Base excess (BE): reloaded.

The base excess value (BE, mmol/L), not standard base excess (SBE), correctly calculated including pH, pCO2 (mmHg), sO2 (%) and cHb (g/dl) is a diagnostic tool for several in vivo events, e.g., mortality after multiple trauma or shock, acidosis, bleeding, clotting, artificial ventilation. In everyday clinical practice a few microlitres of blood (arterial, mixed venous or venous) are sufficient for optimal diagnostics of any metabolic acidosis or alkalosis.The same applies to a therapeutic tool-then referred to as potential base excess (BEpot)-for several in vitro assessments, e.g., solutions for infusion, sodium bicarbonate, blood products, packed red blood cells, plasma. Thus, BE or BEpot has been a parameter with exceptional clinical significance since 2007.

New-onset organ dysfunction as a screening tool for the identification of sepsis and outcome prediction in dogs with systemic inflammation.

Introduction: Sepsis in people is defined as a life-threatening organ dysfunction (OD) caused by a dysregulated host response to infection. In veterinary medicine, sepsis is still defined by the presence of systemic inflammation plus the evidence of infection. Based on recent veterinary studies, multiorgan dysfunction syndrome (MODS) has been associated with a worse outcome in sepsis. Thus, the screening for OD is warranted to identify the most critically ill patients. The aim of this study was to investigate the diagnostic value of new-onset OD for the prediction of sepsis and outcome in a population of critically ill dogs with systemic inflammation. Materials and methods: Dogs admitted to the Emergency Room and/or the Intensive Care Unit with systemic inflammation, defined by a serum C-reactive protein concentration > 1.6 mg/dL, were retrospectively included. Enrolled dogs were categorized according to the presence of sepsis or non-infectious systemic inflammation. The presence of newly diagnosed OD was assessed based on criteria adapted from human literature and previously reported canine criteria. Results: 275 dogs were included: 128 had sepsis and 147 had non-infectious systemic inflammation. The frequency of new-onset OD was not different between these groups. Only the presence of fluid-refractory hypotension was significantly associated with a diagnosis of sepsis (OR 10.51, 3.08-35.94; p < 0.0001). The frequency of at least two ODs was significantly higher in non-survivors compared to survivors, according to both the human and the veterinary criteria considered for the study (p = 0.0001 and p = 0.0004, respectively). Specifically, the presence of acute kidney injury, stupor or coma, prolonged Prothrombin Time and decreased Base Excess were associated with a higher risk of death in the multivariate binary logistic regression. Discussion: In this population of critically ill dogs with systemic inflammation, the detection of newly diagnosed ODs was not able to predict sepsis diagnosis, other than the presence of fluid-refractory hypotension. However, given the strong prognostic significance associated with ODs, our results support the early screening for ODs in any severe inflammatory critical care condition to identify high-risk patients and optimize their management.

Quantifying pH-induced changes in plasma strong ion difference during experimental acidosis: clinical implications for base excess interpretation.

It is commonly assumed that changes in plasma strong ion difference (SID) result in equal changes in whole blood base excess (BE). However, at varying pH, albumin ionic-binding and transerythrocyte shifts alter the SID of plasma without affecting that of whole blood (SIDwb), i.e., the BE. We hypothesize that, during acidosis, 1) an expected plasma SID (SIDexp) reflecting electrolytes redistribution can be predicted from albumin and hemoglobin's charges, and 2) only deviations in SID from SIDexp reflect changes in SIDwb, and therefore, BE. We equilibrated whole blood of 18 healthy subjects (albumin = 4.8 ± 0.2 g/dL, hemoglobin = 14.2 ± 0.9 g/dL), 18 septic patients with hypoalbuminemia and anemia (albumin = 3.1 ± 0.5 g/dL, hemoglobin = 10.4 ± 0.8 g/dL), and 10 healthy subjects after in vitro-induced isolated anemia (albumin = 5.0 ± 0.2 g/dL, hemoglobin = 7.0 ± 0.9 g/dL) with varying CO2 concentrations (2-20%). Plasma SID increased by 12.7 ± 2.1, 9.3 ± 1.7, and 7.8 ± 1.6 mEq/L, respectively (P < 0.01) and its agreement (bias[limits of agreement]) with SIDexp was strong: 0.5[-1.9; 2.8], 0.9[-0.9; 2.6], and 0.3[-1.4; 2.1] mEq/L, respectively. Separately, we added 7.5 or 15 mEq/L of lactic or hydrochloric acid to whole blood of 10 healthy subjects obtaining BE of -6.6 ± 1.7, -13.4 ± 2.2, -6.8 ± 1.8, and -13.6 ± 2.1 mEq/L, respectively. The agreement between ΔBE and ΔSID was weak (2.6[-1.1; 6.3] mEq/L), worsening with varying CO2 (2-20%): 6.3[-2.7; 15.2] mEq/L. Conversely, ΔSIDwb (the deviation of SID from SIDexp) agreed strongly with ΔBE at both constant and varying CO2: -0.1[-2.0; 1.7], and -0.5[-2.4; 1.5] mEq/L, respectively. We conclude that BE reflects only changes in plasma SID that are not expected from electrolytes redistribution, the latter being predictable from albumin and hemoglobin's charges.NEW & NOTEWORTHY This paper challenges the assumed equivalence between changes in plasma strong ion difference (SID) and whole blood base excess (BE) during in vitro acidosis. We highlight that redistribution of strong ions, in the form of albumin ionic-binding and transerythrocyte shifts, alters SID without affecting BE. We demonstrate that these expected SID alterations are predictable from albumin and hemoglobin's charges, or from the noncarbonic whole blood buffer value, allowing a better interpretation of SID and BE during in vitro acidosis.

