Paradoxical metabolic acidosis after vomiting in children with spinal muscular atrophy: A report of 9 patients.

BACKGROUND: Spinal muscular atrophy (SMA) is a hereditary neuromuscular disease that progresses toward restrictive respiratory failure due to muscle paralysis. We observed that SMA patients presented with a specific clinical and laboratory profile, consisting of severe metabolic acidosis following an episode of mild vomiting. This is an unusual, little-known, and life-threatening situation for these patients, as hyperventilation induced by metabolic acidosis can lead to exhaustion and to death by mixed acidosis. OBJECTIVE: The aim of our study was to describe this paradoxical acidosis after vomiting in SMA patients and to discuss the physiological basis of this condition. METHODS: We conducted a retrospective single-center study reviewing the clinical and laboratory data of SMA patients who were hospitalized in the intensive care unit for severe metabolic acidosis after vomiting. RESULTS: Our cohort comprised 11 cases. On arrival, the median pH of the patients was 7.23 with a median bicarbonate concentration of 11.7 mmol/L and almost half of them (45 %) had ketone bodies in the blood and/or urine. The median correction time was 24 h for pH and 48 h for bicarbonate concentrations after receiving intravenous hydration with a glucose solution. CONCLUSIONS: We suggest that SMA patients are particularly sensitive to ketoacidosis induced by fasting, even after a few episodes of mild vomiting. Moreover, they have a low buffering capacity due to their severe amyotrophy, which favors metabolic acidosis. They must be quickly hydrated through a glucose-containing solution to avoid exhaustion, mixed acidosis, and death.

Electrolyte disorders related emergencies in children.

This article provides a comprehensive overview of electrolyte and water homeostasis in pediatric patients, focusing on some of the common serum electrolyte abnormalities encountered in clinical practice. Understanding pathophysiology, taking a detailed history, performing comprehensive physical examinations, and ordering basic laboratory investigations are essential for the timely proper management of these conditions. We will discuss the pathophysiology, clinical manifestations, diagnostic approaches, and treatment strategies for each electrolyte disorder. This article aims to enhance the clinical approach to pediatric patients with electrolyte imbalance-related emergencies, ultimately improving patient outcomes.Trial registration This manuscript does not include a clinical trial; instead, it provides an updated review of literature.

Multimodal Model for Predicting Fetal Acidosis in Delivery Room.

In the delivery room, fetal well-being is evaluated through laboratory tests, biosignals like cardiotocography, and imaging techniques such as fetal echocardiography. We have developed a multimodal machine learning model that integrates medical records, biosignals, and imaging data to predict fetal acidosis, using a dataset from a tertiary hospital's delivery room (n=2,266). To achieve this, features were extracted from unstructured data sources, including biosignals and imaging, and then merged with structured data from medical records. The concatenated vectors formed the basis for training a classifier to predict post-delivery fetal acidosis. Our model achieved an Area Under the Receiver Operating Characteristic curve (AUROC) of 0.752 on the test dataset, demonstrating the potential of multimodal models in predicting various fetal outcomes.

Performance of five cardiotocography classification templates in labor: a cohort study.

