Insights into the Structure of Sucralfate by Advanced Solid- and Liquid-State NMR.

Sucralfate, which is a sucrose octasulfate aluminum complex, is an active pharmaceutical ingredient (API) falling in the category of cytoprotective agents which are very effective for gastric and duodenal ulcers. On interaction with stomach acid, it ionizes into aluminum and sucrose octasulfate ions to form a protective layer over the ulcerated region inhibiting further attack from acid. The mechanism of action of sucralfate in the context of its structure is not well understood. Considering that at least two forms of this API are available in the market, there are no reports on the various forms of sucralfate and differences in their pharmacological action. We characterized the two forms of sucralfate using multinuclear, multidimensional solid-state NMR, and the results show significant structural differences between them arising from variation in the aluminum environment and the level of hydration. The impact of structural differences on pharmacological action was examined by studying acid-induced Al release by 27Al liquid-state NMR. The sucralfate, European pharmaceutical standard, Form I, undergoes faster disruption in acid compared to Form II. The difference is explained on the basis of structural differences in the two forms which gives significant insights into the action of sucralfate in relation to its structure.

Effectiveness and tolerability of rectal ointment and suppositories containing sucralfate for hemorrhoidal symptoms: a prospective, observational study.

BACKGROUND AND AIMS: A high number of topical products are available for the treatment of hemorrhoidal symptoms. Sucralfate-based topical products constitute a new treatment alternative that act as a mechanical barrier to facilitate healing. The aim of this prospective, observational study was to determine patient- and physician-assessed effectiveness and tolerability of rectal ointment and suppositories containing sucralfate for the treatment of hemorrhoidal symptoms in routine clinical practice. METHODS: Adult patients with diagnosed, mild-to-moderate, symptomatic non-bleeding hemorrhoids treated with rectal ointment or suppositories containing sucralfate were enrolled. Patients were administered treatment twice per day for at least 1 week until symptom resolution and/or for a maximum of 4 weeks. The primary endpoint was patient-assessed effectiveness on a modified Symptom Severity Score (mSSS, range 0 to 14). Physician-assessed effectiveness (9 symptoms, 0 to 5 Likert scale), hemorrhoid grade, and patient satisfaction were also determined. RESULTS: Five investigators enrolled 60 patients; mean age was 48.4 ± 16.6 years and 72.4% were female. Pain or pressure sensitivity was reported as the most severe symptom by patients, and pressure sensitivity, discharge, soiling, and prolapse by physicians. Mean patient-assessed mSSS at baseline was 6.6 ± 1.9 and was significantly improved overall and in the ointment and suppository groups individually by -4.6 ± 2.0, -4.4 ± 1.8, and -4.8 ± 2.2, respectively (p < 0.0001). Investigator-assessed mean baseline symptom score was 18.1 ± 3.9 and improved by -7.1 ± 4.5, -6.9 ± 5.4, and -7.3 ± 3.5, respectively (p < 0.0001). Investigator-assessed symptoms of pressure sensitivity, swelling, and discharge were improved to the greatest extent. Hemorrhoid grade was improved in 38% of patients at the end of treatment. Compliance with treatment was 97.4% and patient satisfaction with application and onset of action was high (81.3% and 76.2%, respectively). Both the ointment and suppository were well tolerated. CONCLUSIONS: The effectiveness of topical ointment or suppository containing sucralfate on patient- and investigator-assessed hemorrhoidal symptoms in real-life clinical practice was demonstrated. Patient satisfaction was high and treatments were well tolerated. Larger controlled trials are warranted to confirm the results.

Efficacy of topical agents in oral mucositis prevention: Systematic review and network meta-analysis.

