How Do Symptoms Change for Patients in the Last Days/Hours of Life?

Pain

While a systematic review found the prevalence of pain in the terminal phase to be 53%, one study found that 25% of patients in the final week of life experience unrelieved pain despite the prescription of as-needed opioid medications, suggesting a need for better pain management. Cancer pain has been extensively studied, and moderate to severe pain is experienced by at least 70% of patients with advanced cancer. Similarly, pain at the end of life was recorded in more than 82% of patients dying from human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS), although pain prevalence has declined with the introduction of antiretroviral therapies. Other studies have suggested that as many as 75% of patients with heart failure experience pain, often related to comorbid conditions such as osteoarthritis or diabetes.

Pain in terminally ill patients has many causes. The general causes of pain in patients with serious illnesses are addressed elsewhere in this book. Although many patients may have experienced pain previously, more than half will experience a new pain as they enter the terminal phase, requiring careful observation on the health care provider’s part. It is important for patients who have preexisting pain conditions to continue treatment even when they cannot verbally report pain. New pain may be related to disease progression or other complications related to the dying process. Examples include:

• A change in pain medication or route of administration leading to uncontrolled pain

• A new pathological fracture resulting from movement of the patient

• Development of oral thrush

• Development of urinary retention or constipation

• Development of pressure ulcers

The assessment of pain can be challenging in the last hours to days of life. Often, patients are no longer able to report pain verbally. Nonverbal signs of pain, such as grimacing, moaning, and withdrawing from stimuli, are often good indicators of pain and should be monitored closely. In addition, eliciting the observations of those closest to the patient (nurses, aides, family caregivers, and relatives) can be useful when assessing for pain. Careful physical examination of patients at the end of life also will help identify potential new sources of pain. For example, the recognition of urinary retention on suprapubic examination when the clinician palpates a full bladder can be easily alleviated with the placement of a urinary catheter. A distended abdomen may signify constipation, which can be treated with suppositories. A careful skin examination and communication with bedside nurses and aides can reveal the existence of pressure ulcers, the pain of which may be relieved with local anesthetic gels. Frequently, new pain will require both opioids and nonopioid adjuvant medications for pain control. The practice of providing analgesics before the patient is turned, moved, or cleaned can help reduce incident pain and should be standard practice in the dying patient.

One study found that 60% of patients were able to swallow until their death. For patients unable to swallow, it is necessary to use alternative methods of medication administration to ensure continued treatment of pain. A patient unable to take pills can receive opioid pain medication by the buccal, sublingual, rectal, or transdermal route. In some circumstances, however, a patient may require subcutaneous or intravenous infusion. Patient-controlled analgesia is generally inappropriate as the terminal phase advances because the dying patient will likely not be able to use it properly or reliably. Additionally, families can be tempted to administer bolus doses to the patient, resulting in the patient receiving inappropriately high opioid doses.

Oral solutions of morphine or oxycodone can be given by buccal or sublingual routes with a dropper. Concentrated oral solutions of morphine or oxycodone are available for patients who require larger doses of opioids. Patients requiring multiple doses per day may benefit from transition to a long-acting opioid. Although not approved by the FDA, rectal administration of sustained-release morphine has been demonstrated to provide analgesia, though with somewhat variable pharmacokinetics (with slower absorption) as compared with oral administration. Patients can receive sustained-release morphine 15 to 30 mg rectally every 12 hours. Alternatively, if higher doses are required, or if the family prefers alternative modes of administration, a fentanyl patch can be placed. Liquid or rectal opioids should be provided for the first 12 hours after the patch placement to allow absorption into the bloodstream for adequate pain control.

Some adjuvant medications also can be given rectally or subcutaneously. For example, if a patient has previously benefited from oral acetaminophen or nonsteroidal antiinflammatory drug (NSAID) therapy, both acetaminophen and indomethacin are available in suppository form. Similarly, patients receiving corticosteroids for bone or nerve pain can be given subcutaneous or intravenous dexamethasone. Oral tricyclic antidepressants, often used for neuropathic pain, can be replaced with rectal doxepin.

It is important to educate family members around the use of opioid medications to treat pain at the end of life, as many people mistakenly believe that opioid use will hasten death, whereas studies have found appropriately dosed opioids to improve pain and even extend the time before death. Most patients will require an increase in their opioid dose during their last days, with continuous infusion doses more than doubling on average over the final hours in some studies. If the required opioid dose is too large to be given by the sublingual, rectal, or transdermal route, the medication can be given by subcutaneous infusion (or intravenous infusion, if access is already available). Both types of infusion can be used in the home environment with the aid of hospice or other home nursing support. When infusing opioid medications, the starting dose for a patient with well-controlled pain should be the intravenous equivalent of the oral dose; if the pain is not well controlled, administer a dose that is 25% to 100% higher depending on the level of distress. If a patient is opioid naïve, they should be given bolus doses first to determine opioid requirements, which can then be converted into an intravenous or subcutaneous infusion.

Opioid doses occasionally need to be reduced. Health care providers should consider lowering opioid doses when a patient requires no as-needed or breakthrough doses, or has become significantly more somnolent when previously alert and is known to be drinking less and becoming oliguric. These findings suggest that morphine metabolites are accumulating, and a reduced opioid dose might be appropriate. An alternative to dose reduction is to decrease the frequency with which opioids are administered (e.g., changing from every 4 hours to every 6 hours, particularly in older patients).

