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Lynn was telling me about a case she saw this year – if I recall, it was a young man who developed uncontrollable hiccuping after an inguinal hernia repair. I don’t know what happened to the guy, but I saw my first hiccuping patient shortly thereafter. As I surf the web, I keep coming across remedies for this unusual but vexing complaint:

• Methylcellulose (to expand the stomach) 
• NG Tube (to decompress the stomach)
• An implantable vagal nerve stimulator
• Pressing on the ears while drinking through a straw
• Digital rectal massage (also reported in Annals of EM)
• Chlorpromazine 25-50mg IV (the only FDA-approved agent for intractable hiccups)

Our anesthesia colleagues have looked at this issue, as hiccuping in the OR is a pressing concern. Unfortunately, a systematic review (Kranke, Eur J Anaesthesiol 2003 Mar;20(3):239-44) turned up lots of anecdotes, but only one (inconclusive) RCT:

A large variety of interventions have been proposed for the treatment of hiccup during anaesthesia and sedation. However, perioperative treatment is still based on empirical findings and no treatment is ‘evidence-based’. Thus, no valid recommendations for the treatment of hiccup can be derived. Uncontrolled observations are inadequate to establish treatment efficacy.

More drug suggestions below, along with some background on hiccups…

 EMedicine has an exhaustive list of drug therapies:

Chlorpromazine is the most studied and appears to be the drug of choice. Increments of 25-50 mg IV/IM are effective in 80% of cases. To avoid or minimize hypotension from the agent, it is advisable to preload the patient with 500-1000 mL of IV fluid.

Another major tranquilizer, haloperidol, is effective in doses of 2-5 mg. Metoclopramide has been used successfully in a dose of 10 mg every 8 hours.

Several anticonvulsant agents have been used to treat intractable hiccups. Phenytoin, valproic acid, and carbamazepine have been effective when used in typical anticonvulsant doses. More recently, gabapentin has been shown to be effective where CNS lesions are present.

Of the anesthetic agents, ketamine has been the most successful at a dose of 0.4 mg/kg (one fifth of the usual anesthetic dose). Baclofen, a centrally acting muscle relaxant, administered at 10 mg 4 times a day orally, particularly is useful in patients for whom other agents are contraindicated (eg, those with renal impairment). IV lidocaine in a loading dose of 1 mg/kg, followed by an infusion of 2 mg/min, has cured patients after other agents were unsuccessful.

Other agents reported to be beneficial include muscle relaxants, sedatives, analgesics (eg, orphenadrine, amitriptyline, chloral hydrate, morphine), stimulants (eg, ephedrine, methylphenidate, amphetamine, nikethamide) and a miscellaneous group including edrophonium, dexamethasone, amantadine, and nifedipine. Benzodiazepines have been shown to exacerbate or precipitate hiccups and should be avoided. 

 Also called hiccoughs, and medically termed “singultus”, the pathophysiology of hiccups is still poorly understood.

A hiccup is a sudden, involuntary spasmodic contraction of the diaphragm and external intercostal muscles, that results in inspiration which abruptly ends with closure of the glottis.¹ Although the physiological role remains unknown, hiccups are usually short lived, uncomplicated, and affect healthy subjects on occasion. Rarely, hiccups can become persistent, intractable and even refractory to a variety of therapeutic modalities.

The hiccup reflex arc is comprised of afferent pathwaysvagal, phrenic, and sympathetic (T6-T12) branches. The efferent pathways are composed of the phrenic nerve to the diaphragm and nerves to the glottis and the external intercostal muscles. The central connection is the spinal cord between segments C3 and C5, possibly controlled by supraspinal pathways.

Here’s an evolutionary theory of hiccups:

Hiccoughs are characterized by glottal closure during inspiration and by early development in relation to lung ventilation. They are inhibited when the concentration of inhaled CO2 is increased and they can be abolished by the drug baclofen (an agonist of the GABA-B receptor). These properties are shared by ventilatory motor patterns of lower vertebrates, leading to the hypothesis that hiccough is the expression of archaic motor patterns and particularly the motor pattern of gill ventilation in bimodal breathers such as most frogs. A circuit that can generate hiccoughs may persist in mammals because it has permitted the development of pattern generators for other useful functions of the pharynx and chest wall muscles, such as suckling or eupneic breathing.

Posted on Tuesday, April 10th, 2007 at 7:56 am by Nick. Filed under GI, Procedures, Journal Club.
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