Nausea & Vomiting

Nausea & VomitingBrian H. Black D.O.

Learning Objectives Review the importance of Nausea & Vomiting in both

acute and palliative settings

Discuss and review key anatomic considerations

Discuss receptors important for appropriate medication selection and treatment

Describe a mechanistic approach

Terminology

nau·se·a

ˈnôzēə,-ZHə

noun

a feeling of sickness with an inclination to vomit

synonyms: sickness, biliousness, queasiness, “swimmy”, lothing, gagging, sea/air/car sickness

Terminology

re·gurge

ˈrəˈgərj, rēˈ-, -gəj, -gəij

Verb

Passive retrograde movement of ingested material, usually before it has reached the stomach

synonyms: dry heave, retch, drive the bus, “puke in my own mouth”, “barf a little”, boff, or “be sick”

Terminology vom·it

ˈvämət/

Verb or present participle

eject matter from the stomach through the mouth

synonyms: heave, retch, get sick, throw up, puke, purge, hurl, barf, upchuck, bark, spew, ralph, or “be sick”

How do we avoid toxins? Aka…why do we vomit? Progressive Failsafe Measures are plenty in the human

body which help prevent toxic absorption

Examples include: Appearance Smell Taste GI receptor stimulation AND… VOMITING

Sometimes the dx is just not that difficult…

Epidemiology Nausea & Vomiting is common

cc in 2% a component in > 20%

Only 25% of pts with symptoms visit a physician Thus stats likely significantly under-represent the problem

It is more common in those 15-24 yo as a single presenting complaint, but nausea is a major component of morbidity

Cost estimates - over 4 billion/yr in U.S.

Complications include hypokalemia and metabolic acidosis which can lead to serious illness or death

What pathway could be involved?

A 46 yo obese female presents with nausea s/p cholecysectomy three days ago. She has dysuria. She notes worsening symptoms after she eats at which point she occasionally vomits. She is taking the IR morphine as prescribed for pain on a regular basis and pain is a 4/10.

What pathway is involved this pts nausea? A.) Vagal & splanchnic mechanoreceptor firing d/t stretch d/t Ileus B.) SE of Morphine acting on the chemoreceptor trigger zone C.) Urinary infection s/p unnecessary cath placement D.) Substance P and histamine release from pain and inflammation E.) Any or all of the above

What pathway could be involved?

A 46 yo obese female presents with nausea s/p cholecysectomy 4 days ago. She has dysuria. She notes worsening symptoms after she eats at which point she occasionally vomits. She is taking the IR morphine as prescribed for pain on a regular basis and pain is tolerable

What pathway is involved in her nasuea? A.) Vagal & splanchnic mechanoreceptor firing d/t stretch caused by

Ileus B.) SE of Morphine acting on the chemoreceptor trigger zone C.) Urinary infection s/p unnecessary cath placement D.) Substance P and histamine release from pain and inflammation E.) Any or all of the above

Vomiting Anatomy

Nausea is caused by many disease states and is often multi-factorial.

Some medications are more effective than others for different causes.

What are the common pathways?

How do we approach treatment?

A Categorical Approach

A Machanistic Approach – The Anatomy of Vomiting

Key Receptors

Muscarinic / Acetylcholine (M1)

Histamine (H1)

Serotonin aka 5- HydroxyTryptamine (5-HT3 / 4)

Dopamine (D2)

Neurokinin 1 (NK1)

Gamma-aminobutyric acid (GABA)

Patho-physiology

Pertinent Physiologic Pathways

Central pathway at brainstem

Treatment considerations

The right Rx at the right time

Leveraging of S.E.

Limitation of testing

Consideration for cost

Multi-drug strategies

Non-pharmaceutical options

The Art of War

“It is said that if you know your enemies and

know yourself, you will not be imperiled in a hundred battles…”

Sun Tzu

A Mechanistic Approach(is a rational & focused therapeutic strategy)

VOMIT(c)

Vestibular cOnstipation (and other Enteric Dysfunction) Metabolic Derangement Infection / Inflammation Toxins Cortical / Central

What’s the Neurotransmitter? An 72 yo WF presents to the Emergency room stating she has severe nausea

of sudden onset. She was reaching down to get the trash and suddenly noted ringing in her ears and dizziness. She denies vision changes or difficult swallowing. She has had this before and has several meds at home. She calls you because she is now confused which one to take.

