- Hiccups: Causes, treatments, and complications
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Prednisolone may cause hiccups | SpringerLink. |
Transient Hiccups Associated with Oral Dexamethasone.
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Hiccups, or singulata hiccup is singultusare 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 singultusare 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 [ 1 ]. Hiccups that linger on for some time may become worrisome to the postoperative patient, thus hindering their nutritional and sleep needs [ 23 ]. 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 [ 5 ].
The frequency of hiccups in males and females is equivalent, although intractable hiccups occur at a much higher rate in men [ 67 ]. 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 [ 89 ]. The afferent limb contains the phrenic and vagus nerves together with the sympathetic chain from T6 to T 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 [ 410 ].
One review proposed that the hiccup reflex arc is a myoclonic action and not a true reflex [ 11 ]. Medical conditions that have been associated with the development of hiccups include gastrointestinal, neurological, pulmonary, psychogenic, cardiovascular, metabolic, anesthesia related, and drug induced conditions [ 3481213 ]. Using a strict standard, drugs have not been proven to be a common cause of hiccups [ 714 ]. Nevertheless, many clinicians have alluded to various medications as triggering the hiccup reflex [ 1361315 — 24 ].
The following case describes a patient who experienced transient hiccups following oral presurgical administration of dexamethasone. A 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. 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. 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. There are few reports in the literature on dexamethasone-induced hiccups and none in the dental literature [ 615182324 ].
Other cases of corticosteroid-induced hiccups have been reported [ 125 ], and Dickerman et al. The only other adverse reaction to steroids found in the dental literature was a case of episodic psychiatric disturbance cognitive dysfunction in an year-old female who had taken dexamethasone briefly [ 26 ].
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 listalthough Thompson and Landry state that there is not sufficient proof that any drug can be considered as definitely causing hiccups [ 14 ].
Souadjian and Cain reviewed cases of protracted hiccups and did not mention any medication in the etiology of hiccups [ 7 ]. Garvey, who looked at postoperative cases of hiccups, came to the logical conclusion that the etiologic factor was probably drug related [ 3 ]; however, she also recounted that the intubation itself may be a contributing factor [ 27 ].
The case described here was mild and short term and, even though somewhat inconvenient to the patient, was in practice, clinically insignificant. There are various reports in the literature of different treatments for protracted hiccups, including pharmacologic agents [ 458182228 — 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 [ 61729 ]. Baclofen has been shown to successfully treat chronic hiccups [ 34193034 ], and promising results have been attained with the use of gabapentin alone [ 31 ] or as an add-on to combination therapy [ 532 ].
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 [ 35 ], drugs that are commonly used in medicine, including dental medicine.
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.
Hung, M. Miller, and M. Arnulf, D. Boisteanu, W. Whitelaw, J. Cabane, L. Garma, and J. Kolodzik and M. Smith and A. Ross, M. Eledrisi, and P. Souadjian and J. Launois, J. Bizec, W. Cabane, and J. Takiguchi, R. Watanabe, K. Nagao, and T. Thompson and J. Liaw, C. Wang, H. Chang et al. Dickerman and S. Dickerman, C. Overby, M. Eisenberg, P. Hollis, and M. Cersosimo and M. Jover, J. Cuadrado, and J. Micallef, S. Tardieu, V. Pradel, and O. Marhofer, C. Glaser, C.
Krenn, C. Grabner, and M. Miyaoka and K. LeWitt, N. Barton, and J. Baethge and M. MacKay and S. Mehta, D. Nelson, J. Klinger, G. Buczko, and M. Lipps, B. Jabbari, M. Mitchell, and J. Daigh Jr. Szigeti and G. Moretti, P.
