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Particulate contamination of local anesthetic solutions
Particulate contamination of local anesthetic solutions Robert L. Cooley, D.M.D., M.S.. * and Richard M. Lubobcl, D. M.D., Albuquerque, N. M., and San Antonio, Texas
MS.. **
Particulate contamination was found in one particular lot number of local anesthetic, lidocaine with 1: 100,000 epinephrine. The contaminants were noticed in several cartridges of each container and varied in size from minute to several millimeters. Analysis of the foreign matter revealed the particles to be of a wax or puttylike consistency; however, the sterility of the solution was not altered and the pH was still within acceptable limits. The contaminant was most likely wax or a combination of wax, silicone, and glycerin, which are c&stituents of the rubber stopper and its associated lubricants. This problem was most likely due to temperature changes during storage and shipment, but it was also possibly due to manufacturicg discrepancies.
C
urrently popular local anesthetics, particularly lidocaine with 1: 100,000 epinephrine, have consistently demonstrated their effectiveness, low toxicity, and lack of any significant adverse reactions.‘-3 On occasion, there are problems related to the effects of temperature changes encountered during storage and shipment and to discrepancies in the rubber-stopper aaterial or its associated lubricants.4-6 This particular article describes one such problem discovered in a United States Air Force dental clinic, possible reasons for the occurrence, and a means of redtifying the situation. CASE REPORT
During routine use of lidocaine HClt with 1: 100,000 epinephrine in the clinic, it was discovered that the solution of a new lot contained particuIate matter that was gray in color (Fig. 1). Upon investigation, it was found that six to eight cartridges from each container of the same lot number contained the foreign bodies. The use of all cartridges from this lot number was discontinued immediately, and representative samples were sent to the Food and Drug Administration.
The views expressed herein are those of the authors and do not necessarily reflect the views of the United States Air Force or Department of Defense. *Chief of Restorative Dentisay, United States Air Force Hospital, K&land AFB, Albuquerque, N. M. **Chief of Periodontal Training, General Dentistry Residency, Wilford Hall USAF Medical Center, Lackland AFB, San Antonio, Texas. tXylocaine. Astra PharmaceuticalProducts, Worcester, Mass.
Fig. 1. Particulate contamination in a local anesthetic solution. One large particle and two smaller ones can be visualized in this cartridge. LABORATORY
INVESTIGATION
The particles varied in size from fairly large (approximately 2 mm.) to minute. A dissecting microscope was used to closely visualize the particles, which had the appearance of wax or putty (Fig. 2). Four cartridges with the particulate contamination were analyzed for changes in pH. A digital ionalyzer* (Fig. 3) was used to determine the pH of each solution. The device was calibrated before each test with a single buffer standard of 4.01, which allows a pH test range *Orion Research,Inc., Cambridge, Mass. 481
Oral Surg. May. 1981
Fig. 2. Microscopic examination of a gray particle with wax or puttylike appearance.
Fig.
from 1.Ol to 7.01. Two cartridges from a different lot number were used as controls. The pH of these solutions was 4.65 and 4.66. The pH of the four contaminated solutions was 4.08, 4.45, 4.15. and 4.52. Although the pH of these solutions is below that of the controls, they fall into the pH range of 3.3 to 5.5 as recommended by the United States Pharmacopeia. ’ Two cattridges with particulate contamination were also tested for sterility. The solutions were initially placed on three agar plates and in two media tubes by means of a sterile needle and syringe. The three plates consisted of blood agar, chocolate agar. and EMB (eosin methylene blue). The two media tubes contained thioglycoliate and deep meat. Samples from each of the plates and tubes were restreaked on blood, chocolate, and EMB agar. The samples were incubated both aerobically and anaerobically for 7 days. No growth was identified on either the plates or the tubes, indicating that the solutions were sterile.
thetic solutions. The most serious problem could be loss of sterility of the solution. Lidocaine solutions freeze at approximately 26” F. The ice formation causes the rubber stopper to become unseated and extrude. Air can enter the capsule and may contaminate the solution. Also, oxygen will cause oxidation of the epinephrine, resulting in a loss of its effectiveness. Sodium bisultite is added to the lidocaine solution to protect the epinephrine from oxidation, but it may not be able to provide this protection when air enters the cartridge. Local anesthetic solutions with particulate contamination should never be injected into a patient. In a memorandum,a the Food and Drug Administration warned against the use of any injectable with the slightest evidence of precipitation or crystallization, as some intravenous diagnostic products have been known to cause injury when the crystals themselves were injetted.
