Dr.Kaviya.K.J II yr MD Prof. Dr. R. Subramaniya Bharathiyar ;Professor and H.O.D

COMPARISON OF EFFECT OF ONDANSETRON Vs PALONOSETRON

IN PREVENTION OF POST OP NAUSEA AND VOMITING

FOLLOWINGENT SURGERIES

Dr.Kaviya.K.J II yr MDProf. Dr. R. Subramaniya Bharathiyar ;Professor and H.O.DProf. Dr. R. Lakshmi, Associate ProfessorProf Dr.Ponnambala Namasivayam, Associate ProfessorDr.Carolin von mullai Assistant professorDept of anesthesiology SMC.Dr.MGR University 2010

BACKGROUND

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

Female Nonsmoking history Hx of motion sickness or PONV Use of postoperative opioids

Simplified Scoring System

Incidence of PONVRisk 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 CenterAntagonistAntagonist

AgonistAgonist

Receptor SiteReceptor Site

Are

aA

rea

Po

stre

ma

Po

stre

ma ChemoreceptorChemoreceptor

TriggerTriggerZoneZone(CTZ)(CTZ)

EmeticCenter

5-HT5-HT33 RAs RAs

5-HT5-HT33

PromethazinePromethazine

HistamineHistamine

AtropineAtropine

MuscarinicMuscarinic

DroperidolDroperidol

Dopamine (DDopamine (D22))

Nitrogen mustardNitrogen mustard

CisplatinCisplatin

Digoxin glycosideDigoxin glycoside

Opioid, analgesicsOpioid, analgesics

Vestibular portionVestibular portionof 8th nerveof 8th nerve

NN22OO

GI tract distensionGI tract distension

Higher centers (vision, taste)Higher centers (vision, taste)

PharynxPharynx

ParvicellularParvicellularReticularReticular

FormationFormation

MediastinumMediastinum

??

VagusVagus

NK-1 RANK-1 RA

Substance PSubstance P

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%)

Rojas et al. described the unique pharmacology of palonosetron compared with other 5-HT3 receptor antagonists,

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

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 .

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.

Primary Outcome Measures: proportion of patients with no emetic episodes in the

Time Frame: 0-72 hours post-operatively Secondary Outcome Measures: 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,

Study design

Interventional Single blind Prospective Randomised Non placebo

PATIENTS AND METHODS:

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 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 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

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 .

METHODS 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.

During maintenance of anesthesia Heart rate, Mean arterial blood pressure, ECG Spo2, respiratory rate, end-tidal CO2 concentration,

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

DEMOGRAPHIC DISTRIBUTION:

PALONOSETRON MEAN AGE:24+/-5 [5Yrs-52] SEX:M/F 14/16

0.00%

50.00%

100.00%

EMESIS NAUSEA

ONDANSETRON MEAN AGE 26+/-4

[5yrs-50yr] SEX M/F 15/15

COMPLETE RESPONSE

91

92

93

94

95

96

97

98

99

100

0-12HRS

12-24HRS

PALONOSETRONONDANSETRON

75

80

85

90

95

100

24-72HRS

0-72HRS

PALONOSETRONONDANSETRON

NAUSEA

0%

2%

4%

6%

8%

10%

12%

14%

PALONOSETRON ONDANSETRON

0-12

12--24

24-72

0%

1%

2%

3%

4%

5%

6%

HEADACHE

PALONOSETRONONDANSETRON3-D Column 3

HEADACHE

CONCLUSIONS

• 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 NAME : AGE/SEX: IP NO: WEIGHT: ASA I II

DIAGNOSIS: SURGERY PLANNED: PREMED: TIME OF DRUG ADMINISTERED: TECHNIQUE OF ANESTHESIA:

CONDITION AT THE END OF SURGERY:

PONV FIRST 2 HRS 2-12 HRS 12-24 24-72 NO OF

EMETIC

EPISODES

NAUSEA Mild moderate severe

REFERENCES

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 GroupA Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Three Different Doses of Palonosetron Versus Placebo for Preventing Postoperative Nausea and VomitingAnesth. 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

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