Comparative effectiveness of lactulose and sennosides for the prevention of peritoneal dialysis-related peritonitis: an open-label, randomized, active-controlled trial.

BACKGROUND: To the best of our knowledge, the effectiveness and safety of lactulose in comparison to sennosides, for the prevention of peritoneal dialysis (PD)-related peritonitis, has never been tested in a randomized study. METHODS: We conducted an open-label, randomized, active-controlled trial in a PD-center in Northern Thailand. Adult patients on PD were enrolled and randomly assigned in a 1:1 ratio into two groups; one group received lactulose 15 mL once daily (n = 50) and the other group received sennosides two tablets daily (n = 50). The primary outcome was time-to-first bacterial peritonitis. The secondary outcomes included a composite of bacterial peritonitis and all-cause mortality. Cox proportional hazards regression was calculated and presented as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: One hundred PD patients were recruited (50.0% men; mean age 55.5 ± 13.0 years) in this study. The baseline characteristics of the study participants were similar in both groups. No significant trend towards a higher risk of PD-related peritonitis was observed in the lactulose group (HR, 2.32 [95% CI, 0.92-5.83]; p = .051) compared to the sennosides group. Nevertheless, the secondary outcome was significantly higher in the lactulose group (HR, 2.77 [95% CI, 1.20-6.41]; p = .010). The incidence of adverse events was not substantially different between the two groups; however, diarrhoea was more frequent in the lactulose group (38.0% vs. 18.0%; p = .030) than in the sennosides group. CONCLUSIONS: Treatment with lactulose is not more effective than sennosides and cannot be routinely recommended for the prevention of peritonitis among the PD population. TRIAL REGISTRATION Thai Clinical Trial Registry (clinicaltrials.in.th); ID: TCTR20171012001 KEY MESSAGE To the best of our knowledge, no randomized controlled trial that compares the efficacy and safety profiles of lactulose versus sennosides for the prevention of PD-related peritonitis among the PD population has been conducted. In this open-label, randomized, active-controlled trial, treatment with lactulose is not more effective than sennosides in the prevention of PD-related peritonitis, and it could increase the risk of bacterial PD-related peritonitis. Further studies with a larger sample size by incorporated real-world evidence are needed to confirm our findings and to explore strategies to prevent peritonitis among PD patients.

Effects of flaxseed supplementation on functional constipation and quality of life in a Chinese population: A randomized trial.

BACKGROUND AND OBJECTIVES: This prospective, randomized, controlled study aimed to evaluate the effects of flaxseed supplementation on functional constipation and quality of life in adult men and women in China. METHODS AND STUDY DESIGN: 90 subjects with functional constipation diagnosed by the Rome IV criteria were enrolled. Subjects were randomly assigned to receive either 50 g/day flaxseed flour with meals (n=60) or 15 mL/day of a lactulose solution on an empty stomach (n=30) every morning for 4 weeks. Wexner constipation scores, stool consistency according to the Bristol Stool Form Scale, and bowel habits (frequency of bowel movements/week, the time spent on defecation) were the primary outcomes. The change in Patient Assessment of Constipation Quality of Life score was the secondary outcome. RESULTS: After 4 weeks, the bowel habits in both groups were significantly improved. The median Wexner constipation score decreased from 14 to 6.5 in the flaxseed group (p<0.001) and from 15 to 9 in the lactulose group (p<0.001). The median defecation frequency per week increased significantly (2 to 7 for flaxseed and 2 to 6 for lactulose, p<0.001 for both groups). The Patient Assessment of Constipation Quality of Life score decreased significantly (-1.34 and -0.66 for flaxseed and lactulose, respectively; p<0.001 for both groups). CONCLUSIONS: Flaxseed flour is somewhat more effective at increasing defecation frequency than lactulose, improving bowel movements and promoting life quality of subjects with chronic functional constipation in the Chinese population.

Clinical management of type C hepatic encephalopathy.

