The Prosecution Rests…PPIs on Trial

For physicians who use proton pump inhibitors in a cavalier manner, a recent review (CM Stark, CM Nylund. J Pediatr 168: 16-22) provides a sobering reassessment of the potential side effects and potential complications of proton pump inhibitors (PPIs).  After finishing the article, the impression left was of a lawyer putting these medications on trial for high crimes and misdemeanors.

Here were the key points:

Infectious disease: PPI-induced hypochloridia is known to alter the gastrointestinal bacteria motif, allowing certain normally absent or depleted pathogenetic microorganisms to survive and proliferate.  This can lead to all of the following:

  • small bowel bacterial overgrowth
  • increased gastrointestinal infections (including Clostridium difficile, Salmonella, Campylobacter, and acute viral gastroenteritis)
  • pneumonia (particularly community acquired pneumonia and hospital acquired pneumonia)
  • upper respiratory infections
  • spontaneous bacterial peritonitis.

The magnitude of these associations is discussed in detail in the review.

Gastrointestinal disease: Use of PPIs has been associated with an increased incidence of the following:

  •  celiac disease which persisted after excluding prescriptions in the year preceding diagnosis (association does not prove causation)
  • benign gastric fundic polyps
  • rebound acid hypersecretion

Malabsorption: PPIs can affect absorption of multiple nutrients, though more studies are needed, particularly in the pediatric age group.

  • calcium: “there is significant evidence to suggest that PPI use can alter calcium and bone metabolism…associated with an increased risk of hip fractures in older adults….It is reasonable to hypothesize that PPI administration during adolescence and early adulthood could decrease an individual’s peak bone density.”
  • magnesium: PPI have been hypothesized to affect magnesium absorption.  “A study of 366 Canadian patients hospitalized with hypomagnesemia…found PPIs [were] associated with a 43% increased risk of hospitalization.”  More studies are needed to determine the whether this risk is truly significant.
  • iron, vitamin B12, and vitamin C absorption may be affected by PPI use.

Cardiovascular/Renal/Microbiome:

  • Cardiac: In adults, PPI use has been associated with adverse cardiac events.  The pathophysiology could have been pediatric implications.  PPIs can increase asymmetrical dimethylarginine (ADMA) which is an endogenous inhibitor of nitric oxide synthase.
  • Renal: PPIs have been associated with cases of acute interstitial nephritis
  • Microbiome: “PPIs alter the microbiome.”  Decreased diversity of the microbiome has been associated with a large number of medical conditions, including irritable bowel syndrome, inflammatory bowel disease, nonalcoholic fatty liver disease, necrotizing enterocolitis as well as many non-gastrointestinal conditions.  “The temporality of dysbiosis and subsequent disease development has  not been explored fully for most conditions.”

My take: PPIs can be life-saving and disease-altering medications.  At the same time, (per authors) “PPIs should not be prescribed without consideration for all short- and long-term side effects.”

Related blog posts:

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This Webinar Will Review Issues with Regard to Optimal PPI Usage and Includes My Esteemed Colleagues (Dr. Gold and Dr. Garza)

This NASPGHAN Webinar Will Review Issues with Regard to Optimal PPI Usage and Includes My Esteemed Partners (Dr. Gold and Dr. Garza)

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6 thoughts on “The Prosecution Rests…PPIs on Trial

  1. Jay – interesting provocative piece today – more info for the PPI-haters out there.
    To get the “data”, I would recommend that people register and listen in to the following Webinar for CME credit…Ben

    NASPGHAN Presents!!
    REGISTER NOW
    LIVE WEBINAR: January 26, 2016: 8 – 9:15 P.M. EST
    Proton Pump Inhibitors: To use or not to use… That is the question!
    This program, geared specifically for pediatric gastroenterologists, will arm the specialist with essential education to ensure clarity surrounding current indications for use of proton pump inhibitors in children, as well as a growing understanding of risks associated with their use.
    MODERATOR:
    Jenifer R Lightdale, MD, MPH Professor of Pediatrics University of Massachusetts Medical School, Worcester, MA
    FACULTY:
    Carlo Di Lorenzo, MD Professor of Pediatrics, The Ohio State University
    Nationwide Children’s Hospital, Columbus, OH
    Jose Garza, MD
    Assistant Professor of Pediatrics Children’s Center for Digestive Health Care, LLC, Atlanta, GA
    Benjamin D. Gold, MD Professor of Pediatrics and Microbiology
    Children’s Center for Digestive Health Care, LLC, Atlanta, GA
    Rachel Rosen, MD
    Assistant Professor of Pediatrics Harvard Medical School, Boston, MA
    CME REVIEWER:
    Henry Lin, MD, Assistant Professor of Pediatrics, University of Pennsylvania, Children’s Hospital of Philadelphia, Philadelphia, PA
    NASPGHAN designates this activity for a maximum of 1.25 AMA PRA Category 1 CreditsTM

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