10RC2 - Berger. Resuscitation of the newborn

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1 10RC2 - Berger Resuscitation of the newborn Thomas M. Berger Neonatal and Paediatric Intensive Care Unit Children s Hospital of Lucerne Lucerne, Switzerland Introduction The respiratory and cardiovascular changes that occur at birth are considerable and unparalleled by any other physiological events that may occur during extrauterine life. Transition from intrauterine to extrauterine life is a dangerous time in the life of a human being. Although neonatal mortality has decreased dramatically in industrialised countries over the past 50 years, deaths in the first week of life and in the first month of life account for the largest proportion of childhood mortality. The most common causes of death are related to prematurity, congenital malformations and perinatal asphyxia. Immediate and adequate support of newborn infants who fail to adapt normally in the delivery room is critically important for their prognosis. In many institutions, paediatricians or neonatologists are not immediately available in unexpected emergency situations and midwives, obstetricians or anaesthesiologists must initiate resuscitation of newborn infants. All parties who have the potential to be involved in neonatal resuscitation should be acquainted with the peculiarities of neonatal resuscitation in order to make adequate decisions in emergency situations. Neonatal resuscitation guidelines were recently revised and published by the International Liaison Committee on Resuscitation (IL- COR) [1,2] and adapted by the European Resuscitation Council (ERC) [3] and the American Heart Association (AHA) [4]. This review will focus on fetal physiology, normal neonatal adaptation and the most common causes of adaptation failure to provide a solid basis for understanding neonatal resuscitation guidelines. Fetal Physiology Secretion and absorption of fetal lung liquid In utero, the future air spaces are filled with fetal lung liquid. Its production is mediated by chloride (Clˉ) secretion by alveolar type II cells. Sodium (Na + ) follows passively and water flows down the osmotic gradient [5]. Around the time of birth, however, the lung liquid must be removed to allow the newborn infant to breathe air. Two mechanisms are believed to be involved in this process, both of which are at least in part linked to the process of labour. The first one involves surges of fetal hormones (epinephrine, cortisol, T 3 ) during labour and delivery. Thyroid and glucocorticoid hormones act synergistically to prime the lung to allow epinephrine to enhance transepithelial Na + absorption through an epithelial Na + channel. The second mechanism, thus far only demonstrated in sheep, is characterised by rhythmic fetal trunk muscle contractions, which frequently occur in synchrony with uterine contractions during active labour and lead to the expulsion of lung liquid [6]. More recently, researchers have been able to visualise lung aeration after birth using phase contrast X-ray imaging in newborn rabbits [7]. They have demonstrated that residual lung liquid clearance from the airways is closely associated with inspiratory activity, whereas between breaths, no significant distal movement of the air-liquid interface could be detected. They speculated that trans-pulmonary hydrostatic pressure generated by inspiration provides the predominant driving force for residual lung liquid clearance. When delivery occurs before the onset of labour (e.g. by elective Caesarean section), there are no surges of fetal stress hormones and lung liquid absorption is impaired. This may be coupled with a lack of lung liquid expulsion because of the absence of uterine contractions. These phenomena are likely explanations for the increased respiratory morbidity seen after Caesarean section deliveries that have occurred prior to labour

