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  • Dr Binula Wickramarachchi

Intractable Hiccups

Updated: Apr 9

Dr Binula Wickramarachchi Emergency Physician

Peer Review: Dr David McCreary


THE CASE

A 72-year-old man presents to the emergency department with persistent hiccups for 4 days. As you walk over to his cubicle, you think back to all the different ways you’ve tried to cure your own hiccups. What does holding your breath, drinking water upside down and getting frightened have in common anyway?


AREN'T HICCUPS NORMAL?

Hiccups are a normal everyday experience, usually attributed to a trigger such as a carbonated drink or spicy food. The vast majority of hiccups will last minutes to hours, and almost all benign cases of hiccups will last less than 48 hours. There are a number of theories as to the specific function of hiccups, with the most interesting being that it is a vestigial reflex, primarily involved in the maturation of the respiratory tract in utero. This is thought to be the reason that frequent hiccups in a foetus are a hallmark of the third trimester of pregnancy, as well as in the early neonatal weeks.


WHAT ARE HICCUPS?

Hiccups (AKA ‘singultus’ for those of you who are Latin-inclined) are spontaneous, involuntary and spasmodic contractions of the diaphragm and intercostal muscles, predominantly affecting the left hemidiaphragm. These spasms result in a sudden inspiration, which is immediately followed by the abrupt closure of the glottis, creating the onomatopoeic ‘hiccup’ sound. This process occurs in a reflex arc involving:

  • An afferent limb: phrenic & vagus nerves and the sympathetic chain.

  • A central mediator: thought to be within the medulla, near the respiratory centre.

  • An efferent limb: the phrenic nerve, as well as neural connections to the glottis and inspiratory intercostal muscles.

Anatomy of the hiccups reflux arc. M. Steger et al.

🤓 PHYSIOLOGY PEARL The sudden closure of the glottis is thought to be a protective reflex to prevent the hyperventilation that would result from hiccups. Patients with tracheostomies have been shown to develop hypocapnoea secondary to hiccups, as their airway bypasses the glottis.

WHAT CAUSES HICCUPS?

There are a multitude of causes of hiccups, but the underlying principle is that one or more parts of the above reflex arc are activated. This most commonly includes vagus or phrenic nerve activation due to gastro-oesophageal causes (gastric distension, GORD, gastritis, peptic ulcer disease or gastric cancer), but can also be due to inflammation or mass effect on these nerves anywhere in their course within the neck and thorax. Central nervous system aetiologies are also important to consider. Structural lesions such as tumour, aneurysm and vascular malformations in the medulla are of particular concern, and hiccups are specifically implicated in lateral medullary infarction. Hiccups in this category will however very rarely be an isolated symptom. The most significant consideration is that of malignancy. This can range from locally invasive gastro-oesophageal, pancreatic and lung cancers, to more advanced metastatic malignancies with significant thoraco-abdominal lymphadenopathy. The prevalence of hiccups in this population has been reported as high as 1 – 9%1. Other less frequent causes include:

  • Medication-related

    • Dexamethasone

    • Diazepam, midazolam

    • Tramadol

  • Metabolic

    • Hyponatraemia, hypokalaemia, hypocalcaemia & renal impairment

  • Psychogenic

    • These hiccups typically disappear during sleep

  • Post-operative

    • Related to irritation of the phrenic nerve

ASSESSMENT

Features on assessment that are important to elicit are:

  • Characterise the hiccups and their effects – time course, relieving factors, effects on quality of life (eating, drinking and sleeping)

  • Explore possible aetiologies – to exclude any treatable causes, as well as identify any features of malignancy

  • Examination – seeking features of infection or inflammation in the head, neck, chest or abdomen. Paying particular attention to potential mass lesions or lymphadenopathy.

Investigation with pathology and imaging can then be guided by the findings above. If the initial assessment is unremarkable, consideration should be given to initiating empirical treatment while further investigations are undertaken. If a patient is known to have advanced malignancy, the aetiology of intractable hiccups is likely multifactorial. It is generally recommended that the focus should be on symptomatic treatment of these patients, rather than exhaustive ongoing evaluation.


MANAGEMENT

The mainstay of treatment for hiccups of less than 48 hours is physical manoeuvres. Many of these will be familiar to us as home-cures for hiccups! These can be divided into:

  1. Inducing hypercapnia via breath-holding or breathing into a paper bag. This is thought to interrupt the hiccup reflex arc due to its effect on the medulla and the respiratory centre

  2. Stimulating the nasopharynx via drinking cold water, pulling on the tongue or performing a Valsalva. This increases vagal stimulation to interrupt the reflex arc.

🤓 FUN FACT The mechanism of frightening someone out of their hiccups is believed to occur due to the interruption of the reflex arc at the sympathetic chain, which forms part of the afferent limb of the arc.

For those patients with hiccups for more than 48 hours, empirical pharmacological treatment can be initiated. The evidence base for the use of many of these are not well established. Both single-drug therapy as well as multi-modal therapies may also be trialled.


The main options here are:

  1. Proton-pump inhibitors (PPI)

  2. Baclofen

  3. Gabapentin

  4. Metoclopramide

  5. Chlorpromazine

Various other medications have also been trialled, with very variable reports of efficacy in the literature. Some of these options are: haloperidol, amitriptyline, pregabalin, phenytoin, sodium valproate and carbamazepine.


THERE'S AN ALGORITHM FOR THAT...

Steger et al. (2)

BACK TO THE CASE

The patient tells you of their unfortunate recent diagnosis of advanced pancreatic cancer, and that they’re awaiting their initial oncology appointment in 2 days. The patient was started on regular pantoprazole and metoclopramide, with a plan for the oncology team to initiate baclofen if the hiccups had not resolved by the time of his oncology appointment.

SIMPSONS CONSULT

And finally, further proof that the Simpsons have always been ahead of their time and have an answer for everything...


REFERENCES

  1. Calsina-Berna, A., García-Gómez, G., González-Barboteo, J., & Porta-Sales, J. (2012). Treatment of chronic hiccups in cancer patients: a systematic review. Journal of palliative medicine, 15(10), 1142-1150

  2. Steger, M., Schneemann, M., & Fox, M. (2015). Systemic review: the pathogenesis and pharmacological treatment of hiccups. Alimentary pharmacology & therapeutics, 42(9), 1037-1050.

  3. Kahrilas, P. J., & Shi, G. (1997). Why do we hiccup?. Gut, 41(5), 712-713.

  4. Polito, N. B., & Fellows, S. E. (2017). Pharmacologic interventions for intractable and persistent hiccups: a systematic review. The Journal of Emergency Medicine, 53(4), 540-549.


BINULA WICKRAMARACHCHI

Emergency Physician

Binula is an Emergency Physician at the Alfred Hospital. He grew up among the verdant hills of Auckland, New Zealand, obtaining his medical degree and Postgraduate Diploma in Clinical Education at the University of Auckland. He also has a passion for point of care ultrasound, particularly echo and lung ultrasound. At home, Binula is a devoted parent to his two feline daughters, and is the household co-lead for the acclimatisation to a new human child.

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