Tag Archives: Proton Pump Inhibitors

Enteral Nutrition and Acid-Suppressive Therapy in the PICU: Impact on the Risk of Ventilator-Associated Pneumonia. (Emrath)

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Albert BD, et al. Enteral Nutrition and Acid-Suppressive Therapy in the PICU: Impact on the Risk of Ventilator-Associated Pneumonia. Pediatr Crit Care Med. 2016 Oct;17(10):924-929.

OBJECTIVE: Enteral nutrition has been implicated as a risk factor for ventilator-associated pneumonia. We explored the prevalence of ventilator-associated pneumonia and its association with clinical and nutrition-related therapies in mechanically ventilated children.

DESIGN: Prospective, multicenter, cohort study.

SETTING: Fifty-nine PICU in 15 countries.

PATIENTS: Children less than 18 years old, mechanically ventilated for more than 48 hours.

INTERVENTIONS: None. Multivariable logistic regression to determine factors associated with ventilator-associated pneumonia.

MEASUREMENTS AND MAJOR RESULTS: Data are presented as median (interquartile range) or counts (%). We enrolled 1,245 subjects (45% women; 42% surgical), age 20 months (4-84 mo), and duration of mechanical ventilation 7 days (3-13 d). Culture-positive ventilator-associated pneumonia was diagnosed in 80 patients (6.4%); duration of mechanical ventilation for this subgroup was 17 days (8-39 d). Enteral nutrition was delivered in 985 patients (79%), initiated within 48 hours in 592 patients (60%), and via postpyloric route in 354 patients (36%). Acid-suppressive agents were used in 763 patients (61%). The duration of enteral nutrition (p = 0.21), route (gastric vs postpyloric) of delivery (p = 0.94), severity of illness (p = 0.17), and diagnostic category on admission (p = 0.31) were not associated with ventilator-associated pneumonia. After adjusting for enteral nutrition days, illness severity, and site, ventilator-associated pneumonia was significantly associated with mechanical ventilation more than 10 days (odds ratio, 3.7; 95% CI, 2.2-6.5; p < 0.001), PICU length of stay more than 10 days (odds ratio, 1.8; 95% CI, 1.1-3.1; p = 0.029), and the use of acid-suppressive medication (odds ratio, 2.0; 95% CI, 1.2-3.6; p = 0.011).

CONCLUSIONS: Ventilator-associated pneumonia was diagnosed in 6.5% of mechanically ventilated children in a heterogeneous multicenter cohort. We did not find a link between enteral nutrition duration or route of delivery and ventilator-associated pneumonia. In addition to duration of mechanical ventilation and length of PICU stay, the use of acid-suppressive therapy independently increased the likelihood of developing ventilator-associated pneumonia in this population. This association must be further explored in clinical trials.

Risks and Benefits of Stress Ulcer Prophylaxis for Patients With Severe Sepsis.

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Sasabuchi Y, et al. Risks and Benefits of Stress Ulcer Prophylaxis for Patients With Severe Sepsis. Crit Care Med. 2016 Mar 21. [Epub ahead of print]

OBJECTIVES: The Surviving Sepsis Campaign Guidelines recommend stress ulcer prophylaxis for patients with severe sepsis who have bleeding risks. Although sepsis has been considered as a risk factor for gastrointestinal bleeding, the effect of stress ulcer prophylaxis has not been studied in patients with severe sepsis. Furthermore, stress ulcer prophylaxis may be associated with an increased risk of hospital-acquired pneumonia or Clostridium -difficile infection. The aim of this study was to investigate the risks and benefits of stress ulcer prophylaxis for patients with severe sepsis.

DESIGN: Retrospective cohort study.

SETTING: Five hundred twenty-six acute care hospitals in Japan.

PATIENTS: A total of 70,862 patients with severe sepsis.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: One-to-one propensity score matching created 15,651 pairs of patients who received stress ulcer prophylaxis within 2 days of admission and those who did not. Patient characteristics were well balanced between the two groups. No significant differences were seen between the stress ulcer prophylaxis group and the control group with regard to -gastrointestinal bleeding requiring endoscopic hemostasis (0.6% vs 0.5%; p = 0.208), 30-day mortality (16.4% vs 16.9%; p = 0.249), and Clostridium difficile infection (1.4% vs 1.3%; p = 0.588). The stress ulcer prophylaxis group had a significantly higher proportion of hospital-acquired pneumonia (3.9% vs 3.3%; p = 0.012) compared with the control group.

CONCLUSIONS: Since the rate of gastrointestinal bleeding requiring endoscopic hemostasis is not different comparing patients with and without stress ulcer prophylaxis, and the increase in hospital-acquired pneumonia is significant, routine stress ulcer prophylaxis for patients with severe sepsis may be unnecessary.