OBJECTIVE: New guidelines for the interpretation of cardiotocography (CTG) have been presented by FIGO in 2015 (FIGO-15) and by NICE in 2017 (NICE-17) and 2022 (NICE-22) In Sweden, a previous template from 2009 (SWE-09) was replaced in 2017 (SWE-17).The objective of the study was to compare these five different templates for CTG classification regarding sensitivity, specificity, positive and negative predictive values in identifying neonates with acidemia at birth (cord artery pH <7.10). METHODS: This is a historical cohort study including singleton births in Lund November 2015-February 2016, after spontaneous or induced labor at ≥34 completed gestational weeks with validated umbilical cord acid-base samples.Characteristics of cardiotocographic traces during the last hour before birth were reviewed by two independent assessors blinded to outcome. Each template was then used to classify the CTG as normal, suspicious, or pathological. Traces for which classification differed between the two assessors for any of the templates were assessed by a third assessor. The classification by majority (at least 2 of 3) was used for analyses.Main outcome measures were the sensitivity, specificity, and positive and negative predictive values for each template to identify neonates with cord artery pH <7.10 by the classification pathological. In a secondary analysis, these outcome measures were calculated for the classifications suspicious + pathological together. RESULTS: SWE-09 and NICE-22 had significantly higher sensitivity (both 92%; 95% CI 79-98%) than NICE-17 (68%; 51-82%), FIGO-15 (42%; 26-59%) and SWE-17 (39%; 24-57%) to identify neonates with acidemia by the classification pathological. Specificity was significantly higher for SWE-17 (91%; 88-93%), FIGO-15 (90%; 88-93%) and NICE-17 (78%; 74-81%) than for NICE-22 (63%; 59-67%) and SWE-09 (62%; 58-66%). The positive predictive value of a pathological pattern ranged between 15% (SWE-09 and NICE-22) and 24% (FIGO-15), and negative predictive values between 95% (SWE-17) and 99% (SWE-09 and NICE-22). Combining suspicious and pathological patterns increased the sensitivity and decreased the specificity for all templates. CONCLUSIONS: Current CTG interpretation templates either have low sensitivity to identify fetal acidemia or low specificity. Among current guidelines, NICE 2022 had the highest sensitivity to identify neonates with acidemia and is considered the safest current classification system. Efforts to further improve diagnostic precision are warranted.

Failure to Thrive, Metabolic Acidosis, and Diarrhea in a 7-Week-Old Infant.

A 7-week-old infant presented to the emergency department with fussiness, decreased oral intake, loose stool, and respiratory distress for 2 days. The patient was born full-term with an uncomplicated birth history but had a history of slow weight gain. He was alert, but toxic-appearing at presentation, hypothermic with signs of dehydration, and with respiratory failure. He was found to have severe anion gap metabolic acidosis, hypokalemia, elevated lactate, and hyperammonemia. He responded well to initial resuscitation and was admitted to the ICU for intravenous electrolyte replacement, bowel rest, and respiratory support. A workup was pursued for failure to thrive with severe malnutrition, hyperammonemia, hyperlactatemia, anemia, vitamin D deficiency, and electrolyte abnormalities. After stabilization, he was restarted on enteral feeds and had a recurrence of loose stool and severe electrolyte abnormalities, which were refractory to enteral supplementations and required readmission to the ICU. His hospital course extended several weeks, included several subspecialty consultations, and ended with a surprising diagnosis of exclusion based on his clinical response to therapy.

Determining lactate concentrations in Korean indigenous calves and evaluating its role as a predictor for acidemia in calf diarrhea.

BACKGROUND: Calf diarrhea leads to high mortality rates and decreases in growth and productivity, causing negative effects on the livestock industry. Lactate is closely associated with metabolic acidosis in diarrheic calves. However, there have been no reports on lactate concentrations in Korean indigenous (Hanwoo) calves, especially those with diarrhea. This study aimed to determine the reference range of L-lactate and D-lactate concentrations in Hanwoo calves and to better understand the utility of lactate as predictive factors for acidemia in diarrheic calves. RESULTS: L-lactate and D-lactate concentrations were measured in healthy (n = 44) and diarrheic (n = 93) calves, and blood gas analysis was performed on diarrheic calves. The reference range in healthy calves was 0.2-2.25 mmol/L for L-lactate and 0.42-1.38 mmol/L for D-lactate. Diarrheic calves had higher concentrations of L-lactate and D-lactate than healthy calves. In diarrheic calves, L-lactate and D-lactate each had weak negative correlation with pH (r = - 0.31 and r = - 0.35). In diarrheic calves with hyper-L-lactatemia, the combined concentrations of L-lactate and D-lactate had moderate correlation with pH (r = - 0.51) and anion gap (r = 0.55). Receiver operating characteristic analysis showed D-lactate had fair predictive performance (AUC = 0.74) for severe acidemia, with an optimal cut-off value of > 1.43 mmol/L. The combined concentrations of L-lactate and D-lactate showed fair predictive performance for predicting acidemia (AUC = 0.74) and severe acidemia (AUC = 0.72), with cut-off values of > 6.05 mmol/L and > 5.95 mmol/L. CONCLUSIONS: The determined reference ranges for L-lactate and D-lactate in Hanwoo calves enable the identification of hyper-L-lactatemia and hyper-D-lactatemia. Diarrheic calves exhibited increased lactate concentrations correlated with acid-base parameters. While the concentrations of L-lactate and D-lactate have limitations as single diagnostic biomarkers for predicting acidemia or severe acidemia, their measurement remains important, and L-lactate has the advantage of being measurable at the point-of-care. Assessing lactate concentrations should be considered by clinicians, especially when used alongside other clinical indicators and diagnostic tests. This approach can improve calf diarrhea management, contributing positively to animal welfare and providing economic benefits to farms.

