EVALUATION OF EFFICACY OF PALONOSETRON VERSUS PLACEBO FOR PREVENTION OF POSTOPERATIVE NAUSEA AND VOMITING 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.JeevanandamIIyr 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 Palonosetronversus 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
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 Palonosetroncompared 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(AnesthAnalg 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(AnesthAnalg 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
OBSERVATIONScontd • ‘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)