Review focus will be pearls for palliative patients presenting with GI emergencies in the ED

Discuss mechanism of mbo, including bowel wall edema, fluid loss, electrolyte shifts.

Focus will be on the mechanistic approach to fixing the problem.

Patients w bowel obstruction can have diarrhea due to bacterial liquefaction. In one PIG study, there was found to be a 90 million fold increase in jejunal E coli w ileal obstruction.

Note that there can be FUNCTIONAL mbo, there is motility disorder such as invasion of celiac plexus or other cancer related neuropathy.

4% of pets on opioids can get opioid bowel obstruction or OPIOID BOWEL SYNDROME.

MXM: bowel contents accumulate>damage epithelium>inflammatory response>prostaglandins and vasoactive peptides secreted>bowel dilation and wall edema>colicky pain, n and v.

OCCURENCE IN OVARIAN CA can by up to 42% vs COLORECTAL which can be 28%

MBO medial time of survival is 3 months.

NGT should be placed with some caution as they are not as benign as they appear.

-epistaxis (anticoagulation*)
-aspiration
-erosion
-pain
-sepsis
-nasal cartilage erosion
-otitis

Stunting should be considered if appropriate. Keep in mind that rectal cancers should not have stents placed close to 5 cm from anal verge.

Advocate for your cancer patients with e.g. GI, surgery

Note that patients undergoing surgery and resection have a greater rate of successful anastomoses if octreotide is used beforehand.

Cue for this slide is EDEMA and the mechanistic approach to this problem.

Octreotide and other somatostatin analogues act by:

-inhibiting hormones such as glucagon and insulin
-reduces acid secretion
-slows intestinal mobility
-decreases bile flow
-reduces splanchnic blood flow

THUS reduction in n and v in MBO patients from a reduction in GI secretion.

At rest we produce up to 3l per day of secretions in total.

Studies small but decent:

e.g. 43 terminally ill patients had 300 mcg per day of Octreotide and improved pt quality by 59-72% in 56% of patients.

acts directly on bowel wall deem

NNT is 6

Works well in conjunction w Ranitidine

Mention study of Dex+Ran vs. Octreotide

H2 blocker more effective than PPI at decreasing gastric secretions

Should be your antibnauseant of choice for MBO EXCEPT:

-colicky pain (try Buscopan)
-complete obstruction

Works on 5HT4 and D2 receptors

Easy to titrate

IN/IV/SC

Acts on peripheral receptors in the GI tract without affecting the central effect on pain.

May get similar effects w oral Naltrexone at higher doses.

Contraindicated in setting of bowel obstruction and liver dysfunction.

PRUCALOPRIDE, A SELECTIVE 5HT 4 AGONIST HAS SHOWN BENEFIT IN PERSONS WITH CHRONIC SEVERE FUNCTIONAL* CONSTIPATION, however it has not been studied in opioid induced constipation

Can also consider ORAL NALOXONE, as when given orally there is extensive elimination thru hepatic first pass metabolism resulting in less than 2 % systemic bioavailability

METHYLNALTREXONE AND ALVIMOPAN are quarternary opioid antagonists that are 200 x more potent at selectively blocking peripheral mu receptors over central mu receptors. They have dec lipid solubility and thus do not cross the BBB.

Dose for Resistor is 0.15 mg per kg thus 8-12 mg range. 30 % of patients get relief within 30 min. Up to 80% respond within one hour

Usually give every 48 hours, and no more than every 24 h.

Decrease dose by 50% in CrCL of less than 30 ml per minute.

Pain occurs in a minimum of 75 % of patients w advanced cancer.

Nausea occurs in ~ 25 % of patients w opioids.

Opioids manifest their effect by direct effect/stimulation of the CTZ (4th ventricle of the brain) by increasing vestibular sensitivity to movement and bc of - effect on gut peristalsis.

5HT3 is located in the CRTZ, vagal nerve terminals'

When starting a new opioid, the nausea should improve in 3-5 days.

D2 receptor stimulation by opioids is considered the PRINCIPAL CAUSE of opioid induced nausea and vomiting

Blocks both Dopamine and 5HT3 receptors. Also lowers esophageal sphincter tone, also a prokinetic. Watch for EPS, esp if given quickly or in larger doses.

One of the #1 choices in the Southern Hemisphere for nausea in the ED.

Safe, give at low doses such as 0.5 mg SC/IV

Olanzapine can also be considered based on its dopamine affinity, BUT Risperidone has more affinity to the D2 receptors.

Risperidone blockes D2/5HT 2 receptors and has FEWER EPS SIDE EFFECTS THAN HALDOL

NEUROKININ -1 (NK 1) RECEPTOR ANTAGONIST used mostly for CINV.

Administration of morphine may cause CNS expression of substance P thus might be an alternative

Always consider the dose of the opiate, the route, and CONSIDER ROTATION.

Most antinauseants can cause prolonged QTc so may be wise to review other medications and have a low threshold for ordering ECgs on these patients.

General population has a QTc ranging from 380-400ms.

Prolonged MALE=>450ms
FEMALE=>470

ONES THAT ARE MORE PRONE:
-Diphenhydramine
-Setrons
-Domperidone
-Haldol
-Mirtazapine
-Olanzapine
-Promethazine

Lower risk agents: Metoclopramide and Palonosetron

aka SINGULTUS*

defined as repeated, involuntary spasmodic, diaphragmatic, and inspiratory intercostal muscle contractions with early glottic closure terminating inspiration

There is no physiologic function of the hiccup

Fetal respiration OR some persistent evoluntionary reflex

Phrenic and vagal nerves involved but POORLY UNDERSTOOD.

may be broken down into: disturbance of the phrenic or vagal nerve/disturbance of central CNS control/toxic and metabolic disturbances of drugs/psychogenic causes.

GERD is most frequent cause! Corticosteroids and BDZ are the 2 most common drugs associated with this.

Males 5x more affected than females.

Acute =less than 48 h
Chronic=more than 48 h
Intractable=more than 2 months

Best to start with Metoclopramide and PPI IV

Others to try:

Baclofen (if renal function is OK) at 5 mg tid. Watch for side effects of sedation, vertigo, slurred speech, and weakness. Works as an analog of GABA and is inhibitory at the spinal level.

Gabapentin, again if renal function is ok

Chlorpromazine 25 mg po tied or Haldol

Nifedipine 30-60 mg per day

Sertraline

Acupuncture and vagal nerve stimulation

for some reason, hiccups usually stop during sleep.

they occur in 2-27 % of patients with cancer.

may be the presenting feature of a Gi malignancy

dih=dexamehtasone induced hiccups

Dex has been reported to be associated w hiccups 42 % of the time.

mxm-proposed to lower the synaptic threshold of synaptic transmission in the midbrain and directly stimulate the hiccup reflex arc.

conflict arises in patients with CINV in which dex may be needed.

consider rotation off of dex to other steroid e.g. 15 mg dex to 125 mg methylprednisolone

may be related to large dose of dex.

certainly a male preponderance.

BACLOFEN 5 MG TID

GABAPENTIN START AT 100 TID OR 300 TID.

the only US FDA approved medication for hiccups.

side effects include sedation, urinary retention, hypotension, glaucoma.

Can also give 50 mg IV/sc

Give case in regards to Lower GI bleed in old lady

Stomal bleed and use of octreotide

TO BE DELIVERED TO RESIDENTS FROM BOTH STREAMS

THIS YEAR, TO BE FOR SENIOR RESIDENTS, NEXT YEAR TO ROTATE