Clinical Intelligence

Juan Brañuelas Quiroga, José Urbano García and Julio Bolaños Guedes

Hiccups: a common problem with some unusual causes and cures

INTRODUCTION decreased breath sounds with scattered Hiccups is a reflex consisting of a sudden crackles. His abdomen was normal, and spasmodic contraction of the diaphragm there was no temporal artery tenderness. causing shaking of the inspiratory muscles A chest X-ray (CXR) showed mediastinal of the chest and abdomen, followed by widening. Thoracic computed tomography the sudden closure of the glottis, which angiography was requested, and showed generates a characteristic noise of air being tissue surrounding the aortic wall, with violently expelled from the lungs. The hiccup diffuse circumferential swelling caused reflex consists of the afferent limb (phrenic by an acute thoracic aorta intramural nerve, vagus nerve, or thoracic sympathetic haematoma extending from the left fibres), the central connection (not involving subclavian as far as the renal arteries, with a specific centre), and the efferent limb a maximum transverse diameter of 4.7 cm (primarily the phrenic nerve). (Figure 1). The aortopulmonary window Depending on their duration, hiccups are was occupied by the aortic haematoma classified as transient hiccups (episodes (Figure 2), and there were two ulcers in lasting seconds or minutes), persistent the descending thoracic aorta (Figure 3). hiccups (longer than 48 hours), and No signs of rupture or dissection were recurrent hiccups (episodes of hiccups more seen. A 6.7 cm infra-renal abdominal aortic lasting than transient and often with frequent aneurysm with large intramural thrombus repetition). In most bouts of transient hiccups associated with no signs of rupture was the aetiology is unknown. In the case of also discovered. persistent hiccups the most frequent causes In order to seal the aortic ulcers and are gastro-oesophageal diseases (Table 1).1 prevent haematoma progression, hybrid This article describes an unusual cause of surgery (combining open and endovascular persistent hiccups and considers some of the approaches) was performed several remedies that can be used for the condition. days after admittance. During surgery a haematoma in the ascending aorta CASE REPORT was observed, with a bleeding point at A 68-year-old man with a history of smoking the proximal graft anastomosis, and the (20 pack–years) and a left upper lobe defect repaired. However, at 72 hours after lobectomy for tuberculosis 50 years ago, surgery, the patient became neurologically came to his primary care doctor following unreactive, despite having sedation about 10 days of persistent hiccups, malaise, suspended 36 hours before. A brain CT was Juan Brañuelas Quiroga, degree in medicine, GP, Lagasca Health Center, Madrid. José and costal and lumbar pain of mild intensity. reported as showing diffuse brain oedema Urbano García, MD, PhD, Vascular and A blood test was requested and omeprazole with signs of tonsillar and bilateral uncal Interventional Radiology, Coordinator of the 20 mg daily was prescribed. herniation, and intraventricular bleeding. Unit of Vascular and Interventional Radiology, The patient came back 6 days later to Electroencephalogram (EEG) was reported Fundación Jiménez Díaz, Madrid. Julio Bolaños Guedes, degree in medicine, Internal Medicine collect the blood test results, with symptoms as characteristic of brain electrical silence. Physician, Fundación Jiménez Díaz, Madrid. persisting. The tests revealed slight Address for correspondence leucocytosis, C-reactive protein elevation DISCUSSION Juan Brañuelas Quiroga, CS Lagasca, Calle (14.29 mg/dL), erythrocyte sedimentation Most hiccup episodes are self-limiting and Lagasca 122, Madrid, 28006, Spain. rate (84 mm/hr), total bilirubin (2.6 mg/ disappear after a few minutes. Despite being E-mail: [email protected] dL), direct (0.7 mg/dL), indirect (1.9 mg/dL), very frequent, they do not have any clinical Submitted: 16 March 2016; Editor’s response: 24 March 2016; final acceptance: 4 May 2016. and rheumatoid factor (63 UI/ml). He was repercussions, and medical care is not ©British Journal of General Practice 2016; referred to the emergency department for usually requested. 66: 584–586. evaluation. DOI: 10.3399/bjgp16X687913 On admission his general condition was DIAGNOSIS reasonable: lung auscultation revealed To target the cause of hiccups, it is very

