Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Methemoglobin Levels in Generally Anesthetized Pediatric Dental Patients Receiving Local Anesthetics

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Lauren GutenBerg, Loma Linda University
ClinicalTrials.gov Identifier:
NCT01402869
First received: July 25, 2011
Last updated: March 25, 2014
Last verified: March 2014

July 25, 2011
March 25, 2014
August 2011
July 2012   (final data collection date for primary outcome measure)
Peak Methemoglobin Blood Levels [ Time Frame: Measured at 10 second intervals during dental treatment for an average of 2 hours ] [ Designated as safety issue: No ]
The maximum percentage of methemoglobin in blood
Peak Methemoglobin Blood Level [ Time Frame: 10 second intervals over 2 hour period of dental treatment ] [ Designated as safety issue: No ]
Methemoglobin Blood Levels will be measured non-invasively by a Masimo Radical-7 Pulse Co-Oximeter. Device will monitor and record methemoglobin levels at 10 second intervals. Maximum methemoglobin levels will be documented.
Complete list of historical versions of study NCT01402869 on ClinicalTrials.gov Archive Site
  • Time to Peak Methemoglobin Blood Levels [ Time Frame: Measured at 10 second intervals during dental treatment for an average of 2 hours ] [ Designated as safety issue: No ]
    The length of time between the administration of local anesthetic (Prilocaine and Lidocaine Groups) or start of restorative dental procedures (No local anesthetic Group) and the time at which the maximum methemoglobin blood level is observed.
  • Delta Methemoglobin Blood Level [ Time Frame: From administration of local anesthetic or start of restorative procedures to time at which maximum methemoglobin blood level was documented during dental treatment for an average of 2 hours ] [ Designated as safety issue: No ]
    Change in percentage of methemoglobin in blood from baseline level to peak level
Time to Peak Methemoglobin Blood Level [ Time Frame: 10 second intervals over 2 hour period of dental treatment ] [ Designated as safety issue: No ]
This will be the total length of time from the time of local anesthetic administration to the time the maximum methemoglobin blood level is observed.
Not Provided
Not Provided
 
Methemoglobin Levels in Generally Anesthetized Pediatric Dental Patients Receiving Local Anesthetics
Methemoglobin Levels in Generally Anesthetized Pediatric Dental Patients Receiving Prilocaine Versus Lidocaine

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Methemoglobinemia
  • Drug: 4% prilocaine plain
    5mg/kg via infiltration into multiple sites of the buccal mucosa of mouth 1 time prior to start of restorative dental treatment
    Other Name: Citanest Plain
  • Drug: 2% Lidocaine with 1:100,000 epinephrine
    2.5mg/kg via infiltration into multiple sites of buccal mucosa of mouth 1 time prior to restorative dental treatment
    Other Name: Xylocaine
  • Experimental: Prilocaine
    30 subjects will receive 5mg/kg of 4% prilocaine plain local anesthetic for restorative dental treatment under general anesthesia
    Intervention: Drug: 4% prilocaine plain
  • Experimental: Lidocaine
    30 subjects will receive 2.5mg/kg of 2% lidocaine with 1:100,000 epinephrine local anesthetic for restorative dental treatment under general anesthesia
    Intervention: Drug: 2% Lidocaine with 1:100,000 epinephrine
  • No Intervention: No local anesthetic
    30 subjects will not receive local anesthetic for dental treatment under general anesthesia-Negative control

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
91
July 2012
July 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patient scheduled to undergo comprehensive dental treatment under general anesthesia at the Koppel Special Care Dentistry Center at Loma Linda University School of Dentistry
  • ASA I or II health status
  • Age greater than 3 years but less than 6 years
  • Weigh between 10kg and 25kg

Exclusion Criteria:

  • Patient not requiring restorative dental treatment
  • Have a BMI less than the 5th percentile or greater than the 95th percentile for their age and gender
Both
3 Years to 5 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01402869
5110172
No
Lauren GutenBerg, Loma Linda University
Loma Linda University
Not Provided
Study Director: Lauren L Gutenberg, DDS Loma Linda University Department of Pediatric Dentistry
Principal Investigator: Jung-Wei Chen, DDS, MS, PhD Loma Linda University Department of Pediatric Dentistry
Loma Linda University
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP