Risk Of Acidosis Research Articles

METFORMIN CONTINUATION VERSUS INTERRUPTION FOLLOWING CORONARY ANGIOGRAPHY: CONTEMPORARY RISK OF LACTIC ACIDOSIS. A PILOT SINGLE-CENTER RANDOMIZED CONTROL TRIAL

Metformin-associated lactic acidosis occurs very infrequently; however, with the significantly greater comorbidity burden and acuity of patients with diabetes undergoing coronary angiography/angioplasty (CA), the inherent risk of metformin-associated lactic acidosis may be significantly increased. Additionally, significant variations in contemporary practice pattern around peri-CA metformin use still continue to exist.

Metformin and the Risk of Lactic Acidosis in Patients with CKD Stage 3

Metformin and the Risk of Lactic Acidosis in Patients with CKD Stage 3

THE METFORMIN GAP

SESSION TITLE: Fellows Critical Care Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Metformin is a biguanide widely used as first line therapy for type 2 diabetes mellitus. It improves glycemic control by decreasing glucose production by the liver and increasing the peripheral sensitivity of insulin. A rare but life-threatening toxicity of metformin is lactic acidosis. We present a case of metformin associated lactic acidosis (MALA) with an osmolar gap. CASE PRESENTATION: A 56 year old female with a history of type 2 diabetes mellitus and hypertension, on lisinopril, metoprolol and metformin, presented with altered mental status and abnormal breathing. She had no history of alcohol or other illicit drug use. CT head showed no acute changes and urine drug screen was negative, but blood work was significant for acute renal failure with lactic acidosis and an elevated osmolar gap (Table 1). Her mentation continued to worsen, and arterial blood gas showed pH <6.95, pCO2 68 and pO2 219. She was intubated and mechanically ventilated but remained in shock requiring three high dose vasoactive medications to maintain a MAP of 60mmHg. A sodium bicarbonate infusion was started until continuous renal replacement therapy was able to be initiated. She was started on empiric antimicrobials and was also empirically treated with fomepizole. Serum methanol and ethylene glycol levels later resulted as negative. She improved rapidly with renal replacement therapy; she was weaned off vasopressors within 48 hours, extubated on day 4 of admission and was discharged from hospital 5 days later with normal renal function. DISCUSSION: MALA is a rare but well described entity which can occur with both therapeutic use and overdose states. It is associated with high mortality rate (up to 45% in some case series) without consistent correlation between plasma metformin concentration or lactic acid levels and predicted mortality. The exact mechanism by which metformin induces lactic acidosis is complex (Figure 1). Serum osmolality is determined by plasma solutes, primarily sodium salts, glucose and urea. An increase in the osmolar gap reflects additional plasma solutes, most commonly ethanol or toxic alcohol ingestion (e.g. methanol, ethylene glycol). Ketoacids and lactic acid do not directly raise the serum osmolality but along with chronic renal failure, can cause a mild elevation. No etiology was found for this patient’s osmolar gap. While MALA with an elevated osmolar gap without other etiology has been described in case reports, its frequency and mechanism have not been defined. CONCLUSIONS: Owing to the multiple and often nonspecific signs and symptoms of MALA, it can be difficult to predict or diagnose. Conditions and medications that can predispose a patient to lactic acidosis need to be excluded prior to making a diagnosis of MALA. Early consideration of MALA in patients receiving metformin is important, as early institution of renal replacement therapy can improve survival. Reference #1: Rajasurya V, Anjum H, Surani S (May 23, 2019) Metformin Use and Metformin-associated Lactic Acidosis in Intensive Care Unit Patients with Diabetes. Cureus 11(5): e4739 Reference #2: Ralph DeFronzo, G. Alexander Fleming, Kim Chen, Thomas A. Bicsak. Metformin-associated lactic acidosis: Current perspectives on cause and risk. Metabolism 65 (Feb 2016) p20-29 Reference #3: W.L. Eppenga, A. Lalmohamed, A.F. Geerts, H.J. Derijks, M. Wensing, A. Egberts, et al. Risk of lactic acidosis or elevated lactate concentrations in metformin users with renal impairment: a population-based cohort study Diabetes Care, 37 (2014), pp. 2218-2224 DISCLOSURES: No relevant relationships by Kathryn Lai, source=Web Response

Feeding of bakery by-products in the replacement of grains enhanced milk performance, modulated blood metabolic profile, and lowered the risk of rumen acidosis in dairy cows

