In: Main17 Apr 2010
Conrad and colleagues established the efficacy of IR-OME in reducing the risk of 3 through 14 that had not cleared with 100 ml or more of lavage. Because this was a non-inferiority study, the primary efficacy analysis was conducted on the per-protocol population at the one-sided a = 0.025 level of significance.
Secondary endpoints included the percentage of patients with any evidence of bleeding and the percentage of patients with a gastric pH of 4 or below on two consecutive gastric aspirates. The safety and tolerability of each regimen were also assessed. The mean patient age was 55.7 years (range, 16-91 years). These patients, 58.5% of whom were men and 64% of whom were white, were treated for a mean of 6.8 days. Patient characteristics were similar between the treatment groups. The rates of clinically significant bleeding were 4.5%% with IR-OME and 6.8%% with cimetidine. These results satisfied the criteria for the non-inferiority of IR-OME in preventing upper GI bleeding in critically ill patients compared with IV cime-tidine. IR-OME was more effective than IV cimetidine in maintaining a median gastric pH above 4.0 in critically ill patients. The effects of IR-OME on gastric pH were consistent regardless of patients’ baseline pH values. Median gastric pH values greater than 6 were observed in almost all patients following the first dose of IR-OME. A median gastric pH above 6 was sustained on all days for patients receiving IR-OME but persisted on only 50% of the days for patients receiving cimetidine (Figure 6).
Figure 6 Gastric pH in critically ill patients, by treatment. A median gastric pH above 6 was sustained on all days in patients receiving immediate-release (IR-OME) compared with 50% of the days in patients receiving cimetidine. (Adapted from Conrad S, Gabrielli A, Margolis B, et al. Crit Care Med 2005;33:760-765, Lippincott Williams & Wilkins.) After three days of cimetidine administration, the median gastric pH began to decline, suggesting the development of tachyphylaxis. After day eight, at least 25% of the cimetidine patients had a median gastric pH below 4. During the entire trial, failure of pH control (two consecutive gastric aspirates of pH of 4 or below at least one hour apart on the same day) was observed in 58% of the cimeti-dine patients but in only 18% of the IR-OME patients (P < .001). The incidence and type of adverse drug events (ADEs) reported with IR-OME and cimetidine were similar. For instance, nosocomial pneumonia occurred at a rate of 11.2% with IR-OME and at a rate of 9.4% with IV cimetidine (P = .61). All currently available PPIs, including IR-OME, are effective in relieving GERD symptoms, healing gastroduodenal ulcers, providing treatment of erosive esophagitis, and maintaining healing of lesions. Unlike the other PPIs, IR-OME may control nocturnal gastric acidity when it is given at bedtime. IR-OME is the only PPI that has been subjected to clinical study and carries an FDA indication for reducing the risk of upper GI bleeding in critically ill patients.
In the U.S. trial of canadian omeprazole, the most frequently reported ADEs in 465 patients that were considered possibly, probably, or definitely treatment-related were headache (in 2.4% of patients), diarrhea (in 1.9%), rash (in 1.1%), nausea (in 0.9%), constipation (in 0.9%), dizziness (in 0.6%), vomiting (in 0.4%), abdominal pain (in 0.4%), and asthenia (in 0.2%). Occasional cases of atrophic gastritis have been noted in gastric corpus biopsies of patients receiving long-term drug omeprazole therapy. A symptomatic response to omepra-zole does not preclude the presence of gastric malignancy.
Each 40-mg and 20-mg dose packet of IR-OME contains 460 mg of sodium in the form of sodium bicarbonate (1,680 mg, 20 mEq). This fact should be taken into consideration for patients who are following sodium-restricted diets. The use of IR-OME is contraindicated in patients with metabolic alkalosis and hypocalcemia. Sodium bicarbonate should also be used with caution in patients with Bartter’s syndrome, hypo-kalemia, respiratory alkalosis, and acid-base imbalances. The long-term administration of sodium bicarbonate with calcium or milk can induce the milk-alkali syndrome.
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