Onpharma Onset: Possible Tissue Necrosis

The answer is simple (off label usage guidelines):

  • Dial the Onset Mixing Pen to 8-10 with 4% Articaine
  • 2%, 3% Mepivacaine dialed to 18
  • 2% Lidocaine dialed to 18
Since I changed the dialed mixture to 10 instead of 18 with 4% articaine I have not experienced any tissue necrosis problem.
Update 01/2012: Since writing this blog I have found out that it is not only the pH that we should worry about with local anesthetics, but also the osmolarity. Dialing the pen to 18 with articaine makes the solution hypertonic (having more solute than the tissues) which can be very damaging to the area of injection. The increased pH and osmolarity are why you should not dial 4% Articaine greater than 10. Remember that Onpharma Onset is only FDA approved for 2% lidocaine. Find out more about  Onpharma Onset. Update 10/2011: After further pH studies we are now using 4% Articaine dialed to 5-10; 2%, 3% Mepivacaine dialed to 18 and 2% Lidocaine dialed to 18. Onpharma Onset is a product I use on every patient and if I don't use it I feel guilty.  We have built our practice on the golden rule, "Do onto others as you would have them do onto you."  Word of mouth referrals are the key to a successful dental practice and we feel giving painless, fast acting local anesthetics appeals to our patients.  I have been using this product since January 2011 and didn't really pay too much attention to the fact that it was only approved for lidocaine.  My primary local anesthetics are mepivacaine and articaine, and began using the Onset Mixing Pen at the settings for lidocaine thinking all local anesthetic were basically the same.  My bad!  It has come to my attention through clinical results that articaine has a significantly different reaction to the addition of bicarbonate (see below pH study).  Just like I would not inject anymore than 4 carpules of articaine at any one visit, the Onset systems also has its limits.  Every thing we prescribe is dose limited, just dial down articaine to about half what it is for lidocaine and mepivacaine and you will not have any problems. This is a part TWO continuum from my first post on this remarkable new tool for allowing the dentist to deliver a less painful injection, Onpharma Onset.    Very soon after I began using this technique, it was obvious to me and my staff that every patient in my practice deserved to have this wonderful product.  Patients still do report a little bit of a pinch, but much less pain than usual and is probably due to the needle stick and not the solution itself. We've had a couple instances where we've run out of the product before the next batch came in, and I dreaded giving anesthetic because of the visible difference patients give with and without Onset. Despite all of the positive patient feedback we have been getting since using this product, there are still a couple of areas that Onset does not offer the best pain free results. The purpose of this post is to address some of the issues we've been seeing in our office, and to hopefully have some other user input to see if anyone else is having similar experiences. Some of the areas that  still have trouble with Onset being a "Pain Free Injection":
  1. Injecting right into a painful abscess (expansion of an already painful situation)
  2. Hitting the nerve(s) as you inject an IAN block (direct mechanical stimulation)
  3. All palatal injections still are uncomfortable to patients. Probably because the very tight tissue on the palate (pressure pain of expanding/tearing the tissue) so use your usual good technique in addition to Onset to give these injections
Even with the above listed drawbacks, the pros of rapid and profound anesthesia still greatly outweighs the cons and we use the product with every injection. We also would like to discuss some of our problems we've been seeing with the mechanical workings of the mixing pen. Using the product as much as we do on a daily basis takes a toll on the device, so hopefully this helps anyone having problems.

Troubleshooting:

      • Stuck injector button: After using the Onset Mixing Pen for several weeks it may begin to have bicarbonate/anesthetic crystals build up inside the pen.  This will cause the pen to freeze and not inject properly.  The easiest remedy I have found is to remove the injector dial part of the mixing pen,  use a suitable water filled container, hold the pen underwater, and open it up all theway to 60.  Let it soak then push the button in and out a few time (under water) and within a few seconds it will work just fine.
 
      • The center piece can split in half with heavy usage.  I do the simplest repair possible by wrapping identification tape around the pens that have not split and a zip tie around the ones that have split.                    
      • The carpule of anesthetic is hard to push into the mixing pen:  Occasionally, one of the carpule insert ends will be very tight and the carpule is hard to push all the way in.  The only thing I do is get a better grip and push really hard.  Once the first one goes in all the way the second one is usually easier.  This is because the manufactures of the actual dental anesthetic carpules are not consistent in their diameters (from Onpharma).
      • The bicarbonate doesn't inject into the carpule.  This is actually very hard to detect.  Unfortunately, you usually find this out by having the patient feel your injection more than usual.  The only answer I have found to this problem is replacing the cartridge connector because the needle inside may be plugged or bent.  Look at the end of the carpule to see if the connector needles are centered enough to penetrate the rubber of the anesthetic carpule and not trying to penetrate the metal ring.
      • Keep a spare mixing pen so you can immediately use it if you ever experience technical difficulty or run out of bicarb.
      • Since writing this post the issue of weakening pens has been addressed by the manufacture with a new stronger mixing pen.  

