End-of-Life Symptom Management in the Last 24-48 Hours: A Comprehensive Guide for Hospitalists

Dr Neeraj Manikath , claude.ai

Introduction

The transition from curative to comfort-focused care represents one of the most profound responsibilities in hospital medicine. While medical training emphasizes diagnosis and treatment, the final hours of life demand an equally sophisticated skill set centered on alleviating suffering and supporting families through an inevitable biological process. Studies indicate that approximately 40-50% of hospitalized patients in their last days experience poorly controlled symptoms, with pain, dyspnea, and delirium being predominant.1 This review provides evidence-based strategies for managing common end-of-life symptoms during the terminal phase, with practical approaches for hospitalists managing both inpatient and home hospice scenarios.

Anticipatory Prescribing: The Foundation of Comfort

Anticipatory prescribing—writing PRN (pro re nata, or "as needed") orders before symptoms become severe—represents the cornerstone of effective end-of-life care. This proactive approach prevents the distressing scenario where a patient suffers while staff scramble to obtain orders, particularly problematic during nights and weekends.

Essential PRN Medication Arsenal

For Pain and Dyspnea: Morphine sulfate remains the gold standard opioid for end-of-life symptom control.2 For opioid-naive patients, start with morphine 2.5-5 mg subcutaneously (SC) or intravenously (IV) every 2-4 hours PRN. For patients already on opioids, calculate 10-15% of the total daily opioid dose as the breakthrough dose. Subcutaneous administration offers particular advantages in the dying patient—it avoids the need for IV access and can be given by family caregivers or hospice nurses at home.

Pearl: In renal failure, consider oxycodone or hydromorphone instead of morphine to avoid accumulation of the toxic metabolite morphine-3-glucuronide, which can cause myoclonus and seizures.

For Respiratory Secretions ("Death Rattle"): Glycopyrrolate 0.2-0.4 mg SC/IV every 4-6 hours PRN or scopolamine 0.4 mg SC every 4-6 hours PRN.3 Glycopyrrolate has the advantage of not crossing the blood-brain barrier, thus avoiding central anticholinergic effects and potential worsening of delirium.

Hack: Apply scopolamine transdermal patches (1-3 patches) for sustained effect, though onset takes 6-8 hours. This works well for home hospice patients where frequent dosing may be burdensome.

For Agitation and Delirium: Lorazepam 0.5-2 mg SC/IV/SL every 2-4 hours PRN for anxiety or haloperidol 0.5-2 mg SC/IV every 4-6 hours PRN for delirium with agitation.4 For severe terminal restlessness refractory to these agents, consider levomepromazine 12.5-25 mg SC or chlorpromazine 12.5-25 mg SC.

Oyster: Many physicians hesitate to prescribe adequate opioid doses near the end of life due to unfounded fears of "hastening death." Evidence consistently demonstrates that appropriate symptom-focused opioid use does not shorten survival and is ethically distinct from euthanasia under the doctrine of double effect.5

Documentation That Protects Care

When writing anticipatory orders, document clearly: "Patient is in the active dying phase. These medications are prescribed for symptom management to ensure comfort. The goal is palliation, not life prolongation." This documentation protects both the medical team and clarifies the care plan for all providers.

Continuous Subcutaneous Infusions: The CSCI Approach

For patients requiring frequent dosing (≥4 doses in 24 hours) or those unable to tolerate oral/IV routes, a continuous subcutaneous infusion (CSCI) via a small butterfly needle and portable syringe driver offers superior comfort and consistent symptom control.6

Setting Up a CSCI

Site Selection: The anterior chest wall, abdomen, or outer thigh work well. Avoid edematous areas. The subcutaneous needle typically remains functional for 5-7 days.

Common CSCI Combinations:

Basic comfort cocktail: Morphine + midazolam + glycopyrrolate
Example calculation: For a patient requiring morphine 5 mg SC every 3 hours (approximately 40 mg/24h), set up morphine 40 mg + midazolam 10 mg + glycopyrrolate 1.2 mg in 48 mL normal saline to run at 2 mL/hour over 24 hours.

Pearl: Keep the mixture simple and compatible. Morphine, midazolam, haloperidol, glycopyrrolate, and metoclopramide are generally compatible in combination. Avoid mixing more than 3-4 drugs to prevent precipitation.

Hack: For home hospice, teach families that the butterfly needle site should be checked daily for redness or swelling. If the site becomes indurated, simply place a new butterfly needle a few inches away—families can learn this simple task.

