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Maintenance intravenous fluids are the most frequently ordered medications for hospitalized children. Since the American Association of Pediatrics published national guidelines, there has been an increased reflexive use of isotonic solutions, especially 0.9% saline, as a prophylaxis against hyponatremia. In this educational review, we discuss the potential deleterious effects of using 0.9% saline, including the development of hyperchloremia, metabolic acidosis, acute kidney injury, hyperkalemia, and a proinflammatory state. Balanced solutions with anion buffers cause relatively minimal harm when used in most children. While the literature supporting one fluid choice over the other is variable, we highlight the benefits of balanced solutions over saline and the importance of prescribing fluid therapy that is individualized for each patient., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Maternal oxygen supplementation is usually used as an intrauterine resuscitation technique to prevent fetal hypoxia and acidemia during delivery. However, there has been a great deal of controversy regarding the effects of prophylactic maternal oxygen during cesarean section, during which the incidence of fetal acidemia seems to be higher compared with that during labor. High-flow nasal oxygen (HFNO) can improve oxygenation better in patients with high-flow oxygen airflow. The purpose of this study is to determine whether maternal oxygen supplementation with HFNO has a positive effect on fetal acidemia during cesarean section through umbilical arterial blood gas analysis., Method: This prospective, single-center, randomized, double-blinded trial will enroll 120 patients undergoing cesarean section. Participants will be randomly assigned to the HFNO group or air group at a 1:1 ratio. For parturients in the HFNO group, the flow rate is 40L/min, and the oxygen is heated to 37℃ with humidity 100% oxygen concentration through the Optiflow high-flow nasal oxygen system. And for the air group, the flow rate is 2 L/min with an air pattern through the same device. The primary outcome was umbilical artery (UA) lactate. Secondary outcomes include UA pH, PO 2 , PCO 2 , BE, the incidence of pH < 7.20 and pH < 7.10, Apgar scores at 1 and 5 min, and neonatal adverse outcomes., Discussion: Our study is the first trial investigating whether maternal oxygen supplementation with HFNO can reduce the umbilical artery lactate levels and the incidence of fetal acidemia in cesarean section under combined spinal-epidural anesthesia., Trial Registration: ClinicalTrials.gov NCT05921955. Registered on 27 June 2023., (© 2024. The Author(s).)

Introduction: With category II fetal heart rate tracings, the preferred timing of interventions to prevent fetal hypoxic brain damage while limiting operative interventions remains unclear. We aimed to estimate fetal extracellular base deficit (BD ecf ) during labor with category II tracings to quantify the timing of potential interventions to prevent severe fetal metabolic acidemia., Material and Methods: A longitudinal study was conducted using the database of the Recurrence Prevention Committee, Japan Obstetric Compensation System for Cerebral Palsy, including infants with severe cerebral palsy born at ≥34 weeks' gestation between 2009 and 2014. Cases included those presumed to have an intrapartum onset of hypoxic-ischemic insult based on the fetal heart rate pattern evolution from reassuring to an abnormal pattern during delivery, in association with category II tracings marked by recurrent decelerations and an umbilical arterial BD ecf  ≥ 12 mEq/L. BD ecf changes during labor were estimated based on stages of labor and the frequency/severity of fetal heart rate decelerations using the algorithm of Ross and Gala. The times from the onset of recurrent decelerations to BD ecf 8 and 12 mEq/L (Decels-to-BD8, Decels-to-BD12) and to delivery were determined. Cases were divided into two groups (rapid and slow progression) based upon the rate of progression of acidosis from onset of decelerations to BD ecf 12 mEq/L, determined by a finite-mixture model., Results: The median Decels-to-BD8 (28 vs. 144 min, p < 0.01) and Decels-to-BD12 (46 vs. 177 min, p < 0.01) times were significantly shorter in the rapid vs slow progression. In rapid progression cases, physicians' decisions to deliver the fetus occurred at ~BD ecf 8 mEq/L, whereas the "decisions" did not occur until BD ecf reached 12 mEq/L in slow progression cases., Conclusions: Fetal BD ecf reached 12 mEq/L within 1 h of recurrent fetal heart rate decelerations in the rapid progression group and within 3 h in the slow progression group. These findings suggest that cases with category II tracings marked by recurrent decelerations (i.e., slow progression) may benefit from operative intervention if persisting for longer than 2 h. In contrast, cases with sudden bradycardia (i.e., rapid progression) represent a challenge to prevent severe acidosis and hypoxic brain injury due to the limited time opportunity for emergent delivery., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Subacute ruminal acidosis (SARA) in feedlot cattle during the feed transition to grain-based diets is a significant constraint to animal health and productivity. This experiment assessed an antibiotic-free supplement (ProTect®) effects on ruminal pH variability and methane (CH 4 ) emissions of cattle during the challenge of SARA. Ten 18-month-old Angus steers (472 ± 4.8 kg) were randomly allocated into monensin (n = 5) and ProTect® groups (n = 5) and progressively introduced to grain diets incorporating monensin or ProTect® for 36 days of the experiment [starter (7 days; 45% grain), T1 (7 days; 56% grain), T2 (7 days; 67% grain), finisher (15 days; 78% grain)]. The pH variability on the finisher period was reduced by the ProTect® supplement (6.6% vs. 5.2%; P < 0.01), with CH 4 emissions being significantly higher relative to the monensin group [88.2 g/day (9.3 g CH 4 /kg DMI) vs. 133.7 g/day (14.1 g CH 4 /kg DMI); P < 0.01]. There was no difference between treatments in the time spent on the ruminal pH < 5.6 or < 5.8 (P > 0.05). The model evaluation for the ruminal pH variation indicated that the mean absolute error (MAE) proportion for both groups was good within the same range [4.05% (monensin) vs. 4.25% (ProTect®)] with identical root mean square prediction error (RMSPE) (0.34). It is concluded that the ProTect® supplement is an effective alternative to monensin for preventing SARA in feedlot cattle by managing ruminal pH variation during the transition to high-grain diets. Both monensin and ProTect® supplemented cattle exhibited lower CH 4 yield compared to cattle fed forages and low-concentrate diets., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. While ProAgni staff were involved in the supply of ProTect®, editing the document and initiating the modelling of rumen pH throughout the experiment, they were not involved in the collection or statistical analysis of the data reported., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to determine whether (i) a plasma acidosis contributes to a reduction of mechanical performance and (ii) bicarbonate supplementation blunts plasma acidosis and arterial oxygen desaturation to resist fatigue during the end spurt of a supramaximal trial in elite sprint and endurance cyclists., Methods: Elite/world-class cyclists ( n = 6 sprint, n = 6 endurance) completed two randomized, double-blind, crossover trials at 105%V̇O 2peak simulating 3 min of a 4-km individual pursuit, 90 min after ingestion of 0.3 g·kg -1 BM sodium bicarbonate (BIC) or placebo (PLA). Peak power output (PPO), optimal cadence and optimal peak torque, and fatigue were assessed using a 6-s "all-out sprint" before (PPO1) and after (PPO2) each trial. Plasma pH, bicarbonate, lactate - , K + , Na + , Ca 2+ , and arterial hemoglobin saturation (SpO 2 (%)), were measured., Results: Sprint cyclists exhibited a higher PPO, optimal pedal torque, and anaerobic power reserve (APR) than endurance cyclists. The trial reduced PPO (PLA) more for sprint (to 47% initial) than endurance cyclists (to 61% initial). Optimal cadence fell from ~151 to 92 rpm and cyclists with higher APR exhibited a reduced optimal peak torque. Plasma pH fell from 7.35 to 7.13 and plasma [lactate - ] increased from 1.2 to 19.6 mM (PLA), yet neither correlated with PPO loss. Sprint cyclists displayed a lesser plasma acidosis but greater fatigue than endurance cyclists. BIC increased plasma [HCO 3- ] (+6.8 mM) and plasma pH after PPO1 (+0.09) and PPO2 (+0.07) yet failed to influence mechanical performance. SpO 2 fell from 99% to 96% but was unrelated to the plasma acidosis and unaltered with BIC., Conclusions: Plasma acidosis was not associated with the decline of PPO in a supramaximal trial with elite cyclists. BIC attenuated acid-base disturbances yet did not improve arterial oxygen desaturation or mechanical performance at the end-spurt stage., (Copyright © 2022 by the American College of Sports Medicine.)

