International

International Orthopaedics (SICOT) (1991) 15: 305- 309

Orthopaedics © Springer Verlag 1991

The release of gentamicin after total hip replacement using low or high viscosity bone cement A prospective, randomized study L. Lindberg ~, R. Onnerfiilt 2, E. Dingeldein 3, and H. Wahlig 3 t Department of Orthopaedic Surgery, Centralhospital, Kristianstad, Sweden 2 Department of Orthopaedic Surgery, University Hospital, Lund,Sweden 3 Department of Medical Microbiology,E. Merck, W-6100Darmstadt, Federal Republic of Germany

Summary. Low viscosity bone cement is expected to give improved long term fixation o f prosthetic components by increased intrusion into cancellous bone. Fixation is more difficult to achieve after revision for infection because o f the inferior quality of the bone. We have compared the amount o f gentamicin released from high viscosity and low viscosity bone cements in 41 patients undergoing total hip replacement. The concentration of gentamicin in serum and the wound secretion, and the amount recovered from the urine, was about three times higher for low viscosity cement. A possible explanation for this is an increase in surface area o f the cement body because of improved intrusion o f cement into bone. The improved mechanical fixation and the high concentration of gentamicin o f the bone cement interface favours the use of low viscosity cement, especially in revision for deep infection. R6sum& I1 nous semble que le scellement par un ciment osseux d basse viscositb permet une meilleure fixation des piOces prothbtiques en assurant une meilleure pbnktration du ciment dans l'os spongieux. Cette fixation est encore plus difficile d obtenir quand il s'agit de reprise d'une prothdse infectbe en raison de la mauvaise qualitb de l'os. Nous avons btudib in vivo, chez 41 malades opkrbs d'arthroplastie totale de hanche, les propribtbs pharmacocinbtiques de la gentamicine libbrke d partir de deux types de ciment, l'un d basse et l'autre d haute viscosit& Les concentrations de gentamicine libbrbe dans le sbrum, dans les exsudats de la plaie opkratoire et dans les urines ktaient trois fois plus blevbes

Reprint requests to: R. 13nnerf~ilt, Department of Orthopaedic Surgery, Lasarettet, S-22185, Lund, Sweden

dans les cas o~ on avait util&k un ciment d basse v&cositb. La quantitb de ce ciment n'ktant que lbgbrement supbrieure, la seule explication valable est une meilleure pbnbtration du ciment, augmentant la surface de contact avec l'os. On peut en conclure que le choix d'un ciment d basse viscositb est particulibrement indiqu~ dans les reprises de prothOses infectkes, d'une part parce qu'il assure une meilleure f x a t i o n et d'autre part parce qu'il permet d'obtenir des concentrations klevbes de gentamicine, efficaces m~me sur les bactbries rbsistantes aux concentrations obtenues par voie parentbrale.

Introduction Better intrusion of acrylic cement into cancellous bone is expected to give improved long term fixation of prostheses, since micro movement between cement and bone is minimised. Low viscosity bone cement used with improved cementing technique enhances the interdigitation of acrylic with bone [5, 10, 12], but it is not known whether it offers advantages in the long term compared to the high viscosity. Long term clinical studies comparing both types of cement are still awaited. In revision of infected endoprostheses good interdigitation is vital because of the inferior quality of the bone. It is therefore important to assess the properties of low viscosity cement containing gentamicin for comparison with the high viscosity product. We have assessed the release of gentamicin after primary total hip arthroplasty using both low and high viscosity bone cement mixed with gentamicin.

306

L. Lindberg et al.: Release of gentamicin after total hip replacement

Table 1. The composition of the two bone cements

!Jg/ml 100 -

Cement A (high viscosity) 1 bag contains: Poly(methylacrylate, methylmethacrylate) 12:88 Zirconium(IV):oxide Benzoylperoxide Gentamicin-base 1 ampoule contains 20 ml: Methylmethacrylate N,N-Dimethyl-p-toluidine

33,70 6,00 0,30 0,50

g g g g

18,40 g 0,38 g

Cement B (low viscosity) 1 bag contains: Poly(methylacrylate, methylmethacrylate) 6:94 Zirconium(IV)-oxide Benzoylperoxide Gentamicin-base 1 ampoule contains 15 ml: Methylmethacrylate N,N-Dimethyl-p-toluidine

24,80 4,70 0,30 0,75

g g g g

13,80 g 0,28 g

I

I

I

I

I

I

I

I

I

2

3

4

5

6

7

8

9

10

days

Fig. 1. Release of Oentamicin from cement A and B in vitro, • Gentamicin-Palacos R (A) (0.5 g G e n t a m i c i n - b a s e / 4 0 g polymer-powder), • Gentamicin-Palacos flow (B) (1.0 g Gentamicin-base/40 g polymer-powder)

