Hiccups as the Unlikely Adverse Drug Reaction That Won’t Quit

In the vast pharmacovigilance world, serious adverse reactions often take the spotlight. These include life-threatening conditions, severe allergic reactions, and irreversible organ damage. But amid adverse drug reaction (ADR), a reaction exists that is more of a nuisance than a threat. However, it can be equally persistent and disruptive: hiccups.

Hiccups are a not uncommon occurrence that most people experience at some point in their lifetime. The medical term is singultus, derived from the Latin “singult”, meaning ‘to catch one’s breath while sobbing.’

Yes, the seemingly innocent and often comical hiccup can be a genuine ADR that gets overlooked, yet it can be more than just a passing annoyance for some patients.

The Mechanism of Singultus: Simple but Mysterious

Singultus occur due to involuntary contractions of the diaphragm, followed by a rapid closure of the vocal cords, producing that telltale “hic” sound. While we’ve all experienced brief bouts of hiccups from overeating or drinking carbonated beverages, singultus can last much longer and can be hard to stop. The exact mechanism behind drug-induced hiccups has yet to be fully understood. Still, it is thought that certain medications can irritate or stimulate the phrenic nerve or the diaphragm, leading to these annoying spasms.

Drugs That Cause Hiccups: More Common Than You Think

While hiccups are generally associated with overeating or a sudden gulp of air, some medications have been linked to hiccups. Among them:

• Corticosteroids: Dexamethasone and methylprednisolone are notorious for causing hiccups in some patients, mainly when used in high doses.
• Chemotherapeutic Agents: Certain chemotherapy drugs trigger hiccups, adding a frustrating burden for cancer patients already enduring harsh treatment.
• Benzodiazepines: Medications like midazolam, commonly used for sedation, sometimes induce hiccups.
• Opioids: Morphine, a staple in pain management, can cause hiccups, particularly in patients undergoing long-term therapy.

While not life-threatening, singultus can be persistent and bothersome. In rare cases, it can affect a patient’s quality of life, leading to insomnia, difficulty eating, or even social embarrassment.

Uncommon Cases of Drug-Induced Hiccups: Insights from Medical Literature

Recently, the DrugCard platform uncovered two intriguing cases of drug-induced hiccups in the medical literature.

Hiccups Linked to Moxifloxacin: A Rare Case Report

The first case involved a man in his 40s who experienced persistent hiccups after being treated with moxifloxacin for tuberculous pleurisy. The hiccups began two hours after receiving the intravenous injection and lasted through the evening. The following day, they returned and disrupted his sleep. After ruling out other causes, such as gastrointestinal or nervous system issues, the clinician assessed the adverse drug reaction using the Naranjo scale, scoring a six, which indicated a probable link between moxifloxacin and the hiccups. The hiccups stopped just two minutes after the patient received an intramuscular metoclopramide injection. To the authors’ knowledge, this is the first reported case of moxifloxacin-inducing persistent hiccups.

Hiccups Following Epidural Steroid Injection: A Challenging Case

In the second case, a patient developed unrelenting hiccups after receiving an interlaminar epidural steroid injection (ESI) that included 10 mg of dexamethasone, 10 mg of 1% lidocaine, and 3 millilitres of preservative-free saline. The singultus began within hours of the procedure and persisted for five days. Eventually, it led the patient to seek help due to difficulty eating and shortness of breath. He was prescribed 25 mg of chlorpromazine up to three times daily. After two days of therapy and nearly 12 days post-ESI, the singultus, along with associated symptoms like dyspnea, nausea, and reflux, finally resolved.

Pharmacovigilance and Hiccups: An ADR Worth Noting

As pharmacovigilance specialists, it’s crucial to remember that not all adverse drug reactions are life-threatening. While singultus may seem trivial, they can significantly affect a patient’s well-being. Monitoring patient reports for such seemingly benign ADRs allows us to provide better care by addressing symptoms that, though not dangerous, are undeniably disruptive.

Moreover, given their mild nature, hiccups often go unreported as ADRs. By encouraging healthcare professionals to report these cases, pharmacovigilance databases can offer more comprehensive information, helping to identify patterns that might otherwise go unnoticed.

Conclusion: A Symptom That Deserves Attention

In the realm of pharmacovigilance, even the most innocuous-seeming reactions, like hiccups, deserve our attention. While they might not carry the same urgency as other ADRs, they can cause discomfort and distress, impacting a patient’s overall treatment experience. As pharmacovigilance specialists, it is essential to take these cases seriously. We must work to find solutions that prioritize both the efficacy of treatment and the patient’s comfort.

So next time you hear a “hic,” remember that this small ADR can sometimes have big implications – and it’s up to us to watch out for it!