Acta Otorrinolaringol Esp.

2017;68(2):98---105

www.elsevier.es/otorrino

ORIGINAL ARTICLE

Hiccups. Attitude in Otorhinolaryngology Towards

Consulting Patients. A Diagnostic and Therapeutic
Approach夽
Francisco Javier García Callejo,a,∗ Jaume Redondo Martínez,a
Tomás Pérez Carbonell,a Rafael Monzó Gandía,b M. Paz Martínez Beneyto,a
Inés Rincón Piedrahitaa

a
Servicio de Otorrinolaringología, Hospital Clínico Universitario de Valencia, Valencia, Spain
b
Servicio de Otorrinolaringología, Hospital General de Requena, Requena, Valencia, Spain

Received 10 November 2015; accepted 23 May 2016

KEYWORDS Abstract
Hiccup; Introduction: Hiccup crises are generally benign and self-limiting, but longer episodes affect
Aetiology; quality of life and must be treated. There are recognisable causes that otorhinolaryngologists
Diagnostic; must know and be aware for diagnosis and therapeutic alternatives. The main expression is a
Therapy spasmodic glottic noise with characteristic neck alterations.
Patients and methods: This was a retrospective study from 1979 with patients suffering per-
sistent or recurrent hiccups. Chronobiology, comorbidity, findings from explorations, therapies
and outcomes were noted. Thirty-seven patients were studied (mean age, 45.5±13.5 years; 30
males), with persistent hiccups in 23 (62%).
Results: A potential associated aetiology was observed in 24 cases (65%): oesophageal disor-
ders---mainly gastroesophageal reflux---were detected in 14 cases and concomitant oncological
disease was found in 8. Only 3 cases were admitted for surgery due to these findings. Ther-
apeutic strategies with metoclopramide were used in 18 subjects, chlorpromazine in 17 and
baclofen in 13, while carbamazepine or haloperidol were used in a minority. Phrenic nerve
stimulation was employed in 6 patients. Hiccups disappeared in 32 cases. Out of 22 cases for
which follow-up was possible, the hiccups recurred in 5 subjects (the subjects requiring new
therapies) and 11 patients died.
Conclusions: Chronic hiccup represents a multidisciplinary challenge that includes potential
head and neck affection, a diagnostic schedule for ruling out causes, frequent base oesophageal
alterations and high incidence of malignant neoplasm. Prokinetic and neuroleptic agents with
antidopaminergic and anticholinergic effects are the pillars of its treatment.
© 2017 Published by Elsevier España, S.L.U.

夽 Please cite this article as: García Callejo FJ, Redondo Martínez J, Pérez Carbonell T, Monzó Gandía R, Martínez Beneyto MP, Rincón

Piedrahita I. Hipo. Actitud en otorrinolaringología en pacientes que consultan. Aproximación diagnóstica y terapéutica. Acta Otorrinolaringol
Esp. 2017;68:98---105.
∗ Corresponding author.

E-mail address: jgarciacall@hotmail.com (F.J. García Callejo).

2173-5735/© 2017 Published by Elsevier España, S.L.U.
Hiccups in Otorhinolaryngology 99

PALABRAS CLAVE Hipo. Actitud en otorrinolaringología en pacientes que consultan. Aproximación

Hipo; diagnóstica y terapéutica
Etiología;
Resumen
Diagnóstico;
Introducción: Las crisis de hipo suelen ser autolimitadas y benignas, pero los episodios prolon-
Tratamiento
gados alteran la calidad de vida y requieren asistencia, ya que existen causas identificables que
el otorrinolaringólogo debe conocer para su diagnóstico y tratamiento. Su manifestación última
es un ruido glótico espasmódico con alteraciones cervicales características.
Pacientes y métodos: Desde 1979 se revisaron todos los casos que consultaron por hipo per-
sistente o recidivante, anotando cronobiología, patología concomitante, resultados de las
exploraciones, tratamiento y respuestas al mismo.
Resultados: Se asistieron 37 pacientes con una edad media de 45,5±13,5 años, de los cuales
30 eran varones; 23 pacientes (el 62%) presentaron hipo persistente. En 24 casos (el 65%) se
evidenció una causa potencialmente asociable: enfermedades del esófago en 14 ----la mayoría
reflujo gastroesofágico---- y en 8 se apreció o descubrió patología oncológica concomitante.
Solo 3 casos fueron intervenidos como resultado de los hallazgos efectuados. Los protocolos de
tratamiento incluyeron metoclopramida en 18 sujetos, clorpromazina en 17 y baclofeno en 13,
pero también carbamazepina o haloperidol. Se empleó neuroestimulación del nervio frénico en
6 pacientes. El hipo desapareció en 32 casos. De los 22 sujetos en los que se pudo efectuar
seguimiento, se constató recidiva en 5 ----precisando por ello nuevas terapias---- y 11 fallecieron.
Conclusiones: El hipo crónico implica un reto multidisciplinar con potencial afectación en
cabeza y cuello, una sistemática diagnóstica de descarte, frecuente patología de base esofágica
y una incidencia de neoplasia maligna alta. Los agentes procinéticos y neurolépticos con efecto
antidopaminérgico y anticolinérgico suponen la base del tratamiento.
© 2017 Publicado por Elsevier España, S.L.U.