Below are a few suspicious incidents I have documented with mainly Articaine 4% 1:100,000 epi and Onset dialed to 18.  These are cases that could have happened from just the Articaine alone, but I have never had this many problems before.  This is another reason I am dialing down the Onset to 10 instead of 18 with Articaine.

Above: Post-op cellulitis after Articaine 4% 1:100,000 epi and Onset dialed to 18 given to the long buccal for a simple filling on #19.
Post local anesthetic tissue necrosis
Above: This lesion showed up the next day after an infiltration injection of 1.7ml Articaine 4% 1:100,000 epi and Onset dialed to 18.  The second photo was a week later.  It was painful and swollen.
Post injection local anesthetic tissue necrosisPost local anesthetic injection tissue necrosis
I have been injecting these areas for over 25 years with local anesthetics of all kinds and never have I had this response. Again, lesions showed up immediately after an infiltration injection of 1.7ml Articaine 4% 1:100,000 epi and Onset dialed to 18.
Tori
Simple flap surgery. The patient wanted this small exostosis removed.  1.7ml Articaine 4% 1:100,000 epi and Onset dialed to 18 was used to balloon the tissue up before elevating the flap and removing the small boney projection.  This very atraumatic surgery had a very undesirable post-op die back of the flap.  These post-op photos were taken at the 1 week post-op suture removal and 1 month post-op appointments.  The area completely healed in the long run as expected, but the healing process was less than ideal.
Again, the purpose of this post is not to prevent anyone from using this great product. I just want to share some of the issues we've been seeing in our office. Dr. Malamed has hailed this as one of the greatest achievements in dental anesthesia and it will certainly grow in popularity as more and more patients start hearing and demanding it. The only modification we have made that is different than what the manufacturers recommend for Lidocaine is to dial back the dose to 10 instead of 18 and not using it with 4% Articaine on flaps or in thin tissue areas.  I have literally given 1000's of these injections (with mepivacaine and articaine dialed to 18) and have had a very small incidence of post local anesthetic complications.

Onpharma Onset Mixing Pen with Blue Dye

If you every wanted to know how well this mixing pen mixes the buffering agent with the anesthetic watch this video.  This is mixing 0.10ml (dialed to 10) blue "To-Dye-For" into a 1.7ml carpule of mepivacaine.
Be aware that when you first load up your bicarb ampule and set the plunger to engage the stopper you put a slight amount of pressure on the bicarb ampule.  This is enough pressure to push a small amount of bicarb into the anesthetic carpule once you engage it into the pen.  If you do not use it soon the mix will be incorrect.  What this would mean for your anesthetic is unknown and would probably depend on how much time is allowed before it is used.  The simple solution is NOT to engage the anesthetic carpule until you are ready for its use. One other point.  The injector needles in the pen go into the carpule some distance.  This distance is enough to make a small space of non-mixed solution right at the top of the carpule.  This appears to be countered by the needle hub that you use to inject the anesthetic into the patient.  It extends deep into the carpule as well and this non-mixed solution is not injected into the patient until the end. If the needle tip is not long enough to extend past the non-mixed solution the patient may experience an unwanted sting at the very beginning of the injection.  

Onpharma Onset using 4% Articaine

I was wondering what the pH of the different dialed in concentrations were so I bought some pH paper from Amazon and tested it myself.  The test kit I ordered was for urine and saliva,  and it was a bit hard to read.  I put the test strip for you to read the "zone" of pH for yourself. With each of the below tests the mixing pen was dialed-up, dispensed into a 4% Articaine 1:100,000 carpule, injected into a new plastic drinking cup through a 28 gauge long needle, and the test strip was soaked for at least 15 second as per the test strip instructions. pH of 4% Articaine 1:100,000 epi without any bicarbonate.  It looks acidic to me, but not a pH  of 4.0 which I anticipated. pH of 4% Articaine 1:100,000 epi with bicarbonate dialed to 1.  Just one click and a marked increase in pH. pH of 4% Articaine 1:100,000 epi with bicarbonate dialed to 2.  Not much change. pH of 4% Articaine 1:100,000 epi with bicarbonate dialed to 3.  This looks neutral to me. pH of 4% Articaine 1:100,000 epi with bicarbonate dialed to 4.  Looking pretty close to body pH. pH of 4% Articaine 1:100,000 epi with bicarbonate dialed to 5. Possibly getting a little alkaline? pH of 4% Articaine 1:100,000 epi with bicarbonate dialed to 18. Looks like over kill to me. A pH of 8 may be why I have seen an increase in tissue necrosis?  Remember from basic physiology, the cell can only live between pH of 6.5 and 7.5, but if it goes to pH 8, it will die FAST! I think I will continue to use the Onpharma Onset dialed to 10 with Articaine and NOT 18 as I once did.  This brings the cost down considerable and extends the life of the pen ampule, dramatically.  This may be good and it may be bad.  If you are not doing very many injections and the pen's ampule lasts too long, then it may become contaminates with bacteria?  That's for another blog. Since this post I have used the Onset dialed to 5-10 with good success (since August 8, 2011).  

