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INTRODUCTION — The symptoms of cough, stridor, and hemoptysis are common in palliative care patients who have an advanced life-threatening illness, especially cancer. As with dyspnea, these respiratory symptoms may be particularly frightening to patients, their families, and their caregivers. (See "Assessment and management of dyspnea in palliative care".)
Palliative management focuses on symptom relief; this may occur alongside therapies to treat or reverse the underlying cause(s). Palliative management also includes the amelioration of the psychosocial and spiritual impacts of these potentially life-threatening symptoms, utilizing a team approach. (See "Palliative care for adults with nonmalignant chronic lung disease".)
DIAGNOSTIC TESTING — A common issue for each of these symptoms is the degree to which diagnostic studies should be pursued. This decision must be individualized for each patient. However, a general rule for palliative care patients is that a diagnostic test should be performed only if it will yield information that will affect management. Too often in advanced disease, tests are ordered as a means of palliating the clinician’s feeling of helplessness. Additionally, if a test or intervention is not consistent with the patient’s goals of care, it may add burden or risk without any benefit.
COUGH — This section will summarize cough when it is being managed palliatively in the setting of an advanced serious life-threatening illness. Acute and chronic cough in adults and children, including details about potential mechanisms and treatments, is defined, and differential diagnosis is discussed separately. (See "Evaluation of subacute and chronic cough in adults" and "Treatment of subacute and chronic cough in adults" and "Approach to chronic cough in children" and "Causes of chronic cough in children".)
Acute cough is a mechanism to clear the airways of mucus and foreign bodies when mucociliary transport is insufficient. When a cough becomes chronic, it is disruptive, distressing, and physically exhausting. It impairs social relationships and worsens other symptoms such as pain, dyspnea, incontinence, and sleep disturbance . It can also cause rib fractures . The mildest cough may be almost imperceptible to the patient; yet, its importance to the patient and family is linked to the underlying disease (eg, the cancer is still there). The most severe cough is convulsive, unending, terrifying, and permits no other object of attention for the patient or family.
Pathogenesis and underlying causes — Involuntary cough is initiated when rapidly adapting “irritant” receptors (RARs) that transmit through fast-velocity myelinated vagal nerve fibers are stimulated. Receptors are present in the epithelium of the upper and lower airways, but the most sensitive sites for cough induction are the larynx, carina, and branching points in the tracheobronchial tree. RARs respond to a wide variety of chemical (eg, smoke), inflammatory (eg, histamine), and mechanical (eg, sputum) stimuli. Their stimulation may also lead to bronchoconstriction and mucous hypersecretion . (See "Evaluation of subacute and chronic cough in adults", section on 'Cough reflex arc'.)
In palliative care populations, the cough reflex can be stimulated by attempts to expectorate accumulating secretions. This occurs in up to 80 percent of patients with cough . In many advanced disease processes, asthenia, muscle weakness, and the inability to coordinate an effective swallow near the end of life results in ineffective, persistent coughing.
Other causes are related to the underlying disease.
Malignant disease — Cough in people with malignancy is most commonly associated with cancers of the airways, lungs, pleura, and mediastinum, but can occur with other cancers that metastasize to the thorax .
For patients with advanced cancer, cough is reported in 23 to 52 percent . Up to 90 percent of patients with advanced lung cancer report cough [7,8], and it is rated as moderate to severe in up to one-half . A high rate of cough (over 90 percent) is also reported in palliative care patients with advanced head and neck cancer . The presence of cough has been shown to predict a shorter overall survival in patients with lung cancer .
The causes of cough associated with advanced cancer are listed in the table (table 1). Among patients with lung cancer, cough is more likely to indicate involvement of the central airways than the lung parenchyma because of where the cough receptors are located.
The etiology of cough may be multifactorial. The evaluation of cough should include a search for contributory factors other than the cancer itself (table 2). As an example, for patients with oropharyngeal dysphagia following treatment for head and neck cancer, cough may be an important indicator of aspiration.
Nonmalignant disease — Cough is also common in patients with some chronic progressive illnesses other than cancer, especially chronic obstructive pulmonary disease (COPD) and other chronic lung diseases, and heart failure (table 2):
●In a systematic review of studies of symptom prevalence in people with incurable disease, the pooled prevalence of cough was 28 percent in 24 studies involving almost 12,000 individuals .
●Another review of 109 palliative care patients (49 with cancer and 60 with COPD) noted cough in 78 percent of the cancer patients and 62 percent of those with COPD .
●Cough is also a prominent feature of patients with progressive fibrotic lung disease; in one report, cough was reported in 42 of 45 (93 percent) .
●In another series of 115 patients hospitalized with late-stage nonmalignant disease (61 with organic brain disease, 31 with COPD, 17 with chronic kidney disease, 14 with heart failure, 12 with cirrhosis, and 20 with multiple illnesses), cough was present in 81 percent and was one of the four leading symptoms .
