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Postoperative Nausea and

Vomiting

Dr Amit Kocheta

DNB Trainee

Anesthesiology

BMHRC

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Introduction

The most common and distressing symptoms,which follow anesthesia and surgery, are pain andemesis.

During ether era, reported incidence of PONV was

as high as 7580%. Eighty years ago, Flagg suggested that PONV may

result from causes other than anesthetics : thereare at least three kinds of vomiting,

the first of which has been attributed to anesthetics

such as ether, the second to reflex responses,

the last to opioids.

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The incidence of postoperative emesis in somelarge studies has been reported to be in therange of 2030 %.

Intractable PONV is the most frequent

anesthetic related cause for unexpectedhospital admission of surgical out patients.

PONV causes increase in IOP & ICP, suturedehiscence, esophageal rupture, hematoma

formation & aspiration pneumonitis.

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Definitions

Nausea : It is an unpleasant sensation referredto a desire to vomit, not associated withexpulsive muscular movement.

Retching : When no stomach contents areexpelled even with expulsive muscular efforts.

Vomiting : It is the forceful expulsion of even asmall amount of upper gastrointestinal contents

through mouth.

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Overview

Physiology

Aetiology

Associated factors

Management Prevention

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Physiology

Vomiting reflex

Afferent inputs

Processing centre

Motor efferents

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Vomiting Centre

Located in the medulla

Represents multiple nuclei involved inthe integration of the vomiting reflex

The motor component of the vomiting

reflex is mediated by both autonomicand somatic systems, whose activity iscoordinated in the vomiting centre

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Afferent pathways

Gastrointestinal tract (5HT3, D2)

Mechanoreceptors located in the wall of thegut are activated by abnormal distension,

contraction, physical damage or manipulationduring surgery

Chemo receptors located in the mucosa aretriggered by noxious chemical stimuli

Information relayed via the vagus nerve to thenucleus tractus solarius in the vomiting centre

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Afferent pathways

Chemoreceptor Trigger Zone Area Postrema Located in the floor of the 4th ventricleDefective BBB for detecting circulating toxins in the

blood and CSFWorks through the 5-HT3 receptors as well as

dopamine type 2 receptors

Others Vestibular system: responsible for motion sickness

Cardiovascular system: afferents from cardiacventricles and blood vesselsHigher centers: limbic system, olfactory and visual

cortex Pharyngeal afferents (?gag reflex)

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Chemoreceptor Trigger Zoneand Emetic Center

AntagonistAntagonist

AgonistAgonist

Receptor SiteReceptor Site

Area

Area

Pos

trem

a

Pos

trem

a ChemoreceptorChemoreceptorTriggerTriggerZoneZone(CTZ)(CTZ)

EmeticCenter

5-HT5-HT33 RAsRAs

5-HT5-HT33

PromethazinePromethazine

HistamineHistamine

AtropineAtropine

MuscarinicMuscarinic

DroperidolDroperidol

Dopamine (DDopamine (D22))

Nitrogen mustardNitrogen mustard

CisplatinCisplatin

Digoxin glycosideDigoxin glycoside

Opioid, analgesicsOpioid, analgesics

Vestibular portionVestibular portionof 8th nerveof 8th nerve

NN22OO

GI tract distensionGI tract distension

Higher centers (vision, taste)Higher centers (vision, taste)

PharynxPharynx

ParvicellularParvicellular

ReticularReticularFormationFormation

MediastinumMediastinum

??

VagusVagus

NK-1 RANK-1 RA

Substance PSubstance P

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Efferent pathways

Vomiting reflex is divided into 2 phases

Pre-ejection or Prodromal phase: relaxation ofthe gastric muscles followed by small intestinalretrograde peristalsis

Ejection phase : comprises of retching and vomitingwith expulsion of gastric contents.

Mediated by autonomic and somatic systems,coordinated in the vomiting centre

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Schematic representation of thefactors influencing nausea and

vomiting

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Risk Factors

Patient factors

Preoperative factors

Intraoperative factorsAnesthetic factors

Surgical factors

Postoperative factors

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Patient Factors

Age Highest in 6-16 age group

Gender Women 2-4x more likely than men

Obesity Non-smoker Gastro paresis

Diabetes, hypothyroidism, pregnancy, h/o

swallowing blood, full stomach, intra-abdominalpathology

History of motion sickness, PONV Chemotherapy patients

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Preoperative Factors

FoodProlonged pre-op fasting

Not starved

Anxiety

Premedication

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Intraoperative factors:Anesthetic

Intubation Deeper plane of anaesthesia Gastric inflation during mask ventilation Intraoperative dehydration Drugs : Opioids, Ketamine compared with

Propofol and Thiopentone Inhalation Agents: N20 compared with

Sevoflurane, Isoflurane, Desflurane

General anaesthesia compared with spinaland regional anaesthesia

Neostigmine: in high doses

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Postoperative factors

Head movement of patient afterwaking

Postoperative pain

Early ambulation, dizziness

Early intake of food

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Surgery factors

Duration of surgery

Type of surgeryGynecological

ENT

Abdominal

Head &neck

Squint correction

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Risk Score for Predicting PONVby Apfel

