Myelotoxicity and kidney dysfunction related to the use of trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia: a case report of severe adverse events with a common drug.

Trimethoprim-sulfamethoxazole (TMP-SMX) is the primary therapeutic option for Pneumocystis jirovecii pneumonia (PCP). Gastrointestinal symptoms and cutaneous rash are common side effects, with hyperkalemia being uncommon in patients without kidney dysfunction, and myelotoxicity being even rarer. We present the case of a male patient with hypertension and a recent diagnosis of non-Hodgkin lymphoma, undergoing rituximab treatment for two months. He was admitted to the intensive care unit due to dyspnea, tachypnea, and pleuritic pain, requiring mechanical ventilation. Chest computed tomography showed bilateral and multilobed ground-glass opacities, compromising more than 80% of the lung parenchyma. Pulmonary tuberculosis and COVID-19 were ruled out. An angiotomography and Doppler ultrasound revealed an extensive pulmonary thrombus and deep venous thrombosis. Empiric treatment with TMP-SMX for PCP was initiated, but within four days, the patient experienced metabolic acidosis and severe hyperkalemia, necessitating hemodialysis. He also presented with progressive pancytopenia and critical levels of leukopenia and thrombocytopenia. The hypothesis of TMP-SMX-induced myelotoxicity was suspected. Considering the unavailability of an alternative treatment, it was opted to continue TMP-SMX and initiate a granulocyte-colony-stimulating factor. However, the patient maintained medullary deterioration, becoming refractory to the transfusion of blood derivates. On the 17th day of treatment, a clinical decision was made to suspend TMP-SMX, leading to improvements within 48 hours in marrow and kidney functions, metabolic acidosis, and hyperkalemia. Despite all efforts, the patient died after 35 days of hospitalization due to hospital-acquired infections. This case highlights the importance of clinicians recognizing potential myelotoxicity with TMP-SMX and promptly discontinuing the drug if necessary.

Linezolid-induced lactic acidosis.

Linezolid is a commonly prescribed antibiotic in clinical practice. Although thrombocytopenia and peripheral neuropathy are frequently encountered following prolonged administration of linezolid, lactic acidosis is a rare adverse drug reaction. We present the case of a patient on linezolid for disseminated multidrug-resistant tuberculosis who presented with vomiting, dyspnoea, hypotension and high anion gap metabolic acidosis. The initial presentation mimicked sepsis syndrome. Ketoacidosis and renal dysfunction were ruled out. There was no history of ingestion of toxins/toxic alcohols. Sepsis was unlikely because extensive radiological and microbiological testing could not identify an infection. Given the possibility of linezolid-induced lactic acidosis (LILA), linezolid was discontinued on admission. The patient's lactic acidosis resolved, and his overall condition improved. A retrospective diagnosis of LILA was thus established. LILA should be considered when patients on linezolid present with lactic acidosis and other causes for the lactic acidosis have been ruled out.

Perianesthetic metabolic acidosis is associated with 2% dorzolamide eye drops in dogs that underwent ophthalmic surgery: a retrospective study (2019-2022).

OBJECTIVE: To evaluate whether the administration of 2% dorzolamide ophthalmic solution in dogs undergoing ophthalmic surgery is associated with perianesthetic metabolic acidosis. ANIMALS: 60 dogs, with or without dorzolamide administration, underwent arterial blood gas analysis immediately after anesthesia for ophthalmic surgery between 2019 and 2022; a total of 60 surgeries were evaluated. METHODS: This was a retrospective cross-sectional study. Logistic regression analysis was performed to investigate the association between the administration of 2% dorzolamide ophthalmic solution in dogs and the development of metabolic acidosis. Additionally, the influence of various potential risk factors, including age, body weight, sex, use of topical or systemic NSAIDs, and preoperative medications on the occurrence of metabolic acidosis, was evaluated. RESULTS: A significant association was found between the use of 2% dorzolamide ophthalmic solution and perianesthetic metabolic acidosis (OR, 6.79; 95% CI, 2.00 to 23.02; P = .002). Furthermore, topical dorzolamide administration was significantly associated with both perianesthetic hypokalemia (OR, 3.52; 95% CI, 1.11 to 11.20; P = .033) and perianesthetic hyperchloremia (OR, 9.25; 95% CI, 1.71 to 50.01; P = .010). CLINICAL RELEVANCE: The use of 2% dorzolamide ophthalmic solution is associated with perianesthetic metabolic acidosis, hypokalemia, and hyperchloremia in dogs. It is prudent to be aware of these risks, especially before anesthesia.

