INTRODUCTION — Difficulty swallowing is a disturbing symptom that occurs frequently in terminal illness, especially with malignancies of the upper aerodigestive tract; progressive neurologic disorders such as amyotrophic lateral sclerosis (ALS), Parkinson disease (PD), and multiple sclerosis (MS); dementia; and the general debility that develops in patients near the end of life. In the final weeks to months of life, functional decline can impair the desire or ability to eat or drink; furthermore, dysphagia to solids and liquids is one of the most frequent symptoms that tends to worsen during the last days of life [1-3]. Swallowing dysfunction can impact the essence of pleasurable activities, compromise quality of life (eg, social interaction, communication), increase hospital stays, and impair nutrition and hydration. Swallowing disorders are also a major predisposing condition for aspiration and can lead to several pulmonary syndromes, including pneumonia and, in some cases, even asphyxiation or death. In-hospital mortality is 2.9 percent higher per year in patients with dysphagia [4].
Given the place of food and nutrition as a central focus of social interaction and the common concerns about adequate nutrition for wellbeing, swallowing disorders can also cause frustration and distress for families and caregivers. In addition, for many patients with a terminal illness, the inability to swallow and/or disinterest in food may represent a pivotal symptom that prompts the decision to consider end-of-life or hospice care. Management of patients with an advanced, life-threatening illness who are experiencing swallowing difficulty should focus on the following palliative care principles: the primary goals are prevention and relief of suffering with an emphasis on ensuring comfort, rather than optimal nutrition and hydration; the care plan should reflect the underlying life-threatening disease and be consistent with the overall goals of treatment; care is optimized by involving an interdisciplinary team whereby each specialist contributes their expert knowledge; and the patient and family are the unit of care and their wishes and preferences should guide collaborative decision making.
This topic review will cover the definitions, consequences, and etiology of swallowing disorders in patients receiving palliative care. Assessment and management of swallowing disorders in this patient population, overview of the causes and treatment of aspiration pneumonia in adults, issues related to swallowing problems in patients with head and neck cancer, assessment and management of oropharyngeal and esophageal dysphagia in adults, and aspiration due to swallowing dysfunction in children are presented elsewhere.
●(See "Swallowing disorders and aspiration in palliative care: Assessment and strategies for management".)
●(See "Aspiration pneumonia in adults".)
●(See "Speech and swallowing rehabilitation of the patient with head and neck cancer".)
●(See "Oropharyngeal dysphagia: Etiology and pathogenesis".)
●(See "Oropharyngeal dysphagia: Clinical features, diagnosis, and management".)
●(See "Approach to the evaluation of dysphagia in adults".)
●(See "Aspiration due to swallowing dysfunction in children".)
DEFINITIONS AND CONSEQUENCES OF SWALLOWING DISORDERS — Dysphagia is defined as difficulty swallowing food or liquid including medications in liquid or tablet form. The dysphagia may be due to an obstructive or mechanical etiology (eg, a tumor or esophageal stricture) or may be caused by a motor or sensory dysfunction from a neurologic process. Dysphagia may cause problems with certain types of food or liquids in some patients, while others may not be able to swallow at all. Patients may complain of food getting caught along the upper digestive tract anywhere from the throat to the distal esophagus, cough or choke when eating or drinking, feel pain, or suffer from weight loss. It is important to note that in many cases, swallowing disorders may occur in the absence of symptomatic dysphagia. Silent aspiration may occur when the patient is unaware and there are no signs of struggle such as coughing. This phenomenon is especially common after treatment for head and neck cancer and following a stroke, and it can also be seen in older adults [5-7]. Swallowing problems may also manifest as a symptom such as cough, not necessarily voiced as a complaint related to difficulty swallowing.
Chronic swallowing problems affect the efficiency with which oral nourishment can be maintained, which in turn can lead to generalized weakness, appetite loss, weight loss, dehydration, and malnutrition. In addition, airway protection or swallowing safety can also be threatened by swallowing disorders. Diversion of food or liquid into the trachea may occur, causing aspiration, choking, or, in severe cases, asphyxiation. Several pulmonary syndromes may occur after aspiration, depending on the amount and nature of the aspirated material, the frequency of aspiration, and the host’s response to the aspirated material (see "Aspiration pneumonia in adults"):
●Aspiration pneumonia is an infectious process caused by the inhalation of oropharyngeal secretions that are colonized by pathogenic bacteria. Gram-negative enteric rods and anaerobes are the most common responsible organisms.
●Aspiration pneumonitis (Mendelsohn’s syndrome) is an acute lung chemical injury caused by the inhalation of sterile acidic gastric contents.
●Other aspiration syndromes include airway obstruction, lung abscess, and exogenous lipoid pneumonia.
Pulmonary aspiration is an important cause of serious illness and death among older adults and those with advanced terminal illnesses, particularly neurodegenerative conditions [5,6,8,9]. (See "Aspiration pneumonia in adults".).
The chronically ill patient with swallowing dysfunction may also suffer isolation from social interactions that take place around the consumption of food and abstain from things they enjoy such as socializing. Family members may refrain from eating around the patient, further isolating them [10]. Families, with all good intentions, often focus on food, given its central meaning in nurturing and beliefs about its importance in wellbeing. The focus of family interactions may shift from the patient’s experience to the importance of food. The burden of caring for a dysphagic individual can add additional distress for a family member caring for a patient at the end of life [11].
Finally, for many patients with a terminal illness, the inability to swallow may represent a pivotal symptom that prompts the decision to consider end-of-life or hospice care or whether to pursue alternate means of nutrition and hydration [12-14].
PHYSIOLOGY AND PATHOPHYSIOLOGY OF SWALLOWING
Normal swallowing — The three vital human functions of breathing, swallowing, and phonation all share the same anatomic real estate. Successful execution demands exquisite timing and coordination. Oropharyngeal swallowing is an extremely complex physiologic act that demands exquisite timing and coordination of more than 25 pairs of muscles under voluntary and involuntary nervous control. This intricate process is mediated by the central swallow pattern generator in the medulla oblongata of the brainstem that receives input from both the peripheral nervous system via the cranial nerves and the motor cortex and subcortical regions. Because humans swallow hundreds of times per day and are largely unaware of the activity, it is remarkable that difficulties do not occur more frequently. The cranial nerves involved in the swallowing process, and the clinical consequences of damage to the cranial nerves, are outlined in the table (table 1).
