Hostname: page-component-586b7cd67f-t8hqh Total loading time: 0 Render date: 2024-11-25T07:50:27.212Z Has data issue: false hasContentIssue false

Effects of daily treatment with acid suppressants for stress ulcer prophylaxis on risk of ventilator-associated events

Published online by Cambridge University Press:  10 December 2019

Xiaojuan Li*
Affiliation:
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
Michael Klompas
Affiliation:
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
John T. Menchaca
Affiliation:
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA University of Texas Southwestern Medical Center, Dallas, TX, USA
Jessica G. Young
Affiliation:
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
*
Author for correspondence: Xiaojuan Li, E-mail: [email protected]

Abstract

Objective:

To estimate the effects of continuous daily treatment with different acid suppressants on the risk of ventilator-associated events in critically ill patients.

Design:

Retrospective cohort study.

Patients:

Adult critically ill patients who underwent mechanical ventilation for ≥3 days during an inpatient admission between January 2006 and December 2014.

Methods:

We estimated the 30-day cumulative risk ratios (RRs) for ventilator-associated events comparing daily proton pump inhibitor (PPI) versus daily histamine-2-receptor antagonist (H2RA) strategies while controlling for time-fixed and time-varying confounding and accounting for competing events.

Results:

Of 6,133 patients, on ventilation day 3, 58.8% received H2RAs, 26.1% received PPIs, and 4.1% received sucralfate. Patients frequently changed treatment throughout follow-up. Among 4,595 patients receiving PPIs or H2RAs on day 3, we found no differences in risk estimates for ventilator mortality and extubation alive comparing daily PPI versus daily H2RA strategies: RR, mortality, 1.03 (95% CI, 0.89–1.22); extubation alive, 1.00 (95% CI, 0.96–1.03). We found similar results after accounting for PPI dose. For possible ventilator-associated pneumonia (PVAP) and infection-related ventilator-associated complication (IVAC), point estimates were larger, but the 95% CIs crossed 1.0: RR PVAP, 1.25 (95% CI, 0.80–1.94); IVAC, 0.89 (95% CI, 0.64–1.17). The magnitude of effect estimates depended on PPI dose. The RR for PVAP, high-dose PPI versus H2RA, was 1.53 (95% CI, 0.82–2.51), and for low-dose PPI versus H2RA, the RR was 0.97 (95% CI, 0.47–1.63). For IVAC, high-dose PPI versus H2RA, the RR was 1.01 (95% CI, 0.66–1.42), and for low-dose PPI versus H2RA, the RR was 0.78 (95% CI, 0.50–1.11).

Conclusions:

We estimated no effect of daily PPI versus daily H2RA on risk of mortality or extubation alive in critically ill patients. Further investigation with larger samples is warranted for PVAP and IVAC.

Type
Original Article
Copyright
© 2019 by The Society for Healthcare Epidemiology of America. All rights reserved.

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

PREVIOUS PRESENTATION. An abstract containing some preliminary results was presented at the 34th International Conference for Pharmacoepidemiology and Therapeutic Risk Management (ICPE) on August 24, 2018, in Prague, Czech Republic.