A pragmatic, open-label, randomized controlled trial of Plasma-Lyte-148 versus standard intravenous fluids in children receiving kidney transplants (PLUTO).

Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplant. This is partly because doctors give very large volumes of artificial fluids to keep the new kidney working. When severe, fluid imbalance can lead to seizures, cerebral edema and death. In this pragmatic, open-label, randomized controlled trial, we randomly assigned (1:1) pediatric kidney transplant recipients to Plasma-Lyte-148 or standard of care perioperative intravenous fluids (predominantly 0.45% sodium chloride and 0.9% sodium chloride solutions). We then compared clinically significant electrolyte and acid-base abnormalities in the first 72 hours post-transplant. The primary outcome, acute hyponatremia, was experienced by 53% of 68 participants in the Plasma-Lyte-148 group and 58% of 69 participants in the standard fluids group (odds ratio 0·77 (0·34 - 1·75)). Five of 16 secondary outcomes differed with Plasma-Lyte-148: hypernatremia was significantly more frequent (odds ratio 3·5 (1·1 - 10·8)), significantly fewer changes to fluid prescriptions were made (rate ratio 0·52 (0·40-0·67)), and significantly fewer participants experienced hyperchloremia (odds ratio 0·17 (0·07 - 0·40)), acidosis (odds ratio 0·09 (0·04 - 0·22)) and hypomagnesemia (odds ratio 0·21 (0·08 - 0·50)). No other secondary outcomes differed between groups. Serious adverse events were reported in 9% of participants randomized to Plasma-Lyte-148 and 7% of participants randomized to standard fluids. Thus, perioperative Plasma-Lyte-148 did not change the proportion of children who experienced acute hyponatremia compared to standard fluids. However fewer fluid prescription changes were made with Plasma-Lyte-148, while hyperchloremia and acidosis were less common.

Let's stop talking about 'citrate toxicity'.

PURPOSE OF REVIEW: Continuous renal replacement therapy (CRRT) is a vital medical intervention used in critically ill patients with acute kidney injury (AKI). One of the key components of adequate clearance with CRRT is the use of anticoagulants to prevent clotting of the extracorporeal circuit. Regional citrate anticoagulation is the most often recommended modality. The term 'citrate toxicity' is used to describe potential adverse effects of accumulation of citrate and subsequent hypocalcemia. However, citrate is itself not inherently toxic. The term and diagnosis of citrate toxicity are questioned in this review. RECENT FINDINGS: Citrate is being increasingly used for regional anticoagulation of the CRRT circuit. Citrate accumulation is infrequent and can cause hypocalcemia and metabolic alkalosis, which are potential adverse effects. Citrate itself, however, is not a toxic molecule. The term 'citrate toxicity' has been used to denote hypocalcemia and metabolic acidosis. However, citrate administration is well known to cause systemic and urinary alkalinization and under certain circumstances, metabolic alkalosis, but is not associated itself with any 'toxic' effects.We review the existing literature and debunk the perceived toxicity of citrate. We delve into the metabolism and clearance of citrate and question current data suggesting metabolic acidosis occurs as the result of citrate accumulation. SUMMARY: In conclusion, this article calls into question prevailing concerns about 'citrate toxicity'. We emphasize the need for a more nuanced understanding of its safety profile. We recommend discarding the term 'citrate toxicity' in favor of another frequently used, but more meaningful term: 'citrate accumulation'.

Emerging progressive atypical acute kidney injury in young children linked to ethylene glycol and diethylene glycol intoxication.

