Identifying the Hiccup-Induced Esophagogastric Waveform: A Case Series Report Using High-Resolution Manometry.

Hiccups result from involuntary contractions of the diaphragm, driven by a complex neuromuscular reflex. Three patients with persistent hiccups underwent esophageal high-resolution manometry during hiccup episodes, revealing a consistent finding: sustained contraction of the esophagogastric junction with intermittent pressure peaks. This pattern, termed the "Hiccup-Induced Esophagogastric Waveform," shows significant esophageal pressure changes linked to hiccup reflex. It may reflect a compensatory mechanism to expel excess esophageal residue or gas. These findings suggest hiccups could exacerbate symptoms of esophageal disorders, such as dysphagia and chest pain, and highlight the need for targeted therapeutic strategies. Further research is needed to explore these mechanisms.

The annoyance of singultus: a case report of a rare adverse effect after epidural steroid injection.

OBJECTIVE: Cervical epidural steroid injections (ESIs) can provide effective pain management for patients suffering from chronic neck pain due to various pathological changes of the cervical spine. There are several rare adverse effects reported from interventional pain procedures, including persistent hiccups ("singultus"). Based on a limited number of cases, we propose a modified treatment algorithm for this adverse outcome (Fig. 3). CASE REPORT: Singultus has been documented as an adverse effect of interventional pain procedures, including epidural steroid, facet joint, and sacroiliac joint injections. We describe the case of a general contractor who presented to our clinic with chronic neck pain and central canal stenosis. The patient received an uncomplicated lumbar ESI in the past and was recommended for a cervical interlaminar ESI. After an uneventful C6-C7 interlaminar ESI with dexamethasone, 1% lidocaine, and normal saline the patient developed singultus. Baclofen was sent to his pharmacy, but this was unsuccessful at alleviating his hiccups. The patient was subsequently started on chlorpromazine and found relief from his symptomatology. CONCLUSION: Persistent hiccups after ESI or interventional pain procedures can be treated with conservative measures and non-pharmacologic methods, with escalation to therapy with baclofen, gabapentin, pregabalin, metoclopramide, chlorpromazine, other antipsychotic or antidopaminergic agents, and possible dual or triple therapy if further indicated.

Ultrasound-guided bilateral pulsed radiofrequency of the phrenic nerve for prolonged hiccups: a case report.

Singultus is the sudden onset of erratic diaphragmatic and intercostal muscle contraction immediately followed by laryngeal closure. Pathophysiology involves afferent, central and efferent components. Bilateral phrenic nerve block was performed to a 46-year-old woman with a brain tumor with persistent hiccups, with initially positive response but later symptom recurrence. Bilateral pulsed radiofrequency of the phrenic nerve was performed guided by ultrasonography (US). In the follow-up, absence of hiccups was confirmed. The patient was discharged 24 h later. Persistent or untreatable singultus is an infrequent condition that should not be dismissed. This approach is a safe, accurate and effective therapeutic approach for patient's refractory to conservative treatment. Further studies are needed to establish safety and effectiveness of the treatment.

Intractable hiccups after VNS implantation: a case report.

BACKGROUND: Hiccups (medically termed, "singultus"), when intractable, can cause significant medical consequences such as aspiration, malnutrition, and depression, leading to poor quality of life. Several case reports have shown that vagus nerve stimulator (VNS) implantation can help treat central idiopathic intractable hiccups. However, we present a contrary case of a patient who developed intractable singultus following VNS placement for medically refractory epilepsy. CASE PRESENTATION: We report a 71-year-old male patient with drug-resistant epilepsy who underwent VNS implantation and developed intractable hiccups shortly thereafter. The hiccups were severe and persistent, such that the patient developed a Mallory-Weiss tear, which required intensive care, invasive intubation and mechanical ventilation, and a prolonged rehabilitation course. Despite multiple therapies including phrenic nerve block and Nissen fundoplication, the patient's hiccups persisted and only stopped once the VNS was permanently deactivated. CONCLUSIONS: Little is known about the incidence of hiccups after VNS implantation. We present one case of hiccups as a direct consequence of VNS implantation. The clinical impact of this report is significant given the relative unfamiliarity of hiccups as an adverse effect of VNS implantation. Neurologists and epileptologists, who present VNS implantation as a surgical option for seizure control to their patients, should be aware of the possibility of singultus development and its significant physical and emotional ramifications.