References

Ali, T, Harty, RF.Stress-induced ulcer bleeding in critically ill patients. Gastroenterol Clin North Am 2009;38:245265.CrossRefGoogle ScholarPubMed
Cook, DJ, Fuller, HD, Guyatt, GH, et al.Risk factors for gastrointestinal bleeding in critically ill patients. N Engl J Med 1994;330:377381.10.1056/NEJM199402103300601CrossRefGoogle ScholarPubMed
Cook, DJ, Griffith, LE, Walter, SD, et al.The attributable mortality and length of intensive care unit stay of clinically important gastrointestinal bleeding in critically ill patients. Crit Care 2001;5:368375.CrossRefGoogle ScholarPubMed
Daley, RJ, Rebuck, JA, Welage, LS, et al.Prevention of stress ulceration: current trends in critical care. Crit Care Med 2004;32:20082013.CrossRefGoogle ScholarPubMed
ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. ASHP Commission on Therapeutics and Approved by the ASHP Board of Directors on November 14, 1998. Am J Health Syst Pharm 1999;56:347379.Google Scholar
Cook, DJ, Reeve, BK, Guyatt, GH, et al.Stress ulcer prophylaxis in critically ill patients: resolving discordant meta-analyses. JAMA 1996;275:308314.10.1001/jama.1996.03530280060038CrossRefGoogle ScholarPubMed
Cook, D, Guyatt, G, Marshall, J, et al.A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. N Engl J Med 1998;338:791797.CrossRefGoogle ScholarPubMed
Lin, PC, Chang, CH, Hsu, PI, et al.The efficacy and safety of proton pump inhibitors vs histamine-2 receptor antagonists for stress ulcer bleeding prophylaxis among critical care patients: a meta-analysis. Crit Care Med 2010;38:11971205.10.1097/CCM.0b013e3181d69ccfCrossRefGoogle ScholarPubMed
Barkun, AN, Bardou, M, Pham, CQ, et al.Proton pump inhibitors vs histamine 2 receptor antagonists for stress-related mucosal bleeding prophylaxis in critically ill patients: a meta-analysis. Am J Gastroenterol 2012;107:507520.CrossRefGoogle ScholarPubMed
Toews, I, George, AT, Peter, JV, et al.Interventions for preventing upper gastrointestinal bleeding in people admitted to intensive care units. Cochrane Database Syst Rev 2018;6:Cd008687.Google ScholarPubMed
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;44:111.CrossRefGoogle ScholarPubMed
Krag, M, Marker, S, Perner, A, et al.Pantoprazole in patients at risk for gastrointestinal bleeding in the ICU. N Engl J Med 2018;379:21992208.10.1056/NEJMoa1714919CrossRefGoogle ScholarPubMed
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;45:143158.CrossRefGoogle ScholarPubMed
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;174:564574.CrossRefGoogle ScholarPubMed
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;120:653662.CrossRefGoogle ScholarPubMed
Herzig, SJ, Howell, MD, Ngo, LH, et al.Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA 2009;301:21202128.CrossRefGoogle ScholarPubMed
Eom, CS, Jeon, CY, Lim, JW, et al.Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. CMAJ 2011;183:310319.CrossRefGoogle ScholarPubMed
Bateman, BT, Bykov, K, Choudhry, NK, et al.Type of stress ulcer prophylaxis and risk of nosocomial pneumonia in cardiac surgical patients: cohort study. BMJ 2013;347:f5416.CrossRefGoogle ScholarPubMed
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;59:576585.CrossRefGoogle ScholarPubMed
Dial, S, Delaney, JA, Barkun, AN, et al.Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile–associated disease. JAMA 2005;294:29892995.10.1001/jama.294.23.2989CrossRefGoogle ScholarPubMed
Howell, MD, Novack, V, Grgurich, P, et al.Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection. Arch Intern Med 2010;170:784790.CrossRefGoogle ScholarPubMed
Tleyjeh, IM, Abdulhak, AB, Riaz, M, et al.The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis. PLoS One 2013;8(3):e56498.10.1371/journal.pone.0056498CrossRefGoogle ScholarPubMed
Robins, J.A new approach to causal inference in mortality studies with a sustained exposure period—application to control of the healthy worker survivor effect. Math Model 1986;7:13931512.CrossRefGoogle Scholar
