Clinical Cases in Pharmacology Clinical Cases  ·  Gastroenterology II  ·  Stomach/Duodenum  ·  Medical Escalation in Refractory GERD
Gastroenterology II, Case GIStomachDuo-0013 — Stomach/Duodenum

Optimized on Paper, Still Symptomatic at the Bedside

A single patient whose reflux, confirmed on formal testing, simply hasn't responded to a maximized standard regimen. The disagreement is between the drug matched to her actual test result and the drug better matched to her job.

Abbreviations, terms, and other agents mentioned in this case PPI — proton pump inhibitor  ·  LES — lower esophageal sphincter  ·  GABA-B — gamma-aminobutyric acid type B receptor
Presentation

K.V., a 44-year-old restaurant chef, has spent a career eating standing up between tickets and testing recipes late at night, and has had heartburn most of that time — loud enough now, waking her twice most nights, that she finally agreed to a formal workup rather than continuing to self-treat with whatever antacid was closest. Twice-daily omeprazole at maximum dose for the past three months, taken correctly and confirmed by pharmacy refill records, hasn't meaningfully changed her nighttime symptoms. Ambulatory pH-impedance testing, done specifically to distinguish true ongoing reflux from functional heartburn once PPI dosing is no longer in question, confirmed genuine acid and non-acid reflux events, concentrated overnight — real refractory GERD, not a misdiagnosis or a symptom-perception problem.

Two mechanistically distinct medical options exist once PPI optimization has genuinely failed, short of surgical or endoscopic referral, and they're targeting two different problems that both plausibly contribute to her overnight pattern. Baclofen, a GABA-B agonist, reduces the frequency of transient LES relaxations — the actual physiologic event behind most reflux episodes, acid or non-acid, and directly relevant given her pH-impedance study showed both types occurring. Bedtime H2-receptor antagonist add-on targets a different, narrower phenomenon: nocturnal acid breakthrough, a documented drop in gastric pH that can occur overnight even on twice-daily PPI dosing, related to circadian histamine secretion patterns PPIs don't fully suppress.

Her actual pH-impedance data make this less of a coin flip than it might look: a meaningful fraction of her overnight events were non-acid reflux, which an H2RA — acting purely on acid secretion — cannot address at all, while baclofen's LES mechanism would blunt the underlying event regardless of whether the refluxate is acidic or not. Her refill records matter as much as the testing itself here: a genuinely adherent three-month trial at maximum dose removes "was she actually taking it correctly" as a competing explanation, which is precisely what lets the team treat this as true pharmacologic refractoriness rather than a disguised adherence problem — the distinction that determines whether escalation is even the right move at all.

K.V. · 44 Follow-up after pH-impedance testing
History
Chronic heartburn, ~10 years, worsening over past year; nocturnal symptoms twice most nights
PPI trial
Omeprazole 40mg BID x 3 months, confirmed adherent via refill records — no meaningful improvement
pH-impedance testing
Confirmed both acid and non-acid reflux events, concentrated overnight
Endoscopy
No erosive esophagitis, no Barrett's esophagus
Work schedule
Late-night shifts, frequent recumbent positioning within 2-3 hours of eating
Renal/hepatic function
Normal

Two mechanisms, one test result pointing at only one of them

Clinical Pharmacologist Opening

Baclofen's central nervous system side effects — sedation, dizziness — are a real concern for someone on her feet in a hot kitchen on overnight shifts, and I'd rather not start there if a better-tolerated option addresses her main pattern.

Nocturnal acid breakthrough is well documented even on maximized twice-daily PPI dosing, tied to circadian histamine secretion PPIs don't fully suppress. A bedtime H2-receptor antagonist add-on targets that specific overnight window directly, with a much lower side-effect burden.

Gastroenterologist Response

Tolerability is a fair concern, and I don't want to dismiss what a kitchen shift on her feet actually demands.

But her own pH-impedance study already answered the mechanism question for us — a meaningful share of her overnight events are non-acid reflux, not acid breakthrough. An H2-receptor antagonist works purely on acid secretion; it has no mechanism at all for a non-acid reflux event. Starting there means leaving a real, documented portion of her actual reflux pattern completely untreated.

Clinical Pharmacologist Rebuttal

The non-acid events are real and I'm not going to pretend an H2 blocker touches them. But notice what kind of argument you're making. Baclofen's case here is mechanistic — it reduces transient lower esophageal sphincter relaxations, and her study shows those are what she's having. What it doesn't have is an outcome trial in refractory GERD of the size we'd want; the evidence is small crossover work with short follow-up. So we're weighing a well-matched mechanism with a thin efficacy base against a narrower drug with a much better-characterized safety profile, in a woman who spends her nights upright over open flame. That's a genuine trade, not a case where your side simply has the data.

Gastroenterologist Final

I'd start baclofen at the lowest effective dose, timed to avoid her working hours as much as possible, with explicit counseling on the sedation risk and a plan to reassess quickly rather than push the dose up blindly — matching the drug to what her own testing actually showed, while taking the tolerability concern seriously in how we dose it.

Regimen selected
Baclofen (low starting dose)
GABA-B Agonist · 5-10mg at bedtime, dose-timed around her work schedule
Reduces transient LES relaxations, the mechanism behind both her acid and non-acid reflux events per pH-impedance testing.
Omeprazole (continued)
Proton Pump Inhibitor · 40mg BID, unchanged
Continued at current optimized dose; baclofen added rather than substituted.
Bedtime H2-Receptor Antagonist — Not Selected First
H2-Receptor Antagonist · Considered, deferred
Would address nocturnal acid breakthrough specifically but has no mechanism for the non-acid reflux events her own testing confirmed.
Where this was left

Low-dose baclofen added to her existing maximized PPI regimen, timed to minimize sedation risk during her work hours, with explicit counseling on side effects and a near-term follow-up to confirm both tolerability and symptom response.

Agreed on the plan; the tolerability concern shaped how baclofen is dosed and timed rather than which drug was chosen, since her own testing left little room to argue the mechanism itself.

Educational content only — a composite teaching case, not a real patient encounter or a substitute for clinical guidance. About These Cases →