DISCUSSION
A case demonstrating particulate contamination of local anesthetic solutions has been presented. The particles appeared to be wax, which is used in the formulation of the rubber stopper.“’ This contamination did not alter the sterility or the pH of the solution; however, the use of all cartridges of this lot number was discontinued and representative samples were sent to the Food and Drug Administration for analysis.
Communication with the manufacture? of this product revealed that wax (paraffin) was a part of the formulation of the rubber stoppers used in local anesthetic cartridges. When exposed to cold or freezing, the wax may balloon or flake out. Silicone and glycerin are also placed on the rubber as a lubricant and as a sealing agent. Therefore, the particles found in the local anesthetic solution could be wax or a combination of wax, silicone, and glycerin. These cartridges could have been exposed to cold and freezing temperatures during shipment, while sitting on loading docks, or even in warehouses. Cooleyg indicates that extreme cold leading to freezing may have other deleterious effects on local anes-
3. Digital ionalyzer used to analyze the pH of the local anesthetic solutions. pH electrode is located on the left.
SUMMARY
REFERENCE8 I. Paverson, Roy: Allergic Diseases. Diagnosis and Management. Philadelphia. 1972. J. B. Lippincott Company, pp. 474, 476. 2. Nelson, Harold: Special Problems in Drug Allergy. Adv. Astbma Allergy 4: 29, 1977. 3. Accepted Dental Therapeutics, ed. 36, Chicago, 1975. American Dental Association, pp. 96, 97.
Volume 5 1 Number
Partidate
contamination
qf local
anesthetic
solutions
483
5
4. Food and Drug Administration Memorandum: Effect of Cold Temperatures on Prescription and OTC Drugs, Feb. 10, 1977. 5. USP Pharmacist Advisory Bulletin, Feb. 2, 1977. 6. Carlisle Laboratories, Inc., Inwood, N. Y .: Personal Communication. 7. United States Pharmacopeia XIX, July, 1975, p. 284. 8. Personal Communication, Astra Pharmaceutical Products, Wortester. Mass. 9. Cooley, R. L.: Effects of Freezing on Local Anesthetics, J. Cola. Dent. Assoc. 55: 77, 1977.
10. Powell, Joseph, Dental Investigative Unit, School of Aerospace Medicine, Brooks, AFB, Texas: Personal Communication. Reprint requesrs IO: Dr. Robert L. Cooley Chief of Restorative Dentistry U. S. Air Force Hospital Kirtland Air Force Base Albuquerque, N. M. 87117
MS.. **
Particulate contamination was found in one particular lot number of local anesthetic, lidocaine with 1: 100,000 epinephrine. The contaminants were noticed in several cartridges of each container and varied in size from minute to several millimeters. Analysis of the foreign matter revealed the particles to be of a wax or puttylike consistency; however, the sterility of the solution was not altered and the pH was still within acceptable limits. The contaminant was most likely wax or a combination of wax, silicone, and glycerin, which are c&stituents of the rubber stopper and its associated lubricants. This problem was most likely due to temperature changes during storage and shipment, but it was also possibly due to manufacturicg discrepancies.
C
urrently popular local anesthetics, particularly lidocaine with 1: 100,000 epinephrine, have consistently demonstrated their effectiveness, low toxicity, and lack of any significant adverse reactions.‘-3 On occasion, there are problems related to the effects of temperature changes encountered during storage and shipment and to discrepancies in the rubber-stopper aaterial or its associated lubricants.4-6 This particular article describes one such problem discovered in a United States Air Force dental clinic, possible reasons for the occurrence, and a means of redtifying the situation. CASE REPORT
During routine use of lidocaine HClt with 1: 100,000 epinephrine in the clinic, it was discovered that the solution of a new lot contained particuIate matter that was gray in color (Fig. 1). Upon investigation, it was found that six to eight cartridges from each container of the same lot number contained the foreign bodies. The use of all cartridges from this lot number was discontinued immediately, and representative samples were sent to the Food and Drug Administration.
The views expressed herein are those of the authors and do not necessarily reflect the views of the United States Air Force or Department of Defense. *Chief of Restorative Dentisay, United States Air Force Hospital, K&land AFB, Albuquerque, N. M. **Chief of Periodontal Training, General Dentistry Residency, Wilford Hall USAF Medical Center, Lackland AFB, San Antonio, Texas. tXylocaine. Astra PharmaceuticalProducts, Worcester, Mass.
