Diagnosis and Management of Hiccups in the Patient - Oncology ...

More documents

Recommendations

Info

some role in the generation and/or propogation of hiccups, as they cease after administration of the beta-receptor antagonist carvedilol. 15 The vagus nerve, in particular, can be activated in various anatomic areas (thoracic and abdominal viscera as well as within head and neck structures). For instance, irritation of the auricular branch of the vagus nerve (Arnold’s nerve), which innervates the auditory canal, by cerumen, foreign bodies, bugs, and even hair, has resulted in hiccups. 16 CNS areas such as the brainstem respiratory center, the reticular activating system (rAS) in the medulla oblongata, the hypothalamus, and temporal lobes are also involved in the pathogenesis of hiccups, although their precise contributions remain to be elucidated. 6,17 release of 5-hydroxytryptamine from gut enterochromaffin cells and enteric vagal afferents following administration of various chemotherapeutic agents (especially cisplatinum) may lead to hiccups. 18 An additional mechanism of stimulating the hiccup arc is via stimulation of the chin integument. Stimulation of the chin via shaving produced transient hiccups in two patients. 16 The authors postulated that sensory afferents to the spinal tract of the trigeminal nerve project to the rAS, which subsequently recruits activation of the phrenic nerve nucleus leading to stimulation of the efferent hiccup arc. 16 in these patients, the hiccups disappeared after anesthetizing the mental nerve, suggesting that the trigeminal nerve plays a role in the hiccup mechanism. The efferent pathway of the hiccup arc primarily consists of the phrenic nerve, the primary motor input to the diaphragm. 6,13,14 Additionally, the external intercostal (derived from segments T1–T11) and the scalenus anticus nerves stimulate contraction of the intercostal and scalene muscles, respectively. 1–6 Shortly after activation of the hiccup arc, the recurrent laryngeal nerve stimulates closure of the glottis, resulting in the characteristic “hic” sound. 2 Significant acute negative intrathoracic pressure may occur, resulting as hypotension, bradycardia, pneumomediastinum, and subcutaneous emphysema. 6,19 Mathew 20 studied the effects of neonatal hiccups on systemic arterial pressure and noted acute, transient declines in systolic pressures that were attributed to decreased stroke volume and vascular resistance. This decline in vascular resistance appears to result from increased dilation and volume of the thoracic aorta induced by decreases in hiccup-associated intrathoracic pressure. 20 whether hiccupassociated systolic hypotension is deleterious to cardiovascular function in adults is unclear, but it remains a plausible etiology of pathologic hemodynamic changes in those patients with underlying heart disease. Hiccups often follow acute gastric distention in such situations as endoscopy, rapid ingestion of food or carbonated beverages, gastric outlet obstruction, or small bowel obstruction— all of which are believed to stimulate gastric vagal afferent activity. 2,3,6 Gluck and Pop 21 reproducibly demonstrated the induction of acid-induced hiccups via esophageal acid perfusion in a patient with chronic hiccups. Additionally, esophageal distention has been implicated to cause hiccups via stimulation of mechanoreceptors and is the presumed pathogenic Table 1 Etiologies of Hiccups in the Patient with Cancer Malignancy Esophagogastric cancer Colon cancer Hepatoma Leukemia Lung cancer Lymphoma Pancreatic cancer Renal cancer Liver metastasis Metabolic Derangements Hyponatremia, hypokalemia, hypocalcemia Renal failure Uremia Uncontrolled diabetes mellitus Hypoadrenalism CNS Pathology Brain tumors (eg, gliomas, metastatic tumors) Stroke Hematoma/cerebral hemorrhage Encephalitis/meningitis Brain abscess/toxoplasmosis Cardiovascular Disorders Myocardial ischemia/infarction Pericardial effusion/pericarditis Thoracic/Pulmonary Disorders Pneumonia Pleural effusion/pleuritis Thoracic herpes zoster Mechanical ventilation Gastrointestinal Disorders Erosive esophagitis Infectious esophagitis (eg, herpes simplex, Candida species) Peptic ulcer disease Gastric distention from food, liquid, air, endoscopy Gastric outlet or small bowel obstruction Pancreatitis Ascites Cholecystitis Subdiaphragmatic abscess Surgical Procedures/General Anesthesia Epidural Injections with Local Anesthetics Psychogenic vo l u m e 7, nu m b e r 4 ■ Ju ly/au g u S T 2009 www.SupportiveOncology.net Marinella cause of hiccups associated with achalasia, esophageal tumors, strictures, and food impaction. 2–6,21 indeed, Fass et al 22 induced acute, transient hiccups in 40% of healthy subjects with inflation of proximal esophageal balloons. interestingly, all of the patients in this study who developed hiccups were men. 22 This finding is in keeping with recent studies revealing a significant male predominance of hiccups in patients receiving cytotoxic chemotherapy. 18,23 The mechanisms for male predominance of hiccups in these studies are not explained. Because a variety of processes can result in hiccups, it remains most likely that 123
