Cause Of Metabolic Acidosis Research Articles

A rare and underestimated cause of anion gap metabolic acidosis in a pediatric patient

Abstract Recognized causes of anion gap metabolic acidosis include methanol, uremia, diabetic ketoacidosis, propylene glycol, isoniazid, iron, lactic acidosis, ethylene glycol, and salicylates, which is taught as the mnemonic, MUDPILES. While this mnemonic can be a useful learning tool, it is important to consider other, atypical causes. Here, we present the case of a 9-year-old male patient with a complex medical history, including trisomy 21 and Lennox-Gastaut syndrome who presented to the emergency department (ED) in hypotensive shock. Upon admission, he was noted to have a distended abdomen, evidence of acute pancreatitis and possible sepsis. Of note, his initial labs revealed an anion gap of 30.1 mmol/L, a whole blood lactate of 4.4 mmol/L, a pH of 7.2, and a normal pCO2, indicting an anion gap metabolic acidosis. Importantly, methanol, ethylene glycol, ketones, and salicylates were not detected, and renal function was normal. However, he did have an extensive medication history, including several antiepileptic drugs (AEDs). Over the coming weeks, he recovered from the acute pancreatitis, but developed fluid overload, electrolyte derangements (hypernatremia and hypokalemia), a worsening metabolic acidosis with an anion gap up to 54.6 mmol/L, and hyperammonemia (plasma NH3 of 232 μmol/L). At this point, the metabolism team was contacted for concerns regarding the rising ammonia levels, which subsequently responded to a combination of lactulose and Rifaximin. An inborn error of metabolism (IEM) was considered, and plasma amino acid analysis was performed (Waters Acquity MassTrak AAA solution) but was not diagnostic. Notably, the patient developed a significantly elevated gamma glutamyl transpeptidase (GGT) up to 4088 U/L, suggesting glutathione depletion, however, transaminases and alkaline phosphatase were normal. The laboratory was contacted by the metabolism providers for other possible causes of metabolic acidosis and it was suggested that the patient undergo urine organic acid testing. Urine specimens were analyzed using gas chromatography/mass spectrometry (GC/MS) (Aligent system). The results were notable for marked excretion of pyroglutamic acid (5-oxoproline), which is typically associated with acetaminophen, however, the patient’s acetaminophen levels were less than 5 μg/mL, indicating another, atypical cause of increased pyroglutamic acid. In this case, vigabatrin, an anticonvulsant known to cause glutathione depletion and secondary pyroglutamic aciduria was suspected, and subsequently withdrawn. The patient was also started on a trial of N-acetylcysteine (NAC) to replenish glutathione, which resolved the pyroglutamic aciduria and anion gap, and corrected the metabolic acidosis. This case highlights the importance of recognizing pyroglutamic acid as a rare cause of anion gap metabolic acidosis, even in the setting of normal acetaminophen levels, and the importance of organic acid testing in the work-up of such patients. Wider use of the mnemonic GOLD MARK, where the “O” stands for oxoproline, may help in the differential diagnosis of anion gap metabolic acidosis.

The relationship between anti-seizures medications and metabolic acidosis in craniotomy operations: is topiramate or zonisamide the cause of metabolic acidosis?

Background/aimThe most commonly prescribed anti-seizures medications (ASMs) for the treatment of epilepsy are currently topiramate, zonisamide, lacosamide, carbamazepine and levetiracetam. The objective of this study was to examine the correlation between preoperative, intraoperative, and postoperative metabolic acidosis and the use of ASMs prior to craniotomy operations.Materials and methodsThis retrospective cross-sectional study evaluated patients who underwent intracranial surgery with craniotomy under general anaesthesia between May 2020 and April 2023 and used ASMs. The patients were classified into four groups based on the pharmacological mechanisms of action of the ASMs administered before intracranial surgery (Group-I, zonisamide or topiramate; Group-II, lacosamide; Group-III, carbamazepine; Group-IV, levetiracetam). Metabolic acidosis severity was defined based on base excess (BE) levels: mild (-3 to -5), moderate (-5 to -10), and severe (below − 10). The study investigated the correlation between ASMs and the severity of metabolic acidosis in preoperative, intraoperative, and postoperative blood gas measurements.ResultsOut of 35 patients, 24 patients underwent intracranial surgery and 11 patients underwent epilepsy surgery. There were statistically significant differences in the severity of metabolic acidosis between preoperative (p < 0.001), intraoperative (p < 0.001) and postoperative (p = 0.01) groups. The preoperative mean BE of group-I was − 4.7, which was statistically lower than that of group-III (p = 0.01) and group-IV (p < 0.001). Intraoperatively and postoperatively, group-I had a mean BE of -7.5 and − 3.2, respectively, which was statistically lower than that of groups II (p = 0.007; p = 0.04), III (p = 0.002; p = 0.03), and IV (p < 0.001; p = 0.009). There was no statistically significant difference in BE between groups II, III and IV at all three time points. Group I had the lowest BE at all three time points. Intraoperative bicarbonate was administered to all patients in group I, whereas no intraoperative bicarbonate was required in the other groups. In group I, 50% of patients required postoperative intensive care.ConclusionThe use of ASMs in patients undergoing surgery is important in terms of mortality and morbidity. Topirimat and zonisamide are ASMs that can cause preoperative, intraoperative and postoperative metabolic acidosis. Patients receiving topirimat or zonisamide are particularly susceptible to metabolic acidosis. Special care should be taken in the management of anaesthesia in patients receiving these drugs, and monitoring of the perioperative metabolic status is essential.

