BACKGROUND & P receiving Ondansetron 4mg and Palonosetron 0.075mg



Propofol injection pain is distressing to patients
which interfere with smooth induction. Several pharmacological and non-
pharmacological methods have been used to prevent this pain. 5-HT3 antagonists
are commonly used antiemetics have also been used to prevent Propofol injection
pain. This study was conducted to evaluate and compare efficacy of Ondansetron
and Palonosetron in alleviating Propofol injection pain.

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In this randomised double blind study 100 patients
scheduled for elective laparoscopic surgery were allocated to two groups O
& P receiving Ondansetron 4mg and Palonosetron 0.075mg respectively as
pretreatment with venous occlusion for 1min. Initially one fourth of calculated
dose of Propofol administered over 5s, patients were assessed for pain using
McCrirrick and Hunter scale. Postoperatively patients were observed for nausea,
vomiting and other side effects 24hours. Intravenous Metaclopramide 10mg was
given as rescue antiemetic.



Overall incidence of pain in groupO and groupP was
32% and 26% respectively. Severe pain was complained by 4% and 2% patients in groupO
and groupP respectively. No patient in either group experienced pain during the
injection of pretreatment solution. Incidence of post operative nausea and
vomiting (PONV) was 20% in groupP and 38% in groupO.



Both Ondansetron and Palonosetron are equally effective
in reducing Propofol injection pain, whereas Palonosetron was more effective than
Ondansetron in reducing PONV, hence Palonosetron is a better choice in reducing
both Propofol injection pain and PONV


Propofol; Injection pain; Ondansetron; Palonosetron.


Pain on injection with various
intravenous induction agents in clinical practise like Thiopentone,
Methohexitone, Etomidate, Propofol, Diazepam, etc is an important cause of
patient dissatisfaction. Incidence and intensity of pain varies with individual
agent. 1 Propofol is an induction agent preferred by many
anaesthesiologists due to its fastest onset and shortest duration.  The incidence of pain varies from 28% to 90%
in adults. 1 Compared to other intravenous anaesthetic agents
Propofol has higher incidence of pain on injection, considering as the seventh
most important clinical drawback by the American anaesthesiologists. 2
Propofol is known to cause severe, sharp, aching or burning pain on injection
that can be distressing to the patient. 3 This pain is considered
to be clinically unacceptable as it can cause agitation and interfere with
smooth induction of anaesthesia. The pain on injection of Propofol can be
immediate or delayed in nature. The immediate pain probably results from direct
irritant effect whereas delayed pain results from indirect effect via the kinin
cascade, and has a latency of 10-20seconds. 1 Various
interventions have been made to alleviate the pain due to Propofol injection,
which include both non-pharmacological and pharmacological methods. Non-pharmacological
methods include use of antecubital vein as the injection site, different infusion
rates of Propofol, controlling the speed of intravenous carrier fluid and cold Propofol
injection. 4 Pharmacological interventions include pretreatment
with Lidocaine with venous occlusion, Magnesium sulphate, Meperidine, Fentanyl,
Morphine, Butorphanol, Dexamedetomedine, topical Nitroglycerine application,
etc.5 However none of these
methods are effective in completely eliminating the pain on injection. 5-HT3
receptor antagonists are commonly used for prevention and treatment of postoperative
nausea and vomiting. Ondansetron has been shown to exhibit the property of
local anaesthetic when injected under the skin due to blockade of sodium
channels and 5-HT3 receptor antagonism.6 Ondansetron also shows
agonist activity at the opioid ? receptors in humans. Based on these properties
various 5-HT3 antagonists like Ondansetron, Granisetron, Ramosetron and
Palonosetron have been used to reduce the pain due to Propofol injection with
added advantage of preventing postoperative nausea and vomiting.


