COMPARISON OF ONDANSETRON AND PALONOSETRON FOR …

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Transcript COMPARISON OF ONDANSETRON AND PALONOSETRON FOR …

COMPARISON OF EFFECT OF
ONDANSETRON Vs PALONOSETRON
IN PREVENTION OF POST OP NAUSEA
AND VOMITING FOLLOWING
ENT SURGERIES
Dr.Kaviya.K.J II yr MD
Prof. Dr. R. Subramaniya Bharathiyar ;Professor and H.O.D
Prof. Dr. R. Lakshmi, Associate Professor
Prof Dr.Ponnambala Namasivayam, Associate Professor
Dr.Carolin von mullai Assistant professor
Dept of anesthesiology SMC.
Dr.MGR University 2010
BACKGROUND
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Postoperative nausea and vomiting (PONV) “big
little problem”is a frequent complication of surgery,
which can lead to subject discomfort and
dissatisfaction as well as considerable subsequent
medical and economic consequences .
nausea and vomiting within the 24–72 h period
occur with an incidence of approximately 30% and
5% respectively.
Gupta et al. found a 32.6% incidence of PDNV.15 In
the high-risk patients receiving placebo the
incidence of PDNV was approximately 60% in the
studies by Kovac et al
Schematic representation of the factors
influencing nausea and vomiting
Risk Factors:
Patient Specific
Simplified Scoring System
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Female
Nonsmoking history
Hx of motion sickness or PONV
Use of postoperative opioids
Incidence of PONV
Risk Factors
Incidence
0
10%
1
21%
2
39%
3
61%
4
79%
Apfel CC et al. Anesthesiology 1999;91:693-700.
Chemoreceptor Trigger Zone
and Emetic Center
Antagonist
5-HT3 RAs
Promethazine
5-HT3
Histamine
Atropine
Droperidol
NK-1 RA
Agonist
Area
Postrema
Receptor Site
Chemoreceptor
Trigger
Zone
(CTZ)
Muscarinic Dopamine (D2) Substance P
Nitrogen mustard
Cisplatin
Digoxin glycoside
Opioid, analgesics
Vestibular portion
of 8th nerve
Mediastinum
Parvicellular
Reticular
Formation
Emetic
Center
N2O
?
GI tract distension
Higher centers (vision, taste)
Pharynx
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Palonosetron second generation 5-HT3 RA
a unique chemical structure. T1/2 40 hrs
Exhibits high binding affinity.
allosteric binding and positive cooperativity,
induces receptor internalisation
Palonosetron 0.075 mg IV is approved by FDA
(PONV) for up to 24 hours following surgery.
SIDE EFFECTS:
 headache (3%),
 constipation (2%)
 prolongation of the QTc interval (5%)
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Rojas et al. described the unique pharmacology of
palonosetron compared with other 5-HT3 receptor
antagonists,
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Tang et al. demonstrated a dose response for
palonosetron up to 30 μg/kg, with 1 μg/kg being the
lowest effective dose in the first 24 h for PONV
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Kovac et al.7 and Candiotti et al. At the highest dose
studied (0.075 mg), the incidence of vomiting or need for
antiemetic treatment was reduced during the first 24 h
after surgery by approximately 20%-30% &found a
marked reduction in incidence and severity within the first
24 h .
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Kovac et al. demonstrated continued efficacy compared
with placebo for 24 to 72 h.
AIM OF THE STUDY
The purpose of this study is to investigate Iv palonosetron versus Iv
ondansetron medication for the prevention of nausea and vomiting
through 72 hours postoperatively in patients undergoing ENT
procedures requiring general anesthesia.
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Primary Outcome Measures:
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proportion of patients with no emetic episodes in the
Time Frame: 0-72 hours post-operatively
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Secondary Outcome Measures:
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Proportion of patients with no emetic episodes in different time periods
:Time Frame: 0-6 hours,
6-24 hours,
24-72 hours,
Severity of nausea in different time periods
Time Frame: 0-6 hours,
6-24 hours,
24-72 hours,
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Study design
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Interventional
Single blind
Prospective
Randomised
Non placebo
PATIENTS AND METHODS:
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Institutional Ethics Committee approval was obtained
Informed written consent was obtained
60 patients belonging to ASA PS 1 &2 undergoing ENT
surgeries under general anesthesia were chosen and
randomly divided into 2 groups each n=30
Group O received Inj ondansetron 75mcg/kg upto 8mg
Group P received Inj Palonosetron 1.5mcg/kg upto
0.075mg
30 minutes before start of surgery
MAIN INCLUSION CRITERIA
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Male or female patient aged more than 5 years up to 60
years.
Inpatient scheduled to undergo surgical procedures
requiring general endotracheal anesthesia for ear, nose
and throat surgery;
American Society of Anesthesiologists (ASA) physical
status I, II
Patient scheduled to be hospitalized for at least 72
hours after wake up of surgery
MAIN EXCLUSION CRITERIA
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History of gastro-esophageal reflux.
