Acid‐suppressive medication use in acute stroke and hospital‐acquired pneumonia

Herzig, Shoshana J.; Doughty, Christopher; Lahoti, Sourabh; Marchina, Sarah; Sanan, Neha; Feng, Wuwei; Kumar, Sandeep

doi:10.1002/ana.24262

Cited by 46 publications

(45 citation statements)

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“…Stroke patients are at a higher risk for developing pneumonia, which typically occurs from aspiration [25]. Baseline stroke severity, decreased level of arousal, dysphagia, congestive heart failure, intubation, and acid-suppressive medications have been identified as the major causes for pneumonia in this population [14, 15, 25]. Our analysis further corroborates these findings but some covariates such as total stroke severity as assessed by the total NIHSS score, level of arousal, and acid-suppressive medications were rendered non-significant in the final model.…”

Section: Discussionmentioning

confidence: 99%

Endotracheal Intubation and In-Hospital Mortality after Intracerebral Hemorrhage

et al. 2018

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Background: Many patients with acute intracerebral hemorrhages (ICHs) undergo endotracheal intubation with subsequent mechanical ventilation (MV) for “airway protection” with the intent to prevent aspiration, pneumonias, and its related mortality. Conversely, these procedures may independently promote pneumonia, laryngeal trauma, dysphagia, and adversely affect patient outcomes. The net benefit of intubation and MV in this patient cohort has not been systematically investigated. Methods: We conducted a large single-center observational cohort study to examine the independent association between endotracheal intubation and MV, hospital-acquired pneumonia (HAP), and in-hospital mortality (HM) in patients with ICH. All consecutive patients admitted with a primary diagnosis of a spontaneous ICH to a tertiary care hospital in Boston, Massachusetts, from June 2000 through January 2014, who were ≥18 years of age and hospitalized for ≥2 days were eligible for inclusion. Patients with pneumonia on admission, or those having brain or lung neoplasms were excluded. Our exposure of interest was endotracheal intubation and MV during hospitalization; our primary outcomes were incidence of HAP and HM, ascertained using International Classification of Diseases-9 and administrative discharge disposition codes, respectively, in patients who underwent endotracheal intubation and MV versus those who did not. Multivariable logistic regression was used to control for confounders. Results: Of the 2,386 hospital admissions screened, 1,384 patients fulfilled study criteria and were included in the final analysis. A total of 507 (36.6%) patients were intubated. Overall 133 (26.23%) patients in the intubated group developed HAP versus 41 (4.67%) patients in the non-intubated group (p < 0.0001); 195 (38.5%) intubated patients died during hospitalization compared to 48 (5.5%) non-intubated patients (p < 0.0001). After confounder adjustments, OR for HAP and HM, were 4.23 (95% CI 2.48–7.22; p < 0.0001) and 4.32 (95% CI 2.5–7.49; p < 0.0001) with c-statistics of 0.79 and 0.89, in the intubated versus non-intubated patients, respectively. Conclusion: In this large hospital-based cohort of patients presenting with an acute spontaneous ICH, endotracheal intubation and MV were associated with increased odds of HAP and HM. These findings urge further examination of the practice of intubation in prospective studies.

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Section: Discussionmentioning

confidence: 99%

Endotracheal Intubation and In-Hospital Mortality after Intracerebral Hemorrhage

et al. 2018

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“…In addition, gastrointestinal bleeding (GIB) caused by stress-related mucosal damage is a life-threatening stroke complication [4–6]. To prevent GIB in acute stroke patients, acid-suppressive medications such as histamine H2-blockers (H2B) or proton pump inhibitors (PPI) are commonly administered [7–9], although little evidence supports such preventive therapy.…”

Section: Introductionmentioning

confidence: 99%

Histamine H2-Blocker and Proton Pump Inhibitor Use and the Risk of Pneumonia in Acute Stroke: A Retrospective Analysis on Susceptible Patients

