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Explore and Exploit Copyright: © 2015 Kwok K. Meng, et al.

Case Report Archives of Case Reports in Clinical Medicine Open Access

Use of Baclofen in the Treatment of Persistent Hiccups: Report of
Two Cases
Kwok K. Meng1*, Cheong H. Yiang2, Manohararaj Nijanth2, Larik Ashfaq3
Senior Resident, Department of Rehabilitation Medicine, Singapore General Hospital, Singapore
1

Medical Officer, Department of Rehabilitation Medicine, Singapore General Hospital, Singapore
2

3
Consultant, Department of Rehabilitation Medicine, Singapore General Hospital, Singapore

Received Date: April 11, 2015, Accepted Date: April 30, 2015, Published Date: May 06, 2015.
*Corresponding author: Kwok K. Meng, Department of Rehabilitation Medicine, Singapore General Hospital, Singapore, E-mail: kahmeng.kwok@mohh.com.sg

the laryngopharynx and glottis from endotracheal intubation. In
Abstract addition, toxic or metabolic causes that may affect nerve function,
We present two cases of persistent hiccups attributed to lateral such as alcohol intoxication, uremia, electrolyte imbalances and
medullary syndromes that were refractory to common pharmacological diabetic ketoacidosis will also need to be excluded [8]. Lastly
treatment. Introduction of baclofen resulted in the rapid and sustained
psychiatric issues including emotional upset and stress may be a
resolution of hiccups in these patients, with no significant adverse
effects noted. Our reports serve to strengthen the limited evidence base diagnosis of exclusion [11].
for baclofen as a pharmacological agent for treatment of hiccups, and Lateral medullary syndrome (LMS) remains an interesting
suggest the consideration of its use as a first line treatment specifically
clinical entity with a wide range of clinical presentations of
in hiccups secondary to lateral medullary infarcts.
cerebrovascular accidents [12]. The area of the brain stem involved
Keywords: Baclofen; Persistent Hiccups in LMS is the posterolateral part of the medulla oblongata [6], which
is the portion receiving arterial blood supply from the posterior
inferior cerebellar artery (PICA)[10,13]. The usual symptoms
Introduction of lateral medullary infarction (LMI) include vertigo, dizziness,
Hiccups, or singulata, are repeated involuntary, spasmodic and nystagmus, ataxia, nausea and vomiting, dysphagia, hoarseness,
temporary contractions of the diaphragm accompanied by sudden hiccups, impaired sensation over half the face, impairment of pain
closure of the glottis, producing a distinguishing “hic” sound [1]. and thermal sensation over the contralateral side of the trunk,
Hiccups are commonly experienced by most people at one time or limbs and the ipsilateral face and Horner’s syndrome.
another but are usually brief and self-limiting. The physiological Hiccups are more frequent when the infarct is in the dorsal area
purpose of hiccups is uncertain [1,2]. As fetuses and premature of the medulla, primarily because a number of complex structures
infants hiccup often, it is suggested that hiccups are a programmed which mediate the hiccups reflex, specifically the vagus nerve,
isometric inspiratory muscle exercise, which is useless after the respiratory center, solitary nucleus, nucleus ambiguus, central
neonatal period but may be restimulated by irritation along the sympathetic tract, and spinal tract of trigeminal nucleus are all
reflex arc [1,3]. The neuroanatomical center for hiccups is not located in this area. These lesions may result in a dysfunction
well-known, although the major component of central connection of the vagus nerve, sympathetic nerves, and an incoordination
is presumed to be a part of the brain stem and hypothalamus between the glottis closure complex and inspiratory complex, thus
[4,5,6]. The afferent pathway is made up of the sensory branches generating persistent hiccups [8,14,15].
of the phrenic and vagus nerves and the dorsal sympathetic fibers,
whereas the efferent pathway is formed by the motor fibers of the Case Reports
phrenic nerve.
We present two patients having lateral medullary infarcts
Persistent hiccups (lasting > 48 hours) are uncommon, and complicated with persistent hiccups, with highlights to their
warrant a complete medical work-up to uncover underlying treatment course of events:
pathology[2], as well as to prevent potential undesirable
consequences, including psychological distress, difficulties in Case 1
feeding resulting in dehydration and malnutrition, poor quality A 58 year-old gentleman with past medical history of
of sleep, and even potentially life-threatening complications such hypertension, presented with an unsteady gait of two days
as aspiration pneumonia[7], resulting in increased morbidities duration associated with constant veering towards the left side on
and prolonged hospital stays [8]. The causes of persistent ambulation. His presentation was accompanied by an episode of
hiccups can be classified into central and peripheral [2,6]. vertigo that lasted for about 30 minutes, one episode of vomiting
Central hiccups occur with lesions between the pathway from the and neck pain of same duration as unsteady gait. Neurological
central nervous system to the phrenic nerve, mainly in diseases examination revealed right beating horizontal nystagmus, right
of the brain stem such as ischemic stroke, dolichoectatic basilar
uvula deviation, persistent unsteady gait and left ptosis. MRI brain
artery, tumors, encephalitis, multiple sclerosis, and had also been
revealed restricted diffusion in the left lateral aspect of medulla,
reported in patients with focal seizures [9]. Peripheral hiccups
confirming the diagnosis of an acute left lateral medullary infarct.
can be caused by either diseases at the phrenic nerve level
involving diaphragmatic irritation, such as gastric distention, On the second day of his admission, the patient started
subdiaphragmatic abscess or hepatosplenomegaly,[2,6,10]; complaining of persistent hiccups with the sensation of nausea.
diseases causing vagal nerve stimulation such as pharyngitis, The patient was experiencing up to five to six bouts of hiccups daily,
gastritis, peptic ulcer disease and pneumonia; or irritation of with the longest duration of hiccups lasting several minutes. The

