Acta Pdiatrica ISSN 08035253

VIEWPOINT ARTICLE

New guidelines for newborn resuscitation a critical evaluation

OD Saugstad (odsaugstad@rr-research.no)
Department of Paediatric Research, Oslo University Hospital, University of Oslo, Oslo, Norway

Keywords Guidelines, Newborn, Resuscitation Correspondence Ola Didrik Saugstad, Pediatrisk Forskningsinstitutt, Oslo Universitetssykehus, Rikshospitalet, PB 4950 Nydalen, 0424 Oslo, Norway. Tel.: + 4723072790 | Fax: + 4723072780 | Email: odsaugstad@rr-research.no Received 22 February 2011; revised 28 March 2011; accepted 29 March 2011. DOI:10.1111/j.1651-2227.2011.02301.x Changes made after online publication 11 05 2011. 1st page: reference (1) inserted in introduction. 2nd page: reference (9) changed to (10). 3rd page: reference (14) changed to (4), ILCOR changed to guidelines. 4th page: The heart rate exceeds 100 bpm changed to The heart rate exceeds 100 bpm in normal babies, mouth or pharynx changed to nostril, suctioning of the mouth is not longer recommended changed to suctioning is not longer recommended 07 06 2011.

ABSTRACT
The 2010 International Liaison Committee on Resuscitation guidelines for newborn resuscitation represent important progress. The criteria for assessment are simplied based on heart rate and respiration only and there is no timing of stages after the rst 60 sec. Instead of giving supplemental oxygen, the guidelines state that it is best to start with air. However, the optimal oxygen concentration later in the process and for premature babies is not yet clear. A description of an adequate heart rate response is not given, and the cut-off of 100 bpm may be arbitrary. There are still no clear recommendations regarding ventilation, inspiratory time, use of positive end expiratory pressure or continuous positive airway pressure. The guidelines do not mention which paCO2 level might be optimal. As colour pink assessment and routine suctioning of airways are not recommended anymore, there is an urgent need to obtain international consensus and create a new and revised Apgar score without these two variables. Conclusion: In spite of improved guidelines for newborn resuscitation, there is still a number of unanswered questions and a need for more delivery room studies.

INTRODUCTION The rst international guidelines for newborn resuscitation were issued in 1992 (1). In 1999 the International Liaison Committee on Resuscitation (ILCOR) revised these and more evidence-based guidelines were published (2). In 2005 further revisions were performed (3). There were therefore high expectations regarding the 2010 guidelines published October 18th 2010 (4). These new guidelines have a streamlined algorithm. Since the rst guidelines of 1992 newborn resuscitation has been more focused and it has become clear that many, perhaps most of the routines at that time were not evidence based. The initial question concerned the common practice of giving oxygen (5,6) and later a number of critical questions regarding the routines were posed including initial assessment, stabilization, suctioning, ventilation, drug administration and timing of the events. Even

the clinical ability to assess colour has recently been questioned (7). Still, there is a lack of evidence-based knowledge regarding several of the procedures applied for newborn resuscitation. This is important because newborn resuscitation is one of the most frequent procedures carried out in medicine. Approximately 57 million of about the worlds annual 130

Key notes
New ILCOR guidelines with a simpler algorithm improve newborn resuscitation. The recommendation to start with air instead of oxygen for term/near term babies may save more than 200, 000 lives worldwide each year, A number of unanswered questions still exist, and a revised Apgar score is needed.

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Table 1 Major Changes in International Liaison Committee on Resuscitation Guidelines for Newborn Resuscitation from 2005 to 2010 Progression of the next step following the initial evaluation is dened by the simultaneous assessment of heart rate and respirations. For babies born at term, it is best to begin resuscitation with air rather than 100% oxygen. Administration of supplementary oxygen should be regulated by blending oxygen and air, the concentration delivered should be guided by oximetry. There is no evidence to support or refute routine endotracheal suctioning of infants born through meconium-stained amniotic uid, even when the newborn is depressed. The chest compression-ventilation ratio remains 3:1 unless there is arrest of cardiac aetiology. Then a higher ratio should be considered. Therapeutic hypothermia should be considered for infants born at or near term evolving moderate to severe hypoxic-ischaemic encephalopathy.

