Acid-base Disturbances Research Articles

Impact of Genetic Polymorphisms on Electrochemical Parameters and Acid-Base Disorders in Brazilian Runners During a 105-Kilometer Ultramarathon.

This study focused on a group of 22 elite male mountain runners from Brazil (average age of 35.9 ± 6.5 years) with the objective of exploring the possible roles of the ACTN3 R577X, ACE I/D, and CK MM A/G NcoI genetic variants in shaping electrochemical profiles and maintaining acid-base homeostasis during a 105-km ultramarathon. Genotyping for each polymorphism (ACTN3: RR, RX, XX; ACE: DD, ID, II; CK MM: AA, AG, GG) was conducted using PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism), and saliva samples were used to obtain DNA. Analyses of electrochemical and acid-base disturbances were performed in real time. It was observed that athletes who completed the race in less time had lower calcium concentrations (Rs = 0.35; p = 0.016). Pre-race, the RX genotype showed a 14.19% reduction in potassium levels compared to RR (p = 0.01). The GG genotype showed potassium levels 19.36% higher than AA (p = 0.01) and a 6.11% increase in hematocrit values compared to AA (p = 0.03). Additionally, the AG genotype exhibited hematocrit values 5.44% higher than AA (p = 0.03). Post-race, the XX genotype demonstrated higher hematocrit values compared to RX, with an increase of 8.92% (p = 0.03). The II genotype showed a 0.27% increase in pH compared to ID (p = 0.02) and a 20.42% reduction in carbon dioxide levels (p = 0.01). The findings emphasize the impact of the examined polymorphisms on the modulation of electrochemical factors and the maintenance of acid-base equilibrium in athletes during 105 km ultramarathons.

A Study of Hydroelectrolytic and Acid-Base Disturbances in MIS-C Patients: A Perspective on Antidiuretic Hormone Secretion.

COVID-19-associated multisystem inflammatory syndrome in children (MIS-C) is a rare autoimmune disorder characterized by a range of polymorphic manifestations, similar to but distinct from other well-known inflammatory syndromes in children. We conducted a retrospective-descriptive study in which we summarized the clinical presentation of, biomarker variations in, and complications occurring in patients diagnosed with MIS-C, admitted to the Emergency Clinical Hospital for Children "Sf. Ioan", Galati, between July 2020 and June 2024. A total of 36 children met the MIS-C classification criteria according to the WHO-approved case definitions. A total of 41.7% (n = 15) were male and 58.3% (n = 21) were female. The median age of the study group was 4 years (IQR: 1.75-9.25 years). Surgical involvement was suspected in 16.7% (n = 6) of the patients, while 52.8% (n = 19) required intensive care. Clinically, fever was the most common symptom present in 89% (n = 32) of the cases. Gastrointestinal disorders were also common, with 50% (n = 18) presenting with inappetence, 42% (n = 15) with vomiting, and 39% (n = 14) with abdominal pain from admission, which worsened over time. Paraclinically, all patients exhibited signs of inflammation, and 86.1% (n = 31) had hydroelectrolytic and acid-base imbalances. The median hospital stay was 10 days (IQR: 7-12 days), with a stagnant clinical course in most cases. The inflammatory mechanisms in MIS-C, which can affect the secretion of antidiuretic hormone (ADH), were correlated with hydroelectrolytic disturbances and may lead to severe complications. For this reason, it is imperative to evaluate hydroelectrolytic disorders in the context of MIS-C and use diagnostic and prognostic biomarkers to develop effective therapeutic management strategies, ultimately improving the quality of life of affected children.

Optimizing Continuous Renal Replacement Therapy with Regional Citrate Anticoagulation: Insights from the ORCA Trial-A Retrospective Study on 10 Years of Practice.

(1) Background: Citrate is preferred in continuous renal replacement therapy (CRRT) for critically ill patients because it prolongs filter life and reduces bleeding risks compared to unfractionated heparin (UFH). However, regional citrate anticoagulation (RCA) can lead to acid-base disturbances, citrate accumulation, and overload. This study compares the safety and efficacy of citrate-based CRRT with UFH and no anticoagulation (NA) in acute kidney injury (AKI) patients. (2) Methods: A retrospective analysis was conducted on adult patients (≥18 years) who underwent CRRT from July 2010 to June 2021 in an intensive care unit. (3) Results: Among 829 AKI patients on CRRT: 552 received RCA, 232 UFH, and 45 NA. The RCA group had a longer filter lifespan compared to UFH and NA (56 h [IQR, 24-110] vs. 36.0 h [IQR, 17-63.5] vs. 22 h [IQR, 12-48]; all Padj < 0.001). Bleeding complications were fewer in the RCA group than in the UFH group (median 3 units [IQR, 2-7 units] vs. median 5 units [IQR, 2-12 units]; Padj < 0.001) and fewer in the NA group than in the UFH group (median 3 units [IQR, 1-5 units] vs. 5 units [IQR, 2-12 units]; Padj = 0.03). Metabolic alkalosis was more common in the RCA group (32.5%) compared to the UFH (16.2%) and NA (13.5%) groups, while metabolic acidosis persisted more in the UFH group and NA group (29.1% and 34.6%) by the end of therapy vs. the citrate group (16.8%). ICU mortality was lower in the RCA group (52.7%) compared to the UFH group (63.4%; Padj = 0.02) and NA group (77.8%; Padj = 0.003). (4) Conclusions: Citrate anticoagulation outperforms heparin-based and no anticoagulation in filter patency, potentially leading to better outcomes through improved therapy effectiveness and reduced transfusion needs. However, careful monitoring is crucial to limit potential complications attributable to its use.

