Nausea and Vomiting

PEBC

nausea

unpleasant sensation experienced prior to vomiting with underlying causes (this is a symptom, not diagnosis)

• acute < 1 week

• chronic >1 month

vomiting (emesis)

oral discharge of gastric contents

retching

muscle contraction without expulsion of gastric contents (gagging or dry heaving)

conditions associated with nausea and vomiting

GI:

• PUD

• Pyelonephritis

• Gastroenteritis

• functional dyspepsia

• pancreatitis

• gastric outlet/ bowel obstruction

• gastroparesis

• gastric malignancies

Drug withdrawal

• opiates

• BDZ

Neurological

• HA/Migraines

• vestibular disorders

• ICH, head trauma

Metabolic:

• Diabetic ketoacidosis

• Addison disease

• renal disease

other:

• Pregnancy

• acute infection

• Hyponatremia

• uremia

• Anxiety/ depression disorders

• anticipatory nausea

• anorexia

• otitis media

• post-op

• noxious odours

drug causes

• Cytotoxic chemotherapy

• radiation

• Anticonvulsants

• Antibiotics

  • Erythromycin

• Anti-inflammatories

• Cannabis

• Anti-diabetics

  • Metformin

• Cardiovascular

• Opioids

• Nicotine

• Levodopa

• Theophylline

• Oral Contraceptive

• Acyclovir

• Caffeine

clinical presentation

• Dehydration (assess mucous membranes, skin turgor)

• Abdominal pain

• Distress/Anxiety

• Discomfort

• Electrolyte abnormalities

• Taste alterations

• Weight loss

red flags

• Significant dehydration = dizziness, sunken eyes, repeated vomiting, unable to keep liquids down for > 8hrs

• Blood in vomit (hematemesis)

• Coffee ground emesis

• Altered Mental status, neurological deficits, recent head trauma

• “Thunderclap” headache = severe HA with nausea and vomiting (HA youve never experienced before)

• Fever and Stiff neck

dehydration in children

• dry mouth, tongue, skin

• lack of tears

• decreased urine output (<4 wet diapers/ 24 hr)

• irritability and lethargy

• reduced skin turgor

• sunken eyes

• change in skin colour

• sunken fontanel (infants)

dehydration in adults

• dry mouth and tongue

• feeling more thirsty than usual

• weakness and lethargy

• reduced need to urinate

• sunken eyes

goals of therapy

1. Treat underlying cause and/or condition

2. Minimize the severity and frequency of nausea and/or vomiting

3. Prevent complications and reoccurrence of N/V

4. Minimize side effects of antiemetic medications

5. Decrease or eliminate the day-to-day disruptions caused by Nausea and/or vomiting

non pharm

• ensure adequate hydration (at least 2.5 L of fluid daily); treat with oral rehydration solutions for moderate to severe cases of N/V

• eat small, bland and frequent meals and avoid stimuli (noxious odours)

• consult dietitian when necessary (nausea associated with food intolerances)

• Avoid triggers (spicy foods, high fat foods, strong odours)

pharmacological therapy options

• viral gastroenteritis (food poisoning) = lack of superiority of 1 agent over another

• vestibular = antihistamines, anticholinergics

• problems with GI motility = Metoclopramide or Domperidone

• CTZ stimulation = Dopamine antagonists, serotonin antagonists

• if monotherapy is refractory, combine antiemetics with different MOAs

types of nausea and vomiting

• motion sickness

• post-operative (PONV)

• N/V of pregnancy (NVP)

• chemotherapy induced (CINV)

motion sickness

• normal physiologic response to unusual perception of motion

• occurs due to abrupt changes in motion

  • car sickness

  • air sickness

  • sea sickness

• involves inner ear and vestibular system

• Acetylcholine and histamine = NTs responsible for signalling to medulla oblongata —> antihistamines or anticholinergics for treatment

• Prevention > Treatment = adequate hydration, avoidance of smells/ foods that induce nausea, frequent small meals, relaxation therapy, pain treatment

motion sickness treatment

target Histamine and Acetylcholine!

• take medication 30-60 mins BEFORE motion exposure

• Dimenhydrinate (Gravol) if ≥2yr or Diphenhydramine (Benadryl) if ≥ 6y

  • more effective for short durations

  • onset = 15-30 mins

  • duration = 4-6 hrs

  • S/E (both) = sedation, anticholinergic effects (dry mouth, constipation, urinary retention)

  • S/E (dimenhydrainate/Gravol) = Paradoxical excitation (children)

• Promethazine = longer duration of action than dimenhydrinate (not recommended)

• ginger and acupressure wristbands (SeaBands) = not consistently demonstrated benefit but are widely promoted for antinausea effects

postoperative nausea and vomiting (PONV)

• within 24 hr after surgery

• includes all known pathways!

