The International Liaison Committee on Resuscitation (ILCOR) Consensus on Science With Treatment Recommendations for Pediatric and Neonatal Patients: Neonatal Resuscitation

Consensus on Science

Studies examining blood pressure, cerebral perfusion, and biochemical indicators of cell damage in asphyxiated animals resuscitated with 100% vs 21% oxygen show conflicting results (level of evidence [LOE] 6).^2–6 One study of preterm infants (<33 weeks of gestation) exposed to 80% oxygen found lower cerebral blood flow when compared with those stabilized with 21% oxygen (LOE 2).⁷ Some animal data indicate the opposite effect, that is, reduced blood pressure and cerebral perfusion with air versus 100% oxygen (LOE 6).²

Meta-analysis of 4 human studies showed a reduction in mortality and no evidence of harm in infants resuscitated with air compared with those resuscitated with 100% oxygen (LOE 1).^8,9 The 2 largest newborn human studies of room air versus oxygen resuscitation were not blinded. In those studies, if there was no response after 90 seconds, those resuscitated with air were switched to supplementary oxygen; a similar proportion who failed to respond while receiving oxygen were not crossed over to room air.^10,11 These results require careful interpretation because of significant methodologic concerns (regarding patient selection, lack of blinding, randomization methods, and follow-up).

Trials have not examined in sufficient detail infants with a birth weight of <1000 g, those with known congenital pulmonary or cyanotic heart disease, and those without discernible signs of life at birth.^10–13 Continuous oximetry studies show that term healthy newborns may take >10 minutes to achieve a preductal oxygen saturation >95% and nearly 1 hour to achieve this postductally (LOE 5).^14–16

Treatment Recommendation

There is currently insufficient evidence to specify the concentration of oxygen to be used at initiation of resuscitation. After initial steps at birth, if respiratory efforts are absent or inadequate, lung inflation/ventilation should be the priority. Once adequate ventilation is established, if the heart rate remains low, there is no evidence to support or refute a change in the oxygen concentration that was initiated. Rather, the priority should be to support cardiac output with chest compressions and coordinated ventilations. Supplementary oxygen should be considered for infants with persistent central cyanosis. Some have advocated adjusting the oxygen supply according to pulse oximetry measurements to avoid hyperoxia, but there is insufficient evidence to determine the appropriate oximetry goal because observations are confounded by the gradual increase in oxyhemoglobin saturation that normally occurs following birth. Excessive tissue oxygen may cause oxidant injury and should be avoided, especially in the premature infant.

Intrapartum Suctioning^W206

Tracheal Suctioning^W206

Consensus on Science

When performed properly, positive-pressure ventilation alone is effective for resuscitating almost all apneic or bradycardic newborn infants (LOE 5).²⁴ The primary measure of adequate initial ventilation is prompt improvement in heart rate (LOE 6).^25–27 The presence or absence of chest wall movement has been described but not assessed adequately (LOE 5).²⁸

In term infants, initial inflations, either spontaneous or assisted, create a functional residual capacity (FRC) (LOE 5).^28–33 The optimum pressure, inflation time, and flow required to establish an effective FRC have not been determined. In case series reporting the physiologic changes associated with initial ventilation of term human neonates, peak pressures used to initiate ventilation varied widely (18–60 cm H₂O). Average initial peak inflating pressures of 30 to 40 cm H₂O were used to successfully ventilate unresponsive term infants (LOE 5).^31–35 In a single small series, a sustained inflation pressure of 30 cm H₂O for 5 seconds for the first breath was effective in establishing lung volume in term infants requiring resuscitation (LOE 5)³¹; the risk and benefits of this practice have not been evaluated. Ventilation rates of 30 to 60 breaths per minute are commonly used, but the relative efficacy of various rates has not been investigated (LOE 8).

Treatment Recommendation

Establishing effective ventilation is the primary objective in the management of the apneic or bradycardic newborn infant in the delivery room. In the bradycardic infant, prompt improvement in heart rate is the primary measure of adequate initial ventilation; chest wall movement should be assessed if heart rate does not improve. Initial peak inflating pressures necessary to achieve an increase in heart rate or movement of the chest are variable and unpredictable and should be individualized with each breath. If pressure is being monitored, an initial inflation pressure of 20 cm H₂O may be effective, but a pressure ≥30 to 40 cm H₂O may be necessary in some term infants. If pressure is not being monitored, the minimal inflation required to achieve an increase in heart rate should be used. There is insufficient evidence to recommend optimal initial or subsequent inflation times.

Consensus on Science

Studies on humans and manikins suggest that effective ventilation can be achieved with either a flow-inflating or self-inflating bag or with a T-piece mechanical device designed to regulate pressure (LOE 4^36,37; LOE 5³⁸). The pop-off valves of self-inflating bags are flow-dependent, and pressures generated during resuscitation may exceed the target values (LOE 6).³⁹ Target inflation pressures and long inspiratory times are achieved more consistently in mechanical models when using T-piece devices than when using bags (LOE 6),⁴⁰ although the clinical implications are not clear. To provide the desired pressure, health care providers need more training to use flow-inflating bags than they need to use self-inflating bags (LOE 6).⁴¹

Treatment Recommendation

A self-inflating bag, a flow-inflating bag, or a T-piece mechanical device designed to regulate pressure as needed can be used to provide bag-mask ventilation to a newborn.

