Transfusion Targets in
Brain Injury
Dr Jonathan Tan
Senior Consultant, Anaesthesiology & Intensive Care.
Tan Tock Seng Hospital, Singapore
RBC Transfusion?
What is YOUR transfusion threshold for
TBI? SAH?.... +/- IHD?
Why are you transfusing?? Are you
achieving that Aim??
Monitoring: Benefits? Morbidity? Review
Transfusion: will it help?
TBI
35/M Fall from Height. E2V2M2 ED. Isolated HI. Bifrontal contusions, occipital contra coup contusions.
Sedated. Intubated. ICP monitor inserted. ICP 20. Osmotherapy.
Day 3:Hb 8.3. Coags, Platelets Normal
FiO2 40%, Peep +8. PaO2, PaCO2 target range
Transfuse??
Considerations?? Other Info??
What if….
Age 78?
IHD, DM, Hypertension, Baseline Creat 150
ICP 15? 20? 25? 30?
Multi Trauma:- Hip and pelvic #s, retroperitoneal haematoma? Splenic lac…
Considerations?
Investigations?
Licox ICP monitor?
SAH
35/M Day 7 SAH post coiling Left MCA
aneurysm. E3V2M5 ED
Reintubated; drop GCS; Vasospasm;
Hypervolaemia, Hypertension; Angio
with intra-arterial Nimodipine x 1.
FiO2 30%, Peep+7, PaCO2, PaO2
target range; SBP> 160mmHg
TCDs: vel 140, ratio 4.
Hb: 7.5? 8.3? 9.0? 9.5?
Review
WHY transfuse??
How do we measure adequacy of
perfusion?
DO2 equation?
Factors affecting?
Systemic vs Brain end assessment of
adequacy?
Review
Aim of Neurocritical care: Prevention of
secondary brain injury; salvage penumbra.
DO2= CO x O2 Content (Hb x SaO2 x 1.39) +
(0.003xPaO2)
CO = CBF
CBF: Factors influencing:- Vessel length and
Caliber, Viscosity, CPP (Hagen-Poiseuille
eqn); Local CMRO2; CO2 Reactivity
AIM: Adequate DO2 = adequate PbtO2?
Anaemia: N Brain
WHO: HB<12g/dl in women.
CVS Response: SV, CO, HR, BP, CPP: all
Increase.
Increased Extraction of O2
Cerebral vasodilation
Increased CBF!
CBF well maintained in experimental models
when anaemia or hypotension present, but
not BOTH.
Anaemia: Injured Brain?
Cardiac Stunning? True IHD? Impaired CVS
response
Loss of Cerebral autoregulation and CO2
Reactivity
Anaemia + Hypotension?
Ischaemic Penumbra: O2 balance?
By physiologic principles: Anaemia BAD
Transfusion: BAD!!
Transfusions = Death! MODs! Trauma; SAH;
Liberal vs restrictive; Elective Sx…
Storage Lesions…?
Fragile, rigid, clog up microcirculation with
little O2 release! Tissue DO2 not increased!
TRALI
TACO
Incompatibility
Infection
Marik, Corwin et al CCM 2008
Transfusion Evidence
TRICC: Herbert 1990’s
2011 NEJM Hip Surgery
Cardiac Literature
No RCTs in transfusion in Neurological
injured pts
Restrictive WINS
What about in Neuro injured pts?
TBI
Severe TBI: Ischaemic damage load reduces CBF. Its dead brain.
Regional heterogeneity in CBF and CMRO2
Vulnerable Penumbra will benefit from enhanced DO2
No recommendations from BTF wrt transfusion thresholds
British Committee for Standards in Haematology guidelines British Journal Haematology,2013
160,445-464:
Target Hb 7-9g/dl; and with evidence of cerebral ischaemia > 9g/dl (Grade 2D)
TBI Admission or development of Hb<9g/dL
associated with Increased Mortality
- Sekhon et al Crit Care 2012; McHugh et al J Neurotrauma 2007 (Imact study); Steyerberg et
al PLoS Med 2008
Initial Hb<10g/dL NOT associated with mortality in severe TBI. Yang et al J Trauma 2011
Transfusions worsen outcome in TBI - Malone et al J Trauma 2003; Moore et al Arch Surg 1997
Transfusion and anaemia in TBI, only transfusion worsens outcome. Salim et al J Am Coll Surg
2008
Oddo et alICM2012: Severe TBI, Hb<9g/dl with simultaneous PbtO2<20mmHg, but not anaemia alone assosc worse outcome. Hb<9g/dl more likely to have lower PbtO2
TBI
TBI group: anaemia and transfusions, both assosc worse outcome
Avoid anaemia, but Liberal transfusion not justified: Consider cerebrovascular reserve and impact.
RBC transfusion does generally increase PbtO2 but increment is small, unpredictable, and at times decrease! Zygun et al Crit Care Med 2009; Leal-
Noval et al Intensive Care Med 2006
Age blood issue?
TBI & PbtO2
Much observational data associating low PbtO2 with poor outcome.
