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PubMed2005

Cisplatin-related hiccups: male predominance, induction by dexamethasone, and protection against nausea and vomiting.

Dexamethasone is likely to play a role in the etiology of hiccups in patients receiving cisplatin-based regimens. Two hundred seventy-seven patients received three doses of ondansetron 8mg intravenously (IV) at 4hour intervals plus dexamethasone 20mg IV from the start of chemotherapy, followed by dexamethasone 5mg IV every 12hours, until chemotherapy was complete. Hiccups were observed in 114 (41.2%) patients, of whom 97.4% were men. Nausea and vomiting showed inverse correlations with hiccups (P < 0.0001 and P = 0.001, respectively). In 73 patients who experienced hiccups but lacked nausea/vomiting (H+N/V-), we discontinued dexamethasone in subsequent cycles. Sixty-six patients (90.4%) ceased hiccuping, but complete protection rates of nausea and vomiting decreased to 63% and 74%, respectively. For patients who experienced both hiccups and nausea/vomiting, the onset of nausea/vomiting usually was delayed to Day 3 or 4 and began after the cessation of hiccups. We conclude that cisplatin-related hiccups are predominant in males, dexamethasone-induced, and associated with protection against nausea/vomiting.

Adolescent↗
PubMedDate not supplied

Idiopathic chronic hiccup: combination therapy with cisapride, omeprazole, and baclofen.

Idiopathic chronic hiccup (ICH) is defined as recurring hiccup attacks that last for longer than an arbitrary time limit (eg, 1 month) and for which no organic cause can be found. In patients with ICH, therapy is largely empiric. For practical purposes, idiopathic hiccup can be assumed to have its origin either in the viscera (gastrointestinal tract) or in the central nervous system. Cisapride and omeprazole--through reduction of gastric acid production and facilitation of gastric emptying, respectively--are thought to reduce an assumed afferent input from the periphery to a putative supraspinal hiccup center. Baclofen is thought to reduce excitability and depress reflex hiccup activity. Fifteen male patients (mean [+/- SD] age, 68.2 +/- 11.6 years) who had recurring hiccup attacks for a mean duration of 100.8 +/- 134.1 months (range, 12 to 564 months) were treated for ICH with a combination of cisapride, omeprazole, and baclofen (COB). Therapy led to a total disappearance of hiccup in 40% (6 of 15) of the treated patients. An additional 20% (3 of 15) of patients experienced substantial relief. A Mann-Whitney rank order test showed a highly significant reduction in the severity of the hiccup attacks as reflected in the subjective assessment scale scores taken before therapy (8.6 +/- 1.3) compared with those taken after 20 weeks of therapy (4.1 +/- 3.8). Thus we concluded that COB is an effective empiric therapy in at least some patients with ICH.

Adult↗
PubMed1998

GABAergic inhibition of hiccup-like reflex induced by electrical stimulation in medulla of cats.

We hypothesize that the hiccup reflex is actively inhibited through GABA(B) receptor within central connections of the hiccup reflex arc. Because the hiccup-like reflex can be elicited by electrical stimulation to a limited area within the medullary reticular formation, the hiccup-evoking site (HES), electrical stimulation (50-100 microA, three train pulses at 20 Hz) was delivered to HES by means of a metal electrode containing 1.0 mM baclofen, in anesthetized spontaneously breathing cats. The evoked response was characterized by a brief powerful increase in diaphragmatic activity and a temporal suppression of the posterior cricoarytenoid muscle, laryngeal dilator, which corresponded to the fixed motor pattern of hiccup reflex. The hiccup-like response was rapidly suppressed after microinjection of baclofen (0.1-0.5 nmol) into HES, indicating that HES has GABA(B) receptors. In the other experiments, to histologically examine the inputs to the hiccup reflex arc, unconjugated cholera toxin subunit B (UCTB) was injected into HES. Following injections of UCTB, retrogradely labelled cells were found distributed in various areas of the lower brainstem. Among these areas, the nucleus raphe magnus (RM) is reported to have GABA-containing cells. It is thus hypothesized that RM is most likely to be the source of the GABAergic inhibitory inputs to the hiccup reflex arc.

