Geriatric Medicine/Palliative Care and Hospice

Chapter 12: Palliative Care and HospiceEdit

Objectives:

  1. Describe the types of advance directives and the role of advance directives
  2. Identify ethical issues related to withholding treatment
  3. Describe dysphagia and its impact on functional status
  4. Describe the role of the speech therapist in the diagnosis and treatment of dysphagia
  5. Describe the role of opioid pain medications and their appropriateness of use
  6. Describe complications related to opioid use including constipation and tolerance
  7. Describe how to convert between different opioids using morphine equivalents
  8. Recognize the clinical presentation of undernutrition/malnutrition
  9. Describe frailty and identify potentially reversible factors of frailty
  10. Describe how to appropriately convey a poor prognosis to a patient
  11. Describe and differentiate between hospice and palliative care and the respective roles of each

Advance Care PlanningEdit

Discussion of Advance Directives and goals of care should be undertaken. Physician orders for life sustaining treatment (POLST) form completion is appropriate if the estimated life expectancy is less than one year. (Note: POLST forms may have different names in different states.) Decision-making capacity of the patient must be considered prior to any discussion. End-of-life planning should be done early and discussed often; preferences can and frequently do change. A DNR code status does not mean “do not treat”!

Examples of questions to ask patients regarding goals of care are include:

  • Identifying a durable power of attorney who would make medical decisions for the patient in accordance with their wishes if they are unable to
  • Reviewed scenarios including artificial nutrition, cardiopulmonary respiration, and desire for hospitalization
  • Cardiopulmonary resuscitation in the event of loss of spontaneous circulation or respirations
  • Artificial nutrition/hydration (nasogastric or PEG tube)
  • Intubation
  • Hospitalization
  • IV antibiotics
  • IV fluids
  • Goals of care: To be pain free. To be symptom free. To be made comfortable. Other goals?
  • CODE STATUS: Full code? DNR/DNI? DNH?


Cardiopulmonary resuscitation: “In the event of cardiopulmonary failure, do you want CPR?” CPR is associated with a high risk of failure as well as broken ribs and associated trauma. If successfully resuscitated, may not return to prior functional status. Contraindications to CPR include multiple myeloma and fractures. Approximately 15% of patients who receive CPR in the hospital survive to discharge. Chest wall trauma and aspiration occurs in 25-50%. Patients who are successfully resuscitated to a vegetative state is roughly 10%. CPR was never intended for use of patients dying from an expected death from illness.

Intubation: “In the event of cardiopulmonary failure, do you want a tube placed down your throat to help you breathe?” Mechanical ventilation requires placement in the ICU on a ventilator. Some patients elect for a defined trial period with cessation of mechanical ventilation if hope for recovery is futile.

Artificial nutrition and hydration (ANH): Neither have been shown to be beneficial in patients with end-stage dementia nor to reduce skin breakdown. ANH can prevent or improve delirium but carries a risk of aspiration pneumonia equal to, if not greater, than oral intake. All dying patients at some point will lose their appetite and lose their ability to take in food and water. Feeding tubes have a 25% in-hospital mortality and a 60% one-year mortality in patients with advanced dementia. Some patients/families opt for therapeutic feeding which allows patients to enjoy foods of their choice despite known risk of aspiration or other adverse effects. Withholding or withdrawing artificial nutrition is not euthanasia nor physician-assisted suicide. Artificial nutrition is a medical treatment, not “ordinary care”.


DysphagiaEdit

Dysphagia is defined as difficulty swallowing. It is an ominous sign in frail elderly patients. Speech therapy evaluation is warranted to determine if dietary modification should occur. A speech therapist performs assessments, diagnosis, and treatment for speech, language and social communication. They also assess for swallowing disorders. Dietary consistencies may be made at the recommendation of the speech therapist. Different food and liquid consistencies are assessed. Food consistencies include regular, mechanical soft, and puree. Liquid consistencies include thin, nectar thin, honey thick, and NPO (nothing by mouth or “none per os”). Water is the hardest substance to swallow. Following a stroke, patients will often be asked to drink water to assess swallowing at the bedside by nursing. Dysphagia can lead to recurrent aspiration of food or liquid, leading to aspiration pneumonia, and inadequate oral intake causing weight loss or dehydration. The onset of dysphagia warrants discussion of goals of care and end-of-life care or updating previous discussions.


