Nausea, Vomiting, and Malignant , g, g Bowel Obstruction

Transcription

Nausea, Vomiting, & Malignant Bowel Obstruction
Dr. Nicola Macpherson
Charting a New Course for Improved Patient Care
Hawaiian Highlights CME Cruise
April 20 – May 01, 2015
Nausea, Vomiting, and Malignant ,
g,
g
Bowel Obstruction
Dr. Nicola Macpherson MD FRCPC (Anaesth)
Clinical Assistant Professor, Family Medicine, UBC
Clinical Assistant Professor, Anaesthesiology, Pharmacology & Therapeutics UBC
& Therapeutics, UBC
Clinical Assistant Professor, Academic Family Medicine, University of Saskatchewan
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1
April 20 – May 01, 2015
Faculty/Presenter Disclosure
• Faculty: Dr. Nicola Macpherson
• Relationships with commercial interests:
–
–
–
–
Grants/Research Support: N/A
pp
Speakers Bureau/Honoraria: N/A
Consulting Fees: N/A
Other: N/A
Other: N/A
Slide 1 of 3 Conflict of Interest slides as mandated by the College of Family Physicians of Canada
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2
April 20 – May 01, 2015
Disclosure of Commercial Support
• This program has received financial support from: N/A
• This program has received in‐kind support from: N/A
This program has received in‐kind support from: N/A
• Potential for conflict(s) of interest: N/A
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3
April 20 – May 01, 2015
Mitigating Potential Bias
• N/A
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April 20 – May 01, 2015
Speaker Disclosure
• I will probably cover off ‐ label use of medications!!
April 2015
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5
April 20 – May 01, 2015
Tailoring the Treatment
NAUSEA AND VOMITING
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6
April 20 – May 01, 2015
“M”‐esis
• Metastases
• Mucosal irritation
• Meningeal irritation
• Mechanical obstruction
• Movement
• Motility
• Mentation
• Metabolic
b li
• Medications
• Myocardial
• Microbial
April 2015
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7
April 20 – May 01, 2015
as
Raised
ICP
Limbic System:
Memories
Olfactory Centre
VOMITING CENTRE
Visual Centre:
Sights
Vestibular Apparatus:
Motion, position, opioids,
cerebellar tumours
Chemoreceptor
Zone
(CRTZ):
Ch
t Trigger
T i
Z
(CRTZ)
Some chemotherapies, opioids, septic
toxins, uremia, ketosis, hypercalcemia,
emetogenic peptides - OUTSIDE BBB
Dr. N. Macpherson’s Unified Theory of Barfing
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8
April 20 – May 01, 2015
Smell Centre
Limbic System
Substance P / NK1
Visual Centre
Vestibular Apparatus
Chemoreceptor Trigger Zone
(CRTZ)
VOMITING CENTRE
April 2015
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April 20 – May 01, 2015
ANTIDOPAMINES
ANTIMUSCARINICS
ANTIHISTAMINES
ANTISEROTONINS
Chlorpromazine
Scopolamine
Chlorpromazine
Methotrimeprazine Domperidone (P)
Cyclizine
Cyclizine
Droperidol Meclizine
Dimenhydrinate
Chlorpromazine
Diphenhydramine
Haloperidol Dimenhydrinate
Hydroxyzine
Methotrimeprazine
Diphenhydramine
Meclizine
Metoclopramide
Hydroxyzine
Methotrimeprazine
Perphenazine
Methotrimeprazine
Promethazine
Prochlorperazine
p
p
Olanzapine
Olanzapine
Fluphenazine
Promethazine
Prochlorperazine
Perphenazine
Scopolamine