Type-C hepatic encephalopathy is a complex neurological syndrome, characteristic of patients with liver disease, causing a wide and complex spectrum of nonspecific neurological and psychiatric manifestations, ranging from a subclinical entity, minimal hepatic encephalopathy, to a deep form in which a complete alteration of consciousness can be observed: overt hepatic encephalopathy. Overt hepatic encephalopathy occurs in 30-40% of patients. According to the time course, hepatic encephalopathy is subdivided into episodic, recurrent and persistent. Diagnostic strategies range from simple clinical scales to more complex psychometric and neurophysiological tools. Therapeutic options may vary between episodic hepatic encephalopathy, in which it is important to define and treat the precipitating factor and hepatic encephalopathy and secondary prophylaxis, where the standard of care is non-absorbable disaccharides and rifaximin. Grey areas and future needs remain the therapeutic approach to minimal hepatic encephalopathy and issues in the design of therapeutic studies for hepatic encephalopathy.

Effects of early detection of peritoneal catheter migration on clinical outcomes: 15-years experiences from a single centre.

AIM: Catheter migration is an important cause of catheter malfunction in peritoneal dialysis (PD). The purpose of this study was to investigate the effect of early detection of catheter migration on clinical outcomes. METHODS: A retrospective review of 135 consecutive patients initiating PD immediately following catheter insertion from 2002 to 2017 was undertaken. In order to detect catheter migration without malfunction early, serial abdominal-pelvic radiographic examinations were performed according to a predefined protocol. Conservative management with rigorous catharsis was undertaken to correct catheter migration. A Kaplan-Meier method was used to calculate survival rate. RESULTS: Mean follow-up period was 42.8 ± 34.9 months. Catheter migration occurred in 62.4%. Among them, 85.9% occurred within the first 2 weeks after catheter insertion. There were no significant associations between catheter migration and variables such as gender, obesity, DM and type of catheter. Success rate of conservative management with rigorous catharsis was 91.1%. Catheter survival at 1 and 5 years were 91.5% and 64.6% in the migration group and 81.2% and 69.9% in the non-migration group, respectively (Log-rank test, P = 0.915). Patient survival at 1 and 5 years were 96.8% and 85.8% in the migration group and 91.9% and 82.3% in the non-migration group, respectively (P = 0.792). CONCLUSION: Early detection of PD catheter migration allowed the migrated tip to be easily corrected with conservative management. Once the migrated catheter tip was restored, catheter migration itself did not affect catheter survival. These findings suggest that early detection and correction of catheter migration is important for improving clinical outcomes.

Metabolic encephalopathy caused by nitrous oxide ('laughing gas') induced hyperammonaemia.

A 26-year-old man presented at the emergency department with confusion and decreased consciousness after several days of vomiting. In the preceding 6 months, he had used a 2-litre tank of nitrous oxide (N2O) weekly. His metabolic encephalopathy was caused by hyperammonaemia which probably resulted from interference of N2O-induced vitamin B12 deficiency with ammonia degradation. A catabolic state might have contributed to the hyperammonaemia in this case. After treatment with vitamin B12 and lactulose, both his consciousness and hyperammonaemia improved. He reported no residual complaints after 3 months of follow-up. Since N2O is increasingly used as a recreational drug, we recommend considering hyperammonaemia as a cause of metabolic encephalopathy in cases of N2O use and altered mental status.

The hospital-based evaluation of laxative prophylaxis in ICU (HELP-ICU): A pilot cluster-crossover randomized clinical trial.

PURPOSE: Prophylactic laxative regimens may prevent constipation but may increase diarrhea and subsequent rectal tube insertion. Our aim was to compare three prophylactic laxative regimens on the rate of rectal tube insertion (primary outcome) and major constipation- or diarrhea-associated complications. MATERIAL AND METHODS: We conducted a cluster-crossover trial. Three pods in a single ICU were each randomized to one of three regimens for four months with rolling cross-over. All mechanically-ventilated and enterally-fed adult patients received either regimen: A) one coloxyl with senna BD from day one; B) two coloxyl with senna +20 ml lactulose BD commencing on day 3; or C) two coloxyl with senna tablets +20 ml lactulose BD commencing on day 6. RESULTS: We enrolled 570 patients (A = 170, B = 205, C = 195) with similar baseline features. Overall, 53 (9.3%) patients received a rectal tube, and insertion rate was not statistically different between the three regimens (A = 12.9%, B = 7.8%, C = 7.7%; p = 0.15). The proportions of patients with other major constipation- or diarrhea-associated complications were similar, as were major patient-centred outcomes. CONCLUSION: Earlier commencement of a prophylactic coloxyl-based laxative regimen (day 1 or 3) did not affect the rates of complications associated with constipation or diarrhea when compared to delayed introduction (day 6).

