Correspondence

Propofol and Postoperative Infections

N Engl J Med 1995; 333:1505-1507November 30, 1995

Article

To the Editor:

Bennett et al.1 report on thorough investigations into postoperative infections associated with the use of the intravenous anesthetic propofol, but we would like to add some comments.

Clusters of fever episodes, infections, or sepsis associated with propofol use were reported exclusively in the United States shortly after the approval of this drug by the Food and Drug Administration. Epidemiologic studies conducted subsequently implicated extrinsic contamination of propofol infusions with various microorganisms.2 Although the epidemiologic data constitute convincing indirect evidence that the infectious episodes stemmed from contamination of propofol through the improper use of aseptic techniques, in no single case has it been demonstrated conclusively that an anesthesiologist or any other health care worker transferred microorganisms into a vial of propofol and from the vial to a patient.1,2 The studies failed to provide this conclusive proof because of problems with some of the data. First, the microbiologic methods used — e.g., phage typing of Staphylococcus aureus — severely limited the ability of researchers to distinguish reliably between the outbreak-related strains isolated from health care workers, patients, and propofol syringes (at hospitals 1 and 3).3 Second, the microorganisms cultured from those suspected of being carriers were not identical to those from case patients (at hospital 2). Third, it was possible to analyze pathogens from propofol syringes but not from case patients (at hospital 4). Fourth, the isolate found in opened vials of propofol was not identical to those found in hospital personnel (at hospital 5). Fifth, the causative organisms could not be traced to propofol vials (at hospitals 1, 2, 3, 6, and 7) or to anesthesia personnel (at hospitals 2, 4, 6, and 7). Finally, the organisms causing one outbreak could not be identified at all, and cultures from an anesthesiologist suspected of being a carrier remained negative (at hospital 7).1

It would be interesting to know whether the S. aureus isolates from 26 case patients in hospitals 1 and 3 have been kept for further analysis. Pulsed-field gel electrophoresis of genomic DNA digested with restriction enzymes might provide some conclusive evidence.3

Alfons Bach, M.D.
Heinrich Konrad Geiss, M.D.
University of Heidelberg, D-69120 Heidelberg, Germany

3 References

1. 1

   Bennett SN, McNeil MM, Bland LA, et al. Postoperative infections traced to contamination of an intravenous anesthetic, propofol. N Engl J Med 1995;333:147-154
   Full Text | Web of Science | Medline

2. 2

   Postsurgical infections associated with an extrinsically contaminated intravenous anesthetic agent -- California, Illinois, Maine, and Michigan, 1990MMWR Morb Mortal Wkly Rep 1990;39:426-7, 433
   Medline

3. 3

   Bannerman TL, Hancock GA, Tenover FC, Miller JM. Pulsed-field gel electrophoresis as a replacement for bacteriophage typing of Staphylococcus aureus. J Clin Microbiol 1995;33:551-555
   Web of Science | Medline

To the Editor:

It is well known that propofol is an excellent culture medium.1-3 We reported on the incidence of contamination of propofol bottles used in the intensive care unit for a mean of 8.3 hours (range, 2.5 to 18 hours) and showed that when scrupulous attention is paid to aseptic technique there is no evidence of accidental bacterial contamination or inoculation of the propofol.4 The manufacturers of propofol have stated quite clearly that the agent will support the growth of microorganisms and have emphasized the need for aseptic technique in the preparation of the agent for use. They have also pointed out that the 50-ml and 100-ml bottles should not be used as multidose ampules.

In view of the written recommendations of professional associations, such as the American Society of Anesthesiologists and the American Association of Nurse-Anesthetists, and the published evidence of the potential for infection, it is disturbing that the Food and Drug Administration is still receiving reports of sporadic episodes of fever, infection, or sepsis thought to be associated with extrinsically contaminated propofol. Bennett et al. are quite correct to strongly recommend increased efforts to educate anesthesia personnel about the need for aseptic techniques and basic infection-control practices. This is a problem that exists only because of carelessness or lack of knowledge and training.

R.M. Grounds, M.D.
St. George's Hospital, London SW17 0QT, United Kingdom

4 References

1. 1

   Berry CB, Gillespie T, Hood J, Scott NB. Growth of micro-organisms in solutions of intravenous anaesthetic agents. Anaesthesia 1993;48:30-32
   CrossRef | Web of Science | Medline

2. 2

   Postsurgical infections associated with an extrinsically contaminated intravenous anesthetic agent -- California, Illinois, Maine, and Michigan, 1990MMWR Morb Mortal Wkly Rep 1990;39:426-7, 433
   Medline

3. 3

   McLeod GA, Pace N, Inglis MD. Bacterial growth in propofol. Br J Anaesth 1991;67:665-666
   CrossRef | Web of Science | Medline

4. 4

   Quinn AC, Newman PJ, New LC, Grounds RM. Clinical significance of the growth of micro-organisms in propofol. Anaesthesia 1993;48:923-923
   CrossRef | Web of Science | Medline

