Management and Botulinum Toxin Injection Protocol
Wednesday, June 17, 2026

see also: Botulinum Neurotoxin Preparations

Protocol created June 17, 2026, by Adi Kotla, BS and Matt Hoffman MD PhD

Definitions

  • Retrograde Cricopharyngeal Dysfunction (R-CPD): A disorder characterized by absent or incomplete upper esophageal sphincter (UES) relaxation in response to abrupt esophageal distention by gastroesophageal gas reflux, resulting in the inability to belch. Also referred to as "retrograde cricopharyngeus dysfunction," "inability to belch syndrome," or colloquially as "no-burp syndrome". (Lechien & Bastian, 2026; Mailly et al., 2025; Miller et al., 2024)
  • Cricopharyngeus Muscle (CP): The primary muscular component of the UES, a C-shaped striated muscle that wraps around the posterior aspect of the pharyngoesophageal junction. In normal physiology, the CP relaxes during both antegrade (swallowing) and retrograde (belching, vomiting) events. In R-CPD, antegrade relaxation during swallowing is preserved, but retrograde relaxation during gas venting is impaired. (Lechien & Bastian, 2026; Miller et al., 2024)
  • Botulinum Toxin Injection (BTI): The primary therapeutic intervention for R-CPD, involving injection of botulinum toxin type A (onabotulinumtoxinA) into the cricopharyngeus muscle to induce temporary chemodenervation and facilitate retrograde UES relaxation. (Lechien & Bastian, 2026; Yeo et al., 2025)
  • High-Resolution Impedance Manometry (HRiM): A tool that can support the diagnosis of R-CPD by demonstrating elevated UES pressures during gas reflux episodes and failure of air clearance, particularly when combined with a carbonated drink belch provocation test. A maximum UES pressure during belching >31 mmHg has been proposed as a discriminating threshold. (Raymenants et al., 2025; Sanagapalli et al., 2024)

 

Background

R-CPD was first formally described as a clinical entity by Bastian and Smithson in 2019, who published the initial case series identifying the condition and demonstrating successful treatment with botulinum toxin injection into the cricopharyngeus muscle. Subsequent studies support these findings in adult and pediatric patients (Mailly et al., 2025; Hoffman et al., 2022). Prior to this, the inability to belch was not recognized as a distinct clinical diagnosis, and affected patients were frequently misdiagnosed or dismissed.

The pathophysiology is thought to result from failure of cricopharyngeal sphincter relaxation during periods of esophageal distension from gastric gas, while antegrade relaxation during swallowing remains intact (Miller et al., 2024). This leads to a constellation of symptoms, including the inability to burp, abdominal bloating and distension, gurgling noises from the chest/neck, excessive flatulence, postprandial chest or abdominal discomfort, and occasionally difficulty vomiting (Lechien & Bastian, 2026; Miller et al., 2024).

Symptoms typically begin in childhood (mean age of onset ~13.6 years), though diagnosis is often delayed by many years (mean age at diagnosis ~30.4 years) (Mailly et al., 2025). [HMR1] A family history is present in approximately 28–29% of cases, suggesting a possible genetic predisposition (Lechien & Bastian, 2026; Mailly & Lechien, 2025). [HMR2] 

A notable feature of R-CPD is the role of social media and patient-led online communities, like Reddit's “r/noburp” thread, in driving awareness. The majority of patients self-diagnose after encountering descriptions online, with one large series reporting that 99.1% of patients made the diagnosis themselves despite a mean of 162 prior medical consultations and 113 empirical treatments (Mailly et al., 2025; Miller et al., 2024). A national survey of academic laryngologists found that 75.9% had heard of R-CPD, with botulinum toxin injection being the most common management approach (79.2%) and cricopharyngeal myotomy used less frequently (11.3%) (Razura et al., 2025).

The condition has also been described in pediatric populations, with children as young as 10[HMR3]  years presenting with lifelong inability to burp and responding well to botulinum toxin injection[HMR4]  under general anesthesia (Hoffman et al., 2022; Dorfman et al., 2024).

 

Current Management Options

  1. Botulinum Toxin to the Cricopharyngeus Muscle under General Anesthesia

 

This was the original approach described by Bastian and Smithson (2019) and remains the most widely studied technique. The procedure involves direct rigid esophagoscopy under general anesthesia with injection of botulinum toxin into the cricopharyngeus muscle under direct visualization.

 

Dosing: Ranges from 10[HMR5] –100 U of onabotulinumtoxin A, typically injected across 3–5 sites in the posterior cricopharyngeus. The Jefferson Experience (Siddiqui et al., 2023) favors 80–100 U for optimal response. A 2025 meta-analysis (Yeo et al., 2025) found that higher doses (~100 U) were associated with significantly better sustained success (p = 0.038). 

 

Efficacy: Pooled early symptom relief is 91.5%, with sustained relief of 79.9%. OR injection success rates of ~90–91% have been consistently reported (Yeo et al., 2025; Kutler et al., 2025; Doruk & Pitman, 2024). 

 

Complications: Transient dysphagia and GERD are the most common adverse effects, occurring in 30–51% of patients and typically resolving within 2–3 weeks. No serious complications have been reported in the literature (Yeo et al., 2025; Siddiqui et al., 2023). Diffusion of botulinum toxin to the posterior cricoarytenoid muscles causing bilateral vocal fold paralysis is an inherent though rare risk with botulinum toxin injection to the cricopharyngeus. Injecting a high concentration and low volume of solution to the posterior aspect of the cricopharyngeus can help avoid this potential complication. 

 

Advantages: Direct visualization of the injection site; higher single-injection success rate; ability to perform concurrent diagnostic esophagoscopy.

Disadvantages: General Anesthesia

  1. In-Office Lateral Transcervical EMG-Guided Injection of the Cricopharyngeus Muscle

 

This approach was developed to provide a less invasive, lower-cost alternative to OR injection. The technique involves percutaneous injection through a lateral transcervical approach using EMG guidance to confirm needle placement in the cricopharyngeus muscle.

 

Technique: The patient is seated upright. Surface landmarks are used to identify the cricoid cartilage. An EMG needle is inserted laterally through the skin at the level of the cricoid, and placement is confirmed by characteristic tonic EMG activity that increases with sniffing and decreases with swallowing. Botulinum toxin is then injected through the same needle (Doruk & Pitman, 2024; Lahiff et al., 2026).

 

Dosing: Typically, 30 U per side (unilateral or bilateral). Some practitioners use lower doses (10–30 U unilateral) (Doruk & Pitman, 2024; Cosentino et al., 2025).

 

Efficacy: Single office-based injection success rates range from 55–65% at 1 month. However, when a contralateral office-based injection is performed within 8 weeks for incomplete responders, the cumulative success rate approaches that of OR injection (77.8% vs. 70.5%, p = 0.45). Mailly et al. (2025) reported a cumulative success rate of 90.6% across iterative in-office injections (2, 5, 6, 15[HMR6] ).

 

Complications: Similar side effect profile to OR injection; transient dysphagia and GERD are the most common adverse events (Kutler et al., 2025; Doruk & Pitman, 2024).

 

Advantages: No general anesthesia required; lower cost; can be performed on the same-day in clinic; allows for iterative treatment.

 

Disadvantages: Lower single-injection success rate; may require bilateral or repeat injections; no direct visualization of injection site.

 

  1. Flexible Endoscopic Injection of the Cricopharyngeus Muscle

 

This has primarily been used in gastroenterology using flexible endoscopy to inject botulinum toxin into the cricopharyngeus under direct visualization, however, has also been used in otolaryngology clinics.

 

Technique: Performed via flexible upper endoscopy, with injection into cricopharyngeus under direct endoscopic visualization (Sanagapalli et al., 2024). Can be performed under conscious sedation.

