INTRODUCTION — The symptoms of cough, stridor, and hemoptysis are common in palliative care patients with advanced life-threatening illness, especially cancer. These respiratory symptoms may be frightening to patients, families, and 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".)
COUGH — This section will summarize palliative management of cough in the setting of an advanced life-threatening illness. A more general approach to acute and chronic cough in adults is discussed separately. (See "Causes and epidemiology of subacute and chronic cough in adults" and "Evaluation and treatment of subacute and chronic cough in adults".)
Cough is a mechanism to clear the airways of mucus and foreign bodies when mucociliary transport is insufficient. When a cough becomes chronic, it can be disruptive, distressing, and physically exhausting. It may impair social relationships and worsen other symptoms such as pain, dyspnea, incontinence, and sleep disturbance [1] or cause rib fractures [2]. The mildest cough may be almost imperceptible to the patient, yet its importance to the patient and family or other loved ones is linked to the underlying disease (eg, the cancer is still there). The most severe cough is convulsive, unending, and permits no other object of attention.
Initial evaluation
●A history should be obtained in all patients. Useful historical features include duration (acute, subacute, or chronic) of cough, type of cough (productive/nonproductive), trigger factors, nocturnal versus daytime pattern, severity, impact on quality of life, and past medical history (history or asthma, chronic obstructive pulmonary disease [COPD], interstitial lung disease, heart failure). This can help identify the cause of cough and determine whether therapy is needed.
The initial evaluation for common causes of cough in general is discussed in detail elsewhere. (See "Causes and epidemiology of subacute and chronic cough in adults", section on 'Causes of chronic cough'.)
Many common causes of cough among palliative care populations are similar to those in the general population and can be categorized by duration (table 1). Pulmonary toxicity from chemotherapy drugs is a special consideration among palliative care patients.
●The need for chest radiograph or other diagnostic interventions depends on the individualized goals of care and likelihood of pursuing treatment based on the test result. On the other hand, when imaging or other diagnostic tests are easy to perform and/or low burden to the patient, they should not be disregarded when the goals are comfort-oriented. For example, if a chest radiograph would help determine whether antibiotics should be utilized to treat an infection in a hospitalized patient, this low-burden intervention would provide information to guide a symptomatic benefit even if the goals are comfort-oriented. Often, extensive evaluation is not needed and should not delay appropriate symptomatic therapy. (See 'Symptom-directed treatment' below.)
Treatment of underlying causes
Common general causes — Cough in palliative care patients can be due to causes similar to those in the general population. In some patients, the cough is an indication that there is an exacerbation of a comorbid illness (such as COPD or bronchiectasis) or an acute pulmonary infection that can be treated. Cough may also be due to conditions which can be relatively easily addressed, such as gastroesophageal reflux disease (GERD), or caused by a medication side effect (eg, angiotensin-converting enzyme [ACE] inhibitors). While cessation of cigarette smoking (or other inhaled irritants) is useful as a response to resultant cough in the general population, smoking cessation is often not realistic and/or helpful in patients with a limited prognosis of weeks or a short number of months.
Management of such causes of cough are similar to the general population and are discussed in further detail elsewhere. (See "Treatment of community-acquired pneumonia in adults in the outpatient setting" and "COPD exacerbations: Management" and "Evaluation and treatment of subacute and chronic cough in adults", section on 'Diagnostic trial of therapy for common causes'.)
Specific causes in palliative care — Certain causes of cough are more common in palliative care patients.
Ineffective swallowing — In palliative care populations, the cough reflex is often stimulated by attempts to clear accumulating secretions due to asthenia, muscle weakness, and the inability to coordinate an effective swallow [3]. Typical patient signs may include drooling and cough brought on by eating and/or drinking. Common causes of swallowing disorders in palliative care are described elsewhere. (See "Swallowing disorders and aspiration in palliative care: Definition, pathophysiology, etiology, and consequences", section on 'Etiology of swallowing disorders in palliative care populations'.)