For descriptive purposes, the act of swallowing is divided into three phases: the oral preparatory and transit phase, the pharyngeal phase, and the esophageal phase. In reality, these phases overlap and simultaneous, rather than discrete, actions occur in each phase. It takes one second for the bolus to leave the pharynx and enter the cervical esophagus and between 8 and 20 seconds for the bolus to enter the stomach, with a more viscous bolus taking longer than liquids.
●Oral/oral preparatory phase – The oral phase is responsible for readying the bolus for swallowing. Bolus preparation is under voluntary control and can be halted or changed at any point. The oral cavity (chamber) which is bordered by the upper and lower teeth, extends from the lips anteriorly to the hard palate superiorly and the back of the tongue posteriorly; it is bounded inferiorly by the floor of the mouth and laterally by the buccal musculature. The ability of the oral cavity to fulfill its function as a closed chamber depends on the integrity of the many muscular contractions, which form valves that open and close, keeping the bolus in place or moving it around the mouth (figure 1). The jaw must lower, the mouth must open, and the lips must close around the bolus to ingest the material into the oral cavity [15].
Liquids are ingested into the oral cavity, and after mastication solid boluses are placed on the tongue ready for swallowing. During this oral phase, pleasure (or displeasure) is derived from the flavor, smell, and texture of food through the chemoreceptors of the tongue and palate. The tongue moves the food to the teeth to grind into smaller pieces, collects the bolus, and moves the smaller pieces to another surface for further grinding. Food is crushed by chewing and mixed with saliva to alter the bolus texture. Mastication alters oropharyngeal bolus transport and the timing of swallow initiation [16].
The food bolus is partitioned into a progressively smaller portion and is moistened by enzyme-rich saliva which helps to bind the material together. Sensory receptors within the oral cavity assist in mediating saliva production as well as determining the chewing force and the configuration of the oral cavity to accommodate the bolus type and size. Contraction of the buccinator muscles keeps the bolus on the tongue dorsum. The tongue tip and lateral edges gather particles from the sulci of the cheek and the mouth floor, preventing food from falling out of the anterior oral cavity. The palatoglossus muscle contraction prevents premature spillage of the bolus into the pharynx before it is completely prepared for swallowing [17,18]. Once the bolus is formed, it is positioned on the tongue and propelled posteriorly into the pharynx by contraction of the tongue and muscles of the floor of the mouth. The tongue acts as a piston to create pressure on the bolus and drive it into the pharynx. The soft palate elevates to prevent nasal regurgitation and widen the pharyngeal lumen to accept the bolus.
●Pharyngeal phase – The pharyngeal phase of swallowing is complex and intricate, requiring the most precise timing and coordination. This phase of the swallow begins as the posterior tongue retracts and descends, sending the bolus over the base of the tongue. The bolus passage stimulates sensory fibers of the glossopharyngeal and vagus nerves to coordinate elevation and closure of the laryngeal inlet and opening of the esophagus. The suprahyoid muscles of the floor of the mouth, in concert with the intrinsic tongue muscles, contract to propel the bolus from the oral cavity. At this phase, the oral cavity and the pharynx become one continuous tube with the entrance to the larynx closed off to protect the airway [17]. The pharynx elevates and shortens and progressive contractions of the pharyngeal constrictor muscles pass the bolus through the pharynx.
The process of airway protection (ie, closure of the larynx) is remarkable and complex, demanding split-second timing. There are multiple levels of airway closure, including adduction of the true vocal folds, approximation of the false vocal folds, epiglottic inversion over the entrance to the larynx, and anterior rocking of the arytenoid cartilages to touch the base of the epiglottis, thus closing the laryngeal vestibule (figure 1) [19]. Laryngeal elevation and anterior hyoid movement tucks the larynx under the tongue base. Respiration ceases momentarily as the airway closes and the bolus passes, an average of one second for a sip of liquid. The swallow occurs typically during the expiratory stage of the respiratory cycle during low lung volumes [20]. The expiratory flow of air further helps to prevent material from entering the larynx during the swallow.
The upper esophageal sphincter (UES), comprising the cricopharyngeus muscle, separates the pharynx from the esophagus. At rest it is tonically contracted, preventing air from entering the esophagus and esophageal contents from reentering the pharynx in a retrograde fashion [21]. Opening of the UES is a passive event caused by elevation of the larynx and pharyngeal contraction and shortening, which in turn creates a negative pressure in the esophagus, further helping to propel the bolus through the pharynx and toward the esophagus [18].
The order of contraction of muscles during this complex pharyngeal phase of swallowing is invariable, but the timing and intensity of contraction depends on the viscosity and size of the bolus.
●Esophageal phase – During the esophageal phase of swallowing, the bolus is transported from the UES, through the lower esophageal sphincter (LES), and into the stomach, a distance of approximately 25 cm [18,22]. Like the pharyngeal phase of swallowing, the esophageal phase is under involuntary neuromuscular control, but the speed of propagation is slower (3 to 4 cm/second versus 12 cm/second in the pharynx) [23,24].
The upper portion (cervical esophagus) consists of striated skeletal muscle which contract to produce the primary peristaltic wave.
The lower esophagus is comprised of smooth muscle fibers. The primary peristaltic wave carries the bolus through the LES in a series of relaxation-contraction waves modulated by sensory information from within the esophageal lumen. It is the contraction and relaxation which changes the diameter of the lumen and hence inhibits or promotes flow of the bolus [23,25]. The LES remains open until the peristaltic wave passes. A secondary peristaltic wave, which is initiated by esophageal distention during the primary peristaltic wave, is generated at the point where striated muscle meets smooth muscle, and this clears the esophagus of residue. After passage of the bolus, UES and LES contract to their resting, closed state. This position prevents regurgitation of material into the hypopharynx and airway and contains the gastric contents within the stomach [26,27].
Pathophysiology of dysphagia — Difficulty swallowing can occur during, within, or across any of the above-described phases, depending on the underlying disease or multitude of disease processes. (See "Oropharyngeal dysphagia: Etiology and pathogenesis".)
