A hiccup is a repeated involuntary spasmodic contraction of the diaphragm followed by a sudden closure of the glottis which checks the inflow of air and produces the characteristic sounds. Hiccups result when afferent or efferent nerves to the muscles of respiration, or the medullary centres controlling these muscles are irritated. The underlying pathophysiology of intractable hiccups remains to be elucidated but is believed to involve organic, drug-induced, and/or psychological causes.
Various different therapies have been proposed for the treatment of hiccups. Chlorpromazine is the only licensed medicine for the treatment of intractable hiccups. However, other medicines, as outlined, have also been found to be effective. Combination therapies consisting of cisapride, omeprazole, baclofen, +/- gabapentin, have also been proposed when symptoms are refractory to other treatments. Intractable hiccups can be very distressing, and ultrasound-guided phrenic nerve block offers a plausible treatment modality for symptomatic long-term relief. Pulsed radiofrequency ablation of the phrenic nerve should be considered if phrenic nerve block provides only short-term relief of symptoms.
Hiccups are classified according to their duration:
Hiccups are spontaneous, myoclonic contractions of the diaphragm and, in many cases, the intercostal musculature. As first proposed by Bailey in 1943, it widely accepted that hiccups are generated by a ‘reflex arc’ with afferent, central and efferent components. The afferent impulse is carried by the vagus nerve, phrenic nerves or sympathetic nerve fibres (thoracic outflow T6–T12). Areas of the CNS involved in the hiccup response appear to include the upper spinal cord (C3–C5), the brainstem in the medulla oblongata near the respiratory centre, the reticular formation, and the hypothalamus. Dopaminergic and gamma-amino-butyric-acid (GABA-ergic) neurotransmitters can modulate this central mechanism. The efferent response of the reflex is carried by the phrenic nerve to the diaphragm that has been observed to contract unilaterally or, less often, bilaterally. Activation of the accessory nerves leads to contraction also of the intercostal muscles. This stereotyped sequence of events is completed by the reflex closure of the glottis by the recurrent laryngeal branch of the vagus nerve. The glottal closure is an important protective reflex because, without it, in patients with a tracheotomy hiccups lead to significant hyperventilation.
Hiccups follow irritation of afferent or efferent diaphragmatic nerves or of medullary centers that control the respiratory muscles, particularly the diaphragm. Hiccups are more common among men.
The cause is generally unknown, but transient hiccups are often caused by the following:
No specific evaluation is required for acute hiccups if routine history and physical examination are unremarkable; abnormalities are pursued with appropriate testing. Patients with hiccups of longer duration and no obvious cause should have investigations, probably including serum electrolytes, BUN and creatinine, chest x-ray, and ECG. Upper GI endoscopy and perhaps esophageal pH monitoring should be considered. If these are unremarkable, brain MRI and chest CT may be done.
The treatment of hiccups should address the specific cause. There are many times when the cause of hiccups cannot be identified or addressed, and in these cases, general measures/treatments should be instituted.
Evidence supporting drug treatment for intractable hiccups remains inconclusive. Due to the relatively rare occurrence of intractable hiccups, most of the documented cases are single case reports or retrospective case studies. If intractable hiccups remain resistant to non-pharmacological techniques, the strongest evidence to date supports the use of chlorpromazine 25 to 50 mg administered intravenously, with a second dose within 2 to 4 hours intravenously or intramuscularly. The patient should be monitored carefully for anticholinergic side effects, particularly sedation. If chlorpromazine fails to control intractable hiccups, nifedipine, metoclopramide, baclofen, or sodium valproate may be considered.
Phrenic nerve block can be performed under ultrasound guidance for persistent or intractable hiccups, when conservative and pharmacological treatment is unsuccessful. The phrenic nerve, which is part of the afferent pathway and the main efferent part of the hiccup reflex, is primarily composed of the anterior branch of spinal root C4. However, accessory branches from spinal roots C3 and C5 can contribute. The phrenic nerve travels caudally between the anterior scalene and omohyoid muscles and is sonographically visualized as a solitary round hypoechoic structure of about 0.76 mm. However, visualization of the phrenic nerve can be considered as time-consuming even in expert hands. The transverse cervical artery that crosses superficial to the phrenic nerve in 95% cases can help the operator in identifying the phrenic nerve.
The hiccup center is located in the spinal cord between the third and fifth cervical segments. The afferent limb of the hiccup reflex consists of the vagus and phrenic nerve with contributions of the sympathetic chain arising from the 6th to the 12th thoracic segments, whereas the efferent limb consists mainly from the phrenic nerve. The proposed mechanism attributable for persistent relief from hiccups after resolution of the phrenic nerve block is a neural pathway interruption.
Pulsed radiofrequency ablation of the phrenic nerve can be considered for management of intractable hiccups if the patient gets benefit from the local anaesthetic block. The procedure is performed under ultrasound guidance and is a safe and effective method that can result in long term resolution of the hiccups.