Pharmacological management of perioperative anemia ISBT Congress Madrid 2007

1. PHARMACOLOGICAL MANAGEMENT OF
PERIOPERATIVE ANAEMIA:
Our experience with intravenous iron in
orthopaedic surgery.
XVII Regional Congress Europe ISBT
XVIII National Congress SETS
Madrid, June 23 – 27, 2007
Prof. Manuel Muñoz
Transfusion Medicine
School of Medicine
Málaga - Spain

2. Acknowlegments
Dr. J.A. García Erce
Department of Haematology
University Hospital Miguel Servet, Zaragoza
Dr. J. Cuenca
Department of Orthopaedic Surgery
University Hospita Miguel Servet, Zaragoza
Dr. E. Bisbe
Department of Anaesthesiology
University Hospital Mar-Esperança, Barcelona

3. Where do we use blood?
Stanworth et al. Vox Sang 2002; 83: 352-7
Specialty (Directorate) Hospitals (n: 62) Units issued % of traced units
General Surgery 52 81 011 13·62
General & Orthopaedic Surgery 3 9228 1·55
Orthopaedic Surgery only 53 60 470 10·17
Cardiothoracic Surgery 11 48 148 8·14
Accident and Emergency (A & E) 45 33 256 5·59
A & E and Intensive Therapy 1 1105 0·19
Intensive Therapy 20 7328 1·23
Obstetrics/Gynaecology 53 31 101 5·23
Urology 34 15 093 2·54
Neurosurgery 10 5733 0·96
Vascular Surgery alone 8 5387 0·91
Colorectal Surgery 1 1473 0·25
Ear, Nose & Throat (ENT) 30 1966 0·33
Plastic/Maxillofacial/Burns 17 3220 0·54
Total in surgical specialties 304 519 51·25

4. Regan y Taylor, BMJ 2002
Shander, Semin Hematol 2004
 Costs are increasingly rising
 Limited resource
Reasons for reducing ABT use

5. Kleinman et al. Transfusion 2004; 44: 386-90
60%
6779 patients transfused in 1995
Reasons for reducing ABT use

6. Regan y Taylor, BMJ 2002
Shander, Semin Hematol 2004
Reasons for reducing ABT use
 Costs are increasingly rising
 Limited resource
 Adverse effects
 Clerical errors (Wrong blood)
 Viral transmission
 Inmunological complications
(TRALI, GVHD, TRIM)

7. Regan y Taylor, BMJ 2002
Shander, Semin Hematol 2004
Reasons for reducing ABT use
 Legal issues
 Costs are increasingly rising
 Limited resource
 Adverse effects
 Clerical errors (Wrong blood)
 Viral transmission
 Inmunological complications
(TRALI, GVHD, TRIM)

8. 12. Patients should be informed of the known risks and
benefits of blood transfusion and/or alternative
therapies and have the right to accept or refuse the
procedure. Any valid advance directive should be
respected.
Principle of patient’s autonomy
15. Genuine clinical need should be the only basis for
transfusion therapy.
Ethical principles of beneficence and justice
Blood transfusion: Ethical balance

9. Allogeneic Blood Transfusion Alternatives
Correction of
anaemia
Iron, B12, folic
acid, rHuEpo
Reduction of
blood loss
Tranexamic, EACA,
Aprotinin, rFVIIa, …
Autologous Blood
Preoperative autologous donation
Normovolaemic haemodilution
Perioperative cell salvage
Restrictive
transfusion protocol
Hb <70-80 g/L
Blood
saving
program

10. Preoperative haemoglobin level is the major independent
transfusional risk factor in elective orthopaedic surgery
• Nuttall GA et al. Transfusion 1996; 36: 144-149
• Salido JA et al. J Bone Joint Surg 2002; 84-A: 216-220
• Garcia-Erce JA et al. Rev Esp Anestesiol Reanim 2002;49:254-6
As well as in non-elective orthopaedic surgery
• García Erce JA, et al. Med Clin (Barc) 2003; 120: 161-166.
Anaemia, surgery and transfusion

11. Orthopaedic surgery
 Non-elective procedure
 Hip fracture repair

12.  BLOOD LOST
 Capsule
 Fragmentation
 Displacement
 Surgery
 PREVIOUS CHRONIC ANAEMIA
Transfusion rate: 40-90%
HIP FRACTURE AND ANAEMIA
 INFLAMMATION: “hepcidin”
The standard solution

13. Possible role for IV iron
Muscles
(250 mg)
Bone marrow
(300 mg)
Erythrocytes
(2.000 mg)
Macrophages
(500 mg)
Liver
(1000 mg)
Iron absorption
(1-2 mg/day)
Transferrin
(3 mg)
Iron loss
(1-2 mg/day)
20-30
mg/día
Iron sucrose

14. IV iron and hip fracture

15. IV iron and hip fracture

16. IV iron and hip fracture

17. IV iron and hip fracture

18. IV iron and hip fracture

19. IV iron and hip fracture

20. Orthopaedic surgery
 Non-elective procedure
 Hip fracture repair
 Elective procedures
 Preoperative period

21. Preoperative anaemia
Bisbe E, Lamsfus JA. Alteración de los parámetros hematológicos en el preoperatorio de
cirugía ortopédica mayor: prevalencia y tratamiento. In: Muñoz M, Bisbe E, García-Erce JA,
Giralt M (eds): Actualización en Anemia y Medicina Transfusional Perioperatoria. Málaga,
SPICUM, 2006: 55-62.

