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Persistent singultus (hiccups) can be distressing and challenging to manage in the postoperative setting. While pharmacological interventions such as metoclopramide are commonly used, their effectiveness is often limited. Gentian root (Gentiana lutea) contains intensely bitter secoiridoid compounds known to stimulate vagally mediated reflexes and has a long history of use for digestive complaints. We report a case of a 70-year-old male who developed persistent hiccups following minor urologic surgery under propofol anesthesia. The hiccups were unresponsive to metoclopramide. The patient then self-administered a small amount (~20 mL) of traditional gentian schnapps, resulting in complete cessation of hiccups within 1 min. The effect was reproducible upon two subsequent recurrences later the same day. No further episodes occurred after the third administration. This case raises the hypothesis that bitter taste receptor activation in the oropharyngeal and gastrointestinal tract may modulate the hiccup reflex arc. While spontaneous resolution or the effect of alcohol cannot be excluded, the rapid and reproducible response suggests a possible therapeutic role for bitter-tasting botanical preparations in functional singultus.
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Introduction
Singultus (hiccups) is usually transient but can become persistent or intractable, causing significant discomfort. Its pathophysiology involves a reflex arc comprising afferent signals from the phrenic, vagus and sympathetic nerves, a central “hiccup center” in the medulla and cervical spinal cord, and efferent fibers that trigger diaphragmatic spasms and glottic closure [1]. Various stimuli, including gastrointestinal distension, metabolic disturbances, and pharmacological agents, can interfere with this reflex loop and provoke singultus [2].
General anesthesia, particularly propofol, has been reported to induce hiccups in susceptible individuals. The mechanism involves interference with inhibitory control of phrenic activity, vagal dysregulation or postoperative gastrointestinal dysfunction such as distension or delayed gastric emptying [3].
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Gentian root (Gentiana lutea) contains bitter secoiridoid glycosides such as gentiopicroside and amarogentin, among the most bitter natural substances [4]. These compounds stimulate bitter taste receptors in the oropharynx and gastrointestinal tract, activating the vagus nerve and triggering a cephalic phase digestive response [5]. This includes gastric acid secretion, improved motility, and modulation of gut hormone release [6]. Traditionally, gentian-based preparations have been used for dyspeptic symptoms, loss of appetite and to stimulate digestion [7]. Strong bitter and sour sensory stimuli, such as lemon juice or bitter herbal extracts, have been reported to interrupt singultus via vagally mediated reflex pathways [8]. Recent comprehensive reviews have detailed how bitter taste receptors (TAS2Rs) in the gastrointestinal tract act as chemosensory sentinels, modulating motility, secretion, and gut-brain signaling in response to luminal bitter compounds [9].
Here we report a case of postanesthetic persistent singultus that was refractory to standard therapy with metoclopramide but responded to the oral ingestion of a gentian root preparation.
Case report
Case presentation
We report the case of a 70-year-old male with metabolic syndrome, including hepatic steatosis, type 2 diabetes mellitus with elevated fasting glucose and arterial hypertension. His medication included metformin (1000 mg/day), ramipril (20 mg/day), simvastatin (10 mg/day), and tamsulosin (0.4 mg/day) for benign prostatic hyperplasia. Blood pressure and HbA1c were well controlled. No other comorbidities were present.
The patient underwent elective surgical eversion of the tunica vaginalis for a right-sided hydrocele. General anesthesia was induced with propofol. The procedure and recovery were uneventful. On the first postoperative day, facial flushing and a fasting blood glucose of 160 mg/dL were noted without hemodynamic instability, fever, or gastrointestinal symptoms. He was discharged that day in stable condition.
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Despite resuming metformin therapy, facial flushing and elevated glucose levels persisted. The morning after discharge, the patient reported dyspeptic discomfort after breakfast, leading to administration of a single dose of pantoprazole (20 mg). After temporary relief, hiccup (singultus) developed following lunch and lasted throughout the afternoon. A single dose of metoclopramide (10 mg) was administered without effect.
In the early evening, the patient self-administered a single sip (approximately 20 mL) of gentian schnapps (traditionally prepared from Gentiana lutea root), which resulted in the complete cessation of hiccups within less than 1 min. Remarkably, the hiccup remained absent for more than 2 h before recurring. A second sip produced the same immediate and complete relief. The same response occurred once more at midnight, after which the hiccups did not recur.
In the days following this episode, facial flushing resolved and fasting glucose values returned to baseline. No further gastrointestinal symptoms or episodes of singultus occurred during follow-up.