Administration of proton pump inhibitors in critically ill medical patients is associated with increased risk of developing Clostridium difficile-associated diarrhea. (Teppa)

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Buendgens L, Bruensing J, Matthes M, Dückers H, Luedde T, Trautwein C, Tacke F, Koch A. Administration of proton pump inhibitors in critically ill medical patients is associated with increased risk of developing Clostridium difficile-associated diarrhea. J Crit Care. 2014 Aug;29(4):696.e11-5.

Full-text for Children’s and Emory users.

PURPOSE: Proton pump inhibitors (PPIs) effectively prevent gastrointestinal bleedings in critically ill patients at the intensive care unit (ICU). In non-ICU hospitalized patients, PPI administration increases the risk of infectious complications, especially Clostridium difficile-associated diarrhea (CDAD); but no such data are available for the ICU setting.

MATERIALS AND METHODS: This is a retrospective, observational, single-center analysis (1999-2010) including 3286 critically ill patients.

RESULTS: A total of 91.3% of patients received stress ulcer prophylaxis by PPI (55.6%), histamine 2 receptor antagonists (5.8%), sucralfate (10.1%), or combinations (19.8%). Only 29 (0.9%) of 3286 patients developed gastrointestinal bleedings during the course of ICU treatment, independent from the type of prophylaxis. The PPIs were not an independent risk factor for nosocomial pneumonia. One hundred and ten (3.3%) patients developed CDAD during the course of ICU treatment, which was associated with prolonged ICU stay and increased ICU mortality (odds ratio, 1.59). Similar to fluoroquinolones and cephalosporins, PPI was identified as an independent risk factor (odds ratio, 3.11) for developing CDAD at the ICU by multivariate analysis.

CONCLUSIONS: Proton pump inhibitor therapy was an independent risk factor for CDAD in medical ICU patients. Instead of routine PPI use for bleeding prophylaxis, further trials should investigate risk-adjusted algorithms, balancing benefits, and threats of PPI medication.

Proton pump inhibitors versus histamine 2 receptor antagonists for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis. (from Critical Care Medicine, March 2013 – Krohn)

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Crit Care Med. 2013 Mar;41(3):693-705. PMID: 23318494

Full-text access for Children’s and Emory users.

BACKGROUND: Critically ill patients may develop bleeding caused by stress ulceration. Acid suppression is commonly prescribed for patients at risk of stress ulcer bleeding. Whether proton pump inhibitors are more effective than histamine 2 receptor antagonists is unclear.

OBJECTIVES: To determine the efficacy and safety of proton pump inhibitors vs. histamine 2 receptor antagonists for the prevention of upper gastrointestinal bleeding in the ICU.

SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, ACPJC, CINHAL, online trials registries (clinicaltrials.gov, ISRCTN Register, WHO ICTRP), conference proceedings databases, and reference lists of relevant articles.

SELECTION CRITERIA: Randomized controlled parallel group trials comparing proton pump inhibitors to histamine 2 receptor antagonists for the prevention of upper gastrointestinal bleeding in critically ill patients, published before March 2012.

DATA COLLECTION AND ANALYSIS: Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcomes were clinically important upper gastrointestinal bleeding and overt upper gastrointestinal bleeding; secondary outcomes were nosocomial pneumonia, ICU mortality, ICU length of stay, and Clostridium difficile infection. Trial authors were contacted for additional or clarifying information.

RESULTS: Fourteen trials enrolling a total of 1,720 patients were included. Proton pump inhibitors were more effective than histamine 2 receptor antagonists at reducing clinically important upper gastrointestinal bleeding (relative risk 0.36; 95% confidence interval 0.19-0.68; p = 0.002; I = 0%) and overt upper gastrointestinal bleeding (relative risk 0.35; 95% confidence interval 0.21-0.59; p < 0.0001; I = 15%). There were no differences between proton pump inhibitors and histamine 2 receptor antagonists in the risk of nosocomial pneumonia (relative risk 1.06; 95% confidence interval 0.73-1.52; p = 0.76; I = 0%), ICU mortality (relative risk 1.01; 95% confidence interval 0.83-1.24; p = 0.91; I = 0%), or ICU length of stay (mean difference -0.54 days; 95% confidence interval -2.20 to 1.13; p = 0.53; I = 39%). No trials reported on C. difficile infection.

CONCLUSIONS: In critically ill patients, proton pump inhibitors seem to be more effective than histamine 2 receptor antagonists in preventing clinically important and overt upper gastrointestinal bleeding. The robustness of this conclusion is limited by the trial methodology, differences between lower and higher quality trials, sparse data, and possible publication bias. We observed no differences between drugs in the risk of pneumonia, death, or ICU length of stay.