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.

Interpretation of the effects of rumen acidosis on the gut microbiota and serum metabolites in calves based on 16S rDNA sequencing and non-target metabolomics.

Introduction: Rumen acidosis is one of the most common diseases in beef cattle. It severely affects the normal development of calves and poses a significant threat to the farming industry. However, the influence of rumen acidosis on the gut microbiota and serum metabolites of calves is currently unclear. Objective: The aim of this study is to investigate the changes in the gut microbiota and serum metabolites in calves after rumen acidosis and analyse the correlation. Methods: Eight calves were selected as the rumen acidosis group, and eight health calves were selected as the healthy group. The faecal gut microbiota and serum metabolites of calves were detected respectively using 16S rDNA high-throughput sequencing and non-target metabolomics. The correlation between gut microbiota and serum metabolites was analyzed by Spearman correlation analysis. Results: Differential analysis of the diversity and composition of gut microbiota between eight male healthy (Health) and eight male rumen acidosis (Disease) calves revealed that rumen acidosis increased the abundance of the gut microbiota in calves. At the phylum level, compared to the Healthy group, the relative abundance of Proteobacteria in the Disease group significantly decreased (P<0.05), while the relative abundance of Desulfobacterota significantly increased in the Disease group (P<0.05). At the genus level, compared to the Disease group, the relative abundance of Alloprevotella, Muribaculaceae, Succinivibrio, Prevotella, Agathobacter and Parabacteroides significantly increased in the Healthy group (P<0.05), while the relative abundance of Christensenellaceae_R-7 and Monoglobus significantly decreased in the Healthy group (P<0.05). Differential analysis results showed the Healthy group had 23 genera with higher abundance, while the Disease group had 47 genera with higher abundance. Serum metabolomics results revealed the differential metabolites associated with rumen acidosis, including nicotinamide, niacin, L-glutamic acid and carnosine, were mainly enriched in the nicotinate and nicotinamide pathway and the histidine pathway. Conclusion: The occurrence of rumen acidosis can induce changes in the gut microbiota of calves, with a significant increase of the Christensenellaceae_R-7 genus and a significant decrease of Prevotella and Succinivibrio genera. In addition, the occurrence of rumen acidosis can also induce changes in serum metabolites including niacin, niacinamide, L-glutamine, and carnosine, which may serve as the diagnostic biomarkers of rumen acidosis of calves.

Plasma concentration of serum amyloid A and lipopolysaccharide binding protein in horses with laminitis resulted from hindgut acidosis.

Many studies have shown a strong correlation between Hindgut Acidosis (HGA) and the occurrence of laminitis in horses; therefore, the early diagnosis of HGA is essential. In this study, we investigated changes in the plasma concentrations of lipopolysaccharide-binding protein (LBP) and serum amyloid A (SAA) as inflammatory markers in horses with laminitis. Sixteen healthy male Arabian horses that had cecal cannulation without visible laminitis or general symptoms were randomly divided into two groups. The horses were fed two different diets in a forage-to-concentrate ratio. Blood samples were collected on Days 1, 10, and 20. The primary objective of this study was to analyze plasma levels of LBP and SAA. Cecal specimens were obtained from each equine subject on three designated days: days 1, 10, and 20. The second objective was to assess the levels of pH and volatile fatty acids (VFA) in the samples. Throughout the study period, horses fed a high-concentrate diet exhibited a significantly elevated average lameness grade on days 10 and 20 compared to the initial stage (P < 0.001). On day 20, a significant increase in the concentration of SAA was observed in horses fed a high-concentrate diet, in contrast to the initial stage of the study. LBP levels in the plasma were significantly elevated on days 10 and 20 in horses fed a high-concentrate diet. Based on our findings, it is recommended that the evaluation of plasma LBP concentrations is more effective than SAA for the early identification of HGA in horses fed a high-grain diet.

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.

Blood chloride abnormalities in diarrheic neonatal calves with metabolic acidosis.

