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Management of common GI symptoms in Palliative Medicine • On off the most frequently reported & distressing

symptoms.

Gastrointestinal Symptoms

Dr Sudha SarnaProfessor Palliative Medicine

symptoms. – dry mouth (84 %)– weight loss (76%)– early satiety (71%)– taste change (60%)– constipation(58 %)– anorexia (56%)– bloating (50 %)– nausea (48 %)– abdominal pain (42 %)– vomiting (34 %)

Komurcu et al

Upper GIT– Oral Problems– Nausea and Vomiting– Dysphagia

Lower GIT– Constipation– Diarrhoea– Intestinal Obstruction

Common problems • Painful, Inflammatory, Ulcerative condition• Causes :

– Infection (herpes & candida)

– Ulceration

– Mucositis – post RT / Chemo

– Dry Mouth

– Pain – Infiltration / dental problems

– Iron / Vitamin C deficiency

Sore mouth or Stomatitis :

• General measures– Gargle with cool water or sucking ice chips.– Avoid hot beverages and foods as well as salty, spicy,

and citrus-based foods.– Avoid tobacco & alcohol– Frequent sipping of water and semi frozen drinks.– petroleum jelly to lips– Good oral hygiene.– Apply a one-to-one mixture of hydrogen peroxide

Management �Treatment:

◦ Treat underlying cause

◦ ENT / Dental review if needed

◦ Topical corticosteroid like triamcinolone dental paste

◦ Lignocaine 4% viscous gargles.

◦ Lignocaine gel (2%)

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– Apply a one-to-one mixture of hydrogen peroxide with water or baking soda with water to the ulcers.

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Nausea and

Vomiting

� Occurs in 40 – 70% patients with cancer

Nausea and Vomiting

� Even low-grade nausea is an unpleasant and

distressful to patient awell to relatives�Affects patients daily functioning

� Quality of Life

� Active palliative management is important

� Can be controlled in 90% of patients

Junior Rotation in Hospice and Palliative Medicine

� Forceful oral expulsion of gastric contents through mouth

� Clinical Implication :

– Pain aggravated

– Refusal to eat

– Refusal to take analgesics / other treatment

– Dejection

Poor Quality of Life

Vomiting - Definition

Unpleasant sensation of imminent need to vomit

or may not ultimately lead to vomiting

� Clinical Implication :

– No desire to eat or drink

– May refuse cancer treatment / analgesics

– Psychological distress

Nausea : Definition

� Anxiety / pain.

� Gastric Stasis/ gastritis/ GERD .

� Intestinal Obstruction.

� Constipation.

� Drugs (opioids, radiotherapy, chemotherapy)

� Raised ICP.

� Others: Abdominal carcinomatosis, extensive liver metastases, Ascites, hypercalcemia, uraemia

Causes

• Metastases• Meningeal irritation• Movement• Mental anxiety• Medications• Mucosal irritation

• Mechanical obstruction• Motility• Metabolic• Microbes• Myocardial

M-Esis… the 11 M’s

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Pathophysiology

Organ/component NeurotransmitterOrgan/component Neurotransmitter

Chemoreceptor trigger zone (CTZ) Serotonin, Dopamine, Acetylcholine, Histamine

Cerebral Cortex Complex; Learned responses

Vestibular apparatus Acetylcholine, Histamine (H1)

GI Tract Serotonin, Dopamine, Acetylcholine, Histamine (H2)

Treatment should be Mechanism-based (cause specific), Not generalized!

� Identify & treat principal underlying cause

� Symptomatic management with anti-emetic drugs.

� Control of symptoms possible in 60% patients

� Single antiemetic may not be adequate

General principles of management

� Combination of drugs e.g., for Raised ICP & Uremia ( Dexamethasone, Haloperidol , metoclopromide )

� Select route of administration: – Persistent vomiting – subcutaneous/ IV preferable

– May consider drugs disperse / dissolve in oral cavity

� Keep in mind side-effects (extrapyranidal in metoclopramide,

Constipation in ondansetron and granisetron ……)

General principles of Management• Behavioral treatments - relaxation, imagery, music,

distraction

• Dietary measures – Frequent small meals – Try to avoid fatty / sweet / spicy food – Avoid fibre– Avoid carbonated drinks – Cold, bland food and clear fluids tolerated better– Control of malodour from colostomy,fungating tumor, decubitus ulcer

etc– Calm, reassuring environment away from sight and smell of food.

Non-Drug Therapy

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– Calm, reassuring environment away from sight and smell of food.Patient should avoid cooking.

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Nausea & VomitingCauses Treatment � Raised Intracranial Pressure � Dexamethasone 8 to 36 mg I.V. (

dose to be titrated)

Causes Treatment

• Drug induced

• Radiotherapy

• Chemotherapy

• Metabolic eg. Uremia or hypercalcemia

• Haloperidol 1.5 to 2.5 mg H.S / b.d.