Introduction Hiccups are caused by the stimulus of one or more sec-

A hiccup or synchronous diagphragmatic flutter is the char-
acteristic sound emitted by the violent expulsion of air from
the lungs during a sudden and spasmodic contraction of
the diaphragm with the consequent jerk of inspiratory mus-
cles of the chest and abdomen, followed by glottic closure.
They are usually benign and self-limiting but their inten-
sity, frequency and duration may seriously affect quality of
life. It is believed that 100% of the population worldwide
of any age has presented on some occasion with a hiccup
crisis.1,2
The physiopathology of hiccupping is still unknown, but
it has been argued that it is a reflex arc with afferents
shaped by branches of the vagus, phrenic and sympathetic
cervical nerves. Its regulator centres are located in respi-
ratory encephalic nuclei, the ascending reticular formation
and the hypothalamus. The efferents would comprise laryn-
geal nerves, intercostals muscle nerves and C5 to C7 cervical
branches.2 The parasympathetic component of the X pair
would comprise efferent fibres running through the interme-
diary Wrisberg nerve towards the glossopharyngeal nerve.
Final coordination of the reflex arc would be established at
the vagus dorsal nucleus---at the IV ventricular level---from
where preganglionic nerve fibres start. The postganglionic
nerve fibres start from the vagal tract to several levels for
the majority of the digestive and respiratory system, the
heart, kidneys and major blood vessels, forming the nerve
plexus in the chest and abdomen, together with sympathetic
fibres.3
tions of the reflex arc, with repetitive activity of the central
nucleus in the cervical spinal cord between C3 and C5, or
inhibition of its nerve control. The so-called ‘‘hiccup cen-
tre’’ would be located at this level, as shown by peripheral
stimulation of the reticular formation in the brain-stem of
felines, with mainly GABAergic neurotransmission.4
Acute temporary hiccups is considered to be that which
only presents for seconds or minutes, whilst sub-acute lasts
longer, but for under 48 h, with a frequency of 2---4 emissions
per minute. This is commonly due to eating quickly, sudden
oesophagogastric bloating, thermal changes in the stomach,
stress, a smoking habit or alcohol consumption. Hiccupping
which last for more than 2 days is known as persistent and
if it presents for more than 2 months it is incoercible or
recurrent.
The persistence of hiccupping can limit daily actions such
as eating, sleeping, exercise or working and can lead to
anxiety-depressive disorders, dehydration, aspirations, dif-
ficulty talking and fatigue. Its frequency can entail between
20 and 60 spasms per minute. Over 100 causes of temporary
and persistent hiccupping have been documented,3,5 primar-
ily of gastrointestinal origin. However, they do not usually
lead to medical consultation as clinical repercussions are
rare.
Persistent hiccupping or synchronous diagphragmatic
flutter itself is categorised as severe.6,7 The act of hic-
cupping, which is regarded as an archaic reflex lacking in
any protective or beneficial function, and the doubts sur-
rounding its physiopathology have resulted in it being little
100
studied. It is therefore desirable to increase knowledge
of the possible causes, treatment, evolution and prognosis
of this condition by researching, reviewing and comparing
those individuals who present with persistent hiccup.
Patients and Methods
We present a longitudinal, descriptive, retrospective study
which used the records of patients who had consulted
for hiccups and who belonged to the health areas of the
Clínico Universitario de Valencia hospital and the General
de Requena hospital. This selection was made from the
diagnoses from admittance to outpatients and/or discharges
offered by the medical documentation service and admit-
tance units of both hospitals, between January 1979 and
June 2015.
37 patients who had come from the internal medicine ser-
vices, otorhinolaryngology, neurology, general surgery and
primary care centres were identified. Of these, 81.1% were
males, with a mean age of 45.5±13.5---a range of between
21 and 72 years old---with follow-up of between 5 and 36
months. The duration of hiccups was recorded in months.
The comorbidity of each patient was recorded, as was the
administration of drugs which potentially were the cause,
and clinical events derived from examination---otoscopy,
oesophageal symptoms (heartburn, dysphagia, regurgita-
tions, etc.) thoracic (pain, dyspnoea, etc.), neurological
(headache, vomiting, changes in cranial nerves, medullar
syndrome or cerebellar and dysesthesia), oesophagogas-
troscopy, pH metry, imaging studies using radiography, CT
(from 1992) or MRI (from 1997) and peripheral blood analysis
specifically focused on hormonal disorders.
Since 2006 techniques for the measurement of the
compound muscle action potentials using a Cadwell Sierra III
electromyograph have been available, with a stimulus inten-
sity of 70---100 mA. These techniques enable the non-invasive
evaluation of the presence of secondary anomalies to some
type of disorder of the phrenic nerve, possibly axonopathy,
conduction block, or demyelination in accordance with the
specifications of Aravot et al.8
In relation to these tests, we adopted the topographic
causal criteria of Martínez Rey and Villamil Cajoto from
20079 :
• Neurological events. Those cases where central concom-
itant symptomatology was observed or where tumours
were found in the cranial-cerebral imaging studies.
• Thoracic events. Pulmonary, cardiac or mediastinal
changes observed also in the radiological tests.
• Cervical events. Those cases with a temporary relation-
ship between clinical and radiological detection and its
eventual correction.
The particular involvement of gastroesophageal reflux
disease was made in virtue of the recorded medical his-
tory or endoscopic findings identified in accordance with
the Los Angeles severity classification of reflux oesophagitis
published in 1999.10
Finally, the therapeutic approach adopted was reflected,
showing which drugs had been prescribed, the need for
surgery on suspicion of causal tumour or the use of
F.J. García Callejo et al.
electrostimulation of the phrenic nerve, a procedure which
has been used since the electroneuromyographic system for
measuring nerve conduction times became available.
Results
Epidemiological Traits
Table 1 describes the characteristics of the patients included
in the sample. The detection of cases with continuous or
recurrent hiccups and with a duration of one month or more,
in over 36 years when it has been possible to collect data, is
recorded as an incidence of 1.02 cases per year. Both centres
have coverage of 425 000 individuals and it is therefore to be
assumed that there would be 2.4 cases annually per million
inhabitants.
Frequency in males is 4.28 times higher than in females,
and 70% of cases present at ages between 40 and 60. A total
of 6 patients (16.2%) were hospitalised due to the surgical
requirements of the event detected (adenocarcinoma of the
stomach, multinodular goitre, giant hiatus hernia) or the
need to monitor and reduce the severity of the hiccup cri-
sis (patients numbers 7, 18 and 34). In 23 patients (62.2%)
the hiccups were continuous and in the remainder in crisis
of between 7 and 13 days, with intervals of 25 days. Fre-
quency of hiccupping ranged between one every 15 s and
every 5 min, although in those patients with longer duration
frequency could be highly variable.
Concomitant Pathology
Regarding global volume, 86.5% of the individuals included
presented with some type of associated disease which had
already been known or discovered in the posterior examina-
tions. However, it was only possible to establish a causal
relationship with the observed pathology in 24 patients
(64.%).
There was oesophageal involvement in 14 individuals
(37.8%). Of these, one case was neoplastic, another had a
gigantic hiatus hernia and the others had gastroesophageal
reflux disease with oesophagitis, all of which were grade A
and B of the Los Angeles classification.10
There were 8 cases (21.6%) of malignant neoplasm
diagnosed before or after consultation for hiccupping.
Radiotherapy was used in the 4 patients where detection
was made after consultation. These neoplasms were of var-
ious types and locations (patients numbers 3, 4, 9, 15, 16,
17, 26 and 28).
No iatrogenic causes were found since the patient ho
had undergone a left cervical dissection had done so 10
years prior to the appearance of the hiccups and none
of the patients in the study took stimulants for this con-
ditions, among which are benzodiazepines, neuroleptics,
barbiturates, dexamethasone, valproate, imipenem, or ␣-
methyldopa.3,11 The 3 diabetic patients showed no signs
of significant metabolic imbalances. Evaluations of nerve
conduction times using the percutaneous electromyogram
on both phrenic nerves showed no significantly pathological
values in latencies or amplitudes in the 13 cases where it
was used, although lower amplitudes and longer latencies
Hiccups in Otorhinolaryngology 101

