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Methemoglobin Levels in Generally Anesthetized Pediatric Dental Patients Receiving Local Anesthetics

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

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01402869
Enrollment
91
Registered
2011-07-26
Start date
2011-08-31
Completion date
2012-07-31
Last updated
2014-04-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Methemoglobinemia

Keywords

Methemoglobin, Methemoglobinemia, Prilocaine, Lidocaine

Brief 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.

Interventions

DRUG4% prilocaine plain

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

Sponsors

Loma Linda University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
3 Years to 5 Years
Healthy volunteers
Yes

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

Design outcomes

Primary

MeasureTime frameDescription
Peak Methemoglobin Blood LevelsMeasured at 10 second intervals during dental treatment for an average of 2 hoursThe maximum percentage of methemoglobin in blood

Secondary

MeasureTime frameDescription
Time to Peak Methemoglobin Blood LevelsMeasured at 10 second intervals during dental treatment for an average of 2 hoursThe 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 LevelFrom 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 hoursChange in percentage of methemoglobin in blood from baseline level to peak level

Countries

United States

Participant flow

Recruitment details

Patients that were greater than 3 years but less than 6 years of age that were scheduled to undergo comprehensive dental rehabilitation under general anesthesia at the Koppel Special Care Dentistry Center at Loma Linda University School of Dentistry were recruited for the study.

Pre-assignment details

Enrolled participants were excluded prior to group assignment if they had a body mass index (BMI) less than the 5th percentile or greater than the 95th percentile for their age and gender.

Participants by arm

ArmCount
Prilocaine
5mg/kg of 4% prilocaine plain administered via infiltration into multiple sites of the buccal mucosa of the mouth 1 time prior to start of restorative dental treatment
30
Lidocaine
2.5mg/kg of 2% lidocaine with 1:100,000 epinephrine administered via infiltration into multiple sites of the buccal mucosa of the mouth 1 time prior to start of restorative dental treatment
30
No Local Anesthetic
No local anesthetic was administered prior to restorative dental treatment-Negative control
30
Total90

Withdrawals & dropouts

PeriodReasonFG000FG001FG002
Overall StudyRequired Tooth Extraction001

Baseline characteristics

CharacteristicPrilocaineLidocaineNo Local AnestheticTotal
Age, Continuous50.97 months
STANDARD_DEVIATION 9.84
50.77 months
STANDARD_DEVIATION 10.19
50.63 months
STANDARD_DEVIATION 8.43
50.79 months
STANDARD_DEVIATION 9.41
ASA Health Classification
I-Healthy patients; no systemic disease
26 participants25 participants24 participants75 participants
ASA Health Classification
II-Patients with mild, systemic disease
4 participants5 participants6 participants15 participants
Baseline Methemoglobin Blood Level0.82 percentage
STANDARD_DEVIATION 0.39
0.85 percentage
STANDARD_DEVIATION 0.35
0.84 percentage
STANDARD_DEVIATION 0.43
0.83 percentage
STANDARD_DEVIATION 0.39
Body Mass Index Numerical Value15.62 kg/m^2
STANDARD_DEVIATION 1.12
15.69 kg/m^2
STANDARD_DEVIATION 1.08
15.60 kg/m^2
STANDARD_DEVIATION 1.03
15.64 kg/m^2
STANDARD_DEVIATION 1.07
Body Mass Index Percentile
>35th and <=65th percentiles
6 participants14 participants12 participants32 participants
Body Mass Index Percentile
>=5th and <=35th percentiles
11 participants6 participants6 participants23 participants
Body Mass Index Percentile
>65th and <=95th percentiles
13 participants10 participants12 participants35 participants
Sex: Female, Male
Female
19 Participants12 Participants14 Participants45 Participants
Sex: Female, Male
Male
11 Participants18 Participants16 Participants45 Participants
Weight Continuous17.17 kilograms
STANDARD_DEVIATION 2.94
17.24 kilograms
STANDARD_DEVIATION 2.78
17.19 kilograms
STANDARD_DEVIATION 2.96
17.20 kilograms
STANDARD_DEVIATION 2.86

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
0 / 300 / 300 / 30
serious
Total, serious adverse events
0 / 300 / 300 / 30

Outcome results

Primary

Peak Methemoglobin Blood Levels

The maximum percentage of methemoglobin in blood

Time frame: Measured at 10 second intervals during dental treatment for an average of 2 hours

Population: Per protocol

ArmMeasureValue (MEAN)Dispersion
PrilocainePeak Methemoglobin Blood Levels3.55 percentage of methemoglobin in bloodStandard Deviation 1.22
LidocainePeak Methemoglobin Blood Levels1.63 percentage of methemoglobin in bloodStandard Deviation 0.52
No Local AnestheticPeak Methemoglobin Blood Levels1.60 percentage of methemoglobin in bloodStandard Deviation 0.45
Comparison: Null hypothesis: There is no statistically significant difference in peak methemoglobin blood levels following the administration of prilocaine, lidocaine, or no local anesthetic in pre-cooperative children undergoing comprehensive dental rehabilitation under general anesthesia.p-value: <0.001ANOVA
Comparison: LSD post hoc pairwise comparisonp-value: <0.001Least significant difference post hoc
Comparison: LSD post hoc pairwise comparisonp-value: <0.001least significant difference post hoc
Comparison: LSD post hoc pairwise comparisonp-value: =0.89Least significant difference post hoc
Secondary

Delta Methemoglobin Blood Level

Change in percentage of methemoglobin in blood from baseline level to peak 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

Population: Per protocol

ArmMeasureValue (MEAN)Dispersion
PrilocaineDelta Methemoglobin Blood Level2.73 percentage of methemoglobin in bloodStandard Deviation 1.23
LidocaineDelta Methemoglobin Blood Level0.78 percentage of methemoglobin in bloodStandard Deviation 0.44
No Local AnestheticDelta Methemoglobin Blood Level0.76 percentage of methemoglobin in bloodStandard Deviation 0.48
Comparison: Null hypothesis: There is no statistically significant difference in delta methemoglobin blood levels following the administration prilocaine, lidocaine, or no local anesthetic in pre-cooperative children undergoing comprehensive dental rehabilitation under general anesthesia.p-value: <0.001ANOVA
Comparison: LSD post hoc pairwise comparisonp-value: <0.001Least significant difference post hoc
Comparison: LSD post hoc pairwise comparisonp-value: <0.001Least significant difference post hoc
Comparison: LSD post hoc pairwise comparisonp-value: =0.92Least significant difference post hoc
Secondary

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.

Time frame: Measured at 10 second intervals during dental treatment for an average of 2 hours

Population: per protocol

ArmMeasureValue (MEAN)Dispersion
PrilocaineTime to Peak Methemoglobin Blood Levels62.73 minutesStandard Deviation 23.78
LidocaineTime to Peak Methemoglobin Blood Levels57.50 minutesStandard Deviation 30.67
No Local AnestheticTime to Peak Methemoglobin Blood Levels29.50 minutesStandard Deviation 20.36
Comparison: Null hypothesis: There is no statistically significant difference in the time frame to peak methemoglobin levels following the administration of prilocaine, lidocaine, or no local anesthetic in pre-cooperative children undergoing comprehensive dental rehabilitation under general anesthesia.p-value: <0.001ANOVA
Comparison: LSD post hoc pairwise comparisonp-value: =0.43Least significant difference post hoc
Comparison: LSD post hoc pairwise comparisonp-value: <0.001Least significant difference post hoc
Comparison: LSD post hoc pairwise comparisonp-value: <0.001Least significant difference post hoc

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026