Eur J Pediatr (1997) 156: 428431

Springer-Verlag 1997

HYPOTHESES AND CONTROVERSIES

N. R. C. Roberton

Use of albumin in neonatal resuscitation

Received: 4 May 1996 and in revised form: 7 October 1996 / Accepted: 16 October 1996

Abstract The use of albumin plasma has become popular during resuscitation of the term baby with very low Apgar scores ( 2 at 1 min). There is no evidence of benet from this practice which may actually be damaging to babies with severe asphyxia causing myocardial damage. Key words Resuscitation Birth asphyxia Albumin Abbreviations IPPV Intermittent Positive Pressure Ventilation HIE Hytoxic Ischaemic Encephalopathy
Background

Recent medico-legal experience shows that albumin/ plasma is commonly given to babies requiring resuscitation. In a personal series of 50 consecutive medicolegal cases in which drugs were given during resuscitation of term babies between 1985 and 1995 albumin was given to 15 in the rst 1520 min and to a further 17 before 1 h of age. In only 2 of these 17 was the blood pressure measured and below 60/40 mmHg. All the babies were in very poor condition at birth with 1 min Apgar scores 2 X 14 had 1 min Apgar scores of 0. All received IPPV and 20 (including the 14 Apgar 0 babies) received external cardiac massage. Other drugs used are given in Table 1. All the babies suered long-term CNS sequelae or died as a result of severe HIE. Although giving albumin during resuscitation is hinted at in some textbooks [14] it is not recommended in the majority [29, 30]. In this annotation the view is put that giving albumin in the rst 60 minutes while resuscitating term babies is physiologically unsound and unjustied by a controlled study. Only the use of albumin in term babies is considered, but there is evidence from the late 1970s that when
N. R. C. Roberton The Rosie Maternity Hospital, Cambridge, United Kingdom Present address: Sea Cottage, Lower Harrapool, Isle of Skye IV79 9AQ, Scotland

volume expansion was used liberally in the rst 3060 min in preterm babies it was associated with a marked increase in the complications of being preterm, including patent ductus, necrotising enterocolitis, bronchopulmonary dysplasia and perventricular haemorrhage [34]. Historically it is interesting to try and nd the origins of albumin use. It is certainly not mentioned in the early classical descriptions of treatment for birth asphyxia [7, 9, 10, 17]. Indeed in those reports it is noted that prompt oxygenation and IPPV of asphyxiated newborns promptly restored cardiovascular function to normal. Treatment for shock as part of resuscitation begins to appear in the American literature in the 1980s [8, 25]. These authors make it clear, however, that volume expansion should only be given after stabilization and only if there is clear evidence of hypotension [25]. They also make two other important points; that the choice of appropriate therapy depends on whether there is hypovolaemia or heart failure, and that with hypovolaemia there is no benet of colloid over crystalloid [8]. The current major textbooks in their chapters on resuscitation either do not mention albumin use or state that it is over used, or since hypovolaemia is extremely rare with perinatal asphyxia, volume expansion should only be considered after stabilization and normalization of blood gases [3, 21, 27, 29]. Where volume expansion is indicated albumin is the third choice behind fresh blood and crystalloid and it should be given slowly [3, 27]. Perhaps most signicant of all, volume expansion/ loading is not considered at all in the chapter on resuscitation in Sinclair and Bracken's book on evidencebased neonatology [26]. Assessing the use of albumin in the term baby requiring resuscitation can be done under various headings.
Does a low Apgar score indicate hypotension/hypovolaemia?

The answer is no. The dierential diagnosis of a low 1 and 5 min Apgar score is extensive [29] and blind therapy

429 Table 1 Use of drugs in resuscitation (in addition to Albumin) Bicarbonate alone Adrenaline alone Mannitol alone Bicarbonate plus dextrose Bicarbonate plus adrenaline Bicarbonate plus mannitol Bicarbonate plus atropine Bicarbonate plus adrenaline and dextrose Bicarbonate plus dextrose and calcium Bicarbonate plus dextrose and atropine Bicarbonate plus adrenaline and atropine Bicarbonate plus dextrose and mannitol 8 3 1 8 5 1 1 4 1 1 1 1

load from the placenta and whose cardiac function may already be compromised by asphyxia [6, 33, 36] would seem to be ill advised.
Should acidaemia be corrected after delivery?

