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

BACKGROUND: Alactic 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). METHODS: This 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. RESULTS: Of 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). CONCLUSION: Negative ABE was significantly associated with in-hospital mortality in patients with AMI.

Trends in Apgar scores and umbilical artery pH: a population-based cohort study on 10,696,831 live births in Germany, 2008-2022.

Low Apgar scores and low umbilical arterial (UA) blood pH are considered indicators of adverse perinatal events. This study investigated trends of these perinatal health indicators in Germany. Perinatal data on 10,696,831 in-hospital live births from 2008 to 2022 were obtained from quality assurance institutes. Joinpoint regression analysis was used to quantify trends of low Apgar score and UA pH. Additional analyses stratified by mode of delivery were performed on term singletons with cephalic presentation. Robustness against unmeasured confounding was analyzed using the E-value sensitivity analysis. The overall rates of 5-min Apgar scores < 7 and UA pH < 7.10 in liveborn infants were 1.17% and 1.98%, respectively. For low Apgar scores, joinpoint analysis revealed an increase from 2008 to 2011 (annual percent change (APC) 5.19; 95% CI 3.66-9.00) followed by a slower increase from 2011 to 2019 (APC 2.56; 95% CI 2.00-3.03) and a stabilization from 2019 onwards (APC - 0.64; 95% CI - 3.60 to 0.62). The rate of UA blood pH < 7.10 increased significantly between 2011 and 2017 (APC 5.90; 95% CI 5.15-7.42). For term singletons in cephalic presentation, the risk amplification of low Apgar scores was highest after instrumental delivery (risk ratio 1.623, 95% CI 1.509-1.745), whereas those born spontaneous had the highest increase in pH < 7.10 (risk ratio 1.648, 95% CI 1.615-1.682).          Conclusion: Rates of low 5-min Apgar scores and UA pH in liveborn infants increased from 2008 to 2022 in Germany. What is Known: • Low Apgar scores at 5 min after birth and umbilical arterial blood pH are associated with adverse perinatal outcomes. • Prospective collection of Apgar scores and arterial blood pH data allows for nationwide quality assurance. What is New: • The rates of liveborn infants with 5-min Apgar scores < 7 rose from 0.97 to 1.30% and that of umbilical arterial blood pH < 7.10 from 1.55 to 2.30% between 2008-2010 and 2020-2022. • In spontaneously born term singletons in cephalic presentation, the rate of metabolic acidosis with pH < 7.10 and BE < -5 mmol/L in umbilical arterial blood roughly doubled between the periods 2008-2010 and 2020-2022.

Base excess is superior to creatinine in predicting haemodialysis: A multicenter study conducted Kahramanmaras earthquake victims.

PURPOSE: This study had two main goals: to determine which rhabdomyolysis patients need haemodialysis; and to highlight the significance of blood gas parameters, particularly base excess, as predictors of the need for haemodialysis. METHOD: A total of 270 patients were included in this multicentre, retrospective study. Among the patients who were transferred in from the earthquake region and developed rhabdomyolysis, those with creatine kinase (CK) values >1000 U/L were included in our study. The need for renal replacement in these patients was determined via laboratory tests, urine output monitoring and clinical follow-up. FINDINGS: A total of 270 patients were included in our study. Univariate and multivariate regression analyses of laboratory parameters were performed to identify predictors of HD treatment. According to the univariate regression analysis, BE, HCO3, creatinine, CK, lactate, alanine transaminase (ALT) and aspartate transaminase (AST) levels were found to be significantly associated with receiving HD treatment. According to multivariate regression analysis, only BE (p = 0.003) was found to be a significant predictor of HD treatment. ROC analysis revealed that the optimal cutoff value for BE was -2.6; at this value, the sensitivity and specificity of BE for predicting HD treatment were 89% and 77.1%, respectively (AUC: 0.912; 95% CI: 0.872-0.943; p < 0.001). CONCLUSION: Base excess is an effective predictor of the need for haemodialysis in patients with crush-related injuries that cause rhabdomyolysis and in patients who develop acute renal failure due to elevated CK.

Improving the interpretation of electronic fetal monitoring: the fetal reserve index.

