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?

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.

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.

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.

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.

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

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.

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.

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.

The Continuum of Acid Stress.

Acid-related injury from chronic metabolic acidosis is recognized through growing evidence of its deleterious effects, including kidney and other organ injury. Progressive acid accumulation precedes the signature manifestation of chronic metabolic acidosis, decreased plasma bicarbonate concentration. Acid accumulation that is not enough to manifest as metabolic acidosis, known as eubicarbonatemic acidosis, also appears to cause kidney injury, with exacerbated progression of CKD. Chronic engagement of mechanisms to mitigate the acid challenge from Western-type diets also appears to cause kidney injury. Rather than considering chronic metabolic acidosis as the only acid-related condition requiring intervention to reduce kidney injury, this review supports consideration of acid-related injury as a continuum. This "acid stress" continuum has chronic metabolic acidosis at its most extreme end, and high-acid-producing diets at its less extreme, yet detrimental, end.

Automatic real-time analysis and interpretation of arterial blood gas sample for Point-of-care testing: Clinical validation.

BACKGROUND: Point-of-care arterial blood gas (ABG) is a blood measurement test and a useful diagnostic tool that assists with treatment and therefore improves clinical outcomes. However, numerically reported test results make rapid interpretation difficult or open to interpretation. The arterial blood gas algorithm (ABG-a) is a new digital diagnostics solution that can provide clinicians with real-time interpretation of preliminary data on safety features, oxygenation, acid-base disturbances and renal profile. The main aim of this study was to clinically validate the algorithm against senior experienced clinicians, for acid-base interpretation, in a clinical context. METHODS: We conducted a prospective international multicentre observational cross-sectional study. 346 sample sets and 64 inpatients eligible for ABG met strict sampling criteria. Agreement was evaluated using Cohen's kappa index, diagnostic accuracy was evaluated with sensitivity, specificity, efficiency or global accuracy and positive predictive values (PPV) and negative predictive values (NPV) for the prevalence in the study population. RESULTS: The concordance rates between the interpretations of the clinicians and the ABG-a for acid-base disorders were an observed global agreement of 84,3% with a Cohen's kappa coefficient 0.81; 95% CI 0.77 to 0.86; p < 0.001. For detecting accuracy normal acid-base status the algorithm has a sensitivity of 90.0% (95% CI 79.9 to 95.3), a specificity 97.2% (95% CI 94.5 to 98.6) and a global accuracy of 95.9% (95% CI 93.3 to 97.6). For the four simple acid-base disorders, respiratory alkalosis: sensitivity of 91.2 (77.0 to 97.0), a specificity 100.0 (98.8 to 100.0) and global accuracy of 99.1 (97.5 to 99.7); respiratory acidosis: sensitivity of 61.1 (38.6 to 79.7), a specificity of 100.0 (98.8 to 100.0) and global accuracy of 98.0 (95.9 to 99.0); metabolic acidosis: sensitivity of 75.8 (59.0 to 87.2), a specificity of 99.7 (98.2 to 99.9) and a global accuracy of 97.4 (95.1 to 98.6); metabolic alkalosis sensitivity of 72.2 (56.0 to 84.2), a specificity of 95.5 (92.5 to 97.3) and a global accuracy of 93.0 (88.8 to 95.3); the four complex acid-base disorders, respiratory and metabolic alkalosis, respiratory and metabolic acidosis, respiratory alkalosis and metabolic acidosis, respiratory acidosis and metabolic alkalosis, the sensitivity, specificity and global accuracy was also high. For normal acid-base status the algorithm has PPV 87.1 (95% CI 76.6 to 93.3) %, and NPV 97.9 (95% CI 95.4 to 99.0) for a prevalence of 17.4 (95% CI 13.8 to 21.8). For the four-simple acid-base disorders and the four complex acid-base disorders the PPV and NPV were also statistically significant. CONCLUSIONS: The ABG-a showed very high agreement and diagnostic accuracy with experienced senior clinicians in the acid-base disorders in a clinical context. The method also provides refinement and deep complex analysis at the point-of-care that a clinician could have at the bedside on a day-to-day basis. The ABG-a method could also have the potential to reduce human errors by checking for imminent life-threatening situations, analysing the internal consistency of the results, the oxygenation and renal status of the patient.

Sialoglycan recognition is a common connection linking acidosis, zinc, and HMGB1 in sepsis.