A case report of Paracetamol related pyroglutamic acidosis: mind the gap in a malnourished patient

BackgroundPyroglutamic acidosis is a rare cause of high anion gap metabolic acidosis. Most cases of paracetamol related pyroglutamic acidosis are described in malnourished women and patients with kidney/liver failure, alcohol use or severe sepsis. In this report, we describe how pyroglutamic acidosis could be related to the use of chronic therapeutic paracetamol with only malnutrition as an associated risk factor.Case presentationWe report a case of a 67-year-old male patient developing a pyroglutamic acidosis. The patient was initially admitted to hospital for infectious osteoarthritis and developed a metabolic acidosis during his hospital stay. Analgesics included daily therapeutic doses of paracetamol. What makes our case unusual is that our malnourished male patient did not have renal or hepatic failure. The diagnosis of paracetamol related pyroglutamic acidosis was made after ruling out the main causes of metabolic acidosis. It was further confirmed by urine organic acids measurement showing a markedly elevated level of pyroglutamic aciduria. Paracetamol was discontinued allowing a prompt correction of the anion gap.ConclusionThis case is a representative of pyroglutamic acidosis related to chronic therapeutic paracetamol with only malnutrition as an associated risk factor. Physicians should be aware of such unusual cause of metabolic acidosis, which may be more common than expected in hospitalized patients. A high clinical suspicion is needed when urine organic acids analysis is not available.

#746 Lactic acidosis in patients with acute kidney injury treated with renal replacement therapy in intensive care unit

Abstract Background and Aims Lactic acidosis (LA) is the most common cause of metabolic acidosis in hospitalised patients. LA is frequent in intensive care unit (ICU) patients with acute kidney injury (AKI) treated with renal replacement therapy (RRT). The aim of our study was to analyse the impact of LA on mortality. Method We conducted a retrospective observational study in a tertiary care hospital with a 12-bed ICU. During the study period of 4 years before the COVID pandemic, 2939 patients were admitted to the ICU, 503 patients were diagnosed with AKI and 210 of them required RRT. Due to missing data, we retrospectively analysed only 176 patients. LA was defined as a serum lactate concentration above 4 mmol/L on admission to the ICU. Demographic data, comorbidities, laboratory data at ICU admission and 30-day survival after ICU admission were obtained from the medical record. Survival was estimated using the Kaplan-Meier method, and factors associated with 30-day mortality were assessed in a Cox regression. Results The mean age of patients was 63.4±12.9 years, and 68.2% were men. Sixty-five (36.9%) of patients had LA. The prevalence of comorbidities prior to admission and baseline laboratory values are shown in Table 1. All patients were treated with RRT, 137 (77.8%) with continuous RRT and 39 (22.2%) with intermittent hemodialysis. The mean ICU stay was 14.6 ± 12 days, and 114 (64.8%) patients died during the observational period of 30 days. A Kaplan-Meier survival analysis showed that the survival was statistically significantly lower (log-rank; p = 0.027) in the group of patients with LA (Fig. 1). Univariate Cox regression analysis showed that LA was a significant predictor of 30-day survival (HR 1.51; 95% CI 1.038-2.197; p = 0.031). In the multivariate Cox regression analysis, which included age, gender, diabetes, hypertension, LA and C-reactive protein, only age (HR 1.029; 95% CI 1.011-1.046; p = 0.001) and LA (HR 1.515; 95% CI 1.030-2.228; p = 0.035) were independent predictors of mortality. Conclusion LA on ICU admission is an independent, highly prognostic factor for death within 30 days of admission in patients with AKI treated with RRT.

SAT136 Severe Lactic Acidosis Due To Metformin Use.