Which of the following treatments are likely to act on the main neurotransmitters involved? A.) Haldol B.) Gabapentin C.) Benadryl D.) Ondansetron E.) Vitamin B6

What’s the Neurotransmitter? An 72 yo WF presents to the Emergency room stating she has severe nausea

of sudden onset. She was reaching down to get the trash and suddenly noted ringing in her ears and dizziness. She denies vision changes or difficult swallowing. She has had this before and has several meds at home. She calls you because she is now confused which one to take.

Which of the following treatments are likely to act on the main neurotransmitters involved? A.) Haldol B.) Gabapentin C.) Benadryl D.) Ondansetron E.) Vitamin B6

V is for Vestibular

A Mechanistic Approach

VOMIT(c)

Peripheral Vestibular (VIIIth nerve) Sudden onset Head movement triggers More likely to have auditory symptoms (ringing) Does not require an extensive workup

Central Vestibular Likely involve posterior circulation brainstem symptoms “the D’s”

including Diplopia, Dysphagia, Dysarthria Can indicate more serious disease Often vague symptoms and history Imaging of the brain may be helpful in these cases

A Mechanistic Approach

VOMIT(c)

Peripheral Vestibular Receptors involved: Cholinergic & Histaminic

Scopolamine patch 1.5mg sq q3 days can also be given via IV, or SubQ injection

Meclizine 25mg po tid Promethzaine 25mg po q4-6 hrs prn

A Mechanistic Approach

VOMIT(c)

Vestibular cautions and considerations: Cholinergic/Histaminic blockade can lead to:

Dry mouth Sedation Vision changes Fall risks May exacerbate poor gut motility

Non-rational treatment with H1 / M1 blockade leads to these side effects WITHOUT IMPROVEMENT OF THE NAUSEA!

Anti-cholinergic symptoms are especially concerning in the elderly

What do you do next?

A 52 yo male presents with metastatic lung cancer presents to the clinic with abdominal fullness, nausea, and intermittent vomiting. His sx previously were managed on Ondansetron (zofran), but have become refractory to escalating doses…

What is the next best step? A.) Stop Ondansetron B.) Change Chemo Regimen C.) Add Dexamethethasone D.) Do a Rectal Exam E.) Add Haldol

What do you do next?

A 52 yo male presents with metastatic lung cancer presents to the clinic with abdominal fullness, nausea, and intermittent vomiting. His sx previously were managed on Ondansetron (zofran), but have become refractory to escalating doses…

What is the next best step? A.) Stop Ondansetron B.) Change Chemo Regimen C.) Add Dexamethethasone D.) Do a Rectal Exam E.) Add Haldol

O is for cOnstipation

A Mechanistic ApproachVOMIT(c)

cOnstipation (and other enteric dysfunction) O in this case does not count for a frank obstruction of the

bowel, but instead “obstruction” via constipation and also movement problems of the bowel leading to nausea

Cholinergic, Histaminic, and 5-HT3, 5-HT4 receptors helpful targets

Stimulation of the myenteric plexus (senna) can relieve “obstruction” of the bowel due to constipation

Bowel dysmOtility Loss of bowel movement which impairs food and waste transit Can occur as a result of DM or other dz Prokinetics can be helpful (Metoclopramide stimulates 5HT4

receptors)

A Mechanistic Approach

VOMIT(c)

Laxative therapy can be burdensome & unpredictable Methylnaltrexone

Action: selectively inhibits the Mu receptors of the GI tract Does not affect analgesia 10mg SubQ qod usually effective Rapidly response when effective May be cost prohibitive in some settings

A Mechanistic Approach

VOMIT(c)

cOnstipation (& other enteric dysfunction) cautions and considerations:

Stimulant laxative overuse can lead to … Beware of Prokinetic agents (Meta… Reglan) for

use in frank obstruction! They are contraindicated To prevent constipation you should consider starting a

stool softener with all Narcotic prescriptions… they go together like peas and carrots…

A Mechanistic Approach

Frank and Complete Obstruction of the Bowel Common in ovarian & colon CA Hernias or post-op adhesions can cause partial or

complete obstruction too

Definitive treatment is not pharmaceutical, but surgical Options include: IV fluids and NG tubes, surgical

correction, venting gastrostomy tube, and placing stents across the obstruction

Poor surgical candidates can be approached with endoscopic methods

A Mechanistic Approach

Frank and Complete Obstruction of the Bowel

Opiates and Dopamine antagonists are key

Somatostatin analogues like Octreotide (Sandostatin) used to inhibit secretion of GH, TSH, ACTH, prolactin, and

decrease the release of gastrin, CCK, insulin, glucagon, gastric acid and pancreatic enzymes.