Consensus on Science

Masks that fit over the laryngeal inlet are effective for ventilating newborn term infants (LOE 2⁴²; LOE 5⁴³). There are limited data on the use of these devices in small preterm infants (LOE 5).^44,45 There is currently no evidence directly comparing the laryngeal mask airway with bag-mask ventilation during neonatal resuscitation. Data from 2 case series show that use of the laryngeal mask airway can provide effective ventilation in a time frame consistent with current resuscitation guidelines (LOE 5).^43,46 A single randomized, controlled trial found no significant difference between the laryngeal mask airway and tracheal intubation during resuscitation of infants by experienced providers after cesarean section (LOE 2).⁴² Case reports suggest that when ventilation via a face mask has been unsuccessful and tracheal intubation is unsuccessful or not feasible, the laryngeal mask airway may provide effective ventilation (LOE 5).^47,48

Treatment Recommendation

The laryngeal mask airway may enable effective ventilation during neonatal resuscitation if bag-mask ventilation is unsuccessful and tracheal intubation is unsuccessful or not feasible. There is insufficient evidence to recommend use of the laryngeal mask airway as the primary airway device during neonatal resuscitation or in the settings of meconium-stained amniotic fluid, when chest compressions are required, or for the delivery of drugs into the trachea.

Consensus on Science

Spontaneously breathing newborns establish FRC more quickly and with lower transpulmonary pressures than sick neonates (LOE 5).³² In the sick neonate, CPAP helps stabilize and improve lung function (LOE 4).⁵⁴ Excessive CPAP, however, can overdistend the lung, increase the work of breathing, and reduce cardiac output and regional blood flow (LOE 6).^55,56 There are no prospective, randomized, controlled clinical trials of sufficient power to compare CPAP and positive-pressure ventilation (via bag-mask or bag-tracheal tube) during resuscitation of either the preterm or term neonate. When compared with historical controls, use of CPAP for extremely premature infants in the delivery room was associated with a decrease in requirement for intubation, days on mechanical ventilation, and use of postnatal steroids (LOE 4).⁵³ A small underpowered feasibility trial of delivery room CPAP/PEEP versus no CPAP/PEEP did not show a significant difference in immediate outcomes (LOE 2).⁵⁷

Treatment Recommendation

There are insufficient data to support or refute the routine use of CPAP during or immediately after resuscitation in the delivery room.

Consensus on Science

After tracheal intubation, adequate ventilation is associated with a prompt increase in heart rate (LOE 5).³⁵ Exhaled CO₂ detection is a reliable indicator of tracheal tube placement in infants (LOE 5).^58–61 A positive test (detection of exhaled CO₂) confirms tracheal placement of the tube, whereas a negative test strongly suggests esophageal intubation (LOE 5).^58,60,61 Poor or absent pulmonary blood flow may give false-negative results, but tracheal tube placement is identified correctly in nearly all patients who are not in cardiac arrest (LOE 7).⁶² In critically ill infants with poor cardiac output, a false-negative result may lead to unnecessary extubation.

Exhaled CO₂ detectors identify esophageal intubations faster than clinical assessments (LOE 5).^58,61 Clinical techniques for confirmation of correct tracheal tube placement (eg, evaluation of condensed humidified gas during exhalation, chest movement) have not been evaluated systematically in neonates.

Treatment Recommendation

Tracheal tube placement must be confirmed after intubation, especially in infants with a low heart rate that is not rising. Exhaled CO₂ detection is useful to confirm tracheal tube placement. During cardiac arrest, if exhaled CO₂ is not detected, tube placement should be confirmed with direct laryngoscopy.

Consensus on Science

Despite the widespread use of epinephrine/adrenaline during resuscitation, no placebo-controlled studies have evaluated either the tracheal or intravenous (IV) administration of epinephrine at any stage during cardiac arrest in human neonates. A pediatric study (LOE 7)⁶³ and studies in newborn animals (LOE 6)^64,65 showed no benefit and a trend toward reduced survival rates and worse neurologic status after administration of high-dose IV epinephrine (100 μg/kg) during resuscitation. Animal and adult human studies show that when given tracheally, considerably higher doses of epinephrine than currently recommended are required to show a positive effect (LOE 6).^66–68

One neonatal animal study using the currently recommended dose of tracheal epinephrine (10 μg/kg) showed no benefit (LOE 6).⁶⁹ One neonatal cohort study of 9 preterm infants requiring resuscitation showed that tracheal epinephrine was absorbed, but the study used 7 to 25 times the dose recommended currently (LOE 5).⁷⁰

Treatment Recommendation

Despite the lack of human data, it is reasonable to continue to use epinephrine when adequate ventilation and chest compressions have failed to increase the heart rate to >60 beats per minute. Use the IV route for epinephrine as soon as venous access is established. The recommended IV dose is 0.01 to 0.03 mg/kg. If the tracheal route is used, give a higher dose (up to 0.1 mg/kg). The safety of these higher tracheal doses has not been studied. Do not give high doses of IV epinephrine.

