A randomized, double-blinded feasibility trial of educational materials for hiccups in chemotherapy-treated patients with cancer.

PURPOSE: Chemotherapy can cause hiccups but few randomized controlled trials have focused on hiccups. This trial examined the feasibility of such research. METHODS: This single-institution, multi-site trial used phone recruitment for patients: (1) 18 years or older, (2) able to speak/read English, (3) with a working e-mail address, (4) with hiccups 4 weeks prior to contact, and (5) with ongoing oxaliplatin or cisplatin chemotherapy. The primary outcome was feasibility. Patients were randomly assigned to one of two sets of educational materials, each of which discussed hiccups and palliative options. The experimental materials were almost identical to the standard materials but provided updated content based on the published medical literature. At 2 weeks, patients responded by phone to a 5-item verbally administered questionnaire. RESULTS: This trial achieved its primary endpoint of recruiting 20 eligible patients within 5 months; 50 patients were recruited in 3 months. Among the 40 patients who completed the follow-up questionnaire, no statistically significant differences between arms were observed in hiccup incidence since initial contact, time spent reviewing the educational materials, and the troubling nature of hiccups. Twenty-five patients tried palliative interventions (13 in the experimental arm and 12 in the standard arm), most commonly drinking water or holding one's breath. Eleven and 10 patients, respectively, described hiccup relief after such an intervention. CONCLUSIONS: Clinical trials for chemotherapy-induced hiccups are feasible and could address an unmet need.

Intradermal injection for hiccup therapy in the Emergency Department.

Hiccup is a condition caused by involuntary contraction of inspiratory muscles, especially the diaphragm. Although 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 injection 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.

Medication treatment of singultus in palliative care.

Singultus (hiccup) is caused by periodic involuntary spastic contractions of the respiratory muscles followed by a sharp inspiration and early glottis closure. This results in typical "hic" sound. Brief episodes of hiccups are quite common experience in general population, and they do not indicate serious disease nor require medical treatment. If chronic, they pose a significant problem with plethora of negative consequences on patient condition, particularly in palliative care. Treatment options involve many approaches - both nonmedication and medication options. However, there are no large controlled trials resulting in unambiguous recommendations. Current pharmacologic treatment strategies are therefore only based on small studies and case reports and they report more or less successful outcomes using medications with different mechanisms of action.

Intractable Hiccups.

PURPOSE OF REVIEW: Hiccups are a common problem that crosses multiple disciplines including neurology, gastroenterology and pulmonology, and primary care. There are no formal guidelines to the treatment of intractable hiccups and treatment is based on experience and anecdotal evidence often relying on older medications. We have reviewed the relevant literature with an emphasis on the last five years or so in management of intractable hiccups. RECENT FINDINGS: The production of hiccups is a complex mechanism which involves multiple neurotransmitters and anatomical structure within the central and peripheral nervous system. A number of medications and other therapy have been reported successful for intractable hiccups. Intractable hiccups can occur more often than we realize and present to multiple medical disciplines. A number of pharmacologic option have been found to be useful including dopamine-blocking medication, baclofen, and gabapentin along with anticonvulsants.

Chronic Hiccups: An Underestimated Problem.

Persistent singultus, hiccupping that lasts for longer than 48 hours, can have a tremendous impact on a patient's quality of life. Although involved neurologic structures have been identified, the function of hiccups remains unclear-they have been controversially interpreted as a primitive reflex preventing extent swallowing of amniotic fluid in utero, an archaic gill ventilation pattern, or a fetus' preparation for independent breathing. Persistent singultus often presents as a symptom for various diseases, most commonly illnesses of the central nervous system or gastrointestinal tract; they can also be evoked by a variety of pharmacological agents. It is often impossible to define a singular cause. A wide range of treatment attempts, pharmacological and nonpharmacological, have been concerted to this date; however, chlorpromazine remains the only Food and Drug Administration-approved drug in this context. Large-scale studies on efficacy and tolerance of other therapeutic strategies are lacking. Gabapentin, baclofen, and metoclopramide have been reported to accomplish promising results in reports on the therapy of persistent singultus; they may also be effective when given in combination with other drugs, eg, proton pump inhibitors, or as conjoined therapy. As another approach of note, acupuncture treatment was able to abolish hiccups in a number of studies. When managing hiccup patients within the clinical routine, it is of importance to conduct a comprehensive and effective diagnostic workup; a well-functioning interdisciplinary team is needed to address possible causes for the symptom. Persistent singultus is a medical problem not to be underestimated; more research on options for effective treatment would be greatly needed.