[Persistent hiccup as initial clinical manifestation of SARS-CoV-2 infection]. / Hipo (singulto) persistente como manifestación clínica inicial de infección por SARS-CoV-2.

SARS-CoV-2 infection usually manifests as an acute respiratory syndrome, characterized by fever, cough, sore throat and dyspnea. Nonetheless, since the beginning of the pandemic in December 2019, less frequent initial symptoms were reported, as the sudden appearance of hiccups (singultus). We describe a clinical case of a 62-year-old male with a medical history of arterial hypertension, diabetes and chronic cardiac insufficiency, who complained of persistent hiccups as initial manifestation of COVID-19, followed by respiratory symptoms. After the SARS-CoV-2 infection diagnosis was made, the patient was hospitalized, receiving the corresponding treatment. The singultus partially improved with dopaminergic antagonists and it disappeared on the sixth day of hospitalization. Glycemic correction with regular insulin was required. He presented a favorable outcome, being discharged after 14 days of hospitalization.

La infección por SARS-CoV-2 se presenta generalmente como un síndrome respiratorio agudo, caracterizado por fiebre, tos, odinofagia y disnea. Sin embargo, desde el comienzo de la pandemia, a fines del año 2019, fueron reportados otros síntomas menos frecuentes, como manifestación inicial de la enfermedad, entre ellos la aparición de hipo (singulto). Se describe el caso de un varón de 62 años de edad con antecedentes de hipertensión arterial, diabetes e insuficiencia cardiaca, que sufrió hipo persistente como primer síntoma de COVD-19, seguido de síntomas respiratorios. Luego de efectuado el diagnóstico de infección por SARS-CoV-2, el paciente fue hospitalizado y recibió el tratamiento correspondiente. El singulto mejoró parcialmente con el uso de fármacos anti-dopaminérgicos (metoclopramida) y desapareció al sexto día de internación. Se requirió la corrección de la glucemia con insulina corriente. Evolucionó favorablemente y fue externado luego de 14 días de hospitalización.

Hipo (singulto) persistente como manifestación clínica inicial de infección por SARS-COV-2 / Persistent hiccup as initial clinical manifestation of SARS-CoV-2 infection

Resumen La infección por SARS-CoV-2 se presenta generalmente como un síndrome respiratorio agudo, caracterizado por fiebre, tos, odinofagia y disnea. Sin embargo, desde el comienzo de la pandemia, a fines del año 2019, fueron reportados otros síntomas menos frecuentes, como manifestación inicial de la en fermedad, entre ellos la aparición de hipo (singulto). Se describe el caso de un varón de 62 años de edad con antecedentes de hipertensión arterial, diabetes e insuficiencia cardiaca, que sufrió hipo persistente como primer síntoma de COVD-19, seguido de síntomas respiratorios. Luego de efectuado el diagnóstico de infección por SARS-CoV-2, el paciente fue hospitalizado y recibió el tratamiento correspondiente. El singulto mejoró parcial mente con el uso de fármacos anti-dopaminérgicos (metoclopramida) y desapareció al sexto día de internación. Se requirió la corrección de la glucemia con insulina corriente. Evolucionó favorablemente y fue externado luego de 14 días de hospitalización.

Abstract SARS-CoV-2 infection usually manifests as an acute respiratory syndrome, characterized by fever, cough, sore throat and dyspnea. Nonetheless, since the beginning of the pandemic in December 2019, less frequent initial symptoms were reported, as the sudden appearance of hiccups (singultus). We describe a clinical case of a 62-year-old male with a medical history of arterial hypertension, diabetes and chronic cardiac insufficiency, who complained of persistent hiccups as initial manifestation of COVID-19, followed by respiratory symptoms. After the SARS-CoV-2 infection diagnosis was made, the patient was hospitalized, receiving the corresponding treat ment. The singultus partially improved with dopaminergic antagonists and it disappeared on the sixth day of hospitalization. Glycemic correction with regular insulin was required. He presented a favorable outcome, being discharged after 14 days of hospitalization.