●In HIV infection, cough occurs in 19 to 60 percent, and chronic phlegm production occurs in 42 percent [16,17]. Among HIV-infected individuals, current or past cigarette smoking is the most important predictor for respiratory symptom burden.
●Sixty-nine percent of patients with cystic fibrosis suffer from difficulty expectorating sputum; approximately 80 percent report persistent cough .
For many patients with nonmalignant life-limiting advanced illness, the severity of cough and the importance of its management increase with disease progression.
Differential diagnosis — Distinguishing acute from subacute or chronic cough is important:
●The differential diagnosis for subacute or chronic cough in palliative care includes conditions such as allergic rhinitis with postnasal drip, reactive airways disease, gastroesophageal reflux (GERD), postinfectious chronic cough, and chronic bronchitis. (See "Evaluation of subacute and chronic cough in adults".)
●Acute cough is usually caused by infection (pneumonia and acute bronchitis).
General approach to the patient — A thorough history is fundamental to identify the cause of cough. The assessment should include the type of cough (productive/nonproductive), trigger factors, whether cough is nocturnal or daytime, severity of cough (especially whether sleep is impaired), and effects on quality of life. The timing of the start of cough is important; any change in cough or new cough since the diagnosis of cancer indicates that the cough is likely related to the cancer. On the other hand, a more chronic cough may be related to underlying respiratory morbidity. The assessment should include a careful medication review. Angiotensin-converting enzyme (ACE) inhibitors may cause cough, and some chemotherapy drugs cause pulmonary toxicity, which may manifest as cough. (See "Pulmonary toxicity associated with antineoplastic therapy: Cytotoxic agents" and "Pulmonary toxicity associated with antineoplastic therapy: Molecularly targeted agents".)
A bedside swallowing evaluation may be indicated if patients are noted to cough after swallowing. If abnormal, a barium swallowing study can assist with identifying aspiration. (See "Swallowing disorders and aspiration in palliative care: Definition, consequences, pathophysiology, and etiology".)
Every palliative care patient with a chronic or persistent acute cough does not need a diagnostic evaluation with a chest radiograph. As noted above, the decision to pursue diagnostic studies must be individualized. A general rule for palliative care patients is that a diagnostic test should be performed only if it will yield information that will affect management. (See 'Diagnostic testing' above.)
A reasonable palliative care management strategy is to treat empirically, based upon an assessment of the most likely cause (if treatment is consistent with the goals of care), and pursue diagnostic testing only if there is no response and there is a reasonable likelihood of identifying a potentially treatable cause. Symptomatic treatment should be provided alongside disease-modifying treatment. An algorithmic approach to assessment and management of chronic or persistent acute cough in palliative care patients is outlined in the algorithm (algorithm 1).
Potentially reversible causes — In the palliative care setting, many underlying causes will not be able to be reversed. However, some of the causes of cough are reversible, even in patients with far advanced disease:
●A detailed history may reveal easily resolvable issues, such as exposure to perfumes, a recent medication change (especially the institution of treatment with an ACE inhibitor), or a new infection.
●There are distinct treatments for many of the underlying causes of cough, such as antihistamines for allergic rhinitis, anticholinergic decongestants to dry mucus, and corticosteroids for inflammation.
●Antimicrobials may be the best therapy to treat the symptoms caused by an infection. Even in patients with chronic infection, such as those with cystic fibrosis, the vast majority are receiving intravenous antipseudomonas antibiotics during the terminal phase of their illness for “mixed therapeutic and palliative intent” . Many clinicians utilize oxygen, intermittent positive pressure breathing, and mechanical ventilation for these patients near the end of life as well, given that the timing of death is difficult to predict [20-23].
For other patients with chronic infection, chronic suppressive antibiotics may not clear the infection but may improve cough. The use of preventive antibiotics to reduce acute exacerbations in patients with COPD and a chronic productive cough is discussed in detail elsewhere. (See "Management of infection in exacerbations of chronic obstructive pulmonary disease", section on 'Prophylactic antibiotics'.)
Disease-directed therapy — For patients with cancer who have central airway obstruction, palliative chemotherapy, palliative radiotherapy, endobronchial laser resection , or stent placement may also provide symptomatic improvement, if such treatments are consistent with the goals of care. However, improvement in cough with palliative chemotherapy, radiotherapy, or endobronchial brachytherapy may take several weeks [25-27]. (See "Clinical presentation, diagnostic evaluation, and management of central airway obstruction in adults", section on 'Diagnostic evaluation and initial management'.)
Symptom-directed treatment — Empiric treatment of cough is appropriate when a specific cause cannot be identified or when cause-directed therapy is neither feasible nor rapidly effective. Symptomatic management may be used alongside disease-modifying treatment.