Opioid UseEdit

Opioids are substances that act on opioid receptors that produce pain relief and anesthesia. Though there is significant therapeutic benefit to use of these medications, there is also a high potential for abuse.

The Centers for Disease Control and Prevention have drafted guidelines for opioid use:

  • Non-pharmacologic and non-opioid pharmacologic therapy are preferred for chronic pain
  • Treatment goals should be reviewed and identified before starting opioid therapy for chronic pain
  • Use immediate-release (short-acting) opioids first
  • Start low and go slow
  • For acute pain, prescribe no more opioids than needed
  • Do not prescribe extended-release (long-acting) opioids for acute pain
  • Evaluate risk factors for opioid-related harms
  • Prescription monitoring programs allow physicians to see opioid use and physicians' prescribing opioids (vary by state)
  • Avoid concurrent benzodiazepine and opioid prescribing whenever possible


When prescribing opioids, one should calculate the total daily dose. Higher dosages are associated with higher risk of overdose and death due to respiratory depression. There is no ceiling to opioid use. Naloxone should be given to patients on high opioid doses as a reversal agent. Calculating the total daily dose of opioids helps identify appropriate use:

  1. Determine the total daily amount of each opioid a patient takes.
  2. Convert to morphine equivalents.
  3. Add morphine equivalents together.


Approximate conversions:

Medication Morphine equivalency
codeine 0.15
tramadol 0.25
morphine 1
hydrocodone 1
oxycodone 1.5
oxymorphone 3
fentanyl (in mcg/hr) 2.4
methadone 1-20 mg/day 4
methadone 21-40 mg/day 8
methadone 41-60 mg/day 10
methadone >61-80 mg/day 12
Table 12.1 - Oral opioid medication conversions to morphine equivalents


Example conversion
How many milligrams of morphine is 5 mg of oxycodone? The conversion is oxycodone 1.5 = morphine 1. Therefore, 5 mg oxycodone = 3.33 mg morphine.


Other considerations for opioid dosing include:

  • Methadone conversion is higher at higher doses
  • Fentanyl is dosed in mcg/hr instead of mg/day
  • When changing from one opioid to another, the new opioid should be lower to avoid unintentional overdose
  • Use extra precautions when increasing to 50 morphine equivalents or greater per day
  • Avoid or carefully justify increasing dosages to 90 morphine equivalents or greater per day


Patients with chronic pain will typically be prescribed long-acting medications due to limited abuse potential and longer duration of action. However, there may be times when pain may “breakthrough” the long acting medication and a short acting dose may be necessary to cover acute on chronic pain.

Calculating dosage for breakthrough pain:

  • PRN (as needed) dosing should be 10-20% of the total daily dose given Q4-6 PRN
  • If pain remains after 2 PRN doses, increasing the long-acting medication by 50% of the total daily morphine equivalents
  • Sometimes, it is necessary to rotate opioids due to tolerance or receptor saturation or other causes of pain (i.e. neuropathic pain)
  • Adjuvant drugs include gabapentin and duloxetine for neuropathic pain; NSAID use in elderly is not advisable due to high chronic kidney disease (stage 3 or greater) prevalence


ConstipationEdit

Constipation is characterized by infrequent bowel movements, and small, hard-to-pass, stool. Constipation can be acute (<6 months) or chronic (>6 months). Constipation is defined as less than 3 bowel movements per week. Constipation may be caused by drugs (opioids, anticholinergics, etc.), can have metabolic causes (hypercalcemia, hypothyroidism, dehydration), neurologic cause (diabetes mellitus, gastroparesis, spinal cord lesion), can have mechanical causes (obstruction, Ogilvie/pseudo-obstruction, ascites, ileus, carcinomatosis), and causes may be multifactorial. Complications of constipation include fecal impaction and stercoral colitis (inflammation of the colon due to fecal impaction which can also lead to fatal peritonitis due to rupture analogous to diverticulitis).

Constipation induced by opioids occurs due to activation of mu receptors in the GI tract (which is the same receptor that opioids bind to for pain control) inhibiting bowel movement. (Chronic constipation can be induced by calcium-channel blockers, anticholinergics, or tricyclic antidepressants as well.) While tolerance can develop to opioids in terms of pain relief, little-to-no tolerance to constipation develops. Fentanyl and morphine may cause less constipation than morphine. For opioid-induced constipation prophylaxis or mild constipation, a combination of a laxative and a stool softener (i.e. “mush and push”, such as senna/colace) should be used and titrated to effect.