 

Efficacy: The first prospective controlled study (Sanagapalli et al., 2024) demonstrated 92% of treated patients could belch at 3 months vs. 0% of controls.

 

Advantages: Good endoscopic visualization can be combined with a diagnostic upper endoscopy, some patients may not require general anesthesia.

 

Disadvantages: Less studied than prior OR rigid laryngoscopy/esophagoscopy approach.

 

Investigation Strategies/Recent Research

  1. Dose Optimization

Optimal dosing for botulinum toxin injections remains an area of investigation. The Yeo et al. (2025) meta-analysis (13 studies, N = 699) represents the most comprehensive quantitative synthesis to date and identified two key dose-response findings: (1) higher doses of 100 U were associated with significantly better sustained symptom relief compared to 50 U (p = 0.038), and (2) diminishing returns were projected for dose increments beyond 100 U. 

Low-dose approaches (10-30 U injected unilaterally) have shown variable efficacy, with Cosentino et al. (2025) reporting a 55.2% responder rate at 1 month using 10-30U, rising to 64.4% at the higher end of this range. Pavesi et al. (2023) reported successful treatment with as little as 10 U in a single case, representing the lowest effective dose reported. These findings suggest that a minimum effective dose threshold exists, but the precise dose-response curve is yet to be elicited for in office approaches where low doses are used.

Optimal dosing (weight-based vs. fixed) remains an unresolved question in pediatric R-CPD as well. Hoffman et al. (2022) treated children with 25-50 U under general anesthesia with symptom resolution. 

  1. Diagnostic Standardization

R-CPD currently remains a clinical diagnosis based on symptom history, with no universally accepted objective diagnostic criteria (Lechien & Bastian, 2026; Razura et al., 2025). A national survey by Razura et al. (2025) found that the use of diagnostic tools among laryngologists remains highly variable.  High-resolution impedence manometry (HRiM) with carbonated drink provocation is emerging as a possible diagnostic tool. 

Raymenants et al. (2025) conducted the largest controlled manometric study to date (55 R-CPD patients, 30 controls, 15 healthy volunteers) and demonstrated that R-CPD patients exhibit significantly higher UES pressures during gas reflux episodes compared to controls, with incomplete air clearance. A maximum UES pressure during belching >31 mmHg discriminated R-CPD patients from controls. After BTI, median UES pressures during belching decreased dramatically (56 → 3 mmHg) with corresponding improvement in air clearance (p < 0.0001) (Raymenants et al., 2025; Mailly & Lechien, 2025).

Sanagapalli et al. (2024) independently validated HRM with carbonated drink provocative testing in a prospective controlled study, demonstrating that all R-CPD patients exhibited characteristic esophageal pressurization patterns with failure of UES relaxation, which was not seen in asymptomatic volunteers.

In pediatric patients, Dorfman et al. (2024) adapted the HRiM protocol for adolescents, demonstrating abnormal UES relaxation with concurrent high esophageal impedance reflecting air entrapment and secondary peristalsis following carbonated drink challenge.

  1. Validated Patient-Reported Outcomes Measures

Understanding patient specific outcomes and the severity of symptoms for RCPD is a more recent exploration in the field. Two scoring systems have been developed that are gaining traction:

  • The Burp Score (Lechien et al., 2025): This was the first validated patient-reported outcome questionnaire specifically designed for R-CPD. The score ranges from 0 to 15, and is calculated by multiplying the frequency and severity of symptoms when occurring. A prospective controlled study demonstrated high test-retest reliability (rs = 0.911), high internal consistency (Cronbach's α = 0.870), and significant external validity with correlation to the Reflux Symptom Score-12 (rs = 0.533). The Burp Score showed high responsiveness to change following BTI, with a minimal clinically important difference (MCID) of 11.0 to consider treatment partially or fully effective. Notably, during control screening, 22.4% of screened healthy individuals were excluded because they were unable to burp, further supporting the high population prevalence of R-CPD (Lechien et al., 2025).
  • PROMIS-29 and Social Anxiety Questionnaire (Jacobs et al., 2025): A cross-sectional study of 239 R-CPD patients demonstrated the significant psychosocial burden of the condition: 71.0% reported high anxiety, 55.1% depression, 66.8% fatigue, and 52.0% scored above the cutoff for social anxiety. These findings provide benchmarks for monitoring treatment response and underscore the importance of incorporating quality-of-life measures into R-CPD treatment protocols (Jacobs et al., 2025).

