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Cyclooxygenase-2 inhibitors and knee prosthesis surgery
Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Adverse effects of cyclooxygenase (COX) inhibitors on bone healing have previously been demonstrated in diaphyseal fracture models in animals. In spite of that, they are widely used as postoperative analgesics in orthopaedic surgery. After joint replacement, a bone repair process starts at the interface between bone and cement. If this process is disturbed, the prosthesis may never become rigidly fixed to the bone, leading to migration and with time loosening.

This thesis investigates the effects of a selective COX-2 inhibitor (parecoxib or celecoxib) on bone healing in metaphyseal bone in a rat model and on knee prosthesis migration after total knee replacement, as measured with radiostereometric analysis. Blood loss, postoperative recovery, and the 2-year subjective outcome, were also measured. In addition, a hemoglobin dilution method for blood loss estimation, used in this thesis, was evaluated.

In the first study, pull-out force of a screw inserted in metaphyseal bone of the tibia in rats was only marginally decreased by parecoxib after 7 days but not after 14 days. In the second and third study, celecoxib treatment resulted in less pain postoperatively in conjunction with total knee replacement (TKR), but no effects were seen on blood loss, range of motion, subjective outcome, or prosthesis migration after 2 years.

Comparing the true blood loss of blood donors with the blood loss estimated by the hemoglobin dilution method, this method was found to underestimate the true blood loss. It is therefore not suitable for calculation of the absolute blood loss volume, but may be used for a rough estimate.

In summary, celecoxib and presumably other cyclooxygenase inhibitors seems not likely to increase the risk of prosthesis loosening.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press , 2008. , 48 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1077
Keyword [en]
Non-steroidal anti-inflammatory agents, administration & dosage, Arthroplasty, knee replacement, Surgical blood loss, Surgery, Cyclooxygenase inhibitors, Cyclooxygenase inhibitors, Fracture healing, Isoxazoles, Postoperative pain, Pyrazoles, Sulfonamides
National Category
Surgery
Identifiers
URN: urn:nbn:se:liu:diva-15114ISBN: 978-91-7393-811-2 (print)OAI: oai:DiVA.org:liu-15114DiVA: diva2:54427
Public defence
2008-09-19, Eken, Hälsouniversitet, ingång 65, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2009-08-21Bibliographically approved
List of papers
1. Parecoxib impairs early metaphyseal bone healing in rats
Open this publication in new window or tab >>Parecoxib impairs early metaphyseal bone healing in rats
2006 (English)In: Archives of Orthopaedic and Trauma Surgery, ISSN 0936-8051, E-ISSN 1434-3916, Vol. 126, no 7, 433-436 p.Article in journal (Refereed) Published
Abstract [en]

Introduction Cox2 inhibitors decrease prostaglandin production and therefore influence bone healing especially in unstable long bone models. It is unclear to what extent implant fixation in stable metaphyseal bone is impaired.

Method Male rats numbering 30 and female rats numbering 40 received a stainless steel screw in the metaphyseal bone of the proximal tibia. Half of the rats were treated with 6.4 mg/kg BW parecoxib by continuous release from a subcutaneous mini pump during 7 or 14 days. After treatment, the pull out force, stiffness, and pull out energy of the screw were measured.

Results No effect of parecoxib on the pull out force was found for male rats. In female rats the pull out force was decreased by 16% (P = 0.03) after 7 days treatment with parecoxib. This effect had disappeared after 14 days.

Conclusion Adverse effects of parecoxib on the early phase healing of metaphyseal bone in female rats are small and were not detectable after 14 days. No effect was seen in male rats, possibly due to a faster metabolic elimination of the drug

Place, publisher, year, edition, pages
Springer Link, 2006
Keyword
Cyclooxygenase inhibitors, Parecoxib, Fracture healing, Rats, Bone
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-15108 (URN)10.1007/s00402-006-0160-3 (DOI)
Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2017-12-07Bibliographically approved
2. Effects of celecoxib on blood loss, pain, and recovery of function after total knee replacement: A randomized placebo-controlled trial
Open this publication in new window or tab >>Effects of celecoxib on blood loss, pain, and recovery of function after total knee replacement: A randomized placebo-controlled trial
2007 (English)In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 78, no 5, 661-667 p.Article in journal (Refereed) Published
Abstract [en]

Background: Pain management after surgery has been used as a sales argument for the use of COX-2 inhibitors, but their potential positive and negative effects have not been fully investigated. We thus conducted a controlled evaluation of the effect of celecoxib on perioperative blood loss, pain relief and consumption of analgesics, range of motion, and subjective outcome in conjunction with total knee replacement (TKR).

