Wade Rich

Early CPAP versus surfactant in extremely preterm infants

BACKGROUND There are limited data to inform the choice between early treatment with continuous positive airway pressure (CPAP) and early surfactant treatment as the initial support for extremely-low-birth-weight infants. METHODS We performed a randomized, multicenter trial, with a 2-by-2 factorial design, involving infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. Infants were randomly assigned to intubation and surfactant treatment (within 1 hour after birth) or to CPAP treatment initiated in the delivery room, with subsequent use of a protocol-driven limited ventilation strategy. Infants were also randomly assigned to one of two target ranges of oxygen saturation. The primary outcome was death or bronchopulmonary dysplasia as defined by the requirement for supplemental oxygen at 36 weeks (with an attempt at withdrawal of supplemental oxygen in neonates who were receiving less than 30% oxygen). RESULTS A total of 1316 infants were enrolled in the study. The rates of the primary outcome did not differ significantly between the CPAP group and the surfactant group (47.8% and 51.0%, respectively; relative risk with CPAP, 0.95; 95% confidence interval [CI], 0.85 to 1.05) after adjustment for gestational age, center, and familial clustering. The results were similar when bronchopulmonary dysplasia was defined according to the need for any supplemental oxygen at 36 weeks (rates of primary outcome, 48.7% and 54.1%, respectively; relative risk with CPAP, 0.91; 95% CI, 0.83 to 1.01). Infants who received CPAP treatment, as compared with infants who received surfactant treatment, less frequently required intubation or postnatal corticosteroids for bronchopulmonary dysplasia (P<0.001), required fewer days of mechanical ventilation (P=0.03), and were more likely to be alive and free from the need for mechanical ventilation by day 7 (P=0.01). The rates of other adverse neonatal outcomes did not differ significantly between the two groups. CONCLUSIONS The results of this study support consideration of CPAP as an alternative to intubation and surfactant in preterm infants. (ClinicalTrials.gov number, NCT00233324.)

Target ranges of oxygen saturation in extremely preterm infants.

BACKGROUND Previous studies have suggested that the incidence of retinopathy is lower in preterm infants with exposure to reduced levels of oxygenation than in those exposed to higher levels of oxygenation. However, it is unclear what range of oxygen saturation is appropriate to minimize retinopathy without increasing adverse outcomes. METHODS We performed a randomized trial with a 2-by-2 factorial design to compare target ranges of oxygen saturation of 85 to 89% or 91 to 95% among 1316 infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. The primary outcome was a composite of severe retinopathy of prematurity (defined as the presence of threshold retinopathy, the need for surgical ophthalmologic intervention, or the use of bevacizumab), death before discharge from the hospital, or both. All infants were also randomly assigned to continuous positive airway pressure or intubation and surfactant. RESULTS The rates of severe retinopathy or death did not differ significantly between the lower-oxygen-saturation group and the higher-oxygen-saturation group (28.3% and 32.1%, respectively; relative risk with lower oxygen saturation, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P=0.21). Death before discharge occurred more frequently in the lower-oxygen-saturation group (in 19.9% of infants vs. 16.2%; relative risk, 1.27; 95% CI, 1.01 to 1.60; P=0.04), whereas severe retinopathy among survivors occurred less often in this group (8.6% vs. 17.9%; relative risk, 0.52; 95% CI, 0.37 to 0.73; P<0.001). There were no significant differences in the rates of other adverse events. CONCLUSIONS A lower target range of oxygenation (85 to 89%), as compared with a higher range (91 to 95%), did not significantly decrease the composite outcome of severe retinopathy or death, but it resulted in an increase in mortality and a substantial decrease in severe retinopathy among survivors. The increase in mortality is a major concern, since a lower target range of oxygen saturation is increasingly being advocated to prevent retinopathy of prematurity. (ClinicalTrials.gov number, NCT00233324.)