584 British Journal of General Practice, November 2016 Table 1. Causes of persistent hiccups Central nervous Vascular system disorders Ischaemic/haemorrhagic stroke, AV malformations, temporal arteritis Infections Encephalitis, meningitis, brain abscess, neurosyphilis, subphrenic abscess Structural Head trauma, intracranial neoplasms, brainstem neoplasms, multiple sclerosis, syringomyelia, hydrocephalus Vagus and phrenic Goitre, pharyngitis, laryngitis, hair or foreign-body irritation of tympanic membrane, nerve irritation neck cyst or other tumour Gastrointestinal Gastric distention, gastritis, peptic ulcer disease, pancreatitis, pancreatic cancer, disorders gastric carcinoma, abdominal abscesses, gallbladder disease, inflammatory bowel disease, hepatitis, aerophagia, oesophageal distention, oesophagitis, bowel obstruction Figure 1. CTA sagittal image of thoracic aorta Thoracic disorders Enlarged lymph nodes secondary to infection or neoplasm, pneumonia, empyema, intramural haematoma (arrows). CTA = computed bronchitis, asthma, pleuritis, aortic aneurysm, mediastinitis, mediastinal tumours, tomography angiography. chest trauma, pulmonary embolism Cardiovascular disorders Myocardial infarction, pericarditis Toxic–metabolic Alcohol Diabetes mellitus Herpes zoster Hypocalcaemia Hypocapnia Hyponatraemia Influenza Malaria Tuberculosis Uraemia Postoperative General anaesthesia Gastric distention Intubation (stimulation of glottis) Traction on viscera Neck extension (stretching phrenic nerve roots) Drugs Alpha methyldopa Dexamethasone Short-acting barbituates Diazepam Chemotherapeutic agents (for example, carboplatin) Psychogenic Anorexia nervosa Malingering Conversion reaction Schizophrenia Excitement Stress

Figure 2. MPR coronal image: tissue surrounding aortic wall and diffusely circumferential swell that corresponds to the arterial wall haematoma aortic. important to take a thorough clinical history, diaphragm, which was an initial symptom of (2) Aortic lumen. (1) This haematoma extends, partially occupying the aortopulmonary window asking about smoking and drug misuse, and the patient with hiccups. (arrows). MPR = multiplanar reconstruction. drugs, gastrointestinal symptoms (heartburn, In the differential diagnosis of persistent dysphagia, regurgitation, or abdominal hiccups, the following questions can help pain), cardiorespiratory symptoms (chest us: does it only happen when awake? Or pain, cough, or dyspnoea), and neurological does it occur day and night? In the first case symptoms (headache, diplopia, dizziness, the hiccups are probably functional and the or abnormal sensitivity). An appropriate causes are gastric dilatation, aerophagia, physical examination (vital signs, otoscopic, and gastro-oesophageal reflux disease. In pulmonary and cardiac auscultation, and the second case it is more likely to be due to abdominal and neurological examination) toxic–metabolic causes, chronic alcoholism, must be conducted. When indicated, oesophageal and gastric tumours, pleural additional tests should be requested that involvement, mediastinal or diaphragmatic, are aimed at diagnosis (blood tests, chest or intracranial lesions.2 In children, or in an X-ray, ECG, gastroscopy, abdominal CT, and adult in whom all these causes have been cranial MRI) (Figure 4).1 excluded, the existence of a foreign body in In the present case, the CXR guided us to the ear should be expected.2,3

Figure 3. CTA axial image of thoracic aorta with the diagnosis and CT was needed to confirm parietal haematoma. (1) Aortic lumen. (2) Image of the cause of persistent hiccups: an acute COMPLICATIONS penetrating aortic ulcer (arrow). CTA = computed aortic syndrome that caused thoracic aortic Complications from hiccups are rare but they tomography angiography. enlargement due to an intramural aortic can occur and include discomfort, difficulty haematoma. This haematoma extended to in feeding, gastro-oesophageal reflux, partially occupy the aortopulmonary window respiratory alkalosis (in tracheostomised and presumably caused compression patients), wound dehiscence, sleep of the phrenic nerve that stimulates the deprivation, and psychiatric disorders.4

British Journal of General Practice, November 2016 585 Figure 4. Evaluation of persistent hiccups. CT = computed tomography. CXR = chest X-ray. Hiccups longer ENT = ear, nose, and throat. LFTs = liver function than 48 hours tests. LP = lumbar puncture. MRI = magnetic resonance imaging. Sx = symptoms. History and physical exam (CXR, glucose, creatinine)

Abnormal Toxic- Neurological ENT Sx or Gastrointestinal CXR metabolic Sx or findings findings Sx or findings