Electronic fetal monitoring, particularly in the form of cardiotocography, forms the centerpiece of labor management. Initially successfully designed for stillbirth prevention, there was hope to also include prediction and prevention of fetal acidosis and its sequelae. With the routine use of electronic fetal monitoring, the cesarean delivery rate increased from <5% in the 1970s to >30% at present. Most at-risk cases produced healthy babies, resulting in part from considerable confusion as to the differences between diagnostic and screening tests. Electronic fetal monitoring is clearly a screening test. Multiple attempts have aimed at enhancing its ability to accurately distinguish babies at risk of in utero injury from those who are not and to do this in a timely manner so that appropriate intervention can be performed. Even key electronic fetal monitoring opinion leaders admit that this goal has yet to be achieved. Our group has developed a modified approach called the "Fetal Reserve Index" that contextualizes the findings of electronic fetal monitoring by formally including the presence of maternal, fetal, and obstetrical risk factors and increased uterine contraction frequencies and breaking up the tracing into 4 quantifiable components (heart rate, variability, decelerations, and accelerations). The result is a quantitative 8-point metric, with each variable being weighted equally in version 1.0. In multiple previously published refereed papers, we have shown that in head-to-head studies comparing the fetal reserve index with the American College of Obstetricians and Gynecologists' fetal heart rate categories, the fetal reserve index more accurately identifies babies born with cerebral palsy and could also reduce the rates of emergency cesarean delivery and vaginal operative deliveries. We found that the fetal reserve index scores and fetal pH and base excess actually begin to fall earlier in the first stage of labor than was commonly appreciated, and the fetal reserve index provides a good surrogate for pH and base excess values. Finally, the last fetal reserve index score before delivery combined with early analysis of neonatal heart rate and acid/base balance shows that the period of risk for neonatal neurologic impairment can continue for the first 30 minutes of life and requires much closer neonatal observation than is currently being done.

Umbilical cord pH, blood gases, and lactate at birth: normal values, interpretation, and clinical utility.

