Case Report | Open Access
Mark E. Peacock, "Transient Hiccups Associated with Oral Dexamethasone", Case Reports in Dentistry, vol. 2013, Article ID 426178, 3 pages, 2013. https://doi.org/10.1155/2013/426178
Transient Hiccups Associated with Oral Dexamethasone
Hiccups, or singulata (hiccup is singultus), are commonly experienced by most people at one time or another and are usually brief and self-limiting. Although pharmacotherapeutic agents are not generally considered causal in the etiology of hiccups, many clinicians empirically associate episodic hiccups in their patients as being drug induced. The two classes of drugs most often cited as causing hiccups are corticosteroids and benzodiazepines. This report involved a patient who was given preoperative dexamethasone and developed hiccups before anesthesia and surgery commenced. He at no time was in distress, and the surgical procedure was completed without complication. By the second postsurgical day his hiccups were resolved completely. Although the association may be anecdotal, many clinicians consider hiccups a potential side effect of steroid therapy, especially high doses of steroids. Of interest in this case is the relatively low dose of corticosteroid used, albeit apparently linked to his hiccups. Practitioners should be aware of this potential condition.
Hiccups, or singulata (hiccup is singultus), are very common and are experienced by most people at one time or another. They are usually brief and self-limiting but may become prolonged in some patients . Hiccups that linger on for some time may become worrisome to the postoperative patient, thus hindering their nutritional and sleep needs [2, 3].
Hiccups are sudden, uncontrolled contractions of the diaphragm, followed by immediate inspiration and closure of the glottis over the trachea, producing the “hiccup” sound . The classification of hiccups is as follows: up to 48 hours, acute or transient; longer than 48 hours, persistent; and more than a month or two, intractable . The frequency of hiccups in males and females is equivalent, although intractable hiccups occur at a much higher rate in men [6, 7]. The exact etiology of the hiccup is unknown, but the neural process involves the reflex arc consisting of the afferent limb, the center, and the efferent limb [8, 9]. The afferent limb contains the phrenic and vagus nerves together with the sympathetic chain from T6 to T12. The center is linked to the afferent and efferent limbs and occupies a nonspecific location somewhere between C3 and C5. The efferent limb includes the phrenic nerve, accessory respiratory muscles, the glottis, and autonomic processes involving the medullary reticular formation and hypothalamus [4, 10]. One review proposed that the hiccup reflex arc is a myoclonic action and not a true reflex .
Medical conditions that have been associated with the development of hiccups include gastrointestinal, neurological, pulmonary, psychogenic, cardiovascular, metabolic, anesthesia related, and drug induced conditions [3, 4, 8, 12, 13]. Using a strict standard, drugs have not been proven to be a common cause of hiccups [7, 14]. Nevertheless, many clinicians have alluded to various medications as triggering the hiccup reflex [1, 3, 6, 13, 15–24]. The following case describes a patient who experienced transient hiccups following oral presurgical administration of dexamethasone.
2. Case Report
A 40-year-old male with an unremarkable medical history presented for surgery to place an implant. He was in excellent health, did not take any medications, and was not allergic to any drugs. The patient had taken a single prophylactic dose of 8 mg oral dexamethasone approximately 1 hour earlier. After presurgical vital signs were taken, and before any other medication (sedation, local anesthesia) was administered, the patient developed intermittent bouts of hiccups at a rate of roughly 5 to 7 per minute. He was in no distress and wanted to continue the procedure. Oral triazolam 0.50 mg was given, and by the time the surgery started, the episodic hiccups were reduced greatly allowing the implant to be placed uneventfully. By the time the patient was ready to be escorted from the clinic, the hiccups had returned at about the same rate they occurred preoperatively. He was given postoperative instructions and reassurances and followed up telephonically the next day, where he reported that by late afternoon (32 hours) the rate of hiccup episodes was reduced. The patient’s hiccups resolved completely by 42 hours after he took the dexamethasone. At the 1-week postoperative appointment, the incident was reviewed with the patient and counseling was given on the suspected drug-induced cause of the transient hiccups for his future reference/benefit.
There are few reports in the literature on dexamethasone-induced hiccups and none in the dental literature [6, 15, 18, 23, 24]. Other cases of corticosteroid-induced hiccups have been reported [1, 25], and Dickerman et al. have described the first cases of anabolic steroid-induced hiccups [16, 17]. The only other adverse reaction to steroids found in the dental literature was a case of episodic psychiatric disturbance (cognitive dysfunction) in an 18-year-old female who had taken dexamethasone briefly . The author would be remiss not to mention another suspected dexamethasone-induced transient hiccups case he came across years earlier, but, because other drugs were also given intravenously at the same time, it could not be confirmed.
