1. Prepared by Dr. Mahmoud Abdel-Khalek Risk Stratification and Treatment Post-operative Nausea& Vomiting (PONV)

2. Importance of PONV Patient distress Patient distress Morbidity (aspiration, suture tension, oesophageal rupture, electrolyte disturbances, dehydration) Morbidity (aspiration, suture tension, oesophageal rupture, electrolyte disturbances, dehydration) Prolonged PACU stay Prolonged PACU stay Unexpected hospital admission/re- admission 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 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: 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 CTZ rich in dopamine and serotonin receptors vestibular apparatus uses ACh to transmit vestibular apparatus uses ACh to transmit treatment aimed at afferent supply to VC treatment aimed at afferent supply to VC

5. Apfel Score General anaesthesia (volatiles) with no antiemetic therapy (age ≥ 18) Risk Factors 1. Female Gender 1. Female Gender 2. Non-smoker 2. Non-smoker 3. Post-operative use of opioids 3. Post-operative use of opioids 4. Previous PONV or motion sickness 4. Previous PONV or motion sickness Apfel score 110% 221% 339% 479%

6. Children Studies limited to vomiting Studies limited to vomiting Twice as frequent as adults Twice as frequent as adults Risk increases as child ages! (decrease after puberty) Risk increases as child ages! (decrease after puberty) No difference in sex before puberty No difference in sex before puberty Stronger correlation with type of surgery Stronger correlation with type of surgery

7. Reducing risk factors Avoiding GA (use regional) Avoiding GA (use regional) Avoiding volatiles (use propofol) Avoiding volatiles (use propofol) Intra-operative O 2 (FiO2 80%) Intra-operative O 2 (FiO2 80%) Adequate hydration Adequate hydration Avoiding nitrous oxide Avoiding nitrous oxide Minimising length of operation Minimising length of operation Minimising neostigmine Minimising neostigmine

8. TYPES OF AGENTS USED IN PONV

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

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

11. 1. Dopamine antagonists Benzamides Metoclopramide 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

12. 2. Anticholinergics Hyoscine 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 Atropine: cardiac effects too prominent Glycopyrrolate: does not cross BBB Glycopyrrolate: does not cross BBB

13. 3. Antihistamines Cyclizine Cyclizine –IV/IM painful to inject (pH 3.2) –H1 antagonist, but also anticholinergic properties Promethazine Promethazine –traditional pre-med too –significant anticholinergic/sedative effects –urinary excreted

14. 4. 5-HT3 Antagonists Ondansetron 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

15. 5. Miscellaneous Steroids 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 Acupuncture – Point P6 Cannabinoids Cannabinoids –Use in chemotherapy, not established for PONV Benzodiazepines Benzodiazepines