Examples include anatomic disruptions following surgical resection and reconstruction in head and neck cancer or an obstructive esophageal mass. Dysphagia can also occur as a result of neurologically or medication-induced sensory impairment of the swallowing mechanism, cognitive dysfunction in late-stage dementia, cortical or brainstem stroke, amyotrophic lateral sclerosis (ALS), or general debility that can co-occur with advanced age and concurrent illness. Identification of the specific etiology and level of swallowing dysfunction is critical to determining the appropriate type of intervention and prognostication for improvement or decline.
Swallow dysfunction impacts swallow safety and swallow efficiency. Swallow safety refers to the degree to which the patient can swallow liquids and solids into the esophagus without invasion into the airway, including penetration into the larynx or aspiration into the trachea. Swallow efficiency refers to the degree with which coordinated muscular contraction can propel boluses effortlessly from the oral cavity into the esophagus and eventually the stomach without resulting in unwanted residual along the way. These essential tenets underlie any assessment of dysphagia.
Oropharyngeal dysphagia — Bolus formation and flow are adversely affected if there is dysfunction in the coordination and muscular contractility of parts of the oral cavity or the piston-like tongue. Inefficient bolus flow may result from weakness in the tongue-driving force on the bolus, reduced contraction of the pharynx, or reduced excursion of the hyolaryngeal complex. Patients with muscle weakness or sensory dysfunction of the lips, tongue, and face may experience difficulty containing the bolus in the oral cavity, causing drooling or oral pocketing in the sides of the mouth, thus affecting swallow efficiency. Nasal regurgitation of liquids and particles of solids occurs when the velopharyngeal port is dysfunctional (figure 1). Weak tongue-driving force and/or pharyngeal contraction during swallowing can result in loss of control over the bolus, a significant amount of residue in the pharyngeal recesses, or incomplete laryngeal closure, causing aspiration before, during, or after the swallow. This constellation of symptoms worsens when multiple structures are involved. Failure of opening of the upper esophagus, for whatever physiologic impairment, results in residue in the pyriform sinuses which may spill over into the unprotected larynx and trachea.
Valving of the larynx during the swallow is important for prevention of aspiration into the tracheobronchial tree (figure 1). Failure of the larynx to close due to mistiming or muscular dysfunction can result in aspiration of liquids or solid materials, which turn can increase the risk for pneumonia. A reflexive cough in response to aspirated material can mitigate effects of aspiration. However, reduced sensory function in the pharynx and larynx as well as weakened laryngeal or respiratory musculature can affect patient sensitivity to the aspirated material, as well as the effectiveness of the cough response, and thus affect clearance. Silent aspiration occurs when the patient does not respond to food in the trachea [28,29].
Patients with oropharyngeal dysphagia and aspiration may also present with disorders of coughing or dystussia. The effective production of a reflexive cough requires timely coordination of the respiratory and laryngeal systems [30]. Swallow and cough are closely related and form a continuum with effective swallowing preventing material from entering the airway and effective coughing ejecting the aspirated material when airway compromise is present [30]. A reflexive cough is a brainstem mediated response, different from a volitional cough which is cortically controlled. Reflexive coughing is frequently weak or absent in patients with neurogenic dysphagia, such as Parkinson disease (PD), ALS, and advanced dementia. Inability to clear the airway of aspirated material due to ineffective cough can result in pneumonia and result in life-threatening illness.
Xerostomia and/or hyposalivation causes oral dryness and is commonly experienced by up to 30 percent of patients receiving palliative care due to multiple causes including polypharmacy or dehydration [31-33]. Saliva is necessary to break down food and for the formation of the bolus, and it facilitates chewing and swallowing. Patients experiencing dry mouth may have reduced taste, increased oral infections, pain, and reduced quality of life [34]. (See "Approach to symptom assessment in palliative care", section on 'Dry mouth'.)
Esophageal motility disorders — Esophageal dysphagia may occur if there is an obstruction to passage of the bolus, for example, in the case of a stricture or tumor or an esophageal motility disorder affecting the peristaltic wave [35]. Achalasia, loss of esophageal peristalsis, or esophageal spasm can result in ineffective bolus transit. Gastroesophageal reflux due to dysfunctional LES contraction can result in retrograde flow of stomach contents back into the esophagus, sometimes reaching the level of the clavicle or worse, entering the airway. Patients with esophageal dysmotility are generally accurate in locating their difficulty and typically report the sensation of food being stuck somewhere in the esophagus. Pain or discomfort swallowing solids and weight loss is frequent. However, patients who complain of solid food pharyngeal dysphagia or a globus sensation that they localize to the throat may present either with distal esophageal or oropharyngeal dysfunction. (See "Approach to the evaluation of dysphagia in adults", section on 'Symptom-based differential diagnosis'.)
ETIOLOGY OF SWALLOWING DISORDERS IN PALLIATIVE CARE POPULATIONS — A multitude of diseases can cause swallowing dysfunction in patients receiving palliative care, including progressive neuromuscular diseases, dementia and other neurodegenerative disorders, central nervous system tumors, recurrent or progressive neoplastic obstructive lesions of the gastrointestinal tract, or pervasive debilitation from multisystem diseases. While normal aging-associated loss of muscle mass may not affect swallow function in healthy older adults, the impact of sarcopenia on swallow function in debilitated older adults with multiple comorbidities must be factored into evaluation and management [36]. In some cases, side effects of treatment such as radiation therapy or chemotherapy are the precipitating causative factors of dysphagia, whereas in others, the progressive nature of the disease leads to unsafe and inefficient swallowing.
Understanding the physiological impact of the illness is critical when evaluating the swallowing disorder and selecting an appropriate method of management. As an example, generalized weakness of the oropharyngeal musculature may be evident in a patient who carries a diagnosis of amyotrophic lateral sclerosis (ALS) and in another who has received chemoradiotherapy for a recurrent squamous cell carcinoma of the oropharynx metastatic to the neck. Both patients may experience a weak pharyngeal swallow with difficulty clearing the bolus through the pharynx, but the management approach might differ. In the patient with ALS, vigorous effortful swallows or strengthening exercises would not be indicated due to debilitating muscle fatigue. On the other hand, in the patient with a neck neoplasm, encouraging effortful swallows to preserve motor flexibility may improve airway protection to enable some safe oral intake.