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He was subsequently given Multiple studies have demonstrated the efficacy of baclofen on a range of pharmacological agents including Ondansetron 4mg persistent hiccups in general. for both of our patients. carbonated drinks. In evaluating for possible peripheral causes for his hiccups. and hence there was no requirement to tail down prior frequently ineffective for persistent hiccups [16]. In hiccups associated with cerebrovascular disease. and in turn resulted in the rapid success of hiccups treatment. Currier RD. so it is recommended that the dose be tapered methods. pharmacological and non-pharmacological such as convulsions. a component of References the hiccup centre. impairment of pain sensation over the left upper and lower limbs and mild right hemiparesis. for example. hiccups and those with evidence of esophageal disorder but failed conventional treatment. Dejong RN. Patient was started on a trial of oral Metoclopramide 10mg TDS and Haloperidol 1g ON with no effect. stand to strengthen this acute infarct at the dorsal and lateral aspect of the right medulla. Conclusion Pharmacological treatment of persistent hiccups is generally In conclusion. the rapid onset and maintainence where the hiccups are paroxysmal. Some comments on Wallenberg’s lateral effect of sedation must be recognised. not unexpectedly and numbness of the right upper and lower limbs. and electrolytes. onset occurrence of unsteady gait. Arc Cas Rep CMed 1(1): 101. Of note. Further increase in his Balcofen dose to 10mg hiccup frequency. Domperidone 10mg TDS and Chlorpromazine 25mg TDS to by Ramirez[19]. and non-pharmacological methods are baclofen. Its side 1. been tried with variable results. the underlying cause. Baclofen was administered for a total of five days with no recurrence of symptoms on discontinuation of There may be some concern regarding serious neurotoxicity of the drug. haloperidol and prochloperazine have and his participation in rehabilitation therapy. Yiang CH. 126: 1864–72. Case 2 Specifically. for hiccups occuring post lateral medullary A 64 year-old man with past medical history of hypertension infarction. Neurological however. but not the duration of hiccups. and 10mg at 8pm. professing for the consideration of baclofen confirming the diagnosis of an acute right lateral medullary infarct. However. in contrast to earlier studies [19]. . In particular. 1. as evidenced by the myraid of pharmacological for hiccups attributable to lateral medullary infarction.Arc Cas Rep CMed Vol. consecutive patients. 1961. focal down slowly when discontinuing the medication from prolonged seizures should be considered as a cause. we strongly agents available. vomiting. These drugs were stopped and oral Baclofen was started at 5mg at there was complete resolution of hiccups and the discontinuation 8am and 2pm. It is generally well-tolerated. as first line therapy in treatment of hiccups attributable to lateral medullary infarction. After commencing the patient on Baclofen 5mg TDS. The sudden discontinuation of baclofen The management of hiccups involves searching for and treating after long-term use can be associated with withdrawal symptoms. baclofen The patient developed bouts of paroxysmal hiccups on day was initiated after the trial of multiple. more conventional agents three after onset of presenting symptoms. insomnia and weakness [16]. as not all underlying of therapeutic effects did not necessitate prolonged usage of causes can be corrected. after the first dose was given. symptomatic to discontinuing. and persistent hiccups. presented with a one day history of sudden only drug which had undergone a number of RCTs [21]. with sugars and liver function test done were all unremarkable. chlorpromazine