To the Editor:

Although Bennett et al. in their retrospective study identified lapses in aseptic techniques during preparation of propofol injections or infusions as the most probable cause of postoperative infectious complications, there is still no evidence to prove that the use of meticulous aseptic techniques in preparing propofol injection or infusion solutions can prevent such complications. It is known that aseptic techniques and hygienic guidelines are often neglected in clinical practice.1 At our institution, where more than 30,000 anesthetic procedures are performed per year, we examined in a quality-control study the extent to which precise compliance with the manufacturer's instructions for the preparation of propofol infusions2 can prevent contamination. Anesthesia personnel were watched while preparing propofol infusions in accordance with the manufacturer's instructions for 91 patients scheduled for hemilaminectomy. Samples of propofol were taken for microbial analysis before the infusion system was connected to the patients' intravenous cannulas (sample 1) and after anesthesia (sample 2) (Table 1Table 1Microbial Analysis of Propofol Samples Prepared for 91 Patients.).

Although no postoperative infections occurred in our small study, the question arises whether, as suggested by Bennett et al. and in the accompanying editorial by Nichols and Smith,3 adherence to the manufacturer's recommendations suffices to prevent contamination of propofol with a high level of certainty. Propofol is a medium particularly well suited to germ growth.

Christian Kolbitsch, M.D.
Cornelia Lass-Flörl, M.D.
Arnulf Benzer, M.D.
University of Innsbruck, A-6020 Innsbruck, Austria

3 References

1. 1

   Rosenberg AD, Bernstein RL, Ramanathan S. Albert DS, Marshall MH. Do anesthesiologists practice proper infection control precautions? Anesthesiology 1989;71:Suppl:A949-A949 abstract.
   CrossRef

2. 2

   Diprivan injection. Wilmington, Del.: Stuart Pharmaceuticals, 1993 (package insert).
   

3. 3

   Nichols RL, Smith JW. Bacterial contamination of an anesthetic agent. N Engl J Med 1995;333:184-185
   Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: The purpose of our combined epidemiologic and laboratory investigation of postsurgical infections was to identify the cause or causes of the outbreaks. The investigations were conducted weeks to months after the clusters occurred, and the materials used at the time of the outbreaks had usually been discarded. Drs. Bach and Geiss are correct that at the time of our investigations we were unable to isolate the same organism from the patient, the anesthesia personnel, and the propofol used during the patient's surgical procedure. However, in each instance the laboratory or epidemiologic evidence or both implicated propofol. Concern about phage typing of S. aureus isolates has centered on the proportion of isolates that are nontypable and the labor required for the method; reproducibility of the method has been good.1 Indeed, selected isolates from hospitals 1 and 3 have been typed by molecular methods, including pulsed-field gel electrophoresis; these findings confirm our phage-typing results.2 Our investigation demonstrates the power of combined epidemiologic and laboratory investigations. Although epidemiologic data alone may identify a source for a cluster, one should be cautious about interpreting molecular-typing results alone. Molecular-typing data should be interpreted in conjunction with epidemiologic data.

We agree with Dr. Grounds and with Kolbitsch et al. that further efforts to educate health care personnel about the appropriate handling of propofol are necessary. Without knowledge of the methods used, it is impossible to determine whether the recovery of skin organisms in the study of Kolbitsch et al. reflects contamination during use, during culturing, or both. The continued reports of clusters of postoperative infections associated with the use of propofol in the United States and Europe indicate the need for further efforts. As the use of this product increases throughout the world and in various settings (intensive care units, wards, outpatient departments, and emergency departments), it is important that active surveillance be maintained for propofol-associated complications. When such episodes occur, the materials involved (e.g., syringes with propofol) should be saved and intensive epidemiologic and laboratory investigations should be initiated.

Siiri N. Bennett, M.D.
William R. Jarvis, M.D.
Centers for Disease Control and Prevention, Atlanta, GA 30333

2 References

1. 1

   Bannerman TL, Hancock GA, Tenover FC, Miller JM. Pulsed-field gel electrophoresis as a replacement for bacteriophage typing of Staphylococcus aureus. J Clin Microbiol 1995;33:551-555
   Web of Science | Medline

2. 2

   Tenover FC, Arbeit R, Archer G, et al. Comparison of traditional and molecular methods of typing isolates of Staphylococcus aureus. J Clin Microbiol 1994;32:407-415
   Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   F. Sztark, F. Lagneau. (2008) Médicaments de la sédation et de l’analgésie. Annales Françaises d’Anesthésie et de Réanimation 27:7-8, 560-566
   CrossRef

2. 2

   Peter H Tonner, Jens Scholz. (2000) Total intravenous or balanced anaesthesia in ambulatory surgery?. Current Opinion in Anaesthesiology 13:6, 631-636
   CrossRef

3. 3

   A. Bach, J. Motsch. (1996) Infectious risks associated with the use of propofol. Acta Anaesthesiologica Scandinavica 40:10, 1189-1196
   CrossRef