Botulinum Toxin Injection in Retrograde Cricopharyngeal Dysfunction: A Meta-Analysis.

Objective: Retrograde cricopharyngeal dysfunction (RCPD) is defined by the inability to burp, sometimes with gurgling, chest/abdominal discomfort, and excessive flatulence. Treatment involves cricopharyngeal Botulinum Toxin-A (BonT-A) injection. However, the optimal dose and route are unclear. We quantitatively summarize the efficacy, safety, and optimization of BonT-A injections for RCPD.

Data Sources: PubMed, Embase, Scopus; till October 19, 2024.

Review Methods: We included randomized and non-randomized studies, published as full-length peer-reviewed articles, that investigated the efficacy and safety of BonT-A injections for RCPD among participants of all ages. Two blinded authors selected studies, extracted data, and evaluated bias (ROBINS-I), following a PROSPERO-registered protocol (CRD42024606413). We pooled logit-transformed proportions using random-effects inverse-variance meta-analyzes, identified associated factors using meta-regression, and quantitatively analyzed publication bias.

Results: From 189 records, we included 13 single-arm case series (N = 699), with some concerns for bias. Pooled early (1-4 weeks) and sustained (mean 3-29 months) overall symptom relief were 91.45% (95% CI = 83.66%-95.72%, I = 72%) and 79.90% (95% CI = 70.76%-86.72%, I = 53%) respectively. Complications were minor; the most common was transient dysphagia (51.04%, 95% CI = 37.61%-64.32%, I = 71%). Injections under direct rigid-endoscopic visualization were associated with greater (p = 0.0096) early success (92.19%, 95% CI = 88.29%-94.86%, I = 18%) than percutaneous electromyography-guided injections (85.03%, 95% CI = 21.90%-99.14%, I = 78%). Higher BonT-A dose (from 50 to 100 units) was associated with higher (p = 0.0382) sustained success (71.36%-92.79%); diminishing returns were projected for subsequent increments. Publication bias was not evident.

Conclusions: Cricopharyngeal BonT-A injections are safe and efficacious in RCPD. Larger doses of 100 units, injected under direct rigid-endoscopic visualization, may improve and maintain success. Randomized studies are needed to confirm causality.