Methemoglobin Levels in Generally Anesthetized Pediatric Dental Patients Receiving Local Anesthetics
Condition: Methemoglobinemia
MeSH terms: Methemoglobinemia
Study type: Interventional

Summary: 
      To establish and compare maximum methemoglobin blood levels and times to maximum
      methemoglobin blood levels following the administration of the injectable local anesthetics
      prilocaine and lidocaine when used for dental treatment in pediatric patients under general
      anesthesia. Patients will be randomized into three equal study groups. Two of the study
      groups will receive local anesthetic and the third group will not. Methemoglobin blood levels
      will be non-invasively monitored and recorded throughout dental treatment for all groups
      using a Masimo Radical-7 Pulse Co-Oximeter device.
    

Detailed description: 
      Methemoglobin is an abnormal hemoglobin that is formed by the oxidation of one or more of the
      four heme groups of hemoglobin by oxygen and other exogenous oxidizing agents. The injectable
      local anesthetic prilocaine that is routinely used in the medical and dental professions is a
      well known inducer of methemoglobin. The injectable local anesthetic lidocaine has also been
      suggested to be associated with the development of methemoglobin; however, there is no direct
      evidence supporting these claims.

      The concern with methemoglobin is that it is a dose-dependent toxin. The oxidation of one of
      the iron groups from a ferrous state to a ferric state alters the molecular structure of the
      hemoglobin molecule and impairs its ability to bind oxygen. This ultimately results in less
      oxygen being delivered to peripheral tissues and less carbon dioxide being removed which can
      cause tissue hypoxia. A small amount (0-2%) of methemoglobin is normally present in the blood
      as a result of the oxidation of hemoglobin by the prototypical oxidant oxygen. However, when
      an individual is exposed to an exogenous oxidizing agent of sufficient dosage and potency,
      methemoglobin levels can rise above 2% and a person can develop what is known as acquired
      methemoglobinemia. Signs of cyanosis as a result of acquired methemoglobinemia usually become
      present when methemoglobin blood levels rise above 15%.

      Despite the injectable local anesthetic prilocaine being a well known inducer of
      methemoglobin and lidocaine being a speculated inducer, there are no documented studies or
      trials in the dental literature as to the extent of the amount of methemoglobin that is
      formed following the routine use of these injectable local anesthetics.

      This investigation will examine the peak blood levels of methemoglobin and the time to the
      peak levels of methemoglobin following the use of injectable prilocaine and lidocaine when
      used for dental treatment in pediatric patients under general anesthesia.

      This study population will consist of 90 patients, 3 to 6 years of age, scheduled to undergo
      comprehensive dental rehabilitation under general anesthesia at the Koppel Special Care
      Dentistry Center at Loma Linda University School of Dentistry. Following enrollment, subjects
      will be randomized into three equal study groups: 1) 4% prilocaine plain, 2) 2% lidocaine
      with 1:100,000 epinephrine, and 3) No local anesthetic. All subjects will have a Masimo
      Radical-7 pediatric, non-disposable, pulse co-oximeter sensor placed on the ring finger of
      the right hand following the induction of general anesthesia. The sensor will then be
      connected to a Radical-7 Pulse Co-Oximeter. The pulse co-oximeter will non-invasively monitor
      and record methemoglobin blood levels at 10 second intervals throughout dental treatment.
      Following a routine oral examination, radiographs, and prophylaxis, subjects assigned to
      Groups 1 and 2 will be administered local anesthetic for restorative dental treatment. Group
      1 subjects will receive 5mg/kg of 4% prilocaine plain and Group 2 subjects will receive
      2.5mg/kg of 2% lidocaine with 1:100,000 epinephrine. Group 3 subjects will not receive local
      anesthetic. The time of local anesthetic administration and baseline methemoglobin blood
      levels will be recorded. Methemoglobin blood levels will be monitored and recorded throughout
      the completion of the dental treatment and during recovery from general anesthesia until
      subject movement precludes any further monitoring.
    

Intervention name(s): 4% prilocaine plain; 2% Lidocaine with 1:100,000 epinephrine
Intervention type(s): Drug; Drug
Intervention description(s): 5mg/kg via infiltration into multiple sites of the buccal mucosa of mouth 1 time prior to start of restorative dental treatment; 2.5mg/kg via infiltration into multiple sites of buccal mucosa of mouth 1 time prior to restorative dental treatment
Other intervention name(s): Citanest Plain; Xylocaine
Intervention MeSH terms: Lidocaine; Epinephrine; Prilocaine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Keywords: Methemoglobin; Methemoglobinemia; Prilocaine; Lidocaine