Mechanisms, causes, and treatments for nausea and vomiting

Introductory note

Much of the details in this document are taken from Garrett, K., Tsuruta, K., Walker, S., Jackson, S., & Sweat, M. (2003). Managing nausea and vomiting: Current strategies. Critical Care Nurse, 23 (1), 31-50. So far, this is the best paper I've found on control of PONV and CINV.

For backgrounder on nausea and vomiting, see http://emetophobia.bravepages.com/.

Different pathways triggering vomiting reflex

  1. Sensory input (unpleasant sights, smells, sounds, and extreme physical pain) directly stimulate vomiting centre in medulla oblongata. This can occur in a variety of settings, including post-op. In fact, post-op patients are particularly sensitive to unpleasant sights, smells (including odor of cleaning solutions and disinfectants), and sounds.
  2. When disrupted by motion, vestibular system uses ACH to stimulate muscarinic cholinergic receptors in cerebellum; vomiting centre is then stimulated. This can occur in a variety of settings, including post-op.
  3. When disrupted by motion, vestibular system uses neurotransmitter histamine to stimulate H1 receptors in cerebellum; vomiting centre is then stimulated.
  4. Higher brain centers mediating anxiety, anticipation, fear, memories, and conditioned responses directly stimulate vomiting centre.
  5. Serotonin, dopamine, and/or muscarinic cholingeric receptors in CTZ sense presence of general anesthetics in blood. Vomiting centre then activated by CTZ.
  6. Nitrous oxide directly stimulates GI tract. Stimulation moves along vagal afferents to CTZ, which then stimulates vomiting centre.
  7. Serotonin and dopamine receptors in CTZ sense presence of opioid substances in blood. Vomiting centre then activated by CTZ.
  8. Opioid substances stimulate μ2 receptors, which reduce gastric motility, causing nausea and vomiting, along with constipation. No current opioids avoid stimulation of these receptors. Fortunately, tolerance to this effect can occur within days to weeks.
  9. Serotonin is released from GI tract when neoplastic agents administered (signalling healthy cells are being destroyed). Serotonin stimulates vagal afferents, which in turn stimulates serotonin receptors in CTZ. Vomiting centre activated by CTZ.
  10. Serotonin receptors in CTZ sense presence of neoplastic agents in blood (signalling healthy cells are being destroyed). Vomiting centre then activated by CTZ.
  11. Digoxin and digitalis stimulate CTZ, which then triggers vomiting centre.
  12. Serotonin, dopamine, and/or muscarinic cholingeric receptors in CTZ sense presence of alcohol and ipecac in blood. Vomiting centre then activated by CTZ.
  13. Drugs like NSAIDs, SSRIs, and antibiotics cause gastric irritation which triggers a cascading ending in the trigger of the vomiting reflex.

Specific medical conditions which cause nausea and vomiting

Specific factors increasing risk of nausea and vomiting

PONV

CINV

Anti-emetic agents

Drug Brand Class Action Indications
dimenhydrinate Gravol, Dramamine anti-histamine 1. decrease ACH stimulation of vestibular system (vestibular system stimulates cerebellum, which stimulates vomiting centre in medulla)

2. reduce histamine trigger of CTZ by antagonising H1 receptors in cerebellum

 1. motion sickness

2. gastroenteritis (for gastroenteritis, use anti-histamines first)

3. obstetric
diphenhydramine Benadryl, Dramamine II anti-histamine same same
doxylamine Bendectin anti-histamine same same
meclizine Antivert anti-histamine same same
cyclizine Marezine anti-histamine same same
cyproheptadine

?

 anti-histamine and anti-serotonin 1. same

2. reduce serotonin trigger of CTZ by antagonising serotonin receptors in gut

 same
promethazine Phenergan phenothiazine, but used as anti-histamine and not indicated for use as neuroleptic same 1. motion sickness

2. gastroenteritis (for gastroenteritis, use anti-histamines first)