(Data from personal consecutive series of medio-legal cases who received intravenous drugs as part of resuscitation)

other than intubation and IPPV is always inappropriate with the ready availability of diagnostic procedures. Furthermore when babies with low Apgar scores 6 (cause unspecied) were assessed they had higher blood pressures than those with Apgar scores ! 7 [22].
Is hypotension a likely problem in babies with low Apgar scores who genuinely have intrapartum asphyxia?

This is a contentious issue. There is evidence that cardiac function is depressed by acidaemia and hypoxia [13, 33], that brain function is depressed by acidaemia and respiration returns more rapidly when pH is corrected [1], that surfactant synthesis is pH dependent (perhaps not important at term [20]) and that catecholamines work better with a normal pH [28]. It is also clear, however, that a newborn baby's pH can correct very rapidly in the rst hour with nothing more than eective IPPV and oxygen [32].
Will albumin correct acidaemia?

The answer to this question is also no. The classical experiments in the 1960s showed that at the height of asphyxia when there is bradycardia there is also hypotension but this is completely reversed by intubation and ventilation with oxygen [7, 10]. If asphyxia is very severe myocardial depression and damage does occur with an enlarged heart, tricuspid incompetence, pulmonary oedema, reduced cardiac output and hypotension [5, 6, 33, 36], and volume load is contraindicated.
Is hypovolaemia a likely problem in babies with low Apgar scores who genuinely have intrapartum asphyxia?

In preterm babies maintaining blood pressure by infusions of blood or colloid may prevent acidaemia, but there is no evidence that acidaemia is corrected by i.v. colloid. Indeed why or how could it? Albumin infusions in preterm babies do increase blood pressure albeit only transiently and by 24 mmHg, and inotropes probably work better [12, 15, 16, 18], but these studies give no data on pH.
What about the Apgar 0 baby?

This baby is highly likely to have suered myocardial ischaemia and will have poor myocardial contractility (see above). Adding a volume load to this problem is not intelligent.
Are there any studies relevant to albumin therapy during resuscitation?

Again the answer is no. Considerable data exist to show that the rst fetal response to asphyxia is to empty the placenta into the baby that is the baby's blood volume at birth is likely to be above normal [19, 24, 31, 38].
Is a further volume load likely to help a baby who has received this placental transfusion with or without co-existing asphyxial myocardial damage?

A single study [4] compared i.v. infusions of 8 ml/kg of 25% albumin, 4.2% bicarbonate or both in non-acidaemic babies less than 2 h old, and showed no improvement in mortality or morbidity from Respiratory Distress Syndrome or Intraventricular Haemorrhage. A similar negative result in preterm babies using fresh frozen plasma or Gelofusine with 2 h of birth has recently been reported in Britain [23].
Can i.v. albumin do harm?

The answer is yet another no. Babies who have received large placental transfusions even without asphyxia may show mild heart failure with pulmonary plethora and cardiac dilatation, the syndrome of neonatal polycythaemia [37]. Even the normal fetal and neonatal heart is poor at raising cardiac output in response to increasing the pre-load as it functions at the top of the Frank-Starling curve [2], therefore to increase pre-load by transfusing a baby who has already received a volume

Since most babies with low Apgar scores will do very well with nothing more than IPPV and oxygen, and are designed to accepted sudden volume transfusion at birth from the placenta, if they are not all that ill to start with, giving them extra volume will probably do no harm, but is expensive.

430

For the low Apgar baby who is genuinely asphyxiated, with a cord pH less than 7.0 and who is likely to have multi-organ failure, an albumin transfusion is likely to do harm, particularly if the myocardium is injured and preload increased, and is highly unlikely to do any good.
Is there any place for i.v. albumin at resuscitation?

