UNASSIGNED: The prevalence of type 2 diabetes mellitus has surged globally. Metformin is recommended as the first-line oral treatment. However, metformin-associated lactic acidosis (MALA) is recognized as a rare but potentially dangerous complication. The pathogenesis of MALA is multifactorial, primarily resulting from the interference of metformin with mitochondrial function and hepatic gluconeogenesis, leading to lactate accumulation. Risk of MALA escalates with impaired kidney function, poorly controlled diabetes, fasting, and liver dysfunction.
UNASSIGNED: A 57-year-old woman with diabetes and hypertension presented with prolonged gastrointestinal symptoms. During this episode she continued using metformin. She had severe metabolic acidosis and acute kidney injury. Continuous venovenous hemodiafiltration was initiated, resulting in significant clinical improvement and normalized arterial blood gas parameters within 16 hours.
UNASSIGNED: The pharmacokinetic properties of metformin facilitate efficient elimination via hemodialysis and/or hemofiltration. Continuous venovenous hemodiafiltration emerges as effective for MALA treatment. In the case described the calculated metformin clearance during continuous venovenous hemodiafiltration was notably higher than reported values, possibly due to residual renal clearance. Clinical improvement occurred despite elevated metformin levels, suggesting a lack of correlation between metformin levels and patient outcomes. Comorbidities rather than metformin levels guide treatment decisions in MALA.
UNASSIGNED: This case underscores the efficacy of continuous venovenous hemodiafiltration in the treatment of MALA, suggesting its potential as a standard therapeutic approach. However, further research is needed to elucidate the complex interplay between metformin levels, clinical presentation, (extracorporeal) treatment modalities and outcome in MALA.
CONCLUSIONS: Continuous venovenous hemodiafiltration seems to be an efficient and effective treatment to eliminate metformin in patients with metformin-associated lactic acidosis.The metformin level does not seem to correlate with the clinical condition of the patient.For a comparison between the effectiveness of different renal replacement therapies in metformin-associated lactic acidosis, more research is needed.

β-Adrenergic agonist medications such as albuterol are the mainstay for treatment of patients with acute asthma exacerbations. Patients who present to the emergency department with severe symptoms are often treated with multiple albuterol doses in sequence to maximize the impact of the medications, relax bronchoconstriction, and relieve their breathlessness. Patients who present with acute dyspnea have numerous potential causes of hyperlactatemia and acidosis including an uncommonly recognized outcome of albuterol administration. This clinical case report outlines a scenario where a patient who was treated for an acute asthma exacerbation had rising lactate levels despite improving clinically. Causes of elevated lactate levels are discussed, particularly related to β-adrenergic agonist use, and considerations for monitoring and withdrawal of albuterol administration are outlined.

BACKGROUND: Holocarboxylase synthetase deficiency (HLCS deficiency, OMIM #253270) is an exceedingly rare metabolic disorder resulting in multiple carboxylase deficiencies owing to impaired biotin cycle. Clinical manifestations include severe metabolic acidosis, hyperammonemia, tachypnea, skin rash, alopecia, feeding problems, hypotonia, developmental delay, seizures, and, in severe cases, death.
RESULTS: An 8-day-old female neonate presented with severe lactic acidosis, necessitating sedation and mechanical ventilation. Despite receiving supportive care, no evident clinical improvement was observed, accompanied by the onset of generalized ichthyosis. Genetic analysis of actionable metabolic disorders revealed compound heterozygous variants of HLCS (NM_000411.8), specifically c.[710T>C (p.Leu237Pro)]; [1544G>A (p.Ser515Asn)], prompting the initiation of biotin mega-dose therapy (10 mg/day). Remarkably, dramatic clinical improvement in lactic acidosis was observed the day after initiating biotin administration, leading to the discontinuation of mechanical ventilation within 6 days. The patient remained in stable condition during follow-up, exhibiting normal growth and development along with consistently stable laboratory findings up to 18 months of age.
CONCLUSIONS: Our case highlights the significance of early genetic testing in neonates with unexplained metabolic disorders to enable timely diagnosis and therapy initiation. Biotin therapy has demonstrated remarkable efficacy in improving the clinical condition of patients with HLCS deficiency, leading to favorable outcomes.

