Download Post Operative Nausea & Vomiting

Post Operative
Nausea & Vomiting
Nicole Weiss MD
September 22, 2010
Objectives
Importance PONV
 Risk Factors
 Review of anti-emetics and strategies
aimed at reducing PONV
 Risk based treatment
 Rescue Therapy
 Tulane University Pharmacy
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The Patient
41
y/o female with a h/o of
PONV scheduled for an
outpatient laparoscopic
cholecystectomy
Motion sickness
Non-smoker
PONV: Importance?
1. High Level of patient concern (second to pain)
-willingness to pay $56-$100
2. Major cause of unanticipated hospital admissions
3. Rare complications: pulmonary aspiration, incisional disruption
Physiology
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Vomiting Center
– Located in the Medulla
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Tickling the back of the Throat
Gastric Distension
Vestibular Stimulation (Etoh)
Cerebral Cortex
Chemoreceptor trigger zone
– Outside of the BBB communicates with the vomiting
center
– Blood Borne Drugs or Hormones
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Neurotransmitters involved:
– Dopamine, 5-HT, Substance P, Ach
Apfel. Miller's Anesthesia.
Strategies for
Minimizing PONV
1.
Identify high risk patients
-25-30% incidence of PONV
-0.18% intractable PONV
2.
Avoid emetogenic stimuli
3.
Multimodal antiemetic therapy
Risk Factors
Patient, Procedure, Anesthesia
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History of previous PONV
History of motion sickness
History of migraines
Female gender post puberty
Childhood after infancy and young adulthood
Nonsmoker
The type of surgery: laparoscopic, middle ear, ophthalmologic,
craniotomy
Increasing duration of surgery
Dehydration
Pain
Use of volatile anesthetics, opioids, nitrous oxide or neostigmine
“Up to 70% incidence of PONV in “high risk”
patients (Kim)
Apfel’s Simplified Risk (Adults)
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1,2,3 or 4 risk factors-->10, 20,60,80%
Female
2. H/o of PONV or motion sickness
3. Non smoking
4. Postoperative IV opiods
1.
Apfel, et al. NEJM. 2004.
Drugs associated with PONV
Nitrous oxide
 Volatile agents
 Etomidate
 Neostigmine (high doses)
 Excessive opiods
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Comparison of Agents
Apfel, et al. 2002.
Protective Anesthesia
 Hydration
 Regional
Anesthesia
 TIVA
– Utilizing propofol as effective as
ondansetron
– Dose response relationship for propofol
 Oxygen
 Acupuncture
Antiemetics
1.
2.
3.
4.
5.
6.
Antagonists of 5-HT3
Antagonists of D2
Antagonists of H1
Antagonists of M Receptors
Antagonists of Neurokinin-1
Corticosteroids
Dopaminergic Agents
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Haloperidol
– Similar efficacy to ondansetron
– Not approved for IV use secondary to cardiac
arrhythmias
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Droperidol
– Effective
– Short half life-3 hours
– Increased sedation
– FDA black label
Clinically Relevant?
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Study comparing
ondansetron and
droperidol QT
prolongation
Charbit B, et al. Anesthesiology. 2005.
Dopamine Antagonists
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Metoclopramide
– Prokinetic effects
– Studies show 10mg dose no more
effective than a placebo
– Higher doses (50mg) may be effective
– Dyskinetic and extrapyramidal side
effects
Other Drugs NOT Included in
this Talk
Metoclopramide
 Ranitidine
 Sodium citrate
 Omeprazole
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GERD and aspiration precautions are
different from PONV
5HT-3 Antagonists
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Ondansetron, granisetron & dolasetron
Work at the chemoreceptor trigger zone & at vagal
afferents in the GI tract
Anti-vomiting better than anti-nausea
All three equal in efficacy, few side effects
Four hour half-life, but genetic of polymorphisms of p450
can lead to ultra short metabolism
Palonosetron (Aloxi)
– RCT demonstrated efficacy
– Approved for PONV in 2008
– Duration of up to 72 hours
Anticholinergics
Scopolamine patch showed to be equally
effective to ondansetron
 Side effects include:
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– Dry mouth
– Visual disturbances
– Dizziness
– Agitation
Corticosteroids
Dexamethasone
 Meta-analysis shows 8-10mg effective
 No reports of dexamethasone-related side
effects in small doses
 Slow onset of action, better efficacy if
given in the beginning of a case
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Antihistamines
Dimenhydrinate (Dramamine) &
Diphenhydramine
 Anticholinergic Properties
 Side effects:
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Sedation
Dry Mouth
Blurred vision
Urinary Retention
Prolonged recovery from anesthesia
Vascular necrosis (promethazine)
Neurokinin-1 Antagonists
(Substance P Receptors)
Work on the final common pathway from
the emetic center
 Aprepitant (Emend)
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– Recent studies indicate more effective than
ondansetron in preventing emesis, similar
efficacy in preventing nausea
– Patent expiration 2011-2015
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Casopitant & Rolapitant
Combinations versus single
drugs
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Multiple RCT compare a combination of
antiemetics versus a single agent
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Improved outcomes with combinations of
anti-emetics (except for studies with
metoclopramide)
IMPACT
International Multicenter Protocol to Assess
Antiemetic Combinations, 2004
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Large multicenter RCT
5,199 high risk patients
Six Variables: 2x2x2x2x2x2 (64 groups)
1. Ondansetron
2. Dexamethasone
3. Droperidol
4. Air (versus NO)
5. Propofol (versus inhaled agents),
6. Remifentanil (versus fentanyl)
Primary Outcome- PONV in 1st 24 hours
Relative risk of combined antiemetics equal to multiplying the
relative risk of each single agent together
Apfel, C, et al. IMPACT. Anaesthetist. 2005.
