Diagnosis and management of hiccups in the patient with advanced cancer

Benign, self-limited hiccups are more of a nuisance, but persistent and intractable hiccups lasting more than 48 hours and 1 month, respectively, are a source of significant morbidity in the patient with advanced malignancy.The hiccup reflex is complex, but stimulation of vagal afferents followed by activation of efferent phrenic and intercostal nerve pathways results in contraction of the diaphragm and intercostal muscles, respectively.The etiology of hiccups in the cancer and palliative care population may include chemotherapy, electrolyte derangements, esophagitis, and neoplastic involvement of the central nervous system (CNS), thorax, and abdominal cavity. Prolonged hiccups can result in depression, fatigue, impaired sleep, dehydration, weight loss, malnutrition, and aspiration syndromes. Evaluation should be symptom-directed, focusing mainly upon the CNS and thoracoabdominal cavities as well as assessment of medications and serum chemistries. Most patients with ongoing hiccups require pharmacotherapy, with chlorpromazine being the only US Food and Drug Administration-approved agent. However, numerous other medications have been reported to be efficacious for treating intractable hiccups. Gabapentin has recently been shown to terminate hiccups effecitvely in cancer patients and may emerge as a therapy of choice in the palliative setting due to favorable tolerability, pain-modulating effects, minimal adverse events, and lack of drug interactions.