Author: Daniel Cabrera, M.D. / Reviewer: Dustin Leigh, M.D.

What are hiccups? Why is it important?

Hiccups are funny as long as somebody else is the one suffering. Although described since the beginning of civilization, understanding of this phenomenon is very poor(1) . There is scant medical literature focused on the topic with most of the current knowledge coming from the palliative care world(2).

The technical term for hiccup is singultus or synchronous diaphragmatic flutter(3). Singultus is a rhythmic movement of the diaphragm, occuring more common in males. Eighty percent is caused by unilateral contraction of the left hemi diaphragm, with a frequency of 20-60 hertz, and happening at any point of the respiratory cycle. Utility of singultus is unclear with some scientists speculating it is an evolutionary remnant from amphibian physiology(3).

Hiccups can be acute or chronic, defined by a duration threshold of 48 hours. Although in the ED some of the cases we face are acute, chronic singultus is commonly. In the palliative care population, it is particularly associated with cancer, affecting up to 9% of the patients. The impact of this disease can be significant, resulting in diet and sleep disruption, leading to severe emotional distress and even to death(2).

Why do people get hiccups? Should I be worried?

The pathophysiology of singultus is unclear, but is hypothesized to involve a complex reflex center of dopaminergic neurons in the reticular formation and hypothalamus, with the afferent pathway composed by the vagus and phrenic nerve and the efferent pathway being the phrenic nerve.

Hiccups can be caused by a laundry list of conditions. In the Emergency Department we need to elucidate what system is responsible for the singultus: CNS lesions? Metabolic? Infra or Supradiaphragmatic process? Medications? And ideally treatment should be tailored to the cause.  Here a table from Reference 2:

Management

Multiple interventions, including hundreds of home remedies, have been described; but their effectiveness remains unclear. We are going to discuss the treatments readily available in Emergency Departments, but it is important to consider that for chronic singultus, some patients may even require surgical management(2).

As discussed before, particular attention needs to be placed on managing the primary problem (e.g., small bowel obstruction, uremia, etc.)(1). Once identified, the next step is the symptomatic treatment. This is especially important in patients where the primary problem can’t be controlled. It appears to be reasonable to start with simple mechanical measures such as nebulized saline(2), some type of glottis stimulation or previous simple remedies that worked for the specific patient(1).

After simple mechanical maneuvers have failed, the next step is pharmacological treatment. The current knowledge and recommendations originate from low quality evidence; although a recent systematic review attempted to consolidate the current understanding of the treatment(2). Current evidence is as follows:

• Baclofen. A GABA analogue produces a central anti-spastic response. There is a small RCT using baclofen with modest results, however it is often considered the first line treatment by experts in the topic. The oral form has a very fast absorption which makes it attractive, but it is associated with sedation, particularly when used concurrently with other CNS depressants.
• Gabapentin. Evaluated in a small retrospective chart review. The mechanism of action appears to be the blockade of alpha-2 sensitive calcium channels, which may modulate the contraction of the diaphragm. 83% of the patients in the study had some relief. Gabapentin needs to be used carefully on patients with renal failure.
• Chlorpromazine. Evidence comes from a retrospective chart review of 8 patients and 50 patient case reports. The mechanism is probably due to its anti-dopaminergic effect. Although popular and advertised by the manufacturer to use in singultus for several years, the evidence to support its use is very scant. It only appears to be anecdotally efficacious. Chlorpromazine is poorly tolerated in elderly and hypovolemic patients (may cause marked hypotension).
• Midazolam. Supported by 2 case reports with 3 patients total. Its muscle relaxant and anticonvulsant effect probably supports its benefits. It appears to decrease the frequency of the singultus, particularly in patients who were living the last days of their lives.
• Other. There are other medications with weaker evidence behind their use: methylphenidate, metoclopramide, amantadine, nifedipine, nimodipine and haloperidol.

As a summary, the evidence supporting non-pharmacological and pharmacological treatments for singultus is almost non-existent. Key management principles need to be focused on identifying the etiology.  Treat the symptom as soon as possible, especially in patients with non-reversible causes. In our review of the evidence, it seems reasonable to start with basic glottis stimulating maneuvers. For those who fail mechanical maneuvers, proceed with pharmacologic intervention. Have a keen awareness of the lack of research supporting them and the potential for side effects. Baclofen and gabapentin, although with low level evidence, appear to be the most recommended by experts(2).

BONUS TRACK

These home remedies, although appealing for some folks and sometimes supported by case reports, are probably not efficacious in the treatment hiccups(2):

• Stimulation of the palate or pharynx with cotton applicator or catheter
• Traction on the tongue
• Pressure over the eyebrow area
• Lifting the uvula with a spoon
• Performing a Valsalva maneuver
• Pressing a finger firmly into each ear for approximately 20 seconds, with or without drinking a glass of water through a straw
• Drinking methylcellulose with warm water
• Breath holding
• Biting a lemon
• Breathing into a paper bag
• Sudden fright
• Digital rectal massage
• Drinking water from the opposite side of a cup
• Eating a spoonful of granulated sugar or peanut butter, gargling or drinking ice water, swallowing dry bread
• Black pepper induced sneezing
• Inserting a nasal catheter 8–12 cm so it rests opposite the second cervical vertebra
• Massaging the anterior of the soft palate in the midline for approximately one minute with a cotton-tipped swab
• Gastric aspiration via nasogastric tube
• C3 to C5 dermatome stimulation by percussion of the back of the neck
• Prolonged pressure on the diaphragm
• Compression of the phrenic nerve at the neck
• Irritation of the vagus nerve by supraorbital pressure or carotid sinus massage

REFERENCES

1. Woelk CJ. Managing hiccups. Can Fam Physician. 2011 Jun 1;57(6):672–5.
2. Calsina-Berna A, García-Gómez G, González-Barboteo J, Porta-Sales J. Treatment of chronic hiccups in cancer patients: a systematic review. J Palliat Med. 2012 Oct;15(10):1142–50.
3. Hiccup [Internet]. Wikipedia, the free encyclopedia. 2014 [cited 2014 Oct 24]. Available from: http://en.wikipedia.org/w/index.php?title=Hiccup&oldid=628432561

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