Aug 03

Does warming LAs reduce the pain of injection?

Journal reference: Hogan ME, VanderVaart S, Perampaladas K, et al. Systematic review and meta-analysis of the effect of warming local anesthetics on injection pain. Ann Emerg Med 2011 Jul; 58(1): 86-98.e1


Published: 14 February 2011

Evidence cookie says…

Warming the local anaesthetic probably does reduce pain in general, but not by much in most individuals. 

There is uncertainty in the evidence as the magnitude of this effect, which appears to straddle the the boundary of clinical relevance.

Clinical scenario

Ivy, a medical student sitting in on my clinical sessions, observed me perform a punch biopsy.  Afterwards she politely remarked that she had heard that warming the local anaesthetic would reduce injection pain, something that I did not do.

Over the years, people have suggested to me various ways to reduce local anaesthetic injection pain.  I had dismissed them all as “magic rituals”.  However, Ivy wasn’t the first person to talk about warming… so what is the evidence for this “ritual”?

Clinical question

Does warming the local anaesthetic reduce the pain from injection?

What does the research evidence say?

A search for “local anesthetic/anaesthetic” in the Cochrane Library finds no relevant reviews.  Another useful resource is the “TRIP Database” ( which is a search tool for clinical evidence.  The first result using the search term “warm local anaesthetic” found a systematic review and meta-analysis by Hogan et al. (2011). 1  We will examine this article in detail.

Critical appraisal

This will be a critical appraisal of a systematic review rather than a therapeutic trial.  I will use the appraisal sheet for systematic reviews available from the Centre for Evidence Based Medicine. 2

What PICO question does the systematic review ask?

In healthy children and adults requiring local anaesthetic administration into the skin or subcutaneous tissue (Participants); what is the effect of warming the local anaesthetic (Intervention); compared to the same local anaesthetic at room temperature (Comparator); on pain response from injection (Outcome).

Is it clearly stated?


Is it unlikely that important studies were missed?

Yes.  The authors searched five large databases, including a database of dissertations and theses.  They did not restrict the language (a positive!) and also hand-searched the references of the articles reviewed.

Were the criteria used to select articles for inclusion appropriate?

Yes.  The authors included any randomised trial that tested a warmed local anaesthetic agent against room temperature anaesthetic.  This included studies of healthy volunteers and patients.  The pain rating had to be reported by a visual analogue scale (VAS) or numeric rating.  Studies that injected local anaesthetics to provide regional block, or injected into the spinal canal, joint, or periorbital space were excluded.

Were the included studies sufficiently valid for the question asked?

Unclear.  The authors collected data and formally assessed the methodological quality of the identified studies using the Cochrane Collaboration risk of bias tool. 3  The overall risk of bias was considered unclear for 17 out of 18 studies, and high in 1 study.  Specifically, the blinding of participants and operators was not clear in many studies – which may be of significance in reporting pain outcomes.

Were the results similar between studies?

No.  There is marked heterogeneity between studies and this wasn’t explained by grouping the studies in a number of different ways (e.g., by pH of the solution, type of tissue infiltrated, use of adrenaline, volume of infiltration, drug, and needle size).

What were the results?

The authors identified 18 randomised trials.  Warming local anaesthetics to body temperature resulted in less pain, with an average improvement of 11 mm on a 100 mm VAS compared to room temperature anaesthetics.  There was similarly less pain in warming local anaesthetics with adrenaline to body temperature, with a mean improvement of 20 mm on a 100 mm VAS.


There is some evidence that warming local anaesthetics result in less injection pain.  The magnitude of the effect is unclear given the heterogeneity seen between studies.  The grouped result of 11 mm improvement on the VAS straddles the border of minimum clinical significance for pain – which is an improvement of 13 mm for adults 4 and 10 mm for children. 5

A pragmatic interpretation is that warming the local anaesthetic probably does reduce pain in general, but not by much in most individuals.  However, it is a very simple thing to do in my setting as the hot water tap is set to body temperature.  Warming an ampoule of local anaesthetic could easily take place while setting up for the procedure that requires it.  So I will follow my medical student’s suggestion and warm local anaesthetic prior to injection in the future.

Stats Facts

Study heterogeneity

When similar studies are combined together in a meta-analysis, we expect that there will be some variation in the results.  This may be due to differences with the participants, interventions, outcomes measures, study methodology, as well as chance.  However, it may not be valid to combine the results when the studies are “too different”. 6


  1. Hogan ME, VanderVaart S, Perampaladas K, et al. Systematic review and meta-analysis of the effect of warming local anesthetics on injection pain. Ann Emerg Med 2011 Jul; 58(1): 86-98.e1
  2. Systematic Review: Are the results of the review valid? Centre for Evidence Based Medicine, University of Oxford. Retrieved: 2012 July 4
  3. Higgins JPT, Altman DF, Gøtzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928
  4. Todd KH, Funk KG, Funk JP, Bonacci R. Clinical significance of reported changes in pain severity. Ann Emerg Med 1996;27(4): 485-489
  5. Powell CV, Kelly AM, Williams A. Determining the minimum clinically significant difference in visual analog pain score for children. Ann Emerg Med 2001; 37(1):28-31
  6. Higgins JPT, Green S [editors]. “What is heterogeneity?” (Section 9.5.1) in Cochrane handbook for systematic reviews of interventions (version 5.1.0) [website]. The Cochrane Collaboration, 2011 March (last updated). Retrieved: 2012 July 4
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