• Ondansetron 8 mg stat then 4 mg. tds / granisetron 1 mg. stat then 1 mg. b.d.

• Ondansetron / Granisetron. Dexameth. 8 mg o.d for 3 days. Metoclopr. 10 to 20 mg. q.d.s. po/sc

• Haloperidol – start with 1.5 mg H.S.

Causes Treatment

� Bowel Obstruction

� Delayed Gastric Emptying

� Gastric Irritation

dose to be titrated)

� If partial, no colic, MetoclopramideIf colic, Hyoscine Butylbromide

40 to 100 mg/24 hrs.

Ondansteron 8 to 24 mg/24 hrs. p.o., i.v. or s.c.

� Metoclopramide 10 20 mg q.d.s. Domperidone 10 to 20 mg q.d.s.

� PPI , Stop Irritants

� Mechanism of Opioid induced Nausea & Vomiting� CTZ� increased vestibular sensitivity� gastric stasis� Constipation

� DOC : Haloperidol , Metoclopramide 1st line

� Prevent with initial antiemetics

� Treat N / V aggressively with one or more antiemetic before reducing Opioid doses causing pain.

Nausea & Vomiting in Palliative Care Nausea and vomiting in PC• Document most likely causes.

• Treat potentially reversible causes and exacerbating factors ( e.g. Drugs, constipation, severe pain, infection, cough)

• Review dose after 24 hours

• If N & V persist after 24 – 48 hours, review cause.

• If on parenteral, consider converting to oral after 72 hours of good control to oral regimen

• Schedule antiemetic around the clock

• Chose second and third antiemetic which work

on different receptors

• Consider imaging

– Abdominal for constipation/obstruction

– CNS imaging for masses/increased ICP

Intractable nausea/vomiting

Constipation: TRADITIONALLY defined as three or fewer bowel movements per week

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– CNS imaging for masses/increased ICP

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Constipation in palliative care is fundamentally defined by the patient

�Prevalence of constipation in palliative care patients

23–65% (cancer)fundamentally defined by the patient

� It is the frequency and difficulty of defecation that are the basis for the diagnosis of constipation in comparison with pre-illness pattern

� If the patient complains of constipation or defecates less than three times per week, assessment of bowel habits is warranted

23–65% (cancer)34–35% (AIDS)38–42% (heart disease)27–44% (chronic obstructive pulmonary disease) 29–70% (renal disease)

�Approximately 50% of patients admitted to palliative care centres cite constipation as a problem.

Goodman, M, Low, J, Wilkinson, S. Constipation management in palliative care: a survey of practices in the United Kingdom.J Pain Symptom Manage2005;29:238–244.

Solano, JP, Gomes, B, Higginson, IJ. A comparison of symptom prevalence in far advanced cancer, AIDS, heart disease, chronic obstructive pulmonary disease and renal disease.J Pain Symptom Manage2006;31: 58–69

Chronic constipation

Functional (primary)

Secondary

Functional bowel disorders classification:

1. Irritable bowel syndrome2. Functional constipation3. Functional diarrhea4. Functional abdominal bloating/distension5. Unspecified functional bowel disorders6. Opioid-induced constipation

Bowel Disorders: Lacy, Brian E. et al. Gastroenterology ,2016, Volume 150 , Issue 6 , 1393 - 1407.e5

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Constipation:Ann Intern Med. 2015;162(7):ITC1. Brijen J. Shah, MD; Nisha Rughwani, MD

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Malignancy effects

Direct• obstruction by tumor in wall• external compression by tumor• neural damage• L/S spinal cord• Cauda equina/pelvic plexus• Hypercalcemia

Malignancy effects

Secondary effects• poor p/o intake• dehydration• weakness/inactivity• confusion• depression• unfamiliar toilet arrangements

Intestinal obstruction by tumour or adhesions:

• Known intra-abdominal malignant deposits • previous intestinal surgery• alternating constipation and diarrhoea• gut colic• nausea and vomiting

D/D: Severe constipation

� Attempts to clear ‘constipation’ which is actually obstruction,

suggest the presence of intestinal obstruction

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� Attempts to clear ‘constipation’ which is actually obstruction, by use of stimulant laxatives can cause severe pain.