Following are some of the commonly encountered causes of swallowing disorders in patients on palliative care, who may in turn present with dysphagia due to swallow safety and/or efficiency concerns.
Neoplasms — Tumors involving the central nervous system, head and neck, and the upper aerodigestive tract can interfere with swallowing.
Head and neck cancer — Oropharyngeal dysphagia is ubiquitous in patients with advanced-stage head and neck cancer and one of the most frequently cited adverse impacts on quality of life. Dysphagia may be a direct consequence of the tumor and/or its multi-modality treatment including surgery, radiotherapy, and chemoradiation therapy or disease progression. Dysphagia may occur as a long-term complication of treatment [37]. Tumors occurring in a variety of sites in the oral cavity and tongue, pharynx, larynx, and upper (cervical) esophagus can affect the nerve supply and muscle coordination and strength of movements involved in swallowing as well as debilitating impact on taste sensation and enjoyment of food.
Surgical resection, including reconstructive surgery, can be disfiguring and can lead to profound functional morbidity of speech and swallow. As an example, total glossectomy makes mastication of solids virtually impossible and renders speech unintelligible. Organ preservation approaches using chemoradiotherapy may not necessarily lead to functional preservation [38]. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy".)
Adverse treatment-related effects that may impact swallowing include mucositis, lymphedema, xerostomia, trismus (restricted jaw opening), and fibrosis affecting airway protection and opening of the upper esophagus [39]. Radiation effects are progressive and can result in chronic dysphagia and frequent aspiration, which may worsen for many years after treatment [40,41]. Swallowing typically becomes deliberate and effortful with coughing, the sensation of food getting caught, and the need for large volumes of liquid intake to combat dry mouth [42,43]. (See "Treatment of locoregionally advanced (stage III and IV) head and neck cancer: The oral cavity", section on 'Management' and "Treatment of locoregionally advanced (stage III and IV) head and neck cancer: The larynx and hypopharynx", section on 'Surgery' and "Speech and swallowing rehabilitation of the patient with head and neck cancer".)
Aspiration pneumonia in patients with late radiation-induced dysphagia is increasingly common, particularly in patients who have received chemoradiotherapy for head and neck cancer; many of these patients will require long-term gastrostomy feeding tubes. In one study of 29 previously irradiated head and neck cancer survivors who had persistent dysphagia more than five years following treatment, 86 percent developed pneumonia, and two-thirds eventually required long-term gastrostomy feeding tubes [44,45]. (See "Overview of approach to long-term survivors of head and neck cancer", section on 'Feeding tube utilization'.)
Other patients rely upon oral nutritional supplements delivered by mouth or gastrostomy tube. Non-oral nutritional support is required in over 60 percent of patients receiving multimodality treatment, and some patients are unable to resume an oral diet once their treatment is completed [43]. (See "The role of parenteral and enteral/oral nutritional support in patients with cancer", section on 'Head and neck cancer' and "Management and prevention of complications during initial treatment of head and neck cancer".)
Approximately 20 to 30 percent of patients present with persistent or residual disease where additional treatment options have limited evidence and may be poorly tolerated. Progressive facial and neck lymphedema with fibrosis and pain from either the disease or its treatment may further lead to chronic and progressive discomfort with eating and drinking and even breathing. Immunotherapies such as nivolumab or pembrolizumab have been offered with varying degrees of efficacy and attendant morbidities. Depending on the circumstance in this palliative context, non-oral nutrition may be recommended [46]. (See "Reirradiation for locally recurrent head and neck cancer", section on 'Toxicity' and "Treatment of metastatic and recurrent head and neck cancer".)
Brain and other central nervous system tumors — Dysphagia is rarely the presenting symptom from primary or secondary (metastatic) brain tumors, but swallowing problems can develop directly or indirectly as the tumor increases in size and compresses surrounding structures. In one series of 324 patients with a brain tumor (139 primary, 30 metastatic), 85 percent had dysphagia in the last month of life [47] (see "Overview of the clinical features and diagnosis of brain tumors in adults" and "Epidemiology, clinical manifestations, and diagnosis of brain metastases"). In particular, patients with high-grade gliomas, known as glioblastomas, carry a high symptom burden with a high frequency of swallowing difficulties at the end of life [48]. Swallowing difficulties can be a result of both focal effects of the tumor as well as a side effect of the treatment.
Extrinsic tumors located around the brain stem, such as vestibular schwannomas and meningiomas, as well as those originating in the skull base, such as paragangliomas, chordomas, and chondrosarcomas, may compress or invade the lower medulla and affect the cranial nerves (V, VII, IX, X, and XII) and associated nuclei that are critical for swallowing (table 1). The specific swallowing impairment depends upon which cranial nerves are affected. (See "Paragangliomas: Epidemiology, clinical presentation, diagnosis, and histology" and "Chordoma and chondrosarcoma of the skull base".)
In addition to direct tumor effects, swallowing and/or inability to maintain sufficient oral nutrition in patients with brain tumors may be indirectly affected by a depressed level of consciousness, reduced awareness, dry mouth, fatigue, depression, seizures, sarcopenia, opioid use, mass effect/edema, and associated complications [49-52].
Malignant esophageal tumors — Patients with cervical esophageal carcinomas often present with a globus sensation localized to the throat region. The globus sensation is reported as a persistent sensation of having phlegm, a pill, or some other sort of obstruction in the throat when there is none. Patients present with severe discomfort and a focus on trying to clear the sensation of obstruction [53]. In spite of multimodality intervention, the prognosis for these tumors is poor [54]. (See "Management of locally advanced, unresectable and inoperable esophageal cancer", section on 'Treatment of cervical tumors' and "Radiation therapy, chemoradiotherapy, neoadjuvant approaches, and postoperative adjuvant therapy for localized cancers of the esophagus", section on 'Cervical esophagus tumors'.)
