PowerPoint Presentation · Tangent: Cannabinoid Hyperemesis Syndrome MNHPC 29 th Annual Conference...

4/6/2019

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MNHPC 29th Annual Conference | April 14–16, 2019 www.mnhpcconference.org

I Think I’m Going to be SickNausea Management in Hospice Care

Aaron Goldish, DO

Allina Hospice


• Definition: the action of making new or secret information

known.

• I have no secret or new information to make known

Disclosures


• 1. Demonstrate the causes for nausea

• 2. Provide treatment options with matched indications for

nausea management with various etiologies

• 3. Describe non-pharmacologic options for nausea

management.

Objectives

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• Vomiting is the process of forcefully expelling gastric contents

• It involves a complex array of neurologic functions including: – Relaxation of the gastroesophageal sphincter

– Contraction of the abdominal wall musculature & diaphragm

– Closure of the glottis

• Primarily controlled by the Medulla (Area Postrema):– Vomiting Center

– Chemoreceptor Trigger Zone

• Nausea also involves the cerebral cortex as we consciously perceive it. There have been functional brain imaging studies showing activation of the cortex while inducing nausea.

Nausea


• Would you rather always be kind of tired, kind of nauseous, or

kind of in pain?

– “Kind of” = bothersome throughout the day, at about 5/10

Tangent: Would You Rather


Motion sickness or Labyrinthitis

• Originates in the inner ear, and travel thru the CN VIII*

– Receptors involved: Muscarinic (M1) & Histaminergic (H1)

– Treatments: Scopolamine (M1) & Meclizine (H1)

Gastric irritants or Bowel irritants

• Originate in the GI tract, and travel via CN X*

– Receptors involved: Serotonergic (5-HT3)

– Treatments: Ondansetron (5-HT3), Olanzapine (5-HT2/D2)

– Steroids may also be helpful to reduce GI inflammation

Etiologies (Part 1)

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Chemoreceptor Trigger Zone

• Area Postrema (medulla) detects toxins in the circulation

• Examples include: uremia, ketoacids, bilirubin, bacterial toxins, Rx– Receptors involved: 5-HT3, M1, H1, D2

– Treatments: Take your pick. Many options available

Other Receptors

• Central NK1 receptors (Tx: Aprepitant)– Can be more beneficial with delayed emesis following chemotherapy

• Cannabinoid CB1 receptors (Tx: Dronabinol)

Etiologies (Part 2)


• Spectrum of nausea commonly associated with pregnancy. – Ranges from mild morning sickness to HG

– HG: extreme form of morning sickness with noted weight loss, dehydration, & ketosis

• Risk factors: – Younger/primagravid mothers

– Prior nausea with estrogen meds, motion sickness, or migraines

– Supertasters (but anosmia decreases risk)

– Multiple gestation

– GERD

– Personal or Family history

• Protective: Alcohol and cigarette smoking

• Evaluate using Pregnancy Unique-Quantification of Emesis (PUQE) score– Point system to assess duration and frequency of nausea/emesis

Tangent: Hyperemesis Gravidarum (HG)


• Onset: – How long has it been going on?

– Does it occur more often at specific times of day or immediately before/after activities or medications

• Palliation/Provoking/Prior: – What are the triggers for the nausea?

– What makes it better?

– Have you had nausea like this before?

• Quality/Quantity: – How much emesis?

– Color/Character:

• Green = Bilious

• Bloody = Mallory Weiss tear*, Malignancy, ulcerations

• Feculent = Bowel Obstruction

• Coffee Grounds = Upper GI bleed

H&P: The most important part of work up!