Abstract Disclosure: A. Khan: None. Lactic acidosis is an important cause of metabolic acidosis. Broadly, etiology can be divided into type A (impaired tissue oxygenation), type B (systemic hypoperfusion), and D-lactic acidosis. One such etiology which deserves mentioning is metformin associated lactic acidosis (MALA). The incidence of MALA is more notable in the setting of kidney dysfunction, hepatic failure, and alcohol use. Severe acidosis due to Metformin is an emergency and warrants timely management to avoid further hemodynamic compromise. 73-year-old female with a history of hypertension and type II diabetes mellitus (on metformin) presented to the hospital with acute onset of abdominal pain, nausea, and vomiting. She reported having intermittent vomiting and diarrhea for three days prior to admission, and describes the abdominal pain as 10/10, sharp with radiation to the lower back, and worsening 6 hours prior to arrival. She denies fever, melena, hematochezia, change in appetite. She was brought to the hospital via EMS and was given fentanyl for her pain. Vitals on arrival were stable. On exam, she appeared in distress due to pain, with diffuse tenderness in her abdomen, with normal cardiac and lung exam. Labs showed leukocytosis 15 K/mm3, hemoglobin 11.1 gm/dl, hyperkalemia 5.7 mEq/L, bicarb &amp;lt;5 mEq/L, creatinine 13.4 mg/dl, BUN 107 mg/dl, venous lactate 15.1 mmol/l, lipase 435 U/L, ammonia 229 umol/L, with normal AST, ALT and ALP, and troponin. Urinalysis was negative. Initial ABG showed an unreadable pH, which was then repeated, and pH was noted to be 6.72, pCO2 of 29.4 mm/hg, CTA angiography was negative for dissection, mesenteric or bowel ischemia. Soon she was noted to be hypotensive and went into shock requiring pressors, bicarbonate drip, and broad-spectrum antibiotics. She eventually was intubated for airway protection. Subsequently, she was admitted to the ICU for possibly combined hypovolemic and septic shock with multi-organ dysfunction, severe lactic acidosis, acute kidney failure, and respiratory failure. Nephrology was consulted and dialysis was initiated. It was postulated that the presentation was likely due to metformin associated lactic acidosis (MALA). She required dialysis daily for 4 days and ultimately her kidney function improved. On discharge, she was not dialysis dependent. The case above illustrates the severity of lactic acidosis that can occur due to Metformin use. It is important to bear in mind that such presentation, may not necessarily occur on initiation of Metformin, but rather at any point of use. More importantly, its of utmost importance to consider effective therapeutic options like dialysis once severe academia is noted to allow correction of metformin induced acid-base disorder. Mortality estimates of MALA have been around 25-50%, highlighting the significance of prompt treatment of this condition. Presentation: Saturday, June 17, 2023

THU386 Non-diabetic Ketoacidosis As A Rare Complication Of Colitis And Gastritis

Abstract Disclosure: J. Bosques-Lorenzo: None. J.J. Irizarry-Garcia: None. J. Baez-Torres: None. J. Colon-Castellano: None. Background: Starvation ketoacidosis is a rare cause of metabolic acidosis that is often under-recognized. To our knowledge, no cases of starvation ketoacidosis secondary to colitis and gastritis have been reported. Clinical Case: A 91 y/o male presented to the ER with nausea, vomiting, left lower quadrant abdominal pain, and anorexia that progressed for the previous two days. Physical examination was remarkable for a fragile man, acutely over chronically ill, with reduced skin turgor, dry oral mucosa, but a benign abdominal examination. Vitals signs upon arrival were stable. Basic laboratories showed hypoglycemia at 64 mg/dL (70 - 99 mg/dL), low CO2 17.7 mEq/dL (24 -32 mEq/dL), Na 137 mEq/dL (135 - 145 mEq/dL), Cl 94 mEq/dL (100- 110 mEq/dL). High anion gap metabolic acidosis was demonstrated (25 mEq/L). Renal function was preserved and within the patient's baseline, lactic acidosis was ruled out with normal levels in the laboratory, and CBC was negative for leukocytosis. Patient denied alcohol ingestion upon questioning. There were no suspected infectious foci. Abdomino-pelvic CT scan with oral contrast demonstrated colonic, rectal, and gastric inflammation. Case reevaluation and assessment of the data and history of present illness, led to B-hydroxybutyrate measurement. Surprisingly, ketones levels came back markedly elevated at confirming starvation ketoacidosis in the setting of colitis and gastritis. Patient was treated with aggressive intravenous fluids with normal saline for the first 24 hours, IV glucose to correct hypoglycemia, electrolytes were replaced as needed, and stomach antacids for symptomatic relief of abdominal discomfort. We slowly progressed diet as tolerated and electrolytes were carefully monitored for refeeding syndrome. Few days later the patient was discharged home with full resolution of symptoms. Conclusion: Metabolic acidosis secondary to ketoacidosis is mostly visualized to be exclusive for diabetic patients, leading to under-recognition of starvation ketoacidosis. This is the first case of starvation ketoacidosis secondary to colitis and gastritis. Understanding its association can lead to prompt recognition and treatment, especially in the non-diabetic population. Presentation: Thursday, June 15, 2023

The elevation of the anion gap in steady state chronic kidney disease may be less prominent than generally accepted.