Clinical analysis of neuromyelitis optica presenting as intractable nausea, vomiting and hiccups.

Vomiting and hiccups can be the manifestations of numerous systemic and neurological illnesses. Intractable nausea, vomiting and hiccups (INH) are reported as possible initial manifestations of neuromyelitis optica (NMO), but not correctly identified. Awareness of these atypical presentations is conducive to NMO early diagnosis and proper treatment to prevent further disability. In this paper, 12 NMO were reported, whose intractable vomiting and hiccups were the sole manifestations of the first attack and other attacks involving spinal cord and optic nerves developed later. All the patients were women and serum aquaporin 4 antibody (AQP4-Ab) of 83% patients was positive. MRI of 50% patients showed T2-weighted imaging/fluid attenuated inversion recovery hyperintensity which were longitudinally extensive transverse myelitis or linear signal changes. Sixty-seven percent of patients had medulla lesions, in which dorsomedial and area postrema were involved.

Pharmacologic Interventions for Intractable and Persistent Hiccups: A Systematic Review.

BACKGROUND: Chlorpromazine is the only drug approved by the US Food and Drug Administration for the treatment of hiccups; however, many other pharmacologic treatments have been proposed for intractable and persistent hiccups. Currently, there is little evidence to support the use of one agent over another. OBJECTIVE: This review aims to identify literature concerning the use of pharmacologic treatments for intractable and persistent hiccups with the goal of evaluating therapies in terms of their level of evidence, mechanism of action, efficacy, dosing, onset of action, and adverse effects. METHODS: A systematic literature search of PubMed, Embase, the Cochrane Library, and the New York Academy of Medicine was performed to find articles where a pharmacologic agent was used to treat intractable or persistent hiccups between the years 1966 and 2016. The GRADE method was used to assess the level of evidence for the studies included in this review. RESULTS: This review identified 26 articles involving 10 pharmacologic treatment options that met our inclusion criteria. Amitriptyline, baclofen, gabapentin, haloperidol, metoclopramide, midazolam, nifedipine, nimodipine, orphenadrine, and valproic acid were found in the literature to be successful in treating hiccups. CONCLUSION: Baclofen, gabapentin, and metoclopramide were the only agents that were studied in a prospective manner, while only baclofen and metoclopramide were studied in randomized controlled trials. No specific recommendations can be made for treating intractable and persistent hiccups with the evidence currently available in the literature. Therapy selection should be specific to individual patients, their underlying comorbidities, etiology of hiccups, and take into account the individual properties of the drugs.

[Persistent Chemotherapy-Induced Hiccups Successfully Treated with Pregabalin].

A 62-year-old male was diagnosed with large cell lung cancer(c-Stage IV)based on pathological examination of an anterior chest tumor. He received chemotherapy with cisplatin, pemetrexed, and bevacizumab. He suffered from persistent hiccups from day 2 of the first course of chemotherapy. He was unsuccessfully treated with chlorpromazine, shakuyakukanzoto, and gabapentin. Therefore, we administered pregabalin to him, and his hiccups subsided immediately. To prevent hiccups, he subsequently took pregabalin along with his chemotherapy regimen, and was able to receive 4 courses of chemotherapy without persistent hiccups. Pregabalin is a possible therapeutic option for treating persistent chemotherapy-induced hiccups.

Treatment of resistant idiopathic hiccups with pulse radio frequency on phrenic nerve and gabapentin: A case report.