Leftover bakery by-products (BP) from bakeries and supermarkets may serve as energy-rich ingredient in ruminant diets. The aim of the present study was to evaluate the effect of the successive substitution of cereal grains by BP on dry matter (DM) intake, milk production, and metabolic health as well as ruminal pH and eating and chewing behavior of dairy cows. Twenty-four lactating Simmental cows (149 ± 22.3 d in milk, lactation number 2.63 ± 1.38, 756 ± 89.6 kg of initial body weight) were fed a total mixed ration containing a 50:50 ratio of forage to concentrate throughout the experiment (35 d). During the first week, all cows received a control diet (without BP) as a baseline (d -7 to 0). In the next 4 wk (d 1 to 28), cows were allocated to 3 groups differing in the BP concentrations of diets [0% BP (CON), 15% BP, and 30% BP on a DM basis]. The DM intake and reticuloruminal pH were continuously measured. Blood and milk samples were taken every week, but only results from the experimental period (d 21 and 28) were used for statistical analyses, whereas results from the baseline were considered covariates. Diet analyses showed that BP inclusion increased the ether extract and sugar contents, whereby starch and neutral detergent fiber decreased. Experimental data showed that feeding BP in the diet increased DM intake. Furthermore, the cows fed 30% BP produced roughly 4 kg/d more milk and energy-corrected milk than the CON cows. The milk urea nitrogen was lower in cows fed the BP. Feeding BP reduced the blood glucose and insulin concentrations, whereas nonesterified fatty acids, β-hydroxybutyrate, and cholesterol increased linearly. Cows fed 15% BP had the shortest period of time in which ruminal pH was below 5.8, in contrast to CON cows (+188 min/d). Taken together, the results suggest that the inclusion of up to 30% BP in the diets of mid-lactation dairy cows shifted the nutrient profile from a glucogenic diet to a lipogenic diet, holding the potential to enhance performance and lower the risk of subacute ruminal acidosis in dairy cows.

مراجعة/ جائحة كوفيد- 19: الآثار المترتبة على رعاية مرضى السكري والمعالجة الخاصة

خلفية: برزت جائحة كرونا لعام 2019 (كوفيد- 19) كواحد من أكبر التحديات التي واجهتها البشرية في الماضي القريب. الأشخاص المصابون بداء السكري والأمراض المصاحبة ذات الصلة معرضون بشكل متزايد لخطر الإصابة بمضاعفاته والوفيات المرتبطة به. الشيخوخة، والأمراض المتعددة، وفرط سكر الدم، وإصابة القلب والاستجابة الالتهابية الشديدة هي مؤشرات على نتائج سيئة على مرضى السكري أثناء جائحة كوفيد- 19. الأهداف: تلخص هذه المقالة البيانات الحالية عن العرض السريري ومخاطر كوفيد- 19 على مرضى السكري. كما نقدم بعض التوصيات لإدارة مرضى السكري أثناء كوفيد- 19 النتائج: وفقًا للبيانات الحالية، لا يبدو أن مرضى السكري معرضون بشكل متزايد لخطر الإصابة بالسارس مقارنة بعامة السكان. من ناحية أخرى فإن مرض السكري هو عامل خطر لتطور الأشكال الحاسمة والخطيرة من كوفيد- 19، وهذا الأخير يتطلب القبول في وحدة العناية المركزة و/ أو استخدام التهوية الميكانيكية الغازية، مع معدلات وفيات عالية. تخضع خصائص مرضى السكري للكشف عن أشكال حادة وحرجة من كوفيد- 19، بالإضافة إلى التأثير النذري لمرض السكري على مسار كوفيد- 19، قيد التحقيق الحالي. السمنة عامل الخطر الرئيسي لمرض السكري من النوع 2، أكثر شيوعًا في المرضى الذين يعانون من أشكال حرجة من كوفيد- 19 التي تتطلب تمدد الوريد الميكانيكي الغزوي. من ناحية أخرى، عادة ما يرتبط كوفيد- 19 بسوء التحكم في نسبة السكر في الدم وارتفاع خطر الإصابة بالحماض الكيتوني لدى مرضى السكري. لا توجد حاليًا توصيات لصالح التوقف عن تناول الأدوية الخافضة للضغط التي تتفاعل مع نظام الرينين- أنجيوتنسين- الألدوستيرون. يجب التوقف عن مثبطات الميتفورمين والبروتين الناقل للصوديوم- جلوكوز في المرضى الذين يعانون من أشكال حادة من كوفيد- 19 بسبب علاجات الحماض اللبني والحماض الكيتوني. الخلاصة: لا توجد بيانات حاليًا تظهر زيادة خطر الإصابة بـ كوفيد- 19 في مرضى السكري. من ناحية أخرى، يحتاج مرضى السكري إلى عناية خاصة، لأن مرض السكري مرتبط بخطر أعلى من الأشكال الحادة والخطيرة والمميتة لـ كوفيد- 19. تتطور معرفتنا بهذا الفيروس التاجي الجديد يومًا بعد يوم، وستتيح الدراسات المستمرة تحديد أفضل لتعريف مرضى السكري المعرضين لخطر متزايد من سوء التشخيص. على أي حال، يجب التأكيد على أهمية مراقبة جلوكوز الدم والسيطرة على مسار العدوى، بالإضافة إلى فحص مرض السكري (قبل) في جميع المرضى الذين يعانون من الإصابة المؤكدة بـ كوفيد- 19.

Bradycardia-to-delivery interval and fetal outcomes in umbilical cord prolapse.

