Efficacy of ephedrine in the prevention of vascular pain associated with different infusion rates of propofol.

CONTEXT: Vascular pain is a frequent and hypotension is most important complications of propofol administration. AIMS: The goal of this study is to evaluate frequency of vascular pain during rapid and slow injection of propofol and also effect of ephedrine for decreasing of vascular pain.
MATERIALS AND METHODS: After approval of local ethical committee, 120 patients with American Society of Anesthesiologists status I (ASA I), who were candidates for cataract surgery, were divided randomly into three groups. The first group received 20 mg of lidocaine, and propofol 1% at 1 ml per 5 seconds (slow injection). The second and third groups received propofol at 10 ml per 5 seconds without lidocaine (rapid injection) and also in the third group, 10 mg of ephedrine were injected at first and vascular pain were evaluated with 5-point scale. STATISTICAL ANALYSIS: Data were analyzed with Statistical Package for the Social Sciences (SPSS) v16, Chi-square test, one-way analysis of variance (ANOVA), Kruskel-Wallis. P <0.05 was considered statistically significant.
RESULTS: Demographic characteristics of the three groups were similar. The vascular pain was 52.5%, 40%, and 27.5% in first, second, and third group, respectively. The injection pain was more severe in the slow injection (P = 0.025), but was the same between two rapid groups (P = 0.76). Heart rate and blood pressure changes were similar between all groups (P = 0.45 and P = 0.58, respectively).
CONCLUSION: Rapid propofol injection induced less vascular pain compared with slow injection, but 10 mg ephedrine was not more effective.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Propofol is the drug of choice for anesthesia induction. It has many side effects, including hypotension and injection pain. Hypotension is the most important cardiovascular side effect of propofol, but vascular pain is a common complication. In a review, 9% experienced severe hypotension[1] and frequency of pain after propofol injection has been reported to be as high as 90%.[2]

Different methods have been suggested to decrease propofol injection pain, such as mixing it with lidocaine,[3] pretreatment with lidocaine[4] or sodium thiopental,[5] diluting propofol,[6] and also the most effective way is large and antecubital veins.[7] Rapid injection of propofol is not considered due to risk of hypotension, but it has been observed that rapid injection decreases the incidence and intensity of injection pain.[8] It also increases plasma concentrations quickly, which in turn facilitates insertion of laryngeal mask and tracheal tube without needing muscle relaxants in patients with full stomach and in patients with difficult intubation.[8]

The goal of this study was to evaluate pain incidence after propofol injection at different speeds and that ephedrine due to vasoconstriction can decrease vascular pain.

MATERIALS AND METHODS

With approval of local ethical committee of medical university, assuming a 60% incidence of pain after intravenous (IV) propofol injection and a 30% reduction following therapy, the sample size for α =0.05 and confidence interval of 90% was calculated to be 40 for each group. This prospective, interventional, and double-blinded study was conducted in October to December 2012 on patients with American Society of Anesthesiologists (ASA) status I, who had been operated on for cataracts. Patients with age less than 15 years and more than 70 years, morbid obese (Body Mass Index >35), any type of comorbid disease, and those who had local anesthesia were excluded from the study. One-hundred and twenty patients were divided into three groups with random number generators. Because of the unavailability of antecubital veins in the head and neck surgery, we prefer to use dorsoum of the hand veins. A 20-G venous catheter was placed into the veins on the back of the hands of the patients. Patients monitoring consisted of electrocardiography, pulse oximetry, heart rate, and noninvasive arterial blood pressure. All patients received 1 mg of midazolam and 2 ml/kg of saline initially. Patients were denitrogenated with inhaling 100% oxygen through the mask. The first group (group S, slow propofol injection) received pretreatment with 20 mg of lidocaine, then after 1 minute, 2 mg/kg of propofol 1% at the rate of 1 mL/5 seconds was injected. The second group (group R, rapid propofol injection) received the same amount of propofol at the rate of 10 mL/5 seconds. The third group (group E, fast propofol injection with pretreatment ephedrine) received 10 mg ephedrine and after 15 seconds, propofol at the rate of 10 mL/5 seconds. To prevent drug interaction, narcotics and muscle relaxants were not used before propofol injection. Before induction, evaluation of the pain severity was described for the patients. From the beginning of propofol injection to anesthetic induction, patients were asked to determine propofol injection pain and its severity using a 5-point scale [Table 1]. The patients and the person who assesses the patients’ pain were unaware of the study group. When anesthesia was induced, 1 μg/kg of fantanyl and 0.3 mg/kg of atracurium were injected, and 120 μg/kg/min of propofol was infused for patients. A laryngeal mask was inserted 2 minutes later and patients were placed under mechanical ventilation. Immediate and delayed pain of propofol was not evaluated selectively in the patients; and evaluation of pain was difficult with verbal analogue scale. Data were analyzed using Statistical Package for the Social Sciences (SPSS) v16. Non-parametric data such as injection pain were assessed using Chi-square test and parametric data were analyzed with one-way analysis of variance (ANOVA), Kruskel-Wallis. P <0.05 was considered statistically significant in all calculations.