Resuscitation of Preterm Neonates by Using Room Air or 100% Oxygen

OBJECTIVE. In this study of preterm neonates of <32 weeks, we prospectively compared the use of room air versus 100% oxygen as the initial resuscitation gas. METHODS. A 2-center, prospective, randomized, controlled trial of neonates with gestational ages of 23 to 32 weeks who required resuscitation was performed. The oxygen group was initially resuscitated with 100% oxygen, with decreases in the fraction of inspired oxygen after 5 minutes of life if pulse oxygen saturation was >95%. The room air group was initially resuscitated with 21% oxygen, which was increased to 100% oxygen if compressions were performed or if the heart rate was <100 beats per minute at 2 minutes of life. Oxygen was increased in 25% increments if pulse oxygen saturation was <70% at 3 minutes of life or <80% at 5 minutes of life. RESULTS. Twenty-three infants in the oxygen group (mean gestational age: 27.6 weeks; range: 24–31 weeks; mean birth weight: 1013 g; range: 495–2309 g) and 18 in the room air group (mean gestational age: 28 weeks; range: 25–31 weeks; mean birth weight: 1091 g; range: 555–1840 g) were evaluated. Every resuscitated patient in the room air group met rescue criteria and received an increase in the fraction of inspired oxygen by 3 minutes of life, 6 patients directly to 100% and 12 with incremental increases. Pulse oxygen saturation was significantly lower in the room air group from 2 to 10 minutes (pulse oxygen saturation at 3 minutes: 55% in the room air group vs 87% in the oxygen group). Heart rates did not differ between groups in the first 10 minutes of life, and there were no differences in secondary outcomes. CONCLUSIONS. Resuscitation with room air failed to achieve our target oxygen saturation by 3 minutes of life, and we recommend that it not be used for preterm neonates.

Video Recording as a Means of Evaluating Neonatal Resuscitation Performance

Objective. To determine the compliance to Neonatal Resuscitation Program (NRP) guidelines in our institution, by the use of videotaped newborn resuscitations. Background. NRP is the standard of care for newborn resuscitation. The application of NRP guidelines and resuscitation skills in actual clinical settings is undocumented. Design/Methods. A video recorder, mounted to the radiant warmer in the main obstetrical operating room, was used to record all high-risk resuscitations. All members of the resuscitation team were NRP-certified. The videotapes were reviewed within 14 days of the resuscitation and then erased. This ongoing review was approved as a quality assurance (QA) project ensuring confidentiality under California law. The first 100 resuscitations were evaluated to assess NRP compliance. Each step in the resuscitation (positioning, oxygen delivery, ventilation, chest compressions, intubation, and medication) was graded. A score was devised, with 2 points being awarded for every correct decision and proper procedure, 1 point for delayed interventions or inadequate technique, and zero points for indicated procedures that were omitted or for interventions that were not indicated. The total points were divided by the total possible points for that patient. The scores for the first 25 resuscitations (group 1) and the last 25 resuscitations (group 2) were compared. Results. Fifty-four percent of the 100 resuscitations had deviations from the NRP guidelines. Ten percent received overly aggressive stimulation and 22% had poor suction technique. Of the 78 infants given oxygen, this decision was considered incorrect in 15% and the delivery technique was poor in 10% of the infants given oxygen. Of those requiring mask ventilation (n = 18), 24% had poor chest expansion, 11% used an incorrect rate, and 17% had inadequate reevaluation. Twelve infants were intubated; only 7 were successfully intubated on the first attempt and only 4 were intubated in <20 seconds. The longest intubation attempt was 50 seconds. Naloxone was given to 2 patients. One was breathing spontaneously with a heart rate >100. Resuscitations receiving a perfect evaluation score were more likely to occur in infants needing less intervention. The level of resuscitation required for groups 1 and 2 were statistically similar. There was no difference in resuscitation scores between the 2 groups. Only the inappropriate use of deep suctioning improved, with 8 of 25 events in group 1, and 0 of 25 in group 2. Conclusions. We have found a significant number of deviations from the NRP guidelines. Video recording of actual clinical practice is a useful QA tool for monitoring the conduct of newborn resuscitation. We are now conducting repeat video assessments of individual NRP providers to determine whether there is improved performance.

