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When lactic acidosis accompanies low-flow states or sepsis, mortality rates increase sharply. This review summarizes our current understanding of the pathophysiological aspects of lactic acidosis, as well as the approaches to its diagnosis and management. Lactic acidosis results from the accumulation of lactate and protons in the body fluids and is often associated with poor clinical outcomes. The effect of lactic acidosis is governed by its severity and the clinical context. Mortality is increased by a factor of nearly three when lactic acidosis accompanies low-flow states or sepsis, 1 and the higher the lactate level, the worse the outcome. 2 Although hyperlactatemia is often attributed to tissue hypoxia, it can result from other mechanisms. Control of the triggering conditions is the only effective means of treatment. However, advances in understanding its pathophysiological features and the factors causing . . .

Lactic acidosis and hyperlactatemia are common metabolic disturbances in patients with severe malaria. Lactic acidosis causes physiological adverse effects, which can aggravate the outcome of malaria. Despite its clear association with mortality in malaria patients, the etiology of lactic acidosis is not completely understood. In this review, the possible contributors to lactic acidosis and hyperlactatemia in patients with malaria are discussed. Both increased lactate production and impaired lactate clearance may play a role in the pathogenesis of lactic acidosis. The increased lactate production is caused by several factors, including the metabolism of intraerythrocytic Plasmodium parasites, aerobic glycolysis by activated immune cells, and an increase in anaerobic glycolysis in hypoxic cells and tissues as a consequence of parasite sequestration and anemia. Impaired hepatic and renal lactate clearance, caused by underlying liver and kidney disease, might further aggravate hyperlactatemia. Multiple factors thus participate in the etiology of lactic acidosis in malaria, and further investigations are required to fully understand their relative contributions and the consequences of this major metabolic disturbance.

BackgroundD-lactic acidosis is an uncommon and challenging form of metabolic acidosis that may develop in short bowel syndrome. It has been documented exclusively in case reports and small case series.MethodsWe performed a review of the literature in the National Library of Medicine and Excerpta Medica databases.ResultsWe identified 84 original reports published between 1977 and 2017. D-lactic acidosis was observed in 98 individuals ranging in age from 7 months to 86 years with short bowel syndrome. The clinical presentation included Kussmaul breathing, confusion, slurred speech, and gait disturbances. Furthermore, among 99 consecutive patients with short bowel syndrome, 21 reported having episodes with symptoms consistent with D-lactic acidosis. In addition, D-lactic acid might also contribute to acidosis in diabetes mellitus. Finally, abnormally high D-lactic acid was documented after administration or ingestion of large amounts of propylene glycol, as paraneoplastic phenomenon and perhaps also in a so far poorly characterized inherited inborn error of metabolism.ConclusionsIn humans with short bowel syndrome (or carbohydrate malabsorption), D-lactic acidosis is likely rather common and under-recognized. This condition should be included in the differential diagnosis of unexplained high-gap metabolic acidosis where the anion causing the acidosis is not known. Furthermore, diabetic acidosis might be caused by accumulation of both ketone bodies and D-lactic acid. Finally, there are endogenous sources of D-lactic acid in subjects with propylene glycol intoxication.

Type B lactic acidosis (LA), a rare yet fatal complication of lymphoma with poor prognosis, remains poorly characterized due to reliance on isolated case reports. To systematically delineate clinical characteristics and prognostic determinants in newly diagnosed lymphoma patients presenting with LA as the initial presentation, we conducted an integrated analysis synthesizing unpublished institutional cases with systematically identified cases from PubMed, Web of Science, and hospital databases. Demographic, clinical, laboratory, imaging, histopathological, and therapeutic intervention data were extracted. Prognostic correlates were evaluated using univariate and multivariate logistic regression, with predictive accuracy validated through receiver operating characteristic (ROC) curves. Among the 53 patients analyzed, the predominant manifestations included general malaise and gastrointestinal symptoms (62.3% each), with infrequent superficial lymph node enlargement (15.1%). Key biochemical abnormalities included hyperlactatemia (peak lactate: 15.89 ± 7.82 mmol/L) and elevated lactate dehydrogenase (60.4%). Imaging revealed lymph node enlargement (41.5%) and hepatic abnormalities (39.6%). Non-survivors were significantly older ( P  = 0.007), had a higher incidence of B-symptoms ( P  = 0.032), and were less likely to receive chemotherapy ( P  < 0.001). Chemotherapy emerged as the sole independent predictor of survival (multivariate odds ratio [OR] = 0.020; 95% confidence interval [CI]: 0.002–0.211; P  = 0.001), validated by ROC curve analysis (sensitivity 92.0%, specificity 95.5%). This integrated analysis of a case and literature review underscores that LA signifies aggressive lymphoma with frequent advanced-stage disease. Although advanced age and B-symptoms predicted mortality, chemotherapy was the sole independent survival predictor in multivariate analysis.