Patients with cancer of thoracic esophagus commonly complain of weight loss and progressive dysphagia for solid foods greater than liquids, causing persistent throat pain, and vomiting/regurgitation. An intraluminal obstruction from the tumor itself or from extraluminal compression on the esophagus (eg, from a mediastinal mass) causes the dysphagia. In some cases, an intractable cough may indicate extension of the tumor to the mediastinum or trachea. Although such complications can have pulmonary consequences, the primary etiology is not as a result of misdirection of the bolus from the oral cavity into the trachea but is attributable to the esophageal obstruction or treatment thereof. Patients with adenocarcinomas (located more distally than squamous cell cancers, often involving the esophagogastric junction) may also present with gastroesophageal reflux symptoms [55,56]. (See "Clinical manifestations, diagnosis, and staging of esophageal cancer", section on 'Clinical manifestations'.)
Combined modality therapy is the usual form of treatment for esophageal cancer. Surgical intervention alters the conduit to transport food; in some cases, a gastric pull-up or a colonic interposition alters the rate and efficiency of neo-esophageal clearance. Chemotherapy and radiation therapy are associated with considerable side effects, including radiation-induced esophagitis and stricture, and chemotherapy-induced mucositis, xerostomia, and dysgeusia. Frequently, jejunostomy tubes must be placed for non-oral feeding during treatment. (See "Radiation therapy, chemoradiotherapy, neoadjuvant approaches, and postoperative adjuvant therapy for localized cancers of the esophagus" and "Multimodality approaches to potentially resectable esophagogastric junction and gastric cardia adenocarcinomas" and "The role of parenteral and enteral/oral nutritional support in patients with cancer", section on 'Esophageal cancer' and "Surgical management of resectable esophageal and esophagogastric junction cancers", section on 'Principles of surgical resection'.)
Symptomatic relief of dysphagia can also be accomplished by esophageal dilation, placement of an esophageal stent, laser ablation, or photodynamic therapy. Esophageal perforation during laser surgery (image 1 and image 2) or dilation and migration of the esophageal stents are potential complications from palliative procedures. Pain and recurrent symptoms of dysphagia can occur in almost 40 percent of patients following esophageal stent placement in malignant esophageal obstruction. (See "Management of locally advanced, unresectable and inoperable esophageal cancer", section on 'Treatment of thoracoabdominal tumors' and "Endoscopic palliation of esophageal cancer".)
Esophagorespiratory fistulas (eg, tracheoesophageal fistulas (image 3)) develop in 5 to 15 percent of patients with an esophageal malignancy, typically in those with recurrent disease or as a complication of radiation therapy or chemoradiotherapy. Typical symptoms include coughing, aspiration, and pneumonia.
Other malignancies — Patients with malignancies at sites other than the upper aerodigestive tract and central nervous system may develop transient or persistent oropharyngeal dysphagia due to a wide range of issues including presence of tumor, treatment induced-side effects, cancer-related weakness and fatigue, and neurologic or respiratory compromise [49]. In one study of 11 patients with cancers of the lung, breast, pancreas, colorectum, or blood-forming organs who were receiving palliative care, nine reported either dysphagic symptoms, the need to modify their food texture to softer foods, and/or an impact on their quality of life due to swallowing difficulties at some point in the course of their disease [49]. In addition, cachexia (wasting syndrome) and/or significant weight loss can lead to muscle weakness, fatigue, and metabolic disturbances that impact swallowing safety, efficiency, and enjoyment of eating and impact outcomes and quality of life [57]. (See "Pathogenesis, clinical features, and assessment of cancer cachexia" and "Assessment and management of anorexia and cachexia in palliative care".)
Of particular note, intrathoracic malignancies, such as lung cancer, can invade the left recurrent laryngeal nerve and result in laryngeal nerve palsies, causing impaired airway protection and cough as well as dysphagia and dysphonia [58,59]. (See "Hoarseness in adults", section on 'Neurologic dysfunction'.)
Radiation therapy to the mediastinum may cause esophagitis, which can result in odynophagia (pain on swallowing). (See "Overview of gastrointestinal toxicity of radiation therapy", section on 'Esophagitis'.)
Chemotherapy given for any malignancy can be directly toxic to the oral, pharyngeal, or esophageal mucosa, which may develop secondary infection (bacterial, fungal, or viral) during periods of myelosuppression. This can result in altered taste, pain, reduced appetite, nausea, or mucosal bleeding. (See "Oral toxicity associated with systemic anticancer therapy".)
Cancer patients suffering from severe mucositis, dysphagia, and/or odynophagia may need extra support and nutritional interventions to ensure that their nutritional requirements are met. Carefully prescribed pain medication is often needed to alleviate discomfort during eating and drinking. (See "The role of parenteral and enteral/oral nutritional support in patients with cancer".)
Neurodegenerative disorders — Swallowing difficulty is a common problem in patients with advanced neuromuscular diseases (table 2) [60].
Amyotrophic lateral sclerosis — Approximately one-fourth of patients with ALS present with difficulty swallowing as their initial complaint (bulbar onset), increasing to nearly 80 percent with disease progression. As the disease progresses, involvement of the upper and lower motor neurons affects speaking, swallowing, walking, writing, and ultimately the respiratory system. The usual cause of death in patients with ALS is due to weakness in diaphragmatic, laryngeal, and lingual function with aspiration a precipitating factor. A multidisciplinary team approach is critical in caring for these patients with a focus on both early identification and management of swallowing, nutrition, and decisions around feeding tube placement and ongoing nutritional assessment every three months. Ideally, the team includes a speech-language pathologist, dietician, respiratory therapist, and neurologist [61-63]. (See "Clinical features of amyotrophic lateral sclerosis and other forms of motor neuron disease", section on 'Clinical symptoms and signs'.)
Typically, patients with bulbar ALS experience a reduction in tongue mobility, oral and pharyngeal muscle weakness, and fatigue with eating. As the disease progresses, dense foods (even pureed) are difficult to manipulate, resulting in significant post-swallow residue in the oral cavity. Diminished pharyngeal drive in combination with tongue weakness also results in residue in the pharynx. Diet modifications with calorie-dense foods, thicker liquids, and postural alterations are necessary if oral intake is to continue. (See "Swallowing disorders and aspiration in palliative care: Assessment and strategies for management", section on 'Postural modifications'.)