3. obstetric

4. PONV treatment and prophylaxis (alternative to much better, and also much more expensive SRAs)

5. opioid-induced NV (first-line for longer-term but not shorter-term management, because cheaper than SRAs)

6. problematic side effect: may cause sedation or extrapyramidal symptoms; use an SRA if this is a real problem and if it can accomplish the same thing

7. cheaper than SRAs
chlorpromazine Thorazine neuroleptic reduce dopamine trigger of CTZ by antagonising dopamine receptors 1. severe vomiting, non PONV/CINV/RINV

2. PONV prophylaxis and treatment (alternative to much better, and also much more expensive SRAs)

3. opioid-induced NV (first-line for longer-term but not shorter-term management, because cheaper than SRAs)

4. CINV prevention (but SRAs better because neoplastic agents cause CINV mainly through serotonergic stimulation)

5. problematic side effect: may cause sedation or extrapyramidal symptoms; use an SRA if this is a real problem and if it can accomplish the same thing

6. cheaper than SRAs
droperidol Inapsine neurolepic same 1. PONV prophylaxis and treatment (causes sedation, reduces apprehension, causes state of mental detachment and indifference)

2. problem, can cause cardiac dysrhytmias; so, not first-line for PONV prophylaxis

3. problematic side effect: may cause sedation or extrapyramidal symptoms
haloperidol Haldol neuroleptic same 1. severe vomiting, non PONV/CINV/RINV

2.  PONV treatment (alternative to much better, and also much more expensive SRAs)

3. opioid-induced NV (first-line for longer-term but not shorter-term management, because cheaper than SRAs)

4. breakthrough CINV (first-line)

5. problematic side effect: may cause sedation or extrapyramidal symptoms; use an SRA if this is a real problem and if it can accomplish the same thing

6. cheaper than SRAs
prochlorperazine Compazine, Stemetil neuroleptic same 1. severe vomiting, non PONV/CINV/RINV

2. PONV prophylaxis treatment (alternative to much better, and also much more expensive SRAs)

3. opioid-induced NV (first-line for longer-term but not shorter-term management, because cheaper than SRAs)

4. CINV (with dexamethasone, first-line prophylaxis for neoplastic agents with mild-moderate emetogenic potential)

5. breakthrough CINV (first-line)

6. problematic side effect: may cause sedation or extrapyramidal symptoms; use an SRA if this is a real problem and if it can accomplish the same thing

7. cheaper than SRAs
trimethobenzamide Tigan neuroleptic same 1. severe vomiting, non PONV/CINV/RINV

2. PONV treatment (alternative to much better, and also much more expensive SRAs)

3. opioid-induced NV (first-line for longer-term but not shorter-term management, because cheaper than SRAs)

4. problematic side effect: may cause sedation or extrapyramidal symptoms; use an SRA if this is a real problem and if it can accomplish the same thing

5. cheaper than SRAs
metoclopramide Reglan neuroleptic same 1. this is a mild anti-emetic

2. PONV prevention and treatment (alternative to much better, and also much more expensive SRAs)

3. opioid-induced NV (first-line for longer-term but not shorter-term management, because cheaper than SRAs)

4. CINV (with dexamethasone, first-line prophylaxis for acute CINV by neoplastic agents with mild-moderate emetogenic potential)

5. breakthrough CINV (first-line, with or without dexamethasone)

6. problematic side effect: may cause sedation, extrapyramidal symptoms, or agitation; use an SRA if this is a real problem and if it can accomplish the same thing

7. cheaper than SRAs
thiethylperazine Torecan phenothiazine, but not used as neuroleptic; indicated for anti-emesis only reduce dopamine trigger of CTZ by antagonising dopamine receptors 1. breakthrough CINV (first-line)

2. opioid-induced NV (first-line for longer-term but not shorter-term acute management, because cheaper than SRAs)

3. problematic side effect: may cause sedation or extrapyramidal symptoms; use an SRA if this is a real problem and if it can accomplish the same thing

