Management of PONV

1
Management of PONV

• Dr. Jay A. Avila
• Staff Anesthesiologist
• PACU Medical Officer
• USNH Camp Pendleton

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Objective

• To apply newest evidence-based-medicine to our
  management of PONV
• To increase patient satisfaction
• To maximize cost effectiveness
• To speed up patient discharge from PACU and SDSU

3
Current Practice Pre-operatively

• Patient stratification ranges from none or
  minimal to appropriate
• Bicitra and Reglan for all pregnant or GERD
  patients
• Prophylaxis ranges from none or minimal to triple
  combination
• Anesthetic plan modification based on patient
  stratification ranges from none to appropriate

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Current Practice Pre-operatively

• Agents used
• Ondansetron 4 mg IV
• Metoclopramide 10 mg IV
• Dexamethasone 4-10 mg IV
• Vistaril 25 mg IM and IV
• Scopolamine Patch

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Current Practice - Intraoperatively

• Propofol induction
• Adequate hydration and avoidance of hypotension
• Ondansetron pre-induction, at induction or
  shortly after
• Ondansetron at the end of surgery
• Metoclopramide initially and/or at the end
• Droperidol 0.625-1.25 mg IV at the end
• Dexamethasone 4-10 mg IV initially or at the end
• Reversal usage considerations
• Propofol before emergence (20 mg IV)
• TIVA(Propofol) with or w/o volatile agent with or
  w/o NO

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Current Practice - Postoperatively

• Hydration Crystalloid 1000 cc at 100cc/hr
• Rescue medications
• Zofran 4 mg IV initially and/or repeat
• Reglan 10 mg IV initially and/or repeat
• Phenergan 12.5-25 mg IV

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Pathophysiology of Nausea and Vomiting
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Pathways in CTZ/Emetic Center Stimulation
Antagonist
5-HT3
Anticholinergics
Antidopaminergics
Antihistamine
Agonist
Muscarinic/Cholinergic
Dopamine (D2)
5-HT3
Histamine
Receptor Site
m
CTZ
Area Postrema
Adapted from Watcha MF et al. Anesthesiology.
199277162-184.
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Agonists and Antagonists Associated with Nausea
and Vomiting
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Socio-economic Aspects of PONV

• Common complication of surgery
• Limiting factor in early discharge
• Leading cause of unanticipated hospital admission
• Increased recovery room time, increased nursing
  care and potential hospital admission All
  increase Total Health Costs

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Socio-economic Aspects of PONV

• High Levels of Patient disconfort and
  dissatisfaction
• PONV may be of greater concern than post-op pain
• Patients willing to spend up to 100 out of
  pocket for effective antiemetic

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Socio-economic Aspects of PONV

• 25-30 of surgical patients experience nausea
  and/or vomiting post-operatively
• Intractable PONV about 0.18
• High risk patients may have 70-80 incidence of
  PONV
• Emphasis shift from in-patient to out-patient
  surgery has increased interest in prevention and
  treatment of PONV

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Socio-economic Aspects of PONV

• Optimal approach to PONV remains unclear
• Treat all high risk patients?
• Ideal rescue therapy
• Published evidence suggests universal PONV
  prophylaxis in not cost-effective
• AIMS (Anesthesia Information Management Systems)
  have been created to stratify and predict and
  prevent PONV
• Guidelines for prevention of PONV have been
  published

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Socio-economic Aspects of PONV

• Guidelines previously published have been based
  on data taken from systematic reviews of
  randomized trials
• Evidence from single studies or logistic
  regression data (identifying risks factors for
  PONV) had not been included either

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Consensus Guidelines for Managing PONV

• Multidisciplinary expert panel reviewed available
  literature up to 02/2002
• Recommendations based on best available evidence
  regarding prevention and rescue therapy of PONV

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Goals of Guidelines

• Identify primary risks factors for PONV in adults
  and children
• Reduce baseline risks
• Identify optimal approach to PONV prevention and
  therapy in various patient populations
• Determine optimal choice and timing of
  anti-emetic administration
• Identify most effective mono-therapy and
  combination therapy regimes

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Strength of Evidence

• Panel analyzed and evaluated pertinent medical
  literature using widely used Evidence Rating
  Scales
• In the absence of published data, recommedations
  were based on expert opinion

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Evidence Rating Scale

• Level of Evidence based on Study design
• I Large, randomized, controlled trial, n 100
  per group
• II Systematic review
• III Small randomized, controlled trial, n 100
  per group
• IV Non-randomized, controlled trial or case
  report
• V Expert opinion
• Strength of recommendation based on expert
  opinion
• A Good evidence to support recommendation
• B Fair evidence
• C Insufficient evidence to recommend for or
  against

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Consensus Guidelines

• The following factors were considered
• PONV risk level
• Potential morbidity associated with PONV
• Suture dehiscence
• Esophageal rupture
• Hematoma formation
• Aspiration pneumonitis
• Potential adverse events
• QT prolongation, fatal arrhythmias
• Efficacy of antiemetics
• Cost of therapy
• Increased health care costs associated with PONV

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Consensus Guidelines

• Not all patients should receive prophylaxis
• Low risk patients unlikely to benefit
• Unnecessary risk from potential side effects
• Prophylaxis should be reserved for moderate to
  high risk patients

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Guideline 1

• Identify adults at high risk for PONV

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Adults at High Risk for PONV

• Apfel et al. identified four primary risk factors
  in patients receiving balanced anesthesia
• Female gender IA
• Non-smoking status IVA
• Prior history of PONV/Motion sickness IVA
• Use of opioids Intra-op/Post-op IIA/IVA

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Incidence of PONVApfel et al.

• No factors 10
• One factor 20
• Two factors 40
• Three factors 60
• Four factors 80

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Type of Surgery and PONV

• Sinclair et al. study of 18,000 ambulatory
  patients suggests PONV risk gt 15
• Breast augmentation IVB
• Dental surgery IVB
• Orthopedic shoulder procedures IVB
• Gynecologic laparoscopy IVB
• Varicose vein stripping IVB
• Strabismus repair IVB

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Duration of Surgery and PONV

• Each 30-minute increase in surgery time increases
  PONV incidence by 60, thus,
• A baseline risk of 10 is increased to 16 after
  30 minutes
• IVA evidence

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Guideline 2

• Identify Children at high risk for POV

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Children at High Risk for PONV

• Only POV studied
• Leading post-operative complaint from parents
• Leading cause of re-admission
• POV increases as age increases
• Rare lt 2 yrs
• 40 if gt 3 yrs (2x as frequent as adults)
• Incidence tapers at puberty
• No sex difference before puberty
• Risk increases more specifically with certain
  surgeries TA, strabismus, hernias, orchiopexy,
  penile procedures

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Guideline 3

• Reduce baseline risk factors for PONV

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Baseline Risk Factor Reduction

• Scuderi et al. tested a multimodal approach to
  reducing PONV in a randomized controlled clinical
  trial of women undergoing outpatient laparoscopy
• Multimodal
• Pre-operative anxiolysis
• Aggressive hydration
• Oxygen
• Droperidol Dexamethasone at induction
• Ondansetron at the end
• TIVA with propofol remifentanil
• Ketorolac
• No nitrous oxide or muscle relaxation

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Baseline Risk Factor Reduction

• Patients who received multimodal therapy had 98
  complete response rate
• Antiemetic monotherapy 76
• Saline placebo 59
• Level of satisfaction was the same between
  multimodal and monotherapy respondents

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Baseline Risk Factor Reduction

• Regional anesthesia IIIA
• Induction/maintenance with Propofol IA
• Intra-op supplemental O2 IIIB
• Aggressive hydration IIIA
• Avoidance of Nitrous Oxide IIA
• Avoidance of volatile anesthetics IA
• Minimization of intra-op/post-op opioids IIA/IVA
• Minimization of neostigmine IIA

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Guideline 4

• Antiemetic therapy for PONV prophylaxis in adults

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Antiemetic Therapy for Adults

• Serotonin receptor antagonists
• Steroids
• Butyrophenones
• Phenothiazines
• Anticholenergics
• Benzamides
• Antihistamines
• Others

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Antiemetic Therapy for Adults

• Serotonin receptor antagonists
• No profile difference between them
• FDA approved ondansetron at 4 mg IV prior to
  induction
• Leeser and Scuderi in 91 and 93 respectively
  determined optimal dose at 4 mg at start of
  anesthesia
• Sun et al. For ENT surgery is more effective at
  end of surgery
• Tang et al. and Graczyk et al. For gynecologic
  outpatient surgery more effective at the end of
  surgery

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Antiemetic Therapy for Adults

• Serotonin receptor antagonists
• Ondansetron more effective as antiemetic than
  antinausea (NNT 7 vs 6)
• NTH 36 for HA
• NTH 31 for increased liver enzymes
• NTH 23 for constipation
• MOA specific and selective 5-HT3 antagonism

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Antiemetic Therapy for Adults

• Dexamethasone
• Henzi et al. found that 8-10 mg IV effectively
  prevents nausea and vomiting with NNT of 4
• Liu and Wang found 2.5-5 mg just as effective
• Most effective when used before induction
• Dreaded side effects common with long term
  administration (increased wound infection,
  adrenal suppression, etc.)have not been noted
  after a single bolus dose

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Antiemetic Therapy for Adults

• Dexamethasone
• MOA unknown
• Prostaglandin antagonism
• Release of endorphins
• Anti-inflammatory and membrane stabilizing effect

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Antiemetic Therapy for Adults

• Droperidol (Butyrophenones)
• Efficacy equivalent to ondansetrons
• NNT 5
• Most effective when given at the end of surgery
• Black Box Warning
• ..may cause death or life-threatening events
  associated with QT prolongation and torsades de
  pointes
• Based on 10 reported cases after over 30 years of
  use
• Dolasetron and ondansetron in combo with
  metoclopramide have also been involved in QT
  prolongation
• McCormick (2002) and Scuderi (2003) currently
  performing studies to define effect of droperidol
  on QTc interval

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Antiemetic Therapy for Adults

• Droperidol
• MOA strong D2 antagonism acting at the CTZ and
  area postrema
• Effective dose 0.625-1.25 mg IV IA

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Antiemetic Therapy for Adults

• Phenothiazines
• Act as sedatives and counter effect of opioids at
  CTZ (Howat, 1960 Dundee et al. 1965, Wood 1979)
• Limited use in ambulatory setting due to sedation
  effects
• In 1999 Khalil et al. found promethazine
  effective for middle ear surgery antiemesis when
  used along or in combo with ondansetron

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Antiemetic Therapy for Adults

• Phenothiazines
• MOA direct blocking of D2 receptors in CTZ
• Extrapyramidal effects possible
• Neuroleptic malignant syndrome is rare but
  possible
• promethazine 12.5-25 mg IV and prochlorperazine
  5-10 mg IV at the end of surgery effective

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Antiemetic Therapy for Adults

• Anticholinergics
• Atropine, glycopyrrolate and scopolamine have all
  been tested as antiemetics.
• Cerebral cortex and ponds rich with cholinergic
  and muscarinic receptors
• Dundee et al. found atropine and scopolamine
  better than glycopyrrolate to counter action of
  opioids

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Antiemetic Therapy for Adults

• Scopolamine transdermally was found to prevent
  PONV effectively (Kranke et al. meta-analysis
  2002) however, incidence of side effects was
  inexcusably high
• Side effects visual disturbances, sedation, dry
  mouth, dizziness and memory dysfunction are common

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Antiemetic Therapy for Adults

• Benzamides
• Metoclopramide most effective in this class
• MOA
• Specific D2 antagonism in CTZ
• High dose antagonizes 5-HT3
• Cholinergic action in stomach increases LES tone
  and decreases transit time increasing peristaltic
  motility
• Opioid induced PONV treated as gastric stasis is
  reversed
• Extrapyramidal side effects, cardiac
  dysrhythmias, dysphoria

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Antiemetic Therapy for Adults

• Should metoclopramide be used?
• Metoclopramide has been used for over 40 years
• Wilson et al. studied 230 patients (2001) found
  metoclopramide 10 mg IV as effective as
  ondansetron 4 mg for prophylaxis of PONV after
  lap chole
• Quaynor et al. (2002) found same equivalence
  with 20 mg metoclopramide and 8 mg ondansetron
  during same same surgical procedure

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Antiemetic Therapy for Adults

• Should metoclopramide be used?
• Henzi et al. in 1999 did systematic review of 66
  studies and 3260 patients No evidence of
  dose-responsiveness with oral, intranasal or IV
  in either adults or children
• Panel of experts convened in march 2003
• Although most members agreed that it could not
  be recommended as an antiemetic, agreement was
  not unanimous

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Antiemetic Therapy for Adults

• Should metoclopramide be used?
• Continued use at 10 mg is clearly inadequate
• Chemotherapy induced nausea and vomiting is
  treated with 2 mg/Kg- This regimen is better than
  placebo with only minor side effects
• Cholinergic action may justify its use in
  conjunction with opioids

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Antiemetic Therapy for Adults

• Antihistamines
• MOA Block Acetyl-ch in vestibular apparatus and
  H1 in nucleus of solitary tract
• Act mainly in vomiting center and vestibular
  pathways
• Kranke et al. 2002 meta-analysis showed
  dimenhydranate prevented PONV in early phase with
  NNT 8
• Significant side effects limits outpatient use

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Antiemetic Therapy for Adults

• Ephedrine
• As early as 1991 ephedrine was shown to have
  similar antiemetic effects as droperidol both
  compared to placebo
• Short acting- only 90 min.
• No benefit following next 24 hrs
• Hagemann (2000) et al. found IM Ephedrine was
  effective in reducing emesis during the first
  three hours after abdominal hysterectomy
• No change in BP between groups Thus antiemetic
  effect is specific

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Antiemetic Therapy for Adults

• Non-pharmacological techniques
• Acupuncture
• TENS
• Acupressure
• Hypnosis
• Bispectral monitoring
• Supplemental O2
• Maintainance of BP
• Intraoperative fluids
• NNT approximately 5

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Guideline 5

• Antiemetic therapy for POV prophylaxis in children

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Antiemetic Therapy for Children

• POV twice as frequent
• Unable to assess Nausea
• 5-HT3 antagonists most studied in peds due to
  being better antiemetics than antinausic
• Ondansetron 50-100 mcg/Kg- NNT 2-3
• Dolasetron 350 mcg/Kg
• Dexamethasone 150 mcg/Kg- NNT 4
• Droperidol 50-75 mcg/Kg- NNT 5

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Guideline 6

• Use prophylaxis in patients at high risk for PONV
  and consider prophylaxis in patients at moderate
  risk for PONV

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Algorithm for management of postoperative nausea
and vomiting (PONV)
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Prophylaxis

• Prophylaxis likely useful only for patients in
  moderate to high risk for PONV
• Patients at low risk get prophylaxis only if at
  risk for medical sequelae from vomiting,
• i.e. wired jaws, increased ICP,
  fundoplication,etc.
• Generally, combination therapy superior to
  monotherapy
• Different MOA optimize efficacy

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Prophylaxis

• 5-HT3 antagonists having better antivomiting
  effect but association wit HA can be effectively
  combined with droperidol which has better
  antinausea profile and protective effect against
  HAs
• 5-HT3 and dexamethasone
• 5-HT3 and promethazine

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Guideline 7

• Provide antiemetic treatment to patients with
  PONV who did not receive prophylaxis or in whom
  prophylaxis failed

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Failed or absent prophylaxis

• First response should be bedside exam to exclude
  inciting medication or mechanical factor
• MSO4 PCA
• Blood draining down the throat
• Abdominal obstruction
• Hypotension, hypovolemia

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Failed or absent prophylaxis