Normal birth is a eustress reaction, a beneficial hedonic stress with extremely high catecholamines that protects us from intrauterine hypoxia and assists in the rapid shift to extrauterine life. Occasionally the cellular O2 requirement becomes critical and an O2 deficit in blood (hypoxemia) may evolve to a tissue deficit (hypoxia) and finally a risk of organ damage (asphyxia). An increase in H+ concentration is reflected in a decrease in pH, which together with increased base deficit is a proxy for the level of fetal O2 deficit. Base deficit (or its negative value, base excess) was introduced to reflect the metabolic component of a low pH and to distinguish from the respiratory cause of a low pH, which is a high CO2 concentration. Base deficit is a theoretical estimate and not a measured parameter, calculated by the blood gas analyzer from values of pH, the partial pressure of CO2, and hemoglobin. Different brands of analyzers use different calculation equations, and base deficit values can thus differ by multiples. This could influence the diagnosis of metabolic acidosis, which is commonly defined as a pH <7.00 combined with a base deficit ≥12.0 mmol/L in umbilical cord arterial blood. Base deficit can be calculated as base deficit in blood (or actual base deficit) or base deficit in extracellular fluid (or standard base deficit). The extracellular fluid compartment represents the blood volume diluted with the interstitial fluid. Base deficit in extracellular fluid is advocated for fetal blood because a high partial pressure of CO2 (hypercapnia) is common in newborns without concomitant hypoxia, and hypercapnia has a strong influence on the pH value, then termed respiratory acidosis. An increase in partial pressure of CO2 causes less increase in base deficit in extracellular fluid than in base deficit in blood, thus base deficit in extracellular fluid better represents the metabolic component of acidosis. The different types of base deficit for defining metabolic acidosis in cord blood have unfortunately not been noticed by many obstetrical experts and organizations. In addition to an increase in H+ concentration, the lactate production is accelerated during hypoxia and anaerobic metabolism. There is no global consensus on definitions of normal cord blood gases and lactate, and different cutoff values for abnormality are used. At a pH <7.20, 7% to 9% of newborns are deemed academic; at <7.10, 1% to 3%; and at <7.00, 0.26% to 1.3%. From numerous studies of different eras and sizes, it can firmly be concluded that in the cord artery, the statistically defined lower pH limit (mean -2 standard deviations) is 7.10. Given that the pH for optimal enzyme activity differs between different cell types and organs, it seems difficult to establish a general biologically critical pH limit. The blood gases and lactate in cord blood change with the progression of pregnancy toward a mixed metabolic and respiratory acidemia because of increased metabolism and CO2 production in the growing fetus. Gestational age-adjusted normal reference values have accordingly been published for pH and lactate, and they associate with Apgar score slightly better than stationary cutoffs, but they are not widely used in clinical practice. On the basis of good-quality data, it is reasonable to set a cord artery lactate cutoff (mean +2 standard deviations) at 10 mmol/L at 39 to 40 weeks' gestation. For base deficit, it is not possible to establish statistically defined reference values because base deficit is calculated with different equations, and there is no consensus on which to use. Arterial cord blood represents the fetus better than venous blood, and samples from both vessels are needed to validate the arterial origin. A venoarterial pH gradient of <0.02 is commonly used to differentiate arterial from venous samples. Reference values for pH in cord venous blood have been determined, but venous blood comes from the placenta after clearance of a surplus of arterial CO2, and base deficit in venous blood then overestimates the metabolic component of fetal acidosis. The ambition to increase neonatal hemoglobin and iron depots by delaying cord clamping after birth results in falsely acidic blood gas and lactate values if the blood sampling is also delayed. Within seconds after birth, sour metabolites accumulated in peripheral tissues and organs will flood into the central circulation and further to the cord arteries when the newborn starts to breathe, move, and cry. This influence of "hidden acidosis" can be avoided by needle puncture of unclamped cord vessels and blood collection immediately after birth. Because of a continuing anaerobic glycolysis in the collected blood, it should be analyzed within 5 minutes to not result in a falsely high lactate value. If the syringe is placed in ice slurry, the time limit is 20 minutes. For pH, it is reasonable to wait no longer than 15 minutes if not in ice. Routine analyses of cord blood gases enable perinatal audits to gain the wisdom of hindsight, to maintain quality assurance at a maternity unit over years by following the rate of neonatal acidosis, to compare results between hospitals on regional or national bases, and to obtain an objective outcome measure in clinical research. Given that the intrapartum cardiotocogram is an uncertain proxy for fetal hypoxia, and there is no strong correlation between pathologic cardiotocograms and fetal acidosis, a cord artery pH may help rather than hurt a staff person subjected to a malpractice suit based on undesirable cardiotocogram patterns. Contrary to common beliefs and assumptions, up to 90% of cases of cerebral palsy do not originate from intrapartum events. Future research will elucidate whether cell injury markers with point-of-care analysis will become valuable in improving the dating of perinatal injuries and differentiating hypoxic from nonhypoxic injuries.

Prevention of fetal brain injury in category II tracings.

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 (BDecf ) 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 BDecf ≥ 12 mEq/L. BDecf 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 BDecf 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 BDecf 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 ~BDecf 8 mEq/L, whereas the "decisions" did not occur until BDecf reached 12 mEq/L in slow progression cases. CONCLUSIONS: Fetal BDecf 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.

The association of standard base excess upon emergency admission with outcomes in patients with heat stroke.

OBJECTIVES: Standard base excess (SBE) is a quick and effective tool to identify acid-base disorders in critically ill patients, independent of respiratory factors. The predictive value of SBE for adverse outcomes in patients with heat stroke (HS) is still unclear. This study aimed to explore the prognostic significance of SBE for in-hospital mortality and other adverse outcomes in patients with HS. METHODS: A retrospective, observational multicenter cohort study with consecutive patients between 2021 and 2022 was conducted. The SBE was performed upon emergency department (ED) admission. The primary outcome was in-hospital mortality. Secondary outcomes included the use of vasoactive drugs in the ED, admission to the ICU, acute kidney failure, acute heart failure, acute respiratory failure, sepsis, and coagulation impairment. Logistic regression models and receiver operating characteristic (ROC) curves were used to estimate the association of SBE with outcomes in HS patients. Interaction and stratified analyses were also conducted. RESULTS: The median level of SBE was -4.70 (-8.05- -1.55) mmol/L. Overall hospital mortality in these 151 HS patients was 12.58%. SBE was independently associated with hospital mortality (OR 0.81, 95% CI 0.70-0.95, P = 0.011). Age and HS type played interactive roles in the relationship between SBE and in-hospital mortality. The OR between SBE and hospital mortality was 0.5 (95% CI, 0.3-0.9; p < 0.018) in classic HS participants and 0.62 (95% CI, 0.45-0.87; p = 0.005) in participants aged >65 years. The AUC of SBE to predict in-hospital mortality was 0.868 (95% CI: 0.704-0.962) and 0.883 (95% CI: 0.750-0.951) in these two groups, respectively. SBE was significantly associated with admission to the ICU, acute kidney failure, acute respiratory failure, sepsis, and coagulation impairment. CONCLUSION: SBE upon emergency admission was significantly associated with adverse outcomes in patients with HS.