Table 1 Epidemiological Traits, Diagnoses and Treatments Established for the Patients Included in the Study.
Gender- Date of Months Diagnoses prior to onset Posterior events Treatments Months in
age consulta- with response
tion hiccups
1 M-32 Mar/79 20 Cervical hemangioma, DM MET <1
type 1
2 M-37 Feb/82 7 MET 2
3 M-61 Sep/86 2 Alcoholic cirrhosis, acute Adenocarcinoma of Ct+Rt+BAC 3
pancreatitis, DM type 2 the oesophagus
4 M-57 Nov/88 3 Colonic diverticulitis, Gastric Ct+sur+BAC No
bladder carcinoma HBP, adenocarcinoma
filariasis
5 F-57 Jan/90 8 HBP, stroke, dyslipidaemia GERD CLO+MET 2
6 F-49 Oct/90 6 Hypothyroid goitre, Sur+MET 1
dyslipidaemia, GERD
7 M-44 Jun/92 12 GERD MET 3
8 M-52 Dec/92 2 oesophagitis MET+CLO 2
9 M-62 Mar/93 3 Scalp skin cancer, HBP Metastasis by Ct+Rt+BAC No
melanoma in cavum
10 M-51 Apr/94 2 Anaemia MET+HAL 1
11 M-42 Nov/94 1 Oesophagitis, atrial MET <1
fibrillation
12 M-33 Mar/95 2 HBP, DM type 2, CLO No
dyslipidaemia, GERD
13 M-53 Dec/95 7 Previous pulmonary TBC, CLO+BAC 4
pleural effusion, atrial
fibrillation
14 M-62 Jul/97 10 Prostatic hypertrophy, HBP, Oesophagitis MET+CLO 2
COPD
15 F-48 Ago/98 7 Cervical lymphoma, HCV+ CLO 1
16 M-55 Jan/99 3 Labial carcinoma, cervical CLO+BAC 2
dissection, COPD
17 F-41 Feb/99 7 Multiple sclerosis, CLL, MET+CAR+HAL 3
anaemia, vitiligo
18 M-42 Jul/99 15 CLO 6
19 M-29 Feb/02 4 Cervical trauma (hyoids CLO 2
fracture), COPD
20 M-51 May/03 4 Lupus, CKF, gout CAR+CLO 3
21 M-46 Jun/03 6 HBP BAC 1
22 M-72 Oct/05 8 Prostatic hypertrophy GERD MET 2
23 M-31 Feb/06 10 Dyslipidaemia Multiple sclerosis CLO+CAR+PNS No
24 M-50 May/07 1 HBP BAC 2
25 M-21 Jul/07 8 Myoclonic epilepsy, Gilbert’s GERD MET+CLO 3
syndrome
26 M-58 Mar/08 3 Pulmonary adenocarcinoma Neoplasic Ct+Rt+CLO+BAC 5
infiltrating of clivus
27 M-37 Jan/09 2 GERD MET 3
28 M-42 Sep/09 4 Chondrosarcoma, Right limb CLO 2
29 M-22 Apr/10 3 Lupus CLO 3
30 F-32 Jun/10 5 Dyslipidaemia Multiple sclerosis CAR+BAC+PNS 3
31 M-27 May/11 1 CLO+PNS 3
32 F-66 Nov/12 2 Irritable bowel, HBP Giant hiatus hernia Sur+CLO+BAC 2
33 M-32 Jul/12 3 GERD MET+BAC+PNS 2
34 M-40 Nov/13 1 GERD MET+CLO 3
35 M-28 Dec/13 11 MET+BAC+PNS No
36 F-72 Feb/14 6 Rheumatoid arthritis BAC 4
37 M-50 Feb/15 5 MET+PNS <1
BAC: baclofen; CAR: carbamazepine; Sur: surgery; CLO: chlorpromazine; DM: diabetes mellitus; COPD: chronic obstructive pulmonary
disease; GERD: gastroesophageal reflux disease; M: male; HAL: haloperidol; HBP: high blood pressure; CKF: chronic kidney failure; CLL:
chronic lymphoblastic leukaemia; F: female; MET: metoclopramide; PNS: phrenic neurostimulation; Ct: chemotherapy; Rt: radiotherapy;
TBC: tuberculosis; HCV: hepatitis C virus.
102
Figure 1 Images obtained from a patient with hiccups in those with hiatus hernia (patient no. 32), cervical lymphoma (no. 15)
and neoplasm of the cavum with infiltration (no. 9).
characterised those patients where hiccups took longer to
stop or did not stop.
A potential topographical (vagus-phrenic nerve) relation-
ship was established as the cause of the hiccups by neuronal
irritation at oesophagogastric level in 17 patients. This was
cervical in 5 (patients no. 1, 6, 9, 19 and 26) and central
in 4 (3 patients with multiple sclerosis and another with
myoclonic epilepsy). Fig. 1 shows the radiological findings