Alactic base excess (ABE): a novel internal milieu parameter-its concept and clinical importance.

Inspired by the Stewart-Figge acid-base approach, Gattinoni et al. recently introduced a new internal milieu parameter known as alactic base excess (ABE). The authors defined ABE as the sum of lactate and standard base excess. In the context of sepsis, ABE has been proposed as a valuable marker to discern between metabolic acidosis resulting from the accumulation of lactate and the retention of fixed acids, which can occur in cases of renal failure. Multiple studies have demonstrated that a negative ABE value (<-3 mmol/L) represents an early marker of renal dysfunction, and significantly correlates with higher mortality rates in septic patients. In conclusion, ABE is a simple and useful parameter that can be used to better interpret a patient's acid-base status, assess renal function, and general prognosis in sepsis. By incorporating ABE into clinical practice, healthcare professionals can enhance their understanding of the complex acid-base imbalances in their patients and tailor more individualized, effective treatment plans.

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.

Does base excess predict kidney injury in neonates with hypoxic-ischemic encephalopathy?

In neonates with hypoxic-ischemic encephalopathy (HIE), we studied the correlation between cord blood base excess (BE) and kidney function. Among 225 infants, 29 % had oliguria. BE levels differed significantly between oliguric and non-oliguric infants (p < 0.01), with a negative correlation to kidney injury (r = -0.544, p < 0.01). BE < -18 had 85 % specificity and 76 % sensitivity in predicting kidney injury (AUC = 0.88). These findings suggest BE as a valuable indicator of impending kidney injury in HIE infants, though underlying mechanisms may vary.

Association between peri-transplant acid-base parameters and graft dysfunction types in kidney transplantation.

Perioperative acid-base disturbance could be informative regarding the possible slow graft function (SGF) or delayed graft function (DGF) development. There is a lack of data regarding the relationship between perioperative acid-base parameters and graft dysfunction in kidney transplant (KT) recipients. We aim to determine the incidence of graft dysfunction types and the association between them and acid-base parameters. We performed a prospective, cohort study on 54 adults, KT recipients, between 1st of January 2019 and 31st of December 2019. Graft function was defined and classified in three categories: immediate graft function (IGF) (serum creatinine < 3 mg/dL at day 5 after KT), SGF (serum creatinine ≥ 3mg/dL at day 5 or ≥ 2.5mg dL at day 7 after KT) and DGF (the need for at least one dialysis treatment in the first week after kidney transplantation). Among the 54 KT recipients, the incidence of SGF and DGF was 13% and 11.1%, respectively. SGF was significantly associated with lower intraoperative pH (7.26± 0.05 vs 7.35± 0.06, p= 0.004), preoperative and intraoperative base excess (BE) [-7.0 (-10.0 ߝ -6.0) vs -3.4 (-7.8 ߝ - 2.1) mmol/L, p= 0.04 and -10.3 (-11.0 ߝ -9.1) vs -4.0 (-6.3 ߝ - 3.0) mmol/L, p= 0.002, respectively] and serum bicarbonate (HCO3-) (16.0± 2.7 vs 19.3± 3.4 mmol/L, p= 0.01 and 14.1± 1.9 vs 18.8± 3.2 mmol/L, p= 0.002 respectively), compared to IGF. DGF was significantly associated with lower intraoperative values of pH (7.27± 0.05 vs 7.35± 0.06, p= 0.003), BE [-7.1 (-10.9 ߝ -6.1) vs -4.0 (-6.3 ߝ - 3.0) mmol/L, p= 0.02] and HCO3- (15.9± 2.4 vs 18.8± 3.2 mmol/L, p=0.02) compared to IGF. No differences were observed between SGF and DGF patients in any of the perioperative acid-base parameters. In conclusion we found that kidney graft dysfunction types are associated with perioperative acid-base parameters and perioperative metabolic acidosis could provide important information to predict SGF or DGF occurrence.