Material and methods Bone Cement The high viscosity P M M A 1 chosen for this investigation, cement A, has been used in orthopaedic surgery for about 20 years, and its characteristics are well known [15, 16]. Low viscosity cement ~, cement B, is chemically similar to the high viscosity material, but the relation of polymer and co-polymer is different, and the amount of gentamicin greater (Table 1). Although the chemical composition of the two cements is similar the release of the added gentamicin differs. In an in vitro investigation Wahlig and Dingeldein [17] showed that the release of gentamicin from low viscosity cement is only half of that from the high viscosity, when comparing cylinders of cement of the same standard size for both materials. The concentration of gentamicin in the fluid surrounding cylinders of cement B did not reach the concentration surrounding cement A until the amount of gentamicin in B was doubled (Fig. 1). To achieve the same local concentration in vivo, cement A contained gentamicin sulphate corresponding to 0.5 g of gentamicin base, and cement B gentamicin sulphate corresponding to 1 g of gentamicin base per 40 g of polymer powder. The addition of 1 g of gentamicin base to 40 g of polymer powder, or 0.75 g of gentamicin base to 30 g of powder, resulted in a

reduction of impact and bending strength. This was not inferior to that of Gentamicin-Palacos R (Table 2) (W. Ege, personal communication). Low viscosity cement is fast curing, taking about eight minutes at 22 ° C. After mixing, this cement has a viscosity close to Sulfix 6 or Zimmer LVC, but it quickly rises during handling [6].

Cementing technique Cement A was kept at 4 ° C and taken to the operating theatre immediately before mixing, whereas cement B was kept at room temperature. The technique of cementing was standardized, with plugging of the distal marrow cavity of the femur, the use of a cement gun, sealing of the proximal femur, use of a pressuriser for the acetabulum and high pressure lavage. Both cements were applied with the gun into the femur after one to two minutes, and into the acetabulum as soon as the cement could be handled without sticking to the gloves, which had been moistened with saline. At the end of the operation a deep suction drain was installed, and the weight of the cement implanted into the patient was noted.

Patients ~ Refobacin-Palacos and E M D 42522 both supplied by E. Merck, Darmstadt

Forty seven patients were randomly allocated to either the cement A or cement B groups and underwent total hip arthro-

Table 2. Mechanical strength of the two cement types Bone cement

Young's modulus N/mm 3

Compressivum MPa

High viscosity with gentamicin (Group A)

s =

2226 141

s =

Low viscosity with gentamicin (Group B)

s =

2529 59

s =

95,11 2,57 118,3 118,3

Impact KJ/mm 2

Bending N/mm s

3,05 s = 0,19

74,40 s = 3,40

3,72 1,54

73,70 s = 2,70

s =

307

L. Lindberg et al. : Release of gentamicin after total hip replacement plasty; 28 had operations at the Department of Orthopaedic Surgery, Central Hospital in Kristianstad and 19 at the Department of Orthopaedic Surgery, University Hospital, Lund, Sweden. Six patients were excluded because they had received systemic antibiotics during their stay in hospital. Of the remaining 41 patients, 20 received cement A and 21 cement B. Group A consisted of 13 men and 7 women, with a mean age of 71 (57-83) years, and G r o u p B had 10 men and 11 women, with a mean age of 69 (60-79) years.

Table 3. Gentamicin concentrations in serum (pg/ml)

Hours after operation 2

4

6

24

48

GroupA high viscosity

Mean SEM Min Max Median

0.37 0.04 0.05 0.85 0.36

0.44 0.04 0.11 0.88 0.40

0.38 0.03 0.13 0.67 0.33

0.28 0.03 0.05 0.50 0.23

0.06 0.01 0.02 0.15 0.06

0.03 0.00 0.02 0.09 0.02

Group B low viscosity

Mean SEM Min Max Median

1.40 0.15 0.39 2.86 1.51

1.49 0.14 0.40 2.66 1.47

1.19 0.12 0.37 2.65 1.09

0.86 0.10 0.17 2.10 0.81

0.21 0.02 0.02 0.49 0.20

0.13 0.01 0.02 0.27 0.13

Sample collection The concentration of gentamicin in the serum, the drainage fluid and the urine was measured during the first ten days after operation. Blood samples were taken before operation and at 2, 4, 6, 24 and 48 h after, and on the fourth, sixth, eighth and tenth postoperative days. The wound drainage was collected, the volume measured and samples taken at fixed intervals at 0 - 2 , 2 - 6 , and 6 - 2 4 h after operation, and then every 24 hours until the drainage tube was removed. The urine was collected during each 24 h of the first ten days after operation, and samples were taken from each volume. All samples were immediately frozen at - 2 0 ° C and stored at this temperature until the gentamicin concentration was determined.

0,5

Table4. (,ug/ml)

Gentamicin

concentrations

The concentrations in serum, urine and wound secretion were measured by the agar diffusion test using Bacillus subtilis ATCC 6633 [4]. Standard dilutions were always prepared in appropriate media. The lower level of sensitivity for this technique was 0.05ttg/ml.

secretion

2-6

6-24

24-48

Group A high viscosity

Mean SEM Min Max Median

22.12 2.65 5.90 51.80 22.40

10.88 1.55 0.90 28.10 9.85

6.39 0.74 1.80 11.60 5.50

5.64 0.71 3.00 11.10 4.55

Group B high viscosity

Mean SEM Min Max Median

73.49 11.16 7.30 232.00 66.25

30.85 4.38 8.60 84.60 25.40

26.85 3.64 1.90 58.00 26.85

18.93 3.15 6.00 42.30 18.20

Results

A comparison between the two groups shows that the concentration of gentamicin in the serum was 3 - 4 times higher in Group B (p

The release of gentamicin after total hip replacement using low or high viscosity bone cement. A prospective, randomized study.

Low viscosity bone cement is expected to give improved long term fixation of prosthetic components by increased intrusion into cancellous bone. Fixati...
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