Analysis of CTG patterns in cases with metabolic acidosis at birth with and without neonatal neurological alterations.

OBJECTIVE: To determine cardiotocographic patterns in newborns with metabolic acidosis, based on clinical signs of neurological alteration (NA) and the need for hypothermic treatment. METHODS: All term newborns with metabolic acidosis in a single center from 2016 to 2020 were included in the study. Three segments of intrapartum CTG (cardiotocography) were considered (first 30 min of active labor, 90 to 30 min before birth, and last 30 min before delivery) and a longitudinal analysis of CTG pattern was performed according to the 2015 FIGO classification. RESULTS: Three hundred and twenty-four neonates with metabolic acidosis diagnosed at birth were divided into three groups: the first group included all neonates with any clinical sign of neurological alteration, requiring hypothermia according to the recommendation of the Italian Society of Neonatology (group TNA-Treated neurological Alteration, n = 17), the second encompassed neonates with any clinical sign of neurological alteration not requiring hypothermia (group NTNA-Not Treated neurological Alteration, n = 83), and the third enclosed all neonates without any sign of clinical neurological involvement (group NoNA-No neurological Alteration, n = 224). The most frequent alterations of CTG in TNA group were late decelerations, reduced variability, bradycardia, and tachysystole. Unexpectedly, from the longitudinal analysis of the CTG, 49% of all cases with metabolic acidosis never showed a pathological CTG with normal trace at the beginning of labor followed by normal or suspicious trace in the final part of labor, the same as in TNA and NTNA groups (10 and 39%, respectively). CONCLUSIONS: CTG has limited specificity in identifying cases of acidosis at birth, even in babies who will develop NA.

Transient secondary pseudo-hypoaldosteronism in infants with urinary tract infections: systematic literature review.

Infants with a congenital anomaly of the kidney and urinary tract sometimes present with hyponatremia, hyperkalemia, and metabolic acidosis due to under-responsiveness to aldosterone, hereafter referred to as secondary pseudo-hypoaldosteronism. The purpose of this report is to investigate pseudo-hypoaldosteronism in infant urinary tract infection. A systematic review was conducted following PRISMA guidelines after PROSPERO (CRD42022364210) registration. The National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar without limitations were used. Inclusion criteria involved pediatric cases with documented overt pseudo-hypoaldosteronism linked to urinary tract infection. Data extraction included demographics, clinical features, laboratory parameters, management, and course. Fifty-seven reports were selected, detailing 124 cases: 95 boys and 29 girls, 10 months or less of age (80% of cases were 4 months or less of age). The cases exhibited hyponatremia, hyperkalemia, acidosis, and activated renin-angiotensin II-aldosterone system. An impaired kidney function was found in approximately every third case. Management included antibiotics, fluids, and, occasionally, emergency treatment of hyperkalemia, hyponatremia, or acidosis. The recovery time averaged 1 week for electrolyte, acid-base imbalance, and kidney function. Notably, anomalies of the kidney and urinary tract were identified in 105 (85%) cases. CONCLUSIONS: This review expands the understanding of overt transient pseudo-hypoaldosteronism complicating urinary tract infection. Management involves antimicrobials, fluid replacement, and consideration of electrolyte imbalances. Raising awareness of this condition within pediatric hospitalists is desirable. WHAT IS KNOWN: • Infants affected by a congenital anomaly of the kidney and urinary tract may present with clinical and laboratory features resembling primary pseudo-hypoaldosteronism. • Identical features occasionally occur in infant urinary tract infection. WHAT IS NEW: • Most cases of secondary pseudo-hypoaldosteronism associated with a urinary tract infection are concurrently affected by a congenital anomaly of the kidney and urinary tract. • Treatment with antibiotics and parenteral fluids typically results in the normalization of sodium, potassium, bicarbonate, and creatinine within approximately 1 week.