References

1 Momsen OH, Roman CM, Mohammed BA, Andersen G, Neutralization of Lidocaine-Adrenaline, A Simple Method for Less Painful Application of Local Anesthesia, Ugeskr Laeger, Vol. 162, No. 33, P. 4391 (2000). 2 Bowles WH, Frysh H, Emmons R, Clinical Evaluation of Buffered Local Anesthetic, General Dentistry, Vol. 43, No. 2, P. 182 (1995). 3 Lugo-Janer G, Padial M, Sanchez JL, Less Painful Alternatives for Local Anesthesia, J Dermatol Surg Oncol, vol. 19, pp. 237-40 (1993). 4 Christoph RA, Buchannan L, Begalla K, Schwartz S, Pain Reduction in Local Anesthetic Administration Through pH Buffering, Annals of Emergency Medicine, Vol. 17, No. 2, P 117 (1988). 5 Vossinakis IC, Stavroulaki P, Paleochorlidis I, Badras LS, Reducing the Pain Associated with Local Anesthetic Infiltration for Open Carpal Tunnel Decompression, British Journal of Hand Surgery, Vol. 4, No. 29B, P. 399 (2004). 6 Samdahl F, Arctander K, Skollborg K, Amland PF, Alakalization of Lignocane-Adrenaline Reduces the Amount of Pain During Subcutaneous Injection of Local Anesthetic, Scandanavian Journal of Plastic and Reconstructive Hand Surgery, Vol. 28, P. 33 (1994). 7 Martin AJ, pH-Adjustment and Discomfort Caused by the Intradermal Injection of Lignocaine, Anesthesia, P. 975, Vol. 45 (1990) (pH 3,76). 8 Masters JE, Randomized Control Trial of pH-buffered Lignocaine with Adrenaline in Outpatient Operations, British Journal of Plastic Surgery, P. 385, Vol. 51 (1998) (pH 3.51). 9 McKay W, Morris R, Mushlin P, Sodium Bicarbonate Attenuates Pain on Skin Infiltration, Anesth Analg, vol. 66, pp. 572-74 (1987). 10 Younis I, Bhutiani RP, Taking the ’Ouch’ Out - Effect of Buffering Commercial Xylocaine on Infiltration and Procedure Pain - a Prospective, Randomised, Double-Blind, Controlled Trial, Annals of the Royal College of Surgeons of England, Vol 86, P. 213 (2004). 11 Fitton AR, Ragbir M, Milling AP, The Use of pH Adjusted Lignocaine in Controlling Operative Pain in the Day Surgery Unit: A Prospective, Randomized Trial, British Journal of Plastic Surgery, Vol. 49, P. 404 (1996). 12 Metzinger SE, Rigby PL, Bailey DJ, Brousse RG, Local Anesthetic in Blepharoplasty, A New Look?, Southern Medical Journal, Vol. 87, No. 2, P. 225 (1994). 13 Carvalho B, Fuller A, Brummel C, Cohen SE, Local Infiltration of Epinephrine-Containing Lidocaine with Bicarbonate Reduces Superficial Bleeding and Pain During Labor Epidural Catheter Insertion: A Randomized Trial, Intern J Obstetric Anesth, Vol 16, P. 116 (2007). 14 Yuen VH, Dolman PJ, Comparison of Three Modified Lidocaine Solutions for Use in Eyelid Anesthesia, Ophthalmic Plastic and Reconstructive Surgery, Vol. 15, No. 2, P 143 (1999). 15 Talu H, Elibol O, Yanyali A, Karabas L, Alp B, Caglar Y, Effect of Warming and Buffering Lidocaine on Pain During Facial Anesthesia, Annals of Ophthalmology, vol. 33, no. 1, pp. 43-47 (2001). 16 Burns CA, Ferris G, Feng C, Cooer JZ, Brown MD, Decreasing the Pain of Local Anesthesia: A Prospective, Double-Blind Comparison of Buffered Premixed 1% Lidocaine with Epinephrine Versus 1% Lidocaine Freshly Mixed with Epinephrine, Journal of the Am. Academy of Derm., Vol. 54, No. 1, P. 128 (2006). 17 Stewart JH, Cole GW, Klein JA, Neutralized Lidocaine with Epinephrine for Local Anesthesia, J Dermatol Surg Oncol, vol. 15, no. 10, p. 1081 (1989). 