Blood pH is tightly maintained between 7.35 and 7.45, and acidosis (pH <7.3) indicates poor prognosis in sepsis, wherein lactic acid from anoxic tissues overwhelms the buffering capacity of blood. Poor sepsis prognosis is also associated with low zinc levels and the release of High mobility group box 1 (HMGB1) from activated and/or necrotic cells. HMGB1 added to whole blood at physiological pH did not bind leukocyte receptors, but lowering pH with lactic acid to mimic sepsis conditions allowed binding, implying the presence of natural inhibitor(s) preventing binding at normal pH. Testing micromolar concentrations of divalent cations showed that zinc supported the robust binding of sialylated glycoproteins with HMGB1. Further characterizing HMGB1 as a sialic acid-binding lectin, we found that optimal binding takes place at normal blood pH and is markedly reduced when pH is adjusted with lactic acid to levels found in sepsis. Glycan array studies confirmed the binding of HMGB1 to sialylated glycan sequences typically found on plasma glycoproteins, with binding again being dependent on zinc and normal blood pH. Thus, HMGB1-mediated hyperactivation of innate immunity in sepsis requires acidosis, and micromolar zinc concentrations are protective. We suggest that the potent inflammatory effects of HMGB1 are kept in check via sequestration by plasma sialoglycoproteins at physiological pH and triggered when pH and zinc levels fall in late stages of sepsis. Current clinical trials independently studying zinc supplementation, HMGB1 inhibition, or pH normalization may be more successful if these approaches are combined and perhaps supplemented by infusions of heavily sialylated molecules.

New onset adrenal insufficiency in a patient with COVID-19.

SARS-CoV-2 is the cause of COVID-19. Since the outbreak and rapid spread of COVID-19, it has been apparent that the disease is having multi-organ system involvement. Still its effect in the endocrine system is not fully clear and data on cortisol dynamics in patients with COVID-19 are not yet available. SARS-CoV-2 can knock down the host's cortisol stress response. Here we present a case of a 51-year-old man vomiting for 10 days after having confirmed COVID-19 infection. He had hypotension and significant hyponatraemia. Work-up was done including adrenocorticotropic hormone stimulation test. He was diagnosed as suffering from adrenal insufficiency and started on steroids with subsequent improvement in both blood pressure and sodium level. COVID-19 can cause adrenal insufficiency. Clinicians must be vigilant about the possibility of an underlying relative cortisol deficiency in patients with COVID-19.

Maternal Oxygen Supplementation Compared With Room Air for Intrauterine Resuscitation: A Systematic Review and Meta-analysis.

Importance: Supplemental oxygen is commonly administered to pregnant women at the time of delivery to prevent fetal hypoxia and acidemia. There is mixed evidence on the utility of this practice. Objective: To compare the association of peripartum maternal oxygen administration with room air on umbilical artery (UA) gas measures and neonatal outcomes. Data Sources: Ovid MEDLINE, Embase, Scopus, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials were searched from February 18 to April 3, 2020. Search terms included labor or obstetric delivery and oxygen therapy and fetal blood or blood gas or acid-base imbalance. Study Selection: Studies were included if they were randomized clinical trials comparing oxygen with room air at the time of scheduled cesarean delivery or labor in patients with singleton, nonanomalous pregnancies. Studies that did not collect paired umbilical cord gas samples or did not report either UA pH or UA Pao2 results were excluded. Data Extraction and Synthesis: Data were extracted by 2 independent reviewers. The analysis was stratified by the presence or absence of labor at the time of randomization. Data were pooled using random-effects models. Main Outcomes and Measures: The primary outcome for this review was UA pH. Secondary outcomes included UA pH less than 7.2, UA Pao2, UA base excess, 1- and 5-minute Apgar scores, and neonatal intensive care unit admission. Results: The meta-analysis included 16 randomized clinical trials (n = 1078 oxygen group and n = 974 room air group). There was significant heterogeneity among the studies (I2 = 49.88%; P = .03). Overall, oxygen administration was associated with no significant difference in UA pH (weighted mean difference, 0.00; 95% CI, -0.01 to 0.01). Oxygen use was associated with an increase in UA Pao2 (weighted mean difference, 2.57 mm Hg; 95% CI, 0.80-4.34 mm Hg) but no significant difference in UA base excess, UA pH less than 7.2, Apgar scores, or neonatal intensive care unit admissions. Umbilical artery pH values remained similar between groups after accounting for the risk of bias, type of oxygen delivery device, and fraction of inspired oxygen. After stratifying by the presence or absence of labor, oxygen administration in women undergoing scheduled cesarean delivery was associated with increased UA Pao2 (weighted mean difference, 2.12 mm Hg; 95% CI, 0.09-4.15 mm Hg) and a reduction in the incidence of UA pH less than 7.2 (relative risk, 0.63; 95% CI, 0.43-0.90), but these changes were not noted among those in labor (Pao2: weighted mean difference, 3.60 mm Hg; 95% CI, -0.30 to 7.49 mm Hg; UA pH<7.2: relative risk, 1.34; 95% CI, 0.58-3.11). Conclusions and Relevance: This systematic review and meta-analysis suggests that studies to date showed no association between maternal oxygen and a clinically relevant improvement in UA pH or other neonatal outcomes.

Mild Neonatal Acidemia is Associated with Neonatal Morbidity at Term.

