CO-AUTHORSProf & HOD Dr.I.Chandrasekaran M.D.,D.A.,Prof Dr.S.P.Meenakshisundaram M.D.,D.A.,

Asst. Prof Dr.D.S.Sudhakar M.D.,DNB.,

AUTHOR : G.N.Jeevanandam IIyr M.D. PGINSTITUTE OF ANAESTHESIOLOGY , Madurai Medical College

Post Operative Nausea & Vomiting

Second most common complaints reported

Unpleasant experience often rated worse than

postoperative pain

Medical risks : Aspiration of gastric contents,

Suture dehiscence,

Esophageal

rupture,

Subcutaneous emphysema, Pneumothorax

HR & BP elevation(risk for MI & dysrhythmias )

Bradycardia and hypotension.

RISK FACTORS APFEL Simplified risk scoring for adults

PALONOSETRON•Potent and selective 5-HT3

antagonist

•Plasma elimination T½ ~ 40 h

•Metabolized primarily by

liver.

•Age, hepatic dysfunction or

mild-to-moderate renal

impairment have no clinically

significant effect on the

pharmacokinetics

MECHANISM OF ACTIONAntagonism of 5HT3

receptors

Also has an allosteric binding

site

Causes receptor

interanalisation and

prolonged inhibition

USESPrevention of postoperative nausea and vomiting

Prevention of acute and delayed nausea and vomiting

associated chemotherapy.

Dosage and Administration

Postoperative Nausea and Vomiting

IV 0.075 mg before the induction of anesthesia.

Chemotherapy-Induced Nausea and Vomiting

IV 0.25 mg administered 30 min before the start of

chemotherapy.

PO 0.5 mg administered 1 h prior to the start of chemotherapy.

SIDE EFFECTSCOMMON Headache

Constipation

OTHERS

• Cardiovascular :ECG QT prolongation, bradycardia,

hypotension, tachycardia.

• CNS : Headache, anxiety, dizziness,

weakness.

• Gastro Intestinal: Constipation, diarrhea.

• Genitourinary: Urinary retention.

• Hepatic: Increased ALT, increased AST.

AIMTo evaluate the efficacy of

Palonosetron versus placebo for

prevention of Postoperative

Nausea and Vomiting

DESIGNRandomized double blind control study

Female patients undergoing laproscopic surgery under GA

Inclusion criteria

Age 18 - 60 yrs

ASA I - II

Non - Smokers

Exclusion criteria

Patients received antiemetics 24 hrs prior to surgery

Patients received / undergoing chemotherapy or

radiotherapy

Pre existing heart blocks , bradycardia, QT prolongation,

Duration of procedure <1 hr

METHODSEthical committee approval

Informed consent

Randomised allocation into 2 groups

Group Pn : Inj.Palonosetron 0.o75mg I.V

Group Po : Placebo ( Normal Saline 1.5ml ) I.V

All patients premedicated with Inj.Midazolam 0.05mg/kg &

Inj.Glyco 0.2mg im 45 min before induction

I.V lines will be secured

Preinduction monitors NIBP, Pulse oximetry, ECG, connected

Just prior to Induction of anesthesia patients will receive the

allocated drug or equal volume of normal saline I.V

Induced with Inj.Thio 5mg/kg ,Inj.Fentanyl 2mics/kg ,Inj.Suxa

2mg/kg

Maintainence with intermittent titrated dose of Inj.Atracurium ,

Inj.Fentanyl and N2O : O2 ( 60 : 40 )

Reversal with Inj.Neostigmine 40mics/kg & Inj.Glyco 10mics/kg

and extubation

DATA COLLECTIONEMETIC episodes (vomiting and retching)

Intensity of Nausea (VAS scoring for nausea)

both at 2 ,6 , 24, 48, 72 hrs with respect to their

occurrence over the previous observation period

Rescue therapy Inj.Metoclopromide 10mg I.V when

VAS > 4 / emetic episodes

Complete response (defined as no emetic episodes

and no rescue medication) will be noted for the time

interval of 0 – 24 hrs & 24 – 72 hrs

Patients Age ,Weight,BMI

Risk factors for PONV (H/O PONV , H/O motion

sickness )

Duration of surgery

Total intra operative opioid (fentanyl) dose

Post operative opioid use will be noted (proposed post

operative pain relief : Inj.Tramadol 100mg I.M)

Side effects like headache ,constipation and other

adverse events will be noted

PHYSIOLOGICAL PARAMETERSVARIAB

LE

GROUP Pn

(n = 30)

GROUP

Po

(n = 30)

“p”

Age in

years

27.3 + 4.4 26.3 +

3.9

0.380

8

Weight

(in

kgs)

53.7 + 5.4 54.8 +

3.5

0.542

8

Height

( in

cms)