Treatment of constipation involves the use of laxatives and stimulants:

  • Senna stimulates the myenteric plexus to increase motility but requires GI metabolism to active drug
  • Bisacodyl stimulates the mucosal nerve plexus and requires hepatic metabolism to active drug
  • Colace increases water re-absorption into the stool to prevent hard stool but does not increase frequency of bowel movements
  • Milk of magnesia increases water re-absorption
  • Bulking agents: High-fiber foods draw water into the colon to soften fecal matter
  • Lubricants: Mineral oil can be used for fecal impaction or acute constipation
  • Hyperosmotic agents: Lactulose draws water into the colon but can cause excessive gas or bloating and electrolyte disturbances
  • Prokinetic drugs: Metoclopramide decreases transit time
  • Enemas (various)


Stool softeners: prescribe in this order until effectiveness is achieved:

  1. senna/docusate (together)
  2. miralax
  3. lactulose
  4. enema


FrailtyEdit

Frailty is a state of increased vulnerability to stressors due to age-related declines in physiologic reserve across neuromuscular, metabolic, and immune systems. Frailty is not an inevitable part of aging. It is the end-stage of chronic medical conditions. Frailty is a geriatric syndrome. The incidence of frailty increases with increasing age. Frailty has increased incidence with older age, decreased education level, tobacco use, post-menopausal hormone therapy use, single marital status, depression, and intellectual disability.

Frailty results at the end-stage of chronic medical conditions including:

  • End-stage COPD
  • End-stage systolic/diastolic heart failure
  • End-stage renal disease (+/-) dialysis
  • End-stage coronary artery disease
  • End-stage liver disease
  • End-stage dementia
  • HIV/AIDS
  • CVA/coma


Frailty is also apparent from repeated hospitalizations or ER visits, recurrent infections, dyspnea with minimal exertion despite adequate management of co-morbid conditions, significant decrease of serum albumin or cholesterol, stage 3/stage 4 decubitus ulcers despite appropriate therapy, and uncontrolled pain. These are appropriate prompts for a palliative care and/or hospice referral. Frail patients will have frequent exacerbations of symptoms and will continue to decline from previous functional baseline with no hope of improvement. Goals of care should be frequently re-assessed with family. Weight loss causes should always be investigated – not always caused by frailty!

Frailty is the end-point of a continuum:

  1. pre-frail stage: potentially reversible
  2. mid-stage frailty: is characterized by increased risk of falls, institutionalization in long-term care facilities, and mortality
  3. frailty: characterized by failure to thrive, a progressive and continuous loss of weight and function; it is an irreversible stage of decline, progressive apathy, and decreased appetite which ends with death


Work-up of frailty should include evaluation of depression, malnutrition, cognitive assessment, and functional assessment. Weight loss is an ominous sign in elderly patients. Weight loss requires evaluation for identifiable and reversible causes in the elderly population. In younger patients, the most common cause of weight loss is cancer. Treatment with mirtazapine (an anti-depressant with off-label appetite stimulation) may provide positive results and is often trialed. Functional status is the most important predictor of functional decline and death than specific clinical conditions.

Hospice/Palliative CareEdit

Hospice is a concept of care that provides comfort and quality of life to patients and their families who are facing a terminal illness as well as a type and philosophy of care that focuses on palliative care for the symptoms of a terminal illness. Palliative care is the treatment of disease symptoms. The goals of hospice and palliative care are to provide comfort, relieve physical, emotional, social and spiritual suffering, and promote dignity of the terminally ill. Hospice neither hastens nor promotes the dying process. Palliative care focuses on quality and quantity of life; hospice only focuses on quality of life before death. The hospice benefit is reserved for those with a less than 6-month life expectancy if the patient’s disease follows its expected course; palliative care is the treatment of symptoms regardless of whether the patient is using their hospice insurance benefit. Geriatric physicians are trained in hospice and palliative care, though in recent years this field has emerged as its own subspecialty. Palliative care may or may not transition to hospice.

