Arterial Blood pH Research Articles

Roles of alpha-7 nicotinic acetylcholine receptors and spleen in the lung injury induced by a repeated saline lavage in rat

BackgroundThe study aimed to determine whether or notα7 nicotinic acetylcholine receptors (α7nAChR) induce anti-inflammatory effects directly in the lung or through the spleen pathway in a sterile model of lung injury by saline lavage.MethodsMale Sprague Dawley rats were divided into seven groups; Sham, splenectomy (SPX), saline lavage (LAV), LAV treated with α7nAChR agonist nicotine (LAV + NIC), and LAV treated with NIC and a selective α7nAChR antagonist MLA (LAV+MLA+NIC), LAV and splenectomy (LAV+SPX), and LAV+SPX treated with nicotine (LAV+SPX+NIC). Tracheostomy and catheterization of the femoral artery were performed under deep anesthesia. Animals were subjected to volume-controlled ventilation and lung injury by 10 repeated saline lavages. Splenectomy was achieved one week before the induction of lung injury. The recovery phase lasted for 3 h, and drugs were injected 1 h after the last lavage.ResultsMean arterial blood pressure (MBP), heart rate (HR), PaO2, PaO2/FiO2 ratio, and pH decreased, whereas, maximal inspiratory (MIP) and expiratory (MEP) pressures, and PaCO2 increased 1 h after the saline lavage. Nicotine corrected entirely all the above parameters in the LAV + NIC group. MLA or SPX prevented the effects of nicotine on the above parameters, except that MLA had no extra effect on MIP or MEP. In addition, nicotine improved lung compliance in the LAV + NIC and LAV + SPX + NIC groups, though it was inhibited by MLA in the LAV + MLA + NIC group. The increases of plasma and lung tissue malondialdehyde (MDA) in the LAV group were diminished by nicotine, whereas, MLA and SPX prevented these reductions. Besides, nicotine could reduce plasma MDA in the LAV + SPX + NIC group. Total BAL cell count, protein BAL/protein plasma ratio, and lung histological scores were attenuated by nicotine in the LAV + NIC group, whereas, MLA reversed the mentioned alterations in the LAV + MLA + NIC group. However, splenectomy could not stop the decreasing effect of nicotine on the total BAL cell in the LAV + SPX + NIC group.ConclusionsIn this study, we indicated that α7nAChR and spleen play roles in cholinergic anti-inflammatory pathways in saline lavage-induced lung injury. However, our results are in favor of at least some direct effects of α 7nAChR in the lung.

Association of CTG Diagnosis of Intrapartum Fetal Distress and Immediate Postpartum Acidemia in Foetal Umbilical Artery.

Intrapartum fetal hypoxia which is one of the leading causes of neonatal morbidity and mortality is a preventable cause. Over the past years, many methods have been employed to diagnose fetal distress, a sign of fetal hypoxia, among these, cardiotocography (CTG) is the most widely used method. Diagnosis of fetal distress based on CTG can have high inter and intraobserver variation leading to either delayed or inessential intervention henceforth increasing maternal morbidity and mortality. Fetal cord arterial blood pH is an objective method to diagnose intrapartum fetal hypoxia, hence by observing the incidence of acidemia in cord blood pH among those newborns born through cesarean section (CS) in view of non-reassuring CTG can help make a judicious decision. In this single institutional observational study, patients admitted for safe confinement were subjected to CTG in the latent and active phases of labor. Non-Reassuring traces were further classified based on NICE guideline CG190. The cord blood of these neonates born through CS in view of non-reassuring CTG was drawn and sent for ABG analysis. Among the 87 neonates delivered through CS in view of fetal distress, 19.5% had acidosis. Among those with pathological traces, 16(28.6%) had acidosis and one (100%) which was categorized as the need for urgent intervention showed acidosis. This result showed a statistically significant association (p value-0.003). No statistically significant association was obtained when variation in baseline characters of CTG when taken independently. In our study, neonatal acidemia which is the objective evidence of fetal distress was seen in 19.5% of our study population who underwent cesarean in view of non-reassuring CTG. Among these, acidemia was significantly associated with pathological CTG trace compared to suspicious trace. We also observed that abnormal FHR features when taken independently showed no significant association with acidosis. Acidosis among newborns certainly increased the requirement for active resuscitation and additional hospital stay. Hence, we conclude that by recognizing specific fetal heart rate patterns associated with acidosis in a fetus, a more judicious decision can be made, thereby preventing both delayed as well as inessential intervention.

Changes of Acid-Base Variables in Dairy Cows with Chronically Implanted Fetal and Maternal Catheters during Late Gestation and Calving.

