Methemoglobin Levels in Generally Anesthetized Pediatric Dental Patients Receiving Local Anesthetics

Methemoglobinemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01402869
• Other study ID #: 5110172
• Status: Completed
• Phase: N/A
• First received: July 25, 2011
• Last updated: March 25, 2014
• Start date: August 2011
• Est. completion date: July 2012

Study information

• Verified date: March 2014
• Source: Loma Linda University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 3 Years to 5 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Methemoglobinemia

Intervention

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
• 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

Locations

Country	Name	City	State
United States	Loma Linda University School of Dentistry Koppel Special Care Dentistry Center	Loma Linda	California

Sponsors (1)

Lead Sponsor	Collaborator
Loma Linda University

Country where clinical trial is conducted

United States, 

References & Publications (21)

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. — View Citation

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

Ash-Bernal R, Brophy GM, Kily D. Acquired methemoglobinemia in the clinical setting: an important health issue revealed. CME Zone Special Report 2006 Nov.

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):265-73. — View Citation

Bader AM, Concepcion M, Hurley RJ, Arthur GR. Comparison of lidocaine and prilocaine for intravenous regional anesthesia. Anesthesiology. 1988 Sep;69(3):409-12. — View Citation

Barker SJ, Curry J, Redford D, Morgan S. Measurement of carboxyhemoglobin and methemoglobin by pulse oximetry: a human volunteer study. Anesthesiology. 2006 Nov;105(5):892-7. Erratum in: Anesthesiology. 2007 Nov;107(5):863. — View Citation

Budenz AW. Local anesthetics in dentistry: then and now. J Calif Dent Assoc. 2003 May;31(5):388-96. Review. — View Citation

Dentsply Pharmaceutical. 4% Citanest Plain Package Insert. York, PA.

Feiner JR, Bickler PE, Mannheimer PD. Accuracy of methemoglobin detection by pulse CO-oximetry during hypoxia. Anesth Analg. 2010 Jul;111(1):143-8. doi: 10.1213/ANE.0b013e3181c91bb6. Epub 2009 Dec 10. — View Citation

Feiner JR, Bickler PE. Improved accuracy of methemoglobin detection by pulse CO-oximetry during hypoxia. Anesth Analg. 2010 Nov;111(5):1160-7. doi: 10.1213/ANE.0b013e3181f46da8. Epub 2010 Sep 14. — View Citation

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. — View Citation

Herdevall BM, Klinge B, Persson L, Huledal G, Abdel-Rehim M. Plasma levels of lidocaine, o-toluidine, and prilocaine after application of 8.5 g Oraqix in patients with generalized periodontitis: effect on blood methemoglobin and tolerability. Acta Odontol Scand. 2003 Aug;61(4):230-4. — View Citation

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

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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

Umbreit J. Methemoglobin--it's not just blue: a concise review. Am J Hematol. 2007 Feb;82(2):134-44. Review. — View Citation

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. Epub 2006 May 24. — View Citation

Wilburn-Goo D, Lloyd LM. When patients become cyanotic: acquired methemoglobinemia. J Am Dent Assoc. 1999 Jun;130(6):826-31. Review. — View Citation

Wright RO, Lewander WJ, Woolf AD. Methemoglobinemia: etiology, pharmacology, and clinical management. Ann Emerg Med. 1999 Nov;34(5):646-56. Review. — View Citation

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

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
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.	Measured at 10 second intervals during dental treatment for an average of 2 hours	No
Secondary	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	No