodium bicarbonate, although certain circumstances, such as patients with concomitant acute kidney injury and lactic acidosis may benefit from sodium bicarbonate. Patients with cardiac arrest secondary to sodium channel blockade or hyperkalemia also benefit from sodium bicarbonate therapy. Recent data suggest that the use of sodium bicarbonate in diabetic ketoacidosis does not confer improved patient outcomes and may cause harm in pediatric patients. Available evidence suggests that alkalinization of urine in rhabdomyolysis does not improve patient-centered outcomes. Finally, patients with a nongap acidosis benefit from sodium bicarbonate supplementation. CONCLUSIONS: Empiric use of sodium bicarbonate in patients with nontoxicologic causes of metabolic acidosis is not warranted and likely does not improve patient-centered outcomes, except in select scenarios. Emergency physicians should reserve use of this medication to conditions with clear benefit to patients.

Pulmonary artery catheter usage in diagnosis of Shoshin beriberi presented with unexplained lactic acidosis.

Wet beriberi is a rare but fatal disease in modern society. The nonspecific clinical manifestations, including symptoms of heart failure and recalcitrant lactic acidosis, can prevent timely diagnosis. The use of a pulmonary artery catheter can promptly confirm a high cardiac output state and plays a crucial role in rapidly deteriorating cases. Appropriate treatment with intravenous administration of thiamine leads to dramatic recovery within hours. We present two cases of Shoshin beriberi, a fulminant variant of wet beriberi, diagnosed in 2016 and 2022 at our institute. The patients experienced haemodynamic collapse and refractory lactic acidosis, which were successfully diagnosed with the use of a pulmonary artery catheter and reversed by thiamine supplementation. We also reviewed 19 cases of wet beriberi reported between 2010 and 2022.

Lactic Acidosis Due to Thiamine Deficiency in a Preterm Infant Associated with Inadequate Parenteral Nutrition.

BACKGROUND Premature low birth weight infants may require prolonged parenteral feeding, which can be associated with deficiencies of vitamins and micronutrients. Deficiency in thiamine (vitamin B1) can result in metabolic crisis and lactic acidosis. This report describes a premature male infant born at 30 weeks of gestation with thiamine deficiency and lactic acidosis associated with inadequate parenteral nutrition. CASE REPORT A preterm boy was born at 30 weeks+5 days, with a weight of 0.830 kilograms and Apgar scores of 8 and 9 at 1 and 5 minutes, respectively. Total parenteral nutrition started on day 1 of life. On day 21 of life, while he was on total parenteral nutrition, severe lactic acidosis with a high anion gap was noted. Sepsis work-up along with radiological studies were immediately done, and antibiotics were initiated to cover common suspected organisms. Repeated blood gas analysis showed further increases in lactate levels. A fluid bolus was administered, with no improvement, so sodium bicarbonate was started. Despite all interventions, the lactate level continued to increase up to 13.78 mmol/l. Thiamine deficiency was suspected next, and a dose of vitamin B1 was given intravenously. There was an immediate drop in lactate level, and the patient proceeded to a full recovery. CONCLUSIONS This report shows that lactic acidosis is a potentially life-threatening condition that can result from thiamine deficiency. When standard parenteral nutrition preparations are used for prolonged periods in premature neonates, continuous monitoring of vitamin levels, micronutrient levels, and biochemical parameters is required.

Short bowel syndrome: Complications and management.

Short bowel syndrome (SBS) occurs when a patient loses bowel length or function significantly enough to cause malabsorption, oftentimes requiring lifelong parenteral support. In adults, this occurs most commonly in the setting of massive intestinal resection, whereas congenital anomalies and necrotizing enterocolitis predominate in children. Many patients with SBS develop long-term clinical complications over time related to their altered intestinal anatomy and physiology or to various treatment interventions such as parenteral nutrition and the central venous catheter through which it is administered. Identifying, preventing, and treating these complications can be challenging. This review will focus on the diagnosis, treatment, and prevention of several complications that can occur in this patient population, including diarrhea, fluid and electrolyte imbalance, vitamin and trace element derangements, metabolic bone disease, biliary disorders, small intestinal bacterial overgrowth, d-lactic acidosis, and complications of central venous catheters.

The Association Between Hypophosphatemia and Lactic Acidosis After Cardiac Surgery With Cardiopulmonary Bypass: A Retrospective Cohort Study.