Hiccups affect life quality, career and family life when they become persistent. We present here a 54-year-old man who worked as a mason and a blacksmith with hiccups complaint for nearly one and a half years. In this period, he was admitted to emergency service ten times with fainting or almost fainting, cold sweating and hand stretching complaints. The patient expressed that he frequently threw up when he had hiccups and his social life was negatively affected. He reported that he was treated with baclofen, esomeprazole and hyoscine-n-butyl bromur without relief. He used escitalopram and chlorpromazine for a short time and quit because they negatively affected his sleeping. As he did not have any relief from medications, he refused any oral medical therapy including gabapentin and started to seek remedy from paramedical treatments resulted with no benefit. The patient was referred to algology department and an intervention on phrenic nerve with pulse radio frequency (8 minutes, 45 Volts, 20 milliseconds wavelength) was performed. Symptoms stopped immediately after the procedure but one week later, although the patient reported a significant decline in symptoms he still had hiccups. The patient was offered oral medical therapy again. With considerable relief from symptoms, the patient accepted oral therapy this time. Gabapentin 300 mg bid was prescribed. The symptoms were completely recovered and the patient reported no hiccups after 30 days of Gabapentin administration. Our case suggests that administration of gabapentin after pulsed radiofrequency might be effective for the treatment of persistent hiccups.

Metoclopramide for patients with intractable hiccups: a multicentre, randomised, controlled pilot study.

BACKGROUND: Limited data exist regarding the efficacy of metoclopramide in the treatment of intractable hiccups. AIM: This study aimed to assess the feasibility efficacy of metoclopramide in the treatment of patients with intractable hiccups. METHODS: A total of 36 patients with intractable hiccups was randomly assigned to arm A (n = 18) or arm B (n = 18) in a multicentre, double-blind, randomised, controlled pilot study. Participants in arm A received 10-mg metoclopramide thrice daily for 15 days, whereas those assigned to arm B received 10-mg placebo thrice daily for 15 days. The primary outcome measure was total efficacy against hiccups (including cessation and improvement of hiccups). Secondary outcome measures included a comparison of overall efficacy and adverse events between the two arms. RESULTS: Of the 36 patients enrolled, 34 participants completed the study. The total efficacy was higher in arm A than in arm B (relative risk, 2.75; 95% confidence interval: 1.09-6.94, P = 0.03). Furthermore, comparison between the two arms revealed that overall efficacy was higher in arm A than that in arm B (P < 0.05). No serious adverse events related to the treatment were documented in either arm. The most common adverse events occurring in patients in arm A included fatigue, upset mood and dizziness. CONCLUSION: Metoclopramide appears to be a promising candidate for the treatment of patients with intractable hiccups, with mild adverse events. However, further clinical trials are required to confirm these results.

Gabapentin for the treatment of persistent hiccups.

OBJECTIVE: To report a case of persistent hiccups successfully treated with gabapentin in an elderly male. SETTING: An acute care unit for elders within a large teaching hospital. CASE SUMMARY: An 86-year-old male was admitted to the hospital for treatment of a urinary tract infection. In addition to his infection, the patient complained of bothersome hiccups with an onset several days prior to admission. He received metoclopramide for two days without improvement. Based on his medical history and a probable neurogenic etiology, gabapentin was recommended for his hiccups. Symptoms improved within several hours, with complete resolution after a dose titration to 200 mg twice daily on the second day of gabapentin treatment. The patient was ultimately discharged back to his long-term care facility, but was readmitted three days later for the treatment of pneumonia. His hiccups recurred and were treated unsuccessfully with metoclopramide in the emergency department. Gabapentin was reinitiated by the geriatric medicine team, and the patient's hiccups resolved once again. CONCLUSION: Randomized, controlled trials evaluating the use of gabapentin in the treatment of hiccups associated with neurogenic etiologies are lacking; however, case reports suggest that this agent may be an effective treatment option.

Baclofen for hiccups: a large mixed methods multisite study.

OBJECTIVE: Hiccups can be bothersome and spawn morbidity. Although oral baclofen is perhaps the most prescribed agent for hiccups, a paucity of data supports its use. METHODS: This multisite, single institution study examined the medical records of patients who had hiccups and had been prescribed baclofenas noted in a clinical encounter. Mixed methods were used to assess baclofen's palliative efficacy. In view of the sometimes transient nature of hiccups and other such factors, cessation or palliation of hiccups in 75% of patients was sought to indicate true palliation. RESULTS: A total of 301 patients with a median age of 61 years (range 20-87 years) and a male predominance are the focus of this report. Baclofen was most often prescribed at 10 mg orally three times a day. Only 105 patients (35%) (95% CI: 30% to 41%) acquired hiccup palliation. Corroborative medical record quotations included, 'Still has hiccups.'Quotations such as, 'Responding to baclofen this AM', were also recorded. Baclofen appeared more likely to benefit patients with hiccups of >48 hours (chronic) duration in univariable analyses (OR for benefit: 0.51 (95% CI: 0.29 to 0.91; p=0.02) with similar conclusions drawn from multivariable analyses. Adverse events occurred in 15 patients with drowsiness the most common. CONCLUSIONS: Baclofen did not meet this study's a priori threshold for successful hiccup palliation, but further study is indicated to learn whether baclofen might help patients with chronic hiccups.

