The primary aim of this study will be to assess the effectiveness of LMA over FM ventilation in preventing the need for endotracheal intubation at birth.
This is a single center, prospective, unblinded, randomized clinical trial of LMA ventilation versus FM ventilation in infants weighing >1,500 g or delivered ≥34 weeks’ gestation.
Inborn infants satisfying the following inclusion criteria will be eligible to participate in the study:
gestational age ≥34 weeks (and)
expected birth weight >1,500 g [9, 10] (and)
need for PPV at birth; the need for PPV will be determined by the presence of apnoea or gasping, or heart rate <100 beats per minute (bpm) after initial resuscitation measures (providing warmth, positioning, clearing the airway, drying and stimulation) over the first 30 seconds [1, 2] (and)
parental consent; a written informed consent will be obtained by a member of the neonatal team involved in the study from a parent or guardian before delivery.
Major malformations of the respiratory system.
Congenital heart disease.
Stillbirths; a stillbirth will be diagnosed when a heart rate is never established.
Primary outcome measure
The primary outcome of this study will be the proportion of newborns needing endotracheal intubation.
Secondary outcome measures
Apgar score at 5 minutes.
Time to first breath, defined as the first respiratory effort.
Time to first cry, defined as the first audible cry spontaneously emitted by the infant.
Death or moderate to severe hypoxic-ischemic encephalopathy (HIE) within 7 days of life, according to a modification of Sarnat and Sarnat [15, 16]. According to this classification, HIE grade I (mild) includes irritability, hyperalertness, mild hypotonia, and poor sucking; grade II (moderate) includes lethargy, seizures, marked abnormalities of tone, and requirement of tube feeding; grade III (severe) includes coma, prolonged seizures, severe hypotonia, and failure to maintain spontaneous respiration.
Complications secondary to the procedure.
Admission to NICU/normal nursery.
Other collected data
The following data will be collected during resuscitation: (1) Apgar score at 1 min after birth; (2) LMA insertion time, the rate of successful insertion at the first attempt, and the number of attempts required to insert the LMA successfully; (3) adverse effects during resuscitation.
The findings of this study will be important for other units/settings in high as well low resource countries where neonatal resuscitation is more often performed by pediatricians, midwives, or nurses. Based on the results of the present study, we could speculate whether a short-term educational program on the LMA use will be effective in the clinical practice; furthermore, we will be able to understand whether personnel involved in neonatal resuscitation should be trained to start resuscitation with an FM or with an LMA. Finally, potential complications and side effects due to the LMA will be strictly monitored and collected.
It is estimated that 5% of newborns receive resuscitation with PPV [1, 2]. Therefore, in C hospital, Hanoi, Vietnam with more than 20,000 deliveries per year, approximately 1,000 patients will require resuscitation. Of these, about 90% (900 neonates) are newborns weighing >1,500 g or delivered ≥34 weeks gestation.
The sample size was based on a previous study in which the success rate of LMA and FM were 99% and 84%, respectively . To obtain a 90% power at a 0.05 level of significance (one-sided), at least 58 subjects per group need to be enrolled. The number of patients was increased by 20% for each group considering the possibility of dropouts, leading to a final sample of 142 subjects.
Written and oral information will, whenever possible, be offered to parents prior to the birth of their child if the infant is likely to be eligible. Informed written consent will be signed by a parent or guardian. A senior investigator will be available at all times to discuss concerns raised by parents or clinicians during the course of the trial.
Eligible infants will be assigned to the LMA or the FM group in a 1:1 ratio according to a computer-generated, randomized sequence. The randomized allocation will be concealed in double-enclosed, opaque, sealed, and sequentially numbered envelopes prepared at the University Hospital of Padua.
In the delivery room or operating room, the next sequential randomization envelope will be opened only when the infant will be considered to be eligible by the attending operator. The assigned procedure (PPV with LMA or FM) will then be performed. Multiple births will be separately randomized.
Due to the characteristics of the intervention, neither caregivers nor outcome assessors will be masked to treatment allocation. To minimize bias, strict criteria and definitions will be maintained during the trial.
