Transfusion Targets in

Brain Injury

Dr Jonathan Tan

Senior Consultant, Anaesthesiology & Intensive Care.

Tan Tock Seng Hospital, Singapore

Disclosures

No relevant disclosures

No one dies without…

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?

CASE

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?

Neurocritical Care Review

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

Anaemia is BAD

Transfusion is BAD

Really??

Clinical Studies….

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%

Transfusion Alternatives

Fe supplements

Hb substitutes: Haemodilution with increased CaO2?

EPO?

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?

Thank You