A: Initial steps in stabilization. B: Ventilation. C: Chest compressions. D: Medications or volume expansions. Progression to the next step is based on two vital characteristics: heart rate and respirations. In the previous guidelines, there was 30 sec to make a decision to move from one step to the next. In the new guidelines, only the rst 60 sec have been timed. A. Initial assessment and stabilization Heart rate Heart rate below 100 bpm (beats per minute) and gasping or apnoea are still criteria for starting positive pressure ventilation, and a rst assessment should have been done by 30 sec after birth. A prompt increase in heart rate remains the most sensitive indicator of resuscitation efcacy. Heart rate could be palpated in the umbilical cord although there is a risk for underestimation of the rate. Auscultation of the precordium should remain the primary means of assessing heart rate. For babies requiring ongoing resuscitation or respiratory support, heart rate should be assessed by pulse oximetry. Traditionally, a cut-off for heart rate < or 100 bpm has been practiced. This was based on the assumption that a heart rate <100 bpm in a newborn indicates bradycardia which in most cases is caused by asphyxia. However, recently Dawson et al. (9) published the development of heart rate after birth in normal nonasphyxiated newborns with no medical intervention. At one minute of age, term infants have in median a heart rate of 99 with interquartile range of 66132 bpm. For preterm infants, the values are 96(72122) bpm. This indicates that a large proportion of normal term and preterm infants are considered candidates for resuscitation according to the 2010 guidelines. Further, the guidelines do not indicate which heart rate response one should expect. Data from the Resair 2 study (10) show that in babies in need of resuscitation heart rate increases in mean 23 beats from the age of 6090 sec from a median (595 percentiles) of 90 (40140) to 113 (60 156 bpm. However, the heart rate response is dependent on the severity of asphyxia. If Apgar score at 1 min was <4, the heart rate increased from in mean 80100 bpm (10). An increase of 20 beats from 60 to 90 sec of life is therefore the best estimate of a satisfactory heart rate response. When is the rst breath taken? The literature does not seem clear on this point. However, Palme-Kilander et al. (11) showed almost 20 years ago, it takes 12 min to establish an efcient gas exchange in vaginally delivered babies and a few more minutes are needed after C-section. There is a relation between gas exchange and heart rate; it may therefore be normal not to achieve a heart rate of 100 bpm or more before one minute after birth. As discussed by Dawson and Morley (12), a heart rate of 100 bpm as an indication for resuscitation therefore is rather arbitrary, and an assessment at 30 sec of life may lead to initiation of

million newborns need this. ILCOR estimates this number even higher, that approximately 10% of newborns require some assistance to begin breathing at birth; however, <1% requires extensive resuscitation (4). It has been estimated that 814 000 newborns die of birth asphyxia (8). In addition, several among the approximately 1 million fresh still births in many cases might be rescued if resuscitation had been tried. In the 2010 ILCOR guidelines, there are a number of important changes of the algorithm, and these are summarized and commented underneath. The most important changes from 2005 are listed in Table 1. The committee also maintains, as in 2005, that it is appropriate to consider discontinuing resuscitation if there has been no detectable heart rate for 10 min. Cord clamping is in general recommended to be delayed for at least 1 min; however, no recommendation for the time of cord clamping is given for babies in need of resuscitation.

ASSESSMENT OF A NEWLY BORN INFANT In the new guidelines, there are three criteria that should be used whether a newly born infant needs follow-up actions or not: (i) born at term, (ii) crying or breathing and (iii) good muscle tone. The 1999 guidelines included two additional criteria: colour pink and clear or meconium-stained amniotic uid (2). Colour pink was removed in the 2005 guidelines (3) reecting the accumulating knowledge that a newly born baby is not supposed to be too pink in the rst minutes of life. Meconium-stained amniotic uid was removed in the 2010 guidelines reecting a change in the interpretation and handling of this condition. Therefore, babies born at term that are breathing or crying and have good muscle tone should be given routine care including drying and kept warm. These actions can be provided with the baby lying on the mothers chest and do not require separation of mother and baby. If any of the three criteria mentioned above are not fullled, the classical ABCD actions should be considered and in case followed in sequence:

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resuscitation of some babies who might not need such an intervention. More specic recommendations for heart rate limits and heart rate responses should be included in future ILCOR guidelines. Suctioning Routine intrapartum oropharyngeal and nasopharyngeal suctioning is not recommended for infants born with clear or meconium-stained amniotic uid. Even depressed infants born through meconium-stained amniotic uid seem not to benet from suctioning, and this is no longer either supported or refuted. B. Ventilation Initial breaths The minimal ination pressure applied should not exceed the pressure necessary to achieve improvement in hear rate or chest expansion. According to the guidelines, an opening pressure of 30 Cm H2O is most often sufcient in term babies; however, occasionally higher pressures are needed. In preterm infants, a peak inspiratory pressure of 2025 Cm H2O is usually sufcient. Sustained ination is tested out in some trials; however, in the new guidelines there is no conclusion whether this should be applied or not during the rst breaths. By contrast, the European Resuscitation Council (ERC) in their guidelines for some reason recommends ve initial long breaths, in spite of the fact that there is not yet much evidence for such a practice (13). In premature infants, it has been shown that a few initial inations with high tidal volume may be detrimental (14). Regarding the use of positive end expiratory pressure (PEEP), there seems to be no data to support or refute this in resuscitation of term infants; however, PEEP is likely to be benecial during initial stabilization of apneic preterm infants who require positive pressure ventilation. Spontaneously breathing preterm infants who have respiratory distress may be supported by continuous positive airway pressure or intubation and mechanical ventilation (4). Ventilation can be performed with a ow inating bag, a self-inating bag, or a pressure-limited T-piece resuscitator. Endotracheal ventilation should, however, be considered at several stages. Laryngeal mask airway should be considered if face mask ventilation or tracheal intubation is unsuccessful only among babies >34 weeks or >2 kg. Nasal prongs are an alternative way of giving respiratory support. Exhaled air ventilation (mouth to mask or mouth tube- to mask ventilation) may be considered if bag-mask devices are not available. Routine measuring of tidal volume is not recommended; however, detection of exhaled CO2 to conrm endotracheal position is recommended and is the most reliable method to conrm endotracheal placement. Oxygen A major change in the use of oxygen has occurred in the last 20 years. In 1992 guidelines stated that there is no reason to

be concerned using 100% oxygen for the short duration of newborn resuscitation (1). During the intervening years, a large body of clinical and experimental data accumulated indicating that this approach was wrong (5,6). Already in 1998 the World Health Organization recommended the use of air for basic newborn resuscitation (15). In 1999 the ILCOR guidelines opted for use of air if oxygen was not available (2). In 2005 ILCOR wrote that the optimal fraction of oxygen (FiO2) for newborn resuscitation was not known. However, in spite of the accumulating data demonstrating detrimental effects of the use of 100% oxygen, ILCOR wrote: there is no reason to change the initial FiO2 chosen (3). This was unfortunate advice, it was already well known in 2005 that FiO2 should be turned down as soon as possible. Since 2006 several national guidelines as from Canada, Australia, Sweden, Finland, the Netherlands, Belgium, UK, Spain and Russia recommended to start newborn resuscitation with air and this has been practiced for more than 15 years in several European centres. The 2010 recommendations of ILCOR stating that In term infants receiving resuscitation at birth with positive pressure ventilation, it is best to begin with air rather than 100% oxygen, therefore represents an important leap forward and an adjustment to the practice in more and more countries. Meta-analyses indicate that based on 814 000 asphyxia-related deaths per year (8), mean (95% condence intervals) 252 000 (146 000374 000) lives can be saved annually by this adjustment (16). In addition, availability of air and using a self-inating bag to initiate resuscitation in stillborn infants might be successful in a number of these 1 million infants (8). The ERC and American Academy of Pediatrics (AAP) modications of the ILCOR guidelines have chosen a somewhat different approach (13,17). Although they both also recommend starting with air, it is recommended that FiO2 should be guided by SpO2 values. The ERC guidelines have chosen the 25th percentile for SpO2 as published by Dawson et al. (18) starting at 2 min of age. The AAP guidelines are closer to the 50th percentile starting already at 1 min of age ending up at the 10th percentile at 510 min of age. This means that especially a number of US babies initially might be given oxygen unnecessary. Babies who despite effective ventilation do not have an adequate heart rate increase, as mentioned above, higher concentrations of oxygen should be considered. Also babies with gestational age <32 weeks often need supplementary oxygen, and this supplementation should ideally be guided by pulse oximetry (19). The optimal FiO2 for babies who do not respond with an adequate SpO2 increase in spite of adequate ventilation is however not known. It is important to remember that if available, oxygen should be at hand and given if needed. In the original studies on air versus oxygen resuscitation, those babies started in air and not responding adequately were switched to oxygen after 90 sec (10).This is the reason 90 sec is used as a time frame in some recommendations (17). This is, however, not evidence based.

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C. Circulation Chest compressions to ventilation should still be carried out at the ratio 3:1, that is, 90 compressions and 30 ventilations per minute. Because cardiac arrest in the newborn in most cases is because of asphyxia, ventilation should be prioritized and a ratio of 3:1 is recommended. However, if cardiac arrest is of cardiac aetiology, a higher compressionventilation ratio should be considered and a ratio of 15:2 is suggested. Studies we have carried out in newborn piglets with cardiac arrest show that a ratio of 9:3 is as efcient as 3:1 (20). The 2-thumb-encircling hand technique is the preferred and recently shown to be the superior method (21). Compressions should be centred over the lower third of the sternum and should compress the chest one-third the anteriorposterior diameter. D. Medications and uid administration If successful intravenous vascular access is not established, intraosseous access to provide uids and medications may be indicated. There is not much human neonatal data regarding the use of adrenaline, and studies in adults seem not to show much effect of adrenaline in cardiac arrest (22). ILCOR recommends a dose of 0.010.03 mg kg of adrenaline intravenously, if adequate ventilation and chest compressions have failed to increase the heart rate to >60 bpm. If intravenous access is not available, adrenaline may be administered endotracheally, a dose of 0.050.1 mg kg is recommended. Even experienced resuscitators are not able to administer adrenaline in case it is needed before the age of 45 min of age (23). Volume replacement should not be given routinely in an infant with no blood loss. If blood loss is observed or suspected, volume replacement with crystalloid or red cells is indicated in babies not responding to resuscitation. Other drugs such as naloxone, sodium bicarbonate or vasopressors are very rarely useful. Other items Temperature control and glucose Newborn infants of <28 weeks gestation should immediately be completely covered in a polyethylene wrap or bag up to their necks without drying and then placed under a radiant heater on the resuscitation table. Infants should be kept wrapped until admission and temperature is checked. Delivery room temperatures should be at least 26C for infants <28 weeks of gestation. Intravenous glucose infusion should be considered as soon as possible after resuscitation with the goal of avoiding hypoglycaemia. No specic target glucose concentration range can be identied. Hypothermia Newborn term or near term infants with moderate to severe hypoxic-ischaemic encephalopathy should be offered hypothermia. Protocols used in the randomized clinical trials should still be followed, i.e. start within 6 h

after birth, continue for 72 h and re-warm over at least 4 h. Proper follow-up coordinated through a regional perinatal system is required. However, all the hypothermia studies were performed when oxygen was still used for resuscitation. It is now known that resuscitation with 100% oxygen induces inammatory changes in the brain and other organs (24). Could it be that the hypothermia effect is different when resuscitation is performed with air instead of 100% oxygen? Ethical issues By contrast to earlier recommendations, no specic diagnoses are mentioned as contraindications to resuscitation. Now it is merely stated that when gestation, birthweight, or congenital anomalies are associated with almost certain death and an unacceptable high morbidity is likely among rare survivors, resuscitation is not indicated. If there is a condition with borderline survival and relatively high rate of morbidity, and when the burden to the child is high, the parents view on resuscitation should be supported. It is appropriate to stop resuscitation if there is no heart rate in the rst 10 min of life; however, if there is any heart rate there is insufcient evidence to guide decisions as to whether to withhold or to continue resuscitation. The guidelines also give recommendations regarding personnel at C section at term, education training, and briengs and debriengs. DISCUSSION The 2010 ILCOR guidelines represent an improvement for newborns requiring resuscitation at birth. Still there are a number of unanswered questions and issues as discussed above which need to be dealt with in the future. It is important that the algorithm has been simplied. Assessment of the child is now based on two vital signs only, heart rate and respirations. The new algorithm gives timing for the rst 60 sec only. As mentioned earlier, it may take more than 60 sec before the heart rate exceeds 100 bpm in normal babies and it has been demonstrated that the former algorithm was not easy to follow. Apgar score revisited The Apgar score has become a robust indicator of the childs condition immediately after birth. However, colour pink is one of the variables of the Apgar score which now has been removed from the guidelines. It may have been unfortunate that pink colour is part of the Apgar score, and this may during the years have contributed to the excessive use of oxygen in newborns requiring resuscitation at birth. Another Apgar variable, reex reaction, is usually triggered by suctioning in the nostril. As suctioning is now not routinely recommended even in depressed babies, the Apgar scoring may contribute to unnecessary suctioning which may potentially be detrimental. There is therefore time to reconsider the Apgar score. A modied Apgar score where colour is removed and suctioning is not longer recommended should be tested out. I

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propose that an international committee try to make a consensus statement on a new Apgar score and test this out in clinical studies. PaCO2 levels The new guidelines do not mention which PaCO2 level is optimal. Animal studies clearly demonstrate that hypocapnia may be detrimental and that brain circulation is restored more efciently with a moderate (PaCO2 89 kPa) hypercapnia (25). Severe hypocapnia (<PaCO2 2.6 kPa), the rst hours after birth, also has been reported detrimental (26). This should therefore be subject for further research.

CONCLUSIONS The 2010 ILCOR guidelines for newborn resuscitation may improve outcome in newborn babies. Still there are a number of unanswered questions related to resuscitation of the newly born infant such as ventilation techniques, heart rate assessments, oxygen administration and oxygen targets, PaCO2 levels and the use of Apgar score. The real effect of hypothermia when newborns have been ventilated with air instead of pure oxygen should be retested in new randomized studies.

References
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10. Saugstad OD, Rootwelt T, Aalen O. Resuscitation of asphyxiated newborn infants with room air or oxygen: an international controlled trial: the Resair 2 study. Pediatrics 1998; 102: e1. 11. Palme-Kilander C, Tunell R, Chiwei Y. Pulmonary gas exchange immediately after birth in spontaneously breathing infants. Arch Dis Child 1993; 68: 610. 12. Dawson JA, Morley CJ. Monitoring oxygen saturation and heart rate in the early neonatal period. Semin Fetal Neonatal Med 2010; 15: 2037. 13. Richmond S, Wyllie J. European Resuscitation Council Guidelines for Resuscitation 2010 Section 7. Resuscitation of babies at birth. Resuscitation 2010; 81: 138999. 14. Bjorklund LJ, Ingimarsson J, Curstedt T, John J, Robertson B, Werner O, et al. Manual ventilation with a few large breaths at birth compromises the therapeutic effect of subsequent surfactant replacement in immature lambs. Pediatr Res 1997; 42: 34855. 15. World Health Organisation. Basic newborn resuscitation: a practical guide. Geneva: WHO, 1998. 16. Saugstad OD, Ramji S, Soll RF, Vento M. Resuscitation of newborn infants with 21% or 100% oxygen: an updated systematic review and meta-analysis. Neonatology 2008; 94: 17682. 17. Kattwinkel J, Perlman JM, Aziz K, Colby C, Fairchild K, Gallagher J, et al. Part 15: neonatal resuscitation: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122(Suppl 3): S90919. 18. Dawson JA, Kamlin CO, Vento M, Wong C, Cole TJ, Donath SM, et al. Dening the reference range for oxygen saturation for infants after birth. Pediatrics 2010; 125: e13407. 19. Vento M, Saugstad OD. Oxygen supplementation in the delivery room: updated information. J Pediatr 2011; 2(Suppl): e57. 20. Solevag AL, Dannevig I, Wyckoff M, Saugstad OD, Nakstad B. Extended series of cardiac compressions during CPR in a swine model of perinatal asphyxia. Resuscitation 2010; 81: 15716. 21. Christman C, Hemway RJ, Wyckoff MH, Perlman JM. The twothumb is superior to the two-nger method for administering chest compressions in a manikin model of neonatal resuscitation. Arch Dis Child Fetal Neonatal Ed 2011; 96: F99101. 22. Attaran RR, Ewy GA. Epinephrine in resuscitation: curse or cure? Future Cardiol 2010; 6: 47382. 23. Barber CA, Wyckoff MH. Use and efcacy of endotracheal versus intravenous epinephrine during neonatal cardiopulmonary resuscitation in the delivery room. Pediatrics 2006; 118: 102834. 24. Markus T, Hansson S, Amer-Wahlin I, Hellstrom-Westas L, Saugstad OD, Ley D. Cerebral inammatory response after fetal asphyxia and hyperoxic resuscitation in newborn sheep. Pediatr Res 2007; 62: 717. 25. Solas AB, Kalous P, Saugstad OD. Reoxygenation with 100 or 21% oxygen after cerebral hypoxemia-ischemia-hypercapnia in newborn piglets. Biol Neonate 2004; 85: 10511. 26. Klinger G, Beyene J, Shah P, Perlman M. Do hyperoxaemia and hypocapnia add to the risk of brain injury after intrapartum asphyxia? Arch Dis Child Fetal Neonatal Ed 2005; 90: F4952.

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