Practical Advice for Managing Symptoms in Dying Patients

This is the fifth article in a series entitled: 'The Last Hours of Living'. This article is targeted at health professionals as it contains advice for providing clinical care to people in the final hours of life who have symptoms, other than decreasing levels of consciousness or terminal delirium which have already been discussed in a previous article. See the previous article, Two Roads to Death.

Managing Other Symptoms in Dying Patients

Respiratory dysfunction. Changes in a dying patient's breathing pattern may be indicative of significant neurologic compromise. Breaths may become very shallow and frequent with a diminishing tidal volume. Periods of apnea and/or Cheyne-Stokes pattern respirations may develop. (Cheyne-Stokes is a disorder characterized by recurrent central apneas during sleep, alternating with a crescendo-decrescendo pattern of tidal volume.) Accessory respiratory muscle use may also become prominent. A few (or many) last reflex breaths may signal death.

Families and professional caregivers frequently find changes in breathing patterns to be one of the most distressing signs of impending death. Many fear that the comatose patient will experience a sense of suffocation. Knowledge that the unresponsive patient may not be experiencing breathlessness or "suffocating," and may not benefit from oxygen (which may actually prolong the dying process) can be very comforting. Low doses of opioids or benzodiazepines are appropriate to manage any perception of breathlessness.

Some clinicians express concern that the use of opioids or benzodiazepines for symptom control near the end of life will hasten death. Consequently, they feel they must invoke the ethical principle of "double effect" to justify treatment. The principle of double effect applies in situations where there is a difference in the effects of an intended action (alleviating suffering) and the unintended possible consequences of the same action (hastening death). To be acceptable, the action must comply with the following requirements:

The treatment proposed must be beneficial or at least neutral (relief of intolerable symptoms);
The clinician must intend only the good effect (relieving pain or symptoms), although some untoward effects might be foreseen (hastening death or loss of consciousness);
The untoward effect must not be a means (not necessary) to bring about the good effect; and
The good result (relief of suffering) must outweigh the untoward outcome (hastening death).

Although it is true that patients are more likely to receive higher doses of both opioids and sedatives as they get closer to death, there is no evidence that initiation of treatment or increases in dose of opioids or sedatives is associated with precipitation of death. In fact, the evidence suggests the opposite.

Loss of ability to swallow. Weakness and decreased neurologic function frequently combine to impair the patient's ability to swallow. The gag reflex and reflexive clearing of the oropharynx decline and secretions from the tracheobronchial tree accumulate. These conditions may become more prominent as the patient loses consciousness. Buildup of saliva and oropharyngeal secretions may lead to gurgling, crackling, or rattling sounds with each breath. Some have called this the "death rattle" (a term that should be avoided, as it is frequently disconcerting to families and caregivers).

Once the patient is unable to swallow, cease oral intake. Warn families and professional caregivers of the risk for aspiration. Muscarinic receptor blockers (anticholinergics) are commonly used agents to control respiratory secretions when death is imminent. These agents have been compared in several retrospective studies and in a recent prospective randomized trial, which compared subcutaneous administration of atropine with hyoscine hydrobromide (scopolamine) and hyoscine butylbromide (not available in the United States). All agents were found to be equally effective at controlling secretions, with an effectiveness of 37%-42% at 1 hour, increasing to an effectiveness between 60% and 76% at 24 hours. There was no significant difference in side effects or survival time, and effectiveness increased when treatment was initiated at a lower initial intensity of rattle.

Other studies that compared glycopyrronium (glycopyrrolate) (which has a theoretical advantage over other agents because it does not cross the blood-brain barrier) with other agents such as hyoscine, have yielded conflicting reports of comparative efficacy, with no difference in side effects such as agitation. Although atropine theoretically has the disadvantage of more cardiac effects or agitation, this has not been borne out in clinical studies to date, which have found it to be equally effective without any evident increased incidence of side effects. Although further studies are necessary to provide definitive evidence-based recommendations, current findings support the use of the commonly used agents in the United States: scopolamine, glycopyrrolate, atropine, and hyoscyamine sulfate. Common starting doses of these medications are:

Scopolamine, 0.2-0.4 mg subcutaneously every 4 hours, or
Scopolamine, 1-3 transdermal patches every 72 hours (onset delayed 12 hours), or
Scopolamine, 0.1-1.0 mg/hour by continuous intravenous or subcutaneous infusion
Hyoscyamine sulfate, 0.125-0.25 mg sublingually every 4 hours
Glycopyrrolate, 0.2 mg subcutaneously every 4-6 hours, or
Glycopyrrolate, 0.4-1.2 mg daily by continuous intravenous or subcutaneous infusion, or
Glycopyrrolate, 1 mg sublingually every 4-6 hours
Atropine, 0.1 mg subcutaneously every 4 hours, or
Atropine eyedrops, 1 drop (1%) sublingually every 4 hours

These drugs will minimize or eliminate the gurgling and crackling sounds and may be used prophylactically in the unconscious dying patient. Some evidence suggests that the earlier treatment is initiated, the better it works, as larger amounts of secretions in the upper aerodigestive tract are more difficult to eliminate. However, premature use in the patient who is still alert may lead to unacceptable drying of oral and pharyngeal mucosa.