A bedside swallowing evaluation may be helpful. This will consist of a detailed history and examination by a speech therapist along with observance of swallowing a series of substances. The therapist will note if there are problems chewing, swallowing, or breathing. If the swallow evaluation is abnormal, a barium swallowing study can assist with identifying aspiration. Interventions depend on the patient’s goals of care and include specific swallowing strategies, dietary modifications, and pharmacologic agents. (See "Swallowing disorders and aspiration in palliative care: Assessment and strategies for management".)
Malignant disease — Malignancies likely to cause cough include those of the airways, lungs, pleura, and mediastinum, or cancers that metastasize to the thorax [4,5]. Cough is present in up to 90 percent of patients with advanced lung or head and neck cancer [6-8]. The direct and indirect causes of cough associated with advanced cancer are listed in the table (table 2).
Palliative treatment options for endobronchial tumors include chemotherapy, radiotherapy, endobronchial laser resection, or stent placement. As a general rule, cough improves if directed therapy reduces the impact of the cancer. However, symptom improvement with palliative chemotherapy, radiotherapy, or endobronchial brachytherapy may take several weeks [9-11]. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Diagnostic evaluation and initial management'.)
Chronic infections — In palliative care patients with cystic fibrosis or other chronic lung disease, chronic infections may contribute to cough symptoms. In such cases, antibiotics may be useful for palliative suppression of cough [12]. (See "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection" and "Management of infection in exacerbations of chronic obstructive pulmonary disease", section on 'Prophylactic macrolides'.)
Symptom-directed treatment — The mainstay of symptom-directed pharmacologic therapy is cough suppression with antitussives, which can be used alone or alongside disease-specific treatments. Our approach to treatment is described in the algorithm (algorithm 1).
Mild cough — For patients with mild cough, we suggest a trial of nonpharmacologic therapies as a first step. Options include use of a linctus such as honey, breathing exercises, cough suppression techniques, and patient counseling [13-19]. If these are ineffective, we then suggest a peripherally acting antitussive (eg, benzonatate). If symptoms do not improve with a peripherally acting antitussive, we suggest treatment with a centrally acting antitussive, as for patients with more severe cough. (See 'Moderate to severe cough' below.)
Benzonatate presumably anesthetizes stretch receptors in the lungs and pleura. The recommended dose is 100 to 200 mg three times daily. Data supporting the use of benzonatate are limited, but it is a reasonable first option. Anecdotal evidence suggested benefit in patients with advanced cancer and opioid-resistant cough [20]. However, earlier studies had not shown benefit over placebo in patients with bronchitis or COPD [20,21].
Other peripherally acting antitussives that are available in certain countries include levodropropizine [22,23], moguisteine [24], and levocloperastine [25].
Utilization of a fan is helpful for dyspnea but has scant evidence for palliation of cough, although there is low risk as long as there is no concern for airborne infectious pathogens [26].
Moderate to severe cough — Centrally active agents are appropriate for patients with moderate to severe cough, including cough that impairs sleep and cough that does not respond to peripherally acting agents. We suggest opioids as first-line treatment, or, if opioids are contraindicated, gabapentin or pregabalin.
Nebulized local anesthetics, such as lidocaine or bupivacaine, have been proposed for the most serious cases but may be associated with bronchospasm [27,28]. These agents are most likely to be used in specialized palliative care units.
We do not use dextromethorphan (an antitussive antagonist of the N-methyl-D-aspartate receptor and the major ingredient in most over-the-counter cough syrups) for treatment of chronic cough, due to limited evidence of efficacy [29-31]. Although dextromethorphan is frequently used in the general population, in which cough is often of limited duration, we favor using more effective agents upfront in the palliative care population.
Opioids — Opioids are a mainstay of pharmacologic therapy for palliative care patients with moderate to severe chronic cough, particularly those with intrathoracic cancer. Some clinicians are hesitant to use them due to concern of opioid misuse or addiction; however, such concerns in a palliative care population are rare.
Appropriate options for cough suppression in opioid-naïve patients include:
●Morphine 5 mg by mouth every four hours as needed for moderate to severe cough. If benefits from routine use of immediate release opioids are demonstrated, long-acting preparations can be considered for constant cough. Similar equianalgesic dosing of 1 to 2 mg intravenously (IV) or subcutaneously can be utilized if the patient is unable to take oral medications or for ease of administration especially in the hospital setting.