4. cheaper than SRAs
    butyrophenones, some of which are indicated for use as neuroleptics, and others of which are indicated mainly for anti-emesis   opioid-induced NV (first-line for longer-term but not shorter-term acute management, because cheaper than SRAs)
propiomazine Largon phenothiazine, but not indicated for use as neuroleptic; indicated for use as a sedative-hypnotic   1. opioid-induced NV (first-line for longer-term but not shorter-term acute management, because cheaper than SRAs)

2. problematic side effect: may cause sedation or extrapyramidal symptoms; use an SRA if this is a real problem and if it can accomplish the same thing
ondansetron Zofran serotonin receptor antagonist

reduce serotonin trigger of CTZ by antagonising serotonin receptors in gut

 1. PONV prophylaxis (first-line; efficacy increased if used with dexamethasone, esp. for high-risk patients); but because expensive, use only if PONV is anticipated, if patient at high risk for PONV, if sequelae of vomiting will lead to serious medical complications, if patient wants to avoid PONV, or if PONV occurs and patient is really troubled by it; other drugs may be cheaper (but perhaps less effective) alternatives

2. PONV treatment (first-line); but is expensive, so neuroleptic might be used instead (with less efficacy)

3. opioid-induced NV (first-line for short-term acute, but not first-line for longer-term because very expensive; use alternatives for latter)

4. CINV (first-line for prophylaxis for acute CINV)

5. CINV (with dexamethasone, first-line prophylaxis for delayed onset CINV)

6. breakthrough CINV (but use other drugs first if you can, because very expensive)

7. RINV

8. very expensive; do not use indiscriminately
granisetron Kytril serotonin receptor antagonist same 1. PONV prophylaxis (first-line; efficacy increased if used with dexamethasone, esp. for high-risk patients); but because expensive, use only if PONV is anticipated, if patient at high risk for PONV, if sequelae of vomiting will lead to serious medical complications, if patient wants to avoid PONV, or if PONV occurs and patient is really troubled by it; other drugs may be cheaper (but perhaps less effective) alternatives

2. PONV treatment (first-line); but is expensive, so neuroleptic might be used instead (with less efficacy)

3. opioid-induced NV (first-line for short-term acute, but not first-line for longer-term because very expensive; use alternatives for latter)

4. CINV (first-line for prophylaxis for acute CINV)

5. CINV (with dexamethasone, first-line prophylaxis for delayed onset CINV)

6. breakthrough CINV (but use other drugs first if you can, because very expensive)

7. RINV

8. very expensive; do not use indiscriminately
dolasetron Anzemet serotonin receptor antagonist same 1. PONV prophylaxis (first-line; efficacy increased if used with dexamethasone, esp. for high-risk patients); but because expensive, use only if PONV is anticipated, if patient at high risk for PONV, if sequelae of vomiting will lead to serious medical complications, if patient wants to avoid PONV, or if PONV occurs and patient is really troubled by it; other drugs may be cheaper (but perhaps less effective) alternatives

2. PONV treatment (first-line); but is expensive, so neuroleptic might be used instead (with less efficacy)

3. opioid-induced NV (first-line for short-term acute, but not first-line for longer-term because very expensive; use alternatives for latter)

4. CINV (first-line for prophylaxis for acute CINV)

5. CINV (with dexamethasone, first-line prophylaxis for delayed onset CINV)

6. breakthrough CINV (but use other drugs first if you can, because very expensive)

7. very expensive; do not use indiscriminately
dexamethasone

—

 steroids   1. PONV phophylaxis (when used in combination with SRAs, can reduce PONV in high-risk patients); but because expensive, use only if PONV is anticipated and if patient really wants to avoid it

2. CINV (with prochlorperazine, first-line prophylaxis for acute CINV by neoplastic agents with mild-moderate emetogenic potential)

3. CINV (with SRA's, first-line prophylaxis for delayed onset CINV)

4. with dexamethasone, breakthrough CINV (first-line)
scopalamine (from belladonna)

—

 anticholingeric 1. block cholinergic transmission from vestibular system to higher brain centres