Umbilical cord prolapse is a major obstetric emergency associated with significant perinatal complications. However, there is no consensus on the optimal decision-to-delivery interval, as many previous studies have shown poor correlation between the interval and umbilical cord arterial blood gas or perinatal outcomes. We aim to investigate whether bradycardia-to-delivery or decision-to-delivery interval was related to poor cord arterial pH or adverse perinatal outcome in umbilical cord prolapse. This was a retrospective study conducted at a university tertiary obstetric unit in Hong Kong. All women with singleton pregnancy complicated by cord prolapse during labor between 1995 and 2018 were included. Women were categorized into three groups. Group 1: persistent bradycardia; Group 2: any type of decelerations without bradycardia; and Group 3: normal fetal heart rate. The main outcome was cord arterial blood gas results of the newborns in different groups. Maternal demographic data and perinatal outcomes were reviewed. Correlation analysis between cord arterial blood gas result and time intervals including bradycardia-to-delivery, deceleration-to-delivery, and decision-to-delivery were performed for the different groups with Spearman test. There were 34, 30, and 50 women in Groups 1, 2, and 3, respectively. Cord arterial pH and base excess did not correlate with decision-to-delivery interval in any of the groups, but they were inversely correlated with bradycardia-to-delivery interval in Group 1 (Spearman's ρ=-.349; P=.043 and Spearman's ρ=-.558; P=.001, respectively). The cord arterial pH drops at 0.009 per minute with bradycardia-to-delivery interval in Group 1 (95% CI 0.0180-0.0003). The risk of significant acidosis (pH<7) was 80% when bradycardia-to-delivery interval was >20minutes, and 17.2% when the interval was <20minutes. There is significant correlation between bradycardia-to-delivery interval and cord arterial pH in umbilical cord prolapse with fetal bradycardia but not in cases with decelerations or normal heart rate. The drop of cord arterial pH is rapid and urgent delivery is essential in such situations.

Earlier and improved screening for impending fetal compromise

Objective The use of pH and base excess (FSSPHBE) from fetal scalp sampling (FSS) was abandoned when cardiotocography (CTG) was believed to be sufficiently accurate to direct patient management. We sought to understand the fetus’ tolerance to stress in the 1st stage of labor and to develop a better and earlier screening test for its risk for developing acidosis. To do so, we investigated sequential changes in fetal pH and BE obtained from FSS in the 1st stage of labor as part of a research protocol from the 1970s. We then examined the utility of multiple of the median (MoM’s) conversion of BE and pH values, and the capacity of Fetal Reserve Index (FRI) scores to be a proxy for such changes. We then sought to examine the predictive capacity of 1st stage FRI and its change over the course of the first stage of labor for the subsequent development of acidosis risk in the 2nd stage of labor. Methods Using a retrospective research database evaluation, we evaluated FSSPHBE data from 475 high-risk parturients monitored in labor and their neonates for 1 h postpartum. We categorized specimens according to cervical dilatation (CxD) at the time of FSSPHBE and developed non-parametric, multiples of the median (MOMs) assessments. FRI scores and their change over time were used as predictors of FSSPHBE. Our main outcome measures were the changes in BE and pH at different cervical dilatations (CxD) and acidosis risk in the early 2nd stage of labor. Results FSSPHBE worsens over the course of the 1st stage. The implications of any given BE are very different depending upon CxD. At 9 cm, −8 Mmol/L is 1.1 MOM; at 3 cm, it would be 2.0 MOM. The FRI level and its trajectory provide a 1st stage screening tool for acidosis risk in the second stage. Conclusions Fetal acid-base balance (“reserve”) deteriorates beginning early in the 1st stage of labor, irrespective of whether the fetus reaches a critical threshold of concern for actual acidosis. The use of MoM’s logic improves appreciation of such information. The FRI and its trajectory reasonably approximate the trajectory of the FSSPHBE and appears to be a suitable screening test for early deterioration and for earlier interventions to keep the fetus out of trouble rather than wait until high risk status develops.

Prevalence of Diabetic Keto Acidosis and Associated Factors among Newly Diagnosed Patients with Type One Diabetic Mellitus at Dilla University Referral Hospital, September 9th/2017 – May 30th/2019: South Ethiopia; Crossectional Study

Abstract Background Diabetic Ketoacidosis (DKA) is one of the most serious acute complications of Diabetes Mellitus (DM) and the leading cause of morbidity and mortality in young adults with type 1 diabetes. The mortality rate for DKA ranges from 2 to 5% in developed countries and 6 to 24% in developing countries. Even though many DKA patients were seen in emergency unit of Ethiopian hospitals and health centers, little is known about precipitating factors and clinical-laboratory features of DKA among Ethiopian patients and information is scant to promote better health service to prevent mortality due to DKA. So the aim of this study is to assess the prevalence and associated risk factors of DKA in newly diagnosed Type 1 Diabetic patients in Dilla University Referral Hospital (DURH) from September 9th/2017-May 30th/2019. Methods Quantitative institutional based study was conducted among 421 newly diagnosed type one diabetic patients. Data was double entered from the paper-based abstraction sheet into Epi info version 7 and exported to SPSS version 20 for analysis. A descriptive analysis was performed. Bivariate and multivariate logistic analysis was done to identify factors associated with the magnitude of Keto acidosis. Variables with p-value less than 0.05 were declared as having significant association between factors and dependent variable. Result The magnitude of Diabetic Keto Acidosis (DKA) in newly diagnosed patients with type one diabetic Mellitus (T1DM) was found to be 38%. The significant predictors of Diabetic Keto Acidosis (DKA) among newly diagnosed patients with type one diabetic Mellitus (T1DM) were young age of the adult, family history of diabetes and infection prior to onset of Diabetic Keto Acidosis (DKA). Conclusion The overall magnitude of Diabetic Keto Acidosis (DKA) in adults with newly diagnosed type 1 diabetes is high. In particular, adults between 18-25 years of age have a high risk of Diabetic Keto Acidosis (DKA) at onset of diabetes mellitus. Young Age, first degree relatives with Diabetic Mellitus (DM) and infection prior to Diabetic Keto Acidosis (DKA) are found to be the significant explanatory variable of Diabetic Keto Acidosis (DKA) in primary onset of T1DM.