Demystifying normal-anion-gap metabolic acidosis: pathophysiology, aetiology, evaluation and diagnosis.

Normal-anion-gap metabolic acidosis (NAGMA) is a common but often under-recognised and poorly understood condition, especially by less-experienced clinicians. In adults, NAGMA might be an initial clue to a more significant underlying pathology, such as autoimmune diseases, hypergammaglobulinemia or drug toxicities. However, identifying the aetiology can be challenging due to the diverse processes involved in the development of acidosis. A better understanding of the pathophysiology of NAGMA can help treating physicians suspect and evaluate the condition early and reach the correct diagnosis. This article provides an overview of renal acid-base regulation, discusses the pathophysiological processes involved in developing NAGMA and provides a framework for evaluation to reach an accurate diagnosis.

Metabolic acidosis and sexual dysfunction in chronic kidney disease in predialysis group: Cross-sectional study from a single center.

OBJECTIVES: This study aimed to investigate the prevalence of sexual disorders in stage 2 - 5 chronic kidney disease (CKD) during predialysis and its relationship with laboratory parameters. METHODS AND RESULTS: This cross-sectional study included 110 predialysis patients and 110 healthy controls admitted to clinics. The International Index of Erectile Function (IIEF) and Female Sexual Function Index (FSFI) were used. Sexual dysfunction was detected in 76% of female patients and 31.4% of the control group, and the FSFI total and subscale scores of the patients were significantly lower than those of the control group. The frequency of erectile dysfunction in male patients and controls was 56.7% and 33.3%, respectively. The erectile function, sexual satisfaction, and overall satisfaction scores on the IIEF scale were significantly lower than those in the control group. Low glomerular filtration rate, high calcium levels, increased C-reactive protein, anemia, and metabolic acidosis in male and female patients, and testosterone deficiency in male patients were associated with sexual dysfunction. In multiple regression analysis, eGFR was the only independent variable associated with sexual dysfunction. Luteinizing hormone (LH) and prolactin levels increased as the disease progressed in men and women with sexual dysfunction, while testosterone levels decreased in male patients. Low testosterone levels were related to erectile dysfunction. The increase in parathormone and prolactin levels was related to loss of libido in the male and female patient groups. CONCLUSION: Metabolic acidosis and low eGFR appear to be the most important risk factors contributing to sexual disorders in patients with CKD.

Base excess (BE): reloaded.

The base excess value (BE, mmol/L), not standard base excess (SBE), correctly calculated including pH, pCO2 (mmHg), sO2 (%) and cHb (g/dl) is a diagnostic tool for several in vivo events, e.g., mortality after multiple trauma or shock, acidosis, bleeding, clotting, artificial ventilation. In everyday clinical practice a few microlitres of blood (arterial, mixed venous or venous) are sufficient for optimal diagnostics of any metabolic acidosis or alkalosis.The same applies to a therapeutic tool-then referred to as potential base excess (BEpot)-for several in vitro assessments, e.g., solutions for infusion, sodium bicarbonate, blood products, packed red blood cells, plasma. Thus, BE or BEpot has been a parameter with exceptional clinical significance since 2007.

Umbilical artery eucapnic pH to assess fetal well-being.