Patients with moderate to severe cough — We define moderate to severe cough as that which impairs sleep. The mainstay of therapy for moderate to severe cough is cough suppression with antitussives. Antitussives suppress the cough reflex by acting centrally or peripherally. For most patients, opioids are the first-line pharmacologic therapy to suppress cough. Another alternative, if opioids are contraindicated or if there is another reason to avoid opioids, is gabapentin or pregabalin. (See 'Antitussives' below.)
Mild-severity cough — For patients with mild-severity cough, we try nonpharmacologic therapies first (eg, cough suppression exercises, linctus). If cough continues or worsens, we begin a peripherally acting antitussive, such as benzonatate, switching to a centrally acting antitussive, such as an opioid, if cough continues or worsens. (See 'Nonpharmacologic therapies' below.)
Antitussives — A mainstay of pharmacologic therapy for cough is suppression with antitussives. Antitussives suppress the cough reflex by acting centrally or peripherally.
Centrally acting — A number of agents, both opioid and nonopioid (ie, gabapentin), are thought to suppress cough via an action on the central cough center.
●Opioids – A centrally acting opioid is a mainstay of pharmacologic therapy for palliative care patients with chronic cough, particularly that related to an intrathoracic cancer.
The oldest medication for cough is codeine, which was first introduced over 150 years ago. However, its role as the supposedly best choice was called into question  after two randomized trials (one in patients with the common cold, the other in COPD with stable disease) failed to demonstrate significant improvement over placebo [29,30].
Although antitussive efficacy of several opioids is supported by phase II studies [1,31], there are no placebo-controlled randomized trials of codeine (and very few of other opioids) in palliative care populations . The limitations in the available literature were underscored by a year 2015 Cochrane review of trials examining pharmacologic interventions for cough in patients with primary or metastatic cancer, which concluded that no practice recommendations could be determined given the significant risk of bias in all trials .
In the absence of data specifically derived from palliative care populations, it is reasonable to extrapolate from the experience in patients with chronic cough from a variety of conditions. A systematic review of efficacy and tolerability of various treatments for chronic cough included 49 trials (3067 patients) comparing 68 therapeutic comparisons; few of the trials included cancer patients . The following conclusions were drawn:
•Eight of the 11 comparisons of opioids with placebo for treatment of chronic cough (including eight trials in which the comparator arm was codeine, one dihydrocodeinone, one morphine, and one viminol p-hydroxybenzoate) showed opioids to be more effective than placebo for decreasing cough frequency and severity and for improving quality of life. No one opioid was superior to any other, although a dose-response relationship was shown for codeine.
•Data from 13 studies were analyzed in a mixed-treatment meta-analysis; because the studies used various measures of severity, results were converted to effect sizes (standardized mean differences [SMDs]). For context, values of 0.2, 0.5, and 0.8 represented small, medium, and large effect sizes, respectively. Values for cough frequency were assessed using rate ratios. Compared with placebo, the effect sizes for cough severity and rate ratios for cough frequency for nondextromethorphan opioids were 0.55 (95% CI 0.38-0.72) and 0.57 (95% CI 0.36-0.91), respectively.
•Four of the six trials comparing dextromethorphan (an antitussive antagonist of the N-methyl-D-aspartate receptor and the major ingredient in most over-the-counter cough syrups) with placebo showed that dextromethorphan was effective at reducing cough severity, frequency, or both. Compared with dextromethorphan, codeine was less effective in one small study (n = 16 patients), comparable in another, and more effective in two, but the latter two studies compared standard-dose codeine with low-dose dextromethorphan. In the mixed-treatment meta-analysis, the effect sizes for dextromethorphan were smaller than for other opioids (SMD for cough severity 0.37, 95% CI 0.19-0.56, and rate ratio for cough frequency 0.40, 95% CI 0.18-0.85).
•Of the studies comparing opioids with other active nonopioid antitussives, two trials compared opioids with anesthetic compounds (benzonatate or isoaminile citrate), and neither class of medications showed superiority.
There were no trials comparing opioids with protussives. (See 'Other pharmacologic agents' below.)
•The overall strength of the evidence for any treatment was limited by inconsistency, imprecision, and small numbers of direct comparisons.
In our view, codeine, 15 mg orally every four hours; hydrocodone, 5 mg every four hours; or morphine, 5 mg every four hours, are reasonable starting doses in an opioid-naïve patient. However, many palliative care physicians choose morphine over codeine since codeine is a prodrug that is metabolized to morphine by a cytochrome P450 enzyme. Patients who have allelic variants of this enzyme are predisposed to rapid or poor metabolism and are at risk of experiencing adverse effects of codeine without the benefit . (See "Overview of pharmacogenomics", section on 'Altered pharmacokinetics'.)
For patients already receiving opioids for pain, a 25 to 50 percent dose increase may be tried to suppress the cough. Despite the conclusion of the meta-analysis, we do not use dextromethorphan for treatment of chronic cough, given the small size of older placebo-controlled trials and the fact that two trials failed to show any benefit over placebo [35-40]. (See "Cancer pain management with opioids: Optimizing analgesia".)