2 From fetal to neonatal circulation In utero, the placenta is responsible for fetal gas exchange. The fetal cotyledons are bathed in maternal blood in the intervillous space and CO 2 is removed from and O 2 taken up by the fetal blood. The partial pressure of oxygen (p uv O 2 ) in the umbilical vein only reaches 4 kpa (30 mmhg), but because of the properties of HbF still results in an oxygen saturation of 65-70%. This is the highest oxygen saturation that occurs in the foetus. The fetal blood is then collected in the umbilical vein, bypasses the liver through the ductus venosus Arantii and enters the inferior vena cava just below the right atrium. Mixed with blood from the lower body of the foetus, the umbilical venous blood is preferentially directed from the right atrium across the foramen ovale into the left atrium (intracardiac streaming) [8]. It is then ejected from the left ventricle into the ascending aorta. Thus, well-oxygenated fetal blood reaches the myocardium and the fetal brain. In contrast, deoxygenated blood from the superior vena cava is directed across the right atrium into the right ventricle and pumped into the pulmonary artery. Because pulmonary vascular resistance (PVR) is very high in utero, more than 85-90% of the right ventricular cardiac output bypasses the lung and flows through the ductus arteriosus Botalli into the descending aorta. Through admixture of this poorly oxygenated blood the lower part of the body is perfused with blood that only has an oxygen saturation of 45%. Vascular resistance of the placenta is low and approximately 50% of the combined right and left ventricular cardiac output flows through the internal iliac arteries into the umbilical arteries and eventually reaches the placenta via the umbilical cord [8] (Fig. 1). Figure 1. Fetal circulation: right ventricular output perfuses the descending aorta, the lower part of the body and the placenta, whereas the left ventricular output is directed toward the coronary and cerebral vascular beds with only a small portion crossing the aortic isthmus to perfuse the lower body. Therefore, the right and left ventricles function in parallel to perfuse the fetal body and the placenta (DAB: ductus arteriosus Botalli; DVA: ductus venosus Arantii; FO: foramen ovale; UA: umbilical artery; UV: umbilical vein). After birth, dramatic changes in the circulatory system occur that are vital for normal adaptation. When the umbilical cord is cut, the low resistance placental vascular bed is excluded from the circulation and the systemic vascular resistance (SVR) increases suddenly. At the same time, with the onset of air breathing, high concentrations of oxygen reach the pulmonary blood vessels (alveolar po 2 of 14.2 kpa (107 mmhg) when breathing room air) leading to vasodilatation via an NO-mediated mechanism. With the fall in PVR, pulmonary perfusion increases and pulmonary gas exchange can occur. Pulmonary venous return increases and, when left atrial pressure rises above right atrial pressure, the foramen ovale closes. As pressure in the pulmonary artery falls and pressure in the aorta increases, shunt across the ductus arteriosus Botalli changes from right-to-left to bidirectional and finally left-to-right. The smooth muscle cells of the ductus arteriosus Botalli respond to the increase in pao 2 with constriction, ultimately leading to functional and later anatomical closure of this shunt (Fig. 2)

3 Figure 2. Neonatal circulation after ligation of the umbilical cord: exclusion of the low resistance placental circulation rapidly increases SVR; at the same time PVR falls and pulmonary blood flow increases and pao2 more than doubles. As a consequence, the foramen ovale closes and the ductus arteriosus constricts, thus establishing serial circulations (DAB: ductus arteriosus Botalli; DVA: ductus venosus Arantii; FO: foramen ovale; UA: umbilical artery; UV: umbilical vein). Fetal response to intrauterine hypoxia In utero, fetal hypoxia stimulates a typical sequence of respiratory patterns. Following a period of rapid shallow breathing, a first period of apnoea occurs (i.e., primary apnoea). If intrauterine hypoxia is not corrected, the foetus will then develop gasping respirations followed by a second period of apnoea (secondary apnoea). When delivery occurs during primary apnoea, a newborn infant can be stimulated to restart breathing. In contrast, tactile stimulation alone will be insufficient to correct secondary apnoea and without adequate intervention (i.e. bag-mask ventilation) circulatory collapse will ensue (Fig. 3). Figure 3. Fetal response to hypoxia: Primary and secondary apnoea cannot be distinguished clinically. Since secondary apnoea is rapidly followed by cardiovascular collapse, any newborn not breathing after drying must be provided with positive pressure ventilation. Normal adaptation The most important prerequisite for normal adaptation is the initiation of breathing. With the first breaths, the remaining fetal lung liquid is replaced by air [7]. The forces that are required to establish an air-liquid-interface are surprisingly high (during the first breaths, animals generate intrapleural pressures between -40 to -60 cmh 2 O). Subsequently, compliance normalises to values around 3-5 ml/cmh 2 O so that a pressure gradient of 5-8 cmh 2 O will result in a normal tidal volume of 6 ml/kg in a term infant with a birth weight of 4 kg. Lung aeration and maintenance of a stable functional residual capacity (FRC) are important prerequisites for pulmonary vasodilatation after delivery. Apart from changes in pulmonary vascular geometry, oxygen plays a major role because the increase in alveolar po 2 stimulates endothelial NO synthetase leading to vasodilatation

