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Abstract
Background Current neonatal resuscitation guidelines recommend 3:1 compression:ventilation (C:V) ratio. Recently, animal studies reported that continuous chest compressions (CC) during a sustained inflation (SI) significantly improved return of spontaneous circulation (ROSC). The approach of CC during SI (CC+SI) has not been examined in the delivery room during neonatal resuscitation.
Hypothesis It is a feasibility study to compare CC+SI versus 3:1 C:V ratio during neonatal resuscitation in the delivery room. We hypothesised that during neonatal resuscitation, CC+SI will reduce the time to ROSC. Our aim was to examine if CC+SI reduces ROSC compared with 3:1 C:V CPR in preterm infants <33 weeks of gestation.
Study design Randomised feasibility trial.
Method Once CC was indicated all eligible infants were immediately and randomly allocated to either CC+SI group or 3:1 C:V group. A sequentially numbered, brown, sealed envelope contained a folded card box with the treatment allocation was opened by the clinical team at the start of CC.
Study interventions Infants in the CC+SI group received CC at a rate of 90/min during an SI with a duration of 20 s (CC+SI). After 20 s, the SI was interrupted for 1 s and the next SI was started for another 20 s until ROSC. Infants in the ‘3:1 group’ received CC using 3:1 C:V ratio until ROSC.
Primary outcome Overall the mean (SD) time to ROSC was significantly shorter in the CC+SI group with 31 (9) s compared with 138 (72) s in the 3:1 C:V group (p=0.011).
Conclusion CC+SI is feasible in the delivery room.
Trial registration number Clinicaltrials.gov NCT02083705, pre-results.
- neonatology
- delivery room
- chest compression
- newborn
- sustained inflation
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What is already known on this topic?
Current neonatal resuscitation guidelines recommend 3:1 compression:ventilation ratio.
The most effective chest compression technique in newborns remains controversial.
What this study adds?
Chest compressions during a sustained inflation is feasible in the delivery room.
Chest compressions during a sustained inflation significantly improved return of spontaneous circulation.
Introduction
Chest compressions (CC) are an infrequent event in newly born infants (~0.08% for near-term and term deliveries)1 2 with a higher incidence in preterm infants (10%–15%).1 3 Outcome studies of delivery room resuscitations report high rates of mortality and neurodevelopmental impairment in those infants receiving CC.1 2 4 5 The poor prognosis associated with receiving CC alone or with medications in the delivery room raises questions as to whether improved cardiopulmonary resuscitation (CPR) methods specifically tailored to the newborn could improve outcomes.6 Cardiac arrest in newborns is most commonly due to asphyxia, hence adequate oxygen delivery while providing CC is necessary to achieve return of spontaneous circulation (ROSC).7 8 Current resuscitation guidelines recommend 3:1 compression:ventilation (C:V) ratio, however the most effective CC technique in newborns remains controversial.9 Animal studies have compared various C:V ratios (eg, 3:1 vs 15:2 vs 3:9) and continuous CC with unsynchronised ventilation and reported no difference in ROSC.10–12 However, when continuous CC were delivered during a sustained inflation (SI) ROSC was significantly improved.13 14 The approach of CC during SI (CC+SI) has not been examined in the delivery room during neonatal resuscitation. We aimed to conduct this feasibility trial to compare CC+SI versus standard neonatal resuscitation in the delivery room. We hypothesised that during neonatal CPR, CC+SI will reduce the time needed to achieve ROSC. Our aim was to examine if CC+SI reduces ROSC compared with 3:1 C:V CPR in preterm infants <33 weeks of gestation.
Methods
This study was carried out at The Royal Alexandra Hospital, Edmonton, a tertiary perinatal centre admitting >350 infants with a birth weight of <1500 g to the neonatal nursery annually. The Royal Alexandra Hospital Research Committee and Health Ethics Research Board, University of Alberta approved the study and the trial was registered at Ciinicaltrials.gov NCT02083705. Between January 2014 to October 2014, deliveries of infant s<33 weeks of gestation were attended by the research team when available in addition to the Resuscitation–Stabilisation–Triage team (RST team) (usually a neonatal nurse, neonatal respiratory therapist, neonatal nurse practitioner and neonatal fellow). The research team was not involved in the clinical care of the infants.
Entry criteria
Inborn infants between 23+0 and 32+6 weeks’ postmenstrual age who required CC in the delivery room.
Exclusion criteria
Infants were excluded if they have a congenital abnormality or condition that might have an adverse effect on breathing or ventilation, for example, congenital pulmonary or airway anomalies, congenital diaphragmatic hernia or congenital heart disease requiring intervention in neonatal period. Infants were also excluded if their parents refused to give consent to this study.