●A different opioid at equianalgesic dosing to morphine 5 mg by mouth also can be utilized.
For patients already receiving opioids for pain, a 25 to 50 percent dose increase may be tried to suppress the cough.
Codeine 15 mg orally every four hours as needed is an appropriate dose for cough suppression. However, codeine is metabolized to morphine by a cytochrome P450 enzyme, and patients who have variants of this enzyme, including many Asian patients, are at risk of experiencing adverse effects of codeine without the benefit [32]. We therefore use morphine preferentially.
Data suggest that opioids improve cough in palliative care populations, although the evidence in this population is limited. In a 2013 meta-analysis of trials evaluating various treatments for chronic cough, which included only a few trials with cancer patients, opioids reduced cough severity (standardized mean difference 0.55, 95% CI 0.38-0.72) and cough frequency (rate ratio 0.57, 95% CI 0.36-0.91) compared with placebo [33]. They also improved quality of life. No opioid was superior to another.
A 2015 systematic review of trials examining interventions for cough in patients with primary or metastatic cancer also noted some positive effect with opioids (morphine, codeine, and dihydrocodeine), although there was significant risk of bias in all trials [34].
Gabapentin and pregabalin — Alternative or concurrent treatments for chronic cough are the gamma aminobutyric acid (GABA) analogs gabapentin and pregabalin. We recommend these agents for patients with moderate to severe cough who are unable to take opioids.
●Gabapentin is initiated at a low dose (300 mg/day) with gradual increases until cough relief, dose-limiting adverse effects, or a dose of 900 mg twice daily is achieved [35]. Patients should be monitored for sedation, which typically wanes one to three days after each dose escalation. Additional adverse effects may include dizziness, diarrhea, nausea, emotional lability, somnolence, nystagmus, tremor, weakness, and peripheral edema.
●Pregabalin is initiated at a low dose (eg, 75 mg/day) and gradually increased over a week to 300 mg/day to minimize sedation and dizziness.
While gabapentin may help with treatment of chronic cough, it may also have a more specific role in treating refractory gastroesophageal reflux-induced cough [36].
Support for the use of gabapentin and pregabalin for alleviation of chronic cough in palliative care populations is based on evidence in the general population, which is discussed elsewhere. (See "Evaluation and treatment of subacute and chronic cough in adults", section on 'Gabapentin and pregabalin'.)
Rare use of combination therapy — Concomitant use of opioids and GABA analogs can be attempted if there is concern that a component of the cough may be due to nerve irritation and thus not completely managed with opioids alone. However, this combination of agents must be approached with caution due to the possibility of significant adverse side effects of increased sedation and risk of opioid-related death [37].
We recommend starting these agents sequentially, as there can be significant sedation when starting gabapentin even at low doses. Gabapentin initiation merits its own escalation strategy. (See 'Opioids' above and 'Gabapentin and pregabalin' above.)
Adjunctive therapies — For patients who do not have an adequate response to therapy, we consider adding one or more adjunctive treatments based on additional symptoms, although some of these therapies have uncertain benefit:
●Thick sputum – Add expectorant (eg guaifenesin, nebulized saline) or mucolytic (eg, acetylcysteine) (see 'Pharmacologic therapies of uncertain benefit' below)
●Bronchospasm – Add bronchodilator (eg, inhaled albuterol-ipratropium)
●Excess secretions – Add anticholinergic (eg, glycopyrrolate)
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. In addition to other symptomatic therapies, anticholinergic drugs, such as glycopyrrolate IV, subcutaneously, or sublingually, can be given to minimize bronchial secretions and thus improve cough [38-40]. (See "Palliative care: The last hours and days of life", section on 'Airway secretions'.)
Pharmacologic therapies of uncertain benefit — Other pharmacologic strategies have been used with limited success for certain symptoms.