Background/Aims: Supplementation with certain probiotics can improve gut microbial flora and immune function but should not have adverse effects. This study aimed to assess the risk of D-lactate accumulation and subsequent metabolic acidosis in infants fed on formula containing Lactobacillus johnsonii (La1®). Methods: In the framework of a double-blind, randomized controlled trial enrolling 71 infants aged 4-5 months, morning urine samples were collected before and 4 weeks after being fed formulas with or without La1 (1 x 10(8)/g powder) or being breastfed. Urinary D- and L-lactate concentrations were assayed by enzymatic, fluorimetric methods and excretion was normalized per mol creatinine. Results: At baseline, no significant differences in urinary D-/L-lactate excretion among the formula-fed and breastfed groups were found. After 4 weeks, D-lactate excretion did not differ between the two formula groups, but was higher in both formula groups than in breastfed infants. In all infants receiving La1, urinary D-lactate concentrations remained within the concentration ranges of age-matched healthy infants which had been determined in an earlier study using the same analytical method. Urinary L-lactate also did not vary over time or among groups. Conclusions: Supplementation of La1 to formula did not affect urinary lactate excretion and there is no evidence of an increased risk of lactic acidosis.

Alcoholic ketoacidosis (AKA) is a potentially life-threatening condition due to high anion gap metabolic acidosis in chronic alcohol use. While lactic acidosis (LA) is typically uncommon in AKA, AKA without concurrent acute conditions is occasionally complicated with LA. The aim of this study was to clarify the clinical features in isolated AKA patients with LA and those without LA. This retrospective study was conducted at a tertiary hospital between January 2021 and January 2024. We identified isolated AKA patients aged ≥20 years who presented with high anion gap metabolic acidosis, elevated ketones in serum or urine, and alcohol use disorder. Patients were classified into those with LA (lactate ≥4 mmol/L) and those without LA. We examined the clinical characteristics and outcomes in both groups and analyzed lactate trends during hospitalization in patients with LA. Of 41 patients with AKA, 33 patients (80 %) had LA despite the fact that thiamine levels were similar in the two groups. Total ketone body and β-hydroxybutyrate levels in patients with LA were lower than those in patients without LA. Median lactate levels (10.7 mmol/L, IQR 7.7–14.5) in patients with LA decreased by approximately 1 mmol/L per hour during the first six hours post-admission. None of the patients died during hospitalization. Isolated AKA is likely to be complicated with hyperlactatemia. Higher lactate levels tended to be observed in cases with lower ketone levels. Lactate levels in isolated AKA with LA declined steadily. Further studies are needed to confirm our findings.

Data describing the incidence of phosphate abnormalities in cardiac surgery patients and associated lactic acidosis are limited to single-center studies. This study aimed to determine the incidence of hypo- and hyperphosphatemia after procedures requiring cardiopulmonary bypass (CPB) in a multicenter cohort. We hypothesized that phosphate abnormalities would be associated with severe lactic acidosis. This retrospective multicenter cohort study included patients ≥18 years undergoing procedures with CPB between January 2015 and December 2022 across 45 centers participating in the Multicenter Perioperative Outcomes Group. Only patients who had phosphate and lactate levels obtained within 6 h after the end of surgery were included. Multilevel logistic regression models were used to evaluate the association between phosphate abnormalities and severe lactic acidosis (lactate ≥4.0 mmol/L). Among 34,953 cardiac surgery patients meeting inclusion criteria, 6863 (20%) had hypophosphatemia (phosphate <2.5 mg/dL) and 5013 (14%) had hyperphosphatemia (phosphate >4.5 mg/dL) within 6 h after surgery. After controlling for confounders, both hypophosphatemia and hyperphosphatemia were found to be associated with higher odds of severe lactic acidosis compared to patients with normal phosphate (OR 1.46, 95% CI: 1.33, 1.60 and OR 1.30, 95% CI: 1.16, 1.45, respectively). The odds were even higher (OR 2.53, 95% CI: 1.76, 3.63) in a subgroup of non-transplant patients with severe hypophosphatemia (phosphate <1.0 mg/dL). Phosphate abnormalities in the immediate postoperative period after surgery with CPB are common and associated with a higher risk of severe lactic acidosis. •Phosphate abnormalities after cardiac surgery with cardiopulmonary bypass are common.•Both hypophosphatemia and hyperphosphatemia are associated with a higher risk of severe lactic acidosis.•Determination of phosphate levels in the post-operative period after cardiac surgery should be considered. [Display omitted]