BACKGROUND: There had been a sudden surge of unusually severe and rapidly progressing acute kidney injury (AKI) incidence in Indonesia since August 2022 which did not correspond to the rise of COVID-19 incidence. We suspected this was related to ethylene glycol (EG) and diethylene glycol (DEG) intoxication. This study is aimed at describing the clinical and laboratory characteristics of AKI related to D(EG) intoxication in order to spread awareness of the possibility of intoxication in cases of rapidly progressing AKI with unknown etiology. METHODS: We conducted a cross-sectional study by collecting secondary data from the pediatric AKI registry at a national referral hospital in Jakarta, Indonesia. Data on children admitted from January to November 2022 with diagnosis of stage 3 AKI based on KDIGO criteria were included. Data regarding demographics, symptoms prior to anuria, laboratory results, infection panel including COVID-19 status, treatment administered, and mortality were analyzed. RESULTS: Sixteen patients tested positive for EG and DEG, all with history of consuming syrup-based medications. High anion gap metabolic acidosis was observed in majority of patients with mean pH 7.33 ± 0.07 and mean anion gap 15.6 ± 7.8 mEq/L. No patient had high osmolal gap (mean osmolal gap 3.46 ± 4.68). One deceased patient, who had kidney biopsy performed, showed severe damage and calcium oxalate crystals in the kidney tissue. Mortality was recorded in six patients (37.5%). CONCLUSION: Careful history taking of patient's clinical course, including consumption of syrup-based medications and laboratory findings, might aid clinicians to establish a working diagnosis of D(EG) intoxication without needing to wait for blood toxicology test. Early diagnosis and therapy are crucial to prevent substantial mortality.

Reversible acute blindness in suspected metformin-associated lactic acidosis: a case report.

BACKGROUND: Metformin is commonly used for the treatment of type 2 diabetes mellitus. Its multiple advantages include low risk of hypoglycemia, weight neutrality, low cost, and cardioprotective and anti-inflammatory effects. Renal insufficiency is one of the contraindications for its use. Inadvertent prescription in patients with renal insufficiency may lead to metformin-associated lactic acidosis, which brings a high risk of mortality. The early recognition and management of metformin-associated lactic acidosis are essential. CASE REPORT: We present the case of a 58-year-old Hui woman with a history of type 2 diabetes mellitus with nephropathy and heart disease for which she was treated with metformin, insulin, and heart medications. She developed nausea, vomiting, anion gap metabolic acidosis due to hyperlactatemia, and acute kidney injury. She was hospitalized to receive intravenous hydration and correction of metabolic acidosis after she suddenly developed blindness. The diagnostic workup ruled out central causes and her symptoms resolved briefly after continuous venovenous hemodialysis was initiated, confirming the diagnosis of metformin-associated lactic acidosis. CONCLUSIONS: Metabolic disruption can cause acute blindness. Metabolic acidosis in a patient with a history of metformin intake should suggest the possibility of metformin-associated lactic acidosis, which must be treated immediately, without waiting for the results of other examinations, especially in patients with sudden blindness. Further study of reversible blindness-associated severe metabolic acidosis is needed.

Propofol for Anesthesia in Pediatric Patients With Epilepsy on the Ketogenic Diet: A Single-Center Experience.

BACKGROUND: Propofol use is contraindicated in patients on ketogenic diet (KD) due to higher risk of propofol infusion syndrome (PIS). This study is intended to provide a descriptive analysis of our experience with propofol bolus and short infusions for anesthetic care in patients on the KD and to evaluate if any signs of PIS were observed. METHODS: All patients on the KD who underwent anesthesia with propofol between 2012 and 2022 were reviewed. Anesthetic encounters and charts were studied for type of surgical procedure; signs of PIS, including new cardiac arrhythmias, acidosis, or rhabdomyolysis in the periprocedural period; hypoglycemia; unplanned admissions within 24 hours of the procedure; if procedure was unexpectedly aborted; and increased seizure frequency within one week. RESULTS: We identified 65 patients, aged from one to 20 years who underwent 165 anesthetic encounters with propofol, of which 123 were boluses and 42 were infusions. In bolus dosing, the average dose was 2.8 mg/kg (0.7 to 12.8 ± 1.8 mg/kg). Of these, four encounters developed acidosis, one developed rhabdomyolysis, and one developed increased seizures. With infusions, the average infusion rate was 9 mg/kg/hour, with mean infusion duration of 83 minutes (10 to 352 ± 75 minutes). Of these, one developed acidosis and one increased seizures. No cases of PIS were identified. None of the adverse effects were attributed to propofol. CONCLUSIONS: Boluses and brief infusions of propofol for anesthetic use in patients on the KD did not cause PIS in our cohort.

