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 Thresholds in the Elderly Surgical Patient

Transfusion Medicine Journal Club

Shuen Tan

~ anesthesiologist, skeptic, and budding blood conservationist ~

January 8, 2009


Transfusion thresholds in the elderly surgical patient

  • 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

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?


Transfusion thresholds in the elderly surgical patient

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

    - Amit Chopra


Physiologic effects of age

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 age1

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

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

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

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


Methods1

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


Methods2

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

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

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

    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


    Results1

    Results

    • Transfusion

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

      • More transfusions in liberal group (p<0.0001)


    Mortality

    Mortality

    • 5 patients, all in restrictive group

    • No pre-op CV disease

      • 3 CV deaths

      • 1 sudden death

      • 1 “general exhaustion”


    Validity

    Validity


    Transfusion thresholds in the elderly surgical patient

    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


    Transfusion thresholds in the elderly surgical patient

    “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

    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

    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

    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


    Transfusion thresholds in the elderly surgical patient

    • 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

    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

    Are the results of this study important?


    What is the magnitude and precision of the association between the exposure and outcome

    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


    Mortality1

    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

    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

    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

    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

    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

    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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