Circulation 60,475 • Volume 14, No. 2 • Summer 1999

Sterility of Drawn-Up Drugs an Open Question

Arnold J. Berry, MD, MPH

Editor’s Note: The recent article in Anesthesia and Analgesia (1998;86:994-7) and other papers have generated significant discussion on this issue. Dr. Berry presents an overview of the subject.

Changes in health care economics have mandated that clinicians minimize the cost of patient care while preserving favorable outcomes, and for anesthesiologists, excellent opportunities exist in the areas of drug choice and wastage. In many institutions where emergency trauma, cardiac, or obstetrical anesthetics are performed, pre-drawn syringes of induction drugs, muscle relaxants, and vasopressors remain ready in order to reduce preparation time for anesthetizing critically ill patients. Recently published studies have addressed the safety of this practice by assessing the duration of sterility1 and the chemical stability2 of commonly used medications in pre-drawn syringes. Driver evaluated the sterility of six drugs commonly used in the obstetric operating room (atropine, ephedrine, lidocaine, oxytocin, succinylcholine, and thiopental) for eight days after being prepared in sterile syringes and stored at room temperature.1 The investigators concluded that the true probability of contamination was quite low since there were no positive cultures from the 756 syringes. Based on data from their institution which has two obstetric operating rooms, changing the procedure of daily replacement of pre-drawn syringes of the six drugs to every eight days would save approximately $3,900 annually. In another pertinent publication, Haws assessed the duration of chemical stability and sterility of sodium thiopental which had been reconstituted under a laminar flow hood by a pharmacist and drawn up in syringes.2 Analysis using high-performance liquid chromatography demonstrated chemical stability for thiopental stored at room temperature for six days. There were two positive cultures in 56 syringes maintained for seven days, but since these involved S. epidermidis, the authors suggested that this represented laboratory contaminants.

How can data from these studies be interpreted and what is the implication to our practices? Although Driver and colleagues had no positive cultures in their study syringes, they appropriately calculated a 95% upper confidence limit for the probability of drug syringe contamination of 0.0039.1 This is important since most clinical studies are limited by a small sample size and numerators of zero require this assessment.3 What would be the outcome when data from the small sample is applied to a larger population? Approximately 25 million anesthetics are performed annually in the United States, and with even a low probability of syringe contamination from use of pre-drawn syringes, implementation of this procedure might result in a significant number of patient infections. It has been estimated that a patient with a nosocomial bacteremia requires on average an extra 7.4 days of hospitalization with an attributed increase in cost (1992 US $) of $3,517.4 For an institution incurring a nosocomial bacteremia as a result of an anesthetic practice, any cost saving from the reduced wastage from pre-drawn anesthesia drugs may be negated.

Propofol Again

Shortly after propofol, a lipid-based medication, was introduced into the practice of anesthesiology in the United States, there were multiple reports of outbreaks of blood stream infections produced by extrinsic contamination during preparation or administration of the drug.5 Investigation of these infections demonstrated that proper infection control techniques were not being utilized by some anesthesia personnel. In the studies by Driver and Haws cited above, preparation of syringes was carefully controlled, and undoubtedly, if the same sterile techniques are not applied when implementing the use of pre-drawn syringes, the outcome would differ. The Anesthesia Patient Safety Foundation,6 American Society of Anesthesiologists,7 and Centers for Disease Control and Prevention8 have published guidelines for preventing intravascular infections and the American Society of Health-System Pharmacists has developed a technical bulletin9 to provide information to ensure that products prepared by pharmacists are sterile. Other practices provide alternatives for cost savings related to preparation of medications used during the practice of anesthesiology. At some hospitals, anesthesiologists have arranged for pharmacists to draw up medications from multiple dose vials or other bulk containers. In this manner, wastage from large volume containers would be minimized while breaks in sterility during preparation are less likely. As noted by Haws,2 the cost of thiopental per syringe, including pharmacist and technician wages, is minimized by using 5g bulk packaging rather than 500mg ready-to-mix syringes or single dose kits prepared by anesthesiologists. Similar savings can likely be demonstrated when pharmacists prepare syringes from multiple dose vials. Although Driver1 demonstrated a low probability for contamination of pre-drawn syringes at eight days, one must question why the syringes would not be used more frequently. Since growth of bacteria is more likely with increased time, it appears advisable to rotate inventory so that pre-drawn syringes would be used after one or two days rather than for longer periods, thereby minimizing the risk of infection.

Emphasis on cost saving is warranted within the limits of patient safety. The current studies have suggested a low risk of contamination and chemical stability of pre-drawn syringes when proper infection control techniques are applied. Anesthesiologists should consider their own practices to determine the best methods for preparing for routine and emergency cases in a cost-effective manner. Since the costs to the health care system of any nosocomial infections are quite high, these can negate any savings accrued from minimizing drug costs.

Dr. Berry is with the Department of Anesthesiology, Emory University Hospital, Atlanta, GA.


  1. Driver RP, Snyder IS, North FP, Fife TJ. Sterility of anesthetic and resuscitative drug syringes used in the obstetric operating room. Anesth Analg 1998;86:994-7.
  2. Haws JL, Herman N, Clark Y, Bjoraker R, Jones D. The chemical stability and sterility of sodium thiopental after preparation. Anesth Analg 1998;86:208-13.
  3. Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right? Interpreting zero numerators. JAMA 1983;249:1743-5.
  4. Martone WJ, Jarvis WR, Culver DH, Haley RW. Incidence and nature of endemic and epidemic nosocomial infections. In: Bennett JV, Brachman PS, eds. Hospital infections. Third ed. Boston:Little, Brown and Co., 1992:577-96.
  5. Bennet SN, McNeil MM, Bland LE, et al. Postoperative infections traced to contamination of an intravenous anesthetic, propofol. N Engl J Med 1995;333:147-54.
  6. Berry AJ. Expiration time for a drug drawn into a syringe. In: Recommendations for handling parenteral medications used for anesthesia and sedation. Pittsburgh, PA: Anesthesia Patient Safety Foundation, 1995:7.
  7. American Society of Anesthesiologists. Recommendations for infection control for the practice of anesthesiology, 2nd edition. Park Ridge, IL: American Society of Anesthesiologists, 1998.
  8. Centers for Disease Control. Guideline for prevention of intravascular infections. Am J Infect Control 1983;11:183-93.
  9. American Society of Hospital Pharmacists. ASHP technical assistance bulletin on quality assurance for pharmacy-prepared sterile products. Am J Hosp Pharm 1993;50:2386-98.