All leading to decreased peristalsis & splanchnic blood flow

M is for Metabolic

A Mechanistic ApproachVOMIT(c)

Metabolic Derangement Correction of the abnormality is key Not all cases of nausea need lab testing Consider a metabolic profile in refractory cases Check a metabolic profile: Ca/Na/K. Cause & Effect

Adrenal disorders Parathyroid disorders Uremia Many others exist. These causes should be considered in resistant

cases and in patients who exhibit signs and symptoms of disease

I is for Infection & Inflammation

A Mechanistic ApproachVOMIT(c)

Receptors involved: Cholinergic, Histaminic, 5HT-3, & Neurokinin 1

Infection Tx of infection (Sepsis, Pyleonephritis, Pneumonia)

Inflammation Of the Gut stimulation of NK1 receptors Corticosteroids may have a role but the evidence is limited

Useful Medications Promethazine (eg. Labrinthitis) Prochlorperazine (Sepsis) Coating Agents like Bismuth or Sulcralfate

Medication Induced Sx

A 69yo diabetic pt with hx of heart failure is seen at the ECF. On review of symptoms she has complaints of nausea. You note she is on 12 medications, and recently started a new anti-depressant.

Which of the following is true regarding medication induced Nausea?

A.) Nausea is an uncommon SE of medication B.) The mechanism involved in most causes of nausea are poorly

defined C.) Medication induced nausea is typically associated with brief

periods of symptoms immediately after administration D.) Medication induced nausea occurs early in use and exhibits a

consistent course over time

Medication Induced Sx

A 69yo diabetic pt with hx of heart failure is seen at the ECF. On review of symptoms she has complaints of nausea. You note she is on 12 medications, and has recently started a new anti-depressant.

Which of the following is true regarding medication induced Nausea?

A.) Nausea is an uncommon SE of medication B.) The mechanism involved in most causes of nausea are poorly

defined C.) Medication induced nausea is typically associated with brief

periods of symptoms immediately after administration D.) Medication induced nausea occurs early in use and exhibits a

consistent course over time

T is for Toxin

A Mechanistic ApproachToxins

Receptors involved usually include Dopamine and 5-HT3 Useful classes: Anti-dopaminergic & 5-HT3 antagonists

Many toxins cause nausea due to stimulation of the chemreceptor trigger-zone

Chemotherapy Medications

Opiates (Morphine) Digoxin Clonadine Polypharmacy NSAIDs local irritation

A Mechanistic Approach Chemotherapy Risk Factors

Multi-day Dose-dense IV (vs po) Short infusion time

Chemotherapy induced nausea and vomiting can be limited by judicious use of treatment

Medication rotation may be helpful

A Mechanistic Approach

VOMIT(C) Cortical / Central

CNS disease (brain mets) Dexamethasone 40mg daily

PO, IV, or SubQ Decrease swelling

Anxiety Tx c Benzo’s can be helpful Ativan 1mg po q4 hrs

A Mechanistic Approach

Cortical / Central / Chemo cautions… considerations … and other c’s:

Anxiolytics Can cause over-sedation Not helpful for the tx of nausea Can help decrease anxiety associated with poor sx control

5HT3 drugs – expensive & not always needed

Corticosteroids – can cause S.E.

Special CasesSpecial Cases:

Carcinomatosis Prokinetics Agents are usually agents of choice Steroids as anti-inflammatories can be very useful as well Examples include Metoclopramide & Decadron combos

Treatment resistant cases D2 Blockage can be very effective via central action Haloperidol 1mg q4 hours (po, IV, or SubQ) Prochlorperazine 5mg po q6 hrs or 25mg PR BID

Multiple Vague SxA 15 year old with recent mood swings pt presents with complaint of vague symptoms of nausea. She is also complaining of some mild dysuria & fatigue.

