EVALUATION OF EFFICACY AND SAFETY OF THREE …
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Transcript EVALUATION OF EFFICACY AND SAFETY OF THREE …
CO-AUTHORS
Prof & 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. PG
INSTITUTE 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 ACTION
Antagonism of 5HT3 receptors
Also has an allosteric binding site
Causes receptor interanalisation
and prolonged inhibition
USES
Prevention 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 EFFECTS
COMMON
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.
AIM
To evaluate the efficacy of Palonosetron
versus placebo for prevention of
Postoperative Nausea and Vomiting
DESIGN
Randomized 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
METHODS
Ethical 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 COLLECTION
EMETIC 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
ANALYSIS OF
COLLECTED DATA
PHYSIOLOGICAL PARAMETERS
VARIABLE
Age in
GROUP Pn
GROUP Po
“p”
(n = 30)
(n = 30)
27.3 + 4.4
26.3 + 3.9
0.3808
53.7 + 5.4
54.8 + 3.5
0.5428
151.2 + 3.1
151.7 + 2.7
0.4796
23.4 + 2
23.8 + 1.3
0.4289
years
Weight
(in kgs)
Height
( in cms)
BMI
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
GROUP Pn
GROUP Po
Range
80 - 140
80 – 135
Mean
107.8
105.2
S.D.
15.2
12
PROC
‘p’
0.4898
TOTAL INTEROPERATIVE OPIOID USED
TOT. OPIOD
GROUP Pn GROUP Po
USED
Range
130 - 210
140 – 200
Mean
167
163.3
S.D.
17.4
17.9
‘p’
0.3156
APFEL SCORE
APFEL
GROUP Pn
GROUP Po
SCORE
No.
%
No.
%
3
25
83.3
27
90
4
5
16.7
3
10
Total
30
100
30
100
Range
3–4
3–4
Mean
S.D.
3.17
0.38
3.1
0.31
‘p’
0.4513
INTENSITY OF NAUSEA ( VAS )
INT OF
GROUP
GROUP
NAUSEA
Pn
Po
“p”
0 – 2 hrs
2.43 + 2.21 4.43+ 1.65 0.0008
2 – 6 hrs
1.53 + 1.63 3.07 + 1.31 0.0004
6 – 24 hrs
1.3 + 1.66
2.3 + 1.52
0.0034
24 – 72 hrs 0.9 + 1.49 2.07 + 1.51
0.0013
EMETIC EPISODES 0 – 24 HR Interval
EMETIC
EPISODES
YES
NO
“p”
GROUP Pn
GROUP Po
n
%
n
%
10
33.3
22
73.3
20
66.7
8
26.7
0.0044
EMETIC EPISODES 24 – 72 HR Interval
EMETIC
EPISODES
YES
NO
“p”
GROUP Pn
GROUP Po
n
%
n
%
8
26.7
10
33.3
22
73.3
20
66.7
0.7763
COMPLETE REMISSION 0 – 24 HR Interval
COMPLETE
REMISSION
YES
NO
“p”
GROUP Pn
GROUP Po
n
%
n
%
20
66.7
8
26.7
10
33.3
22
73.3
0.0044
COMPLETE REMISSION 24 - 72HR Interval
COMPLETE
REMISSION
YES
NO
“p”
GROUP Pn
GROUP Po
n
%
n
%
22
73.3
20
70
8
26.7
10
30
0.7763
SUMMARY
Randomised 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
CONCLUSION
PALONOSETRON 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
REFERENCES
A 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
>0.05 insignificant
‘ p ‘ value calculated for the
duration of procedure &
>0.05 insignificant
total dose of fentanyl used
No adverse effects were observed in both groups
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)
< 0.05 significant
0 – 24 hr time interval, ‘ p ‘ value for
emetic episode incidence (p=0.0044)
& complete remission
(p=0.0044)
< 0.05 significant
24-72 hr time interval interval ‘ p ‘ value for
emetic episode incidence (p=0.7763)
& complete remission
(p=0.7782)
> 0.05 insignificant