EVALUATION OF EFFICACY AND SAFETY OF THREE DIFFFERENT DOSES OF PALONOSETRON VERSUS PLACEBO FOR PREVENTION OF POSTOPERATIVE NAUSEA AND VOMITTING

EVALUATION OF EFFICACY OF PALONOSETRON VERSUS PLACEBO FOR PREVENTION OF POSTOPERATIVE NAUSEA AND VOMITINGCO-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 1Post Operative Nausea & VomitingSecond most common complaints reportedUnpleasant experience often rated worse than postoperative painMedical risks : Aspiration of gastric contents, Suture dehiscence, Esophageal rupture, Subcutaneous emphysema, Pneumothorax HR & BP elevation(risk for MI & dysrhythmias ) Bradycardia and hypotension. 2RISK FACTORS APFEL Simplified risk scoring for adults

3PALONOSETRONPotent and selective 5-HT3 antagonistPlasma elimination T ~ 40 hMetabolized primarily by liver.Age, hepatic dysfunction or mild-to-moderate renal impairment have no clinically significant effect on the pharmacokinetics

4MECHANISM OF ACTIONAntagonism of 5HT3 receptorsAlso has an allosteric binding siteCauses receptor interanalisation and prolonged inhibition

5 USESPrevention of postoperative nausea and vomitingPrevention of acute and delayed nausea and vomiting associated chemotherapy.Dosage and AdministrationPostoperative Nausea and VomitingIV 0.075 mg before the induction of anesthesia.Chemotherapy-Induced Nausea and VomitingIV 0.25 mg administered 30 min before the start of chemotherapy.PO 0.5 mg administered 1 h prior to the start of chemotherapy.6SIDE 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.

7AIMTo evaluate the efficacy of Palonosetron versus placebo for prevention of Postoperative Nausea and Vomiting8DESIGNRandomized double blind control studyFemale patients undergoing laproscopic surgery under GA Inclusion criteriaAge 18 - 60 yrsASA I - IINon - SmokersExclusion criteriaPatients received antiemetics 24 hrs prior to surgeryPatients received / undergoing chemotherapy or radiotherapy Pre existing heart blocks , bradycardia, QT prolongation,Duration of procedure 4 / emetic episodesComplete response (defined as no emetic episodes and no rescue medication) will be noted for the time interval of 0 24 hrs & 24 72 hrs12Patients Age ,Weight,BMIRisk factors for PONV (H/O PONV , H/O motion sickness )Duration of surgeryTotal intra operative opioid (fentanyl) dosePost 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 13ANALYSIS OF COLLECTED DATAPhysiological parametersVARIABLEGROUP Pn(n = 30)GROUP Po(n = 30)pAge in years27.3 + 4.426.3 + 3.90.3808Weight (in kgs)53.7 + 5.454.8 + 3.50.5428Height ( in cms)151.2 + 3.1151.7 + 2.70.4796BMI23.4 + 223.8 + 1.30.4289ASA RISKASA GROUP PnGROUP Pon%n%I2686.72790II413.3310p0.691Duration of ProcedureDur of ProcGROUP PnGROUP PoRange80 - 14080 135Mean107.8105.2S.D.15.2 12p0.4898TOTAL INTEROPERATIVE OPIOiD USEDTot. opiod usedGROUP PnGROUP PoRange130 - 210140 200Mean167163.3S.D.17.417.9p0.3156APFEL SCOREAPFEL SCOREGROUP PnGROUP PoNo.%No.%32583.327904516.7310Total3010030100RangeMeanS.D.3 43.170.383 43.10.31p0.4513INTENSITY OF NAUSEA ( VAS )INT OF NAUSEA GROUP PnGROUP Pop0 2 hrs2.43 + 2.214.43+ 1.650.0008 2 6 hrs

1.53 + 1.633.07 + 1.310.00046 24 hrs

1.3 + 1.662.3 + 1.520.003424 72 hrs

0.9 + 1.492.07 + 1.510.0013EMETIC EPISODES 0 24 HR IntervalEMETICEPISODESGROUP PnGROUP Pon%n%YES1033.32273.3NO2066.7826.7p0.0044EMETIC EPISODES 24 72 HR IntervalEMETICEPISODESGROUP PnGROUP Pon%n%YES826.71033.3NO2273.32066.7p0.7763COMPLETE REMISSION 0 24 HR IntervalCOMPLETE REMISSIONGROUP PnGROUP Pon%n%YES2066.7826.7NO1033.32273.3p0.0044 COMPLETE REMISSION 24 - 72HR IntervalCOMPLETE REMISSIONGROUP PnGROUP Pon%n%YES2273.32070NO826.71030p0.7763SUMMARYRandomised controlled study Two groups, 30 patients in eachFemale patients ,non-smokers ,undergoing laproscopy of more than one hour duration receiving opioids for postoperative pain reliefInj.Palonosetron 0.075 mg Vs PlaceboData 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 haveSignificant 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 hrsNo significant difference in Emetic episodes and complete remission over 24-72hr periodTreatment effect of PALONOSETRON in this trial was most pronounced during the first 24 h No side effects

26CONCLUSIONPALONOSETRON 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 effectsIn 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;107:44551)28THANK YOU29OBSERVATIONS 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 contdp 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