18 Primosch RE, Robinson L, Pain Elicited During Intraoral Infiltration with Buffered Lidocaine, American Journal of Dentistry, Vol. 9, No. 1, P. 5 (1996). 19 Whitcomb M, Drum M, Reader A, Nusstein M, Beck M, A Prospective, Randomized, Double-Blind Study of the Anesthetic Efficacy of Sodium Bicarbonate Buffered 2% Lidocaine with 1 : 100,000 Epinephrine in Inferior Alveolar Nerve Blocks, Anesthesia Progress, Vol. 57, P. 59 (2010). 20 Nuttal GA, Barnett MR, Smith RL, Blue TK, Clark KR, Payton BW, Establishing Intravenous Success, a Study of Local Anesthetic Efficacy, Anesth Analg, vol. 77, pp. 950-53 (1993). 21 Erramouspe, Buffering Local Anesthetic Solutions with Sodium Bicarbonate: Literature Review and Commentary, Hosp Pharm, vol. 31, no. 10 (1996). 22 Ruegg TA, Curran CR, Lamb TL, Use of Buffered Lidocaine in Bone Marrow Biopsies: A Randomized, Controlled Trial, Oncology Nursing Forum, Vol. 39, No. 1, P. 52 (2009). 23 Masters, et al, Randomized Control Trial of pH-buffered Lignocaine with Adrenaline in Outpatient Operations, supra. 24 Hinshaw KD, Fiscella R, Sugar J, Preparation of pH Adjusted Local Anesthetics, Ophthalmic Surgery, P. 194, Vol. 26, No. 3, (1996)(pH 3.74). 25 Martin AJ, pH-Adjustment and Discomfort Caused by the Intradermal Injection of Lignocaine,  Anesthesia, P. 975, Vol. 45 (1990) (pH 3,76). 26 Ikuta Pt, Raza SM, Duranni Z, Vasireddy AR; Winnie AP, Masters RW, pH Adjustment Schedule for the Amide Local Anesthetics, Regional Anesthesia, P. 229, Vol. 14, No. 5 (1989) (pH 3.9). 27 Joseph RS, McDonald SB, Facilitating the Onset of Regional Blocks, Techniques in Regional Anesth and Pain Mgmt, P. 110, Vol. 8, No. 3 (2004) (pH 4.1). 28 Crews JC, Clark RB, Effect of Alkalinization on the pH of Local Anesthetic Solutions, Anesthesia and Analgesia, P. 1196, Vol. 66 (1987) (pH 4.16). 29 Kennedy RM, Luhman JD, The ‘Outchless Emergency Department’, Getting Closer: Advances in Decreasing Distress During Painful Procedures in the Emergency Department, Pediatric Clinics of North America, Vol. 46, No. 6, P. 1220 (1999). 30 Bartfield, Buffered Lidocaine as a Local Anesthetic: An Investigation of Shelf Life, Annals of Emergency Medicine, , Vol. 21, No. 1, P. 24 (1992). 31 Gupta RP, Kapoor G, Safety and Efficacy of Sodium Bicarbonate Versus Hyaluronidase in Peribulbar Anesthesia, Medical Journal Armed Forces India, Vol. 62, P. 116 (2006). 32 Burmeister CH, A Practical Method for the Extemporaneous Preparation of a Buffered Anesthetic Solution, Journal of the American Dental Association, Vol. 22, P. 1514 (1935), citing Laewen A, München Med. Wchnschr., P. 2044 (1910). 33 Hille B, The pH Dependent Rate of Action of Local Anesthetics on the Node of Ranvier, The Journal of General Physiology, Vol. 69, P. 475 (1977). 34 Mehta R, Verma DD, Gupta V, Gurwara AK, The Effect of Alakalinization of Lignocaine Hydrochloride on Brachial Plexus Block, Indian Journal of Anesthesia, Vol. 47, No. 4, (2003). See also, Difazio CA, Carron H, Grosslight KR, Moscicki JC, Bolding WR, Johns RA, Comparison of pH-Adjusted Lidocaine Solutions for Epidural Anesthesia, Anesthesia and Analgesia, Vol. 65, P. 760 (1986); Fitton et al, supra. 