Type to search

Pharmacology Supporting Your Practice

Pharmacological Reversal Agents in Dental Practice: Keys to Patient Safety


I had the pleasure to host Dr. Mark Donaldson to speak about the important reversing drugs that are found in the dental emergency kit. Mark goes into detail addressing 6 reversal agents: Naloxone, Flumazenil, Epinephrine, Diphenhydramine, Phentolamine, and Atropine.

Chiraz Guessaier, CDA Oasis Manager


  • Though uncommon, medical emergencies in the dental office are harrowing occurrences that can be the result of adverse drug reactions.
  • Pharmacological antagonists have been developed for administration as reversal agents in emergency situations in which patients may have an untoward effect, typically caused by too much medication.
  • Dental practitioners should be familiar with these agents to keep patients safe and help mitigate drug-induced medical emergencies.
  • Outside of emergency situations, the pharmacological antagonist phentolamine has been developed to reverse the effects of the vasoconstrictor in dental local anesthesia preparations when the effects of the agonist medication are no longer required.
  • Such newer reversal agents are being considered for more routine use once the dental procedure is complete.


Additional Resource

Nitrous oxide–oxygen administration. When safety features no longer are safe (PDF)


  1. Sudha March 24, 2017

    It was good to know about 6 essential emergency drugs in dental office and their safety. In my office I use nitrous oxide not to exceed 50% . Along with this I do music therapy and get very good results. Many children go to sleep depending on which I increase the concentration of oxygen. Sometimes I even work with 30-40% nitrous. Parents sometimes get worried when children sleep. Is this of a concern? I have never had any problems waking them up. Dr. Donaldson talks about reversal agents for benzodiazepines. For nitrous , putting them to 100% oxygen is reversal right?
    I would appreciate if you pass my question to Dr Donaldson.

    1. JCDA Oasis March 27, 2017

      Dr. Mark Donaldson’s Response:

      Great question, thank you.

      Whenever a patient gets into a deeper level of sedation than you may intend with nitrous oxide, the appropriate response is to take the mask off, and get the patient back to breathing room air. There have been a number of instances in which practitioners have elected to simply change the output of gas from a nitrous oxide – oxygen mixture to 100% oxygen, and patients have not responded because of a flaw in the delivery system. In one of these instances the fail-safe had failed such that 100% nitrous was now being delivered. In other cases, lines behind the wall of installed systems have been crossed over.

      If you think about it, if an otherwise normal patient comes into your office and the only intervention you have provided to cause a deeper level of sedation than intended is nitrous, then get them back to their baseline. Remember too, that simply changing to 100% oxygen does not mean the patient breathes 100% oxygen immediately as it takes time to flush the nitrous from the system.

      Lastly, we are always told to put the patient on 100% oxygen for 5 minutes or so at the completion of the procedure. This was thought to help prevent diffusion hypoxia which we now know is not true. This process simply helps to insure that any remaining gas in the system is removed through the scavenging system. Whenever you have a challenge with nitrous oxide, the correct response should always be to remove the mask.

      Please see the added reference to the post for additional information on nitrous oxide – oxygen fail safes and failures to help emphasize this.

      1. Sudha March 27, 2017

        Thank you very much for the reply. I always have patients to do 5 mins of oxygen at the end and then they wait in the waiting room for another15 mns before they go home.
        Thanks again

  2. Nrrvous March 29, 2017

    Why are you saying that diffusion hypoxia doesn’t exist? It most certainly does exist. As the nitrous oxide leaves the alveolus, oxygen is displaced, which can result in diffusion hypoxia and nausea and vomiting. Please clarify your position and don’t forget to post any studies to back up your position with scientific evidence.


    1. Dr. Mark Donaldson March 6, 2018

      Since Dr. Fink’s original description of diffusion hypoxia (The Fink Phenomenon) was first described in 1955 following an in vitro (not in vivo) experiment, there has been significant controversy around whether this is clinically significant.

      Perhaps the language I should have used would have been clearer if I had stated that, “diffusion hypoxia is not a concern in clinical practice.” There are plenty of studies to support this claim and I am more than happy to provide a list:

      Dunn-Russell T, Adair SM, Sams DR, Russell CM, Barenie JT. Oxygen saturation and diffusion hypoxia in children following nitrous oxide sedation. Pediatr Dent. 1993 Mar-Apr;15(2):88-92.

      Khinda VI, Bhuria P, Khinda P, Kallar S, Brar GS. Comparative evaluation of diffusion hypoxia and psychomotor skills with or without postsedation oxygenation following administration of nitrous oxide in children undergoing dental procedures: A clinical study. J Indian Soc Pedod Prev Dent. 2016 Jul-Sep;34(3):217-22

      Jeske AH, Whitmire CW, Freels C, Fuentes M. Noninvasive assessment of diffusion hypoxia following administration of nitrous oxide-oxygen. Anesth Prog. 2004;51(1):10-3.

      Quarnstrom FC, Milgrom P, Bishop MJ, DeRouen TA. Clinical study of diffusion hypoxia after nitrous oxide analgesia. Anesth Prog. 1991 Jan-Feb;38(1):21-3.

      Milles M, Kohn G: Nitrous oxide sedation does not cause diffusion hypoxia in healthy patients. J Dent Res 70:469 (Abstr 1627), 1991.

      There are many more. Best regards,


  3. JP March 31, 2017

    Are you willing to send me the full text of the article so that I may share it with our hospital dental practice?
    Thank you for your consideration


Leave a Comment

Your email address will not be published.

%d bloggers like this: