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 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