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Introduction: Infants with perinatal asphyxia are at risk for organ failure aside from the brain, regardless of the severity of the asphyxial insult. We aimed to evaluate the presence of organ dysfunction other than the brain in newborns with moderate to severe acidosis at birth, in the absence of moderate to severe hypoxic ischemic encephalopathy., Materials and Methods: Data of 2 years were retrospectively recorded. Late preterm and term infants admitted to the intensive care unit with ph < 7.10 and BE < -12 mmol/l in the first hour were included in the absence of moderate to severe hypoxic ischemic encephalopathy. Respiratory dysfunction, hepatic dysfunction, renal dysfunction, myocardial depression, gastrointestinal problems, hematologic system dysfunction, and circulatory failure were evaluated., Results: Sixty-five infants were included [39 (37-40) weeks, 3040 (2655-3380) grams]. Fifty-six (86 %) infants had one or more dysfunction in any system [respiratory: 76.9 %, hepatic: 20.0 %, coagulation: 18.5 %, renal: 9.2 %, hematologic: 7.7 %, gastrointestinal: 3.0 %, and cardiac: 3.0 %]. Twenty infants had at least two affected systems. The incidence of coagulation dysfunctions was higher in the infants with severe acidosis (n = 25, ph < 7.00) than the infants with moderate acidosis (n = 40: pH = 7.00-7.10); 32 % vs 10 %; p = 0.03., Conclusions: Moderate to severe fetal acidosis is associated with the development of extra-cranial organ dysfunctions in infants who do not require therapeutic hypothermia. A monitoring protocol is needed for infants with mild asphyxia in order to identify and manage potential complications. Coagulation system should be carefully evaluated., Competing Interests: Conflict of interest Authors declare no financial or non-financial conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

During the progression of diabetic kidney disease (DKD), renal lactate metabolism is rewired. The relationship between alterations in renal lactate metabolism and renal fibrosis in patients with diabetes has only been partially established due to a lack of biopsy tissues from patients with DKD and the intricate mechanism of lactate homeostasis. The role of lactate dehydrogenase A (LDHA)-mediated lactate generation in renal fibrosis and dysfunction in human and animal models of DKD was explored in this study. Measures of lactate metabolism (urinary lactate levels and LDHA expression) and measures of DKD progression (estimated glomerular filtration rate and Wilms' tumor-1 expression) were strongly negatively correlated in patients with DKD. Experiments with streptozotocin-induced DKD rat models and the rat renal mesangial cell model confirmed our findings. We found that the pathogenesis of DKD is linked to hypoxia-mediated lactic acidosis, which leads to fibrosis and mitochondrial abnormalities. The pathogenic characteristics of DKD were significantly reduced when aerobic glycolysis or LDHA expression was inhibited. Further studies will aim to investigate whether local acidosis caused by renal LDHA might be exploited as a therapeutic target in patients with DKD., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Acetazolamide is contraindicated in patients undergoing dialysis and should be used with caution in patients with chronic kidney disease (CKD). Here, we evaluate the effect of the concomitant use of aspirin by patient with CKD using acetazolamide., Case Report: A 63-year-old man with CKD and multimorbidity presented at our Emergency Department (ED) with general weakness and dyspnea for 4 days. Work-up at the ED revealed severe metabolic acidosis and hyperammonemia, which were initially considered signs of sepsis due to an elevated C-reactive protein level and pyuria. However, subsequent blood work indicated hyperchloremic acidosis with low lactate levels. After reviewing his medical history, we suspected the concomitant use of acetazolamide and aspirin as the etiology. Weakness, acidosis, and hyperammonemia were resolved after the patient discontinued acetazolamide. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Severe acidosis can be life threatening. Acetazolamide is known for causing mild metabolic acidosis, except in patients with severely impaired renal function. Here, we present a patient with mildly impaired renal function and concomitant aspirin use who developed severe metabolic acidosis and hyperammonemia after being prescribed acetazolamide. Regardless of the severity of the disease, patients with CKD should avoid taking acetazolamide concomitantly with aspirin., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Studies in healthy patients undergoing elective caesarean delivery show that, compared with phenylephrine, ephedrine used to treat spinal hypotension is associated with increased fetal acidosis. This has not been investigated prospectively in women with severe preeclampsia., Methods: Patients with preeclampsia requiring caesarean delivery for a non-reassuring fetal heart tracing were randomised to receive either bolus ephedrine (7.5-15mg) or phenylephrine (50-100µg), to treat spinal hypotension. The primary outcome was umbilical arterial base excess. Secondary outcomes were umbilical arterial and venous pH and lactate concentration, venous base excess, and Apgar scores., Results: Among 133 women, 64 who required vasopressor treatment were randomised into groups of 32 with similar patient characteristics. Pre-delivery blood pressure changes were similar. There was no difference in mean [standard deviation] umbilical artery base excess (-4.9 [3.7] vs -6.0 [4.6] mmol/L for ephedrine and phenylephrine respectively; P=0.29). Mean umbilical arterial and venous pH and lactate concentrations did not significantly differ between groups (7.25 [0.08] vs 7.22 [0.10], 7.28 [0.07] vs 7.27 [0.10], and 3.41 [2.18] vs 3.28 [2.44] mmol/L respectively). Umbilical venous oxygen tension was higher in the ephedrine group (2.8 [0.7] vs 2.4 [0.62]) kPa, P=0.02). There was no difference in 1- or 5-min Apgar scores, numbers of neonates with 1-min Apgar scores <7 or with a pH <7.2., Conclusions: In patients with severe preeclampsia and fetal compromise, fetal acid-base status is independent of the use of bolus ephedrine versus phenylephrine to treat spinal hypotension., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Conflicting evidence associates diet acidity with the incidence of chronic diseases such as hypertension, diabetes, kidney disease, and bone-mineral disorders. It is currently unknown whether dietary acidity is associated with death., Objective: We investigated the association of dietary acid load with the risk of all-cause and cardiovascular disease (CVD) mortality., Methods: We used data from 2 prospective cohorts, the Swedish Mammography Cohort and the Cohort of Swedish Men, which included 36,740 women and 44,957 men aged 45-84 y at the start of a 15-y follow-up period (1998-2012). Acid load was estimated from food-frequency questionnaires by use of the validated potential renal acid load (PRAL) algorithm. Deaths were ascertained via record linkage. Associations of PRAL with mortality were modeled by use of restricted cubic splines., Results: The median PRAL was 0.65 mEq/d (range: -109 to 81.5 mEq/d) in women and 12.3 mEq/d (-111 to 121 mEq/d) in men. During a mean of 13.5 ± 3.3 y of follow-up, there were 8576 and 13,332 deaths, of which 3203 and 5427 were attributed to cardiovascular causes in woman and men, respectively. In both sexes, a nonlinear U-shaped relation was observed, with higher mortality rates for both dietary acid and alkali excess. Compared with neutral PRAL (0 mEq/d), the HRs for all-cause mortality for the 10th and 90th percentiles of PRAL were 1.05 (95% CI: 1.01, 1.10) and 1.03 (95% CI: 0.98, 1.08), respectively, in women. The corresponding results for men were HRs 1.01 (95% CI: 1.00, 1.02) and 1.04 (95% CI: 1.00, 1.08) respectively. This relation was slightly stronger for CVD mortality., Conclusions: Excess diet alkalinity and acidity both showed weak associations with higher mortality in Swedish adults. An acid-base balanced diet was associated with the lowest mortality, but the magnitude of mortality reduction was modest. The Swedish Mammography Cohort was registered at clinicaltrials.gov as NCT01127698 The Cohort of Swedish Men was registered at clinicaltrials.gov as NCT01127711., (© 2016 American Society for Nutrition.)