BACKGROUND: Oral mucositis (OM) is considered one of the most common side effects of patients undergoing cancer therapy. OM prevention plays a crucial role in the effectiveness of cancer treatment and the patient's quality of life. Different preventive treatments have been proposed in clinical trials, however with inconclusive results. MATERIALS AND METHODS: A systematic review search was conducted in PubMed, Scopus, Web of Science, and Cochrane Database to answer the PICO question: in cancer patients, do specific topical agents compared to standard treatments or placebo reduce the onset and severity of oral mucositis? The risk of bias was assessed, and a network meta-analysis was conducted. RESULTS: Of 2913 results, 30 randomized clinical trials were considered suitable for inclusion. A total of 2564 patients were analyzed, of which 1284 belonged to the test group and 1280 belonged to the control group. Natural products were the most used, followed mainly by antimicrobial agents, coating agents, and basic oral care measures. Topical sucralfate resulted in the most powerful intervention for the OM prevention (OR = 0.04, 95%C.I. = 0.01-0.25, p-value = 0.001). CONCLUSION: Due to its cytoprotective action, low cost, ease of administration, and safety, sucralfate could become a potential ally to prevent the onset of OM during cancer therapy.

The Efficacy of Three Different Oral Hygiene Regimens in Preventing Chemotherapy-Induced Oral Mucositis in Pediatric Patients Receiving Hematopoietic Stem Cell Transplantation.

BACKGROUND: Oral mucositis is one of the side effects developed post-hematopoietic stem cell transplant. This retrospective study aimed to assess the efficacy of a mouthwash mixture (lidocaine, sodium alginate, sucralfate, pheniramine) versus hyaluronic acid and a solution of sodium bicarbonate in terms of healing time and weight gain in the treatment of oral mucositis in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation with hemato-oncological malignancies. METHODS: A total of 171 patients that received chemotherapy for the hematopoietic stem cell transplant were divided into three groups; group 1, treated with a mixed mouthwash of lidocaine, sodium alginate, sucralfate, and pheniramine; group 2, treated with hyaluronic acid; and group 3, treated with an aqueous solution of 5% sodium bicarbonate. Weight and mucositis scale scores derived from medical records of patients. RESULTS: There was a statistically significant difference in the mucositis scale scores between the groups on the transplant day and days 5, 10, 15 and 20 after the transplantation. At these measurement points, Group 2 (receiving hyaluronic acid) had a lower score, and Group 3 (who received sodium bicarbonate) had a higher score, especially on days 5 and 10 after the transplantation. CONCLUSION: The results suggest that hyaluronic acid is a more effective treatment option than the other oral care solutions that are frequently used for prophylaxis and treatment of oral mucositis.

Effectiveness of preoperative micronized purified flavonoid fraction treatment and sucralfate-based rectal ointment on hemorrhoidal disease: A case-matched analysis.

BACKGROUND: Hemorrhoidal disease (HD) significantly impacts patients' quality of life. This study aimed to evaluate the effectiveness of preoperative treatment with the micronized purified flavonoid fraction (MPFF) and a sucralfate-based rectal ointment in managing HD symptoms and reducing interventions. METHODS: A prospective quasi-experimental study including consecutive cases and controls matched on the basis of sex was performed in a tertiary referral center. Cases received systemic and local therapy for HD, consisting of a rectal ointment containing 3% sucralfate and herbal extracts plus MPFF, in addition to conservative therapy, while controls received conservative therapy alone. The hemorrhoidal disease symptom score (HDSS), the Short Health Scale for HD (SHS-HD) score, and the Vaizey Incontinence Score were used to evaluate symptoms severity and their impact on quality of life and continence. Intervention requirements were assessed at baseline (T0) and after 60 days of treatment (T1). RESULTS: Between January and December 2023, a total of 98 patients were assessed for eligibility. After exclusions, 56 patients were enrolled, with 28 in each group. Significant improvements were observed in HD symptom scores from T0 to T1: the intervention group showed a mean change in HDSS of -9 [95% confidence interval (CI) -10 to -8], and the control group showed no significant change (mean change of 0; 95% CI -1.5 to 0). At T1, a higher proportion of patients in the intervention group underwent less invasive interventions compared with controls (18% versus 11%). Age, treatment group, and baseline symptom severity significantly predicted post-treatment symptom scores. CONCLUSIONS: In our study the preoperative treatment with MPFF and a sucralfate-based rectal ointment demonstrated clinical benefits in managing HD symptoms and reducing interventions. Further prospective trials are warranted to confirm and explore additional therapeutic strategies.

