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 , 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 , 2005

7. Transfusion thresholds
TRICC
Sick but not bleeding
No difference in mortality with Hb vs
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 Secondary CAS analyzed per-protocol
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. Well-defined patient population Restrictive group “sicker” at baseline
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. Technically double-blind Clinical and subjective assessment of anemia
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. Primary outcome measured over 3 days
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?
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. Benefits of avoiding transfusion
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