Advanced Cancer: Diagnosis and Management of Hiccups Table 2 Causes of Drug-induced Hiccups Utilized in Cancer Care Antibiotics Benzodiazepines Corticosteroids (especially dexamethasone) Anabolic steroids Perphenazine General inhalational anesthesia Opioids Chemotherapeutic agents (significant male predominance) Cisplatinum Carboplatin Cyclophosphamide Docetaxel Etoposide Gemcitabine Irinotecan Paclitaxel Vindesine Vinorelbine stimulation of the vagus or phrenic nerves, diaphragm, head and neck structures, or CNS areas by anatomic lesions; metabolic derangements; or drugs induce hiccups through complex neural mechanisms that continue to be elucidated. Etiologies of Hiccups in Patients with Cancer Perhaps more than any patient population in medicine, those with malignancy represent some of the most medically complex situations due not only to cancer and metastasis but also to unrelated comorbidities; supportive pharmacologic treatments; infectious complications; and anticancer therapies such as chemotherapy, radiotherapy, and surgery. As such, many potential mechanisms for induction of the hiccup reflex exist, with many patients possessing several factors, often making it difficult to pinpoint the exact etiology. Tables 1 and 2 display some of the most commonly reported causes of hiccups in the cancer population. Overall, pathology of the gastrointestinal tract, thoracic viscera, and CNS is among the most common etiologies of persistent and intractable hiccups. 2,5,6 For instance, erosive or infectious esophagitis is common in the cancer and palliative care setting, as is gastric distention resulting from malignant gastric outlet and small bowel obstruction. 24–26 in addition, pneumonia, malignant pleural effusion, empyema, and chest wall zoster may invoke the afferent hiccup arc and lead to singultus. 1,6,8,27 Stimulation of various CNS centers involved with the physiology of hiccups by primary or metastatic brain tumors, stroke, cerebral hemorrhage, abscess, meningoencephalitis, or malignant hydrocephalus may also be etiologic. 28–33 various metabolic derangements, most commonly hyponatremia, may induce the hiccup reflex. 34,35 Hypoadrenalism has been reported to result in hiccups. 36 Myocardial infarction is a well-described precipitant of hiccups and likely results from ischemic activation of vagal pathways. 37 Thoracic, abdominal, or pelvic tumors invading the diaphragm or vagus nerve may stimulate hiccups .2–6,38,39 Drug-induced causes are protean, with benzodiazepines, corticosteroids, antibiotics, opioids, and cytotoxic agents among the most common in patients with cancer. A more extensive listing can be found in Table 2. 40–49 A study by Takiguchi et al 23 showed a significant male predominance of hiccups following cytotoxic chemotherapy. Patient Evaluation Acute, self-limited hiccups of less than 48 hours’ duration typically do not require exhaustive evaluation. Persistent and intractable hiccups without obvious explanation, such as those precipitated by a drug, usually require a diagnostic evaluation to exclude potentially treatable or life-threatening precipitants. A meticulous physical examination with attention to head and neck structures, heart, lungs, chest wall, skin, abdomen, and CNS should be performed. The external auditory canals should be examined to exclude inflammation, foreign bodies, hairs, or impacted cerumen. 16,50 Careful neurologic examination with attention to dysfunction of each of the hiccupproducing areas (eg, afferent limb, CNS structures, and efferent limb) should be performed. 2 if cancer is suspected, a search for lymphadenopathy or mass lesions is essential. Site-directed imaging studies such as chest radiography, abdominal radiography, CT, or Mri should be obtained if any element of the history or physical examination suggests an etiology affecting a particular organ system. examples could include pneumonia, ileus or bowel obstruction, brain metastasis, or intra-abdominal malignancy. in patients with odynophagia or dysphagia, upper endoscopy should be performed to detect erosive or infectious esophagitis, stricture, or malignancy. 26 electrocardiography should be obtained to exclude myocardial ischemia. 4,6,37 Basic laboratory studies including serum electrolytes and creatinine levels should be routine, because hyponatremia is a common etiology of hiccups in acutely ill patients, although hypocalcemia, hypokalemia, or renal failure may be discovered. 6,34,35 Other invasive studies such as lumbar puncture to exclude CNS infection or bronchoscopy to exclude infection or a neoplasm should be performed only on a caseby-case basis. Complications of Persistent and Intractable Hiccups Table 3 displays some of the most common complications of ongoing hiccups that may be encountered in the patient with cancer. General complications of intractable hiccups include anxiety and exacerbation of depressive symptoms, both of which are common in patients with advanced or terminal cancer. 1,5,6 Sleep impairment due to nocturnal hiccups minimizes necessary restorative sleep and leads to daytime somnolence and fatigue, which may worsen anxiety, depression, appetite, and cognitive function. 51 Chronic hiccups increase energy expenditure through con- 124 www.SupportiveOncology.net Th e Jo u r n a l o f Su p p o rT i v e on c o l o g y
Page 1: Manuscript submitted July 14, 2008;
Page 5 and 6: Advanced Cancer: Diagnosis and Mana
Page 7: Advanced Cancer: Diagnosis and Mana

Diagnosis and Management of Hiccups in the Patient - Oncology ...

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?