New modes of surfactant delivery.

The provision of exogenous surfactant to premature infants with respiratory distress syndrome has revolutionized the way we care for these patients, significantly improving survival and decreasing morbidity. Currently, the Intubate-SURfactant-Extubate (INSURE) to non-invasive ventilation method remains the standard method for surfactant delivery in the United States. However, the INSURE method requires intubation via direct visualization with a laryngoscope and possible need for sedation. Both carry significant risk to the patients, prompting the development of less invasive ways of safely and efficaciously providing surfactant to newborn infants. The present article reviews and describes the benefits and limitations of several of these alternative methods, including Less Invasive Surfactant Administration (LISA), Minimally Invasive Surfactant Therapy (MIST), via aerosolization, laryngeal mask airway (LMA), and direct nasopharyngeal deposition, focusing on assessment of clinical benefits and the level/risk of invasiveness.

Introduction of less invasive surfactant administration (LISA), impact on diagnostic and therapeutic procedures in early life: a historical cohort study.

BACKGROUND: In preterm infants with Respiratory Distress Syndrome (RDS), Less Invasive Surfactant Administration (LISA) has been established to reduce the need of mechanical ventilation and might improve survival rates without bronchopulmonary dysplasia. The aim of this study was to investigate whether NICU care has changed after introduction of less invasive surfactant administration (LISA), with regard to diagnostic and therapeutic procedures in the first week of life. METHODS: Infants with gestational age < 32 weeks who received surfactant by LISA (June 2014 - December 2017, n = 169) were retrospectively compared to infants who received surfactant after intubation (January 2012 - May 2014, n = 155). Local protocols on indication for surfactant, early onset sepsis, blood transfusions and enteral feeding did not change between both study periods. Besides, as secondary outcome complications of prematurity were compared. Data was collected from electronic patient files and compared by univariate analysis through Students T-test, Mann Whitney-U test, Pearson Chi-Square test or Linear by Linear Association. RESULTS: All baseline characteristics of both groups were comparable. Compared to controls, LISA patients received a higher total surfactant dose (208 vs.160 mg/kg; p < 0.001), required redosing more frequently (32.5% vs. 21.3%; p = 0.023), but needed less mechanical ventilation (35.5% vs. 76.8%; p < 0.001). After LISA, infants underwent fewer X-rays (1.0 vs. 3.0, p < 0.001), blood gas examinations (3.0 vs. 5.0, p < 0.001), less inotropic drugs (9.5% vs. 18.1%; p = 0.024), blood transfusions (24.9% vs. 41.9%, p = 0.003) and had shorter duration of antibiotic therapy for suspected early onset sepsis (3.0 vs. 5.0 days, p < 0.001). Moreover, enteral feeding was advanced faster (120 vs. 100 mL/kg/d, p = 0.048) at day seven. There were no differences in complications of prematurity. CONCLUSION: The introduction of LISA is associated with significantly fewer diagnostic and therapeutic procedures in the first week of life, which emphasizes the beneficial effects of LISA.

Rigid catheters reduced duration of less invasive surfactant therapy procedures in manikins.

AIM: Different catheters can be used for less invasive surfactant therapy (LIST): feeding tubes inserted with or without Magill forceps, different angiocatheters and centre specific devices, such as umbilical catheters affixed to a stylet. This study compared the effectiveness of LIST devices and endotracheal tubes (ETT). METHODS: Video recordings of 20 neonatologists simulating different LIST techniques on two manikin heads were analysed. Procedural effectiveness was evaluated by the duration of procedures and failure rates. Ease of use was scored. RESULTS: The median procedure time for the Neonatal Intubation Trainer was significantly longer with feeding tubes without Magill forceps. For the more difficult ALS Baby Trainer, successful procedures lasted a median of 24 (17-32) seconds with ETT, 24 (15-36) seconds with stylet-guided catheters and 34 (27-46) seconds and 37 (29-42) seconds with 13-cm and 30-cm angiocatheters, respectively. Both methods using feeding tubes were statistically slower than ETT intubation, lasting 32 (25-44) seconds and 39 (27-95) seconds with or without Magill forceps. Failure rates (7-20%) were no different between the LIST methods. Techniques using feeding tubes were rated as more difficult. CONCLUSION: Only rigid or stylet-guided catheters required tracheal catheterisation times similar to those of endotracheal intubation and neonatologists found them easier.

Minimally invasive surfactant therapy with a gastric tube is as effective as the intubation, surfactant, and extubation technique in preterm babies.

AIM: Preterm infants requiring surfactant replacement have been treated using the INSURE technique, which requires sedation and comprises tracheal intubation, surfactant instillation and extubation. However, minimally invasive surfactant therapy (MIST) does not require sedation, minimises airway injury and avoids placing positive pressure ventilation on an immature lung. This study compared the feasibility of the two techniques and the outcomes in preterm babies with respiratory distress syndrome (RDS). METHODS: Preterm infants with RDS prospectively received surfactant via a gastric tube placed in the trachea by direct laryngoscopy with no sedation. Technique-related complications and respiratory outcomes were analysed. RESULTS: We compared 44 patients who received MIST with a historic cohort of 31 patients who received INSURE. This showed no differences in the rate of intubation and mechanical ventilation in the first 72 h, or secondary respiratory outcomes and relevant morbidities, between the babies who received INSURE and those who received MIST. More babies in the MIST group (35%) needed a second dose of surfactant than the INSURE group (6.5%) (p < 0.0001). CONCLUSION: Surfactant administration using MIST, with no sedation, is feasible in preterm infants with RDS. No significant differences in secondary respiratory outcomes were found between the MIST and INSURE techniques.