Hospice is primarily a philosophy and structured approach to care in multiple settings, including the patient’s home (independent living, assisted living, or long-term care), a nursing home, or an in-patient hospital unit. Almost 80% of hospice care takes place within a patient’s home. Hospice serves persons of all ages, pediatric to geriatric; it also focuses as much on the grieving family as well as the patient. Medicare hospice benefit covers virtually all hospice services as a part A benefit. Members of the hospice team include the primary care physician, the hospice physician (with PCP), hospice nurses, hospice home health aides, hospice social workers, hospice volunteers, and chaplains.

Three different levels of hospice care include:

  1. Routine care: most common; routine care from home health aide
  2. Continuous care: severe symptoms, temporary relief; home services for a minimum of 8 hours/day
  3. In-patient care: “actively” dying; severe and intractable symptoms


Respite care is a brief and periodic benefit for the family/caregiver of 5 days per benefit period in an effort to reduce caregiver burden. Hospice services also provide basic ADL care, provide counseling for the patient and family, assist patient with unfinished legal or financial business and funeral arrangements, religious care, and bereavement for family for up to 13 months after patient dies which covers the anniversary of the patient’s death. Societal and cultural considerations and implications are important when considering hospice or palliative care services. Previous experience and circumstances surrounding prior deaths form basis of perception; Many deny the reality of death due to this. Religion and belief systems also impact perception – for example, some Chinese families do not tell the family member death is imminent allowing them to live life without knowing when to go to hospital for end-of-life care. Hospice is appropriate for frail patients who are at the end-stages of chronic diseases.

It is impossible to predict when someone will die. With experience, one may develop a “feeling” of when patients will die. Predicting mortality is useful in short-term and long-term planning. The number and severity of co-morbid conditions and functional impairments are stronger predictors than chronological age.

Common end-of-life symptoms include pain (physical, spiritual, and emotional), shortness of breath, nausea and vomiting, anorexia and cachexia, dysphagia, fatigue, constipation, or delirium.

Treatment of symptoms can be accomplished with:

  • Pain control: morphine liquid if unable to swallow; if on prior pain med regimen may continue as long as able . All patients on narcotics need a bowel regimen! (senna, colace, miralax, lactulose, etc.)
  • Anxiety/Agitation control: lorazepam liquid if unable to swallow; can also use oral benzodiazepine if able
  • Secretions: hyoscyamine liquid; can use other anticholinergics (scopolamine transdermal patch)


Initiation of hospice and/or palliative care does not mean all medications are stopped for chronic medical conditions; patients may continue medications as long as practical (i.e. levothyroxine, warfarin, diabetes medications). Lab monitoring is done only as needed. Goal is quality of life. Avoid unnecessary laboratory studies and do not request patients complete any further preventive screenings.

Conveying a Terminal DiagnosisEdit


Breaking bad news is one of a physician's most difficult duties. The discomfort and uncertainty associated with conveying bad news may lead physicians to emotionally disengage from patients. Patients prefer a frank and empathetic disclosure of a terminal diagnosis or other bad news.

The following procedure will guide the discussion from the perspective of the physician and streamline this difficult process:

  • "Fire off a warning shot" - Inform the patient that you have received their test results and the results are concerning.
  • Ask the patient what they know about their disease. - Do they understand that they are sick? Do they understand the disease process?
  • If a test result is received (i.e., labs or imaging), would the patient want someone to be present when the result is disclosed? - do not underestimate the importance of an emotional support system. This will often be a family member or friend.
  • Disclose the test result. - A common question will likely be, "is this cancer?"
  • Acknowledge that you understand that this is a difficult time for the patient.
  • Offer to help the patient tell other family members to whom they wish to disclose the information.
  • Recommend appropriate referral for further workup. - Who does the patient need to see - a surgeon or an oncologist?
  • Reduce the patient's guilt about the illness being their fault. - For example, if a smoker is being told that they have lung cancer, the physician should try to reduce guilt between the association of smoking and lung cancer.
  • Reassure the patient that the physician will be there to help.
  • Provide the patient the opportunity to ask open-ended questions. - Address any questions or concerns.