• 4 patient risk factors:

  1. Female

  2. Non-smoker

  3. Hx of motion sickness/ PONV

  4. Opioid use

• other risks:

  • type of anesthetic (NO, volatile anesthetics)

  • dehydration

• reducing risk factors = MORE EFFECTIVE management strategy

• preventative therapy with anti-emetics in moderate-high risk patients

• Non-pharm:

  • stimulate P6 acupuncture point

  • Avoid significant food intake 48 hr post-surgery

  • remain hydrated

  • avoid noxious odours

PONV treatment

combination therapy is more effective due to numerous NTs involved

• ondansetron

• haloperidol

• dexamethasone

• metoclopramide

• dimenhydrinate

nausea and vomiting of pregnancy (NVP)

• morning sickness —> can occur any time and may be constant throughout

• normally occurs first trimester of pregnancy —> usually subsides by 16 weeks

• severe, persistent NVP = Hyperemesis gravidarum (HG)

  • can continue throughout entire pregnancy

  • leads to weight loss, electrolyte imbalances, dehydration, nutritional deficiency

• non pharm:

  • Avoid triggers = spicy food, food with high fat content, fried food, strong food odours

  • eat small and bland meals

  • prevent dehydration and electrolyte imbalance

    • fluid intake

    • rehydration solutions (if severe and/or accompanied by diarrhea)

treatment of NVP

1st line for MILD:

• Diclectin (pyridoxine/ doxylamine) or Pyridoxine (Vit B6) alone, Ginger

1st line for Moderate-Severe:

• Dimenhydrinate (gravol), Promethazine (diphenhydramine when necessary)

If NVP persists:

• chlorpromazine, metoclopramide (for up to 5 days), Ondansetron (refractory cases only), Prochlorperazine

Resistant cases AFTER 1st trimester

• Methylprednisolone IV

IV fluids if dehydration

dimenhydrinate (gravol)

• 1st line for motion sickness (short term)

• used in persistent or mod-severe NVP (in addition to Ginger or Pyridoxine)

• onset = 30 mins

• effective in ALL types of N/V (except chemo-induced)

• s/e = Sedation, anticholinergic effects (dry mouth, constipation, urinary retention, blurred vision), confusion, increased IOP

  • The elderly may be particularly susceptible

  • Paradoxical excitation in children

• Additive sedation with alcohol or other sedating medications

diphenhydramine (benadryl)

• 1st line for motion sickness (use short term)

• can be used in persistent or moderate-severe NVP (in addition to ginger or pyridoxine)

  • Dimenhydrainte is a better option!

• onset = 30 mins

• effective in ALL types of N/V (except chemo-induced)

• s/e = sedation, anticholinergic effects (dry mouth, constipation, urinary retention, blurred vision), confusion, increased IOP —>elderly particularly susceptible

• Additive sedation with alcohol or other sedating medications

• Inhibits CYP2D6 and can increase serum levels of many drugs —> antidepressants and cardiovascular drugs

ginger (gravol natural source)

• 1st line in mild NVP (<1000 mg/d)

• used for motion sickness, PONV

• s/e = GI discomfort, diarrhea, dyspepsia, pepper-like irritant effect in mouth/throat

• may inhibit in vitro CYP2c19 = clinical significance unknown

pyridoxine (vitamin B6)

• 1st line in MILD NVP

• may be used alone or combined with doxylamine (diclectin)

• used to treat NVP

• onset = 1-2 hr

• s/e = GI pain, HA, loss of appetite, photosensitivity, somnolence

diclectin (doxylamine succinate/pyridoxine)

• Antihistamine in combo with Vit B6

• 1st line for NVP

• Take at regular intervals (delayed release tablet)

• 2 tablets QHS PO, plus 1 tablet QAM PO, plus 1 tablet mid-afternoon PO

• s/e (antihistamine) = VERY SEDATING, Diarrhea, disorientation, HA, Epigastric pain, Palpitations, Urinary retention

• interactions:

  • MAOIs

  • Antimuscarinics

  • CNS depressants

Metoclopramide

dopamine antagonist

• treatment for drug-induced nausea, migraine-induced nausea, gastroparesis, NVP (persistent), CINV

• cross BBB

• larger concern for EPS and Tardive dyskinesia

• s/e = Diarrhea, abdominal cramps and distention, headache, hyperprolactinemia, drowsiness, fatigue, EPS

• Additive sedation with alcohol or other sedating medications

• interactions with dopaminergic medications/ disease states (Parkinsons disease)

Domperidone

dopamine antagonists

• DO NOT USE IN PREGNANCY!

• treatment for functional dyspepsia, gastroparesis

• does NOT cross BBB

• s/e = QT prolongation! Serious ventricular arrhythmias, hyperprolactinemia, Diarrhea, abdominal cramps and distention, headache, hyperprolactinemia, QT_c prolongation

• Additive sedation with alcohol or other CNS depressants.

• Metabolized by CYP3A4; may be affected by CYP3A4 inhibitors or inducers.

haloperidol

dopamine antagonist

• Low doses

• treatment of PONV and refractory CINV (less effective than metoclopramide for refractory CINV)

• s/e = QT prolongation, sedation, EPS

• caution:

  • when used with other drugs that cause QT prolongation

  • in drugs/ disease states that have dopaminergic involvement (Parkinsons, antipsychotics or prokinetics)

• highest likelihood of causing EPS

• mild anticholinergic effects

dopamine receptor antagonists (Phenothiazines)

• Chlorpromazine = persistent NVP

• Perphenazine = PONV

• Prochlorperazine = PONV, CINV, drug-induced nausea, persistent NVP

• Promethazine = Motion sickness, PONV, gastroenteritis, moderate-severe NVP and persistent NVP

• s/e = anticholinergic effects, sedation, hypotension (when administered IM or IV)

• EPS/QT prolongation rare but possible at higher doses

5HT3 receptor antagonists (5HT3RA)

• Granisetron

• Ondansetron

  • decreases analgesic effects of tramadol

  • CYP3A4 inducers decrease ondansetron (CBZ, Phenytoin, rifmapin, St johns wort)

• Palonsetron

• treatment of PONV and acute CINV

• alternative for persistent, moderate-severe NVP

• s/e = constipation, HA, Diarrhea, QT prolongation, bradycardia, dizziness

• risk for serotonin syndrome when combined with other serotonergic meds