Changing guidelines via the ILCOR process

Representatives of the American Heart Association, the European Resuscitation Council, the Heart and Stroke Foundation of Canada and the Resuscitation Council of South Africa founded the International Liaison Committee on Resuscitation (ILCOR) in 1992. Other organisations subsequently joined and in 1995 the task force of ILCOR established a neonatal subgroup. After the 2005 ILCOR publication,6 this subgroup became an autonomous neonatal task force.

For 2010, as with the previous evidence evaluation processes, the specific questions to be evaluated were informed by priorities identified by task forces and individual councils/organisations, review of the research gaps analysis and a thorough systematic approach called ‘evidence mapping’ based on the previous guidelines.7 The questions were structured into a standardised format (PICO: population/patient, intervention, comparison, outcome; http://www.cebm.net/?o=1036).8 Each question was allocated to two worksheet authors selected to avoid potential conflicts of interest. Worksheets were reviewed by the neonatal task force chair and evidence evaluation experts whose feedback guided subsequent revision, and they were subsequently posted on the ILCOR and American Heart Association websites. They were open to comment, which informed further evaluation and revision.

From this evidence, consensus statements on the science and treatment recommendations were agreed for each question. For the neonatal consensus statements, the international task force attending the evidence evaluation meeting in February 2010 contributed directly to the final consensus document,3 4 which has been used as the basis for constructing national guidelines.1 2 5 9

The 2010 process was international and robust, however, it can be improved with more active involvement of clinicians worldwide commenting on worksheets, influencing the questions to be addressed and especially by participating in resuscitation research.

New guidelines

Changes to guidelines1 always bring a degree of uncertainty and there will be a period of transition. However, much of what was previously practiced will be continued, since the major areas for argument and discussion usually affect relatively few babies.

The newborn resuscitation guidelines have been published elsewhere,1 2 so this paper will address the major changes (table 1) in more detail. However, those who wish to assess all of the evidence should consult the European Resuscitation Council guidelines2 and the original worksheets (http://www.ilcor.org).

Major changes in resuscitation management

Cord clamping

“A quel moment doit-on pratiquer la ligature du cordon ombilical?” was a question posed by Budin in 1875.10 The exact timing of clamping the cord in different clinical situations remains controversial. The modern approach of early or immediate clamping appears to have been an unintended consequence of the introduction of active management of the third stage of labour in the 1970s. This became common practice despite evidence that clamping before the first breath may cause bradycardia11 and may momentarily reduce cardiac output.12 However, studies of placental transfusion rate have not shown a clear relationship between infant blood volume in the first hour of life and the timing of cord clamping in relation to the establishment of regular breathing.13 This may be because the time at which the cord is clamped is only one of a number of mechanisms affecting the volume of placental transfusion. Intrapartum compression of either the cord or the fetal thorax might affect venous return14 15 and the total fetal blood volume at delivery.

Although definitions of ‘early’ and ‘delayed’ cord clamping vary, there have been a number of comparative studies. In term babies, delayed clamping confers an improved iron status due to increased placental transfusion. There were concerns that increased placental transfusion would result in increased jaundice and a number of these studies reported increased use of phototherapy. However, criteria for use of phototherapy were not strictly defined and there was no increase in the need for exchange transfusion. In preterm babies, benefits of later clamping include greater stability in postnatal transition, more stable blood pressure, reduced use of inotropes and fewer subsequent blood transfusions.16,–,19 Concerns about increased risk from hyperbilirubinaemia have not been substantiated.

For uncompromised babies, a delay in cord clamping of at least 1 min from the complete delivery of the infant is now recommended.1,–,4 Unfortunately, most studies have excluded babies who require resuscitation at birth. There is, therefore, insufficient evidence to make a recommendation for babies requiring resuscitation. It should be noted that most preterm babies are uncompromised and in need of stabilisation rather than resuscitation and therefore, the recommendation might be equally applied to them as it is to uncompromised babies at term.

Only one study has addressed the effect of cord clamping upon breathing11 and the effect upon babies who are apnoeic is not known. We do not know exactly as how long to wait after delivery before clamping the cord, or whether waiting longer may have adverse effects for mother, infant or both. More evidence is required, from good-quality randomised trials, ideally with both maternal and neonatal outcome measures.

Starting resuscitation with air

In 2005, ILC0R found insufficient evidence to specify the concentration of oxygen to be used at initiation of resuscitation.6 20 Depending upon the perspective, this was either a step too far or not far enough and the issue was again addressed for 2010. In term babies, who received resuscitation, 100% oxygen conferred no advantage over air in the short term and resulted in an increased time to the first breath and cry.21 22 Furthermore, there was a decreased mortality for the babies in whom resuscitation was commenced using air.23 24

Animal evidence has been difficult to extrapolate as many studies use animals already adapted to extrauterine life. Two models of hypoxic-ischaemic resuscitation found that animals receiving air rather than 100% oxygen showed evidence of abnormal biochemical changes in the brain.25 26 However, no other animal data have demonstrated a clinical advantage for 100% oxygen in resuscitation and there is evidence of harm at the cellular level.27 28

The 2010 ILCOR document recommends using air to commence resuscitation of term infants rather than 100% oxygen.3 4 If, despite effective ventilation, there is no response then a higher concentration of oxygen should be considered. The UK1 and ERC2 guidelines have taken the 25th percentile of pulse oximetry values as published by Dawson et al29 as ‘acceptable’ to guide oxygen use, starting at 2 min of age (when a pulse oximetry reading may be available) (table 2). Supplemental oxygen should not be required in babies with saturation above these values. It is important to note that the American Academy of Paediatrics (AAP) guidelines utilised the 50th percentile starting at 1 min of age and ending at the 10th percentile at 5–10 min of age. Therefore, those following the AAP guidelines may initially be prompted to administer oxygen to many more babies. Although higher concentrations of oxygen should be considered in babies who do not respond, there is little evidence to suggest that increasing the inspired oxygen concentration would be an effective remedy in this situation.