This case report presents a newborn with pyruvate dehydrogenase complex deficiency who developed significant lactic acidosis and acute kidney injury after birth. Peritoneal dialysis with glucose-based peritoneal dialysis fluid was initially started, but the patient had worsening hyperglycemia and lactic acidosis, likely related to excess glucose reabsorption with shunting to lactate due to the underlying metabolic disorder. As amino acid–based dialysis solution was not available in our formulary, a dialysis fluid was manually created with Vaminolact, which was commonly used in neonatal parenteral nutrition. Switching to the new dialysis fluid led to significant biochemical improvement.

Background: The etiology of acute metabolic acidosis (aMA) is heterogeneous, and the consequences are potentially life-threatening. The aim of this article was to summarize the causes and management of aMA from a clinician’s perspective. Summary: We performed a systematic search on PubMed, applying the following search terms: “acute metabolic acidosis,” “lactic acidosis,” “metformin” AND “acidosis,” “unbalanced solutions” AND “acidosis,” “bicarbonate” AND “acidosis” AND “outcome,” “acute metabolic acidosis” AND “management,” and “acute metabolic acidosis” AND “renal replacement therapy (RRT)/dialysis.” The literature search did not consider diabetic ketoacidosis at all. Lactic acidosis evolves from various conditions, either with or without systemic hypoxia. The incidence of metformin-associated aMA is actually quite low. Unbalanced electrolyte preparations can induce hyperchloremic aMA. The latter potentially worsens kidney-related outcome parameters. Nevertheless, prospective and controlled data are missing at the moment. Recently, bicarbonate has been shown to improve clinically relevant endpoints in the critically ill, even if higher pH values (>7.3) are targeted. New therapeutics for aMA control are under development, since bicarbonate treatment can induce serious side effects. Key Messages: aMA is a frequent and potentially life-threatening complication of various conditions. Lactic acidosis might occur even in the absence of systemic hypoxia. The incidence of metformin-associated aMA is comparably low. Unbalanced electrolyte solutions induce hyperchloremic aMA, which most likely worsens the renal prognosis of critically ill patients. Bicarbonate, although potentially deleterious due to increased carbon dioxide production with subsequent intracellular acidosis, improves kidney-related endpoints in the critically ill.

This review mainly focuses on metformin, and considers oral antidiabetic therapy in kidney transplant patients and the potential benefits and risks of antidiabetic agents other than metformin in patients with chronic kidney disease (CKD). In view of the debate concerning lactic acidosis associated with metformin, this review tries to solve a paradox: metformin should be prescribed more widely because of its beneficial effects, but also less widely because of the increasing prevalence of contraindications to metformin, such as reduced renal function. Lactic acidosis appears either as part of a number of clinical syndromes (i.e., unrelated to metformin), induced by metformin (involving an analysis of the drug’s pharmacokinetics and mechanisms of action), or associated with metformin (a more complex situation, as lactic acidosis in a metformin-treated patient is not necessarily accompanied by metformin accumulation, nor does metformin accumulation necessarily lead to lactic acidosis). A critical analysis of guidelines and literature data on metformin therapy in patients with CKD is presented. Following the present focus on metformin, new paradoxical issues can be drawn up, in particular: (i) metformin is rarely the sole cause of lactic acidosis; (ii) lactic acidosis in patients receiving metformin therapy is erroneously still considered a single medical entity, as several different scenarios can be defined, with contrasting prognoses. The prognosis for severe lactic acidosis seems even better in metformin-treated patients than in non-metformin users.