4 Normally, a healthy newborn starts to breathe or cry within seconds after delivery. Preductal oxygen saturation increases from a fetal value of 65% to more than 90% within the first 10 minutes of life [9-11]. During transition from fetal to neonatal circulation venous admixture through a patent ductus arteriosus into the descending aorta can occur and postductal oxygen saturations can be significantly lower than values measured in preductal positions. Therefore, during resuscitation in the delivery room, oxygen saturation should be measured at the right hand in a preductal position to monitor the infant s heart rate and document the expected increase in oxygen saturation over the first minutes of life. Impaired adaptation There are numerous maternal and fetal conditions that are associated with an increased risk of impaired adaptation. Many of these conditions can be recognised antenatally and the need for resuscitative measures can be anticipated. However, some complications occur unexpectedly (e.g., placental abruption, cord prolapse, uterine rupture, etc.) and can affect individual or all aspects of neonatal adaptation. Impairment of lung liquid clearance Delayed or insufficient clearance of lung liquid can occur after elective Caesarean sections, following rapid deliveries or in premature infants. As long as the newborn infant has an adequate respiratory drive, impairment of lung liquid clearance will manifest as respiratory distress with tachypnoea (respiratory rate above 60/minute), retractions, flaring, grunting and possibly cyanosis. Impairment of respiratory drive The two most common scenarios in which respiratory drive is impaired after delivery are perinatal asphyxia and prematurity. In rare cases, drugs that have been administered to the mother during labour can affect the infant s respiratory centre (e.g., opiates) or weaken its muscular strength (e.g. infusion of magnesium sulphate for preeclampsia). Impairment of circulatory adaptation Impaired circulatory adaptation and thus persistence of fetal circulation can occur after perinatal asphyxia and meconium aspiration, following prolonged rupture of membranes with oligohydramnios and consecutive pulmonary hypoplasia, or in the setting of severe sepsis. Even after successful initial transition, a newborn infant can fall back into a fetal circulatory state, particularly when there is hypoxaemia and/or severe acidosis (i.e., conditions that cause pulmonary vasoconstriction). Epidemiology of neonatal resuscitation Approximately 10% of all newborn infants require some minor interventions after delivery (i.e., tactile stimulation, proper positioning and suctioning of mouth and nose, supplemental oxygen); more advanced resuscitative measures are necessary in about 1% of all deliveries and 80% of these neonates will respond to bag-mask ventilation. In term infants, extensive resuscitation with intubation, chest compressions and administration of resuscitation drugs is very rarely required (about in 1:1000 deliveries). Neonatal resuscitation algorithm It is important that midwives, obstetricians, neonatologists and anaesthetists communicate well to facilitate anticipation of potential problems the newborn infant might present with. A well-organised resuscitation team with clearly defined roles for each team member, including the designation of an experienced team leader, as well as the preparation of proper resuscitation equipment are prerequisites for successful resuscitation

5 Once it has been recognised that an infant might be compromised, the infant should be placed on a resuscitation unit without delay as soon as the cord has been cut. Initial measures include drying of the infant to prevent heat loss and to provide tactile stimulation, correct positioning of the head (i.e. in a sniffing position) and clearing the airway by suctioning of mouth and nose if necessary. This is followed by the assessment of both breathing effort and heart rate, and less importantly tone (note that colour is no longer assessed at this point). If the infant is gasping or not breathing at all, or their heart rate is less than 100 beats/minute, positive pressure ventilation (PPV) must be provided (Fig. 4). Since it is impossible to distinguish primary from secondary apnoea (see above), the more serious condition must be considered and no time should be wasted with further stimulation of the infant. Positive pressure ventilation should be initiated with room air (see below). Figure 4. Bag-mask ventilation using a self-inflating bag; alternatively, a flow-inflating bag or a T-piece resuscitator can be used. In the delivery room, either self-inflating, flow-inflating bags or T-piece resuscitators can be used for respiratory support. Positive end-expiratory pressure (PEEP) may be useful to stabilise the infant s labile FRC, particularly in preterm infants. Successful ventilation requires a proper fit of the mask, an open airway and sufficient inflation pressures. Expansion of the chest should be recognisable but not excessive to avoid volutrauma. The heart rate should readily increase above 100 beats/minute and preductal oxygen saturation should reach values above 90% by the age of 10 minutes. In neonatal resuscitation, successful ventilation is the most important intervention and will suffice in the majority of patients. If the heart rate falls to less than 60 beats/minute despite adequate ventilation, more advanced life support measures are indicated. In this situation, chest compressions at a rate of 90/minute must be coordinated with positive pressure ventilations at a rate of 30/minute with a compression to ventilation ratio of 3:1. Chest compressions are applied over the lower third of the sternum and should compress the chest one third of the anterior-posterior diameter. It is important that chest compressions are only briefly interrupted to deliver positive pressure ventilation. The so-called two thumb-encircling hands method is the preferred mode (Fig. 5), however, the two-finger method (Fig. 6) can be used transiently to facilitate the insertion of an umbilical venous catheter. Figure 5: Chest compressions using two thumb-encircling hands method. Figure 6. Chest compressions using the two-finger method