Simple SummaryA fetal catheterization is an efficient tool allowing longitudinal in vivo studies on hormonal and metabolic changes, including fetal blood gases and acid-base changes. These surgical techniques made it possible to take blood samples daily under aseptic conditions to determine arterial and/or venous blood samples for acid-base variables (like pH, blood gas tensions: partial pressure of carbon dioxide and partial pressure of oxygen, oxygen saturation, bicarbonate concentration, total carbon dioxide, and base excess). All these examinations may contribute to a better understanding of the physiological changes that occur during calving, which may help reach a significant reduction in losses caused by perinatal mortality, which is still high today.The objective of the present study was to evaluate the changes in maternal and fetal arterial acid-base variables withdrawn from catheterized dams and fetuses during the last days before and during calving. The average gestation length in nine cows with chronically catheterized fetuses was 285 ± 10 (SD) days. The arterial acid-base variables of a catheterized dam and fetus were very stable during late gestation. Four newborn calves showed small differences between prenatal and postnatal pH values (−0.035). At the same time, pCO2 values started to increase significantly (p = 0.02), indicating a shift towards physiological respiratory acidosis during calving. The partial pressure of oxygen and oxygen saturation values showed some non-significant improvements immediately after birth, while the other acid-base parameters did not differ. The remaining five newborn calves showed a significant decrease in arterial blood pH (p < 0.01) and BE (p = 0.01), while pCO2 tended to be higher (p = 0.06), indicating a shift towards physiological respiratory and metabolic acidosis, while the other acid-base parameters hardly differed. It is essential to mention that physiological (n = 2) and mild metabolic acidosis (n = 2) developed gradually in four newborn calves during the second stage of calving, lasting about ≤ 2 h. In contrast, in the remaining newborn calf the physiological metabolic acidosis developed during the last 3 min of birth because immediately before birth, the BE value was 0.4 mmol/L. After birth, it was −5.4 mmol/L. The results indicate that the acid-base variables may start to move gradually in the direction of expressed respiratory and metabolic acidosis only after appearing the amniotic sac and fetal feet in the vulva during the second stage of labor; therefore, it is essential to complete obstetrical assistance in time.

Freshwater adaptation in prickly sculpin (Pisces: Cottidae): intraspecific comparisons reveal evidence for water pH and Na+ concentration driving diversity in gill H+-ATPase and ion regulation

Phenotypic divergence is a hallmark of adaptive radiation. One example involves differentiation in physiological traits involved in ion regulation among species with contrasting lifestyles and living in distinct environments. Differentiation in ion regulation and its ecological implications among populations within species are, however, less well understood. To address this knowledge gap, we collected prickly sculpin (Cottus asper) from distinct habitat types including coastal rivers connected to estuaries, coastal lakes and interior lakes, all from British Columbia, Canada. We tested for differences in plasma Na+ and Cl-, gill Na+/K+-ATPase and H+-ATPase activity and protein abundance as well as changes in body mass and arterial blood pH in fish sampled from the field and acclimated to two different freshwater conditions in the laboratory: artificial lake water (ALW) and ion-poor water (IPW). We also tested for links between environmental water chemistry and the physiological characteristics associated with ion regulation. Transfer to IPW resulted in upregulation of gill Na+/K+-ATPase and H+-ATPase activity as well as increases in gill H+-ATPase protein expression level in each habitat compared with that in the common ALW treatment. Despite the presence of population-within-habitat-type differences, significant habitat-type effects were revealed in most of the ion regulation characteristics examined under different acclimation conditions. Significantly lower plasma Cl- was detected in fish from coastal rivers than in fish from the other two habitat types during the IPW treatment, which was also significantly lower compared with that in ALW. Similarly, gill Na+/K+-ATPase activity was lower in the coastal river populations in IPW than in fish from coastal and interior lakes, which was not in accordance with the protein expression in the gill. For gill H+-ATPase, fish from interior lake populations had the highest level of activity across all habitat types under all conditions, which was related to the protein levels in the gill. The activity of gill H+-ATPase was positively correlated with the combined effect of water Na+ and pH under the ALW treatment. Our results suggest that variation in habitat may be an important factor driving differences in gill Na+/K+-ATPase and H+-ATPase activity across populations of C. asper. Further, the combined effect of water Na+ and pH may have played a key role in physiological adaptation in C. asper during post-glacial freshwater colonization and dispersal.

Neuraxial anesthesia in ex utero intrapartum therapy for parturients with fetal congenital diaphragmatic hernia: a prospective observational study

BackgroundCongenital diaphragmatic hernia (CDH) is characterized by defects in the fetal diaphragm and thoracic herniation of the abdominal viscera. The ex utero intrapartum treatment (EXIT) procedure is used to establish the fetal airway while on placental support. These EXIT procedures are commonly performed under general anesthesia, which increases maternal bleeding and the risk of insufficient placental perfusion subsequently. This study investigated the feasibility of performing neuraxial anesthesia for the EXIT procedure for fetal congenital diaphragmatic hernia to improve outcomes. MethodsParturients with fetal CDH who underwent an EXIT procedure between January 2019 and May 2021 in our institution were recruited. Variables evaluated included gestational age, surgical time, intra-operative blood loss, peri-operative hemoglobin, maternal complications, fetal lung-to-head ratio, time on placental bypass, and postnatal outcome. ResultsTwenty-two cases were included. All procedures were performed under neuraxial anesthesia. The median gestational age at the time of the EXIT procedure was 37 weeks. The median estimated blood loss was 200 mL. There was no report of an adverse maternal event. The placental bypass time was 142.9 ± 72.6 s, and access to the airway was successfully established within the bypass time. Twenty-one neonates reached an Apgar score of 9 at 5 min. In the first two hours after birth, the average pH of neonatal peripheral arterial blood was 7.35 ± 0.07 (n=19), and lactate level 1.85 ± 0.71 mmol/L (n=19). ConclusionsIn the EXIT procedure to establish an airway for fetal CDH, neuraxial anesthesia proved a feasible technique for maternal anesthesia.

