Tolerance of Anemia in Pediatrics - SABM - Patient Blood ...

Tolerance of Anemia in PediatricsNabil Hassan, MDDirector Pediatric BMP, HDVCHAssociate Professor of Pediatrics, MSU

Disclosures• I could only wish for…• Employed intensivist• SABM board member

Anemia:How Low Can We Go?• Healthy conscious adultvolunteers (n=21)Healthy patients prior to surgery(n=11)• Blood aliquots removed to reduceHb (13 5 gm/dl)• No evidence of critical DO 2• Weiskopf, RB JAMA279;217:1998

Blood Transfusions in PediatricPatients• Pediatric health information system data (2001-2003), part of ChildHealth Corporation of America:• 35 academic centers:• 4.14% transfused• 87% of all transfusions• 1.1% severe complications• Asian, increased severity, neutropenia, and sickle cellAnthony Slonim et al., Transfusion (2008) Vol 48: 73-80.

Number of units2011 PRBC Utilization atHDVCH (January-April)302520151024.5 24.5 25.2 25.222.920.319.52.536NICUPICUHem/OncOutpatient502005 2006 2007 2008 2009 201019%Hem/OncInpatientOthers23•Prorated yearly utilization of 2,265 units(10% of system total) = $1.7million• 1.65 million units nationally = $ 1.25 billion

Anemia in PediatricsAge Hb (g%) Anemic>32 wk 15.0 14Term* (cord) 16.5 13.51-3 dy 18.5 14.52 wk 16.6 13.41 mo 13.9 10.72 mo 11.2 9.46 mo-2 yr 12.0 10.52-6 yr 12.5 11.56-12 yr 13.5 11.512-18 yrMaleFemale14.514.01312201816141210Hgb864202 4 6 8 10 12 14Postnatal WeeksTermPreterm*

Is it only Hb?VO2• Shock• Burns• Trauma• growth• High SADO2• Hb level &Type of Hb• Cardiac output( HR, SV)• Oxygenation

Compensation for Anemia1. CO (HR & Strokevolume)2. Tachypnea (apnea)3. Regional Autoregulation(NEC)4. Viscosity ( flow)5. Extraction

Developmental Changes in Hb

Pediatric Patients Subgroups• Neonates• General floor• Burn• Cardiac• PICU• sepsis

Love all, Serve allHurt never, Serve everSathya Sai-Baba“First do no harm”

Transfusion Management Strategies: A Survey ofPracticing Pediatric Hematology/OncologySpecialists• A web based survey of ASPH/O members• 86% felt EPO not indicatedEd Wong. Pediatric Blood Cancer 2005; Vol. 44: 119-127.

Neonatal: Anemia howbad/Transfusions How Good• Physiologic markers:  HR,  RR, As & Bs, poor weight gain• Higher Hct reduced Apnea & periodic breathing Joshi A 87• HB, SVO 2 and lactate weakly correlate to markersBifano 92• Volume was as effective. Bifano 93• Transfusions improve wt. gain Meyer J. 93.• Transfusions do not improve wt. gain Chen H. 09

Neonatal Anemia• Convalescing infants (< 32W) with Hb

Effect of Transfusion in ELBW• U of W (Seattle), 2006,60 ELBW• Transfused 78% (47/52)• No benefit (weight gain,apnea, vent. days)• No effect on sepsis• Higher ROP grade• Higher NECValieva O, et al, (Sept 2009) J Peds Vol 155, No. 3: 331-37.

Association of NEC with Anemia andTransfusion in Preterm Infants (< 32 weeks)• Single Center,Retrospective: 111 NEC,222 Control(2000-2008)• Anemia: ↑ O.R. 1.1(P. 01)• RBC: ↑ O.R.• 24 hours: 7.60 .001• 48 hours: 5.55 .001• 96 hours: 2.13 .07R. Singh et al. Journal of Perinatology (January 2011) Vol. 31, 176-182.

