Sucralfate-treated Patients Research Articles

Prevention of nosocomial infection in mechanically ventilated patients: selective digestive decontamination versus sucralfate

Objective: To evaluate the efficacy of two regimens, selective digestive decontamination (SDD) and sucralfate, in the prophylaxis of nosocomial infection in critically ill patients requiring prolonged mechanical ventilation. Design: Prospective, randomised, multi-centre trial. Setting: Medical and surgical intensive care units in 10 hospitals in Catalonia, Spain. Subjects: A total of 129 patients requiring mechanical ventilation for at least four days participated in the study. The absence of infection and use of systemic or topical antibiotic therapy prior to the diagnosis of nosocomial pneumonia was also required. Interventions: Patients were randomly assigned to the control group (n=42) in which histamine H2-receptor antagonists were given; the SDD group (n=41) using topical polymyxin E, tobramycin, and amphotericin B in the pharynx and stomach; and the sucralfate group (n=46). Patients in both regimens received intravenous cefotaxime for four days. Endpoints: The follow-up period was limited to ICU stay and included from the patient's entry into the study until extubation with a cutoff limit of 40 days, or until exclusion from the study due to development of nosocomial infection and/or administration of antibiotics for any reason. Mortality attributable to nosocomial pneumonia or another infection was defined as death with progressive respiratory failure and/or septic shock during the course of infection. Measurements and main results: SDD patients showed a lower incidence of nosocomial infection (36.6%) than sucralfate-treated patients (54.3%) and controls (71.4%) (p=0.006). Nosocomial pneumonia was more frequent among controls (50%) than in SDD (17%) and sucralfate (30%) groups (p=0.005). Early-onset pneumonia (within the four days of ICU stay) was less common in either SDD-or sucralfate-treated patients (28.6% and 14.3%) than in controls (61.9%) (p=0.015). A statistically significant difference (p=0.037) in late-onset pneumonia was found between SDD and sucralfate using Kaplan-Meier estimates. The development of infection other than nosocomial pneumonia was also significantly different between the SDD group and controls and between SDD and sucralfate. Conclusions: Both SDD and sucralfate regimens reduced the occurrence of nosocomial infection in mechanically ventilated patients, particularly in the occurrence of nosocomial pneumonia. Selective decontamination was more effective than sucralfate in preventing 'late-onset' pneumonia and nosocomial infection other than pneumonia.

Duodenal Blood Flow in Sucralfate-Treated Patients

Sucralfate is a gastroprotective agent known to strengthen mucosal defensive factors.[ll Local microcirculation plays a pivotal role in maintaining the integrity of the gastroduodenal mucosa and in promoting repair of mucosal injuries,l2l Sucralfate has the ability to increase gastric mucosal blood flow in both animals[3l and humans,[4l but its possible effects on duodenal perfusion are still to be determined. The aim of our study was to assess the behaviour of duodenal blood flow in sucralfate-treated patients with endoscopic gastric abnormalities but normal duodenal appearance.

Role of sucralfate in peptic disease.

Sucralfate, a basic aluminum salt of sucrose, was the first successful drug with a major cytoprotective mechanism of action. It binds bile acids and pepsin and adheres to both ulcerated and nonulcerated mucosa. Sucralfate stimulates the synthesis and release of gastric mucosal prostaglandins as well as bicarbonate and the epidermal growth factor which stimulates healing. Sucralfate is the safest drug available today in the treatment of dyspeptic symptoms and compared to ranitidine and cimetidine it has the following characteristics. (2) The short-term healing of duodenal ulcers is the same for sucralfate, cimetidine and ranitidine. (3) Sucralfate-treated patients have a lower recurrence rate of duodenal ulceration after healing when compared with cimetidine and the recurrence rate is not connected with the presence or absence of Campylobacter pylori.

A comparison of the frequency of stress ulceration and secondary pneumonia in sucralfate- or ranitidine-treated intensive care unit patients

To compare the frequency of acute stress ulceration and secondary pneumonia caused by aerobic Gram-negative bacilli in ICU patients treated with either sucralfate or ranitidine. Prospective, randomized study. ICU, university hospital. Sixty adult patients who were mechanically ventilated and at risk of developing stress ulceration. The patients were randomized to receive either sucralfate (1 g every 6 hrs) via the nasogastric tube or iv ranitidine (50 mg every 6 hrs). If the gastric pH was less than 3.5 in the latter group, 30 mL of 0.3M sodium citrate was given via the nasogastric tube. On admission, the frequency rate of erosion/ulceration (assessed with the endoscope) was 13.5%. After 4 days, this rate had increased to 18% in sucralfate-treated patients and 36% in ranitidine-treated patients (NS). Mean gastric pH was more alkaline in the ranitidine-treated patients (5.50) compared with the sucralfate-treated patients (4.26) (p less than .01). This pH permitted a higher occurrence rate of gastric colonization by aerobic Gram-negative bacilli in ranitidine-treated patients (64.3%) compared with sucralfate-treated patients (23.8%) (p less than .01). Retrograde bacterial colonization from the stomach to oropharynx and trachea occurred more frequently in ranitidine-treated patients compared with sucralfate-treated patients. Ultimately, the occurrence rate of pneumonia was greater in the ranitidine-treated (35.7%) than in the sucralfate-treated patients (10.3%) (p less than .05). Based on our findings, we recommend the adoption of sucralfate for routine prophylaxis against stress ulceration.

