Summary
Acute upper gastrointestinal bleeding in intensive care unit (ICU) patients may occur due to peptic ulcer disease, adverse drug effects, gastric tube lesions, acute renal failure, liver failure or stress-induced gastric mucosal lesions. Gastric acid hypersecretion can be observed in patients with head trauma or neurosurgical procedures. Gastric mucosal ischaemia due to hypotension and shock is the most important risk factor for stress ulcer bleeding.
Preventive strategies aim to reduce gastric acidity (histamine H2 receptor antagonists, antacids), strengthen mucosal defensive mechanisms (sucralfate, antacids, pirenzepine) and normalise gastric mucosal microcirculation (sucralfate, pirenzepine). However, the most important prophylactic measure is an optimised resuscitation and ICU regime aiming to improve oxygenation and microcirculation.
All drugs approved for stress ulcer prophylaxis in Europe (H2 antagonists, antacids, pirenzepine, sucralfate) have been shown to be effective in prospective controlled randomised trials. However, due to insufficient clinical data, prostaglandins and omeprazole cannot be recommended for this use. Stress ulcer prophylaxis is indicated only in patients at risk, and not in every ICU patient.
The selection of drugs today depends not only on efficacy but also on possible adverse effects and on costs. In this regard, the most cost-effective drug is sucralfate. The clinical relevance of nosocomial pneumonia due to gastric bacterial overgrowth has decreased during the past decade due to several changes in the management of critically ill patients.
Similar content being viewed by others
References
Levy MJ, DiPalma JA. Stress ulcer prophylaxis may not be for everyone. Curr Opin Crit Care 1996; 2: 129–33
Tryba M. Stress bleeding prophylaxis with sucralfate: pathophysiologic basis and clinical use. Scand J Gastroenterol 1990; 173 Suppl.: 22–33
Zinner MJ, Zuidema GD, Smith PL, et al. The prevention of upper gastrointestinal tract bleeding in patients in an intensive care unit. Surg Gynecol Obstet 1981; 153: 214–20
Tryba M, Huchzermeyer H, Torok M, et al. Single-drug and combined medication with cimetidine, antacids and pirenzepine in the prophylaxis of acute upper gastrointestinal bleeding. Hepatogastroenterology 1983; 30(4): 154–7
Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group [see comments]. N Engl J Med 1994; 330(6): 377–81
Silen W. The clinical problem of stress ulcers. Clin Invest Med 1987; 10(3): 270–4
Soderstrom CA, Ducker TB. Increased susceptibility of patients with cervical cord lesions to peptic gastrointestinal complications. J Trauma 1985; 25(11): 1030–8
Sigman HH, Poleski MH, Gillich A. Effects of pirenzepine on acute mucosal erosions, gastric acid and mucosal blood flow in the spinal rat stomach. Digestion 1991; 185–91
Zandstra DF, Stoutenbeek CP. The virtual absence of stress-ulceration related bleeding in ICU patients receiving prolonged mechanical ventilation without any prophylaxis: a prospective cohort study [see comments]. Intensive Care Med 1994; 20(5): 335–40
Cullen JJ, Ephgrave KS, Broadhurst KA, et al. Captopril decreases stress ulceration without affecting gastric perfusion during canine hemorrhagic shock. J Trauma 1994; 37(1): 43–9
al-Mashhadani WM, Karim KH, ai-Taie RI, et al. Nifedipine versus cimetidine in prevention of stress-induced gastric ulcers in rats. Eur J Pharmacol 1991; 192(1): 117–21
Tryba M, Leben J, Heuer L. Does active warming of severely injured trauma patients influence perioperative morbidity [abstract]? Anesthesiology 1996; 85 Suppl 3A: A283
Martin LF, Max MH, Polk Jr H. Failure of gastric pH control by antacids or cimetidine in the critically ill: a valid sign of sepsis. Surgery 1980; 88(1): 59–68
Stannard VA, Hutchinson A, Morris DL, et al. Gastric exocrine ‘failure’ in critically ill patients: incidence and associated features. Br Med J Clin Res 1988; 296(6616): 155–6
Simms HH, DeMaria E, McDonald L, et al. Role of gastric colonization in the development of pneumonia in critically ill trauma patients: results of a prospective randomized trial. J Trauma 1991; 31(4): 531–6