22. Patients and methods: We assessed the requirements for ABT in 156 consecutive patients
undergoing surgery for primary TKR, who received iron ferrous sulphate (256 mg/day; 80
mg of Fe2+), vitamin C (1000 mg/day) and folic acid (5 mg/day) during the 30-45 days
preceding surgery, and who were transfused if Hb <80 g/L and/or clinical signs/symptoms
of acute anaemia or hypoxemia (Group 2). A previous series of 156 TKR patients serves as a
control group (Group 1).
Oral iron and knee surgery

23. Oral iron and knee surgery

24. IV iron and orthopaedic surgery

25. Orthopaedic surgery
 Non-elective procedure
 Hip fracture repair
 Elective procedures
 Preoperative period
 Perioperative period

26. IV iron and knee surgery
Blood saving protocol
• In Group A (n=139), consecutive TKR patients received iron sucrose
intravenously (200 mg), 24 hours before surgery and 24 hours after
surgery. Patients with preoperative Hb levels <13 g/dL also received a
single dose of rHuEPO (40,000 IU, sc; Eprex) 24 hours before surgery.
• This protocol plus was applied to a second series of consecutiveTKR
patients who also received postoperative unwashed shed blood (USB) if
preoperative Hb levels <13 g/dL (Group B, n=173).
• In these two groups, transfusion was indicated when patient’s Hb <8 g/dL
or when patient presented symptoms of acute anemia.

27. IV iron and knee surgery
Overall ABT rate:
4.2%

28. IV iron and knee surgery

29. Orthopaedic surgery
 Non-elective procedure
 Hip fracture repair
 Elective procedures
 Preoperative period
 Perioperative period
 Postoperative period

30. Postoperative IV iron and hip surgery

31. Postoperative IV iron and hip surgery

32. Postop oral iron and hip/knee surgery
Randomised controlled trials in orthopaedics
 Ferrous sulphate (200 mg/d) 3 weeks
Mundy et al. JBJS 2005; 87-B: 213-7
 Ferrous sulphate (200 mg/d) 6 weeks
Sutton et al. JBJS 2004; 86-B: 31-3
 Ferrous gluconate (325 mg/d) 10 weeks
Weatherall et al. ANZ J Surg 2004; 74: 1049-51
Oral iron did not improve haemoglobin levels !!!!

33. Conclusions
NATA Expert Panel on Intravenous Iron
ANAEMIA MANAGEMENT IN SURGERY –
CONSENSUS STATEMENT ON THE ROLE OF INTRAVENOUS IRON
Photis Beris, Manuel Muñoz, José A. García-Erce,
Dafydd Thomas, Alice Maniatis & Philippe Van der Linden.
- Grade of recommendation: .
“For patients undergoing orthopaedic surgery expected to develop severe
postoperative anaemia we currently suggest IV iron administration during
the perioperative period”. For all other surgeries no evidence-based
recommendation can be made. We strongly recommend that large prospective
randomised controlled trials are undertaken in patients undergoing surgery
expected to develop severe post operative anaemia.

34. Whenever clinically feasible, patients undergoing orthopaedic elective
surgery with a high risk of severe postoperative anaemia should have
haemoglobin level and iron status tested a minimum of 30 days
before the scheduled surgical procedure.

Unexplained anemia should always be considered as secondary to
some other process and, therefore, elective surgery should be deferred
until an appropriate diagnosis has been made

Good practice points
Patients at risk of receiving perioperative transfusions should be
identified, on the basis of patient’s RBC mass, the transfusion trigger
and the expected blood loss (e.g., using Mercuriali’s algorithm)


35.  Non-anaemic patients with ferritin <100 ng/mL and scheduled for
surgical procedures with an expected blood loss >1500 mL (Hb drop 3-5
g/dL) might benefit from preoperative oral or IV iron administration, as
they may not have enough stored iron to reconstitute their perioperative Hb
loss and keep normal iron stores (ferritin ≥30 ng/mL)

Good practice points
Patients with preoperative IDA or ACD might receive preoperative
treatment with IV iron, with or without rHuEPO. In addition, IV iron
should be given to improve the response to rHuEPO and might allow for a
reduction in the total dose of rHuEPO

The administration of IV iron should be avoided in patients with pre-
treatment ferritin > 500 ng/mL. Nevertheless, IV iron should no be given
to patient with ongoing bacteremia
Thank you for your kind attention!

37. Participan el matrimonio de sus hijos
Isabel y José Antonio
y les invitan a la ceremonia religiosa que se celebrará (D. m.)
el día 22 de Septiembre, a las doce del mediodía, en la
Santa Iglesia Catedral de Jaca y a la comida que se servirá a
continuación en el restaurante La Cocina Aragonesa
C/ Universidad 2, 6º B Plaza Irineo González 5,1º
Jaca (Huesca) S. R. C. Santa Cruz de Tenerife
Tfno: 654767224 Jaca, 2007 Tfno: 670807552
Luis Villar Pérez
Mª Carmen Fernández Larrea
José Emilio García Gómez
Mª Teresa Erce Lizarraga