Algorithms for the prevention of
PONV
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Risk adapted algorithms can reduce PONV
in select patient populations
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None have proved to be universally
applicable
Guidelines for Antiemetic Therapy
Patient Factors
Surgical Factors
•Female
•H/o of PONV or motion
sickness
•Non-smoker
•Use of opiods
•Laparoscopy
•Laparotomy
•Craniotomy
•Strabismus
• ENT
1-2 Factors
1.
2.
3.
4.
5HT-3 Antag.
Decadron
Scopolamine
Droperidol
2-4 Factors
1. Droperidol +5HT-3 Antag
2. Decadron+5HT-3 Antag.
3. Droperidol+Decadron
>4 Factors
Combination of
antiemetics +
TIVA with
propofol
Evidence Based Anesthesia
Rescue Therapy
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Lack of data
Mechanical Factors:
– Secretions, gastric distension, opiates
Choose a different drug class in the first six hours
5HT-3 Antagonists
– Non-sedating
– Better anti-vomiting than anti nausea
– Not dose responsive
– Not indicated if failed ondansetron prophylaxis
Droperiol
Dexamethasone
Tulane Pharmacy Costs
Wholesale Price
 Markup 5x wholesale price
 Submitted to Insurance Company
 Government Reimbursement for Operative
Antiemetic Drugs
 Facility Surgery Fee
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DRUG
WHOLE SALE
INSTITUTION COST
Ondansetron
$0.78
$3.90
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Ondansetron$4.08
$0.78
Droperidol
per dose
$20.40
Droperidol $4.08
Dimenhydrinate
$0.04
 Dimenhydrinate$0.04
$1.00
Scopolamine
$11.90
$47.26
Dexamethasone
$3.12
$15.60
Promethazine
$0.54
$2.70
Prochlorperazine
$3.60
$18.00
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Courtesy of Bob Self, Tulane Pharmacy Director
What does this mean?
High risk patients ALWAYS warrant
aggressive prophylaxis
 Ondansetron
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– 50 patients a day, 260 days a year…costs
Tulane: $57,000 per year
– Puts patients at risk for side effects
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Only 0.18% patients experience severe
PONV requiring hospitalization…almost all
can be identified by risk factors
References
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Costanzo, Linda. Physiology. 4th Ed. Lippincott Williams & Wilkins: Philadelphia, 2007.
Gan TJ. Risk factors for postoperative nausea and vomiting. Anesth Analog 2006;102:1884-98.
Gan, T.J. Effective Management of PONV and Pain in Ambulatory Settings.
Glidden, Randall. NMS Clinical Manuals. Lippincott Williams & Wilkins: Philadelphia, 2003.
Habib, Ashraf. What Is the Best Strategy to Prevent Postoperative Nausea and Vomiting?
Evidence-Based Practice of Anesthesiology. 2nd edition. Sunders Elsevier. 269-275.
Kranke P. Algorithms for the prevention of postoperative nausea and vomiting: an efficacy and
efficiency simulation. European Journal of Anaesthesiology 2007, 24,10:856-867.
Kim, Eun Jin. Combination of Antiemetics for the Prevention of Postoperative Nausea and
Vomiting in High Risk Patients. J Korean Med Sci 2007; 22:878-82.
Apfel, CC. A Factorial Trial Six Interventions for the prevention of postoperative nausea and
vomiting. Anaesthesist. 54 (3). Mar 2005. 201-9.
Apfel CC., Kranke P, Katz MH, et al: Volatile Anesthetics may be the main cause of early, but not
delayed postoperative vomiting: A randomized controlled trial of factorial design. Br J of
Anesthesia. 88: 659-668, 2002.
Apfel, CC, Korttila K, Abdallah M, et al.: A factorial Trial of Six interventions for postoperative
nausea and vomiting. New England Journal of Medicine. 2004; 350, 2441-2451.
Miller, R, et al. Miller’s Anesthesia. 7th ed. Churchill Livingstone: 2009.
Kovac A. A randomized, double-blind controlled trial of three different doses of palonosetron
versus placebo in preventing postoperative nausea and vomiting over a 72-hour period.
Anesthesiology Analogue. 107 (2): 439-44.
Charbit B, et al.. AnesthesioDroperidol and ondansetron-induced QT interval prologation: a
clinical drug interaction studylogy. Aug 2008; 109 (2): 206-12.