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MethemoglobinemiaNCT01402869

Methemoglobin Levels in Generally Anesthetized Pediatric Dental Patients Receiving Local Anesthetics

A study testing 4% prilocaine plain and 2% Lidocaine with 1:100,000 epinephrine in people with Methemoglobinemia, run by Loma Linda University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 3 to 5 yearsHealthy volunteers can take part
Conditions the study is for
Methemoglobinemia
What is being tested?
4% prilocaine plain and 2% Lidocaine with 1:100,000 epinephrine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
91 participants
Where
1 siteUnited States
Study dates
Aug 2011to Jul 2012
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 5 years
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Loma Linda University School of Dentistry Koppel Special Care Dentistry Center

    Loma Linda, California, 92350

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
4% prilocaine plain, 2% Lidocaine with 1:100,000 epinephrine
Keywords
Methemoglobin, Methemoglobinemia, Prilocaine, Lidocaine
Medical subject headings
Methemoglobinemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 4% prilocaine plainDrug

    Also called Citanest Plain

    5mg/kg via infiltration into multiple sites of the buccal mucosa of mouth 1 time prior to start of restorative dental treatment

  • 2% Lidocaine with 1:100,000 epinephrineDrug

    Also called Xylocaine

    2.5mg/kg via infiltration into multiple sites of buccal mucosa of mouth 1 time prior to restorative dental treatment

Study groups in NCT01402869
Study groupRoleWhat they receive
PrilocaineExperimental30 subjects will receive 5mg/kg of 4% prilocaine plain local anesthetic for restorative dental treatment under general anesthesia
Receives: Drug: 4% prilocaine plain
LidocaineExperimental30 subjects will receive 2.5mg/kg of 2% lidocaine with 1:100,000 epinephrine local anesthetic for restorative dental treatment under general anesthesia
Receives: Drug: 2% Lidocaine with 1:100,000 epinephrine
No local anestheticNo intervention30 subjects will not receive local anesthetic for dental treatment under general anesthesia-Negative control

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Peak Methemoglobin Blood Levels

    The maximum percentage of methemoglobin in blood

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

Secondary outcomes (2)
  1. 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: Measured at 10 second intervals during dental treatment for an average of 2 hours

  2. Delta Methemoglobin Blood Level

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

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jul 2011 (estimated)
  2. Study startAug 2011
  3. Primary completionJul 2012
  4. Study completionJul 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
91 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01402869
Sponsor's protocol ID
5110172
Status last verified
Mar 2014
First submitted
25 Jul 2011
Last updated
25 Apr 2014
Data monitoring committee
No

Publications

  • Wright RO, Lewander WJ, Woolf AD. Methemoglobinemia: etiology, pharmacology, and clinical management. Ann Emerg Med. 1999 Nov;34(5):646-56. doi: 10.1016/s0196-0644(99)70167-8.

    PubMed 10533013
  • Ash-Bernal R, Wise R, Wright SM. Acquired methemoglobinemia: a retrospective series of 138 cases at 2 teaching hospitals. Medicine (Baltimore). 2004 Sep;83(5):265-273. doi: 10.1097/01.md.0000141096.00377.3f.

    PubMed 15342970
  • Umbreit J. Methemoglobin--it's not just blue: a concise review. Am J Hematol. 2007 Feb;82(2):134-44. doi: 10.1002/ajh.20738.

    PubMed 16986127
  • Trapp L, Will J. Acquired methemoglobinemia revisited. Dent Clin North Am. 2010 Oct;54(4):665-75. doi: 10.1016/j.cden.2010.06.007. Epub 2010 Aug 7.

    PubMed 20831930
  • Malamed SF. Local anesthetics: dentistry's most important drugs, clinical update 2006. J Calif Dent Assoc. 2006 Dec;34(12):971-6.

    PubMed 17260521
  • Budenz AW. Local anesthetics in dentistry: then and now. J Calif Dent Assoc. 2003 May;31(5):388-96.

    PubMed 12839231
  • Moore PA, Hersh EV. Local anesthetics: pharmacology and toxicity. Dent Clin North Am. 2010 Oct;54(4):587-99. doi: 10.1016/j.cden.2010.06.015.

    PubMed 20831923
  • Bader AM, Concepcion M, Hurley RJ, Arthur GR. Comparison of lidocaine and prilocaine for intravenous regional anesthesia. Anesthesiology. 1988 Sep;69(3):409-12. doi: 10.1097/00000542-198809000-00022. No abstract available.

    PubMed 3415022
  • Vasters FG, Eberhart LH, Koch T, Kranke P, Wulf H, Morin AM. Risk factors for prilocaine-induced methaemoglobinaemia following peripheral regional anaesthesia. Eur J Anaesthesiol. 2006 Sep;23(9):760-5. doi: 10.1017/S0265021506000913. Epub 2006 May 24.

    PubMed 16723054
  • Soeding P, Deppe M, Gehring H. Pulse-oximetric measurement of prilocaine-induced methemoglobinemia in regional anesthesia. Anesth Analg. 2010 Oct;111(4):1065-8. doi: 10.1213/ANE.0b013e3181eb6239. Epub 2010 Aug 12.

    PubMed 20705783
  • Wilburn-Goo D, Lloyd LM. When patients become cyanotic: acquired methemoglobinemia. J Am Dent Assoc. 1999 Jun;130(6):826-31. doi: 10.14219/jada.archive.1999.0306.

    PubMed 10377640
  • Guay J. Methemoglobinemia related to local anesthetics: a summary of 242 episodes. Anesth Analg. 2009 Mar;108(3):837-45. doi: 10.1213/ane.0b013e318187c4b1.

    PubMed 19224791
  • Adams V, Marley J, McCarroll C. Prilocaine induced methaemoglobinaemia in a medically compromised patient. Was this an inevitable consequence of the dose administered? Br Dent J. 2007 Nov 24;203(10):585-7. doi: 10.1038/bdj.2007.1045.

    PubMed 18037845
  • 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

Questions about this trial

What is this clinical trial studying?

A study testing 4% prilocaine plain and 2% Lidocaine with 1:100,000 epinephrine in people with Methemoglobinemia, run by Loma Linda University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Peak Methemoglobin Blood Levels (time frame: Measured at 10 second intervals during dental treatment for an average of 2 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01402869, which also lists 21 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2014.

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