The effect of spinal hypotension and anesthesia-to-delivery time interval on neonatal outcomes in planned cesarean delivery

Maternal hypotension after spinal anesthesia, and time from anesthesia to delivery, are potentially modifiable risk factors for neonatal acidosis. This study aimed to examine the relationship between the time from spinal anesthesia to delivery and spinal hypotension in planned cesarean deliveries and their effect on neonatal outcome, primarily neonatal acidosis. We performed a retrospective analysis of women with singleton pregnancy undergoing spinal anesthesia for planned cesarean delivery between 37 0/7 and 41 6/7 weeks' gestation using electronic medical records. The occurrence of spinal hypotension and anesthesia-to-incision and incision-to-delivery intervals (minutes) were the primarily studied variables. In addition, spinal hypotension index was developed to account for the duration and magnitude of maternal hypotension. The 90th percentile for the spinal hypotension index defined the sustained spinal hypotension group. The primary outcome was neonatal acidosis (pH of ≤7.1 or base deficit of ≥12.0). The odds ratios were calculated using univariate and multivariate logistic regression models. The multivariate analysis included sporadic spinal hypotension or sustained spinal hypotension, use of vasopressor treatment, and anesthesia-to-incision and incision-to-delivery intervals. We included 3150 women in the study. Notably, 43.4% experienced at least 1 event of spinal hypotension (sporadic) and 14.8% experienced sustained spinal hypotension. Neonatal acidosis occurred in 3.4% cases of sporadic spinal hypotension (odds ratio, 1.83; 95% confidence interval, 2.27-2.87) and in 5.8% cases of sustained hypotension (odds ratio, 3.00; 95% confidence interval, 1.87-4.80). Both anesthesia-to-incision and incision-to-delivery intervals were significantly associated with neonatal acidosis as follows: at 90th percentile cutoff, the odds ratios for neonatal acidosis were 3.82 (95% confidence interval, 2.03-7.19) and 2.94 (95% confidence interval, 1.70-5.10), respectively. The use of ephedrine (odds ratio, 2.42; 95% confidence interval, 1.35-4.32) but not phenylephrine (odds ratio, 0.76; 95% confidence interval, 0.34-1.72) treatment was also associated with more cases of neonatal acidosis. The woman's age, gestational age, neonatal birthweight, fetal presentation, and the number of previous cesarean deliveries were not associated with neonatal acidosis. In multivariate analysis, anesthesia-to-incision and incision-to-delivery intervals, use of vasopressor treatment, and sustained spinal hypotension were independently associated with neonatal acidosis. After adjustment, the risk for neonatal acidosis did not increase in women who experienced sporadic spinal hypotension only. Neither neonatal acidosis nor the primary research variables were associated with neonatal complications such as transient tachypnea of the newborn, respiratory distress, or admission to the neonatal unit. Neonatal acidosis in planned cesarean delivery was common. However, serious perinatal consequences were rare. The adverse effects of sustained spinal hypotension and prolonged anesthesia-to-incision and incision-to-delivery intervals on neonatal acid-base balance were additive. This supports the adoption of prevention strategies for spinal hypotension, which is widely evidenced based on the obstetrical anesthesia literature, but still not universally used. Whether the reduction in intraoperative time intervals would benefit the neonate should be determined by future prospective studies.

Linezolid and the risk of lactic acidosis: Data mining and analysis of the FDA Adverse Event Reporting System.

Lactic acidosis (LA) is a rare but potentially lethal side effect of linezolid (LZD). However, limited by the study population, the number of patients with LA is insufficient to summarize all the clinical characteristics and risk factors. We evaluated the association between LZD and LA using the reporting odd ratio (ROR) for mining the adverse event report signals in the FDA Adverse Event Reporting System database from January 2013 to December 2019. There were 6218 reports of LZD as the primary suspected drug or secondary suspected drug, of which 275 (4.42%) reports were of LA. The ROR of LA with the use of LZD was 39.976 (95% CI 35.365-45.189). In the age composition of patients, elderly individuals (aged ≥60years) accounted for the higher proportion, 42.54% (n=117). LA usually occurred two weeks after LZD administration (n=33). LZD was the unique suspected drug, accounting for 37.45% (n=103) of all reports of LA. The drug with the most frequent occurrence of combination with LZD was 'meropenem' and 'warfarin'. The ROR of LA caused by LZD was very high, and the number of reports about LA caused by other antibiotics was significantly different from that of LA caused by LZD. The drug combined with LZD did not seem to affect the occurrence of LA, and the high occurrence of warfarin in the reports deserves the attention of doctors.