where the hiatus hernia, cervical lymphoma and nasopha-
ryngeal neoplastic infiltration may be observed.
Therapeutic Traits
In addition to the surgery chosen as a therapeutic tool in
3 patients with malignant neoplasms or neoplasm occupying
space, plus subsequent concomitant chemotherapy or radio-
therapy, neurostimulation of the phrenic nerve was used in
patients no. 23, 30, 31, 33, 35 and 37, and was particularly
effective in patient 33 and 37, where following application
the hiccups disappeared definitively.
The medication chosen for the crises, administered as
mono or combined therapy were as follows: chlorpromazine:
35 mg every 12 h, no longer than 60 days, in 18 patients
(48.6%); metoclopramide: 10 mg every 8 h, no longer than 15
days, in 17 patients (45.9%); baclofen: 15 mg every 8---12 h,
no longer than 90 days, in 13 patients (35.1%); carba-
mazepine: 300 mg every 8 h, as prescribed, in 4 patients
(23.5%), and haloperidol: 2 mg every 8 h, as prescribed, in
2 patients (5.4%). The most standard combined therapy was
10 mg of metoclopramide every 8 h for 10 days with 35 mg
chlorpromazine every 12 h for 45 days.
The most common adverse reactions described were:
somnolence, headaches (13.5%), dizziness (10.8%), urinary
retention, nausea, hypotension and dryness of the mouth
(5.4%). Neither extrapyramidal reactions nor malignant neu-
roleptic syndromes were reported. Only in 2 cases was any
F.J. García Callejo et al.
urinary retention observed in patients treated with chlor-
promazine and the medication was then withdrawn.
The therapies offered eliminated the hiccupping in 32
patients (86.4%), within an interval of between 12 days and
6 months, and a mean of 72.1±37.5 days. Of the 22 patients
who could be effected a long term follow-up was made
where reappearance of chronic hiccups was observed in 5
patients, newly treated successfully with 10 mg of metoclo-
pramide every 8 h for 10 days. However, of these 22 patients,
11 died due to other causes.
Discussion
Hiccups are often self-limiting and idiopathic. The proce-
dures for controlling them are consequently often reduced
to manoeuvres with little physiopathological basis. Lack-
ing in any functional use and frequently detected in the
third term of pregnancy hiccups may be even found in
several mammals, which leads to the question of whether
they may be an ancient reflex action. However, episodes
of recurrent hiccups or ones which last for over 48 h can
be limiting to basic patient functions and it is known that
in no few cases it is a sign of severe pathology.6,7 The
work of Goñi Murillo1 in 2005 offers a complete review
of the possible aetiology of acute and persistent hiccups,
which are summarised in Table 2. Meticulous clinical history,
detailed physical examination and the before-mentioned
complementary tests available may often lead to a final
diagnosis being established for symptomatic and aetiological
treatment in primary care or specialist centres.1 No gender
predominance exists for acute hiccups but persistent and
untreatable hiccups more frequently affect males, although
there are no obvious differences by race or socio-economic
circumstances.12 Only hysterical hiccups and secondary to
severe aerophagia which is normally acute, stop at night
and reappear during the day.3
Hiccups in Otorhinolaryngology 103