Acute freshwater CO2 exposure does not impair seawater transfer in three different sizes of Atlantic salmon (Salmo salar) subjected to different photoperiod manipulations.

There is a growing interest in Atlantic salmon (Salmo salar) aquaculture to extend the time fish are reared in freshwater (FW) recirculating aquaculture systems (RAS), producing larger FW salmon that can then be induced to undergo smoltification before transfer into marine net pens for grow-out and harvest. Smolts can be produced by photoperiod (PT) manipulation in RASs, but little is known about how delaying smoltification to larger body sizes affects susceptibility to elevated CO2 levels (hypercapnia), which can occur at high stocking densities in FW RAS or during transport from FW RAS rearing facilities to marine net pens. To address this, Atlantic salmon were reared from hatch to one of three different sizes (~230, ~580, or ~1300 g) in FW (3 ppt) under continuous light (24:0, light:dark). Once fish reached the desired sizes, a group of salmon were maintained on continuous light 24L:0D to serve as a control salmon. A second group of salmon were exposed to 8 weeks of 12L:12D and then to 4 weeks of 24L:0D to serve as PT treatment salmon, which is the PT manipulation commonly used in Atlantic salmon aquaculture to induce smoltification. At the end of PT manipulation, both control and PT treatment salmon were exposed to 0% or 1.5% CO2 (30 mg/L) for 96 h in FW and then transferred to air-equilibrated seawater (SW, 35 ppt, normocapnia). Salmon were sampled at the end of the 96-h FW CO2 exposure and at 24 h and 7 days in SW for measurements of blood ion/acid-base status, muscle water content (MWC), and gill and kidney Na+/K+ ATPase (NKA) activity. Exposure to 96 h of CO2 in FW resulted in acid-base disturbances in fish from all three size classes, with decreases in blood pH and increases in blood PCO2 and plasma [HCO3 -] but no mortality. Despite these large acid-base disturbances in FW, after transfer to normocapnic SW, there were no significant effects of CO2 exposure on extracellular blood pH, intracellular red blood cell pH, or plasma osmoregulatory status for all three sizes of post-smolt salmon. In general, SW transfer was associated with significant increases in plasma ions and osmolality, as well as gill and kidney NKA activity after 24 h and 1 week in SW with no significant impacts between different sizes of salmon. Thus, exposure to 30 mg CO2/L that mimics levels experienced during transport from FW RAS to an SW transfer site may have minimal effects on Atlantic salmon smolts up to 1300 g.

A-342 Precision Evaluation of the pH, PO2 and PCO2 tests in the i-STAT® G3+ Cartridge using the i-STAT 1 System for Venous, Arterial and Capillary Whole Blood Specimens in Clinical Settings