Hypoxia during maintenance hemodialysis-the critical role of pH.

The impact and management of subclinical hypoxia during hemodialysis is a significant medical challenge. As key determinants of O2 availability and delivery, proposed mechanisms contributing to hypoxia include ischemia, alkalemia and pulmonary leukocyte sequestration. However, no study has comprehensively investigated and compared these interrelated mechanisms throughout a typical hemodialysis treatment week. This study aimed to comprehensively assess the physiological mechanisms that contribute to hypoxia during hemodialysis. In 76 patients, we measured arterial blood gases and pH at four time-points during hemodialysis (start, 15min, 60min, end) over the course of a standard treatment week. For the mid-week hemodialysis session, we additionally measured central hemodynamics (non-invasive cardiac output monitoring) and white blood cell count. Linear regression modelling identified changes in pH, but not central hemodynamics or white blood cell count, to be predictive of changes in PaO2 throughout hemodialysis (e.g. at 60min, β standardized coefficient pH=0.45, model R2=0.25, P<.001). Alkalemia, hypokalemia, decreased calcium and increased hemoglobin-O2 affinity (leftward shift in the oxyhemoglobin dissociation curve) were evident at the end of hemodialysis. pH and hemoglobin-O2 affinity at the start of hemodialysis increased incrementally over the course of a standard treatment week. These data highlight the important role of pH in regulating O2 availability and delivery during hemodialysis. Findings support routine pH monitoring and personalized dialysate bicarbonate prescription to mitigate the significant risk of alkalemia and subclinical hypoxia.

Perinatal maternal characteristics predict a high risk of neonatal asphyxia: A multi-center retrospective cohort study in China.

ObjectiveThis study aimed to identify various perinatal maternal characteristics that contributed to neonatal asphyxia (NA) in term and late-preterm newborns based on the data obtained from a Chinese birth registry cohort and to establish an effective model for predicting a high risk of asphyxia.MethodWe retrospectively reviewed and analyzed the birth database from July 1, 2016, to June 30, 2017, in the main economically developed regions of China. Asphyxia was defined as an Apgar score <7 at 5 min post-delivery with umbilical cord arterial blood pH < 7.2 in the infant born after 34weeks. We compared the perinatal maternal characteristics of the newborns who developed asphyxia (NA group, n = 1,152) and those who did not (no NA group, n = 86,393). Candidate predictors of NA were analyzed using multivariable logistic regression. Subsequently, a prediction model was developed and validated by an independent test group.ResultOf the maternal characteristics, duration of PROM ≥ 48 h, a gestational week at birth <37, prolonged duration of labor, hypertensive disorder, nuchal cord, and birth weight <2,500 or ≥4,000 g, abnormal fetal heart rate, meconium-stained amniotic fluid, and placenta previa were included in the predicting model, which presented a good performance in external validation (c-statistic of 0.731).ConclusionOur model relied heavily on clinical predictors that may be determined before or during birth, and pregnant women at high risk of NA might be recognized earlier in pregnancy and childbirth using this methodology, allowing them to avoid being neglected and delayed. Future studies should be conducted to assess its usefulness.

Efficacy of fixed-dose phenylephrine bolus for treating post-spinal hypotension: Comparison between pre-eclamptics and normotensives.

Pre-eclamptic parturients may have an exaggerated response to vasopressors. This study compares the efficacy of a 50 μg fixed bolus of phenylephrine for treatment of post-spinal hypotension in pre-eclamptic versus normotensive parturients. After written informed consent and ethics committee approval, 30 normotensive and 30 pre-eclamptic parturients between 18 and 40 years with singleton term pregnancy about to undergo cesarean section (CS) under spinal anesthesia were included. Post-spinal hypotension was treated with a 50 μg fixed bolus of phenylephrine. The cumulative dose of phenylephrine, the number of boluses, and the median dose required to treat the first hypotensive episode, total number of hypotensive episodes, maternal side effects, neonatal appearance, pulse, grimace, activity, and respiration (APGAR) scores, and umbilical arterial cord blood pH were noted. Statistical analysis was done using Student's t-test, Mann-Whitney U-test, Chi-square test/Fisher's exact test as appropriate. A P <0.05 was considered significant. The cumulative dose and number of boluses of phenylephrine required to treat post-spinal hypotension were comparable. The median dose required to treat the first episode of post-spinal hypotension was also similar (p = 0.792). The time to develop the first hypotensive episode was significantly earlier for group N (p = 0.002). The efficacy of a single fixed bolus of 50 μg phenylephrine was similar in both groups (p = 1.000). Neonatal median APGAR scores at 1 min after birth were significantly higher for group N (p = 0.016). A fixed-dose bolus of 50 μg phenylephrine is safe and effective in treating post-spinal hypotension in pre-eclampsia. The efficacy of phenylephrine is comparable in pre-eclamptic and normotensive parturients.