Evaluation of the Acid-Base Status in Patients Admitted to the ICU Due to Severe COVID-19: Physicochemical versus Traditional Approaches.

BACKGROUND: Stewart's approach is known to have better diagnostic accuracy for the identification of metabolic acid-base disturbances compared to traditional methods based either on plasma bicarbonate concentration ([HCO3-]) and anion gap (AG) or on base excess/deficit (BE). This study aimed to identify metabolic acid-base disorders using either Stewart's or traditional approaches in critically ill COVID-19 patients admitted to the ICU, to recognize potential hidden acid-base metabolic abnormalities and to assess the prognostic value of these abnormalities for patient outcome. METHODS: This was a single-center retrospective study, in which we collected data from patients with severe COVID-19 admitted to the ICU. Electronical files were used to retrieve data for arterial blood gases, serum electrolytes, and proteins and to derive [HCO3-], BE, anion gap (AG), AG adjusted for albumin (AGadj), strong ion difference, strong ion gap (SIG), and SIG corrected for water excess/deficit (SIGcorr). The acid-base status was evaluated in each patient using the BE, [HCO3-], and physicochemical approaches. RESULTS: We included 185 patients. The physicochemical approach detected more individuals with metabolic acid-base abnormalities than the BE and [HCO3-] approaches (p < 0.001), and at least one acid-base disorder was recognized in most patients. According to the physicochemical method, 170/185 patients (91.4%) had at least one disorder, as opposed to the number of patients identified using the BE 90/186 (48%) and HCO3 62/186 (33%) methods. Regarding the derived acid-base status variables, non-survivors had greater AGadj, (p = 0.013) and SIGcorr (p = 0.035) compared to survivors. CONCLUSIONS: The identification of hidden acid-base disturbances may provide a detailed understanding of the underlying conditions in patients and of the possible pathophysiological mechanisms implicated. The association of these acid-base abnormalities with mortality provides the opportunity to recognize patients at increased risk of death and support them accordingly.

Decompensated metabolic acidosis in the emergency department: Epidemiology, sodium bicarbonate therapy, and clinical outcomes.

Objective: This article aims to describe the epidemiology of decompensated metabolic acidosis, the characteristics of sodium bicarbonate (SB) administration and outcomes in emergency department (ED) patients. Design: This is a retrospective cohort study. Setting: ED of a tertiary referral hospital in Melbourne, Australia. Participants: Adult patients presenting to the ED between 1 July 2011 and 20 September 2020 with decompensated metabolic acidosis diagnosed on arterial blood gas (ABG). Main outcome measures: We compared characteristics between those treated with or without SB. We studied SB administration characteristics, change in laboratory variables, factors associated with use and dose, and clinical outcomes. Results: Among 753,613 ED patients, 314 had decompensated metabolic acidosis on ABG, with 17.8% receiving SB. Patients in the SB group had lower median pH, CO2, bicarbonate, and base excess (BE) levels compared with the No SB group (P < 0.01). The median number of SB doses in the SB group was one treatment. This was given at a median total dose of 100 mmol and at a median of 2.8 h after the diagnostic blood gas results. Only 42% of patients in the SB group had a subsequent blood gas measured. In such patients, there was no significant change in pH, bicarbonate, or BE. SB therapy was not independently associated with mortality. Conclusions: ABG-confirmed decompensated metabolic acidosis was rare but associated with a high mortality. SB administration occurred in a minority of patients and in more acidaemic patients. However, SB dose was stereotypical and not tailored to acidosis severity. Assessment of SB effect was infrequent and showed no correction of acidosis. Systematic studies of titrated SB therapy are required to inform current practice.

