Parenteral Proton Pump Inhibitors Research Articles

Faktori rizika za produženu hospitalizaciju kod kovid-19 pacijenata

Objective. Although some factors that may influence hospitalization of COVID-19 patients are already known (hypocalcaemia and hyponatremia, bilateral pneumonia), there is a number of other potential predictors that were not investigated previously. The aim of our study was to investigate further potential predictors of the length of hospitalization among patients with COVID-19. Methods. The study was designed as observational, retrospective cohort investigation of factors associated with length of stay in a tertiary care hospital of patients admitted primarily due to COVID-19. Main outcome of the study was length of hospitalization. Secondary outcomes were mortality rate, rate of Acute Respiratory Distress Syndrome (ARDS) and rate of severe sepsis. Results. There were 110 patients whose primary reason for admission was COVID-19. The average age of our study sample was 56 years and the male gender was predominant. The median length of hospitalization was 12 days, and most of the patients lived in a city. Our study suggested that Charlson Comorbidity Index, antipsychotics, beta-blockers, metronidazole and oxygen inhalation therapy could prolong stay of COVID-19 patients in a hospital. On the other hand, corticosteroid therapy, blood transfusion, parenteral proton pump inhibitors, and macrolides reduced the length of hospitalization. Conclusions. Co-morbidities and prescribing drugs that are used for treatment of delirium or post-antibiotic diarrhea are associated with prolonged hospitalization of COVID-19 patients, while medication used for treatment of complications may shorten stay in a hospital and probably improve survival.

FORMULATION AND EVALUATION OF TRANSDERMAL PATCHES OF PANTOPRAZOLE SODIUM

Objective: The present study was an attempt to develop an alternative dosage form for the existing conventional oral, parenteral proton pump inhibitor (PPI) as transdermal patches for treating peptic ulcers. Methods: Transdermal patches of PPI were prepared using HPMC E5 with PVP K 30 and HPMC E5 with Eudragit L100 polymers in different ratios by a solvent evaporation method. All the formulated patches were subjected to various evaluation parameters such as thickness, folding endurance, weight uniformity, content uniformity, swelling index, percentage moisture content, moisture uptake, surface pH and in vitro release studies. Results: All patches exhibited satisfactory characteristics regarding integrity, flexibility, dispersion of drug, and other quality control parameters. In the in vitro release studies of transdermal patches, formulation F1 showed the prolonged release of drug (98.99 %) for 24 h, which indicates the maximum availability of the drug, and the in vitro skin permeability studies also showed that 96.26 % of drug Pantoprazole sodium permeated through the rat abdominal skin in 24 h. The kinetic studies were carried out and it was found that all the formulations follow zero-order and the release mechanism of drugs was found to be diffusion rate-limited, Non-Fickian mechanism which was confirmed by Korsmeyer–Peppas model. Conclusion: This suggests the transdermal application of Pantoprazole sodium holds the promised controlled release of the drug for an extended period of time.

POST-VAGOTOMY GASTROPARESIS – A CASE REPORT

We present Mr M.A. a 27 year old Nigerian of the Yoruba tribe who has been having recurrent dyspeptic symptoms for 5 years but not previously endoscopically evaluated for peptic ulcer disease who now presented with six days history of abdominal pain which was initially epigastric but later became generalized associated with four episodes of vomiting and a day history of abdominal distension and fever. He was acutely ill-looking and dehydrated. The Abdomen was moderately distended, does not move with respiration, generalized tenderness with guarding and rebound tenderness, intra-abdominal organs were difficult to palpate due to the guarding. Bowel sound was absent. Examination of the other systems was not remarkable. A provisional diagnosis of Generalized peritonitis likely secondary to perforated peptic ulcer was made. He had an emergency exploratory laparotomy under general anaesthesia. He was commenced on intravenous fluids and parenteral proton pump inhibitor(PPI) and antibiotics. Intra-op findings include 2 liters of bilious peritoneal fluid, Multiple fibrous adhesions, a 2.5cm x 2cm gastric perforation at the anterior wall of the antrum and a grossly normal bowel. The surgical operation performed was a Graham Omental patch closure of the gastric defect with Bilateral Truncal Vagotomy and Peritoneal lavage. Post-operative state was satisfactory and he was later discharged. He presented at the gastroenterology out-patient clinic eight months later with complaints of early satiety, feeling of indigestion and episodes of vomiting. Vomitus is usually offensive / foul smelling and contains undigested or partially digested stale food substances. Abdominal examination revealed a positive succussion splash. Other clinical examination findings were not remarkable. A Provisional Diagnosis of suspected Gastric outlet obstruction probably secondary to a chronic duodenal ulcer was made. Endoscopy findings revealed copious fluid and food debris in the stomach cavity which had an offensive smell with remnants of partially digested stale food substances seen. There was poor peristaltic activity and the stomach was poorly distensible. There were multiple areas of mucosa erosions seen in the gastric cardia and corpus. No corporal or antral lesion seen. The pyloric ring was normal and the duodenum was normal. Diagnosis- (1) Endoscopic features of Gastroparesis likely secondary to previous Bilateral Truncal Vagotomy. No evidence of mechanical obstruction of the Gastric outlet. (2) Gastric Cardia and Corporal mucosa lesions likely secondary to Stasis Gastritis. Histology of biopsy specimens showed acute on chronic non-specific gastritis and acute duodenitis. He was commenced on empirical first line Helicobacter pylori eradication triple therapy (PPI, Amoxycillin and Clarithromycin) and a prokinetic drug (Domperidone). He had made significant clinical improvement with resolution of the symptoms by the time he was seen in the clinic three weeks later. He was tolerating oral food intake adequately and he had no new complaints. He was counselled on dietary modification and placed on long term prokinetic agent (Domperidone) and long-term PPI therapy with regular clinic follow-up. The initial management of post-vagotomy gastroparesis should be conservative as many symptoms resolve with time, this occurs possibly because the enteric nervous system is able to adapt to the loss of vagal input. Modification of dietary habits, such as regular intake of small meals, and use of prokinetic drugs bring about symptomatic relief in most patients.