Tryba M. Risk of acute stress bleeding and nosocomial pneumonia in ventilated intensive care unit patients: sucralfate versus antacids. Am J Med 1987; 83 Suppl 3B: 117–24
Klein H. Prophylactic treatment of peptic ulcers, gastric dilatation and gastric secretion in head injury. In: Schiefer W, Klinger M, Rock M, editors. Advances in neurosurgery. Vol. 9. Berlin: Springer Verlag, 1981: 423–7
Lunde OC, Kvernebo K, Larsen S. Effect of pentagastrin and cimetidine on gastric blood flow measured by laser Doppler flowmetry. Scand J Gastroenterol 1988; 23(2): 151–7
Levine BA, Schwesinger WH, Sirinek KR, et al. Cimetidine prevents reduction in gastric mucosal blood flow during shock. Surgery 1978; 84(1): 113–9
Breucha G, Kieninger G, Müller G. Stressulkusprophylaxe beim Polytrauma: Einfluss von Pirenzepin und Cimetidin auf Magensäuresekretion und Serumgastrin. Therapiewoche 1981; 31: 5649–52
Kobayashi K, Arakawa T, Nakamura H. Cytoprotective effects of pirenzepine. In: Gastrozepin/Bisvanol: new aspects in research and therapy. Asia Pacific Congress Series No. 40. Amsterdam: Excerpta Medica, 1985: 16–23
Safsten B, Flemstrom G. Stimulatory effect of pirenzepine on mucosal bicarbonate secretion in rat duodenum in vivo. Acta Physiol Scand 1986; 127(2): 267–8
Watanabe Y, Kobayashi R, Yoshigoe F, et al. Effect of pirenzepine on gastric mucus secretion. In: Gastrozepin/Bisvanil: new aspects in research and therapy. Asia Pacific Congress Series No. 40. Amsterdam: Excerpta Medica, 1985: 24–32
Kawamura T, Torii A, Nozawa H, et al. Comparison of effects of pirenzepine and other antiulcer agents on gastric mucosal blood flow and mucus. In: Bettarello A, editor. Pirenzepine: new aspects in research and therapy. Amsterdam, Excerpta Medica, 1985: 48–60
Abate I, Fresini S, Fernlavo G. The effets of pirenzepine on gastric mucosal blood flow in duodenal ulcer patients. Clin Trials 1982; 255–8
Clain JE, Malagelada JR, Chadwick S, et al. Binding properties in vitro of antacids for conjugated bile acids. Gastroenterology 1977; 73(3): 556–9
Domschke W, Hagel J, Ruppin H, et al. Antacid protection of gastric mucosa. Klin Wochenschr 1986; 7: 28–31
Szabo S, Hollander D. Pathways of gastrointestinal protection and repair: mechanisms of action of sucralfate. Am J Med 1989; 86 Suppl 6A: 23–31
Chen BW, Hiu WM, Lam SK, et al. Effect of sucralfate on gastric mucosal blood flow in rats. Gut 1989; 30(11): 1544–51
Frydman GM, Penney AG, Malcontenti C, et al. Inability of cytoprotection to occur during a period of gastric ischemia. Dig Dis Sci 1991; 36(10): 1353–60
Laudanno OM, Bedini OA, Cesolari JA, et al. Sucralphate in the prevention of acute gastric lesions induced by ischemia-reperfusion. Ital J Gastroenterol 1992; 24(7): 380–2
Tryba M. Stressblutungen. Teil 1: Pathogenese und Therapie. Anaesthesist 1994; 43: 821–34
Rees WD. Mucus-bicarbonate barrier — shield or sieve. Gut 1987; 28(12): 1553–6
Baak LC, Jansen JB, Lamers CB. Effect of intravenous omeprazole on intragastric pH during intravenous infusion of amino acids. Dig Dis Sci 1990; 35(5): 596–602
Cook DJ. Stress ulcer prophylaxis: gastrointestinal bleeding and nosocomial pneumonia: best evidence synthesis. Scan J Gastroenterol 1995; 210 Suppl.: 48–52
Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer prophylaxis in critically ill patients: resolving discordant meta-analyses. JAMA 1996; 275(4): 308–14
Tryba M. Stress bleeding prophylaxis 1990 — a meta-analysis. Clin J Gastroenterol 1991; 13 Suppl. 2: 44–55
Basso N, Bagarani M, Materia A, et al. Cimetidine and antacid prophylaxis of acute upper gastrointestinal bleeding in high risk patients: controlled, randomized trial. Am J Surg 1981; 141(3): 339–41
Pinilla JC, Oleniuk FH, Reed D, et al. Does antacid prophylaxis prevent upper gastrointestinal bleeding in critically ill patients? Crit Care Med 1985; 13(8): 646–50
