antiemetics Flashcards
what are the top three reasons for unplanned admissions in outpatient procedures?
- pain
- bleeding
- PONV
what percentage of patients may PDNV affect and how long?
- 35-50%
- may last up to 5 days
- partly d/t ride home, especially if hypovolemic
what are complications of PONV?
- surgical wound dehiscence (especially with abdominal or hernia repair; gagging increases pressure)
- esophageal damage
- aspiration
- dehydration
- alkalosis (vomiting out stomach acid)
- hypokalemia
- intraocular hemorrhage (eye surgery)
- increased ICP (craniotomy)
- myocardial ischemia
what may result from PONV?
- delayed discharge from PACU
- delayed discharge from hospital (increased cost and inconvenience)
- electrolyte imbalance: hypochlorema, hyponatremia, alkalosis
- increased postsurgical bleeding (hypertension)
what are positive risk factors for PONV in adults?
- female
- hx of PONV or motion sickness
- nonsmoking
- younger age (after age 3)
- general vs. regional anesthesia
- use of volatile agents and N2O
- postop opioids
- duration of anesthesia
- type of surgery (cholecystectomy, laparoscopic, gyn, middle ear, thoracic, eye, abd)
- ketamine, etomidate
- full stomach (food, gas) (blood: tonsillectomy, adenoidectomy)
what are possible risk factors for PONV in adults?
- ASA physical status (higher, higher risk)
- menstrual cycle
- level of anesthetist’s experience
- muscle relaxant antagonists (neostigmine)
- fear or anxiety
- obesity
describe risk scores for PONV
- each risk factor present (female, nonsmoker, hx PONV, postop opioids) gives 1 point
- 4 points is an 80% risk of PONV
- 3 points: 60%
- 2 risks 40%
- 1 risk: 20%
- 0 risks: 10%
what are medical causes for N/V?
- hypoxia
- hypotension
- MI
- DKA
- increased ICP
- abd inflammation
- early pregnancy
- systemic infections
- Reye’s syndrome
- adrenal crisis
- dig toxicity
- estrogen
- aminophylline
- L-dopa
describe risk scores for PDNV
- each risk gives 1 point (female, hx PONV, age <50, nausea in PACU, opioids in PACU)
- 5 risks: 80% risk of PDNV
- 4 risks: 60%
- 3 risks: 50%
- 2 risks: 30%
- 1 risk: 20%
- 0 risks: 10%
describe POV risk in children
similar to adults with following differences:
- vomiting 2x more than adults
- risk increases with age over 3 and declines after puberty
- gender doesn’t make a difference before puberty
- risk increases more with specific operations (eye, ears, tonsils, adenoids, etc.)
how can risk factors be reduced?
- avoid general anesthesia by use of regional
- use propofol for induction and maintenance
- avoid N2O
- avoid volatile agents
- minimize intraop and postop opioids (local anesthetic, blocks, NSAIDS)
- adequate hydration
how should treatment be approached with each risk level of PONV?
- low risk: wait and see
- medium risk: 1 or 2 interventions
- high risk: > 2 interventions; multimodal approach
when should droperidol be used in children?
only if other treatment has failed and being admitted to the hospital
*Haldol for adults only
what are options if prophylaxis fails?
- use a different drug
- redose after 6 hrs
- don’t redose scopolamine or dexamethasone
what are indications for TIVA with propofol?
- risk for malignant hyperthermia
- high risk for PONV
- propofol may also be used as a rescue drug on onset of PONV in small dose
what is affected in the brain to cause PONV?
-brainstem vomiting center located in the lateral medullary reticular formation
-receptors include:
muscarinic
histamine H1
serotonin 5-HT3
neurokinin-1
what causes afferent input into the vomiting center?