Glutamate activates peripheral group I metabotropic glutamate receptors (mGluRs) and contributes to inflammatory pain. However, it is still not clear the mechanisms are involved in group I mGluR-mediated peripheral sensitization. Herein, we report that group I mGluRs signaling sensitizes acid-sensing ion channels (ASICs) in dorsal root ganglion (DRG) neurons and contributes to acidosis-evoked pain. DHPG, a selective group I mGluR agonist, can potentiate the functional activity of ASICs, which mediated the proton-induced events. DHPG concentration-dependently increased proton-gated currents in DRG neurons. It shifted the proton concentration-response curve upwards, with a 47.3±7.0% increase of the maximal current response to proton. Group I mGluRs, especially mGluR5, mediated the potentiation of DHPG via an intracellular cascade. DHPG potentiation of proton-gated currents disappeared after inhibition of intracellular Gq/11 proteins, PLCβ, PKC or PICK1 signaling. Moreover, DHPG enhanced proton-evoked membrane excitability of rat DRG neurons and increased the amplitude of the depolarization and the number of spikes induced by acid stimuli. Finally, peripherally administration of DHPG dose-dependently exacerbated nociceptive responses to intraplantar injection of acetic acid in rats. Potentiation of ASIC activity by group I mGluR signaling in rat DRG neurons revealed a novel peripheral mechanism underlying group I mGluRs involvement in hyperalgesia., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Diet-induced metabolic acidosis has been linked to cardiometabolic abnormalities in Westerners, but the evidence on this issue is scarce in Asians., Objective: The present study prospectively examined the association between dietary acid load and type 2 diabetes (T2D) in Japanese adults., Methods: Study participants were 27,809 men and 36,851 women, aged 45-75 y, who completed a dietary questionnaire of the second survey of the Japan Public Health Center-based Prospective Study and had no previous history of T2D. Dietary intake was assessed by using a validated 147-item food-frequency questionnaire. Potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores were derived from the nutrient intake. A multilevel logistic regression model was used to estimate ORs and 95% CIs of self-reported, physician-diagnosed T2D over 5 y, with adjustment for potential confounding variables., Results: A total of 1191 cases of newly diagnosed T2D were reported. PRAL score was positively associated with T2D in men; the multivariable-adjusted ORs (95% CIs) for the lowest through the highest quartiles of PRAL were 1.00, 1.09 (0.87, 1.36), 1.10 (0.88, 1.37), and 1.25 (1.01, 1.55) (P-trend = 0.047). Further adjustment for dietary intake strengthened the association. NEAP score was not associated with the risk of T2D (P-trend = 0.20). In stratified analyses, the positive association between PRAL and T2D was confined to younger men (age <50 y; P-trend = 0.046). There was no association between dietary acid load score and T2D in women., Conclusion: A high dietary acid load score is associated with an increased risk of T2D in Japanese men., (© 2016 American Society for Nutrition.)

Aims: Ischemia/reperfusion (I/R) injury and metabolic acidosis (MA) are two critical conditions that may simultaneously occur in clinical practice. The result of this combination can be harmful to the kidneys, but this issue has not been thoroughly investigated. The present study evaluated the influence of low systemic pH on various parameters of kidney function in rats that were subjected to an experimental model of renal I/R injury., Main Methods: Metabolic acidosis was induced in male Wistar rats by ingesting ammonium chloride (NH4Cl) in tap water, beginning 2 days before ischemic insult and maintained during the entire study. Ischemia/reperfusion was induced by clamping both renal arteries for 45 min, followed by 48 h of reperfusion. Four groups were studied: control (subjected to sham surgery, n=8), I/R (n=8), metabolic acidosis (MA; 0.28 M NH4Cl solution and sham surgery, n=6), and MA+I/R (0.28 M NH4Cl solution plus I/R, n=9)., Key Findings: Compared with I/R rats, MA+I/R rats exhibited higher mortality (50 vs. 11%, p=0.03), significant reductions of blood pH, plasma bicarbonate (pBic), and standard base excess (SBE), with a severe decline in the glomerular filtration rate and tubular function. Microscopic tubular injury signals were detected. Immunofluorescence revealed that the combination of MA and I/R markedly increased nuclear factor κB (NF-κB) and heme-oxygenase 1 (HO-1), but it did not interfere with the decrease in endothelial nitric oxide synthase (eNOS) expression that was caused by I/R injury., Significance: Acute ischemic kidney injury is exacerbated by acidic conditions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Complications occurring at any level of foetal oxygen supply will result in hypoxaemia, and this may ultimately lead to hypoxia/acidosis and neurological damage. Hypoxic-ischaemic encephalopathy (HIE) is the short-term neurological dysfunction caused by intrapartum hypoxia/acidosis, and this diagnosis requires the presence of a number of findings, including the confirmation of newborn metabolic acidosis, low Apgar scores, early imaging evidence of cerebral oedema and the appearance of clinical signs of neurological dysfunction in the first 48 h of life. Cerebral palsy (CP) consists of a heterogeneous group of nonprogressive movement and posture disorders, frequently accompanied by cognitive and sensory impairments, epilepsy, nutritional deficiencies and secondary musculoskeletal lesions. Although CP is the most common long-term neurological complication associated with intrapartum hypoxia/acidosis, >80% of cases are caused by other phenomena. Data on minor long-term neurological deficits are scarce, but they suggest that less serious intellectual and motor impairments may result from intrapartum hypoxia/acidosis. This chapter focuses on the existing evidence of neurological damage associated with poor foetal oxygenation during labour., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Dietary acid load affects acid-base homeostasis, which may be associated with blood pressure (BP). Previous research on dietary acid load and BP in the community has provided conflicting results, which may be confounded by underlying kidney function with inability to eliminate acid excess., Objective: The objective of this study was to determine whether dietary acid load is associated with blood pressure or the incidence of hypertension in older men taking into account each individual's kidney function., Methods: We included 673 men aged 70-71 y and not receiving antihypertensive medication from the Uppsala Longitudinal Study of Adult Men. Of those, 378 men were re-examined after 7 y. Dietary acid load was estimated at baseline by potential renal acid load (PRAL) and net endogenous acid production (NEAP), based on nutrient intake assessed by 7-d food records at baseline. Ambulatory blood pressure monitoring (ABPM) was performed at both visits. Cystatin C-estimated kidney function allowed identification of underlying chronic kidney disease., Results: Median estimated PRAL and NEAP were 3.3 and 40.7 mEq/d, respectively. In cross-section, PRAL was in general not associated with ABPM measurements (all P > 0.05, except for the 24-h diastolic BP). During follow-up, PRAL did not predict ABPM changes (all P > 0.05). When individuals with baseline hypertension (ABPM ≥ 130/80 mm Hg) or nondippers (with nighttime-to-daytime systolic BP ratio > 0.9) were excluded, PRAL was not a predictor of incident cases (P > 0.30). Kidney function did not modify these null relations. Similar findings were obtained with the use of NEAP as the exposure., Conclusion: Our analyses linking estimated dietary acid load with BP outcome measurements both cross-sectionally and after 7 y in community-based older Swedish men of similar age did not reveal an association between dietary acid load and BP., (© 2015 American Society for Nutrition.)