Which of the following is true: A.) Empiric antibiotics and sx recheck is adequate B.) Lab testing is essential for the dx C.) A med acting at the serotonin receptor (5-HT3) will be the

best anti-emetic for treatment D.) These cases are generally self limited, but NSAIDs or

corticosteroids can be helpful E.) The diagnosis is likely to be psychogenic

Multiple Vague SxA 15 year old with recent mood swings pt presents with complaint of vague symptoms of nausea. She is also complaining of some mild dysuria & fatigue.

Which of the following is true: A.) Empiric antibiotics and sx recheck is adequate B.) Lab testing is essential for the dx C.) A med acting at the serotonin receptor (5-HT3) will be the

best anti-emetic for treatment D.) These cases are generally self limited, but NSAIDs or

corticosteroids can be helpful E.) The diagnosis is likely to be psychogenic

Multiple Vague Sx Nausea Gravidarum ( aka morning sickness)

Affects more than half of all pregnant patients. Usually worse in the early AM hours, but can occur anytime of day Usually abates on its own around the 12th week of pregnancy

Felt to be multi-factoral and related to increased estrogen & progesterone levels, increase in salivation, low blood sugar, as well as the hormone BHCG’s effects.

Women with uncomplicated “morning sickness” have a LOWER risk of miscarriage, preterm delivery, low birth wt, & mortality

Consider alternative causes in a pregnant women if worsening sx or if onset AFTER 9 weeks gestation

Helpful Historical Features Timing?

New Medications could be the culprit Lifestyle changes could lead to anxiety & psychosocial distress Vomiting occurs earlier and in larger amounts in proximal obstructions

(as compared to colorectal obstruction)

Location? Sometimes asking “Where is the nausea” can be helpful to elucidate

symptoms of dizziness, pain, or infection

Others with same illness? Travel? Cases of food poisoning or infection can be shared with others, but this is

not always volunteered by the patient in a nurses intake

Helpful Historical Features

Nausea + Heartburn likely GERD

Vomiting + Abd pain likely organic etiology

Early Morning Vomiting Pregnancy

Feculent Vomiting Consider gastrocolic fistula

Vertigo / Nystagmus Likely Vestibular sx

Nausea+Diarrhea+HA+MyalgiasViral Gastroenteritis

Helpful Historical Features

Nausea + dental /parotid gland changes Bulemia

Nausea + “the D’s” Neurogenic vomiting

Nausea + THC use daily Cannabinoid Hyperemesis

Nausea + Bilious Vomiting Small bowel obstruction

Abd pain, then nausea Appendicitis

Symptoms > 1 months Chronic Nausea & Vomiting

Physical Exam Vitals & Volume

Dehydration (tachycardia & skin tenting with dry mm)

Abdominal exam (including rectal) Nausea, Pain, and Distension Obstruction Hypo or Hyperactive bowel sounds? Masses? Ascites? Tenderness? Hard stool in rectal vault?

Neuro exam Nystagmus

Laboratory Evaluation* CMP (Comprehensive Metabolic Profile)

To review: Renal Function, Liver Function, e- levels (Ca / Na) Urine: UA & BHCG Other testing is done as suggested by Hx & PE

CBC TSH Stool Guiac Amylase/Lipase H Pylori testing Stool cultures

*** Labs and testing should only be done as needed to dx problem & assist identification of appropriate management strategy. If it wont change your treatment, then don’t do it!

Radiology & Procedures MRI / CT of brain (CT if acute Ultrasound “Obstruction series” Other GI studies

For pts with significant dysphasia or sx of GERD with failure to resolve with tx trial EGD

Manometry can be done to eval LES pressure and mm contractions if EGD normal

Gastric emptying study is recommended if gastroparesis is suspected.