Quality-by-design driven approach in the formulation of an anti-ulcer and gastro-protective oral suspension.

OBJECTIVE: This work aims to present a Quality-by-Design (QbD) step-by-step methodology to formulate anti-ulcer and gastro-protective oral suspensions. METHODS: Sucralfate was used as a drug model. The Quality Target Product Profile was established early during preformulation. Viscosity, resuspendability, pH, and density were assessed through the screening of several suspension platforms based on different prototype compositions. A compatibility study between the active pharmaceutical ingredient and the excipients was performed by thermal analysis and infrared spectroscopy. An Ishikawa fishbone diagram and Failure Mode and Effect Analysis were employed to identify the Critical Material Attributes (CMAs), Critical Process Parameters (CPPs), and Critical Quality Attributes (CQAs). CMAs' and CPPs' impact on identified CQAs was further assessed through a 22 full factorial experimental design at normal conditions after manufacture and one month at super-accelerated stress conditions. Results: The lead prototype exhibited no physicochemical incompatibilities. The risk assessment tools revealed that the concentration of the wetting agent and the total concentration of thickening agents represented critical factors for the quality profile of the preparation in terms of viscosity. The optimized formulation comprising 1.125 w/v% total concentration of Natrosol 250 HX and Avicel RC 591 exhibited an enhanced performance according to the established profile. CONCLUSIONS: The analytical and physicochemical tests showed the robustness and compliance of the final preparation with the quality profile. The proposed step-by-step methodology based on QbD, Design of Experiments, and Quality Risk Management presented in our research holds practical implications for local industries and formulation scientists involved in the development of oral suspensions.

Comparing the efficacy and safety of different analgesic strategies after open hemorrhoidectomy: a systematic review and network meta-analysis.

PURPOSE: To evaluate the clinical efficacy and safety of different analgesic interventions in the treatment of pain after open hemorrhoidectomy by systematic review and network meta-analysis. METHODS: Randomized controlled trials that met the inclusion criteria in PubMed, Cochrane Library, Embase, Web of Science, Scopus, CNKI, WANFANG DATA, and VIP were searched from the date of database construction to June 28, 2022. RESULTS: Among the 13 randomized controlled trials (RCTs), 731 patients were included in the network meta-analysis. Most interventions are more effective than placebo in relieving postoperative pain. 24 h postoperative Visual Analogue Scale (VAS): glyceryl trinitrate (GTN) (mean difference (MD) - 4.20, 95% CI - 5.35, - 3.05), diltiazem (MD - 1.97, 95% CI - 2.44, - 1.51), botulinum toxin (BT) (MD - 1.50, 95% CI - 2.25, - 0.75), sucralfate (MD - 1.01, 95% CI - 1.53, - 0.49), and electroacupuncture (EA) (MD - 0.45, 95% CI - 0.87, - 0.04). 48 h postoperative VAS: diltiazem (MD - 2.45, 95% CI - 2.74, - 2.15), BT (MD - 2.18, 95% CI - 2.52, - 1.84), and sucralfate (MD - 1.41, 95% CI - 1.85, - 0.97). 7 d postoperative VAS: diltiazem (MD - 2.49, 95% CI - 3.20, - 1.78) and sucralfate (MD - 1.42, 95% CI - 2.00, - 0.85). The first postoperative defecation VAS: EA (MD - 0.70, 95% CI - 0.95, - 0.46). There are few data on intervention safety, and additional high-quality RCTs are expected to study this topic in the future. CONCLUSION: Diltiazem ointment may be the most effective medication for pain relief following open hemorrhoidectomy, and it can dramatically reduce pain within one week of surgery. The second and third recommended medications are BT and sucralfate ointment. GTN has a significant advantage in alleviating pain 24 h after open hemorrhoidectomy, but whether it causes headache is debatable; thus, it should be used with caution. EA's analgesic efficacy is still unknown. There was limited evidence on the safety of the intervention in this study, and it was simply presented statistically.