6 Whenever advanced methods of life support must be provided, it is important to gain vascular access rapidly to administer drugs and isotonic crystalloid solutions (i.e. normal saline, Ringer s lactate) for volume expansion. In depressed neonates, cannulation of peripheral veins is difficult and it is easiest to gain access through the umbilical vein (Fig. 7). In most cases, blood can be aspirated from an umbilical venous line and blood gas analyses and glucose measurements can be performed. If positive pressure ventilation and chest compressions are unsuccessful to restore spontaneous circulation after 30 seconds, intravenous epinephrine should be given at a dose of ug/kg. If no venous access is available but the infant is intubated, epinephrine can be given intratracheally at a dose of ug/kg, however, the efficacy of this route is likely to be inferior to intravenous administration [1-4]. Figure7. Insertion of an umbilical venous catheter: A) using an aseptic technique, the umbilical cord is cut approximately cm above the skin (in case of bleeding, the tape wrapped around the base of the umbilicus can be tightened); B) three vessels can be identified: two small, thick-walled arteries and one larger, thin-walled vein; C) grasping the umbilical cord with a curved forceps, the gaping lumen of the umbilical vein can be seen; D) insertion of the umbilical venous catheter. If the interventions described are unsuccessful or if a stabilised infant deteriorates again, a pneumothorax must be excluded. Its diagnosis can be challenging: unilaterally decreased breath sounds and lateralisation of the heart sounds to the opposite side are the best clinical signs. If the resuscitation area can be darkened, transillumination of the chest with a high intensity light source can be helpful to identify a pneumothorax. The essential steps of neonatal resuscitation are summarised in Fig. 8. Figure 8. Neonatal resuscitation algorithm

7 Oxygen supplementation in the delivery room FiO 2 to be used to start resuscitation For more than 200 years, 100% oxygen has been used in neonatal resuscitation and has remained undisputed until very recently. Although concerns about the ability of newborn infants to cope with oxidative stress and epidemiological reports of potential long-term consequences of perinatal exposure to high oxygen concentrations (i.e. increased risk of developing childhood cancer) have been discussed for many years, the 2005 recommendations for neonatal resuscitation published by the ILCOR, the ERC and AHA still maintained that resuscitation should in general be started with 100% oxygen. They conceded, however, that lower oxygen concentrations and even room air could be chosen as well [12-14]. Based on several meta-analyses [15-19] of prospective randomised controlled trials that demonstrated non-superiority or even a detrimental effect (i.e. increased mortality with a number needed to harm of 20 [19] to 36 [17] associated with resuscitation with 100% oxygen) (Table 3), the revised ILCOR and ERC guidelines of 2010 now uniformly recommend the use of room air rather than 100% oxygen in the resuscitation of term infants [1,2]. In contrast, the 2010 recommendations by the AHA state more conservatively that air or blended oxygen can be used to achieve oxygen saturations in the interquartile range of preductal saturations measured in healthy term infants (Fig. 8). If blended oxygen is not available, resuscitation should begin with room air [1, 2]. In infants who do not respond to resuscitation with room air, the FiO 2 should be increased. The ILCOR and ERC recommendations fail to provide details but simply state [1-3]: If despite effective ventilation there is no increase in heart rate or if oxygenation (guided by oximetry) remains unacceptable, use of a higher concentration of oxygen should be considered. The AHA recommendations are more specific and suggest [4]: If the baby is bradycardic (heart rate < 60 per minute) after 90 seconds of resuscitation with a lower concentration of oxygen, the oxygen concentration should be increased to 100% until recovery of a normal heart rate. Pulse oximetry As discussed previously, changes in oxygen saturation in the first minutes of life are gradual and it takes several minutes before healthy term infants achieve oxygen saturations above 90% [9-11]. Pulse oximetry is the best method to follow this trend. During transition, a preductal location of the oxygen sensor is important since preductal SaO 2 values may be 10-15% higher than postductal SaO 2 values [10]. Pulse oximetry also provides continuous information on heart rate and thus helps to guide resuscitation. Key learning points Up to 10% of all newborn infants require some form of assistance after birth, but more advanced measures of life support are only required by 1% of all neonates Normal adaptation requires timely clearance (absorption, expulsion) of lung liquid, adequate respiratory drive and successful transition from fetal to neonatal circulation Effective ventilation, indicated by chest movement and an increasing heart rate, is the most important intervention in neonatal resuscitation According to updated international resuscitation guidelines, resuscitation of term neonates should be started with room air Supplemental oxygen should only be used if, despite effective ventilation with room air, there is no increase in heart rate or oxygenation remains unacceptably low - 7 -

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