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.

Rate of decline of fetal base excess after neuraxial anesthesia for scheduled cesarean delivery.

BACKGROUND: In scheduled cesarean deliveries, the rate of decrease in the umbilical artery pH is related to the severity of maternal hypotension and the interval from spinal placement to delivery. Base excess values have greater use than umbilical artery pH values to time the duration of fetal acidemia because they demonstrate a linear rather than logarithmic correlation with the degree of acidosis. OBJECTIVE: This study aimed to evaluate the rate of decline in the fetal base excess in scheduled cesarean deliveries that were converted to emergency cesarean delivery owing to fetal bradycardia following spinal anesthesia. STUDY DESIGN: All cases of scheduled cesarean deliveries in gestations at >34 weeks' gestation under spinal anesthesia that were converted to emergency cesarean deliveries owing to fetal bradycardia in the period May 2019 to May 2021 were reviewed. Included were those with (1) a preoperative reactive nonstress test and (2) fetal acidemia (umbilical artery pH <7.20). Excluded were those with anesthesia other than spinal and a birthweight below the 10th percentile for gestational age. Time intervals between the completion of spinal anesthesia and delivery were calculated and related to umbilical cord gas analytes. RESULTS: From a cohort of 1064 scheduled cesarean deliveries, 7 fulfilled the study criteria yielding 8 neonates. Mean ± standard error of the mean interval of spinal anesthesia to delivery was 15.0±1.9 minutes, and the decrease in mean blood pressure after spinal anesthesia was 39.1±3.0 mm Hg. Umbilical artery base excess ranged from -5.2 to -16.6 mmol/L (median, -8.0). Based on published normative data of prelabor fetal umbilical artery base excess (-2±0.6 mmol/L), the mean rate of base excess decrease was 0.38±0.25 mmol/minute. CONCLUSION: The rate of decrease in base excess when scheduled cesarean deliveries are converted to emergency cesarean deliveries owing to fetal bradycardia related to spinal anesthesia (1 mmol/2.6 min) matches the estimated rate of loss of base excess (1 mmol/2-3 minutes) reported in cases of severe bradycardia or sentinel events during labor.

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.

Preoperative Base Excess as a Predictor of Perioperative Complications in Patients with Nonidiopathic Scoliosis who Have High Risk Associated with General Anesthesia.

Introduction: Patients with nonidiopathic scoliosis often have a high risk associated with general anesthesia because of cardiac or pulmonary dysfunction secondary to underlying diseases. Base excess has been reported as a predictor in the management of trauma and cancer, although not yet in scoliosis. This study was performed to clarify the surgical outcomes and the association of perioperative complications with base excess in patients with nonidiopathic scoliosis who have a high risk associated with general anesthesia. Methods: Patients with nonidiopathic scoliosis who were referred to our institution from 2009 to 2020 because of their high risk associated with general anesthesia were retrospectively enrolled. High-risk factors for anesthesia were determined by a senior anesthesiologist and categorized into circulatory or pulmonary dysfunction. Perioperative complications were analyzed using the Clavien-Dindo classification; severe complications were defined as grade ≥III. We investigated high-risk factors for anesthesia, underlying diseases, preoperative and postoperative Cobb angle, surgery-related factors, base excess, and postoperative management. These variables were statistically compared between patients with and without complications. Results: Thirty-six patients (mean age, 17.9 years old; range, 11-40 years old) were enrolled (two patients declined surgery). High-risk factors were circulatory dysfunction in 16 patients and pulmonary dysfunction in 20 patients. The mean Cobb angle improved from 85.1° (36°-128°) preoperatively to 43.6° (9°-83°) postoperatively. Three intraoperative complications and 23 postoperative complications occurred in 20 (55.6%) patients. Severe complications occurred in 10 (27.8%) patients. All patients underwent postoperative intensive care unit management after posterior all-screw construction. A large preoperative Cobb angle (p=0.021) and base excess outliers (>3 or <-3 mEq/L) (p=0.005) were significant risk factors for complications. Conclusions: Patients with nonidiopathic scoliosis who have a high risk associated with general anesthesia have a higher complication rate. Preoperative large deformity and base excess (>3 or <-3 mEq/L) could be predictors of complications.