Method: 50 patients were randomized to either placebo or celecoxib (200 mg) preoperatively and then twice daily. Total blood loss was calculated by the Hb balance method, taking the patient's pre- and postoperative hemoglobin and blood volume into account. Pain scores (VAS), range of motion, and subjective outcome (KOOS) were monitored postoperatively and during the first year after surgery.

Results: No differences in total, hidden, or drainage blood loss were found between the groups. There were 30% lower pain scores during the first 4 weeks after surgery and lower morphine consumption after surgery in the celecoxib group, while no effect was seen on pain, range of motion, and subjective outcome at the 1 year follow-up.

Interpretation: Celecoxib does not increase perioperative blood loss but reduces pain during the postoperative period after TKR. It is not necessary to discontinue celecoxib before surgery. The postoperative use of celecoxib did not increase range of motion or subjective outcome 1 year after TKR.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2007
Keyword
Not available
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-15109 (URN)10.1080/17453670710014365 (DOI)
Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2017-12-07Bibliographically approved
3. Celecoxib does not appear to affect prosthesis fixation in total knee replacement
Open this publication in new window or tab >>Celecoxib does not appear to affect prosthesis fixation in total knee replacement
2009 (English)In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 80, no 1, 46-50 p.Article in journal (Refereed) Published
Abstract [en]

Background and purpose: After joint replacement, a repair process starts at the interface between bone and cement. If this process is disturbed, the prosthesis may never become rigidly fixed to the bone, leading to migration and with time loosening. Cox-2 inhibitors are widely used as postoperative analgesics, and have adverse effects on bone healing. This could tamper prosthesis fixation. We investigated if celecoxib, a selective Cox-2 inhibitor, increases prosthesis migration in total knee replacement (TKR).

Methods: 50 patients were randomized to either placebo or celecoxib 200mg twice daily during 3 weeks after TKR (NexGen®, Zimmer). Maximum total point motion (MTPM) of the tibial component was measured after 2 years using radiostereometric analysis (RSA). In addition, range of motion, pain, and, subjective outcome were evaluated.

Results: No differences in prosthesis migration, pain scores, range of motion or subjective outcome were found after 2 years. Confidence intervals were narrow.

Interpretation: Celecoxib is not likely to increase the risk of loosening and may be used safely in conjunction with TKR.

Keyword
Not available
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-15110 (URN)10.1080/17453670902804976 (DOI)
Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2017-12-07Bibliographically approved
4. Validation of a haemoglobin dilution method for estimation of blood loss
Open this publication in new window or tab >>Validation of a haemoglobin dilution method for estimation of blood loss
2008 (English)In: Vox Sanguinis, ISSN 0042-9007, E-ISSN 1423-0410, Vol. 95, no 2, 120-124 p.Article in journal (Refereed) Published
Abstract [en]

Background and Objectives: Analysis of haemoglobin (Hb) dilution after bleeding is a simple, inexpensive and non-invasive method to estimate blood loss. Blood volume is estimated, taking sex, weight and height into account. The Hb concentration before and after blood loss is analysed and, from the difference, the blood loss volume can be calculated assuming a normovolemic subject. Although widely used this method has never been validated.

Material and Methods: The Hb concentration of 21 blood donors was analysed before and up to 4 days after a standard blood donation and in another 18 blood donors the Hb concentration was analysed before and on day 4, 6, 8, 11 and 14 after blood donation. The blood volume of each donor was calculated and the donated blood volume was estimated by weighing. We calculated the blood loss by the Hb dilution method and compared the calculated value with the donated blood volume.

Results: The mean donated blood volume was 442 ± 10 ml, whereas the mean calculated blood loss was 152 ± 214 ml using the Hb concentration of the first day after donation and 301 ± 145 ml with the Hb concentration of day 6 after blood donation after which no further Hb decrease was observed. The directly measured Hb concentration was always higher than the calculated/expected Hb concentration based on the blood donation volume.

Conclusions: The Hb dilution method underestimates the true blood loss by more than 30% after a moderate blood loss of approximately 10% of the total blood volume.

Place, publisher, year, edition, pages
Wiley InterScience, 2008
Keyword
Blood loss estimation, Hb decrement, Hb dilution
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-15113 (URN)10.1111/j.1423-0410.2008.01071.x (DOI)
Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2017-12-07Bibliographically approved

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