RISK FACTORS:1 -Female sex

2 - Hx. of motion

sickness or PONV

3 - Nonsmoking status

4 - Use of Postoperative

Opioids

NONE 1 Factor 2 Factors 3 Factors 4 Factors

79 %61 %39 %21 %10 %

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Management:Pharmacological Prophylaxis

Multiple receptors involved in thevomiting reflex

5HT-3

D2

M1 ACh

H1Neurokinin-1

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Drugs

Antagonists 5HT-3 :-Dolasetron,

Granisetron,Tropisetron,Ondansetron

D2:- Droperidol,Metoclopramide,Prochlorperazine

Ach :-Cyclizine,Scopolamine

H1 :-Promethazine,Cyclizine

Neurokinin-1:-Aprepitant

Agonists Steroids Dexamethasone

Benzodiazepines Midazolam Cannabinoids

Th i it f ti fThe main sites of action of

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The main sites of action ofThe main sites of action of

drugs affecting nausea anddrugs affecting nausea and

vomitingvomiting

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for the Prophylaxis of PONV in

AdultsAgentAgent DosageDosage

DroperidolDroperidol 0.625 1.25 mg Iv 5 min before termination of0.625 1.25 mg Iv 5 min before termination ofanesthesiaanesthesia

OndansetronOndansetron 4 mg IV immediately before induction4 mg IV immediately before induction8 mg PO 1 h before induction8 mg PO 1 h before induction

Recent data: more effective- end of anesthesiaRecent data: more effective- end of anesthesia

DolasetronDolasetron 12.5 mg IV intraoperatively12.5 mg IV intraoperatively100 mg PO 1 h before induction100 mg PO 1 h before induction

MetoclopramideMetoclopramide 10 (20) mg IV near the end (not effective when10 (20) mg IV near the end (not effective whenused alone)used alone)

PromethazinePromethazine 25 mg PO 1 h before induction25 mg PO 1 h before induction12.5 25 mg IV immediately before ind.12.5 25 mg IV immediately before ind.

ProchlorperazineProchlorperazine 5 15 mg PO 1 h before induction5 15 mg PO 1 h before induction5 10 mg IM 1 2 h before ind.; repeat once in5 10 mg IM 1 2 h before ind.; repeat once in

30 min,30 min,

5 10 mg IV 15 30 min before ind; x15 10 mg IV 15 30 min before ind; x1

GranisetronGranisetron20 40 mcg/kg IV20 40 mcg/kg IV

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Standard Dosages of Antiemetics forthe Treatment of PONV in Adults

AgentAgent DosageDosage

OndansetronOndansetron 1 4 mg IV postoperatively1 4 mg IV postoperatively

MetoclopramideMetoclopramide 10 mg IV q 46 h prn post-operatively10 mg IV q 46 h prn post-operatively

PromethazinePromethazine 10 25 mg PO prn post-operatively10 25 mg PO prn post-operatively12.5 25 mg IM or IV q4h prn post-operatively12.5 25 mg IM or IV q4h prn post-operatively

ProchlorperazineProchlorperazine 5 15 mg PO post-op.5 15 mg PO post-op.

5 10 mg IM; repeat once in 30 min prn5 10 mg IM; repeat once in 30 min prn

5 10 mg IV; may repeat once prn5 10 mg IV; may repeat once prn

ChlorpromazineChlorpromazine 10 25 mg PO q4-6h prn10 25 mg PO q4-6h prn

12.5 25 mg IM if no hypotension; repeat in 1h12.5 25 mg IM if no hypotension; repeat in 1h

DroperidolDroperidol 0.625 1.25 mg IV prn0.625 1.25 mg IV prn

DolasetronDolasetron 12.5 mg IV post-operatively12.5 mg IV post-operatively

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Standard Dosages of Antiemetics forthe Management of POV in Pediatric

PatientsAgentAgent DosageDosage

ProphylaxisProphylaxis

DolasetronDolasetron Age >2y: 1.8 mg/kg IV immediately before ind.Age >2y: 1.8 mg/kg IV immediately before ind.

OndansetronOndansetron 0.05 mg/kg IV (range: 0.05 0.15 mg/kg)0.05 mg/kg IV (range: 0.05 0.15 mg/kg)

DroperidolDroperidol 0.015 0.075 mg/kg per dose IV0.015 0.075 mg/kg per dose IV

TreatmentTreatment

ChlorpromazineChlorpromazine 0.55 mg/kg PO or IM0.55 mg/kg PO or IM

DroperidolDroperidol 0.1 mg/kg per dose IV0.1 mg/kg per dose IV

OndansetronOndansetron 0.05 mg/kg per dose IV0.05 mg/kg per dose IV

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Ondansetron (Emeset)

Serotonin 5HT3 antagonist

Adult dose : 4-8 mg IV

Pediatric dose : 50 100 mcg/kgIV up to 4 mg

Greater efficacy in prevention ofvomiting than nausea

Most effective whenadministered at end of surgery

Headache, dizziness, flushing,

elevated liver enzymes,constipation

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Droperidol

Butyrophenone Blocks dopamine-2 receptors in the

CTZ and area postrema Usual adult dose: 0.625-1.25 mg IV Pediatric dose : 50 -75 mcg/kg up to

1.25mg Duration of action: up to 12-24 hours Adverse effects: sedation, dizziness,

anxiety, hypotension, extra pyramidalside effects

More effective for nausea thanvomiting

FDA BLACK BOX WARNING 2001 Increased risk of lengthening of the QT

intervals in some patients Risk for cardiac patients!!!

