Transfusion Thresholds in the Elderly Surgical Patient

1. Transfusion Thresholds in the Elderly Surgical Patient Transfusion Medicine Journal Club Shuen Tan ~ anesthesiologist, skeptic, and budding blood conservationist ~ January 8, 2009

2. The effects of liberal versus restrictive transfusion thresholds on ambulation after hip fracture surgery • Foss, NB, Kristensen MT, Jensen PS, Palm H, Krasheninnikoff M, Kehlet H • Transfusion epub (accepted for publication August 25, 2008)

3. The Issues • Is age a disease? • If so, what is old? • How do surgical patients differ from medical patients? • How does that affect decisions to transfuse?

4. “There’s chronological age and there’s physiological age.” - Amit Chopra

5. Physiologic effects of age • Decrease in physiological reserve • “This decline is evident by the third decade and is gradual and progressive, although the rate and extent of decline vary.” • Cardiovascular • Hypotensive response to HR, hypovolemia, or arrhythmia •  CO/HR response to stress Harrison’s 16th ed., pp. 44-45, 2005

6. Physiologic effects of age • Respiratory • V/Q mismatch •  lung elasticity,  chest wall compliance •  resting pO2 • MSK/Neuro • Osteopenia • Stiffer gait,  body sway Harrison’s 16th ed., pp. 44-45, 2005

7. Transfusion thresholds • TRICC • Sick but not bleeding • No difference in mortality with Hb 70-90 vs. 100-120 • Surgical patients • Bleeding but not sick • Dilutional anemia / Fluid shifts • Guidelines vague, depending on clinical situation Hebert et al., NEJM 1999; 340: 409 Nuttall et al., Anesthesiology 2006; 105: 198

8. Methods • Prospective, single-centre (Denmark), randomized, double-blind study • Hip fracture patients • February 2004 to July 2006 • Inclusion criteria: • Primary hip #, age >65, independent walking pre-fracture, community dwelling, intact cognition

9. Exclusion criteria • Multiple #s, terminal condition, alcoholism, chronic transfusion, acute cardiac or severe medical condition, contraindication to neuraxial block • Post-op immobilization, transfer for medical complications, return to OR within 4 days

10. Methods • Powered to show 25% reduction in CAS with =0.05 and power of 0.80 • Assumed 69% transfusion rate with liberal threshold • 120 patients, 60 in each arm • Liberal group transfused at Hb<10 g/dL • Restrictive group transfused at Hb<8 g/dL

11. Methods • Standardized perioperative care • Standardized fluid therapy by weight • Hb on admission, in PACU, and OD x 5 • Intraop PRN only • Allocation revealed only if Hb<10, to attending physician only

12. Outcomes • Primary • CAS analyzed per-protocol • Secondary • Length of stay, cardiac complications, infectious complications, 30-day mortality • Measured by intention-to-treat • Anemia score by PT

13. The Cumulated Ambulation Score (CAS) • Locally developed and validated • Length of stay, time to discharge, 30-day mortality, and major medical complications decreased with CAS >9 • Numerical representation of patient’s functional mobility • Three parameters assessed on 3-pt. scale • Max score = 6 • Cumulated over POD 1-3 • Predictive of postop rehabilitation outcome Foss, Clin Rehabil 2006; 20:701.

14. Results • Demographics • More patients with ASA 3 in restrictive group (p=0.02) • More pins/screws in restrictive group (0.05) • More SHS and IMHS in liberal group (0.02) • Predictive of increased blood loss (?) • IMHS and pins/screws are outliers • DHS and arthroplasty similar for blood loss Foss and Kehlet, J Bone Joint Surg Br 2006; 88: 1053

15. Results • Transfusion • More patients exposed in liberal group (74% vs. 37%) • More transfusions in liberal group (p<0.0001)

18. Mortality • 5 patients, all in restrictive group • No pre-op CV disease • 3 CV deaths • 1 sudden death • 1 “general exhaustion”

19. Validity

20. 1. Were there clearly defined groups of patients, similar in all important ways other than exposure to the treatment? • Well-defined patient population • Restrictive group “sicker” at baseline • Larger proportion of ASA 3 patients • Surgeries similar in intention-to-treat analysis • More SHS and IMHS in liberal group • Blood loss similar

21. “You’re forgetting the two most important determinants of intraoperative blood loss -- the surgeon and the anesthesiologist.” - Brian Muirhead

22. 2. Was the assessment of outcomes either objective or blinded to exposure? • Technically double-blind • Patient and PT unaware of allocation • Clinical and subjective assessment of anemia • Attending physician aware of transfusion group • Interaction with PT • Lab reports on chart or computer?

23. 3. Was the follow-up of the study patients sufficiently long and complete? • Primary outcome measured over 3 days • Validated to predict longer-term outcome • Secondary outcomes measured (presumably) over hospital stay • 30 days for mortality • Follow-up complete for all patients • ~10% of patients excluded from per-protocol analysis

24. 4. Do the results fulfill some of the diagnostic tests for causation? • Did the exposure preceed the outcome? • Probably, but timing of transfusion not reported • Is there a dose-response gradient? • Not reported • Is there any positive evidence from a dechallenge-rechallenge study? • Not reported • Is the association consistent from study to study? • One previous study also showed no difference in ambulation with restrictive threshold • 60-day mortality in restrictive group: RR = 2.5 Carson et al. Transfusion 1998; 38:522

25. Does the association make biological sense? • Plausible that increased Hb might lead to less fatigue, less CV complications, and less delirium, thus better ambulation • Hb values were similar throughout study despite different thresholds • Ambulation may be related more to multimodal rehab

27. Multimodal Post-Fracture Rehab • Dedicated hip fracture unit • Surgery within 24 hours • Epidural at admission until 96 hours post-op • Supplemental O2 while supine • Perioperative LMWH • Enforced perioperative nutrition and hydration • Intensive PT starting POD 0 Foss et al. Clin Rehabil 2006; 20:701 Foss and Kehlet. J Bone Joint Surg Br 2006; 88:1053

28. Are the results of this study important?

29. What is the magnitude and precision of the association between the exposure and outcome? • Primary outcome identical (CAS 9) • Range similar between groups • Harm in restrictive group •  CV events: 10% vs. 2%, p=0.05 •  30-day mortality: RR = 2.1, p=0.02 •  Infectious complications: p = 0.19 •  Length of stay: p = 0.61

30. Mortality • 5 patients, all in restrictive group • No pre-existing CV disease • 3 CV conditions • 1 sudden death, unexplained • 1 “general exhaustion”

31. Can this study be applied to our patients?

32. 1. Are our patients so different from those in the study that the results don’t apply? • The uppermost echelon of hip fracture patients • Dr. Shuen’s broken hips • Nursing home • Moderate dementia • Walkers and wheelchairs • Anemic, cachectic, CV disease, anticoagulated, etc…. • 500 patients screened for inclusion

34. 2. What is our patient’s risk of an adverse event, and potential benefit from the therapy? • Average hip fracture patients at higher risk of CV complications than those in the study • Risk difficult to quantify • Unknown if raising transfusion threshold would mitigate risk • Benefits of avoiding transfusion • TRALI and TACO in susceptible population • Coagulopathy • Wound healing and infection?

35. 3. What alternative treatments are available? • Emergent surgery, limited time to optimize pre-op Hb • Other blood conservation • Early surgery, Cell-saver, anti-fibrinolytics, limited blood draws, nutritional supplements • Aggressive multi-modal rehab • Increased monitoring and index of suspicion for CV events

36. Summary • Liberalizing transfusion thresholds for elderly hip fracture patients does not improve post-op ambulation • Restrictive thresholds may put patients at higher risk of CV morbidity/mortality • Any benefit associated with transfusion may be outweighed by the benefits of multimodal rehabilitation