Frequency and Symptomatology of Hiccups in Patients With Cancer: Using an On-Line Medical Community to Better Understand the Patient Experience.

BACKGROUND: Cancer patients are at risk for hiccups, but the incidence and impact on quality of life are unclear. METHODS: A survey (modified from the Functional Living Index with the inclusion of qualitative elements) was developed and launched on an 80,000-member medical social media platform, Mayo Clinic Connect https://connect.mayoclinic.org/. RESULTS: Among 213 respondents, 34 (16%; 95% CI: 11, 22%) reported "yes" that they had experienced hiccups with cancer therapy. Of those patients who reported hiccups, only 12 (35%) were men, and most were older than 50 years of age. Over 25% noted that hiccups occurred frequently around the time of cancer therapy; 30% described that hiccups interfered with their leisure or recreational activities; and over 15% described hiccups interfered with their ability to enjoy a meal. A few patients seemed to express frustration with hiccups with comments such as, "Totally uncontrollable," "It's extremely pain[ful] with throat cancer," and "Once I had them bad. Almost choked." CONCLUSION: Hiccups occur in16% of patients who are receiving cancer therapy and, by our estimates and extrapolation, appear highly problematic in approximately 5%.

Hiccups in Cancer Patients Receiving Chemotherapy: A Cross-Sectional Study.

CONTEXT: Hiccups are a symptom in cancer patients but it's less researched. OBJECTIVES: The aimed to determine of prevalence of hiccups and treatment approach used in hiccup management in cancer patients receiving chemotherapy for nursing care. METHODS: This study used a descriptive cross-sectional design with self-reported questionnaires and was conducted from November 2018-May 2019 in Turkey. For collection of the data, a Patient Information Form (sociodemographic and disease characteristics), and a Hiccups Evaluation Form were used for the patients. RESULTS: Hiccups were observed in 37 (23%) of the 160 patients who met the criteria for inclusion in the study. The great majority of the patients suffering from hiccups were male (65.9%) and the type of cancer in the majority of these patients was gastrointestinal cancer (54.1%). It was determined that the duration of hiccups in 83.8% of patients observed with hiccups was between 0 and 48 hours, that the average severity of their hiccups was 3.81 ± 2.25 (0-10), and that hiccups in 59.5% of these patients was of low severity. It was found that only 10.8% of patients suffering from hiccups used pharmacological methods for relief and that 27% used nonpharmacological methods. CONCLUSION: The results of the study showed that over one-fifth of cancer patients suffered from hiccups. This situation reveals that hiccups are an important symptom that needs to be carefully emphasised in oncology practice.

The effect of gender differences in protracted hiccups.

BACKGROUND: Although little importance is attached to hiccups, they may be associated with several diseases. The purpose of this study was to investigate the effects of gender differences on types of hiccups and the relation with diseases involved in the etiology. MATERIALS AND METHODS: Patients presenting to the Kirikkale University Medical Faculty Hospital with hiccups were investigated retrospectively. Patients' age, sex, duration of hiccups, additional diseases, advanced imaging results, laboratory tests, and clinical follow-up were recorded. Patients were divided into two groups; Group transient hiccup (TH) consisted of subjects with a duration of hiccups less than 48 h, and Group protracted hiccup (PH) of patients with a duration exceeding 48 h. The Chi-square test was used for comparisons, and P < 0.05 were regarded as significant. RESULTS: Eighty-four patients were enrolled, 44.1% (n = 37) in Group TH, and 55.9% (n = 47) in Group PH. Male patients comprised 67.5% (n =25) of Group TH and 89.4% (n = 42) of Group PH (P = 0.027). The conditions most associated with hiccups were gastrointestinal system (GIS) diseases. Correlation was determined between GIS diseases and male gender (P = 0.034), no relation between other system diseases and gender. Correlation was determined between GIS diseases and protracted hiccups (P = 0.037), but no relation between other system diseases and type of hiccups. CONCLUSION: Protracted hiccups are more common in males. This gender variation applies particularly to hiccups of GIS origin.

Analysis of factors associated with hiccups based on the Japanese Adverse Drug Event Report database.

