Elsevier

Journal of Critical Care

Volume 24, Issue 4, December 2009, Pages 627.e7-627.e13
Journal of Critical Care

Ranitidine is unable to maintain gastric pH levels above 4 in septic patients☆

https://doi.org/10.1016/j.jcrc.2009.02.012Get rights and content

Abstract

Purpose

The study aimed to evaluate whether ranitidine and pantoprazole are able to maintain gastric pH ≥4 in septic patients.

Materials and methods

Twenty intensive care unit patients from a university teaching hospital with sepsis were included in this study. Ten patients received ranitidine (50 mg as an intermittent bolus 3 times a day) and 10 received pantoprazole (40 mg as an intermittent bolus twice a day). Gastric pH was measured continuously for 48 hours. Endoscopy of the upper digestive tract, gastric biopsy, and investigation for Helicobacter pylori were carried out before and at the end of the study.

Results

pH values ≥4 were maintained for 46.27% ± 38.21% and 81.57% ± 19.65% of study time in the ranitidine and pantoprazole groups, respectively (P = .04).

Conclusions

Intravenous ranitidine was unable to maintain gastric pH above 4 in septic patients. All cases in the ranitidine group in whom pH remained above 4 had gastric hypotrophy or atrophy. Pantoprazole successfully maintained pH levels above 4.

Introduction

Stress erosive gastritis is the most common cause of upper gastrointestinal (GI) bleeding in patients in intensive care units (ICUs) [1]. The pathogenesis of stress-induced gastric mucosa lesions has yet to be fully clarified. Gastric acid appears to be essential for the occurrence of stress ulceration; however, it is not the only factor in the pathogenesis of this disorder. Clinical studies have shown that maintaining gastric pH between 3.5 and 5.0 may prevent lesions to the mucosa [2], [3], [4], [5], whereas maintaining pH above 5.0 neutralizes 99.9% of gastric acid [6]. With regard to stress ulcer prophylaxis through the use of histamine-2 (H2) receptor blocking agents (H2 receptor antagonists) or proton pump inhibitors (PPIs), it has been recommended that pH should be maintained above 4 [4]. Recent publications [7], [8], [9] show that both the incidence and severity of bleeding resulting from stress ulcers have now decreased, independently of prophylaxis. On the other hand, various authors have pointed to excessive prescription of prophylactic antacid therapy for hospitalized patients [10] as causing increased risk of side effects and incurring higher costs [11], [12]. Despite the fact that many patients are no longer at risk of developing gastric lesions, they are discharged from the ICU with prophylactic medication such as PPI or H2 receptor antagonist [13]. The prescription of prophylactic medication after discharge from ICU is very debatable and probably not justified in most cases [14].

The Surviving Sepsis Campaign (SSC) recommends, as level 1A evidence, that all patients with sepsis and septic shock receive H2 receptor antagonists to prevent upper GI bleeding [15].

Nevertheless, these inhibitors of gastric acid secretion have a short half-life and are unable to maintain sustained elevated pH; usually, pH remains elevated from 4 to 8 hours after intravenous injection [16].

Despite the widespread use of ranitidine for stress ulcer prophylaxis in ICUs, no consensus has yet been reached regarding the ideal drug for this purpose [17], [18].

Therefore, the objective of the current study was to evaluate the effect of intravenous ranitidine compared to pantoprazole on gastric pH of septic patients who were at risk of developing stress ulcers. The use of ranitidine in this study was due to the fact it is more potent that the cimetidine and present fewer side effects [19] as well as the H2 receptor antagonist used in most ICUs in Brazil. In recent meta-analysis, ranitidine was the most studied H2 receptor antagonist [20].

Section snippets

Materials and methods

This is a prospective, open-label, randomized clinical trial.

Results

No statistically significant differences were found between the 2 groups regarding demographic and clinical characteristics. The mean age for the ranitidine group was 44 ± 20 and 45 ± 15 years for the pantoprazole group (P = .64). The baseline mean APACHE II was 12 ± 7 in the ranitidine group and 16 ± 4 in the pantoprazole group (P = .08). For all patients who were under sedation, the Ramsay scale was 5 (Table 1).The mean delay of admission in ICU and inclusion was 5 days in ranitidine group

Discussion

Various publications report overuse of antacids as prophylactic therapy for hospitalized patients [10], resulting in higher costs and possible side effects [11], [12]. Nonetheless, the prescription is based on clear scientific data. To prevent upper GI bleeding in patients with severe sepsis, the 2008 revision of the SSC [15] recommends the use of H2 receptor antagonists (level 1A evidence) or PPIs (level 1B evidence). However, SSC drew attention to the fact that no benefit of stress ulcer

Conclusion

Intermittent intravenous ranitidine used as prophylaxis for stress ulcers in septic patients was unable to maintain gastric pH above 4. In the ranitidine group, most of the patients who maintained a pH above 4 had gastric hypotrophy or atrophy. Pantoprazole maintained pH above 4 for a longer period. These results suggest the need to review the use of ranitidine to increase gastric pH, which is only one element among others responsible of upper gastrointestinal bleeding. The systematic

Acknowledgments

The authors would like to thank Prof Dr Gilberto de Nucci, Prof Dr Jose Murilo Robilotta Zeitune, and Prof Dr Luciana Rodrigues de Meirelles.

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    Support funds for research and development were provided by FAEPEX. Fundação de Apoio ao Ensino, à Pesquisa e à Extensão.

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