The present study investigated the prevalence of blood chloride (Cl) abnormalities in diarrheic neonatal calves with metabolic acidosis and attempted to identify the most relevant electrolyte abnormality to these abnormalities. A retrospective analysis was conducted on the medical records of 157 diarrheic neonatal calves aged 10.3 ± 4.2 days old with metabolic acidosis. Hypochloremia, normochloremia, and hyperchloremia were observed in 8.9% (14/157), 43.3% (68/157), and 47.8% (68/157), respectively, of diarrheic calves with metabolic acidosis. This distribution remained similar regardless of age (under 8 days or 8 days and older). Furthermore, a multiple logistic regression analysis showed that variations in values for blood sodium [Na (regression coefficients 0.877; 95% confidence interval (CI) 13.977-134.195; P<0.01)], pH (regression coefficients -10.719; 95% CI -19.076- -2.362; P<0.05), and bicarbonate [HCO3- (regression coefficients -0.555; 95% CI -0.820- -0.290; P<0.01)] were associated with blood Cl abnormalities. The present results revealed that blood Na concentrations were more strongly associated with blood Cl concentrations than blood pH and HCO3- values. In the present study, diarrheic calves with hyperchloremia were characterized by normonatremia and extremely severe metabolic acidosis.

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.

Changes in metabolic acidosis following birth in intensive care unit neonates.

BACKGROUND: Little is known about how and why metabolic acidosis changes within the first six hours of life in intensive care unit neonates. OBJECTIVE: To determine changes in pH and base excess between paired umbilical cord arterial and neonatal arterial blood samples during the first 6 h of life, to identify factors associated with the direction and magnitude of change, and to examine morbidity and mortality in newborns with acidosis at birth or as neonates. STUDY DESIGN: Retrospective cohort study of all deliveries from a single institution between 2016-2020 with paired umbilical cord arterial and neonatal arterial samples obtained within 6 h of life meeting rigorous criteria to ensure sample integrity. The primary outcomes were the direction and magnitude of change of pH and base excess. Multiple factors were assessed for possible correlation with pH and base excess change. The secondary outcome was the association between a composite outcome of death or cerebral palsy and pathologic acidosis (pH ≤ 7.1) at birth or as a neonate. RESULTS: 102 patients met inclusion criteria. Newborn arterial gasses were obtained at a median of 1.5 h (74 % < 2 h). pH improved in 71 % of cases and worsened in 29 %, and base excess improved in 52 % and worsened in 48 %, with wide observed ranges in both parameters. The paired pH and base excess values were moderately (r = 0.38) and strongly (r = 0.63) positively correlated, respectively, but were not correlated with time since birth (r = 0.14). Low birth weight, prematurity or respiratory failure were associated with worsening or less improvement, while worse initial acidosis was associated with greater improvement. Death or survival with cerebral palsy was more common with pathologic acidosis in either cord or newborn sample as compared with those without acidosis (27.3 % vs 3.7 %, p = 0.003), and was more common in those with isolated neonatal acidosis as compared to those without acidosis (50 % vs 3.7 %, p = 0.016). CONCLUSIONS: Changes in pH and base excess occurred over a wide range between delivery and the first newborn blood gas in the first 6 h of life, and we identified several factors associated with direction of change. Metabolic acidosis at birth cannot reliably be inferred from neonatal arterial values. Neonatal acidosis, including acidosis following a normal pH and base excess at birth, was associated with morbidity and mortality.

The Correlation Between the Total Decelerations and Accelerations Areas and Cord Blood pH in Women with Low-Risk Pregnancies.

Fetal acidosis among low-risk pregnancies is not common; however, identifying those at risk for this complication antenatally is of great interest. We aimed to assess the correlation between the total decelerations area during the last 120 min of fetal monitoring prior to delivery and neonatal acidemia in low-risk pregnancies and whether the total acceleration area has a protective effect in the presence of decelerations. A retrospective cohort study was conducted among women with term low-risk pregnancies. A researcher blinded to fetal outcomes interpreted electronic fetal monitor patterns during the 120 min prior to delivery. The primary outcome was fetal acidemia, defined as umbilical artery pH below 7.10. The correlation between the total decelerations and accelerations areas and cord blood pH was tested using the Spearman correlation coefficient. A total of 109 women were included and of these, six (5.5%) delivered infants with cord blood pH < 7.10. A significant correlation was demonstrated between the total decelerations area and cord blood pH (p = 0.01). No correlation was found between the total accelerations area and cord blood pH. Among low-risk pregnancies, a correlation was found between the total decelerations area but not the total accelerations area during the final 120 min of labor and cord blood pH.

Effects of veverimer on serum bicarbonate and physical function in women with chronic kidney disease and metabolic acidosis: a subgroup analysis from a randomised, controlled trial.