Milk production responses, rumen fermentation, and blood metabolites of dairy cows fed increasing concentrations of forage rape (Brassica napus ssp. Biennis)

The aim of this study was to determine animal performance, rumen fermentation, and health-related blood metabolites of dairy cows in mid lactation fed with increasing levels (30 and 45%) of forage rape (FR) in the diet. Twelve pregnant multiparous lactating Holstein-Friesian dairy cows were randomly allocated to 1 of 3 dietary treatments in a replicated 3 × 3 Latin square design. The experiment was divided into three 21-d periods. For the control diet, 13.0 kg (dry matter, DM) of grass silage, 3.0 kg DM of commercial concentrate, 2.7 kg of DM cold-pressed extracted canola meal, and 0.45 kg DM of solvent-extracted soybean meal were offered daily. For the other two treatments, 30 and 45% of the DM from silage, canola meal, and commercial concentrate were replaced in equal proportions with FR. Data were analyzed individually using linear and quadratic orthogonal polynomials. Ingestive behavior was altered by the inclusion of FR. We observed a linear increase in eating time at the expense of rumination time. Nevertheless, total DM intake was not affected by dietary treatments, averaging 19.5 ± 0.24 kg of DM/d. Milk yield increased linearly with increasing concentration of FR in the diet. Thus, feed efficiency of cows (kg of milk/kg of DM intake) increased linearly with the percentage of FR in the diet. Inclusion of FR in the diet had no effect on milk composition or milk sensory characteristics. Mean rumen pH of cows decreased linearly from the control to the 45% FR diet; however, dietary treatments had no effect on the daily amount of time that rumen pH was below 5.8 (252 ± 71.4), indicating no risk of subacute ruminal acidosis. Concentrations of total volatile fatty acids in the rumen and molar proportions of acetate and butyrate were increased with FR inclusion, whereas the proportion of propionate was linearly reduced. Excretion of uric acid and total purine derivatives tended to be greater for cows fed FR, which resulted in a trend toward a linear increase in estimated microbial N flow. However, N use efficiency was not affected by FR inclusion. Although differences for some hematological measures (increased white blood cell and neutrophils counts) and a quadratic response for glutamate dehydrogenase for cows fed FR in the diet (decreased with inclusion of 30% and increased with 45% in the diet) were observed, all values were within appropriate ranges for dairy cows. These results indicated that including FR to dairy cow diets, up to 45% of diet DM, improved milk production due to changes in volatile fatty acids and predicted microbial N flow and had no negative effects on dairy cow health or sensory characteristics of milk.

Supplementation of Spring Pasture with Harvested Fodder Beet Bulb Alters Rumen Fermentation and Increases Risk of Subacute Ruminal Acidosis during Early Lactation.

Simple SummaryFodder beet (FB) is widely used in grazing dairy systems of New Zealand to support early- and late-lactation milk production, however, the large fraction of water-soluble carbohydrate present in FB bulbs presents a risk of subacute and acute ruminal acidosis. Despite widespread use of FB across New Zealand, the incidence of ruminal acidosis using industry-recommended methods of feeding FB has not been investigated. This study analyzed the time-dependent changes to rumen fermentation, apparent dry matter intake, milk production, milk composition and plasma amino acid concentration of grazing dairy cows supplemented with moderate amounts (40% of dry matter intake) of FB during early lactation. Our findings indicate that incidence of subacute ruminal acidosis due to FB is greater than currently realized, as 25% of cows developed severe subacute ruminal acidosis following transition to target FB allocation (40% of daily intake). Across all cows, FB reduced rumen pH, feed conversion efficiency and was not advantageous to milk production. These results suggest methods for adapting cows to a diet containing FB require further evaluation to reduce the risk of subacute ruminal acidosis (SARA) experienced by individuals within the herd.In a cross-over design, eight rumen cannulated dairy cows were used to explore the industry-recommended method for dietary transition to fodder beet (FB: Beta vulgaris L.) on changes to rumen fermentation and pH, milk production, dry matter intake (DMI) and the risk of subacute ruminal acidosis (SARA) during early lactation. Cows were split into two groups and individually allocated a ryegrass (Lolium Perenne L.) and white clover (Trifolium repens L.) diet (HO) or the same herbage supplemented with 6 kg DM/cow of harvested fodder beet bulbs (FBH). Dietary adaptation occurred over 20 days consisting of: stage 1: gradual transition to target FB intake (days 1–12, +0.5 kg DM of FB/d); stage 2: acclimatization (days 13–17) and stage 3: post-adaption sampling (days 18–20). Response variables were analyzed as a factorial arrangement of diet and stage of adaption using a combination of ANOVA and generalized linear mixed modelling. Dietary proportion of FB represented 22, (stage 1), 32 (stage 2) and 38% (stage 3) of daily DMI. One cow during each period developed SARA from FB and the duration of low pH increased with FBH compared to the HO treatment (p < 0.01). Rumen concentrations of lactic and butyric acid increased with FBH but concentrations of acetate, propionate and total volatile fatty acids (VFA) declined by 9.3% at day 20, compared to the HO treatment (p < 0.01). Treatments did not affect milk production but total DMI with supplemented cows increased during the final stage of adaptation and feed conversion efficiency (FCE kg milk/kg DM) declined with the FBH treatment. The occurrence of SARA in 25% of animals fed FB suggest it is a high-risk supplement to animal health and further evaluation of industry-recommended methods for feeding FB at the individual- and herd-scale are needed.

