What physiological changes occur in older adults with terminal illnesses or significant comorbidities at the end of life?

Physiological Changes in the End-of-Life Process

Older adults with terminal illnesses experience predictable physical, psychological, and functional decline characterized by decreased performance status, progressive organ failure, and increasing symptom burden that requires proactive management focused on comfort rather than cure.

Physical Deterioration and Performance Decline

The end-of-life trajectory is marked by measurable functional decline that helps clinicians estimate prognosis and guide care planning:

• Performance status deteriorates progressively, with indicators of the final 6 months including ECOG score ≥3 or Karnofsky performance score ≤50, signaling severe functional impairment 1
• Metabolic complications emerge including hypercalcemia, cachexia (muscle wasting and weight loss), and progressive weakness that reflects the body's declining ability to maintain homeostasis 1
• Organ system failures develop such as liver failure, kidney failure, and respiratory compromise, often accompanied by malignant effusions and other complications 1
• Swallowing function diminishes as death approaches, necessitating transition from oral to sublingual, transdermal, or rectal medication administration 2

Common Physical Symptoms Requiring Management

Pain

• Pain affects approximately 196,000 of the 1 million Americans who die in hospitals annually, with 300,000 individuals wanting more pain relief than they receive 3
• Opioids remain the medication of choice for pain control at end of life, with evidence supporting NSAIDs, bisphosphonates for bone pain, and radiotherapy as adjunctive therapies 1
• Pain may be difficult to distinguish from delirium in dying patients, as delirium can cause groaning when stimulated that mimics pain behavior 1

Dyspnea

• Dyspnea affects approximately 1.4 million individuals in the weeks before death, with 244,000 hospitalized dying patients experiencing this symptom 3
• Opioids provide proven effectiveness for treating unrelieved dyspnea in advanced lung disease and terminal cancer (standardized mean difference -0.31), though nebulized opioids show no advantage over oral forms 1
• Oxygen therapy should be reserved for hypoxemia in conditions like advanced COPD, as evidence comparing oxygen to room air shows mixed results for dyspnea relief 1
• Beta-agonists benefit dyspnea in COPD though this has not been specifically studied in end-of-life populations 1

Gastrointestinal Symptoms

• Nausea affects 140,000 hospitalized dying patients, with vomiting occurring in 88,000, requiring medications targeting the specific etiology 3
• Constipation commonly results from decreased oral intake and opioid use, necessitating preventive regimens combining stimulant laxatives with stool softeners 2
• Anorexia affects 280,000 hospitalized dying patients, reflecting the body's natural decline in nutritional needs 3
• Xerostomia (dry mouth) occurs in 232,000 hospitalized dying patients, requiring oral care interventions 3

Respiratory Secretions

• Oropharyngeal secretions lead to noisy breathing (death rattle) commonly at end of life, which is distressing to families but typically not to unconscious patients 2
• Anticholinergic medications can modestly reduce secretions, though families benefit most from anticipatory guidance normalizing this symptom 2
• Atropine use requires caution as it adds anticholinergic burden and may increase fatigue 1

Neuropsychiatric Symptoms

• Depression affects 148,000 hospitalized dying patients, with strong evidence supporting tricyclic antidepressants, SSRIs, or psychosocial interventions in cancer patients 1, 3
• Delirium occurs in 148,000 hospitalized dying patients and may masquerade as pain or vice versa, requiring careful assessment 1, 3
• Haloperidol and risperidone are effective options when medications are required for delirium management 2
• Anxiety and panic attacks occur at higher rates in patients with advanced respiratory diseases compared to healthy persons 1
• Confusion and insomnia affect 148,000 and 92,000 hospitalized dying patients respectively 3

Other Common Symptoms

• Fatigue affects 324,000 hospitalized dying patients, representing the most prevalent symptom in this population 3
• Cough occurs in 208,000 hospitalized dying patients 3

Psychological and Existential Changes

Emotional Distress Patterns

• Depression is associated with preferences to limit life-sustaining therapy, though these preferences may change after successful depression treatment, requiring reassessment of end-of-life preferences after adequate treatment time 1
• Functional impairments correlate more strongly with depression than pain-related symptoms in adult hospice patients 1
• Parents with dependent children experience unique distress, with 20% more likely to worry, meet criteria for panic disorder (P=0.0004), and be half as likely to feel peaceful (P=0.01) compared to patients without dependent children 1

Spiritual and Existential Suffering

• Existential suffering does not respond to pharmacotherapy but benefits enormously from empathetic listening and spiritual support 1
• An interdisciplinary approach involving healthcare providers, social workers, and religious advisors increases likelihood of meeting patient and family support needs 1