Liberal vs Restrictive Transfusions(Iowa Trial)• 100 neonates randomized• 950 gm, 28 wks (mean)• Liberal gp received EPO & PRBCLiberal RestrictiveVentilated Hct < 46 < 34%CPAP Hct < 38 < 28Room Air < 30 < 22Bell Pediatric 2005; 115: 1685-91

Liberal vs. Restrictive RBC‟sTransfusions (Iowa Trial)Liberal Restrictive PTransfusions 5.2 3.3 .025DonorExposure2.8 2.2 .08IVH G IV 0 4 .054PVL 0 4 .115Either or Both 0 6 .012Apneas > 20seconds32 52 .004No early and no late ultrasound in 50% Bell ,Pediatric 2005; 115: 1685-91

Kirpalani: (PINT) Trial (2006)• 451 ELBW, 770gm, high vs low threshold• No difference in death, ROP, BPD, brain injury• Low Hb gp (89% transfused, 3.7 donors)High Hb gp (95% transfused, 4.2 donors)• Number of transfusions (4.9 vs. 5.7 ,P0.07)Mean eventual Hb difference (1.1 gm)No difference in NDI at 18-22 m (low 45%, high 39%)Whyte Kirpalani Pediatrics (2006) 123 (1): 207-13

Neurodevelopmental Outcome of Extremely LowBirthweight Infants Randomly Assigned to Restrictive orLiberal Hemoglobin Thresholds for Blood TransfusionsOR (95% CI)PDeath 1.18 (0.72-1.93) 0.52Cerebral palsy 1.32 (0.53-3.27) 0.07Cognitive delay, Bailey MDI

Long-term Outcome of the IowaTrial•MRI studies of 44 of the original 100 and 40 FT controls•Girls more affected in the liberal sp.I.C. VolumeLiberal n=26 Restricted n=18nCortex Volume n nWhite Matter VolumeB.G. VolumeNopoulos, Conrad, Bell, Strauss, Widness et al. Arch Pediatric Adolescent Medicine. May 2011; 165(5): 443-50.

summarycompensation• Increased CO• Increased flow• Increased RRdecompensation• Lethargy• Poor feeding• Apnea, PB• Bradycardia• Lactic acidosis• PVL / IVH• NEC

Survey of Canadian NeonatalTransfusion Practices (1990)Heather Hume, Ronald Strauss, G. Levy (1997). Transfusion Science Vol. 18 (No. 1), pp 71-80.• Pediatric Hemotherapy Committee of AABB• Transfusion Triggers (variable):1. Removal of 10% of TBV2. Specific Hematrocrit3. Signs of Anemia4. OthersBoth transfusion and anemia are bad

Beyond the Neonate• Transfusion of (9) pediatric ICUpatients with• septic shock: DO 2 but notVO 2Mink. CCM.1990.• Transfusion of H/O (17)outpatients: VO 2 (19%)Grant M (Utah). PCCM. Vol. 4, No. 4,2003:450-64.• Background pathology• Ability to compensate

PercentEffect of Blood Transfusion on Survival AmongChildren in a Kenyan Hospital• 2433 pediatric admissions (1989-1990)• 29% had Hb< 5 gm% (20%transfused), median age 10months• Hb< 5, MR 18%, > 5 MR 8% (p.001) (66% within 48 hrs.)9080706050403020100Transfused• Hb< 4.7 + RD, Transfusiondecreased MR (OR 0.9)• Hb< 3.9 gm%. Transfusion within48 hrs, Decreased MR (OR 0.37)Hemoglobin (g/dl)Fig 1- Transfusion of children according to admission Hb.Eve M. Lackritz et al. The Lancet, Vol. 340. August 29, 1992.

Longitudinal Evaluation of Severely AnemicChildren in Kenya• 1991, 6 moth duration,admission – 8 week follow-up• 25% (n=303) Hb < 5,MR 16 % while in-hospitalMR 30% overall63% with respiratorydistress• 72% transfusedWithout RDWith RDEve M. Lackritz et al. AIDS, Vol. 11, No. 12: June 1997: pp 1487-1494.

Blood Transfusion for Severe Anemia inChildren in a Kenyan Hospital• Retro (‟98-99) and Pro (‟99-00)• 15% of admission had Hb < 5 gm%• MR 8% regardless of transfusions (65%)• Respiratory Distress MR odds 5.3, Tr 4.1• Prostration MR odds 22.8, Tr 5Mike English et al. The Lancet, Vol 359, February 9, 2002.

Effects of a Restrictive Blood TransfusionPolicy on Outcomes in Children with BurnInjuryHb >10 (n= 146) Hb > 7 (n= 127)Transfusions* 12.3 ± (1.8) 7.2 ± (1.2)Vent Days 13.2 ± (2.3) 8.4 ± (1.5)Complications** 1.03 0.9*P .001**P .05LOS 4.8 ± (4) 3.9 ± (3)MR 8.2% 5.7%•Retrospective, sequential (2000 2002 2005)•Similar Total Body Surface Area (TBSA), degrees, inhalationinjury, and # operationsTina L. Palmieri et al. Journal of Burn Care and Research, January/February 2007.

