Propofol produces a good quality of anaesthesia with rapid recovery. However, pain or discomfort on injection is a very commonly reported adverse event with this agent. A number of drugs including lidocaine, opioids, thiopental, metoclopramide, ondansetron and ephedrine have been used to reduce the incidence of propofol injection pain . Ondansetron, a 5HT3 receptor antagonist, has been shown to be effective in alleviating this pain along with a reduction in postoperative nausea and vomiting . Another drug found to be effective for this purpose, ketorolac, is a non-steroidal anti-inflammatory agent and acts by inhibition of prostaglandin production . It was postulated that a drug having both these mechanisms of action, i.e. 5HT3 receptor antagonism and prostaglandin synthesis inhibition would be able to reduce the incidence of propofol injection pain. Dexamethasone, a corticosteroid, prevents release of serotonin in the gut , decreases 5HT3 turnover in the central nervous system and also inhibits prostaglandin synthesis . Thus the present study was conducted to ascertain the efficacy of dexamethasone pretreatment for alleviation of propofol injection pain.
After approval from the Institutional Ethics Committee, a prospective, randomized, placebo-controlled, double-blinded study was planned. Seventy ASA I or II patients, 18-60 yr of age, undergoing elective abdominal surgical procedures under general anaesthesia, were included in the study. Patients taking regular analgesics or sedatives, suffering from acute or chronic pain syndromes, having a history of hypersensitivity to propofol or dexamethasone, or having contraindications to the use of dexamethasone were excluded. Informed consent was obtained from all the participants and no premedication was administered on the morning of surgery. In the operating theatre, after instituting monitoring, an 18-G intravenous (i.v.) cannula was inserted in the dorsum of left hand without local anaesthetic infiltration and ringer lactate infusion was started. The patients were randomly allocated to two groups of 35 patients each. In the first group normal saline 5 mL was injected as pretreatment solution whereas in the other group the patients received dexamethasone in a dose of 0.15 mg kg−1 up to a maximum of 8 mg and diluted to a volume of 5 mL. This dose of 0.15 mg kg−1 was chosen as this is the most frequently used dose of dexamethasone for an antiemetic action . The maximum dose was limited to 8 mg as dexamethasone has been shown to have a plateau effect for its antiemetic action at 8 mg . After stopping ringer lactate infusion, the test solution was administered over 10 s without occluding the vein. One minute after administration of the test solution, 25% of the calculated induction dose of propofol (1% w/v, M/S Claris Lifesciences Limited, India) was administered at the rate of 0.5 mL s−1. An independent blinded anaesthesiologist assessed the degree of pain of injection after test solution and propofol injection in accordance with the scale advocated by McCrirrick and Hunter  (Table 1). The adverse effects, if any, were noted. The remaining propofol was then injected followed by resumption of Ringer lactate infusion and administration of morphine and vecuronium. Assuming the incidence of pain following i.v. propofol to be 70%, one would need to study at least 31 patients in each group to detect a 50% reduction of propofol injection pain at 80% power (α = 0.05). Thus it was decided to include 35 patients in each group. The data obtained were analysed statistically using unpaired t-test for age and weight of the patients and χ2-test for degree of pain. A P value of <0.05 was accepted as statistically significant.
The two groups were comparable with respect to age, weight and gender ratio. Twenty-seven patients (77%) reported pain in the saline group whereas only 11 patients (31%) felt pain in the dexamethasone group (P = 0.01) (Table 1). Six patients complained of moderate to severe pain following dexamethasone compared with 16 after saline. Transient dizziness was experienced by one patient during dexamethasone injection. This subsided within a few seconds and did not require any intervention. Two patients complained of perineal itching whereas two other patients had shooting pain in the perineum immediately following dexamethasone injection. These problems were also self-limiting in nature and subsided within seconds without any treatment.
Thus the present study shows that dexamethasone pretreatment causes significant reduction in propofol injection pain. Though dexamethasone can cause side effects such as increased incidence and severity of infection, adrenal suppression and delayed healing in surgical patients, a single dose has not been reported to cause any such adverse effects [4,6]. However, perineal itching is a frequent side effect during i.v. administration of dexamethasone . Neff and colleagues  reported excruciating perineal pain immediately after dexamethasone injection. The mechanism responsible for these phenomena is not well understood but is thought to be related to the phosphate ester of the corticosteroid [8,9]. Slow i.v. infusion of diluted dexamethasone can prevent these side effects.
To conclude, dexamethasone in an antiemetic dose of 0.15 mg kg−1 (maximum of 8 mg, diluted to 5 mL volume) decreases the incidence of propofol injection pain significantly when administered i.v. 1 min before injection of propofol. But it may be associated with perineal itching and pain in some cases. Therefore, it cannot be routinely administered for alleviation of propofol injection pain. However, it can be administered as a slow i.v. infusion before injecting propofol to have this added advantage in patients who are already receiving dexamethasone for other indications.
A. K. Sethi
1Department of Anaesthesiology and Critical Care, University College of Medical Sciences and G.T.B. Hospital Delhi, India
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