Post Operative Nausea & Vomiting

POST OPERATIVE NAUSEA
AND VOMITING
Dr Kiran Rajagopal DA DNB.
Anaesthesiologist

• PONV - two of the most common and unpleasant side effects following
anaesthesia and surgery
• Incidence of nausea - 22% to 38%
Incidence of vomiting - 12% to 26%.
• An episode of vomiting prolongs postanaesthetic care unit stay by about
25 minutes

VOMITING CENTER
Includes multiple sensory, motor, and
control nuclei mainly in the medullary
and pontine reticular formation but
and extending into the spinal cord.
Receives afferent inputs
from
 Higher cortical centers
 Cerebellum
 Vestibular apparatus
 Vagal and
 Glossopharyngeal nerves
Receives afferent inputs from
Higher cortical centers
Cerebellum
Vestibular apparatus
Vagal and
Glossopharyngeal nerves
CTZ & NTS

• Further interactions occur with the nucleus tractus solitarius and the
chemoreceptor trigger zone (CTZ)
• CTZ is located in Area postrema, a circumventricular organ at the
bottom of the fourth ventricle
• The CTZ is outside the blood-brain barrier and in contact with
cerebrospinal fluid (CSF).
• The CTZ enables substances in the blood and CSF to interact

Motor impulses that cause the actual vomiting are transmitted from the
vomiting center by
• 5th, 7th, 9th, 10th, and 12th cranial nerves to the upper git
• Vagal and sympathetic nerves to the lower tract
• Spinal nerves to the diaphragm and abdominal muscles

Post Operative Nausea & Vomiting

 TOXIC MATERIALS IN THE GASTROINTESTINAL LUMEN
 ABSORBED TOXINS AND DRUGS
 STIMULATION OF THE VESTIBULAR SYSTEM

Ingestion of toxic substances Release of serotonin (5HT) from
enterochromaffin cells in
gut wall
Indirect release of 5 HT
through
M3 , β , H3 receptors
Serotonin lies in close
proximity to vagus
Vagal endings travel to dorsal brainstem
via NTS
Stimulation of GABA B ,5 HT4,
α2 receptors ,VIP, Somatostatin
Reduce serotonin release

Absorbed toxins or drugs circulating in the blood
Stimulation of the chemoreceptor trigger zone
Emetogenic triggers to the vomiting center
Vomiting reflex activated

•
Movement
Stimulates receptors in the vestibular labyrinth of the inner ear
Impulses transmission via brain stem vestibular nuclei
Cerebellum CTZ
Vomiting center

•
ANTI PERISTALSIS
occurs in the early stages of gastric irritation or
distension
at a rate of 2 to 3 cm/sec
CONTRACTIONS DUODENUM &
STOMACH
RELAXATION OF GE SPINCHTER
VOMITING ACT

(1) A deep breath
(2) Raising of the hyoid bone and larynx to pull the upper esophageal
Sphincter open
(3) Closing of the glottis to prevent vomitus flow into the lungs, and
(4) Lifting of the soft palate to close the posterior nares
(5) Strong downward contraction of the diaphragm along with
simultaneous contraction of all the abdominal wall muscles
(6) Squeezes the stomach between the diaphragm and the abdominal
muscles  inc intra gastric pressure
(7) Lower esophageal sphincter relaxes completely  expulsion

 Conscious recognition of subconscious excitation in an area of the
medulla closely associated with or part of the vomiting center
 Causes
(1) Irritative impulses coming from the gastrointestinal tract
(2) Impulses that originate in the lower brain associated
with motion sickness or
(3) Impulses from the cerebral cortex to initiate vomiting.