Table 1

The 5-point scale for the severity of vascular pain

RESULTS

Independent parameters and demographic characteristics such as age, gender, weight, preinduction heart rate, and blood pressure did not have any significant differences between the groups [Table 2]. The frequency of vascular pain was 52.5% in first group (slow injection), 40% in second group (rapid injection), and 27.5% in third group (rapid injection with ephedrine) that is shown in Table 3. Statistically, pain at the rapid injection groups was significantly less than slow injection group (P = 0.025). There was not any significant difference for pain between the two groups with rapid propofol injection (P = 0.76). There was not any significant difference between the three groups for heart rate [P = 0.45; Figure 1] and blood pressure [P = 0.58; Figure 2]. Postinduction hypotension was statistically significant, but the same in all groups (P = 0.001).

Table 2

Participants demographic parameters, mean (standard deviation)

Table 3

Frequency of pain after propofol injection n (%)

Figure 1

Heart rate changes in three groups

Figure 2

Mean arterial pressure changes in three goups

DISCUSSION

Propofol is the drug of choice for inducing anesthesia although it can cause pain at the time of injection due to its high lipid solubility. A mixture of medium and long-chain lipid solvents reduces vascular pain.[9] Midazolam administrated before propofol does not have any effect on reducing propofol pain.[10] In this study, in order to prevention of drug interactions, narcotics and muscle relaxants were administrated after anesthesia induction by propofol.

Propofol injection causes immediate pain because of local stimulation. It can also cause delayed pain after 15 seconds due to activation of the kallikerin and bradykinin systems, vascular dilatation, and increasing propofol permeability to the nerve terminals.[11] To prevent propofol injection pain, various drugs have been administrated. Agrawal et al., have suggested administration of sodium thiopental before propofol to reduce pain.[5] Nafamostat, a kallikerin inhibitor, has been successfully used by Iwama et al., but it is not readily available because of its high price.[12] Based on Nishiyama et al.'s study, flurbiprofen injection right before propofol injection decreases pain by up to 100%, but this drug is not readily available either.[13] Other analgesics like ketorolac[14] and narcotics[15] also reduce propofol pain. The most commonly used drug is lidocaine, which decreases pain by up to 20-30%.[1617]

The aim of this study was to evaluate the effects of rapid propofol injection on the frequency of pain and comparing it with lidocaine administration before propofol injection. In slow injection group with 20 mg of lidocaine, the frequency of pain was 52.5%. The frequency of pain was 40% in rapid injection group without ephedrine and finally, in rapid group with ephedrine was 27.5%. In another study, the effects of ephedrine 70 μg/kg, ketamine 0.5 mg/kg, and saline 2 mL/kg on vascular pain and hypotension were compared.[18] The frequency of pain was similar between the three groups (84%, 80%, and 72%), but its severity was less in the ketamine group. In ketamine and ephedrine groups, blood pressures were better controlled and heart rate did not change very much. In our study, ephedrine 10 mg had not more effective pain relief and also had not significant effect on heart rate and could not prevent postinduction hypotension.

In a study on 200 patients, Gamlin et al., compared the effects of pretreatment with 15 mg, 20 mg, and 25 mg of ephedrine with control group and showed that ephedrine at any dose was effective in controlling blood pressure but induced tachycardia in most of the patients.[19] In our study, all three groups experienced the initial decrease of blood pressure after propofol injection and 10 mg of ephedrine did not have a significant effect on preventing hypotension compared with other groups with rapid and slow propofol injection. Heart rate decreased slightly in all three groups, but was not statistically and clinically significant and was similar. In our study, almost 4% of patients had significant hypotension, and we did not find any significant relation between age and hypotension (P = 0.97).

CONCLUSION

In this study, rapid propofol injection reduced vascular pain frequency and that was more significant in the ephedrine group. Slow injection, 2 ml/kg saline and 10 mg ephedrine were unable to prevent hypotension after induction. Heart rate did not change in three groups.