●Gabapentin and pregabalin – Another alternative treatment for chronic unexplained cough is gabapentin or pregabalin, gamma aminobutyric acid (GABA) analogs that bind to the voltage-gated calcium channels and inhibit neurotransmitter release [41,42]. It is hypothesized that these agents may act to reduce chronic cough via a central mechanism. Neither medication is approved for use in chronic cough, although gabapentin is recommended for unexplained chronic cough in updated American College of Chest Physicians (ACCP) guidelines . However, this recommendation does not relate to superior efficacy as compared with opioids. It appears to be made in response to concerns about opioid diversion or abuse. For palliative care populations, the prescribing clinician will want to make an individual assessment but not withhold an effective treatment for cough (opioid therapy) because of fear of abuse, unless such concerns are valid. The evidence in favor of gabapentin and pregabalin for alleviation of chronic cough is presented elsewhere. (See "Treatment of subacute and chronic cough in adults", section on 'Gabapentin and pregabalin'.)
To reduce adverse effects of sedation and dizziness, gabapentin is initiated at a low dose (300 mg once a day) with gradual increases until cough relief, dose-limiting adverse effects, or a dose of 1800 mg a day in two divided doses is achieved . Adverse effects may include diarrhea, nausea, emotional lability, somnolence, nystagmus, tremor, weakness, and peripheral edema.
Peripherally acting — Benzonatate, a peripherally acting antitussive, presumably anesthetizes stretch receptors in the lungs and pleura. Although at least one older study suggests that benzonatate was not superior to placebo for treatment of chronic cough in patients with asthmatic bronchitis or COPD , when added to opioids, there is anecdotal evidence that it may provide additional benefit for refractory cough . However, the available evidence for additive benefit is quite limited. The recommended dose is 100 to 200 mg three times daily.
Other pharmacologic agents — Selected patients may benefit from other pharmacologic strategies:
●Bronchodilators may help if there is a bronchoconstrictive component to the cough.
●Corticosteroids such as dexamethasone 4 to 12 mg daily may diminish inflammation and mucus production, and they are regularly used in patients with asthma or COPD.
●Sodium cromoglycate is a mast cell stabilizer that is useful for mild asthma. In a single trial conducted in a small sample of 20 patients with advanced lung cancer, inhaled sodium cromoglycate (two puffs four times daily) was shown (albeit using an unvalidated measurement tool) to be better than placebo . No other trials are available, and the benefit of inhaled sodium cromoglycate in palliative care patients remains unconfirmed [24,33]. (See "The use of chromones (cromoglycates) in the treatment of asthma".)
●If the sputum is thick, expectorants (eg, glyceryl guaiacolate) or mucolytics (eg, acetylcysteine) may be used in order to reduce the viscosity of secretions and make each cough more productive. However, these agents, which are referred to as “protussives,” are not cough suppressants, and there is no evidence that they reduce the frequency or severity of cough. Neither expectorants nor mucolytics have proven helpful in common upper respiratory infections . Furthermore, the systematic review of therapies for chronic cough cited above included 10 comparisons of protussives in eight studies and concluded that only one study showed benefit from guaifenesin in reducing cough intensity . There was no significant benefit from mucolytics. (See "The common cold in adults: Treatment and prevention".)
Additional fluid ingestion may be a factor in the potential efficacy of expectorants, particularly if the patient is dehydrated. Expectorants should not be used in patients with neuromuscular diseases such as amyotrophic lateral sclerosis, many of whom will not be able to cough out the liquified mucus .
●Nebulized saline, which functions as an expectorant, has been advocated for intractable cough.
Nonpharmacologic therapies — For mild cough, it is traditional to treat using a linctus (a thick, sweet liquid, such as honey) . However, there is no strong evidence for or against this form of therapy [24,33].
Chest physical therapy could be considered for selected patients (eg, those with bronchiectasis) if such therapy is consistent with the goals of care. (See "Treatment of bronchiectasis in adults", section on 'Airway clearance techniques'.)
Modalities such as speech therapy, breathing exercises, cough suppression techniques, and patient counseling have been tried in the management of chronic cough [57-63]. A systematic review of five trials in non-lung cancer respiratory disease reported that studies of such interventions showed improved cough severity and frequency, but few of them used validated cough measurement tools . One randomized feasibility trial of a nonpharmacologic intervention that included cough suppression exercises in 101 patients with primary lung cancer and a bothersome respiratory distress cluster (breathlessness, cough, and/or fatigue) demonstrated feasibility and a potentially clinically meaningful improvement in the trial arm using a cough scale . However, the statistical validity of the results was compromised by extensive dropout by week 4. The robustness of these studies’ findings is limited. (See "Treatment of subacute and chronic cough in adults", section on 'Non-pharmacologic interventions'.)