PbtO2< 10-15mmHg worse outcome. Maloney-
Wilensky E, Le Roux et al. Crit Care Med 2009
70pts, severe TBI. ICP alone vs ICP + PbtO2
Target ICP< 20mmHg CPP> 60mmHg PbtO2>20mmHg. Spiotta AM, Leroux et al. J Neurosurg sept 2010
Mortality 25.7% v 45.3% P<0.05 PbtO2 arm.
Duration of compromised PbtO2 <20mmHg, Brain hypoxia PbtO2<15mmHg, failure to treat compromised PbtO2: worse outcome.
TBI & PbtO2
PbtO2 directed strategy was associated with better outcome vs ICP/CPP strategy. OR 2.1; 95% CI 1.4-3.1. Nangunoori R, Le Roux et al. Neuro Crit Care Aug 2012.
Summary results suggest combined ICP/CPP + PbtO2 strategy better.
Spontaneous ICH
Imaging modalities confirm surrounding rim of hypoperfusion
However O2 extraction is this region not increased, suggesting reduce CMRO2 as cause.
Unknown if these areas tolerate anaemia as well as normal brain tissue.
SAH
Vasospasm causing ischaemic injury: anticipated complication of SAH
Opportunity to protect, reverse, limit the insult
Anaemia common. Only 16% pts maintain Hb >11g/dl
Worse outcomes with both anaemia and transfusions! Kramer et al CCM 2008 Jul:36(7)
Hb>11g/dL assosc less cerebral infarction and better outcome. Naidech et al Crit Care Med 2007
RBC transfusion worsens outcome in SAH - Festic et al Neurocrit Care 2012; Levine et al Neurosurgery 2010; Smith et al J Neurosurg
2004
SAH
RBC transfusion more effective than hypervolaemia, hypertension, angioplasty. Dhar
et al J Neurosurg 2012
Hemodilution: increase CBF not sufficient to overcome CaO2 reduction and regional ischaemic needs; small increases in CBF with anaemia shown to cause drop in PbtO2.
Vulnerable areas with high O2 extraction benefit from RBC transfusion
Small study of 20 pts found Hb<9g/dl assosc lower PbtO2. Oddo et al Stroke 2009
SAH
Stored RBC transfusions (Free Hb) scavenge NO and may worsen vasospasm
British guidelines: optimal Hb undefined. Remains unclear if RBC transfusions improve or worsen outcome. Target Hb 8-10g/dl (Grade 2D)
Systematic reviewof studies: 4 TBI, 1 SAH, 1 mixed neurocritically ill.
Low Hb Group: 7-10g/dL
Higher Hb group: 9.3-11.5g/dL
No difference in Mortality, MV duration, Multiple Organ Failure.
Cannot recommend any Hb target, liberal or restrictive strategy
Stored Blood
Is stale blood the issue??
Increasing age: Impairs deformability of RBCs, decreased 2,3DPG and O2 delivery; acid and K+ load increased
TBI: >3U RBC > 14days old in 24hrs worsens outcome. Weinberg et al J Trauma 2010
SAH: age of RBCs no impact on outcome. Naidech et al Transfu Med 2011
Increase in PbtO2 more frequent if RBC < 14days. Leal-Noval et al Crit Care Med 2008
Issue of dose and rate of “poisoning”? Takes 24-48hrs for RBC storage changes to reverse in vivo
Where do we go from here?
No robust clinical trials in neuro patients
Guidelines not helpful
Anaemia: Bad vs not Bad
Transfusions: Good v Bad v Confused
Moving Forward…
Transfusion: Therapeutic Intervention
Anaemia not equal transfusion
Optimise other modalities in DO2
Hb 9-10g/dl if cerebral ischemia a issue
Cerebral Ischaemia Risk =
- TBI with high ICP
- PbtO2 < 20? < 15?
- Vasospasm
Fresh RBCs?
Monitoring
Aims of transfusion achieved?
Target Cerebral Oxygenation achieved?
PbtO2 target >20mmHg
Reduction in Lactate:Pyruvate ratio (<40?) in brain metabolite sampling
NIRS Cerebral oximetry: Aneurysmic SAH? Restore to baseline if < 20%
Algorithm?...
Signs, symptoms, monitoring, investigations indicating Cerebral Oxgenation problem?
Cerebral Ischaemia Risk?
- TBI with high ICP
- PbtO2 < 20? < 15?
- Vasospasm
- Cerebral oximetry < 20%baseline??
Anaemia alone not equal transfusion
Algorithm?...
Optimise other modalities in DO2
-CBF, O2,
Hb 9-10g/dl if cerebral ischemia a issue
Fresh RBCs?
Goal directed transfusion vs Transfusion trigger!
PbtO2> 20mmHg; Restore baseline Cerebral oximetry; Lactate:Pyruvate < 40:1; reversible Improvement in neuro state.
Conclusion
Lack of clear, firm evidence based recommendations
Brain Tissue probes not standard of care yet
Transfusion algorithms based on Brain DO2, PbtO2 matching of at risk areas rather than just Hb threshold
Not one size fits all. Consider indication and review therapeutic interventions.
Goals achieved? Will transfusion help?