Robins, JM, Hernán, MA.Estimation of the causal effects of time-varying exposures. In Longitudinal Data Analysis. Fitzmaurice, G, Davidian, M, Verbeke, G, Molenberghs, G, editors. New York: Chapman and Hall/CRC Press; 2009:553599.Google Scholar
Greenland, S.Quantifying biases in causal models: classical confounding vs collider-stratification bias. Epidemiology 2003;14:300306.10.1097/01.EDE.0000042804.12056.6CCrossRefGoogle ScholarPubMed
Mansournia, MA, Etminan, M, Danaei, G, Kaufman, JS, Collins, G.Handling time varying confounding in observational research. BMJ 2017;359:j4587.CrossRefGoogle ScholarPubMed
Lederer, DJ, Bell, SC, Branson, RD, et al.Control of confounding and reporting of results in causal inference studies. Guidance for authors from editors of respiratory, sleep, and critical care journals. Ann Am Thorac So. 2019;16:2228.CrossRefGoogle ScholarPubMed
Young, JG, Cain, LE, Robins, JM, et al.Comparative effectiveness of dynamic treatment regimes: an application of the parametric g-formula. Stat Biosci 2011;3:119143.CrossRefGoogle ScholarPubMed
Surveillance for ventilator-associated events. Centers for Disease Control and Prevention website. https://www.cdc.gov/nhsn/acute-care-hospital/vae/index.html. Accessed July 15, 2016.Google Scholar
Magill, SS, Klompas, M, Balk, R, et al.Developing a new, national approach to surveillance for ventilator-associated events. Crit Care Med 2013;41:24672475.CrossRefGoogle ScholarPubMed
Geskus, RB.Data Analysis with Competing Risks and Intermediate States. New York: Chapman and Hall/CRC Press; 2015.CrossRefGoogle Scholar
Lodi, S, Phillips, A, Logan, R, et al.Comparative effectiveness of immediate antiretroviral therapy versus CD4-based initiation in HIV-positive individuals in high-income countries: observational cohort study. Lancet HIV 2015;2(8):e335e343.CrossRefGoogle ScholarPubMed
Zhang, Y, Young, JG, Thamer, M, Hernan, MA.Comparing the effectiveness of dynamic treatment strategies using electronic health records: an application of the parametric g-formula to anemia management strategies. Health Serv Res 2018;53:19001918.CrossRefGoogle ScholarPubMed
Taubman, SL, Robins, JM, Mittleman, MA, Hernán, MA.Intervening on risk factors for coronary heart disease: an application of the parametric g-formula. Int J Epidemiol 2009;38:15991611.CrossRefGoogle ScholarPubMed
van Mourik, MS, Moons, KG, Murphy, MV, et al.Severity of disease estimation and risk-adjustment for comparison of outcomes in mechanically ventilated patients using electronic routine care data. Infect Control Hosp Epidemiol 2015;36:807815.CrossRefGoogle ScholarPubMed
Elixhauser, A, Steiner, C, Harris, DR, et al.Comorbidity measures for use with administrative data. Med Care 1998;36:827.CrossRefGoogle ScholarPubMed
Klompas, M, Li, L, Kleinman, K, Szumita, PM, Massaro, AF.Associations between ventilator bundle components and outcomes. JAMA Intern Med 2016;176:12771283.10.1001/jamainternmed.2016.2427CrossRefGoogle ScholarPubMed
Laheij, RJ, Sturkenboom, MC, Hassing, RJ, et al.Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA 2004;292:19551960.CrossRefGoogle ScholarPubMed
Torres, A, El-Ebiary, M, Soler, N, et al.Stomach as a source of colonization of the respiratory tract during mechanical ventilation: association with ventilator-associated pneumonia. Eur Respir J 1996;9:17291735.CrossRefGoogle ScholarPubMed
Bonten, MJ, Gaillard, CA, de Leeuw, PW, et al.Role of colonization of the upper intestinal tract in the pathogenesis of ventilator-associated pneumonia. Clin Infect Dis 1997;24:309319.CrossRefGoogle ScholarPubMed
Li, X, Young, JG, Toh, S.Estimating effects of dynamic treatment strategies in pharmacoepidemiologic studies with time-varying confounding: a primer. Curr Epidemiol Rep 2017;4:288297.CrossRefGoogle ScholarPubMed
Barletta, JF, Kanji, S, MacLaren, R, et al.Pharmacoepidemiology of stress ulcer prophylaxis in the United States and Canada. J Crit Care 2014;29:955960.CrossRefGoogle ScholarPubMed
Supplementary material: File

Li et al. supplementary material

Li et al. supplementary material

Download Li et al. supplementary material(File)
File 110.3 KB