Sprayable fibrin sealants (Evicel, Tisseel and Artiss): updated guidance
- Medicines and Healthcare products Regulatory Agency
- 20 February 2013
- Therapeutic area:
- Anaesthesia and intensive care
Updated guidance on minimising risk of life-threatening and fatal air embolism.
Article date: February 2013
Fibrin sealants (also known as tissue adhesives or glues) are used in a wide range of surgical procedures to rapidly arrest bleeding and assist in subsequent wound healing. They can be applied by dripping the solution, or by spraying the solution using a pressure regulator, onto bleeding tissue where they form a fibrin clot.
Four sprayable fibrin sealants are authorised in the UK:
- Tisseel Lyo
- Tisseel Ready to use
- Artiss solution for sealant, deep frozen
A European review on the safety of these products was started in 2012, following reports of life-threatening and fatal cases of air embolism occurring in association with the use of spray devices that use a pressure regulator to administer fibrin sealants.
Worldwide, a total of six reports of life-threatening or fatal air embolism have been received with the sprayable fibrin sealants Evicel (5 reports) and Tisseel (1 report), and a further four reports in association with Quixil, a sprayable fibrin sealant which is no longer available in the UK. These events appear to be related to the use of the spray device at higher-than-recommended pressures, and/or in closer proximity than recommended to the tissue surface. We first informed you of this risk in October 2010 and provided updated advice for Evicel in December 2012.
The review considered all available information on this issue, including clinical study data, case reports of suspected adverse reactions and published scientific literature1 2 3 4. The review concluded that the benefits of fibrin sealants in surgery for improvement of haemostasis outweigh the risks, when the instructions for use are followed.
Air embolism has been reported very rarely, however a small risk cannot be excluded. Therefore, a number of recommendations have been made for Evicel, Tisseel and Artiss to minimise the risk of air embolism when these medicines are applied as a spray during surgery.
Advice for healthcare professionals:
To prevent life-threatening air embolism during spray application of a fibrin sealant during surgery, it is important that the following advice on pressure and distance is followed:
|Type of surgery||Product||Maximum pressure (do not exceed)||Minimum distance from tissue (do not spray closer)|
|Open-wound surgery||Evicel||1.7 bar (25 psi)||10 cm|
|Tisseel Lyo/Ready for use||2.0 bar (28.5 psi)|
|Artiss, deep frozen||2.0 bar (28.5 psi)|
|Laparoscopic procedures*||Evicel||1.4 bar (20 psi)||4 cm|
|Tisseel Lyo/Ready for use||1.5 bar (22 psi)||2 cm|
- Only use Evicel or Tisseel in laparoscopic procedures if the minimum spray distance can be accurately judged.
For all products
Prior to applying fibrin sealants by spray application using a pressure regulator device, the surface area of the wound should be dried using standard techniques (eg, intermittent application of compresses, swabs, and use of suction devices).
Closely monitor blood pressure, heart rate, oxygen saturation and end-tidal CO2 when spraying fibrin sealants because of the possibility of air embolism.
For Evicel only
For any spray application using a pressure regulator device, use only CO2 gas (not pressurised air).
In laparoscopic procedures only use when the minimum spray distance of at least 4 cm can be accurately judged.
Do not use in other endoscopic procedures.
For Tisseel only
For spray application in laparoscopic or minimally invasive procedures, use only CO2 gas (not pressurised air). The product should only be used when the minimum spray distance of at least 2 cm can be accurately judged.
For Artiss only
Artiss is recommended for use in open-wound surgery only.
Artiss is not recommended for laparoscopic use (or any other endoscopic procedures).
Report adverse incidents
Please report suspected adverse reactions with fibrin sealants to the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.
Article citation: Drug Safety Update February 2013 vol 6, issue 7: A2.
Chalmers et al. Randomised clinical trial of tranexamic acid-free fibrin sealant during vascular surgical procedures. BJS 2010; 97:1784-1789 ↩
D’Andrilli et al. A prospective randomized study to assess the efficacy of a surgical sealant to treat air leaks in lung surgery. European journal of cardio-thoracic surgery: Official journal of the European Association for Cardio-thoracic Surgery (2009); 35 (5): 817-820; discussion 820-821 ↩
Fischer et al. A randomized trial of aprotinin-free fibrin sealant versus absorbable haemostat. Clin Appl Thromb Hemost 2011 Nov-Dec; 17(6):572-577. Epub 2011 Aug 25 ↩
Foster et al. Efficacy and safety of a fibrin sealant for adherence of autologous skin grafts to burn wounds: results of a phase 3 clinical study. Journal of burn care & research: official publication of the American Burn Association (2008) 29 (2) p 293-303 ↩
Published: 20 February 2013
Therapeutic area: Anaesthesia and intensive care