Source: Euasobhon P, Dej-arkom S, Siriussawakul A, Muangman S, Sriraj W, Pattanittum P, Lumbiganon P. Lidocaine for reducing Propofol-induced pain on induction of anaesthesia in adults. Cochrane Database of Systematic Reviews 2016, Issue 2. Art. No.: CD007874.
Study Population: 10,350 participants from 82 studies were included for quantitative analysis, (age range 13 to 89 years) with American Society of Anesthesiologists (ASA) status I-III undergoing elective surgery who received IV propofol for induction of anesthesia.
Efficacy Endpoints: Overall pain & high intensity pain (according to the definition of the scoring system of each included trial)
Harm Endpoints: Thrombophlebitis, cardiac arrhythmia, allergic reaction, or local anesthetic toxicity
Narrative: Localized pain at the injection site and up the course of the cannulated vein upon IV propofol injection is an unpleasant side effect that is frequently seen during induction of anaesthesia and during moderate sedation used in Emergency Departments across the globe. IV lidocaine injection has been commonly used to attenuate this effect. Many studies have reported that lidocaine is effective in reducing the incidence and severity of pain. This topic was recently analyzed by the Euasobhon et al1 in the 2016 Cochrane Collaboration systematic review and is the primary source for this summary.
A total of 85 studies were included in this systematic review, 82 of which (10,350 participants) were eligible for quantitative analysis. All studies were single-center and were performed in a range countries worldwide. 12/84 trials used co-induction medications as an adjunct in both groups: remifentanil (4 trials), nitroglycerine ointment (1 trial), 50% Nitrous Oxide (3 trials), sevoflurane (1 trial), dexamethasone (1 trial), ketamine (1 trial) or dexmedetomidine (1 trial). 82 of the studies were assessed to be of satisfactory methodological quality to be included in the meta-analysis. All compared propofol to placebo (saline) and participants were randomly allocated to placebo or treatment groups.
Administration of lidocaine, either mixed with propofol or given IV before propofol, significantly reduced the overall incidence of pain associated with propofol injection when compared to placebo: 30% vs. 64%; absolute risk difference (ARD): 34%; NNT: 3. Similarly, lidocaine reduced the risk of experiencing high-intensity pain during propofol injection: 12% vs. 38%; ARD: 26%; NNT: 4. ‘High-intensity pain’ included moderate pain, severe pain, pain mentioned when questioned and accompanied by behavioral signs, or pain reported spontaneously, not as a result of questioning, pain associated with grimacing, withdrawal movement of forearm or tears. Regarding lidocaine/propofol admixture, subgroup analyses using different doses of lidocaine admixed with the propofol i.e. ≤20 mg or ≤0.2 mg/kg, or >20 mg or >0.2 mg/kg, found no statistically significant difference between the two – both reduced pain.
Regarding lidocaine pretreatment with IV injection prior to propofol, during subgroup analyses they compared four different techniques of lidocaine pre-treatment administration: 1. Low dose lidocaine pretreatment alone (≤ 20 mg or ≤ 0.2 mg/kg), 2. High dose lidocaine pretreatment alone (> 20 mg or > 0.2 mg/kg), 3. Low dose lidocaine pretreatment with venous occlusion upstream (≤ 20 mg or ≤ 0.2 mg/kg), 4. High dose lidocaine pretreatment with venous occlusion upstream (> 20 mg or > 0.2 mg/kg). All of these techniques decreased pain on injection. However low dose lidocaine pretreatment without venous occlusion appeared to be the least effective of the four “pretreatment” techniques (OR 0.40, 95% CI 0.29 to 0.55, seven studies, 713 participants, high-quality evidence). Whilst high dose lidocaine pretreatment with venous occlusion was the most effective of the pretreatment techniques (OR 0.11, 95% CI 0.09 to 0.15)
Thirty two of the studies commented on incidence of adverse events. Thrombophlebitis was the only reported adverse effect and was noted in only two studies, the incidence of which was not significantly different between lidocaine and placebo groups.
Caveats: The systematic review reports the quality of evidence to be high, with a low risk of bias. The only area with a low rating for quality of evidence was the incidence of adverse events. It is not possible to estimate accurately the harms and adverse events associated with this practice, as only a few trials included in the systematic review assessed adverse events and they suffered from serious imprecision and inconsistency.
The trials analyzed in the systematic review reported here included trials that studied propofol as an induction agent. Propofol is frequently used for procedural sedation in the emergency department (ED). The safety and efficacy of lidocaine to reduce pain associated with propofol injection could be similar during moderate sedation. A literature search revealed no papers related to lidocaine use to attenuate propofol-related injection pain in settings outside of the operating theatre. However, ED-based trials should confirm these findings before they are generalized to ED procedural sedation.
Author: Samuel Desbruslais, MBBS
Published/Updated: August 13, 2018
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