Patient scheduled to undergo emergency surgery.
Patient scheduled to receive propofol during the
maintenance phase of anesthesia.
Patient with vomiting from any organic cause.
Any drug with a potential anti-emetic effect within 24
hours prior to the administration of anesthesia.
Any vomiting, retching, or nausea in the 24 hours
preceding the administration of anesthesia.
Materials
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IV cannulae
Monitors
Drugs for general anaesthesia
Drug O Ondansetron 4mg
Drug P Palonosetron 0.075 mg
METHODS
Premedication:
Inj. Glycopyrolate 0.004 mg/kg iv,
 Inj. Midazolam 0.02mg /kg iv,
 Inj. Fentanyl 2 mcg/kg iv.
 Anaesthesia was induced with
 Inj. Thiopentone 5mg/kg iv and
 Inj succinylcholine 2mg /kg iv
 Intubated with appropriate sized ETT
 placement confirmed .
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METHODS
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Anaesthesia was maintained with
 N2O: O2 70:30%,
 Isoflurane 1% with controlled ventilation
 Muscle relaxant Inj Atracurium loading dose of
0.5mg/kg followed by a maintanence dose of 0.1mg/kg
was used
 After adequate spontaneous respiratory effect
reversed with Inj neostigmine 50mcg/kg with Inj
glycopyrrolate 40mcg/kg.
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During maintenance of anesthesia
Heart rate, Mean arterial blood pressure, ECG
Spo2, respiratory rate, end-tidal CO2 concentration,
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Post operative: Data collected over 72 hrs post op.
No of emetic episodes recorded and time at which it
occurred.
Emetic episode is defined as single vomit or retch or
a combination
Complete response: No emetic episode
Major response :one emetic episode
Treatment failure: 2 or more episode or the receipt
of an rescue anti emetic
Data recorded & results were statistically evaluated
RESULTS
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DEMOGRAPHIC
DISTRIBUTION:
PALONOSETRON
MEAN AGE:24+/-5 [5Yrs-52]
SEX:M/F 14/16
100.00%
50.00%
0.00%
EMESIS
NAUSEA
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ONDANSETRON
MEAN AGE 26+/-4
[5yrs-50yr]
SEX M/F 15/15
COMPLETE RESPONSE
100
100
99
95
98
97
PALONO
SETRON
ONDANS
ETRON
96
95
94
93
90
85
80
92
91
0-12
HRS
1224HRS
75
24072HRS 72HRS
PALONO
SETRON
ONDANS
ETRON
NAUSEA
14%
12%
10%
8%
0-12
12--24
24-72
6%
4%
2%
0%
PALONOSETRON
ONDANSETRON
HEADACHE
6%
5%
4%
PALONOSETRON
ONDANSETRON
3-D Column 3
3%
2%
1%
0%
HEADACHE
CONCLUSIONS
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Emesis and nausea female>male
Emesis early 0-12 hrs comparable
Emesis delayed 12-72 hrs palonosetron
superior
Palonosetron superior in controlling nausea
Headache symptoms comparable
PROFORMA
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NAME :
WEIGHT:
AGE/SEX:
ASA I
II
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DIAGNOSIS:
SURGERY PLANNED:
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PREMED:
TIME OF DRUG ADMINISTERED:
TECHNIQUE OF ANESTHESIA:
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CONDITION AT THE END OF SURGERY:
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PONV FIRST 2 HRS
 NO OF
EMETIC
EPISODES
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NAUSEA
2-12 HRS
Mild
IP NO:
12-24
24-72
moderate
severe
REFERENCES
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Apfel CC, Laara E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for predicting
postoperative nausea and vomiting: conclusions from cross-validations between two centers.
Anesthesiology.1999;91(3):693–700.
Management of PONV focus on palonosetron Neil muchatuta michael peach 2008
K. A. Candiotti, A. L. Kovac, T. I. Melson, G. Clerici, T. Joo Gan, and The Palonosetron 04-06
Study Group
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., August 1, 2008; 107(2): 445 - 451
Palonosetron Hcl in the prevention of PONV Jane wallenborn and Peter crank dept of
anesthesiology University of leizpig.Germany
Gralla R, Lichinitser M, Van der Vegt S, Sleeboom H, Mezger J, Peschel C, Tonini G, Labianca R,
Macciocchi A, Aapro M. Palonosetron improves prevention of chemotherapy-induced nausea and
vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized
phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol
2003;14:1570–7
Stoltz R, Cyong J-C, Shah A, Parisi S. Pharmacokinetic and safety evaluation of palonosetron, a
5-hydroxytryptamine-3 receptor antagonist, in U.S. and Japanese healthy subjects. J Clin
Pharmacol 2004;44:520–31
THANK U