BACKGROUND: Umbilical artery gas results help obstetricians assess fetal well-being during labor and guide screening decisions on eligibility for therapeutic hypothermia (ie, whole-body or head cooling). The accuracy of results, especially for the base deficit on arterial cord gas analysis, in predicting brain injury is questioned. A novel biomarker specifically calculated for fetal acid-base physiology and response to asphyxia-neonatal eucapnic pH as a marker of neonatal metabolic acidosis-has the potential to be an accurate predictor of hypoxic-ischemic encephalopathy. OBJECTIVE: We aimed to compare false-negative rates of hypoxic-ischemic encephalopathy for umbilical artery pH, base deficit, and neonatal eucapnic pH in assessing fetal acid-base balance as a marker of fetal well-being and predicting acute brain injury. STUDY DESIGN: This is a retrospective single-center cohort study of newborns ≥ 35 weeks of gestation diagnosed with hypoxic-ischemic encephalopathy. We compared false-negative rates for any grade of hypoxic-ischemic encephalopathy using unilateral paired chi-square statistical analysis based on cutoff values for umbilical artery pH ≤7.00, base deficit ≥16 mmol/L, base deficit ≥12 mmol/L and neonatal eucapnic pH ≤7.14. We performed an analysis of variance between umbilical artery pH, base deficit, and neonatal eucapnic pH for each hypoxic-ischemic encephalopathy grade. RESULTS: We included 113 newborns. False-negative rate for hypoxic-ischemic encephalopathy was significantly higher for base deficit <16 mmol/L (n=78/113; 69.0%) than <12 mmol/L (n=46/113; 40.7%), pH >7.00 (n=41/113; 36.3%), or neonatal eucpanic pH >7.14 (n=35/113; 31.0%) (P<.0001). All true-positive cases were identified using only umbilical artery pH and neonatal eucapnic pH. Base deficit ≥16 or ≥12 mmol/L did not add any value in identifying newborns with hypoxic-ischemic encephalopathy when using umbilical artery pH and neonatal eucapnic pH. No association emerged between any marker and hypoxic-ischemic encephalopathy severity grading. CONCLUSION: Our findings support the accuracy of neonatal eucapnic pH to assess fetal well-being during labor and to improve predictive performance for acute brain injury. Neonatal eucpanic pH, in addition to umbilical artery pH, may be a viable alternative in identifying newborns at risk for hypoxic-ischemic encephalopathy.

The utility of fetal heart rate deceleration's descending slope in searching for a non-National Institute of Child Health and Human Development parameter for the detection of fetal acidosis.

OBJECTIVE: To identify new parameters predicting fetal acidemia. METHODS: A retrospective case-control study in a cohort of deliveries from a tertiary referral hospital-based cohort deliveries in Zaragoza, Spain between 2018 and 2021 was performed. To predict fetal acidemia, the NICHD categorizations and non-NICHD parameters were analyzed in the electronic fetal monitoring (EFM). Those included total reperfusion time, total deceleration area and the slope of the descending limb of the fetal heart rate of the last deceleration curve. The accuracy of the parameters was evaluated using the specificity for (80%, 85%, 90%, 95%) sensitivity and the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 10 362 deliveries were reviewed, with 224 cases and 278 controls included in the study. The NICHD categorizations showed reasonable discriminatory ability (AUC = 0.727). The non-NICHD parameters measured during the 30-min fetal monitoring, total deceleration area (AUC = 0.807, 95% CI: 0.770, 0.845) and total reperfusion time (AUC = 0.750, 95% CI: 0.707, 0.792), exhibited higher discriminatory ability. The slope of the descending limb of the fetal heart rate of the last deceleration curve had the best AUC value (0.853, 95% CI: 0.816, 0.889). The combination of total deceleration area or total reperfusion time with the slope demonstrated high discriminatory ability (AUC = 0.908, 95% CI: 0.882, 0.933; specificities of 71.6% and 72.7% for a sensitivity of 90%). CONCLUSIONS: The slope of the descending limb of the fetal heart rate of the last deceleration curve is the strongest predictor of fetal acidosis, but its combination with the total reperfusion time shows better clinical utility.

Pyroglutamate acidosis 2023. A review of 100 cases.

This review concerns the rare, acquired, usually iatrogenic, high-anion-gap metabolic acidosis, pyroglutamic acidosis. Pyroglutamate is a derivative of the amino acid glutamate, and is an intermediate in the 'glutathione cycle', by which glutathione is continuously synthesized and broken down. The vast majority of pyroglutamic acidosis cases occur in patients on regular, therapeutic doses of paracetamol. In about a third of cases, flucloxacillin is co-prescribed. In addition, the patients are almost always seriously unwell in other ways, typically with under-nourishment of some form. Paracetamol, with underlying disorders, conspires to divert the glutathione cycle, leading to the overproduction of pyroglutamate. Hypokalaemia is seen in about a third of cases. Once the diagnosis is suspected, it is simple to stop the paracetamol and change the antibiotic (if flucloxacillin is present), pending biochemistry. N-acetyl-cysteine can be given, but while the biochemical justification is compelling, the clinical evidence base is anecdotal.

Is it time to end the use of base deficit for fetal well-being assessment?

