Davy Tawadrous1, Stephanie Dixon2, Salimah Z Shariff3, Jamie Fleet4, Sonja Gandhi5, Arsh K Jain5, Matthew A Weir5, Tara Gomes6, Amit X Garg7. 1. Schulich School of Medicine, Western University, London, Canada; Division of Nephrology, Western University, London, Ontario, Canada. 2. Schulich School of Medicine, Western University, London, Canada; Division of Nephrology, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada; Institute for Clinical Evaluative Sciences, Ontario, Canada. 3. Schulich School of Medicine, Western University, London, Canada; Institute for Clinical Evaluative Sciences, Ontario, Canada. 4. Division of Nephrology, Western University, London, Ontario, Canada. 5. Schulich School of Medicine, Western University, London, Canada; Division of Nephrology, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada. 6. Institute for Clinical Evaluative Sciences, Ontario, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; Keenan Research Centre, Li Ka Shing Knowledge Institute, Toronto, Ontario, Canada. 7. Schulich School of Medicine, Western University, London, Canada; Division of Nephrology, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada; Institute for Clinical Evaluative Sciences, Ontario, Canada. Electronic address: amit.garg@lhsc.on.ca.
Abstract
BACKGROUND: Standard doses of histamine2-receptor antagonists (H2RAs) may induce altered mental status in older adults, especially in those with chronic kidney disease (CKD). METHODS: Population-based cohort study of older adults who started a new H2RA between 2002 and 2011 was conducted. Ninety percent received the current standard H2RA dose in routine care. There was no significant difference in 27 baseline patient characteristics. The primary outcome was hospitalization with an urgent head computed tomography (CT) scan (proxy for altered mental status), and the secondary outcome was all-cause mortality also within 30days of a new H2RA prescription. RESULTS: Standard vs. low H2RA dose was associated with a higher risk of hospitalization with an urgent head CT scan (0.98% vs. 0.74%, absolute risk difference 0.24% [95% CI 0.11% to 0.36%], relative risk 1.33 [95% CI 1.12 to 1.58]). This risk was not modified by the presence of CKD (interaction P value=0.71). Standard vs. low H2RA dose was associated with a higher risk of mortality (1.07% vs.0.74%; absolute risk difference 0.34% [95% CI 0.20% to 0.46%], relative risk 1.46 [95% CI 1.23 to 1.73]). INTERPRETATION: Compared to a lower dose, initiation of the current standard dose of H2RA in older adults is associated with a small absolute increase in the 30-day risk of altered mental status (using neuroimaging as a proxy), even in the absence of CKD. This risk may be avoided by initiating older adults on low doses of H2RAs for gastroesophogeal reflux disease, and increasing dosing as necessary for symptom control.
BACKGROUND: Standard doses of histamine2-receptor antagonists (H2RAs) may induce altered mental status in older adults, especially in those with chronic kidney disease (CKD). METHODS: Population-based cohort study of older adults who started a new H2RA between 2002 and 2011 was conducted. Ninety percent received the current standard H2RA dose in routine care. There was no significant difference in 27 baseline patient characteristics. The primary outcome was hospitalization with an urgent head computed tomography (CT) scan (proxy for altered mental status), and the secondary outcome was all-cause mortality also within 30days of a new H2RA prescription. RESULTS: Standard vs. low H2RA dose was associated with a higher risk of hospitalization with an urgent head CT scan (0.98% vs. 0.74%, absolute risk difference 0.24% [95% CI 0.11% to 0.36%], relative risk 1.33 [95% CI 1.12 to 1.58]). This risk was not modified by the presence of CKD (interaction P value=0.71). Standard vs. low H2RA dose was associated with a higher risk of mortality (1.07% vs.0.74%; absolute risk difference 0.34% [95% CI 0.20% to 0.46%], relative risk 1.46 [95% CI 1.23 to 1.73]). INTERPRETATION: Compared to a lower dose, initiation of the current standard dose of H2RA in older adults is associated with a small absolute increase in the 30-day risk of altered mental status (using neuroimaging as a proxy), even in the absence of CKD. This risk may be avoided by initiating older adults on low doses of H2RAs for gastroesophogeal reflux disease, and increasing dosing as necessary for symptom control.
Authors: Lavanya Bathini; Racquel Jandoc; Paul Kuwornu; Eric McArthur; Matthew A Weir; Manish M Sood; Marisa Battistella; Flory T Muanda; Aiden Liu; Arsh K Jain; Amit X Garg Journal: Clin J Am Soc Nephrol Date: 2019-01-10 Impact factor: 8.237
Authors: Justin X G Zhu; Danielle M Nash; Eric McArthur; Alexandra Farag; Amit X Garg; Arsh K Jain Journal: Nephrol Dial Transplant Date: 2019-04-01 Impact factor: 5.992
Authors: Namisha Singh; Sonja Gandhi; Eric McArthur; Louise Moist; Arsh K Jain; Aiden R Liu; Manish M Sood; Amit X Garg Journal: CMAJ Date: 2015-04-27 Impact factor: 8.262
Authors: Jamie L Fleet; Stephanie N Dixon; Paul John Kuwornu; Varun K Dev; Manuel Montero-Odasso; Jorge Burneo; Amit X Garg Journal: PLoS One Date: 2018-03-14 Impact factor: 3.240