A presumed cause of metabolic acidosis in chronic kidney disease (CKD) is accumulation of unmeasured anions, leading to a high anion gap (AG). In patients with CKD with a high AG, only minor increases are expected. The aim of this study is to evaluate the magnitude of the AG in documented steady state CKD to examine the effect of CKD on a high-AG metabolic acidosis (HAGMA). In this cross-sectional study the AG, bicarbonate, and chloride were evaluated in 1045 blood and urine samples of 501 patients with steady state CKD in the outpatient clinic. The influence of phosphate, albumin and potassium on the AG were evaluated. The mean AG increased from 8.8mEq/l (±1.57) in CKD stage 1 to 11.2mEq/l (±2.22) in CKD stage 5 (P<0.001). Correction for albumin or phosphate did not influence the magnitude of the AG. Correction for potassium did alter the prevalence of HAGMA, but not the severity. [HCO3-] decreased between CKD stages 1 and 5 by 5.1mEq/l. The [Cl-] increased by 2.6mEq/l between CKD stages 1 and 5. The elevation of the AG in patients with steady state CKD is limited and less pronounced than the decrease in [HCO3-]. Normal AG metabolic acidosis seems to be more important in CKD than HAGMA. The CKD stage and the magnitude of the AG should be taken into account when evaluating a patient with HAGMA. This study suggests that an AG >15mEq/l is rarely due to renal failure alone.

A Review of Bicarbonate Use in Common Clinical Scenarios

BackgroundThe use of sodium bicarbonate to treat metabolic acidosis is intuitive, yet data suggest that not all patients benefit from this therapy. ObjectiveIn 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. DiscussionSodium 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. ConclusionsEmpiric 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.

Severe lactic acidosis with euglycemic diabetic ketoacidosis due to metformin overdose.

Metformin-associated lactic acidosis is a well-known metformin treatment complication; however, the development of euglycemic diabetic ketoacidosis (euDKA) has rarely been reported. Here we report a case of lactic acidosis and euDKA after metformin overdose. A 57-year-old female patient was transferred to our hospital with severe metabolic acidosis and acute kidney injury. She had type 2 diabetes mellitus and was on oral antidiabetic therapy of vildagliptin metformin hydrochloride daily. On the admission day, she had committed suicide by overdosing 50 tablets of vildagliptin metformin hydrochloride, which was equivalent to 25,000mg of metformin and 2500mg of vildagliptin. She had severe lactic acidosis 5h after overdosing. However, after 34h of overdosing, serum lactate levels decreased while serum anion gap levels increased. She received single hemodialysis treatment. Serum total ketone bodies, β-hydroxybutyrate acetoacetic acid, and acetone were increased even after hemodialysis treatment. Her blood glucose levels have never exceeded 250mg/dL since admission. Therefore, we considered that the cause of metabolic acidosis in this patient was not only lactic acidosis but also euDKA. The causes of euDKA in our patient might be hepatic production of ketone bodies due to metformin overdose in addition to type 2 diabetes mellitus, starvation, infection, and stressful physical conditions such as vomiting and diarrhea. We propose that not only lactic acidosis but also ketoacidosis is one of the important pathological conditions in patients with metformin overdose.

Renal Tubular Acidosis in Pregnant Critically Ill COVID-19 Patients: A Secondary Analysis of a Prospective Cohort.