Chest CT MRI with Endoscopy; with contrast abdominal CT scan; contrast LP LFTs; oesophogeal manometry Drug and Refer for REFERENCES alcohol screen, ENT 1 Lembo AJ. Overview of hiccups. 2016. http:// in addition to evaluation www.uptodate.com/contents/overview-of- screening blood hiccups (accessed 6 Sep 2016). tests 2 Balboa Rodríguez A, Bixquert Jiménez M. Gastroparesia, náuseas, vómitos, hipo y bezoar. [Gastroparesis, nausea, vomiting, MANAGEMENT from ejaculation, which may terminate the hiccups, and bezoars]. In: Ponce García J, ed. Tratamiento de las enfermedades The recommendations for treatment of reflex arc causing the hiccups), and even gastroenterológicas. [Treatment of transient hiccups are nasopharyngeal smoking marijuana.14 gastroenterological diseases]. 3rd edn. stimulation (drinking a glass of water, or Asociación Española de Gastroenterología, CONCLUSION 2011: 91–92. inserting a tube through the nose as far as the back wall of the pharynx for 20seconds), Most hiccup episodes are self-limiting and 3 Lossos IS, Breuer R. A rare case of hiccups. N Engl J Med 1988; 318(11): 711–712. vagal stimulation (carotid sinus massage, disappear after a few minutes. Despite being 4 Juan Rey R, Solari LA. El paciente con hipo. cold compress to face, or induced vomiting), very frequent, they do not have any clinical [The patient with hiccups]. Lo cotidiano, lo and respiratory manoeuvres (holding repercussions, and medical care is not agudo, lo complejo 2010; 1(7): 18–19. the breath, cough, Valsalva manoeuvre, usually requested. But sometimes hiccups 5 Friedman NL. Hiccups: a treatment review. or breathing into a paper bag). These are a manifestation of a major disease, as Pharmacotherapy 1996; 16(6): 986–995. manoeuvres are, in general, effective only in the case described in this article. Here, 6 Newsholme Davis J. An experimental study in shortening an attack of acute hiccups the origin of the hiccups was a thoracic of hiccup. Brain 1970; 93(4): 851–872. and not in the treatment of persistent or aortic enlargement due to an intramural 7 Steger M, Schneemann M, Fox M. aortic haematoma likely to encourage Systemic review: the pathogenesis and recurrent hiccups. pharmacological treatment of hiccups. The purpose of these manoeuvres direct contact with the phrenic nerve, which Aliment Pharmacol Ther 2015; 42(9): 1037– is the attempt to interrupt the reflex arc stimulated the diaphragm. To target the 1050. thought to maintain repetitive diaphragmatic cause of hiccups, it is extremely important to 8 Askenasy JJ, Boiangiu M, Davidovitch S. contractions.5 This is most often attempted obtain a thorough clinical history. Persistent hiccup cured by amantadine. N Engl J Med. 1988; 318(11): 711. by breath holding, the Valsalva manoeuvre, 9 Bendersky G, Baren M. Hypnosis in the or breathing into a paper bag. Physiological termination of hiccups unresponsive to studies have demonstrated a mechanism by conventional treatment. Arch Intern Med which these manoeuvres improve hiccups, 1959; 104: 417–420. with the frequency of hiccups decreasing as Patient consent 10 Schiff E, River Y, Oliven A, Odeh M. 6 arterial PCO2 rises. The patient’s family consented to the Acupuncture therapy for persistent hiccups. publication of this article and the images. Am J Med Sci 2002; 323(3): 166–168. In the case of persistent hiccups, the 11 Fesmire FM. Termination of intractable following drugs are used: haloperidol Provenance hiccups with digital rectal massage. Ann 2–5 mg/24 hr, metoclopramide 10 mg, Freely submitted; externally peer reviewed. Emerg Med 1988; 17(8): 872. baclofen7 5 mg/8 hr, phenytoin, valproic acid, 12 Petroianu GA. Treatment of singultus by carbamazepine, gabapentin, amitriptyline, Competing interests sexual stimulation: who was George T and amantadine.8 Chlorpromazine 25–50 mg The authors have declared no competing Dexter, MD (c1812–?)? J Med Biogr 2016; interests. 24(2): 252–261 intramuscularly or intravenously is effective in up to 80% of cases. 13 Peleg R, Peleg A. Case report: sexual Acknowledgements When hiccups fail to respond to the intercourse as potential treatment for The authors would like to thank the patient’s intractable hiccups. Can Fam Physician 2000; above therapies, other treatment options family. 46: 1631–1632. can be tried, including surgery, hypnosis,9 14 Gilson I, Busalacchi M. Marijuana for acupuncture,10 rectal massage,11 sexual Discuss this article intractable hiccups. Lancet 1998; 351(9098): 12 13 Contribute and read comments about 267. stimulation, ejaculation (possibly as a result of the sympathetic stimulus stemming this article: bjgp.org/letters

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