INFORMATION FOR HEALTH PROFESSIONALS
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One component is supplied in a polyethylene coated paper packet and consists of 40.8 g of powder (polymer) with the following composition:
The other component is supplied in an amber glass ampoule and consists of 18.8g of a liquid (monomer) with the following composition:
One component is supplied in a polyethylene coated paper packet and consists of 41.8 g of powder (polymer) with the following composition:
The other component is supplied in an amber glass ampoule and consists of 18.8g of a liquid (monomer) with the following composition:
Palacos bone cements with gentamicin are a radiopaque cement-like substance which allows seating and fixation of prostheses to bone and provide antimicrobial activity at the site of implantation. It is formed from the mixture of two separate premeasured sterilised components.
Palacos R with Garamycin is a standard viscosity cement. Palacos E with Garamycin is a low viscosity cement designed for syringe use.
When the powder (polymer) and the liquid (monomer) are mixed, the diemthyl-p-toluidine in the liquid activates the benzoyl peroxide polymerisation catalyst in the powder. This initiates the polymerisation of the monomer which then binds together granules of polymer. As polymerisation proceeds, a dough-like mass is formed which, over a period of 5-6 minutes, hardens into a mechanically uniform solid. Polymerisation is an exothermic reaction with temperatures rising to as high as 80°C. Although the spontaneous generation of heat accelerates the reaction, the polymerisation of this self-curing resin occurs even if the temperature is reduced by irrigation with a cool, physiological saline solution.
Gentamicin is a broad spectrum bactericidal aminoglycoside antibiotic having activity against Gram-negative and Gram-positive bacteria. It is water soluble and heat stable.
In vitro, gentamicin has been shown to be released in active form from the bone cement complex for periods of greater than one year. In man, following total hip replacement in which Palacos was used as a bone cement, the antibiotic was found in joint fluid, blood and urine. Generally levels stay below the levels obtained after parenteral administration of recommended doses of gentamicin and stay far below toxic levels (peak: <10mcg/mL - trough: <2mcg/mL).
Palacos Bone Cement is indicated for fixation of prostheses to bone in partial or total arthroplastic procedures of the hip, knee or other joints in which infection by gentamicin-sensitive organisms is confirmed or suspected.
The amount of bone cement needed will depend upon the specific surgical procedure and the techniques employed. Two units of Palacos bone cement with gentamicin (two sachets and two ampoules) should be available before starting a surgical procedure. The first dose is prepared by mixing the entire contents of one sachet of powder with one ampoule of liquid. If required, a second dose may be used. The maximum recommended dose is two units. Each dose is prepared separately.
An overdose of gentamicin need not to be feared upon the use of Palacos bone cements with gentamicin since at the recommended dose only low serum concentrations are reached during the first post-operative hours.
For special mixing and application techniques, the surgeon must be acquainted with the directions for use applicable to them (for instance, vacuum mixing, vacuum application, use of a medullary-space barrier).
The following are required for preparation of the bone cement:
The polyethylene package and the blister pack are opened by a circulating nurse or assistant and the sterile paper packet and ampoule are aseptically placed on a sterile table. The paper sachet and the ampoule are opened under sterile conditions.
The application technique for Palacos R with Garamycin differs from the technique used with cements of low viscosity (Palacos E with Garamycin).
The mixing can be achieved by two different methods:
The liquid monomer is poured into a bowl and the powder added. The mixture is then stirred slowly and carefully, for 30 to 40 seconds until a dough-like mass is formed, which does not adhere to rubber gloves. At this stage, the mass is kneadable and will remain so for about 4-5 minutes. The kneading time may be affected by temperature, humidity and atmospheric pressure. The ideal working consistency of Palacos R with gentamicin for application to bone is best determined by the surgeon's experience in using the preparation. When the desired consistency is obtained, the preparation may be applied to bone and prosthesis as required. To ensure adequate fixation, the prosthesis should be inserted within five minutes and held securely in place without movement until the bone cement has fully hardened. Generally, this occurs 7-8 minutes after the onset of mixing the powder with the liquid. Excessive cement must be removed while it is still soft.
If during the surgical procedure additional cement is required, another sachet of powder and ampoule of liquid may be mixed as described above. The resulting kneadable mass must be applied to previously applied bone cement before it sets.
Since each sachet contains a premeasured quantity of polymer to react with a premeasured quantity of monomer, care should be taken to mix the entire contents of one sachet with the entire contents of one ampoule.
The mixing and subsequent kneading of the polymerising mass should be thorough. Because of the volatile nature of the monomer, the above procedure may assist in causing its evaporation and thereby reduce the amount to which the patient is exposed. On the other hand, if the kneading process is extended too long, the polymerisation may proceed to a point where the mass is no longer soft and pliable, making manipulation and application to bone difficult. The working time may be affected by temperature.