Abstract Background Precise and accurate measurements of blood gases are important for the diagnosis, monitoring and treatment of respiratory, metabolic, and acid-base disturbances. This study demonstrates the precision of the pH, partial pressure of oxygen (PO2), and partial pressure of carbon dioxide (PCO2) tests in the i-STAT G3+ cartridge with the i-STAT 1 System in arterial, venous, and capillary whole blood specimens in point-of-care or clinical laboratory settings. Methods The precision of the i-STAT pH, PO2, and PCO2 tests in the i-STAT G3+ cartridge was assessed at external clinical sites by end-users using whole blood specimens across the measurement range for each test: pH (6.500 - 7.800 pH units), PO2 (5 - 700 mmHg), PCO2 (5.0 - 130.0 mmHg). The study included venous whole blood samples from ∼140 adult subjects (≥ 18 years) and arterial whole blood samples from ∼140 adult subjects at 3 clinical sites. Each whole blood sample was run in duplicate on the i-STAT G3+ cartridge. In addition, ∼140 specimens were collected in capillary tubes using two fingerstick draws from adult subjects and ∼20 capillary heel-stick specimens were collected into two capillary tubes from neonate subjects (birth - 28 days) at two clinical sites. Specimens used in this study were prospectively collected venous, arterial, or capillary specimens under an Institutional Review Board approved informed consent or were de-identified leftover venous or arterial specimens. For each specimen type, duplicates from each subject were grouped into subintervals based on their mean values. The subintervals included the medical decision levels of 7.300, 7.350 and 7.450 pH units for pH, 30, 45 and 60 mmHg for PO2 and 35, 45, 50 and 70 mmHg for PCO2. The estimates of the pooled standard deviation (SD) and pooled coefficient of variation (%CV), as well as their respective 95% confidence intervals were calculated for each subinterval. Results Across all specimen types (excluding outliers), the pooled SD for pH ranged from 0.00591 - 0.01747 pH units for subintervals 6.500 - 7.300, &amp;gt;7.300 - 7.450, &amp;gt;7.450 - 7.800 pH units. For PO2, the pooled SD ranged from 0.71 - 3.76 mmHg for subintervals 10 - 40 mmHg and &amp;gt;40 - 50 mmHg and the pooled %CV ranged from 1.63 - 8.76 %CV for subintervals &amp;gt;50 - 100 mmHg, &amp;gt;100 - 250 mmHg and &amp;gt;250 - 700 mmHg. For PCO2, the pooled SD ranged from 0.000 - 1.709 mmHg for subintervals 5.0 - 35.0 mmHg, &amp;gt;35.0 - 50.0 mmHg and &amp;gt;50.0 - 62.5 mmHg and the pooled %CV ranged from 1.10 - 3.62 %CV for subinterval &amp;gt;62.5 - 130.0 mmHg. Conclusions The precision study demonstrated that the pH, PO2 and PCO2 tests in the i-STAT G3+ cartridge when tested using the i-STAT 1 System deliver precise results within ∼2 minutes for venous, arterial, and capillary whole blood patient specimens when tested by end users in a point-of-care or clinical laboratory setting. These studies were funded by Abbott Laboratories.

A-329 Accuracy of the pH, PO2, and PCO2 Tests in the i-STAT® G3+ Cartridge Using the i-STAT 1 System for Venous, Arterial and Capillary Whole Blood Specimens in Clinical Settings

Abstract Background Precise and accurate measurements of blood gases are important for the diagnosis, monitoring and treatment of respiratory, metabolic, and acid-base disturbances. This study demonstrates the accuracy of the pH, partial pressure of oxygen (PO2), and partial pressure of carbon dioxide (PCO2) tests in the i-STAT G3+ cartridge with the i-STAT 1 System in arterial, venous, and capillary whole blood specimens in point of care or clinical laboratory settings. Methods The accuracy of the PO2, and PCO2 tests in the i-STAT G3+ cartridge was assessed at external clinical sites in a method comparison study using whole blood specimens across the measurement range for each test: pH 6.5-7.8, PO2 5-700 mmHg, PCO2 5.0-130.0 mmHg. Specimens used in this study were venous, arterial, and capillary specimens prospectively collected under Institutional Review Board-approved informed consent or were leftover de-identified venous or arterial specimens. The study included venous and arterial whole blood samples from ∼140 adult subjects (≥ 18 years) at 3 clinical sites, and capillary whole blood samples from ∼180 adult subject at 3 clinicals sites and ∼25 neonate subjects (birth to 28 days) at 2 clinical sites. The RapidPoint System was used as comparator. For venous and arterial whole blood, samples were collected and tested in duplicate on the i-STAT G3+ cartridge and in singlicate on the RapidPoint System. For capillary whole blood samples, adult fingerstick samples and neonate heel-stick samples were collected in capillary tubes and tested in singlicate on the i-STAT G3+ cartridge and on the RapidPoint System. Passing-Bablok regression was performed for venous and arterial whole blood samples combined, using the first replicate from the i-STAT G3+ cartridge versus the singlicate result from the comparator, and for capillary whole blood samples (adult and neonate combined) using the singlicate result from the i-STAT G3+ cartridge versus the singlicate result from the comparator. Results Passing-Bablok regression of i-STAT G3+ cartridge results versus the comparator was used to calculate slope and correlation coefficient (r). For adult venous and arterial whole blood results, pH had slope = 0.96 and r = 0.99, PO2 had slope = 1.05 and r = 1.00, and PCO2 had slope = 1.04 and r = 0.98. For adult and neonate capillary whole blood results, pH had slope = 1.02 and r = 0.98, PO2 had slope = 1.09 and r = 0.99, and PCO2 had slope = 1.07 and r = 0.96. Conclusions These results demonstrate that the i-STAT 1 System delivers accurate pH, PO2, and PCO2 test results with ∼2 minutes using the i-STAT G3+ cartridge for venous, arterial and capillary whole blood samples for adult and neonate subjects when tested by end-users in a point of care or clinical laboratory setting. This study was funded by Abbott Laboratories.