The Pediatric Heartache• Myocarditis,cardiomyopathy,arrhythmia, anomalouscoronary• TOF,TGA• VSD,TAPVR,CTT• CoA• Single ventricleContractilityrhythmPulmonarycongestionHeartfailureCyanosisObstruction

Red Blood Cell Transfusion for Infants withSingle Ventricle Physiology• < 1 yr., no 72˚ post-op ,no active bleeding••n= 59, transfusion= 183•Best at 12 hoursHBDiastolicBPO2SaturationNIRS7.8-12.3 + + +12.4-13.2 + + -13.3-15.7 + - -James Kno et al., Pediatric Cardiology (2011) vol. 32: 461-468.

RCT of high vs low HB in post-op singleventricle cavopulmonary connection• n 60, >13 vs

Anemia, Blood Loss & Transfusions inNorth American PICU (PALISI)• Observational study, 6 m, 30 PICUs (2004-2005)• N = 977, > 48° PICU stay• Anemia (74%): 33% on admission, 41% after admission(more in neonates & adolescents)• Phlebotomy: 8.25 ml/day (.32 ml/kg/day)(73% of blood loss)• Transfused: 49% (74% within 48°)• Trigger (anemia in 42%), Hb 9.7 + 2.7Scot Bateman, et al(2008), Am J. Respir Crit Care Med, Vol 178, P 26-33.

Pretransfusion Hb and LOS98.37.9Hassan, Sanfilippo,Rajasekaran, SABM, 2010

TRIPICU Study•19 PICUs, n=648, 4 different countries•3 days to 14 years of age•Hb of < 9.5 g/dl in first 7 days of PICU admit•Hemodynamically stable•Transfusion at

Subgroup ReportingPost Surgical*Post Cardiac Surgery**R (60) L (64) R (63) L (62)PRISM 3.5 4.4 3.4 3.2MODS 35% 29% 46% 44%New or 8% 9% 12.7% 6.5%ProgressiveMODSMV Days 7.7 d 7.4 d 62% 60%PICU Stay 7.7 7.9 (p 03) 7 528 Day MR 2% 2% 3.2% 3.2%Hb Start 7.7 7.9 8.3 8Hb Differenceat 28d2.3 gm 2.1 gm*Justine Rouette. Annals of Surgery, Vol. 251, No. 3, March 2010: pp 421-4**Ariane Willems. Critical Care Medicine 2010, Vol. 38, No. 2: pp 649-656.

Anemia and Sepsis• Keep Hb > 10 gm/dL> 12gm in neonatees(Level II evidence)J. Brierley. “2007 Update from the American College of Critical CareMedicine.” Critical Care Medicine 2009, Vol 37, No 2: pp 666-88.• Keep Hb > 7 gm/dL“Surviving the Sepsis Campaign.” Phil Dellinger (ACCP, ATS, AACCN, etc.),Critical Care Medicine 2004, Vol 32, No 3: 856-873.

RBC Transfusion Thresholds inPediatric Patients with SepsisStable sepsis patients (TRIPICU):– Restrictive group (R) < 7 g% (n=69)– Liberal group (L) < 9.5 g% (n=68)– MOD (R=18.8%, L=19.1%)– LOS (p=0.74)– MR (p=0.44)Karam O., Tucci M., Canadian Critical Care Trial Group, 31 st International Symposium on Intensive Care and EmergencyMedicine, March 2011: Brussels, Belgium.

Take Home Message•ANEMIA has a potential harm (NEC,CNS,MORTALITY).•Threshold could be lower than 7 gm in stablepatients(PICU,BURN,NICU,SEPTIC) but more than 5grams•Hb of 11 is adequate in post op. cyanotic•No good data on acute shock, increase ICP,ARDS,trauma,hyperthermia

Neonatal Anemia• Physiologic• Early Anemia of Prematurity– Acute Illness– Blood losses• Late Anemia of Prematurity– Low Erythropoietin– Rapid growth– Chronic Illness• Other Anemias– Hematological Disorders201816141210Hgb8642– Surgical Anemia 02 4 6 8 10 12 14Postnatal WeeksTermPreterm