Nausea/Vomiting 2

nausea

unpleasant sensation associated with an inclination to vomit

vomiting

autonomic response that results in the forceful expulsion of gastric contents through mouth

drug-induced N/V

• cancer therapies (ex: radiation therapy, chemotherapy)

• cardiac antiarrhythmics (ex: digoxin)

• opioids

• antibiotics

• volatile general anesthetics

• anticonvulsants

• methylxanthines (ex: caffeine)

• oral hypoglycemics

• oral contraceptives

• drug withdrawal

  • opioids

  • benzodiazepines

N/V: risk factors

• chemotherapy (CINV)

  • 70-80% of chemotherapy patients

• surgery (PONV)

  • common within 24 hours of anesthesia

• pregnancy

  • 80% experience nausea

  • 50% experience vomiting

  • 3% develop hyperemesis gravidarum

    • serious condition that can result in medical complications and hopsitalization

N/V: symptoms

• simple → self-limiting, resolves spontaneously, requires symptomatic treatment only

• comlex → refractory to antiemetic medications, worsening of patient’s clinical state, secondary to fluid/electrolyte imbalances

N/V: signs

• simple → patient’s report of queasiness, discomfort

• complex → weight loss, fever, abdominal pain

N/V: labs

• simple → not necessary

• complex → serum electrolyte concentrations, upper/lower GI evaluation

N/V: physical exam

• dehydration

  • low blood pressure

  • skin turgor

  • mucus membranes

• abdomen

  • bowel sounds

  • pain

• CNS

  • ocular findings

  • headache

skin turgor test

• skin fold persists after a “pinch and release"

• marker of dehydration

N/V: assessment

• labs:

  • CMP → electrolytes, BUN/SCr, AST/ALT

  • CBC → WBC

• imaging:

  • abdominal imaging

  • invasive imaging (ex: colonoscopy, endoscopy)

N/V: complications

• metabolic:

  • dehydration

  • electrolyte abnormalities

  • acid/base abnormlities

• GI:

  • esophageal tears

  • aspiration

• malnutrition

N/V: non-pharmacologic therapy

• diet:

  • identify and reduce dietary triggers

  • avoid large, fatty, spicy meals and fried foods

  • eat smaller, more frequent meals

  • BRAT diet

  • electrolyte drinks

• behavioral:

  • identify and avoid other triggers

  • relaxation, biofeedback, hypnosis, acupuncture, yoga

  • chewing gum

  • ginger, pyridoxine → pregnancy-related N/V

PONV: risk factors

• < 50 years

• female

• non-smoker

• history of PONV/motion sickness

• hydration status

• use of general anesthesia

• use of volatile anesthetics

• nitrous oxide use for > 1 hr

• use of opioids

• type of surgical procedure

• duration of surgery

PONV: risk score

• Apfel simplified risk score:

  • female = +1

  • non-smoker = +1

  • history of PONV/motion sickness = +1

  • postoperative opiods = +1

• risk level:

  • 0-1 = low risk

  • 2 = medium risk

  • 3-4 = high risk

PONV: prophylaxis

• no risk factors or children:

  • consider 5-HT₃RA or dexamethasone

• 1-2 risk factors:

  • 2-drug regimen

  • combination of  5-HT₃RA and dexamethasone

• > 2 risk factors:

  • 3-4 drug regimen

  • should have different MOAs

PONV: minimizing risk

• IV hydration

• local > systemic anesthesia

• avoid use of extended duration nitrous oxide/volatile anesthetics

• non-opioid pain control (other analgesics)

PONV: rescue therapy

• patients who received prophylactic treatment with a combination of 5-HT₃RA or dexamethasone should try different drug classes

  • phenothiazine (ex: prochlorperazine)

  • metoclopramide

  • droperidol

• if emetic episode occurs > 6 hours post-surgery, a repeat dose of 5-HT₃RA can be considered

  • dexamethasone should not be repeated

• if no prophylaxis treatment given:

  • low-dose 5-HT₃RA (ondansetron)

N/V: treatment approach

• simple:

  • oral fluid intake (electrolytes)

  • OTC treatment

  • non-pharmacologic therapy

• complex:

  • oral → IV fluids/electrolytes

  • combination medication regimens (different MOAs)

    • ex: ondansetron + dexamethasone

N/V: OTC medications

• symptoms related to GERD/PUD:

  • antacids

  • PPIs

  • H₂RAs

  • bismuth compounds

• symptoms related to motion sickness/vertigo:

  • antihistamines

  • anticholinergic agents

serotonin (5-HT₃R) antagonists

• palonosetron (IV)

• dolasetron (oral)

• granisetron (oral, IV, SC, patch)

• ondansetron (oral, SC)

• alosetron (oral)

5-HT₃R antagonists: MOA

block serotonin receptors on sensory vagal fibers located in wall of GI tract

5-HT₃R antagonists: role in therapy

• considered standard of care in management of:

  • CINV

  • RINV

  • PONV

5-HT₃R antagonists: clinical pearls

• ondansetron is “gold-standard” for PONV

  • IV doses should not exceed 16 mg (risk of QT prolongation)

• dose-related QT prolongation can occur

corticosteroids

• dexamethasone

• methylprednisolone

• prednisone

corticosteroids: MOA

• not well understood

• may be related to reduced permeability of BBB to 5-HT or anti-inflammatory effects

corticosteroids: role in therapy

• not indicated for treatment of simple N/V due to side effects

• used for prevention of CINV and PONV, either as a single agent or in combination with other antiemetics

