Lipid composition and lidocaine effect on immediate and delayed injection pain following propofol administration.

BACKGROUND: Propofol has been used for the induction and maintenance of anesthesia. However, patients experience vascular pain during its injection. AIMS: The objective of this study was to compare the effect of the lipid type used in propofol preparations and that of lidocaine on the immediate and delayed vascular pain induced by propofol administration.
MATERIALS AND METHODS: In this double-blinded clinical study, 150 patients at American Society of Anesthesiologists level I-II were randomly divided into three equally sized groups. A propofol with medium and long-chain triglycerides (propofol-MCT/LCT) was administered to the first group. The second group received propofol containing propofol-LCT, and the third group received propofol-LCT and pretreatment lidocaine 20 mg. The incidence and the intensity of immediate (during injection) and delayed injection pain (after 20 s) were evaluated on a verbal analog scale (1-10) until patients' unconsciousness. STATISTICAL ANALYSIS: Sample size was calculated with SigmaPlot version 12.5 software. Data were analyzed with Statistical Package for the Social Sciences (SPSS) version 16, one-way analysis of variance, and post-hoc Tukey. P < 0.05 was considered statistically significant.
RESULTS: The demographic parameters of the three groups were similar. The lidocaine group experienced the least immediate vascular pain. The intensity of pain was highest in the propofol-LCT group (P = 0.04). Additionally, the intensity of delayed pain was lowest in the propofol-MCT/LCT group (P = 0.01). The incidence of pain associated with the propofol administration was 26.5, 44, and 18%, respectively, in propofol-MCT/LCT, propofol-LCT, and lidocaine and propofol-LCT groups.
CONCLUSION: The results indicate an effect of the lipid type on delayed pain reduction, especially propofol-MCT/LCT. On the other hand, the lidocaine decreases immediate propofol-LCT vascular pain.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Due to the fast recovery, the anti-emetic effects, and postoperative pleasant feeling, propofol has been widely used for the induction and maintenance of anesthesia.[1] However, vascular pain and hypotension are common side effects of propofol administration.

The pain experienced during the administration of propofol can be discomforting to patients. It has been reported that the prevalence of propofol injection pain among patients is between 28% and 90% in adults and between 28% and 85% in children.[23] One study found that there was no gender difference in the prevalence of vascular pain associated with propofol administration.[4] The factors that influence propofol pain include vascular size, infusion rate, propofol concentration, chemical structure, and the temperature of propofol preparation.[4]

The postinjection pain can be immediate or delayed. Immediate pain occurs due to the direct irritant effect. Klement and Arndt postulated that vascular pain is evoked via a direct effect by osmolality and pH, however, propofol is isotonic and has a pH between 6 and 8.5.[5] It has been shown that pain after intravenous injection of propofol was related to its free aqueous concentration.[6] Also, delayed injection pain (10–20 s later) is due to the plasma kallikrein-kinin system and vascular effect of bradykinin by contact with propofol.[7]

There are different methods to decrease propofol injection pain, such as mixing it with lidocaine,[4] pretreatment with lidocaine,[8] although the most effective way is large and antecubital veins.[9]

The purpose of this study was to evaluate the effect of the triglyceride-associated lipid type, and that of lidocaine on the incidence and intensity of immediate and delayed pain experienced following propofol infusion.

MATERIALS AND METHODS

This prospective randomized and double-blinded clinical trial, which enrolled 150 American Society of Anesthesiologists I-II patients, was conducted after receiving approval from the Mashhad University of Vice Chancellor for Research and local Ethics Committee No. 900184 on 2012/2/2. Patients who provided informed consent for their participation and who did not have any contraindication for propofol infusion were equally and randomly divided into three groups with random number generator and numbered envelops. Pregnant or breastfeeding mothers, patients with epilepsy and conduction disorders, patients on anti-arrhythmic drugs, those with lipid metabolism disorders, patients with a history of allergy to eggs, propofol, or lidocaine, as well as those who had taken sedative drugs during the 24 h preceding the study, were excluded. Prior to the study, the quality of pain evaluation and verbal analog scoring was explained to the patients. Before inducing anesthesia, the patients did not receive any topical anesthetics or tranquilizers. A 20 gauge catheter was placed in the largest vein on the back of the hand and 150 mL of saline was infused. Following this, the patients were monitored for vital signs. For each patient, two syringes were prepared, 5 ml syringe was filled with distilled water or lidocaine and 20 ml syringe was filled with long-chain triglycerides (LCT) or medium chain triglycerides-LCT (MCT-LCT) propofol (LCT-propofol was from Claris Company and MCT-LCT propofol was from Fresenius Kabi Company). The patients and anesthesia nurse who evaluated the vascular pain were blind to the study groups. In the first group, distilled water and propofol mixed with MCT/LCT was administered. In the second group, distilled water and propofol mixed with LCT was administered. The third group received 1 mL (20 mg) of lidocaine, followed by a preparation of propofol containing LCT (lidocaine + propofol-LCT) (prepared by Claris). The rate of propofol infusion was 10 mg/s in all patients. The propofol solution was equilibrated to room temperature before administration.

The incidence and the intensity of pain were assessed by means of verbal analog scoring (1–10) based on the answers to questions asked to the patients at two stages, the start of the injection, and 20 s after the propofol injection. After the pain evaluation and the induction of anesthesia, fentanyl and atracurium were administered, and the patients were intubated after 2–3 min.