Nitrogen-Phosphorus-Potassium containing liquid fertilizer intoxication presenting with extreme hyperkalemia, metabolic acidosis and ECG changes.

Liquid fertilizers are widely used for fertilizing in- and outdoor vegetation. Despite the easy accessibility and widespread use, serious intoxications are rare. This case report describes a 61-year-old woman who was treated for life-threatening hyperkalemia, metabolic acidosis and ECG changes after intentional ingestion of liquid fertilizer. Our case shows that intake of liquid fertilizer, though infrequent, can cause serious, life threatening complications.

Administration of alendronate exacerbates ammonium chloride-induced acidosis in mice.

Bone disease is highly prevalent in patients with chronic kidney disease (CKD), leading to an increased risk of bone fractures. This is due in part to metabolic acid-induced bone dissolution. Bisphosphonates (BPPs) are a potential treatment for inhibiting bone dissolution; however, there are limited studies observing the use of BPPs on acidotic patients. We aimed to determine efficacy of BPPs on maintaining bone health and pH regulation in acid-exposed mice. Using a diet-induced murine model of metabolic acidosis, we examined bone structure, composition, and mechanics as well as blood gases for three groups: control, acidosis, and acidosis + bisphosphonates (acidosis+BPP). Acidosis was induced for 14 days and alendronate was administered every 3 days for the acidosis+BPP group. The administration of BPP had little to no effect on bone structure, mechanics, and composition of the acidosis bones. However, administration of BPP did cause the mice to develop more severe acidosis than the acidosis only group. Overall, we discovered that BPPs may exacerbate acidosis symptoms by inhibiting the release of buffering ions from bone. Therefore, we propose that BPP administration should be carefully considered for those with CKD and that alkali supplementation could help minimize acidifying effects.

Evaluation of the efficacy and associated complications of regional citrate anticoagulation in neonates: experience from a fourth level neonatal intensive care unit.

Continuous kidney replacement therapy (CKRT) use has increased in recent years, but anticoagulation is a challenge for neonates. Regional citrate anticoagulation (RCA) is rarely preferred in neonates because of citrate accumulation (CA) and metabolic complications. We aimed to demonstrate the efficacy and safety of RCA in neonates. We retrospectively analyzed the medical records of 11 neonates treated with RCA-CKRT between 2018 and 2023. The initial dose of RCA was 2.1-3 mmol/l, and then, its dose was increased according to the level of ionized calcium (iCa+2) in the circuit and patients. The total/iCa+2 ratio after-treatment > 2.5 was indicated as CA. We evaluated to citrate dose, CA, circuit lifespan, and dialysis effectivity. The median gestational age was 39 (36.4-41.5) weeks, the median body weight (BW) was 3200 (2400-4000) grams, and the mean postnatal age was 4 (2-24) days. The most common indication for CKRT was hyperammonemia (73%). All neonates had metabolic acidosis and hypocalcemia during CKRT. Other common metabolic complications were hypophosphatemia (90%), hypokalemia (81%), and hypomagnesemia (63%). High dialysate rates with a median of 5765 ml/h/1.73 m2 allowed for a rapid decrease in ammonia levels to normal. Four patients (36.3%) had CA, and seven (63.7%) did not (non-citrate accumulation, NCA). Mean BW, median postnatal age, biochemical parameters, coagulation tests, and ammonia levels were similar between the CA and NCA groups. Low pH, low HCO3, high lactate, and SNAPPE-II scores could be associated with a higher T/iCa ratio. CONCLUSION:  RCA was an efficient and safe anticoagulation for neonates requiring CKRT. Metabolic complications may occur, but they could be managed with adequate supplementation. WHAT IS KNOWN: • Continuous kidney replacement therapy (CKRT) has become popular in recent years due to its successful treatment of fluid overload, electrolyte imbalance, metabolic acidosis, multi-organ failure, and hyperleucinemia/hyperammonemia associated with inborn errors of metabolism. • The need for anticoagulation is the major difficulty in neonatal CKRT. In adult and pediatric patients, regional citrate anticoagulation has been shown to be effective. WHAT IS NEW: • RCA is an effective and safe anticoagulation method for neonates who require CKRT. • Electrolyte imbalances and metabolic acidosis could be managed with adequate supplementation and appropriate treatment parameters such as citrate dose, blood flow rate, and dialysate flow rate.