Prochlorperazine
Olanzapine
Scopolamine Scopolamine
ANTISEROTONINS
CANNABINOIDS
BENZODIAZEPINES
SUBSTANCE P/NK1
Dolasetron
Dolasetron Granisetron
Ondansetron
Tropisetron
Olanzapine www.seacourses.com
Nabilone
Dronabinol Lorazepam
Lorazepam Diazepam
Midazolam Aprepitant
Aprepitant ANTISEROTONINS
Metoclopramide
10
April 20 – May 01, 2015
Matching MoA to Mechanism of Nausea 1
CRTZ
Nausea predominates, N
d i t
NOT relieved by vomiting:
Opioids, chemo, liver failure, uremia, other toxins, tumour emetogenic peptides, hypomagnesemia, yp
,
hypercalcemia, hyponatremia, infection April 2015
Drug Classes
Antidopamines
Mixed D2 & 5‐HT
Antiserotonins
A ti
t i
Drugs of Choice
Methotrimeprazine
p
Prochlorperazine
Haloperidol
Droperidol
p
Metoclopramide
Ondansetron
Granisetron
G i t
Dolasetron
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11
April 20 – May 01, 2015
Vestibular
Motion sickness, ,
opioids, acoustic neuroma, metastases at base of skull, labyrinthitis
April 2015
Drug Classes
Antihistamines
Anticholinergics
Drugs of Choice
Dimenhydrinate
y
Methotrimeprazine
Meclizine
Hyoscine hydrobromide
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12
April 20 – May 01, 2015
GI Irritants
Drug Classes
Antiserotonins
Mixed D2 & 5HT
Mixed D
& 5HT
Blood and drugs
Antihistamines
Antidopamines
April 2015
Drugs of Choice
Ondansetron
Granisetron
Dolasetron
Metoclopramide
Dimenhydrinate
Methotrimeprazine
Meclizine
Methotrimeprazine
Prochlorperazine
Haloperidol
Droperidol
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13
April 20 – May 01, 2015
Dysmotility
St i il
Stasis, ileus
April 2015
Drug Classes
Mixed D2 & 5HT
Peripheral D2
Drugs of Choice
Metoclopramide
p
Domperidone
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14
April 20 – May 01, 2015
Obstruction
Bowel Obstruction
Drug Classes
Somatostatin Analogue
Antidopamines
Anticholinergics
April 2015
Drugs of Choice
O t tid
Octreotide
Haloperidol
Hyoscine butylbromide
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April 20 – May 01, 2015
Higher CNS
Drug Classes
Drugs of Choice
Anxiety, fear, pain,
Anxiety
fear pain
anticipation, sights,
smells, memories
BZDPs
Lorazepam
Dronabinol
Nabilone
April 2015
Cannabinoids
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16
April 20 – May 01, 2015
Raised ICP
Primary or secondary lesions
April 2015
Drug Classes
Steroids
Antihistamines
Drugs of Choice
Dexamethasone
Dimenhydrinate
Methotrimeprazine
Meclizine
Promethazine
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April 20 – May 01, 2015
Summaryy
• Make first choice based on best guess at mechanism for
nausea
• If first drug doesn’t work, pick one that covers the
missing receptors
• Don’t add a second from the same class
• Strong anticholinergics (antikinetics) counteract
metoclopramide (prokinetic)
• Very little need for an antiserotonin
• Very often need for combination therapy
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April 20 – May 01, 2015
Questions??
April 2015
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April 20 – May 01, 2015
MALIGNANT BOWEL
OBSTRUCTION
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April 20 – May 01, 2015
The sun CAN Th
CAN
rise (or set) on an obstructed bowel!
