Ketamine pretreatment with venous occlusion attenuates pain on injection with propofol

Abstract

EDITOR: Injection of propofol into a peripheral vein is associated with a high incidence of local pain and discomfort. Different manoeuvres have been tried to reduce this pain, but with varying success. The addition of a small dose of lidocaine to propofol is the most commonly used technique, but this does not eliminate the pain in all cases [1]. Lidocaine also has its maximum effect when given as a pretreatment with a venous tourniquet occluding the proximal part of the arm [1]. Recent work suggests that prior administration of ketamine 10 mg, 30 s before propofol (without temporary venous occlusion) reduces the propofol associated pain [2]. In this prospective, randomized, double blind, placebo-controlled study, we further investigated whether a small dose of ketamine reduces pain on injection with propofol in the same magnitude as does lidocaine with a tourniquet. After obtaining institutional Ethics Committee approval and informed written consent, we studied 150 adult ASA I or II patients aged 20-60 yr, who were scheduled for elective surgery. Patients taking regular analgesics or sedatives, suffering from acute or chronic pain syndromes, or any neurological diseases, thrombophlebitis, known allergy to local anaesthetics, propofol or ketamine, were excluded. All patients were premedicated with diazepam 10 mg orally 90-120 min before induction of anaesthesia. When the patient arrived in the operating room, routine monitoring was applied and, following baseline homodynamic values, a 20-G IV cannula was inserted on the dorsum of the non-dominant hand without the use of local anaesthetic. The cannula was flushed with normal saline. No other solution was injected before the induction of anaesthesia with propofol. Patients were randomly assigned using a sealed envelope technique to one of three groups: Group saline (n = 50) received physiological saline 2 mL with venous occlusion for 1 min; Group lidocaine (n = 50) received lidocaine 20 mg in 2 mL saline with venous occlusion for 1 min; Group ketamine (n = 50) received ketamine 10 mg in 2 mL saline with venous occlusion for 1 min. Venous occlusion was performed using a rubber tourniquet placed on the upper arm after elevating the arm for 30 s for gravity drainage of venous blood [3]. Before induction of anaesthesia, the patients were informed that they would be receiving an intravenous (i.v.) anaesthetic that may cause pain in the forearm. Sixty seconds after the pretreatment bolus, the occlusion was released and propofol 2.5 mg kg−1 was administered through the same 20-G catheter at the rate of 1 mL s−1. Fifteen seconds after injection of 25% of the dose of propofol, patients were asked by an independent, second anaesthesiologist to grade their pain in accordance with the criteria shown in Table 1. After assessment of the pain intensity, the rest of the dose of propofol was given and anaesthesia was continued as planned. Statistical comparisons were carried out using ANOVA and the Kruskal- Wallis test where appropriate; P < 0.05 was considered significant. The distribution of pain scores in each group is shown in Table 2. With saline, 40 of 50 patients (80%) experienced pain on propofol injection, and in 14 of those, pain was graded as severe (28%). After lidocaine, five of 50 patients (10%) experienced pain; this was significantly less than with the control group (P < 0.0001). After ketamine, six of 50 patients (12%) experienced pain; this, again, was significantly less than with the control group (P < 0.0001). No statistically significant difference was noted between the ketamine and lidocaine groups (P > 0.05). Pain intensity was significantly less in patients who received ketamine and lidocaine as compared to saline (P < 0.0001) (Table 2). This investigation suggested that i.v. ketamine, when applied with a tourniquet, reduced injection pain with propofol in the same magnitude as lidocaine. The incidence of pain with lidocaine supported the findings of previous studies where a venous tourniquet was used. Previous investigators have found 20 mg lidocaine with a venous occlusion for 10, 20 or 30 s to be significantly better than placebo, suggesting that venous occlusion is important. Mangar and colleagues demonstrated that administering lidocaine after a tourniquet was inflated to 50 mmHg for 1 min virtually abolished the pain associated with propofol injection [4].Table 1: Pain scores at 15 s after injection of 25% of the propofol dose.Table 2: Incidence of pain on injection with propofol.The tourniquet isolates the arm veins from the rest of the circulation and increases the action of locally acting substances. Tan and colleagues recently reported that the incidence of pain was significantly less (26%) with prior administration of ketamine 10 mg compared to a saline control group (86%) [2]. In a similar study, Suzuki and colleagues administered 1% ketamine (2 mL) prior to propofol and reduced the incidence of pain from 68% to 33% [5]. In none of these studies, venous retention was used. We found ketamine to be very effective in preventing propofol injection pain, especially moderate to severe pain in the presence of a venous tourniquet. Ketamine has analgesic properties that are mediated by a number of mechanisms. Ketamine in low doses is a potent non-competitive NMDA antagonist, and the analgesic action of ketamine is linked to an action at the NMDA receptor. Clements and Nimmo showed that the analgesic effect of ketamine occurs at much lower plasma concentrations (100 ng mL−1) than the anaesthetic effect (700 ng mL−1) [6]. Ketamine resembles cocaine in chemical structure and shares some of its effects [7]. The results of this study suggest that ketamine modulates its effect at the peripheral site by a local mechanism as it has been reported to have local anaesthetic properties when given i.v. for regional anaesthesia. Durrani and colleagues reported that >0.3% ketamine (approximately 10−2 mol L−1) produced adequate regional anaesthesia with complete sympathetic, sensory and motor block [8]. We used 2 mL of a 0.5% solution in our study. At this concentration, ketamine could produce analgesia and protect against propofol-induced pain. In conclusion, it is reasonable to consider i.v. ketamine with a tourniquet for 1 min as an effective alternative to lidocaine for reducing pain on injection with propofol. Y. K. Batra A. R. Al Qattan H. M. Marzouk M. Smilka A. Agzamov 1Department of Anaesthesia and Intensive Care, Al-Sabah Hospital, Kuwait