Soluble adenylyl cyclase is an acid-base sensor in rainbow trout red blood cells that regulates intracellular pH and haemoglobin-oxygen binding.

To identify the physiological role of the acid-base sensing enzyme, soluble adenylyl cyclase (sAC), in red blood cells (RBC) of the model teleost fish, rainbow trout. We used: (i) super-resolution microscopy to determine the subcellular location of sAC protein; (ii) live-cell imaging of RBC intracellular pH (pHi) with specific sAC inhibition (KH7 or LRE1) to determine its role in cellular acid-base regulation; (iii) spectrophotometric measurements of haemoglobin-oxygen (Hb-O2) binding in steady-state conditions; and (iv) during simulated arterial-venous transit, to determine the role of sAC in systemic O2 transport. Distinct pools of sAC protein were detected in the RBC cytoplasm, at the plasma membrane and within the nucleus. Inhibition of sAC decreased the setpoint for RBC pHi regulation by ~0.25 pH units compared to controls, and slowed the rates of RBC pHi recovery after an acid-base disturbance. RBC pHi recovery was entirely through the anion exchanger (AE) that was in part regulated by HCO3 --dependent sAC signaling. Inhibition of sAC decreased Hb-O2 affinity during a respiratory acidosis compared to controls and reduced the cooperativity of O2 binding. During invitro simulations of arterial-venous transit, sAC inhibition decreased the amount of O2 that is unloaded by ~11%. sAC represents a novel acid-base sensor in the RBCs of rainbow trout, where it participates in the modulation of RBC pHi and blood O2 transport though the regulation of AE activity. If substantiated in other species, these findings may have broad implications for our understanding of cardiovascular physiology in vertebrates.

COVID-19 and DKA of Type 2 Diabetes, Impact and Outcome

Abstract Background Recent evidence suggests a potential link between COVID-19 infection and the development of insulin dependence in individuals with diabetes, particularly through direct damage to pancreatic insulin-producing beta-cells mediated by the virus's affinity for ACE2 receptors. This association bears similarities to the role of other viruses like enteroviruses and mumps in causing fulminant ketoacidosis. While it is feasible that the insulin dependence seen in diabetic ketoacidosis (DKA) during COVID-19 arises from SARS-CoV-2-induced beta cell dysfunction, stronger evidence supports an alternate pathway involving indirect factors like systemic hypoxia, sepsis, inflammatory responses, and cytokine storms resulting from the infection. Aim of the Work This study aimed to assess the risk factors and outcomes related to DKA in COVID-19-infected patients with type 2 diabetes. Patients and Methods The research analyzed data from 70 patients, comprising 35 with DKA and 35 without DKA, focusing on variables such as age, sex, comorbidities, laboratory results, and clinical symptoms. The mean age was found to be significantly higher in the DKA group, aligning with previous studies that linked older age to increased DKA susceptibility during COVID-19. Sex distribution did not show significant differences between the DKA and non-DKA groups. Results Notably, patients with DKA displayed longer diabetes duration and significantly higher hemoglobin A1c levels, suggesting a potential role of poor glucose control in precipitating DKA during COVID-19 infection. Furthermore, DKA patients exhibited more severe acid-base disturbances and electrolyte imbalances compared to their non-DKA counterparts. These imbalances, along with respiratory and cardiovascular symptoms, characterized the clinical presentation of DKA during COVID-19. Conclusion Ultimately, the mortality rate was found to be markedly higher among DKA patients than among non-DKA patients. These findings emphasize the importance of recognizing the complex interplay between COVID-19 infection, diabetes, and DKA, especially in older individuals with longer diabetes duration and poor glycemic control. This study provides valuable insights into the risk factors and clinical outcomes associated with DKA in COVID-19-infected patients with type 2 diabetes, contributing to our understanding of the multifaceted relationship between these medical conditions. Further research is needed to elucidate the underlying mechanisms and optimize management strategies for this vulnerable patient population.

Metabolic alkalosis treatment standard.

The kidney is poised to defend against development of metabolic alkalosis through non-adaptive mechanisms in the proximal nephron and adaptive processes in the distal nephron. Despite a prodigious capacity to excrete base, metabolic alkalosis is the most common acid-base disturbance in hospitalized patients. Development of this disorder requires pathophysiologic changes leading to generation of new HCO3- combined with an augmentation in the capacity of the kidney to reclaim filtered HCO3-. The initial approach to these patients is careful assessment of effective arterial blood volume focusing on the physical examination and urine electrolytes. Identifying the mechanisms by which the kidney's ability to correct alkalosis are perturbed provides an understanding of the clinical approach to differential diagnosis and appropriate treatment. While metabolic alkalosis is frequently not dangerous, in certain settings, metabolic alkalosis may contribute to mortality and should be aggressively managed.

