“If You Never Give Up, You Cannot Possibly Lose”

Recently I was reviewing the “Black Knight scene” from Monty Python’s Holy Grail.  This scene in which the Black Knight continues to insist on fighting King Arthur even after losing all of his limbs came to mind as I was reading a recent study (JPGN 2014; 58: 226-36).  The blog title comes from an explanation of the scene from John Cleese who intended the scene to mock this philosophy. (Wikipedia link: Black Knight (Monty Python) – Wikipedia, the free encyclopedia)

The study is another trial of a proton pump inhibitor (rabeprazole) for 1- to 11-month old infants with symptomatic GERD.  In the discussion the authors note that this is the “fourth DB randomized placebo-controlled study published in the last 4 years that fails to show the efficacy of PPIs to treat symptomatic GERD in infants younger than 1 year.”

If anything, the design of this study should have allowed a therapeutic effect to be witnessed if present.  Infants selected for participation (n=268 in the double-blind phase) had been responsive to a 10 mg open-label usage of rabeprazole before randomization.  Yet, those infants who continued to receive 5 mg or 10 mg daily fared no better than placebo-treated patients.

The good news: no new safety signals in those who were treated compared to placebo.

The findings of this study are in marked distinction to clinical practice which has embraced PPIs in all age groups. In the same issue of JPGN, using a national database, De Bruyne et al (JPGN 2014; 58: 220-25) show a huge increase in PPI usage over the past decade in the Netherlands, especially in children ages 2 years and younger.  From 2004 to 2008, use of PPIs nearly doubled in this population.

The rabeprazole study manuscript which had nearly as many pediatric GI investigators as enrolled patients discusses the potential drawbacks of PPI therapy in infants including enteric infections like Clostridium difficile, lower respiratory infections (e.g.. pneumonia), and “perhaps even an increased incidence of necrotizing enterocolitis in premature infants.”  Unlike the Black Knight, after four blows to the PPI cause, the authors recommend yielding on PPIs except under much more stringent criteria (1 of 3):

  • Nonimproving symptoms at 1 year of age & resistant to conservative measures
  • Presence of underlying conditions that predispose to a natural history of severe chronic unremitting reflux
  • Erosive reflux esophagitis proven on endoscopy

Take-home message: PPIs have not been shown to be effective in infants…again!

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4 thoughts on ““If You Never Give Up, You Cannot Possibly Lose”

  1. Changing the mindset among parents and docs re: GERD is like moving a mountain. Years of vague speculation blamed all sorts of symptoms on the dreaded GERD, and since ranitidine and PPIs seemed safe, we were all eager to give it a go. That medicalized a “problem” that usually didn’t even exist.

    Still: there are plenty of genuinely fussy babies, screaming and arching. Some don’t gain well. What do we do with them, and how can be better define the line between them and their happy spitter neighbors? It’s the pediatricians (me!), not the GI specialists, who need to do a better job at the front line. Doing nothing (or, being perceived as doing nothing)… it isn’t easy!

    PS. Great blog, glad I found it! Thanks Jay.

    • Thanks for your comments. I think GI specialists and pediatricians alike overuse acid blockers in infants. It is hard to ‘do nothing,’ though sometimes that is what is best. In some cases, infants will improve with a hypoallergenic diet trial (would stop if not effective), probiotics (especially breastfed infants), or “conservative measures.” In most studies, a lot of infants improve with placebos. One of my colleagues treated her own child with simethicone. She said she knew it was no more effective than placebo, but placebo worked in at least 30%. In infants with worrisome symptoms, obtaining additional workup like an upper GI may be helpful, too.

  2. Pingback: Will This Change ALTE-GERD Practice? | gutsandgrowth

  3. Pingback: GERD Treatment in Infants: “Friend or Foe” | gutsandgrowth

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