Protective effect of salidroside on lung tissue in rats exposed rapidly to high altitude.

To study the protective effect and mechanism of salidroside on lung tissue of rats exposed rapidly to high altitude. Thirty-six Wistar male rats were randomly divided into blank control group, model control group, Rhodiola rosea capsule (137 mg/kg) group, salidroside low-dose (14 mg/kg), medium-dose (28 mg/kg) and high-dose (56 mg/kg) groups, with 6 rats in each group. After 5 continuous days of drug administration in the plain lab, rats were rapidly moved to 4010 m plateau field lab. After exposure to hypoxia condition for 3 days the blood gas indexes were detected; the serum levels of inflammatory factors were measured by enzyme linked immunosorbent assay (ELISA); the oxidative stress index of lung tissue was measured; the pathological changes of lung tissue were observed by microscopy with hematoxylin and eosin (HE) staining; and the expression of occludin in lung tissues was determined by western blotting. Compared with blank control group, arterial oxygen saturation (SaO 2), arterial oxygen partial pressure (PaO 2), blood pH, standard bicarbonate (SBC) and actual bicarbonate levels in model control group were significantly decreased, and hemoglobin level was significantly increased (all P<0.05). In the model control group, the contents of mast cell protease (MCP) 1, interleukin (IL)-6 and IL-1β were significantly increased, while the contents of interferon-γ were significantly decreased (all P<0.01). The contents of glutathione and total superoxide dismutase in the lung tissues of model control group were significantly decreased, while the content of malondialdehyde was significantly increased (all P<0.01). After Rhodiola rosea and salidroside were given, SaO 2, pH, hemoglobin, SBC and actual bicarbonate were improved compared with the model control group. Compared with the model control group, the Rhodiola rosea group and salidroside groups had different degrees of improvement in the contents of the above inflammatory factors and oxidative stress indexes, and the salidroside groups had better improvement in MCP-1 and IL-6 than the Rhodiola rosea group. HE staining showed that, after the administration of Rhodiola rosea capsules and salidroside at low, medium and high doses, the hypoxic injury was significantly improved, the cell wall gradually became thinner, and the alveolar wall gradually became complete. The expression of occludin in the model control group was lower than that in the blank control group ( P<0.05), while the expression of occludin in the salidroside high-dose group was significantly higher than that in the model control group ( P<0.01). Salidroside can improve the abnormality of blood gas index, hypoxia symptoms and acid-base balance disorder, dysregulation of inflammatory factors caused by hypoxia in rats, and improve lung tissue injury and oxidative stress injury, which has a protective effect on lung tissue injury of rats exposed rapidly to the high-altitude plateau, and the effect is better than Rhodiola rosea capsule on the whole.

Correlation between Intrapartum Cardiotocogram Findings and Cord Blood pH in Term and Preterm Labors

Background: The purpose of intrapartum fetal monitoring by cardiotocograph (CTG) is to identify early signs of developing hypoxia so that appropriate action can be taken to improve the perinatal outcome. Although CTG findings are well known to monitor the progress of the labor due to the paucity of recommendations, there has always been a clinical dilemma as the term fetuses respond differently than a preterm fetus. However, umbilical cord blood pH can distinguish the infant at high risk for asphyxia and related sequel. Therefore, because of differences in fetal physiology in term and preterm fetuses, CTG findings vary, and hence the validity of CTG to determine fetal acidosis should be different. Aims and Objectives: This study aimed to correlate abnormal intrapartum CTG findings with umbilical cord blood pH in term and preterm labor and thus evaluate the success of CTG in predicting fetal acidosis during labor. Methods: The present study included 210 women in labor (70 preterm and 140 term) with abnormal intrapartum CTG that was classified as per 2015 revised International Federation of Gynecologists and Obstetrician (FIGO) guidelines. Immediately after delivery, 2 ml Umbilical artery cord blood sample was taken in a pre-heparinized syringe for analysis, pH &lt;=7.2 was taken as acidosis and pH &gt;7.2 was taken as normal. The measured data were general maternal characteristics which included gravida status, associated comorbidities, method of induction and character of liquor, the intrapartum CTG tracings recorded, the cord arterial blood pH and the neonatal characteristics such as APGAR score and neonatal outcome. Results: Data from 70 preterm labor was compared with 140 term labor. In this study, 20.9% of the babies had acidosis. Suspicious CTG due to decreased variability were more common in the preterm group than in the term group (21.4% vs. 8.6% p&lt;0.05). Positive predictive value (PPV) of abnormal CTG for fetal acidosis in the preterm group was found to be higher than that in the term group, PPV of pathological CTG being even higher than suspicious CTG. Women with suspicious CTG had 82% less risk of fetal acidosis as compared to pathological CTG. Women with Bradycardia had 5.9 times the risk of fetal acidosis as compared with normal and tachycardia. Conclusion: Abnormal CTG should be managed appropriately without any delay to prevent acidosis and cord blood pH should be done in all labors with abnormal CTG. However, our findings of a higher incidence of lower cord blood pH and suspicious CTG due to decreased variability alone highlight the limitation of criteria currently used for interpretation of CTG in preterm labors.

