PONV – Risk Stratificati on and Treatment Jimmy Fu
Importance of PONV Patient distress Morbidity (aspiration, suture tension,
oesophageal rupture, electrolyte disturbances, dehydration)
Prolonged PACU stay Unexpected hospital admission/re-
admission
Physiology Vomiting Centre: no anatomical site, collection of effector
neurones in medulla, travels down vagus, phrenic nerves, spinal motor, to abdominal muscles/diaphragm/stomach/gut
VC input from: Chemoreceptor Trigger Zone: floor of 4th ventricle (functionally
outside BBB) Vestibular apparatus Higher centres Limbic cortex Peripheral pain pathways Vagal afferents
CTZ rich in dopamine and serotonin receptors vestibular apparatus uses ACh to transmit treatment aimed at afferent supply to VC
1. Dopamine antagonistsPhenothiazineChlorpromazineThioridazineProchlorperazine
less sedation/anticholinergic effects than other D2 antagonists
more extrapyramidal effects: dystonias and akathisia
erratic oral bioavailability, marked hepatic first-pass metabolism
1. Dopamine antagonistsButyrophenonesDroperidol
FDA black box warning: QT prolongation/torsades, based on 10 reported cases. ?validity, nil case-reports in a peer-reviewed journal of these complications in doses used for PONV
sedation more pronounced, can occur 12hrs after administration
SE: hyperprolactinaemia, hypotension from alpha-adrenoceptor blockade
extensively metabolised by liver
Domperidone no IV formulation secondary to arrhythmias less likely to have extrapyramidal SE as does not cross BBB
1. Dopamine antagonistsBenzamidesMetoclopramide
D2 antagonist, 5-HT antagonist (some) and prokinetic for stomach
conflicting studies, some demonstrated equal efficacy to placebo in PONV
more effective given at end vs induction variable oral bioavailability (30-90%),
conjugated in liver
2. Anticholinergics Hyoscine
previously used as pre-med for PONV, sedation and amnesia
less cardiac effects compared with atropine/glycopyrrolate
short duration of action, extensively metabolised by liver, variable oral bioavailability
Atropine: cardiac effects too prominent Glycopyrrolate: does not cross BBB
3. Antihistamines Cyclizine
IV/IM painful to inject (pH 3.2) H1 antagonist, but also anticholinergic
properties
Promethazine traditional pre-med too significant anticholinergic/sedative effects urinary excreted
4. 5-HT3 Antagonists Ondansetron
very good for chemo/radio or post anaesthetic nausea (peripheral and central)
Most effective for PONV when given at end of case
ineffective for motion sickness/dopamine induced nausea
SE: headache, flushing, constipation, deranged LFTs, bradycardia (if rapid IV)
conjugated in liver
5. Miscellaneous Steroids
Dexamethasone Uncertain mechanism - ?prostaglandin
antagonism ?release of endorphins More effective at start of anaesthesia SE of wound infection and adrenal suppression,
but not demonstrated in single bolus dose Acupuncture – Point P6 Cannabinoids
Use in chemotherapy, not established for PONV Benzodiazepines
Risk Stratification Patient factors
Gender Non-smoker History of PONV/motion sickness
Anaesthetic factors Use of volatile agents Nitrous Oxide Use of intra/post operative opioids
Surgical factors Duration of surgery Type of surgery
(laparoscopy/ENT/neuro/breast/strabismus/laparotomy/plastics)
Apfel ScoreGeneral anaesthesia (volatiles) with no antiemetic therapy (age ≥ 18)Risk Factors1. Female Gender2. Non-smoker3. Post-operative use of opioids4. Previous PONV or motion sickness
Apfel score1 10%2 21%3 39%4 79%
Type of Surgery? Distribution of risk factors? Different anaesthetic technique? Different length of operation? Operation itself?
Inconclusive, conflicting results, evidence rating B
Children Studies limited to vomiting Twice as frequent as adults Risk increases as child ages! (decrease
after puberty) No difference in sex before puberty Stronger correlation with type of surgery
Reducing risk factors Avoiding GA (regional) Avoiding volatiles (propofol) Intra-operative O2 (FiO2 80%) Adequate hydration Avoiding nitrous Minimising length of operation Minimising neostigmine
“Consensus Guidelines” Identify and stratify risk Reduce risk factors (previous slide) Multimodal approach for high risk Children do better with 5-HT3 antagonists Rescue therapy should not be same agent
as prophylactic unless > 6hrs since dose Dexamethasone works well for prophylaxis
but not rescue
References Apfel et al: A Simplified Risk Score for Predicting
Postoperative Nausea and Vomiting: Conclusions from Cross-validations between Two Centers. ANESTHESIOLOGY 1999; 91:693
Gan et al: Consensus Guidelines for Managing Postoperative Nausea and Vomiting. ANESTHESIA & ANALGESIA 2003; 97:62-71
Apfel et al: A Factorial Trial of Six Interventions for the Prevention of Postoperative Nausea and Vomiting. The New England Journal of Medicine 2004; 350:2441-2451
Henzi et al: Dexamethasone for the Prevention of Postoperative Nausea and Vomiting: A Quantitative Systematic Review. ANESTHESIA & ANALGESIA 1999; 90(1):186