April 2015
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April 20 – May 01, 2015
Definition
• Mechanical or functional obstruction of the
progress off food
f d and
d fluids
fl id th
through
h th
the
gastrointestinal tract
April 2015
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April 20 – May 01, 2015
Incidence
• Overall 3-5%
• Most common:
– Ovarian cancer (up to half of women with
ovarian cancer may develop an obstruction)
– Colon cancer (up to a quarter of patients with
colon cancer may develop an obstruction)
– Melanoma lung, breast, gastric, biliary, and
pancreatic cancers
April 2015
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April 20 – May 01, 2015
gy - Mechanical
Aetiology
• Extrinsic intestinal
compression
i
E d l i l
• Endoluminal
obstruction
• Intramural
infiltration
April 2015
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April 20 – May 01, 2015
gy - Mechanical
Aetiology
• Intraluminal tumors may
occlude
l d th
the b
bowell llumen
or provoke intussusception
• Mesenteric and omental
tumor involvement may
angulate the bowel and
provoke extramural bowel
occlusion
April 2015
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April 20 – May 01, 2015
gy - Functional
Aetiology
• Extensive mesenteric infiltration
• Infiltration of the enteric or celiac plexus
may cause severe impairment in
peristalsis and consequent obstruction due
to dysmotiliy
April 2015
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April 20 – May 01, 2015
p y
gy
Pathophysiology
Venous
Outflow
Obstruction,
Ischemia
Gut
Distension
Increase in
Gut
Secretion
April 2015
Fluid
Backup,
Vomiting
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April 20 – May 01, 2015
(
y)
Examination (History)
•
•
•
•
•
Nausea: 100%
Vomiting: 87%–100%
Colic pain: 72%–80%
Constant pain: 56%–90%
Absence of stools or flatulence in the
previous
pre io s 72 hours:
ho rs 85%–93%
85% 93%
• May see paradoxical diarrhea in partial
obstruction
April 2015
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April 20 – May 01, 2015
(
y)
Examination (History)
• In proximal obstruction:
– Nausea is intense and presents early
– Vomiting is frequent, with an aqueous, mucous or
biliary appearance and has little odor.
I lower
l
b t ti
• In
obstruction:
– Vomiting usually occurs later, is dark, and has a
strong odor
– Bacterial liquefaction of the retained intestinal
content proximal to the obstruction causes the
characteristic appearance and smell of feculent
vomit
April 2015
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April 20 – May 01, 2015
( y
)
Examination (Physical)
• The more distal the obstruction, the more
marked
k d th
the abdominal
bd i l di
distention
t ti
• Borborygmi occurs earlier
B
l sounds
d d
t
• Bowel
decrease or di
disappear llater
• Ascites (41%)
• Cachexia
Cache ia (22%)
• Palpable abdominal tumor masses (21%)
• Marked cognitive deterioration (23%)
April 2015
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April 20 – May 01, 2015
Results - Lab
•
•
•
•
Anemia (70%)
Hypoalbuminemia (68%)
Alterations in hepatic enzymes (62%)
Dehydration and prerenal failure (44%)
April 2015
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April 20 – May 01, 2015
y
Results – Lab and X-ray
Gastric Outlet/ Proximal
Duodenum
• P
Primary
i
loss
l
off gastric
ti
(acid) secretions:
– Metabolic alkalosis
H
hl
i
– Hypochloremia
– Hypokalemia
– Later:
• Development of
acidosis due to
sepsis
April 2015
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April 20 – May 01, 2015
y
Results – Lab and X-ray
Proximal Small Bowel
• Loss
L
off biliary,
bili
pancreatic, AND
gastric secretions
– Hypochloremia
– Hyponatremia
– Hypokalemia
– Lower bicarb levels
earlier in course
April 2015
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33
April 20 – May 01, 2015
y
Results – X-ray
More Distal SBO
April 2015
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April 20 – May 01, 2015
y
Results – X-ray
LBO with Competent Ileocecal Valve
April 2015
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35
April 20 – May 01, 2015
y
Results – X-ray
LBO with Incompetent Ileocecal Valve
April 2015
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36
April 20 – May 01, 2015
p
Complications
of MBO
• Death from:
– Perforation
– Ischemic bowel
– Sepsis
p
– Fluid and electrolyte abnormalities
– MSOF
– CV-Respiratory
Collapse
CV R
i t
C ll
• Elevation of the diaphragm impairs ventilation
• Increased intra-abdominal pressure reduces
venous return
t
to
t the
th heart
h t
April 2015
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April 20 – May 01, 2015
g y
Rx - Surgery
• Few patients with advanced cancer are suitable for
surgery
• If ALL of the following are present, the patient should
have surgical opinion:
g postoperative
– Suspected easily reversible cause e
e.g.