When to Escalate

If symptoms remain uncontrolled despite optimal CSCI dosing, consider adding methadone for its unique NMDA-receptor antagonism in opioid-resistant pain, or consult palliative care for consideration of palliative sedation with propofol or phenobarbital infusions in the inpatient setting.7

The "Death Rattle": Understanding and Managing Terminal Secretions

The death rattle—noisy, gurgling respirations caused by pooled oral and bronchial secretions—occurs in 35-92% of dying patients and often causes more distress to families than to the unconscious patient.8

Pathophysiology and Prevention

As patients become too weak to swallow or cough, secretions accumulate. Salivary flow continues even when consciousness fades. Prevention works better than treatment—start antimuscarinic agents at the first sign of inability to manage secretions, rather than waiting for audible gurgling.

Management Strategies

Pharmacologic:

First-line: Glycopyrrolate 0.2-0.4 mg SC every 4-6 hours (doesn't cross blood-brain barrier)
Alternative: Scopolamine 0.4 mg SC every 4-6 hours or transdermal patches
Atropine 1% ophthalmic solution: 1-2 drops sublingual every 4 hours (off-label use, but effective and inexpensive)

Non-pharmacologic:

Position patient on their side to allow secretions to drain
Gentle oropharyngeal suctioning only if secretions are in the mouth (deep suctioning may increase secretion production and cause distress)
Discontinue IV hydration and artificial nutrition, which can exacerbate secretions

Oyster: Once the death rattle is established (audible from across the room), anticholinergics may not resolve it completely, as they only reduce new secretion production. Early initiation prevents the symptom from developing.

Family Counseling

This requires explicit discussion: "You're hearing noisy breathing because your father is too weak to clear the natural moisture in his throat. This sound is coming from his throat, not his lungs, and is not causing him to feel like he's drowning or choking. He is not conscious enough to be aware of it. The medications we're giving will reduce new secretions." Provide reassurance that this is a normal part of the dying process and does not indicate suffering.

Terminal Delirium and Restlessness: Recognition and Response

Terminal delirium occurs in 50-85% of dying patients and represents one of the most challenging end-of-life symptoms.9 It manifests as confusion, agitation, hallucinations, and sometimes combativeness during the final hours to days of life.

Differential Diagnosis: Agitation vs. Pain

This distinction is crucial and not always straightforward:

Suggestive of Pain:

Grimacing, moaning, or crying out with movement
Guarding or resistance to position changes
Increased heart rate or blood pressure with stimulation
Relief with opioid administration

Suggestive of Delirium:

Plucking at bedclothes or pulling at tubes (carphology)
Hallucinations or talking to people not present
Attempting to climb out of bed without clear purpose
Agitation that does not respond to opioid escalation

Pearl: When uncertain, treat both. Give a dose of opioid first. If no improvement in 20-30 minutes, address delirium/agitation with benzodiazepines or antipsychotics.

Reversible Causes: The Brief Assessment

While the focus in the last 24-48 hours is comfort rather than diagnosis, some rapidly reversible causes should be considered if treatment aligns with goals of care:

Urinary retention (place Foley catheter)
Fecal impaction (consider gentle suppository)
Severe hypercalcemia (consider one-time IV fluid bolus if easy IV access)

Avoid extensive blood draws or imaging—the goal is comfort, not diagnosis.

Pharmacologic Management

First-line: Haloperidol 0.5-2 mg SC/IV every 4-6 hours PRN for hyperactive delirium. Typical antipsychotics work better than atypical agents for terminal delirium.10

For anxiety-predominant restlessness: Lorazepam 0.5-2 mg SC/IV/SL every 2-4 hours PRN. Midazolam 2.5-5 mg SC is an excellent alternative with faster onset.

Refractory terminal restlessness: This represents a palliative care emergency. Options include:

Levomepromazine 12.5-50 mg SC every 8-12 hours
Chlorpromazine 12.5-25 mg SC every 8-12 hours
Phenobarbital 100-200 mg SC loading dose, then 50-100 mg every 8-12 hours
Palliative sedation with propofol or midazolam infusions (requires specialist consultation)

Hack: Create a "terminal restlessness protocol" in your hospital's order sets that allows nursing to give sequential doses without repeated phone calls: "If restlessness persists 30 minutes after haloperidol, may give lorazepam 1 mg SC once. If still restless 30 minutes later, notify physician for further management."

Communication with Family: The Art of Anticipatory Guidance

Inadequate communication about the normal dying process accounts for much of the family distress and inappropriate interventions in the final hours. Explicit anticipatory guidance empowers families and reduces crisis calls.

What to Tell Families: The Script

Breathing Changes: "In the final days, you'll notice changes in your mother's breathing. She may breathe rapidly for a while, then slowly, then pause for 10-20 seconds before breathing again. This is called Cheyne-Stokes breathing and is normal at the end of life. She may also develop noisy breathing from secretions—we'll treat this, but it may not go away completely. These changes don't mean she's suffering."