et al. 2017

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BackgroundAlthough histamine H2-blockers (H2B) and proton pump inhibitors (PPI) are used commonly to prevent gastrointestinal bleeding in acute stroke, they are implicated in the increased risk of pneumonia in other disease populations. In acute stroke, the presence of distinctive risk factors of pneumonia, including dysphagia and impaired consciousness, makes inclusive analysis vulnerable to confounding. Our aim was to assess whether acid-suppressive drugs increase pneumonia in acute stroke in a population controlled for confounding.MethodsWe analyzed acute stroke patients admitted to a tertiary care hospital. To minimize confounding, we only included subjects who could not feed orally during 14 days of hospitalization. Exposure was defined as H2B or PPI, given in days; the outcome was development of pneumonia within this period. The incidence was calculated from the total number of pneumonias divided by the sum of person-days at risk. We additionally performed multivariate Poisson regression and propensity score analyses, although the restriction largely eliminated the need for multivariate adjustment.ResultsA total of 132 pneumonias occurred in 3582 person-days. The incidence was 3.69%/person-day (95% confidence interval (CI); 3.03–4.37%/day). All subjects had dysphagia. Stroke severity and consciousness disturbances were well-balanced between the groups exposed to H2B, PPI, or none. The relative risk (RR) compared with the unexposed was 1.22 in H2B (95%CI; 0.83–1.81) and 2.07 in PPI (95% CI; 1.13–3.62). The RR of PPI compared with H2B was 1.69 (95%CI; 0.95–2.89). In multivariate regression analysis, the RRs of H2B and PPI were 1.24 (95% CI; 0.85–1.81) and 2.00 (95% CI; 1.12–3.57), respectively; in propensity score analyses they were 1.17 (95% CI; 0.89–1.54) and 2.13 (95% CI; 1.60–2.84).ConclusionsThe results of this study suggested that prophylactic acid-suppressive therapy with PPI may have to be avoided in acute stroke patients susceptible to pneumonia.

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“…PPI administration correlates with an increased risk for hospital- and community-acquired pneumonia (Fohl and Regal, 2011). Depending on study design, daily dose, and duration of PPI treatment, the increased risk of developing pneumonia is substantial, but is highly variable (0.91–6.53 fold; confidence interval 95%; de Jager et al, 2012; Fohl and Regal, 2011; Herzig et al, 2014; Jena et al, 2013; Ramsay et al, 2013; Sheen and Triadafilopoulos, 2011). Proposed molecular mechanisms include effects on the immune system or bacterial overgrowth in the stomach, due to increase in gastric pH, enrichment of potential pathogenic microorganisms, and subsequent microaspiration causing airway infections (Fohl and Regal, 2011; Herzig et al, 2014; Reimer, 2013).…”

Section: Introductionmentioning

confidence: 99%

ATP4a is required for development and function of the Xenopus mucociliary epidermis – a potential model to study proton pump inhibitor-associated pneumonia

Walentek

Beyer

Hagenlocher

et al. 2015

Developmental Biology

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Proton pump inhibitors (PPIs), which target gastric H+/K+ATPase (ATP4), are among the most commonly prescribed drugs. PPIs are used to treat ulcers and as a preventative measure against gastroesophageal reflux disease in hospitalized patients. PPI treatment correlates with an increased risk for airway infections, i.e. community- and hospital-acquired pneumonia. The cause for this correlation, however, remains elusive. The Xenopus embryonic epidermis is increasingly being used as a model to study airway-like mucociliary epithelia. Here we use this model to address how ATP4 inhibition may affect epithelial function in human airways. We demonstrate that atp4a knockdown interfered with the generation of cilia-driven extracellular fluid flow. ATP4a and canonical Wnt signaling were required in the epidermis for expression of foxj1, a transcriptional regulator of motile ciliogenesis. The ATP4/Wnt module activated foxj1 downstream of ciliated cell fate specification. In multiciliated cells (MCCs) of the epidermis, ATP4a was also necessary for normal myb expression, apical actin formation, basal body docking and alignment of basal bodies. Furthermore, ATP4-dependent Wnt/β-catenin signaling in the epidermis was a prerequisite for foxa1-mediated specification of small secretory cells (SSCs). SSCs release serotonin and other substances into the medium, and thereby regulate ciliary beating in MCCs and protect the epithelium against infection. Pharmacological inhibition of ATP4 in the mature mucociliary epithelium also caused a loss of MCCs and led to impaired mucociliary clearance. These data strongly suggest that PPI-associated pneumonia in human patients might, at least in part, be linked to dysfunction of mucociliary epithelia of the airways.

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Acid‐suppressive medication use in acute stroke and hospital‐acquired pneumonia

Cited by 46 publications

References 42 publications

Endotracheal Intubation and In-Hospital Mortality after Intracerebral Hemorrhage

Endotracheal Intubation and In-Hospital Mortality after Intracerebral Hemorrhage

Histamine H2-Blocker and Proton Pump Inhibitor Use and the Risk of Pneumonia in Acute Stroke: A Retrospective Analysis on Susceptible Patients

ATP4a is required for development and function of the Xenopus mucociliary epidermis – a potential model to study proton pump inhibitor-associated pneumonia

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