0
Communications to the Editor |

Propofol Containing Sulfite—Potential For Injury FREE TO VIEW

Paul B. Langevin, MD
Author and Funding Information

University of Florida College of Medicine, Gainesville, FL

Correspondence to: Paul B. Langevin, MD, Department of Anesthesiology, PO Box 100254, Gainesville, FL 36210-0254; e-mail: anita@anest2.anest.ufl.edu



Chest. 1999;116(4):1140-1141. doi:10.1378/chest.116.4.1140-a
Text Size: A A A
Published online

To the Editor:

In 1986, the Food and Drug Administration (FDA) issued a warning stating that drugs that contain sulfites were hazardous and should be withdrawn whenever alternative formulations were available.1 Since this warning, there has been an effort within the pharmaceutical industry to avoid the addition of sulfites to virtually all compounds when possible. Indeed, only two drugs commonly used by anesthesiologists still contain sulfite: curare and the generic form of propofol, which was recently approved by the FDA despite its decade-old admonition to avoid this agent.1

The incidence of sulfite allergy is estimated at > 1 in 1,000 patients.2The manifestations of sulfite allergy range from a mild dermatitis, to bronchospasm, to outright anaphylaxis.3The exact toxicity of the additive is unknown in humans, although chronic exposure can result in renal failure.4The median lethal dose (LD50) of sodium metabisulfite in rats is < 125 mg/kg.5

Given that generic propofol contains 0.25 mg/mL sodium metabisulfite (see package insert for generic propofol [Gensia; Irvine, CA]), infusion at a rate of only 50 μg/kg/min will result in sulfite administration approaching toxic levels (ie, near the LD50 for rats) in about 24 h. More important, children frequently exhibit toxicity to many compounds at lower concentrations than adults, but typically they require higher doses of propofol to achieve the desired effect. Therefore, the addition of sulfites to this drug is particularly worrisome for the potential effects in the pediatric population.

Clinicians are likely to simply substitute the generic propofol for Diprivan (Zeneca Pharmaceuticals; Wilmington, DE) because the FDA gave the generic drug AB status, which for many physicians implies an equally safe preparation. Indeed, there is no evidence to indicate that generic propofol is harmful or likely to cause an adverse event. Unfortunately, there is also no evidence to the contrary. Well-designed laboratory and clinical studies are needed to determine its harmful effects. Unfortunately, the clinical studies may require large numbers of patients, which makes laboratory data even more critical when a drug is being used prior clinical to testing. Until such data become available, clinicians may wish to use generic propofol only in selected cases.

References

Department of Health and Human Services, Food and Drug Administration. Sulfiting agents: labeling in drugs for human use. 51FR43900, December 5, 1986.
 
Papazian R. Sulfites: safe for most, dangerous for some. Washington, DC: US Food and Drug Administration, FDA Consumer, December 1996.
 
Schwartz, HJ Sensitivity to ingestion of metabisulfite: variations in clinical presentation.J Allergy Clin Immunol1983;71,487-489. [CrossRef]
 
Akanji, MA, Olagoke, OA, Oloyede, OB Effect of chronic consumption of metabisulphite on the integrity of the rat kidney cellular system.Toxicology1993;81,173-179. [CrossRef]
 
US Circuit Court of Appeals. 54FR2324 et seq, June 1988.
 

Figures

Tables

References

Department of Health and Human Services, Food and Drug Administration. Sulfiting agents: labeling in drugs for human use. 51FR43900, December 5, 1986.
 
Papazian R. Sulfites: safe for most, dangerous for some. Washington, DC: US Food and Drug Administration, FDA Consumer, December 1996.
 
Schwartz, HJ Sensitivity to ingestion of metabisulfite: variations in clinical presentation.J Allergy Clin Immunol1983;71,487-489. [CrossRef]
 
Akanji, MA, Olagoke, OA, Oloyede, OB Effect of chronic consumption of metabisulphite on the integrity of the rat kidney cellular system.Toxicology1993;81,173-179. [CrossRef]
 
US Circuit Court of Appeals. 54FR2324 et seq, June 1988.
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543