Comparative efficacy of palonosetron-dexamethasone

combination, palonosetron or dexamethasone

alone for prevention of postoperative nausea and vomiting in
patients undergoing laparoscopic
surgeries: A prospective randomized double-blinded clinical
trial.
Name of the Post Graduate: Dr. Michelle Raphael
Name of Guide: Dr. Arun Kumar
Name of Co-guide: Dr. Vijay Kumar
 Introduction
Postoperative nausea and vomiting is a distressing problem in patients
undergoing surgery under general anaesthesia, especially so with laparoscopic
procedures with an estimated incidence of 50 – 70 %, often causing delay in
discharge of proposed day-care cases in addition to the potentially dangerous
complications like aspiration, suture dehiscence and esophageal rupture. This
fact necessitates routine use of antiemetic prophylaxis in patients undergoing
surgery under general anaesthesia and laparoscopic procedures, in particular.
Thus, antiemetic prophylaxis forms an essential part of standard of care in
perioperative setting.
With the advent of few potent antiemetic drugs such as palonosetron
and dexamethasone,perioperative physicians have claimed remarked
success in reducing the incidence of this unpleasant sensation. Hence
we intend to compare the efficacy of palonosetron-dexamethasone
combination,dexamethasone alone and palonosetron alone in
reducing the incidence of postoperative nausea and vomiting in
patients undergoing laparoscopic surgeries.
 Review of Literature
Post operative nausea and vomiting is a highly distressing sypmtome which is not
only an unpleasant experience for the patient but can also lead to can lead to more
serious consequences such as dehydration, electrolyte imbalance, heightened
perception of pain, aspiration of gastric contents and suture dehiscence. PONV
leads to dysphoria, dissatisfaction and is an overall poor experience for the patient.
Especially in patients undergoing laproscopic procedures incidence of PONV is as
high as 50 – 70 % when no prophylactic antiemetic is used in the peri operative
period.The high incidence of of PONV in patients undergoing laproscopic
procedures can be attributed to effect of intraperitoneal CO2 insufflation leading to
stretching and irritation of peritoneum in addition to the residual effect of the use
of emetic anaesthetic agents (like N2O) intra operatively.Thus prophylaxis against
PONV becomes essential.
 PONV has been found to have a multifactorial origin and a better understanding
of its pathophysiology has lead to a multimodal approach for PONV prophylaxis.
Recent studies have shown that combination of steroids like dexamethasone with
other anti emetics improves the total antiemetic effect by the combined action on
different receptors.
New antiemetic agents like palonosetron, a second generation 5-HT3 receptor
antagonist, is said to have far greater affinity and more potent binding tendency
with 5 –HT3 receptors as compared to 1st generation 5-HT3 receptor antagonists.
Furthermore, it exhibits functional effects which persist beyond its binding to the
5 –HT3 receptor at cell surface which in turn leads to prolonged duration of action
and a longer half life (40hrs). In contrast to other 5-HT3 receptor antagonist,
Palonosetron also has anti nauseatic property which increase its efficacy as an
antiemectic agent.
On the other hand Dexamethasone has also been found to be effective in reducing
PONV during first 24hrs after a laproscopic surgery.It is said to potentiate the
effect of other antiememtic agents by various mechanisms like – prostagaldin
antagonism, release of endorphins and bradykinin reduction.
In recent studies the combination therapy using dexamethasone and 5-HT3
antagonist has been found to be more effective than single drug prophylaxis.33%
of the patients receiving only palonosetron experienced PONV in the 0-24 hr post
operative period while 11.9% patients receiving Palonosetron and dexamethasone
combination experienced PONV. The use of intra operative Palonosetron and
dexamethasone combination also reduced the use rescue anti emetics and is
associated with greater patient satisfaction.
In a recent study it has also been noted that the for rescue analgesic is much lesser
in patients receiving dexamethasone. This can be attributed to decreased
prostaglandin synthesis mediated by dexamethasone. Furthermore perioperative
use of dexamethasone enhances the post discharge quality of recovery, reduced
pain, nausea and fatigue in the postoperative period.