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Metoclopramide (Reglan)

Benzamide

Blocks dopamine-2 receptors inthe CTZ and vomiting center

Prokinetic properties that

quicken esophageal clearance,enhance gastric emptying, andshorten bowel-transit time

Less effective than Ondansetronor Droperidol

Most commonly administereddose of 10 mg IV is not effectivefor prevention of PONV

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Metoclopramide (Reglan)

Usual adult dose for PONV: 25-50 mg IV

10-20 mg IV for rescue N/V

Duration of action: up to 6hours

Adverse effects: sedation,hypotension, extra pyramidalsymptoms, restlessness

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Promethazine (Phenergan)

Phenothiazine

Blocks dopamine-2 receptors in theCTZ and other areas of the brain

Also blocks histamine-1 receptors

and msucarinic-1 receptors Usual adult dose: 6.25-12.5 mg IV

Duration of action: 4-6 hours

Adverse effects: sedation,hypotension, extra pyramidal

symptoms

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Diphenhydramine(Benadryl)

Antihistamine

Suppresses motor-enhanced

vestibular neuronal firing

Adverse reactions: sedation,

dry mouth, blurred vision,urinary retention

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Scopolamine

Anticholinegic Transdermal patch

Blocks the muscarinic-1 receptors inthe cerebral cortex and pons andhistamine-1 receptors in thehypothalamus and vomiting centerto exert its antiemetic effects

Suppresses the noradrenergicsystem (improved adaptation tovestibular stimulation)

4 hour onset of action Needs to be placed the night before for

patients with increased risk of PONV

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Dexamethasone

Corticosteroid

Antiemetic action not fullyunderstood

Thought to work by antagonizing

prostaglandins or releasingendorphins that elevate mood,improving ones sense of well-being and stimulating appetite

Most effective when administered

before induction of anesthesia

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NK1 Antagonists

Future development in anti-emesis is looking at theneurokinin 1 (NK-1) receptor, where substance Pis the natural ligand. This receptor is found in thenucleus tractus solitarius and the area postrema,as well as the peripheralnervous system. Early

studies of NK-1 antagonists have been promising,especially in combination with Ondansetron

Neurokinin (substance P, NK1) antagonists -impressive antiemetic in the animal model. However,early clinical data have been disappointing, except forAprepitant (Emend) - has demonstratedsuperiority over Ondansetron in chemotherapyinduced nausea and vomiting.

Complementary Therapies:

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Complementary Therapies:Acupuncture and Related

Techniques Traditional Chinese medicinetreated nausea and vomiting withacupuncture

Uses needles that are inserted into

traditional acupuncture points inthe body, initiating a series ofphysiological events that counterPONV

Certain nerve fibers are stimulatedthat result in nerve impulses beingsent to the spinal cord Endorphogenic cells are stimulated to

release endorphins


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Techniques Nerve impulses produced byacupuncture also transmit to theperiaqueductal gray area of themidbrain where enkephalin isreleased Causes a release of the monoamine

neurotransmitters serotonin andnorepinephrine in the spinal cord

3rd effect is release of beta-endorphins andadrenocorticotropic hormone(ACTH) from the pituitary glandinto the bloodstream andcerebrospinal fluid

Calming of the GI tract


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Techniques Acupressure

Uses physical andmechanical pressure

instead of needlesover the samemeridians of thebody

P6 point stimulation

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Complementary Therapies:Aromatherapy

Dates back as far as2800 BC

Herbal preparations and

plant extracts Use of oil of ginger as a

prophylactic therapy

Isopropyl alcohol Oil of peppermint

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Complementary Therapies:Peppermint

Remedy formorningsickness,

dyspepsia, andother GIcomplaints

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Inhalation of Isopropyl AlcoholVapors

Study of 100 healthywomen undergoingoutpatient gynecologiclaparoscopic procedures

Randomly received 4 mgOndansetron or 70%isopropyl alcohol forpostoperative nausea

Use of alcohol padsresulting in quicker reliefof nausea

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Complementary Therapies:Oral Ginger

Oral ginger has beenused in China fortreating GI symptomssuch as nausea andvomiting

Ginger root, gingerpowder, ginger candy,and ginger gum

Ginger oil in form ofaromatherapy

Role not clearlydefined by research

St t i t R d

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Strategies to ReduceBaseline Risk

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ThanksThanks

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