- chemoreceptor trigger zone (4th ventricle): dopamine, serotonin 5-HT3, opioid receptors
- vestibular system (motion sickness): muscarinic, H1 receptors
- irritation of the pharynx (vagus nerve): gag and retch response
- vagal and enteric afferents (mucosa of the GI tract: 5-HT3 receptors activated by serotonin released by the mucosa, then stimulate vagal input to CTZ and vomiting center
- CNS: stress and anticipatory vomiting (midazolam helps)
what causes visceral afferents to signal the vomiting center?
disease of:
- heart
- digestive tract
- biliary tract
- GU tract
what causes stimulation of the CTZ that then signals the vomiting center?
- motion leads to vestibular labyrinth which signals the cerebellum then CTZ
- drugs
- radiation
- metabolic disturbances
what causes cortical afferents to signal the vomiting center?
- hypoxia
- pain
- increased ICP
- smell, sight, taste
- psychotropic factors
how do benzodiazepines help with PONV?
- decrease dopamine input at the CTZ as well as anxiolysis
- may also decrease adenosine reuptake leading to decreased synthesis, release, and postsynaptic action of dopamine at the CTZ
- anxiolysis from anticipatory vomiting
how do antihistamines work?
- anticholinergic effect (muscarinic receptors)
- histamine receptor blockade (H1 receptors)
what antihistamines are used with PONV?
- diphenhydramine (Benadryl), meclizine (Bonine), dimenhydrinate (Dramamine)
- phenothiazines
- prochlorperazine (Compazine)
- promethazine (Phenergan)
describe diphenhydramine, meclizine, and dimenhydrinate use in PONV
- weak effect except specific to MOTION SICKNESS
- good if pts. are “stuffy” and PONV tx may be a bonus
- give towards beginning of case to allow sedation to wear off
what are limitations of use of diphenhydramine, meclizine, and dimenhydrinate?
- sedation
- dizziness
- confusion
- dry mouth
- urinary retention
- anticholinergic effects
describe phenothiazine class use in PONV
- inhibition of dopamine muscarinic, and histamine receptors
- marked sedation potentiates effect of postop narcotics
what are limitations of phenothiazine class use?
- sedation (anticholinergic effect)
- extrapyramidal effects (dopamine blocked)
- pseudoparkinson’s (dopamine blocked)
- lowers seizure threshold
- hypotension (alpha blockade)
what is the dose of prochlorperazine (Compazine)?
2.5-10 mg IV
what is the dose of promethazine (Phenergan)?
25 mg IV
what is the MOA of scopolamine?
antimuscarinic (vestibular system)
-antagonizes histamine and serotonin
describe scopolamine
- lipid soluble: crosses BBB, transdermal absorption (patich)
- apply 60 minutes prior to induction
- can provide adequate drug levels 48-72 hrs
what is the dose of a scopolamine patch?
1.5 mg patch releases 1 mg dose
what are limitations of scopolamine?
- ocular effects (caution with glaucoma pts.)
- restlessness
- delirium
- sedation (not typically a lot)
- dry mouth
- tachycardia (uncommon)
- caution pts. on touching patch and rubbing eyes
describe butyrophenones (droperidol, Inapsine)
- dopamine blockade (alpha blockade)
- extremely sedating, dissociative state
- causes vasodilation d/t peripheral alpha blockade (decreased in BP)
- give up front so dissociative state wears off before emergence
what is the dose of butyrophenones (droperidol, Inapsine)?
0.625-1.25 mg IV (0.05 mg/kg)
what are limitations of butyrophenones (droperidol, Inapsine)?
- prolonged QT interval (DOSE 25mg)(torsade de pointes)
- extrapyramidal effects (avoid in Parkinson’s and elderly)
- hypotension
- sedation
describe metoclopramide
- dopamine blockade in the CTZ
- gastrokinetic: moves everything forward (aspiration prophylaxis)
- if used with phenothiazines or droperidol, increases incidence of extrapyramidal effects (restlessness, dystonias, parkinsonian)
what is the dose of metoclopramide?