Optimal duration of cardiotocography assessment using the iPREFACE score to predict fetal acidemia

Cardiotocography (CTG) applicability to improve fetal outcomes remains controversial. This study aimed to determine the clinically optimal CTG assessment duration using the integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring (iPREFACE score). This single-center, retrospective observational study included 325 normal full-term singleton vaginal deliveries at the Toho University Omori Medical Center, from September 2018 to March 2019. The iPREFACE(10), iPREFACE(30), and iPREFACE(60) scores were calculated at 10, 30, and 60 min immediately before delivery. The primary outcome was fetal acidemia (umbilical artery blood pH < 7.2). The secondary outcome was the correlation between all iPREFACE scores and the umbilical artery blood pH, base excess (BE), and lactate values. Patients without accurate CTG findings or with failure of umbilical artery blood sampling immediately after birth were excluded, leaving 145 patients in the final analysis. Of these, 16, three, and two had umbilical artery blood pH of < 7.2, < 7.1, and < 7.0, respectively. All iPREFACE scores significantly correlated with umbilical artery blood pH, BE, and lactate values. iPREFACE(30) had the highest predictive capacity for fetal acidemia, suggesting that 30 min immediately before delivery may be a useful scoring time in clinical practice.

Low-dose antenatal betamethasone treatment achieves preterm lung maturation equivalent to that of the World Health Organization dexamethasone regimen but with reduced endocrine disruption in a sheep model of pregnancy

The intramuscular administration of antenatal steroids to women at risk of preterm delivery achieves high maternal and fetal plasma steroid concentrations, which are associated with adverse effects and may reduce treatment efficacy. We have demonstrated that antenatal steroid efficacy is independent of peak maternofetal steroid levels once exposure is maintained above a low threshold. This study aimed to test, using a sheep model of pregnancy, whether the low-dose antenatal steroid regimen proposed as part of the Antenatal Corticosteroids for Improving Outcomes in Preterm Newborns trial would achieve preterm lung maturation equivalent to that of the existing World Health Organization dexamethasone treatment regimen, but with reduced risk of adverse outcomes. Following ethical review and approval, date-mated ewes with single fetuses received intramuscular injections of either (1) four 6-mg maternal intramuscular injections of dexamethasone phosphate every 12 hours (n=22), (2) 4 2-mg maternal intramuscular injections of betamethasone phosphate every 12 hours (n=21), or (3) 4 2-mL maternal intramuscular injections of saline every 12 hours (n=16). Of note, 48 hours after first injection, (124±1 day), lambs were delivered, ventilated for 30 minutes, and euthanized for sampling. Arterial blood gas, respiratory, hematological, and biochemical data were analyzed for between-group differences with analysis of variance according to distribution and variance, with P<.05 taken as significant. After 30 minutes of ventilation, lambs from both steroid-treated groups had significant and equivalent improvements in lung function relative to saline control (P<.05). There was no significant difference in arterial blood pH, pO2, pCO2, lung compliance, ventilator efficiency index, or lung volume at necropsy with a static pressure of 40 cmH2O. The messenger RNA expression of surfactant protein (Sp)a, Spb, Spc, Spd, aquaporin (Aqp)1, Aqp5, and sodium channel epithelial 1 subunit beta (Scnn1b) was equivalent between both steroid groups. Maternal and fetal plasma neutrophil, glucose, and fetal plasma C-peptide levels were significantly elevated in the dexamethasone group, relative to the betamethasone group. Fetal plasma insulin-like growth factor 1 was significantly reduced in the dexamethasone group compared with the betamethasone group (P<0.05). Fetal adrenocorticotropic hormone (r=0.53), maternal glucose value (r=-0.52), and fetal glucose values (r=-0.42) were correlated with maternal weight in the betamethasone group (P<.05), whereas fetal pCO2 and pO2 were not correlated. There was no significant difference between male and female lamb outcomes in any groups for any of the items evaluated. This study reported that in preterm lambs, a low-dose treatment regimen of 8 mg betamethasone achieves lung maturation equivalent to that of a 24-mg dexamethasone-based regimen, but with smaller perturbations to the maternofetal hypothalamic-pituitary-adrenal axis. These data suggested that given steroid pharmacokinetic differences between sheep and humans, a betamethasone dose of 2 mg may remain above the minimum dose necessary for robust maturation of the preterm lung. Maternal weight-adjusted betamethasone doses might also be a key to reducing perturbations to the maternofetal hypothalamic-pituitary-adrenal axis.