151.2 +

3.1

151.7 +

2.7

0.479

6

BMI 23.4 + 2 23.8 +

1.3

0.428

9

ASA RISK

ASA GROUP Pn GROUP Po

n % n %

I 26 86.7 27 90

II 4 13.3 3 10

‘p’ 0.691

DURATION OF PROCEDURE

DUR OF

PROC

GROUP Pn GROUP Po

Range 80 - 140 80 – 135

Mean 107.8 105.2

S.D. 15.2 12

‘p’ 0.4898

TOTAL INTEROPERATIVE OPIOID USED

TOT. OPIOD

USED

GROUP

Pn

GROUP

Po

Range 130 - 210 140 –

200

Mean 167 163.3

S.D. 17.4 17.9

‘p’ 0.3156

APFEL SCORE

APFEL

SCORE

GROUP Pn GROUP Po

No. % No. %

3 25 83.3 27 90

4 5 16.7 3 10

Total 30 100 30 100

RangeMeanS.D.

3 – 43.170.38

3 – 43.1

0.31

‘p’ 0.4513

INTENSITY OF NAUSEA ( VAS )

INT OF

NAUSEA

GROUP

Pn

GROUP

Po

“p”

0 – 2 hrs 2.43 +

2.21

4.43+

1.65

0.000

8

2 – 6 hrs 1.53 +

1.63

3.07 +

1.31

0.000

4

6 – 24

hrs

1.3 +

1.66

2.3 +

1.52

0.003

4

24 – 72

hrs

0.9 +

1.49

2.07 +

1.51

0.001

3

EMETIC EPISODES 0 – 24 HR Interval

EMETIC

EPISOD

ES

GROUP Pn GROUP Po

n % n %

YES10 33.3 22 73.3

NO20 66.7 8 26.7

“p” 0.0044

EMETIC EPISODES 24 – 72 HR Interval

EMETIC

EPISOD

ES

GROUP Pn GROUP Po

n % n %

YES8 26.7 10 33.3

NO22 73.3 20 66.7

“p” 0.7763

COMPLETE REMISSION 0 – 24 HR Interval

COMPLE

TE

REMISSI

ON

GROUP Pn GROUP Po

n % n %

YES20 66.7 8 26.

7

NO10 33.3 22 73.

3

“p” 0.0044

COMPLETE REMISSION 24 - 72HR Interval

COMPLE

TE

REMISSI

ON

GROUP Pn GROUP Po

n % n %

YES22 73.3 20 70

NO8 26.7 10 30

“p” 0.7763

SUMMARYRandomised controlled study

Two groups, 30 patients in each

Female patients ,non-smokers ,undergoing

laproscopy of more than one hour duration

receiving opioids for postoperative pain relief

Inj.Palonosetron 0.075 mg Vs Placebo

Data collected regarding the incidence of emetic

episodes & the intensity of nausea by VAS scoring

Statistical analysis revealed that both groups were

comparable with regared to their demography

OBSERVATIONS Patients receiving Palonosetron compared to

control group have

Significant reduction in incidence of Emetic

episodes and greater Complete remission in

the first 24 hrs following surgery

Significantly low VAS scores for nausea over

the period of 72 hrs

No significant difference in Emetic episodes and

complete remission over 24-72hr period

Treatment effect of PALONOSETRON in this trial

was most pronounced during the first 24 h

No side effects

CONCLUSIONPALONOSETRON 0.075mg was

statistically superior to placebo for all

end-points during the first 24 h, including

Complete remisison ,emetic episode

incidence & intensity of nausea with no

adverse effects

In the 24-72 hr it has the advantage of

having good control of intensity of nausea

REFERENCESA Randomized, Double-Blind Study to Evaluate the

Efficacy and Safety of Three Different Doses of

Palonosetron Versus Placebo in Preventing Postoperative

Nausea and Vomiting Over a 72-Hour Period(Anesth Analg

2008;107:439 –44)

A Randomized, Double-Blind Study to Evaluate the

Efficacy and Safety of Three Different Doses of

Palonosetron Versus Placebo for Preventing Postoperative

Nausea and Vomiting(Anesth Analg 2008;107:445–51)

OBSERVATIONS ‘ p ‘ value calculated for

age, weight, height,

BMI, ASA

status&Apfel scores

‘ p ‘ value calculated for the

duration of procedure &

total dose of fentanyl

used

No adverse effects were observed in both groups

>0.05 insignificant

>0.05 insignificant

OBSERVATIONS contd‘p ‘ value for VAS scoring of nausea in the interval

0 – 2 hr ( p=0.0008) 2 – 6 hr (p=0.0004)

6 -24 hr (p=0.0034) 24 – 72

hr(p=0.0013)

0 – 24 hr time interval, ‘ p ‘ value for

emetic episode incidence (p=0.0044)

& complete remission (p=0.0044)

24-72 hr time interval interval ‘ p ‘ value for

emetic episode incidence (p=0.7763)

& complete remission

(p=0.7782)

< 0.05 significant

> 0.05 insignificant

< 0.05 significant