PS01.044: PER-ORAL ENDOSCOPIC PYLOROMYOTOMY (G-POEM) IN THE TREATMENT OF REFRACTORY GASTROPARESIS: MID—TERM SINGLE CENTRE EXPERIENCE

Abstract Background Gastroparesis is a chronic, debilitating motility disorder. Effective treatment is challenging especially in patients with severe symptoms. G-POEM is an emerging modality for refractory gastroparesis with promising preliminary results. The aim of this prospective case series was to assess the first single-center experience with G-POEM. Main outcomes were: the clinical efficacy defined by an improvement of GCSI ≥ 40% from baseline; gastric emptying study (GES) and safety. Methods Since Nov 2015, a total of 8 patients have undergone G-POEM. The etiology of gastroparesis was post-operative in 5, diabetic in 2 and idiopathic in 1 patient. One patient underwent G-POEM for gastroparesis following a multivisceral transplantation; one underwent G-POEM and POEM as a single procedure for coexisting refractory idiopathic gastroparesis and achalasia. All patients had abnormal GES. F-u visit at 3, 6, 12 and 24M were completed in 7/8 (87.5%), 7/8 (87.5%), 5/8 (62.5%) and 1/8 (12.5%) of patients, respectively. Upper GI endoscopy and GES were performed 3M after G-POEM. Results G-POEM was successfully performed in all patients. Mean procedure time was 75 minutes (range 43–106). After G-POEM, in 7 patients mean GCSI decreased from 3.26 ± 0.96 to 0.79 ± 0.76 (at 3M; P = 0.018), 0,72 ± 0.69 (6M; P = 0.018) and 1.24 ± 0.85 (12M; P = 0.028). One women finished the 24M follow maintaining excellent outcome (mean GCSI 0.77). Treatment success was reached in 6/7 (85%) of patient at 3 and 6 months. GES normalized in all patients, mean T1/2 of GES decreased from 108 ± 30 to 62 ± 23min (P = 0.018); mean residual % at 4h decreased from 17 ± 9.2% to 2.0 ± 2.0% (P = 0.018). One patient developed bleeding ulcer 10 days after G-POEM, which was successfully managed endoscopically (clips) and by a parenteral proton pump inhibitor. Conclusion We report our first experiences with G-POEM for refractory gastroparesis, demonstrating its feasibility and safety with promising mid-term efficacy. A clinical effectiveness of G-POEM needs to be assessed in a large clinical trial. Disclosure All authors have declared no conflicts of interest.

Approach to a Child with Upper Gastrointestinal Bleeding

Upper gastrointestinal bleeding (UGIB) is a potentially life threatening medical emergency requiring an appropriate diagnostic and therapeutic approach. Therefore, the primary focus in a child with UGIB is resuscitation and stabilization followed by a diagnostic evaluation. The differential diagnosis of UGIB in children is determined by age and severity of bleed. In infants and toddlers mucosal bleed (gastritis and stress ulcers) is a common cause. In children above 2 y variceal bleeding due to Extra-Hepatic Portal Venous Obstruction (EHPVO) is the commonest cause of significant UGIB in developing countries as against peptic ulcer in the developed countries. Upper gastrointestinal endoscopy is the most accurate and useful diagnostic tool to evaluate UGIB in children. Parenteral vitamin K (infants, 1-2 mg/dose; children, 5-10 mg) and parenteral Proton Pump Inhibitors (PPI's), should be administered empirically in case of a major UGIB. Octreotide infusion is useful in control of significant UGIB due to variceal hemorrhage. A temporarily placed, Sengstaken-Blakemore tube can be life saving if pharmacologic/ endoscopic methods fail to control variceal bleeding. Therapy in patients having mucosal bleed is directed at neutralization and/or prevention of gastric acid release; High dose Proton Pump Inhibitors (PPIs, Pantoprazole) are more efficacious than H2 receptor antagonists for this purpose.