Introduction: Most hemodialysis machines deliver a fixed bicarbonate concentration. Higher concentrations may improve acidosis, but risk post-hemodialysis alkalosis, whereas lower concentrations potentially increase acidosis but reduce alkalosis. We reviewed the effects of lowering dialysate bicarbonate., Methods: We reviewed peri-dialysis chemistries in patients switching to a lower bicarbonate dialysate at 4 time points over 19 months., Results: We studied 126 patients, mean age 63.7 ± 16.3 years, 57.9% males. Post-hemodialysis alkalosis fell from 1.6 to 0.3% sessions, but pre-hemodialysis acidosis increased from 11.9 to 23.8% sessions (p = 0.005) reducing dialysate bicarbonate from 32 to 28 mmol/L. After 3 months, pre-hemodialysis serum bicarbonate fell (21.1 ± 2.3 to 19.8 ± 2.2 mmol/L), and post-hemodialysis (24.9 ± 2.1 to 22.5 ± 2.0 mmol/L, p < 0.001) with a fall in pre-hemodialysis weight from 74.6 ± 20.7 to 71.7 ± 18.2 kg, normalized protein nitrogen accumulation rate 0.8 ± 0.28 to 0.77 ± 0.2 g/kg/day, p < 0.05, and serum albumin 39.7 ± 4.2 to 37.7 ± 4.9 g/L, p < 0.001. Thereafter, apart from pre- and post-hemodialysis serum bicarbonate, weight and normalized protein nitrogen accumulation stabilized, although albumin remained lower (37.6 ± 4.0 g/L, p < 0.001). On multivariate logistic analysis, serum bicarbonate increased more with lower pre-hemodialysis bicarbonate standardized coefficient β 0.5 (95% confidence interval -0.6 to -0.42), increased normalized protein nitrogen accumulation β 0.2 (0.96 to 2.38), p < 0.001, and session time β 0.09, (0.47 to 5.98), p < 0.022, and less with lower dialysate bicarbonate 0.0-0.23 (-1.54 to -0.74), p < 0.001., Conclusion: Increases in SE-Bic with hemodialysis, depend on the bicarbonate gradient, session time and nPNA. Lower D-Bic reduces post-hemodialysis alkalosis but increases pre-hemodialysis acidosis and may initially have adverse effects on weight and normalized protein nitrogen accumulation., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Exercise training can increase both mitochondrial content and mitochondrial respiration. Despite its popularity, high-intensity exercise can be accompanied by mild acidosis (also present in certain pathological states), which may limit exercise-induced adaptations to skeletal muscle mitochondria. The aim of this study was to determine if administration of ammonium chloride (0.05 g/kg) to Wistar rats before each individual exercise session (5 high-intensity exercise sessions/wk for 8 wk) reduced training-induced increases in mitochondrial content (measured by citrate synthase activity and protein content of electron transport system complexes) and respiration (measured in permeabilized muscle fibers). In the soleus muscle, the exercise-training-induced increase in mitochondrial respiration was reduced in rats administered ammonium chloride compared to control animals, but mitochondrial content was not altered. These effects were not present in the white gastrocnemius muscle. In conclusion, ammonium chloride administration before each exercise session over 8 wk reduced improvements in mitochondrial respiration in the soleus muscle but did not alter mitochondrial content. This suggests that mild acidosis may affect training-induced improvements in the respiration of mitochondria in some muscles.

Contemporary diets in Western countries are largely acid-inducing and deficient in potassium alkali salts, resulting in low-grade metabolic acidosis. The chronic consumption of acidogenic diets abundant in animal-based foods (meats, dairy, cheese and eggs) poses a substantial challenge to the human body's buffering capacities and chronic retention of acid wherein the progressive loss of bicarbonate stores can cause cellular and tissue damage. An elevated dietary acid load (DAL) has been associated with systemic inflammation and other adverse metabolic conditions. In this narrative review, we examine DAL quantification methods and index observational and clinical evidence on the role of plant-based diets, chiefly vegetarian and vegan, in reducing DAL. Quantitation of protein and amino acid composition and of intake of alkalising organic potassium salts and magnesium show that plant-based diets are most effective at reducing DAL. Results from clinical studies and recommendations in the form of expert committee opinions suggest that for a number of common illnesses, wherein metabolic acidosis is a contributing factor, the regular inclusion of plant-based foods offers measurable benefits for disease prevention and management. Based on available evidence, dietary shifts toward plant-based nutrition effectively reduces dietary-induced, low-grade metabolic acidosis., (© The Author(s) 2022.)

Background: In recent years, researchers have become increasingly interested in developing natural feed additives that can stabilize ruminal pH and thus prevent or eliminate the risk of severe subacute rumen acidosis. Herein, 3 experiments were conducted using a semi-automated in vitro gas production technique. In the experiment (Exp.) 1, the efficacy of 9 plant extracts (1.5 mg/ml), compared to monensin (MON; 12 μg/ml), to counteract ruminal acidosis stimulated by adding glucose (0.1 g/ml) as a fermentable carbohydrate without buffer was assessed for 6 h. In Exp. 2, cinnamon extract (CIN) and MON were evaluated to combat glucose-induced acidosis with buffer use for 24 h. In Exp. 3, the effect of CIN and MON on preventing acidosis when corn or barley grains were used as substrate was examined., Results: In Exp. 1, cinnamon, grape seeds, orange, pomegranate peels, propolis, and guava extracts significantly increased (P < 0.05) pH compared to control (CON). Both CIN and MON significantly increased the pH (P < 0.001) but reduced cumulated gas production (P < 0.01) compared to the other treatments. In Exp. 2, the addition of CIN extract increased (P < 0.01) pH value compared to CON at the first 6 h of incubation. However, no significant differences in pH values between CIN and CON at 24 h of incubation were observed. The addition of CIN extract and MON decreased (P < 0.001) lactic acid concentration and TVFA compared to CON at 24 h. The CIN significantly (P < 0.01) increased acetate: propionate ratio while MON reduced it. In Exp. 3, both CIN and MON significantly increased (P < 0.05) ruminal pH at 6 and 24 h and reduced lactic acid concentration at 24 h compared to CON with corn as substrate. However, CIN had no effect on pH with barley substrate at all incubation times., Conclusions: It can be concluded that CIN can be used effectively as an alternative antibiotic to MON to control ruminal acidosis when corn is used as a basal diet., (© 2022. The Author(s).)

Introduction: Recent experimental evidence suggests normothermic machine perfusion of the vascularized composite allograft results in improved preservation compared to static cold storage, with less reperfusion injury in the immediate post-operative period. However, metabolic acidosis is a common feature of vascularized composite allograft perfusion, primarily due to the inability to process metabolic by-products. We evaluated the impact of combined limb-kidney perfusion on markers of metabolic acidosis and inflammation in a porcine model., Methods: Ten paired pig forelimbs were used for this study, grouped as either limb-only (LO, n = 5) perfusion, or limb-kidney (LK, n = 5) perfusion. Infrared thermal imaging was used to determine homogeneity of perfusion. Lactate, bicarbonate, base, pH, and electrolytes, along with an inflammatory profile generated via the quantification of cytokines and cell-free DNA in the perfusate were recorded., Results: The addition of a kidney to a limb perfusion circuit resulted in the rapid stabilization of lactate, bicarbonate, base, and pH. Conversely, the LO circuit became progressively acidotic, correlating in a significant increase in pro-inflammatory cytokines. Global perfusion across the limb was more homogenous with LK compared to LO., Conclusion: The addition of a kidney during limb perfusion results in significant improvements in perfusate biochemistry, with no evidence of metabolic acidosis., (© 2021 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Despite remarkable scientific advances in the understanding of molecular mechanisms for sepsis, therapeutic options are far from satisfactory. High mobility group box 1 (HMGB1), one of the ligands of receptor for advanced glycation end products (RAGE), is a late mediator of lethality in septic mice. We have recently found that the DNA-aptamer raised against RAGE (RAGE-aptamer) significantly blocks experimental diabetic nephropathy and melanoma growth and metastasis. We examined the effects of RAGE-aptamer on sepsis score, survival rate, and inflammatory and oxidative stress responses in serum, peripheral monocytes, kidneys and livers of lipopolysaccharide- (LPS-) injected mice, and on LPS-exposed THP-1 cells. RAGE-aptamer inhibited the binding of HMGB1 to RAGE in vitro . RAGE-aptamer significantly ( P = 0.002) improved sepsis score at 8 hours after LPS injection and survival rate at 24 hours ( P < 0.01, 70%) in septic mice compared with LPS+vehicle- or LPS+control-aptamer-treated mice. RAGE-aptamer treatment significantly decreased expression of p-NF- κ B p65, an active form of redox-sensitive transcriptional factor, NF- κ B and gene or protein expression of TNF- α , IL-1 β , IL-6, and HMGB1 in serum, peripheral monocytes, and kidneys of septic mice in association with the reduction of oxidative stress and improvement of metabolic acidosis, renal and liver damage. LPS-induced oxidative stress, inflammatory reactions, and growth suppression in THP-1 cells were significantly blocked by RAGE-aptamer. Our present study suggests that RAGE-aptamer could attenuate multiple organ damage in LPS-injected septic mice partly by inhibiting the inflammatory reactions via suppression of HMGB1-RAGE interaction., Competing Interests: There is no conflict of interests to declare in this paper., (Copyright © 2021 Yoshinori Koga et al.)