Preparation of the gentian root extract
The gentian schnapps used was a traditional homemade preparation (Fig. 1). About 100 g of whole dried gentian roots (Gentiana lutea) was immersed in 1 l of 40% ethanol, matching standard vodka’s alcohol concentration.
Fig. 1
The traditional homemade gentian root extract (Gentiana lutea) used in this case consisted of whole dried roots soaked in 40% ethanol (vodka) and stored in a sealed bottle for 2 years. This preparation was used as a phytotherapeutic intervention for persistent postoperative singultus
The intact roots were placed into the ethanol base and remained throughout the 2‑year storage period. The plant material was cultivated by Alpe Pragas GmbH-Srl in San Candido/Innichen, South Tyrol, Italy, using gentian plants from the Research Institute for Special Cultures (Versuchsstation für Spezialkulturen) Wies, part of the Regional Government of Styria, Austria (Steiermark).
The preparation was used for digestive purposes over this period and was 2 years old when used. It was stored in a dark, cool environment without additional herbs, sweeteners or flavoring agents.
Discussion
This is the first reported case of post-propofol singultus responding immediately to oral gentian root preparation. The temporal relationship and repeated reversibility after gentian exposure suggest a causal link.
The secoiridoid bitter compounds amarogentin and gentiopicroside stimulate TAS2Rs in the oropharynx and gastrointestinal tract [4‐6]. This triggers vagally mediated reflex activation of digestive secretions and motility [5, 6]. This afferent activation of the vagus nerve may engage the reflex circuits involved in hiccup generation [1, 2, 10].
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Traditional singultus remedies use sensory stimulation to “reset” the hiccup reflex arc [8]. Methods, such as swallowing sugar, cold water or biting lemons activate glossopharyngeal and vagal afferents, interrupting pathological reflex activity [8]. A 1981 case reported hiccup cessation after ingestion of lemon wedges with Angostura bitters containing gentian extract [11]. Similarly, pure gentian was effective after failed pharmacological intervention.
Singultus onset in our patient may have been multifactorial. Although mask ventilation during anesthetic induction may lead to gastric insufflation and vagal irritation, the prolonged duration of hiccups and their rapid resolution upon gentian ingestion argue against transient gastric distension as the sole cause. General anesthesia with propofol can dysregulate central and peripheral inhibitory controls of diaphragmatic function [3], and postoperative hyperglycemia or vagal irritation from dyspepsia could have acted as triggers. Metoclopramide’s failure supports the hypothesis that vagal afferent stimulus may be more effective in such reflex-mediated cases.
The concurrent resolution of facial flushing and elevated glucose values after gentian intake raises questions about the metabolic and autonomic effects of bitter compounds. This observation, although anecdotal, aligns with studies suggesting interactions between bitter taste receptor activation and glycemic control or neurovascular tone [6].
While gentian root preparations contain well-characterized bitter compounds such as amarogentin and gentiopicroside, similar effects might be elicited by other intensely bitter substances. The rapid cessation of hiccups observed here likely reflects TAS2R-mediated vagal activation, which is not unique to Gentiana lutea. Alcohol may also contribute a gustatory or trigeminal stimulus but the reflex interruption seems primarily linked to bitter receptor stimulation. Future studies should examine the comparative effects of various bitter agents, alcoholic and non-alcoholic, on hiccup suppression.
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This case report, by nature, cannot establish causality or exclude spontaneous remission of hiccups as an alternative explanation. The lack of a control condition, quantitative dosing, or standardized outcome assessment limits generalizability. Nonetheless, the consistent and reproducible pattern of rapid hiccup relief following gentian ingestion across three separate episodes strengthens the hypothesis of a pharmacologically relevant reflex modulation.
Conclusion
Taken together, this case raises the hypothesis that bitter taste receptor activation in the upper gastrointestinal tract may help interrupt persistent singultus through a reflex mechanism. The case adds to the historical and physiological rationale for the use of gentian bitters in singultus management and highlights a low-risk, non-invasive option when standard pharmacological interventions fail. Further studies, either mechanistic or controlled clinical trials, could explore the role of bitter taste receptor agonists as reflex modulators in hiccup pathophysiology.
Acknowledgements
The authors thank the patient for consenting to publication and for careful documentation of the sequence of events.
Funding
Open access funding provided by College of Health Professions—Claudiana, Bolzano, Italy.
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Declarations
Conflict of interest
C.J. Wiedermann, M. Scheer and A. Pycha declare that they have no competing interests.
Ethical standards
The patient provided written informed consent for the anonymized publication of this case report.
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