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• Last Bowel movement

• Recent Drug/Alcohol use

• Other contacts with similar symptoms

Other pertinent questions


• Ondansetron: Anti-5HT3, PO/SL/IV

– Side Effect: headache, constipation, fatigue

– Consideration: Serotonin syndrome, QT prolongation

• Prochlorperazine: Anti-D>Anti-M, alpha adrenergic, PO/IV

– Side Effect: Anticholinergic properties

– Consideration: Extrapyramidal symptoms (EPS), QT prolongation

• Metoclopramide: Anti-D & Pro-kinetic (5-HT4), PO/IV

– Side Effect: Anticholinergic properties

– Consideration: EPS, QT prolongation, CNS depression

Pharmacologic Treatments


• Haloperidol: Anti-D, Anti-cholinergic, PO/SL/IV

– Side Effect: headache, tremor, dystonia, constipation

– Consideration: EPS, QT prolongation, CNS depression, falls,

• Black box warning: elderly dementia-related psychosis treatment have increased risk of death compared to placebo

• Scopolamine: Anti-cholinergic > Anti-histamine, Anti-Serotonin– Transdermal

– Side Effect: dry mouth, confusion, tachycardia, flushing, closed angle glaucoma

• Olanzapine: Anti-5HT2 > Anti 5-HT3, Anti-D & Anti-cholinergic, PO/SL/IV

– Side Effect: drowsiness, weight gain, orthostatic hypotension, weakness

– Consideration: Extrapyramidal symptoms (< other antipsychotics), QT prolongation (< other antipsychotics), CNS depression


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• Aprepitant: Anti-Neurokinin/Substance P, PO/IV

– Side Effect: fatigue, headache, pruritus, diarrhea/constipation

– Consideration: caution with severe liver impairment

• Meclizine: Anti-Cholinergic, PO

– Side Effect: dry mouth, blurry vision, drowsy, fatigue, headache

– Consideration: drug buildup with liver/renal impairment

• Dronabinol: Cannabinoid receptor agonist, PO

– Side Effect: euphoria, abnormal thinking, abdominal pain, N/V

– Consideration: exacerbate psych disorders, Hyperemesis synd



Anti-Dopamine

Anti-Serotonin

Anti-Histamine

Anti-cholinergic

Other

Ondansetron xxx

Prochlorperazine xxx x α adrenergic

Metoclopramide xxx X (high dose)

Pro-Motility

Haloperidol xxx

Scopolamine x x xxx

Olanzapine x xxx x x Anti-α1adrenergic, GABA

Aprepitant Anti-NK-1Augments 5-HT3blockers/steroids

Meclizine xxx xx

Dronabinol CBD


• Risk Factors: women, younger, no prior EtOH use

• Types:

– Acute: Often within 1-2 hours post-chemotherapy. Peaks 4-6 hours post-infusion.

– Delayed: Occurs >24 hours post-chemotherapy (common with cisplatin). Peaks 48-72 hours post-infusion.

• More common in those who have had prior acute CINV

– Anticipatory: conditioned response to prior nausea following chemotherapy.

• Treatment: Utilization of Anti-5HT3, Anti-NK1, and Steroids

– Recent research added olanzapine as adjunctive therapy

Tangent: Chemotherapy induced nausea/vomiting CINV

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• Ginger: Variably effective– Post-op N/V: Probably effective (some studies for and others against

use, but some benefit has been repeatedly noted for post-op nausea)

– CINV: insufficient evidence

• Capsicum: – Post-op N/V: Possibly effective (a couple of studies on application of

cream applied to hand/forearm acupoints)

• Spearmint/Peppermint: – Post-op N/V: Insufficient evidence (some research on essential oil

blend showed some improvement compared to inhaling saline)

Integrative Medicine (Non-pharmacologic treatments)


• Acupuncture/Acupressure– Pressure point P-6 (anterior forearm, three fingers below wrist)

– Some evidence showing benefit for acute CINV and post-op nausea decreased but not post-op vomiting

• Aromatherapy– Ginger, Peppermint, Spearmint

• Self-Hypnosis

• Biofeedback

• Guided imagery

• Music therapy

Integrative Medicine (Non-pharmacologic treatments)


• Polyanna is a 54 yo female with history of metastatic ovarian cancer for the past 2 months she has been receiving neoadjuvantchemotherapy prior to a planned surgical resection. You see her in your palliative care clinic with her husband. She has an emesis basin at the ready, and has been putting her lunch in reverse for the past 36 hours.