Metabolic acidosis is a severe complication of chronic kidney disease (CKD) which is associated with nefarious impairments such as bone demineralization, muscle wasting, and hormonal alterations, for example, insulin resistance. Whilst it is possible to control this condition with alkali treatment, consisting in the oral administration of sodium citrate or sodium bicarbonate, this type of intervention is not free from side effects. On the contrary, opting for the implementation of a targeted dietetic-nutritional treatment for the control of CKD metabolic acidosis also comes with a range of additional benefits such as lipid profile control, increased vitamins, and antioxidants intake. In our review, we evaluated the main dietary-nutritional regimens useful to counteract metabolic acidosis, such as the Mediterranean diet, the alkaline diet, the low-protein diet, and the vegan low-protein diet, analyzing the potentialities and limits of every dietary-nutritional treatment. Literature data suggest that the Mediterranean and alkaline diets represent a valid nutritional approach in the prevention and correction of metabolic acidosis in CKD early stages, while the low-protein diet and the vegan low-protein diet are more effective in CKD advanced stages. In conclusion, we propose that tailored nutritional approaches should represent a valid therapeutic alternative to counteract metabolic acidosis.

While sudden loss of perfusion is responsible for ischemia, failure to supply the required amount of oxygen to the tissues is defined as hypoxia. Among several pathological conditions that can impair brain perfusion and oxygenation, cardiocirculatory arrest is characterized by a complete loss of perfusion to the brain, determining a whole brain ischemic-anoxic injury. Differently from other threatening situations of reduced cerebral perfusion, i.e., caused by increased intracranial pressure or circulatory shock, resuscitated patients after a cardiac arrest experience a sudden restoration of cerebral blood flow and are exposed to a massive reperfusion injury, which could significantly alter cellular metabolism. Current evidence suggests that cell populations in the central nervous system might use alternative metabolic pathways to glucose and that neurons may rely on a lactate-centered metabolism. Indeed, lactate does not require adenosine triphosphate (ATP) to be oxidated and it could therefore serve as an alternative substrate in condition of depleted energy reserves, i.e., reperfusion injury, even in presence of adequate tissue oxygen delivery. Lactate enriched solutions were studied in recent years in healthy subjects, acute heart failure, and severe traumatic brain injured patients, showing possible benefits that extend beyond the role as alternative energetic substrates. In this manuscript, we addressed some key aspects of the cellular metabolic derangements occurring after cerebral ischemia-reperfusion injury and examined the possible rationale for the administration of lactate enriched solutions in resuscitated patients after cardiac arrest., Competing Interests: All authors declare not to have any conflict of interest regarding the manuscript.

High-flow nasal oxygen is increasingly used for oxygenation during apnoea. Extending apnoea duration using this technique has mainly been investigated during minor laryngeal surgery, but it is unclear how long it can be administered for before it should be discontinued due to acidosis. We aimed to describe the dynamics of arterial blood gases during apnoeic oxygenation with high-flow nasal oxygen with jaw thrust only, to explore the limits of this technique. We included adult orthopaedic patients scheduled for general anaesthesia. After pre-oxygenation, anaesthesia with neuromuscular blockade was induced and high-flow nasal oxygen (70 l.min -1 ) was continued with jaw thrust as the only means of airway management, with monitoring of vital signs and arterial blood gas sampling every 5 minutes. Apnoeic oxygenation with high-flow nasal oxygen was discontinued when arterial carbon dioxide tension (PaCO 2 ) exceeded 12 kPa or pH fell to 7.15. This technique was used in 35 patients and median (IQR [range]) apnoea time was 25 (20-30 [20-45]) min and was discontinued in all patients when pH fell to 7.15. The mean (SD) PaCO 2 increase was 0.25 (0.06) kPa.min -1 but it varied substantially (range 0.13-0.35 kPa.min -1 ). Mean (SD) arterial oxygen tension was 48.6 (11.8) kPa when high-flow nasal oxygen was stopped. Patients with apnoea time > 25 minutes were significantly older (p = 0.025). We conclude that apnoeic oxygenation with high-flow nasal oxygen resulted in a significant respiratory acidosis that varies substantially on the individual level, but oxygenation was maintained., (© 2020 Association of Anaesthetists.)

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.

In ruminants, the ruminal epithelium not only has the function of absorbing nutrients but also is an important tissue to prevent harmful substances in the rumen from entering the blood circulation. Thus, the normal function of ruminal epithelium is critical for ruminants. However, subacute ruminal acidosis induced by high-concentrate diets often damages the barrier function of ruminal epithelium in ruminants. Recently, many studies have shown that dietary supplementation with thiamine is an effective method to alleviate subacute ruminal acidosis. In order to provide theoretical reference for the in-depth study of subacute ruminal acidosis and the application of thiamine in the future, this review introduces the effects of subacute ruminal acidosis on morphological structure, inflammatory response, and tight junction of ruminal epithelium. In addition, this paper summarizes the role of thiamine in maintaining ruminal epithelial function of ruminants during subacute ruminal acidosis challenge., (© 2021 Japanese Society of Animal Science.)

High-producing ruminants need high-concentrate diets to satisfy their nutrient requirements and meet performance objectives. However, such diets induce sub-acute ruminal acidosis (SARA), which will adversely affect dry matter intake and lead to lower production performance. This work develops a novel modelling approach to quantify the capacity of dairy goats to adapt to a high-concentrate diet challenge at the individual level. The animal model used was dairy goats (from Saanen or Alpine breed), and rumen pH was used as the indicator of the response. A three-step modelling procedure was developed to quantify daily scores and produce a single global index for animals' adaptive response to the new diet. The first step summarizes the post-prandial kinetics of rumen acid status using three synthetic variables. In the second step, the effect of time on the response of goats is described, in the short and long terms. In the last step, a metric based on phase trajectories ranks goats for their resilience capacity. This modelling procedure showed a high variability among the goats in response to the new diet, highlighting in particular their daily and general strategies to buffer the effect of the diet change. Two main categories of adaptive strategies were observed: (i) acid status increased, but the goats tried to minimize its variations, and (ii) acid status oscillated between increases and decreases. Such phenotyping, alongside other behavioral, digestive, and metabolic measures, can help to determine biomarkers of goats' capacity to adapt to diets of higher nutritive value and to increase production performance without compromising their health status. Quantifying the capacity of goats to buffer the effect of highly fermentable diets helps to better adapt feed to animals in precision livestock farming. This procedure is generic and can be adapted to any indicator of animal health and performance. In particular, several indicators can be combined to assess multi-performance, which is of major interest in the context of selection for robust animals.

Importance: Saline (0.9% sodium chloride), the fluid most commonly used to treat diabetic ketoacidosis (DKA), can cause hyperchloremic metabolic acidosis. Balanced crystalloids, an alternative class of fluids for volume expansion, do not cause acidosis and, therefore, may lead to faster resolution of DKA than saline., Objective: To compare the clinical effects of balanced crystalloids with the clinical effects of saline for the acute treatment of adults with DKA., Design, Setting, and Participants: This study was a subgroup analysis of adults with DKA in 2 previously reported companion trials-Saline Against Lactated Ringer's or Plasma-Lyte in the Emergency Department (SALT-ED) and the Isotonic Solutions and Major Adverse Renal Events Trial (SMART). These trials, conducted between January 2016 and March 2017 in an academic medical center in the US, were pragmatic, multiple-crossover, cluster, randomized clinical trials comparing balanced crystalloids vs saline in emergency department (ED) and intensive care unit (ICU) patients. This study included adults who presented to the ED with DKA, defined as a clinical diagnosis of DKA, plasma glucose greater than 250 mg/dL, plasma bicarbonate less than or equal to 18 mmol/L, and anion gap greater than 10 mmol/L. Data analysis was performed from January to April 2020., Interventions: Balanced crystalloids (clinician's choice of Ringer lactate solution or Plasma-Lyte A solution) vs saline for fluid administration in the ED and ICU according to the same cluster-randomized multiple-crossover schedule., Main Outcomes and Measures: The primary outcome was time between ED presentation and DKA resolution, as defined by American Diabetes Association criteria. The secondary outcome was time between initiation and discontinuation of continuous insulin infusion., Results: Among 172 adults included in this secondary analysis of cluster trials, 94 were assigned to balanced crystalloids and 78 to saline. The median (interquartile range [IQR]) age was 29 (24-45) years, and 90 (52.3%) were women. The median (IQR) volume of isotonic fluid administered in the ED and ICU was 4478 (3000-6372) mL. Cumulative incidence analysis revealed shorter time to DKA resolution in the balanced crystalloids group (median time to resolution: 13.0 hours; IQR: 9.5-18.8 hours) than the saline group (median: 16.9 hours; IQR: 11.9-34.5 hours) (adjusted hazard ratio [aHR] = 1.68; 95% CI, 1.18-2.38; P = .004). Cumulative incidence analysis also revealed shorter time to insulin infusion discontinuation in the balanced crystalloids group (median: 9.8 hours; IQR: 5.1-17.0 hours) than the saline group (median: 13.4 hours; IQR: 11.0-17.9 hours) (aHR = 1.45; 95% CI, 1.03-2.03; P = .03)., Conclusions and Relevance: In this secondary analysis of 2 cluster randomized clinical trials, compared with saline, treatment with balanced crystalloids resulted in more rapid resolution of DKA, suggesting that balanced crystalloids may be preferred over saline for acute management of adults with DKA., Trial Registration: ClinicalTrials.gov Identifiers: NCT02614040; NCT02444988.

