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Methemoglobin Levels in Generally Anesthetized Pediatric Dental Patients Receiving Local Anesthetics

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ClinicalTrials.gov Identifier: NCT01402869
Recruitment Status : Completed
First Posted : July 26, 2011
Results First Posted : April 25, 2014
Last Update Posted : April 25, 2014
Sponsor:
Information provided by (Responsible Party):
Lauren GutenBerg, Loma Linda University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label)
Condition Methemoglobinemia
Interventions Drug: 4% prilocaine plain
Drug: 2% Lidocaine with 1:100,000 epinephrine
Enrollment 91
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.
Arm/Group Title Prilocaine Lidocaine No Local Anesthetic
Hide Arm/Group Description 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 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 No local anesthetic was administered prior to restorative dental treatment-Negative control
Period Title: Overall Study
Started 30 30 31
Completed 30 30 30
Not Completed 0 0 1
Reason Not Completed
Required Tooth Extraction             0             0             1
Arm/Group Title Prilocaine Lidocaine No Local Anesthetic Total
Hide Arm/Group Description 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 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 No local anesthetic was administered prior to restorative dental treatment-Negative control Total of all reporting groups
Overall Number of Baseline Participants 30 30 30 90
Hide Baseline Analysis Population Description
1 subject was withdrawn from the no local anesthetic group as the subject required 1 or more dental tooth extractions and required local anesthetic
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 30 participants 30 participants 30 participants 90 participants
50.97  (9.84) 50.77  (10.19) 50.63  (8.43) 50.79  (9.41)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 30 participants 90 participants
Female
19
  63.3%
12
  40.0%
14
  46.7%
45
  50.0%
Male
11
  36.7%
18
  60.0%
16
  53.3%
45
  50.0%
Weight Continuous  
Mean (Standard Deviation)
Unit of measure:  Kilograms
Number Analyzed 30 participants 30 participants 30 participants 90 participants
17.17  (2.94) 17.24  (2.78) 17.19  (2.96) 17.20  (2.86)
ASA Health Classification  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 30 participants 90 participants
I-Healthy patients; no systemic disease 26 25 24 75
II-Patients with mild, systemic disease 4 5 6 15
Body Mass Index Numerical Value  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 30 participants 30 participants 30 participants 90 participants
15.62  (1.12) 15.69  (1.08) 15.60  (1.03) 15.64  (1.07)
Body Mass Index Percentile  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 30 participants 90 participants
>=5th and <=35th percentiles 11 6 6 23
>35th and <=65th percentiles 6 14 12 32
>65th and <=95th percentiles 13 10 12 35
Baseline Methemoglobin Blood Level   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage
Number Analyzed 30 participants 30 participants 30 participants 90 participants
0.82  (0.39) 0.85  (0.35) 0.84  (0.43) 0.83  (0.39)
[1]
Measure Description: Methemoglobin blood level recorded non-invasively by the Masimo Radical-7 Pulse Co-Oximeter prior to the administration of local anesthetic or start of restorative dental procedures.
1.Primary Outcome
Title Peak Methemoglobin Blood Levels
Hide Description The maximum percentage of methemoglobin in blood
Time Frame Measured at 10 second intervals during dental treatment for an average of 2 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol
Arm/Group Title Prilocaine Lidocaine No Local Anesthetic
Hide Arm/Group Description:
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
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
No local anesthetic was administered prior to restorative dental treatment-Negative control
Overall Number of Participants Analyzed 30 30 30
Mean (Standard Deviation)
Unit of Measure: percentage of methemoglobin in blood
3.55  (1.22) 1.63  (0.52) 1.60  (0.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Prilocaine, Lidocaine, No Local Anesthetic
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power of 80
Statistical Test of Hypothesis P-Value <.001
Comments LSD post hoc test was used for multiple group comparisons. P<.05
Method ANOVA
Comments LSD post hoc test was used for multiple group comparisons.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Prilocaine, Lidocaine
Comments LSD post hoc pairwise comparison
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power of 80
Statistical Test of Hypothesis P-Value <.001
Comments P<.05
Method Least significant difference post hoc
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Prilocaine, No Local Anesthetic
Comments LSD post hoc pairwise comparison
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power of 80
Statistical Test of Hypothesis P-Value <.001
Comments P<.05
Method least significant difference post hoc
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lidocaine, No Local Anesthetic
Comments LSD post hoc pairwise comparison
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power of 80
Statistical Test of Hypothesis P-Value =.89
Comments P<.05
Method Least significant difference post hoc
Comments [Not Specified]
2.Secondary Outcome
Title Time to Peak Methemoglobin Blood Levels