D-Cysteine Ethyl Ester Reverses the Deleterious Effects of Morphine on Breathing and Arterial Blood-Gas Chemistry in Freely-Moving Rats.

Cell-penetrant thiol esters including the disulfides, D-cystine diethyl ester and D-cystine dimethyl ester, and the monosulfide, L-glutathione ethyl ester, prevent and/or reverse the deleterious effects of opioids, such as morphine and fentanyl, on breathing and gas exchange within the lungs of unanesthetized/unrestrained rats without diminishing the antinociceptive or sedative effects of opioids. We describe here the effects of the monosulfide thiol ester, D-cysteine ethyl ester (D-CYSee), on intravenous morphine-induced changes in ventilatory parameters, arterial blood–gas chemistry, alveolar–arterial (A-a) gradient (i.e., index of gas exchange in the lungs), and sedation and antinociception in freely-moving rats. The bolus injection of morphine (10 mg/kg, IV) elicited deleterious effects on breathing, including depression of tidal volume, minute ventilation, peak inspiratory flow, and inspiratory drive. Subsequent injections of D-CYSee (2 × 500 μmol/kg, IV, given 15 min apart) elicited an immediate and sustained reversal of these effects of morphine. Morphine (10 mg/kg, IV) also A-a gradient, which caused a mismatch in ventilation perfusion within the lungs, and elicited pronounced changes in arterial blood–gas chemistry, including pronounced decreases in arterial blood pH, pO2 and sO2, and equally pronounced increases in pCO2 (all responses indicative of decreased ventilatory drive). These deleterious effects of morphine were immediately reversed by the injection of a single dose of D-CYSee (500 μmol/kg, IV). Importantly, the sedation and antinociception elicited by morphine (10 mg/kg, IV) were minimally affected by D-CYSee (500 μmol/kg, IV). In contrast, none of the effects of morphine were affected by administration of the parent thiol, D-cysteine (1 or 2 doses of 500 μmol/kg, IV). Taken together, these data suggest that D-CYSee may exert its beneficial effects via entry into cells that mediate the deleterious effects of opioids on breathing and gas exchange. Whether D-CYSee acts as a respiratory stimulant or counteracts the inhibitory actions of µ-opioid receptor activation remains to be determined. In conclusion, D-CYSee and related thiol esters may have clinical potential for the reversal of the adverse effects of opioids on breathing and gas exchange, while largely sparing antinociception and sedation.

Prognostic Relevance of Pre- and Postoperative Arterial Blood Lactate Measurements, Procalcitonin and pH as Predictors of Outcomes in Secondary Peritonitis

Secondary peritonitis is the most common form that follows an intra-peritoneal source usually from perforation of hollow viscera. Acute generalized peritonitis due to underlying hollow viscous perforation is a critical &amp; life-threatening condition. It is a common surgical emergency in most of the general surgical units across the world. It is often associated with significant morbidity and mortality. In the present study Perforation peritonitis is associated with 12.8% mortality. Initial lactate, postoperative (24 hours) lactate is significant variables for mortality with critical values up to 3.78 mmol/L and 3.67 mmol/L respectively. Initial lactate, postoperative (24 hours) lactate values up to 2.29 mmol/L and 1.45 mmol/L respectively were reported in case of survivors. The lactate value of more than 2.5 mmol/L ascertained to have 64 % mortality. Initial pH, postoperative (24 hours) pH are significant variables for mortality with critical value of 7.16 and 7.17 respectively. Initial pH, postoperative (24 hours) pH value of 7.36 and 7.38 respectively were reported in case of survivors. Procalcitonin values of more than 2.58 ng/ml (normal range 0.01-0.05 ng/ml) ascertained to have 56.25 % mortality.

Cardiotocography combined with ST analysis versus cardiotocography combined with fetal blood sampling in deliveries with abnormal CTG: a randomized trial.

The aim was to investigate if intrapartum monitoring with cardiotocography (CTG) in combination with ST analysis (STAN) results in an improved perinatal outcome. We performed a two-center randomized trial. 1013 women with term fetuses in cephalic presentation entered the trial. If a CTG showed intermediate or pathological abnormalities, they were offered fetal blood sampling (FBS) and inclusion if the pH value was above 7.25. They were randomized to either CTG + FBS or CTG + STAN. The primary outcome was neonatal metabolic acidosis, defined as umbilical cord arterial blood pH below 7.05, and base excess equal to or below -10. The secondary outcomes included operative vaginal delivery for fetal distress. The rate of metabolic acidosis was 0.8% in the CTG + FBS group and 1.5% in women in the CTG + STAN (P = 0.338). More women in the CTG + STAN group delivered by operative vaginal delivery (25.6% vs 33.5%, P = 0.006). Significantly fewer women in the CTG + STAN group had three to five (28.8% vs 11.0%, P = < 0.001) and six to ten fetal blood samples taken (3.4% vs 0.4%, P = < 0.001). CTG + STAN did not reduce the incidence of neonatal metabolic acidosis compared to CTG + FBS. CTG + STAN was, however, associated with an increased risk of operative vaginal delivery and a reduced use of FBS. If STAN is used for fetal surveillance, we recommend that it is combined with other methods, such as FBS, for confirmation of the need for operative delivery. gov ID: NCT01699646. Date of registration: October 4, 2012 (retrospectively registered). https://clinicaltrials.gov/ct2/show/NCT01699646?id=NCT01699646&draw=2&rank=1.