[Acupuncture with smoothing liver and regulating qi for post-stroke slow transit constipation and its gastrointestinal hormone level].

OBJECTIVE: To compare the efficacy between acupuncture with smoothing liver and regulating qi and lactulose for post-stroke slow transit constipation(STC) and to explore the mechanism. METHODS: Sixty patients were randomized into an acupuncture group and a medication group,30 cases in each one. Based on the comprehensive stroke unit care,acupuncture with smoothing liver and regulating qi was used at Danzhong(CV 17),Qihai(CV 6),Tianshu(ST 25),Neiguan(PC 6),Gongsun(SP 4) and Taichong(LR 3) in the acupuncture group,once a day. Lactulose oral liquid was taken at a draught in the morning in the medication group,20 to 30 mL a time,once a day. The study period was 11 weeks,including 1-week baseline evaluation,6-week treatment and 4-week follow-up. We recorded the time of the first independent defecation,constipation symptom score,and gastrointestinal hormone level,including somatostatin(SS),motilin(MTL),P substance(SP) and vasoactive intestinal peptide(VIP). Also,the side effects were recorded at any time. RESULTS: The time of the first independent defecation was (30.18±16.14) h in the acupuncture group,which was significantly different from (43.22±28.42) h in the medication group(P<0.05). The constipation scores after 6-week treatment and at follow-up were lower than those before treatment in the two groups (all P<0.05),with better results in the acupuncture group(both P<0.05). MTL and SP increased,as well as SS and VIP decreased after treatment in the two groups(all P<0.05). The changes were better in the acupuncture group(all P<0.05). The side effect was not observed in the two groups. CONCLUSIONS: Acupuncture with smoothing liver and regulating qi achieves better effect than lactulose for post-stroke STC in terms of efficacy onset,extent,and long term. The mechanism may relate to increasing excitatory regulatory peptide and reducing inhibitory regulatory peptide.

Lactulose enemas in the treatment of hepatic encephalopathy. Do we help or harm?

The administration of lactulose enemas instead of or in combination with oral lactulose is common practice in patients with hepatic encephalopathy. Lactulose is a non-absorbable disaccharide that is catabolized by the bacterial flora to short chain fatty acids (e.g., lactic acid and acetic acid) which lower the colonic pH. This pH favors the formation of non-absorbable NH4+ from NH3, trapping NH4+ in the colon and thus reducing plasma ammonia concentrations. Lactulose therapy is considered as a first-line treatment and can be administered both orally and rectally.

Effect of dietary lactulose supplementation on growth performance, nutrient digestibility, meat quality, relative organ weight, and excreta microflora in broilers.

A 35 d trial was conducted to evaluate the effects of dietary lactulose on growth performance, nutrient digestibility, meat quality, relative organ weight, and excreta microflora in broilers. A total of 816 1-day-old male Ross broilers (40.2 ± 0.4 g) were allotted to 4 dietary treatments using 12 cages with 17 chicks per cage. Treatments were: 1) CON, basal diet; 2) L05, CON + 0.05% lactulose; 3) L10, CON + 0.10% lactulose; and 4) L15, CON + 0.15% lactulose. Higher (P < 0.05) body weight gain (BWG) and lower (P < 0.05) feed conversion ratio (FCR) were observed in broilers fed the L15 diet compared with those fed the CON diet during d 22 to 35. During d 0 to 35, BWG was higher (P < 0.05) and FCR was lower (P < 0.05) in broilers fed lactulose diets than those fed the CON diet. Additionally, broilers fed L15 diets had the highest BWG (P < 0.05) and lowest FCR (P < 0.05). The apparent total tract digestibility (ATTD) of DM and nitrogen (N) was increased (P < 0.05) in broilers fed the L15 diet compared with those fed the CON diet. Drip loss was decreased (P < 0.05) in L10 and L15 treatments compared with CON treatment on d 1, d 3, and d 5. On d 3, lowest (P < 0.05) drip loss was observed in the L15 treatment. Excreta E. coli counts in the L15 treatment were decreased (P < 0.05) on d 14, but Lactobacillus counts in the L15 treatment were increased (P < 0.05) on d 14 and d 35 compared with the CON diet. A linear effect (P < 0.05) was observed on BWG (d 22 to 35), FCR (d 0 to 35), the ATTD of DM and N, drip loss, E. coli (d 14), and Lactobacillus (d 14 and d 35) counts. In conclusion, dietary supplementation of 0.15% lactulose can improve growth performance and nutrient digestibility; as well as increase the proliferation of Lactobacillus and decrease E. coli counts in excreta.