OBJECTIVES: The clinical significance of hypophosphatemia in cardiac surgery has not been investigated extensively. The aim of this study was to evaluate the association of postoperative hypophosphatemia and lactic acidosis in cardiac surgery patients at the time of intensive care unit (ICU) admission. DESIGN: A retrospective cohort study. SETTING: At a single academic center. PARTICIPANTS: Patients who underwent nontransplant cardiac surgery with cardiopulmonary bypass between August 2009 and December 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum phosphate and lactate levels were measured upon ICU admission in patients undergoing nontransplant cardiac surgery with cardiopulmonary bypass. There were 681 patients in the low-phosphate (<2.5 mg/dL) group and 2,579 patients in the normal phosphate group (2.5-4.5 mg/dL). A higher proportion of patients in the low phosphate group (26%; 179 of 681; 95% CI: 23-30) had severe lactic acidosis compared to patients in the normal phosphate group (16%; 417 of 2,579; 95% CI: 15-18). In an unadjusted logistic regression model, patients in the low phosphate group had 1.9-times the odds of having severe lactic acidosis (serum lactate ≥4.0 mmol/L) when compared to patients in the normal phosphate group (95% CI: 1.5-2.3), and still 1.4-times the odds (95% CI: 1.1-1.7) after adjusting for several possible confounders. CONCLUSIONS: Hypophosphatemia is associated with lactic acidosis in the immediate postoperative period in cardiac surgery patients. Future studies will need to investigate it as a potential treatment target for lactic acidosis.

Diagnostic Dilemma of Lactic Acidosis in an Infant After Liver Transplant: A Case Report.

Thiamine is the cofactor of many enzymes involved in energy metabolism. Patients under total parenteral nutrition are at risk for thiamine deficiency if there is renal thiamine loss or increased thiamine requirements to mitigate systemic diseases. Thiamine deficiency symptoms include seizures, neuropathy, ataxia, peripheral vasodilation, myocardial insufficiency, sudden collapse, and death. In this report, we present an infant liver transplant recipient with progressive lactic acidosis that responded well to thiamine replacement to mitigate a lack of thiamine in total parenteral nutrition.

[Severe lactic acidosis in a pregnant woman with partial HELLP syndrome and COVID-19]. / Acidosis láctica grave en una mujer embarazada con síndrome HELLP parcial y COVID-19.

The present report describes the case of a 23-year old pregnant woman who was in the 36.5th week of gestation of her second pregnancy. She was attended at the emergency room because of dry cough and progressive dyspnea, in association with headache and myalgia. The nasopharyngeal swab for SARS-CoV-2 polymerase chain reaction (PCR) was positive. Oxygen saturation and chest x-ray were normal. Laboratory tests showed elevated values of bilirubin, aminotransferases, alkaline phosphatase and lactic dehydrogenase, and mild thrombocytopenia. Shortly after being admitted she began with labor. Faced with the lack of progression, the termination of the pregnancy by cesarean section was decided. Arterial blood gases showed severe lactic acidosis. She never presented evidence of clinical signs of tissue hypoperfusion or sepsis that could explain it. The patient completed her postoperative period in the intensive care unit, undergoing supportive treatment. All laboratory parameters were normalized after 72 hours, evolving favorably from the clinical point of view. It was interpreted that she had a partial HELLP syndrome. Lactic acidosis is not a component of this syndrome. Nor can it be ascribed to a mild disease by SARS-Cov-2. It probably responded to a summation of causes, including hyperproduction of lactic acid during labor, as well as its reduced clearance because of liver dysfunction related to HELLP syndrome.

Se presenta el caso de una mujer embarazada secundigesta, cursando la semana 36.5 de gestación, que concurrió a guardia general por tos seca y disnea progresiva de 3 días de evolución, asociadas a cefalea y mialgias. Se realizó hisopado nasofaríngeo para reacción en cadena de la polimerasa (PCR) para SARS-CoV-2, resultando positivo. La saturación de oxígeno era normal, al igual que la radiografía de tórax. En el laboratorio presentó elevación de bilirrubina, transaminasas, fosfatasa alcalina y LDH, además de plaquetopenia leve. Poco después de su ingreso, comenzó con trabajo de parto. Frente a la falta de progresión del mismo se decidió la finalización del embarazo por cesárea. La gasometría arterial reveló la presencia de acidosis láctica grave. Nunca hubo evidencia clínica de hipoperfusión tisular o sepsis que pudieran explicarla. Cursó su postoperatorio en la unidad de terapia intensiva, realizándose tratamiento de sostén. Todos los parámetros de laboratorio se normalizaron al cabo de 72 horas, evolucionando favorablemente desde el punto de vista clínico. Se interpretó que cursó un síndrome HELLP parcial. La acidosis láctica no es un componente descripto en este síndrome. Tampoco puede adscribirse a la enfermedad leve por SARS-CoV-2. Podría deberse a una sumatoria de causas, incluidas la hiperproducción de ácido láctico en el marco del trabajo de parto, como la disminución de su aclaramiento por la disfunción hepática asociada al síndrome HELLP.