Dose-dependent relationship between SGLT2 inhibitor hold time and risk for postoperative anion gap acidosis: a single-centre retrospective analysis.

BACKGROUND: Use of sodium-glucose transporter-2 (SGLT2) inhibitors has dramatically increased over the past decade. This medication class predisposes patients to euglycaemic diabetic ketoacidosis, particularly during times of physiologic stress, including fasting and surgery. Beyond case reports and series, a systematic description of perioperative metabolic effects of SGLT2 inhibitors is lacking. METHODS: We examined the degree of anion gap acidosis, controlling for non-ketone anions, in patients undergoing surgery at Massachusetts General Hospital in 2016-22. We constructed a multivariable regression model incorporating known non-ketone contributors to the postoperative anion gap (albumin, lactate, estimated glomerular filtration rate, and preoperative anion gap), hold time, and interaction terms between hold time and three previously suggested risk factors for euglycaemic diabetic ketoacidosis: emergency surgery, cardiac surgery, and insulin use. RESULTS: In 463 patients on SGLT2 inhibitors, we observed a strong association between decreased hold time and postoperative anion gap (P<0.001 in a univariable analysis; -0.43, 95% confidence interval [-0.76 to -0.11] change in anion gap per day held, P=0.01 in a multivariable analysis). A significant interaction between hold time and emergency surgery was observed, whereas there was no apparent interaction with insulin use or cardiac surgery. CONCLUSIONS: These findings provide the first evidence that an anion gap acidosis, likely from ketoacids, develops in all patients who do not hold SGLT2 inhibitors before surgery rather than in an idiosyncratic few. If an SGLT2 inhibitor is unable to be stopped, postoperative monitoring of anion gap and serum ketones can help detect clinically significant euglycaemic diabetic ketoacidosis, particularly in those undergoing emergency surgery.

Assessing the Role of Initial Serum Calcium Concentration in Patients with Ethylene Glycol Poisoning.

INTRODUCTION: Assays for ethylene glycol (EG) with a rapid turn-around time are not routinely available. Clinicians must rely on historical features and readily available clinical tests, combined with clinical acumen, to guide the initial management of suspected EG poisoning. Hypocalcemia has been suggested as a clue supporting the diagnosis of EG poisoning in patients presenting with an unexplained high anion gap metabolic acidosis (HAGMA). A previous small study challenged this assumption. METHODS: This was a retrospective case series of one state's poison control system of confirmed EG-poisoned patients between September 2017 and April 2021. The definition of EG poisoning was based on suspected EG ingestion and a serum EG concentration > 5 mg/dL. Patients who were suspected to have EG toxicity but did not have a confirmed EG concentration or the EG concentration was less than 5 mg/dL were excluded. Routine laboratory studies were recorded for all patients. Comparisons between serum calcium on presentation to presenting blood pH, bicarbonate, anion gap, and creatinine were assessed for correlation. RESULTS: There was no correlation between the presenting calcium and either pH or creatinine. There was a weak positive correlation between the initial serum calcium and anion gap, a weak negative correlation between the initial serum calcium and bicarbonate. CONCLUSION: On hospital presentation, hypocalcemia was not associated with EG poisoning, even in patients with a HAGMA. A normal serum calcium on presentation does not exclude the diagnosis of EG poisoning.