BACKGROUND: Globally, the prevalence of chronic kidney disease (CKD) is higher in women than in men; however, women have been historically under-represented in nephrology clinical trials. Metabolic acidosis increases risk of progressive loss of kidney function, causes bone demineralization and muscle protein catabolism, and may be more consequential in women given their lower bone and muscle mass. Veverimer, an investigational, non-absorbed polymer that binds and removes gastrointestinal hydrochloric acid, is being developed as treatment for metabolic acidosis. METHODS: This was a Phase 3, multicenter, randomised, blinded, placebo-controlled trial in 196 patients with CKD (eGFR: 20-40 mL/min/1.73 m2) and metabolic acidosis who were treated for up to 1 year with veverimer or placebo. We present the findings from a pre-specified subgroup analysis evaluating the effects of veverimer on metabolic acidosis and physical function among women (N = 77) enrolled in this trial. RESULTS: At week 52, women treated with veverimer had a greater increase in mean (± standard error) serum bicarbonate than the placebo group (5.4 [0.5] vs. 2.2 [0.6] mmol/L; P < 0.0001). Physical Function reported by patients on the Kidney Disease and Quality of Life - Physical Function Domain, a measure that includes items related to walking, stair climbing, carrying groceries and other activities improved significantly in women randomized to veverimer vs placebo (+ 13.2 vs. -5.2, respectively, P < 0.0031). Objectively measured performance time on the repeated chair stand test also improved significantly in the veverimer group vs. placebo (P = 0.0002). CONCLUSIONS: Veverimer was effective in treating metabolic acidosis in women with CKD, and significantly improved how they felt and functioned. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03390842 . Registered on January 4, 2018.

Estimated Glomerular Filtration Rate in Chronic Kidney Disease: A Critical Review of Estimate-Based Predictions of Individual Outcomes in Kidney Disease.

Chronic kidney disease (CKD) is generally regarded as a final common pathway of several renal diseases, often leading to end-stage kidney disease (ESKD) and a need for renal replacement therapy. Estimated GFR (eGFR) has been used to predict this outcome recognizing its robust association with renal disease progression and the eventual need for dialysis in large, mainly cross-sectional epidemiological studies. However, GFR is implicitly limited as follows: (1) GFR reflects only one of the many physiological functions of the kidney; (2) it is dependent on several non-renal factors; (3) it has intrinsic variability that is a function of dietary intake, fluid and cardiovascular status, and blood pressure especially with impaired autoregulation or medication use; (4) it has been shown to change with age with a unique non-linear pattern; and (5) eGFR may not correlate with GFR in certain conditions and disease states. Yet, many clinicians, especially our non-nephrologist colleagues, tend to regard eGFR obtained from a simple laboratory test as both a valid reflection of renal function and a reliable diagnostic tool in establishing the diagnosis of CKD. What is the validity of these beliefs? This review will critically reassess the limitations of such single-focused attention, with a particular focus on inter-individual variability. What does science actually tell us about the usefulness of eGFR in diagnosing CKD?

Proposed cutoff for fetal scalp blood lactate in intrapartum fetal surveillance based on neonatal outcomes: a large prospective observational study.

OBJECTIVE: Determination of lactate in fetal scalp blood (FBS) during labour has been recognised since the 1970s. The internationally accepted cutoff of >4.8 mmol/l indicating fetal acidosis is exclusive for the point-of-care device (POC) LactatePro™, which is no longer in production. The aim of this study was to establish a new cutoff for scalp lactate based on neonatal outcomes with the use of the StatstripLactate® /StatstripXpress® Lactate system, the only POC designed for hospital use. DESIGN: Observational study. SETTING: January 2016 to March 2020 labouring women with indication for FBS were prospectively included from seven Swedish and one Australian delivery unit. POPULATION: Inclusion criteria: singleton pregnancy, vertex presentation, ≥35+0 weeks of gestation. METHOD: Based on the optimal correlation between FBS lactate and cord pH/lactate, only cases with ≤25 minutes from FBS to delivery were included in the final calculations. MAIN OUTCOME MEASURES: Metabolic acidosis in cord blood defined as pH <7.05 plus BDecf >10 mmol/l and/or lactate >10 mmol/l. RESULTS: A total of 3334 women were enrolled of whom 799 were delivered within 25 minutes. The areas under the receiver operating characteristics curves (AUC) and corresponding optimal cutoff values were as follows; metabolic acidosis AUC 0.87 (95% CI 0.77-0.97), cutoff 5.7 mmol/l; pH <7.0 AUC 0.83 (95% CI 0.68-0.97), cutoff 4.6 mmol/l; pH <7.05 plus BDecf ≥12 mmol/l AUC 0.97 (95% CI 0.92-1), cutoff 5.8 mmol/l; Apgar score <7 at 5 minutes AUC 0.74 (95% CI 0.63-0.86), cutoff 5.2 mmol/l; and pH <7.10 plus composite neonatal outcome AUC 0.76 (95% CI 0.67-0.85), cutoff 4.8 mmol/l. CONCLUSION: A scalp lactate level <5.2 mmol/l using the StatstripLactate® /StatstripXpress® system will safely rule out fetal metabolic acidosis. TWEETABLE ABSTRACT: Scalp blood lactate <5.2 mmol/l using the StatstripLactate® /StatstripXpress system has an excellent ability to rule out fetal acidosis.

