SICK NEONATE.

1. SICK NEONATE. Dr. M.Thomas. CUHT.

2. Sick Neonates are one of the most heavily transfused group of patients in modern medicine. • Survival has increased. • ELBW - 50% receive first transfusion by 2 weeks and 80% get atleast 1 transfusion before discharge. N.Bishara et 2008. • Should I transfuse this baby today, or would I better wait ? • Packed red cells are the most common blood product administered to sick neonates.

3. History. • 1492 – Pope Innocent VIII. • 1615 – Andreas Libavius, techniques. • 1628 – William Harvey. • 1818 – James Blundell. • 1900 – Karl Landsteiner. • 1910s – anticoagulants added & refrigerating. • 1950s – separation of blood products. • 1960s – plastic collection bags.

4. Why do we transfuse ? • To ensure adequate tissue oxygenation. • To treat clinically significant anaemia. • Tissue oxygenation – type and con: Hb, 2,3DPG, and cardiopulmonary function. • How can we assess TO ? • Peripheral fractional O2 extraction- NIRS. • Capillary whole blood lactate.

5. It is not that simple, ….. when to transfuse pretem babies ? • Anaemia experienced by the small pretem depends on a lot of factors. • Benefits of blood transfusion – can be life-saving when given to replace blood lost acutely. • But given to anaemic preterm to ( ? ) replace that lost by natural attrition and phlebotomy IS NOT THAT CLEAR. • Anaemia of prematurity.

6. Anaemia of Prematurity. • In the third trimester, foetal RBC production transitions from liver to the marrow. • EPO a glycoprotein hormone is the driving force. • EPO production also switches from liver to the kidney near term. • After birth term infants show a physiologic drop in haematocrit accompanied by a fall in EPO levels. • This leads to the ‘physiologic nadir’ at around 3 months. • Oxygen delivery to tissues is well preserved and signs of anaemia are rarely seen in the term infants.

7. Anaemia of Prematurity. • Preterm experience a lower nadir resulting in a normocytic, normochromic anaemia. • Nadir is inversely related to gestational age. • Most preterms tolerate AOP well. • The smallest and sickest develop signs & symptoms like tachycardia, tachypnoea, apnoea, poor weight gain, O2 requirement, decreased activity, pallor etc: • The above symptoms lead to increased hospital stay and infectious complications. • Natural history of AOP is exacerbated by iatrogenic factors like low haematocrit at birth, phlebotomy and endogenous factors as rapid growth, shortened RBC lifespan and expansion of blood volume.

8. AOP – Management. • Red blood cell tranfusion. • Erythropoietin (EPO). • Nutrition. • Limiting blood loss by phlebotomy. • Newer trends or practices ???

9. AOP – RBC Transfusion. • For many years was the ONLY effective treatment. • Protocols for transfusion were largely unstandardized. • Although given to improve tissue oxygenation………… • Hebert et al,1999 in an RCT compared the outcomes in critically ill adult patients managed with liberal (Hb >10 g/dl) to a restrictive (Hb >7 g/Dl), found ICU and hospital mortality rates were lower in the restrictive group. • This study kick-started a rethink of transfusion strategies in the ICU.

10. RBC Transfusion. • As the ICU world was getting used to the idea that smaller might be better in terms of Hb concentrations, along came the bombshell in the form of SOAP study. • Evaluated 3147 pt; across 198 ICUs across Europe, reported that red cell transfusions were NOT associated with increased mortality in multivariate analysis or propensity case matching. • What about neonatal studies ?

11. RBC Transfusion. • Infection risk - lowest now with donor screening, testing for infection, leucoreduction and irradiation. • Donor exposure has been minimized by single donor techniques like pedipacs. • A lot of transfusion studies became largely irrelevant.

12. RBC Transfusion. • Iowa – single centre, randomised, 100 pt:, mean birth wt: 0.95kg, mean age 28wk, transfusion thresholds – Hb or haematocrit, compared a ristrictive to liberal thresholds, restrictive Hb – 7.3g/dl, primary outcome whether using restrictive criteria would reduce the number of transfusions in the 500 – 1300g babies. • PINT – multicentre , randomised, 451 pt:, birth wt: 0.77kg, capillary Hb, restrictive to liberal, looked at impact of tranfusion on incidence of a composite outcome of death, ROP, BPD, abnorm: brainUSS in babies <1kg.

13. RBC Transfusion. • Iowa – restrictive group got less topup, but no: of donor exposure was not reduced. • PINT – topup less in restrictive, but total no: not different as transfusion was given outside study protocol, no: of donor exposure alone not decreased, but total donor exposure including platelet, plasma etc: decreased. • Total no: of pt: who got no transfusion at all decreased, Iowa – restrictive 10 v 12 liberal and in PINT- rest: 11 v 5% liberal.

14. RBC Transfusion. • Iowa – adverse outcomes were more common in restrictive group , major cranial USS findings, and composite outcomes of severe brain injury / death was more in restrictive, 16% v 2%. • PINT – no effect of transfusion practices on brain injury / death, 31% in both group. • Apnoeas more in Iowa restrictive, but no different in PINT. • Conclusions………

15. Erythropoetin. • Dose related effect. • Few trials done, few awaited. • Does reduce transfusion volume and number. • Best works in the stable, growing prem. • Early versus late administration regimes. • So why are we not routinely using it ? • Adverse effects. • Most important findings from earlier r-EPO trials was that implementing standard transfusion critera alone safely reduced the no: of transfusions.

16. Newer trends. • Delayed cord clamping. • Aladangady et al: Infants blood volume in a controlled trial of placental transfusion at preterm delivery, Pediatrics 2006; 117:93-8. • Strauss RG et al: A RCT comparing immediate versus delayed cord clamping in preterm infants, Transfusion 2008; 48:658-65. • Rabe H et al: A systematic review and meta-analysis of a brief delay in clamping the cord of preterm infants, Neonatology 2008, 93:138-44. • Milking the umbilical cord at birth. • Hosono s et al: Cord milking reduces need for RBC transfusions and improve neonatal adaptations in infants born <29 weeks, a RCT, Arch Dis Child Fetal Neo Ed 2008, 93: F14-19.

17. Decrease Phlebotomy. • Microsampling techniques. • Batching of blood labs. • Cord blood sampling for immediate postnatal labs. • Removing central lines as soon as possible. • Ordering tests judiciously. • Point of care (POC) devices. • In-line umbilical catheter analyzer.

18. Conclusions. • When should we transfuse preterm neonates ? • PROBABLY AT BIRTH. • Think of strategies to minimize procedures which worsens Anaemia of Prematurity. • Have agreed written, transfusion guidelines….. IT HELPS. • Have we enough strategies to completely aviod transfusions yet ? NO.

19. FUTURE. • Are there better indicators of transfusion than Hb: or haematocrit ? • More accurate but still practical transfusion triggers have so far eluded researchers.

20. THANK YOU.

21. Questions ?

22. Transfusion criteria: then & now. • In the 1990s. • When 5 – 10% blood vol; lost in 48 hr, in <1500g to keep Hb: > 13g% in the first week, to treat symptoms of anaemia in convalescent infants (3-8wk). • Current restrictive guidelines for VLBW infants. • Moderate to significant vent: to keep Hb: >11g% or Hct: >35%. • Infants with mini: vent: to keep Hb: >10g% or Hct: >30. • Infant with supplemental O2 alone to keep Hb: >8g% or Hct: >25, if they are tachycardic, tachypnoeic, increased O2 need, poor wt: gain, multiple A & Bs, before surgery etc: • Asymptomatic infants to keep Hb: > 7g% or Hct: >20.