Ondansetron a prototype of 5-HT3
receptor antagonist has been used in various studies to reduce Propofol
injection pain. Ondansetron was found to be as effective as Lignocaine in
reducing pain on Propofol injection. Palonosetron is a novel, highly potent and
selective second generation 5-HT3 receptor antagonist that has a strong
receptor binding affinity and a long plasma elimination half-life. Palonosetron
has been shown to be effective in reducing the Propofol injection pain. 6
Among the pretreatment drugs for reducing Propofol injection pain 5HT3
antagonists can be preferred over other drugs due to their dual antiemetic and
analgesic properties. Various authors have successfully used different 5-HT3 receptor
antagonist in reducing the incidence of Propofol injection pain, but in
literature studies comparing the efficacy of two 5-HT3 antagonists are minimal.
Hence in this study we compared the efficacy of Ondansetron and Palonosetron in
reducing the incidence of pain on injection of Propofol and in PONV in patients
undergoing laparoscopic surgery under general anaesthesia



A randomized
double blind clinical study on 100 adults of either sex in the age group of
18-60 years of ASA physical status one and two posted for elective laparoscopic
surgeries under general anaesthesia. Patients with infection on dorsum of
non-dominant hand, thin dorsal veins, hypersensitive to study drugs, history of
epilepsy, pregnant/ lactating women were excluded from the study. Hundred
patients were randomised into two groups of 50 each by computer generated
closed envelop technique. Group O received Ondansetron 4mg diluted to 4ml with
saline and group P received Palonosetron 0.075mg diluted to 4ml with saline as IV
pretreatment drugs. Pretreatment drug was prepared in the patient receiving
room by an anaesthesiologist who did not participate further in the study. Both
patient and investigator were blinded for the composition of pretreatment study

admission a thorough pre-operative evaluation was done and written informed
consent was taken after explaining the procedure. All the patients were
pre-medicated with tablet Alprazolam 0.5 mg overnight and the morning of
surgery. Patients were kept nil orally for at least 8h.

On arrival of the patient to operating room, basal
vital parameters were recorded then a 20 gauge IV cannula was inserted into the
largest vein on the dorsum of non-dominant hand. No analgesics or sedatives
were given before induction. A pneumatic tourniquet was placed on the same
upper arm and inflated to 70 mmHg to produce venous occlusion and the test drug
was injected. After the injection of the study drug the patient was assessed
for any pain at the injection site and tourniquet was released after one

Initially one fourth of the total calculated dose of
Propofol (Profol 1%, Claris Injectables Limited) was administered over a period
of 5s and patients were assessed for pain using McCrirrick and Hunter scale.
All patients were followed up after the surgery for the first 6h to assess
pain, swelling or allergic reaction at the site of injection of Propofol.
Patients complaining of nausea and/or vomiting and requirement of rescue antiemetics
was noted for 24h  postoperatively. Rescue
antiemetic Injection Metoclopramide 10mg was given.


1: McCrirrick and Hunter scale of evaluation of Propofol injection pain

Pain score

Degree of Pain




response to questioning



reported in response to questioning only,
any behavioural signs.



reported in response to questioning and
by a behavioural sign, or
reported spontaneously without questioning.



vocal response or response accompanied
facial grimacing, arm withdrawal or tears.


Descriptive and inferential statistical analysis has
been carried out in the present study. Results on continuous measurements are
presented on Mean ± Standard
Deviation (Min-Max) and results on categorical measurements are presented in
Number (%). Significance is assessed at 5% level of significance. Independent Student
t test has been used to find the significance of study parameters on continuous
scale between two groups (Inter group analysis) on metric parameters. Chi-square/
Fisher Exact test has been used to find the significance of study parameters on
categorical scale between two groups, Non-parametric setting for Qualitative
data analysis. The Statistical software namely SAS 9.2, SPSS 15.0, Stata 10.1,
MedCalc 9.0.1, Systat 12.0 and R environment ver.2.11.1 were used for the analysis
of the data and Microsoft word and Excel have been used to generate graphs, tables

