PONV – Risk Stratification and Treatment

1. PONV – Risk Stratification and Treatment Jimmy Fu

2. Importance of PONV • Patient distress • Morbidity (aspiration, suture tension, oesophageal rupture, electrolyte disturbances, dehydration) • Prolonged PACU stay • Unexpected hospital admission/re-admission

3. 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

5. Types of agents used in PONV

6. 1. Dopamine antagonists Phenothiazine • Chlorpromazine • Thioridazine • Prochlorperazine • less sedation/anticholinergic effects than other D2 antagonists • more extrapyramidal effects: dystonias and akathisia • erratic oral bioavailability, marked hepatic first-pass metabolism

7. 1. Dopamine antagonists Butyrophenones • Droperidol • 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-adrenoceptorblockade • extensively metabolised by liver • Domperidone • no IV formulation secondary to arrhythmias • less likely to have extrapyramidal SE as does not cross BBB

8. 1. Dopamine antagonists Benzamides • Metoclopramide • 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

9. 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

10. 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

11. 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

12. 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

13. 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)

14. Apfel Score General anaesthesia (volatiles) with no antiemetic therapy (age ≥ 18) Risk Factors • 1. Female Gender • 2. Non-smoker • 3. Post-operative use of opioids • 4. Previous PONV or motion sickness Apfel score 1 10% 2 21% 3 39% 4 79%

15. Type of Surgery? • Distribution of risk factors? • Different anaesthetic technique? • Different length of operation? • Operation itself? • Inconclusive, conflicting results, evidence rating B

16. 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

17. Reducing risk factors • Avoiding GA (regional) • Avoiding volatiles (propofol) • Intra-operative O2 (FiO2 80%) • Adequate hydration • Avoiding nitrous • Minimising length of operation • Minimising neostigmine

18. “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

20. 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