Postoperative Nausea and Vomiting

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Postoperative Nausea and Vomiting

• Jonathan Wallace

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Overview

• Physiology of PONV and risk factors
• Review of literature
• PONV prophylaxis
• Treatment of PONV - a possible protocol for PACU
  and the wards

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Overview of PONV
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Patient perceptions

• Macario A. et al. Which Clinical Anesthesia
  Outcomes Are Important to Avoid? The Perspective
  of Patients. Anesth Analg 199989652-8.
• Patients studied rated nausea and vomiting as the
  1st or 2nd most undesirable outcome from surgery
  (equal to or more important than adequate pain
  relief)

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Physiology of PONV

• Vomiting is primarily controlled by the vomiting
  centre in the dorsolateral reticular formation of
  the medulla.
• The vomiting center receives input from several
  anatomical sites and vomiting is effected via
  neuromuscular responses in the gut,
  thoracoabdominal wall and pharynx.
• Nausea is poorly understood but is likely to
  involve the cortex as requires conscious
  perception.
• EEG activation of temporofrontal cortical areas

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ACTIVATORS and neurotransmitters

• CTZ (chemoreceptor trigger zone) emetic drugs,
  bacterial toxins, metabolic disorders (5-HT3, M1,
  H1, D2 receptors)
• Gastric irritants gastroduodenal vagal afferents
  (5-HT3 receptors)
• Noxious thoughts or smells cortex
• Gag reflex activation cranial nerves
• Labyrinthine apparatus (M1 and H1 receptors)
• Peripheral pain receptors

Fig.1 Vomiting activators and neurotransmitters (h
ttp//www.frca.co.uk/article.aspx?articleid354)
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Coordination of emesis

• Vomiting centre integrates responses gt brainstem
  nuclei
• Contraction of inspiratory thoracic and abdominal
  wall muscles increases intrathoracic and
  intra-abdominal pressure
• Gastric cardia herniates across diaphragm
  larynx moves upwards
• Normal gut slow waves replaced by retrograde
  spikes

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Risk Factors for PONV
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Risk factors for PONV

• There are few independent predictors for PONV1,2

Patient Anaesthetic Surgical
Female Volatile agents Duration
Nonsmoking Nitrous oxide Type of surgery strabismus, laparoscopy, laparotomy, gynaecological, neurological, maxillofacial
History of PONV/motion sickness Intra-/postoperative opioids Type of surgery strabismus, laparoscopy, laparotomy, gynaecological, neurological, maxillofacial
1. Gan et al. Society for Ambulatory Anesthesia
Guidelines for the Management of Postoperative
Nausea and Vomiting. Anesth Analg
2007105161528 2. Apfel CC et al. Comparison of
surgical site and patients history with a
simpli?ed risk score for the prediction of
postoperative nausea and vomiting. Anaesthesia,
2004 59 1078-1082
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A Simplified Risk Score for PONV - Adults
Score Risk of PONV
0 10
1 20
2 40
3 60
4 80
Risk Factor Score
Female 1
Non-smoker 1
History of PONV 1
Postoperative opioids 1
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A Simplified Risk Score for PONV - Children
Score Risk of PONV
0 10
1 10
2 30
3 55
4 70
Risk Factor Score
Surgery 30 mins 1
Age 3 yrs 1
Strabismus surgery 1
History of/relatives with PONV 1
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Questions

• What drug (or combination of drugs) is most
  effective at preventing PONV?
• Which patients would benefit from prophylaxis and
  what is the most effective strategy?
• How can treatment of PONV be optimised in PACU
  and on the wards?

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Evidence
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Cochrane Review 2006

• Carlisle JB, Stevenson CA. Drugs for preventing
  postoperative nausea and vomiting. Cochrane
  Database of Systematic Reviews 2006, Issue 3.
  Art. No. CD004125. DOI 10.1002/14651858.CD004125
  .pub2.
• 737 studies, n 103 237
• 8 drugs were effective in preventing PONV
  compared with placebo
• Droperidol, metoclopramide, ondansetron,
  tropisetron, dolasetron, granisetron,
  dexamethasone, cyclizine
• Relative risk reduction 0.6-0.8
• We did not find reliable evidence that one drug
  was better than another.
• Effects were additive when drugs were given
  together