CHRONIC DIARRHEA IN AN ELDERLY MAN

CHRONIC DIARRHEA IN AN ELDERLY MAN

Intensive Care in Ulcerative Gastroduodenal Hemorrhages

Objective: to retrospectively evaluate the efficiency of using an algorithm of intensive medical therapy for ulcerative gastroduodenal hemorrhage (UGDH). This algorithm combines earlier initiation of intensive care, identification of groups at increased risk for poor outcomes of hemorrhage, endoscopic treatment, and the present-day antisecretory treatment regimens using proton pump inhibitors (PPI). Subjects and methods. The authors analyzed 108 cases of intensive therapy for UGDH at two emergency care hospitals in 2005—2006, including 57 patients from intensive care units (ICU) who received antisecretory therapy with parenteral ^-histamine blockers and 51 patients who took par-enteral PPI. The Rockall scale was used to predict the outcome of treatment and to determine needs for intensive care. The formed groups were similar in age, gender, the pattern, frequency, and nature of comorbidity, the sources and severity of hemorrhage, and the level of blood loss on admission. Results. The rates of recurrent hemorrhages and deaths were significantly higher among high-risk patients having a Rockall Score of 5 or more. As compared ^-histamine blockers, the use of PPI showed a reliable and clinical significant (39.3%) reduction in the rate of recurrences in high-risk patients. The frequency of emergency operations for a relapse reduced by 18.1%, the duration of ICU treatment and the mean length of hospital stay decreased by 23.7 hours and 2.5 days, respectively. Red blood cell transfusion volume showed a 25% reduction per dose. Overall mortality, a need for surgery, and the length of hospital stay remained unchanged. Conclusion. The study has provided evidence for the predictive value of the Rockall scale in determining a relapse and a fatal case in patients with UGDH and demonstrated the higher efficiency of prevention of recurrent hemorrhage during ICU treatment with PPI versus ^-histamine blockers. Key words: ulcerative gastro-duodenal hemorrhage, Rockall scale, proton pump inhibitors.

Proton Pump Inhibitor Formulary Considerations in the Acutely III: Part 1: Pharmacology, Pharmacodynamics, and Available Formulations

To review important proton pump inhibitor (PPI) pharmacologic, pharmacokinetic, and pharmacodynamic principles in acutely ill patients, compare PPI formulation options for patients unable to swallow a tablet or capsule, and provide clinicians with guidance when making hospital formulary decisions with this class of agents. MEDLINE (1966-May 2005) and the Cochrane Library databases were searched using the key words proton pump inhibitor, acid suppression, peptic ulcer disease, gastrointestinal bleeding, stress ulcer prophylaxis, and critical illness. Bibliographies of cited references were reviewed, and a manual search of abstracts from recent gastroenterology, critical care, and surgery scientific meetings was completed. All articles identified from the data sources were evaluated, and all information deemed relevant was included for this review. PPIs have become a mainstay for acute acid suppression in hospitalized patients over other therapeutic options. Various commercially available PPI products are available for administration, either enterally or parenterally, to patients unable to swallow a tablet or capsule. Newer oral PPI formulations offer numerous advantages over older products. The results of studies comparing the pharmacokinetics and pharmacodynamics of different PPI dosage forms and routes of administration are among the factors to consider when making formulary decisions. While the introduction of new PPI products has expanded the therapeutic options for acid suppression in acutely ill patients, a number of unresolved questions remain surrounding the interchangeability of these products, the clinical significance of one PPI formulation over the other, and how oral/enteral PPI therapy should be used as step-down therapy after parenteral PPI therapy.

Rational Use of Parenteral Proton Pump Inhibitors

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Intravenous pantoprazole: a new tool for acutely ill patients who require acid suppression.

Until now, oral proton pump inhibitors have not been available as parenteral therapy in the acute care setting. Pantoprazole is the first parenteral proton pump inhibitor to become available in Canada. This agent is superior to the parenteral histamine 2 receptor antagonists with respect to acid suppressive effects and is not associated with tolerance development. Another advantage over the histamine 2 receptor antagonists is that pantoprazole does not require dosage adjustment in patients with renal impairment. Dosage adjustments are also not required for elderly patients or those with hepatic impairment when the drug is used at the usual dose for a limited period of time. Contrary to intravenous cimetidine and ranitidine, which have negative inotropic and chronotropic effects, intravenous pantoprazole is well tolerated and has no significant effect on heart rate, contractility or blood pressure. The lack of drug interactions for this agent also simplifies its use, especially in patients who may require multiple drugs during hospitalization. Parenteral pantoprazole is effective in the treatment of reflux esophagitis. It is also promising for the treatment of upper gastrointestinal bleeding and in the perioperative care of patients with Zollinger-Ellison syndrome, but further research in these areas is necessary. Once the patient is able to tolerate oral medications, parenteral therapy can be easily converted to oral therapy using an oral dose that was equivalent to the parenteral dose (ie, 40 mg given intravenously is equivalent to 40 mg given orally).