Methemoglobin Levels in Generally Anesthetized Pediatric Dental Patients Receiving Local Anesthetics

Study Overview
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Brief Summary
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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
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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.

Official Title
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Methemoglobin Levels in Generally Anesthetized Pediatric Dental Patients Receiving Prilocaine Versus Lidocaine

Conditions
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Methemoglobinemia

Intervention / Treatment
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* Drug: 4% prilocaine plain
* Drug: 2% Lidocaine with 1:100,000 epinephrine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prilocaine<br>30 subjects will receive 5mg/kg of 4% prilocaine plain local anesthetic for restorative dental treatment under general anesthesia | Drug: 4% prilocaine plain<br>* 5mg/kg via infiltration into multiple sites of the buccal mucosa of mouth 1 time prior to start of restorative dental treatment<br>* Other names: Citanest Plain;|
| Experimental: Lidocaine<br>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<br>* 2.5mg/kg via infiltration into multiple sites of buccal mucosa of mouth 1 time prior to restorative dental treatment<br>* Other names: Xylocaine;|
| No Intervention: No local anesthetic<br>30 subjects will not receive local anesthetic for dental treatment under general anesthesia-Negative control | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Methemoglobin Blood Levels | The maximum percentage of methemoglobin in blood | Measured at 10 second intervals during dental treatment for an average of 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Peak Methemoglobin Blood Levels | 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. | Measured at 10 second intervals during dental treatment for an average of 2 hours | 
| Delta Methemoglobin Blood Level | Change in percentage of methemoglobin in blood from baseline level to peak level | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Methemoglobin, Methemoglobinemia, Prilocaine, Lidocaine