EVALUATION OF EFFICACY OF PALONOSETRON VERSUS PLACEBO FOR PREVENTION OF POSTOPERATIVE NAUSEA AND VOMITING

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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.Jeevanandam IIyr M.D. PG
• INSTITUTE OF ANAESTHESIOLOGY , Madurai Medical
  College

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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.
  
  

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RISK FACTORS

• APFEL Simplified risk scoring for adults

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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

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MECHANISM OF ACTION

• Antagonism of 5HT3 receptors
• Also has an allosteric binding site
• Causes receptor interanalisation and prolonged
  inhibition

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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.

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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.

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AIM

• To evaluate the efficacy of Palonosetron versus
  placebo for prevention of Postoperative Nausea
  and Vomiting

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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 lt1 hr

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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

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• 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

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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 gt 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

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• 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

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ANALYSIS OF COLLECTED DATA
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Physiological parameters
VARIABLE GROUP Pn (n 30) GROUP Po (n 30) p
Age in years 27.3 4.4 26.3 3.9 0.3808
Weight (in kgs) 53.7 5.4 54.8 3.5 0.5428
Height ( in cms) 151.2 3.1 151.7 2.7 0.4796
BMI 23.4 2 23.8 1.3 0.4289
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ASA RISK
ASA GROUP Pn GROUP Pn GROUP Po GROUP Po
ASA n n
I 26 86.7 27 90
II 4 13.3 3 10
p 0.691 0.691 0.691 0.691
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Duration of Procedure
Dur of Proc GROUP Pn GROUP Po
Range 80 - 140 80 135
Mean 107.8 105.2
S.D. 15.2 12
p 0.4898 0.4898
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TOTAL INTEROPERATIVE OPIOiD USED
Tot. opiod used GROUP Pn GROUP Po
Range 130 - 210 140 200
Mean 167 163.3
S.D. 17.4 17.9
p 0.3156 0.3156
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APFEL SCORE
APFEL SCORE GROUP Pn GROUP Pn GROUP Po GROUP Po
APFEL SCORE No. No.
3 25 83.3 27 90
4 5 16.7 3 10
Total 30 100 30 100
Range Mean S.D. 3 4 3.17 0.38 3 4 3.17 0.38 3 4 3.1 0.31 3 4 3.1 0.31
p 0.4513 0.4513 0.4513 0.4513
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INTENSITY OF NAUSEA ( VAS )
INT OF NAUSEA GROUP Pn GROUP 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
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EMETIC EPISODES 0 24 HR Interval
EMETIC EPISODES GROUP Pn GROUP Pn GROUP Po GROUP Po
EMETIC EPISODES n n
YES 10 33.3 22 73.3
NO 20 66.7 8 26.7
p 0.0044 0.0044 0.0044 0.0044
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EMETIC EPISODES 24 72 HR Interval
EMETIC EPISODES GROUP Pn GROUP Pn GROUP Po GROUP Po
EMETIC EPISODES n n
YES 8 26.7 10 33.3
NO 22 73.3 20 66.7
p 0.7763 0.7763 0.7763 0.7763
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COMPLETE REMISSION 0 24 HR Interval
COMPLETE REMISSION GROUP Pn GROUP Pn GROUP Po GROUP Po
COMPLETE REMISSION n n
YES 20 66.7 8 26.7
NO 10 33.3 22 73.3
p 0.0044 0.0044 0.0044 0.0044
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COMPLETE REMISSION 24 - 72HR Interval
COMPLETE REMISSION GROUP Pn GROUP Pn GROUP Po GROUP Po
COMPLETE REMISSION n n
YES 22 73.3 20 70
NO 8 26.7 10 30
p 0.7763 0.7763 0.7763 0.7763
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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

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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

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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

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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 2008107439 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
  200810744551)

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THANK YOU
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OBSERVATIONS

• p value calculated for
  
  age,
  weight, height, BMI,
  ASA
  statusApfel scores
• p value calculated for the
  duration of
  procedure
  
  total dose of fentanyl used
• No adverse effects were observed in both groups

gt0.05 insignificant
gt0.05 insignificant
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OBSERVATIONS contd

• p value for VAS scoring of nausea in the
  interval
  0 2 hr ( p0.0008) 2 6 hr (p0.0004)
  
  6 -24 hr (p0.0034) 24 72 hr(p0.0013)
• 0 24 hr time interval, p value for
  
  emetic episode incidence (p0.0044)
  
  complete remission (p0.0044)
• 24-72 hr time interval interval p value for
  
  emetic episode incidence
  (p0.7763)
  complete remission
  (p0.7782)

lt 0.05 significant
lt 0.05 significant
gt 0.05 insignificant