Review QuestionsEdit


1. A long-term care patient in the nursing home with end-stage Alzheimer’s disease who is bedbound, has no recognizable speech, dysphagia, and is incontinent of urine and feces is seen by his primary care physician. The patient’s son is insisting of placement of a percutaneous endoscopic gastrostomy (PEG) tube to administer feedings. After a review of this patient’s advance directive, it is indicated that his daughter is the designated medical power of attorney. However, his daughter passed away two years ago. His son is not listed in the document. The advance directive clearly states that he does not want cardiopulmonary resuscitation, does not want mechanical ventilation, does not want artificial nutrition or hydration, and does not want to be transferred to the hospital for further care if he needs cannot be met at his current location. How do you proceed?

A. Place the feeding tube as the son is the only living next-of-kin and is therefore able to make medical decisions regarding his father
B. Place the feeding tube and begin artificial nutrition and hydration as it is considered standard of care
C. Place the feeding tube for a defined trial period and remove it in two weeks if there is no improvement in the patient
D. Do not place the feeding tube and begin palliative measures if not already in place
E. Transfer the patient to an inpatient hospice unit

Questions 2-3: An 87-year-old female with a medical history of recurrent bronchitis, COPD, and multiple episodes of acute on chronic diastolic heart failure is seen in the hospital by her attending physician. She has no history of cognitive impairment. She was brought to the hospital on 3 separate occasions for “shortness of breath” which was diagnosed as pneumonia on one occasion and COPD exacerbation for two occasions. She was treated each time and discharged back to her home with her family. She is dependent on her family for all of her IADLs and ADLs. Her medications include budesonide/formoterol, furosemide, metoprolol tartrate, lisinopril, simvastatin, albuterol nebulizer treatments, mirtazapine, prednisone, senna, docusate, and chronic supplemental oxygen at 4 L/min. Her vital signs are stable. Her physical exam is notable for +2 lower extremity edema bilaterally. Her serum creatinine is 1.3 mg/dL and her serum albumin is 2.8 g/dL.

2. She asks her attending physician why her symptoms are not improving. Why didn’t her symptoms improve?

A. She was not treated with the proper antibiotics and her infection is still present.
B. Her baseline functional status has not yet been reached but she will return to her baseline over time.
C. She requires evaluation from a cardiologist and pulmonologist to optimize her medical management.
D. She is not going to improve from her baseline as a result of end-stage chronic medical conditions.

3. She lives with her family and is content to stay in her home. What is the next best step in the management of this patient?

A. Assess goals of care of this patient with a discussion of the patient, her family, and caregivers.
B. Refer to hospice because she is not expected to live beyond the next 6 months.
C. Advise this patient that she should receive CPR and intubation in the event of cardiopulmonary arrest.
D. Advise this patient that she should obtain long-term artificial nutrition and hydration in the event she becomes unable to feed herself.
E. Discharge this patient to a sub-acute rehabilitation facility.

4. A 72-year-old male nursing home resident with end-stage renal disease on hemodialysis and no history of cognitive impairment expresses a desire to stop hemodialysis. His next hemodialysis session is scheduled for tomorrow. His daughter, who is his medical power of attorney, insists that he does not understand the ramifications of such a decision and asks for his physician to intervene. If the patient expresses a desire to stop undergoing hemodialysis treatments, what is the correct course of action?

A. He cannot stop receiving hemodialysis treatments as they are essential to his survival.
B. He cannot stop receiving hemodialysis treatments because his daughter is his medical power of attorney, makes medical decisions for her father, and she does not want his treatments to stop.
C. Honor the desires of the patient and stop the treatments immediately.
D. He cannot stop receiving hemodialysis treatments if his physician does not agree to stop them.
E. His nephrologist must be consulted and see the patient prior to any modification of his current treatment plan.

Questions 5-6: An 86-year-old man is evaluated in preparation for hospital discharge. He was admitted for exacerbation of chronic systolic heart failure and pneumonia. His medical history is notable for advanced coronary artery disease, diabetes mellitus, and chronic kidney disease. He has not completed an advance directive. Pre-hospitalization functional status was independent for 6/6 ADLs. Present functional status is independent of feeding and continence, requiring maximum assistance for the others. In discussion with his wife, she is concerned that his shortness of breath is not improved and that his pain has not been adequately treated. Physical therapy has recommended that the patient be discharged to a sub-acute rehabilitation facility, but neither the patient nor his wife wish for him to be transferred there and are opting to bring him home with his wife and family.