Hiccups may result in severe dehydration, malnourishment, and distress [1]. Among corticosteroids, dexamethasone has the greatest risk of. Prednisolone is the active metabolite of the drug prednisone and is preferred years and older, with hiccups following administration of prednisolone. Hiccups may result in severe dehydration, malnourishment, and distress [1]. Among corticosteroids, dexamethasone has the greatest risk of. Prednisone Side Effects by Likelihood and Severity scaling of the skin; headache; hiccups; nausea; abdominal bloating; high blood sugar; a feeling of. The drugs that are known to cause hiccups in patients include steroids, benzodiazepines, barbiturates, antibiotics, phenothiazines, opioids, and. On this page. Takiguchi, R. There is a need for a high index of suspicion whenever a patient develops hiccups while taking dexamethasone. The aetiology of hiccups is largely unknown, but the neural pathway consists reflex arc of 3 components, the afferent limb including phrenic, vagus and sympathetic nerves to convey somatic and visceral sensory signals, the central processing unit in the midbrain and the efferent limb traveling in motor fibers of phrenic nerves to diaphragm and intercostal nerves to the intercostal muscles, respectively [9] [10] [11].Hiccups are common, usually mild with no obvious cause and often resolve spontaneously. They are classified as transient, persistent and intractable depending on the duration.
Drug induced hiccups have been reported in medical literature but not common and corticosteroids are often cited. This report involved 2 male patients who developed persistent hiccups following use of oral dexamethasone for inflammatory conditions. The hiccups were severe and intolerable and could not stop despite use of metoclopramide and chlorpromazine. The hiccups only stopped following discontinuation of the dexamethasone. It should be noted that low dose of dexamethasone was used.
Management of dexamethasone induced hiccups involves discontinuation of the drug, steroid rotation if the patient is steroid dependent and use of metoclopramide and chlorpromazine. Clinicians should be aware of this known but rare adverse effect of dexamethasone as it could be severe, distressful and negatively impart patients care. There is a need for a high index of suspicion whenever a patient develops hiccups while taking dexamethasone.
Hiccups are sudden, uncontrolled contractions of the diaphragm, followed by immediate inspiration and closure of the glottis over the trachea [1]. They are also known as Singulta. They are very common, usually mild with no obvious cause and often resolve spontaneously.
They occasionally become severe, prolonged and distressful. The self limited episodes of hiccups transient are common in healthy individuals and believed to be induced by the rapid stomach distension and irritation caused by overeating, eating too fast, ingesting spicy food, drinking carbonated drinks, aerophagia and sudden change in ingested food temperature [5].
Persistent hiccups are most likely to be associated with an underlying pathological, anatomic or organic disease process [6]. Intractable hiccups are usually indicative of a serious organic disturbance and if left untreated, can cause severe discomfort, depression, reduced physical strength, and even death [7] [8].
The aetiology of hiccups is largely unknown, but the neural pathway consists reflex arc of 3 components, the afferent limb including phrenic, vagus and sympathetic nerves to convey somatic and visceral sensory signals, the central processing unit in the midbrain and the efferent limb traveling in motor fibers of phrenic nerves to diaphragm and intercostal nerves to the intercostal muscles, respectively [9] [10] [11].
Dopaminergic and gamma-amino-butyric-acid GABA-ergic neurotransmitters modulate this central mechanism. Activation of above pathway by chemical, mechanical and psychological stimuli results in hiccups.
It has been proposed that dexamethasone decreases the threshold for synaptic transmission in the midbrain and eventually induces hiccups [12]. Several medical conditions have been associated with the development of hiccups and they include gastrointestinal, neurological, pulmonary, psychogenic, cardiovascular, metabolic, anesthesia related and drug induced conditions [13] [14].
Although steroid induced hiccups are rare, they are much more frequent with dexamethasone than with other corticosteroids [15] [16]. There has not been any reported case of dexamethasone induced hiccups in Nigeria despite its wide use in management of inflammatory conditions. It is against this background that we reported these 2 cases of persistent hiccups following use of oral dexamethasone. A year-old male civil servant presented to the outpatient clinic with recurrent cough and nasal congestion of about 4 weeks.
There was associated sneezing and mild frontal headache but there was no history of fever or hemoptysis. The above symptoms were worsened by exposure to cold environment. He is known to have atopy with previous history of cough and nasal congestion. Physical examination was essentially normal.
HIV serology was seronegative. COVID test was also non-reactive. Radiological investigations were normal. He was placed on Levofloxacin and sinufed which gave him significant relief but symptoms recurred immediately the medications were stopped after 7 days. He was later given Dexamethasone 6 mg daily and sinufed tablets. The cough, nasal congestion and headache subsided following use of above medications for 3 days but he developed persistent hiccups.