is poorly tolerated by those with a recent brain infarction and should be avoided. Baclofen is a gama-aminobutyric acid (GABA) agonist used there were no known triggers (eg. hepatitis or liver abscess. Giles CL. with the most was also no ictal phenomenon to suggest focal seizures as a cause. renal impairment. Other agents with dopaminergic antagonistic properties of 130 acute. but these are mainly in patients with significant renal failure with resultant impairment in Discussion the clearance of baclofen. in view of the rarity of both lateral medullary infarction examination revealed gait ataxia with increased swaying to the right.23]. Citation: Meng KK. inhibition of the hiccups reflex [16]. 2003. no clinical evidence of sepsis. the and statistically significant improvement in hiccup severity with patient reported subjective improvements in the frequency and baclofen. However. Nijanth M. Baclofen therapy 71% complete resolution of hiccups with baclofen treatment (doses was continued for five days and subsequently ceased with no ranging from 15-75mg/day) in patients with idiopathic persistent further recurrence of hiccups. Pure lateral medullary infarction: Clinical-radiological correlation dyskinesia. both subjectively and by hiccup-free periods. baclofen probably has the best evidence base. There a half-life of 3-4 hours. no primarily to treat spasticity and the therapeutic effects of baclofen symptoms suggestive of gastro-esophageal reflux disease (GERD) on hiccups is due to the decrease in excitability and increase in or respiratory tract infections (RTI). A later trial done by Guelaud [20] revealed a 40- TDS resulted in complete resolution of hiccups. potential causes were failed. particularly in cases use [24]. baclofen arising from case reports [22. post-meal). therefore. limited evidence base. 29000101 hiccups were severe enough to interfere with our patient’s sleep including metoclopramide. when considering pharmacological treatment still unsatisfactory. excluded. treatment with medications may be necessary [17] to avoid the negative consequences described earlier. Hiccups were initially treated This suggests that the resolution of hiccups is probably more with oral Metoclopramide for a total of three days and then with related to the effects of baclofen rather than being attributable to oral Prochlorperazine for a total of five days with no improvement. However. Issue. Brain. specifically an additional treatment target. 1. based on current available evidence chlorpromazine and metoclopramide [18]. after oral administration and is eliminated via renal excretion. well-controlled clinical trials. being the and diabetes mellitus. which are purportedly strengthened by our personal experiences. Neurology. In both our cases. and long-term administration medullary syndrome. dizziness. 11: 778–91. particularly if there is concomitant spasticity as Traditional choices include dopaminergic antagonists. Hiccups resolved within 48 hours of baclofen did not lead to a return of hiccups in both our patients. acting via dopamine blockade in the hippocampus. showed that there was a consistent no effect. Baclofen is absorbed rapidly in particular pneumonia. MRI Brain revealed the presence of an Our case studies above. spontaneous recovery. Ashfaq L (2015) Use of Baclofen in the Treatment of Persistent Hiccups: Report of Page 2 of 3 Two Cases. The infrequent occurrence of hiccups makes suggest baclofen as the first-line option in the absence of significant it difficult to perform large. weakness all these trials are limited in statistical size. is not recommended because of possible irreversible tardive 2. The randomised controlled trial done TDS. common side effects being sedation. in a similar fashion as Case 1. Kim JS.

