No useful function has been found for the hiccup, which occurs as a result of synchronous clonic spasm of intercostal muscles and diaphragm that causes sudden inspiration followed by prompt closure of the glottis and inhibition of respiratory activity. It is believed to be a reflex. There is debate about whether it is centrally mediated. The afferent pathway is from T10 to T12, and the efferent limb is along the phrenic nerve. During the hiccup, the glottis is closed. Some investigators believe that the hiccup is related more to gastrointestinal than to respiratory function. Current understanding of pathophysiology does not permit an explanation of how the presumptive etiologies operate to produce the hiccup, although the classic explanation is that it is due to stimulation of the phrenic nerve.

It is often unclear whether the reported causes of hiccup are etiologies or only associations. In a series of 220 cases seen at the Mayo Clinic, men outnumbered women by five to one, and most were in their 60s. More than 90% of the women had no concurrent illness other than an emotional problem, whereas only 7% of men were labeled as having a psychogenic disorder. About 20% of men who experienced hiccup did so after undergoing intra-abdominal, intrathoracic, or neurologic surgery. About 25% had a diaphragmatic hernia, another 20% had cerebrovascular disease or another central nervous system (CNS) problem, 5% had a metabolic illness, and in 10%, no associated disease or psychiatric problem was identified.

The typically listed causes of persistent hiccup are clinical associations and cannot be considered proven etiologies (Table 221-1).

Persistent hiccup that proves refractory to simple measures is an indication for further investigation. Of particular importance is check for a previously unsuspected metabolic, intrathoracic, or subdiaphragmatic pathology.