He was given metoclopramide, 10 mg thrice daily for two days. Chlorpromazine was later introduced and the dose was progressively escalated to 50 mg thrice daily. The hiccups still persisted. At this point, drug induced hiccups were suspected and dexamethasone was eliminated from his medications. A year-old male trader presented to the outpatient clinic with progressive low back pains of about 5 years duration. The pain was progressive, left sided and radiated to the left thigh, leg and foot.
There was associated difficulty with ambulation, insomnia and the pain was not relieved by use of over the counter medications. There were normal bowel and urinary functions. He was diagnosed to have type 2 diabetes in and is well-controlled on diet alone. He is not known to have any other chronic medical condition.
Physical examination was normal except bilateral positive straight leg raising sign worse on the left. Radiological investigation suggested lumbosacral spondylosis with disc prolapse. Complete blood count and kidney function test were normal. After one week on above medications, the symptoms did not improve significantly. Tablets Celecoxib mg bd, Dihydrocodene 30 mg bd, and Pregabalin 75 mg bd were added to the previous medications.
There was mild improvement of the symptoms but was limited by drowsiness. Following the use of above medications for 2 days, the low back pain subsided significantly but he developed hiccups and worsening blood glucose control. A suspicion of dexamethasone induced hiccups was made and the dose was reduced to 2 mg tds but the hiccups and hyperglycemia persisted. Dexamethasone was then discontinued after next 2 days and the hiccups and hyperglycemia resolved. He was then continued on the other medications with significant pain control.
This study reported 2 cases of dexamethasone induced hiccups in Abakaliki Nigeria. The above 2 cases were noted within a space of 4 weeks amongst two men. The male predilection in this study is similar to previously reported study [17]. The reason for male predilection could stern from higher male prevalence of the risk factors for hiccups [18].
Both of them developed persistent hiccups following use of oral dexamethasone for treatment of inflammatory conditions. The hiccups were severe and intolerable that they were distressed, exhausted and unable to sleep.
They reported the side effect because it was severe, persistent and intolerable as their quality of life was significantly diminished. The hiccups persisted despite reduction of the dose of dexamethasone to 6 mg daily. This suggests that the dexamethasone induced hiccups may not be dose related as previously reported [19]. The pharmacologic treatment of steroid induced hiccups, including steroid rotation [15], chlorpromazine, metoclopramide, haloperidol, and baclofen had been reported to stop hiccups [20].
Chlorpromazine and metoclopramide could not stop the hiccups in case 1 as it was drug induced. The author used hind sight of case 1 to discontinue the dexamethasone in case 2 without use of chlorpromazine and metoclopramide. Steroid rotation was not applied as the patients were not steroid dependent but rather the dexamethasone was discontinued.
If above interventions could not resolve the hiccups, non-pharmacologic treatment which involves the interruption of the vagal afferent limb of reflex arc or stimulating the vagal nerve was shown to successfully resolve intractable hiccups [20].
There is a need for future studies to determine the hospital prevalence and epidemiology of steroid induced hiccups and also investigate the potential biomarkers that can help identify susceptible individuals. Dexamethasone has been reported to cause hiccups. Although hiccups are not usually life-threatening, they are important because they can be severe, intolerable and significantly diminish quality of life in patients.
Discontinuation of dexamethasone or switching from dexamethasone to other corticosteroids has been reported to relieve hiccups. Dexamethasone should be used with caution due to this adverse effect.
Written informed consent was obtained from the patients for their information to be published in anonymous form in this article. Chukwuemeka O EZE contributed to acquisition of data, analysis and interpretation of data and wrote the paper.
The authors declare no conflicts of interest regarding the publication of this paper. Annals of Emergency Medicine, 20, Journal of Clinical Rheumatology, 9, American Journal of Hospice and Palliative Medicine, 20, Journal of Neurogastroenterology and Motility, 18, Journal of the National Medical Association, 94, Psychosomatics, 41, Hiccups—Etilogy and Treatment.
Anesthesia Progress, 57, BMJ, , Acta Anaesthesiologica Scandinavica, 37, The Oncologist, 18, Transactions of the American Neurological Association, 92, Journal of the National Cancer Institute, 94, American Journal of Case Reports, 20, The Oncologist, 22, Journal of Pain and Symptom Management, 51, Cancer, 82, CO; [ 20 ] Abbasi, A.
Home Journals Article. Chukwuemeka O. Nnaji , Monday U.
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