Leftover bakery by-products (BP) from bakeries and supermarkets may serve as energy-rich ingredient in ruminant diets. The aim of the present study was to evaluate the effect of the successive substitution of cereal grains by BP on dry matter (DM) intake, milk production, and metabolic health as well as ruminal pH and eating and chewing behavior of dairy cows. Twenty-four lactating Simmental cows (149 ± 22.3 d in milk, lactation number 2.63 ± 1.38, 756 ± 89.6 kg of initial body weight) were fed a total mixed ration containing a 50:50 ratio of forage to concentrate throughout the experiment (35 d). During the first week, all cows received a control diet (without BP) as a baseline (d -7 to 0). In the next 4 wk (d 1 to 28), cows were allocated to 3 groups differing in the BP concentrations of diets [0% BP (CON), 15% BP, and 30% BP on a DM basis]. The DM intake and reticuloruminal pH were continuously measured. Blood and milk samples were taken every week, but only results from the experimental period (d 21 and 28) were used for statistical analyses, whereas results from the baseline were considered covariates. Diet analyses showed that BP inclusion increased the ether extract and sugar contents, whereby starch and neutral detergent fiber decreased. Experimental data showed that feeding BP in the diet increased DM intake. Furthermore, the cows fed 30% BP produced roughly 4 kg/d more milk and energy-corrected milk than the CON cows. The milk urea nitrogen was lower in cows fed the BP. Feeding BP reduced the blood glucose and insulin concentrations, whereas nonesterified fatty acids, β-hydroxybutyrate, and cholesterol increased linearly. Cows fed 15% BP had the shortest period of time in which ruminal pH was below 5.8, in contrast to CON cows (+188 min/d). Taken together, the results suggest that the inclusion of up to 30% BP in the diets of mid-lactation dairy cows shifted the nutrient profile from a glucogenic diet to a lipogenic diet, holding the potential to enhance performance and lower the risk of subacute ruminal acidosis in dairy cows., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: Oxytocin is effective in reducing labor duration, but can be associated with fetal and maternal complications such as neonatal acidosis and post-partum hemorrhage. When comparing discontinuing oxytocin in the active phase with continuing oxytocin infusion, previous studies were underpowered to show a reduction in neonatal morbidity. Thus, we aim at evaluating the impact of discontinuing oxytocin during the active phase of the first stage of labor on the neonatal morbidity rate., Methods: STOPOXY is a multicenter, randomized, open-label, controlled trial conducted in 20 maternity units in France. The first participant was recruited January 17th 2020. The trial includes women with a live term (≥37 weeks) singleton, in cephalic presentation, receiving oxytocin before 4 cm, after an induced or spontaneous labor. Women aged < 18 years, with a lack of social security coverage, a scarred uterus, a multiple pregnancy, a fetal congenital malformation, a growth retardation <3rd percentile or an abnormal fetal heart rate at randomization are excluded. Women are randomized before 6 cm when oxytocin is either continued or discontinued. Randomization is stratified by center and parity. The primary outcome, neonatal morbidity is assessed using a composite variable defined by an umbilical arterial pH at birth < 7.10 and/or a base excess > 10 mmol/L and/or umbilical arterial lactates> 7 mmol/L and/or a 5 min Apgar score < 7 and/or admission in neonatal intensive care unit. The primary outcome will be compared between the two groups using a chi-square test with a p-value of 0.05. Secondary outcomes include neonatal complications, duration of active phase, mode of delivery, fetal and maternal complications during labor and delivery, including cesarean delivery rate and postpartum hemorrhage, and birth experience. We aim at including 2475 women based on a reduction in neonatal morbidity from 8% in the control group to 5% in the experimental group, with a power of 80% and an alpha risk of 5%., Discussion: Discontinuing oxytocin during the active phase of labor could improve both child health, by reducing moderate to severe neonatal morbidity, and maternal health by reducing cesarean delivery and postpartum hemorrhage rates., Trial Registration: Clinical trials NCT03991091 , registered June 19th, 2019.

Hypoxic-ischemic encephalopathy (HIE) is still a major cause of neonatal death and disability as therapeutic hypothermia (TH) alone cannot afford sufficient neuroprotection. The present study investigated whether ventilation with molecular hydrogen (2.1% H 2 ) or graded restoration of normocapnia with CO 2 for 4 h after asphyxia would augment the neuroprotective effect of TH in a subacute (48 h) HIE piglet model. Piglets were randomized to untreated naïve, control-normothermia, asphyxia-normothermia (20-min 4%O 2 -20%CO 2 ventilation; T core = 38.5 °C), asphyxia-hypothermia (A-HT, T core = 33.5 °C, 2-36 h post-asphyxia), A-HT + H 2 , or A-HT + CO 2 treatment groups. Asphyxia elicited severe hypoxia (pO 2 = 19 ± 5 mmHg) and mixed acidosis (pH = 6.79 ± 0.10). HIE development was confirmed by altered cerebral electrical activity and neuropathology. TH was significantly neuroprotective in the caudate nucleus but demonstrated virtually no such effect in the hippocampus. The mRNA levels of apoptosis-inducing factor and caspase-3 showed a ~10-fold increase in the A-HT group compared to naïve animals in the hippocampus but not in the caudate nucleus coinciding with the region-specific neuroprotective effect of TH. H 2 or CO 2 did not augment TH-induced neuroprotection in any brain areas; rather, CO 2 even abolished the neuroprotective effect of TH in the caudate nucleus. In conclusion, the present findings do not support the use of these medical gases to supplement TH in HIE management.

Use of intrapartum fetal heart rate (FHR) monitoring has had limited success in preventing hypoxic injury to neonates. One of the most common limitations of FHR interpretation is the failure to consider chronic and acute clinical factors that may increase the risk of evolving acidemia. This manuscript reviews common clinical factors that may affect the FHR and should be considered when determining the need for early intervention based on changes in the FHR.

Intrapartum fetal heart rate (FHR) decelerations may represent interrupted oxygen transfer to the fetus. In many cases, these interruptions are transient and do not result in progressive fetal acidemia with risk for asphyxia and neurological compromise. When significant FHR decelerations are present, reversible causes of reduced fetal oxygen delivery should be considered and corrective measures should be undertaken to optimize oxygenation. In this review, we describe potential intrapartum causes of reduced fetal oxygen delivery and the efficacy of common interventions for an abnormal FHR tracing.

Objectives: As a vasodilator, nitric oxide is considered to play a significant role in the homeostatic regulation of renal hemodynamics. To test the hypothesis that a kidney graft is capable of producing nitric oxide immediately after renal transplant surgery, we examined the possibility that it positively affects local metabolic acidosis., Materials and Methods: In kidney transplant recipients, we analyzed renal vein and central vein blood samples, which reflect local and systemic metabolic alterations, respectively. Samples were taken immediately after kidney recirculation (that is, the first blood passing through after clamps are released) and at 5, 15, and 30 minutes thereafter. Levels of nitric oxide metabolites (nitrites, nitrates, and their sum), malondialdehyde (an indicator of oxidative damages), and parameters of acid-base balance (pH level, actual excess base, hemoglobin, actual bicarbonate, partial pressure of carbon dioxide, partial pressure of oxygen) were analyzed. Living kidney donors (the recipients' parents) were controls., Results: In renal vein samples, nitrates and the sum of nitrites and nitrates were significantly higher than that shown in control (P < .001) and central vein (P < .05) samples, suggesting an immediate increase in nitric oxide production in the transplanted organ. Metabolic acidosis occurred in both the renal and central vein, indicated by decreased pH and actual bicarbonate level as well as by negative actual base excess level. Only in the renal vein was an increased nitrite and nitrate associated with a reduction of negative actual excess base, thereby suggesting a decrease in anion formation., Conclusions: Transplanted kidneys increase nitric oxide production immediately after organ transplant surgery, which positively affects local metabolic acidosis. The mechanism for this effect is likely local circulation improvement.

Objective: To evaluate whether intrapartum cardiotocography with computer analysis decreases the incidence of newborn metabolic acidosis or obstetric intervention when compared with visual analysis through a systematic review with meta-analysis of randomized controlled trials. Methods: The research was conducted using Medline, Embase, Web of Science, Scopus, ClinicalTrial.gov, Ovid and Cochrane Library as electronic databases from the inception of each database to May 2018. Selection criteria included randomized trial evaluating women with cephalic presentation at term or late preterm term during labor who were randomized to electronic fetal heart rate monitoring with either computer analysis (i.e. intervention group) or standard visual analysis (i.e. control group). Trials evaluating antenatal fetal heart rate monitoring in women not in labor were excluded. The primary outcome was incidence of newborn metabolic acidosis, defined as pH less than 7.05 and base deficit greater than 12 mmol/L. Secondary outcomes were mode of delivery, admission to neonatal intensive care unit, hypoxic-ischemic encephalopathy, and perinatal death. The summary measures were reported as relative risk (RR) with 95% confidence interval (CI). Results: Three randomized controlled trials (RCTs), including 54,492 participants, which met inclusion criteria for this meta-analysis, were analyzed. All the included trials enrolled women with cephalic presentation at term or late preterm. Women were randomized in the active first stage of labor and all of them received continuous cardiotocography (CTG) from randomization until delivery. Women who received continuous CTG during labor with computerized analysis had similar risk of newborn metabolic acidosis. No between group differences were found in the secondary outcomes. Conclusions: Compared with visual analysis, use of computer analysis of fetal monitoring signals during labor did not significantly reduce the rate of metabolic acidosis or obstetric intervention.