Table 2 Aetiological Possibilities of Hiccups.

1. Temporary hiccups
1.1. Aerophagia and copious meals
1.2. Gastric distension and cooling down of suckling infants
1.3. After imbibing alcohol or carbonated beverages
1.4. Emotional state of stress, anxiety, laughing or lability
1.5. Sharp changes of temperature in a liquid imbibed
2. Persistent hiccups
2.1. Neuronal vagus-phrenic irritation
Irritation of the external auditory canal
Oesophagitis from GERD, candidiasis, achalasia, diverticulosis or oesophageal neoplasm
Goitre, mediastinal tumours, aortic aneurysm
Chronic gastritis, bloating, ulcer or gastric neoplasm
Abdominal hyperpressure from intestinal obstruction, cholangiopancreatis, portal hypertension, ascites, pregnancy, after
laparoscopies or laparotomies
Pericardial effusion, ischaemic cardiopathology
Subphrenic abscess, tumour infiltrating of the diaphragm, hiatus diaphragmatic hernia or Bochadaleck hernia
2.2. CNS involvement
Meningoencephalitis, HIV, tertiary syphilis
Syringomyelia, occlusion of the PICA, infratentorial LOE, demyelinating processes
Alcoholism, head injury, intracranial hypertension
2.3. Metabolic causes: uraemia, diabetic ketoacidosis, hyperuricaemia, hyponatremia, hypocalcaemia
2.4. Agents: corticosteroids, alphamethyldopa, benzodiazepines, neuroleptics, anticonvulsants, barbiturates
2.5. Acts under general anaesthesia
2.6. Hysteric
Source: Goñi Murillo.1

