Post Operative Nausea & Vomiting: The Role of Antiemetics

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Post Operative Nausea Vomiting The Role of
Antiemetics

• Cedric Dupont-Eisner M.D.

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Post Operative Nausea Vomiting (PONV)

• 25 - 30 have nausea /or vomiting during the
  postoperative period.
• Occurs in as many as 70 of high-risk patients1,2
• Nausea and vomiting post op pain3

1Apfel CC et al. Anesthesiology.
199991693700. 2Gan TJ et al. Anesthesiology.
19968510361042.
3Macario A et al. Anesth Analg. 199989652658.
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5 Most Undesirable Surgical Outcomes
Perspective of Pts vs Anesthesiologists
1Macario A et al. Anesth Analg.
199989652658. 2Macario A et al. Anesth Analg.
19998810851091.
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MECHANISM OF PONV

• Peripheral
• GI stimulation of CN X
• Central
• Pathways that affect the CTZ include
• Cerebellum
• Afferents from Vestibular System
• CN X
• CN VIII

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Chemoreceptor Trigger Zone and Emetic Center
Antagonist
5-HT3 RAs
Droperidol
Promethazine
Atropine
NK-1 RA
Agonist
5-HT3
Muscarinic
Dopamine (D2)
Histamine
Substance P
Receptor Site
Nitrogen mustard Cisplatin Digoxin
glycoside Opioid, analgesics Vestibular
portion of 8th nerve N2O GI tract
distension Higher centers (vision, taste) Pharynx
Chemoreceptor Trigger Zone (CTZ)
Area Postrema
Mediastinum
Parvicellular Reticular Formation
Emetic Center
?
Vagus
Watcha MF, White PF. Anesthesiology.
199277162184.
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Just The Facts

• Numerous publications state universal PONV
  prophylaxis is not cost effective
• Pts at ? risk for PONV should not receive
  prophylaxis 2º to antiemetic side effects and
  increased cost

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Identify PONV Pts

• ? or lt 16 yrs
• ?
• ?
• ?
• Prior Hx of PONV

• Volatile anesthetics
• Opioids
• Nitrous
• Concomitant Dz
• Duration of surgery
• Procedure type

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Risk Factors Scores

• ?
• Previous PONV
• ?
• Surgery time gt 60 min
• ?

• Factors Risks
• 0 17
• 1 18
• 2 42
• 3 54
• 4 74
• 5 87

Koivuranta, Apfel et al.
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Identify POV Pediatric Patients

• Risks are similar to adults, except
• Twice as frequent as in adults
• ? w/ age, ? after puberty
• ??
• Risk ? more consistently w/ certain procedures

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? Baseline PONV Risks

• Avoid
• opioids hypnotics
• Nitrous
• high-dose reversal agent (neostigmine)
• dehydration ?

• Attempt
• ? O2
• ? air entry into stomach
• Propofol is a protective antiemetic

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PONV Prophylaxis

• Prior to Surgery
• Dexamethasone
• Scopolamine

• Post Operative
• Ondansetron
• Dolasetron
• Granisteron
• Droperidol
• Prochlorperazine
• Promethazine

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POV Prophylaxis

• Dexamethasone
• Ondanestron
• Dolasteron
• Droperidol
• Dimenhydrinate
• Perphenazine

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PONV Consensus Conference

• Guidelines for Managing PONV
• Gan TJ, Meyer T, Apfel CC, Chung F, Davis PJ,
  Eubanks S, Kovac A, Philip BK, Sessler DI, Temo
  J, Tramer MR, Watcha M.
• Anesth Analg. 2003976271

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Consensus Guidelines for Managing PONV

• All 5-HT3 receptor antagonists are equally
  effective for both prophylaxis PONV tx
• Preinduction Metoclopramide 10 mg is ineffective
  for PONV prophylaxis

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AntiemeticsMembers by Class

• Phenothiazines
• Chlorpromazine, prochlorperazine, promethazine
• Butyrophenones
• Droperidol (haloperidol)
• Benzamides
• Metoclopramide
• Anticholinergics
• Scopolamine

• Antihistamines
• Dimenhydrinate, hydroxyzine
• 5-HT3 antagonists
• Dolasetron, granisetron, ondansetron
• Others
• Dexamethasone
• Dronabinol (9THC)