Corticosteroids and benzodiazepines are the drug groups referenced most frequently in the literature as being associated with hiccups (see the following list), although Thompson and Landry state that there is not sufficient proof that any drug can be considered as definitely causing hiccups . Souadjian and Cain reviewed 220 cases of protracted hiccups and did not mention any medication in the etiology of hiccups . Garvey, who looked at postoperative cases of hiccups, came to the logical conclusion that the etiologic factor was probably drug related ; however, she also recounted that the intubation itself may be a contributing factor .
Drugs Possibly Associated with Triggering Hiccups: Steroids (dexamethasone, methylprednisolone, oxandrolone, and progesterone) Benzodiazepines (midazolam, lormetazepam, and lorazepam) Barbiturates (methohexital) Antibiotics (azithromycin) Phenothiazines (perphenazine) Opioids (hydrocodone) Alcohol.
The case described here was mild and short term and, even though somewhat inconvenient to the patient, was in practice, clinically insignificant. Hiccups that become persistent or intractable however can interfere with a patient’s daily activities and cause them to seek medical assistance. There are various reports in the literature of different treatments for protracted hiccups, including pharmacologic agents [4, 5, 8, 18, 22, 28–34]. Chlorpromazine is at present the only medication approved by the FDA for the treatment of hiccups, although many practitioners have reported less than desirable results with this drug [6, 17, 29].
Baclofen has been shown to successfully treat chronic hiccups [3, 4, 19, 30, 34], and promising results have been attained with the use of gabapentin alone  or as an add-on to combination therapy [5, 32].
The evidence for medication-induced hiccups may be empirical, yet for many the association is strong enough that clinicians should take notice. This is especially true for treatments involving steroids , drugs that are commonly used in medicine, including dental medicine. Being able to recognize the potential “drug-hiccup link” will better prepare health care practitioners manage any unexpected complications.
There are many uses for steroids in medicine and dentistry, and clinicians should be attentive to any possible side effects of medications prescribed. This paper and case explain the correlation between hiccups and steroid treatment in the perioperative setting. Although drug-induced hiccups have not been absolutely confirmed with controlled studies, the incidence is sufficient enough to raise questions by many practitioners. Fortunately, most cases of corticosteroid-related hiccups appear to be transient and usually end after the drug is withdrawn.
Conflict of Interests
The authors declare that they have no conflict of interests.
- Y.-M. Hung, M. A. Miller, and M. M. Patel, “Persistent hiccups associated with intravenous corticosteroid therapy,” Journal of Clinical Rheumatology, vol. 9, no. 5, pp. 306–309, 2003.
- I. Arnulf, D. Boisteanu, W. A. Whitelaw, J. Cabane, L. Garma, and J.-P. Derenne, “Chronic hiccups and sleep,” Sleep, vol. 19, no. 3, pp. 227–231, 1996.
- D. Garvey, “Post-operative hiccups,” Proceedings of UCLA HealthCare, vol. 4, pp. 19–21, 2000.
- P. W. Kolodzik and M. A. Eilers, “Hiccups (singultus): review and approach to management,” Annals of Emergency Medicine, vol. 20, no. 5, pp. 565–573, 1991.
- H. S. Smith and A. Busracamwongs, “Management of hiccups in the palliative care population,” American Journal of Hospice and Palliative Medicine, vol. 20, no. 2, pp. 149–154, 2003.
- J. Ross, M. Eledrisi, and P. Casner, “Persistent hiccups induced by dexamethasone,” Western Journal of Medicine, vol. 170, no. 1, pp. 51–52, 1999.
- J. V. Souadjian and J. C. Cain, “Intractable hiccup. Etiologic factors in 220 cases,” Postgraduate Medicine, vol. 43, no. 2, pp. 72–77, 1968.
- J. H. Lewis, “Hiccups: causes and cures,” Journal of Clinical Gastroenterology, vol. 7, no. 6, pp. 539–552, 1985.
- S. Launois, J. L. Bizec, W. A. Whitelaw, J. Cabane, and J. Derenne, “Hiccup in adults: an overview,” European Respiratory Journal, vol. 6, no. 4, pp. 563–575, 1993.
- J. J. M. Askenasy, “About the mechanism of hiccup,” European Neurology, vol. 32, no. 3, pp. 159–163, 1992.
- E. C. Lauterbach, “Hiccup and apparent myoclonus after hydrocodone: review of the opiate-related hiccup and myoclonus literature,” Clinical Neuropharmacology, vol. 22, no. 2, pp. 87–92, 1999.
- C. M. Fisher, “Protracted hiccup—a male malady,” Transactions of the American Neurological Association, vol. 92, pp. 231–233, 1967.
- Y. Takiguchi, R. Watanabe, K. Nagao, and T. Kuriyama, “Hiccups as an adverse reaction to cancer chemotherapy,” Journal of the National Cancer Institute, vol. 94, no. 10, pp. 772–774, 2002.