Persistent Hiccups as an Atypical Presentation of SARS-CoV-2 Infection: A Systematic Review of Case Reports.

Symptoms, such as fever, dry cough, dyspnoea, and respiratory distress, are commonly described in patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Recently, a growing number of cases pertained to persistent hiccups have been reported by SARS-CoV-2 infected patients. The aim of this systematic review was to screen the current literature and provide a summary of the reported cases of SARS-CoV-2 infected patients presenting with persistent hiccups. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, PubMed, Scopus, and Web of Science databases were searched from inception until October 2021. Case reports or case series that provided a separate clinical description for patients with presenting complaints of persistent hiccups before or after COVID-19 diagnosis were retrieved. The critical appraisal checklist for case reports provided by the Joanna Briggs Institute (JBI) was employed to evaluate the overall quality of the eligible studies. We identified 13 eligible studies that included 16 hospitalized COVID-19 patients who complained of persistent hiccups. The mean duration of hiccups was 4.6 days reported in 88% (14/16) patients. Hypertension was the most common comorbidity present in 50% (8/16) of patients followed by diabetes mellitus (4/16). Moreover, 44% (7/16) of patients received only one medication for managing the hiccups with metoclopramide (5/16) followed by chlorpromazine and baclofen (4/16) used as primary treatment. Equally, 44% of patients (7/16) received dexamethasone followed by azithromycin (5/16), ivermectin (4/16), and ceftriaxone (4/16) for managing the infection from SARS-CoV-2. The majority of patients (14/16) improved after initiation of treatment. Persistent hiccups are possibly a rare symptom that clinicians may expect to encounter in patients infected with SARS-CoV-2. Although there is not ample proof to propose causation, increased awareness about the diversity of presentations of SARS-CoV-2 infection could be crucial in the early recognition of the disease.

[Hiccups, not always unremarkable]. / Les hoquets : pas toujours banals.

Hiccups are most often benign and of short duration. However, they may also be persistent (superior to 48h) or even refractory (superior to 1 month). In such cases, they markedly alter the quality of life and can lead to severe impairment of health. We here review hiccups pathophysiology, etiologies, work up and treatment. We suggest that hiccups should be considered as a non-epileptic myoclonic movement disorder.

Le hoquet est le plus souvent bénin et de courte durée, mais il peut aussi être persistant (sup�rieur a 48h), voire réfractaire (sup�rieur a 1 mois). Dans ces cas, il altère la qualité de vie et peut avoir des conséquences graves sur la santé. Nous en revoyons ici la physiopathologie, les étiologies, la mise au point diagnostique et les traitements. Nous concluons par une réflexion sur la nature du hoquet que nous considérons comme un mouvement anormal appartenant au groupe des myoclonies non épileptiques.

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%.

Hipo y anestesia / Hiccups and anesthesia

Hiccups are a spasmodic and intermittent contraction of the diaphragm and accessory muscles of inspiration, which ends abruptly with the closure of the glottis. It prevents activities of daily living, decreases the quality of life of those who suffer from it and can predispose to regurgitation and dehiscence of the surgical wound. It is usually benign, of unknown cause, being more frequent in men than in women. 70% of the cases present in the ages of 40-60 years and it is the left hemidiaphragm that is affected in most of the cases. There are many causes that originate it, some of them related to anesthesia. In the anesthetized patient, hiccups can interfere with diagnostic studies such as magnetic resonance imaging (MRI), procedures such as radiotherapy and prevent the performance of surgical interventions. The therapeutic options are varied, including non-pharmacological alternatives, pharmacological and invasive procedures.