The dying patient — In the last hours and days of life, cough can affect up to 80 percent of patients; contributory factors are asthenia, muscle weakness, and increased respiratory secretions. Anticholinergic drugs, such as glycopyrrolate, can minimize bronchial secretions and may improve cough [65-67]. (See "Palliative care: The last hours and days of life", section on 'Accumulation of upper airway secretions'.)
Guidelines from expert groups — Comprehensive guidelines for the management of chronic cough are available from the British Thoracic Society (BTS) , the European Respiratory Society (ERS) , and the ACCP [43,68]. These focus on the most common causes of chronic cough (asthma, bronchitis, GERD, and upper airways cough syndromes resulting from rhinosinusitis). While neither guideline specifically deals with intractable cough related to advanced progressive cancer or nonmalignant life-limiting illness, clinicians should remember that conditions such as these may cause chronic cough in palliative care populations. For unexplained chronic cough, the ACCP recommends the use of gabapentin or pregabalin as an alternative to opioids, with less potential for diversion or abuse, a point which may not be relevant to palliative care populations .
The Association for Palliative Medicine of Great Britain and Ireland has made recommendations for the management of chronic cough in patients receiving palliative care. Grade D (weak) recommendations include linctus, therapeutic trial of sodium cromoglycate, and prescription of an opioid or opioid derivative .
Updated guidelines are available for symptom management in patients with lung cancer from the ACCP . For patients with cough related to lung cancer, the guidelines recommend evaluation for other treatable causes of cough in addition to cancer-related etiologies. For those without a treatable cause, an algorithmic stepwise approach is suggested. Unfortunately, this stepwise approach does not advocate treating cough symptomatically in parallel with disease-directed or empiric treatment.
Consensus-based guidelines for supportive care in patients with advanced malignancy from the National Comprehensive Cancer Network (NCCN) do not include specific management suggestions for chronic cough.
STRIDOR — Stridor is a harsh, high-pitched wheezing or vibrating sound that results from turbulent airflow in the upper airways. It can occur during inspiration, expiration, or both, although it most typically occurs with inspiration.
Pathogenesis and underlying causes — Generally, stridor results from a narrowing of a central airway or the larynx caused by a foreign body, a tumor pushing extrinsically or growing intrinsically, infection, or edema. For patients with cancer, stridor can occur with squamous cell carcinomas of the larynx, trachea, or esophagus. In addition, superior sulcus tumors of the right upper lobe (the so-called “Pancoast” tumors) can extrinsically compress the superior vena cava (SVC) leading to SVC syndrome. This and other causes of SVC syndrome cause secondary interstitial edema of the head and neck, which may narrow the lumen of the nasal passages and larynx, and cause dyspnea, stridor, cough, hoarseness, and dysphagia. (See "Superior pulmonary sulcus (Pancoast) tumors" and "Malignancy-related superior vena cava syndrome".)
The degree of obstruction or narrowing and the rapidity of onset can precipitate a palliative care emergency. While the underlying cause may not be changing quickly, the severity of anxiety and dyspnea associated with panic affects patients, families, and health care professionals, heightening the drama and emotional ferment, necessitating urgent action.
Management — Patients who present with stridor due to severe tracheal or mainstem obstruction or severe laryngeal edema and respiratory compromise represent a true medical emergency. They are at high risk for respiratory failure and death, and require initial stabilization to secure ventilation and oxygenation, if this is consistent with the goals of care:
●Endotracheal intubation is preferred.
●In cases of severe tracheal obstruction, use of the open ventilating rigid bronchoscope is the preferred method of airway control. (See "Rigid bronchoscopy: Intubation techniques".)
●Occasionally, emergency tracheostomy is needed for palliation of upper airway tumors so the patient does not suffocate.
The initial management of central airway obstruction is presented in detail elsewhere. (See "Clinical presentation, diagnostic evaluation, and management of central airway obstruction in adults", section on 'Diagnostic evaluation and initial management'.)
In all cases, management of the experience of the patient and those who are watching is important. When the underlying cause cannot be reversed, it is paramount that symptomatic control be swift and confident. Dyspnea and anxiety should be managed with opioids and benzodiazepines (see "Assessment and management of dyspnea in palliative care", section on 'Opioids' and "Management of psychiatric disorders in patients with cancer", section on 'Pharmacotherapy'):
●In an opioid-naïve patient, 5 to 10 mg morphine may be administered intravenously, or subcutaneously if there is no intravenous access. The dose may be repeated every 10 minutes (time to maximum serum concentration) intravenously or every 30 minutes subcutaneously in order to titrate to comfort. The dose may also be doubled with each subsequent dose until the patient reports relief. Once comfort is achieved, a total dose can be calculated and administered every half-life for steady-state maintenance or given as a continuous infusion. Sometimes the maintenance dose is less than that needed to achieve initial comfort because anxiety is reduced; you will have demonstrated to the patient and family that you can control the symptom.