Burgess P, Larson GM, Davidson P, et al. Effect of ranitidine on intragastric pH and stress-related upper gastrointestinal bleeding in patients with severe head injury. Dig Dis Sci 1995; 40(3): 645–50
Fiorucci S, Clausi GC, Farinelli M, et al. Intragastric pH monitoring during antisecretory therapy in patients with gastrointestinal bleeding. Am J Gastroenterol 1989; 84(11): 1416–20
Alijani MR, Benjamin SB, Collen MJ, et al. Misoprostol: a prostaglandin E1 analogue versus antacid in the prevention of stress ulcers in kidney transplant patients. Transplant Proc 1989; 21 (1 Pt 2): 2145–6
Martin LF, Booth FV, Reines HD, et al. Stress ulcers and organ failure in intubated patients in surgical intensive care units. Ann Surg 1992; 215(4): 332–7
Skillman JJ, Lisbon A, Long PC, et al. 15 (R)-15-methyl prostaglandin E2 does not prevent gastrointestinal bleeding in seriously ill patients. Am J Surg 1984; 147(4): 451–5
van Essen HA, van Blankenstein M, Wilson JH, et al. Intragastric prostaglandin E2 and the prevention of gastrointestinal hemorrhage in ICU patients. Crit Care Med 1985; 13(11): 957–60
Zinner MJ, Rypins EB, Martin LR, et al. Misoprostol versus antacid titration for preventing stress ulcers in postoperative surgical ICU patients. Ann Surg 1989; 210(5): 590–5
Barandun J, Leutenegger A, Frutiger A, et al. Prevention of gastroduodenal stress lesions with secretion inhibitors in accident patients needing intensive care: incidence of lesions and adverse effects; consequences [in German]. Schweiz Med Wochenschr 1985; 115(20): 1022–3
Tritthart H, Heppner F. Prevention of stress ulcer in patients with severe head injury: effect of pirenzepine. In: Dotevall G, editor. Advances in gastroenterology with the selective anti-muscarinic compound pirenzepine. Amsterdam: Excerpta Medica, 1982: 145–51
Engelhardt D, Karl R, Kolb HJ, et al. Comparison between cimetidine-pirenzepine and antacids for the prevention of stress hemorrhage in intensive care patients: a controlled clinical study on 125 patients [in German]. Dtsch Med Wochenschr 1985; 110(23): 908–14
Koelz HR, Aeberhard P, Hassler H, et al. Prophylactic treatment of acute gastroduodenal stress ulceration: low-dose antacid treatment without and with additional ranitidine. Scand J Gastroenterol 1987; 22(9): 1147–52
Krakamp B, Rommel T, Edelmann M, et al. Prevention of stress-induced hemorrhage of the upper gastrointestinal tract in neurosurgical intensive care patients: a controlled, randomized double-blind study with ranitidine alone and in combination with pirenzepine [in German]. Med Klin 1989; 84(3): 133–4, 172
More DG, Raper RF, Watson CJ, et al. Combination therapy with ranitidine and pirenzepine for control of intragastric pH in the critically ill. Crit Care Med 1985; 13(8): 651–5
Behrens R, Hofbeck M, Singer H, et al. Frequency of stress lesions of the upper gastrointestinal tract in paediatric patients after cardiac surgery: effects of prophylaxis. Br Heart J 1994; 72(2): 186–9
Lopez-Herce J, Dorao P, Elola P, et al. Frequency and prophylaxis of upper gastrointestinal hemorrhage in critically ill children: a prospective study comparing the efficacy of almagate, ranitidine, and sucralfate. The Gastrointestinal Hemorrhage Study Group. Crit Care Med 1992; 20(8): 1082–9
Probst S, Lischke V, Wiederspahn T, et al. Kardiale Nebenwirkungen nach intravenöser Injektion von Pirenzepin sind Ausdruck mangelnder Rezeptorspezifität. Anaesthesiol Intensivmed Notfallmed Schmerzther 1991; 26: 199–203
Hinrichsen H, Halabi A, Kirch W. Clinical aspects of cardiovascular effects of H2-receptor antagonists. J Clin Pharmacol 1995; 35(2): 107–16
Rixen D, Neugebauer E, Lechleuthner A, et al. Beneficial effect of H2-antagonism and H1-antagonism in rat endotoxic shock. Shock 1994; 2(1): 47–52
Baumann G, Loher U, Felix SB, et al. Deleterious effects of cimetidine in the presence of histamine on coronary circulation: possible clinical implications in anaphylactic states in individuals with coronary heart disease. Res Exp Med (Berl) 1982; 180(3): 209–13