Sclerotherapy-associated esophageal ulcers: lessons from a double-blind, randomized comparison of sucralfate suspension versus placebo

We undertook a double-blind randomized trial to assess whether sucralfate suspension would accelerate healing of sclerotherapy-associated esophageal ulcers. Consecutive patients who underwent sclerotherapy were evaluated. Patients were prospectively endoscoped 4 days (range, 3 to 5 days) after sclerotherapy. Those with ulcers greater than 5 mm in diameter were randomized to receive sucralfate suspension, 4 g/day (10 ml four times a day), or placebo. Endoscopic evaluations were done weekly for the 4 weeks of therapy. Nineteen patients survived long enough to be evaluated; complete ulcer healing was scored as success. Nine patients (13 ulcers) received sucralfate and 10 patients (17 ulcers) received placebo. At the end of 4 weeks, 78% of ulcers in sucralfate-treated patients had healed compared with 40% in the placebo group (p = not significant). Large ulcers were found to heal more slowly (p = 0.03, life table analysis) and small ulcers were disproportionally represented in patients receiving sucralfate (67% compared with 40% in the placebo group). When ulcer size was taken into account, the possible drug advantage disappeared; ulcer size appears to be a major determinant of rate of healing of sclerotherapy-associated esophageal ulcers. A large multicenter trial will be required to identify whether sucralfate accelerates postsclerotherapy esophageal ulcer healing.

Differences in mucosal appearances and in relapse rates in duodenal ulceration treated with sucralfate or cimetidine

A total of 46 patients with duodenal ulcer were randomly assigned, without the knowledge of the investigators, to treatment with cimetidine 200 mg three times daily and 400 mg at night or sucralfate 1 g four times daily followed by one year of maintenance treatment with cimetidine 400 mg at night or sucralfate 1 g twice daily, respectively, in those patients with healed ulcers. The endoscopic healing rates and relapse rates during the maintenance period were similar, four relapses occurring in each group. All four relapses in the sucralfate group occurred at 12 months and only two were symptpomatic. All the cimetidine relapses were symptomatic, two occurring at six months, one at nine months, and one at 12 months. Following the one year maintenance period, 13 cimetidine patients and 11 sucralfate patients were followed up for 36 months. During the first two years, nine of 13 (69 percent) cimetidine-treated and two of 11 (18 percent) sucralfate-treated patients had relapses. During the third year, three more sucralfate-treated patients and one more cimetidine-treated patient had relapses, making a total of 10 of 13 (77 percent) and five of 11 (45 percent) in the cimetidine and sucralfate groups, respectively. Duodenal biopsy specimens obtained before and after healing and after one year of maintenance were examined by light and electron microscopy. The sucralfate group showed greater improvement after one year of maintenance therapy than did the cimetidine group, although the appearances in either group were not predictive of subsequent relapse. The results show that relapses are less frequent and occur later after sucralfate therapy and also that the morphologic appearances are more normal after treatment with sucralfate than after treatment with cimetidine.

Sucralfate versus ranitidine in the treatment of gastric ulcer: Randomized clinical results in short-term and maintenance therapy

This clinical study compared the healing capacities of sucralfate and ranitidine in the treatment of gastric ulcer. Sixty patients were assigned at random to treatment with either sucralfate (1 g four times per day) or ranitidine (150 mg twice per day). The patients underwent endoscopy before inclusion in the study, after four weeks, and after eight weeks if the ulcers had not completely healed after the fourth week (phase I). Patients whose ulcers had healed were invited to participate in phase II, consisting of maintenance treatment for one year. The dosage was 1 g sucralfate twice per day or 150 mg ranitidine before going to bed. The patients underwent a clinical examination every three months and endoscopy every six months, and whenever symptoms suggested a relapse. After four weeks, the ulcers in 53 percent of the sucralfate-treated patients (16 of 30) had healed, compared with 56 percent of the ranitidine-treated patients (17 of 30). After eight weeks, the cumulative healing rates were 83 percent (25 of 30) and 86 percent (26 of 30), respectively. At the six-month follow-up visit, the relapse rates were seven of 21 (33.3 percent) in the sucralfate group and nine of 18 (50 percent) in the ranitidine group. After 12 months, the accumulative relapse rates were eight of 18 (44.4 percent) and nine of 18 (50.0 percent). The only side effects worth noting were mild constipation in four patients treated with sucralfate. One patient in the ranitidine group had myalgia and one reported headache in phase I. In conclusion, sucralfate appears to be as effective as ranitidine in the short-term treatment of gastric ulcers and in relapse prophylaxis.