There might be in the extremely rare situation where there has been a feto-maternal transfusion or a tight nuchal cord in which the vein but not the artery is occluded [35] causing fetal anaemia/hypovolaemia. If this is suspected transfusion is indicated but blood (because haemoglobin carriers more oxygen than elbumin) is the preferred therapy and is present on most labour wards. If this is not available then albumin might be used. Acceptable standards of neonatal care now demand that it should always be possible by the time a baby is 10 minutes old to know his pH (cord blood or umbilical sample), glucose (dextrostix) and a blood pressure (Dinamapp). Until that time the appropriate treatment is oxygen and IPPV with cardiac massage as indicated and perhaps adrenaline for asystole. If investigation reveals any abnormality it should be treated. If hypotension is present, and in particular if there is evidence of myocardial compromise (heart rate, CXR) dopamine should be given, a treatment that has at least been validated in such babies [11, 36]. Blood should be given to hypotensive neonates with evidence of intrapartum blood loss
References
1. Adamsons K, Behrman S, Dawes GS, James LS, Koford C (1964) Resuscitation by positive pressure ventilation and trishydroxymethylaminomethane of rhesus monkeys asphyxiated at birth. J Pediatr 65:807818 2. Anderson PAW (1992) Physiology of the fetal neonatal and adult heart. In: Polin RA, Fox WW (eds) Fetal and neonatal physiology. W.B. Saunders, Philapdelphia pp 722758 3. Ballard RA (1991) Resuscitation in the delivery room. In: Taeusch HW, Ballard RA, Avery ME (eds) Diseases of the Newborn, 6th edn. W.B. Saunders, Philadelphia, pp 193 206 4. Bland RD, Clarke TL, Harden LB (1976) Rapid infusion of sodium bicarbonate and albumin into high risk premature infants soon after birth. A controlled trial. Am J Obstet Gynecol 124:263267 5. Bucciarelli RJ, Nelson RM, Egan EA, Eitzman DV, Gessner IH (1977) Transient tricuspid insuciency of the new born. A form of myocardial dysfunction in stressed newborns. Pediatrics 59:330337 6. Cabal LA, Devaskar U, Siassi B, Hodgman JE, Emmanouilides G (1980) Cardiogenic shock associated with perinatal asphyxia in preterm infants. J Pediatr 96:705710 7. Cross KW (1966) Resuscitation in the asphyxiated infant. Br Med Bull 22:7378