5. Which of the following is most appropriate to include on discharge recommendations?

A. Arrange a patient and family meeting to discuss the patient’s wishes and options.
B. Arrange a family meeting to discuss his need for sub-acute rehabilitation to improve functional status.
C. Arrange a family meeting to discuss the need for hospice care.
D. Meet separately with the patient’s wife to address her concerns regarding the patient.
E. Arrange an appointment with the patient’s primary care physician in 1 month.

6. When are hospice services indicated if the patient’s disease follows its natural course?

A. Life expectancy is less than 12 months.
B. Life expectancy is less than 9 months.
C. Life expectancy is less than 6 months.
D. Life expectancy is less than 3 months.
E. Life expectancy is less than 1 week.

7. A 68-year-old female with a 20-year history of diabetes mellitus type 2 with moderate control is placed on hospice services due to stage 3 nasopharyngeal carcinoma diagnosed 3 months ago. She complaints of frequent nausea. She experienced nausea for the first two days following her chemotherapy cycles but this typically spontaneously resolved. She notes the nausea is "different" from the "chemotherapy nausea". For the last three years, she has had early satiety but maintained her weight. Which of the following is the most appropriate medication to prescribe for the management of this patient?

A. Ondansetron
B. Prochlorphenazine
C. Metoclopramide
D. Diazepam
E. Meclizine

8. An 86-year-old female who is now actively dying due to end-stage pulmonary fibrosis presents to the hospital from home. She was being followed at home by palliative care services. Her symptoms were well controlled for the last several months. She lived at home independently until she developed pneumonia 2 days ago. She was placed on antibiotics and is currently on day 8/10 of treatment. Upon presentation to the hospital one day ago, she was oriented between periods of increased fatigue and sleep. She now requires 6 L of oxygen continuously via nasal cannula. She was noted to have increased respiratory congestion yesterday and was started on a transdermal scopolamine patch in addition or liquid morphine and liquid lorazepam. Today, she is now agitated, moaning, and flailing at times. She required placement of a Foley catheter and was found to have 350 mL of urine when it was placed yesterday. Her family is becoming quite distressed by this change. Which of the following is the next best step in the management of this patient?

A. Remove the Foley catheter due to risk of catheter-associated urinary tract infection
B. Stop lorazepam
C. Stop morphine
D. Stop scopolamine
E. Counsel family regarding terminal hypoactive terminal delirium

9. You are seeing a patient in the nursing home with end-stage Alzheimer’s disease who is bedbound, has no recognizable speech, dysphagia, and is incontinent of urine and feces. The patient’s son is insisting of placement of a percutaneous endoscopic gastrostomy (PEG) tube to administer feedings. Which of the following statements is accurate?

A. Artificial nutrition and hydration may prolong life in some patients, and has been shown to be beneficial in patients with end-stage dementia
B. Artificial nutrition and hydration are an often-implicated cause of acute delirium
C. Artificial nutrition and hydration maintain the appearance of life-giving sustenance
D. Artificial nutrition and hydration have been shown to reduce skin breakdown
E. The risk of aspiration pneumonia is less with tube feedings than with a modified diet in a patient with dysphasia

Answers to Review QuestionsEdit

  1. D - The son does not have decision-making capacity. The patient’s wishes must be followed per his advance directive. Advance directives should be updated regularly because patient preferences may change as their circumstances change.
  2. D - This patient is frail. She is not going to improve from her baseline as a result of end-stage chronic medical conditions.
  3. A - For frail patients, assess goals of care of with a discussion of the patient, her family, and caregivers.
  4. C - The patient is capable of making his own medical decisions and his wishes must be honored.
  5. A - This patient is frail. She is not going to improve from her baseline as a result of end-stage chronic medical conditions. (Similar to Question #2)
  6. C - Hospice services are indicated if life expectancy is less than 6 months provided the patient’s disease follows its natural course.
  7. C - Metoclopramide is most appropriate to prescribe in a patient experiencing nausea with a component of gastroparesis.
  8. D - Her symptoms are due to the anticholinergic effects of the scopolamine patch. Hypoactive delirium (not hyperactive) is seen in terminal patients.
  9. C - Artificial nutrition and hydration (1) has not been shown to be beneficial in patients with end-stage dementia, (2) can prevent or improve delirium, (3) has not been shown to reduce skin breakdown, and (4) carries a risk of aspiration pneumonia equal to, if not greater, than oral intake.