 

References

Retrograde Cricopharyngeus Dysfunction: What the Gastroenterologist Should Know. Lechien JR, Bastian RW. Current Opinion in Gastroenterology. 2026;:00001574-990000000-00252. doi:10.1097/MOG.0000000000001177.

Origin and In-Office Treatment of Retrograde Cricopharyngeus Dysfunction. Mailly M, Baudouin R, Thibault C, Hans S, Lechien JR. JAMA Otolaryngology-- Head & Neck Surgery. 2025;151(4):396-400. doi:10.1001/jamaoto.2024.5046.

Retrograde Cricopharyngeal Dysfunction: A Review. Miller ME, Lina I, Akst LM. Journal of Clinical Medicine. 2024;13(2):413. doi:10.3390/jcm13020413.

Botulinum Toxin Injection in Retrograde Cricopharyngeal Dysfunction: A Meta-Analysis. Yeo WX, Tan BKJ, Gao EY, Yeap SYY, Leong ZH. The Laryngoscope. 2025;. doi:10.1002/lary.32296.

Office v OR Injection for Retrograde Cricopharyngeal Dysfunction: Evidence-Based Treatment Algorithm. Kutler RB, Siddiqui SH, Tipton CB, Born HL, Pitman MJ. The Laryngoscope. 2025;. doi:10.1002/lary.32322.

Lateral Transcervical in-Office Botulinum Toxin Injection for Retrograde Cricopharyngeal Dysfunction. Doruk C, Pitman MJ. The Laryngoscope. 2024;134(1):283-286. doi:10.1002/lary.30871.

Diagnosis of Retrograde Cricopharyngeus Dysfunction Using High Resolution Impedance Manometry and Comparison With Control Subjects. Raymenants K, Vulsteke F, Vanuytsel T, et al. Clinical Gastroenterology and Hepatology : The Official Clinical Practice Journal of the American Gastroenterological Association. 2025;:S1542-3565(25)00070-9. doi:10.1016/j.cgh.2024.12.014.

Prospective Controlled Study of Endoscopic Botulinum Toxin Injection for Retrograde Cricopharyngeus Dysfunction: The Inability to Belch Syndrome. Sanagapalli S, Eid M, Kim MB, Tudehope F. The American Journal of Gastroenterology. 2024;120(9):2051-2058. doi:10.14309/ajg.0000000000003242.

"I've Never Been Able to Burp": Preliminary Description of Retrograde Cricopharyngeal Dysfunction in Children. Hoffman MR, Schiffer B, Patel RA, Smith ME. International Journal of Pediatric Otorhinolaryngology. 2022;161:111261. doi:10.1016/j.ijporl.2022.111261.

Retrograde Cricopharyngeal Dysfunction: An Update of Pathophysiological Mechanisms and Future Directions. Mailly M, Lechien JR. Toxins. 2025;18(1):8. doi:10.3390/toxins18010008.

A National Survey on Retrograde Cricopharyngeus Dysfunction Practice Patterns Among Laryngologists. Razura DE, Ulloa R, Lin ME, et al. The Laryngoscope. 2025;135(8):2838-2845. doi:10.1002/lary.32125.

 

Pediatric Retrograde Cricopharyngeal Dysfunction Diagnosed by High-Resolution impedance Manometry. Dorfman L, El-Chammas K, Mansi S, Graham K, Kaul A. Journal of Pediatric Gastroenterology and Nutrition. 2024;78(5):1098-1107. doi:10.1002/jpn3.12193.