Daily laxative therapy reduces organ dysfunction in mechanically ventilated patients: a phase II randomized controlled trial.

INTRODUCTION: Constipation is a common problem in intensive care units. We assessed the efficacy and safety of laxative therapy aiming to promote daily defecation in reducing organ dysfunction in mechanically ventilated patients. METHODS: We conducted a prospective, randomized, controlled, nonblinded phase II clinical trial at two general intensive care units. Patients expected to remain ventilated for over 3 days were randomly assigned to daily defecation or control groups. The intervention group received lactulose and enemas to produce 1-2 defecations per day. In the control group, absence of defecation was tolerated up to 5 days. Primary outcome was the change in Sequential Organ Failure Assessment (SOFA) score between the date of enrollment and intensive care unit discharge, death or day 14. RESULTS: We included 88 patients. Patients in the treatment group had a higher number of defecations per day (1.3 ± 0.42 versus 0.7 ± 0.56, p < 0.0001) and lower percentage of days without defecation (33.1 ± 15.7% versus 62.3 ± 24.5%, p < 0.0001). Patients in the intervention group had a greater reduction in SOFA score (-4.0 (-6.0 to 0) versus -1.0 (-4.0 to 1.0), p = 0.036) with no difference in mortality rates or in survival time. Adverse events were more frequent in the treatment group (4.5 (3.0-8.0) versus 3.0 (1.0-5.7), p = 0.016), including more days with diarrhea (2.0 (1.0-4.0) versus 1.0 (0-2.0) days, p < 0.0001). Serious adverse events were rare and did not significantly differ between groups. CONCLUSIONS: Laxative therapy improved daily defecation in ventilated patients and was associated with a greater reduction in SOFA score. TRIAL REGISTRATION: Clinical Trials.gov NCT01607060, registered 24 May 2012.

Efeito da lactulose sobre os teores séricos de ureia, creatinina, cálcio e fósforo em cães não azotêmicos / Effect of lactulose on serum urea, creatinine, calcium and phosphorus in non-azothemic dogs

The present study evaluated serum levels of urea, creatinine, calcium and phosphorus in non-azothemic dogs by continued use of lactulose orally. Serum levels of urea, creatinine, calcium and phosphorus were determined in Beagle dogs, clinically healthy and without biochemical changes (non-azothemic), undergoing oral treatment with lactulose (n = 6), for a period of 30 days. The prebiotic showed no significant lowering effect on serum urea and creatinine, but the values of calcium and phosphorus, as well as their relation, were modified with reduced serum phosphorus levels in animals treated with lactulose compared to controls, with a significant difference...

Relation between ghrelin level and treatment response in functional constipation.

BACKGROUND/AIMS: Ghrelin stimulates gastrointestinal motility. Although there are some experimental and clinical studies supporting the role of ghrelin for gastrointestinal motility disorders, limited research for constipation has been published. The purpose of this study was to evaluate the possible role of ghrelin in the pathophysiology of functional constipation in childhood. MATERIAL AND METHODS: Forty-three newly diagnosed constipated children aged 1-6 years and 25 healthy age-matched controls were included. Serum ghrelin levels were analyzed initially in both groups. Treatment protocol consisted of dietary modification, lactulose, and administration of pediatric enema. Ghrelin levels of children with functional constipation were reanalyzed after two monthsof treatment. RESULTS: Initial serum ghrelin levels of constipated patients were found to be lower than those of healthy children (p<0.001). Ghrelin levels increased during therapy. The differences between initial and second month serum ghrelin levels of constipated patients were found to be statistically significant (p<0.05). CONCLUSION: Our data supports the potential role of ghrelin in children with functional constipation. Observation of an increase in serum ghrelin levels with nonspecific treatment supports the hypothesis that low serum ghrelin levels might be a result rather than the cause of constipation.