Agreement between arterial and central venous blood pH and its contributing variables in anaesthetized dogs with respiratory acidosis.

OBJECTIVE: To determine the accuracy of variables that influence blood pH, obtained from central venous (jugular vein) blood samples compared with arterial (dorsal pedal artery) samples in anaesthetized dogs with respiratory acidosis. STUDY DESIGN: Prospective, comparative, observational study. ANIMALS: A group of 15 adult male dogs of various breeds weighing 17 (11-42) kg [median (range)]. METHODS: Dogs were premedicated with buprenorphine (0.03 mg kg-1) and medetomidine (0.01 mg kg-1) administered intramuscularly by separate injections, anaesthetized with propofol intravenously to effect and maintained with isoflurane in 50% air-oxygen. Arterial and central venous catheters were placed. After 15 minutes of spontaneous breathing, arterial and central venous blood samples were obtained and analysed within 5 minutes, using a bench-top gas analyser. Differences between arterial and central venous pH and measured variables were assessed using Wilcoxon rank sum test and effect size (r: matched-pairs rank-biserial correlation) was calculated for each comparison. The agreement (bias and limits of agreement: LoAs) between arterial and central venous pH and measured variables were assessed using Bland-Altman; p < 0.05. Data are reported as median and 95% confidence interval. RESULTS: Arterial blood pH was 7.23 (7.19-7.25), and it was significantly greater than central venous samples 7.21 (7.18-7.22; r = 0.41). Agreement between arterial and venous pH was acceptable with a bias of 0.01 (0.002-0.02) and narrow LoAs. PCO2 [arterial 54 (53-58) mmHg, 7.2 (7.1-7.7) kPa; venous 57 (54-62) mmHg, 7.6 (7.2-8.3) kPa], bicarbonate ion concentration and base excess did not differ between samples; however, agreement between arterial and venous PCO2 was not acceptable with a bias of -2 (-5 to 0) mmHg and wide LoAs. CONCLUSIONS AND CLINICAL RELEVANCE: Blood pH measured from central venous (jugular vein) blood is an acceptable clinical alternative to arterial blood (dorsal pedal artery) in normovolaemic anaesthetized dogs with respiratory acidosis.

Utility of ETCO2 to predict hemorrhagic shock in multiple trauma patients.

BACKGROUND: For identifying hemorrhagic shock in trauma patients, some objective data are needed. The use of base excess (BE) and lactate values have been originated. In this study, it was aimed to determine the usability of end tidal carbon dioxide (ETCO2) in patients with multiple trauma for recognizing hemorrhagic shock. METHODS: Patients who were admitted to the emergency department between June 2019 and February 2020 with highenergy multiple trauma were included in the study. ETCO2 and BE values were measured. Correlation coefficients were calculated to determine correlations between ETCO2 and BE levels. RESULTS: One hundred and twenty-two patients were included in the study. Eighty-nine (73%) were men and 33 (27%) were women, and the mean age of the study population was 38.70 ± 19.18. The mortality rate was 14.8% in the study population. The correlation between ETCO2 and BE values was significant (r: 0.27) and in the same range in the Bland-Altmann analysis. ETCO2 levels above 35 were specific for stage 1 hemorrhagic shock. ETCO2 levels below 30 were sensitive for stage 2 and 3 hemorrhagic shocks and when the levels were measured below 22 it was found specific for stage 4 shock. The specificity increased to 99% at levels below 18. The sensitivity for ETCO2 values below 22 for predicting mortality was 33.33%, the specificity was 89.42%, the positive predictive value was 35.29% and the negative predictive value was 88.57%. The sensitivity for BE values below -10 for predicting mortality was 50%, the specificity was 93.27%, the positive predictive value was 56.25% and the negative predictive value was 91.51%.