El hipo es una contracción espasmódica e intermitente del diafragma y de los músculos accesorios de la inspiración, que finaliza de forma brusca con el cierre de la glotis. Impide las actividades de vida diaria, disminuye la calidad de vida de quien lo padece y puede predisponer a la regurgitación y la dehiscencia de la herida quirúrgica. Habitualmente es benigno, de causa desconocida, siendo más frecuente en el hombre que en la mujer. El 70% de los casos se presenta en las edades de 40-60 años, siendo el hemidiafragma izquierdo el más afectado en la mayoría de los casos. Son numerosas las causas que lo originan, algunas de ellas relacionadas con la anestesia. En el paciente anestesiado, el hipo puede interferir con estudios de diagnóstico como la resonancia magnética nuclear (RMN), procedimientos como la radioterapia e impedir la realización de intervenciones quirúrgicas. Las opciones terapéuticas son variadas, incluyendo alternativas no farmacológicas, farmacológicas y procedimientos invasivos.

Enfoque del hipo intratable en el paciente con cáncer: Revisión de la literatura / Approach of intractable hiccups in cancer patients: Literature review

Approximately 80% of episodes of hiccups or singultus involve unilateral contraction of the right hemidiaphragm and typically follow an inspiratory peak. The pathophysiologic mechanism is not entirely clear. The hiccup centers are thought to be located in the hypothalamus, reticular formation, brain stem, dorsomedial nucleus, and cervical spinal cord between C3 and C5. The vast majority of hiccup episodes are benign and self-limited, ceasing within minutes; but persistent or intractable hiccups can also be found, which are usually associated with malignancy such as cancer and require timely medical management given the discomfort it produces and the negative impact on the patients quality of life. There are no specific guidelines for the management of intractable hiccups in cancer patients; however, pharmacological, non-pharmacological and interventional therapies have been reported to be effective.

Aproximadamente el 80% de los episodios de hipo o singulto involucran contracción unilateral del hemidiafragma derecho y típicamente sucede después de un pico inspiratorio. El mecanismo fisiopatológico no es del todo claro. Se cree que los centros del hipo se encuentran localizados en el hipotálamo, la formación reticular, tallo cerebral, núcleo dorsomedial y la médula espinal cervical. La gran mayoría de los episodios de hipo son benignos y autolimitados, cesando en cuestión de minutos, pero también se puede presentar el hipo persistente o intratable que por lo general se asocia a patologías malignas como el cáncer y que requiere de un manejo médico oportuno dado el disconfort que produce y el impacto negativo sobre la calidad de vida. No existen guías específicas para el manejo del hipo intratable en el paciente con cáncer, sin embargo, se han reportado terapias farmacológicas, no farmacológicas e intervencionistas que han resultado eficaces.

Intractable Hiccups in a Young Male: Is it a Tell-Tale Sign of Pseudocyst of Pancreas?

Although encountered routinely in the outpatient department, hiccups or singultus are mostly neglected by the clinicians owing to its benign presentation and self-limiting nature. However, an innocent-looking symptom such as a hiccup can be a warning sign of serious underlying medical conditions and hence should be addressed seriously. Hiccups can seriously alter the quality of life and induce anxiety when they become intractable. We present an atypical case of a 30-year-old male who presented with intractable hiccups for four months and upon investigations revealed to be a case of chronic pancreatitis with pseudocyst of the pancreas. The patient's intractable hiccups were not responding to metoclopramide and responded well to gabapentin. The patient was managed conservatively for chronic pancreatitis and pseudocyst of the pancreas. This case report highlights the importance of investigating the cause of a simple symptom like hiccup as it can be a tell-tale sign of a chronic underlying pathology such as pseudocyst of the pancreas in our case. After an extensive review of literature, it was found that this is the first case to report intractable singultus as a result of the pseudocyst of the pancreas.

Intractable singultus as an initial symptom of medulla oblongata tuberculoma: A rare case report.

Tuberculoma of medulla oblongata is a rare manifestation of central nervous system tuberculosis (CNS TB), which may manifest as intractable singultus as the initial symptom. It is almost impossible to obtain definite diagnosis through biopsy consider its location. Immediate thorough diagnostic workup is needed, and empirical treatment should be started. We report a case of medulla oblongata tuberculoma in an HIV-negative 38-year-old man with intractable singultus as one of the early symptoms. He was treated empirically with anti-tuberculosis therapy and his symptoms subsided within 2 weeks.