Current and emerging strategies for treating hepatic encephalopathy.

Hepatic encephalopathy (HE) is caused by liver impairment and has a multitude of symptoms in affected patients, including change in level of consciousness, intellectual function, and neuromuscular function. Pharmacologic therapy includes use of nonabsorbable disaccharides (lactulose and lactitol), and antibiotics such as neomycin, paromycin, metronidazole, and rifaximin. Probiotics, acarbose, and drugs such as L-carnitine and flumazenil, may also be helpful in treating HE.

Iatrogenic hyperammonemia after anorexia.

High-protein dietary supplements were started for 2 patients, who had a period of anorexia before hospital admission but no history of liver disease. Subsequent altered mental status with ataxia developed in both patients. After excluding other causes, hyperammonemia was noted, while liver function test results remained normal. Removal of the high-protein dietary supplements led to reversal of symptoms and normalization of the ammonia level. With the ubiquity of nutrition supplement use outside of liver failure, SHAKE (supplement-associated hyperammonemia after c[k]achetic episode) syndrome may be commonplace in modern hospitals.

The effects of lactulose supplementation to enteral feedings in premature infants: a pilot study.

OBJECTIVE: To assess the safety and prebiotic effects of lactulose in preterm infants. STUDY DESIGN: This was a prospective, double-blinded, placebo-controlled, single-center study in 23- to 34-weeks premature infants. The study group received 1% lactulose, and control infants received 1% dextrose in all feeds (human milk or formula). RESULTS: Twenty-eight infants participated (15 lactulose, 13 placebo). Small doses of lactulose appeared to be safe and did not cause diarrhea. Premature infants on lactulose had more Lactobacilli-positive stool cultures that appeared earlier with larger number of colonies. The lactulose group tended to have less intolerance to enteral feedings, to reach full oral feeds earlier, and to be discharged home earlier. They also tended to have fewer episodes of late-onset sepsis, lower Bell stage necrotizing enterocolitis, and their nutritional laboratory indices were better, especially calcium and total protein. CONCLUSIONS: This pilot study supports the safety of supplementing preterm infants' feeds with low doses of lactulose. It also demonstrated trends that may suggest positive prebiotic effects.

Evaluation of the inclusion of a mixture of organic acids or lactulose into the feed of pigs experimentally challenged with Salmonella Typhimurium.

A mixture of organic acids and lactulose for preventing or reducing colonization of the gut by Salmonella Typhimurium was evaluated in pigs. A total of 63 4-week-old commercial piglets were randomly distributed into three different experimental dietary groups: a plain diet without additives (PD) and the same diet supplemented with either 0.4% (w/v) formic acid and 0.4% lactic acid (w/v) (AC) or 1% (w/v) lactulose (LC). After 7 days of adaptation, two-thirds of the pigs (14 from each diet) were challenged with a 2-mL oral dose of 10(8)CFU/mL of Salmonella Typhimurium, leaving the remaining animals unchallenged (UC). After 4 and 10 days post-challenge, pigs were euthanized and the ileum and caecum content were aseptically sampled to (a) quantify lactic, formic, and short-chain fatty acids (SCFA), (b) quantify bacterial populations and Salmonella by fluorescence in situ hybridization and (c) qualitatively analyse bacterial populations through denaturing gradient gel electrophoresis (DGGE). Modification of fermentation products and counts of some of the bacterial groups analysed in the challenged pigs receiving the treatments AC and LC were minimal. Treatments only influenced the bacterial diversity after 10 days post-challenge, with AC generating a lower number of DGGE bands than UC (P<0.05). Neither the inclusion of a mixture of 0.4% (w/v) formic and 0.4% (w/v) lactic acids nor of 1% (w/v) lactulose in the feed influenced numbers of Salmonella in the ileum and caecum of experimentally challenged pigs.

