Hiccups are the sudden involuntary contractions of the diaphragm and intercostal muscles. They are generally benign and self-limited, however, in some cases they are chronic and debilitating. There are approximately 4000 admissions for hiccups each year in the United States. The hiccup reflex arc is composed of three components: (1) an afferent limb including the phrenic, vagus, and sympathetic nerves, (2) the central processing unit in the midbrain, and (3) the efferent limb carrying motor fibers to the diaphragm and intercostal muscles. Hiccups may be idiopathic, organic, psychogenic, or medication-induced. Data obtained largely from case studies of hiccups either induced by or treated with medications have led to hypotheses on the neurotransmitters involved. The central neurotransmitters implicated in hiccups include GABA, dopamine, and serotonin, while the peripheral neurotransmitters are epinephrine, norepinephrine, acetylcholine, and histamine. Further studies are needed to characterize the nature of neurotransmitters at each anatomical level of the reflex arc to better target hiccups pharmacologically.

/pdf/neurotransmitters-in-hiccups-2s8mkji1b9.pdf

Neurotransmitters in hiccups.

Persistent hiccups are a frustrating experience for palliative care patients, and can have a profound impact on their quality of life. This article provides an evidence-based approach overview of the causes and treatment of this not infrequently debilitating condition for such patients, with a management algorithm. In situations where no readily reversible cause is identified, or where simple physical manoeuvres, such as breath holding have failed, a systematic approach is required. Hiccups can be broadly divided into central and peripheral types. These respond differently to pharmacological intervention. The drug of choice for central causes of persistent hiccups is baclofen, with metoclopramide recommended as the first choice for peripheral causes. Midazolam may be useful in cases of terminal illness. Interventional procedures such as vagal or phrenic nerve block or stimulation should be considered in patients who are refractory to medications. The management of persistent hiccups still presents an ongoing clinical challenge however, requiring further research on pathophysiology and treatment strategies. Multinational randomised controlled trials to evaluate and compare both current and new medications or procedures to better manage this difficult condition are suggested as a means of reaching this goal.

https://spcare.bmj.com/content/bmjspcare/8/1/1.full.pdf

Management of hiccups in palliative care patients

Hiccups is a reflex consisting of a sudden spasmodic contraction of the diaphragm causing shaking of the inspiratory muscles of the chest and abdomen, followed by the sudden closure of the glottis, which generates a characteristic noise of air being violently expelled from the lungs The hiccup reflex consists of the afferent limb (phrenic nerve, vagus nerve, or thoracic sympathetic fibres), the central connection (not involving a specific centre), and the efferent limb (primarily the phrenic nerve)

Depending on their duration, hiccups are classified as transient hiccups (episodes lasting seconds or minutes), persistent hiccups (longer than 48 hours), and recurrent hiccups (episodes of hiccups more lasting than transient and often with frequent repetition) In most bouts of transient hiccups the aetiology is unknown In the case of persistent hiccups the most frequent causes are gastro-oesophageal diseases (Table 1)1

View this table:

Table 1 
Causes of persistent hiccups



This article describes an unusual cause of persistent hiccups and considers some of the remedies that can be used for the condition

A 68-year-old man with a history of smoking (20 pack–years) and a left upper lobe lobectomy for tuberculosis 50 years ago, came to his primary care doctor following about 10 days of persistent hiccups, malaise, and costal and lumbar pain of mild intensity A blood test was requested and omeprazole 20 mg daily was prescribed

The patient came back 6 days later to collect the blood test results, with symptoms persisting The tests revealed slight leucocytosis, C-reactive protein elevation (1429 mg/dL), erythrocyte sedimentation rate (84 mm/hr), total bilirubin (26 mg/dL), direct (07 mg/dL), indirect (19 mg/dL), and rheumatoid …

/pdf/hiccups-a-common-problem-with-some-unusual-causes-and-cures-4ygs662lc6.pdf

Hiccups: a common problem with some unusual causes and cures.

Symptoms, such as fever, dry cough, dyspnoea, and respiratory distress, are commonly described in patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Recently, a growing number of cases pertained to persistent hiccups have been reported by SARS-CoV-2 infected patients. The aim of this systematic review was to screen the current literature and provide a summary of the reported cases of SARS-CoV-2 infected patients presenting with persistent hiccups. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, PubMed, Scopus, and Web of Science databases were searched from inception until October 2021. Case reports or case series that provided a separate clinical description for patients with presenting complaints of persistent hiccups before or after COVID-19 diagnosis were retrieved. The critical appraisal checklist for case reports provided by the Joanna Briggs Institute (JBI) was employed to evaluate the overall quality of the eligible studies. We identified 13 eligible studies that included 16 hospitalized COVID-19 patients who complained of persistent hiccups. The mean duration of hiccups was 4.6 days reported in 88% (14/16) patients. Hypertension was the most common comorbidity present in 50% (8/16) of patients followed by diabetes mellitus (4/16). Moreover, 44% (7/16) of patients received only one medication for managing the hiccups with metoclopramide (5/16) followed by chlorpromazine and baclofen (4/16) used as primary treatment. Equally, 44% of patients (7/16) received dexamethasone followed by azithromycin (5/16), ivermectin (4/16), and ceftriaxone (4/16) for managing the infection from SARS-CoV-2. The majority of patients (14/16) improved after initiation of treatment. Persistent hiccups are possibly a rare symptom that clinicians may expect to encounter in patients infected with SARS-CoV-2. Although there is not ample proof to propose causation, increased awareness about the diversity of presentations of SARS-CoV-2 infection could be crucial in the early recognition of the disease.

Persistent Hiccups as an Atypical Presentation of SARS-CoV-2 Infection: A Systematic Review of Case Reports

https://www.researchsquare.com/article/rs-88175/v1.pdf?c=1613843461000

Efficacy of acupuncture for persistent and intractable hiccups: A protocol for systematic review and meta-analysis of randomized controlled trials.

SummaryBackground
Hiccups are familiar to everyone, but remain poorly understood. Acute hiccups can often be terminated by physical manoeuvres. In contrast, persistent and intractable hiccups that continue for days or months are rare, but can be distressing and difficult to treat.

Aim
To review the management of hiccups, including a systematic review of reported efficacy and safety of pharmacological treatments.

Methods
Available articles were identified using three electronic databases in addition to hand searching of published articles. Inclusion criteria were any reports of pharmaceutical therapy of ‘hiccup(s)’, ‘hiccough(s)’ or ‘singultus’ in English or German.

Results
Treatment of 341 patients with persistent or intractable hiccups was reported in 15 published studies. Management was most effective when directed at the underlying condition. An empirical trial of anti-reflux therapy may be appropriate. If the underlying cause is not known or not treatable, then a range of pharmacological agents may provide benefit; however, systematic review revealed no adequately powered, well-designed trials of treatment. The use of baclofen and metoclopramide are supported by small randomised, placebo-controlled trials. Observational data suggest that gabapentin and chlorpromazine are also effective. Baclofen and gabapentin are less likely than standard neuroleptic agents to cause side effects during long-term therapy.

Conclusions
This systematic review revealed no high quality data on which to base treatment recommendations. Based on limited efficacy and safety data, baclofen and gabapentin may be considered as first line therapy for persistent and intractable hiccups, with metoclopramide and chlorpromazine in reserve.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/apt.13374

Systemic review: the pathogenesis and pharmacological treatment of hiccups

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Systemic review: the pathogenesis and pharmacological treatment of hiccups