� A plain abdominal radiograph may help clarify the diagnosis

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Aims of management Opioid induced constipation

�Re-establish comfortable bowel habits

�Relieving the pain and discomfort

�Restore satisfactory level of independence

�Prevention of related gastrointestinal symptoms

such as nausea, vomiting, abdominal distension

and abdominal pain

Prevalence of OIC in cancer patients ranges from 23% to over 90%

Oosten AW, Oldenmenger WH, Mathijssen RH, et al. A systematic review of prospective studies reporting adverse events of commonly used opioids for cancerrelated pain: a call for the use of standardized outcome measures. J Pain.2015;16:935 –946

�Opioid administration causes oesophageal and gallbladder dysmotility, increased stomach tone, and delays in gastric emptying, oral-coecal transit and colonic transit

� Inactivation of chloride channels and decreased chloride transport from the enterocyte into the gut lumen � less water follows due to lower osmotic gradient � decreased gut secretion and absorption of water together with less gastric and pancreatico-biliary secretion

Wood JD, Galligan JJ. Function of opioids in the enteric nervous system. Neurogastroenterol Motil 2004;16:17 –28

Smith K, Hopp M, Mundin G, Bond S, Bailey P, Woodward J, Palaniappan K, Church A, Limb M, Connor A. Naloxone as part of a prolonged release oxycodone/naloxone combination reduces oxycodone-induced slowing of gastrointestinal transit in healthy volunteers. Expert Opin Investig Drugs 2011;20:427–39

Pathogenesis� Most constipating : morphine and hydromorphone

� Transdermal fentanyl < morphine or oxycodone

� Buprenorphine and alfentanil- required in less doses, thus less constipating

� Methadone less constipating : action only partly mediated through opioid receptors

� Tramadol and tapentadol: actions partly mediated though other receptor types

� Lack of awareness among clinicians

� If clinicians are aware, they may not ask patients questions about constipation

�Patients might feel ashamed to disclose their symptoms

�Absence of universal diagnostic criteria

Barriers to diagnosis of OIC�Bowel Function Index (BFI) → measurement of

OIC from the patient’s perspective

�Composed of three questions :• ease of defecation• feeling of incomplete bowel evacuation• personal judgment of the patient regarding constipation

�Each question scored: 0 (no symptoms) to 100 (severe symptoms)

Assessment of OIC

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�Absence of a standard protocol for the treatmentCamilleri M, Drossman DA, Becker G, Webster LR, Davies AN, Mawe GM Neurogastroenterol Motil. 2014 Oct; 26(10):1386-95.

�A 12-point change in score → clinically relevant change in constipation

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Non-pharmacological treatment� Life style changes� Life style changes

�Ensuring privacy and comfort to

� Increasing fluid & fibre intake

�Anticipating the constipating effects of drugs e.g.

opioids, and provide laxatives prophylactically

�Abdominal massage

�Complementary therapies- eg. acupuncture and

acupressure

�Herbal teas, juices, and thin soups

�Warm to hot liquids � increase peristalsis

� Avoid Coffee, caffeinated teas & alcohol �diuretic

�Beans, lentils, peas, nuts, oat bran and seeds ( flax)

�Pectin-containing eg. apples, carrots, beets,

bananas, cabbage, citrus fruits, dried peas, okra

� Ideal daily fiber consumption -- 20 to 30 g

�Regular exercise, or activity� promotes normal

motility of the bowel

Food and lifestyle

�Every morning, before getting out of bed � gentle massage to abdomen in a clockwise motion

�Stimulation of the colon through massage �increases colonic motility

�Massaging in a clockwise motion � encourages normal flow of stool towards rectum.

Abdominal massage

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Commonly used laxative agents

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The hand that writes the opioid prescription �Despite this recommendation, a significant proportion of patients are prescribed opioids The hand that writes the opioid prescription

should write the laxative prescription

-Cicely Saunders

proportion of patients are prescribed opioids without concomitant laxative prescription.

�In a retrospective analysis of 2982 cancer outpatients on opioid therapy, � 44.4% did not receive laxatives at all�Only 24.7% of patients received laxatives at the time

of opioid prescription� 22.0% received laxative after opioid prescription !!!

Skollerud LM, Fredheim OM, Svendsen K, et al. Laxative prescriptions to cancer outpatients receiving opioids: a study from the Norwegian prescription database. Support Care Cancer.2013;21:67 –73.

Algorithm for management of OIC

� The most frequent switch is from morphine, hydromorphone, or fentanyl to methadone.

� Success rates of 40–80% have been reported

� A systemic review concluded that there is a low level of evidence for opioid rotation or switching

Opioid switch Recent advances in management of OIC

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Caraceni A, Hanks G, Kaasa S, et al. Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. Lancet Oncol. 2012;13:e58–681 Dale O, Moksnes K, Kaasa S. European Palliative Care Research Collaborative pain guidelines: opioid switchingto improve analgesia or reduce side effects. A Systematic Review. Palliat Med.2011;25:494 –503

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PAMORAsAdministered either orally or subcutaneous in conjunction with the opioids

Narcotic bowel syndromeconjunction with the opioids

Methylnaltrexone � first PAMORAadministered subcutaneously

Naloxegol � approved for chronic useorally administeredNo dose adjustment in renal failure & mild-to-moderate hepatic impairment