Consensus on Science

Three randomized, controlled trials in neonates showed that isotonic crystalloid is as effective as albumin for the treatment of hypotension (LOE 7).^71–73 No studies have compared the relative effectiveness of crystalloid during resuscitation.

Treatment Recommendation

In consideration of cost and theoretical risks, an isotonic crystalloid solution rather than albumin should be the fluid of choice for volume expansion in neonatal resuscitation.

Consensus on Science

There are no studies examining the use of naloxone in infants with severe respiratory depression from maternal opioids. Vigorous newborns whose mothers received opioids had brief improvement in alveolar ventilation with naloxone without affecting Apgar score, pH, Paco₂, or respiratory rate (LOE 7).⁷⁴ Compared with intramuscular naloxone, IV naloxone produces higher plasma concentrations but has a shorter half-life (LOE 5).⁷⁵ Tracheal or subcutaneous administration has not been examined in neonates, nor has the current recommended dose of 0.1 mg/kg been studied.

Naloxone may interfere with critical functions of endogenous opioids and exacerbate long-term neurohistologic injury of cerebral white matter in asphyxiated animals (LOE 6).^76,77 Cardiac arrhythmias, hypertension, and noncardiogenic pulmonary edema have been reported in adolescents and adults, especially when high doses have been used (LOE 7).⁷⁸ Naloxone given to an infant born to an opioid-addicted mother was associated with seizures.⁷⁹

Treatment Recommendation

Naloxone is not recommended as part of the initial resuscitation of newborns with respiratory depression in the delivery room. Before naloxone is given, providers should restore heart rate and color by supporting ventilation. The preferred route should be IV or intramuscular. Tracheal administration is not recommended. There is no evidence to support or refute the current dose of 0.1 mg/kg.

Consensus on Science

Numerous observational studies showed an association between hypothermia and increased mortality in premature newborns. Premature infants continue to be at risk for hypothermia when treated according to current recommendations (dry the infant, remove wet linens, place the infant on a radiant warmer) (LOE 5).⁸⁰ Two randomized, controlled trials (LOE 2)^81,82 and 3 observational studies (LOE 4^83,84; LOE 5⁸⁵) confirm the efficacy of plastic bags or plastic wrapping (food-grade, heat-resistant plastic) in addition to the customary radiant heat in significantly improving the admission temperature of premature infants of <28 weeks' gestation when compared with standard care (LOE 2^81,82; LOE 4^83,84; LOE 5⁸⁵). There is no direct evidence that this improves mortality or long-term outcomes. Temperature must be monitored closely because there is a small risk that this technique may produce hyperthermia (LOE 2).⁸²

Other techniques have been used to maintain temperature in the delivery room during stabilization (drying and swaddling, warming pads, placing the newborn skin-to-skin with the mother and covering both, etc) but have not been compared with the plastic wrap technique for premature infants (LOE 8).^86,87

Treatment Recommendation

Very low birth weight preterm infants remain at risk for hypothermia. Consider the use of plastic bags or plastic wrapping under radiant heat as well as standard techniques to maintain temperature. All initial resuscitation steps, including intubation, chest compression, and insertion of lines, can be performed with these temperature-controlling interventions in place.

Hyperthermia^W201

Therapeutic Hypothermia^W211A,W211B

Consensus on Science

Low blood glucose is associated with adverse neurologic outcomes in a neonatal animal model of asphyxia and resuscitation (LOE 6).¹⁰³ Hypoglycemia in animals at the time of an anoxic or hypoxic-ischemic insult resulted in larger areas of cerebral infarction and/or decreased survival rates when compared with controls (LOE 6).^104,105 One clinical study showed an association between hypoglycemia (blood glucose <40 mg/dL) measured shortly after resuscitation and poor neurologic outcome following perinatal asphyxia (LOE 4).¹⁰⁶

Hyperglycemia induced in neonatal animal models of hypoxia-ischemia had conflicting effects on the extent of brain injury (LOE 6).^107,108 No clinical neonatal studies have investigated this topic.

Treatment Recommendation

Based on available evidence, the optimal range of blood glucose concentration to minimize brain injury following asphyxia and resuscitation cannot be defined. Infants requiring resuscitation should be monitored and treated to maintain glucose in the normal range.

Consensus on Science

Although delayed cord clamping (30–120 seconds after birth) in premature infants was associated with higher mean blood pressure and hematocrit and less intraventricular hemorrhage, most study subjects did not require resuscitation (LOE 1¹⁰⁹; LOE 2¹¹⁰). Delayed cord clamping in term infants not requiring resuscitation resulted in no clinically significant improvement in stability over the first 4 to 6 hours after birth (LOE 3).^111,112

Treatment Recommendation

No recommendation can be made about the timing of cord clamping when resuscitation is required.