35 Bonhomme L, Postaire E, Touratier S, Benhamou D, Martre-Savageon H, Preaux N, Chemical Stability of Lignocaine (Lidocaine) and Adrenaline (Epinephrine) in pH Adjusted Parenteral Solutions, Journal of Clinical Pharmacy and Therapeutics, Vol. 13, P. 257 (1988). 36 Gardner JH, Semb J, The Relation of pH and Surface Tension to the Activity of Local Anesthetics, Journal of Pharmacology and Experimental Therapeutics, Vol. 54, P. 309 (1935). 37 Tuckley JM, The Pharmacology of Local Anesthetics, Update in Anesthesia, Vol. 4, No. 7 (1994). 38 Mehta et al, The Effect of Alakalinization of Lignocaine Hydrochloride on Brachial Plexus Block, supra; see also, Difazio et al, Comparison of pH-Adjusted Lidocaine Solutions for Epidural Anesthesia, supra; and Fitton et al, The Use of pH Adjusted Lignocaine in Controlling Operative Pain in the Day Surgery Unit: A Prospective, Randomized Trial, supra. 39 Talu, et al, Effect of warming and buffering lidocaine on pain during facial anesthesia, supra. 40 Richtsmeier, et al, Buffered Lidocaine for Skin Infiltration Prior to Hemodialysis, J Pain and Sympt Man, vol 10(3), p.198 (1998). 41 Burns et al, Decreasing the Pain of Local Anesthesia: A Prospective, Double-Blind Comparison of Buffered Premixed 1% Lidocaine with Epinephrine Versus 1% Lidocaine Freshly Mixed with Epinephrine, supra. 42 Ackerman WE, Ware TR, Juneja M, The Air-Liquid Interface and the pH and PCO2 of Alkalinized Local Anaesthetic Solutions, Canadian Journal of Anaesthesiology, Vol. 39, No. 4, P. 387 (1992). 43 Catchlove RFH, The Influence of C02 and pH on Local Anesthetic Action, The Journal of Pharmacology and Experimental Therapeutics, Vol. 181, No. 2, P. 208 (1972). 44 Condouris GA, Shakalis A, Potentialtion of the Nerve-Depressant Effect of Local Anesthetics by Carbon Dioxide, Nature, Vol. 204, No. 4953, P. 57 (1964). 45 Otsuguro K, Yasutake S, Yoshihiko Y, Ban M, Ohta T, Ito S, Why Does Carbon Dioxide Produce Analgesia? AATEX, Vol. 14, P. 101 (2007). 46 Catchlove, The Influence of C02 and pH on Local Anesthetic Action. 47 Talu, et al, Effect of Warming and Buffering Lidocaine on Pain During Facial Anesthesia, supra. 48 Richtsmeier, et al, Buffered Lidocaine for Skin Infiltration Prior to Hemodialysis, supra. 49 Burns et al, Decreasing the Pain of Local Anesthesia: A Prospective, Double-Blind Comparison of Buffered Premixed 1% Lidocaine with Epinephrine Versus 1% Lidocaine Freshly Mixed with Epinephrine, supra. 50 Ikuta PT, Raza SM, Durrani Z, Vasireddy AR, Winnie AP, Masters R, pH Adjustment Schedule for the Amide Local Anesthetics, Regional Anesthesia, Vol. 14, No. 5, P. 232 (1989). 51 Christoph RA, Buchanan L, Begalla K, Schwartz S, Pain Reduction in Local Anesthetic Administration Through pH Buffering, Emergency Medicine, Vol. 17, No. 2, P. 27 (1988). For other articles recommending immediate of local anesthetic use after buffering, see: Erramouspe J, Buffering Local Anesthetic Solutions with Sodium Bicarbonate, Literature Review and Commentary, Hospital Pharmacy, Vol. 31, No. 10, P. 1275 (1996); Armel HE, Horowitz M, Alkalinization of Local Anesthesia with Sodium Bicarbonate - Preferred Method of Local Anesthesia, Urology, Vol. 43, No.1, P. 101 (1994). 52. Pharmacol Biochem Behav. 1984;21 Suppl 1:1-5. The high pH therapy for cancer tests on mice and humans. Brewer AK. 53. Killing Cancer Cells With High pH Therapy

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