Effectiveness of sucralfate in preventing esophageal stricture in children after ingestion of caustic agents.

Ingestion of caustic agents by children is a serious health issue that can affect the patient for the rest of his life. The role of sucralfate in preventing stricture caused by caustic agents is controversial, and limited studies have been conducted in this field. We aimed to investigate the effect of sucralfate on preventing esophageal stricture in children. Sixty children with mean age of 36.69 ± 20.50 months and grade II B esophageal burns due to ingestion of caustic agents were enrolled in the study. In the intervention group, in addition to the usual treatment, sucralfate was administered orally at a dose of 80 mg/kg every 2 h for 3 days. For the control group, only the usual treatment was prescribed. Stricture development was compared between groups based on endoscopic and radiologic findings. Of the 60 patients enrolled in the study, 53 were examined. The incidence of esophageal stricture in the intervention group was significantly lower than in the control group (37% versus 67%, P-value = 0.042). In addition, the odds of esophageal stricture after sucralfate intervention was significantly reduced after adjustment for potential confounders (OR = 0.198, P-value = 0.031).  Conclusions: The results of this study showed that sucralfate may reduce the development of esophageal stricture in children when used to manage IIB esophageal burns due to ingestion of caustic agents. What is Known: • Ingestion of caustic agents by children is a serious health issue that can affect the patient for the rest of his life. • The role of sucralfate in preventing stricture caused by caustic agents is controversial and limited studies have been conducted in this field. What is New: • It seems that sucralfate significantly reduces the incidence of esophageal stricture following the ingestion of caustic agents in children compared to the control group. • We believe that the prognosis may be improved and the risk of stricture formation may be reduced with high doses of sucralfate therapy in grade IIB esophageal injury.

Evaluation of Physicians' Knowledge About Honey/Sucralfate Treatments in Children With Button Battery Ingestion.

OBJECTIVES: Ingestion of button batteries (BBs) causes serious mortality and morbidity. We aimed to evaluate the knowledge level of physicians working in pediatric emergency departments about the updated guidelines for BB ingestion and whether they used honey and sucralfate, which have proven positive effects in preventing mucosal damage, in their daily practice. METHODS: A "Google Form" questionnaire was prepared and used to evaluate the approach of physicians who worked in pediatric emergency department with questions about pediatric patients who were admitted with the suspicion of BB swallowing. RESULTS: A total of 263 physicians, 169 women (64.3%), with a mean age of 34.5 ± 7.3 years, participated in the study. Seventy-five percent of the participants were from tertiary care hospitals, and 60.8% had less than 5 years of pediatric emergency experience. Some 71.9% of the physicians who participated in the survey (n = 189) had no algorithm at their hospitals. Fifty-eight percent (n = 152) of the participants completely and correctly answered all our survey questions about battery swallowing. Fifty-eight (22.1%) of the participants administered sucralfate, and 12.2% (n = 32) used honey treatments in patients who swallowed BBs; 68.1% (n = 179) had never heard of the use of sucralfate, and 77.6% (n = 204) had never heard of honey applications before in the management of swallowed batteries. CONCLUSION: It was determined that the physicians who managed pediatric battery swallowing cases had deficiencies in their treatment approaches, they had no protocol in their institutions, and the use of mucosal damage mitigation and neutralization treatments, such as honey and sucralfate, was insufficient.

The efficacy of topical sucralfate in improving pain and wound healing after haemorrhoidectomy procedure: A systematic review, meta-analysis, and meta-regression of randomised clinical trials.