Aim: Minimally invasive repair of esophageal atresia with tracheoesophageal fistula (EA/TEF) and congenital diaphragmatic hernia (CDH) is feasible and confers benefits compared to thoracotomy or laparotomy. However, carbon dioxide (CO 2 ) insufflation can lead to hypercapnia and acidosis. We sought to determine the effect of lower insufflation pressures on patients' surrogate markers for CO 2 absorption - arterial partial pressure of CO 2 (PaCO 2 ), end tidal CO 2 (EtCO 2 ) and pH., Methods: Single center retrospective review, including neonates without major cardiac anomaly. Selected patients formed 2 groups: Historical pressure (HP) group and low pressure (LP) group. We reported on the patients' preoperative characteristics that potentially confound the degree of CO 2 absorption or elimination. Outcome measures were perioperative PaCO 2 , EtCO 2 , arterial pH and anesthetic time., Results: 30 patients underwent minimally invasive surgery for CDH and 24 patients for EA/TEF with similar distribution within the HP and LP group. For CDH patients as well as for EA/TEF patients, there were no significant differences in their preoperative characteristics or surgery duration comparing HP and LP groups. With a decrease in insufflation pressure in CDH patients, there were a significant decrease (p = 0.002) in peak PaCO 2 and an improvement in nadir pH (p = 0.01). For the EA/TEF patients, the decrease in insufflation pressure was associated with a significant decrease (p = 0.03) in peak EtCO 2 . Considering all 54 patients, we found EtCO 2 to be highly significantly inversely correlated with pH and positively correlated with intraoperative PaCO 2 (p < 0.001). Baseline Hb was inversely correlated with mean EtCO 2 (p < 0.001)., Conclusion: With lower insufflation pressures, CDH patients had significantly improved hypercapnia and acidosis, while EA/TEF patients had significantly reduced EtCO 2 . EtCO 2 was correlated with acidosis and hypercapnia., Type of Study: Retrospective case control study., Level of Evidence: Level III., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Acidosis in the brain plays an important role in neuronal injury and is a common feature of several neurological diseases. It has been reported that the sodium-hydrogen exchanger-1 (NHE-1) is a key mediator of acidosis-induced neuronal injury. It modulates the concentration of intra- and extra-cellular sodium and hydrogen ions. During the ischemic state, excessive sodium ions enter neurons and inappropriately activate the sodium-calcium exchanger (NCX). Zinc can also enter neurons through voltage-gated calcium channels and NCX. Here, we tested the hypothesis that zinc enters the intracellular space through NCX and the subsequent zinc accumulation induces neuronal cell death after global cerebral ischemia (GCI). Thus, we conducted the present study to confirm whether inhibition of NHE-1 by amiloride attenuates zinc accumulation and subsequent hippocampus neuronal death following GCI. Mice were subjected to GCI by bilateral common carotid artery (BCCA) occlusion for 30 min, followed by restoration of blood flow and resuscitation. Amiloride (10 mg/kg, intraperitoneally ( i.p. )) was immediately injected, which reduced zinc accumulation and neuronal death after GCI. Therefore, the present study demonstrates that amiloride attenuates GCI-induced neuronal injury, likely via the prevention of intracellular zinc accumulation. Consequently, we suggest that amiloride may have a high therapeutic potential for the prevention of GCI-induced neuronal death.

The objectives were to nutritionally induce or blunt ruminal acidosis in young calves and to compare indicators of rumen and systemic health. Ten bull calves (n = 5/diet) were ruminally cannulated at 3 wk of age and received milk replacer and 1 of 2 calf starter diets that were designed to cause (AC; pelleted, 42.7% starch, 15.1% neutral detergent fiber, 57.8% nonfiber carbohydrates) or blunt (BL; texturized, 35.3% starch, 25.3% neutral detergent fiber, 48.1% nonfiber carbohydrates) ruminal acidosis. Mean birth weight was 38.7 ± 1.3 kg. Body weight and calf starter intake were measured weekly. Rumen contents were sampled at -8, -4, 0, 2, 4, 8, 12, and 24 h relative to starter feeding during wk 6, 8, 10, 12, 14, and 16 of age. Blood was collected from the jugular vein during the same weeks for complete blood cell count, blood pH, and partial pressures of oxygen and carbon dioxide. Rate of starter consumption was assessed during wk 16. Marker systems were used to estimate liquid passage and volatile fatty acid absorption rates. Calves were slaughtered at 17 wk, and rumen tissue was collected and assessed for papillae length, width, and degree of tissue degradation. Mean ruminal pH ± standard error was 5.37 ± 0.24 and 5.63 ± 0.24 for AC and BL calves, respectively. Lowest pH values were observed the week after weaning. Total ruminal volatile fatty acid concentrations were 131.5 and 124.8 ± 2.4 mM in AC and BL calves, respectively, and increased with age and time after feeding. Dry matter intake was lower in AC calves at wk 4 and remained lower through wk 16. Rate of starter consumption was also lower in AC calves at wk 16. Body weight also was also lower for AC calves from wk 5 through 16. Blood hemoglobin and hematocrit were lower in AC calves, but other blood characteristics were not different. Rumen volume increased with age and tended to be greater in BL calves. Passage rate and papillae length and width were not different between diets, but AC calves experienced a greater degree of tissue degradation. Ruminal acidosis symptoms in calves appear similar to those in adult cattle, and the etiology of the disease seems to follow similar mechanisms. It is clear from this study that symptoms can be moderated by diet, but further research is needed to determine whether symptoms can be nutritionally prevented or whether calves that experience ruminal acidosis are more susceptible to the disease as adults., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Objectives: Normal saline is the most common crystalloid solution that is used in renal transplant surgery. In this study, our aim was to determine the effects of a combination of half saline and bicarbonate versus normal saline as a routine solution., Materials and Methods: For this double-blind random-ized clinical trial, we enrolled 100 adult patients undergoing kidney transplant. Patients were divided into 2 groups: those who received normal saline and those who received half saline and bicarbonate infusion as fluid replacement therapy during renal transplant. All patients received about 40 mL/kg of crystalloids during surgery. Serial creatinine con-centrations (primary outcomes) were compared between groups at 1, 2, 3, and 7 days after surgery. Urine output (secondary outcome) was compared between groups at recovery and at 6 and 24 hours after surgery. In addition, base excess, chloride, and sodium levels were measured before and 6 hours after surgery. Each liter of half saline-bircarbonate, which is relatively isoosmotic to human plasma, was composed of 70 mEq bicarbonate, 77 mEq chloride, and 147 mEq sodium., Results: Patients who received half saline-bicarbonate had significantly lower postoperative creatinine levels at all time points than patients who received normal saline (P = .019). Serum chloride and sodium levels (P = .001) were significantly higher and base excess (P = .007) was significantly lower in the normal saline group at 6 hours after transplant. At all time points, urine output levels were significantly higher in the half saline-bicarbonate group (P = .001)., Conclusions: The use of half saline-bicarbonate was associated with better early graft function compared with normal saline in the first 7 days after transplant.

Aim: To investigate if potassium citrate, a mild alkaline compound, can prevent metabolic acidosis in children with epilepsy treated with the ketogenic diet without reducing antiepileptic efficacy., Method: In this prospective controlled study, we investigated the frequency of initial uncompensated metabolic acidosis in 51 participants. There were 22 participants with and 29 without potassium citrate supplementation. The ketogenic diet was used as add-on treatment to children with drug resistant epilepsy. We also estimated the proportion of participants with a greater than 50% seizure reduction after 7 months., Results: None of the 22 participants (15 males, seven females; median age 1y 7mo, interquartile range [IQR] 3y 3mo) with, and 10 of 29 (12 males, 17 females; median age 6y 1mo, IQR 4y 8mo) without potassium citrate developed metabolic acidosis (odds ratio=0.04, 95% CI 0.00-0.75 [p<0.01]); median pH 7.32 vs 7.24; [p<0.001]), and median bicarbonate 19.7mmol/L vs 14.0mmol/L (p<0.001). The number of seizures was reduced by more than 50% in 9 of 22 with potassium citrate and 8 of 29 participants without potassium citrate, 7 months after introducing a ketogenic diet (p=0.4)., Interpretation: In the ketogenic diet, potassium citrate supplementation can prevent metabolic acidosis, without reducing antiepileptic efficacy., What This Paper Adds: Citrate supplementation prevents metabolic acidosis in children treated with a ketogenic diet. Efficacy of the ketogenic diet is not affected by supplementation with citrate. Citrate supplementation does not affect beta-hydroxybuturate concentration. Potassium citrate reduces the time needed to reach an optimal ketogenic ratio. This article is commented on by Schoeler on page 8 of this issue., (© 2019 Mac Keith Press.)