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.

Association between base excess and 28-day mortality in sepsis patients: A secondary analysis based on the MIMIC- IV database.

Objective: The relationship between base excess (BE) and 28-day death in sepsis patients remains to be elucidated. The aim of our clinical study is to explore the association of BE with 28-day mortality in patients with sepsis by using a large sample, multicenter Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Methods: We extracted the data of 35,010 patients with sepsis from the MIMIC-IV database, in which we used BE as an exposure variable and the 28-day mortality as an outcome variable, respectively, so as to explore the impact of BE on the 28-day mortality of patients with sepsis after adjusting for covariates. Results: BE and the 28-day mortality of patients with sepsis appeared to have a U-shaped relationship. The calculated inflection points were -2.5 mEq/L and 1.9 mEq/L, respectively. Our data demonstrated that BE was negatively associated with 28-day mortality in the range of -41.0 mEq/L to -2.5 mEq/L (odds ratio: 0.95; 95% confidence intervals (95%CI): 0.93 to 0.96), p < 0.0001. When BE was in the range of 1.9 mEq/L to 55.5 mEq/L, however, a positive association existed between BE and 28-day mortality of patients with sepsis (odds ratio: 1.03; 95% CI: 1.00 to 1.05; p < 0.05). Conclusion: The BE levels have a U-shaped relationship with the 28-day mortality in patients with sepsis, in which the mortality of patients will gradually decrease with a BE value from -41.0 mEq/L to -2.5 mEq/L, while the mortality will increase with a BE value from 1.9 mEq/L to 55.5 mEq/L.

Hemorrhagic Shock: Blood Marker Sequencing and Pulmonary Gas Exchange.

BACKGROUND: The early identification of internal hemorrhage in critically ill patients may be difficult. Besides circulatory parameters, hemoglobin and lactate concentration, metabolic acidosis and hyperglycemia serve as laboratory markers for bleeding. In this experiment, we examined pulmonary gas exchange in a porcine model of hemorrhagic shock. Moreover, we sought to investigate if a chronological order of appearance regarding hemoglobin, lactatemia, standard base excess/deficit (SBED) and hyperglycemia exists in early severe hemorrhage. METHODS: In this prospective, laboratory study, twelve anesthetized pigs were randomly allocated to exsanguination or a control group. Animals in the exsanguination group (n = 6) endured a 65% blood loss over 20 min. No intravenous fluids were administered. Measurements were taken before, immediately after, and at 60 min after the completed exsanguination. Measurements included pulmonary and systemic hemodynamic variables, hemoglobin concentration, lactate, base excess (SBED), glucose concentration, arterial blood gases, and a multiple inert gas assessment of pulmonary function. RESULTS: At baseline, variables were comparable. Immediately after exsanguination, lactate and blood glucose were increased (p = 0.001). The arterial partial pressure of oxygen was increased at 60 min after exsanguination (p = 0.04) owing to a decrease in intrapulmonary right-to-left shunt and less ventilation-perfusion inequality. SBED was different to the control only at 60 min post bleeding (p < 0.001). Hemoglobin concentration did not change at any time (p = 0.97 and p = 0.14). CONCLUSIONS: In experimental shock, markers of blood loss became positive in chronological order: lactate and blood glucose concentrations were raised immediately after blood loss, while changes in SBED lagged behind and became significant one hour later. Pulmonary gas exchange is improved in shock.

Alactic base excess is an independent predictor of death in sepsis: A propensity score analysis.

PURPOSE: Alactic base excess (ABE) is a novel biomarker defined as the sum of lactate and standard base excess and estimates the renal capability of handling acid-base disturbances in sepsis. The objective of this study is to see if ABE is an independent predictor of mortality in septic patients with and without renal dysfunction. MATERIALS AND METHODS: We retrospectively studied 1178 patients with sepsis and septic shock. Patients were divided according to ABE values: 1) negative ABE (<-3 mmol/L); 2) neutral ABE (≥ - 3 and < 4 mmol/L); and 3) positive ABE (≥4 mmol/L). The effect of ABE on mortality was evaluated using Cox regression weight by inverse probability weighting (IPWT) analysis after propensity score assessment. Additionally, we performed a stratified analysis in patients with GFR > 60 mL/min/1.73 m2. RESULTS: Negative ABE patients had higher mortality than patients with neutral ABE (adjusted HR 1.43; 95%CI 1.02-2.01). Also, in patients with GFR > 60 mL/min/1.73 m2 (n = 493), we observed higher mortality in patients with negative ABE (adjusted HR 2.43; 95%CI 1.07-5.53). CONCLUSIONS: Negative ABE is an independent predictor of in-hospital mortality in septic patients with and without renal dysfunction.