2. block cholinergic transmission from reticular activating system to vomiting center

3. inhibit the secretion of saliva, and decrease gastrointestinal secretions and motility

 1. motion sickness (first-line drug)

2. PONV (experimental)

3. anticholinergics are indicated for opioid-induced NV (first-line for longer-term but not shorter-term acute management, because cheaper than SRAs)
dronabinol Marinol cannabinoid   1. refractory breakthrough CINV when other drug classes ineffective.
    motility agents increase gastric motility opioid-induced NV (first-line for longer-term but not shorter-term management, because cheaper than SRAs)
phosphoric acid Emetrol other reduce gastric contractions 1. good for gastoenteritis due to virus, food, or drink

2. alternative to Rx for motion

3. not too effective
— Pepto-Bismol other suppress vomiting centre can suppress even small amounts of Ipecac!
— chamomile other reduce gastric motility? —
— peppermint and/or peppermint oil (with or without menthol) other same

1. general NV

2. peppermint oil with large amount of menthol can be used to help relieve post-op nausea, reduce need for anti-emetics, and can help create more analgesic tolerance
— ginger (fresh or dried in capsules) other same

1. general nausea

2. motion sickness

3. obstetrical nausea

4. helpful for post-op nausea

5. reduces chemotherapy-induced nausea
— cinnamon other same —
—

Relief Band

 other accupressure 1. motion sickness

2. lessens intensity of CINV

lorazepam

 Ativan benzodiazepine reduce anticipatory anxiety; calm higher centres that can directly stimulate vomiting centre 1. anticipatory nausea and vomiting, especially before chemotherapy

2. for children in chemotherapy

3. breakthrough CINV

Additional notes and measures

  1. NV must be prevented in patients with suspected aneurysms, in order to avoid hemorrhage.
  2. NV can cause deadly intracranial pressure in patients with brain injury.
  3. For eye, neck, or facial surgery, PONV can disrupt surgical site.
  4. PONV can displace carefully placed tubes and wires, especially cranial and cardiac ones
  5. Drugs are better at anti-emetic prophylaxis than at suppression
  6. No single drug can block all the receptors that cause NV
  7. Traditional, cost-effective emesis control for most patients is phenothiazines and metoclopramide.
  8. Take special prophylatic care of patient at high risk of PONV. They should receive a combination prophylactic treatment.
  9. For high-risk patients, administer drugs on scheduled basis and not PRN.
  10. When one drug fails, increase the dose to the maximum level safely possible, or use combination of drugs (especially from different classes, because they work on different mechanisms of NV; exception is in CINV, in which case you should add a second SRA). Combination drugs increase efficacy for patients at high risk of PONV.
  11. Dopamine antagonists like prochlorperazine (Compazine, Stemetil) and metoclopramide (Reglan); children more sensitive to extrapyramidal symptoms when given prochlorperazine (and sometimes they can actually become over-excited when given the drug)
  12. If opioids make patient feel very nauseated, try ketorolac (Toradol), an NSAID which can be used for post-op pain; but, may cause GI irritation and toxic kidney effects.
  13. You can determine is PONV is opioid-induced by seeing if onset corresponded with admin of opioids.
  14. Accupressure and 10-minute foot massage can relieve intensity of CINV.
  15. Helping patient with breathing can cause relieving distraction. Also, deep breathing can help get rid of anaesthetic agents.
  16. Relaxation imagery can relieve NV (including recalling pleasant memories and thinking of positive thoughts). Therapeutic touch also effective for treating NV.
  17. Music has beneficial effect on CINV when used with drugs.
  18. Nothing by mouth post-op until bowel sounds resume. Otherwise, NV will occur because of decreased GI motility.
  19. Eat dry crackers/toast (this turns stomach contents into a big ball, making it harder to vomit), suck on ice chips, and drink clear liquids (esp. carbonated beverages like ginger ale).
  20. Check regularly for bowel sounds to ensure decent motility.

Copyright © 2003, by Eddy M. Elmer

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