Although it has been suggested that gastroesophageal
reflux and oesophagitis may be an independent cause of
hiccups the role of gastric overdistension as the aetiolog-
ical mechanism and the oesophagus as the trigger organ
of the reflex arc needs yet to be clarified, unlike their
onset after endoscopic insufflations, copious meals and lack
of coordination between swallowing and digestion which
are unquestionable.3,9,13 During hiccups the following have
been observed: disappearance of oesophageal peristaltism,
reduction in cardia pressure and fluctuations at the base line
of the oesophagus with the reflex action, all of which disap-
pear when the hiccups disappear. The oesophagus and reflux
were the most standard diagnosis detected in our group, pre-
senting in 15 cases. Other studies also emphasise this data,
albeit with variations of incidence of between 20.8% and
50%,9,12,14---16 but they coincide in reporting that the level of
involvement of the oesophagitis is slight.
Central involvement is the second potential cause of
hiccups in our series. Three patients presented with
demyelinating disease and a fourth with myoclonic epilepsy.
As a result we share the idea of other authors in carrying
out central imaging studies using MRI in case oesophageal
involvement should not be detected.17 Hiccups is not
unusual either, in the evolution of equivalent processes---as
shown by one case in our series---and although it has been
reported that in these situations its onset may obscure a
state of epilepsy, further assessment of this is needed.18,19
Malignant tumoural pathology was found in up to 45% of
other reviews made,9 higher than in our findings, where we
only identified 2 new cases of neoplasms and metastasis of
the skull base of the other 2 known cases. Notwithstanding,
there were 5 deaths in our series, in patients attended to
for hiccups where the primary cause of death was from a
tumour.
We were unable to confirm any drug iatrogenesis in our
series, but series we consulted refer to up to 50% of patients
with hiccups having an immediate or chronic background
of potentially involved agents in the production of the hic-
cups. This may be the most complicated aetiopathogenic
trait to demonstrate since multi-pathology leading to drug
administration could bias the cause-effect ratio in any given
circumstance. It is somewhat disconcerting to note that
drugs such as anticonvulsants or diazepam are used in both
senses, and it is therefore not easy to consider that the drug
is the trigger if the onset of the condition does not occur
with its use. Equally, chlorpromazine and diazepam may
produce both effects, and the efficacy of the first against
the induction of hiccups from the second is based on the
antidopaminergic effect in its D2 receptors, with high anti-
nausea effects and thus blocking the phrenic nerve, but also
anticolinergic and ␣-adrenergic antagonist. Similarly, sev-
eral imipenem type agents would interfere in the afferent
branch of the reflex arc activating the hiccup mechanism
through slowing down of the epileptogen threshold. This
would justify the use of anticonvulsants as possible drug
treatment.
In our series we found 64.8% of potential organic
causes of hiccups, a fact that is similar to that reported by
Martínez, but very much below the 90% suggested by Encinas
Sotillos and Cañones Garzón.12 It is not uncommon to find
high incidence rates since these are patients with multiple
pathologies in the digestive tract, chest and central nervous
104
system. In general, establishing the aetiological part played
by every factor is complicated, as is justifying the poor
prognosis of this patient group.
Aetiologic therapy is obviously the best, although only
60% of cases manifest a plausible cause and there is often no
definitive confirmation of this. Numerous physical manoeu-
vres exist, which may or may not help, designed to cause
parasympathetic hypertension: pressure on both external
auditory canals, nasopharyngeal irritation with a probe or
of the nasal mucosa to provoke sneezing, stimulus on the
oropharynx through tongue traction, endoscopic massage of
cardiac, swallowing of sugar lumps, sipping water, raising
the uvula with a cold spoon, holding in of breath whilst rais-
ing diaphragm pressure (Valsalva manoeuvre), breathing into
a paper bag---the increase in the arterial concentration of
CO2 inhibits it---imbibing a bitter soft drink when induced by
alcohol, or even rectal massage.3,6,13,20 None of these actions
are initially rejected and should therefore be made known
to the person in question.
The success rate is very high for the recommended
pharmacological treatments---in our series only 5 cases
were refractory---and the patient needs to be aware of
the need to prolong visits and consider other alterative,
such as ablation or electrical stimulation of the phrenic
nerve, with a recommendation of a fluoroscopic study of
the hemidiaphragms due to the inherent risk of respira-
tory arrest21,22 ---vagal neurostimulation,23 cervical epidural
blockage or the intrathecal administration of some of the
available agents.
With regards to pharmacotherapy, baclofen appears to
be the only drug to offer several medical trials, although
with somewhat conflicting results.24,25 Its antispastic effect
in several neurological diseases, such as multiple sclerosis
and other myelopathies is well documented. It appears to
work at an oral dose of 15 mg every 8 h for months, blocking
the hiccup focal point derived from GABA receptors which
inhibit the presynaptic motor neuron.26
Affinity by the GABAergic receptors interrupting the
myoclonus of the diaphragm and the sole activity of
the nucleus of the hiccups make carbamazepine another
associable alternative, its side effects of drowsiness and
dyskinesia being less probable.27
However, the only drug which has been recognised by the
FDA for this indication is chlorpromazine, a hypothalamic
dopaminergic antagonist, although it is poorly tolerated in
patients with recent strokes due to its side effects of seda-
tion and dyskinesia over prolonged periods of administration
at the recommended therapeutic dose of 35 mg every 8 h.28
The same antidopaminergic mechanism appears to be
responsible for the optimum use of metoclopramide and
domperidone. The former is well known by primary health-
care professionals and could be administered as an initial
therapy at a dose of 10 mg every 8 h from 10 to 20 days, and
although the risk of extrapyramidalism at the start of treat-
ment is documented,29 it is much less usual than with other
neuroleptics.
Haloperidol has demonstrated its efficacy as a tran-
quiliser at a dose no higher than 12 mg per day, and
is particularly effective for the control of hiccups in
emergency services.30 Several authors consider the triple
association prokinetics, omeprazol and baclofen as a broad
spectrum therapy for the treatment of hiccups of central
F.J. García Callejo et al.
and peripheral causes.31 However, as of yet there is nei-
ther elective therapy for persistent or recurrent hiccups
nor any certainty that combined therapy would be more
effective in times or dose. Other agents have demonstrated
efficacy which has not been sufficiently contrasted to date,
and these include corticosteroids, risperidone, gabapentin
or tetrabenazine.
Conclusions
Hiccups is a universal phenomenon where persistence is
unusual, disconcerting and frequently belies circumstance
of poor prognosis which may potentially suggest a multitude
of conditions, the true nature of each to be discovered.
The fact that over one third of patients present with
an oesophageal condition suggests that it is highly recom-
mendable to evaluate secondary oesophagitis. This second
diagnostic option is required to rule out central nervous
disorders using imaging studies.
Symptomatic treatment may be established as soon as
diagnosis has been made with easily administered proki-
netics such as metoclopramide, and the therapeutic effect
may be enhanced by association with chlorpromazine or
baclofen, depending on the results of the function and imag-
ing tests.
It should finally be noted that incoercible hiccups occurs
in a neoplasic context in a fifth part of affected patients,
with no obvious organic location.
Conflict of Interests
The authors have no conflict of interests to declare.
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