adhesion, single obstructing lesion
– Patient in good general condition i.e. independent,
active,
nutritional
acti e reasonable n
tritional state without
itho t
widespread disease
– Patient willing to undergo surgery
• Surgical opinion may also be sought where there is an
element of doubt, or if patient requests surgical opinion
April 2015
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April 20 – May 01, 2015
g y
Rx - Surgery
• Studies involving a series of surgical cases of
MBO have shown:
–
–
–
–
30-day mortality of 25% (9%–40%)
postsurgical
morbidity
p
g
y of 50% (9%–90%)
(
)
rate of reobstruction of 48% (39%–57%)
median survival of 7 months (2–12 months)
• More
recently
better
M
tl published
bli h d results
lt are no b
tt
than those published in the past
– Improvements in surgical techniques and
perioperative care have not improved outcome
April 2015
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April 20 – May 01, 2015
g y
Rx - Surgery
• Worse outcome (higher mortality):
– Age > 65
– Advanced disease elsewhere
– Previous RT to abdo/pelvis
P it
l carcinomatosis
i
t i
– Peritoneal
– Multiple occlusive levels
– More than 3 L of ascites
– Palpable tumour masses
– Malnutrition (hypoalbuminemia)
– Poor general status
• Even in cases where surgery may be technically
possible
April 2015
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April 20 – May 01, 2015
p
Rx – Suck and Drip
•
•
•
•
Control symptoms
R
Reestablish
t bli h flfluid/electrolyte
id/ l t l t b
balance
l
Allow spontaneous resolution
Buy time for further investigations and
decision making
• Maximum one week!!
• In hospitalized patients, removal of the NG
tube was less likely in patients receiving
greater amounts of parenteral hydration
April 2015
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41
April 20 – May 01, 2015
Rx – Suck
• Complications
– Esophagitis
– Gastroesophageal reflux
– Nasal erosions
– Aspiration pneumonia
– Extremelyy uncomfortable!
• If necessary for control of symptoms,
consider conversion to a venting
gastrostomy tube
April 2015
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42
April 20 – May 01, 2015
Rx – Percutaneous Gastrostomy
• For venting, not feeding!
• For
F those
th
who
h cannott gett
good symptom control
without maintaining
digestive aspiration
• Can be placed with the
aid of endoscopy,
endoscopy with
fluoroscopic guidance, or
by surgical means
April 2015
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43
April 20 – May 01, 2015
Rx - Stents
Duodenum
April 2015
Colon
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44
April 20 – May 01, 2015
p
Rx - Drip
• Administration of 1-1.5 L per day IV or SC may
be useful in maintaining electrolyte balance and
preventing adverse effects such as opioid
toxicity and delirium
• BUT:
• Hydration may make some symptoms worse due
to increased third spacing and edema
• Nausea is worse with higher total fluid intake
• Does NOT relieve thirst and dryy mouth
April 2015
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April 20 – May 01, 2015
g
Rx - Gastrografin
• For patients with partial SBO, Gastrografin
may be
b therapeutic
th
ti
• Gastrografin draws fluid into the lumen of
the bowel due to its hypertonicity
– Decreases intestinal wall edema
– Stimulates intestinal peristalsis
• Gastrografin has been found in several
studies to improve
p
bowel function and
decrease length of hospital stay
April 2015
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46
April 20 – May 01, 2015
g
Rx - Gastrografin
• The volume of Gastrografin administered
generally ranges from 7
7.5
5 mL over 30
minutes to 22.5 mL over a course of two
hours
• Can be repeated if initially ineffective, to a
total dose of 100 mL
• The appearance of contrast in the colon 4
to 24 hours later predicted resolution of
SBO with a sensitivityy of 96% and
specificity of 98%
April 2015
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47
April 20 – May 01, 2015
Rx - TPN
• The aim of TPN is the recovery of nutritional
status in patients who are candidates for
surgery
• More controversial in advanced cancer
patients with inoperable MBO
• Should be reserved for patients with:
–
–
–
–
–
Preserved general status
Slow growing tumors
Possibility of response to chemotherapy
Reasonable expectation of survival > 3 mos
No extra-abdominal
extra abdominal complications of cancer
April 2015
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April 20 – May 01, 2015
p
First Report
- 1985
• 40 consecutive patients (16 men
men, 24 women) with bowel
obstruction who were treated at St Christopher’s Hospice
April 2015
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April 20 – May 01, 2015
p
First Report
- 1985
• Aged 26 to 94 years (mean 59)
• 37 of the 40 patients had undergone abdominal surgery
at least once
• 10 patients had previously had a laparotomy for bowel
obstruction at which no further procedures were possible
• Surgical treatment of intestinal obstruction was
considered for every case
• 2 of the 40 patients were considered suitable for
operation.