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The IMPACT Trial

• Apfel CC et al. A Factorial Trial of Six
  Interventions for the Prevention of Postoperative
  Nausea and Vomiting. N Engl J Med 2004 350
  2441-51
• RCT (factorial design) involving 28 centers,
  n5199
• Evaluated 6 individual treatments and in
  combination
• Ondansetron 4mg dexamethasone 4mg droperidol
  1.25mg propofol instead of volatile agent
  nitrogen or nitrous oxide remifentanil or
  fentanyl

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IMPACT Trial Results

• Each antiemetic drug had a similar relative risk
  reduction (Table 1)
• No significant differences between antiemetics

Intervention RRR (95 CI) p value
Ondansetron 4mg -26 (-31.5 to -19.9) lt0.0001
Dexamethasone 4mg -26.4 (-31.9 to -20.4) lt0.0001
Droperidol 1.25mg -24.5 (-30.2 to -18.4) lt0.0001
Propofol -18.9 (-25 to -12.3) lt0.0001
Nitrogen as carrier -12.1 (-19.3 to -4.3) 0.003
Remifentanil 5.2 (-2.9 to 13.8) 0.21
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IMPACT Trial Results

• 26 relative risk reduction for each additional
  antiemetic used
• This has implications for who benefits most from
  prophylaxis

10 risk of PONV 80 risk of PONV
Risk after 1 intervention 7 59
ARR 3 21
NNT 40 5
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Maxolon

• There and back again.

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Maxolon

• Wallenborn J et al. Prevention of postoperative
  nausea and vomiting by metoclopramide combined
  with dexamethasone randomised double blind
  multicentre trial. BMJ 2006 333 (7653) 324-330.
• Previous meta-analysis 10mg ineffective1
• Complex mode of action metoclopramide binds to
  dopamine, serotonin and histamine receptors.
• Double blind RCT of 3140 patients
• Dexamethasone alone vs in combination with 10mg,
  25mg and 50mg of metoclopramide (iv 30-60 min
  before anticipated end of surgery)

1. Henzi I, Walder B, Tramer MR. Metoclopramide
in the prevention of postoperative nausea and
vomiting a quantitative systematic review of
randomized, placebo-controlled studies. Br J
Anaesth 199983761-71.
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Results
Dexamethasone 8mg plus metoclopramide Incidence of PONV (CI) NNT
0mg 23.1 (20.2-26)
10mg 20.6 (17.8-23.4) 40
25mg 17.2 (14.6-19.8) 17
50mg 14.5 (12-17) 12
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Conclusions

• 25mg as effective as 50mg but 50mg more effective
  at preventing late PONV (gt12 hrs post-op)
• But its a high dose!
• Adverse effects?
• Contraindications

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Aprepitant

• Lai M et al. Combining aprepitant with
  dexamethasone for the prevention of postoperative
  nausea and vomiting. Abstract presented at
  ANZCA/ASM2008 3-7 May 2008 p76-77.
• Substance P/Neurokinin 1 Receptor antagonist
• Double blind, randomised study. n240
• Groups Aprepitant 80mg, dexamethasone 4mg, and
  in combination.

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Results

• Similar efficacy to dexamethasone
• Significantly more effective in combination
• Used mainly in chemotherapy at present

Aprepitant 80mg Dexamethasone 4mg Aprepitant 80mg dexamethasone 4mg
0-6h 27 21 6
6-48h 5 7 2
0-48h 31 28 8
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Prophylaxis
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Optimising prophylaxis

• Relative risk reduction of approximately 26 for
  each antiemetic (and each additional antiemetic)
• Patients who will benefit the most (lower NNT)
  are those at higher risk
• Also important for optimising cost/benefit and
  minimising adverse effects

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Prophylactic Strategy1
1. Gan et al. Society for Ambulatory Anesthesia
Guidelines for the Management of Postoperative
Nausea and Vomiting. Anesth Analg 2007105161528
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PACU Ward Protocols
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RPAH

• Protocol initiated with signed order PONV
  Treatment Protocol (do not require
  countersigning)
• Stepwise protocol with
• Prochlorperazine (Stemetil)
• Tropisetron
• Droperidol
• Takes account of intraoperative dosing

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North Shore Hospital, Auckland NZ
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Royal Adelaide Hospital

• Metoclopramide no longer recommended
• Identifies high risk patients with intraoperative
  therapy and postoperative standing orders
• Coming soon...

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Conclusion
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Conclusion

• Prophylaxis is effective
• Identify patients at moderate to high risk
• Most patients should get at least one form of
  prophylaxis consider other interventions (e.g.
  TIVA)
• Most of the commonly used drugs are equally
  effective
• PACU and ward protocols/standing orders can be
  effective

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