nausea, vomiting, bowel obstruction
TRANSCRIPT
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Nausea, Vomiting, Bowel
Obstruction
Gordon J. Wood, MD, MSCI, FAAHPM
Coleman Palliative Care Intensive
February 13, 2015
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Objectives
• Describe a three step approach to the
management of N/V at the end of life
• Identify strategies to manage refractory
N/V in persons near the end of life
• Describe how to medically manage a
malignant bowel obstruction
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Mechanism-Based Therapy
1. Careful assessment to determine
etiology
2. Use knowledge of pathophysiology to
determine receptors underlying
symptoms
3. Choose antiemetic to block implicated
receptors
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Mechanism-Based Therapy
1. Careful assessment to determine
etiology
2. Use knowledge of pathophysiology to
determine receptors underlying
symptoms
3. Choose antiemetic to block implicated
receptors
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Evaluation
• History
• Physical examination
…think “Head-to-Toe”
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Evaluation
• Laboratory Testing
– What labs should you consider?
• Radiology
– What imaging should you consider?
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Evaluation
• Confident in cause of N/V in 45 of 61
hospice patients
• Chemical abnormalities 33% (metabolic,
drugs, infection)
• Impaired gastric emptying 44%
• Visceral and serosal causes 31% (bowel
obstruction, GI bleed, enteritis,
constipation)
Stephenson J et al. Support Care Cancer. 2006;14(4)348-353.
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Evaluation
• 40 patient episodes of nausea and/or
vomiting on inpatient palliative care unit
• 59 reversible etiologies
– 51% medications
– 11% constipation
Bentley A et al. Palliat Med. 2001;15(3):247-253
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Mechanism-Based Therapy
1. Careful assessment to determine
etiology
2. Use knowledge of pathophysiology to
determine receptors underlying
symptoms
3. Choose antiemetic to block implicated
receptors
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Mechanism: The 4 Pathways
1. Chemoreceptor Trigger Zone
2. Cortex
3. Peripheral Pathways
4. Vestibular System
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Mechanism: The 4 Pathways
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Mechanism: The 4 Pathways
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Mechanism-Based Therapy
1. Careful assessment to determine
etiology
2. Use knowledge of pathophysiology to
determine receptors underlying
symptoms
3. Choose antiemetic to block implicated
receptors
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Antiemetics
Antiemetic Receptor Anatagonized
Metoclopramide (Reglan) ?
Haloperidol (Haldol) ?
Prochlorperazine
(Compazine)
?
Chlorpromazine
(Thorazine)
?
Promethazine
(Phenergan)
?
Wood, G. J. et al. JAMA 2007;298:1196-1207.
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Antiemetics: Continued
Antiemetic Receptor Anatagonized
Diphenhydramine
(Benadryl)
?
Scopolamine
(Transderm Scop)
?
Hyoscyamine (Levsin) ?
Ondansetron (Zofran) ?
Mirtazapine (Remeron) ?
Wood, G. J. et al. JAMA 2007;298:1196-1207.
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Mechanism-Based Therapy
• 40 patient episodes of N/V in inpatient
palliative care unit
• Most common causes: gastric
stasis/outlet obstruction (35%),
chemical/metabolic (30%)
• Nausea resolved in 28 of 34 cases (82%)
• Vomiting resolved in 26 of 31 cases (84%)