If excessive fluid accumulates in the back of the throat and upper airways, it can be cleared by repositioning the patient or performing postural drainage. Turning the patient onto one side or into a semiprone position may reduce gurgling. Lowering the head of the bed and raising the foot of the bed while the patient is in a semiprone position may cause fluids to move into the oropharynx, from which they can be easily removed. Do not maintain this position for more than a few minutes at a time, as stomach contents may also move unexpectedly, increasing the risk for aspiration.

Oropharyngeal suctioning is not recommended. Suctioning is frequently ineffective, as fluids are beyond the reach of the catheter, and may only stimulate an otherwise peaceful patient and distress family members who are watching.

Loss of sphincter control. Fatigue and loss of sphincter control in the last hours of life may lead to incontinence of urine and/or stool. Both can be very distressing to patients and family members, particularly if they are not warned in advance that these problems may arise. If they occur, attention needs to be paid to cleaning and skin care. A urinary catheter may minimize the need for frequent changing and cleaning, prevent skin breakdown, and reduce the demand on caregivers. However, it is not always necessary if urine flow is minimal and can be managed with absorbent pads or surfaces. If diarrhea is considerable and relentless, a rectal tube may be similarly effective.

Pain. Although many people fear that pain will suddenly increase as the patient dies, there is no evidence to suggest that this occurs. Although difficult to assess, continuous pain in the semiconscious or obtunded patient may be associated with grimacing and continuous facial tension, particularly across the forehead and between the eyebrows. The possibility of pain must also be considered when physiologic signs occur, such as transitory tachycardia that may signal distress. However, do not overdiagnose pain when fleeting forehead tension comes and goes with movement or mental activity (eg, dreams or hallucinations). Do not confuse pain with the restlessness, agitation, moaning, and groaning that accompany terminal delirium. If the diagnosis is unclear, a trial of a higher dose of opioid may be necessary to judge whether pain is driving the observed behaviors.

Knowledge of opioid pharmacology becomes critical during the last hours of life. The liver conjugates codeine, morphine, oxycodone, and hydromorphone into glucuronides. Some of their metabolites remain active as analgesics until they are renally cleared, particularly the metabolites of morphine. As dying patients experience diminished hepatic function and renal perfusion, and usually become oliguric or anuric, routine dosing or continuous infusions of morphine may lead to increased serum concentrations of active metabolites, toxicity, and an increased risk for terminal delirium. To minimize this risk, discontinue routine dosing or continuous infusions of morphine when urine output and renal clearance stop. Titrate morphine breakthrough (rescue) doses to manage expressions suggestive of continuous pain. Consider the use of alternative opioids with inactive metabolites such as fentanyl or hydromorphone.

Loss of ability to close eyes. Eyes that remain open can be distressing to onlookers unless the condition is understood. Advanced wasting leads to loss of the retro-orbital fat pad, and the orbit falls posteriorly within the orbital socket. Because the eyelids are of insufficient length to both extend the additional distance backward and cover the conjunctiva, they may not be able to fully appose. This may leave some conjunctiva exposed even when the patient is sleeping. If conjunctiva remains exposed, maintain moisture by using ophthalmic lubricants, artificial tears, or physiologic saline.

Medications. As patients approach death, reassess the need for each medication and minimize the number of drugs that the patient is taking. Continue only those medications needed to manage symptoms such as pain, breathlessness, excess secretions, and terminal delirium and to reduce the risk for seizures. Choose the least invasive route of administration: the buccal mucosa or oral routes first, the transcutaneous/transdermal route if appropriate, the subcutaneous or intravenous routes only if necessary, and the intramuscular route almost never. Rectal administration can also be considered, especially if the oral route is not possible.

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Reference(s):
1). Medscape Internal Medicine. The Last Hours of Living: Practical Advice for Clinicians. Retrieved 2.3.2011. Available online: https://www.medscape.com/viewarticle/716463_5