Hiccups are occasionally experienced by most individuals. Although hiccups are not life-threatening, they may lead to a decline in quality of life. Previous studies showed that hiccups may occur as an adverse effect of certain medicines during chemotherapy. Furthermore, a male dominance in hiccups has been reported. However, due to the limited number of studies conducted on this phenomenon, debate still surrounds the few factors influencing hiccups. The present study aimed to investigate the influence of medicines and patient characteristics on hiccups using a large-sized adverse drug event report database and, specifically, the Japanese Adverse Drug Event Report (JADER) database. Cases of adverse effects associated with medications were extracted from JADER, and Fisher's exact test was performed to assess the presence or absence of hiccups for each medication. In a multivariate analysis, we conducted a multiple logistic regression analysis using medication and patient characteristic variables exhibiting significance. We also examined the role of dexamethasone in inducing hiccups during chemotherapy. Medicines associated with hiccups included dexamethasone, levofolinate, fluorouracil, oxaliplatin, carboplatin, and irinotecan. Patient characteristics associated with hiccups included a male gender and greater height. The combination of anti-cancer agent and dexamethasone use was noted in more than 95% of patients in the dexamethasone-use group. Hiccups also occurred in patients in the anti-cancer agent-use group who did not use dexamethasone. Most of the medications that induce hiccups are used in chemotherapy. The results of the present study suggest that it is possible to predict a high risk of hiccups using patient characteristics. We confirmed that dexamethasone was the drug that has the strongest influence on the induction of hiccups. However, the influence of anti-cancer agents on the induction of hiccups cannot be denied. We consider the results of the present study to be helpful for the prevention and treatment of hiccups.

Hiccups. Attitude in Otorhinolaryngology Towards Consulting Patients. A Diagnostic and Therapeutic Approach. / Hipo. Actitud en otorrinolaringología en pacientes que consultan. Aproximación diagnóstica y terapéutica.

INTRODUCTION: Hiccup crises are generally benign and self-limiting, but longer episodes affect quality of life and must be treated. There are recognisable causes that otorhinolaryngologists must know and be aware for diagnosis and therapeutic alternatives. The main expression is a spasmodic glottic noise with characteristic neck alterations. PATIENTS AND METHODS: This was a retrospective study from 1979 with patients suffering persistent 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 disorders -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. Therapeutic 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.

Gender Differences in Hiccup Patients: Analysis of Published Case Reports and Case-Control Studies.

CONTEXT: Although sporadic male predominance in hiccup patients has been reported, the association between gender differences and triggering factors has rarely been evaluated in patients with hiccups. OBJECTIVES: The aim of this study was to investigate whether gender differences exist in hiccup patients by analyzing all previously published hiccup literature containing gender and etiology information. METHODS: Published literature on this topic was identified using a standardized search strategy in the PubMed, SCOPUS, and CINAHL electronic databases. The literature search included studies published from January 1990 to December 2013. Searches were limited to English-language publications. Of 476 identified studies, 318 studies were eligible including eight case-control studies that contained nonhiccup control groups. Triggering factors for hiccups were categorized into two types: central nervous system (CNS) and non-CNS causes. Odds ratios (ORs) were calculated for the eight case-control studies and event rates for the other studies by meta-analysis. In addition, gender differences and mean ages were analyzed for the case studies. RESULTS: Pooled OR was 2.42 (95% confidence interval [CI] 1.40-4.17) with inclination for male predominance. Subgroup analysis by cause showed clear male predominance in the non-CNS type with OR of 11.72 (95% CI 3.16-43.50), whereas indistinct in the CNS type with OR of 1.74 (95% CI 0.95-3.16). Of the remaining 310 studies with 864 patients, previous findings were consistent. Male predominance was consistent in non-CNS (85.1%, 95% CI 78.2-90.2) and unknown origin (82.2%, 95% CI 75.8-87.2) patients, whereas mitigating the sex discrepancy in those with CNS origin (65.8%, 95% CI 53.1-76.5). CONCLUSION: We demonstrated male predominance in hiccup patients. This gender difference for hiccups was more pronounced in patients with non-CNS causes, whereas indistinct in patients with CNS causes.

Orphan symptoms in advanced cancer patients followed at home.