– Both of them had a single pelvic obstruction
– 1 patient
ti t died
di d 24 h after
ft surgery
– The second lived for another 3 months
April 2015
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April 20 – May 01, 2015
p
First Report
- 1985
• The remaining 38 patients were managed
medically
• 2 received effective palliative chemotherapy
April 2015
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51
April 20 – May 01, 2015
g
Rx – Palliative Management
• Symptom control with aimed at maintaining the
maximum comfort possible
–
–
–
–
Control of nausea, vomiting, and pain
Allowing minimum food intake
Avoiding or withdrawing NG tube
Getting patient home
• Using combination of:
–
–
–
–
Antiemetic(s)
A ti
ti ( )
Potent analgesic
Glucocorticoid
A ti
Antisecretory
t
drugs
d
April 2015
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April 20 – May 01, 2015
Rx – Palliative “5 Anti” Approach
Anti-Pain
Anti-Emesis
Anti Inflammatory
Anti-Inflammatory
Anti-Motility
Anti-Secretory
April 2015
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April 20 – May 01, 2015
Anti-Pain
• Calculate patient’s previous TDD of opioid
and convert to SC dose
• No studies to show any opioid to be better
than any other
• In theory, fentanyl might be best
option due to better tolerance in
dehydrated patients
April 2015
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April 20 – May 01, 2015
Anti-Emesis
• Metoclopramide (use only in patients with
partial obstruction and mild to no colicky
pain)
• Neuroleptics
– Haloperidol (5–15 mg/day)
– Methotrimeprazine
M h i
i ((50–150
0 1 0 mg/day)
/d )
• Anticholinergic agent
– Hyoscine butylbromide (Buscopan®)
120mg/day)
April 2015
(60(60
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55
April 20 – May 01, 2015
Anti-Inflammatory
• Steroids
St id
– Antiemetic
– Anti-inflammatory action reduces peritumour edema
– A meta-analysis in 1999 demonstrated that
dexamethasone, 6-16 mg per day favoured resolution
of MBO in advanced gyne and GI cancer
– Spontaneous resolution 62%-68% with steroids,
33%-57% with placebo
• Most researchers recommend glucocorticoids in
th palliative
the
lli ti ttreatment
t
t off MBO
April 2015
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56
April 20 – May 01, 2015
Anti-Motility
• Anticholinergics:
• (40-120 mg/day)
• Octreotide
• (200 - 900 mcg/day)
/d )
April 2015
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April 20 – May 01, 2015
Anti-Secretory
• Anticholinergics:
• (40-120 mg/day)
• Octreotide
• (200 - 900 mcg/day)
/d )
April 2015
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58
April 20 – May 01, 2015
Rx - Octreotide
• The most important drug in the therapy of MBO
• A somatostatin
t t ti analogue
l
• Inhibits VIP activity in the gut
– Reduces gastric and pancreatic juices
– Reduces and water and electrolyte excretion in the
lumen
– Reduces splanchnic blood flow
– Decreases gut wall edema
– Decreases peristalsis
– Decreases excretion
April 2015
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April 20 – May 01, 2015
Rx - Octreotide
Gut
Distension
Increase in
Gut
Secretion
April 2015
Fluid
Backup,
Vomiting
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60
April 20 – May 01, 2015
Rx - Octreotide
• Not just for MBO!!
