Transcript 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
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
Foss, Clin Rehabil 2006; 20:701.


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
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)
16
17
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


Secondary outcomes measured
(presumably) over hospital stay



Validated to predict longer-term outcome
30 days for mortality
Follow-up complete for all patients
~10% of patients excluded from perprotocol analysis
24
4. Do the results fulfill some of the diagnostic tests for
causation?

Did the exposure preceed the outcome?


Is there a dose-response gradient?


Not reported
Is there any positive evidence from a dechallengerechallenge study?


Probably, but timing of transfusion not reported
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
26
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
33
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