●Expectorants and mucolytics for thick secretions – Thick secretions are common in palliative care patients with cough, and expectorants (eg, guaifenesin, nebulized saline) or mucolytics (eg, acetylcysteine) may be used to reduce the viscosity of secretions. However, these agents, which are referred to as “protussives,” are not cough suppressants, and they do not reduce the frequency or severity of cough. As an example, a systematic review of therapies for chronic cough found only limited data describing benefit of guaifenesin in reducing cough intensity and no benefit from mucolytics [33,41]. Additionally, patients who are dehydrated may need additional fluid ingestion if treated with expectorants, and these agents 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 [42].
●Neurokinin (NK)-1 receptor inhibition – Activation of NK-1 receptors by substance P may contribute to chronic cough, and treatments that block this pathway have been studied as antitussives with variable results [43,44]. Aprepitant is an NK-1 receptor inhibitor traditionally used for treatment of chemotherapy-related nausea and vomiting. In a randomized crossover trial of 20 patients (mean age 66 years) with lung cancer and bothersome cough, patients who received three days of aprepitant had greater cough reduction while awake (22.2 percent) and while asleep (59.8 percent) compared with those who received placebo [45]. It is not known whether a higher dose of aprepitant would have had greater efficacy. Additional research is needed with a larger study population, longer duration, and optimized dosing; cost considerations may limit use. (See "Characteristics of antiemetic drugs", section on 'Neurokinin receptor antagonists'.)
●Paroxetine – There is a small amount of evidence that paroxetine may have a role in treating cough in cancer patients [46].
●Thalidomide for idiopathic pulmonary fibrosis – Thalidomide may have a role in treating cough in patients with idiopathic pulmonary fibrosis [47].
●Antiseizure agents for intractable cough from seizures – While rare, intractable cough from seizure may require benzodiazepines with antiseizure and sedative properties to assist with management especially near the end of life. [48].
STRIDOR — Stridor is a harsh, high-pitched wheezing or vibrating sound that results from turbulent airflow in the upper airways. It most typically occurs with inspiration but can also occur during expiration.
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. Information on the diagnostic evaluation of stridor is presented elsewhere. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults".)
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. In this setting, secondary interstitial edema of the head and neck may narrow the lumen of the nasal passages and larynx, resulting in dyspnea, stridor, cough, hoarseness, and dysphagia. (See "Superior pulmonary sulcus (Pancoast) tumors" and "Malignancy-related superior vena cava syndrome".)
Rapid obstruction or narrowing can precipitate a palliative care emergency, associated with significant anxiety for patients, families, and health care professionals.
Management — Patients who present with stridor due to severe tracheal or mainstem bronchial obstruction or severe laryngeal edema and respiratory compromise represent a true medical emergency. They are at high risk for respiratory failure and death, and they require initial stabilization to secure ventilation and oxygenation, if this is consistent with the goals of care.
●Emergency intervention to stabilize the airway
•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".)
•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.
•While somewhat controversial, the use of continuous positive pressure ventilation has been studied in head and neck cancer patients for palliative management of stridor [49]. If possible, care should be taken to assess potential for airway management to suddenly become more urgent, risk for skin issues related to excessive mask pressure, and risk of bleeding with high inspiratory pressure and mask-related pressure [50].
The initial management of central airway obstruction is presented in detail elsewhere. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Diagnostic evaluation and initial management'.)
●Treatment of dyspnea and anxiety – 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 (IV), or subcutaneously if there is no IV access. The dose may be repeated every 10 minutes (time to maximum serum concentration) IV 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 IV 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 or other loved ones. (See "Palliative sedation".)
●Palliation of central airway obstruction – 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 [51]. 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 malignant central airway obstruction in adults", section on 'Diagnostic evaluation and initial management'.)
●Establishing patient preferences regarding alertness vs sedation – 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. Information on the diagnostic evaluation of hemoptysis is presented elsewhere. (See "Evaluation of nonlife-threatening hemoptysis in adults".)
Life-threatening 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 life-threatening hemoptysis are controversial. Some define life-threatening hemoptysis as ≥150 mL of expectorated blood over a 24-hour period or bleeding at a rate ≥100 mL/hour. (See "Evaluation and management of life-threatening hemoptysis", section on 'Definition'.)