Background: Renal tubular acidosis (RTA) is an extremely rare cause of metabolic acidosis (10 in 100,000). RTA has been linked neither to pregnancy nor to severe coronavirus disease 2019 (COVID-19). The purpose of this study was to analyze the prevalence and clinical course of normal anion gap metabolic acidosis in critically ill pregnant COVID-19 patients and to compare them to an age-matched nonpregnant female patient cohort. Methods: Secondary analysis was conducted on a prospective observational cohort of critically ill patients suffering from COVID-19 consecutively admitted to a tertiary intensive care unit (ICU) between February 2020 and April 2021. Results: A total of 321 COVID-19 patients required admission to the ICU; 95 (30%) were female, and 18 (19%) were of childbearing age. Seven of eight (88%) pregnant women (all in the last trimester) required advanced respiratory support due to COVID-19. The estimated glomerular filtration rate was 135 (123–158) mL/min/m2 body surface area, and six pregnant women (86%) were diagnosed with a normal, respiratory compensated, anion gap metabolic acidosis (pHmin 7.3 (7.18–7.31), HCO3−min 14.8 (12.8–18.6) mmol/L, and paCO2 3.4 (3.3–4.5) kPa). Three (43%) acidotic pregnant women fulfilled diagnostic criteria for RTA. All women recovered spontaneously within less 7 days. Conclusions: Metabolic acidosis seems to be very common (85%) in pregnant critically ill COVID-19 patients, and the prevalence of RTA might be higher than normal. It remains to be demonstrated if this observation is an indirect epiphenomenon or due to a direct viral effect on the tubular epithelium.

Beyond the Urine Anion Gap: In Support of the Direct Measurement of Urinary Ammonium

Ammonium is a major urinary buffer that is necessary for the normal excretion of the daily acid load. Its urinary rate of excretion (UNH4) may be increased several fold in the presence of extrarenal metabolic acidosis. Therefore, measurement of UNH4 can provide important clues about causes of metabolic acidosis. Because UNH4 is not commonly measured in clinical laboratories, the urinary anion gap (UAG) was proposed as its surrogate about 4 decades ago, and it is still frequently used for that purpose. Several published studies strongly suggest that UAG is not a good index of UNH4 and support the concept that direct measurement of UNH4 is an important parameter to define in clinical nephrology. Low UNH4 levels have recently been found to be associated with a higher risk of metabolic acidosis, loss of kidney function, and death in persons with chronic kidney disease, while surrogates like the UAG do not recapitulate this risk. In order to advance the field it is necessary for the medical community to become more familiar with UNH4 levels in a variety of clinical settings. Herein, we review the literature, searching for available data on UNH4 under normal and various pathological conditions, in an attempt to establish reference values to interpret UNH4 results if and when UNH4 measurements become available as a routine clinical test. In addition, we present original data in 2 large populations that provide further evidence that the UAG is not a good predictor of UNH4. Measurement of urine NH4 holds promise to aid clinicians in the care of patients, and we encourage further research to determine its best diagnostic usage.

Effectiveness of Sodium Bicarbonate Infusion on Mortality in Critically Ill Children With Metabolic Acidosis.

Objective: Metabolic acidosis often occurs in the paediatric intensive care unit (PICU). Although sodium bicarbonate (SB) has been widely used in paediatrics, data on the effect of SB on children with metabolic acidosis in the PICU are scarce. Methods: Patients with metabolic acidosis who were treated with SB within 48 h of PICU admission were screened. Multivariate logistic regression, subgroup analysis, and propensity score matching (PSM) were used to investigate the relationships between SB infusion and clinical outcomes. Results: A total of 1,595 patients with metabolic acidosis were enrolled in this study. In the multivariate logistic regression model, SB infusion was not correlated with in-hospital mortality (odds ratio (OR) 0.87, 95% confidence interval (CI) 0.47–1.63, p = 0.668), but was significantly correlated with hypernatraemia (OR 1.98, 95% CI 1.14–3.46, p = 0.016), hypokalaemia (OR 2.01, 95% CI 1.36–2.96, p < 0.001), and hypocalcaemia (OR 4.29, 95% CI 2.92–6.31, p < 0.001). In the pH value, lactate level, acute kidney injury level, age grouping, and anion gap level subgroups, the ORs for SB and in-hospital mortality were not statistically significant. After PSM, the results remained unchanged. Conclusion: SB infusion does not reduce the in-hospital mortality of severely ill children with metabolic acidosis and increases the risk of hypernatraemia, hypokalaemia, and hypocalcaemia. More effort should be focused on eliminating the causes of metabolic acidosis rather than SB infusion.

Hyperchloremic metabolic acidosis due to saline absorption during laser enucleation of the prostate: a case report

BackgroundRecent technological advancements have enabled the use of electrolyte solutions such as saline or buffered electrolyte solution during transurethral resection or laser enucleation of the prostate. However, saline absorption may cause hyperchloremic metabolic acidosis.Case presentationA male in his late seventies underwent holmium laser enucleation of the prostate under a combination of subarachnoid block and general anesthesia. Intraoperatively, abdominal distension prompted the attending anesthesiologist to consider the possibility of SGA malposition, and the trachea was intubated. Oropharyngeal and neck edema was observed, and laboratory examination revealed considerable acidosis with hyperchloremia. Further evaluation confirmed the absorption of a large amount of saline into the circulation via the perforated bladder. Application of the simplified Stewart approach clearly suggested that hyperchloremia was the principal cause of metabolic acidosis. The dilution of albumin attenuated acidosis.ConclusionsAbsorption of normal saline during laser enucleation of prostate caused hyperchloremic metabolic acidosis and airway edema.