• PMH: HTN, Depression

• PSH: Tonsillectomy at age 14 & C-section 20 years ago

• SocHx: denies drug or alcohol use, married with two kids, works as firewoman

Case 1 “Poor Polyanna”

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• Differential Diagnosis?

• Further work-up?

• PP has been unable to keep anything down for days and has

not noted any green or bloody emesis. She feels like the room

is spinning and she has largely been in bed since symptom

onset. She has never had anything like this before. Her son

had a recent URI, but no one else is sick at home/work.

Case 1 continued (History)


• Her mucous membranes are dry and she has skin tenting

• The nausea is worse with turning her head side to side.

• She has a hard time walking from the door to the chair relying

on her husband to help her balance.

• You notice she has a hard time looking at you.

https://www.youtube.com/watch?v=OFl2Rs-wPa4

Case 1 continued (Exam)


• Semi-circular canal inflammation leads to rapid onset severe

nausea with vomiting that is often preceded by URI.

• Frequently presents with vertigo and exam can show

horizontal nystagmus

• Treatment: Meclizine (H1) or Scopolamine help with

symptoms, occasionally steroids can decrease the

inflammation, but caution should be used as this can worsen

bacteria/fungal infections.

Labyrinthitis/Vestibulitis

https://www.youtube.com/watch?v=OFl2Rs-wPa4

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• Occurs in acute or chronic marijuana users

• Phases

– Prodromal: abdominal discomfort, mild nausea

– Hyper-emetic: Lasts 24-48 hours, relieved by hot showers

– Recovery: symptom resolution until marijuana is used again

• Treatment: IV fluids, anti-emetics, and benzodiazepines

– Residual symptoms may be treated with Haloperidol

Tangent: Cannabinoid Hyperemesis Syndrome


• Acute Illness Associated With Cannabis Use, by Route of Exposure: An Observational Study

– Recent study out of Annals of Internal Medicine from Denver, CO ED

• 2567 visits attributed in part due to cannabis over 5 years

– Most common: 788 (30.7%) related to GI symptoms including CHS

– 2nd Most common: 762 (29.7%) due to Intoxication

– 3rd Most common: 633 (24.7%) with psychiatric symptoms.

• Edible vs Inhalation (If not documented as edible, assumed inhalation)

– Inhalation had higher incidence of CHS compared to edible

– Edible had higher rate of intoxication, acute psych issues, & CV symptoms

• Edibles make up 0.32% of sales (by weight THC), but caused 10.7% of ED visits

Tangent: Cannabinoid Hyperemesis Syndrome


• Polly recovers well from her vertigo and nausea with meclizine,

and returns home with planned surgical resection after

completion of her neoadjuvant chemotherapy.

• She is made NPO before presenting for surgery and is given

Keflex prior to her surgery. She is put under general

anesthesia and wakes up with nausea and vomiting.

• She has no prior listed allergies, and has tolerated penicillin &

amoxicillin in the past.

Case 2 “Pollyanna Returns”

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• What are the possible etiologies for her nausea?

– Post-anesthesia nausea

– Keflex: Nausea/vomiting rare side effect

• What treatment would you use in this situation?

Case 2 continued


• Nausea/Vomiting in the first 24 hours after surgery

• Risk Factors: Pre-op N/V, female, prior PONV or CINV, non-smoker, age <50– Anesthesia related: general>regional, volatile anesthetics, longer

anesthesia, Nitrous oxide, post-op opioids

– Surgery related: cholecystectomy, GYN procedures, Laparoscopy

• Treatment options: based on risk can use a number of options– Pretreat with variety of meds (ondansetron, metoclopramide,

dexamethasone, aprepitant, scopolamine, haldol)

– Acupuncture

Post-operative nausea & vomiting (PONV)


• Polly is given ondansetron with rapid resolution of her post-

anesthesia nausea. Her pain is managed with Percocet 5-325

mg (taking 3-4 per day) on the medicine ward. She has had

good oral intake, but has started to feel nauseated on the day

of planned TCU discharge.