Guidelines for management
Before starting the study, all those involved in the neonatal resuscitation participated in a one-day theoretical and practical (manikin) course based on the Neonatal Resuscitation Program (NRP). During the course, one section was dedicated to the preparation and insertion of the size 1 Supreme LMA™ . In November 2011, three courses were held by three certificated NRP teachers in collaboration with an expert in the LMA use (DT). A total of 44 participants (15 physicians and 29 nurses) were trained.
After the course, a period of 3 months was left to routinely introduce LMA use in the delivery rooms. Five successful LMA insertions in the manikin and three LMA insertions in the clinical setting were required to all participants before starting the study.
The American Heart Association and American Academy of Pediatrics Guidelines for Neonatal Resuscitation will be followed in this study [1, 2]. After initial steps (warming, clearing airway, drying, stimulation), PPV with FM or LMA and bag will be initiated in the case of apnea and/or gasping and/or heart rate < 100 bpm. The neonate’s trachea will be intubated if the heart rate does not rise or remains less than 60 bpm after 30 seconds of PPV with the LMA or FM. A maximum of three attempts for obtaining effective PPV with an LMA or an FM will be allowed.
Manual ventilation will be initiated in room air at a frequency of 40 to 60 breaths per minute [1, 2]. The FiO2 will be increased to 1,0 (flow rate 6 to 8 L/min) in case of persistent cyanosis and/or heart rate <100 bpm after 90 seconds from the beginning of PPV. At least two trained people involved in the study will take part in the resuscitation of all enrolled patients.
Resuscitation will start immediately after delivery of the infant, when a stop watch will be switched on by one of the members of the resuscitation team.
The duration of resuscitation will be defined as the time period from starting resuscitation to the establishment of a spontaneous and sustained respiratory pattern of efficacious respiratory movements, which allowed the neonate to maintain adequate clinical parameters (heart and respiratory rate).
In this study, the last model of size 1 LMA Supreme (LMA Supreme™, LMA Company, UK) will be used . Previous studies conducted in adult patients showed the efficacy and the safety of the LMA Supreme [19, 20]. The LMA Supreme is superior to the LMA Classic™ with regard to insertion time and oropharyngeal seal pressure ; a further advantage consists in the gastric access.
A previous neonatal manikin study confirmed these findings, including a higher level of satisfaction expressed by users .
Data will be recorded from clinical records and from a data sheet designed for this study, where all the data obtained during resuscitation procedures will be collected by an observer not involved in the resuscitation maneuvers. Registered clinical information will be: eligibility, antenatal history, randomization, and all data above listed in the ‘Primary outcome measure’, ‘Secondary outcome measures’ and ‘Other collected data’ sections. Further information will be collected on expected serious adverse events (SAEs).
Categorical data will be expressed as number and percentage and compared using Fisher’s test. Continuous data will be expressed as mean and standard deviation or median and interquartile range. The normality assumption of continuous variables will be evaluated using Shapiro-Wilk test. Continuous data will be compared using Student’s t-test or the Mann-Whitney non-parametric test. Correlation between continuous data will be evaluated using the Pearson correlation coefficient or the Spearman correlation coefficient. A P-value less than 0.05 will be considered significant. Statistical analysis will be performed using the R 2.12 language .
Duration of study
In this study, 142 infants will be recruited. The trial will terminate when the last recruited infant is discharged from hospital, or dies.
Ethics committee approval
The C hospital, Hanoi, Vietnam Ethis Committees for Human Investigation approved the study (SO:901/QD-PSTW; Ha Noi, 9 August 2012).
Compliance to protocol
Compliance will be defined as full adherence to protocol. Compliance with the protocol will be ensured by two members of the project (TDC, NTTH) responsible for local data collection. They will weekly monitor the adherence to the study protocol and will input the patients’ data in an Excel data sheet.
Safety measures will include incidence, severity, and causality of reported SAEs, represented by changes in occurrence of the expected common neonatal complications and the development of unexpected SAEs. All SAEs will be followed until complete resolution or until the clinician responsible for the care of the recruited patient considers the event to be chronic or the infant to be stable. If there is a reasonable suspected causal relationship with the intervention, SAEs will be reported to the Ethics Committee to guarantee the safety of the participants.