Tryba M, Kurz-Muller K, Donner B. Plasma aluminium concentrations in long-term mechanically ventilated patients receiving stress ulcer prophylaxis with sucralfate. Crit Care Med 1994; 22(11): 1769–73
Catalano G, Catalano MC, Alberts VA. Famotidine-associated delirium: a series of six cases. Psychosomatics 1996; 37(4): 349–55
Kimelblatt BJ, Cerra FB, Calleri G, et al. Dose and serum concentration relationships in cimetidine-associated mental confusion. Gastroenterology 1980; 78(4): 791–5
Feron B, Adair CG, Gorman SP, et al. Interaction of sucralfate with antibiotics used for selective decontamination of the gastrointestinal tract. Am J Hosp Pharm 1993; 50(12): 2550–3
Lehto P, Kivisto KT. Effect of sucralfate on absorption of norfloxacin and ofloxacin. Antimicrob Agents Chemother 1994; 38(2): 248–51
Krupp KB, Johns P, Troncoso V. Esophagael bezoar formation in a tube-fed patient receiving sucralfate and antacid therapy: a case report. Gastroenterol Nurs 1995; 18(2): 46–8
Lewis JH. Hepatic effects of drugs used in the treatment of peptic ulcer disease. Am J Gastoenterol 1987; 82(10): 987–1003
Tryba M. Side effects of stress bleeding prophylaxis. Am J Med 1989; 86 Suppl 6A: 85–93
Tryba M. The gastropulmonary route of infection — fact or fiction? Am J Med 1991; 91 Suppl 2A: 135S–46S
Ampil I, Cupino I, Luz Grey A, et al. Bacterial gut translocation: the use of a cytoprotectant and gastric lavage in the prevention of opportunistic infection. Asian J Surgery 1992; 15: 114–8
Georgopoulos A, Feistauer SM, Makristathis A, et al. Influence of stress ulcer prophylaxis on translocation of bacteria from the intestinal tract in rats. Wien Klin Wochenschr 1996; 108(11): 321–5
Daschner F, Kappstein I, Engels I, et al. Stress ulcer prophylaxis and ventilation pneumonia: prevention by antibacterial cytoprotective agents? Infect Control Hosp Epidemiol 1988; 9(2): 59–65
West AP, Abdul S, Sherratt MJ, et al. Antibacterial activity of sucralfate against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa in batch and continuous culture. Eur J Clin Microbiol Infect Dis 1993; 12(11): 869–71
Driks MR, Craven DE, Celli BR, et al. Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers: the role of gastric colonization. N Engl J Med 1987; 317(22): 1376–82
Bonten MJ, Gaillard CA, van Tiel FH, et al. Continuous enteral feeding counteracts preventive measures for gastric colonization in intensive care unit patients. Crit Care Med 1994; 22(6): 939–44
Tryba M, Cook DJ. Gastric alkalinization, pneumonia, and systemic infections: the controversy. Scand J Gastroenterol 1995; 210 Suppl.: 53–9
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(8): 653–62
Side effects of omeprazole [editorial]. Arznei-Telegramm 1995 5: 53–4
Schonhofer PS. Safety of omeprazole and lansoprazole. Lancet 1994; 343: 1369–70
Tran DD, Cuesta MA, van Leeuwen PA, et al. Risk factors for multiple organ system failure and death in critically injured patients. Surgery 1993; 114(1): 21–30
Thomason MH, Payseur ES, Hakenewerth AM, et al. Nosocomial pneumonia in ventilated trauma patients during stress ulcer prophylaxis with sucralfate, antacid, and ranitidine. J Trauma 1996; 41(3): 503–8
Ben-Menachem T, McCarthy BD, Fogel R, et al. Prophylaxis for stress-related gastrointestinal hemorrhage: a cost effectiveness analysis. Crit Care Med 1996; 24(2): 338–45
Maier RV, Mitchell D, Gentilello L. Optimal therapy for stress gastritis. Ann Surg 1994; 220(3): 353–60
Richter J, Huse D, Thompson D, et al. Sucralfate suspension versus acid neutralization as stress-ulcer prophylaxis during mechanical ventilation: economic implications for critical-care medicine. Am J Gastroenterol 1989; 84: 1168
Tryba M, Kurz-Muller K, Zschachlitz L, et al. Rational prevention of stress hemorrhage — effectiveness, side effects, costs [in German]. Klin Wochenschr 1991; 26: 196–207
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tryba, M., Cook, D. Current Guidelines on Stress Ulcer Prophylaxis. Drugs 54, 581–596 (1997). https://doi.org/10.2165/00003495-199754040-00005
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-199754040-00005