This case report describes a 65-year-old male who presented to the emergency department with significant lactic acidosis after self-poisoning by ingesting bispyribac sodium, a commonly known herbicide. This case highlights the rarity of poisoning with freely available herbicides in the literature, which may be elusive in clinical history and life-threatening in presentation. The patient had attempted to commit suicide with ingestion of an unidentified herbicide and was brought to the emergency department post two hours after the incident. He complained of abdominal pain. The hemodynamics of the patient were within normal limits. However, his initial lactate levels were elevated along with a high anion gap metabolic acidosis. The patient was provided symptomatic care and close monitoring. The ingested substance was later found to be bispyribac sodium. The patient symptomatically improved over time, with lactate levels attaining normal ranges, and was discharged after observation of 24 hours. Human ingestion of bispyribac sodium is mostly asymptomatic and non-fatal. The management in this case mainly consisted of symptomatic care. The initial presentation of herbicide poisoning in an emergency department setting as lactic acidosis and the subsequent evaluation to rule out other possible causes of lactic acidosis in the patient was challenging for the treating physician. The possibility of herbicide-mediated cellular damage and subsequent lactic acidosis is thought to be the reason for this rare presentation.

Artificial neural networks (ANNs) are versatile tools capable of learning without prior knowledge. This study aims to evaluate whether ANN can calculate minute volume during spontaneous breathing after being trained using data from an animal model of metabolic acidosis. Data was collected from ten anesthetized, spontaneously breathing pigs divided randomly into two groups, one without dead space and the other with dead space at the beginning of the experiment. Each group underwent two equal sequences of pH lowering with pre-defined targets by continuous infusion of lactic acid. The inputs to ANNs were pH, ΔPaCO2 (variation of the arterial partial pressure of CO2), PaO2, and blood temperature which were sampled from the animal model. The output was the delta minute volume (ΔVM), (the change of minute volume as compared to the minute volume the animal had at the beginning of the experiment). The ANN performance was analyzed using mean squared error (MSE), linear regression, and the Bland-Altman (B-A) method. The animal experiment provided the necessary data to train the ANN. The best architecture of ANN had 17 intermediate neurons; the best performance of the finally trained ANN had a linear regression with R2 of 0.99, an MSE of 0.001 [L/min], a B-A analysis with bias ± standard deviation of 0.006 ± 0.039 [L/min]. ANNs can accurately estimate ΔVM using the same information that arrives at the respiratory centers. This performance makes them a promising component for the future development of closed-loop artificial ventilators.

Comorbidities in the elderly not only make them more susceptible to kidney disease, but also increase the risk of drug interactions due to polypharmacy. Such patients require regular kidney function tests when treated with renally excreted drugs. We conducted a retrospective study of post-mortem cases over a five- year period. Of 3040 toxicologically investigated cases, 3.8% had a history of renal failure. Thirteen deaths were directly attributable to inadequate drug dosing, 46% of which were related to lactic acidosis due to metformin accumulation. Appropriate dose adjustment could prevent fatal drug toxicity in patients with renal insufficiency.

Lactic acidosis is a common finding in the intensive care unit and is associated with increased mortality. We present the case of a 42-year-old male with alcohol use disorder and cirrhosis who developed sudden onset shortness of breath while smoking marijuana. He was found to have a lactic acid level of 25.6 mmol/L with a significant anion gap metabolic acidosis requiring emergent dialysis. He was hypertensive without evidence of tissue hypoperfusion. His profound type B lactic acidosis was primarily attributed to a rare manifestation of cannabinoid toxicity. At a clinic visit 3 months later, he was doing well and had not smoked marijuana since his discharge.