Laboratory Markers of Acidosis and Mortality in Cardiogenic Shock: Developing a Definition of Hemometabolic Shock.

BACKGROUND: Acidosis and higher lactate predict worse outcomes in cardiogenic shock (CS) patients. We sought to determine whether overall acidosis severity on admission predicted in-hospital mortality in CS patients. METHODS: This retrospective descriptive analysis included CS patients admitted to a single academic tertiary cardiac intensive care unit from 2007 to 2015. Admission arterial pH, base excess, and anion gap values were used to generate a Composite Acidosis Score (range 0-5, with a score ≥2 defining Severe Acidosis). Adjusted in-hospital mortality was analyzed using multivariable logistic regression. RESULTS: We included 1,065 patients with median age of 68.9 (59.0, 77.2) years (36.4% females). Concomitant diagnoses included cardiac arrest in 38.1% and acute coronary syndrome in 59.1%. Severe Acidosis was present in 35.2%, and these patients had worse shock and more organ failure. In-hospital mortality occurred in 34.1% and was higher among patients with Severe Acidosis (54.9% vs. 22.4%, adjusted odds ratio [OR] 2.01, 95% CI 1.43-2.83, P < 0.001). Increasing Composite Acidosis Score was associated with higher in-hospital mortality (adjusted OR 1.25 per point, 95% CI 1.11-1.40, P < 0.001). Severe Acidosis was associated with higher hospital mortality at every level of shock severity and organ failure (all P < 0.05). Admission lactate level had equivalent discrimination for in-hospital mortality as the Composite Acidosis Score (0.69 vs. 0.66; P = 0.32 by De Long test). CONCLUSION: Given its incremental association with higher in-hospital mortality among CS patients beyond shock severity and organ failure, we propose Severe Acidosis as a marker of hemometabolic shock. Lactate levels performed as well as a composite measure of acidosis for predicting mortality.

Relationship Between Umbilical Cord Gas Values and Neonatal Outcomes: Implications for Electronic Fetal Heart Rate Monitoring.

OBJECTIVE: To evaluate the relationship between umbilical artery cord gas values and fetal tolerance of labor, as reflected by Apgar score. We hypothesized the existence of wide biological variability in fetal tolerance of metabolic acidemia, which, if present, would weaken one fundamental assumption underlying the use of electronic fetal heart rate (FHR) monitoring. METHODS: We conducted a retrospective cohort study of term, singleton, nonanomalous fetuses delivered in our institution between March 2012 and July 2020. Universally obtained umbilical cord gas values and Apgar scores were extracted. We calculated Spearman correlation coefficients and receiver operating characteristic curves for various levels of umbilical artery pH, base excess, and Apgar scores. RESULTS: We analyzed data from 29,787 deliveries. The statistical correlation between umbilical artery pH and base excess and both 1- and 5-minute Apgar scores was weak or nonexistent in all pH range subgroups (range 0.064-0.213). Receiver operating characteristic curve analysis suggested umbilical artery pH value of 7.22 yields the best discrimination for prediction of a severely depressed newborn (5-minute Apgar score less than 4), but sensitivity and specificity for this predictive value remains poor to moderate. CONCLUSION: The use of electronic FHR monitoring is predicated on a documented relationship between FHR patterns and umbilical artery pH, and an assumed correlation between pH and fetal outcomes, reflecting fetal tolerance of labor and delivery. Our data demonstrate a weak-to-absent correlation between metabolic acidemia and even short-term fetal condition, thus significantly weakening this latter assumption. No amount of future modification of FHR pattern interpretation to better predict newborn pH is likely to lead to improved newborn outcomes, given this weakness in a fundamental assumption on which FHR monitoring is based.

Can we improve our ability to interpret category II fetal heart rate tracings using additional clinical parameters?