Orphan symptoms are rarely assessed, particularly at home. The aim of this multicenter prospective study was to assess the prevalence of these symptoms and eventual factors possibly associated in advanced cancer patients at admission of a home care program. A prospective study was performed at three home care programs in Italy. Patients' data were collected, including age, sex, diagnosis, and Karnofsky status. Possible contributing factors were analyzed; preexisting neurological diseases, cerebral metastases, hyperthermia, diabetes, a state of dehydration clinically evident and/or oliguria, possible biochemical parameters when available, data regarding recent chemotherapy, opioids and doses, use of neuroleptics, benzodiazepine or anticonvulsants, corticosteroids, anti-inflammatory, and antibiotics were collected. Myoclonus, hiccup, sweating, pruritus, and tenesmus, either rectal or vesical, were assessed, according to a preliminary definition, at time of home care program admission. Three hundred sixty-two patients were surveyed at the three home care programs. Globally, 48 patients presented one or more orphan symptoms in the period taken into consideration, and 7 patients presented more than 1 symptom. One patient presented occasional and diffuse myoclonus. Nineteen patients presented sweating, 13 patients presented pruritus, and 14 patients presented hiccup. Finally, nine patients presented rectal or vesical tenesmus. There was a significant correlation between sweating and transdermal fentanyl use (P = 0.044), fever (P = 0.001), hiccup (P < 0.0005), and vesical tenesmus (P = 0.028). Pruritus was not associated to any factor. Hiccup was associated with gender (males, P = 0.006) and sweating (P < 0.0005). Vesical tenesmus was associated with fever (P = 0.019) and sweating (P = 0.028). Although the symptoms examined have a low prevalence in advanced cancer patients admitted to home care, the distress for patients may be high and deserve further analyses. Given the low prevalence of these symptoms, large studies are needed to find possible associated factors.

[A search for the risk factors for hiccups and evaluation of antiemetic therapy in CDDP-based chemotherapy, using cluster analysis].

Hiccups are often observed in patients treated with cisplatin(CDDP)-based chemotherapy. It has been reported that gender and specific dosages of CDDP and antiemetic drugs(e.g., dexamethasone and 5-HT3 receptor antagonist)using standard therapy are major risk factors in the onset of hiccups. Recently, aprepitant has been added to the antiemetic therapy in CDDP-based chemotherapy. However, it is not known how the onset of hiccups takes place in antiemetic therapy including aprepitant according to the guideline. In this study, we used cluster analysis to classify 229 patients treated with CDDP-based chemotherapy, to investigate the effect of antiemetic therapy on the onset of hiccups and chemotherapy-induced nausea and vomiting(CINV). Our analysis indicated that aprepitant was not a major risk factor for the onset of hiccups in the high CDDP dose group(≥70 mg/m(2)). However, an effect of antiemesis was confirmed in the standard therapy with aprepitant. In conclusion, we suggest that aprepitant is effective for CINV, without causing the onset of hiccups in patients treated with high-dose CDDP-based chemotherapy.

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.

Sedation-associated hiccups in adults undergoing gastrointestinal endoscopy and colonoscopy.

AIM: To investigate whether the incidence of hiccups in patients undergoing esophagogastroduodenoscopy (EGD) or same-day bidirectional endoscopy (EGD and colonoscopy; BDE) with sedation is different from those without sedation in terms of quantity, duration and typical onset time. METHODS: Consecutive patients scheduled for elective EGD or same-day BDE at the gastrointestinal endoscopy unit or the health examination center were allocated to two groups: EGD without sedation (Group A) and BDE with sedation (Group B). The use of sedation was based on the patients' request. Anesthesiologists participated in this study by administrating sedative drugs as usual. A single experienced gastroenterologist performed both the EGD and the colonoscopic examinations for all the patients. The incidence, duration and onset time of hiccups were measured in both groups. In addition, the association between clinical variables and hiccups were analyzed. RESULTS: A total of 435 patients were enrolled in the study. The incidences of hiccups in the patients with and without sedation were significantly different (20.5% and 5.1%, respectively). The use of sedation for patients undergoing endoscopy was still significantly associated with an increased risk of hiccups (adjusted odds ratio: 8.79, P < 0.001) after adjustment. The incidence of hiccups in males under sedation was high (67.4%). The sedated patients who received 2 mg midazolam developed hiccups more frequently compared to those receiving 1 mg midazolam (P = 0.0028). The patients with the diagnosis of gastroesophageal reflux disease (GERD) were prone to develop hiccups (P = 0.018). CONCLUSION: Male patients undergoing EGD or BDE with sedation are significantly more likely to suffer from hiccups compared to those without sedation. Midazolam was significantly associated with an increased risk of hiccups. Furthermore, patients with GERD are prone to develop hiccups.