Statistical studies and analysis

The sample size was calculated based on our previous study[10] in three groups with SigmaPlot software version 12.5, 2015 (Systat Software Inc. San Jose, USA). Considering incidence of 55% for propofol-LCT vascular pain, meaningful reduction of pain for 20%, first type error of 0.05 (α = 0.05), confidence coefficient of 80% (β = 0.2), and sample size of 144 people, were found and 150 people were selected for facilitating the study.

The data were analyzed with SPSS software (version 16, Chicago, SPSS Inc). The analysis of variance, post-hoc Tukey, Chi-square, and the Fischer's exact test were used for the comparison of the parametric data such as age, weight, and vascular pain intensity. For the analysis of nonparametric data, the Kruskal–Wallis test was adopted such as sex and injection pain incidence. P < 0.05 was statistically significant.

RESULTS

Demographic parameters, including the age, gender, and weight, are presented in Table 1. There was no statistically significant difference between the demographic parameters of the three groups. The intensity of immediate and delayed pain in the three groups during propofol injection are shown in Table 2. There was a significant difference regarding the intensity of immediate and delayed pain between the three groups (P = 0.04 and P = 0.01, respectively). The intensity of immediate pain was least in the lidocaine + propofol-LCT group (2.9 ± 0.5), whereas, the propofol-LCT group showed the highest value (4.5 ± 0.9) (P = 0.011). There was no statistically significant difference between the intensities of immediate pain reported by propofol-MCT/LCT and propofol-LCT groups (P = 0.061) and also there was no significant difference between propofol-MCT/LCT and lidocaine group (P = 0.14). But, the intensity of delayed pain in propofol-MCT/LCT group was less than that in the propofol-LCT group (2.2 ± 0.9 vs. 3.8 ± 1.1) and meaningful (P = 0.001). There was no significant difference between propofol-MCT/LCT and lidocaine + LCT propofol groups. Totally, the minimum and maximum incidences of immediate and delayed injection pain were related to lidocaine + propofol-LCT (18%) and propofol-LCT (44%) groups, respectively, and the differences in the pain incidence of the three groups were statistically significant (P = 0.042).

Table 1

Demographic parameters in three groups

Table 2

Immediate and delayed vascular pain with verbal analog scale

DISCUSSION

Propofol has been widely used for anesthesia induction. However, injection pain is common and sometimes discomforting.[11] Previous studies have shown that the prevalence of propofol injection pain is up to 90% in adults.[4] A systematic review identified that administration of a combination of lidocaine and tourniquet is the most effective method for controlling the pain.[2] An independent study not only confirmed these results but also suggested that the administration of the drugs via forearm veins (instead of hand veins) might further reduce the pain.[912] On the other hand, Jalota et al. showed that premixed lidocaine and propofol-MCT/LCT was same effective as lidocaine + tourniquet,[9] and also Walker et al. showed difference of premixed propofol-MCT/LCT and lidocaine with propofol-MCT/LCT and tourniquet is statistically, not clinically.[13]

In our study, of the 150 patients who received propofol, 29.5% reported pain during injection. The incidence of pain was lowest in the lidocaine group (18%) and highest in LCT group (44%). The immediate pain intensity in propofol-LCT and propofol-MCT/LCT groups was higher than that in lidocaine + propofol-LCT group. In contrast, the delayed pain intensity in propofol-MCT/LCT group was lesser than that in lidocaine + propofol-LCT and propofol-LCT groups. To date, various methods have been used for controlling the pain experienced during propofol infusion. However, it appears that the most effective method is the administration of lidocaine prior to propofol with or without tourniquet.

Change in lipid composition of propofol decreases the incidence and severity of propofol injection pain.[14151617] In some previous studies, the pretreatment lidocaine reduced propofol-MCT/LCT injection pain,[1819] but in other studies, differences were not significant.[2021] In our study, the propofol-MCT/LCT decreased delayed injection pain, but not on immediate vascular pain versus propofol-LCT.

In a study, lidocaine reduced the intensity of propofol injection pain with three different doses.[22] Parmar and Koay compared the incidence of pain following the administration of cold propofol, two different doses of lidocaine (0.1 and 0.2 mg), and normal saline, and showed that the administration of cold propofol was associated with high prevalence of pain, which could be reduced by the administration of lidocaine before propofol.[23] The studies have revealed a potential of inhibition generation of bradykinin by pretreatment lidocaine.

Propofol induces immediate pain through topical stimulation and induces delayed pain by activation of the kallikrein cascade. The precise mechanism by which lidocaine or lipid composition reduces the propofol-induced pain is not known. However, it is likely that lidocaine acts by inhibiting the kinin cascade.[69] In our study, pretreatment lidocaine reduced immediate injection pain.

CONCLUSION

Our study revealed that the prevalence of delayed pain was least in propofol-MCT/LCT group, which might indicate an influence of the lipid type on delayed vascular pain. Also, immediate propofol injection pain reduced in patients by pretreatment lidocaine.

Financial support and sponsorship

Deputy for Research of Mashhad University of Medical Sciences.

Conflicts of interest

Deputy for Research of Mashhad University of Medical Sciences