Alvimopan � used for short-term (less than 7 days)not approved for chronic treatment of OIC � increasing risk of ischemic cardiac events

�Incidence � estimated between 4.2% and 6.4%�Characterized by chronic or periodic abdominal

pain that gets worse when the effect of the narcotic drug wears down

�Other symptoms may include:• nausea• bloating• periodic vomiting• abdominal distension• constipation

Diagnostic criteria(a) for narcotic bowel syndrome/opioid-induced gastrointestinal hyperalgesia:

Must include all of the following:�Chronic or frequently recurring abdominal

pain(b) that is treated with acute high-dose or chronic narcotics�The nature and intensity of the pain is not explained

by a current or previous GI diagnosis(c)

�Two or more of the following:• The pain worsens or incompletely resolves with continued or

escalating dosages of narcotics• There is marked worsening of pain when the narcotic dose

wanes and improvement when narcotics are re-instituted (soar and crash)

• There is a progression of the frequency, duration, and intensity of pain episodes

(a) Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis.(b) Pain must occur most days.

The key to diagnosis � Long-term or increasing dosages of narcotics lead to continued or worsening symptoms rather than benefit.

Keefer L, et al. Centrally mediated disorders of gastrointestinal pain. Gastroenterology . 2016; 150:1408–1419

Bowel Obstruction

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• Incidence – 3%– Ovarian Cancer: 5% to 42%– Colorectal Cancer: 10% to 30%

• Mechanism: mechanical, paralytic• Symptoms:

– Intestinal colic 72-76%– Distension & pain 92%– Nausea / Vomiting 68-100%

• Plain X-ray Abdomen /CT may help• Surgery...limited usefulness in terminally ill cancer patients

Bowel Obstruction... In cancer

• Surgery...limited usefulness in terminally ill cancer patients• Consider Quality of life while planning treatment.

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Partial Obstruction may resolve –

ManagementDrugs used : � Dexamethasone : 8 –16mg S.C / I.V

Medical Management

Aim to :1. Reduce Bowel wall oedema: dexamethasone2. Stimulate Gut Motility: Metoclopramide

If not resolved (? Complete obstruction)General Measures� Reduce intestinal secretions:octreotide � Treat nausea and vomiting: haloperidol,

promethazine � Nasogastric tube - Decompression

� Dexamethasone : 8 –16mg S.C / I.V

� Metoclopramide : 30 to 120mg / 24h S.C. inf

� Hyoscine butylbromide : 40-100mg / 24h S.C. inf

� Haloperidol : 3-5mg / 24 h SC infusion

� Promethazine 25mg tds S.C.

�Octreotides 300-1200microgram/24 hrs

• Management– Steroids– Opioids (morphine) 89% control– Antiemetics (prochlorperazine) 13% control– Antispasmodics (scopolamine) 67% control

Bowel Obstruction: Medical Management• 14 amino acid Polypeptide

– serum half-life 3 minutes• Central Action

– Inhibits release of GH and Thyrotropin• Peripheral Action

– Inhibits glandular secretion• Pancreas, GI tract

Somatostatin

• Octreotide 10 mg/hr continuous infusion• Titrate to complete control of n/v• If NG tube in place, clamp when volume

diminished to 100 cc and remove if no n/v

• Try convert to intermittent sc• Continue until death

Octreotide for Bowel Obstruction

Definition:�Passage of frequent loose stools�More than 5 unformed stools within 24

hoursPrevalence : � About 10% of patients in PC� 27% of HIV patients report diarrhea

Diarrhea

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Most common causes in Palliative care setting

Diarrhea

Diagnosis : Helpful hints :

DiarrheaMost common causes in Palliative care setting

� Imbalance of laxative therapy

� Drugs: antibiotics, antacids, Iron preparations

� Faecal Impaction – Overflow diarrhoea

� Radiotherapy to abdomen / pelvis area

� Malabsorption of fat or water - (Gastrectomy, Colectomy)

Diagnosis : Helpful hints :

�2 to 3 times without warning - incontinence

�Profuse watery stools - faecal impaction

�Alternating with constipation - laxative therapy / Bowel

Obstruction

�Steatorrhea - malabsorption

PR useful to exclude faecal impaction

Treatment:

• Treat cause

• General measures:

• Fluid intake, frequent sipping

• Reassure self – limiting nature

Diarrhea

� Specific Drug treatmentAntibiotics

� Nonspecific Drug TreatmentOpioids – Codiene Antimotility –loperamideAbsorbents – Attapulgit, Polycarbophil

Diarrhea

Guiding Principles / Summary:

� Anticipation of problems� Ensure compliance � Effectiveness of treatments� Appropriate medications� Prescribe for ’breakthrough’ symptom

Conclusion

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