nausea & vomiting
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Nausea & Vomiting. Brian 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 - PowerPoint PPT PresentationTRANSCRIPT
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…
References: Glare P, et al. Systemic review of the efficacy of antiemetics in the treatment of
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?