PONV – Risk Stratification 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

Types of agents used in PONV

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

1. Dopamine antagonists Butyrophenones Droperidol Domperidone 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 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

2. Anticholinergics Hyoscine Atropine: cardiac effects too prominent 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 Promethazine 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 Acupuncture – Point P6 Cannabinoids 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 Anaesthetic 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 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%

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