Decreased Intake: "Your father will likely stop eating and drinking. This is the body's natural shutting-down process, not starvation. Forcing food or fluids can actually cause discomfort, increasing secretions and swelling. We'll keep his mouth moist with swabs and lip balm. This is normal and not painful."

Skin Changes: "The skin on her hands and feet may become mottled—looking purple or blotchy—as circulation slows. Her extremities may feel cool. These are normal signs that the body is directing blood to vital organs. Keep her covered for comfort and dignity, but this isn't making her cold in a way she can feel."

Decreased Responsiveness: "He will likely become less responsive, sleeping more until he doesn't wake up. Assume he can still hear you—hearing is often the last sense to fade. Say whatever you need to say. Hold his hand. Play his favorite music. It's okay to give him permission to go."

Timing: "I cannot tell you exactly when this will happen. It may be hours or a few days. Bodies don't follow textbooks. But these are signs that time is getting short: [list specific signs]. Call the nurse or hospice team if you're worried or if something doesn't seem right, but know that many of these changes are expected."

The Burden of Witness: Supporting Families

Oyster: Family members often experience moral distress about "letting" their loved one die, even when they intellectually understand there are no other options. Normalize this: "Many families feel torn between wanting their loved one's suffering to end and not wanting to say goodbye. Both feelings are normal and coexist. You are not giving up on him—you are honoring what he wanted and making sure he's comfortable."

Pearl: Schedule a family meeting within 24 hours of transitioning to comfort care. Identify the healthcare decision-maker, ensure goals of care are documented, and give the family explicit permission to be present or to step away as needed. Not everyone can or should witness the final moments—that choice is deeply personal.

Special Considerations and Clinical Pearls

Managing Opioid Tolerance

Patients on chronic high-dose opioids require proportionally higher doses for symptom control. Don't undertaper in the final days out of fear—calculate their baseline 24-hour opioid requirement and provide 10-20% of that total as each breakthrough dose.

When Death is Imminent: The Final Signs

Mandibular breathing (jaw drop with each breath)
Apnea lasting >30 seconds
Peripheral cyanosis and mottling extending to trunk
Loss of radial pulse (palpable carotid only)
Loss of response to verbal and painful stimuli
Fixed, dilated pupils or eyes half-open and unfocused

After Death: Completing the Care

Give families time with the body. There is no rush. Offer to call chaplaincy, remove medical equipment if the family wishes, and provide explicit next steps. This final act of care for the family extends your therapeutic relationship beyond the patient's last breath.

Conclusion

End-of-life symptom management in the final 24-48 hours represents both a clinical and humanistic imperative. Through anticipatory prescribing, proactive use of continuous subcutaneous infusions, effective management of terminal secretions and delirium, and skilled communication with families, hospitalists can transform the dying process from one of potential suffering and chaos into a dignified, peaceful transition. These skills—often absent from residency training—are learnable, evidence-based, and among the most meaningful interventions physicians provide. Every hospitalist should consider end-of-life care not as an admission of failure but as the full expression of our commitment to relieve suffering across the entire continuum of illness.

References

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Wiffen PJ, Derry S, Moore RA. Impact of morphine, fentanyl, oxycodone or codeine on patient consciousness, appetite and thirst when used to treat cancer pain. Cochrane Database Syst Rev. 2014;(5):CD011056.
Lokker ME, van Zuylen L, van der Rijt CC, van der Heide A. Prevalence, impact, and treatment of death rattle: a systematic review. J Pain Symptom Manage. 2014;47(1):105-122.
Hui D, Frisbee-Hume S, Wilson A, et al. Effect of lorazepam with haloperidol vs haloperidol alone on agitated delirium in patients with advanced cancer receiving palliative care: a randomized clinical trial. JAMA. 2017;318(11):1047-1056.
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Cherny NI, Radbruch L. European Association for Palliative Care (EAPC) recommended framework for the use of sedation in palliative care. Palliat Med. 2009;23(7):581-593.
Campbell ML, Yarandi HN. Death rattle is not associated with patient respiratory distress: is pharmacologic treatment indicated? J Palliat Med. 2013;16(10):1255-1259.
Lawlor PG, Gagnon B, Mancini IL, et al. Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study. Arch Intern Med. 2000;160(6):786-794.
Agar MR, Lawlor PG, Quinn S, et al. Efficacy of oral risperidone, haloperidol, or placebo for symptoms of delirium among patients in palliative care: a randomized clinical trial. JAMA Intern Med. 2017;177(1):34-42.

Author's Note: This review synthesizes evidence-based practices with practical clinical wisdom accumulated over decades of bedside care. For hospitalists seeking deeper expertise, consider formal palliative care training through programs such as the EPEC (Education in Palliative and End-of-Life Care) curriculum or partnership with institutional palliative care teams for complex cases.

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