Ruminal cellulolytic bacteria abundance leads to the variation in fatty acids in the rumen digesta and meat of fattening lambs.

Ruminal cellulolytic bacteria could be a diagnostic tool for determining the subacute rumen acidosis (SARA) risk in individual ruminants; however, a limited number of studies have investigated the effects of the abundance of ruminal cellulolytic bacteria on the fatty acid (FA) composition of the rumen digesta and the muscle of sheep. Thus, the objective of this study was to evaluate the effect of the variation of rumen cellulolytic bacteria on the rumen fermentation, rumen digesta, and muscle FA composition of fattening lambs fed an identical diet. Forty-eight lambs were reared in individual units and fed a high-concentrate diet consisting of 20% forage and 80% concentrate. All lambs were adapted to diets and facilities for 14 d, and sampling was for 63 d. At the end of the experiment, the rumen fluid, rumen digesta, and longissimus dorsi were collected after slaughter for the measurement of volatile fatty acids, ruminal bacterial DNA, rumen digesta, and muscle FAs. The lambs were classified into the lower cellulolytic bacteria (LCB, n = 10) group and the higher cellulolytic bacteria (HCB, n = 10) group according to the abundance of pH-sensitive cellulolytic bacteria (Ruminococcus albus, Ruminococcus flavefaciens, Fibrobacter succinogenes, and Butyrivibrio fibrisolvens) in the rumen. Ruminal acetate concentration was positively correlated with the number of R. flavefaciens, F. Succinogenes, and B. fibrisolvens (P < 0.05, r > 0.296), whereas propionate and valerate concentrations were negatively correlated with the amount of F. succinogenes and B. fibrisolvens (P < 0.05, r > 0.348). Compared with the LCB group, the acetate (P = 0.018) as well as acetate to propionate ratio (P = 0.012) in the HCB group was higher, but the valerate ratio was lower (P = 0.002). The proportions of even-chain FAs and odd- and branched-chain fatty acid in the rumen digesta of lambs with the HCB were higher (P < 0.05), while the polyunsaturated fatty acids decreased than those in the LCB lambs (P < 0.05), but those FA proportions in the meat were similar between the two groups. The proportion of C17:0 in the meat of lambs in the HCB group was lower than that of lambs in the LCB group (P = 0.033). The proportions of conjugated linoleic acid in rumen digesta and meat were both higher in the HCB group than that in the LCB group (P = 0.046). These results indicated that the ruminal cellulolytic bacteria can alter the FA compositions in rumen digesta and further influenced the FA compositions in the meat of sheep.

Distinct responses in feed sorting, chewing behavior, and ruminal acidosis risk between primiparous and multiparous Simmental cows fed diets differing in forage and starch levels

During early lactation, both primiparous (PP) and multiparous (MP) cows are commonly fed diets rich in starch and low in forages to support their high energy requirements. Yet, the PP cows experience this dietary challenge for the first time, which might result in higher odds for them to develop rumen and systemic health disorders. The primary objective of this study was to evaluate the effect of decreasing the amount of forages in the diet on chewing and sorting behaviors and rumen and systemic health variables in PP and MP dairy cows. Twenty-four lactating Simmental cows [8 PP, average dry matter intake (DMI) of 19.1 ± 1.1 kg/d; 16 MP, average DMI of 22.5 ± 1.1 kg/d] with a body weight of 737 ± 90 kg and 50 ± 22 days in milk were used in this study. Cows were first fed a total mixed ration with 60% forage and 40% concentrate [on a dry matter (DM) basis] considered marginal in forages for 2 wk. Then, cows were switched to a diet low in forages with 40% forage and 60% concentrate (on a DM basis) for 4 wk. Reticular pH was measured continuously with wireless pH-sensors inserted into the reticulum to calculate the subacute ruminal acidosis (SARA) index. Chewing activity was measured with noseband-sensor halters, and feed sorting was measured weekly. Blood samples were collected weekly and analyzed for metabolic and inflammation markers. Switching PP and MP cows from a marginal to low-forage diet decreased the time spent eating and ruminating per kilogram of DM. Primiparous cows chewed longer per kilogram of DMI than MP cows. Also, the PP cows sorted more pronounced for longer particles and against fine particles than MP cows did. Despite higher rumination activity per kilogram of DMI and the adaptive sorting behavior, the PP cows spent on average 4.6 h/d longer below a pH of 5.8 and had a higher SARA index (i.e., area pH <5.8/DMI) than MP cows, especially during the first week of the low-forage diet (9.5 vs. 4.8). The concentration of liver enzymes increased with the low-forage diet, which was especially pronounced in the PP cows. In conclusion, this study demonstrated greater susceptibility of PP cows to SARA and liver damage than MP cows fed the same diets. Although PP cows demonstrated greater chewing and ruminating activity per kilogram of DMI, as well as adapted sorting behavior in favor of large particles during the low-forage high-starch feeding, they developed more severe signs of SARA. This suggests higher forage fiber requirements for PP cows and the need for improved feeding strategies to mitigate rumen fermentation disorders during early lactation in these cows.