Pain and wound after haemorrhoidectomy constantly bothered the patient's convenience. Recurrently, topical sucralfate is used to treat excoriations and burns. It is considered to enhance epidermal growth and tissue granulation, thus, alleviating patients' problems. This study evaluated topical sucralfate's feasibility, safety, and superiority after haemorrhoidectomy. We searched randomised controlled trial (RCT) studies in PubMed, Google Scholar, Europe PMC, and ClinicalTrials.gov until March 29th, 2022. We investigated the influence of topical sucralfate on pain score postoperatively (24 hours, 7 days, and 14 days), pethidine usage, diclofenac usage, and wound healing rate compared to placebo. This study was conducted following the PRISMA guidelines. This study sorted the final six studies with 439 patients underwent haemorrhoidectomy. Topical sucralfate demonstrated significant outcomes on VAS 24 hours post-operative [Std. Mean Difference -1.00 (95% CI -1.70, -0.31), P = .005], VAS 7 days post-operative [Std. Mean Difference -2.29 (95% CI -3.34, -1.25), P < .0001], VAS 14 days post-operative [Std. Mean Difference -1.88 (95% CI -2.74, -1.01), P < .0001], pethidine usage within 24 hours post-operative [Std. Mean Difference -0.62 (95% CI -0.96, -0.27), P = .0004], diclofenac usage 7 days post-operative [Std. Mean Difference -1.76 (95% CI -2.61, -0.92), P < .0001], diclofenac usage 14 days post-operative [Std. Mean Difference -1.64 (95% CI -2.38, -0.91), P < .0001], and wound healing rate at 28-day post-operative [RR 1.45 (95% CI 1.25-1.68), P < .00001]. Topical sucralfate alleviated pain, improved wound healing, and minimised the usage of pethidine and diclofenac compared to placebo.

Comparison of topical sucralfate with dexpanthenol in rat wound model.

Wound healing is a dynamic process initiated in response to injury. There are many factors that have detrimental effects on the wound healing process. Numerous studies have been conducted for improving wound healing processes. Dexpanthenol is widely used to accelerate wound healing. Sucralfate is used for the treatment of peptic ulcers. We aimed to compare the efficacy of topical Dexpanthenol and Sucralfate in an experimental wound model in rats via histopathological examinations and immune histochemical determinations, as well, to evaluate their effects on EGF levels. Three different groups were formed: the Control Group, the Dexpanthenol Group and the Sucralfate Group. Full-thickness skin wounds were created on the back of each rat and isotonic saline was applied to the wounds of the rats in the control group, Bepanthol® cream was applied in Dexpanthenol Group and 10% Sucralfate cream was applied in Sucralfate Group, once a day. On the 7th, 14th and 21st days the wounds were measured and seven rats from each group were sacrificed and the wounds were excised for histopathological examination. Sucralfate increased wound healing rates by increasing neovascularization, fibroblast activation, reepithelialization and collagen density, as well as dexpanthenol. Our study revealed that the dexpanthenol and sucralfate groups were better than the control group in terms of their effects on wound healing, however there was no statistically significant difference among these two groups. Sucralfate improves EGF expression in skin wounds and has positive results on skin wound healing comparable to dexpanthenol.

Topical sucralfate for treatment of mucocutaneous conditions: A systematic review on clinical evidences.

Sucralfate is an aluminum salt of sucrose octasulfate, generally considered safe in terms of adverse effects. Systemic sucralfate is FDA-approved for the treatment of duodenal ulcers. Since 1991, topical sucralfate has been used in various mucocutaneous conditions, but it is not approved by the FDA yet. In this systematic review, the online databases were searched with appropriate keywords, and the papers were screened by the authors. After screening steps, the relevant articles were selected according to the inclusions and exclusions criteria. Finally, the full texts of 18 articles were included for final evaluations. In conclusion, topical sucralfate has some clinical benefit in several mucocutaneous conditions, including mucocutaneous inflammatory conditions (e.g., post-radiotherapy reaction, diaper dermatitis, keratoconjunctivitis sicca, etc.), mucocutaneous infectious disorders (e.g., peristomal wound reaction/infection); ulcers; burns, and also pain relief.