●If anxiety is prominent, a benzodiazepine such as lorazepam may be added at a dose of 0.5 to 1 mg intravenously every 15 minutes or subcutaneously every hour to titrate to comfort. For highly symptomatic patients, sedation may be required to relieve distress to the satisfaction of the patient and family. (See "Palliative sedation".)
●When stridor is of sudden onset, administration of racemic epinephrine for a potentially allergic cause of anaphylaxis may be used in a therapeutic trial before opioids and benzodiazepines are initiated. (See "Anaphylaxis: Emergency treatment".)
Once initial control of the symptom is achieved, attention to the underlying cause can be entertained. A diagnostic evaluation may lead to more definitive therapy, if doing so is consistent with the goals of care. In one study, urgent therapeutic bronchoscopy allowed 52 percent of patients with malignant central airway obstruction to come off of the ventilator . For selected patients with a central airway obstruction, single-fraction radiotherapy, endoscopic stent placement, endobronchial laser ablation, or argon plasma coagulation may have a role, if treatment of the underlying cause is consistent with the goals of care. For patients with SVC syndrome, endovascular stenting or thrombolytic therapy are also options. (See "Malignancy-related superior vena cava syndrome", section on 'Treatment' and "Clinical presentation, diagnostic evaluation, and management of central airway obstruction in adults", section on 'Diagnostic evaluation and initial management'.)
Standard approaches to discussing the benefits and burdens of treatment require special modification in the setting of a palliative care emergency such as severe stridor. A question such as “How would you like me to manage your stridor?” is not a helpful approach in the heat of the moment. Rather, an opening statement such as the following is more appropriate: “We are going to make every attempt to bring your symptoms under control. Sometimes, there is a tension between providing enough to keep you comfortable but not so much as to make you sleepy. If we have to err on one side or the other, on which side should we err: alertness or comfort?”
HEMOPTYSIS — Hemoptysis is blood coughed up from a pulmonary source. Hemoptysis must be differentiated from pseudohemoptysis (expectoration of blood originating in the nasopharynx or oropharynx) and hematemesis (vomiting of blood). Pseudohemoptysis can be diagnosed by inspection of the nasopharynx and oropharynx, and hematemesis by other gastrointestinal symptoms and risk factors for gastrointestinal tract bleeding. Characteristics of the expectorated material that suggest that a gastrointestinal source is unlikely include an alkaline pH, foaminess, and/or the presence of pus. (See "Etiology and evaluation of hemoptysis in adults".)
Massive hemoptysis is generally used to describe the expectoration of a large amount of blood and/or a rapid rate of bleeding, although the precise thresholds that constitute massive hemoptysis are controversial. Some define massive hemoptysis as ≥500 mL of expectorated blood over a 24-hour period or bleeding at a rate ≥100 mL/hour. (See "Overview of massive hemoptysis", section on 'Definition'.)
Pathogenesis and underlying causes — In palliative care populations, hemoptysis can occur in patients with primary or secondary lung cancer, terminal hematological malignancy, lung infection or abscess, bronchiectasis, pulmonary embolism, cystic fibrosis , bleeding disorders, anticoagulant use, Goodpasture’s syndrome, Wegener’s granulomatosis, and other less common conditions (table 3). (See "Etiology and evaluation of hemoptysis in adults".)
Among patients with cancer, hemoptysis is most common in lung cancer. It is the presenting symptom in 7 to 10 percent of lung cancer patients, and approximately 20 percent will have hemoptysis during the course of their illness . Pulmonary hemorrhage is a known complication of the antiangiogenic agent bevacizumab, especially in patients with squamous cell bronchogenic carcinoma. The use of bevacizumab is contraindicated in patients with squamous cell lung carcinoma and in any patient with hemoptysis (>2.5 mL of blood) within three months. (See "Toxicity of molecularly targeted antiangiogenic agents: Non-cardiovascular effects", section on 'Pulmonary hemorrhage and cavitation'.)
Although hemoptysis is common in bronchogenic carcinoma, massive terminal hemoptysis (eg, from erosion of the tumor into a blood vessel) is rare, occurring in only 3 percent of 877 patients in one series . When it does occur, massive hemoptysis associated with bronchogenic carcinoma has an extremely grim prognosis (mortality 59 to 100 percent), making it a palliative care emergency. Other causes of massive hemoptysis are bronchiectasis, pulmonary tuberculosis, and fungal pulmonary infection. (See "Massive hemoptysis: Causes", section on 'Causes of massive hemoptysis'.)
Management — Hemoptysis, even of small amounts, may be extremely frightening for the patient and those who watch. At one end of the spectrum, the distress from a bit of blood-flecked sputum associated with cough may be relieved by reassurance. At the other extreme, if hemoptysis is massive, it may herald a life-ending event, and witnessing what may be exsanguination requires urgent attention to all who are witnesses.
