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Postoperative Nauseaostoperative Nausea

& VomitingVomiting

Annlynn Annlynn KuokKuok



One of the most common and distressingOne of the most common and distressingsymptoms to followsymptoms to follow anaesthesiaanaesthesia and surgery isand surgery isPONVPONV

Considered by some patients to be even worseConsidered by some patients to be even worsethanthan postoppostop painpain

Intractable PONV is the most frequentIntractable PONV is the most frequent

anaestheticanaesthetic-related cause for unanticipated-related cause for unanticipatedhospital admission of surgical day caseshospital admission of surgical day cases

Reported incidence is around 20-30% for up toReported incidence is around 20-30% for up to

24 hours24 hours postoppostop



Overviewverview

PhysiologyPhysiology

Aetiology Aetiology

Associated factors Associated factors

ManagementManagement

PreventionPrevention



Physiologyhysiology

Vomiting reflexVomiting reflex

Afferent inputs Afferent inputs

Processing centreProcessing centre

Motor Motor efferentsefferents



Vomiting Centreomiting Centre

Located in the medullaLocated in the medulla

Represents multiple nuclei involved in the

integration of the vomiting reflex

The motor component of the vomiting

reflex is mediated by both autonomic and

somatic systems, whose activity iscoordinated in the vomiting centre



Afferent pathwaysfferent pathways

Gastrointestinal tract (5HT3, D2)Gastrointestinal tract (5HT3, D2)

MechanoreceptorsMechanoreceptors located in the wall of the gut are

activated by abnormal distension, contraction,

physical damage or manipulation during surgery

ChemoreceptorsChemoreceptors located in the mucosa arelocated in the mucosa are

triggered by noxious chemical stimulitriggered by noxious chemical stimuli

Information relayed via theInformation relayed via the vagusvagus nerve to thenerve to thenucleusnucleus tractustractus solariussolarius in the vomiting centrein the vomiting centre



Afferent pathwaysfferent pathways

Chemoreceptor Trigger ZoneChemoreceptor Trigger Zone

Area Area PostremaPostrema

Located in the floor of the 4Located in the floor of the 4thth ventricleventricle

Defective BBB for detecting circulatingDefective BBB for detecting circulating

toxins in the blood and CSFtoxins in the blood and CSF



Afferent Pathwaysfferent Pathways

OthersOthers

Vestibular system: responsible for motionVestibular system: responsible for motion

sicknesssickness

Cardiovascualr Cardiovascualr system: afferents fromsystem: afferents fromcardiac ventricles and blood vesselscardiac ventricles and blood vessels

Higher Higher centrescentres: limbic system, olfactory and: limbic system, olfactory andvisual cortexvisual cortex

Pharyngeal afferents (?gag reflex)Pharyngeal afferents (?gag reflex)



Efferent pathwaysfferent pathways

Vomiting reflex is divided into 2 phasesVomiting reflex is divided into 2 phases

Pre-ejection or Pre-ejection or ProdromalProdromal phase: relaxationphase: relaxationof the gastric muscles followed by smallof the gastric muscles followed by small

intestinal retrograde peristalsisintestinal retrograde peristalsis

Ejection phase : comprises of retching and

vomiting with expulsion of gastric contents.

Mediated by autonomic and somaticMediated by autonomic and somaticsystems, coordinated in the vomitingsystems, coordinated in the vomiting

centrecentre



Diagram toDiagram to

summarisesummarise



Risk Factorsisk Factors

Patient factorsPatient factors

Preoperative factorsPreoperative factors

IntraoperativeIntraoperative factorsfactors

Anaesthetic Anaesthetic factorsfactors

Surgical factorsSurgical factors

Postoperative factorsPostoperative factors



Patient Factorsatient Factors

Age Age Highest in 6-16 age groupHighest in 6-16 age group

Gender Gender Women 2-4x more likely than menWomen 2-4x more likely than men

ObesityObesity

Non-smoker Non-smoker GastroparesisGastroparesis

Diabetes, hypothyroidism, pregnancy,Diabetes, hypothyroidism, pregnancy, h/oh/o swallowing blood,swallowing blood,

full stomach, intra-abdominal pathologyfull stomach, intra-abdominal pathology History of motion sickness, PONVHistory of motion sickness, PONV

Chemotherapy patientsChemotherapy patients



Preoperative Factorsreoperative Factors

FoodFood

Prolonged pre-op fastingProlonged pre-op fasting

Not starvedNot starved

Anxiety Anxiety

PremedicationPremedication



Intraoperativentraoperative factors:factors:

Anaestheticnaesthetic Intubation

Deeper plane of anaesthesia

Gastric inflation during mask ventilation

Intraoperative dehydration

Drugs : Opioids, Ketamine compared with propofol andthiopentone

Inhalation Agents: N20 compared with sevoflurane,isoflurane, desflurane

General anaesthesia compared with spinal andregional anaesthesia

Neostigmine: in high doses



Postoperative factorsostoperative factors

Head movement of patient after waking

Postoperative pain

Early ambulation, dizziness

Early intake of food



Surgery factorsurgery factors

Duration of surgeryDuration of surgery

Type of surgeryType of surgery

GynaecologicalGynaecological

ENTENT

Abdominal Abdominal

Head+neckHead+neck

Squint correctionSquint correction



Management:anagement:

Pharmacological Prophylaxisharmacological Prophylaxis

Multiple receptors involved in theMultiple receptors involved in the

vomiting reflexvomiting reflex

5HT-35HT-3

D2D2

M1M1 ACh ACh

H1H1 Neurokinin-1Neurokinin-1



Diagram toDiagram to

summarisesummarise



Antagonists Antagonists

5HT-35HT-3 DolasetronDolasetron,, GranisetronGranisetron,, TropisetronTropisetron,,

OndansetronOndansetron

D2D2

DroperidolDroperidol,, MetoclopramideMetoclopramide,, ProchlorperazineProchlorperazine

ACh ACh CyclizineCyclizine, Scopolamine, Scopolamine

H1H1

PromethazinePromethazine,, CyclizineCyclizine

Neurokinin-1Neurokinin-1

Aprepitant Aprepitant



Agonists Agonists

SteroidsSteroids

DexamethasoneDexamethasone

BenzodiazepinesBenzodiazepines MidazolamMidazolam

CannabinoidsCannabinoids



Managementanagement

Prevention is the aimPrevention is the aim

As a general rule the relative indication As a general rule the relative indicationfor prophylaxis increases as the number for prophylaxis increases as the number

of risk factors increasesof risk factors increases



5HT-3 Antagonists5HT-3 Antagonists

NNT = 5NNT = 5 Timing?Timing?

At the end of At the end of surgeysurgey

DolasetronDolasetron Dose?Dose?

12.5mg is sufficient12.5mg is sufficient

Which one?Which one? DolasetronDolasetron 12.5 =12.5 = OndansetronOndansetron 4 =4 = TropisetronTropisetron 22

RamosetronRamosetron Longer acting- effective for up to 48 hoursLonger acting- effective for up to 48 hours

Side effectsSide effects

TramadolTramadol interaction?interaction?



D2 AntagonistsD2 Antagonists

DroperidolDroperidol NNT = 4-6 when used alone for prevention of PONVNNT = 4-6 when used alone for prevention of PONV

Dose? 0.625-1.25mgDose? 0.625-1.25mg

Cheap and cost effectiveCheap and cost effective

Also good for PCA Also good for PCA opioidopioid-induced nausea/vomiting-induced nausea/vomiting

Main side effect: sedatingMain side effect: sedating

Black box warning: relevance?Black box warning: relevance?

MetoclopramideMetoclopramide Conflicting evidenceConflicting evidence

Numerous trials demonstrating that asNumerous trials demonstrating that as monotherapymonotherapy it is noit is no

better than placebobetter than placebo

Apparently effective in combination with Apparently effective in combination with dexamethasonedexamethasonewhen given in larger doseswhen given in larger doses

As effective as As effective as ondansetronondansetron or or droperidoldroperidol in combinationin combination

withwith dexamethasonedexamethasone??



DexamethasoneDexamethasone

Timing is importantTiming is important

As effective as 5-HT3 antagonists and As effective as 5-HT3 antagonists and

droperidoldroperidol

NNT = 4NNT = 4

Mechanism of action: various theoriesMechanism of action: various theories

Central inhibition of PG synthesisCentral inhibition of PG synthesis Decreased turnover of 5-HT in the CNSDecreased turnover of 5-HT in the CNS

Most effective dose?Most effective dose?

Side effectsSide effects

Flushing,Flushing, perinealperineal itchingitching

One-off dose is not associated with adverseOne-off dose is not associated with adverseeventsevents

C li iC li i



CyclizineCyclizine 50mg as good as the 5HT-3 antagonists50mg as good as the 5HT-3 antagonists

NNT = 4-5NNT = 4-5 Expensive, not readily available at RPHExpensive, not readily available at RPH

ScopolamineScopolamine TransdermalTransdermal patch 1.5mg placed 1hr pre-op aspatch 1.5mg placed 1hr pre-op as

good asgood as intraoperativeintraoperative 5HT-3 antagonists or 5HT-3 antagonists or DroperidolDroperidol

Dry mouth major side effectDry mouth major side effect Not available at RPH anywayNot available at RPH anyway

PromethazinePromethazine

Prevention or rescuePrevention or rescue Effective in doses as low as 6.25mg IVEffective in doses as low as 6.25mg IV

More effective in middle ear surgery?More effective in middle ear surgery?



Neurokinin-1 Receptorseurokinin-1 Receptors

The final pathway?The final pathway?

Aprepitant Aprepitant

Highly selective NK-1 antagonist, givenHighly selective NK-1 antagonist, given

orallyorally Phase 3 trial recently completedPhase 3 trial recently completed

Better thanBetter than OndansetronOndansetron for up to 48 hours for for up to 48 hours for

vomitingvomiting Same nausea rates and rescue requirementsSame nausea rates and rescue requirements

Expensive and disappointing results!Expensive and disappointing results!



Cochrane reviewCochrane review

Just as good asJust as good as

pharmacologicalpharmacological

agents in preventingagents in preventing

postoppostop vomitingvomiting

Even better inEven better in

preventingpreventing postoppostop

nauseanausea

NNT = 5NNT = 5

P6 acupuncture point6 acupuncture point



Acupressurecupressure



Summary..ummary..

New thoughts..ew thoughts..

Numerous trials confirming combinationNumerous trials confirming combinationtherapy is more effectivetherapy is more effective

CombinationCombination antiemeticsantiemetics need to have differentneed to have different

sites of actionsites of action

MetoclopramideMetoclopramide might be usefulmight be useful

intraoperativelyintraoperatively in combination within combination withdexamethasonedexamethasone (20mg + 8mg)(20mg + 8mg)

Acupuncture works! Acupuncture works!

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