• symptomatic treatment

corticosteroids: clinical pearls

• AE → hyerglycemia, fluid retention, insomnia, psychosis, mood changes, infection risk

• one time dose = minimal risk

dopamine antagonists

• metoclopramide

• amisulpride

• phenothiazines

  • ex: promethazine, prochlorperazine, chlorpromazine

• butyrophenones

  • ex: haloperidol, droperidol

dopamine antagonists: MOA

antagonize D₂ receptors in CTZ

dopamine anatagonists: role in therapy

• not considered first-line due to side effects

  • sedation, orthostatic hypotension, extrapyramidal symptoms (EPS)

• used as rescue therapy for PONV

• phenothiazines → simple N/V

• butyrophenones → anticipatory and acute CINV, PONV

• metoclopramide → not very effective

dopamine antagonists: clinical pearls

• avoid chronic use (> 12 weeks)

  • can cause EPS

• QT prolongation → dysrhythmias → Torsades de Pointes

  • higher risk with butyrophenones

• metoclopramide can cause hyperprolactinemia → gynecomastia

extrapyramidal symptoms (EPS)

• neuroleptic malignant syndrome (NMS)

• rigidity

• tremors

• hyperthermia

• death

benzodiazepines (BZD)

• alprazolam (oral)

• lorazepam (oral, IV)

• midazolam (oral, nasal, IV)

BZD: MOA

GABA receptor antagonist, causes relaxation

BZD: role in therapy

• relatively weak antiemetics

• used as adjunct to other antiemetics

• used to prevent anxiety or anticipatory N/V (ANV)

BZD: clinical pearls

• AE → dizziness, sedation, memory impairment

• avoid in older adults (increased fall risk)

• risk of dependence

labyrinthal N/V

• vertigo, motion sickness

• symptoms → imbalance, dizziness

labyrinthal N/V: treatment

• antihistamines/antimuscarinics

• OTC → diphenhydramine, meclizine, dimenhydrinate

• use prior to anticipated motion event (ex: boat, plane)

antihistamines/antimuscarinics

• scopolamine (patch)

• diphenhydramine (oral, IM, IV)

• dimenhydrinate (oral)

• doxylamine (oral)

• meclizine (oral)

antihistamines/antimuscarinics: MOA

histamine/muscarinic receptor antagonists in the VC and vestibular system

antihistamines/antimuscarinics: role in therapy

• used for prevention of labyrinthal N/V

• frequently used as self-care therapies

antihistamines/antimuscarinics: clinical pearls

• AE → sedation, dry mouth, blurry vision, urinary retention (anticholinergic effects)

  • avoid use in older adults

• second generation antihistamines → ineffective for labyrinthal N/V

neurokinin-1 (NK-1R) antagonists

• rolapitant (oral, IV)

• aprepitant (oral, IV)

• fosaprepitant (IV)

• netupitant (oral, in combination with palonosetron)

NK-1R antagonists: MOA

• prevents activity of substance P

• substance P is considered a trigger of CINV (CTZ trigger)

NK-1R antagonists: role in therapy

• used in combination with other antiemetics (ex: 5-HT₃RAs)

• standard of care for prevention of CINV

  • especially in patients receiving highly emetogenic chemotherapy

NK-1R antagonists: clinical pearls

• aprepitant → many DDIs 

  • substrate/moderate inhibitor of CYP3A4

  • weak inducer of CYP2C9

• rolapitant:

  • longer half-life

  • inhibitor of P-gp, CYP2D6

  • caution → severe hypersensitivity (IV)

• netupitant/palonosetron → moderate inhibitor of CYP3A4

  • avoid with dexamethasone

cannabinoids

• dronabinol (oral)

• nabilone (oral)

cannabinoids: MOA

acts on cannabinoid receptor 1 (CB1), effective in preventing CINV

cannabinoids: role in therapy

• not indicated as first-line

• used for breakthrough N/V, when CINV is refractory to other antiemetics

• symptomatic treatment in combination with other antiemetics

cannabinoids: clinical pearls

• dronabinol = CIII

• nabilone = CII

• AE → CNS depression, sedation

  • avoid in older adults

• chronic use of cannabis/related substances can cause cannabinoid hyperemesis syndrome

N/V: pregnancy

• prevention:

  • diet modifications

    • avoid spicy, fatty, large meals

    • eat smaller, more frequent meals

    • avoid triggers

  • ginger

• treatment:

  • first line → pyridoxine ± doxylamine

  • second line → dimenhydrinate, diphenhydramine, prochlorperazine, promethazine

  • IV fluids + thiamine for fluid loss

  • glucocorticoids (ex: methylprednisolone)

    • should only be considered after 10 weeks of gestation in patients with severe N/V or hyperemesis gravidum

N/V: children

• usually self-limiting and improves with correction of dehydration

  • can be treated with oral rehydration therapy

• ondansetron for intractable vomiting

• CI → promethazine

  • risk of fatal respiratory depression

N/V: geriatric patients

• first line → ondansetron

• avoid…

  • first-generation antihistamines, scopolamine → anticholinergic effects

  • metoclopramaide → EPS

N/V: monitoring

• severity

  • frequency

  • impact on ADLs

  • associated symptoms

• lab work

  • electrolytes

  • acid/base balance

• fluid status

  • ins and outs