Pain on injection is a recognized side-effect of propofol and can be very distressing to the patient. The incidence of pain varies between 28 and 90% in adults during induction of anaesthesia with this drug [1,2]. Although the cause of any pain when drugs are injected intravenously (i.v.) is unknown, multiple factors are believed to be involved. Many studies have shown the use of i.v. lidocaine to be an effective prophylactic [3–5].
Metoprolol has β-adrenergic receptor antagonist properties and its selectivity of β1-antagonism is unclear . We thought that metoprolol may have a vasodilator effect so resulting in an increase in venous flow and thereby decreasing the contact of propofol with the endothelium of the vein used for the injection. To our knowledge, metoprolol has not been studied for this purpose before. Therefore, this study was designed to determine whether metoprolol given before the injection of propofol was effective in reducing the incidence and severity of pain associated with propofol injection and how it compared with lidocaine.
We obtained institutional Ethics Committee approval and informed written consent from the patients. Ninety ASA I-II patients scheduled for elective surgery under general anaesthesia were enrolled into the study. Patients were premedicated 1 h before surgery with atropine 0.5 mg and meperidine 50mg intramuscularly. Routine monitoring was instituted when the patients arrived in the operating room (three-lead electrography, non-invasive blood pressure and pulseoximetry). Patients were randomly allocated to one of three groups to receive metoprolol 2 mg, lidocaine 20 mg or saline 2 mL. Each patient was given one of the three solutions through a 20-G i.v. cannula on the dorsum of the hand while the venous drainage was occluded manually at the middle of the forearm for 45 s. The patients were informed that the propofol may cause pain on injection and that they should report any pain or discomfort felt during injection. After the arm had been released, propofol 2.0–2.5 mg kg−1 at room temperature was injected at 2 mL (20 mg) every 4 s.
Pain was assessed verbally and scored as none (0), mild (1) or severe (2). Every 4 s during the injection of propofol, an independent investigator – blinded to the pretreatment solution used – asked the patients if they had any discomfort or pain in their arm. If the answer was ‘yes’, they were then asked if it was mild or severe. Mild pain was defined as discomfort in the hand or arm and was considered acceptable, while severe pain was considered as unacceptable. Patients were questioned until they fell asleep.
Results were analysed using ANOVA for patient characteristics data and the Χ2-test for incidence of pain. P < 0.05 was as considered significant.
There were no differences between the groups with respect to age, weight or gender. Details of patients who experienced pain in each group are shown in Tables 1 and 2. When the groups were compared, the number of patients without pain in both the metoprolol and lidocaine groups was significantly higher than in the saline group at all times (P < 0.05) (Table 1). The incidence of pain in the metoprolol group at 8 s was higher than in the lidocaine group (P < 0.05), but there was no difference between metoprolol and lidocaine at 16 s. The incidence rate of clinically unacceptable severe pain at 16 s in the metoprolol and lidocaine groups (16.6 and 10%, respectively) was significantly less than in the saline group (56.7%) (Table 2).
The results have shown that pretreatment with i.v. metoprolol was equally effective as lidocaine in reducing the pain associated with the i.v. injection of propofol. The incidence rate of pain when propofol was injected varied between 28 and 90% in adults [1,2]. In our study, 93.3% of patients who received only saline pretreatment experienced propofol-induced pain.
The mechanism of pain on injection of propofol remains unclear, although many factors appear to affect its occurrence, which include the following: the site of injection [7–10], the speed of injection , the propofol concentration in the aqueous phase , the buffering effect of the blood , the speed of any i.v. carrier fluid , the temperature of propofol [14,15], the syringe material , and the concomitant use of drugs such as local anaesthetics [3–5,7,17] and opioids [18,19]. However, none of the pharmacological agents have proved entirely successful. Administration of lidocaine – either before or premixed with propofol – is the most widely used method. Lidocaine is more effective when is added to the propofol and not injected before it . The use of tourniquets with the preinjection of lidocaine technique can reduce the incidence of pain . The failure rate with the use of lidocaine is between 13 and 32% [1,9,20]. Our study found the failure rate to be 20%, which is consistent with the results from other studies.
Scott and colleagues  reported that a slow rate of injection of propofol is associated with more pain than a rapid bolus. In our study, the rate of injection was controlled at 20 mg over 4 s, which is a reasonable rate to use in clinical practice.
Endothelial irritation is one of the factors thought responsible for the pain of propofol injection. Injection into a large vein reduces pain by reducing the contact between the drug and the endothelium . Immediate pain is thought to be from this direct irritant effect, whereas delayed pain – which has a latency of between 10 and 20 s – probably results from an indirect effect, e.g. activation of pain mediators (kininogens) via the kinin cascade [8,21]. In the present study, metoprolol and lidocaine have reduced the incidence of both immediate and delayed pain.
It is difficult to explain why metoprolol was nearly as effective as lidocaine. β-adrenergic receptor antagonists such as metoprolol and atenolol have greater affinity for β1- than for β2-receptors. However, the selectivity of β1-antagonists is not absolute . There-fore, metoprolol may have a vasodilating effect to some extent, thus increasing venous flow, so diluting the drug, and reducing the contact between propofol and the endothelium. It is also possible that metoprolol by some unknown mechanism may prevent the activation of unmyelinated and myelinated nosiceptors by bradykinin and other mediators. In conclusion, whatever the mechanism, metoprolol appears to be an effective drug in reducing propofol-induced pain.
This study was conducted entirely from departmental resources.
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