Association of alactic base excess with in-hospital mortality in patients with acute myocardial infarction: a retrospective cohort study

BackgroundAlactic base excess (ABE) is a novel biomarker to evaluate the renal capability of handling acid-base disturbances, which has been found to be associated with adverse prognosis of sepsis and shock patients. This study aimed to evaluate the association between ABE and the risk of in-hospital mortality in patients with acute myocardial infarction (AMI).MethodsThis retrospective cohort study collected AMI patients’ clinical data from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The outcome was in-hospital mortality after intensive care unit (ICU) admission. Univariate and multivariate Cox proportional hazards models were performed to assess the association of ABE with in-hospital mortality in AMI patients, with hazard ratios (HRs) and 95% confidence intervals (CI). To further explore the association, subgroup analyses were performed based on age, AKI, eGFR, sepsis, and AMI subtypes.ResultsOf the total 2779 AMI patients, 502 died in hospital. Negative ABE (HR = 1.26, 95%CI: 1.02–1.56) (neutral ABE as reference) was associated with a higher risk of in-hospital mortality in AMI patients, but not in positive ABE (P = 0.378). Subgroup analyses showed that negative ABE was significantly associated with a higher risk of in-hospital mortality in AMI patients aged>65 years (HR = 1.46, 95%CI: 1.13–1.89), with eGFR<60 (HR = 1.35, 95%CI: 1.05–1.74), with AKI (HR = 1.32, 95%CI: 1.06–1.64), with ST-segment elevation acute myocardial infarction (STEMI) subtype (HR = 1.79, 95%CI: 1.18–2.72), and without sepsis (HR = 1.29, 95%CI: 1.01–1.64).ConclusionNegative ABE was significantly associated with in-hospital mortality in patients with AMI.

Biochemical Approach of Acid-Base Disturbances: Diagnosis Algorithm

Context: The biochemical approach to acid-base balance classifies disturbances in two categories based on cellular mechanisms. The first one being cellular respiration (ATP), which presents high anion gap and changes in carbon dioxide levels, and the second one, cellular metabolism (ion transport through membrane channels), which evidences normal anion gap and changes in other cations and anions. Objective: To present a new diagnostic algorithm for acid-base disturbances, based on the biochemical approach. Method: Original research with systematic analysis and data organization, following biochemical processes that affect acid-base balance. Results: A simple, three-step algorithm which classifies information in a diagnostic table that connects blood gas analysis results (pH, anion gap or base excess, bicarbonate, carbon dioxide and unmeasured anions) with the biochemical cause and most probable clinical findings. Conclusions: The biochemical approach is considered the new model to understand, explain and diagnose acid-base balance and disturbances. All high anion gap disturbances occur in cellular respiration, while all normal anion gap disturbances occur in membrane channel function. The diagnosis algorithm simplifies and organizes the information to describe medical conditions with data from a blood gas analysis. This approach is the first model to establish a linear correlation between lab results, biochemical cause, and clinical findings of acid-base disturbances.

Metabolic alkalosis: a new red flag in status epilepticus

BackgroundStatus epilepticus (SE) is a heterogeneous neurological emergency with significant variability in prognosis, influenced by underlying disease and pathophysiological context. Acid–base disturbances are common in critically ill patients, yet their distribution and impact in SE patients remain poorly understood.MethodsThis was an observational cohort study including non-hypoxic SE patients with available blood gas analysis within the first 24 h of SE, treated at the University Hospital of Geneva, Switzerland between 2015 and 2023. Acid–base disturbances were classified using the Henderson–Hasselbalch equation, with prevalent metabolic alkalosis confirmed through the Stewart approach. Primary outcomes were in-hospital mortality, Glasgow Outcome Scale (GOS) at discharge, and return to premorbid neurologic function.FindingsAmong 540 SE patients, 365 were included. Half of patients exhibited acid–base disturbances within the initial 24 h of SE, with metabolic and respiratory acidosis being the most prevalent, though not prognostically significant. After correction for possible confounders, metabolic alkalosis (6%) was associated with increased in-hospital mortality (P = 0.011; OR = 4.87, 95% CI = 1.29–7.84), worse GOS (P = 0.012; OR = 3.18, 95% CI = 1.29–7.84), and reduced likelihood of returning to premorbid function (P = 0.017; OR = 3.30, CI95% = 1.24–8.80). Following the Stewart approach, 9% of patients had predominant metabolic alkalosis, associated with worse GOS (P = 0.005; OR:3.37, 95%CI = 1.45–7.82), and reduced chance of returning to baseline (P = 0.012; OR = 3.29, CI95% = 1.30–8.32). Metabolic alkalosis was related to hypoalbuminemia and lower serum potassium.ConclusionMetabolic alkalosis strongly predicts mortality and adverse functional outcome in SE patients. Prospective studies should assess whether early detection and correction of metabolic alkalosis and related electrolyte imbalances can improve SE prognosis.