Evaluation of personalized methylprednisolone therapy in critically ill COVID-19 patients: an observational comparative study using real-life data.

Methylprednisolone is commonly used to attenuate the cytokine storm and prevent mortality in COVID-19 pneumonia. However, the optimal methylprednisolone dose and duration are unclear. Additional data are required on the effectiveness of methylprednisolone in reducing mortality in COVID-19. This real-life retrospective study aimed to analyze the data of a COVID-19 dedicated ICU and compare the mortality rates of standard care, low-dose, and pulse-dose methylprednisolone in patients requiring mechanical ventilatory support. Methylprednisolone's indication, dose, and duration were determined according to the severity of COVID-19 pneumonia based on the patient's demographic parameters, comorbidities, laboratory data, radiology, and arterial blood gas analysis results. 867 patients were grouped as: no methylprednisolone (standard care), low-dose (0.5-1 mg/kg/day) methylprednisolone or pulse-dose (250-1,000 mg/day) methylprednisolone. The overall mortality rate was 63.78%. Adjusting the dose of methylprednisolone according to the severity of the disease resulted in statistically similar mortality rates despite the increase in disease severity. Mortality was 62.71% in standard treatment, 65.76% in low-dose, and 62.10% in pulse-dose methylprednisolone groups (p = 0.633). Invasive mechanical ventilation at admission was associated with increased mortality (HR: 1.826 [95% CI: 1.542-2.161]; p < 0.001). Hematologic disorders and malignancies, arterial blood pH and HCO3, neutrophil count, and NLR at admission were also associated with mortality. Personalizing the dose and duration of methylprednisolone according to the patient's disease severity assessed with demographic, clinical, and laboratory results may benefit mortality in severe COVID-19 patients receiving ventilatory support in the ICU. Hematologic disorders and malignancies, arterial blood pH and HCO3, neutrophil count, and NLR at admission were associated with mortality in our patient cohort.

Ingestion of Alcohol-Based Hand Sanitizer: A case report

IntroductionAlcohol-based hand sanitizers containing ethanol or isopropanol are being used in order to prevent person-to-person transmission during the COVID-19. Early signs and symptoms of this ingestion include nausea, vomiting, headache, abdominal pain, blurred vision, loss of coordination, and decreased level of consciousness. After hand sanitizer ingestion we have to suspect about methanol poisoning, monitoring the start of anion-gap metabolic acidosis, seizures, and blindness is essential. Treatment includes supportive care, acidosis correction, and the administration of an alcohol dehydrogenase inhibitor. In servere cases hemodialysis may be required.Objectives To present a case of an 29-year-old woman who was taken to the emergency department after voluntary ingestion of alcohol-based hand sanitizer in a suicide attempt. To describe the most common side effects of hand sanitizer ingestion and the literature review.MethodsClinical case presentation and literature review of similar cases.ResultsA 29-year-old woman, with diagnosis of borderline personality disorder and previous suicide attempts was taken to the emergency department after 3 hours of voluntary ingestion of an unknown quantity of alcohol-based hand sanitizer. Initial laboratory findings showed laboratory a blood methanol concentration of 66 mg/dL, with an anion gap of 30 mEq/L, arterial blood pH of 7.2, serum bicarbonate concentration of 12 mEq/L. Patient complained of abdominal pain and nervoussness.ConclusionsMost common signs and symptoms of alcohol-based hand sanitizer ingestion include nausea, vomiting, headache, abdominal pain, blurred vision, loss of coordination, and decreased level of consciousness. Treatment includes supportive care, acidosis correction, the administration of an alcohol dehydrogenase inhibitor and sometimes may be required.DisclosureNo significant relationships.