Objective: In most cases of pediatric liver transplantation, the clinical scenario of large-for-size transplants can lead to hepatic dysfunction and a decreased blood supply to the liver graft. The objective of the present experimental investigation was to evaluate the effects of ischemic preconditioning on this clinical entity., Methods: Eighteen pigs were divided into three groups and underwent liver transplantation: a control group, in which the weights of the donors were similar to those of the recipients, a large-for-size group, and a large-for-size + ischemic preconditioning group. Blood samples were collected from the recipients to evaluate the pH and the sodium, potassium, aspartate aminotransferase and alanine aminotransferase levels. In addition, hepatic tissue was sampled from the recipients for histological evaluation, immunohistochemical analyses to detect hepatocyte apoptosis and proliferation and molecular analyses to evaluate the gene expression of Bax (pro-apoptotic), Bcl-XL (anti-apoptotic), c-Fos and c-Jun (immediate-early genes), ischemia-reperfusion-related inflammatory cytokines (IL-1, TNF-alpha and IL-6, which is also a stimulator of hepatocyte regeneration), intracellular adhesion molecule, endothelial nitric oxide synthase (a mediator of the protective effect of ischemic preconditioning) and TGF-beta (a pro-fibrogenic cytokine)., Results: All animals developed acidosis. At 1 hour and 3 hours after reperfusion, the animals in the large-for-size and large-for-size + ischemic preconditioning groups had decreased serum levels of Na and increased serum levels of K and aspartate aminotransferase compared with the control group. The molecular analysis revealed higher expression of the Bax, TNF-alpha, I-CAM and TGF-beta genes in the large-for-size group compared with the control and large-for-size + ischemic preconditioning groups. Ischemic preconditioning was responsible for an increase in c-Fos, IL-1, IL-6 and e-NOS gene expression., Conclusion: Ischemia-reperfusion injury in this model of large-for-size liver transplantation could be partially attenuated by ischemic preconditioning.

Renal tubular acidosis (RTAs) are a group of metabolic disorders characterized by metabolic acidosis with normal plasma anion gap. There are three main forms of RTA: a proximal RTA called type II and a distal RTA (type I and IV). The RTA type II is a consequence of the inability of the proximal tubule to reabsorb bicarbonate. The distal RTA is associated with the inability to excrete the daily acid load and may be associated with hyperkalaemia (type IV) or hypokalemia (type I). The most common etiology of RTA type IV is the hypoaldosteronism. The RTAs can be complicated by nephrocalcinosis and obstructive nephrolithiasis. Alkalinization is the cornerstone of treatment., (Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Background: The relationship between cord arterial pH (CA-pH) > 7.000 and the neonatal outcome is not clear., Aims: To evaluate if asymptomatic infants born with unexpected cord arterial pH (CA-pH) between 7.000 and 7.100 develop clinical, biochemical, and instrumental signs of hypoxic cerebral, renal, and heart failure more frequently than symptomatic infants., Study Design: Term infants with CA-pH of 7.000-7.100 and appropriate birth weight were prospectively and consecutively enrolled and classified as asymptomatic, when they had no resuscitation, early respiratory distress or early abnormal neurologic signs, and symptomatic infants. Clinical, biochemical, and instrumental signs of hypoxic cerebral, renal, and heart failure were evaluated in the two groups., Results: A total of 53 infants were enrolled. Twenty-eight (53%) were asymptomatic. CA-pH was similar in both the groups, while the cTnI serum concentration in the first day of life and the occurrence of poor feeding were higher in the symptomatic than in asymptomatic infants. An arterial lactate level of ≥ 4.1 mmol/l measured in the first hour of life was an independent risk factor for the development of a symptomatic course., Conclusions: In our population the majority of infants born with a CA-pH between 7.000 and 7.100 were asymptomatic and would not have needed immediate admission to the neonatal care unit. Symptomatic infants showed a higher occurrence of subclinical heart injury and poor feeding., (© 2013.)