A randomized controlled trial evaluating the effect of providing a rest period during long-distance transportation of surplus dairy calves: Part II. Effect on hematological variables

The objective of this randomized controlled trial was to determine if providing a rest stop including provision of feed and water between periods of continuous transportation mitigates the effect of long-distance transportation on markers of energy status and hydration in calves transported by road for 16 h. This study was conducted between September 2022 to January 2023 and included male and female Holstein and crossbred dairy calves ≥7 d old from 2 commercial dairy farms in Ontario, Canada (n = 96). On the day before transportation, calves were enrolled and randomly assigned to one of 2 treatment groups: (1) continuous transportation by road for 16 h or (2) 8 h of transport, 8 h of rest, and a further 8 h of transport to a single calf-raising facility. Calves that received a rest stop were fed 2 L of milk replacer at the time of unloading for the rest period and again immediately before reloading for the second leg of the journey. Blood samples were collected before and after transportation as well as daily for 3 d following arrival to the calf-raising facility. Serum was analyzed for concentrations of BHB, nonesterified fatty acids (NEFA), haptoglobin, and creatine kinase, and acid-base disturbances were evaluated within 1 h of collection of whole blood to assess glucose, sodium, potassium, ionized calcium, hematocrit, hemoglobin, pH, base excess, partial pressure of oxygen, total carbon dioxide, bicarbonate, partial pressure of carbon dioxide, and oxygen saturation. Mixed linear regression models with repeated measures were built to assess the effect of treatment group, age at transportation, breed, and sex on these parameters. Immediately after transportation, calves that received the rest period had lower BHB (-68.04 μmol/L, 95% CI: -99.59 to -36.49), NEFA (-0.14 mmol/L, 95% CI -0.22 to -0.07), and sodium (-1.10 mmol/L, 95% CI = -2.18 to -0.02), and higher glucose (0.48 mmol/L, 95% CI = 0.21 to 0.74), potassium (0.27 mmol/L, 95% CI = 0.11 to 0.43), ionized calcium (0.06 mmol/L, 95% CI = 0.03 to 0.08), and oxygen saturation (8.76%, 95% CI = 1.61 to 15.91) compared with calves that were continuously transported for 16 h. Additionally, calves transported between 11 and 12 d old had lower hematocrit (-1.22%, 95% CI = -2.19 to -0.25), hemoglobin (-3.07 g/L, 95% CI = -5.70 to -0.43), haptoglobin (-0.13 g/L, 95% CI = -0.23 to -0.02), and potassium (-0.13 mmol/L, 95% CI = -0.22 to -0.04) and higher sodium (0.83 mmol/L, 95% CI = 0.03 to 1.63) than 7 to 8 d old calves. Furthermore, calves that were 13 to 24 d old at transport had lower haptoglobin (-0.16 g/L, 95% CI = -0.27 to -0.06) and potassium (-0.14 mmol/L, 95% CI = -0.23 to -0.05), and higher sodium (1.02 mmol/L, 95% CI = 0.22 to 1.82) and ionized calcium (0.02 mmol/L, 95% CI = 0.002 to 0.035) compared with calves transported at 7 to 8 d old. The results of this trial demonstrate that a rest period improves energy status upon arrival to a calf-raising facility, suggesting that the benefit of a rest period may be mostly related to the provision of mid-journey milk meals.

Chloride Modulates Central pH Sensitivity and Plasticity of Brainstem Breathing-Related Biorhythms in Zebra Finch Embryos.

All terrestrial vertebrate life must transition from aquatic gas exchange in the embryonic environment to aerial or pulmonary respiration at birth. In addition to being able to breathe air, neonates must possess functional sensory feedback systems for maintaining acid-base balance. Respiratory neurons in the brainstem act as pH sensors that can adjust breathing to regulate systemic pH. The central pH sensitivity of breathing-related motor output develops over the embryonic period in the zebra finch (Taeniopygia guttata). Due to the key role of chloride ions in electrochemical stability and developmental plasticity, we tested chloride's role in the development of central pH sensitivity. We blocked gamma-aminobutyric acid-A receptors and cation-chloride cotransport that subtly modulated the low-pH effects on early breathing biorhythms. Further, chloride-free artificial cerebrospinal fluid altered the pattern and timing of breathing biorhythms and blocked the stimulating effect of acidosis in E12-14 brainstems. Early and middle stage embryos exhibited rebound plasticity in brainstem motor outputs during low-pH treatment, which was eliminated by chloride-free solution. Results show that chloride modulates low-pH sensitivity and rebound plasticity in the zebra finch embryonic brainstem, but work is needed to determine the cellular and circuit mechanisms that control functional chloride balance during acid-base disturbances.