Animals↗
PubMed2003

Treatment of hiccup during general anaesthesia or sedation: a qualitative systematic review.

BACKGROUND AND OBJECTIVE: Acute hiccup is a minor complication that can occur during sedation or general anaesthesia. The disorder can disturb the surgical field, might interfere with lung ventilation or could hamper diagnostic procedures. The objective was to perform a systematic search for interventions aimed at treating hiccup occurring during anaesthesia or sedation. METHODS: A systematic search for reports describing interventions to treat hiccup in conjunction with anaesthesia was carried out (MEDLINE, EMBASE, Cochrane-Library, manual screening of reference lists and review articles, up to December 2001). Search terms were 'hiccup', 'singultus' or 'hiccough'. RESULTS: Twenty-six reports involving approximately 581 patients focused on hiccup remedies in the anaesthesia setting. Only one report was substantiated by a randomized controlled trial. This investigated methylphenidate 10 mg intravenously in 51 patients, which did not show a beneficial effect compared with placebo. Hiccup was a self-limiting phenomenon. Case series and case reports focused on various systemically applied drugs in 12 reports, stimulating techniques (e.g. pharyngeal stimulation) in seven, topical applied remedies (e.g. intranasal ice-cold water) in four, and ventilation techniques (e.g. continuous positive pressure ventilation) in two. CONCLUSIONS: A large variety of interventions have been proposed for the treatment of hiccup during anaesthesia and sedation. However, perioperative treatment is still based on empirical findings and no treatment is 'evidence-based'. Thus, no valid recommendations for the treatment of hiccup can be derived. Uncontrolled observations are inadequate to establish treatment efficacy.

Anesthesia, General↗
PubMed1999

Incidence and therapy of midazolam induced hiccups in paediatric anaesthesia.

A prospective, randomized and double blind study was undertaken to determine the incidence and a possible dose- or age-dependence of hiccups in children premedicated with rectal midazolam and to investigate the treatment of hiccups by intranasal ethyl chloride spray application. Two hundred ASA physical status 1 and 2 children, weighing 3.0 to 15.0 kg, scheduled for minor surgery, were randomly assigned to be given either 0.5 mg.kg-1 midazolam(n=100) or 1.0 mg. kg-1 midazolam (n=100) administered rectally. If hiccups were observed during a period of 20 min after premedication with midazolam, these children were treated after 3 min of hiccups with two short intranasal applications of ethyl chloride spray. Hiccups occurred in 22% of children in the 0.5 mg.kg-1 group and 26% in the 1.0 mg.kg-1 group (n.s.). The intranasal application with ethyl chloride was successful in 100% in both groups. The mean age levels between children with or without hiccups were 5+/-9 months vs 21+/-19 months (P<0.01) in the 0.5 mg.kg-1 group and 6+/-7 months vs 20+/-14 months (P<0.01) in the 1.0 mg.kg-1 group. Intranasal application of ethyl chloride spray seems to be an effective therapy for midazolam induced hiccups in paediatric anaesthesia. The incidence of these hiccups is highly age significant, but not dose dependent.

Adjuvants, Anesthesia↗
PubMed1985

Hiccups: causes and cures.

Hiccups result from a wide variety of conditions that act on the supraspinal hiccup center or that stimulate or disinhibit the limbs of its reflex arc. While scores of hiccup remedies have been reported over the centuries, no single "cure" stands out as being the most effective. Measures that stimulate the uvula or pharynx or disrupt diaphragmatic (respiratory) rhythm are simple to use and often help to speed the end of a bout of otherwise benign, self-limited hiccups. Such manueuvers may also terminate persistent hiccups. Drug therapy usually becomes necessary for more intractable hiccups; chlorpromazine and metoclopramide being two of the most widely employed agents for this purpose. Physical disruption of the phrenic nerve, hypnosis, and acupuncture are other modes of therapy that have been used in severe cases. Because so many reports of hiccup "cures" are based on anecdotal experience rather than controlled clinical studies, I review the available treatments to provide a rational approach for the management of hiccups.