RISK FACTORS
STRATEGIES TO
REDUCE BASELINE RISK
PREVENTION TREATMENT
PONV

(Anesth Analg 2014;118:85–113)

Guideline 1. Identify Patients Risk for
PONV

PATIENT RELATED ANAESTHESIA RELATED SURGERY
RELATED

 Female Gender
 History of PONV
 Not Smoking
 History of motion sickness
 Age < 50
Female gender strongest patient-
specific predictor
PONV increases during menstruation
and preovulatory phase 
Due to sensitization of the CTZ and
vomiting center to follicle-stimulating
FSH and oestrogen
Reason for increased female
susceptibility
to PONV is not clear
Long term smokers are desensitized
to nausea
Nonsmokers
were 1.8 times more likely than
smokers to have PONV
Incidence of PONV decreases with
age
In children age >= 3 yrs increased risk

 Opioids
 Propofol & Inhaled
Anesthetics
 Nitrous Oxide
 Duration of Anesthesia
Preop / Periop / Postop use
Post operative use carries more risk
Post op use doubles the risk
Dose of opiod more predictive than type
Opioid-sparing strategies reduce the
incidence of PONV
GA risk factor for PONV
Propofol has antiemetic properties
Volatile anaesthetics are the main
cause of PONV within the first two
postoperative hours
Dose dependent emetogenic effect
No differences among iso, sevo ,des
Substituting propofol for a volatile
anesthetic reduced the risk by about
19 %
Less emetogenic than volatile agents
Effects of N2O & volatile agents are
additive (independent)
Increasing the duration by 30 min
increases the risk of PONV by 60%
The use of volatile anesthetics is
the strongest anesthesia-related
predictor
followed by the duration of
anesthesia,
postoperative opioid and nitrous
oxide

 Major abdominal and gynecologic
procedures
 Laparoscopy
 Cholecystectomy
 Middle ear surgeries
 Thyroid, breast, plastic surgery
neurosurgery
 Strabismus Sx in children
Only laparoscopy ,gynec procedures
cholecystectomy and strabismus Sx
found to be independent predictors
PONV in laparoscopy - due to gas
insufflation of abdomen  pressure on
vagus nerve  relays to vomiting
center
Emetogenic procedures 
laparoscopy, adult strabismus
surgery, middle ear surgery,
herniorrhaphy, tonsillectomy,
adenoidectomy, and
uvulopalatopharyngoplasty

• Low incidence of PONV after
regional techniques
• PNB < SAB < EPIDURAL < GA
INTRA OP N&V IN SAB
INDEPENDENT PREDICTORS
FEMALE GENDER
HISTORY OF MOTION SICKNESS
PREOPERATIVE TACHYCARDIA
PREOPERATIVE INTRAVENOUS
OPIOIDS
USE OF PHENYLEPHRINE/
EPINEPHRINE
HYPOTENSION
HIGH INTRATHECAL BLOCK

 Only vomiting is reported due to difficulties in eliciting nausea in the
young age group
 High risk (POV) surgeries -
strabismus, adenotonsillectomy, hernia repair, orchidopexy, and penile
surgery
 Rare in children younger than 2 years
 Risk increases with age >=3
 The increased vomiting incidence tapers when children reach puberty

 Common after outpatient surgery
 Risk factors different from those
of PONV.
Female gender
Age less than 50 years
History of PONV after previous
anesthesia
Opioid administration in the
PACU and
Nausea in the PACU

Guideline 2. Reduce Baseline Risk Factors
for PONV

Opiod sparing – NSAIDS, COX 2 inhibitors
Intra op ketamine has morphine sparing in post op

Strategies not recommended
in 2014 guidelines
Minimizing neostigmine
dose to 2.5 mg
Supplemental oxygen
New Information
Minimization of neostigmine dosage
has been removed from the list of
strategies to reduce baseline risk
as new evidence did not find this to
be helpful, and the evidence is
contradictory.
In children, subhypnotic
doses(bolus
of 1 mg/kg followed by an infusion
at 20 mcg/kg/min )of propofol
infusion in combination with an
antiemetic significantly reduce
incidence of PONV

HYPOTENSION
HYPOVOLAEMIA
INADEQUATE OXYGENATION
PAIN
TEMPERATURE – HYPOTHERMIA,
OR PATIENT FEELS TOO WARM
INFECTION
HUNGER
POOR ORAL HYGIENE
FOUL OR UPSETTING SMELLS IN
THE VICINITY OF THE PATIENT

Guideline 3. Administer PONV Prophylaxis Using 1 to 2
Interventions in Adults at Moderate Risk for PONV

 Intraoperative antiemetics form the cornerstone of antiemetic therapy
 Apfel and colleagues demonstrated that using one or more antiemetic
therapies (up to 4) decrease the incidence of nausea and vomiting
significantly
 With each additionally administered antiemetic, the risk of PONV was
further reduced by 30% (the so-called rule of 1/3).
 Multimodal therapy effective than single drug

 CHOLINERGIC
 DOPAMINERGIC (D2)
 HISTAMINERGIC (H1)
 SEROTONERGIC (5HT3)
 DEXAMETHASONE
 OPIOD ANTAGONISTS
 NEUROKININ-1(NK-1)
ANTAGONISTS
A
N
T
A
G
O
N
I
S
T
S

METOCLOPRAMIDE
 Anti dopaminergic
 Phenothiazine
 Weak anti emetic
 Prokinetic
 10 mg dose
 25 mg or 50 mg more
effective for PONV
SIDE EFFECTS
HYPOTENSION
TACHYCARDIA
EXTRAPYRAMIDAL SYMPTOMS

 D2-antagonist
 Butyrophenones group
 0.625 to 1.25 mg iv
 Similar efficacy against both
nausea and vomiting
 Short t1/2 = 3 hrs
 Given at the end of the surgery
At lowest dose of 0.625mg
 FDA Black Box warning
DROPERIDOL
SIDE EFFECTS
ANXIETY AND RESTLESSNESS
AKATHISIA
DYSTONIA
TORSADES DE POINTES
DEATH

 Efficacy similar to that of
ondansetron
 Cardiac arrhythmias and death
reported
 Approved only for intramuscular
administration
 0.5 to 2 mg IM
HALOPERIDOL

Diphenhydramine H1 antagonism &
weak anti cholinergic
Cyclizine H1 antagonism &
Promethazine equal anti cholinergic activity
Given at the start  sedative side effects may
delay recovery if given at
the end of surgery
SIDE EFFECTS
DROWSINESS
URINARY RETENTION,
DRY MOUTH,
BLURRED VISION
Promethazine –
vascular necrosis

SCOPOLAMINE
Centrally acting anticholinergic
Short half life
Transdermal formulation-up to 72 hours
Effective for the prevention of PONV in
the first 24 postoperative hours
Applied the evening before surgery or
2 to 4 hours before the start of anesthesia
SIDE EFFECTS
VISUAL DISTURBANCES
PUPILLARY DILATATION

SIDE EFFECTS
HEADACHE,
LIGHTHEADEDNESS,
DIZZINESS,
CONSTIPATION.
FIRST GEN DRUGS- QT
PROLONGATION
TORSADES D POINTES
ONDANSETRON
 First serotonin antagonist
 Used for chemo induced N &V
 Similar efficacy against both
Nausea and vomiting – IMPACT TRIAL
 Half-life of 4 hours
 More effective when it is given at the
end of a Surgical procedure
 4mg is the effective dose
MOST EFFECTIVE ANTI EMETIC FOR PONV( GOLD STANDARD)

 Liver-converted active metabolite
hydrodolasetron
 Are highly specific 5-HT3
antagonists with plasma half-lives
roughly twice as long as that of
ondansetron
 Dose =12.5 mg
 Not recommended due to QT
prolongation
 Highly specific 5-HT3 antagonist
 Half-life that is approximately
twice as long as that of
ondansetron.
 Dose = 1 mg
DOLASETRON MESYLATE GRANISETRON

PALONOSETRON
 Second generation
 Long half-life of approximately 40 hours
 Exhibits allosteric binding to 5-HT3 receptors with subsequent receptor
internalization, as well as negative cooperativity with Neurokinin-1 (NK1)
receptors
 Superior to ondansetron in PONV
 Dose – 0.075 mg
 Can be given at the start of surgery

• Central inhibition of the NTS but not
the area postrema.
• Slow onset of action
• Given at the beginning of surgery
• Efficacy is similar to that of
ondansetron and droperidol
• Dose - 2.5 to 5 mg
• 4 mg of ondansetron, 4 mg of
dexamethasone, and 1.25 mg of
Droperidol have same efficacy
• SIDE EFFECTS
• POSTOPERATIVE INFECTION
• INCREASES IN BLOOD
GLUCOSE