Ultimately, most patients with ALS reach a point where the effort involved in eating and drinking by mouth outweighs the pleasure derived or the efficiency of eating. Significant weight loss and frequent choking may occur in the late stages; this may generate formidable anxiety and a sense of helplessness in the family and/or caregivers. Depending on the overall goals of care expressed by the patient and family, a gastrostomy feeding tube can be placed percutaneously (PEG) or via interventional radiology to provide nutrition and hydration. Sometimes a hybrid arrangement with nutritional formula for primary nutrition and supplemental oral intake for pleasure is possible. Best evidence suggests early placement of a PEG tube is a favorable prognostic indicator and may prolong survival, reduce complications, and improve quality of life in some ALS patients. Some studies indicated that optimal placement of the feeding tube occurs when weight loss is 5 to 10 percent of usual body weight or before the body mass index has significantly dropped and before vital capacity drops below 50 percent [64-66]. (See "Symptom-based management of amyotrophic lateral sclerosis", section on 'Management of swallowing and nutrition' and "Gastrostomy tubes: Uses, patient selection, and efficacy in adults", section on 'Stroke, brain injury, or neurodegenerative disease' and "Swallowing disorders and aspiration in palliative care: Assessment and strategies for management", section on 'Artificial nutrition and hydration'.)
Managing secretions, saliva, and aspirated material in patients with ALS includes oral and sometimes tracheal suctioning and airway clearance, such as a mechanical insufflator/exsufflator (a mechanical cough-assist machine) [67]. These devices remove pulmonary secretions and may be especially helpful if the patient elects to eat orally by mouth but aspiration is a real concern. (See "Respiratory muscle weakness due to neuromuscular disease: Management", section on 'Mechanical insufflation-exsufflation'.)
Parkinson disease — PD is a relatively common, slowly progressive disease of the central nervous system affecting many key motor functions including oropharyngeal swallowing. (See "Clinical manifestations of Parkinson disease", section on 'Cardinal features' and "Clinical manifestations of Parkinson disease", section on 'Other motor features'.)
Swallowing difficulty occurs in up to 80 percent of patients with late-stage PD [68] and is caused by movement abnormalities in all phases of the swallow because of changes in striated muscles that are under dopaminergic control and in smooth muscles that are under autonomic control. Rigidity and/or tremor of the lingual musculature and small-amplitude, ineffective tongue-rolling movements result in slow oral transit time. Delayed pharyngeal swallow responses and decreased pharyngeal contraction can result in residue and aspiration [69]. Expectoration of cough-aspirated material is weak because of rigidity of the laryngeal musculature. In addition, there may be incomplete relaxation of the upper esophageal sphincter (UES) and esophageal dysmotility during swallowing. Aspiration with resultant pneumonia is one of the most prevalent causes of death in patients with PD [70,71].
Oral complaints include sialorrhea, or excessive salivation and drooling. Contrary to popular belief, patients with PD do not produce an overabundance of saliva that they cannot manage. Instead, drooling occurs in patients with PD due to impaired swallowing function, reduced frequency of swallowing, reduced oropharyngeal or laryngeal sensation, poor head posture, inability to close the oral cavity, and a weak cough with poor clearance of secretions [72]. (See "Clinical manifestations of Parkinson disease", section on 'Other motor features'.)
There are some reports that in the early stages of the disease, dysphagia in PD is responsive to medications such as levodopa or dopamine agonists, although this remains controversial and inconclusive and may result in motor complications [73]. Medical therapy does not halt progression of the disease; rather, it aims to increase time spent at the patient’s best level of functioning. The majority of patients continue to decline [73]. Other advanced therapies, such as device-assisted treatment or deep brain stimulation (DBS), have had mixed results with respect to improvement in swallow function [74,75].
Dementia — Advanced dementia typically refers to a state of profound physical and cognitive disability that is the end result of a variety of neurodegenerative diseases. Dysphagia in patients with advanced dementia is extremely prevalent and may be as high as 93 percent [76,77].
Swallowing problems in patients with advanced dementia are multifactorial and may present as:
●Holding food in the oral cavity for prolonged periods without attempts at forming the bolus or mastication, especially with uniformly textured foods such as pureed items or bland foods. Pocketing food or liquid in the cheeks or on the tongue as well as spitting food may be observed.
●Pharyngeal and laryngeal sensory impairments in combination with diminished awareness or inattention to environmental stimuli.
●Poor oral control with premature loss of the bolus over the tongue base into the larynx before the pharyngeal swallow has been elicited. This may result in aspiration, which is often silent (no reflexive cough is elicited).
●Decreased consciousness and sedation can also predispose patients to aspirate food and liquid. Inability to maintain focus can also result in poor bolus coordination, delayed swallowing, and aspiration. In the later stage of dementia, a swallow response may not be elicited at all.
Swallowing problems in the late stages of dementia are not reversible, although treating concomitant infections, metabolic disarray, and/or dehydration may result in improved functioning. Various conservative measures to try to improve oral intake may be tried, including altering the texture of food; offering finger foods, smaller portions, or favorite foods; and oral nutritional supplements. Despite conservative efforts to improve oral intake, most advanced dementia patients will continue to have chewing and swallowing problems in the final stages of their illness. Towards the end of life, patients with dementia eventually do not engage with eating or drinking.
Initiation or continuation of nutritional support are common but vexing treatment decisions faced by the proxies of patients with advanced dementia. Tube feeding is generally not recommended in patients with advanced dementia, and focus is placed on reducing treatment burden; the best available evidence fails to demonstrate any health benefits or improved outcomes in respect to death, comfort, and functional status in advanced dementia and there are risks associated with the intervention [78-80].
This subject is discussed in detail elsewhere. (See "Care of patients with advanced dementia", section on 'Eating problems' and "Swallowing disorders and aspiration in palliative care: Assessment and strategies for management", section on 'Management'.)
Other neurologic disorders
Stroke — The incidence of dysphagia is high following acute stroke: anywhere from 40 percent for hemispheric strokes to 55 percent for mixed lesions [81]. There is a ≥3-fold increase in pneumonia risk among acute stroke patients who present with dysphagia. Stroke-associated pneumonia is one of the most common post-stroke infections and is associated with an increased risk of mortality and prolonged hospital stay [82]. Although about half of all stroke patients with dysphagia resolve within several weeks, longstanding inability to feed a patient orally after a stroke may be closely linked to the provision and timing of end-of-life care, as decisions surrounding placement of a gastrostomy tube may herald the need for end-of-life care decisions. These discussions should include attention to the burden of stroke impairments and impact on quality of life [83].