Topical sucralfate for prevention of peristomal wound reaction related to percutaneous endoscopic gastrostomy in children: A randomized controlled trial.

There are no standard protocols for peristomal skin care in children with percutaneous endoscopic gastrostomy (PEG) tubes. This clinical study aimed to evaluate the efficacy of topical sucralfate as a prophylactic intervention in the peristomal wound reaction (PWR)/infection-associated PEG insertion in children. This study was a randomized, single-blind, controlled trial recruiting child under 18 years old who submitted for PEG insertion. Patients were randomly divided to receive topical sucralfate + peristomal wound care (intervention) or peristomal wound care alone (control). In the intervention group, the participants used topical 4% sucralfate cream four times a day for 2 months. Participants were assessed using the total peristomal infection score and PWR grading system at baseline week 1, and monthly up to 5 months after the initiation of the study. Forty-four children after PEG insertion were randomly assigned to two groups. Baseline characteristics of both groups were statistically similar (p > 0.05). Friedman test demonstrated statistically significant differences in grades of PWR during the follow-up period in the control group (p = 0.01); while there was not significantly different in the intervention group (p = 0.47). This finding suggests that the intervention had a prophylaxis effect. Also, there were statistically differences in the score of erythema (p = 0.001) and exudate (p = 0.06) at the seven-time points in the control group. Topical 4% sucralfate can be considered an affordable and available prophylactic treatment for reducing the PWR/infection associated with PEG insertion in children.

Inhibition of the BMP pathway prevents development of Barrett's-associated adenocarcinoma in a surgical rat model.

INTRODUCTION: Esophageal adenocarcinoma (EAC) is an aggressive cancer, associated with reflux esophagitis and intestinal metaplasia (IM). One underlying biological mechanism, which possibly drives the development of EAC, is the dysregulated expression of Bone Morphogenetic Proteins (BMPs). AIM: To investigate if local delivery of Noggin, a BMP antagonist, reduced EAC. METHODS: After obtaining proof of principal on local delivery of a Noggin/Sucralfate substance, a randomized controlled trial to test the effects of Noggin on EAC development was performed in a surgical rat model. In the model, an esophago-jejunostomy leads to development of reflux-esophagitis, IM and eventually EAC. Rats were treated by Noggin/Sucralfate or Sucralfate alone. Treatment was administered from 26 to 29 weeks after the operation. RESULTS: Of the 112 operated rats, 52 survived beyond 26 weeks. Finally, 25 rats treated with Noggin/Sucralfate and 21 with Sucralfate, were evaluated. At the end, 39 (85%) of the animals had IM while 28 (61%) developed cancer. There were significantly more cancers in the Noggin/Sucralfate arm (50%) versus the Sucralfate group (73%) (Chi square, P < 0.05). Most cancers were mucous producing T3 adenocarcinomas. There were no significant differences in the amount of IM, size or grade of the cancers, or expression of columnar and squamous markers between the two groups. CONCLUSION: In this study, we demonstrated that inhibition of BMPs by Noggin reduced development of EAC in a surgical esophagitis-IM-EAC rat model. In future, effective targeting of the BMP pathway with selective BMP-inhibitors could become an important asset to improve EAC patient outcome.

Sucralfate as an Adjunct to Analgesia to Improve Oral Intake in Children With Infectious Oral Ulcers: A Randomized, Double-Blind, Placebo-Controlled Trial.