• Total symptom control in mean of 3.4 days
Bentley A et al. Palliat Med. 2001;15(3):247-253
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Empiric Treatment
• Mechanism-based therapy effective1,2
• Some advocate empiric D2 antagonists3 in
all cases
• No head-to-head comparison
• D2 antagonists are our first choice in
acutely symptomatic patients undergoing
workup
1. Stephenson J et al. Support Care Cancer. 2006;14(4)348-353.
2. Lichter I et al. J Palliat Care. 1993;9(2):19-21.
3. Bruera E et al. J Pain Symptom Manage. 1996;11(3):147-153.
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Benefits of mechanism-based
therapy
• Potentially more effective in certain
scenarios
• Facilitates systematic approach that
identifies all possible contributors
• Guides treatment of underlying causes
• Informs choices of second and third
antiemetics
• Minimizes risks of side-effects
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Opioid-induced Nausea and Vomiting
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Opioid-induced Nausea and Vomiting
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Opioid-induced Nausea and Vomiting
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Opioid-induced Nausea and Vomiting
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Opioid-induced Nausea and Vomiting
Metoclopramide
Haloperidol
Prochlorperazine
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Opioid-Induced N/V
• D2 antagonists first-line
• Generally resolves within 3-5 days of
continued use
• 10-20% dose reduction may alleviate
nausea without loss of analgesia1
• Opioid rotation also effective2
1. Fallon MT et al. BMJ. 1998;317(7150):81.
2. De Soutz ND et al. J Pain Symptom Manage. 1995;10(5):378-384.
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Chemotherapy-induced nausea and vomiting
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Chemotherapy-induced nausea and vomiting
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Chemotherapy-induced nausea and vomiting
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Chemotherapy-induced nausea and vomiting
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Chemotherapy-induced nausea and vomiting
Ondansetron
Dexamethasone
Aprepitant
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Impaired GI Motility
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Impaired GI Motility
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Impaired GI Motility
Metoclopramide
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Radiation-associated N/V
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Radiation-associated N/V
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Radiation-associated N/V
5HT3 antagonists
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Brain Tumor
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Brain Tumor
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Brain Tumor
Dexamethasone
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Motion-associated N/V
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Motion-associated N/V
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Motion-associated N/V
Scopolamine
Diphenhydramine
Promethazine
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Malignant Bowel Obstruction
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Malignant Bowel Obstruction
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Malignant Bowel Obstruction
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Wood, G. J. et al. JAMA 2007;298:1196-1207.
Malignant Bowel Obstruction
Metoclopramide
Haloperidol
Dexamethasone
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Malignant Bowel Obstruction
• Most common in ovarian, colorectal CA
• Interventional management
– Surgery if prognosis > 2 mos
– Stent, NG tubes, venting PEG tubes
• Medical Management
– Analgesic: opioid
– Antisecretory: Octreotide/anticholinergic
– Antiemetic: Metoclopramide/haloperidol
– Steroid: Dexamethasone
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Nonpharmacological Therapy
• Avoid strong smells or other triggers
• Small, frequent meals
• Limit oral intake during severe episodes
• Relaxation techniques
• Acupuncture and acupressure (P6
stimulation)1
1. Vickers AJ. J R Soc Med. 1996;89(6):303-311.
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Refractory/Intractable N/V
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Refractory/Intractable N/V
• Schedule around-the-clock
• Add second agent to block other
implicated receptors
• Prophylactic dosing
• Treat underlying cause if possible
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Refractory/Intractable N/V
• Less traditional agents
– Dexamethasone (Decadron)
– Mirtazapine (Remeron)
– Dronabinol (Marinol)
– Olanzapine (Zyprexa)
– Megestrol (Megace)
– Thalidomide (Thalomid)
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5HT3 Antagonists
• Effective for:
– Chemotherapy-induced N/V1
– Radiation therapy-induced N/V2
– Post-operative N/V3
– Smaller studies suggest efficacy for nausea due to opioids4 or uremia5
• Otherwise, no more effective than cheaper D2 antagonists for most common causes of N/V6
1. Kris MG et al. J Clin Oncol. 2006;24(18):2932-2947.
2. Roberts JT et al. Oncology. 1993;50(3)173-179.
3. Gan TJ et al. Anesth Analg. 2003;97(1):62-71.
4. Sussman G et al. Clin Ther. 1999;21(7)1216-1227.
5. Ljutic D et al. Kidney Blood Press Res. 2002;25(1)61-64.
6. Weschules DJ et al. Am J Hosp Palliat Care. 2006;23(2):135-149.
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Polypharmacy
• Most anti-emetics are centrally active
• Mechanism-based therapy prevents use of
multiple medications antagonizing same
receptor
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Conclusions
1. Mechanism-based approach
• Careful assessment to determine etiology
• Use knowledge of pathophysiology to determine receptors underlying symptoms
• Choose antiemetic to block implicated receptors
• Also treat underlying etiology
2. Refractory/Intractable N/V
• Multiple agents, around-the-clock and prophylactically
• Less traditional agents
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Questions?