Introduction: The use of recombinant factor VIIa (rFVIIa) in trauma patients is usually part of rescue therapy when haemorrhage and coagulopathy have not responded to conventional treatment. In this scenario, trauma patients are likely to have one or more components of the 'triad of death' (coagulopathy, acidosis and hypothermia). The aim of this study was to report on the outcome of trauma patients with the 'triad of death' immediately prior to receiving rFVIIa., Materials and Methods: Trauma patients receiving rFVIIa with the 'triad of death' were identified from the Australia and New Zealand Haemostasis Registry (ANZHR) and included in the study. The 'triad of death' was defined as an INR of >1.5, serum pH of <7.2 and a core temperature of <35 °C. Pre-dose clinical signs, investigations, adverse events and outcomes were analysed., Results: There were 2792 patients in the ANZHR, of which 386 were trauma patients and 45 patients had the 'triad of death'. Patients with the 'triad of death' were significantly older and had higher injury severity scores than other trauma patients, with a mortality of 68.9%. Survivors were significantly less acidaemic (p<0.001) and had significantly less packed red blood cell (PRBC) transfusion prior to rFVIIa administration (p=0.041) than non-survivors with the triad of death., Discussion: In the face of refractory bleeding, coagulopathy, acidosis and hypothermia following conventional resuscitation, the use of rFVIIa in trauma patients was associated with survival in 31% of patients and may be considered as a management option. Administration of rFVIIa in patients with a pH of <6.91 appears futile., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Mild metabolic acidosis, which can be caused by diet, may result in elevated blood pressure (BP)., Design: The analyses included 2241 participants aged ≥55 y who were free of hypertension at baseline (1990-1993) and who had complete dietary and BP data. Dietary data were obtained from a 170-item food-frequency questionnaire. We used 2 measures to characterize dietary acid load: (1) potential renal acid load (PRAL) by using an algorithm including protein, phosphorus, potassium, calcium, and magnesium, and (2) estimated net endogenous acid production (NEAP) based on protein and potassium. HRs for 6-y incidence of hypertension were obtained in tertiles of PRAL and NEAP with adjustment for age, sex, BMI, smoking, education, and intakes of alcohol, fiber, and total energy., Results: We identified 1113 incident cases of hypertension during 8707 person-years of follow-up. The median dietary acid load ranged from -14.6 to 19.9 mEq/d across categories of PRAL. Hypertension risk was not significantly associated with dietary acid load. The multivariate HRs (95% CIs) in consecutive tertiles of PRAL were 1.00 (reference), 1.01 (0.87, 1.17), and 1.02 (0.88, 1.18) (P trend = 0.83). The median dietary acid loads were 30.4, 36.7, and 43.7 mEq/d, respectively, in consecutive tertiles of NEAP. Corresponding HRs for NEAP were 1.00 (reference), 0.92 (0.80, 1.07), and 0.94 (0.81, 1.10) (P-trend = 0.46)., Conclusion: The findings from this prospective cohort study provided no evidence of an association between dietary acid load and risk of hypertension in older adults.

Background: Spectral analysis of fetal heart rate (FHR) variability is a useful method to assess fetal condition. There have been several studies involving the change in spectral power related to fetal acidemia, but the results have been inconsistent., Aims: To determine the change in spectral power related to fetal umbilical arterial pH at birth, dividing cases into preterm (31-36 weeks) and term (≥37 weeks) gestations., Study Design: Case-control study. The 514 cases of deliveries were divided into a low-pH group (an umbilical arterial pH <7.2) and a control group (pH≥7.2)., Subjects: FHR recorded on cardiotocography during the last 2h of labor., Outcome Measures: The spectral powers in various bands of FHR variability., Results: In preterm fetuses, the total, low (LF), and movement (MF) frequency spectral powers and LF/HF ratio were significantly lower in the low-pH group than the control group (all P<0.05). In contrast, in term fetuses, the total frequency, LF, and MF powers were significantly higher in the low-pH group than the control group (all P<0.05). The area under the receiver operating characteristic of LF power to detect a low pH at birth was 0.794 in preterm fetuses and 0.595 in term fetuses. The specificity was 86.8% and 93.3% in preterm and term fetuses, respectively., Conclusions: The changes in spectral power responding to a low pH are different between term and preterm fetuses. Spectral analysis of FHR variability may be useful fetal monitoring for early detection of fetal acidemia., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The patients suffering from acidosis usually sign psychological deficits. The cerebral dysfunction is reportedly caused by an acid-induced functional impairment of GABAergic neurons; however, the role of pyramidal neurons in this process remains unclear. By using electrophysiological method and changing extracellular pH, we investigated the influence of acidic environment on pyramidal neurons in the cortical slices, such as their ability of firing spikes and response to synaptic inputs. A low pH of artificial cerebral spinal fluid elevates the responses of pyramidal neurons to excitatory synaptic inputs and their ability of encoding digital spikes, as well as reduces the signal transmission at GABAergic synapses. The elevated ability of neuronal spiking is associated with the decreases of refractory periods and threshold potentials. Therefore, acidosis deteriorates brain functions through making the activities between cortical pyramidal neurons and GABAergic neurons imbalanced toward the overexcitation of neural networks, a process similar to neural excitotoxicity., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: In asphyxiated term and near-term infants, therapeutic hypothermia increases survival without neurologic morbidity, and extending this new treatment to preterm infants is being debated., Aims: To investigate the association of low pH and base excess (BE) at birth or admission, as used as entry criteria in cooling trials, and evolving brain damage in preterm infants., Study Design and Measurements: Rates of death and neurodevelopmental impairment at 12 and 20 months corrected age were assessed in a cohort of 1137 preterm infants with a gestational age <35 weeks and birth weight <1500 g in relation to severe perinatal acidosis (umbilical artery pH≤7.0, pH at admission ≤7.0, BE at admission ≤-16 mmol/l, lowest BE during first 12 h of life ≤-16 mmol/l)., Results: Umbilical artery pH was not linked to death or neurodevelopmental impairment. There was only weak predictive power of pH or BE at admission for death (positive predictive values [PPV] 0.36/0.30, receiver operator characteristics [ROC] areas 0.591/0.701), and lowest 12-h BE for death or neurodevelopmental impairment at 12 or 20 months (PPV 0.29/0.30/0.27, ROC 0.720/0.656/0.658)., Conclusion: In very preterm infants, there is little association between laboratory markers of severe perinatal acidosis and neurodevelopmental outcome at 12 or 20 months., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: Damage control is a strategy of care for bleeding trauma patients, involving minimal rescue surgery associated to perioperative resuscitation. The purpose of this review is to draw up a statement on current knowledge available on damage control., Data Sources: References were obtained from recent review articles, personal files, and Medline database research of English and French publications. All categories of articles on this topic have been selected., Data Synthesis: Historical damage control surgery, that consist of abbreviated laparotomy with second-look after resuscitation, is now included in a wider concept called "damage control resuscitation", addressing the lethal triad (coagulopathy, hypothermia and acidosis) at an early phase. Care is focused on coagulopathy prevention. Early resuscitation, or damage control ground zero, has been improved: aggressive management of hypothermia, bleeding control techniques, permissive hypotension concept and early use of vasopressors. Transfusion practices also have evolved: early platelets and coagulation factors administration, use of hemostatic agents like recombinant FVIIa, whole blood transfusion, denote the damage control hematology. Progress in surgical practices and development of arteriographic techniques lead to wider indications of damage control strategy., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Acidosis, associated with metabolic disorders, leads to the pathological changes of cognition and behavior in the clinical practices of neurology and psychology. The cellular mechanisms underlying these cerebral dysfunctions remain unclear. By using electrophysiological approach and changing extracellular pH, we have investigated the effects of acidic environment on cortical GABAergic neurons in terms of their abilities of firing spikes and responses to synaptic inputs. Artificial cerebral spinal fluid in low pH impairs the responses to excitatory synaptic inputs and the abilities of encoding sequential spikes at these GABAergic neurons. The impairments of neuronal spiking are associated with the increases of refractory periods and threshold potentials. Our studies reveal that acidosis may impair cortical GABAergic neurons and in turn deteriorate brain functions, in which their final targets are voltage-gated sodium channels and glutamate receptor-channels., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Occipital lobe seizures caused by nonketotic hyperglycemia (NKH) have been reported in only a few cases and are not fully characterized. We report two cases of NKH-related occipital lobe seizures with high hemoglobin A1C (HbA1C), epileptiform electroencephalograph (EEG) and MRI abnormalities. Both patients had moderate hyperglycemia (310-372 mg/dl) and mildly elevated serum osmolarity (295-304 mOsm/kg) but markedly elevated HbA1C (13.8-14.4%). One patient had a clinico-EEG seizure originating from the right occipital region during sleep. The other patient had an interictal epileptiform discharge consisting of unilateral occipital beta activity in sleep. None of the previously reported cases fulfilled the criteria of a nonketotic hyperglycemic hyperosmolar (NKHH) state, or showed any interictal beta paroxysms, spikes, sharp waves, or spike/sharp-slow wave complexes. We suggest that prolonged exposure to uncontrolled hyperglycemia, as indicated by HbA1C, rather than an acute NKHH state is crucial in the development of this peculiar seizure. We also suggest clinicians look for the presence of interictal focal beta paroxysms in addition to the usual epileptiform discharges while reading the EEG of these patients., (2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: We hypothesized that in term infants low Apgar score with normal umbilical artery pH (UApH) indicates prenatal damage to the neuromuscular system., Study Design: Retrospective database search of 42,117 liveborn infants born 1993-2005. Medical record analysis of 3104 term infants with cardiorespiratory maladaptation referred for special neonatal care. Focus on infants with UApH >7.00 and 5-min Apgar <6 (group A, n=74), UApH <7.00 and 5-min Apgar >5 (group B, n=49), and UApH <7.00 and 5-min Apgar <6 (group C, n=14)., Results: Incidence of 5-min Apgar score <6 was 0.50% in term infants. Mean (SD) UApH was 7.262 (0.075, P=0.075); incidence of UApH <7.00 was 0.30% in term infants. Nucleated red blood cells were elevated without differences in all three groups. Parental consanguinity was present in 39 of the 137 maladapted infants. In groups A/B/C, 10/18/2 infants were small for gestational age (P=0.002 for A vs B) and in 16/1/0 neuromuscular anomalies were identified (P=0.004 for A vs B). Eight of the 17 anomalies had been suspected prenatally. Logistic regression proved neuromuscular disorder the only independent variable discriminating between groups A and B., Conclusions: Neuromuscular problems are the cause rather than the result of maladaptation. For unexplained low Apgar score, especially without acidosis, meticulous examination of the infant including brain imaging and EEG is justified.