Significance of Metformin Use in Diabetic Kidney Disease.

Metformin is a glucose-lowering agent that is used as a first-line therapy for type 2 diabetes (T2D). Based on its various pharmacologic actions, the renoprotective effects of metformin have been extensively studied. A series of experimental studies demonstrated that metformin attenuates diabetic kidney disease (DKD) by suppressing renal inflammation, oxidative stress and fibrosis. In clinical studies, metformin use has been shown to be associated with reduced rates of mortality, cardiovascular disease and progression to end-stage renal disease (ESRD) in T2D patients with chronic kidney disease (CKD). However, metformin should be administered with caution to patients with CKD because it may increase the risk of lactic acidosis. In this review article, we summarize our current understanding of the safety and efficacy of metformin for DKD.

Anesthesia management in neonatal congenital bronchobiliary fistula: case report and literature review

BackgroundThere is very little published literature and none that discussed care in a neonate regarding anesthetic risk and management of neonate with congenital bronchobiliary fistula during thoracoscopy and thoracotomy. This article analyzes related risk factors and literature review from perioperative ventilation, circulation and other aspects of management.Case presentationA neonate diagnosed as congenital bronchobiliary fistula combined with severe chemical pneumonia, consolidation of the lungs, and infection was facing the risk of anaesthesia under thoracoscopy exploration surgery, who experiened more than 20 days diagnostic period before operation. Many risk factors have led to conversion from minimally invasive surgery to thoracotomy, including persistent hypoxemia, hypercapnia, difficult surgical exposure and extremly difficulty of intraoperative ventilation management. Anesthesia maintenance after conversion to open access remained problematic. Fortunately the patient showed no sign of any adverse CNS effects after 4 months of follow-up.ConclusionsThe most prominent anesthesia challenges are hypoxemia, increased airway resistance, impaired ventilation, and the risk of metabolic acidosis. Close cooperation among the entire neonatal medical team is the key factors in successful management of this rare case.

P0601SAFETY AND EFFICACY OF INTRAVENOUS ADMINISTRATION OF RINGER'S LACTATE VERSUS NORMAL SALINE 0.9% SOLUTION IN PATIENTS WITH ACUTE KIDNEY INJURY AND ESTABLISHED CHRONIC KIDNEY DISEASE

Abstract Background and Aims Crystalline solutions, such as normal saline 0.9% (N/S 0.9%) and Ringer's Lactate (L/R), are readily administered for increasing plasma volume. Despite the utility of administering N/S 0.9% to hypovolemic patients, the dose of 154 mmol of sodium (Na) contained in 1 L exceeds the recommended daily dose increasing the risk of sodium overload and hyperchloremic metabolic acidosis. In contrast, L/R solution has the advantage of lower Na content, significantly less chlorine and contains lactates which may be advantageous in patients with significant acidemia such as patients with acute kidney injury (AKI) and chronic kidney disease (CKD). The aim of the present study is to investigate the safety and efficacy of administration of L/R versus N/S 0.9% in patients with prerenal AKI and established CKD. Method The study included adult patients with known CKD stage II to V without need for dialysis, with prerenal AKI (AKIN Stage I to III Criteria). Patients with other forms of AKI as well as hypervolemia, heart congestion or hyperkalemia (serum K&amp;gt;5.5 meq/l) were excluded from the study. Patients were randomized in 1:1 ratio to receive intravenously either N/S 0.9% or L/R solution at a dose of 20 ml/kg body weight/day. We studied kidney function (eGFR: CKD-EPI) and response to treatment at discharge and at 30 days after discharge, duration of hospitalization, improvement in serum bicarbonate levels (HCO3), acid-base balance, serum potassium levels and the need for dialysis. Results The study included 26 patients (17 males) with a mean age of 59.1 ± 16.1 years. Thirteen patients received treatment with N/S 0.9% and the rest with L/R solution. Baseline demographic and clinical characteristics at hospital admission and historical data did not show any significant differences in both groups of patients. Renal function at the onset of AKI did not show significant differences between the two groups (16.4 ± 5.8 vs 16.9 ± 5.7 ml/min/1.73 m2, p=ns, treatment with N/S and L/R respectively). The mean volume of solutions received by the two groups (N/S 0.9% 1119 ± 374 vs L/R 1338 ± 364 ml/day, p=ns) as well as the mean total volume of liquids received per day, did not differ significantly (2888 ± 821 vs 3069 ± 728 ml/d, p=ns). Patients treated with L/R were discharged 1 day earlier than patients treated with N/S (5.2 ± 3.2 vs 6.2 ± 4.9 days of hospitalization, p=ns). Renal function improvement during hospitalization and 30 days after discharge did not differ significantly between the two groups. Patients that received L/R showed a higher increase in plasma HCO3 (ΔHCO3) concentration at discharge than those that received N/S 0.9% (4.9 ± 4.1 vs 2.46 ± 3.7 meq/l, p=ns) and pH increase (ΔpH) was slightly higher in those that received L/R solution (0.052 ± 0.066 vs 0.023 ± 0.071, p=ns). Patients treated with N/S 0.9% showed a greater decrease in serum potassium (ΔK) at discharge compared to those treated with L/R (-0.39 ± 1.03 vs -0.17 ± 0.43 meq/l, p=ns, respectively). No patient received acute dialysis treatment. Conclusion Administration of L/R solution as a hydration treatment to patients with prerenal AKI and established CKD is not inferior concerning safety and efficacy to N/S 0.9% solution. In addition, L/R administration seems to marginally improve acid-base balance in this specific group of patients.