Consent
For this study, our Health Ethics Research Board granted deferred consent because the use of CC in the delivery room is an unpredictable event. Therefore, consent was sought from the parents of these infants as soon as possible after the birth.
Randomisation
Once CC was indicated (after persistent bradycardia or asystole despite effective ventilation), all eligible infants were immediately and randomly allocated to either CC+SI group or 3:1 C:V group (figure 1). A sequentially numbered, brown, sealed envelope contained a folded card box with the treatment allocation was opened by the clinical team immediately before start of CC. The folded card box allocated contained the unique trial number with the treatment allocation to the CC+SI group or the 3:1 C:V group.
Study flow chart. CC, chest compressions; C:V, compression:ventilation ratio; ROSC, return of spontaneous circulation; SI, sustained inflation.
Blinding
There was no blinding of the RST team, as it would not be feasible to conduct a study were either different respiratory support approaches or CC are delivered without the RST team knowing the actual intervention that the subject will receive. However, the data collector and outcome assessor were both unaware of the group allocation.
Description of interventions
Intervention in both groups
Resuscitation was started with air for infants >29 weeks and with 30% oxygen for infants <29 weeks gestation according to our institutional guidelines. Respiratory support was performed using an appropriate size round silicone facemask (Fisher & Paykel Healthcare, Auckland, New Zealand or Laerdal Inc, Stavanger, Norway) and a T-piece device (Giraffe Warmer, GE Healthcare, Burnaby, Canada), a continuous flow, pressure-limited device with a built-in manometer and a positive end expiratory pressure (PEEP) valve (for mask ventilation and during CC in both groups). The default settings used were a gas flow of 8 L/min, peak inflation pressure of 24 cm H2O and PEEP of 6 cm H2O. The RST team attending deliveries were trained to use the device and were familiar with the facemasks. Infants who were apnoeic, had irregular breathing or heart rate <100/min received mask ventilation. In cases of ineffective mask ventilation (eg, no increase in heart rate >100/min) the RST team would perform MRSOPA as well as increase oxygen to 100%.15 If CC were needed (eg, heart rate decreased to <60/min, despite MRSOPA) the clinical team would intubate to establish an adequate airway prior the start of CC. Once CCs were needed, infants received CC according to group allocation using the two-thumb encircling technique (figure 1).15
Study interventions
CC+SI group
Infants randomised to CC+SI received CC at a rate of 90/min during an SI with a duration of 20 s (CC+SI). After 20 s, the SI was interrupted for 1 s and the next SI was started for another 20 s.13 Throughout this time, CC was continued until ROSC. Every 45 s, (approximately two SIs) the clinical team would pause CC to determine heart rate and rhythm, as per current neonatal resuscitation guidelines.15 CC+SI was continued until ROSC (figure 1).
3:1 C:V group
Infants randomised to the ‘3:1 group’ received CC using the current 3:1 C:V ratio recommend in the neonatal resuscitation guidelines.16 Every 45 s the clinical team would pause CC to determine heart rate and rhythm, as per current neonatal resuscitation guidelines.15 3:1 C:V CPR was continued until ROSC (figure 1).
Sample size calculation and primary outcome
For this pilot study, based on the local incidence of CPR in preterm neonates, a convenient sample size of five patients per group was enrolled. Our primary outcome was time to achieve ROSC measured using ECG.
Details of continuous monitoring systems used are available in the online supplementary file.
Supplementary file 1
Data collection
All variables were stored continuously in a multichannel system ‘alpha-trace digital MM’ (B.E.S.T. Medical Systems, Austria) for subsequent analysis. Values of gas flow, tidal volume (VT), airway pressure and exhaled CO2 were recorded at 200 Hz, arterial and regional oxygen saturation, and heart rate were stored every second and the sample rate of regional cerebral oxygenation was 8 s (0.13 Hz). Description of the monitoring system is available in the online supplementary file.
Statistical analysis
Demographics of study infants were recorded. Primary outcome was time to achieve ROSC defined as a heart rate of >60/min for 15 s measured using ECG. Secondary outcomes include: all mortality prior to discharge from hospital, delivery room interventions (rate of intubation and use of epinephrine), mechanical ventilation, use of inotropes, necrotising enterocolitis, bronchoplumonary dysplasia (defined as oxygen and/or respiratory support at 36 weeks), retinopathy of prematurity and brain injury as indicated by abnormal neuroimaging. The data are presented as mean (SD) for normally distributed continuous variables and median (IQR) when the distribution was skewed. Data were compared using Student’s t-test for parametric and Mann-Whitney U test for non-parametric comparisons of continuous variables, and χ2 for categorical variables. p Values are two-sided and p<0.05 was considered statistically significant. Statistical analyses were performed with Stata Intercooled V.12 (Statacorp).
