Blood Management in Orthopedic Surgery (TOMaat)

• Peri- and post-operative complications during hospitalization [ Time Frame: up to 3 months after surgery ] [ Designated as safety issue: No ]
• Rehabilitation time [ Time Frame: in hospital ] [ Designated as safety issue: No ]
• Hb/Ht post-operative [ Time Frame: at 14 days and 3 months after surgery ] [ Designated as safety issue: No ]
• Quality of life [ Time Frame: Up to 3 months after surgery ] [ Designated as safety issue: No ]
• Transfusion reactions [ Time Frame: up to 3 months after surgery ] [ Designated as safety issue: Yes ]
• Harris hip / knee society score (for determination of the mobility of the operated joint) [ Time Frame: pre-operative and after 3 months ] [ Designated as safety issue: No ]
• Cost analysis [ Time Frame: up to 3 months after surgery ] [ Designated as safety issue: No ]
• Length of hospital stay [ Time Frame: In hospital ] [ Designated as safety issue: No ]

Aim: to investigate whether the use of several transfusion alternatives (erythropoietin, the cell-saver or postoperative drainage and reinfusion systems) in patients undergoing elective total knee or hip replacement surgery can lead to allogeneic red blood cell (RBC) saving if a restrictive transfusion policy is used.

Study design: a prospective, double randomized, open, multicenter study in which patients are stratified according to their preoperative hemoglobin(Hb) level: stratum I= Hb between 6,1 and 8,2 mmol/l. These patients are first randomized for Erythropoetin (Epo) or no Epo.

Stratum II= Hb of 6,1 and lower or 8,2 mmol/l and higher, are not eligible for Epo and thus not randomized. Patients in both strata will be randomized for three modalities: a cell saver (CS)(to wash, filter and reinfuse autologous shed blood) which is used intra- and postoperatively or a postoperative autologous reinfusion drainage system (D) only (to filter and reinfuse autologous shed blood) or a restrictive transfusion trigger only (controls).

Inclusion criteria: All orthopedic patients of 18 years and older being considered for a primary or revision total knee- (TKR) or total hip replacement (THR).

Outcome measures:

Primary outcome: number of allogeneic red blood cell (RBC) transfusions.

Secondary outcome: transfusion reactions, rehabilitation time, length of hospital stay (days), peri- and post-operative complications during hospitalization, quality of life, cost analysis

Power/data analysis: In order to be able to detect a 75% reduction of allogeneic transfusions by Epo and a reduction of 30% by autologous (shed blood) transfusions (CS or D) with a power= 0.9 and an alpha= 0.05, inclusion of 2250 surgery patients (in a worst case scenario of high standard deviations) are required for intention-to-treat analysis.

Knee surgery patients are not randomized for cell saver (no intra-operative blood loss).

• Other: erythropoietin and cell saver
  weekly 40.000 IU s.c. for 4 weeks pre-operatively; use of cell saver includes intra- and post-operative drainage and reinfusion
  Other Names:

  • Eprex, Ortho-Biotech
  • Neorecormon, Roche
  • OrthoPAT, Haemonetics
• Drug: erythropoietin
  weekly 40.000 IU s.c. for 4 weeks pre-operatively
  Other Names:

  • Eprex, Ortho-Biotech
  • Neorecormon, Roche
• Device: OrthoPAT
  for intra- and post-operative re-infusion of autologous wound blood
  Other Name: OrthoPAT, Haemonetics
• Device: Post-operative drain device
  For post-operative re-infusion of unwashed wound blood
  Other Names:

  • Bellovac-ABT, Astra-Tech, The Netherlands
  • DONOR-drain, Van Straten Medical, The Netherlands
• Other: Erythropoietin and OrthoPAT
  weekly 40.000 IU s.c. for 4 weeks pre-operatively
  Other Names:

  • Eprex, Ortho-Biotech
  • Neorecormon, Roche
  • OrthoPAT, Haemonetics
• Other: Erythropoietin and drain device
  weekly 40.000 IE s.c.for 4 weeks pre-operatively; drain use in post-operative period
  Other Names:

  • Eprex, Ortho-Biotech
  • Neorecormon, Roche
  • Bellovac-ABT, Astra-Tech
  • DONOR-drain, Van Straten Medical
• Device: OrthoPAT
  For intra- and post-operative reinfusion of autologous blood
  Other Name: OrthoPAT, Haemonetics

• Experimental: Erythropoietin
  Intervention: Drug: erythropoietin
• No Intervention: Control arm
• Experimental: cell saver
  Interventions:

  • Device: OrthoPAT
  • Device: OrthoPAT
• Experimental: drain
  Intervention: Device: Post-operative drain device
• Experimental: Erythropoietin and cell saver
  Interventions:

  • Other: erythropoietin and cell saver
  • Other: Erythropoietin and OrthoPAT
• Experimental: Erythropoietin and drain
  Intervention: Other: Erythropoietin and drain device

Inclusion Criteria:

• Orthopaedic patients of 18 years and older being scheduled for a primary or revision total knee (TKR) or total hip replacement (THR).

Exclusion Criteria:

• Patients who refuse homologous blood (e.g.Jehovah's witnesses),
• Patients with untreated hypertension (diastolic blood pressure > 95 mm Hg),
• Patients with a serious disorder of the coronary artery, peripheral arteries and/or carotid arteries,
• A recent myocardial infarction or CVA,
• Sickle cell anaemia patients,
• Malignancy in the operated area,
• Pregnancy,
• Unsuitability for peri-operative anticoagulation prophylaxis,
• Known allergy to erythropoietin,
• An infected wound bed,
• Revision of an infected prosthesis which is being treated with antibiotics, OR
• Patients with difficulty understanding the Dutch language (unable to give informed consent or patients who insufficiently control the Dutch language).

• ZonMw: The Netherlands Organisation for Health Research and Development
• Roche BV Netherlands
• Haemonetics Corporation