Risks of Topical Carbonic Anhydrase Inhibitors in Glaucoma Patients With Chronic Kidney Disease: A Nationwide Population-Based Study.

PURPOSE: To investigate the risks of metabolic acidosis and renal outcomes after topical carbonic anhydrase inhibitor (CAI) use in patients with both primary open-angle glaucoma (POAG) and advanced chronic kidney disease (CKD). DESIGN: Nationwide, population-based cohort study. METHODS: This study was conducted with population data from Taiwan's National Health Insurance (NHI) Research Database between January 2000 and June 2009. Patients with advanced CKD who were diagnosed with glaucoma (International Classification of Diseases, Ninth Revision [ICD-9] code 365) and had been receiving eye drops for glaucoma (including carbonic anhydrase inhibitors selected by NHI drug code) were enrolled. Using Kaplan-Meier methods, we compared the cumulative incidence of mortality, long-term dialysis, and cumulative incidence of metabolic acidosis over time between CAI users and CAI non-users. Primary outcomes comprised mortality, renal outcome (progression to hemodialysis), and metabolic acidosis. RESULTS: In this cohort, topical CAI users had a higher incidence of long-term dialysis than non-users (incidence = 1,216.85 vs 764.17 events per 100 patient-years; adjusted hazard ratio = 1.17, 95% CI = 1.01-1.37). Hospital admissions due to metabolic acidosis were higher in CAI users compared with non-users (incidence = 21.54 vs 11.87 events per 100 patient-years; adjusted hazard ratio = 1.89, 95% CI = 1.07-3.36). CONCLUSIONS: Topical CAIs may be associated with higher risks of long-term dialysis and metabolic acidosis in patients with POAG and pre-dialysis advanced CKD. Therefore, topical CAIs should be used with caution in advanced CKD patients.

Empagliflozin-associated postoperative mixed metabolic acidosis. Case report and review of pathogenesis.

BACKGROUND: Euglycemic diabetic ketoacidosis associated with SGLT2 inhibitors is a rare, relatively new and potentially fatal clinical entity, characterized by metabolic acidosis with normal or only moderately elevated glycemia. The mechanisms are not fully understood but involve increased ketogenesis and complex renal metabolic dysfunction, resulting in both ketoacidosis and hyperchloremic acidosis. We report a rare case of fatal empagliflozin-associated acidosis with profound hyperchloremia and review its pathogenesis. CASE PRESENTATION: A patient with type 2 diabetes mellitus treated with empagliflozin underwent an elective hip replacement surgery. Since day 4 after surgery, he felt generally unwell, leading to cardiac arrest on the day 5. Empagliflozin-associated euglycemic diabetic ketoacidosis with severe hyperchloremic acidosis was identified as the cause of the cardiac arrest. CONCLUSIONS: This unique case documents the possibility of severe SGLT2 inhibitor-associated mixed metabolic acidosis with a predominant hyperchloremic component. Awareness of this possibility and a high index of suspicion are crucial for correct and early diagnosis.

High risk and low prevalence diseases: Toxic alcohol ingestion.

INTRODUCTION: Toxic alcohol ingestion is a rare but serious condition that carries with it a high rate of morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of toxic alcohol ingestion, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: Toxic alcohols include ethylene glycol, methanol, isopropyl alcohol, propylene glycol, and diethylene glycol. These substances can be found in several settings including hospitals, hardware stores, and the household, and ingestion can be accidental or intentional. Toxic alcohol ingestion presents with various degrees of inebriation, acidemia, and end-organ damage depending on the substance. Timely diagnosis is critical to prevent irreversible organ damage or death and is based primarily on clinical history and consideration of this entity. Laboratory evidence of toxic alcohol ingestion includes worsening osmolar gap or anion-gap acidemia and end organ injury. Treatment depends on the ingestion and severity of illness but includes alcohol dehydrogenase blockade with fomepizole or ethanol and special considerations for the initiation of hemodialysis. CONCLUSIONS: An understanding of toxic alcohol ingestion can assist emergency clinicians in diagnosing and managing this potentially deadly disease.