• Upcoming class for PONV already approved
  for CINV
• NK1-receptor antagonists

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Phenothiazines

• Chlorpromazine, Prochlorperazine, Promethazine
• Antipsychotic agents
• Blocks D2 receptors in CTZ and CNX
• SIDE EFFECTS EPS, sedation, dizziness, blurred
  vision, skin reactions, orthostatic hypotension

chlorpromazine
Prochlorperazine-heterocyclic side chain
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Butyrophenones

• Droperidol
• a blocker, D2 receptor antagonist
  (binds to D2 receptor)
• Acts at both CTZ and area postrema
• SIDE EFFECTS EPS, sedation, QTc prolongation

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FDA Advisory For Droperidol

• Risk of fatal cardiac arrhythmia
• The black box warns
• consider alternative medications in pts at high
  risk for cardiac arrhythmia
• use only low doses when other initially
  recommended antiemetics fail
• use as a 2nd agent when an initial treatment
  fails.

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Benzamide

• Metoclopramide
• Specific dopamine D2 antagonist
• ? LES tone which enhances gastric motility
• Short (1 to 2 hours) duration of action.
• SIDE EFFECTS EPS, restlessness, drowsiness,
  fatigue, agranulocytosis, methemoglobinemia

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Anticholinergics

• Scopolamine
• Inhibit cholinergic and muscarinic CNS receptors.
  
• Crosses the blood-brain barrier.
• More effective against motion-induced emesis than
  against motion-induced nausea.
• SIDE EFFECTS sedation, CNS excitation, dry
  mouth, urinary retention, blurred vision,
  confusion, disorientation, hallucinations

Night Shade
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Antihistamines

• Dimenhydrinate, Hydroxyzine, Cyclizine
• Block acetylcholine in the vestibular apparatus
  and histamine H1 receptors in the nucleus of the
  solitary tract.
• SIDE EFFECTS blurred vision, urinary retention,
  dry mouth, and sedation

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5-HT3 Antagonists

• (Ondansetron (Zofran), Granisetron (Kytril),
  Tropisetron (Navoban), and Dolasetron (Anzemet)
• No sedation, extrapyramidal reactions, adverse
  effects on vital signs or laboratory tests, or
  drug interactions with other anesthetic
  medications.
• SIDE EFFECTS Headache, dizziness, constipation

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PROPOFOL

• mechanism unknown

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Dexamethasone

• Synthetic steroid not indicated for treatment of
  PONV in the United States.
• Hypotheses
• inhibition of prostaglandin syn.
• ? tryptophan
• release of endorphins
• change in csf opening pressure
• psychological effects of steroids
• ACUTE SIDE EFFECTS flushing
  and perineal itching.

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DRONABINOL Marinol

• 9THC
• Unknown mechanism involves inhibition of CTZ
• SIDE EFFECTS dizziness, drowsiness, nausea (not
  emesis)
• Schedule II drug

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Algorithm for PONV Prophylaxis
Evaluate risk of PONVin surgical patient
Low
Consider regionalanesthesia
No prophylaxis unless there is medical risk of
sequelae from vomiting
Not indicated
If general anesthesia is used, reduce baseline
risk factors when clinically practical
consider using nonpharmacologic therapies
Patients at moderate risk
Patients at high risk
Consider antiemetic prophylaxiswith monotherapy
(adults) or combination therapy (children and
adults)
Initiate combination therapy with 2 or 3
prophylactic agents from different classes
Gan TJ et al. Anesth Analg. 2003976271.
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Antiemetic Therapy for PONV Prophylaxis in
Adults ? FDA

• 1st Line
• 5-HT3 antagonists
• Ondansetron 4-8mg I.V.
• Dolasetron 12,5mg I.V.
• Granisetron 0.35mg 1mg I.V.
• Tropisetron
• Dexamethasone 5-10mg I.V. before induction
• Droperidol 0.65 1.25mg I.V.

• 2nd Line
• Dimenhydrinate
• Ephedrine
• Prochlorperazine
• Promethazine
• Scopolamine
• Nonpharmacologic techniques
• Acupuncture
• Hypnosis

Currently not FDA-approved for PONV in the US
Adapted from Gan TJ et al. Anesth Analg.
2003976271.
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PONV Tx in Pts Who Did Not Receive Prophylaxis
or Whom Prophylaxis Failed
Low-dose 5-HT3 RA dosing (dolasetron 12.5 mg
granisetron 0.1 mg ondansetron 1 mg tropisetron
5 mg)
Adapted from Gan TJ et al. Anesth Analg.
2003976271.

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Questions
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