Authors have expressed reservations regarding the use of base deficit measured in umbilical artery blood samples to assess fetal well-being during the course of labor and to predict neonatal neurologic morbidity. Despite its integration into clinical practice for more than 50 years, obstetricians and maternal-fetal medicine specialists may not realize that this marker has significant limitations in accurately identifying neonatal metabolic acidosis as a proxy for fetal well-being. In brief, there are 2 large families of base deficit, namely whole blood and extracellular fluid. Both rely on equations that use normal adult acid-base characteristics (pH 7.40 and partial CO2 pressure of 40 mm Hg) that overlook the specificity of the normal in utero acid-base status of pH 7.27 and partial CO2 pressure of 54 mm Hg. In addition, it ignores the unique characteristic of the in utero fetal response to acute hypoxia. The dependence on placental circulation for CO2 elimination may lead to extremely high values (up to 130 to 150 mm Hg) during hypoxic events, a phenomenon that is absent in adults with acute metabolic acidosis who can hyperventilate. The dispute over if to include a correction for high partial CO2 pressure in the bicarbonate estimation, as presented in the Great Trans-Atlantic Debates, remains unresolved. The key constants computed for adult acid-base physiology in the current base deficit algorithms, without accounting for the impact of high partial CO2 pressure or other fetal characteristics of buffering capacity (eg, differences in body water content composition, plasma protein, and hemoglobin attributes), may lead to an overestimation of metabolic acidosis, especially in newborns who are experiencing hypercarbia during the early stages of the hypoxic response. These unrecognized limitations impact the base deficit results and may mislead clinicians on fetal well-being assessments when discussing the management of fetal heart rate monitoring and neonatal outcomes. Based on our arguments, we believe that it is prudent to consider an alternative to base deficit for drawing conclusions regarding fetal well-being during the course of birth management. We propose a marker specifically related to the newborn acid-base physiology--the neonatal eucapnic pH correction. This marker can be added to arterial cord blood gas analysis, and we have described how to interpret it as a marker of neonatal metabolic acidosis.

Should Ocular Hemorrhage Screening Be Conducted in Newborns with Acidosis?

OBJECTIVE: Ocular hemorrhages (OHs) may cause visual disturbances and incidence vary from 18 to 39% in newborns. Precipitated/instrumental delivery and perinatal asphyxia were predefined risk factors. Acidosis can interfere with coagulation and disrupt the pressure of ocular capillaries and put infants with moderate acidosis with or without hypoxic-ischemic encephalopathy at risk for OH. We aimed to evaluate the OH in neonates with fetal acidosis. STUDY DESIGN: Neonates >34 weeks are included if pH < 7.10 and BE < -12 mmol/L within the first hour. Ophthalmologic examinations for retinal (RH), vitreous, and anterior chamber (hyphema) hemorrhage were done within the third day. RH was staged according to Egge's classification. Follow-up of the patients was continued until the age of 2. Clinical characteristics of newborns were analyzed. RESULTS: Sixty-two neonates (38 ± 2.3 weeks, 2,971 ± 612 g) were included. pH = 6.91 ± 0.16, BE = - 17.2 ± 5.3 mmol/L. OH was found in 22 (36.7%) neonates (hyphema n = 2, vitreous n = 2, RH n = 21). Thirty-eight eyes with RH were staged (Stage 3: n = 15 [39.5%]; Stage 2: n =11 [28.9%]; Stage 1: n = 12 [31.6%]). Vaginal delivery (OR: 4.9, 95% CI [1.4-17.8]) and advanced resuscitation at the delivery room (OR: 8.8; 95% CI [1.9-41.7]) were found to increase the risk of RH. CONCLUSION: Approximately one-third of neonates with moderate to severe acidosis exhibited RH when examined on the third day. Contrary to previous studies that reported mild RH in otherwise healthy neonates, our findings revealed that neonates with moderate to severe acidosis predominantly presented with Stage 3 RH. While the higher incidence of RH in vaginally delivered infants is consistent with previous studies, the identification of advanced resuscitation as a risk factor is a new addition to the literature. The findings in our study highlight the importance of retinal examination in neonates with acidosis in the presence of intubation during resuscitation. KEY POINTS: · One-third of neonates with moderate to severe acidosis exhibited RH.. · Stage 3 RH was identified as the most prevalent.. · Advanced resuscitation was identified as an independent risk factor for RH..