Transfusion Thresholds in the Elderly Surgical Patient

Transfusion Medicine Journal Club

Shuen Tan ~ anesthesiologist, skeptic, and budding blood conservationist ~

January 8, 2009

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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)

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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?

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“There’s chronological age and there’s physiological age.”

- Amit Chopra

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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

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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

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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

situationHebert et al., NEJM 1999; 340: 409Nuttall et al., Anesthesiology 2006; 105: 198

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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

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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

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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

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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

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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

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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.

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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

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Results

Transfusion More patients exposed in liberal group (74%

vs. 37%) More transfusions in liberal group (p<0.0001)

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Mortality

5 patients, all in restrictive group No pre-op CV disease

3 CV deaths 1 sudden death 1 “general exhaustion”

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Validity

201. 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

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

- Brian Muirhead

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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?

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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

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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

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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

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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; 20:701Foss and Kehlet. J Bone Joint Surg Br 2006; 88:1053

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Are the results of this study important?

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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

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Mortality

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

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Can this study be applied to our patients?

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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

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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?

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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

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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