STUDY HYPOTHESIS: We hypothesized that sucralfate along with oral analgesics (acetaminophen or ibuprofen) administered in the emergency department leads to a clinically significant improvement in oral intake in children with acute infectious oral ulcers. METHODS: This was a randomized, double-blind, placebo-controlled trial of sucralfate versus placebo conducted between 2017 and 2018 in an urban pediatric emergency department. Children aged 6 months to 5 years with acute, infectious oral ulcers and poor oral intake received either acetaminophen at 15 mg/kg or ibuprofen at 10 mg/kg and were then randomized to receive sucralfate at 20 mg/kg per dose up to 1 g or a placebo solution. The primary outcome was oral fluid intake within 60 minutes of medication administration. The secondary outcomes were repeat ED visits, length of stay in ED, intravenous hydration rate, admission rate, adverse event rate, and emergency physician's determination of the adequacy of oral intake. RESULTS: One hundred subjects with mild dehydration (clinical dehydration score of 1) and a median age of 1.38 years were enrolled and analyzed (49 in the sucralfate group and 51 in the placebo group). Oral intake 1 hour after drug administration was similar in both the groups: the median intake in the sucralfate group was 9.7 mL/kg and 10.7 mL/kg in the placebo group (difference -1 mL/kg; 95% confidence interval [CI] -2.0 to 4.8). According to the emergency physician's report, the secondary outcomes were significant only for adequate oral intake: 71% in the sucralfate group versus 88% in the placebo group (difference -16.8%; 95% CI -32.2 to -1.4). CONCLUSION: Sucralfate as an adjunct to oral analgesics was not superior to placebo in improving oral intake in children with acute oral infectious ulcers.

Acute Anisakiasis: Pharmacological Evaluation of Various Drugs in an Animal Model.

BACKGROUND: The accidental ingestion of the third larval stage of Anisakis can cause acute clinical symptoms, which are relieved via extraction of the larvae. Although this is a highly effective technique, it can only be practiced when the larvae are found in accessible areas of the gastrointestinal tract, and therefore instead the condition has often been treated using various different drugs. AIMS: This study evaluates the effectiveness of gastric acid secretion inhibitors (omeprazole and ranitidine), gastric mucosal protectants (sucralfate) and anthelmintics (mebendazole and flubendazole) in treating anisakiasis in Wistar rats. METHODS: Rats were infected with Anisakis-type I larvae and administered the drugs via a gastric probe. Data were recorded regarding the number of live and dead larvae, their location both within the animal and in its feces, and the presence of gastrointestinal lesions. Additionally, gastric pH was measured and histology performed. RESULTS: While rats in all experimental groups exhibited lesions; those treated with ranitidine and mebendazole showed significantly fewer lesions (50% and 35% of rats exhibited lesions, respectively). Histological examination of the gastric lesions revealed infection-induced changes, but no significant differences were observed between the treated and untreated rats. CONCLUSIONS: Mebendazole was found to be most efficacious in preventing gastrointestinal lesions, followed by ranitidine, which was the most effective antacid of those studied. Both these drugs could thus be considered as part of the conservative management of anisakiasis.

Mitigating Risks of Swallowed Button Batteries: New Strategies Before and After Removal.

Despite ongoing efforts of the national Button Battery Task Force (BBTF), cases of major morbidity and mortality continue to be reported at a higher rate after ingestion of higher voltage and larger button batteries. Initiation of sucralfate or honey shortly after some button battery ingestions is crucial to prevent further injury while awaiting emergent removal. Endoscopic acetic acid irrigation post removal of button battery may halt deeper injury. Gastroenterologists need to be aware of the updates to the National Capital Poison Center algorithm for button battery ingestion.

Anesthetic Implications of the New Guidelines for Button Battery Ingestion in Children.

Button battery ingestions result in significant morbidity and mortality in children-before, during, and even after removal. The injuries created by a button battery lodged in the esophagus develop rapidly and can be severe. The current of the button battery, conducted through saliva and the tissue drives a highly alkaline caustic injury, leading to liquefactive tissue necrosis. In June 2018, new guidelines were released from the National Capital Poison Center, which include the use of preoperative protective, pH-neutralizing and viscous barrier interventions with honey and/or sucralfate administered within 12 h of ingestion. In addition, the use of postremoval irrigation of the esophagus with 50-150 mL 0.25% acetic acid is done in the operating room to help neutralize the site of tissue injury. Given that anesthesiologists play an important role in the management of esophageal foreign body removal, the entire specialty needs to be aware of the supporting data behind this and general perioperative considerations for management and potential complications of button battery ingestion.