Prognostic dynamic nomogram integrated with metabolic acidosis for in-hospital mortality and organ malperfusion in acute type B aortic dissection patients undergoing thoracic endovascular aortic repair.

BACKGROUND: Organ malperfusion is a lethal complication in acute type B aortic dissection (ATBAD). The aim of present study is to develop a nomogram integrated with metabolic acidosis to predict in-hospital mortality and organ malperfusion in patients with ATBAD undergoing thoracic endovascular aortic repair (TEVAR). METHODS: The nomogram was derived from a retrospectively study of 286 ATBAD patients who underwent TEVAR from 2010 to 2017 at a single medical center. Model performance was evaluated from discrimination and calibration capacities, as well as clinical effectiveness. The results were validated using a prospective study on 77 patients from 2018 to 2019 at the same center. RESULTS: In the multivariate analysis of the derivation cohort, the independent predictors of in-hospital mortality and organ malperfusion identified were base excess, maximum aortic diameter ≥ 5.5 cm, renal dysfunction, D-dimer level ≥ 5.44 µg/mL and albumin amount ≤ 30 g/L. The penalized model was internally validated by bootstrapping and showed excellent discriminatory (bias-corrected c-statistic, 0.85) and calibration capacities (Hosmer-Lemeshow P value, 0.471; Brier Score, 0.072; Calibration intercept, - 0.02; Slope, 0.98). After being applied to the external validation cohort, the model yielded a c-statistic of 0.86 and Brier Score of 0.097. The model had high negative predictive values (0.93-0.94) and moderate positive predictive values (0.60-0.71) for in-hospital mortality and organ malperfusion in both cohorts. CONCLUSIONS: A predictive nomogram combined with base excess has been established that can be used to identify high risk ATBAD patients of developing in-hospital mortality or organ malperfusion when undergoing TEVAR.

Comparison of base excess, lactate and pH predicting 72-h mortality of multiple trauma.

OBJECTIVE: To compare the predictive values of base excess (BE), lactate and pH of admission arterial blood gas for 72-h mortality in patients with multiple trauma. METHODS: This was a secondary analysis based on a publicly shared trauma dataset from the Dryad database, which provided the clinical data of 3669 multiple trauma patients with ISS > = 16. The records of BE, lactate, pH and 72-h prognosis data without missing values were selected from this dataset and 2441 individuals were enrolled in the study. Logistic regression model was performed to calculate the odds ratios (ORs) of variables. Area under the curve (AUC) of receiver operating curve (ROC) was utilized to evaluate the predictive value of predictors for 72 h in-hospital mortality. Pairwise comparison of AUCs was performed using the Delong's test. RESULTS: The statistically significant correlations were observed between BE and lactate (r = - 0.5861, p < 0.05), lactate and pH (r = - 0.5039, p < 0.05), and BE and pH (r = - 0.7433, p < 0.05). The adjusted ORs of BE, lactate and pH for 72-h mortality with the adjustment for factors including gender, age, ISS category were 0.872 (95%CI: 0.854-0.890), 1.353 (95%CI: 1.296-1.413) and 0.007 (95%CI: 0.003-0.016), respectively. The AUCs of BE, lactate and pH were 0.693 (95%CI: 0.675-0.712), 0.715 (95%CI: 0.697-0.733), 0.670 (95%CI: 0.651-0.689), respectively. CONCLUSIONS: There are significant correlations between BE, lactate and pH of the admission blood gas, all of them are independent predictors of 72-h mortality for multiple trauma. Lactate may have the best predictive value, followed by BE, and finally pH.

The impact of COPD on polyneuropathy: results from the German COPD cohort COSYCONET.