The incidence, severity, and prognosis of dysphagia are greatly affected by the locus of neurologic damage, age, recurrence of strokes, premorbid functional status, and the interplay of multiple chronic illnesses. Those with the most devastating damage may never fully recover a level of consciousness or motor control to safely or efficiently maintain oral nourishment. Dysphagia after stroke is quite varied and can be due to reduced lingual control, an absent/delayed swallowing reflex, delayed laryngeal closure, and weakened laryngopharyngeal musculature, which predispose the patient to aspiration. In general, anterior and subcortical strokes result in the highest rates of dysphagia, while patients with brainstem strokes typically cause the most severe dysphagia affecting all phases of swallowing, particularly if the medulla is affected. One study discusses the gap in support systems and follow-up for those left with a more chronic dysphagia post-stroke [84]. (See "Complications of stroke: An overview", section on 'Dysphagia'.)
Long-term nutritional support in patients with severe stroke does not completely alleviate the risk of pulmonary aspiration; oral care, patient positioning, and careful administration of tube feeding formula are necessary safeguards. Artificial nutrition may be started on a time-limited trial while swallowing rehabilitation is undertaken with periodic reassessments for recovery of swallowing function. The decision to withhold or withdraw enteral nutrition in a dysphagic patient nearing the end of life is fraught with ethical challenges and patient, family, and surrogate decision-makers should be provided with safest options for natural feeding as well as risks and benefits to assist with decision-making [83]. (See "Ethical issues in palliative care" and "Stopping nutrition and hydration at the end of life", section on 'Legal and ethical concerns'.)
Myopathies — The group of myopathies known as muscular dystrophies are chronic and progressive, resulting in progressive muscle weakness that often affects oral, pharyngeal, and esophageal muscles. Three in particular are associated with dysphagia:
●Oculopharyngeal muscular dystrophy (OPMD) includes, among other symptoms, dysphagia affecting the pharyngeal muscles. The leading causes of death for patients with OPMD are recurrent aspiration pneumonia and malnutrition. Pharyngeal weakness affects bolus drive, increases the frequency of a cricopharyngeal prominence, and reduces swallow efficiency [85,86]. (See "Oculopharyngeal, distal, and congenital muscular dystrophies".)
●Duchenne's muscular dystrophy typically results in severe dysphagia by age 12. The dysphagic symptoms include reduced palatal elevation, weak pharyngeal contraction, reduced hyolaryngeal excursion, and reduced esophageal motility. Patients tend to have secretions that pool in their pharynx, aspiration, reflux, and poor esophageal motility. Treatment focuses on symptom management. Surgically, there is some evidence that a myotomy of the pharyngoesophageal segment or cricopharyngeus with or without dilation may be beneficial in cases of moderate to severe dysphagia where there has been no significant weight loss and with adequate pharyngeal contraction [87]. (See "Duchenne and Becker muscular dystrophy: Clinical features and diagnosis".)
●Myotonic dystrophy includes myotonic dystrophy type 1 (DM1; previously known as Steinert’s disease) and DM2, which was recognized in 1994 as a milder version of DM1. In DM1, smooth muscle involvement is more common than in other muscular dystrophies and manifests with gastrointestinal symptoms. Upper gastrointestinal tract involvement is seen in most patients and results in dysphagia with resulting aspiration; aspiration pneumonia is an important cause of morbidity and mortality in DM1. (See "Myotonic dystrophy: Etiology, clinical features, and diagnosis".)
Pharyngeal myotonia or weakness, sometimes triggered by cold liquids, may impair swallowing; if present, it might be relieved by avoiding cold liquids. Weakness of the diaphragm and susceptibility to aspiration from swallowing problems increases the risk of respiratory compromise and aspiration pneumonia, usually in advanced disease [88]. There is no cure or treatment specific to myotonic dystrophy; therefore, the focus is on managing the complications of the disease. (See "Myotonic dystrophy: Treatment and prognosis", section on 'Dysphagia and nutrition'.)
Multiple sclerosis — Multifocal scattered inflammatory white matter lesions in multiple sclerosis (MS) result in varying combinations of motor, sensory, and cognitive deficits, which may lead to dysphagia. (See "Manifestations of multiple sclerosis in adults", section on 'Clinical symptoms and signs'.)
Difficulty with swallowing occurs in more than one-third of patients with MS and is most severe in those with brainstem involvement, especially if nonambulatory and in the advanced stages of the disease [89]. If left untreated, it can lead to dehydration, malnutrition, choking, and reduced quality of life [90]. Difficulties can also arise with respect to the feeding process because of hand tremors and spasticity.
Chronic illness, general deconditioning, and frailty — Neuromuscular weakness (flaccidity) presenting as critical illness myopathy and polyneuropathy can occur in critically ill patients with lengthy stays in the intensive care unit (ICU), and as systemic complications of sepsis and/or mechanical ventilation. Although nonspecific in etiology, dysphagia can ensue during this time due to prolonged intubation, generalized weakness and deconditioning, poor airway protection, and weak respiratory muscles. (See "Neuromuscular weakness related to critical illness".)
Multisystem chronic diseases, including the more frequently encountered progressive diseases such as end-stage chronic obstructive pulmonary disease (COPD), heart failure, and chronic kidney disease, can cause insidious weakness and frailty, which, in turn, may contribute to dysphagia [91]. (See 'Normal swallowing' above and "Palliative care for adults with nonmalignant chronic lung disease", section on 'Symptom management in chronic lung disease' and "Palliative care for patients with advanced heart failure: Decision support and management of symptoms", section on 'Symptom management' and "Palliative care: Overview of mouth care at the end of life" and "Kidney palliative care: Principles, benefits, and core components", section on 'Terminal symptom management'.)
General immobility impairs spontaneous pulmonary clearance, resulting in an inability to expectorate material if it is aspirated. Dysphagia is often encountered within the hospital or long-term care setting (eg, nursing home) in which patients may have complex medical issues resulting in cachexia, loss of muscle mass, or significantly compromised pulmonary systems that impede airway protection. These patients are at much higher risk for pulmonary infections and poor outcomes should they aspirate [92]. (See "Medical care in skilled nursing facilities (SNFs) in the United States", section on 'Nutrition' and "Hospital management of older adults", section on 'Malnutrition' and "Aspiration pneumonia in adults", section on 'Predisposing conditions'.)