The advent of balanced solutions for i.v. fluid resuscitation and replacement is imminent and will affect any specialty involved in fluid management. Part of the background to their introduction has focused on the non-physiological nature of 'normal' saline solution and the developing science about the potential problems of hyperchloraemic acidosis. This review assesses the physiological significance of hyperchloraemic acidosis and of acidosis in general. It aims to differentiate the effects of the causes of acidosis from the physiological consequences of acidosis. It is intended to provide an assessment of the importance of hyperchloraemic acidosis and thereby the likely benefits of balanced solutions.

The association of nephrogenic systemic fibrosis (NSF) with the use of gadolinium-based magnetic resonance contrast agents (GBMCAs) has greatly affected the care of patients with kidney disease. Nephrogenic systemic fibrosis has been reported in patients with end-stage renal disease, chronic kidney disease (CKD) and acute kidney injury. The majority of cases have occurred in patients with end-stage renal disease, but cases of NSF have been reported in CKD patients with glomerular filtration rates less than 30 mL/min/1.73 m(2). Odds ratios have ranged between 8.97 and 32.5 among patients exposed to GBMCAs. Given the significant morbidity, disability, and mortality associated with NSF, it is imperative to properly and preemptively identify those patients at risk. Patients with end-stage renal disease seem to be at highest risk, particularly those maintained on peritoneal dialysis (PD). Although there are no data to support a role for hemodialysis in reducing the risk for NSF after the administration of GBMCAs, hemodialysis is recommended within 2 to 3 hours. Patients maintained on PD and those with CKD present a challenge, as they do not typically have vascular access for hemodialysis, yet the clearance of GBMCAs is very low, and it may be prudent to consider hemodialysis especially for PD patients. Gadolinium-based magnetic resonance contrast agents are removed by dialysis, with estimates that about 99% of a dose is removed after 3 to 4 sessions of hemodialysis. The elimination half-life averaged 9 hours in patients with stage 4 CKD (glomerular filtration rate <30 mL/min/1.73 m(2)) compared with 1.5 hours in those with normal glomerular filtration rates. This prolonged elimination and longer exposure may be important factors in predisposing to NSF.

In 1997, a new fibrosing skin disorder became apparent among patients with renal disease. Nephrogenic systemic fibrosis, as this disorder has come to be known, has recently been tied to the administration of contrast agents containing gadolinium. This overview examines the discovery and elucidation of the major research accomplishments to date. It was presented as the keynote address at the First Annual Scientific Symposium on Nephrogenic Systemic Fibrosis and MRI Contrast, conducted at Yale University on May 4, 2007.

A retrospective study of cerebrospinal fluid (CSF) levels of markers of brain parenchymal damage was conducted in Kenyan children with severe falciparum malaria. Two markers were analysed by immunoassays: the microtubule-associated protein tau for degenerated axons and S-100B for astrocytes. The level of tau proteins in the CSF was significantly elevated in children with cerebral malaria compared with either malaria with prostration or malaria with seizures but normal consciousness (p<0.001). Elevated tau was also found to be associated with impaired delivery of oxygen (severe anaemia), severe metabolic acidosis manifesting as respiratory distress (increased respiratory rate and deep acidotic breathing) and at higher parasite densities. Elevated S-100B in children was associated with an increased risk of repeated seizures. This study provides evidence that axonal injury is associated with malaria coma and identifies the potential role of severe anaemia, acidosis and hyperparasitaemia to causing brain parenchymal damage in children with malaria.