BACKGROUND: Peripheral neuropathy is a common comorbidity in COPD. We aimed to investigate associations between alterations commonly found in COPD and peripheral neuropathy, with particular emphasize on the distinction between direct and indirect effects. METHODS: We used visit 4 data of the COPD cohort COSYCONET, which included indicators of polyneuropathy (repeated tuning fork and monofilament testing), excluding patients with diabetes a/o increased HbA1c. These indicators were analysed for the association with COPD characteristics, including lung function, blood gases, 6-min walk distance (6-MWD), timed-up-and-go-test (TUG), exacerbation risk according to GOLD, C-reactive protein (CRP), and ankle-brachial index (ABI). Based on the results of conventional regression analyses adjusted for age, BMI, packyears and gender, we utilized structural equation modelling (SEM) to quantify the network of direct and indirect relationships between parameters. RESULTS: 606 patients were eligible for analysis. The indices of polyneuropathy were highly correlated with each other and related to base excess (BE), ABI and TUG. ABI was linked to neuropathy and 6-MWD, exacerbations depended on FEV1, 6-MWD and CRP. The associations could be summarized into a SEM comprising polyneuropathy as a latent variable (PNP) with three measured indicator variables. Importantly, PNP was directly dependent on ABI and particularly on BE. When also including patients with diabetes and/or elevated values of HbA1c (n = 742) the SEM remained virtually the same. CONCLUSION: We identified BE and ABI as major determinants of peripheral neuropathy in patients with COPD. All other associations, particularly those with lung function and physical capacity, were indirect. These findings underline the importance of alterations of the micromilieu in COPD, in particular the degree of metabolic compensation and vascular status.

Understanding Lactatemia in Human Sepsis. Potential Impact for Early Management.

Rationale: Hyperlactatemia in sepsis may derive from a prevalent impairment of oxygen supply/demand and/or oxygen use. Discriminating between these two mechanisms may be relevant for the early fluid resuscitation strategy.Objectives: To understand the relationship among central venous oxygen saturation (ScvO2), lactate, and base excess to better determine the origin of lactate.Methods: This was a post hoc analysis of baseline variables of 1,741 patients with sepsis enrolled in the multicenter trial ALBIOS (Albumin Italian Outcome Sepsis). Variables were analyzed as a function of sextiles of lactate concentration and sextiles of ScvO2. We defined the "alactic base excess," as the sum of lactate and standard base excess.Measurements and Main Results: Organ dysfunction severity scores, physiologic variables of hepatic, metabolic, cardiac, and renal function, and 90-day mortality were measured. ScvO2 was lower than 70% only in 35% of patients. Mortality, organ dysfunction scores, and lactate were highest in the first and sixth sextiles of ScvO2. Although lactate level related strongly to mortality, it was associated with acidemia only when kidney function was impaired (creatinine >2 mg/dl), as rapidly detected by a negative alactic base excess. In contrast, positive values of alactic base excess were associated with a relative reduction of fluid balance.Conclusions: Hyperlactatemia is powerfully correlated with severity of sepsis and, in established sepsis, is caused more frequently by impaired tissue oxygen use, rather than by impaired oxygen transport. Concomitant acidemia was only observed in the presence of renal dysfunction, as rapidly detected by alactic base excess. The current strategy of fluid resuscitation could be modified according to the origin of excess lactate.

Comparison of cord blood lactate measurement by gas analyzer and portable electrochemical devices.