Fig. 1. Particulate contamination in a local anesthetic solution. One large particle and two smaller ones can be visualized in this cartridge. LABORATORY
INVESTIGATION
The particles varied in size from fairly large (approximately 2 mm.) to minute. A dissecting microscope was used to closely visualize the particles, which had the appearance of wax or putty (Fig. 2). Four cartridges with the particulate contamination were analyzed for changes in pH. A digital ionalyzer* (Fig. 3) was used to determine the pH of each solution. The device was calibrated before each test with a single buffer standard of 4.01, which allows a pH test range *Orion Research,Inc., Cambridge, Mass. 481
Oral Surg. May. 1981
Fig. 2. Microscopic examination of a gray particle with wax or puttylike appearance.
Fig.
from 1.Ol to 7.01. Two cartridges from a different lot number were used as controls. The pH of these solutions was 4.65 and 4.66. The pH of the four contaminated solutions was 4.08, 4.45, 4.15. and 4.52. Although the pH of these solutions is below that of the controls, they fall into the pH range of 3.3 to 5.5 as recommended by the United States Pharmacopeia. ’ Two cattridges with particulate contamination were also tested for sterility. The solutions were initially placed on three agar plates and in two media tubes by means of a sterile needle and syringe. The three plates consisted of blood agar, chocolate agar. and EMB (eosin methylene blue). The two media tubes contained thioglycoliate and deep meat. Samples from each of the plates and tubes were restreaked on blood, chocolate, and EMB agar. The samples were incubated both aerobically and anaerobically for 7 days. No growth was identified on either the plates or the tubes, indicating that the solutions were sterile.
thetic solutions. The most serious problem could be loss of sterility of the solution. Lidocaine solutions freeze at approximately 26” F. The ice formation causes the rubber stopper to become unseated and extrude. Air can enter the capsule and may contaminate the solution. Also, oxygen will cause oxidation of the epinephrine, resulting in a loss of its effectiveness. Sodium bisultite is added to the lidocaine solution to protect the epinephrine from oxidation, but it may not be able to provide this protection when air enters the cartridge. Local anesthetic solutions with particulate contamination should never be injected into a patient. In a memorandum,a the Food and Drug Administration warned against the use of any injectable with the slightest evidence of precipitation or crystallization, as some intravenous diagnostic products have been known to cause injury when the crystals themselves were injetted.
DISCUSSION
A case demonstrating particulate contamination of local anesthetic solutions has been presented. The particles appeared to be wax, which is used in the formulation of the rubber stopper.“’ This contamination did not alter the sterility or the pH of the solution; however, the use of all cartridges of this lot number was discontinued and representative samples were sent to the Food and Drug Administration for analysis.
Communication with the manufacture? of this product revealed that wax (paraffin) was a part of the formulation of the rubber stoppers used in local anesthetic cartridges. When exposed to cold or freezing, the wax may balloon or flake out. Silicone and glycerin are also placed on the rubber as a lubricant and as a sealing agent. Therefore, the particles found in the local anesthetic solution could be wax or a combination of wax, silicone, and glycerin. These cartridges could have been exposed to cold and freezing temperatures during shipment, while sitting on loading docks, or even in warehouses. Cooleyg indicates that extreme cold leading to freezing may have other deleterious effects on local anes-
3. Digital ionalyzer used to analyze the pH of the local anesthetic solutions. pH electrode is located on the left.
SUMMARY
REFERENCE8 I. Paverson, Roy: Allergic Diseases. Diagnosis and Management. Philadelphia. 1972. J. B. Lippincott Company, pp. 474, 476. 2. Nelson, Harold: Special Problems in Drug Allergy. Adv. Astbma Allergy 4: 29, 1977. 3. Accepted Dental Therapeutics, ed. 36, Chicago, 1975. American Dental Association, pp. 96, 97.
Volume 5 1 Number
Partidate
contamination
qf local
anesthetic
solutions
483
5
4. Food and Drug Administration Memorandum: Effect of Cold Temperatures on Prescription and OTC Drugs, Feb. 10, 1977. 5. USP Pharmacist Advisory Bulletin, Feb. 2, 1977. 6. Carlisle Laboratories, Inc., Inwood, N. Y .: Personal Communication. 7. United States Pharmacopeia XIX, July, 1975, p. 284. 8. Personal Communication, Astra Pharmaceutical Products, Wortester. Mass. 9. Cooley, R. L.: Effects of Freezing on Local Anesthetics, J. Cola. Dent. Assoc. 55: 77, 1977.
10. Powell, Joseph, Dental Investigative Unit, School of Aerospace Medicine, Brooks, AFB, Texas: Personal Communication. Reprint requesrs IO: Dr. Robert L. Cooley Chief of Restorative Dentistry U. S. Air Force Hospital Kirtland Air Force Base Albuquerque, N. M. 87117