Prevention of upper gastrointestinal bleeding in long-term ventilated patients: Sucralfate versus ranitidine

Thirty-two long-term ventilated patients were randomly selected for a study of the efficacy of sucralfate (1 g six times per day via gastric tube) versus ranitidine (six 50-mg to six 100-mg doses per day intravenously) for the prevention of upper gastrointestinal bleeding. The patients of the two treatment groups (each 16) were comparable with respect to diseases precipitating acute respiratory failure and risk factors of bleeding, e.g., renal failure, thrombopenia, coagulopathy, and anticoagulant treatment. Mean duration of mechanical ventilation was 7.4 in sucralfate- and 7.7 days in ranitidine-treated patients. During mechanical ventilation, macroscopically visible bleeding developed in three of the sucralfate-treated (18.7 percent) and seven of the ranitidine-treated (43.7 percent) patients. Until the end of the study, only three of the sucralfate-treated but nine of the ranitidine-treated (56.2 percent) patients bled; the difference between the two treatment groups was at all times significant (p <0.05). Packed red blood cells had to be administered to the three bleeding patients in the sucralfate group and to seven bleeding in the ranitidine group. Therefore it seems that sucralfate prevented mostly minor bleeding. The high bleeding rate during ranitidine treatment was presumably due to the high number of pH-nonresponders, as almost 30 percent of the gastric aspirates of this group had a pH less than 5. During treatment no difference was found in positive blood culture specimens and bronchial secretions between the two groups. However, nosocomial pneumonia developed in two ranitidine-treated patients, whereas that complication developed in none of the sucralfate-treated patients. In long-term ventilated patients, sucralfate prevented minor upper gastrointestinal bleeding significantly better than ranitidine. However, this does not imply that major upper gastrointestinal bleeding can be prevented by either sucralfate or ranitidine in these patients.

Sucralfate suspension 1 g four times per day in the short-term treatment of active duodenal ulcer

Sucralfate suspension 1 g/10 ml four times per day was found to be significantly better than placebo for the healing of active duodenal ulcer. An eight-week, double-blind, randomized, placebo-controlled, parallel-group multicenter study was conducted. A total of 292 patients were evaluated. Ulcer healing was evaluated by endoscopy and symptom assessment occurred at baseline and at two, four, and eight weeks, or upon symptom worsening as determined by the investigator. Healing was defined as complete re-epithelialization of the crater, without residual erosion. Patients completed eight weeks of treatment regardless of whether or not they were healed at two or four weeks. Treatment groups were comparable with regard to age, sex, ulcer history, cigarette smoking, alcohol and caffeine consumption, ulcer size, and ulcer symptoms. Analysis of procedurally correct cases demonstrated that sucralfate suspension was significantly more effective in healing duodenal ulcers than placebo at two, four, and eight weeks. Ulcer-healing rates efficacy analysis are as follows. At two weeks, the healing rate of sucralfate suspension was 22 of 125 patients (18 percent) and the healing rate of placebo suspension was eight of 130 patients (6 percent; p = 0.006). At four weeks, 58 of 114 patients (51 percent) for sucralfate and 38 of 112 patients (34 percent) for placebo (p = 0.011) were healed. At eight weeks, 80 of 105 (76 percent) for sucralfate and 53 of 100 (53 percent) for placebo (p = 0.001) were healed. Sucralfate-treated patients experienced significantly greater reductions in both daytime and nighttime pain scores at two weeks. A significant difference between treatment groups was also found for daytime symptoms at four weeks. At four and eight weeks, patients who smoked cigarettes had significantly lower healing rates than those who did not, regardless of treatment group. Sucralfate suspension was found to be effective for the treatment of active duodenal ulcer.