Abdomen↗
PubMed1993

Persistent postoperative hiccups: a review.

The pathogenesis of persistent postoperative hiccups is not known. Hiccups can present as a symptom of a subphrenic abscess of gastric distention, and metabolic alterations may also cause hiccups. The hiccups may develop because of increased activity in neural reflex pathways not yet fully defined. Numerous treatment modalities have been tried but with questionable success. Valproate has proven effective in two trials investigating persistent non-surgical hiccups. The simple application of a nasogastric tube may successfully treat the hiccups, possibly because of an alteration of the activity in the reflex neural pathways involved. The available literature on the treatment of persistent hiccups is reviewed, and a treatment protocol for persistent postoperative hiccups is provided.

Hiccup↗
PubMedDate not supplied

Hyponatraemia and hiccups.

BACKGROUND: Hiccups are observed in many patients with hypohatraemia. We performed a case-control study to evaluate their association in a referral teaching hospital in South India. METHODS: Fifty consecutive patients who developed hiccups during an 18-month period were studied. They were categorized according to age group and diagnosis and controls matched for age and sex were selected from patients admitted on the same day in the medical wards. Hiccups were graded on a four-point severity scale at recruitment and every day till day 7 or till hiccups subsided. RESULTS: The step-wise logistic regression analysis done to establish independent association showed that for every 10 mEq/L reduction in serum sodium, patients were 17 times (p = 0.001; confidence interval: 4-87) at risk of developing hiccups. The only other significant determinant of the symptom was the diagnostic category of renal failure (odds ratio = 128; confidence interval: 1-1420). The number of patients who had hyponatraemia with varying severity of hiccups showed a dose-response relationship. The crude odds ratios were 7, 58 and 320 for mild, moderate and severe hiccups. CONCLUSION: There is a strong and independent association between hyponatraemia and hiccups in hospitalized patients. A causative association is suggested by the dose-response relationship demonstrated in the study. In many hospitals in developing countries where measurement of serum sodium is difficult and unreliable, it is important to be aware of this association since it can be easily corrected.

Female↗
PubMed1999

[Hiccup].

Hiccup is defined as involuntary contractions of the diaphragm and the auxiliary respiratory muscles, mostly in irregular series, followed by glottic closure, thereby producing a typical "hiccupping" inspiration. This is a physiologic phenomenon, which already exists in utero. Hiccup is believed to be a gastrointestinal reflex; however, function and the reflex arch are hypothetical. Acute hiccup is distinguished from pathological, chronic hiccup, defined by a duration executing 48 h, or recurrent episodes. Among approximately 100 causes for hiccup, the most common are located in the gastrointestinal tract, with gastro-esophageal reflux as the most important. While the respiratory effect is generally negligible, alkalosis may ensue in tracheotomized patients due to hyperventilation. A stepwise management plan for patients with hiccup is presented. If simple physical maneuvers and causal therapy fail, or causal therapy is impossible, the treatment of choice is medical, with baclofen. Interruption of the reflex arch may be causal therapy or be considered as a last resort.

Adult↗
PubMed1999

Perphenazine-induced hiccups.