The completion of polymerisation occurs in the patient and is associated with the liberation of heat. The long-term effects of this heat on the tissues surrounding the bone cement are not known.
Please note recommendations from instrumentation supplier.
Vacuum mixing normally entails cooling the components to 4°C.
In order to obtain a bone cement of reduced porosity, the components of the cement may be mixed together under vacuum after cooling (at least 24 hours at 4°C). The prerequisites for this are the use of an air-tight system and the rapid building-up of a sufficient vacuum in the mixing beaker (normally<200mbar). For vacuum mixing the same stirring time (30 sec) generally applies as upon mixing without vacuum. The times previously given for working, application and hardening apply at approximately 23°C. Higher temperatures will reduce the required time and lower temperatures will prolong it. By the cooling of the components to 4°C, the working and hardening times are increased. The details with regard to the working can be noted from the instructions for use of the instrumentation used. After mixing and where relevant, filling into a cement cartridge, the application window starts approximately 3 to 4 minutes after the start of the mixing. The vacuum-mixed cement and the endoprosthesis should be introduced into the bone within the application window which ends at approximately 7 to 8 minutes after the start of mixing. After insertion the prosthesis must be held securely in place without movement until the bone cement has fully hardened. The cement is completely hard within about 14 minutes.
Low viscosity cements tend to be too fluid for convenient handling. Generally a higher viscosity form of the cement is recommended for manual insertion into the femoral canal and into the prepared acetabulum.
The mixing can be achieved by different methods:
The liquid is poured into a bowl and the powder added. The mixture is stirred slowly and carefully for 20 to 30 seconds and left to stand for the escape of air and until a dough-like mass, which does not adhere to rubber gloves, is formed. Then, the mass is kneaded for approximately two to three minutes. The ideal working consistency of Palacos E with gentamicin is best determined by the surgeon's experience. When the desired consistency is obtained, the preparation may be applied to bone and prosthesis as required. To ensure adequate fixation, the prosthesis should be inserted within five minutes and held securely in place without movement until the bone cement has hardened fully. The entire procedure - from mixing to completion of insertion - takes approximately eight to ten minutes.
Mixing in the barrel of the cement gun may be difficult because Palacos E with gentamicin is liquid in the early stage of mixing, and leakage can occur from the bottom of the barrel.
Therefore, when using a cement gun, the mixing procedure as described above may be followed. A double dose will generally be required. After one minute to allow the escape of air, the cement can be poured into the syringe. Cement can be injected from the gun from approximately 1½ minutes onwards, but has to be controlled carefully by the surgeon, or it may flow out of the bony cavity since it is still runny at this stage. The use of a bone cement restrictor or a bone plug in the femoral canal is recommended. If the femoral canal is filled from the distal end, an air vent is not necessary. The implant should be in place approximately 5½ minutes after mixing the components of the cement, which heats up at approximately 7½ minutes and generally polymerizes by 9½ minutes.
Whether applied by hand or by using a cement gun, pressure should be applied to the cement, until the prosthesis is inserted. Excess cement must be removed while it is still soft.
When using a cement gun, time intervals may be longer due to reduced handling of the cement. Handling the cement warms it slightly during the early stages of polymerization and accelerates the process.
The times previously given for kneading, working and setting apply at approximately 23°C. Higher temperatures will reduce the required time and lower temperatures will prolong it. If during surgery, additional cement is required, another packet of powder and ampoule of liquid may be mixed. The kneadable mass must be applied to the hardened cement without delay to form a continuous mass; delay will increase the risk of laminations forming in the relatively unsupported proximal femoral end, with the possibility of resultant weakness in the cement core.
Since each pack contains premeasured quantities of components, care should be taken to mix the entire contents of one packet with the entire contents of one ampoule.
The working time may be affected by temperature.
The completion of polymerisation occurs in the patient and is associated with the liberation of heat. The long-term effects of this heat on the tissues surrounding the bone cement are not known. To more rapidly dissipate the heat, the polymerising cement may be irrigated with a cool physiologic saline solution.
Please note recommendations from instrumentation supplier.
In order to obtain a bone cement of reduced porosity, the components of the cement may be mixed together under vacuum. The prerequisites for this are the use of an air-tight system and the rapid building-up of a sufficient vacuum in the mixing beaker (normally<200mbar). For vacuum mixing the same stirring time (30 sec) generally applies as upon mixing without vacuum. The times given for working, application and hardening apply at approximately 23°C. Higher temperatures will reduce the required time and lower temperatures will prolong it. The details with regard to the working can be noted from the instructions for use of the instrumentation used. After mixing and where relevant, filling into a cement cartridge, the application window starts 2 to 4 minutes after the start of the mixing. The vacuum-mixed cement and the endoprosthesis should be introduced into the bone within the application window which ends at approximately 5½ to 7 minutes after the start of mixing. After insertion the prosthesis must be held securely in place without movement until the bone cement has fully hardened. The cement is completely hard within about 14 minutes.
