Preanaesthetic H2 antagonists for acid aspiration pneumonia prophylaxis. Is there evidence of tolerance?

A. Timmins1, K. Hirota2 and T. Kushikata2

1 Colchester, Essex 2 Hirosaki, Japan

Editor—The editorial by Hirota and Kushikata1 advocates the use of proton pump inhibitors in intensive care unit patients who have developed tolerance to H2 antagonists, without discussing the reduced host defences caused by these drugs. Omeprazole impairs production of reactive oxygen intermediates by neutrophils, and diminishes bactericidal activity in healthy human subjects.2 An accompanying editorial to this paper highlighted the risk of raising intragastric pH with a drug that diminishes neutrophil function in critically ill patients, as it could lead to an increase in upper gastrointestinal colonization and nosocomial pneumonia.3

Before using proton pump inhibitors more widely in critically ill patients, the prevalence of tolerance to H2 antagonists should therefore be identified, and the risks of infectious complications from alternative therapies be determined by outcome studies.

A. Timmins

Colchester, UK

Editor—Thank you for giving us the opportunity to reply to the correspondence regarding our editorial,1 with which we agree. We do not recommend that drugs altering gastric pH are routinely given to critically ill patients without careful consideration. However, prophylaxis against stress-related gastric mucosal lesions is standard in many intensive care units (ICU). In our editorial, we would have liked to review tolerance to H2 antagonists but space was limited. We therefore avoided discussing the risks of upper gastrointestinal colonization and nosocomial pneumonia in ICU patients treated with drugs altering gastric pH. Clearly, as clinical anaesthetists we should be aware of the protective role of gastric acid as a primary bactericidal barrier. A reduction in gastric acidity produced by agents such as proton pump inhibitors and H2 antagonists may increase the incidence of infectious gastroenteritis and ventilation associated pneumonia.4 In addition, as indicated in several reports, proton pump inhibitors2 5 and H2 antagonists6 7 may impair some aspects of neutrophil function such as production of oxygen free radicals. Several authors2 3 have concluded that this impairment may increase the risk of infectious complications. In contrast, others5 8 suggest that this impairment represents an anti-inflammatory response, which may be beneficial for suppression of systemic inflammation and healing of gastric ulceration. Therefore, we feel that these agents should be given to ICU patients only following careful consideration of the potential adverse and beneficial effects.

K. Hirota

T. Kushikata

Hirosaki, Japan

References

1 Hirota K, Kushikata T. Preanaesthetic H2 antagonists for acid aspiration pneumonia prophylaxis. Is there evidence of tolerance? Br J Anaesth 2003; 90: 576–9[Free Full Text]

2 Zedtwitz-Liebenstein K, Wenisch C, Patruta S et al. Omeprazole treatment diminishes intra- and extracellular neutrophil reactive oxygen production and bactericidal activity. Crit Care Med 2002; 30: 1118–22[ISI][Medline]

3 Noble DW. Proton pump inhibitors and stress ulcer prophylaxis: pause for thought? Crit Care Med 2002; 30: 1175–6[ISI][Medline]

4 Prod’hom G, Leuenberger P, Koerfer J, et al. Nosocomial pneumonia in mechanically ventilated patients receiving antacid, ranitidine, or sucralfate as prophylaxis for stress ulcer. A randomized controlled trial. Ann Intern Med 1994; 120: 653–62[Abstract/Free Full Text]

5 Yoshida N, Yoshikawa T, Tanaka Y, et al. A new mechanism for anti-inflammatory actions of proton pump inhibitors—inhibitory effects on neutrophil–endothelial cell interactions. Aliment Pharmacol Ther 2000; 14 [Suppl.]: 74–81[CrossRef][ISI][Medline]

6 Okajima K, Harada N, Uchiba M. Ranitidine reduces ischemia/reperfusion-induced liver injury in rats by inhibiting neutrophil activation. J Pharmacol Exp Ther 2002; 301: 1157–65[Abstract/Free Full Text]

7 Okajima K, Murakami K, Liu W, Uchiba M. Inhibition of neutrophil activation by ranitidine contributes to prevent stress-induced gastric mucosal injury in rats. Crit Care Med 2000; 28: 2858–65[ISI][Medline]

8 Mikawa K, Akamatsu H, Nishina K, Niwa Y. Effects of pirenzepine, omeprazole, lansoprazole, and rabeprazole on human neutrophil functions. Can J Anaesth 2001; 48: 421–2[Free Full Text]





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