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Hello by adding epinephrine to local anesthetics in dental procedures and creatate vasoconstriction we cause lower plasma level of LA drug that can not cause CNS toxicity.

Thank you Juan Ignacio, for your rather laconic answer. Could you develop your opinion : what do you personnally think of John Meechan's statement ? Do you think that he is obviously wrong or misleaded by some clinical considerations? Or that his assertion should be simply  considered as an expert's opinion?

I would greatly appreciate further details.

Un cordial saludo,

Thierry.

In theory John Meechan's comments make sense as the effects of the adrenaline as described can increase the delivery of lignocaine to brain. But i am not sure the small amount of epinephrine injected locally (1 in 80,000 adrenaline is 12.5 microgm per ml) can cause a significant systemic effect. 

I am sure you already know that epinephrine added to lignocaine is known to cause local vasoconstriction which helps to minimise the bleeding and also decrease the systemic absorption of lignocaine thus causing decreased plasma levels while improving the depth and duration of block. Hence the actual risks of increased toxicity if there are any as suggested by him hopefully would be nullified. I haven't come across any studies or any other expert opinion to support that there is risk of increased toxicity when combining adrenaline with lignocaine. The confounding factors, i suppose, are the higher dose that is allowable with adrenaline and inadvertent intravascular injection of some of it.  

At the end of the day, the sensible thing to do is to keep the dose to as minimum as possible and exercising caution in detecting and avoiding intravascular spillage especially when using LA combinations in highly vascular areas.   

Thank you for your comments.

Of course I know all the facts you point out in your 2nd and 3rd paragraphs.

The only thing that I have a problem with is precisely your first sentence : "In theory John Meechan's comments make sense as the effects of the adrenaline as described can increase the delivery of lignocaine to brain."

You also said : "I haven't come across any studies or any other expert opinion to support that there is risk of increased toxicity when combining adrenaline with lignocaine", and I'm afraid we all have to agree with you.

So, if there is no study or expert opinion on this point, how can J. Meechan's comment make sense, even theoretically? What is the theory behind this?

What I would like to understand is why and how (on which  theoretical  or clinical basis) John Meechan's comments may make sense  if  there is actually no study or no other expert opinion ( except his own opinion) corroborating the assertion that epinephrine could increase LA brain toxicity.

So, as far as we are aware, there is no evidence supporting J. Meechan's view. And  the question remains unsolved, unless John Meechan himself provides us with more convincing explanations and evidences.

Again many thanks for commenting.

The theory i was eluding to is that adrenaline given as intravenous infusion increases cerebral blood flow and metabolic rate and in higher plasma concentrations (such as when used in critical situations, cardiac arrest etc ) it is described to cause vasoconstriction in rest of the body while preserving visceral perfusion. This is what is my understanding anyway. Similar effects, in theory could be produced when injecting the LA and adrenaline mixture in highly vascular areas especially following inadvertent intravasular injection of some of it, leading to increased delivery of lignocaine to brain. 

Again i am not sure, in what context John Meechan described this in his text. But i haven't come across any evidence to say that this actually happens during uncomplicated dental anaesthesia. Hope this helps!!     

Thank you for your new comment.

Would you have a bibliographical reference for the theory that"adrenaline given as intravenous infusion increases cerebral blood flow and metabolic rate and in higher plasma concentrations (such as when used in critical situations, cardiac arrest etc ) it is described to cause vasoconstriction in rest of the body while preserving visceral perfusion" ?

I would greatly appreciate if you could provide me with a text on that theory.

Kindest regards,

Thierry.

Dear Thierry

Would you be intetested in our study results?

The compative effect of common local anaesthetics on human fibroblasts.

METHODS: The culture of human fibroblasts cell line (NHDF-Neo) was performed in standard conditions. The fibroblasts were exposed to different concentrations of each LA, from 1.17 μg/ml to 150 μg/ml: 2% lidocaine with epinephrine 1:80000 (LID), 4% articaine with epinephrine 1:100000 (ARTforte), 4% articaine with epinephrine 1:200000 (ART) and plain 3% mepivacaine without vasoconstrictor (MEP). The cell apoptosis/necrosis ratio was measured by flow cytometry (annexin V–FITC and propidium iodide). Additionally, changes of intracelullar levels of reactive oxygen species (ROS) and pro-inflammatory interleukins IL6 and IL8 (RT-qPCR) genes expressions were assessed. RESULTS: After 24h all LAs did not induce cell death via apoptosis/necrosis pathway. MEP in concentration 112.5 μg/ml sligthly decreased cell viability (MTS asay). What is more, a concentration-dependent manner was not observed for any of tested LAs. Moreover, LID and ARTforte diminished the percentage of apoptotic cells, revealing slightly ‘protective’ action and ARTforte seemed to increase a cell viability. Apart from ARTforte in the highest concentration (150 μg/ml), no significant differences were noticed between LA’s in terms of ROS production. ARTforte stimulated an intracellular ROS secretion (3300 a.u. fluorescence) compared to control, untreated cells (2000 fluorescence a.u.). Interestingly, up-regulation of pro-inflammatory IL6 and IL8 was detected for mepivacaine (9.38-18.75 μg/ml) and articaine with epinephrine 1:200000 (150 μg/ml) respectively, compared with two other LAs (P< 0.05, stastistical differences). For LID and ARTforte we observed an attenuation of both genes expressions. CONCLUSIONS: With the limitations of in vitro study, the investigated local anaesthetic agents appeared not to be cytotoxic towards human fibroblasts. The LAs with the highest concentration of epinephrine: Lidocaine and articaine(forte) could even potentially increase fibroblasts cell viability in vitro conditions, however articaine(forte) triggered ROS secretion. None of LAs was found to be significantly more toxic than others and tested LAs did not exhibit differences in toxicity compared with the control. Cells exposure to mepivacaine induced the significant increase in IL-6 level in culture supernatants. CLINICAL RELEVANCE: Fibroblasts cells play a key role in healing following surgical procedures. This may have clinical implications while providing a local anaesthesia in dental practice.