Descriptive Study On Starvation Ketoacidosis In Covid-19 Obstetric Patients In A Tertiary Hospital in Central Region of Malaysia

PurposeThis study describes the presentation of starvation ketoacidosis in cases of pregnancy related Covid 19 pneumonia and their outcomes toward Cytokine Release Syndrome (CRS), Intensive Care Unit (ICU) admission, overall maternal and fetal outcome.Methods & MaterialsProspective study on all obstetric admissions for Covid 19 pneumonia in a tertiary hospital in central region of Malaysia (Hospital Ampang) from 1st July to 31st August 2021 was done. Starvation ketoacidosis cases as defined as serum bicarbonate less than 20mmol/L, with serum ketone of more than 3mmol/L or urine ketone more than 4+ were selected. Their outcome related to CRS, ICU admission and fetal outcome was monitor. Patients with incomplete data, and other cause of metabolic acidosis were excluded from this study.Results31 patients been isolated to have starvation ketoacidosis based on our study criteria. The median age of our study population was 31 years old. Patients mostly presented in stable condition before the onset of starvation ketoacidosis whereby 23 cases (74.19%) presented with Category 1 to 3 Covid-19 infection and only 8 cases (25.81%) require oxygen (Category 4) on presentation. Starvation ketoacidosis has commonly been observed in gestational diabetes mothers (61.29%) and those with obesity (51.61%). It happened mostly at day 6 to day 10 of covid infection (54.83%) with commonly lower CRP count of less than 50 (61.29%) during onset of acidosis. The mean random blood sugar (RBS) among patients who diagnosed with starvation ketoacidosis was 5.95 mmol/L. Total of 25 from 31 patients (80.64 %) went into CRS, and required oxygen supplementation and 13 patients (41.94%) required ICU care. We also observed 21 out of 31 patients (67.74%) in our sample population whom needed delivery of the fetusConclusionStarvation ketoacidosis in Covid 19 Obstetric patients may precede CRS and ICU admission. The association of starvation ketoacidosis with CRS and ICU admission or worsening Covid 19 pneumonia need to be further evaluated in a bigger study sample. A prompt early multidisciplinary treatment involving Infectious Disease team, Intensive Care team and Obstetric Team could avoid undesirable patient outcome.

SEVERE LACTIC ACIDOSIS SECONDARY TO ACUTE ALCOHOL INTOXICATION

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients. Alcoholic ketoacidosis is one of the several etiologies where serum lactate level rarely exceeds 3 mmol/L. We present to you an interesting case of severe lactic acidosis (24 mmol/L) in a patient with acute alcohol intoxication. CASE PRESENTATION: Patient is a 62-year male who presented with intractable abdominal pain for 2 days. Past medical history was significant for alcohol use disorder. On presentation, patient had tachycardia, tachypnea, was restless with slurred speech with mild abdominal tenderness. Laboratory findings were remarkable for leukocytosis of 22.7, serum bicarbonate of 4 mmol/L, serum glucose 104 mg/dL, serum lactate 24 mmol/L. ABG showed pH of < 7.00, pCO2 12 mmHg, HC03 4.6 mmol/L. Anion gap was 41.0. Serum ethanol level was elevated at 0.185 g/dl. Patient was started on bicarbonate infusion, IV thiamine with 5% dextrose fluid and CIWA protocol. Serum beta hydroxybutyrate was elevated at 2.9, serum osmolality was elevated at 344 with osmolar gap of 13. LFT was deranged with unremarkable liver ultrasound. Patient was admitted to the ICU. Serum isopropanol, methanol, and ethylene glycol were negative. Infectious workup including blood culture, urine culture, pneumonia workup were negative. Acetaminophen and salicylate levels were normal. Urine drug screen was unremarkable. No history of GI malabsorption (short-bowel syndrome), renal failure or recent phenobarbital administration. Lactic acidosis was therefore attributed to alcoholic ketoacidosis in a setting of alcoholic hepatitis. Patient gradually improved with final pH 7.38, lactate 1.80 and serum HC03 24.6 by day 2. DISCUSSION: Lactate level of > 4 mmol/L with arterial pH < 7.35 suggests lactic acidosis. Lactic acidosis is broadly classified into type A which occurs due to impaired systemic tissue oxygenation and type B due to toxin induced cellular metabolism impairment and regional ischemia, commonly in alcoholism, HIV, antiretroviral medications, beta adrenergic medications, D lactic acidosis (short-bowel syndrome), diabetes mellitus, metformin, malignancy. Alcoholic ketoacidosis remains important etiology as if missed may result in fatal consequences including sudden death. Occasionally, alcoholic ketoacidosis can be misdiagnosed as diabetic ketoacidosis with subsequent mismanagement resulting in increased morbidity and mortality. CONCLUSIONS: Alcoholic ketoacidosis typically presents with metabolic acidosis but rarely with lactate > 3mmol/L in absence of other contributing factors. Oftentimes, the diagnosis is missed or misdiagnosed as diabetic ketoacidosis resulting in mismanagement contributing to increased morbidity and mortality. REFERENCE #1: Adeva-Andany, M., et al. 'Comprehensive Review on Lactate Metabolism in Human Health'. Mitochondrion, vol. 17, July 2014, pp. 76–100. PubMed, doi:10.1016/j.mito.2014.05.007. REFERENCE #2: Kreisberg, R. A. 'Lactate Homeostasis and Lactic Acidosis'. Annals of Internal Medicine, vol. 92, no. 2 Pt 1, Feb. 1980, pp. 227–37. PubMed, doi:10.7326/0003-4819-92-2-227 REFERENCE #3: Madias, N. E. 'Lactic Acidosis'. Kidney International, vol. 29, no. 3, Mar. 1986, pp. 752–74. PubMed, doi:10.1038/ki.1986.62 DISCLOSURES: No relevant relationships by Luna Khanal, source=Web Response No relevant relationships by Adarsha Ojha, source=Web Response

