Pejovic NJ, Höök SM, Byamugisha J, Alfvén T, Lubulwa C, Cavallin F, Nankunda J, Ersdal H, Blennow M, Trevisanuto D, Tylleskär T. A Randomized Trial of Laryngeal Mask Airway in Neonatal Resuscitation. N Engl J Med. 2020 Nov 26; 383 (22):2138-2147. PMID: 33252870
Ashajyothi M Siddappa, MD
Staff Neonatologist, Hennepin Healthcare, Minneapolis, Minnesota, USA
In neonates with asphyxia needing positive pressure ventilation at birth treated by midwifes in low income countries (P), does use of cuffless laryngeal mask airway ventilation (LMA) (I) compared to face mask ventilation (C) reduce mortality and morbidity (O) during first week of life (T)?
- Design: An investigator initiated, single-site, randomized, phase 3, open-labeled, superiority, controlled trial involving neonates who needed resuscitation at birth in two parallel groups: resuscitation with an LMA (i-gel, size 1, Intersurgical) or with a face mask (round-shaped, silicone, size 1, Laerdal Medical). Two-tier procedure used to get consent. The trial protocol and statistical plan along with full text of the article is available at NEJM.org.
- Blinding: Day by day cluster randomization with assignments remained concealed in opaque, sealed, and dated envelopes, pending the actual date of randomization.
- Follow up: Follow up data was available for 99.2% of neonates through hospitalization.
- Patients: Infants born > 34 weeks gestation, birth weight ≥2000g or both, born in Mulago National Referral Hospital in Kampala, Uganda and required positive pressure ventilation (PPV) at birth were included in the study. Infants with major malformations and stillbirths were excluded.
- Intervention: At birth-resuscitated infants with asphyxia received 3 minutes of ventilation by midwives with device of the day, after 3 minutes if ventilation was inadequate LMA was repositioned or the facemask was reapplied before switching to the other device. The decision to switch was followed per recommendations from the International Liaison Committee on Resuscitation (ILCOR). In every case, the reason for switching was documented. All the midwives involved in neonatal resuscitation participated in training session based on Helping Baby Breathe (HBB) curriculum. Main aim of the training was to teach providers to recognize the need for PPV, support the management of resuscitation, teach use of a facemask and an LMA, adherence to protocol. The severity of hypoxic-ischemic was assessed using Thompson score, a validated clinical and prognostic tool that is used in setting where sophisticated technology is not available. Infants with 5 minute APGAR score less than 7, infants with persistent respiratory distress or with signs of hypoxemic ischemic encephalopathy were transferred to NICU.
- Primary outcome: Death within 7 days of birth or admission to NICU with moderate to severe encephalopathy at day 1 to 5 during hospitalization
- Secondary outcomes:
- Safety of an LMA ventilation by midwives
- Need for advanced resuscitation
- Neonatal early death (<7days)
- Very early neonatal death (<24 hrs)
- Admission to NICU with Moderate to severe encephalopathy at day 1 to 5 during hospitalization
- Admission to NICU with mild to severe encephalopathy at day 1 to 5 during hospitalization
- Any hospital admission during first 7 days of life
- Analysis and sample size:
- A sample size of 954 neonates needed to detect 90% chance of an absolute difference of 10 percentage points in the primary outcome (30% in the LMA group vs 40% in the facemask group) at a two-sided significance level of 5%. The sample size increased to 1150 to account for day-by-day cluster randomization, under the assumption of an intraclass correlation of coefficient 0.10 and daily enrollment of three neonates. The statistical analysis included use of chi-square test or Fisher’s exact test to compare outcome measures between the groups. Effect size reported as relative risk with 95% confidence interval. All tests were two sided and a P value of less than 0.05 was considered statistically significant.
- 17, 505 neonates were eligible for the study. 16,791neonates had mother provide oral consent, 714 mothers did not provide consent. Only 1439 neonates needed PPV at birth. After exclusion of 268 neonates, 1171 neonates underwent randomization, 8 more neonates were withdrawn from trial after video review leaving 566 neonates assigned to an LMA ventilation and 597 to face mask ventilation. For final analysis, after 9 infants lost to follow up, there were 563 neonates in LMA group and 591 in facemask group.
