Article, Neurology

Intradermal injection for hiccup therapy in the Emergency Department

a b s t r a c t

Hiccup is a condition caused by involuntary contraction of inspiratory muscles, especially the diaphragm. Al- though it is generally considered as a physiological. response, if hiccup persists for a long time, it can lead to many undesirable conditions such as depression, weight loss, insomnia, and fatigue. A 35-year-old male patient was admitted to our emergency department with hiccup lasting for 15 h. He had a history of several hiccup attacks. Classical non-pharmacological and pharmacological therapies were used to treat the condition without any response. As an alternative method, an intradermal injec- tion was applied. A mixture of thiocolchicoside and lidocaine was administered intradermally to a depth of 1-3 mm at the epigastric region and adjacent to the sternocleidomastoid muscle. The patient’s hiccup ended after the intradermal injection procedure. During 48 h of follow-up the hiccup attack did not develop again. No complications related to the process were detected. This is the first case in the literature demonstrating the use of intradermal injection to terminate hiccups. The intradermal injection approach can be administered in cases of hiccups that do not respond to medical treatment.

(C) 2020

Introduction

Hiccup (hiccough or singultus) is the sound that occurs during the sudden closure of the glottis as a result of involuntary, rhythmic, and re- current contraction of the inspiratory muscles, especially the dia- phragm. Although it usually ends in minutes or hours, it can sometimes last for days. Stubborn hiccups that persist for a long time can cause unwanted conditions such as depression, weight loss, malnu- trition, insomnia, and fatigue [1]. Almost every individual experiences hiccup some time during life, but its incidence and prevalence have not been studied. However, according to a retrospective study, 55 of the 100,000 patients admitted to the hospital had hiccups [2,3].Al- though there is no consensus on its classification, hiccups lasting less than 48 h are considered as transient or acute, while those continuing more than 48 h are categorized as persistent, and hiccups lasting more than one week are regarded as chronic. Most cases are acute, and these hiccups are considered physiological. The duration of pathological hiccups has not been determined with strict limits [1,4]. Hiccups of 4-60 per minute can be observed [5].

* Corresponding author at: Department of Emergency Medicine, Faculty of Medicine, Ataturk University, 25240 Erzurum, Turkey.

E-mail address: [email protected] (A.O. Kocak).

There is no consensus on the pathophysiology and treatment of hiccups. Although most of the cases are benign, long-term hiccups may decrease the comfort of daily life. There is a wide range of treat- ments extending from simple non-pharmacological options such as drinking water and breathing maneuvers to pharmacological treat- ments or even surgical procedures. Although hiccup is generally seen as a simple clinical condition, some patients are treated by hospitaliza- tion [5].

With this case, we aimed to present a new alternative treatment op- tion in the management of acute hiccups.

The case

A 35-year-old male patient presented with a complaint of hiccups that had been going on for 15 h. The patient’s hiccup episode started early in the morning and continued uninterruptedly until midnight. He hiccupped on averAge SIx to eight times a minute. He stated that he drank ice water several times at home, held his breath, swallowed granulated sugar, and bitten lemon, but nevertheless, came to the hos- pital when he could not pass the complaint. He had a history of 12 hic- cup attacks in the last 5 years. These attacks continued for 12-60 h. The past attacks had been treated in the hospital with medication. His med- ical investigation concerning the source of the hiccup attacks revealed no pathology. There was no history of chronic disease or medication

https://doi.org/10.1016/j.ajem.2020.03.044

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use. Also, he did not use cigarettes and alcohol. The vital findings were normal. No pathological condition was found in the detailed systemic examination. Routine Biochemical tests and complete blood count re- sults were normal too.

As no source of hiccups could be found, intravenously (IV) 40 mg empirical esomeprazole and orally 10 cc reflux-suppressant sodium al- ginate were administered. However, the hiccup did not cease. There- upon, IV infusion of metoclopramide HCl and chlorpromazine hydrochloride (Largactil 25 mg ampoule, Eczacibasi Pharmaceuticals, Turkey) were initiated in 500 cc isotonic solution within 30 min. How- ever, there was no change in the hiccup complaint. The patient was followed up and observed in the emergency room. During the follow- up, the chlorpromazine hydrochloride infusion was repeated twice. The patient was hospitalized. Since the symptoms did not regress 24 h after the first hiccup attack, considering the effect of the vagal nerve on hiccups for the patient, it was decided to perform mesotherapy with intradermal injection as an alternative method.

After obtaining approval from the patient, the first intradermal injec- tion was made adjacent to the vagal nerve and the sternocleidomastoid muscle. In this region, the intradermal injection was performed around the sternocleidomastoid muscle according to the course of the vagal nerve (Picture 1). The second injection was directed to the diaphragm, which is the primary muscle responsible for hiccups. Three points were determined in the epigastrium region immediately adjacent to the diaphragm; intradermal injections were applied to these points (Picture 2).The book of Dr. Jacques Le Coz was taken as a reference in de- termining these points [6].