Another set of patients at risk for chronic dysphagia at the end of life are frail older adults, or older adults with “failure to thrive.” Aging can result in changes to the muscle bulk and strength (sarcopenia) and tissue elasticity in the tongue and pharynx and also in the larynx, whereby the vocal folds may not close sufficiently or timely enough to protect the airway. Sensorimotor changes may occur that impact salivary production, taste, and smell [91,93,94]. Frailty, a biologic syndrome characterized by diminished reserve and resistance to stressors, results from cumulative declines across multiple physiologic systems [95]. It can occur in older adults but also in younger patients with critical illnesses and leads to reduced functional reserve and increased vulnerability [91]. Frailty can directly affect swallowing function via general deconditioning, slowness, and weak or ineffective airway protection, and it can contribute to an increased risk of decline should a frail patient aspirate or receive insufficient nutrition. While there is some evidence that direct muscle strengthening may be effective, some patients may experience irreversible declines. The reduction in functional reserve leaves older individuals highly vulnerable to insults to the swallowing system for which they may be unable to compensate. Swallowing management should emphasize overall health status as well as safety. (See "Frailty" and "Failure to thrive in older adults: Evaluation" and "Failure to thrive in older adults: Management".)
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted a subset of patients with a wide ranging symptoms related to swallowing safety. Many patients, especially early in the pandemic, presented with acute respiratory disease syndrome, often requiring endotracheal intubation. Patients received high doses of paralytic medicines to facilitate treatment of respiratory infections, and many patients were proned. Those who survived this severe disease were often left with marked weakness and overall debility, and some suffered severe cognitive dysfunction. Laryngeal dysfunction and subglottic stenosis, albeit infrequent, emerged post-hospitalization. SARS-CoV-2 patients with multiple comorbidities including obesity, diabetes, kidney disease, heart disease, and pulmonary disease were at greater risk for complications related to safe swallowing.
Medications — Medications should always be reviewed to determine if they may be contributing to or causing dysphagia. Many pharmacologic agents can create or worsen dysphagia. There are approximately 160 known medications that list dysphagia as a potential adverse side effect [96,97]. Medications can alter lubrication of the oral cavity and pharynx, affect taste and smell [98], impair coordination or motor function, depress consciousness, and reduce gastrointestinal motility [96]. Dysphagia may be a side effect of the drug or a complication of the drug’s therapeutic action, or it may represent a medication-induced mucosal injury. As examples:
●Antipsychotic or neuroleptic medications may result in extrapyramidal motor disturbances and impaired function of the striated musculature of the oral cavity, pharynx, and esophagus [99,100]. Long-term use of antipsychotics may result in tardive dyskinesia [101], with choreiform tongue movements affecting the coordination of swallowing. Delayed swallow initiation is also a reported side effect of some neuroleptic medications.
●Anticonvulsants such as phenobarbital, carbamazepine, and phenytoin may impact central nervous system functioning, as well as benzodiazepines causing drowsiness and motor incoordination, both of which may impact swallowing.
●Antihistamines, antipsychotics, and antidepressants may decrease oral lubrication, leading to dysphagia.
In addition, xerostomia is reported with angiotensin-converting enzyme (ACE) inhibitors, antiarrhythmics, antiemetics, diuretics, and selective serotonin reuptake inhibitors (SSRIs) [34,102].
●Many medications alter gastrointestinal motility or increase reflux, including antipsychotics, antidepressants, and antihistamines [96].
●Mucositis may be caused by conventional cytotoxic chemotherapy agents but is also seen with some orally active molecularly targeted treatments [103]. (See "Oral toxicity associated with systemic anticancer therapy".)
●Local irritation of the esophageal mucosa may be induced by orally ingested drugs, including bisphosphonates, potassium chloride, and nonsteroidal antiinflammatory agents (NSAIDs). Swallowing medications in a supine position, taking them immediately before bedtime, or taking medications without enough fluid all increase the risk of esophageal injury [102]. (See "Risks of bisphosphonate therapy in patients with osteoporosis", section on 'Reflux, esophagitis, ulcers'.)
●ACE inhibitors do not cause dysphagia per se but may increase cough due to thromboxane synthesis in the back of the throat, which may raise suspicion for aspiration. (See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Subacute and chronic cough in adults".)
SUMMARY
●Difficulty swallowing is a disturbing symptom that occurs frequently in progressive terminal illness. (See 'Introduction' above.)
●Chronic swallowing problems affect the efficiency of oral alimentation, compromising nutrition; generalized weakness, anorexia, weight loss, and malnutrition may ensue. Airway protection or swallowing safety can also be threatened by swallowing disorders, exposing the patient to the risk of aspiration. Swallowing difficulties cause significant distress for patients and their families and impact quality of life. For many patients with a terminal illness, the inability to swallow may represent a pivotal symptom that prompts the decision to consider end-of-life or hospice care. (See 'Definitions and consequences of swallowing disorders' above.)
●Swallowing is an extremely complex physiological act and demands exquisite timing and coordination of more than 30 pairs of muscles under both voluntary and involuntary nervous control. There are three phases, the oral, pharyngeal, and esophageal phases, but they overlap and occur simultaneously. The pathophysiology of swallowing disorders can be broadly categorized as oropharyngeal or esophageal. (See 'Normal swallowing' above and 'Pathophysiology of dysphagia' above.)
●The most common etiologies of swallowing disorders in palliative care populations are neoplasms of the brain and upper aerodigestive tract, stroke, progressive neurologic diseases such as amyotrophic lateral sclerosis (ALS), Parkinson disease (PD), and multiple sclerosis (MS); dementia; and general deconditioning/debility, as may be seen in hospitalized older adults or nursing home residents. Identification of the specific etiology and level of swallowing dysfunction is critical to determining the appropriate type of intervention and prognostication for improvement or decline.
●Medications can contribute to or cause dysphagia by affecting all stages of swallowing, including lubrication of the oral cavity and pharynx, reduced coordination or motor function, impaired consciousness, gastrointestinal dysfunction, and local mucosal toxicity. (See 'Medications' above.)