Dyspnea

Dyspnea, or the subjective sensation of breathlessness, is a common distressing symptom for patients with serious illness. One systematic review found dyspnea to be more common than the symptoms of pain, respiratory secretions, or confusion, with over 56% of all patients in the terminal phase experiencing dyspnea. While dyspnea is prevalent among all patients at the end of life, it is most prevalent in patients with heart failure and chronic obstructive pulmonary disease (COPD), with as many as 85% of patients with heart failure and 95% of patients with COPD reporting dyspnea. Studies in patients with cancer demonstrate prevalence rates ranging from 20% to 60%. One study found that the severity of dyspnea tended to increase during the final days to hours of life, with distress strongly correlated with nearness to death, raising concerns that dyspnea is likely underrecognized and undertreated when close to death. By the time patients have reached the terminal phase, all treatable causes of dyspnea have likely been addressed. At this stage, the most common causes of dyspnea include:

• Extensive lung metastases

• Secondary pneumonia

• Pulmonary edema

• Anxiety or panic

• Stridor from extratracheal pressure from nodes

• Large pleural effusions

• Large pericardial effusions with tamponade

• Anemia

• Metabolic acidosis from organ failure

Some of the more invasive treatments (e.g., draining an effusion) that might have served a palliative role at an earlier stage are no longer appropriate when death is imminent. Similarly, antibiotics usually are not beneficial at this stage. The symptomatic management of dyspnea in the terminal phase may include nonpharmacological and pharmacological methods and is the same as that for patients at earlier stages of the disease. Simple repositioning may be effective. Patients with COPD may be more comfortable sitting up, whereas patients with unilateral lung disease may prefer lying on one side more than the other. A narrative review performed by Pisani and colleagues found that most studies evaluating the relief of dyspnea at the end of life with oxygen therapy to be no better than room air. However, given that a few studies have shown benefit, a trial of oxygen therapy is recommended, but if patients are intolerant or not deriving benefit, oxygen therapy should be removed. Studies have also found mixed results with noninvasive ventilation and high-flow oxygen, and their use should be considered within the context of the patient’s goals of care, knowing that such treatments may only be administered in settings of higher acuity of care and may prolong the dying process. Air from a fan can reduce the sensation of breathlessness regardless of its lack of effect on tachypnea or hypoxia. Dyspnea experienced in the home setting can be exacerbated by warm, dry rooms. Families should be advised to open windows, reposition patients to benefit from a stream of air, use fans, and humidify the ambient air with a humidifier or by placing a bowl of water in the room.

Pharmacological management of dyspnea relies on the use of opioids, usually morphine, titrated to effect. As in the management of pain (see earlier discussion), morphine can be given orally or, if the patient is unable to take oral medications, as a suppository or by subcutaneous administration. In addition to opioids, anxiolytics should be used to treat the panic that frequently accompanies the sensation of breathlessness. While studies have not demonstrated beneficial effects of benzodiazepines on dyspnea by themselves, one uncontrolled study demonstrated that in combination with opioids, lorazepam was found to significantly decrease dyspnea and respiratory rate. Furthermore, the combination of a benzodiazepine and opioid to treat dyspnea had no effect on gas exchange, and both medications have never been found to hasten death when titrated appropriately. Benzodiazepines should thus be used as second-line medications to treat breathlessness, particularly in patients experiencing a sense of anxiety or panic. Lorazepam (0.5–2 mg every 4–6 hours as needed) can be given sublingually for anxiety related to dyspnea. For refractory anxiety, a low dose of diazepam (2–10 mg at bedtime or divided into 2 or 3 doses daily) can be administered orally or rectally as needed, or midazolam (5–10 mg every 4–6 hours as needed) can be administered subcutaneously. Chlorpromazine (25 mg orally or rectally or 12.5 mg intravenously) also can be useful as needed.

As patients approach the last hours or days of life, changes in breathing patterns may occur that family members interpret as dyspnea and suffering. Rapid, shallow breathing; periods of apnea; respiration with mandibular movement; and a Cheyne-Stokes respiratory pattern are common observations at the end of life (see later discussion of the final hours). Relatives of patients should be educated that this is a natural part of the dying process and that the patient does not experience these breathing patterns as dyspnea. If despite reassurance, the family perceives the patient to be distressed, offering low-dose opioids or benzodiazepines as needed may be appropriate.

Anorexia and Decreased Oral Intake

Families often struggle with a patient’s lack of interest in eating and drinking. Preparing food for an ill loved one can have significant cultural, familial, or personal significance. When a patient is no longer interested in eating, their loved ones may experience this as a rejection of their love or support. Additionally, they may worry that by not providing nutrition or hydration they are contributing to their loved one’s suffering or “starving” and ultimately to the patient’s death. After responding to the significant emotion present around this symptom, clinicians can help educate families about the natural loss of appetite and the diminished benefit of nutrition at this stage in a patient’s illness because of the inability to metabolize food. A study by McCann and colleagues demonstrated that comfort could be achieved with sips of fluid, moistening the lips, and excellent oral care, obviating the need for intravenous hydration in the dying patient. Furthermore, clinicians can remind families of other meaningful ways to demonstrate their love and support.