Results
Throughout the study period, a total of 11 infants required CC and were included. All infants were randomised to either study group prior to the commencement of CC. One infant was diagnosed with thanatophoric dwarfism (CC+SI group) and parents of one infant (the infant survived) declined to give consent (3:1 C:V group) and therefore were excluded from further analysis (figure 2). A total of nine infants (n=5 for CC+SI and 4 for 3:1 C:V) were included in the final analysis (figure 2). Demographics of included infants are presented in table 1. Secondary neonatal outcomes are presented in table 2. Overall, two out of five infants in the CC+SI group and none out of four infants in the 3:1 C:V group died during their neonatal intensive care unit stay (p=0.114).
Patient flow chart. CC, chest compressions; C:V, compression:ventilation ratio; SI, sustained inflation.
Demographics of study infants
Secondary neonatal outcomes
Primary outcome: ROSC
Overall the mean (SD) time to ROSC was significantly shorter in the CC+SI group with 31 (9) s compared with 138 (72) s in the 3:1 C:V group (p=0.011).
Delivery room outcomes
All infant in the CC+SI 5/5 and 4/4 in the 3:1 C:V groups were intubated; there were nine and seven intubation attempts in the CC+SI and 3:1 C:V group, respectively. One infant in the 3:1 C:V group received epinephrine and none in the CC+SI group. Surfactant was administered in 4/5 and 2/4 in the CC+SI and 3:1 C:V groups, respectively. The admission temperature was 35.9 (±1.1) and 36.3 (±0.3) in the CC+SI and 3:1 C:V groups, respectively. Heart rate, oxygen saturation, cerebral oxygenation and fraction of inspired oxygen from the first 15 min after birth are presented in figure 3.
Heart rate (/min), oxygen saturation (%), cerebral oxygenation (%) and fraction of inspired oxygen during the first 15 minutes after birth. CC, chest compressions; C:V, compression:ventilation ratio; SI, sustained inflation
Analysis of the respiratory parameter are available as an the online supplementary file.
Arterial blood gas within the first hour after birth
All infants had an umbilical artery catheter placed after resuscitation. The first arterial blood gas was obtained at 49 (±12) and 49 (±25) min after birth in the CC+SI and 3:1 C:V group, respectively. In the CC+SI group: pH 7.1 (±0.09), pCO2 66 (57–78) mm Hg, base excess −9 (±−3) and sodium bicarbonate 20 (±4) mmol/L. In the 3:1 C:V group: pH 7.06 (±0.19), pCO2 55 (42–62) mm Hg, base excess −13 (±−8), sodium bicarbonate 15 (±7) mmol/L and lactate 8 (6–10).
Discussion
The optimal CPR technique to optimise coronary and cerebral perfusion while providing adequate ventilation to an asphyxiated newborn remains unknown.15 Rationales for using the currently recommended 3:1 C:V ratio include the higher physiological heart rate of 120–160 beats/min and breathing rates of 40–60 breaths/min in a newborn compared with an adult. The main cause of cardiovascular collapse in most newborn infants is asphyxia resulting in either serve bradycardic or asystole at birth as a consequence therefore, providing ventilation is more likely to be beneficial in neonatal CPR compared with adult CPR.15 Recently, Schmölzer et al reported that using CC during a SI significantly improved haemodynamics, minute ventilation and time to ROSC compared with the current approach of 3:1 C:V ratio in asphyxiated newborn piglets.13 In the current pilot trial, we randomised infants to either receive 3:1 C:V or CC+SI just before they required CC during initial resuscitation in the delivery room. The results of our pilot study could be summarised as (i) ROSC was significantly faster during CC+SI, and (ii) CC+SI provided higher minute ventilation and inflation rates. The findings in this pilot study were similar to our observations in postnatal newborn piglets, which are equivalent to near-term human neonates.