Hiccup is a spasmodic, involuntary contraction of the inspiratory muscles, associated with delayed and abrupt glottic closure causing a peculiar sound (Launois et al., 1993). A number of medical conditions are known to cause persistent and intractable hiccups. Among the drugs reported to induce hiccups, Thompson et al. stated that corticosteroids and benzodiazepines are the drug classes most frequently associated with the development of hiccups (Thompson and Landry, 1997). Antidopaminergic agents such as chlorpromazine and haloperidol are the preferred drugs used for the treatment of chronic hiccups (Launois et al., 1993). We report a case of severe hiccups occurring in association with the administration of perphenazine, which is a dopamine antagonist. To the best of our knowledge, this is the first report of hiccups occurring as a side effect of antidopaminergic drugs.

Adult↗
PubMed2005

Lesional location of lateral medullary infarction presenting hiccups (singultus).

BACKGROUND: Hiccups are an infrequent result of lateral medullary infarction. Their importance may be underestimated and they can cause distress, exhaustion, and aspiration. Hiccups in lateral medullary infarction remain poorly understood OBJECTIVE: To evaluate the relation between the lesional loci of lateral medullary infarction and hiccups. METHODS: 51 patients with lateral medullary infarction were investigated by magnetic resonance imaging within three days of the onset of infarction. Seven of the 51 patients developed hiccup. RESULTS: All patients with hiccups had middle level lateral medullary lesions, including two with lower level lesions and four with upper level lesions. In the middle level lateral medullary lesions, dorsolateral lesions were most often involved. All patients with lateral medullary infarction presenting with hiccups also had vertigo, dizziness, nausea, vomiting, and dysphagia. CONCLUSIONS: The observations suggest that middle level and dorsolateral lesion locations in lateral medullary infarction frequently induce hiccups.

Adult↗
PubMed1993

Intractable hiccups: treatment by microvascular decompression of the vagus nerve. Case Report.

Idiopathic hiccups are usually managed with pharyngeal stimulation or a plethora of pharmacological agents. Hiccups that persist and prove intractable to these medical measures are treated by crush or ablation of the phrenic nerve, which denervates the major respiratory muscle. This is the first reported case of nondestructive microvascular decompression of the vagus nerve for the treatment of intractable idiopathic hiccups. The success of microvascular decompression has been documented with other conditions, such as trigeminal neuralgia and hemifacial spasm, that are characterized by hyperactive dysfunctional neurovascular contact. The vagus nerve was separated from the posterior inferior cerebellar artery by inserting a Teflon pledget between the nerve and vessel which eliminated the neurovascular contact. One year after the initial surgery, the hiccups recurred. The Teflon pledget had fallen out of place and the nerve was once again in contact with the artery. Once the contact was eliminated by wrapping the artery with a tuft of Teflon, the hiccups stopped. The patient has remained free of hiccups for 3 years. It is concluded that patients with intractable idiopathic hiccups who fail medical therapy should be considered for microvascular decompression of the vagus nerve.

Adolescent↗
PubMed1983

Fetal hiccups: an associated fetal heart rate pattern.

Fetal hiccups are commonly diagnosed during the antepartum period, and they have a tendency to recur. The reflex of hiccuping is similar to that of gasping, except hiccuping efforts are made against a closed airway. An episode of intrapartum hiccups was confirmed via real-time ultrasound scanning during monitoring with a direct fetal scalp electrode. A neonatal heart rate pattern during hiccuping is also included. Distinctive fetal and neonatal heart rate patterns were observed during the hiccuping episode. It is speculated that the fetal heart rate pattern seen with hiccups may resemble that of fetal gasping.

Female↗
PubMed1980

Intractable hiccups. (singultus).

Intractable hiccups (singultus) is an uncommon disorder with various etiologies. The majority of reported studies of intractable hiccups has claimed ipsilateral spasm of the hemidiaphragm based solely on clinical or radiographic evidence. A case of intractable hiccups is presented. Documentation of normal phrenic nerve latencies with bilateral synchronous firing of anterior scalene, intercostal muscles and bilateral hemidiaphragm involvement is presented. This combination of muscle group involvement supports the concept of a "supraspinal hiccup center." A systematic trial of chemotherapeutic agents described as effective against hiccups was employed. Relief lasting for three to four week periods has been obtained by the intravenous administration of a specially prepared sterile solution of methylphenidate. The nerve pathways pertinent to hiccup are discussed. The etiology of intractable hiccups and the various treatment modalities are presented.

