What is the management of intractable hiccups (singultus)?

From the Guidelines

Intractable hiccups should be managed with chlorpromazine, a phenothiazine, as it has been used to treat nausea/vomiting and intractable hiccups, as stated in the study 1.

Management Approach

When managing intractable hiccups, it's essential to consider a stepwise approach, starting with simple physical maneuvers before progressing to medications.

• Physical techniques like breath holding, drinking cold water, gargling with ice water, or applying gentle pressure on the eyeballs can be tried first.
• If these fail, medications like chlorpromazine (25-50 mg intramuscularly or intravenously) can be considered, as mentioned in the study 1.

Medication Considerations

• Chlorpromazine has anticholinergic properties, which may worsen the condition of patients with intoxication from drugs with anticholinergic properties or with an anticholinergic delirium, as noted in the study 1.
• The coadministration of chlorpromazine with other medications, such as benzodiazepines, may be considered for an additive effect, but close monitoring is necessary due to potential cardiac adverse effects, including QTc prolongation, as mentioned in the study 1.

Underlying Causes

• Throughout treatment, it's crucial to identify and address any underlying causes of intractable hiccups, such as gastroesophageal reflux, CNS disorders, metabolic disturbances, or medication side effects.
• Effective management of intractable hiccups is important for patient comfort and wellbeing, as persistent cases can lead to significant distress, sleep disruption, and nutritional problems.

From the FDA Drug Label

If symptoms persist for 2-3 days after trial with oral therapy, give 25 to 50 mg (1-2 mL) IM. Should symptoms persist, use slow IV infusion with patient flat in bed: 25 to 50 mg (1-2 mL) in 500 to 1000 mL of saline. Follow blood pressure closely. To manage intractable hiccups, the recommended dosage of chlorpromazine is:

• 25 to 50 mg (1-2 mL) IM if symptoms persist for 2-3 days after trial with oral therapy
• If symptoms persist, use slow IV infusion with patient flat in bed: 25 to 50 mg (1-2 mL) in 500 to 1000 mL of saline, and follow blood pressure closely 2

From the Research

Management of Intractable Hiccups

• Intractable hiccups can be managed with various pharmacologic treatments, including chlorpromazine, amitriptyline, baclofen, gabapentin, haloperidol, metoclopramide, midazolam, nifedipine, nimodipine, orphenadrine, and valproic acid 3
• The selection of therapy should be specific to individual patients, their underlying comorbidities, etiology of hiccups, and take into account the individual properties of the drugs 3
• Baclofen, gabapentin, and metoclopramide have been studied in a prospective manner, and baclofen and metoclopramide have been studied in randomized controlled trials 3

Pharmacological Treatment Options

• Metoclopramide has been reported to have effects on intractable hiccup, and its effectiveness and safety are being investigated in a systematic review and meta-analysis 4
• A systematic review of reported efficacy and safety of pharmacological treatments for hiccups found that baclofen and metoclopramide are supported by small randomized, placebo-controlled trials, and observational data suggest that gabapentin and chlorpromazine are also effective 5
• A multicentre, randomised, controlled pilot study found that metoclopramide appears to be a promising candidate for the treatment of patients with intractable hiccups, with mild adverse events 6

Treatment Considerations

• Management of hiccups is most effective when directed at the underlying condition, and an empirical trial of anti-reflux therapy may be appropriate 5
• The use of baclofen and gabapentin may be considered as first-line therapy for persistent and intractable hiccups, with metoclopramide and chlorpromazine in reserve 5
• Intractable hiccups can occur more often than realized and present to multiple medical disciplines, and a number of pharmacologic options have been found to be useful, including dopamine-blocking medication, baclofen, and gabapentin along with anticonvulsants 7