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Three Part Question

In [adult patients requiring conscious sedation with propofol], does [pre-treatment with intravenous lidocaine] [reduce pain on injection]?

Clinical Scenario

A 30-year-old male attends the Emergency Department with a dislocated shoulder, confirmed by plain film x-rays. This requires manipulayion and reduction under conscious sedation. You prepare your drugs, drawing up propofol. The patient however mentions that he had experienced some severe pain on the injection site during a previous sedation with a propofol. You remember one of your colleagues mentioning lidocaine use to prevent pain on propofol injection and wonder if there is any evidence for its use. 

Search Strategy

Ovid MEDLINE 1946 to present
 
{[Propofol.exp,mp,ti,ab] AND [(lidnocaine.exp, mp, ti, ab) OR (lignocaine.mp)]} AND {(conscious sedation.exp, mp, ti, ab) OR (sedation.ecp,mp,ti,ab) OR (procedural sedation.mp)} 
 
Limits: Humans and English language 
 
106 Results 
 
EMBASE 
 
{[(Propofol.exp,mp,ti,ab)] AND [(lidnocaine.ti,ab,mp,exp) OR l(ignocaine.mp)]} AND {(sedation.exp,ab,ti,mp) OR (conscious sedation.exp) OR (procedural sedation.mp)} 
 
Limits: Humans and English language 
 
975 Results

Search Outcome

1081 papers were found using the above-described search strategy. Seven papers addressed the question of lidocaine use with propofol to reduce pain on injection following abstract review. Two papers however covered research conducted on the paediatric population, and one was an editorial letter. Four therefore were retained for final analysis. The results are in Table 1.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Bachmann-Mennenga et al, 2007, Germany	464 patients undergoing regional elective anesthesia with 4 treatment arms: propofol long chain triglycerides (LCT), and propofol with both medium (MCT) and long chain triglycerides, each with and without the addition of lidocaine 1% at a mix ratio of 20:1	Single Centre, Double blinded randomised control trial	Expression of pain was recorded using a 4 point scale at time of injection (facial grimace or arm withdrawal were considered severe pain)	The lidocaine groups showed lower incidences of pain LCT propofol +lidnocaine 31% pain vs 60% LCT propofol alone and MCT/LCT propofol + lidnocaine 18% incidence of pain vs 47% in the MCT/LCT propofol only group  The adjusted RR for injection pain was 0.58 (95% CI 0.36–0.94) for patients treated with MCT/LCT lidocaine compared to LCT lidocaine, P=0.024.  The NNT was 7.7	All patients received 7.5mg of midazolam as premedication Use of lidocaine was not the studies primary outcome No validated pain recording tool Unclear how much the formulation of propofol influenced the pain perceived by patients
Aldrete et al, 2010, USA	Patients receiving para-vertebral lumbar injection treatment. 22 patients had 16 sedations each for injections. Two different preparations of propofol were used at random, each patient received 8 injections of each preparation. 4 syringes of each preparation of propofol contained 5ml 2% lidocaine and the other four had 5ml of NaCl 0.9%. Both the patient and the physician were blinded to syringe content	Randomised control trial.	Pain as reported by the patient at time of injection and on discharge, and objective measures of pain such as withdrawing arm or body at time of propofol injection	Baxter propofol + Saline 84% reported pain vs 50.2% in Baxter Propofol + lidnocaine group  Gray Propofol + Saline 2% reported pain vs 1% in Gray propofol + Lidocaine group (p <0.01)	Small patient sample, with repeated exposures. No sample size calculations
Mohite et al, 2010, India	136 patients were randomized to the group lipid-free propofol and lignocaine (LFPL) (n = 86) and lipid emulsion of propofol group (LEP) (n = 50) for short surgical procedures.	Prospective, open, controlled, multicentre study	Pain at the site of injection was evaluated using a Visual Analogue Scale (VAS-P) graded as follows: mild (score 1-3), moderate (score 4-6), severe (score 7-10).	In LFPL group, 27 patients complained of pain on injection of drug vs. 35 in LEP; it was absent in 59 (68.6%) and mild in 22 (25.6%), moderate in 5 (5.8%) in LFPL group. In LEP group, pain was absent in 15 (30.0%), mild in 29 (58.0%), moderate in 5 (10.0%) and severe in 1(2.0%). The pain on injection was significantly less (p < 0.0001) in the LFPL	No sample size calculation    Confounders (analgesics and anxiolytics given to each group)
Kwon et al, 2012, South Korea	121 patients undergoing diagnostic upper GI endoscopy: 61 and 60 subjects randomly assigned to the lidocaine pre-treatment and saline (placebo) groups respectively Investigators blinded to interventions	Randomised Control Trial	Pain intensity estimated on a four-point verbal rating scale (VRS)	The lidocaine group showed a lower incidence of pain than the placebo group (37.7% vs. 60.0%, P = 0.018). The lidocaine group perceived significantly less pain than the placebo group (median pain score, 0 vs. 1, P = 0.008). Using multivariate regression analysis, only lidocaine pretreatment was found to be an independently associated factor against pain perception (OR=0.380; 95% CI, 0.177 – 0.815; P = 0.013).	Small sample size Selected population and all patients pre-treated with cimetropium bromide

Comment(s)

Conscious sedation with propofol has gained huge popularity in emergency medicine, mostly because of its rapid onset, recovery, its safety and minimal organ toxicity. Pain along the injection site is however a commonly reported side-effect. One theory is that pain on injection might be due not to irritation of the veins, but to changes in the formulation of propofol. Significant changes in the formulation of propofol have been made but they did not eliminate the pain on injection completely, although it has been diminished substantially. Attempting to reduce this elicited pain, the most commonly used medication has been lidocaine in a variety of rates, doses and concentrations combined with different formulations of propofol. The retrieved, analysed and above tabulated studies seem do suggest that lidocaine is effective at relieving pain at the injection site.

Clinical Bottom Line

Lidnocaine pre-treatment or mixed with propofol reduced pain at the injection site. Further research is however required to see how much of this effect is that of lidocaine alone or the change in propofol formulation.

References

1. Bachmann-Mennenga B, Ohlmer A, Boedeker RH et al Preventing pain during injection of propofol: effects of a new emulsion with lidocaine addition. European Journal of Anaesthesiology 2007; 24: 33–38.
2. Aldrete JA, Otero P, Alcover J et al. Pain on injection from propofol may be avoided by changing its formulation. Acta Anaesthesiol Scand 2010; 54: 442–446.
3. Mohite SN, Kudalkar AG, Dalvi NP. A Comparative Study of Premixed Lipid Free Propofol and Lignocaine Vs Lipid Emulsion of Propofol in Conscious Sedation. J Anaesth Clin Pharmacol 2010; 26(3): 303-306.
4. Kwon JS, Kim ES, Cho JB et al. Incidence of Propofol Injection Pain and Effect of Lidocaine Pretreatment During Upper Gastrointestinal Endoscopy. Dig Dis Sci 2012 57:1291–1297.