Treatment should be tailored to the patient’s overall status, the severity of hemoptysis, the underlying cause, and the wishes of the patient and family. The patient and family can often be best supported by the provision of goal-directed information and recommendations for management. It may be necessary to share prognostic information quickly with the patient and/or family to help them determine the best goals of care and, subsequently, the best medical decisions. Using a team approach, psychosocial and spiritual needs can be addressed just as quickly as the physical symptoms. (See "Massive hemoptysis: Initial management".)
The palliative treatment of hemoptysis is primarily related to managing the patient and family’s experience, and efforts to stop the bleeding, if this is consistent with the overall goals of care. At a minimum, reassurance when the amount of blood is small is all that is required. Dark towels, dark sheets, dark blankets, and absorptive dressings with an impermeable backing can be used to diminish the visual impact. The environment can be managed by assuring that blood-tinged sputum is not collecting in a visible white cup at the bedside and that brilliant red-streaked blood on white tissues is kept from view.
Patients with massive hemoptysis should be immediately placed into a position in which the presumed bleeding lung is in the dependent position (eg, a patient whose right lung is bleeding should be placed in the right-side down decubitus position). The purpose of these positions is to protect the nonbleeding lung, since spillage of blood into the nonbleeding lung may prevent gas exchange by blocking the airway with clot or filling the alveoli with blood.
In the rare instances where the underlying cause can be reversed, diagnostic tests (bronchoscopy and, if an endobronchial lesion is not identified, angiogram to identify a feeder vessel that might be amenable to bronchial artery embolization [embolotherapy] ) and interventional procedures may be considered, if this is consistent with the goals of care. For patients with massive hemoptysis, this might require urgent supportive care with blood or platelet transfusion, reversal of anticoagulation, and administration of procoagulant agents. Radiotherapy in a single dose may stop bleeding of a malignant source if the patient is stable enough for imaging and planning. Therapeutic bronchoscopy with balloon tamponade and infusion of vasoactive agents, such as epinephrine, may be successful as a temporizing measure. Antifibrinolytics given orally or via nebulized routes have been used, but utility is guided mostly by anecdote and some small case reports [74,75]. One case series suggests nebulized vasopressin could be effective for mild to moderate hemoptysis in palliative care patients . If the area of bleeding can be directly visualized, bronchoscopic techniques such as laser coagulation or electrocautery may also be used, with response rates of 60 to 100 percent. (See "Overview of massive hemoptysis", section on 'Treatment' and "Massive hemoptysis: Initial management", section on 'Nonsurgical'.)
If hemoptysis is overwhelming and/or accompanied by severe hemodynamic instability and the goals of care do not support attempts at diagnosis or intervention, urgent sedation may be required. When urgent sedation is required, midazolam at 0.2 mg/kg administered intravenously (if there is vascular access) or subcutaneously will be effective in the patient who is not chronically taking benzodiazepines (table 4). This is generally administered in 5 mg increments every five minutes until sedation is achieved. A continuous infusion may be instituted to maintain sedation.
For the patient who is tolerant to benzodiazepines, an alternative agent, such as a barbiturate, will be effective (table 4). For example, phenobarbital may be administered in a loading dose of 10 mg/kg intramuscularly. Because of the relatively low concentration (it is available in 130 mg/mL vials), splitting of the total dose into two or three syringes with administration into separate intramuscular sites may be required because of volume constraints. If sedation is not achieved, the loading dose of 10 mg/kg can be repeated every two hours to a maximum of 30 mg/kg total in the first 24 hours. If phenobarbital is administered intravenously, the rate should not exceed 50 mg/minute. After sedation is achieved, a continuous infusion of 10 to 25 mg/hour can be instituted. A total dose of 600 to 2400 mg/day (25 to 100 mg/hour) is often sufficient to sustain sedation . (See "Palliative sedation".)
Guidelines from expert groups — Guidelines are available for symptom management in patients with lung cancer from the American College of Chest Physicians (ACCP) . For patients with hemoptysis, they recommend the following:
●For large volume hemoptysis, the airway should be secured with a single-lumen endotracheal tube. Bronchoscopy is recommended to identify the source of bleeding, followed by endobronchial management options (eg, argon plasma coagulation, laser endobronchial resection, or electrocautery for visible central airway lesions).
●For non-large volume hemoptysis, bronchoscopy is recommended to identify the source of bleeding. For visible central airway lesions, endobronchial management options are recommended; for distal or parenchymal lesions, external beam radiotherapy is recommended.
●If these measures are unsuccessful, consideration should be given to bronchial artery embolization to temporize the bleeding.
Palliative measures were not addressed.
SUMMARY AND RECOMMENDATIONS — The symptoms of cough, stridor, and hemoptysis are common in palliative care patients who have an advanced life-threatening illness, especially cancer. In most cases, diagnostic testing should only be pursued if it will yield information that will affect management. (See 'Diagnostic testing' above.)