Markers of tissue perfusion and their relation to mortality in dogs with blunt trauma.

OBJECTIVE: To evaluate admission Animal Trauma Triage (ATT) score, shock index (SI), and markers of perfusion, including base excess (BE), plasma lactate, and lactate clearance in dogs with blunt trauma. DESIGN: Prospective observational clinical study from 2013 to 2015. SETTING: Private veterinary referral and emergency center. ANIMALS: Forty-four client-owned dogs hospitalized following blunt trauma. INTERVENTION: Within 1 hour of presentation and prior to fluid administration an initial hematocrit, total plasma protein, blood glucose, plasma lactate, blood gas, and electrolytes were obtained for analysis. Plasma lactate concentrations were also measured 4 and 8 hours following initial measurement, and a 4-hour lactate clearance was calculated if patients had an increased admission plasma lactate. ATT score and SI were calculated for each patient based on admission data. Outcome was defined as survival to hospital discharge. MEASUREMENTS AND MAIN RESULTS: Twenty-nine dogs survived, 14 were euthanized, and 1 died. Nonsurviving dogs had a lower mean pH (7.28 ± 0.03 vs 7.36 ± 0.01, P = 0.006), lower median HCO3 (15.7 vs 18.8 mmol/L, P = 0.004), lower median admission BE (-11.0 vs -7.0 mmol/L, P = 0.004), and higher median admission lactate (3.1 vs 2.4 mmol/L, P = 0.036) than those who survived. Median ATT was significantly higher in nonsurvivors (5 vsF 2, P < 0.001). The SI was not significantly different between survivors and nonsurvivors (P = 0.41). There was no difference in median 4-hour lactate (P = 0.34), median 8-hour lactate (P = 0.19), or 4-hour lactate clearance (P = 0.83) in survivors compared to nonsurvivors. No other statistically significant differences were noted between groups. CONCLUSION: Dogs hospitalized following blunt trauma with a lower admission pH, HCO3 , and BE and a higher admission plasma lactate were less likely to survive to hospital discharge. Median ATT score was also significantly higher in nonsurvivors. Although lactate clearance was not predictive of survival, the sample size was small, and additional studies with a larger study population are warranted.

Non-carbonic buffer power of whole blood is increased in experimental metabolic acidosis: An in-vitro study.

Non-carbonic buffer power (ßNC) of blood is a pivotal concept in acid-base physiology as it is employed in several acid-base evaluation techniques, including the Davenport nomogram and the Van Slyke equation used for Base excess estimation in blood. So far, ßNC has been assumed to be independent of metabolic acid-base status of blood, despite theoretical rationale for the contrary. In the current study, we used CO2 tonometry to assess ßNC in blood samples from 10 healthy volunteers, simultaneously analyzing the electrolyte shifts across the red blood cell membrane as these shifts translate the action of intracellular non-carbonic buffers to plasma. The ßNC of the blood was re-evaluated after experimental induction of metabolic acidosis obtained by adding a moderate or high amount of either hydrochloric or lactic acid to the samples. Moreover, the impact of ßNC and pCO2 on the Base excess of blood was examined. In the control samples, ßNC was 28.0 ± 2.5 mmol/L. In contrast to the traditional assumptions, our data showed that ßNC rose by 0.36 mmol/L for each 1 mEq/l reduction in plasma strong ion difference (p < 0.0001) and was independent of the acid used. This could serve as a protective mechanism that increases the resilience of blood to the combination of metabolic and respiratory acidosis. Sodium and chloride were the only electrolytes whose plasma concentration changed relevantly during CO2 titration. Although no significant difference was found between the electrolyte shifts in the two types of acidosis, we observed a slightly higher rate of chloride change in hyperchloremic acidosis, while the variation of sodium was more pronounced in lactic acidosis. Lastly, we found that the rise of ßNC in metabolic acidosis did not induce a clinically relevant bias in the calculation of Base excess of blood and confirmed that the Base excess of blood was little affected by a wide range of pCO2.