Lactic acidosis is associated with poorer clinical outcomes in critical care. The causes of this condition are divided into two groups: type A (tissue hypoxia) and type B (metabolic abnormalities). Of these, drug-induced lactic acidosis is categorized as type B and is often overlooked due to clinicians\' poor awareness. We herein report a rare case of drug-induced lactic acidosis due to excessive use of a long-acting beta agonist (LABA) in a patient with asthma-chronic obstructive pulmonary disease overlap exacerbation. He initially presented with markedly elevated lactate and metabolic acidosis with unknown etiology. A detailed medical interview revealed that he had inhaled a large amount of LABA on the day of admission, which led to our final diagnosis. The patient\'s respiratory status and lactate levels gradually improved with the appropriate use of inhalation therapy. While there have been many recent reports of lactic acidosis caused by short-acting beta agonists, our case suggests that excessive use of LABAs may also lead to lactic acidosis. Clinicians should be aware of the possibility that LABAs can cause lactic acidosis because poor awareness of the condition may lead to inappropriate patient care.

Asthma is one of the most prevalent chronic respiratory diseases, characterized by bronchial hyper-responsiveness and intermittent airflow obstruction. Short-acting β2 agonists (SABA) remain the cornerstone of acute asthma management due to its properties in smooth muscle relaxation and bronchodilatation. Rarely, these drugs might be associated with adverse effects, including the development of metabolic and hydro-electrolytic imbalances. We report a case of lactic acidosis secondary to β2 agonists in a young female patient admitted with severe acute asthma. After initial management and significant improvement of the respiratory distress with nebulized and subcutaneous salbutamol, the patient developed high anion gap metabolic acidosis due to hyperlactacidemia and hypokalemia. Alternative causes of lactic acidosis were discarded, such as severe hypoxemia, systemic hypoperfusion, sepsis, and organ dysfunction, and SABA-related lactic acidosis was suspected. This treatment was halted, and tachypnea, metabolic acidosis, and lactate levels rapidly resolved. The remainder of the hospital stay was uneventful, and the patient was discharged after a period of five days. Although rare, the development of unexplained lactic acidosis in a SABA-treated patient should alert the treating physician to this β2 agonist side-effect.

UNASSIGNED: The objective of this study was to investigate the correlation between metformin exposure and the incidence of lactic acidosis in critically ill patients.
UNASSIGNED: The patients with type 2 diabetes mellitus (T2DM) were included from Medical Information Mart for Intensive Care IV database (MIMIC-IV). The primary outcome was the incidence of lactic acidosis. The secondary outcomes were lactate level and in-hospital mortality. Propensity score matching (PSM) method was adopted to reduce bias of the confounders. The multivariate logistic regression was used to explore the correlation between metformin exposure and the incidence of lactic acidosis. Subgroup analysis and sensitivity analysis were used to test the stability of the conclusion.
UNASSIGNED: We included 4939 patients. There were 2070 patients in the metformin group, and 2869 patients in the nonmetformin group. The frequency of lactic acidosis was 5.7% (118/2070) in the metformin group and it was 4.3% (122/2869) in the nonmetformin group. There was a statistically significant difference between the two groups (P < 0.05). The lactate level in the metformin group was higher than in the nonmetformin group (2.78 ± 2.23 vs. 2.45 ± 2.24, P < 0.001). After PSM, the frequency of lactic acidosis (6.3% vs. 3.7%, P < 0.001) and lactate level (2.85 ± 2.38 vs. 2.40 ± 2.14, P < 0.001) were significantly higher in the metformin group compared with the nonmetformin group. In multivariate logistic models, the frequency of lactic acidosis was obviously increased in metformin group, and the adjusted odds ratio (OR) of metformin exposure was 1.852 (95% confidence interval (CI) = 1.298-2.643, P < 0.001). The results were consistent with subgroup analysis except for respiratory failure subgroup. Metformin exposure increased lactate level but did not affect the frequency of lactic acidosis in patients of respiratory failure with hypercapnia. However, the in-hospital mortality between metformin and nonmetformin group had no obvious difference (P = 0.215). In sensitivity analysis, metformin exposure showed similar effect as the original cohort.
UNASSIGNED: In critically ill patients with T2DM, metformin exposure elevated the incidence of lactic acidosis except for patients of respiratory failure with hypercapnia, but did not affect the in-hospital mortality.