We report the case of a 6-year-old girl with congenital adrenal hyperplasia, who showed 'forced mouth opening reaction' during the course of acute encephalopathy due to adrenal crisis. When an object was moved towards her mouth, or when the corner of her mouth was stroked with a tongue depressor, she would immediately open her mouth fully and hold it open. This reaction appeared transiently during the course of her illness in association with other frontal release signs including the rooting, groping and palmomental reflexes. Magnetic resonance imaging showed bilateral widespread lesions involving the gray and white matters in the frontal lobes, and less severe lesions in the temporal and parietal areas. We propose that this unique reaction is a sign of a release phenomenon, and represents the emergence of primitive reflexes in the absence of cortical inhibition in some types of encephalopathies.

Objective: Neonatal cerebral white matter injury represents a major precursor for neurological impairment and cerebral palsy. Our objective was to identify risk factors associated with its development., Study Design: This retrospective case-control study of all births between 23 and 34 weeks gestation at a single university hospital between May 1994 and September 2001 identified 150 cases with white matter injury characterized by periventricular leukomalacia or ventricular dilatation from white matter atrophy that were chromosomally normal and did not have other congenital anomalies. Cases were matched to controls without brain injury by the next delivery within 7 days of their gestational age., Results: There were small differences between controls and cases in gestational age (27.5 +/- 2.7, 27.4 +/- 2.6 weeks, P = .01) and birth weight (1053 +/- 402, 966 +/- 285 g, P = .002) that were statistically but not clinically significant. There was no difference in the percentage of controls and cases delivered by cesarean (45%, 49%, P = .64). There were no differences between controls and cases in umbilical arterial pH (7.27 +/- 0.11, 7.25 +/- 0.15, P = .19), base excess (-2.1 +/- 2.7, -3.0 +/- 4.1 mmol/L, P = .28), pH less than 7.0 (2/122 [2%], 3/107 [3%], P = 1.0), or base excess less than -12 mmol/L (4/121 [3%], 6/106 [6%], P = .75). The cases had a significant increase in positive blood (19%, 29%, P = .036), cerebrospinal fluid (6%, 17%, P = .002), and tracheal (9%, 22%, P = .003) cultures during the neonatal period. Conditional logistic regression showed a significant association among multiple gestations ( P = .02), intraventricular hemorrhage ( P < .001), and positive tracheal cultures ( P = .02) with cerebral white matter injury., Conclusion: Culture-positive infection was associated with an increased risk of cerebral white matter injury in preterm neonates. Intrapartum hypoxia-ischemia as manifested by metabolic acidosis was rarely associated with white matter injury and was not different from the incidence in premature neonates without injury.

Background & Aims: Decreased ureagenesis and gluconeogenesis from alanine have been reported during chronic renal failure in rat. This study addressed the respective roles of plasma-membrane transport and intracellular metabolism in these abnormalities of alanine pathways., Methods: In hepatocytes isolated from uremic and control rats, we investigated: (1) the influence of uremia on gluconeogenesis and ureagenesis during incubations with alanine; (2) the kinetics of alanine plasma-membrane transport; (3) the relationships between intracellular alanine concentrations and its metabolism. Plasma-membrane alanine transport was assessed after addition of alanine (2 mM) by measuring its intracellular accumulation from 0 to 10 min, in the presence of a transaminase inhibitor. Alanine metabolism was studied in perifused hepatocytes by measuring intracellular alanine concentration together with urea, glucose and lactate production in the presence of increasing concentrations of alanine (0-8 mM)., Results: Uremic rats showed decreased plasma bicarbonate. Uremia induced (P<0.05) a decrease in both gluconeogenesis (36%) and ureagenesis (22%). Alanine plasma-membrane transport decreased by 20% during uremia. During perifusions, uremia induced a 30-40% decrease in urea, glucose, and lactate production without modifying intracellular alanine concentration., Conclusions: In uremic rats with acidosis, hepatocyte alanine utilization was impaired at both plasma-membrane transport and intracellular transamination steps.

Study Objective: To determine the effects of hyperchloremic acidosis, induced by dilute HCl infusion, on BP and circulating inflammatory mediators in an experimental model of severe sepsis in the rat., Design: Randomized, open-label, controlled experiment., Setting: University research laboratory., Participants: Twenty-four adult, male, Sprague-Dawley rats., Intervention: Eighteen hours after inducing lethal sepsis by cecal ligation and puncture, animals were randomized and classified into three groups. In groups 2 and 3, we began an IV infusion of 0.1 N HCl to reduce the standard base excess (SBE) by 5 to 10 mEq/L and 10 to 15 mEq/L, respectively. In group 1, we infused a similar volume of lactated Ringer solution. In all groups, infusions were continued for 8 h or until the animals died., Measurements: We measured mean arterial pressure (MAP), arterial blood gases, electrolytes, plasma nitrate/nitrite, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10 levels at 0 h, 3 h, 6 h, and 8 h., Results: MAP remained stable in group 1 but decreased in groups 2 and 3 (p < 0.001), such that at 8 h MAP was much higher in group 1 (94 +/- 9.2 mm Hg) [+/- SD] compared to either group 2 (71.6 +/- 20.1 mm Hg) or group 3 (49.4 +/- 33.2 mm Hg) [p = 0.01]. This change in MAP correlated with the increase in plasma Cl(-) (R(2) = 0.50, p < 0.0001) and less well with the decrease in pH (R(2) = 0.24, p < 0.001). After 6 h of acidosis, plasma nitrite levels were significantly higher in group 2 animals compared to either group 1 or group 3 animals (p < 0.05). Plasma TNF-alpha, IL-6, or IL-10 levels were not significantly different from control animals., Conclusion: Moderate acidosis (SBE of 5 to 10 mEq/L), induced by HCl infusion, worsened BP and increased plasma nitrate/nitrite levels but had no effect on circulating cytokines in septic rats. However, severe acidosis (SBE of 10 to 15 mEq/L), while still causing hypotension, did not affect plasma nitrate/nitrite levels.