Effects of topiramate therapy on serum bicarbonate concentration in a sample of 10,279 veterans.

BACKGROUND: Topiramate, which is increasingly being used to treat alcohol use disorder (AUD), is commonly associated with reduced serum bicarbonate concentrations. However, estimates of the prevalence and magnitude of this effect are from small samples and do not address whether topiramate's effects on acid-base balance differ in the presence of an AUD or by topiramate dosage. METHODS: Veterans Health Administration electronic health record (EHR) data were used to identify patients with a minimum of 180 days of topiramate prescription for any indication and a propensity score-matched control group. We differentiated patients into two subgroups based on the presence of a diagnosis of AUD in the EHR. Baseline alcohol consumption was determined using Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scores in the EHR. Analysis also included a three-level measure representing mean daily dosage. The topiramate-associated changes in serum bicarbonate concentration were estimated in difference-in-differences linear regression models. A serum bicarbonate concentration <17 mEq/L was considered to represent possible clinically significant metabolic acidosis. RESULTS: The cohort comprised 4287 topiramate-treated patients and 5992 propensity score-matched controls with a mean follow-up period of 417 days. The mean topiramate-associated reductions in serum bicarbonate concentration were <2 mEq/L in the low (≤88.75), medium (>88.75 and ≤141.70), and high (>141.70) mg/day dosage tertiles, irrespective of AUD history. Concentrations <17 mEq/L occurred in 1.1% of topiramate-treated patients and 0.3% of controls and were not associated with alcohol consumption or an AUD diagnosis. CONCLUSIONS: The excess prevalence of metabolic acidosis associated with topiramate treatment does not differ with dosage, alcohol consumption, or the presence of an AUD. Baseline and periodic serum bicarbonate concentration measurements are recommended during topiramate therapy. Patients prescribed topiramate should be educated about the symptoms of metabolic acidosis and urged to report their occurrence promptly to a healthcare provider.

Severe methanol intoxication with atypical symptoms and imaging changes: a fatal case report.

Acute methanol intoxication can occur as accidental ingestion of adulterated spirits. We report a 51-year-old male patient with high anion-gap metabolic acidosis (pH 6.71, HCO3-4.2 mmol/l, K + 6.5mmol/l) because of severe methanol intoxication (450 mg/L, reference level <2.9 mg/L) who presented with atypical symptoms of dizziness and rapidly developed extensive subarachnoid hemorrhage and diffuse cerebral edema and died within several days. Clinicians should have suspicion for subarachnoid hemorrhage in patients with long-term drinking poisoned by methanol with dizziness, consciousness disturbances and severe metabolic acidosis.

Mass Poisoning From Ethylene Glycol at a U.S. Military Base.

Ethylene glycol (EG) toxicity is an important cause of toxic alcohol poisoning in the USA with over 5,000 exposures reported annually. While classically characterized by solitary accidental or intentional ingestions, mass toxic alcohol poisoning outbreaks and more rarely collective consumptions (typically of methanol) have been described. We describe an ethylene glycol poisoning from collective ingestion that involved soldiers presenting at William Beaumont Army Medical Center in El Paso, Texas. Eleven soldiers presented to the emergency department over a 12-h period after ingestion of an unknown substance. The first two patients exhibited severe neurologic symptoms, while the remainder were asymptomatic. As serum EG levels were not immediately available, treatment decisions were based on surrogate laboratory values. Two patients received immediate hemodialysis, and fomepizole (FOM) because of severe acidosis with elevated anion and osmolal gaps. These patients developed acute kidney injury with renal recovery within a 3-week period. Two patients with elevated lactate received bicarbonate-based intravenous (IV) fluids and FOM. Two patients received IV fluids only and required prolonged observation for worsening acidosis and/or acute kidney injury. Five patients with normal laboratory values were treated with IV fluids and observation. All patients received cofactors including thiamine and pyridoxine. All patients survived. The outbreak occurred in the setting of limited dialysis resources, limited FOM availability, and in a resource-limited community. Additional guidelines are needed to determine allocation of limited resources, optimal dialysis and FOM treatment course, and comorbid conditions, which may prolong recovery.