AJNR Am J Neuroradiol. AH.a case 6. Tzu Chi Med J. Tsai KW. Department of Rehabilitation Medicine. controlled. of lateral medullary infarction presenting hiccups (singultus). distribution. 1996. 5. doi: 10. Lee HW. Pharmacotherapy. which permits unrestricted use. Hsu MC. Friedman NL. Marsot-Dupuch K. Lee DH.23. Derenne JP.4103/0253-7176. 2012. 87(12): 1789-1791. 102(1): 13–7. 2010. Treatment of intractable hiccups with an oral agent monotherapy of baclofen . Lateral medullary syndrome: An 2006. Korean J Pain. 2015. Baclofen for stroke patients with persistent hiccups: a randomized. Zhang C. Ahmed RA. Baclofen-induced neurotoxicity in chronic renal failure patients with intractable hiccups. Liang CY. 19(4): 343-349.sg Received Date: April 11. 2000. Clin Neurol Neurosurg. Hong SS. 2014. Zhang S. 99(11): 1308-9. 36(3): 341-343. 41(5): 712–3. and reproduction in any medium. Moon SY. Asia 2014. Yiang CH. Lesional location of 18. 2008.3265/Nefrologia.12320. placebo-controlled 11. 1992. Zhang R. Similowski T. Seizure. Lateral Medullary Syndrome. Chen CA. Victor M. doi: 10. Koh SB. Neurosurg Psychiatry. 2005. Kwon SB. 7(3): 255–60. Dromerick AW. symptom in medulla oblongata cavernoma: A case report and review of the literature. Musumeci A. Persistent hiccup as presenting Baclofen therapy for chronic hiccup. 1. Turkyilmaz A. Graham DY. In: Bogousslavsky stent-related hiccups. 23(1): 42-5. 34(4): 536-8. Ponnusamy A. Tubiana JM. E-mail: kahmeng. doi: 10. Eroglu A. 24. 1992. 79(6): 697–9. Cabane J. 5(2):89–92. Published Date: May 06. About the mechanism of hiccup. Jung S. Baclofen neurotoxicity in a patient with end-stage chronic renal failure. Shi G. Meng. Sampath V. provided the original work is properly cited. 2015. Arc Cas Rep CMed 1(1): 101. Why do we hiccup? Gut. Park MH.seizure. Chou CL. Indian J and Central Post-Stroke Pain in a Lateral Medullary Infarction-Two Case Psychol Med. 85(1): 328-30. Singapore General Hospital. Noshi MS.2012. Cabane J. In: Victor M. Ann Thorac Surg. Bhattacharyya D. Norrving B. Compte-Jove MT. Medullary infarcts and hemorrhages. .42. Alix JJ1. Cambridge Arch Phys Med Rehabil.pre2014. 20. 8(2): 235-7. 820-2. Fernández-Antuña L. Treatment of intractable hiccup with baclofen: 9. Eur Respir J. Use of baclofen in the treatment of esophageal 14. Arc Cas Rep CMed 1(1): 101. 21(10): Gastroenterol. Lesional location Nefrologia. Br J Neurosurg. 1998. Gállego-Gil C. 2001: 534-9. Citation: Meng KK. eds: Adams and Victor’s principles of neurology. Neurology 16(6): 986-995. Preethi S. report.2nd ed. Lee JH. Bizec JL. Moon CO. 16.kwok@mohh. double-blind. 2013. 8. Ropper AH.001. Guelaud C. Nijanth M. 17: 365-368. 19. Bricolo A. 13. Whitelaw WA. South Med J. 22. doi: 10. Huang HH. 21. Kahrilas PJ. Copyright: © 2015 Kwok K. 2005. J Med Biomed Sci. 10. J Neurol Apr. Am J Complex partial seizures: Going out with a hiccup. unusual central cause for unilateral vocal cord palsy. Citation: Meng KK. the role of cerebral MRI in cases without systemic cause. Grünewald RA. Eur Neurol. Nijanth M. Zhang S. Nilsson S. Shaheen M. Bousson V. 4. Kim TY. 2015. Cheong YK. University Press. J. Kumar A. 1. Cambridge. 76(1): 95–8. 1997. Vinay HR. Park MK. Hoggard N.com. Park KW. Ashfaq L (2015) Use of Baclofen in the Treatment of Persistent Hiccups: Report of Page 3 of 3 Two Cases. Results of a double-blind randomized. Meng. Reports and Literature Review. Ashfaq L (2015) Use of Baclofen in the Treatment of Persistent Hiccups: Report of Two Cases. Singapore. doi: 10. cross-over study. Persistent hiccups (singultus) 17. Intractable hiccups during stroke rehabilitation.3344/kjp. 2014. This is an open access article distributed under the Creative Commons Attribution License. Hwang SH.1186/1745-6215-15-295. Lin SH. Caplan L. 2014.16(10):2093-100.09. Gabapentin Therapy for Persistent Hiccups as the presenting symptom of lateral medullary syndrome. Ropper 159–63. Askenasy JJ. Fodstad H.Arc Cas Rep CMed Vol. 29000101 3. Kim BJ. Hiccups: A treatment review. et al. intractable hiccups in acute pure lateral medullary infarction. 1995. Gowda MR. Yiang CH. 1993. Issue. *Corresponding author: Kwok K. Ramirez FC. Xu M.135397.1. 7. Intractable hiccups: trial. Choi YS. 23. 15: 295. eds: Stroke syndromes.2010. 12. Justo-Ávila P. 1995. Cristofori L. Intractable singultus: A diagnostic and therapeutic challenge. Trials. 2001: 678-82. Accepted Date: April 30. 32(3): 15. New York: McGraw- Hill.1016/j.