• Can sometimes eliminate the need for
surgery
I
id electrolyte
l t l t and
d
• Improves
overallll flfluid,
hemodynamic status
– Lowers perioperative risk
• Can improve the outcome of surgery by
gg
gut wall damage
g such as
minimizing
necrosis (Time is gut!)
April 2015
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April 20 – May 01, 2015
Cocktails to Consider - Bolus
• If bowel completely obstructed or colicky
pain
i is
i significant:
i ifi
t NO M
Metoclopramide!
t l
id !
• Goal is complete bowel rest
 Bolus with IV or SC:





BT opioid dose (10% of TDD)
Haloperidol 0.5-1 mg
Dexamethasone 4-8 mg
Hyoscine butylbromide 10 mg
Octreotide 100-150
100 150 mcg
April 2015
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62
April 20 – May 01, 2015
Cocktails to Consider – 2 Day Inf’n
• Add 2 days of medications to a final
volume
l
off 100 cc NS and
d run att 2 mL/hr
L/h
 2 TDDs of opioid
 Haloperidol 5 mg
 Dexamethasone 20 mg
y
y
g
butylbromide
80 mg
 Hyoscine
 Octreotide 1000 mcg
April 2015
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63
April 20 – May 01, 2015
Cocktails to Consider - Bolus
 Partial obstruction, where colicky pain is
nott significant,
i ifi
t and
d patient
ti t iis passing
i gas:
 Bolus with IV or SC:





BT opioid dose (10% of TDD)
Haloperidol 0.5-1 mg
Dexamethasone 4-8 mg
Metoclopramide 10 mg
Octreotide 100-150 mcg
April 2015
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64
April 20 – May 01, 2015
Cocktails to Consider – 2 Day Inf’n
• Add 2 days of medications to a final
volume
l
off 100 cc NS and
d run att 2 mL/hr
L/h
 2 TDDs of opioid
 Haloperidol 5 mg
 Dexamethasone 20 mg
p
g
80 mg
 Metoclopramide
 Octreotide 1000 mcg
April 2015
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65
April 20 – May 01, 2015
y Agents
g
Rx – Promotility
• Can be used if cramping is not present
and
d if th
the iintention
t ti iis tto normalize
li and
d use
the proximal gut
• More widespread use in Europe
• Still controversial in North America
April 2015
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66
April 20 – May 01, 2015
g
(
Prognosis
(fixed
obstruction))
• The mean survival is 4–5 weeks in
patients
ti t with
ith consolidated
lid t d MBO
• Devastating clinical picture develops
– Intense symptoms
– Rapid deterioration
• Polymodal medical treatment achieves
very high symptomatic control
April 2015
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April 20 – May 01, 2015
g
p
Prognosis
– Inoperable
• Spontaneous resolution in a third
• More than 60% will recur
• Median survival 1 to 3 months
– Unless chemotherapy is an option, which
might prolong survival to 1 to 2 years
re obstruct
– During which time they may re-obstruct
April 2015
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68
April 20 – May 01, 2015
g
p
Prognosis
– Inoperable
• Prevention of recurrence:
– Low residue diet
– Avoid stimulant laxatives
• Magnolax® preferred
– Longterm antisecretory drugs
p ((octreotide
• ? Sandostatin® LAR Depot
acetate)?
April 2015
Sea Courses Hawaii
www.seacourses.com
69
April 20 – May 01, 2015
Questions for the Bartender?
www.seacourses.com
70

Nausea, Vomiting, and Malignant , g, g Bowel Obstruction

Transcription

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