OBJECTIVES: This study examined predictive factors, in addition to Category II Fetal Herat Rate (FHR) monitoring that might imply fetal acidosis and risk of asphyxia. METHODS: This retrospective cohort study compared three groups of patients with Category II FHR monitoring indicating need for imminent delivery. Groups were divided based on fetal cord blood pH: pH≤7.0, 7.0

Five repeated maximal efforts of apneas increase the time to exhaustion in subsequent high-intensity exercise.

Ten subjects were tested on a cycle ergometer to exhaustion with intensity corresponding to 150 % of their peak power output (TF150) under three conditions [C: base line measurement; PRE: after five repeated breath hold maneuvers (BH); and POST: after 5BH, preceded by two weeks of BH training]. Respiratory and blood measurements were carried out. Upon cessation of 5BH, subjects compared to C condition started TF150 with reduced arterialized blood pH (C:7.428±0.023, PRE:7.419±0.016, POST:7.398±0.021) and elevated bicarbonate concentration (mmol/l), ventilation (l/min) and oxygen uptake (ml/min) (C:28.4±1.5, PRE:29.9±1.2, POST:30.0±1.8; C:10.4±2.5, PRE:13.3±3.3, POST:15.6±5.6; C:333.0±113.8, PRE:550.1±131.1, POST:585.1±192.8, respectively). After TF150, subjects had significantly reduced pH and elevated ventilation, and oxygen uptake in PRE and POST, in comparison to the C condition. TF150 (sec) significantly improved after 5BH without being further affected by BH training (C:44.8±8.1, PRE:49.2±4.8, POST:49.3±8.2). Priming breath holds prior to middle-distance racing may improve performance.

Ratio of venous-to-arterial PCO2 to arteriovenous oxygen content difference during regional ischemic or hypoxic hypoxia.

The purpose of the study was to evaluate the behavior of the venous-to-arterial CO2 tension difference (ΔPCO2) over the arterial-to-venous oxygen content difference (ΔO2) ratio (ΔPCO2/ΔO2) and the difference between venous-to-arterial CO2 content calculated with the Douglas' equation (ΔCCO2D) over ΔO2 ratio (ΔCCO2D/ΔO2) and their abilities to reflect the occurrence of anaerobic metabolism in two experimental models of tissue hypoxia: ischemic hypoxia (IH) and hypoxic hypoxia (HH). We also aimed to assess the influence of metabolic acidosis and Haldane effects on the PCO2/CO2 content relationship. In a vascularly isolated, innervated dog hindlimb perfused with a pump-membrane oxygenator system, the oxygen delivery (DO2) was lowered in a stepwise manner to decrease it beyond critical DO2 (DO2crit) by lowering either arterial PO2 (HH-model) or flow (IH-model). Twelve anesthetized and mechanically ventilated dogs were studied, 6 in each model. Limb DO2, oxygen consumption ([Formula: see text]), ΔPCO2/ΔO2, and ΔCCO2D/ΔO2 were obtained every 15 min. Beyond DO2crit, [Formula: see text] decreased, indicating dysoxia. ΔPCO2/ΔO2, and ΔCCO2D/ΔO2 increased significantly only after reaching DO2crit in both models. At DO2crit, ΔPCO2/ΔO2 was significantly higher in the HH-model than in the IH-model (1.82 ± 0.09 vs. 1.39 ± 0.06, p = 0.002). At DO2crit, ΔCCO2D/ΔO2 was not significantly different between the two groups (0.87 ± 0.05 for IH vs. 1.01 ± 0.06 for HH, p = 0.09). Below DO2crit, we observed a discrepancy between the behavior of the two indices. In both models, ΔPCO2/ΔO2 continued to increase significantly (higher in the HH-model), whereas ΔCCO2D/ΔO2 tended to decrease to become not significantly different from its baseline in the IH-model. Metabolic acidosis significantly influenced the PCO2/CO2 content relationship, but not the Haldane effect. ΔPCO2/ΔO2 was able to depict the occurrence of anaerobic metabolism in both tissue hypoxia models. However, at very low DO2 values, ΔPCO2/ΔO2 did not only reflect the ongoing anaerobic metabolism; it was confounded by the effects of metabolic acidosis on the CO2-hemoglobin dissociation curve, and then it should be interpreted with caution.