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
per protocol
Arm/Group Title Prilocaine Lidocaine No Local Anesthetic
Hide Arm/Group Description:
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
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
No local anesthetic was administered prior to restorative dental treatment-Negative control
Overall Number of Participants Analyzed 30 30 30
Mean (Standard Deviation)
Unit of Measure: minutes
62.73  (23.78) 57.50  (30.67) 29.50  (20.36)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Prilocaine, Lidocaine, No Local Anesthetic
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power of 80
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method ANOVA
Comments LSD post hoc test was used for multiple group comparisons.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Prilocaine, Lidocaine
Comments LSD post hoc pairwise comparison
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power of 80
Statistical Test of Hypothesis P-Value =.43
Comments P<.05
Method Least significant difference post hoc
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Prilocaine, No Local Anesthetic
Comments LSD post hoc pairwise comparison
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power of 80
Statistical Test of Hypothesis P-Value <.001
Comments P<.05
Method Least significant difference post hoc
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lidocaine, No Local Anesthetic
Comments LSD post hoc pairwise comparison
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power of 80
Statistical Test of Hypothesis P-Value <.001
Comments P<.05
Method Least significant difference post hoc
Comments [Not Specified]
3.Secondary Outcome
Title Delta Methemoglobin Blood Level
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol
Arm/Group Title Prilocaine Lidocaine No Local Anesthetic
Hide Arm/Group Description:
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
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
No local anesthetic was administered prior to restorative dental treatment-Negative control
Overall Number of Participants Analyzed 30 30 30
Mean (Standard Deviation)
Unit of Measure: percentage of methemoglobin in blood
2.73  (1.23) 0.78  (0.44) 0.76  (0.48)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Prilocaine, Lidocaine, No Local Anesthetic
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power of 80
Statistical Test of Hypothesis P-Value <.001
Comments P<.05
Method ANOVA
Comments LSD post hoc test was used for multiple group comparisons.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Prilocaine, Lidocaine
Comments LSD post hoc pairwise comparison
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power of 80
Statistical Test of Hypothesis P-Value <.001
Comments P<.05
Method Least significant difference post hoc
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Prilocaine, No Local Anesthetic
Comments LSD post hoc pairwise comparison
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power of 80
Statistical Test of Hypothesis P-Value <.001
Comments P<.05
Method Least significant difference post hoc
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lidocaine, No Local Anesthetic
Comments LSD post hoc pairwise comparison
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power of 80
Statistical Test of Hypothesis P-Value =.92
Comments P<.05
Method Least significant difference post hoc
Comments [Not Specified]
Time Frame Reported adverse events include those that occurred at or after the administration of local anesthetic in the Prilocaine and Lidocaine Groups or the start of restorative dental procedures in the No Local Anesthetic Group.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Prilocaine Lidocaine No Local Anesthetic
Hide Arm/Group Description 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 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 No local anesthetic was administered prior to restorative dental treatment-Negative control
All-Cause Mortality
Prilocaine Lidocaine No Local Anesthetic
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Prilocaine Lidocaine No Local Anesthetic
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/30 (0.00%)   0/30 (0.00%)   0/30 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Prilocaine Lidocaine No Local Anesthetic
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/30 (0.00%)   0/30 (0.00%)   0/30 (0.00%) 
Did not compare locals anesthetics with equivalent concentrations of epinephrine; unable to control length of time methemoglobin blood levels were monitored as all subjects varied in extent of restorative dental procedures needed.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Lauren Gutenberg
Organization: Loma Linda University
Phone: 909-558-4690
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
Ash-Bernal R, Brophy GM, Kily D. Acquired methemoglobinemia in the clinical setting: an important health issue revealed. CME Zone Special Report 2006 Nov.
Dentsply Pharmaceutical. 4% Citanest Plain Package Insert. York, PA.
Responsible Party: Lauren GutenBerg, Loma Linda University
ClinicalTrials.gov Identifier: NCT01402869     History of Changes
Other Study ID Numbers: 5110172
First Submitted: July 25, 2011
First Posted: July 26, 2011
Results First Submitted: October 15, 2013
Results First Posted: April 25, 2014
Last Update Posted: April 25, 2014