In a previous study we have observed that NH4Cl-induced metabolic acidosis halted the progression of renal disease in azotemic rats with a high phosphate diet. We hypothesized that NH4Cl-induced metabolic acidosis may exert its protective effect by decreasing renal calcium content independent of serum levels of PTH and phosphate loading. To test this hypothesis we studied azotemic rats with very low phosphate diet or parathyroidectomy. Rats with low phosphate diet and parathyroidectomized rats developed renal failure after 5/6 nephrectomy, and in both groups the acid loading significantly decreased the progression of renal disease. Calcium renal content increased in both groups, even in rats with low phosphate diet, and this effect was also significantly decreased after an acid loading. Rats with acid loading developed greater hypertrophy of renal tissue than rats without acid loading. We conclude that NH4Cl-induced metabolic acidosis halted the progression of renal disease by decreasing calcium precipitation on renal tissue. Parathyroidectomy did not prevent progression of renal disease nor calcium precipitation, and a low phosphate diet in azotemic rats did not prevent increased calcium content on remnant renal tissue.

We investigated the pathogenic mechanism(s) of small intestinal injury during acidosis in relation to circulating nitric oxide (NO) in an experimental rat model. Rats were anesthetized, paralyzed, and mechanically ventilated with room air. Hydrochloric acid (0.16 mmol bolus followed by 0.132 mmol/kg/h) was infused through the jugular vein for 5 hours. Control rats received a saline infusion. Arterial blood gases, blood pressure, and blood pH were measured every 30 minutes. The involvement of NO in this acidosis model was assessed by measuring plasma concentration of nitrite/nitrate (NOx) and by evaluating inducible NO synthase (iNOS) expression in small intestinal mucosa. Intestinal injury was assessed by measuring myeloperoxidase (MPO) activity, thiobarbituric acid reactants (TBARS), and histologic scores. HCl infusion was associated with hypotension, decreased blood pH, increased plasma concentration of NOx, augmented intestinal mucosal iNOS expression, MPO activity, TBARS, and histopathologic injury scores. Pretreatment with an iNOS inhibitor, aminoguanidine (AG, 50 mg/kg), reversed HCl-induced hypotension without a change in blood pH. HCl-induced lesions, MPO activity, TBARS, and plasma NOx production were decreased by AG. Our data show that the pathogenic mechanisms of acidosis-induced small intestinal lesions involve up-regulation of NO production by increased expression of iNOS and augmentation of superoxide radicals and MPO activity.

Background: The chronic low-grade metabolic acidosis that occurs in various renal disorders and in normal people, and that is related both to dietary net acid load and age-related renal functional decline, may contribute to osteoporosis by increasing urine calcium excretion. Administration of potassium (K) alkali salts neutralizes acid and lowers urine calcium excretion. Urine calcium excretion also can be reduced by the administration of thiazide diuretics, which are often given with supplemental K to avoid hypokalemia. We determined whether the K alkali salt potassium bicarbonate (KHCO3) and the thiazide diuretic hydrochlorothiazide (HCTZ) combined is more effective in reducing urinary calcium than KHCO3 alone or HCTZ combined with the conventionally coadministered nonalkalinizing K salt potassium chloride (KCl)., Methods: Thirty-one healthy men and women aged 50 or greater were recruited for a four-week, double-blind, randomized study. After a baseline period of 10 days with three 24-hour urine and arterialized blood collections, subjects were randomized to receive either HCTZ (50 mg) plus potassium (60 mmol daily) as either the chloride or bicarbonate salt. Another 19 women received potassium bicarbonate (60 mmol) alone. After two weeks, triplicate collections of 24-hour urines and arterialized bloods were repeated., Results: Urinary calcium excretion decreased significantly in all groups. KHCO3 alone and HCTZ + KCl induced similar decreases (-0.70 +/- 0.60 vs. -0.80 +/- 1. 0 mmol/day, respectively). Compared with those treatments, the combination of HCTZ + KHCO3 induced more than a twofold greater decrease in urinary calcium excretion (-1.8 +/- 1.2 mmol/day, P < 0. 05). Both HCTZ + KHCO3 and KHCO3 alone reduced net acid excretion significantly (P < 0.05) to values of less than zero., Conclusions: KHCO3 was superior to KCl as an adjunct to HCTZ, inducing a twofold greater reduction in urine calcium excretion, and completely neutralizing endogenous acid production so as to correct the pre-existing mild metabolic acidosis that an acid-producing diet usually induces in older people. Accordingly, for reducing urine calcium excretion in stone disease and osteoporosis, the combination of HCTZ + KHCO3 may be preferable to that of HCTZ + KCl.

Background: Several reports suggest that metabolic acidosis may induce significant alterations in protein metabolism and that its outbreak may even result in growth retardation in children with chronic renal failure (CRF). However, the effects of metabolic acidosis on protein metabolism kinetics have never been investigated in these settings., Methods: Postabsorptive leucine metabolism, a marker of whole-body protein metabolism, was measured by using a primed, continuous intravenous infusion of L-[1-13C]leucine in 10 CRF children who were one to four years old., Results: Interindividual values of whole-body protein turnover exhibited a very large range, which was mainly accounted for by acidotic status (plasma HCO3-) and body composition [fat-free mass (FFM)]. After correction for differences in FFM, plasma HCO3- was highly correlated with protein breakdown (R2 = 0.65, P < 0.001), so that CRF children were divided in two groups according to their acid-base status: Group A had a mean plasma HCO3- level of 15.8 +/- 1.5 mmol. L-1 (mean +/- SD, N = 5), whereas group B had near-normal values (HCO3-, 22.6 +/- 3.0 mmol. L-1, N = 5). The leucine rate of appearance from protein breakdown was markedly higher in group A than in group B (4.15 +/- 1.43 vs. 2.46 +/- 0.47 micromol. kg-1. min-1, respectively, P < 0.05), and the net leucine balance tended to be more negative in group A (-0.73 +/- 0.34 vs. -0.44 +/- 0.26 micromol. kg-1. min-1, respectively)., Conclusions: Metabolic acidosis in children with CRF results in an excessive catabolic state, suggesting that acidosis-related protein wasting could contribute to growth retardation.

A characteristic of solid tumors is their heterogeneous distribution of blood flow, with significant hypoxia and acidity in low-flow regions. We review effects of heterogeneous tumor perfusion are reviewed and propose a conceptual model for its cause. Hypoxic-acidic regions are resistant to chemo- and radiotherapy and may stimulate progression to a more metastatic phenotype. In normal tissues, hypoxia and acidity induce angiogenesis, which is expected to improve perfusion. However, aggressive tumors can have high local microvessel density simultaneously with significant regions of hypoxia and acidosis. A possible explanation for this apparent contradiction is that the mechanisms regulating growth and adaptation of vascular networks are impaired. According to a recent theory for structural adaptation of vascular networks, four interrelated adaptive responses can work as a self-regulating system to produce a mature and efficient blood distribution system in normal tissues. It is proposed that heterogeneous perfusion in tumors may result from perturbation of this system. Angiogenesis may increase perfusion heterogeneity in tumors by increasing the disparity between parallel low- and high-resistance flow pathways. This conceptual model provides a basis for future rational therapies. For example, it indicates that selective destruction of tumor vasculature may increase perfusion efficiency and improve therapeutic efficacy.

Patients and Methods: In a prospective multicentric study, 152 of 10,065 live term births had birth asphyxia, defined by the association of three indicators (fetal distress, depression at birth and metabolic acidosis)., Results: The incidence of birth asphyxia was 1.5% of live term births when birth asphyxia was defined by the presence of at least two indicators, and 1% of live term births when birth asphyxia was defined by the association of metabolic acidosis and another indicator. Neurological complications were observed in 66 cases (43%). The incidence of post-asphyxial encephalopathy (PAE) was 5.9/1000 of live term births (mild PAE: 3/1000; moderate PAE: 2.7/1000; severe PAE: 0.2/1000). Systemic complications were observed in 87 patients (57%). Renal injury and coagulopathy were associated with moderate or severe PAE. Respiratory complications (39%), infections (17%) and gastro-intestinal intolerance (15%) often complicated the course. Severe complications were never seen in the absence of significant metabolic acidosis at 30 minutes of life., Conclusion: Our study has many implications concerning the diagnosis of birth asphyxia and its complications. A terminology based on clinical observation and arterial pH evaluation is proposed in order to clarify the situation.

We report a case of reversible blindness associated with severe acidosis. A 49-year-old female presented with sudden onset of bilateral blindness. A work up for possible etiologic factors including computed tomography failed to reveal any abnormalities except for ethanol induced severe ketoacidosis. Methanol was not detectable in the serum despite an ethanol level of 14.76 mmol/L, effectively ruling out the diagnosis of methanol intoxication. Treatment of the acidosis led to rapid resolution of her blindness. Review of the literature revealed two case reports of reversible blindness associated with severe acidosis in diabetics. The current case underscores the necessity for a clear understanding of the role of severe acidosis as the sole causative factor of reversible bilateral blindness.

Objective: Our goal was to evaluate the impact of fetal compromise on the outcome of borderline viable babies., Study Design: All 142 babies born in our hospital from 1990 to 1995 with a gestational age of 23 to 25 weeks were included. Fetal compromise was considered present if one of the following was documented: a major anomaly, congenital sepsis, chronic intrauterine infection, intrauterine drug exposure, congenital anemia, severe growth restriction, fetal acidosis, or cardiorespiratory and neurologic depression in the delivery room., Results: The 43 babies who had at least one cause of fetal compromise had a lower birth weight (p < 0.001), but there were no other differences in demographics or complications of prematurity. The survival rate was significantly better for babies free of fetal compromise (75% vs 33%, p < 0.001), particularly for babies born at 23 weeks of gestation (75% vs 6%, p < 0.001). For surviving babies free of fetal compromise, the outcome at 23 weeks was comparable to that at 24 to 25 weeks for major causes of long-term neurologic morbidity., Conclusions: Like advancing gestational age and increasing birth weight, the absence of fetal compromise has a major beneficial impact on the outcome of borderline viable babies that might be important when decisions are made about the appropriate level of support.

We report the occurrence of severe ventricular arrhythmias in a patient with isovaleric acidemia during general anesthesia for suction lipectomy. The timing of events and character of the ECG changes are most consistent with bupivacaine toxicity after subcutaneous injection of tumescence solution containing this local anesthetic. The patient had previously documented carnitine deficiency, a condition which, we speculate, may lower the threshold for bupivacaine induced cardiotoxicity. We review clinical considerations in isovaleric acidemia and conclude that the use of bupivacaine in these patients probably should be avoided.

Objective: Our purpose was to determine the threshold of metabolic acidosis at delivery associated with newborn complications., Study Design: This study was a matched case-control study of 174 term newborn infants. Three groups defined by umbilical artery base deficit at birth were 4 to 8 mmol/L, 8 to 12 mmol/L, and 12 to 16 mmol/L. Newborn complications during the 5 days after birth were documented. A composite complication score defined the magnitude of all complications in each neonate., Results: Moderate and severe newborn encephalopathy and respiratory complications and composite complication scores >3 were increased in the group with an umbilical artery base deficit of 12 to 16 mmol/L. Moderate or severe newborn complications occurred in 10% of newborns in the same group, whereas such complications occur in 40% of neonates with an umbilical artery base deficit >16 mmol/L at birth., Conclusion: The threshold of fetal metabolic acidosis at delivery when moderate or severe newborn complications may occur is in an umbilical artery base deficit of 12 mmol/L. Thereafter, increasing metabolic acidosis is associated with a progression of severity of newborn complications.

Objective: Fewer than 50% of neonates with an umbilical arterial pH < 7.00 have neonatal complications. Our objective was to identify clinical predictive factors for adverse outcomes in this group of neonates., Study Design: In this case-control study both cases and controls had an umbilical arterial cord pH < 7.00. Cases were defined as those neonates who had seizures, grade 3 to 4 intraventricular hemorrhage, gastrointestinal dysfunction, respiratory distress syndrome requiring intubation, sepsis, or death. Controls had an umbilical arterial cord pH < 7.00 and no complications. A multivariable prediction model was created, with variables having an association with adverse outcome by bivariate analyses, attempting to predict which neonates in this umbilical arterial pH range are at greatest risk for adverse outcomes., Results: We identified 73 of 10,705 neonates born between July 1992 and October 1996 with an umbilical arterial cord pH < 7.00. Thirty-five neonates met our case definition, and the remaining 38 composed the control group. Cases had significantly lower arterial pH values and 1- and 5-minute Apgar scores, greater arterial base deficit values, and a higher incidence of abruptio placentae and maternal cocaine use. More cases were delivered before 34 weeks. There were three neonatal deaths, two cases of grade 3 or 4 intraventricular hemorrhage, five cases of gastrointestinal dysfunction, and four cases of neonatal seizures. In our predictive model for adverse neonatal outcome, an arterial base deficit > or = 16 mmol/L and a 5-minute Apgar score < 7 had a sensitivity and a specificity of 79% and 80.8%, respectively., Conclusion: Neonatal morbidity in neonates with an umbilical arterial cord pH < 7.00 can be predicted by a high arterial base deficit value and low 5-minute Apgar score.

Studies of fetal monkeys and lambs have demonstrated the association between a single prolonged episode of severe fetal hypoxia and the occurrence of neurologic abnormality. This case represents a single episode of fetal hypoxia with severe metabolic acidosis at delivery accounting for neurologic abnormality on postmortem examination that closely parallels the results of experimental studies.