Caregiver and Family Impact

Family Burden

• Substantial life changes occur in families, with nearly one-third reporting loss of most or all family savings and 29% losing the family's major income source 1
• More than half of families report major practical negative impacts, with 12% experiencing stress-related illness or loss of function 1
• Caregivers of patients with advanced respiratory disease experience depression in up to one-third of cases, requiring monitoring and referral resources 1
• Families benefit from advance care planning that relieves them of decision-making burden, as knowing the patient's wishes reduces negative emotional effects that can last years 1

Prognostic Timeframes and Care Adjustments

Years to Months

• Patients require information about what to expect and anticipatory guidance on the dying process 1
• Life priorities should be reviewed and revised, with assistance in resolving unfinished business and arranging financial and personal affairs 1
• Decision-making styles should be determined to facilitate congruence between patient goals and family expectations 1

Months to Weeks

• Assessment of quality versus length of life preferences becomes critical for treatment planning 1
• Preparation for death should include helping family members prepare to continue without the patient 1
• Education on the dying process benefits both patients and families 1

Final Weeks to Days

• Monitoring focuses on comfort parameters rather than routine vital signs (pulse, blood pressure, temperature) 1
• Respiratory rate monitoring ensures absence of respiratory distress and tachypnea, though gradual respiratory deterioration is expected and should not prompt sedation reduction 1
• Downward titration of sedation is not recommended in most instances for imminently dying patients, as it risks recurrent distress 1
• Arrangements should ensure the patient does not die alone unless that is their preference 1

Medication Management Considerations

Simplification in Advanced Disease

• Strict glucose and blood pressure management are not necessary in palliative care, with simplification of medication plans appropriate 1
• Lipid management intensity can be relaxed, with withdrawal of statins improving quality of life in multicenter trials of people with diabetes in palliative care 1
• Agents causing gastrointestinal symptoms such as nausea or excess weight loss should be avoided 1
• Oral agents may be used as first line, followed by simplified insulin plans without rapid-acting insulin if needed, with slow tapering and discontinuation as symptoms progress 1

Sedation for Refractory Symptoms

• Midazolam is commonly prescribed for palliative sedation due to its short half-life and rapid onset, with alternatives including levomepromazine, chlorpromazine, phenobarbital, and propofol 1
• Mild sedation should progress to deeper levels if ineffective, especially in cases of refractory suffering when death is imminent or during catastrophic events like massive hemorrhage or asphyxia 1
• Doses can be titrated down to re-establish lucidity if desired by the patient before sedation, enabling re-evaluation of condition and preferences and allowing family interactions, though patients should be advised that lucidity may not be restored, symptoms may recur, or death may intervene 1, 4

Opioid Safety

• Respiratory depression is the chief hazard of opioid agonists, occurring more commonly in elderly or debilitated patients, following large initial doses in non-tolerant patients, or with concomitant CNS depressants 5
• Fentanyl transdermal systems require extreme caution in patients with significant COPD, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression, as even usual therapeutic doses may decrease respiratory drive to apnea 5
• CYP3A4 inhibitors increase fentanyl plasma concentrations, potentially causing fatal respiratory depression, requiring careful monitoring when used with ritonavir, ketoconazole, clarithromycin, diltiazem, erythromycin, fluconazole, grapefruit juice, or verapamil 5
• Concomitant CNS depressants including benzodiazepines, sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, skeletal muscle relaxants, and alcohol may cause respiratory depression, hypotension, and profound sedation or coma 5

Cardiovascular Medication Adjustments

• Anticoagulation requires shared decision-making, as time to benefit may exceed life expectancy and bleeding risk increases with age >75 years, renal impairment, falls, and frailty, though some patients prefer continuing therapy to avoid stroke-related debilitation 1
• Antiarrhythmic medications that exacerbate myocardial dysfunction (flecainide, dronedarone, sotalol, disopyramide) should be avoided or dosed appropriately according to renal function 1

Critical Pitfalls to Avoid

• Do not underestimate symptom prevalence: Multiple symptoms typically coexist, with patients experiencing an average of several concurrent problems requiring simultaneous management 6
• Do not delay palliative care consultation: Integration should begin at diagnosis for patients with limited life expectancy (stage IV lung cancer, pancreatic cancer, glioblastoma multiforme) rather than waiting until the final weeks 1
• Do not assume pain causes all agitation: Delirium may be the root cause and requires different treatment approaches 1
• Do not force aggressive hydration or nutrition: Decisions about these interventions are independent of palliative sedation decisions, with practices varying based on individual patient, family, and clinician perspectives 1
• Do not use fentanyl patches in opioid-naive patients: This is contraindicated and may lead to fatal respiratory depression, as the system is ONLY for opioid-tolerant patients receiving at least 60 mg oral morphine equivalent daily 5
• Do not routinely monitor vital signs in imminently dying patients: Focus monitoring on comfort parameters only, as physiological deterioration is expected and should not trigger interventions that compromise comfort 1