Intractable hiccup and nausea in neuromyelitis optica with anti-aquaporin-4 antibody: a herald of acute exacerbations.

BACKGROUND: Intractable hiccup and nausea (IHN) are unique symptoms in neuromyelitis optica (NMO). Recent studies have strongly suggested that the pathogenesis of NMO is closely associated with anti-aquaporin-4 (AQP4) antibody. However, clinical implications of IHN and the relationship with anti-AQP4 antibody remain unknown. METHODS: The past medical records of 35 patients with seropositivity for anti-AQP4 antibody were reviewed. We also followed the titres of anti-AQP4 antibody in a patient with NMO, who had newly developed IHN. RESULTS: Of the 35 patients, 15 patients (43%) had episodes of IHN. There was a total of 35 episodes of IHN in these 15 patients and, of the 35 episodes, hiccup was seen in 23 episodes (66%) and nausea was seen in 28 episodes (80%). The IHN frequently preceded (54%) or accompanied (29%) myelitis or optic neuritis. The IHN was often preceded by an episode of viral infection. The titres of anti-AQP4 antibody were remarkably increased when the intractable hiccup appeared in a case. CONCLUSIONS: IHN could be a clinical marker for the early phase of an exacerbation. Careful observation may be needed when INH is seen in patients with NMO, and the early initiation of the treatment could prevent subsequent neurological damage.

Metoclopramide does not influence the frequency of propofol-induced spontaneous movements.

STUDY OBJECTIVE: To evaluate the effects of metoclopramide on the frequency and severity of propofol-induced movements. DESIGN: Randomized, double blind, placebo-controlled trial. SETTING: Veterans Administration Medical Center. PATIENTS: One hundred thirty-seven consenting adults scheduled to receive general anesthesia with propofol induction. INTERVENTIONS: Patients were randomized to receive either metoclopramide 10 mg intravenously (IV) or placebo (saline) 3 min before induction of general anesthesia. All patients received midazolam 1 to 2 mg IV, fentanyl 50 to 150 microg IV, and lidocaine 50 to 80 mg IV before induction of anesthesia. MEASUREMENTS: Occurrence of spontaneous movements and severity during the observation period were recorded after propofol induction by observing movement in the hands/arms and feet/legs, as well as presence of a hiccup. The dosage of anesthetic medications administered was also recorded for each patient. MAIN RESULTS: No differences were noted in the frequency and severity of spontaneous movement in the patients who had received metoclopramide and placebo. However, compared with the patients who did not move, patients who experienced movements received a significantly higher dose of propofol (P = 0.025) and a lower dose of fentanyl (P = 0.049). CONCLUSIONS: Metoclopramide does not affect the frequency of propofol-induced movements, but propofol and fentanyl doses influence the frequency of movements during propofol induction.

Prevalence of atypical symptoms and their association with typical symptoms of gastroesophageal reflux in Spain.

BACKGROUND: The association between typical and atypical symptoms of gastroesophageal reflux (GER) has received little attention in population-based studies. This study therefore sought to examine the prevalence of atypical symptoms, and their association with typical GER symptoms in Spain. METHODS: A telephone survey using a validated questionnaire was conducted in 2002 on 2500 subjects aged 40-79 years, randomly selected from the general population of Spain. The questionnaire included items on typical GER symptoms (heartburn and acid regurgitation) and several atypical symptoms (chest pain, dysphagia, belching, dyspepsia, globus, hoarseness, hiccups, chronic cough and asthma). The association between typical GER symptoms and each atypical symptom was summarized using odds ratios obtained from logistic regression. RESULTS: The response rate was 71.2%. A total of 60.8% (95% confidence interval 59.0-62.8%) of subjects reported suffering from at least one atypical symptom during the year preceding the interview. The prevalence rates varied from 26.7% for hoarseness to 6.6% for asthma. The prevalence of atypical symptoms was higher among the 791 subjects with typical GER symptoms than among the 1709 subjects reporting no typical GER symptoms (79.6 versus 52.2%). It was also higher among those reporting frequent typical GER symptoms compared with those reporting occasional symptoms (87.8 versus 58%). After adjustment for age, sex, coffee, alcohol and tobacco consumption, and psychosomatic symptoms, an association (P<0.05) was observed between typical symptoms and the respective atypical symptoms, with odds ratios ranging from 1.4 for asthma to 4.6 for belching. After additional adjustment for the remaining atypical symptoms, chest pain, dysphagia, dyspepsia, belching and globus were each independently associated with typical reflux symptoms. CONCLUSION: The prevalence of atypical GER symptoms is extremely high. There is an association between typical and atypical GER symptoms, particularly chest pain, dysphagia, dyspepsia, belching and globus.

