Cisplatin-Related Hiccups: Male Predominance, Induction by Dexamethasone, and Protection Against Nausea and Vomiting

Abstract

Dexamethasone is likely to play a role in the etiology of hiccups in patients receiving cisplatin-based regimens. Two hundred seventy-seven patients received three doses of ondansetron 8mg intravenously (IV) at 4hour intervals plus dexamethasone 20mg IV from the start of chemotherapy, followed by dexamethasone 5mg IV every 12hours, until chemotherapy was complete. Hiccups were observed in 114 (41.2%) patients, of whom 97.4% were men. Nausea and vomiting showed inverse correlations with hiccups (P < 0.0001 and P = 0.001, respectively). In 73 patients who experienced hiccups but lacked nausea/vomiting (H+N/V-), we discontinued dexamethasone in subsequent cycles. Sixty-six patients (90.4%) ceased hiccuping, but complete protection rates of nausea and vomiting decreased to 63% and 74%, respectively. For patients who experienced both hiccups and nausea/vomiting, the onset of nausea/vomiting usually was delayed to Day 3 or 4 and began after the cessation of hiccups. We conclude that cisplatin-related hiccups are predominant in males, dexamethasone-induced, and associated with protection against nausea/vomiting.

Treatment of Dexamethasone-Induced Hiccup in Chemotherapy Patients by Methylprednisolone Rotation

“…Liaw et al asserted that cisplatin and dexamethasone have synergistic stimulatory effects on the hiccup reflex arc [4]. In addition, most patients in our study (n ϭ 34, 85%) received platinum-containing regimens.…”

“…Our study had more detailed information on hiccup intensity and duration per episode compared with other hiccuprelated studies [4,9,23]. The recruited patients experienced moderate hiccup severity (median NRS: 5).…”

Severe hiccups associated with intra-articular corticosteroid injection — A case report

“…The central connection between the afferent and efferent limbs is not ascribed to a specific anatomic location in the spinal cord; it probably lies between C3 to C5, and involves interactions within the brainstem and the midbrain areas as well. The efferent portion of the arc primarily consists of the phrenic nerve, the glottis, accessory respiratory muscles, and multiple interactions between the brainstem and midbrain areas that involve the respiratory center, phrenic nerve nuclei, medullary reticular formation, and hypothalamus [9].…”

“…It has been suggested in animal studies that corticosteroids may stimulate the hiccup reflex arc and reduce the synaptic transmission threshold in the midbrain, thus affecting the metabolism of brain neurotransmitters. Moreover, stimulation of numerous steroid receptors within the efferent limb, including the medullary reticular formation, respiratory center, and hypothalamus in the hiccup reflex arc, lead to hiccups [9]. Standard doses of corticosteroids penetrate the brain only to a limited degree, but an exceedingly high dose can activate receptors in the hippocampus and hypothalamus as well as within the efferent limb of the hiccup reflex arc, thus leading to hiccups [10].…”

“…Hiccups can occur at any age and are equally prevalent in both sexes. However, persistent or intractable hiccup attacks are more common in men [2].…”