Comparison of methods of bag and mask ventilation for neonatal resuscitation

BACKGROUND There are a variety of manual bagging devices used for neonatal resuscitation. To our knowledge, there has been no comparison of the ability of different operators to utilize such devices for the delivery of predetermined inspiratory and end-expiratory pressures. In addition, the use of prolonged inflation may be of benefit for infants who require bag and mask ventilation, and there has been no evaluation of the ability of a variety of operators to reliably deliver such breaths using currently available equipment. METHODS We utilized a neonatal manikin (Laerdal Armonk, NY) with a functional larynx and lungs, and a clear cushioned mask (Owens-BriGam, Morganton, NC). We studied a latex-free disposable anesthesia type bag (Model 5126 Vital Signs, Totawa, NJ), a Jackson-Rees (JR) type anesthesia bag (Model E191 Anesthesia Associates, San Marcos, CA) fitted with a Norman elbow and a flow-control tail-piece (Dupaco, Oceanside, CA), and the Neopuff (Fisher and Paykel, Auckland, New Zealand), an FDA approved mechanical device that is flow-controlled and pressure-limited, specifically designed to facilitate neonatal resuscitation. The ventilating pressures were continuously recorded throughout the process. We evaluated neonatal nurses, neonatal nurse practitioners, neonatal staff and fellows, pediatric residents and neonatal respiratory therapists. RESULTS The peak inspiratory pressure (PIP) was significantly different between operators using either anesthesia bag, P<0.001. Similar results were found for positive end-expiratory pressure (PEEP) with a significant difference among the operator groups, P<0.001. All the differences in post hoc analysis were between the therapists and the other groups, P<0.05. Therapists produced significantly higher pressures than the other groups for both PIP and PEEP (P<0.001). The PIP was similar for all groups using the Neopuff device. The PIP and PEEP delivered by the Neopuff differed from the other two devices independent of the operators (P<0.05). On post hoc analysis, there was a significant difference between the disposable anesthesia bag and Neopuff for both PIP and PEEP for the therapists, whereas among the non-therapists, there was a difference in PIP with the JR device producing a greater PIP (26.6+/-3.8 cmH(2)O) compared with the Neopuff and disposable anesthesia bag (24.8+/-1.1 cmH(2)O, 24.8+/-4.3 cmH(2)O). The level of PEEP was significantly different among all three devices for the non-therapists (1.3+/-1.6 cmH(2)O, Disposable; 2.9+/-1.2 cmH(2)O, JR; 4.7+/-0.5 cmH(2)O, Neopuff; P<0.05). Only the therapists were able to consistently deliver PEEP with the anesthesia bags, whereas all operators could generate the target PEEP with the Neopuff (P<0.05). We compared the pressure delivered during the first second to the pressure delivered during the fifth second during prolonged 5-s inflations. The absolute differences between the first and fifth second for the Neopuff versus the anesthesia bags were significantly different with a median of 7.1 cmH(2)O for the anesthesia bags compared with 0.2 cmH(2)O for the Neopuff, P<0.001, reflecting the difficulty in obtaining and maintaining the target inflation pressures. CONCLUSIONS Our experience suggests that the Neopuff, a purpose-built neonatal resuscitator ventilator, facilitates the delivery of the desired airway pressures while maximizing the operators ability to obtain and maintain a patent airway, and facilitates the delivery of prolonged inflations. Further research is required to determine the clinical benefit of end-expiratory pressure and prolonged inflations in neonatal resuscitation.

Neurodevelopmental Outcomes in the Early CPAP and Pulse Oximetry Trial

BACKGROUND Previous results from our trial of early treatment with continuous positive airway pressure (CPAP) versus early surfactant treatment in infants showed no significant difference in the outcome of death or bronchopulmonary dysplasia. A lower (vs. higher) target range of oxygen saturation was associated with a lower rate of severe retinopathy but higher mortality. We now report longer-term results from our prespecified hypotheses. METHODS Using a 2-by-2 factorial design, we randomly assigned infants born between 24 weeks 0 days and 27 weeks 6 days of gestation to early CPAP with a limited ventilation strategy or early surfactant administration and to lower or higher target ranges of oxygen saturation (85 to 89% or 91 to 95%). The primary composite outcome for the longer-term analysis was death before assessment at 18 to 22 months or neurodevelopmental impairment at 18 to 22 months of corrected age. RESULTS The primary outcome was determined for 1234 of 1316 enrolled infants (93.8%); 990 of the 1058 surviving infants (93.6%) were evaluated at 18 to 22 months of corrected age. Death or neurodevelopmental impairment occurred in 27.9% of the infants in the CPAP group (173 of 621 infants), versus 29.9% of those in the surfactant group (183 of 613) (relative risk, 0.93; 95% confidence interval [CI], 0.78 to 1.10; P=0.38), and in 30.2% of the infants in the lower-oxygen-saturation group (185 of 612), versus 27.5% of those in the higher-oxygen-saturation group (171 of 622) (relative risk, 1.12; 95% CI, 0.94 to 1.32; P=0.21). Mortality was increased with the lower-oxygen-saturation target (22.1%, vs. 18.2% with the higher-oxygen-saturation target; relative risk, 1.25; 95% CI, 1.00 to 1.55; P=0.046). CONCLUSIONS We found no significant differences in the composite outcome of death or neurodevelopmental impairment among extremely premature infants randomly assigned to early CPAP or early surfactant administration and to a lower or higher target range of oxygen saturation. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute; SUPPORT ClinicalTrials.gov number, NCT00233324.).

