Propofol is the most commonly used intravenous induction agent during general anaesthesia. Main advantages of Propofol are rapid onset, short duration of action and easy titration [1]. Despite  ve patients
these advantages, about three out of  experience pain on injection of propofol, with one of these patients reporting severe or excruciating pain. Pain on Propofol injection is considered as a seventh most important problem faced by anesthesiologists [2]. Explanations given for pain on injection include endothelial irritation, osmolality difference, and activation of pain mediators [3]. Many methods have been introduced to reduce the incidence of pain which includes adding lidocaine to propofol, cooling of propofol, diluting the propofol solution, injecting propofol into a larger vein, and pretreatment with IV injection of lidocaine, metoclopramide, ondansetron or ketamine with or without a tourniquet [4-6]. Ketamine, an NMDA receptor agonist mainly used as an induction agent found to reduce the pain on propofol injection in smaller doses by virtue of its local anaesthetic property [7]. The present study was conducted to evaluate the effect of a small dose of ketamine in the prevention of propofol-induced pain on injection.

This was a prospective, randomised, double blind study undertaken after taking approval from our Institutional ethical. The study involved 100 patients from either gender aged 20-50 years, of the American Society of Anaesthesiologists (ASA) grade I or II, scheduled for various elective surgeries under general anaesthesia. Excluded from the study were patients with known hypersensitivity to propofol, history of drug abuse, psychiatric, cardiovascular, renal, hepatic and thyroid disease. All patients were visited on the day prior to the surgery, explained in detail about the anaesthetic procedure and written informed consent was obtained. Patients were kept nil orally from 12 O’clock midnight prior to the day of surgery. Inside the operating room monitors like pulse oximetry, non-invasive blood pressure, electrocardiogram were connected and basal values were recorded. An 18 gauge IV cannula was secured in the vein on the non-dominant hand. Patients were randomly allocated to two groups (Group K or Group S) using a computer-generated table with random numbers. Group K received 0.5 mg/kg Ketamine loaded in 10 ml syringe and group S received 10 ml normal saline. The study drugs were given as a slow infusion over 10 min. Immediately after infusion, we occluded venous drainage manually. One minute later occlusion was released. This was followed by injection of propofol 2 mg/kg IV over 25s. Starting from the time of injection the patients were assessed for pain during injection every 5s until the patient became unresponsive, and the degree of pain was scored as advocated by McCririck and Hunter scale [8] (Table 1).

Neither the patients nor the anesthesiologist monitoring the respondents were aware of the group allocation and thus the study was double blinded. It was followed by a standard anaesthesia technique consisting of Inj. Fentany l 1.5 µg/kg I.V and Inj. Vecuronium as appropriate for the weight of the patient. Patients were intubated with an appropriate sized oral endotracheal tube and anaesthesia was maintained with nitrous oxide,  urane and intermittent positiveoxygen, sevo pressure ventilation. Heart rate (HR), blood pressure, peripheral oxygen saturation (SpO2 ) and end-tidal carbon dioxide (Et CO2 ) were monitored intra operatively. Patients developing Hypotension (SBP 20% baseline values) was treated with Inj. Ephedrine 6 mg IV and heart rate less than 50 bpm was considered as bradycardia and treated with Inj Atropine 0.6 mg IV. The sample size was calculated based on previous studies [9]. To detect a 30% difference in severity of pain between the two groups with a power of 85% and at an alpha value of 0.05, we required 38 patients in each group. To increase statistical power, we included 50 patients in each group. Mean and standard deviation were used for age and weight, and the independent t-test was used to compare if the difference between the two groups  cant. Categorical variables are expressed
was signi as frequencies and percentages and compared using Fisher’s exact test. For all statistical tests, p < 0.05  cant difference.
was taken to indicate a significant difference.

Table 1: McCririck and Hunter pain scale

Table 2: Patient Parameters Age and Weight are presented as mean ± SD. Test done was unpaired t-test. n-number of patients; SD- standard deviation

Table 3: Pain scores

Analysis was done by fisher’s exact test

Table 4: Hemodynamic data

Analysis was done by fisher’s exact test

In group K and 50 patients in group S. Group K received 0.5 mg /kg propofol and group S received saline over 10 minutes. There was no statistical difference between the two groups in age, weight, height [Table 2]. An incidence of pain on injection and complications like increased secretions, emergence agitation were noted. Nine patients in group K (18%) and 42 patients in group S (84%) developed pain on propofol injection. The incidence cant between the
of pain was statistically signi cant between the
two groups (p = < 0.001) [Table 3]. Three patients in group K (6%) and 23 (46%) patients in group S had severe pain (p = < 0.001). Three patients in group K experienced increased secretions, which cant in comparison with the other
was not signi group (6% vs 0%, p = 0.242). Four patients in group K had emergence agitation, but this was again not cant when compared to group S
statistically signi (8% vs 0%, p = 0.117) [Table 4].

Propofol is the most widely used intravenous (IV) induction agent. Its properties are almost similar to an ideal IV anesthetic agent, but pain on its injection still remains a problem. The pain on propofol injection may not be a serious complication, but most patients remember it as one of the unpleasant experience during conduction of anaesthesia. The incidence of pain on propofol injection varies between 28-90% [10]. Propofol is an alkylphenol (2,6 diisopropylphenol); oil at room temperature and insoluble in aqueous solution but is highly lipid soluble. Mechanisms behind pain on injection include irritation of endothelium, the difference in osmolality and activation of pain mediators. Pain is immediate as well as delayed after 10–20 s.[11] The immediate pain is due to irritation of vein endothelium whereas delayed pain is due to the release of mediators such a kininogen from kinin cascade [12]. Many methods have been introduced to reduce the incidence of pain on propofol injection with variable results. The most widely used method is pretreatment with preservative-free lignocaine before injection of propofol, other methods include cooling of the propofol which reduces pain possibly by delaying the activation of enzyme cascade of pain mediators and Injecting propofol into a large forearm vein which reduces the pain, probably by reducing contact between drug and endothelium. Recently ketamine an NMDA receptor agonist found effective in reducing pain. Ketamine produces analgesia both by local mechanism due to its structural similarity with local anaesthetic cocaine and also by analgesic modulation via NMDA and μ-opiate receptors at the neuraxial level. Not many studies are conducted on ketamine usage in the prevention of pain on propofol injection.  cacy in
So we conducted this study to assess its ef preventing pain due to propofol injection. The dose of ketamine was based on a study conducted by Barbi et al.[9] Our study demonstrated the decreased incidence of pain in ketamine group when compared to control group. Incidences of complications like increased secretions and emergence agitation do occurred in ketamine group but they were not  cant.
statistically signi Ashok Chaudhari [13] et al. conducted a study  cacy of ketamine pretreatment to
to assess the ef alleviate the propofol injection pain. The incidence of pain was 14% in the ketamine group and 96% in the control group. When compared to our study the incidence of pain on injection is almost similar in ketamine group but the incidence was higher in their control group. Tan and Kua [14] et al. studied the effect of ketamine pretreatment on propofol injection pain and found that the incidence of pain was reduced from 84% to 26%. The incidence of pain is similar to our study. Elsayed A et al. [15] conducted the study to  cacy of ketamine in the prevention
compare the ef of pain on propofol injection. They found out that the incidence of pain in the ketamine group was 16% and in the saline group was 84%. The incidences of pain in the two groups were similar to our study. Conclusion Pretreatment with a smaller dose of ketamine provides a simple and safer method in the prevention of pain on injection of propofol without major side effects.

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