Transfusion thresholds in the elderly surgical patient
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Transfusion Thresholds in the Elderly Surgical Patient. Transfusion Medicine Journal Club Shuen Tan ~ anesthesiologist, skeptic, and budding blood conservationist ~ January 8, 2009. The effects of liberal versus restrictive transfusion thresholds on ambulation after hip fracture surgery

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Transfusion Thresholds in the Elderly Surgical Patient

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Transfusion Thresholds in the Elderly Surgical Patient

Transfusion Medicine Journal Club

Shuen Tan

~ anesthesiologist, skeptic, and budding blood conservationist ~

January 8, 2009


  • 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)


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?


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

    - Amit Chopra


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


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


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


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


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


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


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


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


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.


    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


    Results

    • Transfusion

      • More patients exposed in liberal group (74% vs. 37%)

      • More transfusions in liberal group (p<0.0001)


    Mortality

    • 5 patients, all in restrictive group

    • No pre-op CV disease

      • 3 CV deaths

      • 1 sudden death

      • 1 “general exhaustion”


    Validity


    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


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

    - Brian Muirhead


    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?


    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


    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


    • 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


    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


    Are the results of this study important?


    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


    Mortality

    • 5 patients, all in restrictive group

      • No pre-existing CV disease

      • 3 CV conditions

      • 1 sudden death, unexplained

      • 1 “general exhaustion”


    Can this study be applied to our patients?


    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


    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?


    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


    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


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