A Survey of Delivery Room Resuscitation Practices in the United States

Objective. To determine current resuscitation practices of neonatologists in the United States. METHODS. A 15-question survey was developed and mailed to neonatal directors in May 2004. ELRESULTS. Of the total of 797 surveys mailed, 84 were returned undeliverable or unanswered and 450 were returned completed (63% response rate). Respondents were mainly (70%) from level III NICUs. Most programs resuscitate newborns in the delivery room (83%), rather than in a separate room. The number and background of individuals attending deliveries vary greatly, with 31% of programs having <3 individuals attending deliveries. Flow-inflating bags are most commonly used (51%), followed by self-inflating bags (40%) and T-piece resuscitators (14%). Pulse oximeters are used during resuscitation by 52% of programs, and 23% of respondents indicated that there was a useful signal within 1 minute after application. Blenders are available for 42% of programs, of which 77% use pure oxygen for the initial resuscitation and 68% use oximeters to alter the fraction of inspired oxygen. Thirty-two percent of programs use carbon dioxide detectors to confirm intubation, 48% routinely and 43% when there is difficulty confirming intubation. Preterm infants are wrapped with plastic wrap to prevent heat loss in 29% of programs, of which 77% dry the infant before wrap application. A majority of programs (76%) attempt to provide continuous positive airway pressure or positive end expiratory pressure (PEEP) during resuscitation, most commonly with a flow-inflating bag (58%), followed by a self-inflating bag with PEEP valve (19%) and T-piece resuscitator (16%). A level of 5 cm H2O is used by 55% of programs. CONCLUSIONS. Substantial variations exist in neonatal resuscitation practices, some of which are not addressed in standard guidelines. Future guidelines should include recommendations regarding the use of blenders, oximeters, continuous positive airway pressure/PEEP, and plastic wrap during resuscitation.

Thoracoabdominal motion in newborns during ventilation delivered by endotracheal tube or nasal prongs

Preterm infants have asynchronous thoracoabdominal motion (TAM) secondary to a highly compliant chest wall and different lung mechanics compared to term infants. We compared TAM during continuous positive airway pressure (CPAP) administered through an endotracheal tube (ETT‐CPAP) or nasal prongs (nasal‐CPAP), and during synchronized intermittent mandatory ventilation administered by nasal prongs (nasal‐SIMV) in 14 preterm newborn infants. Asynchrony of TAM was quantified by measuring relative motion of chest wall and abdomen with strain gauges and calculating phase angles (θ).

Premedication for Nonemergent Neonatal Intubations: A Randomized, Controlled Trial Comparing Atropine and Fentanyl to Atropine, Fentanyl, and Mivacurium

OBJECTIVE. The purpose of this work was to investigate whether using a muscle relaxant would improve intubation conditions in infants, thereby decreasing the incidence and duration of hypoxia and time and number of attempts needed to successfully complete the intubation procedure. PATIENTS/METHODS. This was a prospective, randomized, controlled, 2-center trial. Infants requiring nonemergent intubation were randomly assigned to receive atropine and fentanyl or atropine, fentanyl, and mivacurium before intubation. Incidence and duration of hypoxia were determined at oxygen saturation thresholds of ≤85%, ≤75%, ≤60%, and ≤40%. Videotape was reviewed to determine the time and number of intubation attempts and duration of action of mivacurium. RESULTS. Analysis of 41 infants showed that incidence of oxygen saturation ≤60% of any duration was significantly less in the mivacurium group (55% vs 24%). The incidence of saturation level of any duration ≤85%, 75%, and 40%; cumulative time ≥30 seconds; and time below the thresholds were not significantly different. Total procedure time (472 vs 144 seconds) and total laryngoscope time (148 vs 61 seconds) were shorter in the mivacurium group. Successful intubation was achieved in ≤2 attempts significantly more often in the mivacurium group (35% vs 71%). CONCLUSIONS. Premedication with atropine, fentanyl, and mivacurium compared with atropine and fentanyl without a muscle relaxant decreases the time and number of attempts needed to successfully intubate while significantly reducing the incidence of severe desaturation. Premedication including a short-acting muscle relaxant should be considered for all nonemergent intubations in the NICU.

Low Oxygen Saturation Target Range is Associated with Increased Incidence of Intermittent Hypoxemia

OBJECTIVE To test the hypothesis that preterm infants randomized to a low vs high O(2) saturation target range have a higher incidence of intermittent hypoxemia. STUDY DESIGN A subcohort of 115 preterm infants with high resolution pulse oximetry enrolled in the Surfactant, Positive Pressure, and Oxygenation Randomized Trial were randomized to low (85%-89%) or high (91%-95%) O(2) saturation target ranges. Oxygen saturation was monitored until 36 weeks postmenstrual age or until the infant was breathing room air without respiratory support for ≥72 hours. RESULTS The low target O(2) saturation group had a higher rate of intermittent hypoxemia (≤80% for ≥10 seconds and ≤3 minutes) prior to 12 days and beyond 57 days of life (P < .05). The duration shortened (P < .0001) and the severity increased (P < .0001) with increasing postnatal age with no differences between target saturation groups. The higher rate of intermittent hypoxemia events in the low target group was associated with a time interval between events of <1 minute. CONCLUSION A low O(2) saturation target was associated with an increased rate of intermittent hypoxemia events that was dependent on postnatal age. The duration and severity of events was comparable between target groups. Further investigation is needed to assess the role of intermittent hypoxemia and their timing on neonatal morbidity.