Cough — In palliative care populations, asthenia, muscle weakness, and the inability to coordinate an effective swallow near the end of life result in ineffective, persistent coughing in an attempt to clear accumulating airway secretions. Among patients with cancer, cough may be attributed to direct or indirect effects of the tumor (table 1). All patients should be evaluated for other potentially treatable causes of cough.
The following represents our approach to treatment, which is outlined in the algorithm (algorithm 1):
●Potentially reversible causes should be sought (eg, exposure to an inhaled irritant, postnasal drip, infection, inflammation, new medication), for which specific treatment may be available. (See 'Potentially reversible causes' above.)
●For patients with cancer who have airway obstruction, palliative chemotherapy, palliative radiotherapy, laser treatment, or stent placement may provide symptomatic improvement, if such treatments are consistent with the goals of care. However, improvement with chemotherapy, palliative radiotherapy, and endobronchial brachytherapy may take several weeks. (See 'Nonpharmacologic therapies' above.)
●Empiric treatment of cough is appropriate when a specific cause cannot be identified or when cause-directed therapy is neither feasible nor rapidly effective. Symptomatic management should be provided alongside disease-modifying treatment.
●For most patients with moderate to severe cough, particularly those with malignancy-related cough, we recommend treatment with a centrally acting opioid (Grade 1B). (See 'Patients with moderate to severe cough' above.)
There is little reason to choose one agent over any other. Codeine, 15 mg orally every four hours; hydrocodone, 5 mg every four hours; or morphine, 5 mg every four hours, are reasonable starting doses in an opioid-naïve patient. For patients already receiving opioids for pain, a 25 to 50 percent dose increase may be tried to suppress the cough. (See 'Centrally acting' above.)
●For patients with mild-severity cough, we try nonpharmacologic therapies first (eg, cough suppression exercises, linctus [honey or a demulcent cough syrup]). If cough continues or worsens, we begin a peripherally acting antitussive, such as benzonatate, switching to a centrally acting antitussive, such as an opioid, if cough continues or worsens. (See 'Nonpharmacologic therapies' above.)
●Selected patients may benefit from other pharmacologic strategies, such as bronchodilators (if there is a bronchoconstrictive component to the cough), glucocorticoids (if there is an inflammatory component), or an expectorant (if the sputum is thick and the patient is able to cough out liquified mucus).
Stridor — Stridor is a harsh, high-pitched wheezing or vibrating sound that results from a narrowing of a central airway or the larynx caused by a foreign body, a tumor pushing extrinsically or growing intrinsically, infection, or edema. The degree of obstruction or narrowing and the rapidity of onset can precipitate a palliative care emergency. (See 'Pathogenesis and underlying causes' above.)
●Patients who present with stridor due to severe tracheal or mainstem obstruction or severe laryngeal edema and respiratory compromise represent a true medical emergency; they require initial stabilization to secure ventilation and oxygenation. (See 'Management' above.)
●The dyspnea and anxiety should be managed with opioids and benzodiazepines. For highly symptomatic patients, sedation may be required to relieve distress to the satisfaction of the patient and family. (See "Palliative sedation".)
Once initial control of the symptom is achieved, attention to the underlying cause can be entertained. Prudent imaging, either radiographically or endoscopically, may lead to more definitive therapy (eg, palliative radiotherapy, stenting). (See 'Management' above.)
Hemoptysis — Hemoptysis, blood coughed up from a pulmonary source, must be differentiated from pseudohemoptysis (expectoration of blood originating in the nasopharynx or oropharynx) and hematemesis. (See 'Hemoptysis' above.)
●In palliative care populations, hemoptysis can occur in patients with primary or secondary lung cancer, lung infection or abscess, bronchiectasis, pulmonary embolism, cystic fibrosis, bleeding disorders, anticoagulant use, Goodpasture’s syndrome, Wegener’s granulomatosis, and other less common conditions (table 3). (See 'Pathogenesis and underlying causes' above.)
●The palliative treatment of hemoptysis is primarily related to managing the patient and family’s experience, and efforts to stop the bleeding, if this is consistent with the overall goals of care (see 'Management' above):
•At a minimum, reassurance when the amount of blood is small is all that is required.
•Patients with massive hemoptysis should be immediately placed into a position in which the presumed bleeding lung is in the dependent position. (See "Massive hemoptysis: Initial management", section on 'Position the patient'.)
•In the rare instances where the underlying cause of massive hemoptysis can be reversed, diagnostic tests and interventional procedures may be considered, if this is consistent with the goals of care. For patients with massive hemoptysis, this may require urgent supportive care with blood or platelet transfusion, reversal of anticoagulation, and/or administration of procoagulant agents. (See "Massive hemoptysis: Initial management", section on 'Control the bleeding and correct coagulopathy'.)
•If hemoptysis is overwhelming and/or accompanied by hemodynamic instability and the goals of care do not support attempts at diagnosis or intervention, urgent sedation may be required. (See "Palliative sedation".)
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