IDENTIFICATION OF RISK FACTORS PREDICTING MORTALITY IN PATIENTS WITH ARDS RELATED TO SEVERE COVID-19

TYPE: Late Breaking Abstract TOPIC: Chest Infections PURPOSE: Acute respiratory distress syndrome (ARDS) is one of the common clinical manifestations of severe COVID19 and it is also responsible for the high ventilators demand in worldwide.The aim of our study was to assess the risk factors predicting mortality in patients with ARDS developing as complication of severe COVID19 and use appropriate treatment approaches for improving clinical outcomes in such patients. METHODS: Our study was retrospective and we collected clinical data of 289 patients with severe COVID19 complicated with ARDS from five COVID19 hospitals ,from 01 August 2021 to 30 December 2021.The clinical characteristics of the survivors ARDS group(168[58.1%])and non-survivors ARDS group(121[41.9%]) of COVID19 patients were clinically,laboratory ,and radiographically compared. RESULTS: Median age of non-survivors with ARDS was older than those with survivors with ARDS(p<0.001),male and BMI >30 were more likely to die.The incidence of consolidation/ground glass opacities ratio (C/GGO) >1 in lung parenchyma,secondary bacterial infection,mechanical ventilation and lack of use dexamethasone before intubation were common findings among non-survivors with ARDS(p<0.002;<0.01;<0.001;and <0.003 ).High SOFA score and low Pa O2/FiO2(P/F) ratio were associated with higher mortality rate among non-survivors with ARDS . Predictors of death in patients with ARDS were:D-dimer (p<0.0004),creatinine(p<0.009),lymphocytes <0.6x109/L(p<0.001),procalcitonin(p<0.008),and BNP(p<0.0003).Among non-survivors with ARDS high PaCO2 and low arterial blood pH were common findings compared to those survive to the end of investigation(p<0.001). CONCLUSIONS: We identified predictors of mortality in patients with ARDS related to severe COVID19.Our findings may be helpful for healthcare providers take appropriate measures and impact to clinical outcomes in patients with severe COVID19 complicated with ARDS. CLINICAL IMPLICATIONS: critical care ohysicians ,nurses,pulmonologists,respiratory therapist DISCLOSURE: No significant relationships. KEYWORD: Severe COVID19.ARDS,RIsk Factors,Predicting ,Mortality

Predictive value of new onset versus primary meconium-stained amniotic fluid.

Transition of clear amniotic fluid to meconium-stained fluid is a relatively common occurrence during labor. However, data regarding the clinical significance and the prognostic value of the presence of meconium-stained amnionic fluid (MSAF) are scarce. This study aimed to investigate delivery and neonatal outcomes according to the presence of MSAF and the timing of the meconium passage. We used an historical cohort study at a single tertiary medical center in Israel between the years 2011 and 2018. Women were divided into two groups according to timing of meconium passage: primary MSAF (MSAF present at membrane rupture) and secondary MSAF (clear amnionic fluid that transitioned to MSAF during labor). Neonatal complication rates were compared between groups. Composite adverse neonatal outcome was defined as arterial cord blood pH &lt;7.1, 5 min Apgar score ≤7, and/or neonatal intensive care unit admission. The study cohort included 56 863 singleton term births. Of these, 9043 (15.9%) were to women who had primary MSAF, and 1484 (2.6%) to those with secondary MSAF. Secondary MSAF compared with primary MSAF increased the risks of cesarean birth and operative vaginal delivery, increased the risks of low one- and five-minute Apgar scores and low arterial cord blood pH, and increased hospital stay duration. Multivariate analysis revealed that secondary MSAF was independently associated with an increased risk of composite adverse neonatal outcome (OR1.68, 95% CI 1.25-2.24, p&lt; 0.001) compared with primary MSAF. In this sample, secondary MSAF was associated with more adverse neonatal outcomes than primary MSAF. Closer monitoring of fetal well-being may be prudent in these cases.

Association between placental location and neonatal outcomes in manual fundal pressure-assisted vaginal deliveries: A retrospective single-center study in Japan.

Manual fundal pressure (MFP) is still used to assist vaginal deliveries during the second stage of labor in predominantly lower-middle income countries; however, there is insufficient evidence on the risk factors in MFP-assisted vaginal deliveries for adverse neonatal outcomes. The aim of the present study was to investigate the association between placental location and neonatal outcomes in MFP-assisted vaginal deliveries. The present study was a single-center retrospective cohort study in patients with all MFP-assisted vaginal singleton deliveries from January 2016 to December 2020. Placental location was divided into two categories: posterior-lateral and anterior-fundal. The primary outcome was a neonatal adverse composite including umbilical artery blood pH <7.2, Apgar score <7 at 5min, neonatal intensive care unit admission and neonatal resuscitation. We used multivariable logistic regression models to investigate the association between placental location and neonatal outcomes. We extracted 522 MFP-assisted deliveries among 5053 vaginal deliveries. The proportion of posterior-lateral and anterior-fundal placentation was 239 (45.8%) and 283 (54.2%), respectively. The crude prevalence of neonatal composite outcome in the anterior-fundal group was significantly higher than that in the posterior-lateral group (39.6% vs. 28.9%; p=0.013). Multivariable logistic regression analysis found that the prevalence of neonatal adverse outcome in the anterior-fundal group was significantly higher compared with the posterior-lateral group (adjusted odds ratio, 1.52; 95% confidence interval, 1.04-2.23). Anterior-fundal placentation was significantly associated with an increased risk of neonatal adverse outcomes compared to posterior-lateral placentation in MFP-assisted vaginal deliveries.