High-Dose Compared With Standard-Dose Oxytocin Regimens to Augment Labor in Nulliparous Women: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether a high-dose oxytocin regimen reduces the risk for primary cesarean birth and other obstetric morbidities when compared with standard dosing. METHODS: In a double-blind randomized clinical trial of nulliparous women at or beyond 36 weeks of gestation who were undergoing augmentation of labor, participants were assigned to high-dose (initial and incremental rates of 6 milliunits/min) or standard-dose (initial and incremental rates of 2 milliunits/min) oxytocin regimens. The primary outcome was cesarean birth. Prespecified secondary outcomes included labor duration, clinical chorioamnionitis, endometritis, postpartum hemorrhage, Apgar score 3 or less at 5 minutes, umbilical artery acidemia, neonatal intensive care unit admission, perinatal death, and a severe perinatal morbidity composite. A sample size of 501 per group (n=1,002) was planned to detect a 6.6% absolute reduction in rate of the primary outcome, from 20% in the standard-dose group to 13.4% in the high-dose group with 80% power. RESULTS: From September 2015 to September 2020, 1,003 participants were randomized-502 assigned to high-dose and 501 assigned to standard dosing. The majority of participants were of White race, were married or living as married, and had commercial insurance. Baseline characteristics between groups were similar. The primary outcome occurred in 14.5% of those receiving high-dose compared with 14.4% of those receiving standard-dose oxytocin (relative risk, 1.01; 95% CI 0.75-1.37). The high-dose group had a significantly shorter mean labor duration (9.1 vs 10.5 hours; P<.001), and a significantly lower chorioamnionitis incidence (10.4% vs 15.6%; relative risk, 0.67; 95% CI 0.48-0.92) compared with standard dosing. Umbilical artery acidemia was significantly less frequent in the high-dose group in complete case analysis, but this finding did not persist after multiple imputation (relative risk, 0.55; 95% CI 0.29-1.04). There were no significant differences in other secondary outcomes. CONCLUSION: Among nulliparous participants who were undergoing augmentation of labor, a high-dose oxytocin regimen, compared with standard dosing, did not affect the cesarean birth risk but significantly reduced labor duration and clinical chorioamnionitis frequency without adverse effects on perinatal outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02487797.

Malnourishment-Associated Acetaminophen Toxicity in Pregnancy.

BACKGROUND: Although acetaminophen is commonly used in pregnancy, it can deplete glutathione concentrations and cause accumulation of 5-oxoproline, with subsequent metabolic acidosis. CASE: A malnourished 25-year-old woman, G2P1001, with chronic acetaminophen use presented with abdominal pain and high anion gap metabolic acidosis. After ruling out other potential causes, her urine 5-oxoproline level was found to be elevated. She received N-acetylcysteine, with resolution of the acidosis. CONCLUSION: Those who care for pregnant patients should remain alert to 5-oxoprolinemia as a cause of metabolic acidosis during pregnancy. Care must be taken when using acetaminophen in states of malnutrition. N-acetylcysteine seems to be an effective antidote.

Pseudohyperchloremia and Negative Anion Gap - Think Salicylate!

BACKGROUND: Pseudohyperchloremia results in a very low or negative anion gap. Historically, the most common cause of this artifact was bromide poisoning. Bromide salts have been removed from most medications and bromism has become very uncommon. More recently, the introduction of chloride ion selective sensing electrodes (Cl-ISE) has generated a new cause of pseudohyperchloremia-salicylate poisoning. We describe 5 such patients and quantitate the error generated by this measurement artifact. METHODS: The magnitude of artifactual hyperchloremia generated by high salicylate levels was quantified in 5 patients by measuring chloride concentration with several Cl-ISEs from different manufacturers and with Cl-ISEs of different "ages," and comparing these results to measurements with a chloridometer (coulometric titration), which is free of the salicylate artifact. RESULTS: Cl-ISEs from different manufacturers generated a wide range of artifactual chloride concentration elevation. Furthermore, the same Cl-ISE generated increasingly severe pseudohyperchloremia as it was repeatedly reused over time and "aged." CONCLUSIONS: Salicylate interferes with measurement of the blood chloride concentration when a Cl-ISE is used. The severity of this artifact is related to the salicylate level, the specific Cl-ISE, and the "age" of the electrode. Toxic blood salicylate levels can generate marked pseudohyperchloremia, and consequently, an artifactual very small or negative anion gap. The large anion gap metabolic acidosis typical of salicylate poisoning is masked by this artifact. Salicylate has become the most common cause of pseudohyperchloremia, and physicians should immediately consider salicylate poisoning whenever the combination of hyperchloremia and a very small or negative anion gap is reported by the laboratory.