• Tramer et al., (1997)If patient has received no
  prophylaxis, generally, 5-HT3 treatment doses are
  ¼ of prophylactic doses
• 1.0 mg ondansetron
• 12.5 mg dolasetron
• 0.1 mg granisetron
• 0.5 mg tropisetron

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Failed or absent prophylaxis

• Droperidol no different from ondansetron as
  therapy for established PONV
• Promethazine as effective in the general surgical
  population
• If prophylaxis with 5-HT3 blocker ineffective
  do not initiate rescue tx with 5-HT3 within 6 hrs
  after surgery as it confers no additional
  benefit, Kovac et al. 1999
• As a general rule, failure of one drug class
  should be treated with a different class (V)

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Failed or absent prophylaxis

• Triple therapy regimes have not been tested
• If triple therapy prophylaxis fails, it should
  not be repeated within the first 6 hrs (IIIA)
• Rescue therapy with propofol 20 mg as needed can
  be considered (IIIB)
• Dexamethasone should not be used more often than
  q8hrs

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Conclusion

• First step in reducing PONV is to reduce baseline
  risk factors among patients at risk
• Adult prophylaxis at moderate risk treated with
  either mono or combination therapy
• Double and triple combo recommended for patients
  at high risk
• Children at moderate to high risk should be
  treated with combo therapy that includes 5-HT3
  antagonists

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Conclusion

• Antiemetic therapy should be used with all
  patients who have an emetic episode after surgery
• PONV occurring within six hours of surgery should
  not receive a repeat dose of the same antiemetic
• PONV occurring more than 6 hours after surgery
  may be treated with any antiemetic except
  dexamethasone and transdermal scopolamine

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References

• Gan TJ, et al,. Consensus guidelines for managing
  PONV. Anesth Analg 2003 9762-71
• Jokela R, Prevention of PONV Studies on
  different antiemetics, their combinations and
  dosing regimes. Academic Dissertation, Department
  of anesthesiology, University of Oulu, Finland
  20031-66
• Kovac AL. Antiemetic use in PONV- online
  monograph. www.ponvupdate.org.online_monograph.asp
  
• Ku CM, Ong BC. PONV A review of current
  literature. Singapore Med J 20344(7)366-374
• Henzi I, et al,. Metoclopramide in the prevention
  of PONV A quantitative systematic review of
  randomized, placebo-controlled studies. British
  Journal Anesth 199983(5)761-71
• Scuderi PE et al,. Multimodal antiemetic
  management prevents early postoperative vomiting
  after outpatient laparoscopy. Anesth Analg.
  200091(6)1408-14
• Sanchez-Ledesma MJ. A comparison of three
  antiemetic combinations for the prevention of
  PONV. Anesth Analg 200295(6)1590-5
• Nelskyla KA. Sevoflurane titration using
  bispectral index decreases postoperative vomiting
  in phase II recovery after ambulatory surgery.
  Anesth Analg 200193(5)1165-9
• Goll V. Ondansetron is no more effective than
  supplemental intraoperative oxygen for prevention
  of PONV. Anesth Analg 200192(1)112-7
• Purhonen S. Supplemental oxygen does not reduce
  the incidence of PONV after ambulatory
  gynecological laparoscopy. Anesth Analg
  200396(1)91-6
• Moretti EW. Intraoperative colloid administration
  reduces PONV and improves postoperative outcomes
  compared with crystalloid administration. Anesth
  Analg 200396(2)611-7
• Pusch F. The effects of systolic arterial blood
  pressure variation on PONV. Anesth Analg
  200294(6)1652-5.
• Kovac AL et al,. Efficacy of repeat intravenous
  dosing of ondansetron in controlling PONV A
  randomized, double-blind, placebo-controlled
  multicenter trial. J Clin Anesth 199911(6)453-9

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References- continuation.

• Kazemi-Kjellberg F et al,. Treatment of
  established PONV A quantitaive systematic
  review. BMC Anesthesiol 20011(1)2
• Junger A, et al,. The use of an anesthesia
  information management system for prediction of
  antiemetic rescue treatment at the PACU. Anesth
  Analg 200192(5)1203-9