• What other details would you want to know?

Case 3 “Pollyanna Forever”

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• Other important details:

– Last BM = 5 days ago

– Associated symptoms = abdominal distension and pain

– Emesis character = brown and foul smelling

• What is the most likely etiology for this nausea?

– Partial versus complete bowel obstruction

Case 3 continued


• What treatments would you use in this case?

Case 3 continued


• Types– Partial vs Complete

– Proximal (more vomiting, yellow/green emesis) vs Distal (feculent, abdominal distension)

• Differential: Ileus (Peristalsis halted)

• Treatment geared towards symptomatic relief– Opioids for pain

– Metoclopramide if partial obstruction to help clear it and for nausea

– Haldol or Compazine may also help relieve nausea

– Continued vomiting may require initiation of:

• Dexamethasone

• Scopolamine patch (helps with nausea and secretions)

• Octreotide (Somatostatin analog, SQ infusion): reduce GI secretions & slow gut transit

Bowel obstruction

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• Nausea is common following initiation of opioids.

• Mechanism: triggers chemoreceptor trigger zone, stimulate

vestibular apparatus, and induce constipation

• Variable sensitivity on a case by case basis

• Tolerance often occurs within a few days, but can be up to a

week.

Tangent: Opioid associated nausea


• Polly has returned home with her daughter Robin, and enrolled in hospice after her disease progressed despite adjuvant chemotherapy. Her bowel obstruction has resolved, and although she initially became nauseated with morphine this cleared in a few days. Unfortunately she is now only eating bites but still feels nauseated throughout the day.

• She has also started to progress to active dying and is losing the ability to swallow and is demonstrating terminal delirium with pulling at her sheets and clothes.

Case 4 “Pollyanna and Robin”


• This is a fairly common presentation in hospice, and we try our

best to minimize polypharmacy.

• What medication would you use for this nausea?

– Would you do anything differently if she had QT prolongation on

her last EKG?

– What if she was having trouble managing secretions?

Case 4 continued

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• Polyanna’s nausea & agitation improved, and she was able to

die peacefully at home surrounded by her family per her

wishes. Her family are very appreciative for your and your

hospice teams assistance to provide her with a good death.

Case 4 continued


Questions?


1. Hasler WL. Nausea, Vomiting, and Indigestion. In: Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Jameson J, Fauci A.S., Kasper D.L., Hauser S.L., Longo D.L., Loscalzo J Eds. J. Larry Jameson, et al. eds. Harrison's Principles of Internal Medicine, 20e New York, NY: McGraw-Hill; Retrieved March 19, 2019, from http://accessmedicine.mhmedical.com/content.aspx?bookid=2129&sectionid=192012750.

2. Periyakoil, VS. & Quill, TE. Primer of palliative care, 6e. Chicago, IL: American Academy of Hospice and Palliative Medicine. 2019. 72-80. Print.

3. Hallenbeck, J. (2015, May). Fast Facts and Concepts #5, The Causes of Nausea and Vomiting (V.O.M.I.T.). Retrieved March 19, 2019, from https://www.mypcnow.org/blank-ggr79

4. Von Gunten, CF. Muir, CJ. & Marks S. Fast Facts and Concepts #45, Medical Management of Bowel Obstructions. Retrieved March 19, 2019, from https://www.mypcnow.org/blank-lwvgm

5. Longstreth, GF. Approach to the adult with nausea and vomiting. Retrieved March 18, 2019, from https://www.uptodate.com/contents/approach-to-the-adult-with-nausea-and-vomiting?search=nausea&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

