Postoperative Nausea

and Vomiting
Jonathan Wallace
Overview
Physiology of PONV and risk
factors
Review of literature
PONV prophylaxis
Treatment of PONV - a
possible protocol for PACU
and the wards
Overview of PONV
Patient perceptions
Macario A. et al. Which Clinical Anesthesia Outcomes
Are Important to Avoid? The Perspective of Patients.
Anesth Analg 1999;89:652-8.
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)
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
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
(http://www.frca.co.uk/article.aspx?articleid=354)
Coordination of emesis
Vomiting centre integrates responses => 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
Risk Factors for PONV
Risk factors for PONV
There are few independent predictors for PONV:
1,2
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
1. Gan et al. Society for Ambulatory Anesthesia Guidelines for the Management of Postoperative Nausea and Vomiting.
Anesth Analg 2007;105:161528
2. Apfel CC et al. Comparison of surgical site and patients history with a simplied risk score for the prediction of
postoperative nausea and vomiting. Anaesthesia, 2004; 59: 1078-1082
A Simplified Risk Score for PONV -
Adults
Risk Factor Score
Female 1
Non-smoker 1
History of PONV 1
Postoperative
opioids
1
Score Risk of PONV
0 10%
1 20%
2 40%
3 60%
4 80%
A Simplified Risk Score for PONV -
Children
Risk Factor Score
Surgery 30 mins 1
Age 3 yrs 1
Strabismus surgery 1
History of/relatives
with PONV
1
Score Risk of PONV
0 10%
1 10%
2 30%
3 55%
4 70%
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?
Evidence
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
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, n=5199
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
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) <0.0001
Dexamethasone 4mg -26.4 (-31.9 to -20.4) <0.0001
Droperidol 1.25mg -24.5 (-30.2 to -18.4) <0.0001
Propofol -18.9 (-25 to -12.3) <0.0001
Nitrogen as carrier -12.1 (-19.3 to -4.3) 0.003
Remifentanil 5.2 (-2.9 to 13.8) 0.21
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
Maxolon
There and back again.
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 ineffective
1

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 1999;83:761-71.

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
Conclusions
25mg as effective as 50mg but 50mg more effective at
preventing late PONV (>12 hrs post-op)
But its a high dose!
Adverse effects?
Contraindications
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. n=240
Groups: Aprepitant 80mg, dexamethasone 4mg, and in
combination.
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%
Prophylaxis
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
Prophylactic Strategy
1
1. Gan et al. Society for Ambulatory Anesthesia Guidelines for the Management of Postoperative Nausea and Vomiting.
Anesth Analg 2007;105:161528
PACU & Ward Protocols
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
North Shore Hospital, Auckland NZ
Royal Adelaide Hospital
Metoclopramide no longer recommended
Identifies high risk patients with intraoperative therapy
and postoperative standing orders
Coming soon...
Conclusion
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