 More recent studies increasingly use the higher dose of
dexamethasone 8 mg IV rather than the minimum effective dose of
4 to 5 mg
 Dexamethasone also has dose-dependent effects on quality of
recovery
 A meta-analysis evaluating the dose-dependent analgesic effects of
perioperative dexamethasone found that doses >0.1 mg/kg are an
effective adjunct in multimodal strategies to reduce postoperative
pain and opioid consumption

Methylprednisolone 40 mg IV is effective for the prevention of late
PONV

 Substance P binds to NK1 receptors found in vagal afferents in the
gastrointestinal tract. It is found near vomiting center
 APREPITANT - the first drug in its class approved for clinical use by the
FDA.
 Superior for preventing vomiting but not nausea
 Dose = 40 mg
 Half-life 40-hour
 Aprepitant is rarely used for PONV because of its relatively high cost
 Newer receptor antagonists are CASOPITANT and ROLAPITANT

• Peripheral opioid antagonist
• Reduce nausea severity in the late postoperative period without affecting
the central analgesic effects of opioids.
• Alvimopan appears to work by decreasing postoperative ileus and opioid-
induced bowel dysfunction

• The median plasma propofol concentration associated with an antiemetic
response was 343 ng/ mL, which is much lower than the concentration
ranges associated with general anesthesia
(3–6 mcg/mL) or sedation (1–3 mcg/mL)
• Propofol, in small doses (20 mg as needed), can be used
for rescue therapy
• TIVA
• Induction and maintenance

 Clonidine and dexmedetomidine showed a significant but weak and
short Lived antinausea effect
 Opiod sparing effect
• 600 mg orally given 2 hours before surgery
• 800mg 1 hour before surgery

• A small dose (2 mg) of midazolam when given 30 min before end of
surgery is effective in reducing PONV

• Acupuncture P6 point (the sixth point on the pericardial meridian at the volar
side of the wrist) .
• Stimulation of the P6 wrist point by means of acupuncture,
electroacupuncture, Transcutaneous nerve stimulation, laser stimulation,
acu-stimulation device, and acupressure
• The timing of acupoint P6 electrical stimulation did not impact PONV with
similar reductions in PONV achieved when the stimulation was initiated either
before or after anesthesia induction
• Neuromuscular stimulation over the median nerve reduced PONV in the early
postoperative period, particularly when tetanic stimulation was used.

• Liberal fluid supplementation
• Hypovolemia can trigger the release of emetogenic arginine vasopressin
from the posterior pituitary
• Crystalloid or colloid – same effect

Guideline 4. Administer Prophylactic Therapy With Combination (≥2)
Interventions/Multimodal Therapy in Patients at High Risk for PONV

5 HT3 antagonists and dexamethasone are the most effective
antiemetics in the prophylaxis of pediatric POV.
Guideline 5. Administer Prophylactic Antiemetic Therapy to
Children at Increased Risk for POV;As in Adults, Use of
Combination Therapy Is Most Effective

.
Guideline 6. Provide Antiemetic Treatment to Patients With
PONV who did not Receive Prophylaxis or in whom
Prophylaxis Failed

• Early rescue treatment with 1 mg of ondansetron seems to have
comparable efficacy and better effectiveness than 4 mg of prophylactic
ondansetron.
• After administering an antiemetic, it is most effective to choose an
antiemetic of another class for later rescue treatment
• Repeating the medication given for PONV prophylaxis within the first 6
hours after the initial dose conferred no additional benefit

.
Guideline 7. Ensure PONV Prevention and Treatment
Is Implemented in the Clinical Setting

.
Guideline 8. Use General Multimodal Prevention
to Facilitate Implementation of PONV Policies

 MILLER 8TH
 WYLIE 7TH
 GUYTON PHYSIOLOGY
 CONSENSUS GUIDELINES FOR THE MANAGEMENT OF POSTOPERATIVE
NAUSEA AND VOMITING
JANUARY 2014 • VOLUME 118 • WWW.ANESTHESIA-ANALGESIA.ORG
 MULTIMODAL THERAPIES FOR POSTOPERATIVE NAUSEA AND VOMITING
BRITISH JOURNAL OF ANAESTHESIA 107 (S1): I27–I40 (2011)

Post Operative Nausea & Vomiting

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