6. Hesketh, PJ. Prevention and treatment of chemotherapy-induced nausea and vomiting in adults. Retrieved March 18, 2019, from https://www.uptodate.com/contents/prevention-and-treatment-of-chemotherapy-induced-nausea-and-vomiting-in-adults?search=nausea&source=search_result&selectedTitle=4~150&usage_type=default&display_rank=4

7. Non-drug Treatments for Nausea and Vomiting | American Cancer Society. (2017, Feb 13). Retrieved March 20, 2019, from https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/nausea-and-vomiting/other-treatments.html

8. Acupressure for Nausea and Vomiting. (2017, Sept 11). Retrieved March 20, 2019, from https://www.mskcc.org/cancer-care/patient-education/acupressure-nausea-and-vomiting

9. Smith, JA. Fox, KA. & Clark, S. Clinical features and evaluation of nausea and vomiting in pregnancy . Retrieved March 24, 2019, from https://www.uptodate.com/contents/clinical-features-and-evaluation-of-nausea-and-vomiting-of-pregnancy

10. Hesketh, PJ. Prevention and treatment of chemotherapy-induced nausea and vomiting in adults. Retrieved March 25, 2019, from https://www.uptodate.com/contents/prevention-and-treatment-of-chemotherapy-induced-nausea-and-vomiting-in-adults?search=cinv&source=search_result&selectedTitle=1~79&usage_type=default&display_rank=1

11. Navari, RM. Qin, R. Ruddy, KJ. Liu, H. Powell, SF. Bajaj, M. Dietrich, L. Biggs, D. Lafky, JM. Liprinzi, CL. (2016). Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. NEJM, 375(2), 134-142.

12. Comparative Effectiveness Chart for Postoperative nausea and vomiting (PONV). Retrieved March 25, 2019, from https://naturalmedicines.therapeuticresearch.com/databases/comparative-effectiveness/condition.aspx?condition=Postoperative+nausea+and+vomiting+(PONV)

13. Galli, JA. Sawaya, RA. Friedenberg, FK. Cannabinoid Hyperemesis Syndrome. Retrieved March 25, 2019, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576702/

14. Feinleib, J. Kwan, LH. Yamani, A. Postoperative nausea and vomiting. Retrieved March 25, 2019, from https://www.uptodate.com/contents/postoperative-nausea-and-vomiting?search=post%20anesthesia%20nausea&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

15. Monte, AA. Shelton, SK. Mills, E. Saben, J. Hopkinson, A. Sonn, B. Devivo, M. Chang, T. Fox, J. Brevik, C. Williamson, K. Abbott, D. Acute Illness Associated with Cannabis Use, by Route of Exposure: An Observational Study. Annals of Internal Med. [Epub ahead of print] doi: 10.7326/M18-2809

References

http://accessmedicine.mhmedical.com/content.aspx?bookid=2129&sectionid=192012750

https://www.mypcnow.org/blank-ggr79

https://www.mypcnow.org/blank-lwvgm

https://www.uptodate.com/contents/approach-to-the-adult-with-nausea-and-vomiting?search=nausea&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

https://www.uptodate.com/contents/prevention-and-treatment-of-chemotherapy-induced-nausea-and-vomiting-in-adults?search=nausea&source=search_result&selectedTitle=4~150&usage_type=default&display_rank=4

https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/nausea-and-vomiting/other-treatments.html

https://www.mskcc.org/cancer-care/patient-education/acupressure-nausea-and-vomiting

https://www.uptodate.com/contents/clinical-features-and-evaluation-of-nausea-and-vomiting-of-pregnancy

https://www.uptodate.com/contents/prevention-and-treatment-of-chemotherapy-induced-nausea-and-vomiting-in-adults?search=cinv&source=search_result&selectedTitle=1~79&usage_type=default&display_rank=1

https://naturalmedicines.therapeuticresearch.com/databases/comparative-effectiveness/condition.aspx?condition=Postoperative+nausea+and+vomiting+(PONV)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576702/

https://www.uptodate.com/contents/postoperative-nausea-and-vomiting?search=post anesthesia nausea&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

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