Alcoholic ketoacidosis: an underdiagnosed entity

Alcoholic ketoacidosis (AKA) is a common and underdiagnosed cause of metabolic acidosis in patients with an alcohol-related disorder. It is a cause of non-hypoxic hyperlactatemia and its identification is particularly interesting in order to not multiply medical exams. Indeed, AKA will be cured by a simple management. Clinically, patients have digestive signs such as nausea, vomiting and abdominal pain after a bout of heavy drinking following by few days of fasting. On clinical examination, they have no impairment of consciousness and most often have a relatively well-preserved general condition. Biologically, there is a metabolic acidosis with an elevated anion gap associated with electrolyte disturbances and moderate hyperlactatemia. The pathophysiology of this acidosis is complex and involves an accumulation of ketone bodies, lactate and acetate. This diagnosis is unknown and often delayed or missed while its identification is essential in order to not confuse it with diabetic ketoacidosis. In fact, insulin treatment is at major risk of hypoglycemia, sometimes fatal, in these malnourished patients. The treatment consists of vitamin therapy and the correction of hydro-electrolyte disorders. Insulin and bicarbonate infusion should be avoided. The evolution is favorable and the acidosis is corrected in a few hours after this treatment. The risk is the recurrence of episodes. The purpose of this article is to describe the clinical, biological and pathophysiology of AKA so that it will be better recognized and its management more quickly implemented.

Euglycemic DKA Associated With SGLT2 Inhibitors

Background: DKA associated with SGLT2 inhibitors also known as Euglycemic DKA (EDKA) is a rare condition characterized by milder degrees of hyperglycemia with a blood glucose level < 200 mg/dl. Unfortunately, this unusual feature can often lead to missed or delayed diagnosis with potential life-threatening outcomes. Clinical Case: The patient is a 53-year-old Caucasian male with PMH of type 2 diabetes mellitus treating with Metformin and Empagliflozin. He presented to the emergency room with shortness of breath, flu-like symptoms, and decreased oral intake for a couple of days. Vital signs at presentation were: Temperature 98.2 °F, pulse rate 108 beats/min, respiratory rate 28 breaths/min, and blood pressure 134/72 mmHg. He was alert but ill-looking, moderately dehydrated with dry mucus membranes. The rest of the physical examination was unremarkable at the time of admission. In the initial blood work, sugar was found to be mildly elevated (163mg/dl), and hemoconcentration besides mild pre-renal acute kidney injury was detected. He was also found infected by the COVID-19 virus without hypoxemia or signs of pneumonia. Arterial blood gases showed metabolic acidosis with an elevated anion gap (PH 7.21, CO2 39.93mmHg, HCO3− 10mEq/L, anion gap 21mEq/L). Urine analysis was positive for ketones and glucose. After ruling out other causes of metabolic acidosis by screening for alcohols, salicylates, acetaminophen, lactic acid, and urine toxicology; the diagnosis of EDKA was made. He was treated with a 3L bolus of IV normal saline and an insulin drip with dextrose solution started as per the protocol based on his glucose levels and promptly admitted to the intensive care unit (ICU). Serial blood tests showed gradual resolution of ketoacidosis and anion gap normalized after 36 hours when insulin drip was stopped and replaced by subcutaneous insulin therapy. Conclusion: SGLT2 inhibitors increase the urinary excretion rate of glucose and subsequent fall in plasma glucose level. Thus, In the absence of exogenous insulin use, increase glucagon release resulting in upregulation of lipolysis and activation of the ketogenesis. Factors such as low oral intake, concurrent infection, and alcohol use can also exacerbate the process. Timely diagnosis of EDKA can be a challenge for physicians unfamiliar with this class of medications, additionally, ketone studies and blood gas analyses are not part of the routine workup for diabetic patients in the emergency department. We recommend all first-line care providers to consider ketosis in ill patients with diabetes and metabolic acidosis, despite the normal or near-normal serum glucose levels. EDKA is mainly a diagnosis of exclusion, but treatment is not different from DKA; correcting dehydration by using intravenous fluids and then, initiating insulin drip along with dextrose-containing solutions, and frequent monitoring of serum anion gap.