Laryngeal Manifestations of Intractable Singultus.

Hiccup is a common phenomenon experienced by almost everyone in life. Although the exact physiology of this phenomenon remains unknown, it is associated with multiple central and peripheral etiologic causes. Vocal fold granulomas are benign laryngeal lesions typically caused by iatrogenic trauma, voice misuse, or chronic irritation. We present, for the first time, an association between intractable hiccups and vocal fold granulomas with good response to acupuncture and voice therapy in a 62-year-old male patient. This is an important contribution to the literature as the first report describing the co-occurrence of these pathologies in the context of a patient with several treatment failures, including vagal nerve stimulator.

The Role of Serotonin in Singultus: A Review.

The use of dopamine receptor blockers for chronic singultus treatment is based-at least partially-on circular thinking: chlorpromazine is FDA-approved for hiccups, chlorpromazine is a neuroleptic, neuroleptics are dopamine receptor blockers, and therefore hiccup is due to dopaminergic dysfunction. Chlorpromazine interacts with high affinity with a multitude of receptors and ion channels. This promiscuity is the basis for many of the therapeutic effects and adverse drug reactions of this drug. While an involvement of dopamine is certain, it is by no means clear that dopaminergic dysfunction is the hallmark of singultus. The common denominator of most remedies for transient hiccup is their ability to activate the vagus nerve. Both afferent and efferent vagal activity and the central integration of the Xth cranial nerve function are modulated, inter alia, via serotonergic mechanisms; beneficial (therapeutic) effects for hiccup are to be expected from serotonin (5-HT) receptor subtype ligands that enhance vagal activity. Taken together, it appears that the ability to increase vagus output is mainly associated with 5-HT1A, 5-HT3, and 5-HT7 agonists and with 5-HT2C antagonists. The plausibility of the serotonergic singultus hypothesis is examined against available pharmacokinetic, pharmacodynamic, and clinical data for a number of drugs.

Hiccups: A Non-Systematic Review.

BACKGROUND: Hiccups are a universal phenomenon. They are usually benign and selflimited. Persistent or intractable hiccups, although rare, can be debilitating and may indicate the presence of an underlying pathological process. OBJECTIVE: To familiarize physicians with the pathophysiology, etiology, evaluation, and management of children with hiccups. METHODS: A search was conducted on December 10, 2019, in Pubmed Clinical Queries using the key terms "hiccup" OR "hiccough" OR "singultus". The selected publication types included all clinical trials (including open trials, non-randomized controlled trials, and randomized controlled trials), observational studies, and reviews (including meta-analysis and narrative reviews) published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article. RESULTS: Overdistension of the stomach is the most commonly identifiable cause of acute hiccups, followed by gastroesophageal reflux and gastritis. Other causes of hiccups, notably persistent and intractable hiccups, include an underlying gastrointestinal, neurological, cardiovascular, pulmonary, infectious, and psychogenic disorder. Persistent or intractable hiccups can be a harbinger of serious medical pathology. A detailed history and thorough physical examination may provide clues for the etiology of the hiccups. The treatment of hiccups should be directed at the underlying cause whenever possible. Bouts of acute hiccups less than 48 hours rarely require medical intervention as they usually resolve within minutes. Treatment may be considered when hiccups are bothersome, persistent, or intractable. Treatment modalities include lifestyle changes, physical maneuvers, pharmacotherapy and, very rarely, surgical intervention. CONCLUSION: Acute hiccups are usually benign and self-limiting. Persistent or intractable hiccups can be a harbinger of serious medical pathology. The underlying cause should be treated if possible. There are no formal guidelines for the treatment of hiccups. Currently, most of the methods proposed are based on case reports and anecdotal evidence. Terminating an episode of hiccups can be very challenging for a clinician but may tremendously improve the patient's quality of life. It is hoped that future well-designed and better-powered studies will provide us with more information on the efficacy of various treatment modalities for hiccups.

Chronic Hiccups.