Prebióticos en las fórmulas para lactantes. ¿Podemos modificar la respuesta inmune? / Prebiotics in infant formulae. Could we modify the immune response?

Introducción: La microflora intestinal de los lactantes amamantados tiene un papel primordial en la función intestinal y en el desarrollo del sistema inmune. Los oligosacáridos presentes en la leche materna estimulan selectivamente el crecimiento de Bifidobacterias y Lactobacilos en el intestino. En los últimos años se han realizado varios intentos para obtener una flora similar en lactantes alimentados con fórmulas infantiles. Una de las posibilidades para obtener este efecto es proporcionar nutrientes selectivos para esta microflora beneficiosa (prebióticos). Objetivo: Realizar una revisión de la evidencia científica disponible sobre la incorporación de prebióticos a los alimentos para lactantes y su posible influencia en la respuesta inmune. Material y métodos: Se realizó un amplia búsqueda bibliográfica con los siguientes términos de búsqueda: "prebióticos OR oligosacáridos OR microflora intestinal AND fórmula infantil AND resultados". Se hizo especial análisis de los estudios clínicos con fórmulas infantiles que incorporaran prebióticos. Resultados: Un prebiótico es una sustancia no absorbible en el intestino delgado y susceptible de fermentación por la flora colónica. El empleo de una mezcla determinada de galactooligosacáridos y fructooligosacáridos en una fórmula infantil aumenta el número de bifidobacterias de una forma dependiente de la dosis (el efecto máximo obtenido a una concentración de 0,8 g/dl) y reduce el número de gérmenes patógenos tanto en lactantes pretérminos como a término cuando se comparaban con lactantes que recibían una fórmula no suplementada. El efecto de los oligosacáridos sobre el metabolismo bacteriano se estudió midiendo la producción de ácidos grasos de cadena corta y el pH fecal. Estudios más recientes han mostrado beneficios clínicos de la incorporación de una mezcla de prebióticos a una fórmula infantil. En primer lugar, se ha visto una disminución en el riesgo de aparición de dermatitis atópica en lactantes de riesgo; en segundo lugar, una reducción en el número de episodios infecciosos, fundamentalmente intestinales e infecciones de vías respiratorias superiores en el primer año de vida. Puede especularse que los prebióticos pueden tener un papel importante en la prevención de la alergia y de las infecciones leves en el lactante (AU)

Introduction: The intestinal microflora of breast-fed infants is an important physiological factor in gut function and the development of the immune system. Human milk oligosaccharides have been shown to selectively stimulate the growth of Bifidobacteria and Lactobacilli in the intestine. In the last few years several attempts have been made to establish the presence of similar microbiota in formula-fed infants. One of the approaches to modify the balance of intestinal microflora is to supply the potentially helpful microbiota with selective nutrients (prebiotics). Goal: To review the current scientific evidence related to the addition of prebiotics to infant feeds and their possible role in the immune function. Material and methods: A bibliographic search with Mesh terms: Prebiotics OR oligosaccharides OR intestinal microflora AND infant formula AND results was performed. Special analysis was done on clinical studies. Results: Prebiotics are substances that are not absorbed through the small intestine and are fermented by colonic bacteria. A prebiotic mixture from galacto-oligosaccharides and fructo-oligosaccharides has been used to mimic the effect of human milk oligosaccharides. It has been demonstrated that such a mixture significantly increases the number of bifidobacteria in a dose-related way (maximum effect at 0.8 g/dl) and reduces the number of pathogens in term as well as in preterm infants when compared with a group of infants fed a non-supplemented formula. The effect of oligosaccharides on bacterial metabolism was studied by measuring short chain fatty acid production and fecal pH. More recent studies have been able to show clinical benefits with the use of a prebiotic mixture in infant formulas. Firstly, it has been shown to decrease the risk of developing atopic dermatitis in high risk infants; secondly a reduced incidence of intestinal as well as upper airway infections in the first year of life. It can be hypothesized that prebiotics might play an important role as a new concept in allergy and infection prevention in infants (AU)