Objective To compare the accuracy of cord blood lactate measurement using gas analyzer and portable devices in order to assess possibility of implementation of these devices in clinical practice. Methods We performed a prospective observational study using 30 umbilical cord samples which were obtained immediately after birth. Portable electrochemical devices Lactate Scout (SensLab GmbH, Leipzig, Germany) and StatStrip Lactate (NOVA Biomedical, Waltham, MA, USA) were used to determine lactate level. A gas analyzer ABL800 FLEX (Radiometer Medical ApS, Brønshøj-Husum, Denmark) was used as a reference. Base excess (BE), pH, partial oxygen (pO2) and carbon dioxide (pCO2) pressure, hemoglobin (ctHb) and bilirubin (ctBl) levels were measured. Results The mean umbilical cord blood lactate level determined by the gas analyzer was 5.85 ± 2.66 mmol/L (ranging from 1.4 mmol/L to 13.4 mmol/L). Lactate level estimated by Lactate Scout was 5.66 ± 2.65 mmol/L and did not significantly differ from the reference method level (P = 0.2547). The mean lactate level determined by StatStrip Lactate was significantly lower than by the gas analyzer - 4.81 ± 2.38 mmol/L (P < 0.0001). Umbilical cord blood pH, BE, pO2 and pCO2, ctHb and ctBl levels did not affect the accuracy of the lactate measurement in absolute units (mmol/L). Conclusion Umbilical cord blood lactate level measured by StatStrip Lactate was lower than estimated by the ABL800 FLEX gas analyzer. This shows the necessity to develop decision-making reference points separately for each device. Umbilical cord blood pH, BE, pO2 and pCO2, ctHb and ctBl levels did not affect the accuracy of measurements by electrochemical portable devices.

A simplified quantitative acid-base approach for patients with acute respiratory diseases.

The Stewart-Figge acid-base model has been criticized for being mathematically complex. We aimed to develop simpler formalisms, which can be used at the bedside. The following simplifications were used: (1) [Ca2+] and [Mg2+] are replaced by their mid-reference concentrations (2) pH is set to 7.4. In the new model [SIDa] is replaced by its adjusted form, [SIDa, adj] = [Na+] + [K+] - [Cl-] + 6.5 and [SIG] is replaced by "bicarbonate gap", [BICgap] = [SIDa, adj] - (0.28⋅[Albumin]) - (1.82⋅[Phosphatei])- [HCO3̄]. The diagnostic performance of the model was tested in 210 patients with acute respiratory diseases and 17 healthy volunteers. [BICgap] was also compared to albumin-corrected anion gap ([AGc]). The concordant correlation coefficient between [SIDa, adj] and [SIDa] and between [BICgap] and [SIG] was 0.98 in both comparisons. The mean bias (limits of agreement) of [SIDa, adj] - [SIDa] and of [BICgap] - [SIG] were 0.53 meq/l (- 0.46 to 1.53) and 0.50 meq/l (- 0.70 to 1.70), respectively. A [SIDa, adj] < 50.4 meq/l had an accuracy of 0.995 (p < 0.001) for the diagnosis of strong ion (SI) acidosis, while a [SIDa, adj] > 52.5 meq/l had an accuracy of 0.997 (p < 0.001) for the diagnosis of SI alkalosis. A [BICgap] > 11.6 meq/l predicted unmeasured ion (UI) acidosis with an accuracy of 0.997 (p < 0.001), while an [AGc] > 19.88 meq/l predicted UI acidosis with an accuracy of 0.994 (p < 0.001). The "[BICgap] model" is a reliable tool for the assessment of acid-base disorders in patients with acute respiratory diseases. [BICgap] is not inferior to [AGc] in the diagnosis of UI acidosis.

Tonicity of oral rehydration solutions affects water, mineral and acid-base balance in calves with naturally occurring diarrhoea.

Recommendations for composition of oral rehydration solutions (ORS) for calves, particularly concerning Na+ , glucose, and their combined effect on tonicity, are not in line with guidelines for humans. Thus, this study aimed to determine the effect of ORS tonicity on water, mineral and acid-base balance. Seventy-two calves were selected based on the severity of dehydration and blood base excess (BE) on day 0. Five calves that did not develop diarrhoea were removed post-inclusion from the study. Calves were allocated to blocks of four animals based on blood BE on day 1. Within each block, calves were randomly assigned to one of four treatments: (a) hypotonic ORS with low Na+ and lactose (HYPO); (b) isotonic ORS with low Na+ and glucose (ISO); (c) hypertonic ORS with high Na+ and glucose (HYPER); and (d) control consisting of warm water including 5 g/L of whey powder (CON). Treatments were administered twice daily over a 3-day period, in which calves were offered 2.0 L of treatment at 1300 and 2100 hr. Calves were fed 2.5 L of milk replacer at 0700 and 1630 hr from day 1 to 3 and 3.0 L from day 4 to 5, and had access to water. Calves were monitored for 5 days in which measurements included intakes, BW, blood sampling and collection of faeces on day 1 and urine from day 1 to 3. All ORS treatments maintained normal serum Na+ , whereas CON did not. Calves in the HYPER group had lower blood pH and greater faecal Na+ losses than HYPO and ISO. Plasma expansion relative to baseline was higher in low tonicity ORS (+4.8%) when compared with CON (+1.0%). Urine osmolality was 30% higher in HYPER calves. In this experiment, low tonicity ORS were more effective at restoring water, mineral and acid-base balance than the hypertonic ORS.

