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
  Purpose

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.


Condition Intervention
Methemoglobinemia
Drug: 4% prilocaine plain
Drug: 2% Lidocaine with 1:100,000 epinephrine

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Methemoglobin Levels in Generally Anesthetized Pediatric Dental Patients Receiving Prilocaine Versus Lidocaine

Resource links provided by NLM:


Further study details as provided by Loma Linda University:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Enrollment: 91
Study Start Date: August 2011
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prilocaine
30 subjects will receive 5mg/kg of 4% prilocaine plain local anesthetic for restorative dental treatment under general anesthesia
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
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
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
No Intervention: No local anesthetic
30 subjects will not receive local anesthetic for dental treatment under general anesthesia-Negative control

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.

  Eligibility

Ages Eligible for Study:   3 Years to 5 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01402869

Locations
United States, California
Loma Linda University School of Dentistry Koppel Special Care Dentistry Center
Loma Linda, California, United States, 92350
Sponsors and Collaborators
Loma Linda University
Investigators
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
  More Information

Publications:
American Academy of Pediatric Dentistry. American Academy of Pediatric Dentistry 2010-2011 Definitions, Oral Health Policies, and Clinical Guidelines: Guidelines on use of local anesthetic for pediatric dental patients. Pediatr Dent 2010;32(6):156-61
Yagiela, J. Injectable and topical local anesthetics. In: ADA/PDR guide to dental therapeutics. 5th Edition. Chicago: American Dental Association Publishing Co; 2009 p. 11-2

Responsible Party: Lauren GutenBerg, Pediatric Dental Resident, Loma Linda University
ClinicalTrials.gov Identifier: NCT01402869     History of Changes
Other Study ID Numbers: 5110172
Study First Received: July 25, 2011
Results First Received: October 15, 2013
Last Updated: March 25, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Loma Linda University:
Methemoglobin
Methemoglobinemia
Prilocaine
Lidocaine

Additional relevant MeSH terms:
Methemoglobinemia
Hematologic Diseases
Anesthetics
Lidocaine
Prilocaine
Anesthetics, Local
Epinephrine
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Sensory System Agents
Peripheral Nervous System Agents
Anti-Arrhythmia Agents
Cardiovascular Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Adrenergic beta-Agonists
Bronchodilator Agents
Autonomic Agents
Anti-Asthmatic Agents
Respiratory System Agents
Mydriatics

ClinicalTrials.gov processed this record on September 18, 2014