Metabolic acidosis is a frequent complication of chronic kidney disease. Although it is known to appear at advanced stages, many studies suggest a state of "global protonic retention" starting at early stages of the disease, responsible of tissue damage, particularly musculoskeletal, alteration of protidic metabolism and endocrine disorders, promoting malnutrition and chronic inflammation, and finally increasing mortality. The majority of international recommandations suggest of supplementation by alkali, most of the time by sodium bicarbonate, to struggle against this complication. An interesting alternative to correct acidosis would consist on the modulation of the endogenous production of acid by playing with the alimentary incomes. In fact, it has been demonstrated that some different types of food produce or consume protons during their metabolism. Low protein diet and rich fresh fruits and vegetables diet would manage to correct at least as well as the supplementation by sodium bicarbonate the metabolic acidosis, and to struggle against its complications, noteworthy by slowing the decline of glomerular filtration rate by limiting the toxic adaptative fibrotic mechanisms, demonstrated by the decrease of urinary tubulo-interstitial suffering markers. Of the condition of being well led, those diets do not seem to expose patients to an over-risk of malnutrition or hyperkaliemia. They therefore appear to be an attractive alternative, efficiency and safe, to fight against chronic kidney disease metabolic acidosis and its complications., (Copyright © 2019. Published by Elsevier Masson SAS.)

Kidney disease affects almost 15% of the US population, and prevalence is anticipated to grow as the population ages and the obesity epidemic continues due to Western dietary practices. The densely caloric Western diet, characterized by high animal protein and low fruit and vegetable content, has fueled the growth of chronic diseases, including chronic kidney disease. The glomerulus or filtering unit of the kidney is very susceptible to barotrauma, and diets high in animal protein impede the glomerulus' ability to protect itself from hemodynamic injury. High animal protein intake combined with low intake of fruits and vegetables also leads to a high net endogenous acid production requiring augmentation of ammonium excretion in order to prevent acidosis. This higher workload of the kidney to maintain a normal serum bicarbonate level may further exacerbate kidney disease progression. This article reviews the potential mechanisms whereby several key characteristics of the typical Western diet may impact kidney disease incidence and progression. Reducing animal protein intake and egg yolk and increasing intake of fruits and vegetables and fiber may prevent or delay end-stage renal disease, but few clinical trials have examined vegetarian diets for management of chronic kidney disease. More research is needed to determine optimal dietary patterns for the prevention of kidney disease and its progression., (Copyright © The Author(s) 2019.)

Intravenous crystalloid therapy is one of the most ubiquitous aspects of hospital and critical care medicine. In recent years, there has been increasing focus on the electrolyte composition, and particularly chloride content, of crystalloid solutions. This has led to increasing clinical adoption of balanced solutions, containing substrates for bicarbonate generation and consequently a lower chloride content, in place of 0.9% saline. In this article we review the physiochemical rationale for avoidance of 0.9% saline and the effects of hyperchloremic acidosis on renal physiology. Finally, we review the current evidence and rationale for use of balanced solutions greater than 0.9% saline in acutely ill patients in a variety of clinical settings, as well as considering the role for sodium bicarbonate in preventing or correcting metabolic acidosis. In conclusion, there is a strong physiological rationale for avoidance of iatrogenic hyperchloremic acidosis from 0.9% saline administration in acutely unwell patients and an association with adverse renal outcomes in several studies. However, evidence from large definitive multicenter randomized trials is not yet available to establish the dose-relationship between 0.9% saline administration and potential harm and inform us if some 0.9% saline use is acceptable or if any exposure confers harm., (Copyright © 2019 Elsevier Inc. All rights reserved.)

According to recent literature sodium bicarbonate (NaHCO 3 ) has been proposed as a performance enhancing aid by reducing acidosis during exercise. The aim of the current review is to investigate if the duration of exercise is an essential factor for the effect of NaHCO 3 . To collect the latest studies from electronic database of PubMed, study publication time was restricted from December 2006 to December 2016. The search was updated in July 2018. The studies were divided into exercise durations of > 4 or ≤ 4 minutes for easier comparability of their effects in different exercises. Only randomized controlled trials were included in this review. Of the 775 studies, 35 met the inclusion criteria. Study design, subjects, effects as well as outcome criteria were inconsistent throughout the studies. Seventeen of these studies reported performance enhancing effects after supplementing NaHCO 3 . Eleven of twenty studies with exercise duration of ≤ 4 minutes showed positive and four diverse results after supplementing NaHCO 3 . On the other hand six of fifteen studies with an exercise duration of >4 minutes showed performance enhancing and two studies showed diverse results. Consequently, the duration of exercise might be influential for inducing a performance enhancing effect when supplementing NaHCO 3 , but to which extent, remains unclear due to the inconsistencies in the study results.

Purpose of Review: The composition and type of intravenous fluids during paediatric anaesthesia have been subjects of debates for decades. Errors in perioperative fluid management in children may lead to serious complications and a negative outcome. Therefore, in this review, historical and recent developments and recommendations for perioperative fluid management in children are presented, based on physiology and focused on safety and efficacy., Recent Findings: Optimized fasting times and liberal clear fluid intake until 1 h improve patient comfort and metabolic and haemodynamic condition after induction of anaesthesia. Physiologically composed balanced isotonic electrolyte solutions are safer than hypotonic electrolyte solutions or saline 0.9% to protect young children against the risks of hyponatraemia and hyperchloraemic acidosis. For intraoperative maintenance infusion, addition of 1-2% glucose is sufficient to avoid hypoglycaemia, lipolysis or hyperglycaemia. Modified fluid gelatine or hydroxyethyl starch in balanced electrolyte solution can safely be used to quickly normalize blood volume in case of perioperative circulatory instability and blood loss., Summary: Physiologically composed balanced isotonic electrolyte solutions are beneficial for maintaining homeostasis, shifting the status more towards the normal range in patients with preexisting imbalances and have a wide margin of safety in case of accidental hyperinfusion.

Decreases in pH (acidosis) in vitro can alter skeletal muscle mitochondrial function [respiration and reactive oxygen species (ROS) emission]. However, because skeletal muscles readily adapt to exercise, the effects of acidosis may be different on sedentary vs. trained muscle. The aim of this work was to compare the effects of pH on skeletal muscle mitochondrial function between sedentary vs. exercise-trained male Sprague-Dawley rats ( n = 10 in each cohort). Rates of mitochondrial respiration and ROS emission were determined from the soleus muscle of both cohorts over a physiologic range of pH values (pH 6.2-7.1). Exercise-trained rats had 14% higher mean muscle buffering capacities; 46 and 40% greater enzyme activity of citrate synthase and lactate dehydrogenase, respectively; and greater activity of respiratory complexes I-IV. ADP-stimulated respiration with complex I and II substrates was ∼25% greater in exercise-trained rats but was unaffected by pH in either cohort. In both cohorts, lowering pH decreased respiration only in complex I- and complex II-supported nonphosphorylating (leak) state. However, as pH decreased, ROS emissions in complex I- and complex II-supported leak state decreased only in sedentary rats; in exercise-trained rats, ROS emissions in this state remained constant. We hypothesize that this effect may result from modulation at complex III, which declined 47% per unit pH in sedentary rats, in comparison to 23% in exercise-trained rats. Taken together, these data suggest that pH regulates mitochondrial respiratory complexes and that exercise training can decrease the effects of pH on skeletal muscle mitochondrial function.-Hedges, C. P., Bishop, D. J., Hickey, A. J. R. Voluntary wheel running prevents the acidosis-induced decrease in skeletal muscle mitochondrial reactive oxygen species emission.

The idea of damage control (DC) is grounded on a sequential therapeutic strategy that supports physiological restoration over anatomic repair in critically injured patients. This concept is firstly described as damage control surgery (DCS) for war-wounded patients with abdominal exsanguinating trauma. The goal was to avoid prolonged operative times and prevent the outset of the lethal cycle of hypothermia, acidosis and coagulopathy. Damage control orthopedics (DCO) is also based on this concept and it is applied in the treatment of some polytrauma patients with pelvic and long bones fractures as to avoid the "second hit" of a lengthy definitive operation and eliminate initial morbidity and mortality. It is in favor of primary fracture stabilization utilizing provisional external fixation. When the patient is in stable condition, conversion to definitive open reduction and intramedullary nailing can be done. This stepwise approach should be considered as a part of the resuscitation process, and it follows the saying "do no further harm".

The aim of this study was to perform a systematic review and meta-analysis on the acute and chronic effects of sodium bicarbonate (NaHCO 3 ) ingestion on Wingate performance. Following a search through PubMed, Scopus and Web of Science, 9 studies were found meeting inclusion criteria (6 acute and 3 chronic). Random-effects meta-analysis of standardized mean difference (SMD) for peak and mean power was performed. Study quality was assessed using the QualSyst. Results of the meta-analysis showed that acute ingestion of NaHCO 3 did not improve Wingate test peak (weighted average effect size Hedges's g = 0.02, 95%CI: - 0.19 to 0.23, P = 0.87) or mean power (weighted average effect size Hedges's g = 0.15, 95%CI: -0.06 to 0.36, P = 0.92). However, chronic ingestion of NaHCO 3 improved Wingate test peak (weighted average effect size Hedges's g = 1.21, 95%CI: 0.83 to 1.42, P = 0.001) and mean power (weighted average effect size Hedges's g = 1.26, 95%CI: 0.96 to 1.56, P = 0.001). Quality assessment of selected articles was classified as strong. This meta-analysis provides evidence that chronic, but not acute, ingestion of NaHCO 3 increases both Wingate test peak and mean power.

The objective of this trial was to determine the benefits of supplementing active dried yeast (ADY; 3 × 1010 CFU/d of Saccharomyces cerevisiae) in diets of growing and finishing steers on ruminal pH and liver health, and evaluate the relationship of these variables with performance traits. Growing beef steers (n = 120) were blocked by weight (i.e., heavy and light) and allocated to 1 of 4 pens in an automated feed intake monitoring system. Steers were fed either control (CON; no ADY) or ADY supplemented in 4 sequential diets: grower diet from days 0 to 70, 2 step up diets (STEP1 and STEP2) for 7 d each, and finishing diet from days 85 to 164. Indwelling rumen boli were administered to monitor rumen pH during days 56 to 106 during the dietary transition. An exchange of pen assignment, within block, occurred on day 70 resulting in 4 final treatment (TRT) assignments: steers fed CON before and after the exchange (CC; n = 30), steers fed CON before and ADY after the exchange (CY; n = 30), steers fed ADY before and CON after the exchange (YC; n = 30), and steers fed ADY (YY; n = 30). Ruminal parameters were analyzed as a randomized complete block design with repeated measures of day, diet and TRT as fixed effects, and block as random effects, using 2 approaches: preliminary analysis of the means or drift analysis (DA; units change from basal values over time). Ruminal pH duration (DUR) below 6.0 (P = 0.05) and 5.8 (P = 0.05) was greater for CY steers than CC steers. Acidosis bout prevalence (pH < 5.6 for 180 consecutive minutes; P < 0.01) and bout DUR (P = 0.05) were greater for CY than other TRT groups. The DA indicated that the ruminal pH variables range, variance, and amplitude of steers in the YC group drifted further from basal pH values than CY and YY steers during the dietary transition (P ≤ 0.02), indicating that removing ADY during the dietary transition was not favorable, but including ADY may reduce ruminal fluctuation. Steers with fewer days experiencing bouts (DEB) had numerically greater ADG (P = 0.11) and tended to have greater G:F (P = 0.06). Liver abscess severity negatively affected ADG (P = 0.04). However, liver abscess severity was not affected by DEB (P = 0.90). There is evidence to suggest that the addition of the specific ADY strain in the diets of beef cattle during the dietary transition may aid in ruminal stabilization, but our study did not find evidence that acidosis bouts were related to abscess prevalence or severity., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Cardiovascular (CV) complications are common in chronic kidney disease (CKD). Numerous metabolic disturbances including hyperphosphatemia, high circulating calciprotein particles (CPP), hyperparathyroidism, metabolic acidosis, and magnesium deficiency are associated with, and likely pathogenic for CV complications in CKD. The goal of this feasibility study was to determine whether effervescent calcium magnesium citrate (EffCaMgCit) ameliorates the aforementioned pathogenic intermediates., Methods: Nine patients with Stage 3 and nine patients with Stage 5D CKD underwent a randomized crossover study, where they took EffCaMgCit three times daily for 7 days in one phase, and a conventional phosphorus binder calcium acetate (CaAc) three times daily for 7 days in the other phase. Two-hour postprandial blood samples were obtained on the day before and on the 7th day of treatment., Results: In Stage 5D CKD, EffCaMgCit significantly increased T50 (half time for conversion of primary to secondary CPP) from baseline by 63% (P = 0.013), coincident with statistically non-significant declines in serum phosphorus by 25% and in saturation of octacalcium phosphate by 35%; CaAc did not change T50. In Stage 3 CKD, neither EffCaMgCit nor CaAc altered T50. With EffCaMgCit, a significant increase in plasma citrate was accompanied by statistically non-significant increase in serum Mg and phosphate. CaAc was without effect in any of these parameters in Stage 3 CKD. In both Stages 3 and 5D, both drugs significantly reduced serum parathyroid hormone. Only EffCaMgCit significantly increased serum bicarbonate by 3 mM (P = 0.015) in Stage 5D., Conclusions: In Stage 5D, EffCaMgCit inhibited formation of CPP, suppressed PTH, and conferred magnesium and alkali loads. These effects were unique, since they were not observed with CaAc. In Stage 3 CKD, neither of the regimens have any effect. These metabolic changes suggest that EffCaMgCit might be useful in protecting against cardiovascular complications of CKD by ameliorating pathobiologic intermediates.

The effect of wood kraft pulp (KP) feed on dietary digestibility, ruminal fluid pH, rumen fermentation characteristics, and milk production performance in lactating dairy cows was examined. Four lactating dairy cows were used for the feeding experiment by the cross-over design. The control group and KP group were set up as treatments. The control group was fed total mixed ration (TMR) (40% roughage and 60% concentrate) and the KP group was fed TMR containing 12% KP that replaced half of the rolled corn in the control diet. The dry matter intake, digestibility of the feed components, and milk yield were not significantly different between control group and KP group. The number of times that the ruminal fluid pH was below 6.1 tended to decrease in the KP group compared to the control group (p < 0.10). The acetic acid ratio in the ruminal fluid of the KP group increased compared to the control group (p < 0.05) and the propionic acid ratio in the ruminal fluid of the KP group decreased compared to the control group (p < 0.05). The acetate:propionate acid ratio was increased in the KP group compared with the control group (p < 0.05). Lipopolysaccharide levels in the ruminal fluid of the KP group tended to decrease compared to the control group (p < 0.10). Based on these results, it was indicated that the use of KP feed for lactating dairy cows induced the same rumen fermentation characteristics as those in cows given a large amount of roughage without depressing milk productivity. Therefore, KP could be a valuable feed resource substitute for grains, which would also reduce the risk for subacute rumen acidosis., (© 2018 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.)

Objectives: Geophagy has several hypothesized functions, among them (1) detoxification of plant secondary compounds, for example, tannins, (2) buffering stomach pH to alleviate acidosis caused by high sugar intake, and (3) supplementing the diet with mineral nutrients. We tested these hypotheses in Nepal gray langurs (Semnopithecus schistaceus), a foregut fermenter for which fruits and leaves dominate the diet at different times of the year., Materials and Methods: We collected data on feeding time per food item for 21 unprovisioned adult langurs at Ramnagar, Nepal, for 1 year using instantaneous sampling (773 observation hours). We combined these data with relative sugar and tannin content of food items to estimate diet content. We collected rainfall data to distinguish the wet season (May-September) from the dry season (October-April). We collected soil samples from consumption and control sites to test for pH and sodium, potassium, magnesium, and calcium concentrations., Results: Langurs consumed soil from two sources: termite structures (in almost all months) and river banks and beds (mainly in the dry season). Soil feeding was not positively correlated with dietary tannin or sugar content (GLMM). Soil pH was not high enough to buffer stomach contents. Only sodium was significantly higher in consumed soil., Discussion: The most likely function of geophagy was the acquisition of sodium. This conclusion is consistent with reports for other animals. Buffering stomach pH, an often-suggested function for animals with ruminant-like digestion, was not supported. Detoxification, often proposed for animals with a diet high in secondary compounds, was also not supported., (© 2018 Wiley Periodicals, Inc.)

Background: Spinal anesthesia is the standard technique for elective cesarean section, but the incidence of maternal hypotension in this setting is reportedly about 80%, without any prophylactic management. Vasopressors are the most reliable method for counteracting the hypotension induced by spinal anesthesia. However, studies investigating the effects of vasopressors have yielded inconsistent and debatable results. Therefore, we plan to conduct a systematic review and network meta-analysis to identify the most effective vasopressor to prevent maternal hypotension, and to decrease fetal acidosis in women undergoing spinal anesthesia for elective cesarean section., Methods: A systematic and comprehensive search to detect all the randomized controlled studies on vasopressors for the management of maternal hypotension during cesarean section under spinal anesthesia will be performed using information in the databases, MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar, beginning from their inception to October 2018. We will conduct a network meta-analysis to combine the direct and indirect comparisons of the vasopressors. We will use the surface under the cumulative ranking curve (SUCRA) values and rankograms to present the hierarchy of vasopressors. A comparison-adjusted funnel plot will be used to assess the presence of small-study effects. The quality of the studies included will be assessed using the risk of bias tool. All statistical analyses will be performed using Stata SE version 15.0., Ethics and Dissemination: This systematic review and meta-analysis will be published in a peer-reviewed journal. Ethical approval and informed consent are not required, as the study will be a literature review and will not involve direct contact with patients or alterations to patient care., Trial Registration Number: The protocol for this review has been registered in the PROSPERO network (registration number: CRD42018111852).