The usefulness of measuring the anion gap in diagnosing metformin-associated lactic acidosis: a case series

BackgroundMetformin-associated lactic acidosis (MALA) is a widely documented adverse event of metformin. Despite being considered one of the main causes of metabolic acidosis, the association between an anion gap and MALA diagnosis is still uncertain.Case presentationCases involving six Caucasian patients with suspected MALA who were admitted to the emergency department were analysed. All these patients presented with pH values < 7.35, lactate levels > 2 mmol/L, and estimated glomerular filtration < 30 mL/min. Metformin plasma concentrations were > 2.5 mg/L in all the patients. The highest metformin concentrations were not found in the patients with the highest lactate levels. The anion gap values ranged from 12.3 to 39.3, with only two patients exhibiting values > 14.ConclusionsIn patients with MALA, there is a significant variability in the anion gap values, which is not related to the level of metformin accumulation, and therefore, it is doubtful whether measuring anion gaps is useful as an approach for MALA diagnosis.

Disorders of Acid-Base and Potassium Balance

Water accounts for approximately half of an adult human's body weight. Two thirds of body water is intracellular, and the remaining one third is contained in the extracellular fluid compartment, which includes intravascular (plasma) and interstitial fluid. Small amounts of water are also contained in bone, dense connective tissue, digestive secretions, and cerebrospinal fluid. To maintain stability of the internal milieu, body fluids are processed by the kidney, guided by intricate physiologic control systems that regulate fluid volume and composition. This chapter reviews the principles of body fluid hemostasis and discusses disorders of water excess (hyponatremia), water deficiency (hypernatremia), water conservation (diabetes insipidus), saltwater excess (edematous states), and saltwater deficiency (volume depletion). Figures illustrate the relation between the plasma hydrogen ion concentration and the blood pH, proximal tubular bicarbonate reabsorption, renal secretion of hydrogen ions, renal glutamine metabolism and ammonia diffusion, metabolic alkalosis, and the electrocardiographic changes in and approach to causes of hypokalemia and hyperkalemia. Tables describe causes of metabolic acidosis with a high and a normal ion gap; causes of type 1 renal tubular acidosis; causes of type 4 renal tubular acidosis and aldosterone resistance; causes of metabolic alkalosis, respiratory acidosis, and respiratory alkalosis; evaluation of the renal defect in hyperkalemia; and treatment of hyperkalemia. This chapter contains 10 figures, 12 tables, and 53 references.

Dietary Acid Load and Cardiometabolic Risk Factors-A Narrative Review.

The Western, diet rich in acidogenic foods (e.g., meat, fish and cheese) and low in alkaline foods (e.g., vegetables, fruits and legumes), is deemed to be a cause of endogenous acid production and elevated dietary acid load (DAL), which is a potential cause of metabolic acidosis. Multiple authors have suggested that such a dietary pattern increases the excretion of calcium and magnesium, as well as cortisol secretion. In addition, it is associated with decreased citrate excretion. All of these seem to increase blood pressure and insulin resistance and may contribute to the development of cardiometabolic disorders. However, there are inconsistencies in the results of the studies conducted. Therefore, this narrative literature review aims to present the outcomes of studies performed in recent years that investigated the association between DAL and the following cardiometabolic risk factors: blood pressure, hypertension, carbohydrate metabolism and lipid profile. Study outcomes are divided into (i) statistically significant positive association, (ii) statistically significant inverse association, and (iii) no statistically significant association.