A maintenance regimen of sucralfate 2 g at night for reduced relapse rate in duodenal ulcer disease: A one-year follow-up study

One hundred seventeen patients with recently healed duodenal ulcers were entered into a one-year maintenance study. Patients were randomly assigned to treatment with sucralfate 2 g at night, cimetidine 400 mg, or placebo. The sucralfate versus placebo leg of the study was double-blind, whereas the cimetidine leg was single-blind. Endoscopy was repeated on clinical relapse and routinely at six and 12 months. Ninety-six of the 117 patients were followed up for one year or to an endoscopically proven recurrence. The remaining 21 patients were excluded from analysis because of default or protocol violation. The one-year analysis showed by endoscopy that ulcers had recurred in 17 of the 31 sucralfate-treated patients, 19 of the 32 cimetidine-treated patients, and in 28 of the 33 placebo-treated patients. These data included asymptomatic recurrences in four, four, and three patients, respectively. The relapse rate at 24 weeks was greater in patients healed initially with a histamine (H 2-blocker alone than in those healed initially with sucralfate alone, a combination of sucralfate with a H 2-blocker or an antacid alone.

Sucralfate in Duodenal Ulcer Disease: A Double-Blind Trial

ABSTRACT Seventy-five patients with endoscopically confirmed duodenal ulcer disease received either sucralfate (34 patients) or placebo (41 patients) for 6 weeks in a double-blind clinical trial. N...

Sucralfate treatment of nonsteroidal anti-inflammatory drug-induced gastrointestinal symptoms and mucosal damage

In a randomized, double-blind trial, sucralfate therapy, 1 g four times daily, was compared with placebo in 143 symptomatic patients to assess the treatment of gastrointestinal symptoms and gastric mucosal damage associated with nonsteroidal anti-inflammatory drugs (NSAIDs). All patients followed a fixed regimen of NSAIDs, were assigned to one of two groups based on the presence or absence of gastric erosions at baseline endoscopy, and were then assigned randomly to receive sucralfate or placebo for four weeks. Patients were then followed for up to six months while receiving open-label sucralfate 1 g twice daily to up to 1 g four times daily. After four weeks of double-blind therapy, patients taking either nonsalicylate NSAIDs or long half-life NSAIDs and who were treated with sucralfate experienced a significant reduction in both peptic symptom frequency and intensity (p <0.03) as compared with patients receiving placebo. Sucralfate-treated patients with baseline endoscopic lesions showed a significant reduction in lesion scores (p <0.005) at four weeks as compared with baseline, whereas no improvement was observed in gastric mucosal lesions of patients given placebo. Long-term sucralfate therapy resulted in continued improvement in gastrointestinal symptoms and gastric lesion scores in patients receiving all types of NSAIDs. The results indicate that sucralfate used in conjunction with NSAIDs may allow patients to continue therapy by relieving gastrointestinal symptoms and mucosal damage associated with NSAID therapy.

Comparison of the effect of sucralfate and ranitidine in reflux esophagitis

A total of 49 patients with primary reflux esophagitis were treated in a randomized controlled study at six trial centers. Treatment was given for eight weeks and consisted of daily doses of either 1 g of sucralfate suspension four times daily or one 150-mg ranitidine film-coated tablet twice daily. The evaluation of effect was based on data from 41 patients; 22 of these had received sucralfate, and 19 had received ranitidine. Reflux esophagitis was healed after eight weeks of treatment in 14 sucralfate-treated patients and in 13 ranitidine-treated patients. Alterations in the esophageal mucosa were established by endoscopic examination; the severity of these alterations was expressed in degrees using the Savary-Miller method of classification. The greater the degree of severity as assessed before treatment, the lower were the chances of the condition being completely healed. The endoscopic findings after treatment did not show any difference in the effect of the sucralfate and ranitidine treatments (p >0.05). Both forms of treatment were also found to have a similar positive effect on the subjective symptoms recorded. Overall tolerance of the two forms of treatment was good. One patient treated with ranitidine had to discontinue treatment because of an allergic rash. Based on these results, sucralfate seems to be an effective alternative for the treatment of reflux esophagitis.

Relapse rate of healed duodenal, prepyloric, and gastric ulcers treated either with sucralfate or cimetidine

A multicenter double-blind study was designed to compare the relapse rates of peptic ulcers after initial healing with a cytoprotective agent and a histamine (H 2)-receptor antagonist. Patients with endoscopically verified prepyloric or duodenal ulcers were treated with cimetidine 400 mg twice daily or sucralfate 1 g four times daily for a maximum of eight weeks; gastric ulcers were treated for up to 12 weeks. Patients with healed ulcers were followed up to 12 months, during which time anti-ulcer medication was not permitted. Control endoscopy was performed two to four and nine to 11 months after healing and at the time of symptomatic relapse. A total of 258 patients were followed for 12 months; of these, 143 had been previously treated with cimetidine and 115 had been treated with sucralfate. The relapse rates and the median time to relapse did not differ between the two groups. After 12 months, 71 percent of the previously cimetidine-treated patients and 68 percent of the sucralfate-treated patients had experienced a relapse. Smoking significantly increased the relapse rate and shortened the time to relapse in the total study population and among cimetidine-treated patients; it had no such effect in the sucralfate-treated group.