The Effects of Early-Phase, Low- or Standard-Intensity Continuous Renal Replacement Therapy on Acid-Base Control and Clinical Outcomes: An Observational Study

Introduction: The Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline recommends administering an effluent volume of 20–25 mL/kg/h during continuous renal replacement therapy (CRRT) for acute kidney injury. Recent evidence on CRRT initiation showed that less intervention might be beneficial for renal recovery. This study aimed to explore the association between early-phase low CRRT intensity and acid-base balance corrections and clinical outcomes. Methods: This was a single-centre, retrospective, observational study at a tertiary intensive care unit (ICU) in Japan. All adult patients requiring CRRT in the ICU were included. Eligible patients were classified into the Low group (dialysate flow rate [QD] 10.0–19.9 mL/kg/h) and the Standard group (QD ≥20 mL/kg/h) by the intensity of CRRT at the beginning. The primary outcomes were acid-base parameters 6 h after CRRT initiation. We used an inverse probability of treatment weighting analysis to estimate the association between the intensity group and the outcomes. Results: Overall, 194 patients were classified into the Low group (n = 144) and the Standard group (n = 50). The Standard group presented with more severe acid-base disturbances, including lower pH and base excess (BE) at baseline. At 6 h after CRRT initiation, pH, BE, and strong ion difference values were comparable, even after adjusting for baseline severity. Despite the efficient correction, no evident differences were observed in clinical outcomes between the two groups. Conclusions: The initial standard intensity appeared to be efficient in correcting acid-base imbalance at the early phase of CRRT; however, further studies are needed to assess the impact on clinical outcomes.

Prognostic role of unmeasured anions determined by the Stewart approach in septic shock: A prospective cohort study

Background: Unlike standard methods for the analysis of acid-base disturbances, the Stewart approach allows for a precise quantification of unmeasured anions (strong ion gap, SIG). The prognostic value of these unmeasured anions has been reported in various clinical situations in the intensive care unit (ICU), but not specifically in septic shock. The aim of the present study was to assess whether or not the SIG could be a prognostic marker for 28-day mortality in critically ill patients admitted to the ICU for septic shock. Methods: This prospective cohort study was conducted from June 2016 to December 2017 in three ICUs of a French teaching hospital. All patients admitted to the ICU for septic shock and equipped with an arterial blood line were eligible. Oral consent was collected after delivering oral and written information to the patient or his/her family. The SIG was calculated from a complete blood sampling (blood electrolytes and arterial blood gas) collected immediately upon ICU admission. Receiver operating characteristics (ROC) curves were determined to assess the ability of SIG to predict 28-day mortality. Results: A total of 116 patients were analyzed. The 28-day mortality rate was 41.4%. Median (interquartile range [IQR]) SIG at admission was 7.1 (4.6-9.6) mEq/L for the 28-day survivors and 8.0 (6.1-10.3) mEq/L for non-survivors (P = 0.051). The area under ROC of SIG at admission for 28-day mortality prediction was 0.607 (95% confidence interval [CI] 0.504-0.710; P = 0.051). Conclusion: SIG is not a relevant prognostic marker for mortality in septic shock.

The Influence of Acid-Base Balance on Anesthetic Muscle Relaxants: A Comprehensive Review on Clinical Applications and Mechanisms.

Muscle relaxants have broad application in anesthesiology. They can be used for safe intubation, preparing the patient for surgery, or improving mechanical ventilation. Muscle relaxants can be classified based on their mechanism of action into depolarizing and non-depolarizing muscle relaxants and centrally acting muscle relaxants. Non-depolarizing neuromuscular blocking drugs (NMBDs) (eg, tubocurarine, atracurium, pipecuronium, mivacurium, pancuronium, rocuronium, vecuronium) act as competitive antagonists of nicotine receptors. By doing so, these drugs hinder the depolarizing effect of acetylcholine, thereby eliminating the potential stimulation of muscle fibers. Depolarizing drugs like succinylcholine and decamethonium induce an initial activation (depolarization) of the receptor followed by a sustained and steady blockade. These drugs do not act as competitive antagonists; instead, they function as more enduring agonists compared to acetylcholine itself. Many factors can influence the duration of action of these drugs. Among them, electrolyte disturbances and disruptions in acid-base balance can have an impact. Acidosis increases the potency of non-depolarizing muscle relaxants, while alkalosis induces resistance to their effects. In depolarizing drugs, acidosis and alkalosis produce opposite effects. The results of studies on the impact of acid-base balance disturbances on non-depolarizing relaxants have been conflicting. This work is based on the available literature and the authors' experience. This article aimed to review the use of anesthetic muscle relaxants in patients with acid-base disturbances.

