Prophylactic use of acid suppressants in adult acutely ill hospitalised patients: A systematic review with meta-analysis and trial sequential analysis.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 0370270 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1399-6576 (Electronic) Linking ISSN: 00015172 NLM ISO Abbreviation: Acta Anaesthesiol Scand Subsets: MEDLINE

Publication: Oxford, UK : Wiley-Blackwell
Original Publication: Aarhus, Denmark : Universitetsforlaget, 1957-

Inpatients*; Anti-Ulcer Agents/*therapeutic use ; Critical Care/*methods ; Gastrointestinal Hemorrhage/*prevention & control ; Histamine H2 Antagonists/*therapeutic use ; Proton Pump Inhibitors/*therapeutic use; Adult ; Critical Illness ; Hospitalization ; Humans

Background: Acutely ill patients are at risk of stress-related gastrointestinal (GI) bleeding and prophylactic acid suppressants are frequently used. In this systematic review, we assessed the effects of stress ulcer prophylaxis (SUP) with proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) versus placebo or no prophylaxis in acutely ill hospitalised patients.
Methods: We conducted the review according to the PRISMA statement, the Cochrane Handbook and GRADE, using conventional meta-analysis and trial sequential analysis (TSA). The primary outcomes were all-cause mortality, clinically important GI bleeding and serious adverse events (SAEs). The primary analyses included overall low risk of bias trials.
Results: We included 65 comparisons from 62 trials (n = 9713); 43 comparisons were from intensive care units. Only three trials (n = 3596) had overall low risk of bias. We did not find an effect on all-cause mortality (RR 1.03, 95% CI 0.94 to 1.14; TSA-adjusted CI 0.90 to 1.18; high certainty). The rate of clinically important GI bleeding was lower with SUP (RR 0.62, 95% CI 0.43 to 0.89; TSA-adjusted CI 0.14 to 2.81; moderate certainty). We did not find a difference in pneumonia rates (moderate certainty). Effects on SAEs, Clostridium difficile enteritis, myocardial ischaemia and health-related quality of life (HRQoL) were inconclusive due to sparse data. Analyses of all trials regardless of risk of bias were consistent with the primary analyses.
Conclusions: We did not observe a difference in all-cause mortality or pneumonia with SUP. The incidence of clinically important GI bleeding was reduced with SUP, whereas any effects on SAEs, myocardial ischaemia, Clostridium difficile enteritis and HRQoL were inconclusive.
Study Registration: PROSPERO registration number CRD42017055676; published study protocol: Marker, et al 2017 in Systematic Reviews.
(© 2020 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Marik PE, Vasu T, Hirani A, Pachinburavan M. Stress ulcer prophylaxis in the new millennium: a systematic review and meta-analysis. Crit Care Med. 2010;38:2222-2228.
Skillman JJ, Silen W. Stress ulceration in the acutely ill. Annu Rev Med. 1976;27:9-22.
Peura DA. Stress-related mucosal damage. Clin Ther. 1986;8:14-23.
Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian critical care trials group. N Engl J Med. 1994;330:377-381.
Krag M, Perner A, Wetterslev J, et al. Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients. Intensive Care Med. 2015;41:833-845.
Cook D, Griffith L, Walter S, et al. The attributable mortality and length of intensive care unit stay of clinically important gastrointestinal bleeding in critically ill patients. Crit Care. 2001;5:368-375.
MacLaren R, Reynolds PM, Allen RR. Histamine-2 receptor antagonists vs proton pump inhibitors on gastrointestinal tract hemorrhage and infectious complications in the intensive care unit. JAMA Intern Med. 2014;174:564-574.
Selvanderan SP, Summers MJ, Finnis ME, et al. Pantoprazole or placebo for stress ulcer prophylaxis (POP-UP). Crit Care Med. 2016;44:1842-1850.
Alhazzani W, Guyatt G, Alshahrani M, et al. Withholding pantoprazole for stress ulcer prophylaxis in critically ill patients: a pilot randomized clinical trial and meta-analysis. Crit Care Med. 2017;45:1121-1129.
Krag M, Marker S, Perner A, et al. Pantoprazole in patients at risk for gastrointestinal bleeding in the ICU. N Engl J Med. 2018;379:2199-2208.
Granholm A, Zeng L, Dionne JC, et al. Alhazzani W, The GUIDE group. Predictors of gastrointestinal bleeding in adult ICU patients: a systematic review and meta-analysis. Intensive Care Med. 2019;45:1347-1359.
Cook D, Heyland D, Griffith L, Cook R, Marshall J, Pagliarello J. Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian critical care trials group. Crit Care Med. 1999;27:2812-2817.
Krag M, Perner A, Wetterslev J, et al. Stress ulcer prophylaxis in the intensive care unit: an international survey of 97 units in 11 countries. Acta Anaesthesiol Scand. 2015;59:576-585.
Qadeer MA, Richter JE, Brotman DJ. Hospital-acquired gastrointestinal bleeding outside the critical care unit: risk factors, role of acid suppression, and endoscopy findings. J Hosp Med. 2006;1:13-20.
Alhazzani W, Alshamsi F, Belley-Cote E, et al. Efficacy and safety of stress ulcer prophylaxis in critically ill patients: a network meta-analysis of randomized trials. Intensive Care Med. 2018;44:1-11.
Cook D, Guyatt G. Prophylaxis against upper gastrointestinal bleeding in hospitalized Patients. N Engl J Med. 2018;378:2506-2516.
Herzig SJ, Howell MD, Ngo LH, Marcantonio ER. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA. 2009;301:2120-2128.
Marker S, Perner A, Wetterslev J, et al. Stress ulcer prophylaxis versus placebo or no prophylaxis in adult hospitalised acutely ill patients-protocol for a systematic review with meta-analysis and trial sequential analysis. Syst Rev. 2017;6:118.
Higgins JPT, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928-d5928.
Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Medicine. 2009;6:e1000100.
Jakobsen JC, Wetterslev J, Winkel P, Lange T, Gluud C. Thresholds for statistical and clinical significance in systematic reviews with meta-analytic methods. BMC Med Res Methodol. 2014;14:120.
Guyatt GH, Oxman AD, Vist GE, et al. An emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336:924e6.
International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. ICH harmonised tripartite guideline. Guideline for good clinical practice. Updated July 2002. 1997.
Barbateskovic M, Marker S, Granholm A, et al. Stress ulcer prophylaxis with proton pump inhibitors or histamin-2 receptor antagonists in adult intensive care patients: a systematic review with meta-analysis and trial sequential analysis. Intensive Care Med. 2019;45:143-158.
Savović J, Turner RM, Mawdsley D, et al. Association between risk-of-bias assessments and results of randomized trials in cochrane reviews: the robes meta-epidemiologic study. Am J Epidemiol. 2018;187:1113-1122.
Higgins JPT, Green S. Cochrane Handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration. 2011. www.handbook.cochrane.org. Accessed December 20, 2019.
Harbord RM, Egger M, Sterne JAC. A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints. Stat Med. 2006;25:3443-3457.
Thorlund KEJ, Wetterslev J, Brok J, Imberger G, Gluud C. User manual for trial sequential analysis (TSA). www.ctu.dk/tsa/files/tsa_manual.pdf. Accessed December 22, 2019.
Wetterslev J, Thorlund K, Brok J, Gluud C. Estimating required information size by quantifying diversity in random-effects model meta-analyses. BMC Med Res Methodol. 2009;9:86.
Mantel N, Haenzel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719-748.
Demets D. Methods for combining randomized clinical trials: strengths and limitations. Stat Med. 1987;6:341-350.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177-188.
Deeks JJ, Higgins JP. Statistical algorithms in review manager 5. Statistical methods group of the Cochrane. Collaboration. 2010;1-11.
Brok J, Thorlund K, Gluud C, Wetterslev J. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses. J Clin Epidemiol. 2008;61:763-769.
Brok J, Thorlund K, Wetterslev J, Gluud C. Apparently conclusive meta-analyses may be inconclusive - Trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta-analyses. Int J Epidemiol. 2009;38:287-298.
Higgins JPT, Whitehead A, Simmonds M. Sequential methods for random-effects meta-analysis. Stat Med. 2011;30:903-921.
Imberger G, Gluud C, Boylan J, Wetterslev J. Systematic reviews of anesthesiologic interventions reported as statistically significant: problems with power, precision, and type 1 error protection. Anesth Analg. 2015;121:1611-1622.
Mascha EJ. Alpha, beta, meta: guidelines for assessing power and type I error in meta-analyses. Anesth Analg. 2015;121:1430-1433.
Pogue JM, Yusuf S. Cumulating evidence from randomized trials: utilizing sequential monitoring boundaries for cumulative meta-analysis. Control Clin Trials. 1997;18:580-593.
Terkawi AS, Mavridis D, Flood P, et al. Does ondansetron modify sympathectomy due to subarachnoid anesthesia? Anesthesiology. 2016;124:846-869.
Thorlund K, Devereaux PJ, Wetterslev J, et al. Can trial sequential monitoring boundaries reduce spurious inferences from meta-analyses? Int J Epidemiol. 2009;38:276-286.
Wetterslev J, Jakobsen JC, Gluud C. Trial sequential analysis in systematic reviews with meta-analysis. BMC Med Res Methodol. 2017;17:39.
Apte NM, Karnad DR, Medhekar TP, Tilve GH, Morye S, Bhave GG. Gastric colonization and pneumonia in intubated critically ill patients receiving stress ulcer prophylaxis: a randomized, controlled trial. Crit Care Med. 1992;20:590-593.
Basso N, Bagarani M, Materia A, Fiorani S, Lunardi P, Speranza V. Lunardi P, Speranza V. Cimetidine and antacid prophylaxis of acute upper gastrointestinal bleeding in high risk patients. Controlled, randomized trial. Am J Surg. 1981;141:339-341.
Ben-Menachem T, Fogel R, Patel RV, et al. Prophylaxis for stress-related gastric hemorrhage in the medical intensive care unit: a randomized, controlled, single-blind study. Ann Intern Med. 1994;121:568-575.
Van Den Berg B, Van Blankenstein M. Prevention of stress-induced upper gastrointestinal bleeding by cimetidine in patients on assisted ventilation. Digestion. 1985;31:1-8.
Burgess P, Larson GM, Davidson P, Brown J, Metz CA. Effect of ranitidine on intragastric pH and stress-related upper gastrointestinal bleeding in patients with severe head injury. Dig Dis Sci. 1995;40:645-650.
Cartier F, Gauthier-Lafaye P, Lareng L. Cimetidine in patients at risk of stress ulcers: a multicentre controlled trial (Abstract 115). Intensive Care Med. 1980;6:54.
Chan KH, Lai ECS, Tuen H, et al. Prospective double-blind placebo-controlled randomized trial on the use of ranitidine in preventing postoperative gastroduodenal complications in high-risk neurosurgical patients. J Neurosurg. 1995;82:413-417.
Darlong V, Jayalakhsmi TS, Kaul HL, Tandon R. Stress ulcer prophylaxis in patients on ventilator. Trop Gastroenterol. 2004;24:124-128.
Domingues S, Stoeber G, Modena A. Injectable ranitidine in patients of high risk. Folha Med. 1985;91:225-228.
El-Kersh K, Jalil B, McClave SA, et al. Enteral nutrition as stress ulcer prophylaxis in critically ill patients: a randomized controlled exploratory study. J Crit Care. 2018;43:108-113.
Essardas Daryanani H, Santolaria Fernandez F, Gonzalez Reimers C, et al. Acute pancreatitis: comparative therapeutic study among cimetidine, oxyphenonium and simple nasogastric aspiration. Med Clin (Barc). 1983;81:4-6.
Friedman CJ, Oblinger MJ, Suratt PM, et al. Prophylaxis of upper gastrointestinal hemorrhage in patients requiring mechanical ventilation. Crit Care Med. 1982;10:316-319.
Gao QP, Sun Y, Sun YX, Wang LF, Fu L. Early use of omeprazole benefits patients with acute myocardial infarction. J Thromb Thrombolysis. 2009;28:282-287.
Groll A, Simon JB, Wigle RD, Taguchi K, Todd RJ, Depew WT. Cimetidine prophylaxis for gastrointestinal bleeding in an intensive care unit. Gut. 1986;27:135-140.
Gundogan K, Karakoc E, Teke T, Zerman A, Coruh A, Sungur M. Effects of enteral nutrition on stress ulcer hemorrhage in critically ill patients: Multicenter randomized controlled trial. Intensive Care Med Exp. 2017;5(Suppl 2):44.
Gursoy O, Memiş D, Sut N. Effect of proton pump inhibitors on gastric juice volume, gastric pH and gastric intramucosal pH in critically ill patients: A randomized, double-blind, placebo-controlled study. Clin Drug Investig. 2008;28:777-782.
Halloran LG, Zfass AM, Gayle WE, Wheeler CB, Miller JD. Prevention of acute gastrointestinal complications after severe head injury: a controlled trial of cimetidine prophylaxis. Am J Surg. 1980;139:44-48.
Hanisch EW, Encke A, Naujoks F, Windolf J. A randomized, double-blind trial for stress ulcer prophylaxis shows no evidence of increased pneumonia. Am J Surg. 1998;176:453-457.
Hummer-Sigiel M, Jacquier A, Girard A. The effect of ranitidine is compared of that of a placebo in 22 patients who are treated in intensive care for severe cerebral injuries. Ann Medicales Nancy l’Est. 1986;25:101-103.
Jakob SM, Parviainen I, Ruokonen E, Uusaro A, Takala J. Lack of effect of ranitidine on gastric luminal pH and mucosal PCO2 during the first day in the ICU. Acta Anaesthesiol Scand. 2005;49:390-396.
Kam J, Pi J, Abdul-Jawad S, et al. Role of gastrointestinal ulcer prophylaxis in critically ill patients. Chest. 2011;140:1009A.
Kantorova I, Svoboda P, Scheer P, et al. Stress ulcer prophylaxis in critically ill patients: a randomized controlled trial. Hepatogastroenterology. 2004;51:757-761.
Karlstadt RG, Iberti TJ, Silverstein J, et al. Comparison of cimetidine and placebo for the prophylaxis of upper gastrointestinal bleeding due to stress-related gastric mucosal damage in the intensive care unit. J Intensive Care Med. 1990;5:26-32.
Kaushal S, Midha V, Sood A, Chopra SC, Gupta C. A comparative study of the effects of famotidine and sucralfate in prevention of upper gastro-intestinal bleeding in patients of head injury. Indian J Pharmacol. 2000;32:246-249.
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;22:1147-1152.
Larson G, Davidson P, Brown J. Comparison of ranitidine versus placebo on 24 hour gastric pH and upper gastrointestinal (UGI) bleeding in head injuries. Am J Gastroenterol. 1989;84:1165.
Lin CC, Hsu YL, Chung CS, Lee TH. Stress ulcer prophylaxis in patients being weaned from the ventilator in a respiratory care center: a randomized control trial. J Formos Med Assoc. 2016;115:19-24.
Liu B, Li B, Zhang X, et al. A randomized controlled study comparing omeprazole and cimetidine for the prophylaxis of stress-related upper gastrointestinal bleeding in patients with intracerebral hemorrhage. J Neurosurg. 2013;118:115-120.
Liu F, Zhang X, Yang X, Lu J, Xie R, Cui W. Influence of different proton pump inhibitors on the antiplatelet action of clopidogrel associated with aspirin. Circulation. 2012;125:e854.
Lu Y. Cimetidine for preventing stress ulcer associated with cerebral hemorrhage resulting from high pressure. Chinese Crit Care Med. 1998;10:446.
Luk G, Summer W, Messersmitl J. Cimetidine and antacid in prophylaxis of acute gastrointestinal bleeding, a randomized double-blind controlled study. Gastroenterology. 1982;82:1121.
Macdougall B, Bailey R, Williams R. H-2 receptor antagonists and antacids in the prevention of acute gastrointestinal hemorrhage in fulminant hepatic failure: 2 controlled trials. Lancet. 1977;1:617-619.
Martin LF, Booth FVM, Karlstadt RG, et al. Continuous intravenous cimetidine decreases stress-related upper gastrointestinal hemorrhage without promoting pneumonia. Crit Care Med. 1993;21:19-30.
Metz CA, Livingston DH, Smith JS, et al. Impact of multiple risk factors and ranitidine prophylaxis on the development of stress-related upper gastrointestinal bleeding: a prospective, multicenter, double-blind, randomized trial. Crit Care Med. 1993;21:1844-1849.
Misra UK, Kalita J, Pandey S, Mandal SK, Srivastava M. A randomized placebo controlled trial of ranitidine versus sucralfate in patients with spontaneous intracerebral hemorrhage for prevention of gastric hemorrhage. J Neurol Sci. 2005;239:5-10.
Moesgaard F, Jensen LS, Christiansen PM, et al. The effect of ranitidine on postoperative infectious complications following emergency colorectal surgery: a randomized, placebo-controlled, double-blind trial. Inflamm Res. 1998;47:12-17.
Nielsen HJ, Witt K, Moesgaard F, Kehlet H. Ranitidine for improvement of delayed hypersensitivity response in patients with sepsis. Acta Chir Scand. 1989;155:445-449.
Nikcevic G, Raspopovic S, Pejic M, et al. Prognostic implications of acute gastrointestinal bleeding in acute coronary syndrome: intrahospital follow up. Eur Heart J. 2011;32:100.
Nourian A, Mohammadi M, Beigmohammadi MT, et al. Comparing efficacy of enteral nutrition plus ranitidine and enteral nutrition alone as stress ulcer prophylaxis. J Comp Eff Res. 2018;7:493-501.
Orłowski T, Smogorzewski M. The influence of the H-2 receptor antagonist ranitidine on cadaver kidney allograft function. Int Urol Nephrol. 1986;18:205-210.
Peura DA, Johnson LF. Cimetidine for prevention and treatment of gastroduodenal mucosal lesions in patients in an intensive care unit. Ann Intern Med. 1985;103:173-177.
Ren Y, Zhao M, Chen Y, et al. Omeprazole affects clopidogrel efficacy but not ischemic events in patients with acute coronary syndrome undergoing elective percutaneous coronary intervention. Chin Med J. 2011;124:856-861.
Rigaud D, Accary JP, Chastre J, et al. Persistence of circadian rhythms in gastric acid, gastrin, and pancreatic polypeptide secretions despite loss of cortisol and body temperature rhythms in man under stress. Gastroenterol Clin Biol. 1988;12:12-18.
Rohde H, Lorenz W, Fischer M. A randomized clinical study of stress ulcer prophylaxis with cimeytidine in severe multiple injuries. Z Gastroenterol. 1980;18:328.
Ruiz-Santana S, Ortiz E, Gonzalez B, Bolanos J, Ruiz-Santana AJ, Manzano JL. Stress-induced gastroduodenal lesions and total parenteral nutrition in critically ill patients: Frequency, complications, and the value of prophylactic treatment. A prospective, randomized study. Crit Care Med. 1991;19:887-891.
Schiessel R, Starlinger M, Wolf A, et al. Failure of cimetidine to prevent gastroduodenal ulceration and bleeding after renal transplantation. Surgery. 1981;90:456-458.
Silvestri N, Curzio M, Motta U, De Pietri P, Bonacina F, Minoja G. Cimetidine to prevent stress ulcers. Lancet. 1980;315:885.
Soria F, Perez H, Mathier V. Incidence of acute gastroduodenal lesions in patients with intracranial lesions. Prophylactic value of treatment with ranitidine. Rev Fac Cienc Med Cordoba. 1985;1:32-35.
Spapen H, Diltoer M, Nguyen DN, Ingels G, Ramet J, Huyghens L. One week treatment with cimetidine does not attenuate the cortisol response to a short corticotropin test in stable intensive care patients: a prospective, randomized, and controlled study. Acta Anaesthesiol Belg. 1995;46:133-140.