The role of the clinical laboratory in diagnosing acid-base disorders.

Acid-base homeostasis is fundamental for life. The body is exceptionally sensitive to changes in pH, and as a result, potent mechanisms exist to regulate the body's acid-base balance to maintain it in a very narrow range. Accurate and timely interpretation of an acid-base disorder can be lifesaving but establishing a correct diagnosis may be challenging. The underlying cause of the acid-base disorder is generally responsible for a patient's signs and symptoms, but laboratory results and their integration into the clinical picture is crucial. Important acid-base parameters are often available within minutes in the acute hospital care setting, and with basic knowledge it should be easy to establish the diagnosis with a stepwise approach. Unfortunately, many caveats exist, beginning in the pre-analytical phase. In the post-analytical phase, studies on the arterial reference pH are scarce and therefore many different reference values are used in the literature without any solid evidence. The prediction models that are currently used to assess the acid-base status are approximations that are mostly based on older studies with several limitations. The two most commonly used methods are the physiological method and the base excess method, both easy to use. The secondary response equations in the base excess method are the most convenient. Evaluation of acid-base disorders should always include the assessment of electrolytes and the anion gap. A major limitation of the current acid-base laboratory tests available is the lack of rapid point-of-care laboratory tests to diagnose intoxications with toxic alcohols. These intoxications can be fatal if not recognized and treated within minutes to hours. The surrogate use of the osmolal gap is often an inadequate substitute in this respect. This article reviews the role of the clinical laboratory to evaluate acid-base disorders.

Umbilical artery pH and base excess at birth are poor predictors of neurodevelopmental morbidity in early childhood.

AIM: We sought to evaluate the associations between umbilical artery pH and base excess and neurodevelopmental outcome at four years of age. METHODS: This study comprised 84 588 singleton children born alive at term in 2005-2011 in the hospital district of Helsinki and Uusimaa in Finland. Data from the maternity hospital information system were linked to the data from the Medical Birth Register and the Hospital Discharge Register. Neurodevelopmental morbidity included cerebral palsy, epilepsy, intellectual or sensorineural impairment. RESULTS: After adjustment for maternal and perinatal factors, a combination of pH <7.00 and base excess <-16.00 was associated with infant death (adjusted odds ratio 19.97; 95% confidence interval 5.38-74.17). Values of pH 7.00-7.10 were associated with cerebral palsy (adjusted odds ratio 2.40; 95% confidence interval 1.05-5.47). A combination of low five-minute Apgar score and umbilical artery base excess <-16.00 showed the highest positive predictive value (9.1%) for neurodevelopmental impairments. When umbilical artery pH <7.00 was included, a positive predictive value of 25.0% was observed for infant mortality. CONCLUSION: Low umbilical artery pH and base excess at birth were the poor predictors of long-term neurodevelopmental morbidity in an unselected population. However, these parameters might be useful in assessing the risk of infant mortality.

Metabolic acidosis and the role of unmeasured anions in critical illness and injury.

Acid-base disorders are frequently present in critically ill patients. Metabolic acidosis is associated with increased mortality, but it is unclear whether as a marker of the severity of the disease process or as a direct effector. The understanding of the metabolic component of acid-base derangements has evolved over time, and several theories and models for precise quantification and interpretation have been postulated during the last century. Unmeasured anions are the footprints of dissociated fixed acids and may be responsible for a significant component of metabolic acidosis. Their nature, origin, and prognostic value are incompletely understood. This review provides a historical overview of how the understanding of the metabolic component of acid-base disorders has evolved over time and describes the theoretical models and their corresponding tools applicable to clinical practice, with an emphasis on the role of unmeasured anions in general and several specific settings.