Pathogenesis and underlying causes — In palliative care populations, hemoptysis often arises from high-pressure bronchial circulation but can occur in patients via erosion of tumor or when low-pressure pulmonary capillaries are affected by inflammation. This can occur with primary or secondary lung cancer, terminal hematological malignancy, lung infection or abscess, bronchiectasis, pulmonary embolism, cystic fibrosis [52], bleeding disorders, anticoagulant use, anti-GBM (Goodpasture) disease, granulomatosis with polyangiitis, and other less common conditions (table 3) (see "Evaluation of nonlife-threatening 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 [53].
Pulmonary hemorrhage is also 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, life-threatening 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 [54]. When it does occur, life-threatening hemoptysis associated with bronchogenic carcinoma has an extremely grim prognosis (mortality 59 to 100 percent), making it a palliative care emergency. Other causes of life-threatening hemoptysis are bronchiectasis, pulmonary tuberculosis, and fungal pulmonary infection. (See "Etiology of hemoptysis in adults", section on 'Causes of life-threatening hemoptysis'.)
Management — 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 or other loved ones. The patient and family/loved ones 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 to help 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 "Evaluation and management of life-threatening hemoptysis".)
●Minimizing patient and family distress – The palliative treatment of hemoptysis is primarily related to managing the experience of the patient, family, and other loved ones, as well as 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.
●Life-threatening hemoptysis – Patients with life-threatening 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.
●Urgent palliative sedation – 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 (IV; 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 (IM). 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 IM 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 IV, 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 [55]. (See "Palliative sedation".)
●Temporizing measures – 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] [56]) and interventional procedures may be considered, if this is consistent with the goals of care. However, for patients with life-threatening 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 [57,58]. One case series suggests nebulized vasopressin could be effective for mild to moderate hemoptysis in palliative care patients [59]. Similarly, nebulized tranexamic acid has been helpful in case reports [60]. 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 "Evaluation and management of life-threatening hemoptysis".)
Guidelines from expert groups — Guidelines are available for symptom management in patients with lung cancer from the American College of Chest Physicians (ACCP) [40]. 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.
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" and "Society guideline links: Palliative care for advanced lung disease".)
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.
●Cough
•In many cases, causes of and approach to cough in palliative care patients is the same as in the general population. All patients with cough should be evaluated for potentially treatable causes (eg, acute infection, exacerbation of chronic condition, medication effect), for which specific treatments may be available. (See 'Initial evaluation' above and 'Common general causes' above.)
•Causes of cough more common in the palliative care population include swallowing abnormalities, chronic infections, and, among patients with cancer, direct or indirect effects of the tumor (table 2). Directed therapies against these can help ameliorate cough. (See 'Specific causes in palliative care' above and "Swallowing disorders and aspiration in palliative care: Assessment and strategies for management".)
•Symptomatic treatment of cough is appropriate when a specific cause cannot be identified or when cause-directed therapy is neither feasible nor rapidly effective. Our approach is described in the algorithm (algorithm 1).
-For patients with mild-severity cough, we try nonpharmacologic therapies first (eg, cough suppression exercises, linctus [eg, honey]). If cough continues or worsens, we begin with a peripherally acting antitussive, such as benzonatate. (See 'Mild cough' above.)
-For most patients with moderate to severe cough or for those with milder cough who do not respond to peripherally acting antitussives, we suggest a centrally acting opioid (Grade 2C). We typically use morphine 5 mg every four hours as needed. Gabapentin and pregabalin can be used either as alternative or concurrent treatments to opioids. (See 'Moderate to severe cough' above.)
●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 bronchial 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, anti-GBM (Goodpasture) disease, granulomatosis with polyangiitis, 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):
-Patients with life-threatening hemoptysis should be immediately placed into a position in which the presumed bleeding lung is in the dependent position.
-In the rare instances where the underlying cause of life-threatening hemoptysis can be reversed, diagnostic tests and interventional procedures may be considered, if this is consistent with the goals of care. For patients with life-threatening hemoptysis, this may require urgent supportive care with blood or platelet transfusion, reversal of anticoagulation, and/or administration of procoagulant agents. (See "Evaluation and management of life-threatening hemoptysis".)
-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 'Management' above and "Palliative sedation".)
