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Filtration and Emulsion Drugs
  Filtration and Emulsion Drugs


Emulsion drugs are used increasingly in intensive care and anaesthesia
Emulsion drugs such as propofol are used increasingly as sedation and anaesthetic agents. Large volumes of such drugs can be administered during intensive care sedation or in anaesthesia for long surgical procedures.Lipid emulsions support the growth of microbes

It has been demonstrated that lipid emulsions, including nutrient lipid emulsions and emulsion drugs, support the rapid growth of micro-organisms1,2,3,4. Bacterial species such as Staphylococcus, Moraxella and Escherichia, and fungi such as Candida, can proliferate rapidly at room temperature in drugs such as propofol and diazepam emulsion.






Inadvertent microbial contamination is a risk associated with all IV therapy

Each manipulation carries a risk of introducing microbial contamination. It has been demonstrated that extrinsic contamination of emulsion drugs can occur during normal procedures involved in handling emulsion drugs5.

Clusters of infection have been linked to contaminated emulsion drugs

At least 38 clusters of infection, involving more than 150 patients with at least four deaths, have been reported to the US FDA to be linked to extrinsic contamination of emulsion drugs. Seven independent investigations of outbreaks of post-surgical infections, implicating extrinsic contamination of an emulsion anaesthetic agent and involving 62 patients, were reviewed by the US Centre for Disease Control, who concluded that

"..no other single intravenous agent has been associated with such widespread outbreaks of extrinsic contamination or has been contaminated by such a wide variety of organisms."6

In Europe, a cluster of Klebsiella infection was similarly attributed to extrinsic emulsion drug contamination7. Nosocomial bloodstream infections increase mortality and add significantly to the cost of patient care.It has been estimated that nosocomial bloodstream infections add 7-21 days to hospital stay and between $3,061 and $40,000 to the cost of hospitalisation8. The excess mortality rate in ICU patients attributable to bloodstream infections has been reported to vary between infecting organisms, from 13.8% for coagulase staphylococci and 38% for Candida, with an overall excess mortality rate of 28%9.

It is now possible to filter emulsion drugs

Until recently, it has not been possible to pass emulsions through microbiological filters. With the development of new filter technology, pioneered in the field of parenteral nutrition, it is now possible to use highly efficient filters with emulsion drugs. The Pall Lipipor membrane allows filtration of emulsions at clinical flow rates, whilst retaining contaminants of clinical significance, with no adverse effect on emulsion stability10 or drug delivery11.

Test # Pre-filtration Post-filtration
at 1440mL/hr
Post-filtration
at 60mL/hr
1 0.982 0.996 0.97
2 0.99 1.005 0.986
3 1.044 0.964 0.986
Mean 1.005 0.98 0.981
Table 1. Concentration of propofol determined by HPLC in samples before and after filtration

Filtration provides an additional safety measure for patients receiving emulsion drugs

Filtration can offer additional patient protection against extrinsic microbial contamination of emulsion drugs10.

Challenge
organism
Total
challenge
Removal
efficiency
Candida albicans 2.5 x 104 complete
Klebsiella pneumoniae 1.7 x 104 complete
Moraxella osloensis 1.7 x 104 complete
Staphylococcus aureus 4.5 x 104 >99.8%
Table 2. Removal of micro-organisms from propofol by Pall Lipipor EDF

It also protects against particulate contamination, which has occurred in emulsion drugs presented in glass


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Summary
  • Emulsion drugs are used increasingly in intensive care and anaesthesia.
  • Lipid emulsions support the growth of microbes.
  • Inadvertent microbial contamination is a risk associated with all IV therapy.
  • Clusters of infection have been linked to contaminated emulsion drugs.
  • Nosocomial bloodstream infections increase mortality and add significantly to the cost of patient care.
  • It is now possible to filter emulsion drugs.
  • Filtration provides an additional safety measure for patients receiving emulsion drugs.

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References
  1. CB Berry et al. Growth of micro-organisms in solutions of intravenous anaesthetic agents. Anaesthesia 1993; 48:30-32.
  2. MJ Arduino et al. Microbial growth and endotoxin production in the intravenous anesthetic propofol. Infection Control and Hospital Epidemiology 1991;12:535-539.
  3. MB Sosis et al. Propofol, but not thiopentone, supports the growth of Candida albicans. Anesthesia and Analgesia 1995; 81:132-134.
  4. M Tessler et al. Growth curves of Staphylococcus aureus, Candida albicans and Moraxella osloensis in propofol and other media. Canada J Anaesthesia 1992; 39:509-511.
  5. GA MacLeod et al. Bacterial growth in propofol. British J Anaesthesia 1991; 67:665-666.
  6. SN Bennett et al. Postoperative infections traced to contamination of an intravenous anesthetic agent, propofol. New England Journal of Medicine 1995; 333:147-154.
  7. B Veber et al. Severe sepsis after intravenous injection of contaminated propofol. Anesthesiology 1994; 80:712-713.
  8. WR Jarvis. Selected aspects of the socioeconomic impact of nosocomial infections: morbidity, mortality, cost and prevention. Infection Control and Hospital Epidemiology 1996;17:552-557.
  9. S Harbath & D Pittet. Excess mortality and impact of intensive care unit-acquired infections. Current Opinion in Anaesthesiology 1996; 9:139-145.
  10. AJ Hunter et al. End-line filtration of lipid emulsions used in intravenous therapy. Presented at the Parenteral Drug Association congress, Vienna, February 1996.
  11. TG Baumgartner et al. The safety and efficacy of 0.45 micron filtration of the first parenteral medication in a lipid vehicle. Journal of Parenteral and Enteral Nutrition 1996; 20:No1.295.

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