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
GROUP Pn
(n = 30)
GROUP Po
“p”
28
AGE & BMI
GROUP Pn
27.3
(n = 30)
GROUP Po
27
26.3
Age in
27.3 + 4.4
26.3 + 3.9
0.3808
years
Weight
26
25
53.7 + 5.4
54.8 + 3.5
0.5428
24
23.8
23.4
(in kgs)
Height
151.2 + 3.1
151.7 + 2.7
0.4796
22
( in cms)
BMI
23
23.4 + 2
23.8 + 1.3
0.4289
21
AGE (in years)
BMI
ASA RISK
35
ASA
GROUP Pn
ASA I
GROUP Po
30
II
%
n
%
26
86.7
27
90
4
13.3
3
10
4
3
26
27
GROUP Pn
GROUP Po
25
No.of Patients
I
n
ASA II
20
15
10
‘p’
0.691
5
0
DURATION OF PROCEDURE
120
100
GROUP Pn
GROUP Po
80
PROC
Range
80 - 140
80 – 135
Mean
107.8
105.2
S.D.
15.2
12
‘p’
0.4898
Time (mins)
DUR OF
60
107.8
105.2
GROUP Pn
GROUP Po
40
20
0
TOTAL INTEROPERATIVE OPIOID USED
170
160
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
Dose (mics)
150
140
130
167
163.3
120
110
100
GROUP Pn
GROUP Po
APFEL SCORE
APFEL 3
SCORE
No.
%
GROUP Po
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
GROUP Po
GROUP Pn
27
GROUP Pn
APFEL
APFEL 4
3
25
0
5
10
5
15
20
No.of Patients
25
30
35
INTENSITY OF NAUSEA ( VAS )
INT OF
GROUP
GROUP
NAUSEA
Pn
Po
2 – 6 hrs
6 – 24 hrs
4.5
1.3 + 1.66
2.3 + 1.52
0.0034
4.43
4
2.43 + 2.21 4.43+ 1.65 0.0008
1.53 + 1.63 3.07 + 1.31 0.0004
3.5
3.07
3
2.5
2.43
0.0013
2.3
2.07
2
1.53
1.5
1.3
0.9
1
24 – 72 hrs 0.9 + 1.49 2.07 + 1.51
GROUP Po
5
VAS for Nausea
0 – 2 hrs
GROUP Pn
“p”
0.5
0
0-2 hrs
2-6 hrs 6-24 hrs 24-72 hrs
Time interval hrs
EMETIC EPISODES 0 – 24 HR Interval
EMETIC EPI YES
EMETIC
EPISODES
YES
GROUP Pn
GROUP Po
100%
90%
n
%
n
%
33.3
22
73.3
8
80%
70%
10
EMETIC EPI NO
20
60%
50%
NO
20
66.7
8
26.7
40%
22
30%
“p”
0.0044
20%
10
10%
0%
GROUP Pn
GROUP Po
EMETIC EPISODES 24 – 72 HR Interval
EMETIC EPI YES
EMETIC
EPISODES
YES
GROUP Pn
GROUP Po
EMETIC EPI NO
100%
90%
n
%
n
%
80%
70%
8
26.7
10
33.3
60%
22
20
50%
NO
22
73.3
20
66.7
40%
30%
“p”
0.7763
20%
10%
8
10
0%
GROUP Pn
GROUP Po
COMPLETE REMISSION 0 – 24 HR Interval
COMP REMS YES
COMPLETE
REMISSION
YES
GROUP Pn
GROUP Po
COMP REMS NO
100%
90%
n
%
n
%
80%
10
70%
20
66.7
8
26.7
22
60%
50%
NO
10
33.3
22
73.3
40%
30%
20
20%
“p”
0.0044
8
10%
0%
GROUP Pn
GROUP Po
COMPLETE REMISSION 24 - 72HR Interval
COMP REMS YES
COMPLETE
REMISSION
YES
GROUP Pn
GROUP Po
100%
90%
n
%
n
%
COMP REM NO
8
9
22
21
GROUP Pn
GROUP Po
80%
70%
22
73.3
20
70
60%
50%
NO
40%
8
26.7
10
30
30%
20%
“p”
0.7763
10%
0%
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