Power calculation indicated that recruitment of 40
patients in each group would be significant to demonstrate a reduction of pain
score of one at a level of significance of P<0.05 and power of 99.3%. Considering the dropouts we have taken a 50 in each groups. RESULTS All patients in both group belong to ASA I and II were undergone Laparoscopic surgeries. Both the groups were comparable with respect to age, weight and gender distribution. Table 2: Demographic Data Characteristics           Group O(Mean±SD)                         Group P(Mean±SD) Age (in years)              34.02 ±10.36                                       37.92±11.90 Weight (in kg)             63.14±13.19                                        61.84±10.61    Gender (M/F)              18/36                                                   12/38 ASA (I/II)                   43/7                                                     41/9     Original; Values expressed as mean±SD; SD- Standard deviation; ASA- American Society of Anaesthesiologist;                         The incidence and severity of pain in both the groups were comparable and no statistical significant difference was noted in respect to pain on Propofol injection (P 0.502). Thirty four (68%) patients in Group O and 37 (74%) patients in Group P were free from propofol injection pain. Over all incidence of propofol injection pain was 32% and 26% in Group O and P respectively. Only one patient in group P and two patients in group O had severe pain on injection. Incidence and severity of Propofol injection pain P 0.502, Not significant, student t test   Patients vital parameters were well maintained throughout the procedure and no significant hemodynamic variations were noted in both the study groups.   We observed a statistically significant difference between the two groups in relation to PONV. Thirty eight percent of patients in GroupO and 20% of patients in GroupP had PONV. P value being 0.047. No other side effects were noted in both the study groups.   Incidence of PONV in two groups of patients studied P 0.047, significant, Chi-Square test DISCUSSION Propofol a 2,6- diisoprophylphenol is a sedative hypnotic with additional antiemetic property is widely using intravenous inducing agent especially for short surgical procedures, day care surgeries, in TIVA and ICU sedation. 1 The common worrying problem that has been most extensively studied is pain on injection of Propofol. 1 The injection pain is sharp, stinging or burning in nature which can be either immediate or delayed. 3 Contributing factor for pain on injection are Vessel size, Composition of propofol, temperature of the injection, pH, volume and speed of injection etc, Incidence of propofol injection pain is comparatively less when forearm veins are used for induction than dorsal hand veins.7 The formulation of Propofol used by different authors were different. Some used LCT propofol where as some used LCT/MCT Propofol, which is proved to cause lesser injection pain. Ji-Yeon sim et al demonstrated that microemulsion Profofol (clear) is more painful than lipid emulsion Propofol.8 The probable mechanism reported to cause pain on injection of Propofol are direct endothelial irritation, difference in osmolarity, non-physiologic pH of the drug and activation of pain mediators. Immediate pain may be due to stimulation of nociception and free nerve endings where as delayed pain occurring within half a minute is promoted by local vasodilation and hyperpermiability with the mediation of neurotransmitter such as bradykinine and prostaglandins. 9 Pretreatment with drugs like Ketamine, Lidocaine, fentanyl, Ramifentanyl, 5HT3 receptor antagonist, etc., have been tried by various authors to reduce the incidence and severity of pain. Ondensetron and Palenosetron are selective 5HT3 receptor antagonists basically used as antiemetics in the prevention and treatment of nausea and vomiting, they suppress nausea and vomiting by inhibiting the serotonin binding to 5HT3 receptors located peripherally at vagus afferent and centrally at CTZ. These 5HT3 antagonists bind to opoid µ receptor and exhibit agonistic activity. In our study both the study groups were comparable with respect to age, weight and gender distribution. Though different authors have used different scale to assess the Propofol injection pain, one proposed by McCrirrick and Hunter is the most commonly used scale because it is simple and easy to perform, where patient's verbal, behavioural response for simple question will be taken into consideration to assess the degree of pain. Mariya et al used VAS to assess the Propofol injection pain.10 Hand eye coordination to VAS might not be proper in all patients during the rapidly changing state of consciousness after Propofol injection, hence we adopted McCrirrick and Hunter scale for assessment of Propofol injection pain. The overall incidence of pain was 32% in Ondensetron group and 26% in Palonosetron group, where as 4% and 2% of our patients complained of