Mesotherapy was performed by an experienced and trained doctor using 4-mm-long 30-Gauge needles (Meso-relle, Biotekne SRL, Italy). A mixture of 1 cc (2 mg) thiocolchicoside (Tyoflex, Abdi Ibrahim Phar- maceuticals, Turkey) and 1 cc (16.2 mg) lidocaine (Aritmal, Osel Phar- maceuticals, Turkey) was prepared for intradermal injection. Of this mixture, 0.1-0.2 cc was injected into each determined point intrader- mally at 1-3 mm depth. The point-to-point intradermal injection method was used. No papules were created during the intradermal in- jection procedure.

The hiccup ended 15 min after the mesotherapy procedure, but the patient was kept under observation for another 48 h. No recurrence was observed. The patient was seen a week later, and no complications

Fig. 1. Determination of several points in the neighborhood of the sternocleidomastoid muscle, and application of the intradermal injection.

Fig. 2. The points indicated with stars are determined as intradermal injection points.

secondary to intradermal injection were observed, neither had he an- other hiccup attack.

Discussion

This is the first and only patient in the literature to show that hiccups can be terminated with intradermal injections in the emergency room. Our case offers a new approach to hiccup treatment.

Hiccups are produced by a reflex arc formed by afferent fibers, the hiccup center, and efferent components. Afferent stimulation is carried to the central nervous system through the phrenic nerve and sympa- thetic nerve fibers, especially the vagal nerve. The upper spinal cords (C3-5) form the part of the central nervous system of the reflex arc, the medulla oblongata, the brainstem, the hypothalamus, and the retic- ular formation. The phrenic nerve, intercostal, and anterior scalene muscles form the efferent part of the reflex arc. The stimuli are transmit- ted via the phrenic nerve to the diaphragm [4,7].

Any process that stimulates this reflex arc can initiate hiccups. Hic- cup is a symptom, not a disease, and more than a hundred causes have been identified that may cause this symptom. gastric distension due to overeating and especially carbonated drinks are the most com- mon causes. Apart from these, metabolic and toxic irritation, infectious processes, gastrointestinal diseases, thoracic pathologies, neurological diseases, side effects of some medications (benzodiazepines, steroids), and psychogenic causes may cause hiccups. As in our patient, hiccups are idiopathic in a substantial proportion of the patients [3,5,7].

Determining the reason that stimulates the reflex arc and eliminat- ing the underlying cause constitutes the basis of hiccup treatment. However, in most patients, causation cannot be determined, and defin- itive treatment is not possible. In these cases, several pharmacological and non-pharmacological treatment options can be used empirically to stop hiccups [3,5].

pharmacological agents used in the treatment of hiccups act by inhibiting the reflex arc that creates hiccups. However, experience with many drugs is based only on case reports. Therefore, there is no clear consensus in the literature on optimal primary medical therapy for persistent hiccups. Among the existing drugs, there is FDA approval only for the use of chlorpromazine. Apart from this, metoclopramide is often preferred in the treatment of hiccups. When chlorpromazine and metoclopramide are used together, it usually shows effectiveness within 30 min. However, they can cause different side effects, especially extrapyramidal [3,4].There are many non-pharmacological treatment alternatives for the termination of hiccups. The effectiveness of many physical maneuvers is based on the hypothesis that stimulation of the pharynx will block the vagal part of the reflex arc, and thus, eliminate hiccups. Nasopharyngeal stimulation (vinegar, ice application), respira- tory maneuvers (Valsalva maneuver, CPAP application), and vagal

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stimulation (cold application to the face, carotid message) are among the non-pharmacological treatment methods [3].

Due to the effect of vagal stimulation on the termination of an acute hiccup, vagal stimulation has been emphasized throughout the history of its acute treatment. Many Treatment methods mentioned above were basically developed based on this concept [1].Also, the intradermal injections around the sternocleidomastoid muscle stimulate the vagal nerve [6]. We think that intradermal injections around the sternocleidomastoid muscle stimulate the vagal nerve, eventually end- ing the hiccup.

In a study involving 28 patients who did not respond to pharmaco- logical treatments, hiccup status was terminated by applying continu- ous ropivacaine infusion with a cervical epidural block at the C3-C5 level [8]. In another study, hiccups were ended by using phrenic nerve block to hiccups who did not respond to chlorpromazine, metoclopramide, and gabapentin [9].

Intradermal mesotherapy is a more straightforward procedure than cervical Epidural anesthesia and phrenic nerve block. Additionally, the risk of developing complications with intradermal injection is lower. In our case, hiccups were successfully terminated after intradermal in- jection. For these reasons, we recommend intradermal injection as first-line therapy in the treatment of persistent hiccups. Besides, since drug therapy has extrapyramidal side effects, intradermal mesotherapy may be a better choice in the treatment of hiccups.

In conclusion, the application intradermal injections successfully ended hiccup in a patient that did not respond to medical treatment, and no complications developed during the follow-up.

Acknowledgements

None.

Declaration of competing interest

The authors declare no competing interests to disclose.

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