8. David R (1988) Neonatal resuscitation. Historical perspective and current practice. In: Guthrie RD (ed) Neonatal intensive care. Churchill Livingstone, New York, pp 120 9. Davies PA, Robinson RJ, Scopes JW, Tizard JPM, Wigglesworth JS (1972) Medical care of the newborn babies. Spastics International Medical Publications, W. Heinemann, London, pp 3239 10. Dawes GS (1965) The circulation, respiration and general metabolism of the newborn. In: Gardiner DMT (ed) Recent advances in paediatrics, 3rd edn. Churchill, London, pp 1 35 11. Di Sessa TG, Leitner H, Ti CC, Gluck L, Coen R, Friedman WF (1981) The cardiovascular eects of dopamine in the severely asphyxiated infant. J Pediatr 99:772776 12. Emery EF, Greenough A, Gamsu HR (1992) Randomised controlled trial of colloid infusions in hypotensive preterm infants. Arch Dis Child 67:11851188 13. Fanconi S, Burger R, Ghel D, Uehlinger J, Arbenz U (1993) Haemodynamic eects of sodium bicarbonate in critically ill neonates. Int Care Med 19:6569 14. Fleming P, Speidel B, Marlow N, Dunn PM (1991) A neonatal vade mecum. Edward Arnold, London, p 30 15. Gill AB, Weindling AM (1993) Randomised controlled trial of plasma protein fraction versus dopamine in hypotensive very low birthweight infants. Arch Dis Child 69:284287 16. Greenough A, Greenall F, Gamsu HR (1988) Immediate eects of albumin infusion in ill premature neonates. Arch Dis Child 63:307309 17. Hull D (1972) Asphyxia neonatorum. In: Gardiner DMT, Hull D (eds) Recent advances in paediatrics, 4th ed. Churchill, London, pp 5387 18. Lay KS, Bancalari E, Malkus H, Baker R, Strauss J (1980) Acute eects of albumin infusion on blood volume and renal function in premature infants with respiratory distress syndrome. J Pediatr 97:619623 19. Linderkamp O, Versmold HT, Messow-Zahn K, Muller-Holve N, Reigel KP, Betke K (1978) The eect of intrapartum and intrauterine asphyxia on placental transfusion in premature and full term infants. Eur J Pediatr 127:9199 20. Merritt TA, Farrell PM (1976) Diminished pulmonary lecithin synthesis in acidosis: experimental ndings as related to RDS. Pediatrics 57:3240 21. Milner AD (1996) Resuscitation. In: Greenough A, Milner AD, Roberton NRC (eds) Neonatal respiratory disorders. Edward Arnold, London, pp 196209 22. Modanlou H, Yeh SY, Siassi B, Hon EH (1974) Direct monitoring of arterial blood pressure in depressed and normal newborn infants during the rst hour of life. J Pediatr 85:553 559 23. The Northern Neonatal Nursing Initiative Trial Group (1996) A randomised trial comparing the eect of prophylactic intravenous fresh frozen plasma, gelatin or glucose on early mortality and morbidity in preterm babies. Eur J Paediatr 155:580588 24. Oh W, Omori K, Emmanouilides K, Phelps DL (1975) Placenta to lamb fetus transfusion in utero during acute hypoxia. Am J Obstet Gynecol 122:316322 25. Ostheimer GW (1982) Resuscitation of the newborn infant. Clin Perinatol 9:177190 26. Pelowski A, Finer NN (1992) Birth asphyxia in the term infant. In: Sinclair JC, Bracken MB (eds) Eective care of the newborn infant. Oxford Uniersity Press, Oxford, pp 249279 27. Phibbs RH (1994) Delivery room amagement. In: Avery GB, Fletcher MA, MacDonald MG (eds) Neonatology: pathophysiology and management of the newborn, 4th ed. J.B, Lippincott, Philadelphia, pp 248268 28. Preziosi MP, Roig JC, Hargrove N, Burcheld DJ (1993) Metabolic acidemia with hypoxia attenuates the hemodynamic responses to epinephine during resuscitation in lambs. Crit Care Med pp 173195

431 29. Roberton NRC (1992) Resuscitation In: Textbook of neonatology, 2nd edn. Roberton NRC (ed) Churchill Livingstone, London, pp 173195 30. Roberton NRC (1993) A manual of neonatal intensive care. Edward Arnold, London, p 157 31. Richardson BS (1989) Fetal adaptive responses to asphyxia. Clin Perinatol 16: 595611 32. Spencer JAD, Robson SC, Farkas A (1993) spontaneous recovery after severe metabolic acidaemia at birth. Early Hum Dev 32:103112 33. Talner NS, Lister G, Fahey JT (1992) Eects of asphyxia on the myocardium of the fetus and newborn. In: Polin RA, Fox WW (eds) Fetal and neonatal physiology. W.B. Saunders, Philadelphia, pp 759769 34. Tooley WH (1979) Epidemiology of bronchopulmonary dysplasia Pediatr 85:851855 35. Van Haesebronck P, Vanneste K, Pretere C, Trapper Y de van, Thiery M (1987) Tight nuchal cord and neonatal hypovolaemic shock. Arch Dis Child 62:12761277 36. Walther FJ, Siassi B, Ramadan NA, Wu PYK (1985) Cardiac output in newborn infants with transient myocardial dysfunction. J Pediatr 107:781785 37. Werner EJ (1995) Neonatal polycythemia and hyperviscosity. Clin Perinatol 22:693710 38. Yao AC, Lind J (1972) Blood volume in the asphyxiated term neonate Biol Neonate 21:199209

Copyright of European Journal of Pediatrics is the property of Springer Science & Business Media B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.