severe pain respectively in Ondensetron and Palonosetron group. In our study though both the study drugs failed in relieving pain in all the patients studied, 68% of patients who received Ondensetron pre-treatment and 74% of patients who received Palonosetron pre-treatment before Propofol injection experienced no pain. In contrast to our results, Ansari M Umar et al showed the incidence of Propofol pain was only 15% and the incidence of severe pain was 2.5% in their Ondensetron group. This difference may be attributed to the difference in the volume of the Propofol injected initially. We have given one fourth of the calculated dose of Propofol and assessed the pain, where as they have used only 2ml of  Propofol as bolus irrespective of body weight and the pain was assessed after 15s of giving the bolus. 11 The intensity and severity of the pain also depends on the volume of Propofol injected and the speed of carried fluid infusion. 1 Scott et al suggested that the intensity of Propofol pain is inversely proportional to the size of the vein and also stated that rapid injection of Propofol causes less pain than slow bolus. 12 With respect to Palanosetron free treatment in reducing the Propofol injection pain, our results are in par with the results in the study conducted by Han-Bon Ryu and Sujin Kim.9 In contrast Kye Hyeok Lee et al, demonstrated a very high incidence of Propofol injection pain in their Palonosetron group(73%), but rate of severe pain is almost equal to our study. This high incidence of pain may be due to slow intravenous infusion of Propofol. Target controlled infusion pump(TCI pump) to achieve a 6µg effect site concentration. 13 Jae-Hwa Yoo et al, also showed a higher incidence of Propofol injection pain in the Palonosetron group that may be the dose of Propofol used before evaluating pain. They used full dose of Propofol where as in other studies they have used either 2ml initial bolus or one fourth of calculated dose of Propofol. 14 Post operative nausea and vomiting are distressing symptoms commonly reported by patients after Laproscopic surgery performed under General Anaesthesia(.........). 5HT3 receptor antagonist are widely used as prophylactic anti-emetics in reducing PONV. Ondestron prevents emetic symptoms by acting on the 5HT3 receptor located in the CTZ and gastrointestinal tract, where as Palonostron is a second generation 5HT3 antagonist  with different mechanism in preventing PONV. 15 Different structural characteristics, lower plasma half life, inhibition of substance P mediated delayed emesis are some of the unique features of Palonosetron in other 5HT3 receptor antagonist. 16 The incidence of post operative nausea and vomiting in our study was 38% in Ondesteron group and 20 % in Palanosetron group. The difference between the groups was statistically significant. In comparison with our study, S.K.Park et al and Y.Y.Kim et al showed that Palanosetron was better than Ondensetron in reducing the incidence of PONV.17 18 K.Gupta et al stated that Palanosetron was more effective than Ondensetron and Granisetron in reducing nausea and vomiting. 19 Vital parameters were well maintained in all the patients. We observed no side effects in respect to study drugs. Headache, dizzness ,drowsiness are some of the  adverse effects noted with 5HT3 antagonist. S.K.Park , et al observed that the incidence of head ache and dizziness were comparable between Ondesetron and Palanosetron, where as J.Bhall et al stated that the incidence of the head ache was more with Ondesetron than Palanosetron.17 20 In our study, baseline incidence of injection pain has not measured as we did not include control group or placebo group, considering not taking any preventive measures to reduce pain in placebo group is unethical.   CONCLUSION: Both Ondensetron and Palonosetron are equally effective in reducing the Propofol injection pain, where as Palonosetron was statistically more effective in reducing the incidence of PONV than Ondensetron. Therefore considering the dual actions of these drugs we observed that Palonosetron pretreatment is a better choice than Ondensetron in reducing the Propofol injection pain in patients undergoing laparoscopic surgeries. Since cause of Propofol injection pain is multifactorial a combination of  non-pharmacological and pharmacological methods may be a better choice.   REFERENCES: 1.      Tan CH, Onsiong MK. Pain on injection of propofol. Anaesthesia. 1998 May 1;53(5):468-76. 2.      Macario A, Weinger M, Truong P, Lee M. Which clinical anesthesia outcomes are both common and important to avoid? The perspective of a panel of expert anesthesiologists. Anesthesia & Analgesia. 1999 May 1;88(5):1085-91. 3.      Kang HJ, Kwon MY, Choi BM, Koo MS, Jang YJ, Lee M. Clinical factors affecting the pain on injection of propofol. Korean journal of anesthesiology. 2010 Mar 1;58(3):239-43. 4.      Jalota L, Kalira V, George E, Shi YY, Hornuss C, Radke O, Pace NL, Apfel CC. 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