OBJECTIVE: The aim of this study is to determine the association between mild acidemia (umbilical artery [UA] pH: 7.11-7.19) and neonatal morbidity in neonates at term. STUDY DESIGN: This is a secondary analysis of a prospective cohort of women admitted for labor at ≥37 weeks of gestation within a single institution from 2010 to 2015. Universal umbilical cord blood gas assessment was performed and validated. A composite neonatal morbidity index was created including respiratory distress, mechanical ventilation, meconium aspiration syndrome, suspected or confirmed sepsis, hypoxic-ischemic encephalopathy, need for therapeutic hypothermia, seizures and death. The cohort was stratified by UA pH into normal (≥7.20), mild acidemia (7.11-7.19), acidemia (7.00-7.10), and severe acidemia (≤7.00). A subanalysis was also performed where neonates with UA pH between 7.11 and 7.19 were further stratified into two groups (7.11-7.14 and 7.15-7.19) to determine if mildly acidotic infants at the lower end of the pH range were at increased risk of morbidity. Multivariable logistic regression was used to estimate the association between UA pH and neonatal morbidity. RESULTS: Among 6,341 participants, 614 (9.7%) had mild acidemia. These infants were more likely to experience morbidity compared with those with normal UA pH (adjusted odds ratio [aOR]: 2.14; [1.68-2.73]). Among neonates with mild acidemia, UA pH 7.11 to 7.14 was associated with increased risk of composite neonatal morbidity (aOR: 3.02; [1.89-4.82]), as well as respiratory distress and suspected or confirmed sepsis when compared with UA pH 7.15 to 7.19. CONCLUSION: These data demonstrate that term neonates with mild acidemia at birth are at higher odds for short-term morbidity compared with neonates with normal UA pH. Furthermore, among neonates with mild acidemia, those with lower UA pH had worse neonatal outcomes than those with higher UA pH. This suggests that closer evaluation of neonates with UA pH higher than traditionally used could allow for earlier detection of morbidity and possible intervention. KEY POINTS: · Neonates with mild acidemia (umbilical artery [UA] pH: 7.11-7.19) demonstrated an increased risk of composite morbidity compared with those with normal UA pH (≥7.20).. · Among neonates with mild acidemia, those with lower UA pH (7.11-7.14) had a greater risk of morbidity compared with those with higher UA pH (7.15-7.19), suggesting a progression of risk of morbidity as UA pH decreases.. · The majority of prior research has focused on severe acidemia (UA pH ≤ 7.00) using outcomes of severe neurologic morbidity and mortality. These data suggest that an increased risk of morbidity exists at higher pH values when more proximal and less severe outcomes are included, such as respiratory distress and neonatal sepsis..

Semiquantitative acid-base analysis in dogs with typical hypoadrenocorticism.

OBJECTIVE: To describe the semiquantitative acid-base status of dogs with untreated naturally occurring typical hypoadrenocorticism and to compare this to the status determined by traditional acid-base analysis. DESIGN: Retrospective study. SETTING: University teaching hospital. ANIMALS: Thirty-three dogs with newly diagnosed typical hypoadrenocorticism between 2000 and 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Dogs were included if they had newly diagnosed hypoadrenocorticism, post-ACTH stimulation serum cortisol concentration <2 µg/dL, and blood collected within 6 hours of presentation for acid-base, electrolyte, and serum biochemical assays. Dogs were excluded if the Na+ :K+ ratio was ≥28 or the dog had received a mineralocorticoid-containing corticosteroid medication within the preceding month. Traditional acid-base analysis identified normal acid-base status in 1 dog, simple respiratory acid-base abnormalities in 2 of 33 dogs, and simple metabolic acidosis in 14 of 33 dogs. A mixed disorder was most common, noted in 16 of 33 dogs. The semiquantitative approach identified metabolic abnormalities in all cases. All dogs had ≥1 acidifying process, and 29 of 33 had both acidifying and alkalinizing processes. Acidosis attributable to excess free water was present in all dogs, and an acidifying phosphate effect was present in 27 of 33. Hyperlactatemia contributed to the acidosis in 8 of 33 dogs, with a median (range) lactate concentration of 1.5 mmol/L (13.5 mg/dL) (0.3-4.2 mmol/L [2.7-37.8 mg/dL]). CONCLUSIONS: Dogs with untreated Addison's disease have complex acid-base derangements. The semiquantitative approach to acid-base analysis provides greater insight into the underlying mechanisms of metabolic acid-base abnormalities in these dogs, particularly because lactic acidosis appears to be a minor influence in most cases.

Practical Management of ECPELLA.

Veno-arterial extracorporeal membrane oxygenation (ECMO) is a strong mechanical circulatory device for patients with hemodynamic deterioration due to cardiogenic shock, but its drawback is an increase in left ventricular afterload. The Impella axial-flow transcatheter left ventricular assist device is a recently developed promising device to mechanically unload the left ventricle, although its support flow may not necessarily be sufficient to support shock vital. Recently, ECMO and concomitant Impella support (ECPELLA) is increasingly being used to treat cardiogenic shock by maintaining systemic circulation and unloading the left ventricle. There are several pitfalls to maintaining ECPELLA, and one useful tool is the pulmonary artery pulsatility index. The clinical advantages of ECPELLA compared to conventional ECMO alone should be demonstrated in larger scale studies in the near future.