Both groups had similar baseline characteristics. Crossover to other device occurred 18/20 neonates in the LMA group and 44/65 neonates in the face mask group. The crossover occurred after a median duration of 11 minutes in LMA group and 8 minutes in the facemask group. Primary outcome occurred in 27.4% infants in LMA group and 24.4% infants in facemask group with adjusted RR 1.16, 95% confidence interval of 0.90-1.51; p =0.26. Secondary outcomes were not different between the LMA vs facemask ventilation groups; advanced resuscitation (6.9% vs 6.5%), early neonatal death (21.7% vs 18.4%), very early neonatal death (15.8 % vs14.4%) , admission to NICU with Thompson score of 11 at days 1-5 during hospitalization (11.2% vs 10.1%), admission to NICU with Thompson score of 7 at days 1-5 during hospitalization (21.1% vs 22.8%), any hospital admission during first 7 days of life (95.6% vs 95.7%). There was no statistically significant difference between the groups with regard to secondary outcomes. There were no difference between the groups with regard to adverse events including severe adverse events (Trauma/ bleeding/vomiting, stridor/sepsis/omphalitis) during resuscitation and during hospitalization.
In neonates with asphyxia in low-income countries, an LMA was used safely by midwives for ventilation but was not superior to face mask ventilation with respect to early neonatal death or moderate to severe hypoxemic ischemic encephalopathy
Birth asphyxia is the leading cause of neonatal mortality in low-income countries (1). Improving resuscitation and outcomes from neonatal resuscitation at birth is crucial (2). Asphyxiated newborns often require bag-mask ventilation (BMV) as part of their initial resuscitation. When this fails, intubation is necessary. However, intubation is a difficult skill to practice especially for non-doctor staff present at delivery in low-income countries (2). Thus, improving the effectiveness of initial efforts to provide ventilation in asphyxiated newborn may decrease the need for extensive resuscitation and improve neonatal outcomes. Previous studies have shown an LMA is effective in providing positive pressure ventilation (PPV) ventilation at delivery, (3) while other benefits of an LMA include ease of placement, minimal trauma, less air leak and improved seal (4). In this study, Pejovic and colleagues tested whether PPV provided in low-income countries by midwives using an LMA was superior to BMV. This large, RCT demonstrated that using an LMA to provide PPV at birth by midwives in neonates with asphyxia did not decrease mortality and morbidity when compared with facemask ventilation at birth.
Although the current study did not show a benefit of using an LMA for initial resuscitative efforts when compared with facemask ventilation, it still may have a role in providing PPV at birth in low-income countries. The current phase three trial was done at a high volume delivery hospital in Uganda. Whether conducting the study in a hospital with low volume where midwives are less familiar with traditional BMV would have a different result is unknown. Furthermore, access to fetal monitoring would have increased the pre-test probability of birth asphyxia, and potentially increased the ability of the study to detect a therapeutic effect. Previous studies have shown an LMA can be used in place of intubation for advanced airway management; it would be interesting to know if the transition from initial resuscitation to advanced resuscitation was improved with use of an LMA. Additional studies are needed to determine effectiveness of an LMA ventilation in infants with asphyxia with different study design; including fetal monitoring, patient selection, resuscitative steps, and selection of hospital.
This study shows an LMA can be used safely by midwives for providing ventilation at birth as measured by these short-term in-hospital experience. Along with these short-term morbidity and mortality data, assessment of long-term outcomes is needed. Furthermore, it would be interesting to know whether additional studies of an LMA vs facemask ventilation at birth would demonstrate a beneficial role for an LMA in neonatal resuscitation. Finally, although an LMA ventilation provided by midwives at birth in neonates with asphyxia while not superior to facemask ventilation with regard to in hospital morbidity and mortality in low-income countries, it was shown to be safe, which opens the door to future study of an LMA in neonatal resuscitation in low-income countries.
- Levels & trends in child mortality: report 2018, estimates developed by the United Nations Inter-agency Group for Child Mortality Estimation. New York: UNICEF, 2018.
- Niermeyer S, Robertson NJ, Ersdal HL. Beyond basic resuscitation: what are the next steps to improve the outcomes of resuscitation at birth when resources are limited? Semin Fetal Neonatal Med 2018; 23: 361-8.
- Kamath-Rayne BD, Berkelhamer SK, Ashish KC, Ersdal HL, Niermeyer S. Neonatal resuscitation in global health settings: an examination of the past to prepare for the future. Pediatr Res 2017; 82:194-200.
- Tracy MB, Priyadarshi A, Goel D, Lowe K, Huvanandana J, Hinder M. How do different brands of size 1 laryngeal mask airway compare with face mask ventilation in a dedicated laryngeal mask airway teaching manikin? Arch Dis Child Fetal Neonatal Ed 2018; 103: F271-F276.