Editor’s Note: The last issue of the Newsletter contained a pair of Letters to the Editor under the headline “Sevoflurane Containing Toxic Acid Prompts Recall.” The following letter was received by the Editor as part of the follow-up effort by the manufacturer.
To The Editor
The following letter was mailed to Chiefs of Anesthesiology and Directors of Pharmacies on January 22, 1997: On November 18, 1996, Abbott Laboratories initiated a voluntary recall on one (1) lot of Sevoflurane, Lot 10-590-DK. This action was taken following the evaluation of a bottle of Sevoflurane with an uncharacteristic pungent odor. Evaluation of this product indicated that the product was outside its acidity specification (pH <1) and contained hydrogen fluoride (863 ppm).
The presence of hydrogen fluoride can be detected by smell at very low levels (0.3 parts per million). Fifty (50) ppm for 1 hour will result in serious adverse effects. Symptoms of exposure may include the following: eye and skin irritation; burning sensation; respiratory tract irritation (coughing, laryngitis, bronchospasm, etc.) respiratory tract injury (pulmonary edema, respiratory failure, pulmonary fibrosis) tachycardia and hypertension. Treatment of exposure includes oxygen and calcium gluconate or carbonate. Incidental exposure to contaminated/degraded Sevoflurane may cause short-term symptoms as previously described. There are no reports of any injury to patients exposed to the recalled product from Lot 10-590-DK.
Analysis of Cause of Degraded Sevoflurane
Abbott Laboratories has conducted a number of experiments to characterize the reaction that caused the degradation of Sevoflurane. Based on the data generated, we have come to the following conclusions. The process was initiated by the presence of an impurity in a single valve connected to the bulk Sevoflurane drug shipping container. After initiation by the valve material, a necessary part of the reaction involves the preferential consumption of moisture in Sevoflurane. This reaction continues at a very slow rate until all of the water is consumed, at which point reaction with the solution container rapidly occurs resulting in the pungent odor (SiF4).
Past Lots Tested
Abbott has reexamined final product retained samples from all lots produced and found them to be within specification. We have also tested a large number of bottles in the field and found all to be within specification. We are confident that all product in the field and that currently being produced is safe to use. If for some reason you should be concerned that any bottle of Sevoflurane may be contaminated, you can easily conduct a pH test which is outlined in the attachment [to the original letter]. If you have any questions on conducting this test, please contact your Abbott representative for assistance.
Effect of Degraded Sevoflurane on Anesthesia Equipment
Fifty-two (52) of 220 bottles (approximately 25%) returned from the recall lot (7,770 bottles) tested positive for hydrogen fluoride and were acidic. Each of the accounts having the degraded products was notified of these results. Vaporizers in these accounts were drained and then the drug tested for acidity. A total of six vaporizers contained acidic product. These vaporizers and the associated anesthesia machines were immediately removed from service and sent for testing. Testing confirmed that this equipment had not been affected by the exposure to degraded Sevoflurane and passed all functional requirements. At the request of some hospitals, testing was also conducted on vaporizers that had not been exposed to degraded Sevoflurane. All were shown to function within normal limits.
More Work in Progress
Additional studies are being conducted by both the equipment manufacturers and by independent equipment companies in which vaporizers and anesthesia machines are exposed to high levels of acidic Sevoflurane for prolonged periods of time. Although results are not yet complete, the short-term tests also show the equipment continues to function within specifications. The only abnormality detected is a small amount of white powder inside the vaporizer, primarily in the wick area, which has been identified as a known non-volatile degradant of Sevoflurane. We are confident that the function of any equipment that has been exposed to degraded Sevoflurane has not been impacted and the equipment is safe to use.
Should you have any questions on the information presented in this letter, please contact Abbott at 1-800-222-6883. We appreciate your continued support.
Clair M. Callan, M.D. Vice President, Medical, Regulatory Affairs and Advanced Research Abbott Hospital Products Division