[Drug-induced hiccup: a review of the France pharmacologic vigilance database]. / Hoquet d'origine médicamenteuse: enquête à partir de la Banque Nationale de Pharmacovigilance.

Hiccup is a sudden contraction of the inspiratory muscles, followed by an abrupt closure of the glottis, thus producing a characteristic sound. Some drugs have been reported to induce hiccup. Using the French Pharmacovigilance Database, the aim of the present study was to investigate reports of such an adverse drug reaction (ADR). Between 1985 and 1997, 53 cases were reported to the French pharmacovigilance network. The sex ratio was 16.6. Mean age was 52 years (range 18-83). Of the total number, 23 per cent were related to corticosteroids. 15 per cent to psychiatric (mainly non-imipraminic antidepressants), 13 per cent to neurologic (mainly dopaminergic antiparkinsonians), 12 per cent to anti-infectious (beta-lactams, macrolides, fluoroquinolones), 7 per cent to cardiovascular (mainly digitalic compounds), 6 per cent to analgesic (opioid drugs), 6 per cent to non-steroidal anti-inflammatory drugs.... Rechallenge was positive in 7 cases. Two cases were 'serious' according to the WHO definition. The diagnosis of drug-induced hiccup is difficult and often achieved only by a process of elimination. The mechanism of this drug-induced ADR remains often not clearly explained.

[Stopping persistent hiccups in the adult by endoscopic maneuver]. / Arrêt du hoquet persistant de l'adulte par manoeuvres endoscopiques.

Thirty-four patients with persistent hiccups (median duration 10 days) were treated by gentle endoscopic massage of the region of the cardia. Hiccups stopped in all cases. Its early recurrence in one patient only required a second massage, which was also effective. This simple technique is recommended for the treatment of persistent hiccups.

[Chronic hiccups]. / Le hoquet chronique.

We report 18 cases of chronic hiccup (defined as lasting for more than 48 hours) in adults. Among the numerous possible causes, reflux esophagitis proved to be by far the most frequent (50% of the cases). However, hiccup often initiated a self-perpetuating vicious circle. This is possibly because hiccup per se can give esophageal dyskinesia, which in turn leads to gastro-esophageal reflux. The treatment was difficult and whenever possible has been directed chiefly towards the cause. However hiccup remained intractable in many cases even after a possible cause had been adequately cured (e.g., successful Nissen procedure in reflux cases). Central nervous system depressants and myorelaxing drugs were not very helpful, except for baclofen (initial response rate = 60%).

Vibroacoustic stimulation and fetal hiccoughs.

Hiccoughs are a physiological phenomenon, beginning in the second trimester of pregnancy, increasing in frequency throughout gestation, and continuing into the neonatal period. There is concern about the safety of the use of vibroacoustic stimulation of the third-trimester fetus as part of the evaluation of fetal well-being. This study was directed to determine whether the evoked fetal startle response would accentuate or decrease the incidence of hiccoughs. Of the 342 nonstress tests (NSTs) performed, fetal hiccoughs were heard during 39 (11.4%) tests. The incidence of hiccoughs was 10.6% (25/236) of patients stimulated with sound and 13.2% (14/106) of these without sound (P = NS). Hiccoughs were found to increase in frequency throughout the third trimester. In all nonreactive NSTs, hiccoughs were absent. This vibroacoustic stimulation did not affect the fetal physiologic response of hiccoughs, and the absence of hiccoughs in nonreactive NSTs may be another indicator of fetal compromise.