Rare case report of moxifloxacin-induced persistent hiccups.

Moxifloxacin is a broad-spectrum antimicrobial agent that is commonly used in clinical practice. Here we report an unusual case of a patient with persistent hiccups caused by moxifloxacin. A man aged in his 40s was treated with moxifloxacin for tuberculous pleurisy. Hiccups occurred 2 hours after intravenous injection of moxifloxacin and lasted into evening. On the second day after injection, hiccups occurred again and made it difficult for him to fall asleep. The clinician ruled out gastrointestinal disease, nervous system disease, electrolyte disturbance and other factors. On assessing causality of the adverse drug reaction, the Naranjo scale for moxifloxacin was six, indicating a probable relationship of hiccups with moxifloxacin. Hiccups stopped 2 min after intramuscular injection of metoclopramide. To our knowledge, this is the first case report about moxifloxacin-induced persistent hiccups. Clinicians should be aware of the rare adverse reaction.

Intractable cough and hiccups after resuscitation and acute coronary syndrome treatment successfully treated using the Kampo medicine bukuyoingohangekobokuto: A case report.

BACKGROUND: Even in patients who survive resuscitation through multidisciplinary treatment, minor persistent symptoms can make hospital discharge difficult. Herein, we report a case of myocardial infarction with intractable symptoms following resuscitation, which were successfully treated using Kampo medicine. CASE PRESENTATION: A 71-year-old man experienced intractable cough and hiccups following resuscitation for acute myocardial infarction. Despite successful invasive treatment for his cardiac condition, the patient's persistent symptoms hindered his recovery and discharge from hospital. The patient was diagnosed with qi and blood deficiency, qi stagnation, and fluid retention, before being prescribed the Kampo medicine "bukuryoingohangekobokuto (BRIHK)". Within days of treatment initiation, his symptoms notably improved, allowing him to be discharged. CONCLUSION: This case highlights the potential of Kampo medicine for addressing post-resuscitation symptoms that are refractory to conventional treatments, and emphasizes the importance of integrating Kampo medicine with Western medical practices to enhance patient care and quality of life.

Persistent hiccups after acute COVID-19 successfully treated with chlorpromazine: a case report.

INTRODUCTION: Hiccups are among the rare complications of COVID-19 infections. There are several published reports of persistent hiccups presenting during the acute COVID-19 period. However, there are very few published reports of persistent hiccups occurring in the post-acute COVID-19 period. Consequently, most clinicians may not be aware of this rare presentation. This case highlights an atypical presentation of persistent hiccups that manifested during the post-acute COVID -19 period that clinicians need to be aware of. The caseadds to the ever increasing body of knowledge about symptoms and signs associated with Severe Acute Respiratory Syndrome Corona Virus type 2 (SARS CoV-2) infection. CASE PRESENTATION: A 27 year old male black Zambian patient presented to the emergency department of our hospital with persistent hiccup, 35 days after the initial acute episode of COVID-19. This was associated with breathlessness. There were no other symptoms. He had no history of pulmonary, gastrointestinal, neurological disease or malignancy. He did not take any alcohol or smoke. He had never used any recreational drugs. He was employed as a monitoring and evaluation officer at one of the main COVID centres in the capital. On examination, the patient was anxious. Blood pressure was 141/82, pulse rate was 95 beats per minute, respiratory rate was 26 breaths per minute, temperature was 36.8C and oxygen saturation was 97% on room air. Systemic examination was normal. Chest X-ray and abdominal ultrasonography were normal. A rapid COVID-19 antigen test, and COVID-19 Polymerase Chain Reaction (PCR) test that were done the following day were negative. All other haematological and biochemical tests, including D-dimer and C-reactive protein (CRP), were also normal. A diagnosis of post-acute COVID-19 associated hiccups was made. The patient responded well to treatment with chlorpromazine 25 mg 8 hourly. The hiccups disappeared completely after the fourth dose of chlorpromazine. CONCLUSION: This is one of the few published cases of COVID-19 associated persistent hiccups, occurring more than a month after the initial presentation. Most of the published cases report hiccups occurring in the acute COVID-19 period. Consequently, hiccups occurring in the post-acute COVID-19 period may not be attributable to COVID-19. This case has highlighted the need to consider post-acute COVID-19 in the differential diagnosis of persistent hiccup.