In the current study, we observed a significantly shorter time to ROSC in the CC+SI group compared with the 3:1 C:V group. Our results are similar to our previously published animal data from our group.13 14 Our initial animal study used a CC rate of 120/min during CC+SI compared with a CC rate of 90/min in the 3:1 C:V group, which showed faster ROSC in the CC+SI group.13 However, the study used a higher rate during CC+SI which might have contributed to the faster ROSC. Further animal studies by our group compared CC rates of 90/min and 120/min with similar time of ROSC.14 During CC carotid blood flow, mean arterial pressure, and % change in ejection fraction and cardiac output were higher in the CC+SI 90/min group compared with CC+SI 120/min.14 This further supports that higher CC rates do not improve systemic perfusion and that the current recommendation of 90 CC per minute are sufficient to achieve systemic perfusion. A further randomised animal trial comparing SI+CC 90/min with 3:1 C:V ratio showed a significant reduction in median (IQR) time to ROSC 34 (28–156) s versus 210 (72–300) s (p=0.05).17 However, a recent animal study using a perinatal cardiac arrest lamb model with transitioning fetal circulation and fluid-filled lungs CC+SI was as effective as 3:1 C:V to achieve ROSC.18 These difference might be partly due to the different model used.19 20
Infants receiving CC in the delivery room have high rates of mortality and neurodevelopmental impairment.1 2 4 5 The poor prognosis associated with receiving CC alone in the delivery room raises questions as to whether improved CPR methods specifically tailored to the newborn could improve outcomes.6 Current resuscitation guidelines recommend a 3:1 C:V ratio,15 however, the most effective technique to resuscitate newborn infants remains unknown. Current best practice is to provide 90 CC and 30 ventilations that are coordinated during a pause.15 The purpose of inflations during CC is to deliver an adequate VT to facilitate gas exchange. However, delivery of an adequate VT during CPR remains difficult. Several mannequin studies reported decreased expiratory VT once CC were started resulting in inadequate oxygen delivery to any asphyxiated newborn.17 18 21 Similar, Li et al reported large mask leak during mask ventilation in the delivery room, which resulted in severe bradycardia and the need for neonatal CC.22 In addition, once CC were started leak further increased.22 These studies suggest a decrease in expiratory VT once CCs are initiated. Furthermore, Li et al reported that during 3:1 C:V each CC results in lung derecruitment with a net VT loss of 4.5 mL/kg per 3:1 C:V cycle.23 In contrast, during CC+SI, no VT loss and a continuous lung recruitment and establishment of functional residual capacity were observed.23 This suggests that CC+SI has improved alveolar oxygen delivery and lung aeration potentially resulting in faster ROSC. This is similar to our study with higher minute ventilation in the CC+SI group compared with the 3:1 C:V group.
Using SI in the delivery room has been associated with increased incidence of pneumothoraxes and intraventricular haemorrhages.24 25 However, a recent randomised trial comparing SI with positive pressure ventilation alone by our group did not find any difference in either pneumothoraxes and intraventricular haemorrhages.26 Similar, in the current trial we observed similar rates of pneumothoraxes and intraventricular haemorrhages between groups (table 2). Overall, there was apparent lack of harm from CC+SI when compared with 3:1 C:V in our pilot study, which suggests safety of CC+SI for a larger randomised control trial.
Limitation
This study aimed to examine if this new CC approach is feasible in the delivery room. We acknowledge that the number of subjects is too small to draw any conclusions regarding the relative efficacy of the two different methods of resuscitation. However, our sample size is similar to other delivery room pilot trials to examine feasibility of the intervention.27 28 We are currently organising a multicentre cluster randomised trial ‘CC+SI versus 3:1 C:V Ratio During Neonatal CPR (SURV1VE)—NCT02858583’ to study this in a larger patient population. Although, this very small sample size, this is the first randomised study in the delivery room examining neonatal CC and proof that it is possible to study it.
A deferred consent approach was used as per Tri-Council Policy Statement in Human Research guidelines for research in ‘Individual Medical Emergencies’, which we believe is a strength of this study. Furthermore, using CC+SI might be difficult to perform using a self-inflating bag or a flow-inflating bag.
Conclusion
CC during SI was feasible in the delivery room and reduced the time to ROSC. A large randomised controlled trial is needed to examine this further. In the meantime, clinicians should continue to use the current recommendation of 3:1 CV ratio.
Acknowledgments
The authors would like to thank the parents and infants agreeing to be part of the study. They would also like to thank the Resuscitation-Stabilization-Triage team of the Royal Alexandra Hospital for helping and supporting the study.
References
Footnotes
Contributors GMS, SvO, MOR and P-YC: conception and design. GMS, SvO, CF, MOR and P-YC: collection and assembly of data; analysis and interpretation of the data; drafting of the article; critical revision of the article for important intellectual content; final approval of the article.
Funding The public did donation to the following funding agencies: GMS is a recipient of the Heart and Stroke Foundation/University of Alberta Professorship of Neonatal Resuscitation and a Heart and Stroke Foundation Canada and a Heart and Stroke Foundation Alberta New Investigator Award.
Competing interests None declared.
Ethics approval The Royal Alexandra Hospital Research Committee and Health Ethics Research Board, University of Alberta.
Provenance and peer review Not commissioned; externally peer reviewed.
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