Buffered Local Anaesthetic
The administration of local anaesthetic can be painful. There are many factors that influence pain. These are needle insertion, pH of the solution, osmolarity, temperature of the solution, pressure from fluid distension, and genetic variants of the patients sodium channels. In the US, many doctors routinely buffer their lidocaine as an evidence based way to reduce patient discomfort. In the authors experience, it is relatively unknown in New Zealand and this low usage rate is believed to be based on cultural factors rather than the evidence. Sodium bicarbonate is easily available on Practitioners Supply Order in New Zealand.
Lidocaine is a weakly basic amide and is unstable at its pH of 7.9. It is therefore prepared in acidic formulations to increase stability and shelf life, with a resultant pH of 2.5-4.0. This acidity, which is 1000 times more acidic than physiological pH, can cause tissue irritation with a stinging or burning pain.
In addition, raising the pH increases the amount of the non-ionized (active) form, and reduces the charged hydrophilic (non-active) form. The active form readily permeates the nerve membrane, and at the physiological pH, there are 2,500 more of the active form than at a pH of 3.8. With non-buffered lidocaine, the body has to first naturally buffer the solution which causes a longer duration of burning.
When sodium bicarbonate is mixed with an acidic lidocaine solution, water and carbon dioxide are formed. CO₂ has an independent direct local anaesthetic effect, and it enhances the action of lidocaine. CO₂ directly deactivates the nerve axon, and indirectly increases the anaesthetic effect by changing its electrical charge.
It is recommended that osmolarities of solutions should not exceed 600mOsm/kg for injections, and 1,000mOsm/kg for infusions. There is some evidence that solutions with lower osmolarities are more painful. Sodium bicarbonate increases the osmolarity of the solution.
There is limited guidance as to how long buffered solutions can be stored before use, but there is some evidence that it has a shelf life of around one month. In practice the buffering is done immediately prior to the procedure.
There have been many studies that have looked at buffering lidocaine with sodium bicarbonate to reduce its acidity. Sodium bicarbonate is safely metabolised by the kidneys. A Cochrane review in 2010 included 23 studies, and found that increasing the pH of lidocaine decreased pain with infiltration. Parallel group studies include 2 independent groups receiving different treatments, whereas in crossover trials, each patient receives both treatments. The difference was -1.98 on a 0 to 10 scale in the cross-over studies, and -0.98 in the parallel group studies. There was a greater decrease in pain when the injectate contained adrenaline. Patients also preferred buffered lidocaine. It was safe with no adverse events or toxicity. Buffering also does not reduce the anaesthetic effect.
A common mixture is 9:1 of 1% lidocaine and 8.4% sodium bicarbonate. It can also be used with adrenaline. Various other ratios have been used (10:1 - 5:1). More recently an RCT of 48 participants found that a 3:1 mixing ratio was significantly less painful than a 9:1 ratio. Median numerical pain ratings where 2.0 for 3:1, 3.0 for 9:1, 4.5 for unbuffered, and 6.0 for normal saline. While both a 9:1 and 3:1 solution effectively neutralises the pH, it is thought that the extra CO₂ that is produced in the 3:1 could explain the extra analgesic effect. In the 48 participants, one person had a deep subcutaneous nodule that disappeared after two months, and five people had local tenderness for 1-2 days.
Zaiac et al compared diluted lidocaine in a 1:10 ratio with saline, versus buffered lidocaine in a 1:10 ratio with sodium bicarbonate. The diluted lidocaine group was reported to be less painful by 28 out of 31 participants.
TODO: check maths
- Plain buffered, 10mL volume
- 9:1 = 9mL lidocaine, 1mL sodium bicarbonate
- 3:1 = 7.5mL lidocaine, 2.5mL sodium bicarbonate
- Plain buffered, 5mL volume
- 9:1 = 4.5mL lidocaine, 0.5mL sodium bicarbonate
- 3:1 = 3.75mL lidocaine, 1.25mL sodium bicarbonate
- Dextrose Solutions 20%, 10mL volume
- 9:1 = 4mL dextrose, 1mL sodium bicarbonate, 5mL lidocaine
- 3:1 = 4mL dextrose, 2.5mL sodium bicarbonate, 3.5mL lidocaine
- Vent et al. Buffered lidocaine 1%/epinephrine 1:100,000 with sodium bicarbonate (sodium hydrogen carbonate) in a 3:1 ratio is less painful than a 9:1 ratio: A double-blind, randomized, placebo-controlled, crossover trial. Journal of the American Academy of Dermatology 2020. 83:159-165. PMID: 31958526. DOI.
- Frank & Lalonde How acidic is the lidocaine we are injecting, and how much bicarbonate should we add?. The Canadian journal of plastic surgery = Journal canadien de chirurgie plastique 2012. 20:71-3. PMID: 23730153. DOI. Full Text.
- Wu et al. Cost analysis of the use of buffered lidocaine 1%, epinephrine 1:100,000 with sodium bicarbonate in a 3:1 ratio over a 9:1 ratio. Journal of the American Academy of Dermatology 2021. . PMID: 33516771. DOI.
- Cepeda et al. Adjusting the pH of lidocaine for reducing pain on injection. The Cochrane database of systematic reviews 2010. CD006581. PMID: 21154371. DOI.
- Zaiac et al. Virtually painless local anesthesia: diluted lidocaine proves to be superior to buffered lidocaine for subcutaneous infiltration. Journal of drugs in dermatology : JDD 2012. 11:e39-42. PMID: 23134997.