Red Flags & Patient Guidelines

Nausea/Vomiting >48 hours Hematochezia or Melena Sustained High Fever Weakness or Altered (focal neuro change) No urination in > 8hrs / or other dehydration signs Diarrhea or severe abd pain Lack of charting

“return if worsening or new symptoms” Rick Bukata

Rx Reference Rapid Review Aprepitant (NK-1 blocker mainly for use in CINV)

Decadron 10mg po/IV (Anti-inflammatory Corticosteroid)

Haldol 1mg po, im, subq q4 hrs prn (D2 Blockade)

Lorazepam 1mg po q4hrs prn (Benzodiazepine Anxiolytic)

Meclizine 25mg po tid (Antihistamine)

Methylnaltrexone 10mg SQ qod (Mu Receptor Antagonist)

Rx Reference Rapid Review

Metoclopramide 10mg po/iv ac&hs (Dopamine agonist & Prokinetic agent)

Ondansetron 4mg po/sl/iv q4 hr prn (5HT3 blockade)

Prochlorperazine 5mg po qid (D2 blockade)

Prochlorperazine 25mg pr bid (D2 blockade)

Scopolamine patch (1.5 mg patch) (Anticholinergic)

Senekot S 1-2 tabs po tid (Stimulant Laxative)

Complementary and Non-Pharmacologic Therapies

Frequent small meals

Removal of all unpleasant and strong scents AVOID ALL PERFUMES LIMIT HARSH CLEANERS

Removal triggering visual stimuli

Coke syrup, B12, Ginger, Cinnamon, Marijuana (dronabaniol)

Accupressure / Accupuncture (Sea Bands on anterior wrist)

Alternative Therapy

Alternative Therapy Accupuncture Accupressure

Sea Bands Herbs

Clove Cinnamon Cumin Ginger Mint

Cold Compress Avoiding Spicy Foods and offending foods Alka-Seltzer

Avoid due to the fact it contains ASA and can irritate stomach lining

Treatment Algorithm

Final Thoughts Promethazine & Prochlorperazine

Sound similar but are very different drugs

Promethazine (Phenergan) MOA: Strong Antihistamine with weak anti-dopaminergic effects most useful for vertigo and gastroenteritis due to infections and inflammation

Prochlorperazine (Compazine) MOA: Antidopaminergic preferred agent for opioid related nausea Can be given 5-10mg po qid Very helpful PR at 25mg PR BID!!!

Both meds: Are commonly used to treat nausea and especially OINV (Opiate induced Nasusea & Vomiting), but no trials (that I know) have compared them head-to-head…

Final Thoughts There is NO EVIDENCE for the use of anxiolytics as isolated

agents in the treatment of nausea

Anxiolytics ARE useful for tx of anxiety as associated with severe nausea & vomiting. SE can include sedation, fall risk, and aspiration

Constipation is a frequent SE of narcotics (and multiple other meds)

Consider starting laxatives when starting opiates and other meds that are associated with constipation

Final Thoughts Nausea & Vomiting is common

Control can dramatically improve quality of life

A rational symptomatic approach can yield improved control & minimize side effects

All approaches should: Identify the etiology of disease Correct the complications Target the receptor for therapy

Fun Fact

Several animals do not vomit: Rats Horses Rabbits Guiena pigs Japanese quail

But Pandas apparently do vomit and there is an entire subculture of artists capturing the thought… and vision… in rainbows…

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nausea in patients with far-advanced cancer. Support Care Cancer. 2004; 12:432-440 Hallenbeck J. Palliative Care Perspectives. New York, NY: Oxford University Press;

2003: pp75-86 Vol. 8, No. 1, January/February 2009 issue of ASHA's Access Audiology. Clark K, Smith JM, Currow DC. The prevalence of bowel problems reported in a

palliative care population. J Pain Symptom Manage 2012;43:993-1000. Basch E, Prestrud AA, Hesketh PJ, et al. American Society of Clinical Oncology.

Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2011;29:4189-98.

Maceira E, Lesar TS, Smith H. Medication related nausea and vomiting in palliative medicine. Ann Palliat Med 2012;1(2):161-176. DOI: 10.3978/ j.issn.2224-5820.2012.07.11

Keith Scorza, MD, et al., Dewitt Army Community Hospital Family Medicine Residency, Fort Belvoir, Virginia. Am Fam Physician. 2007 Jul 1;76(1):76-84

William D. Anderson, MD, et al, University of South Carolina School of Medicine, Columbia, South Carolina, Am Fam Physician. 2013 Sept 15; 99(6): 371-379

Questions?