Metabolic acidosis is the most common acid-base disorder in septic patients and is associated with increased mortality. Previously, we demonstrated that sepsis induced by cecal ligation and puncture (CLP) impairs [Formula: see text] absorption in the medullary thick ascending limb (MTAL) by 1) decreasing the intrinsic [Formula: see text] absorptive capacity and 2) enhancing inhibition of [Formula: see text] absorption by LPS through upregulation of Toll-like receptor (TLR) 4 signaling. Both effects depend on ERK activation. Monophosphoryl lipid A (MPLA) is a detoxified TLR4 agonist that enhances innate antimicrobial immunity and improves survival following sepsis. Pretreatment of MTALs with MPLA in vitro prevents LPS inhibition of [Formula: see text] absorption. Here we examined whether pretreatment with MPLA would protect the MTAL against sepsis. Vehicle or MPLA was administered to mice 48 h before sham or CLP surgery, and MTALs were studied in vitro 18 h postsurgery. Pretreatment with MPLA prevented the effects of sepsis to decrease the basal [Formula: see text] absorption rate and enhance inhibition by LPS. These protective effects were mediated through MPLA stimulation of a Toll/IL-1 receptor domain-containing adaptor-inducing IFN-β-(TRIF)-dependent phosphatidylinositol 3-kinase-Akt pathway that prevents sepsis- and LPS-induced ERK activation. The effects of MPLA to improve MTAL [Formula: see text] absorption were associated with marked improvement in plasma [Formula: see text] concentration, supporting a role for the kidneys in the pathogenesis of sepsis-induced metabolic acidosis. These studies support detoxified TLR4-based immunomodulators, such as MPLA, that enhance antimicrobial responses as a safe and effective approach to prevent or treat sepsis-induced renal tubule dysfunction and identify cell signaling pathways that can be targeted to preserve MTAL [Formula: see text] absorption and attenuate metabolic acidosis during sepsis.

We investigated the effect of sodium butyrate feeding on the disruption of ruminal epithelium barrier function in goats fed a high-concentrate diet. A total of 18 male Boer goats (live weight of 31.75 ± 1.35 kg, aged 1 year) were randomly assigned to three groups, which were fed a low-concentrate diet (LC), a high-concentrate diet (HC), or a high-concentrate diet with 1% sodium butyrate by weight (SH) for 9 weeks. We found that the pH of rumen fluid in the SH and LC groups was higher than that in the HC group. The activity of protein kinase C (PKC) kinase in the rumen epithelium was higher in the HC group than that in the LC and SH groups. The mRNA expression and phosphorylated protein levels of mitogen-activated protein kinases (MAPKs) in the rumen epithelium were lower in the SH and LC groups than those in the HC group. The DNA methylation rate of occludin was higher in the HC group than that in the SH and LC groups. The mRNA and protein expression of claudin-1, claudin-4, occludin, and zona occludin-1 was greater in the SH and LC groups than that in the HC group. In addition, sodium butyrate mitigated damage to the rumen epithelium caused by the HC diet. Together, our results suggest that the supply of sodium butyrate reverses the damage of rumen epithelium tight junction by inhibiting PKC and MAPK signaling pathways and is protective to the rumen epithelium during subacute rumen acidosis.

Background: In developed countries, ambulances normally carry oxygen cylinders, but not compressed air. Treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with oxygen-driven nebulisers can result in hypercapnia and acidosis. Attempts to avoid this have involved interrupted administration of oxygen. However, small battery-powered air nebulisers are now available. This study aims to compare the prehospital oxygen saturations and treatment of patients suffering from AECOPD before and after the introduction of air nebulisers., Methods: The oxygen saturations and treatment of 200 AECOPD patients before and 200 AECOPD patients after the introduction of air nebulisers were compared. Compliance with a target saturation of 88-92% was calculated., Results: The median final oxygen saturation was lower for the post-intervention category (94%) than the pre-intervention category (96%). There was an increase in air nebuliser use from 0 to 56% (P < 0.001) and a decrease in oxygen use from 100 to 71.5% (P < 0.001). There was a numerical increase in the proportion of patients arriving at hospital with oxygen saturations of 88-92% following introduction of the air nebulisers (24 vs 16.5%) and a decrease in patients arriving with high saturations (67.5 vs 76.5%). The likelihood of achieving the target oxygen saturations following introduction of air nebulisers increased (odds ratio 1.598; 95% confidence interval 0.974, 2.621)., Conclusion: The introduction of prehospital air nebulisers resulted in a reduction in oxygen therapy in patients with AECOPD and a lower median prehospital oxygen saturation. This study supports the use of air nebulisers in the prehospital setting., (© 2017 Royal Australasian College of Physicians.)

Acid hydrarthrosis is another important pathological character in rheumatoid arthritis (RA), and acid-sensing ion channel 1a (ASIC1a) plays a destructive role in acidosis-induced articular chondrocyte cytotoxicity. Recently, ASIC2a has been reported to possess neuroprotective effect on acidosis-induced injury of neuronal cells. However, whether ASIC2a has an enhanced effect on the protective effect of blocking ASIC1a and ASIC3 against acid-induced chondrocyte apoptosis is still unclear. The aim of present study was to investigate the chondroprotective effect of ASIC2a with PcTx1 (ASIC1a specific blocker) and APETx2 (ASIC3 specific blocker) on acidosis-induced chondrocyte apoptosis. Our results revealed that acid (pH 6.0) decreased the cell viability and induced apoptosis of articular chondrocytes. PcTx1 and APETx2 combination significantly attenuated acidosis-induced chondrocyte cytotoxicity due to inhibit apoptosis, and this role could be enhanced by ASIC2a overexpression compared with the PcTx1 and APETx2 combination alone group. Moreover, both the [Ca 2+ ] i levels and the levels of phosphorylated ERK1/2 as well as p38 were further reduced in acidosis-induced chondrocytes after ASIC2a overexpression in the presence of PcTx1 and APETx2. Furthermore, ASIC2a overexpression also reduced acid-induced the expression of ASIC1a. In addition, ASIC2a overexpression further promoted the PcTx1 and APETx2-increased levels of type II collagen in acidosis-induced chondrocytes. Taken together, the current data suggested that ASIC2a overexpression might enhance the anti-apoptotic and protective role of PcTx1 and APETx2 against acid-induced rat articular chondrocyte apoptosis by regulating ASIC1a expression and the [Ca 2+ ] i levels and at least in part, suppressing p38 and ERK1/2 MAPK signaling pathways., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Rumen health is of vital importance in ensuring healthy and efficient dairy cattle production. Current feeding programs for cattle recommend concentrate-rich diets to meet the high nutritional needs of cows during lactation and enhance cost-efficiency. These diets, however, can impair rumen health. The term "subacute ruminal acidosis" (SARA) is often used as a synonym for poor rumen health. In this review, we first describe the physiological demands of cattle for dietary physically effective fiber. We also provide background information on the importance of enhancing salivary secretions and short-chain fatty acid absorption across the stratified squamous epithelium of the rumen; thus, preventing the disruption of the ruminal acid-base balance, a process that paves the way for acidification of the rumen. On-farm evaluation of dietary fiber adequacy is challenging for both nutritionists and veterinarians; therefore, this review provides practical recommendations on how to evaluate the physical effectiveness of the diet based on differences in particle size distribution, fiber content, and the type of concentrate fed, both when the latter is part of total mixed ration and when it is supplemented in partial mixed rations. Besides considering the absolute amount of physically effective fiber and starch types in the diet, we highlight the role of several feeding management factors that affect rumen health and should be considered to control and mitigate SARA. Most importantly, transitional feeding to ensure gradual adaptation of the ruminal epithelium and microbiota; monitoring and careful management of particle size distribution; controlling feed sorting, meal size, and meal frequency; and paying special attention to primiparous cows are some of the feeding management tools that can help in sustaining rumen health in high-producing dairy herds. Supplementation of feed additives including yeast products, phytogenic compounds, and buffers may help attenuate SARA, especially during stress periods when the risk of a deficiency of physically effective fiber in the diet is high, such as during early lactation. However, the usage of feed additives cannot fully compensate for suboptimal feeding management., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate long-term effects of staff training and electronic clinical decision support (CDS) on adherence to lung-protective ventilation recommendations., Materials and Methods: In 2012, group instructions and workshops at two surgical intensive care units (ICUs) started, focusing on standardized protocols for mechanical ventilation and volutrauma prevention. Subsequently implemented CDS functions continuously monitor ventilation parameters, and from 2015 triggered graphical notifications when tidal volume (V T ) violated individual thresholds. To estimate the effects of these educational and technical interventions, we retrospectively analyzed nine years of V T records from routine care. As outcome measures, we calculated relative frequencies of settings that conform to recommendations, case-specific mean excess V T , and total ICU survival., Results: Assessing 571,478 V T records from 10,241 ICU cases indicated that adherence during pressure-controlled ventilation improved significantly after both interventions; the share of conforming V T records increased from 61.6% to 83.0% and then 86.0%. Despite increasing case severity, ICU survival remained nearly constant over time., Conclusions: Staff training effectively improves adherence to lung-protective ventilation strategies. The observed CDS effect seemed less pronounced, although it can easily be adapted to new recommendations. Both interventions, which futures studies could deploy in combination, promise to improve the precision of mechanical ventilation., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)