Metformin associated lactic acidosis: A case report

Metformin, together with lifestyle intervention, is considered first-line treatment for glycemic management in people with type 2 diabetes. Despite this widespread use, one of the areas of longstanding debate has been whether metformin can be used safely in those with chronic kidney disease (CKD). The concern is the possibility of an increased risk for lactic acidosis resulting from metformin accumulation in those with renal impairment. Metformin associated lactic acidosis (MALA) is a rare complication of long-term metformin therapy and the risk is increased in patients who have concomitant risk factors like cardiac, renal or liver failure. This condition is associated with high mortality and morbidity.

Increasing the content of physically effective fiber in high-concentrate diets fed to beef heifers affects intake, sorting behavior, time spent ruminating, and rumen pH.

AbstractThe importance of fiber particle size in ruminal health is well known, but there are fewer studies to assess the requirements of physically effective NDF (peNDF) in beef cattle than in dairy cattle. The objective of this study was to establish the optimal peNDF proportion in high-concentrate diets fed to beef cattle, to reduce the risk of subacute ruminal acidosis. The experimental design was a replicated Latin Square 4 × 4, with four periods of 21 d. Treatments consisted of four diets with different peNDF proportions: 6.4%, 10.4%, 13.6%, and 15.4%, offered ad libitum as total mixed ration, and containing 15% barley straw and 85% concentrate. Diets, which differed in proportions of straw > 4 mm (considered peNDF) and straw < 4 mm, were manually mixed with concentrate. This concentrate was the same for all diets. A ruminal bolus was orally administered to each heifer for pH measurement. Intake, water consumption, intake by particle size, feed sorting, feeding behavior, behavioral activities, and rumen pH were recorded. Chemical composition and particle sizes of diets offered were assessed in the last week of each period. Data were analyzed using the MIXED procedure of SAS. Orthogonal contrasts determined the linear and quadratic effects of increasing peNDF proportion. T-test procedure determined whether heifers carried out sorting behavior. Particles >4 mm linearly increased (P = 0.001), and particles <4 mm linearly decreased (P = 0.001) as peNDF increased. Water consumption and feeding behavior were unaffected by treatment. As peNDF increased, intakes of DM and NDF linearly decreased (P = 0.001), whereas peNDF intake increased (P = 0.001). Intake of particles > 4 mm linearly increased, whereas intake of particles < 4 mm linearly decreased (P = 0.001) as peNDF increased. Diet 6.4% performed sorting for particles > 4 mm (P < 0.01), and diets 13.6% and 15.4% against particles > 4 mm (P < 0.01). Diet 10.4% tended to sort against particles > 4 mm (P < 0.10). Time spent ruminating linearly increased (P = 0.001) as peNDF increased. Diets did not differ in mean and minimum rumen pH, but time under rumen pH thresholds (5.8, 5.7, 5.6, and 5.5) linearly decreased as peNDF increased (P < 0.05). The results suggested that the diet that best met the requirements of not compromising intake, limiting sorting behavior, and promoting time spent ruminating to reduce the number of hours under rumen pH thresholds, was the 10.4% diet.

Discovery of AdipoRon analogues as novel AMPK activators without inhibiting mitochondrial complex I

Activation of AMPK emerges as a potential therapeutic approach to metabolic diseases. AdipoRon is claimed to be an adiponectin receptor agonist that activates AMPK through adiponectin receptor 1 (AdipoR1). However, AdipoRon also exhibits moderate inhibition of mitochondrial complex I, leading to increased risk of lactic acidosis. In order to find novel AdipoRon analogues that activate AMPK without inhibition of complex I, 27 analogues of AdipoRon were designed, synthesized and biologically evaluated. As results, benzyloxy arylamide B10 was identified as a potent AMPK activator without inhibition of complex I. B10 dose-dependently improved glucose tolerance in normal mice, and significantly lowered fasting blood glucose level and ameliorated insulin resistance in db/db diabetic mice. More importantly, unlike the pan-AMPK activator MK-8722, B10 did not cause cardiac hypertrophy, probably owing to its selective activation of AMPK in the muscle tissue but not in the heart tissue. Together, B10 represents a novel class of AMPK activators with promising therapeutic potential against metabolic disease.