10-20 mg IV
when should metoclopramide be avoided?
intestinal obstruction (increased pressure may cause perforation)
Parkinson’s
describe serotonin
- serotonin is an endogenous vasoactive substance and neurotransmitter (emesis and pain), cerebral stimulant
- 90% stored in the enterochromaffin cells of the GI tract
describe 5-HT receptors
1: cerebral vasoconstriction (cause migraines)
2: coronary artery and pulmonary vessel vasoconstriction
3: PNS-visceral pain; CNS- emesis, appetite, addiction, pain, and anxiety
4: gastrokinesis (constipation, IBS)
how do 5-HT3 receptor antagonists work?
- block peripheral receptors on the intestinal vagal afferents and central receptors in the vomiting center, CTZ (vagal stimulation)
- no effect on dopamine, histamine, adrenergic, or muscarinic receptors (no parkinsonian, restlessness, hypotension, or sedation)
- *minimal side effects
- *good for chemotherapy induced NV, PONV (not motion sickness)
what are side effect of 5-HT receptor antagonists?
headache, constipation, theoretically cardiac arrhythmias (Anzemet)
what are limitation of 5-HT receptor antagonists?
- cost
- prolonged QT interval (caution if QT interval already prolonged)
- effectiveness of droperidol
- propofol induction and maintenance
what is the dose of ondansetron (Zofran)?
4-8 mg (0.15 mg/kg) IV
what is the dose of dolasetron (Anzemet)?
12.5 mg IV
what is the dose of granisetron (Kytril)?
1 mg (0.01 mg/kg) IV
what is the dose of palonosetron (Aloxil)?
0.075 mg IV
describe corticosteroid use in PONV
- unknown mechanism
- enhances the effectiveness of 5-HT3 antagonists (6-10mg)
- increases blood sugar (caution with diabetics)
- give at beginning of case
what is the dose of dexamethasone (Decadron)?
0.5 mg/kg (4-8 mg)
pediatrics up to 6 mg
what are the limitations of dexamethasone?
with chronic therapy: interference with healing, immune suppression, avascular necrosis (?)
what drugs antagonize the dopamine receptors at the CTZ?
- droperidol
- metoclopramide
what drugs antagonize the ACh receptors at the CTZ?
- scopolamine; atropine
- diphenhydramine
what drugs antagonize the histamine 1 receptors at the CTZ?
- diphenhydramine
- promethazine
what drugs antagonize the 5-HT3 receptors at the CTZ?
- ondansetron
- high dose metoclopramide
describe guidelines for PONV prophylaxis and treatment
- identify pts. at high risk
- reduce baseline risks of PONV
- use prophylaxis with high risk and moderate risk (5-HT antagonist + 2nd agent like decadron or scopolamine if history of motion sickness)
- use appropriate rescue treatment
what are appropriate rescue treatment guidelines?
- if not previously given, give 5-HT3 antagonist (Zofran)
- do not repeat initial therapy
- if within 6 hrs., don’t redose 5-HT3 antagonist
- if after 6 hrs., repeat 5-HT3 antagonist dose and second agent from a different class
what is neurokinin (NK1) or substance P
the natural ligand of the neurokinin receptor found in the area postrema, nucleus of the solitary tract and afferent fibers of the vagus nerve
how does aprepitant (Emend) work?
antagonist of the NK1 receptor
-approved for PONV prophylaxis
what is the dose of Emend?
40 mg po one hour prior
what are alternative treatments for PONV?
- acupressure: relief band or inject D50 between flexor tendons, 3 finger widths below hand-wrist crease
- hypnosis
- propofol: 0.5 mg/kg
- ephedrine: IM dose 0.5 mg/kg
- ephedrine equal to droperidol IV and increases BP
explain PONV prevention algorithm
low risk: prophylaxis either none or use drug A + (drug B or TIVA); treatment if no prophylaxis 1) drug B 2) drug C if prophylaxis used then 1) drug C 2) drug D
medium risk: prophylaxis drug A + (drug B or TIVA); treatment 1) drug C 2) drug D
high risk: prophylaxis drug A + drug B + TIVA; treatment 1)drug C 2)drug D
-drug A: dexamethasone 4 mg
-drug B: ondansetron 4 mg
-drug C: droperidol 1 mg
-drug D: dimenhydrinate 1 mg/kg