Prior to using Palacos bone cements with gentamicin, surgeons should be thoroughly familiar with its properties, handling characteristics and application to arthroplasty. (See Presentation, Dosage and Administration) It is advisable for the surgeon to go through the entire mixing, handling and setting process before using the material in an actual surgical procedure. Thorough familiarity is also required when using mixing systems and syringe application of cement.
The liquid monomer is highly volatile and flammable; therefore, appropriate precaution should be taken particularly with its use in the operating room. The monomer is also a potent lipid solvent and should not be allowed to come in direct contact with the body. Contact with rubber, including surgical rubber gloves, should be avoided.
Care should be exercised during the mixing of the two components to prevent excessive exposure to the concentrated vapours of the monomer. These may irritate the respiratory tract and eyes, and may possibly be harmful to the liver. Skin reactions apparently resulting from contact with the monomer have been reported.
It is recommended by the manufacturer of soft contact lenses that such lenses should be removed in the presence of noxious and irritating vapours. Since soft contact lenses are quite permeable, they should not be worn in an operating room where methylmethacrylate is being mixed.
Blood pressure, pulse and respiration should be carefully monitored during and immediately after implantation of the bone cement. Any significant alteration in these vital signs should be corrected with appropriate measures.
When Palacos bone cements with gentamicin are used in total hip replacements, care should be taken to clean, aspirate and dry the proximal portion of the femoral medullary canal and acetabulum just prior to insertion of the bone cement.
In order to reduce the large increase in pressure in the medullary space during the implantation of the prosthesis, relief of pressure by medullary-space drainage with suction is advisable. In the case of pulmonary cardiovascular disturbances, verification and eventual augmentation of the blood volume may be necessary and anesthesiological measures as in the case of acute respiratory insufficiency should be taken.
As with other aminoglycosides, recommended plasma levels are 1hour peak <10mcg/mL and trough <2mcg/mL as relevant to a tid regimen. These levels are intended to be a guide for the minimisation of risk of nephro- and ototoxicity.
See CONTRAINDICATIONS
Safety in children has not been established.
Transitory fall in blood pressure immediately after implantation of the bone cement and endoprosthesis is frequently observed. Rare cases have been reported in which the hypotension was associated with anaphylaxis, including anaphylactic shock, cardiac arrest and sudden death.
The following additional adverse reactions have been reported with the use of methyl methacrylate bone cements:
thrombophlebitis, superficial wound infection, deep wound infection, pulmonary embolism, haemorrhage and haematoma, trochanteric bursitis, loosening or displacement of the prosthesis, trochanteric separation.
Others which have been observed: heterotopic new bone, myocardial infarction, short-term irregularities in cardiac conduction, cerebrovascular accident.
Since the concentration of gentamicin reaching the VIII nerve and the kidney will be quite small, ototoxic and nephrotoxic reactions are very unlikely to result from the use of Palacos bone cements with gentamicin (see Contraindications for patients with severe renal impairment).
Neuromuscular blockade and respiratory paralysis have been reported in cats receiving high doses (40mg/kg) of gentamicin. The possibility of these phenomena occurring in man should be considered if any aminoglycoside is administered by any route to patients receiving neuromuscular blocking agents, such as succinylcholine, tubocurarine or decamethonium, anaesthetics or massive transfusions of citrate anticoagulated blood. If neuromuscular blockade occurs, calcium salts reverse these phenomena.
Aqueous (antibiotic-containing) solutions should not be admixed in the bone cement since they considerably impair the strength of the cement.
To prevent premature polymerisation, do not store Palacos bone cements with gentamicin in direct sunlight. Resterilisation of any of the components should not be attempted under any circumstances.
Store below 30°C.
Store below 25°C
Prescription Medicine
Palacos bone cements with gentamicin are double packaged. The inner polyethylene coated paper sachet is enclosed in a polyethylene package which is sterilised with ethylene oxide. The polyethylene package(s) are enclosed in a non-sterile aluminium foil protective pack.
The ampoule containing the liquid monomer is packaged in a protective plastic blister pack.
Two sachets containing 40.8 g sterilised powder (polymer), and 2 ampoules containing 18.8g sterilised liquid (monomer).
Two sachets containing 41.8 g sterilised powder (polymer), and 2 ampoules containing 18.8g sterilised liquid (monomer).
The liquid monomer is sterile filtered and the powder polymer is sterilised by ethylene oxide. The polyethylene coated paper sachet containing the powder as well as the exterior of the ampoule containing the liquid, are also sterilised with ethylene oxide.
Palacos bone cements with gentamicin are pigmented light green in order to make it clearly visible in the operative field.
Schering-Plough Pty Ltd
54 Carbine Road
Mt Wellington
Auckland
NEW ZEALAND
July 1998