Acid-base disturbances and effects on oxygen uptake rates in Nile tilapia (Oreochromis niloticus) following acute and prolonged CO2 exposure

High levels of dissolved carbon dioxide (CO2) occur nightly in earthen ponds characterized by high respiration rates. Exposure to high CO2 conditions (hypercapnia) leads to acidosis in fish, which can be compensated by an accumulation of HCO3− to recover intra- and extracellular pH levels, with a capacity that appears to be species-specific. For Nile tilapia, a freshwater tropical teleost traditionally produced in earthen ponds, little information is available on the tolerance to dissolved levels of CO2 and associated acid-base disturbances. Here, we investigated first the effects of acute and progressively increasing CO2, from normocapnic conditions to 60 mg CO2 L−1, on oxygen uptake rates (MO2). This was followed by exposure to three concentrations of CO2; 10, 30, and 60 mg L−1 (equivalent to pCO2 of 5.4, 16.2, and 32.4 mmHg) against a normocapnic control (pCO2 0.3 mmHg), to investigate acute (1 h) or prolonged (24 h) effects on standard (SMR) and maximum metabolic rates (MMR), haematology, and extra- and intracellular acid-base status in adult Nile tilapia (mean BM 435 ± 16 g ± SE). Acute exposure to hypercapnia led to concentration-dependent decreases in both SMR and MMR. Fish were able to fully or partially recover MMR and metabolic scope (MS) after 24 h, while depression of SMR persisted at all CO2 levels. Acute exposure to CO2 caused intra- and extracellular pH levels to decrease by up to 0.5 units in a concentration-dependent manner. Only the lowest hypercapnic treatment (pCO2 5.4 mmHg) was able to fully recover within 24 h. Changes in haematological variables appeared minor, being restricted to increasing haematocrit, haemoglobin concentration, and mean cell volume in the highest CO2 treatments after 24 h exposure. Although the Nile tilapia is generally considered a species able to tolerate poor water quality, the modest or slow acid-base regulation following hypercapnic exposure suggests sensitivity to hypercapnia.

Beyond the Nephron: Exploring Systemic Implications of Renal Tubular Acidosis

Renal Tubular Acidosis (RTA) is a complex renal disorder characterized by impaired acid-base regulation, leading to metabolic acidosis. While traditionally classified into several subtypes based on renal tubular dysfunction, emerging evidence highlights the systemic implications of RTA beyond nephron physiology. This article explores the multifaceted systemic manifestations of RTA, including cardiovascular, endocrine, neurological, and psychosocial implications, and discusses the importance of recognizing and addressing these systemic effects in patient care. Through interdisciplinary collaboration and personalized medicine approaches, tailored therapeutic strategies can be developed to mitigate renal and extrarenal manifestations of RTA, thereby improving overall patient well-being. Furthermore, future research directions aimed at elucidating the intricate interplay between acid-base disturbances and systemic organ systems hold promise for advancing our understanding and management of RTA, ultimately enhancing patient care outcomes

Fluid management and active fluid removal practices: a global survey of paediatric critical care physicians

AimsFluid accumulation (FA) in critically ill children is associated with poor clinical outcomes. While conservative fluid management has been proposed, evidence to guide practice is scarce. We surveyed paediatric critical care (PCC) physicians worldwide regarding their perceptions of FA, active fluid removal (AFR) practices, safety parameters, and willingness to participate in a clinical trial on the topic.MethodsCross-sectional international electronic survey of PCC physicians, distributed through research networks worldwide.ResultsA total of 409 PCC physicians from 48 countries participated in the survey; 40% (164/409) cared for cardiac patients. The majority believed FA was a modifiable source of morbidity (88%, 359/407) and expressed support for a trial on conservative fluid management trial (94%, 383/407). Restriction of maintenance fluid was more commonly practiced (87%, 335/387) than resuscitation fluid (54%, 210/387), with variability observed among individuals and patient categories. AFR was widely practiced (93%, 361/387), yet significant differences existed in patient selection, timing, modality, and rate. The most common reported time for starting AFR was 48 h (49%, 172/384), with most respondents (92%, 355/385) comfortable doing so in the setting of catecholamine infusions. While most respondents would continue diuretics with mild electrolyte or acid–base disturbances, 52% (179/342) would withhold them in cases of mild hypotension.ConclusionsFluid accumulation remains a significant concern among paediatric intensivists. The observed practice variability underscores the challenges in establishing evidence-based guidelines. Our survey highlights an urgent need for randomized trials in this field and provides valuable insights to inform the design of such future studies.