Vlatten A, Wiedeck H, Reinelt H, Stanescu A, Georgieff M. Stress ulcer prophylaxis in high risk intensive care patients: comparison of omeprazole, pirenzepine and placebo. Wien Klin Wochenschr. 1998;110:38.
Walter S, Thorup Andersen J, Christensen U, et al. Effect of cimetidine on upper gastrointestinal bleeding after renal transplantation: a prospective study. BMJ. 1984;289:1175-1176.
Wei P, Zhang YG, Ling L, et al. Effects of the short-term application of pantoprazole combined with aspirin and clopidogrel in the treatment of acute STEMI. Exp Ther Med. 2016;12:2861-2864.
Wu H, Jing Q, Wang J, Guo X. Pantoprazole for the prevention of gastrointestinal bleeding in high-risk patients with acute coronary syndromes. J Crit Care. 2011;26:434.e1-434.e6.
Yang HX, Luo D, Zou YY. Effect of ranitidine on the gastric acid, plasma endothelin, and calcitonin gene-related peptide in patients undergoing the brain operation. J Cent South Univ (Medical Sci). 2007;32:295-298.
Yao HY, Liu XJ, Cheng K, Liu P, Xu JP, Jiang DL. Early enteral nutrition combined with omeprazole for prevention of stress ulcer in patients with cerebral apoplexy. World Chinese J Dig. 2017;25:1016-1020.
Zach GA, Gyr KE, von Alvensleben E, et al. A double-blind randomized, controlled study to investigate the efficacy of cimetidine given in addition to conventional therapy in the prevention of stress ulceration and haemorrhage in patients with acute spinal injury. Digestion. 1984;29:214-222.
Zhang JR, Wang DQ, Du J, et al. Efficacy of clopidogrel and clinical outcome when clopidogrel is coadministered with atorvastatin and lansoprazole: a prospective, randomized, controlled trial. Medicine. 2015;94:e2262.
Zinner MJ, Zuidema GD, Smith PL, Mignosa M. The prevention of upper gastrointestinal tract bleeding in patients in an intensive care unit. Surg Gynecol Obstet. 1981;153:214-220.
Muzlovič I, Stubljar D. Stress ulcer prophylaxis as a risk factor for tracheal colonization and hospital-acquired pneumonia in intensive care patients: Impact on latency time for pneumonia. Acta Clin Croat. 2019;58:72-86.
Krag M, Perner A, Wetterslev J, Wise MP, Hylander MM. Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis. Intensive Care Med. 2014;40:11-22.
Toews I, George A, Peter J, et al. Interventions for preventing upper gastrointestinal bleeding in people admitted to intensive care units. Cochrane Database Syst Rev. 2018;6:CD008687.
Bin HH, Jiang W, Wang CY, Qin HY, Du B. Stress ulcer prophylaxis in intensive care unit patients receiving enteral nutrition: a systematic review and meta-analysis. Crit Care. 2018;22:20.
Ridgeon EE, Bellomo R, Aberegg SK, et al. Young PJ. Effect sizes in ongoing randomized controlled critical care trials. Crit Care. 2017;21:132.
Marker S, Perner A, Wetterslev J, et al. Pantoprazole prophylaxis in ICU patients with high severity of disease: a post hoc analysis of the placebo-controlled SUP-ICU trial. Intensive Care Med. 2019;45:609-618.
Young PJ, Bagshaw SM, Forbes A, et al. A cluster randomised, crossover, registry-embedded clinical trial of proton pump inhibitors versus histamine-2 receptor blockers for ulcer prophylaxis therapy in the intensive care unit (PEPTIC study): Study protocol. Crit Care Resusc. 2018;20:182-189.

Keywords: acid suppressants; adverse effects; gastrointestinal bleeding; histamine-2 receptor antagonists; proton pump inhibitors; stress ulcer prophylaxis

0 (Anti-Ulcer Agents)
0 (Histamine H2 Antagonists)
0 (Proton Pump Inhibitors)

Date Created: 20200216 Date Completed: 20210810 Latest Revision: 20210810

20221213

10.1111/aas.13568

32060905