- D. F. Thompson and J. P. Landry, “Drug-induced hiccups,” Annals of Pharmacotherapy, vol. 31, no. 3, pp. 367–369, 1997.
- C.-C. Liaw, C.-H. Wang, H.-K. Chang et al., “Cisplatin-related hiccups: male predominance, induction by dexamethasone, and protection against nausea and vomiting,” Journal of Pain and Symptom Management, vol. 30, no. 4, pp. 359–366, 2005.
- R. D. Dickerman and S. Jaikumar, “The hiccup reflex arc and persistent hiccups with high-dose anabolic steroids: is the brainstem the steroid-responsive locus?” Clinical Neuropharmacology, vol. 24, no. 1, pp. 62–64, 2001.
- R. D. Dickerman, C. Overby, M. Eisenberg, P. Hollis, and M. Levine, “The steroid-responsive hiccup reflex arc: competitive binding to the corticosteroid-receptor?” Neuroendocrinology Letters, vol. 24, no. 3-4, pp. 167–169, 2003.
- R. J. Cersosimo and M. T. Brophy, “Hiccups with high dose dexamethasone administration: a case report,” Cancer, vol. 82, pp. 412–414, 1998.
- F. Jover, J. M. Cuadrado, and J. Merino, “Possible azithromycin-associated hiccups,” Journal of Clinical Pharmacy and Therapeutics, vol. 30, no. 4, pp. 413–416, 2005.
- J. Micallef, S. Tardieu, V. Pradel, and O. Blin, “Benzodiazepine and hiccup: three case reports,” Therapie, vol. 60, no. 1, pp. 57–60, 2005.
- P. Marhofer, C. Glaser, C. G. Krenn, C. M. Grabner, and M. Semsroth, “Incidence and therapy of midazolam induced hiccups in paediatric anaesthesia,” Paediatric Anaesthesia, vol. 9, no. 4, pp. 295–298, 1999.
- H. Miyaoka and K. Kamijima, “Perphenazine-induced hiccups,” Pharmacopsychiatry, vol. 32, no. 2, p. 81, 1999.
- P. A. LeWitt, N. W. Barton, and J. B. Posner, “Hiccup with dexamethasone therapy,” Annals of Neurology, vol. 12, no. 4, pp. 405–406, 1982.
- J. J. Vazquez, “Persistent hiccup as a side-effect of dexamethasone treatment,” Human and Experimental Toxicology, vol. 12, no. 1, p. 52, 1993.
- B. A. Baethge and M. D. Lidsky, “Intractable hiccups associated with high-dose intravenous methylprednisolone therapy,” Annals of Internal Medicine, vol. 104, no. 1, pp. 58–59, 1986.
- S. MacKay and S. Eisendrath, “Adverse reaction to dental corticosteroids,” General Dentistry, vol. 40, no. 2, pp. 136–138, 1992.
- S. Mehta, D. L. Nelson, J. R. Klinger, G. B. Buczko, and M. M. Levy, “Prediction of post-extubation work of breathing,” Critical Care Medicine, vol. 28, no. 5, pp. 1341–1346, 2000.
- D. C. Lipps, B. Jabbari, M. H. Mitchell, and J. D. Daigh Jr., “Nifedipine for intractable hiccups,” Neurology, vol. 40, no. 3, pp. 531–532, 1990.
- N. L. Friedman, “Hiccups: a treatment review,” Pharmacotherapy, vol. 16, no. 6, pp. 986–995, 1996.
- N. Szigeti and G. Fábián, “Prolonged hiccups—successful medical therapy,” Orvosi Hetilap, vol. 146, no. 41, pp. 2117–2119, 2005.
- R. Moretti, P. Torre, R. M. Antonello, M. Ukmar, G. Cazzato, and A. Bava, “Gabapentin as a drug therapy of intractable hiccup because of vascular lesion: a three-year follow up,” Neurologist, vol. 10, no. 2, pp. 102–106, 2004.
- G. Petroianu, G. Hein, A. Stegmeier-Petroianu, W. Bergler, and R. R. Gabapentin, ““Add-on therapy” for idiopathic chronic hiccup (ICH),” Journal of Clinical Gastroenterology, vol. 30, pp. 321–324, 2000.
- Y.-C. Lin, “Acupuncture for persistent hiccups in a heart and lung transplant recipient,” Journal of Heart and Lung Transplantation, vol. 25, no. 1, pp. 126–127, 2006.
- P. Walker, S. Watanabe, and E. Bruera, “Baclofen, a treatment for chronic hiccup,” Journal of Pain and Symptom Management, vol. 16, no. 2, pp. 125–132, 1998.
- P. Gilbar and I. McPherson, “Severe hiccups during chemotherapy: corticosteroids the likely culprit,” Journal of Oncology Pharmacy Practice, vol. 15, no. 4, pp. 233–236, 2009.
Copyright © 2013 Mark E. Peacock. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.