The situation for preterm babies is more complicated, with less human evidence but more potential for harm with the use of higher concentrations of oxygen. For babies less than 32 weeks gestation, resuscitation or stabilisation should be commenced in air and the ILCOR treatment recommendation states that use of oxygen should be guided by oximetry avoiding both hyperoxaemia and hypoxaemia.3 In the UK, the same 25th percentile has been taken as an acceptable upper limit for pulse oximetry readings (table 2) for preterm babies. Such didactic approaches are necessary for the implementation of guidelines but it is important to realise the level of evidence upon which they are based.

This change will necessitate the availability of both air and oxygen in delivery areas. It will also require pulse oximeters to guide any oxygen supplementation, although the initial introduction of oximetry is likely to reduce the use of oxygen. Pulse oximeters have also been recommended to assess the heart rate of babies requiring resuscitation or stabilisation.1 2

Initial assessment and stabilisation

The initial assessment remains as before, taking into account tone, breathing, heart rate and colour. Response to resuscitation is best judged by heart rate and later by breathing efforts. Clinical estimation of colour is not an accurate way to estimate oxygenation30 and therefore pulse oximetry should be considered in preterm births, where the infant may have problems with transition or may need resuscitation. A number of different studies have addressed the accuracy of pulse oximetry in measuring heart rate31 32 in the delivery room at all gestations and have shown the feasibility of pulse oximetry during newborn resuscitation. However, none of these studies examined the impact of these measurements on resuscitation outcomes. An accurate reading is available approximately 90 s after application of the pulse oximeter33 and auscultation is therefore necessary to assess heart rate initially, although the accuracy of auscultation by professionals has also been questioned.34 35 There continues to be a requirement for a rapid and accurate method of heart rate assessment at birth and subsequently.

Meconium

Routine intrapartum oropharyngeal and nasopharyngeal suctioning for infants born with clear and/or meconium-stained amniotic fluid is not recommended. If presented with a floppy, apnoeic baby born through meconium, it is reasonable to inspect the oropharynx rapidly to remove potential obstructions. Tracheal intubation and suction may be useful if the practitioner is skilled in this technique. However, if attempted intubation is prolonged or unsuccessful, start mask ventilation, particularly with persistent bradycardia. While non-vigorous infants born through meconium-stained amniotic fluid are at increased risk of meconium aspiration syndrome, the practice of routine tracheal suctioning of such babies has never been evaluated in a prospective controlled study. The guidelines state that suctioning of the airway and/or trachea should depend upon the likelihood of obstruction.1 2 Meconium, blood clots, thick tenacious mucus or vernix all have the potential to cause airway obstruction. There is no evidence to support suctioning of the mouth and nose of babies born through clear amniotic fluid.

Drugs

Despite the widespread use of epinephrine in neonatal resuscitation, there is no evidence of efficacy from randomised controlled trials for clinically important outcomes. However, if adequate ventilation and chest compressions have failed to increase the heart rate to >60 beats per minute, it is reasonable to use epinephrine and the intravenous route is recommended. In comparison with intravenous administration, the tracheal route is less effective in babies,36 produces lower blood concentrations37,–,40 and may interfere with control of airway and breathing.41 42 Therefore, the tracheal route cannot be recommended, but if used a dose of 50–100 µg/kg is likely to be needed to achieve an effect similar to an intravenous dose of 10 µg/kg.3 4 Evidence for efficacy at birth, the most appropriate dose and route of administration all require further study.

Capnography

Detection of exhaled carbon dioxide confirms tracheal intubation in neonates with a cardiac output more rapidly and more accurately than clinical assessment alone.43 False-negative readings may occur in very low birthweight neonates and in infants during cardiac arrest. False positives may occur with colorimetric devices contaminated with epinephrine, surfactant and atropine. Detection of exhaled carbon dioxide in addition to clinical assessment is recommended as the most reliable method to confirm tracheal placement in neonates with spontaneous circulation.2 Further research with clinically important outcomes is needed to identify the best technique for the detection of carbon dioxide for differing birth weights and gestations.

Temperature

Discontinuation of resuscitative efforts

In contrast to previous guidelines, no specific diagnoses are mentioned as contraindications to resuscitation. However, examples are given where ‘gestation, birth weight and/or congenital anomalies are associated with almost certain early death and unacceptably high morbidity is likely among the rare survivors, resuscitation is not indicated’.2 It is appropriate to consider stopping resuscitation if there is no detectable heart rate in the first 10 min of life. However, it is recognised that the decision to stop is often complex and influenced by arrest aetiology, gestation and the presence of complications as well as the previously expressed feelings of parents about acceptable risk of morbidity. A senior, experienced clinician should lead such decisions.

In cases where the heart rate is less than 60/min at birth and does not improve after 10 or 15 min of continuous and apparently adequate resuscitative efforts, the choice is much less clear. In this situation, there is insufficient evidence about outcome to enable firm guidance on whether to withhold or to continue resuscitation.

Resuscitation or stabilisation

Most preterm babies are reasonably healthy at birth and required assistance in making the transition to extrauterine life. Intervention is aimed at maintaining a healthy, warm, infant and instituting appropriate longer-term supportive measures. The guidelines therefore attempt to differentiate between stabilisation of preterm babies and resuscitation, which is more usually required in the few near term babies who have suffered significant perinatal stress or hypoxia. This will require a shift in thinking and in documentation following birth.