Brain Stem↗
PubMed1997

[Diabolic hiccup].

Hiccup is a brief involuntary inspiratory movement followed by glottal closure. Transitory hiccup is usually caused by epigastric irritation. Rarely, hiccup may last for a long time, and is known as diabolic hiccup. A case is described of diabolic hiccup due to a unilateral lesion of nucleus tractus solitarius in the brainstem. This probably resulted in release of inhibition of the hiccup reflex. Therapeutic suggestions in diabolic hiccup are chlorpromazine, baclofen, valproate and nifedipine.

Baclofen↗
PubMed1998

The Significance of Umbilical Vein Doppler Changes during Fetal Hiccups

> Objective: The physiology of hiccups is a sharp inspiratory gasp against a closed glottis, causing a sudden sharp fall in intrathoracic pressure. This would be expected to cause an increase in venous return to the chest; however, we noticed that umbilical venous Doppler waveforms indicated a cessation of flow during hiccups. We observed other hiccuping fetuses to ascertain the range of response of the fetal umbilical vein Doppler waveforms and derive an explanation for them. Methods: Fetuses who were hiccuping at the time of their antepartum testing had observations of umbilical vein flow made, and representative recordings of the trace were obtained. Results: Ten Doppler traces were obtained from fetuses during hiccuping. In every case there was a brief fall of the umbilical vein Doppler waveform to base line, indicating an arrest of flow. Conclusions: Fetal hiccups are associated with arrest of flow in the umbilical vein as demonstrated by Doppler waveforms. This is contrary to predictions based on previously demonstrated fetal physiology of hiccups. We speculate that the findings result from obstruction of the venous return by a combination of the contracting diaphragm at the level of the inferior vena cava as it passes through the diaphragm, by raised intra-abdominal pressure from the descending diaphragm, and possibly from kinking of the umbilical vein at the umbilical ring.

Journal Article↗
PubMed1989

Hiccups and gastroesophageal reflux: cause and effect?

Chronic hiccups may be a problem of great significance to the affected patient. A 62-year-old man with severe heartburn and persistent hiccups despite numerous diagnostic tests and therapeutic drug trials presented to our clinic. Esophageal motility and intraluminal pH studies demonstrated decreases in intraesophageal pressure during hiccups and acid exposure during 68% of the measured time. The patient underwent Nissen fundoplication, which improved his heartburn but not his hiccups. The association between gastroesophageal reflux and hiccups is discussed. Our experience suggests that the presence of hiccups and gastroesophageal reflux in the same patient may be coincidental rather than having a cause-and-effect relationship.

Chronic Disease↗
PubMed1991

Intractable hiccup induced by brainstem lesion.

Four patients with brainstem lesions presented with intractable hiccup and mild to moderate neurological signs. Two of the patients had been initially diagnosed as having a psychogenic cause for their hiccup. Magnetic resonance imaging (MRI) demonstrated brainstem infarction in one case, tuberculoma at the junction of the medulla oblongata and the cervical spinal cord in two, and a vermian tuberculoma compressing the brainstem in one. The brainstem infarct and one of the medullary tuberculoma were not detected on high resolution enhanced computed tomography. The 3 patients with CNS tuberculoma were free of hiccup 1-5 months after antituberculous chemotherapy. It is proposed that hiccup is not an abnormal reflex, but a myoclonus generated by repetitive activity of the "inspiratory solitary nucleus" due to release of higher nervous system inhibitory/-regulatory control. The neuroanatomical network and the mechanisms underlying the formation of intractable hiccup are outlined. The value of MRI in the initial diagnosis and follow-up of patients with intractable hiccup due to brainstem lesions is emphasised.

Adult↗