Pharmacokinetics of levofloxacin after single intravenous and oral administration, and its interaction with sucralfate in mixed-breed dogs.

The study aims to establish the plasma pharmacokinetic parameters of levofloxacin in mixed-breed dogs, at a single dose of 5 mg/kg, intravenously, orally only and orally with sucralfate pre-treatment (1 g per animal), to evaluate its influence on antimicrobial absorption. Concentrations of levofloxacin in plasma were determined using high-performance liquid chromatography (HPLC) with fluorescence detection. After iv of levofloxacin, the mean (±SD) of AUC0-24, Vz, t½λz and MRT, was 19.05 ± 6.4 µg-h/ml, 2.43 ± 0.5 L/kg, 7.93 ± 1.41 hours and 8.7 ± 1.5 hours, respectively. After oral administration, the C max, t½λz and bioavailability were 1.95 ± 0.7 µg/ml, 7.65 ± 1.38 hours and 71.93 ± 9.75%, respectively. In animals given an oral dose of levofloxacin with sucralfate pre-treatment, there was a significant decrease (p < 0.05) in C max (0.57 ± 0.23 µg/ml), AUC (5.73 ± 2.26 µg-h/ml) and bioavailability (31.92 ± 14.19%). In the dogs studied, it is suggested that the dose 5 mg/kg of levofloxacin for both routes is inadequate to meet PK-PD targets for susceptible bacteria using breakpoints established by the Institute of Clinical and Laboratory Standards (CLSI).

Stress Ulcer Prophylaxis in Critically Ill Children: A Multicenter Observational Study.

OBJECTIVE: To describe current stress ulcer prophylaxis practice in Canadian PICUs. DESIGN: Multicenter cohort study. We defined stress ulcer prophylaxis as the use of a proton-pump inhibitor, histamine-2 receptor antagonist, or sucralfate within the first 2 PICU days among children who had not been on these medications at home and had no evidence of gastrointestinal bleeding. SETTING: Seven PICUs in Canada. PATIENTS: Three hundred seventy-eight children requiring mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children were ventilated for a median (interquartile range) of 2 days (1-6 d) and stayed in the PICU for a median (interquartile range) of 4 days (2-10 d). The median (interquartile range) age was 1.3 years (0.3-6.7 yr). Seventy percent of all children received acid suppression during their PICU stay. One hundred sixty-seven (54%) of the 309 children eligible for stress ulcer prophylaxis received it. Histamine-2 receptor antagonists were the most frequently used class (66%), followed by proton-pump inhibitors (47%) and sucralfate (4%), and 20% received more than one class. Stress ulcer prophylaxis was continued on the PICU transfer orders for 34% of these children. Children who received prophylaxis were older and had a higher Pediatric Risk of Mortality III score, more often received nonsteroidal anti-inflammatory drugs and systemic corticosteroids and received less enteral nutrition. In multivariate analysis, age and invasive mechanical ventilation were independently associated with an increased likelihood of receiving stress ulcer prophylaxis and receiving feeds was independently associated with a decreased likelihood of receiving stress ulcer prophylaxis. Gastrointestinal bleeding was reported in 21 (6%) of 378 children; three (0.8%) were clinically important. Eighteen percent were treated for a new respiratory tract infection, and 1% developed Clostridium difficile-associated diarrhea. CONCLUSIONS: Stress ulcer prophylaxis is common in Canadian PICUs. Clinically important gastrointestinal bleeding and C. difficile-associated diarrhea are rare, and the utility of routine prophylaxis should be examined.