PURPOSE OF REVIEW: Nearly 4000 patients will be admitted to hospital in the US this year for hiccups. Hiccups are controlled by a complex reflex arc between peripheral receptors and the brainstem. Any disruption along this pathway may produce hiccups. Typically, hiccups resolve spontaneously but in certain pathologies symptoms may persist. Persistent hiccups may be considered a sign of underlying pathology. The most common cause involves GERD. RECENT FINDINGS: Based on etiologies, studies have shown that first-line therapy should use a proton pump inhibitor (PPI) and involve appropriate gastrointestinal consultation. If symptoms persist, other etiologies such as central causes need to be explored. SUMMARY: We review the pathophysiology of hiccups including multiple causes and the appropriate work up for each. We review several studies examining new treatments, both pharmacological and interventional, that may help patients. Initial therapy should still involve a PPI but several new therapies may be beneficial.

Singultus, paper-bag ventilation, and hypercapnia.

Sir Louis Francis Knuthsen (1869-1957), the physician who painstakingly listed almost all treatments known for obstinate hiccough, ascribes the holding of breath method to Philip Henry Pye-Smith, FRS (1840-1914), consultant at Guy's Hospital in London. In fact, the strategy is much older and was mentioned by greats such as Francis Bacon (1561-1626), Aristoteles (384-322 BC), and Eryximachus (late-fifth century bce). Hypoventilation to reduce central nervous system excitability was used in antiquity as evidenced by Cyriacus' treatment of Artemia, the daughter of Emperor Diocletian (≈ 244-311). She was suffering from (among others) seizures that Cyriacus was apparently controlling by tightening a scarf around her neck, as depicted by Mathias Grünewald (1460-1528) on a wing of the so-called Heller Altar now on display at the Historical Museum, Frankfurt, Germany. In modern times, around 1920, inducing hypercapnia by CO2 inhalation as therapy for hiccups was suggested and tried by a number of anesthetists, such as Americans Russel Firth Sheldon (1885-1960) and Brian Collins Sword (1889-1956) in Boston; Briton Christopher Langton Hewer (1896-1986) at St. Bartholomew's Hospital in London; Austrian Karl Doppler (1887-1947) in Vienna; and the German/Polish Arthur Dzialoszynski (1893-1977) in Berlin. Although various authors assign the scientific primate to any of them, the first mention of carbon dioxide inhalation as treatment of singultus in the scientific literature is of French origin and was made by Paris pharmacist Henri Bocquillon-Limousin (1856-1917) in his 1892 Formulaire des médicaments nouveaux et des médications nouvelles.

Intraoperative Laryngeal Mask Airway-Related Hiccup: An Overview.

Hiccup is an involuntary contraction of the diaphragm and intercostal muscles resulting in sudden inspiration and closure of the glottis. The presence of hiccup in the perioperative period can be a challenging problem. Sudden movements of the patient from hiccups can interfere preoperative diagnostic procedures, intraoperative hiccup may delay the beginning of surgery, interfere with the surgical process, and affect intraoperative monitoring, and postoperative hiccup may affect would healing and hemodynamic stability. Hiccup can lead to have increased aspiration risk. Hiccup are is an incompletely understood phenomenon with multiple etiologies. Intraoperative hiccup related to laryngeal mask airway placement has been reported, and it presents unique challenges in diagnosis and management. Both pharmacological and non-pharmacological interventions have been utilized with various level of success. All treatment strategies are primarily aimed at interrupting the hiccup reflex arc.

Perspectives on the Medical, Quality of Life, and Economic Consequences of Hiccups.

PURPOSE OF REVIEW: Singultus or hiccups (HU) is a common, usually temporary, event. Its potentially serious consequences are often overlooked. This review explores published evidence describing HU burden (clinical, economic, and quality of life [QoL] consequences) across patient populations. RECENT FINDINGS: Literature review identified 81 articles (including 57 individual case reports). We extracted relevant information to better understand the burden of HU and to identify knowledge gaps for future study. HU are physiologic events that can complicate existing medical conditions and treatments regardless of duration. Relatively short episodes can have devastating consequences in patients who have pre-existing conditions. HU appear to impact physical and psychological health, diminish QoL, increase healthcare resource use, and increase costs. A better understanding of HU burden is needed.