Can delorazepam facilitate laryngopharyngeal reflux even when esophagogastroduodenoscopy (EGD) findings are normal?

Can Delorazepam Facilitate Laryngopharyngeal Reflux Even with Normal EGD?

Yes, benzodiazepines like delorazepam can theoretically facilitate laryngopharyngeal reflux regardless of EGD findings, because they reduce lower esophageal sphincter (LES) pressure through smooth muscle relaxation, and a normal EGD does not exclude the presence of reflux disease.

Mechanism: Benzodiazepines and LES Dysfunction

• Benzodiazepines cause dose-dependent reduction in LES pressure, with diazepam 5 mg causing an 18.9% reduction and 10 mg causing a 37.8% reduction in LES pressure, lasting approximately 7 minutes 1.
• The mechanism appears to involve smooth muscle relaxation, as myogenic influences contribute to LES pressure maintenance 1.
• This pharmacologic effect can facilitate reflux episodes by reducing the primary barrier preventing gastric contents from entering the esophagus and potentially reaching the laryngopharynx 1.

Why Normal EGD Doesn't Rule Out Reflux

• EGD is normal in the majority of patients with GERD, as objective findings like erosive esophagitis or Barrett's esophagus are present in only a minority of cases 2.
• EGD findings do not confirm or exclude that extraesophageal symptoms are caused by reflux, making it an inappropriate diagnostic tool for establishing causation between reflux and laryngopharyngeal symptoms 2.
• Only highly specific findings (Los Angeles grades B, C, D erosive esophagitis or long-segment Barrett's esophagus) confirm GERD, but their absence does not exclude the diagnosis 2.

Laryngopharyngeal Reflux Can Occur Without Esophageal Injury

• Up to 75% of patients with laryngopharyngeal reflux have no typical gastrointestinal symptoms like heartburn or acid regurgitation 3.
• The laryngeal mucosa is significantly more sensitive to refluxate than esophageal tissue, requiring fewer reflux episodes to produce symptoms 3.
• Only 6% of otolaryngology patients with laryngopharyngeal reflux report heartburn, despite 100% having hoarseness, highlighting the disconnect between esophageal and laryngeal manifestations 3.

Clinical Implications

• Laryngoscopic findings alone are unreliable for diagnosing LPR, with sensitivity and specificity less than 50%, and substantial inter- and intra-observer variability 2, 3.
• Ambulatory pH monitoring or pH-impedance monitoring is the appropriate diagnostic test when LPR is suspected, as it can detect acid and non-acid reflux events that may not cause esophageal mucosal injury 2.
• The presence of weak-acid or non-acid reflux (pH 4-7 or >7) can contribute to extraesophageal symptoms, particularly chronic cough and laryngeal symptoms, which would not be detected by standard pH monitoring alone 2.

Important Caveats

• Awareness of benzodiazepine's ability to lower LES pressure is needed to avoid falsely diagnosing reflux during endoscopy if the medication is taken before the procedure 1.
• If LPR is suspected in a patient taking delorazepam, consider that the medication may be contributing to or exacerbating reflux symptoms through its pharmacologic effect on the LES 1.
• Empiric PPI therapy should not be based on laryngoscopic findings alone, as these findings can be present in asymptomatic individuals or result from non-reflux causes 2, 3.