Prolonged hiccups induced by renal infarction: a case report.

BACKGROUND: Hiccups are common symptoms that last for less than 48 hours. However, we encountered a case of renal infarction in a patient with prolonged hiccup. The relationship between hiccups and renal infarction is important in differentiating patients with prolonged hiccups. CASE PRESENTATION: An 87-year-old Japanese man with atrial fibrillation and receiving antithrombotic therapy presented to the emergency department with prolonged hiccups. The patient discontinued antithrombotic therapy for atrial fibrillation due to subcortical bleeding, after which he experienced right back pain. He was diagnosed with right renal infarction based on computed tomography images, and the antithrombotic therapy was continued. The patient's hiccups ceased, and he was discharged on hospital day 11. CONCLUSION: Hiccups can be induced by various clinical conditions. It is hypothesized that the inflammation of the right kidney infarction stimulated the diaphragm and induced prolonged hiccups in this patient; this theory is supported by the computed tomography images. This case report shows that internal organ diseases irritating the diaphragm can cause hiccups, and renal disease should be considered in patients with prolonged hiccups.

Refractory singultus and area postrema syndrome as a presentation of neurocysticercosis.

Neurocysticercosis (NCC) is the most common parasitic infection of the central nervous system, caused by the pork tapeworm, Taenia solium Common presenting features are seizures, headaches and focal neurodeficits. The present report details the anecdote of a middle-aged Asian man, who presented with subacute onset of persistent nausea, vomiting and hiccups. Following unsuccessful trials with numerous prokinetic, antipsychotic, muscle relaxant and anticonvulsant medications, as well as an uneventful battery of gastrointestinal tests, he was referred for neurological evaluation. The constellation of symptoms was congruent with the diagnosis of area postrema syndrome. Although initial CT scan of brain was normal, MRI with contrast evaluation revealed a circumscribed, ring-enhancing lesion of the dorsal medulla oblongata, reminiscent of colloid vesicular stage of NCC. The patient was successfully treated with steroids and albendazole. The association of refractory singultus, nausea and vomiting and NCC is thus far, not reported in the literature.

Gabapentin therapy of hiccups.

OBJECTIVE: To determine whether gabapentin is effective in the treatment of persistent or intractable hiccups. DATA SOURCES: A search of MEDLINE (1966-March 2013) using the MeSH search terms gabapentin, hiccups, and hiccups/drug therapy was performed. Additional databases searched included Web of Science (1945-March 2013) and International Pharmaceutical Abstracts (1970-March 2013) using the text words gabapentin and hiccups. Bibliographies of relevant articles were reviewed for additional citations. STUDY SELECTION AND DATA EXTRACTION: All data sources were considered for inclusion. Preference was given for articles written in English, although one abstract in German was used. DATA SYNTHESIS: Because of the low incidence of persistent or intractable hiccups, few if any controlled clinical trials are conducted on the efficacy of drug treatment. Therefore, most of the data involve case reports or case series. We evaluated 17 case reports and 2 case series involving gabapentin therapy for persistent or intractable hiccups. Therapeutic outcomes with gabapentin were positive in all cases, with temporal evidence suggesting an effect, but outcomes often were obscured by combination therapy and comorbidities in some cases. Case reports suggest that gabapentin might be useful as a second-line agent in patients undergoing stroke rehabilitation or in the palliative care setting where chlorpromazine adverse effects are undesirable. Gabapentin was very well tolerated, with only a few minor adverse effects. CONCLUSIONS: Gabapentin has a similar body of evidence as other pharmacotherapeutic agents used to treat hiccups. Gabapentin is well tolerated and should be considered as a second-line agent in selected patients.