 Objective
Palonosetron-dexamethasone combination were better than
dexamethasone or palonosetron alone for preventing PONV in patients
undergoing laproscopic surgeries.
Patients receiving dexamethasone-palonosetron combination require
less rescue antiemetic during 24 h after surgery.
 Methodology
• Study design: A prospective randomized double-blinded clinical trial.
We propose to include patients aged 20 – 60 years, belonging to American
Society of Anaesthesiologists physical status I and II, scheduled for elective
laparoscopic procedures under general anaesthesia (other than intestinal
surgeries), with Body Mass Index 15 – 24.9 kg/m 2 as participants in this study.
We propose to exclude pregnants, intestinal surgeries, those with history of
motion sickness/long term opiod use/those in whom antiemetic medications
were administered 24 h prior to surgery. After obtaining written informed
consent, eligible participants shall be instructed standard Nil-per-oral advice
and administered tablet alprazolam 0.5 mg night before surgery and 2 h before
surgery, standard anti-aspiration prophylaxis with tablet pantoprazole 40 mg
and tablet metoclopramide 10 mg 2 h before scheduled procedure.
 Participants shall be allocated to one of the three groups : group C
(palonosetron and dexamethasone), group P (palonosetron) or group D
(dexamethasone) through a computer generated table of random
numbers and the same is sealed, as well as concealed from the principal
investigator. Induction and maintainance of general anaesthesia, pain
relief and extubation all have been designed to be of standard of care
and uniform in all patients.
 Anaesthesia technician loads the study drug as per group allocation,
dilutes it upto 5 ml and labels it as ‘antiemetic’ so as to conceal the group
allocation by the principal investigator. After intubation, following study
drugs shall be administered intravenously:0.075 mg palonosetron and 8
mg dexamethasone in group C, palonosetron 0.075 mg in group P and
dexamethasone 8 mg in group D.Patients shall be interviewed in
postoperative period at following intervals: immediately after transfer to
post-anaesthesia care unit, 1 h, 2 h, 4 h, 6 h, 12 h and 24 h. Intravenous
metoclopramide 10 mg shall be used as rescue antiemetic in
postoperative period.
 Outcomes
We propose to include the following observations for statistical analysis and
interpretation:
Demographics, surgical procedure performed, duration of anaesthesia, incidence
& severity of nausea as per VAS scale, incidence of vomiting, need for and
timing of rescue antiemetic and any other associated complications.
 References
1.BALA, N. BHARTI, S. MURUGESAN, R. GUPTA. Comparison of palonosetron with palonosetron-
dexamethasone combination for prevention of postoperative nausea and vomiting in patients undergoing
laparoscopic cholecystectomy. Minerva Anestesiologica. 2014
2. Chatterjee A, Sahu S, Paul M, Singh T,Singh S, Mishra P. Comparison of efficacy of palonosetron-
dexamethasone combination with palonosetron or dexamethasone alone for prophylaxis against post-
operative nausea and vomiting in patients undergoing laparoscopic cholecystectomy. Indian J Anaesth
2017;61:978-84.
3. Qili Liu,Chengamao Zohu,Zinqing Bao,Yu Zuhu. Effects of palonosetron and ondansetron on preventing
nausea and vomiting after laparoscopic surgery. J Int Med Res. 2018 Jan; 46(1): 411–420.
4.Kama Awad, Hussein Ahmed, Abdelrehman Ibrahim Abushouk, Safwat Al Nahrawl, Mohammed Yasser
Elsherbeny, Salma Muhammad Mustafa, Attia Attia.Dexamethasone combined with other antiemetics
versus single antiemetics for prevention of postoperative nausea and vomiting after laposopic
cholecystectomy:An updated systematic review and meta analysis. International Journal of surgery 36
(2016) 152-163.
5. Mokhtar Elhakim MD, Magdy Nafie MD, Khalaf Mahmoud MD, Azza Atef MD. Dexamethasone 8 mg in
combination with ondansetron 4 mg appears to be the optimal dose for the prevention of nausea and
vomiting after laparoscopic cholecystectomy. CAN J ANESTH 2002 / 49: 9 / pp 922–926.
THANK YOU