Application of Video Laryngoscopy for Minimally Invasive Surfactant Therapy: A Retrospective Comparative Cohort Study.

Minimally invasive surfactant therapy (MIST) has emerged as a preferred method of surfactant delivery. Pioneers of this technique have described the use of direct laryngoscopy (DL) for MIST. With the increasing application of video laryngoscopy (VL) for neonatal airway management, it is speculated that MIST techniques can be adapted for use with VL. OBJECTIVE: To compare procedural success, operator ease of use, and complication of MIST using VL vs. MIST using DL. METHODS: This was a retrospective, observational cohort study conducted at a tertiary-level neonatal intensive care unit after obtaining ethical approval. We included neonates who received MIST between 1 October 2020 and 31 October 2022. Baseline demographic characteristics, along with procedural data, were collected. Primary outcome measures included the overall procedural success rate, the need for multiple attempts, and the total number of attempts. Secondary outcome measures included the occurrence of adverse events, the need for a second dose of surfactant, and the need for intubation within 7 days of the procedure. Means and SDs, independent t-tests, frequencies, and chi-square were used as appropriate. p-values < 0.05 were considered statistically significant. RESULTS: Of the 79 neonates included, 37 neonates received MIST via VL, while 42 received MIST via DL. The median gestational age was lower in the VL group at 29.0 weeks vs. 30.5 weeks (p = 0.011) in the DL group. The median birthweight in the VL group was 1260 g, IQR (1080, 1690), which was significantly lower than the DL group, which was 1575 g, IQR (1220, 2251), p = 0.028. Purpose-built catheter use was higher in the DL group. The overall procedural success was similar between groups. The need for multiple attempts was lower with VL in comparison to DL [4 (11%) vs. 13 (31%); p = 0.034)] at the univariate level but not significant at multivariate analysis (p = 0.131). Procedural complications, the need for a second dose of surfactant, the need for mechanical ventilation post-MIST, and operator ease of use were similar. User comments emphasized the value of VL in providing real-time visual information to confirm catheter placement and guide operators/trainees. CONCLUSION: Overall, in our cohort, despite VL being a more recently adapted technology used more in smaller, sicker, and more premature neonates, procedural success, complications, and operator ease of use for MIST using VL and DL were comparable. Our findings show the successful application of VL for MIST and suggest procedural advantages that might facilitate universal adoption.

The Outcomes of Preterm Infants with Neonatal Respiratory Distress Syndrome Treated by Minimally Invasive Surfactant Therapy and Non-Invasive Ventilation.

In recent years, the utilization of minimally invasive surfactant therapy (MIST) and Non-invasive ventilation (NIV) as the primary respiratory assistance has become increasingly prevalent among preterm infants with neonatal respiratory distress syndrome (RDS). This study aims to compare the outcomes between MIST administered with nasal continuous positive airway pressure (NCPAP) versus nasal intermittent positive pressure ventilation (NIPPV), with the objective of exploring the respiratory therapeutic benefits of these two approaches. This retrospective study collected data from the neonatal intensive care unit of Kaohsiung Medical University Hospital spanning from January 2016 to June 2021. Infants were divided into two groups based on the type of NIV utilized. The NCPAP group comprised 32 infants, while the NIPPV group comprised 22 infants. Statistical analysis revealed significant differences: the NIPPV group had a smaller gestational age, lower birth weight, higher proportion of female infants, and earlier initiation of MIST. Additionally, the NIPPV group exhibited higher incidence rates of retinopathy of prematurity, longer respiratory support duration, prolonged hospitalization, and mortality. However, upon adjustment, these differences were not statistically significant. Analysis of venous blood gas and respiratory parameter changes indicated that both the NCPAP and NIPPV groups experienced improvements in oxygenation and ventilation following MIST.

Management of respiratory distress syndrome in moderate/late preterm neonates: A Delphi consensus.

INTRODUCTION: Respiratory distress syndrome (RDS) is the most frequent cause of respiratory distress in preterm neonates. In the management of RDS, surfactant plays a pivotal role, but there are no evidence-based recommendations for moderate/late preterm neonates (32-36 weeks). METHODS: A scientific committee developed a questionnaire with 53 questions addressing diagnosis, treatment, potential complications and future trends in RDS specifically focused on moderate and late preterm neonates. This was followed by the performance of a Delphi survey of expert neonatologists. RESULTS: Consensus was reached on 98 of the 109 items. The recommendations for the diagnosis of RDS included performing a lung ultrasound and including mild respiratory distress, transient tachypnoea of the newborn, congenital pneumonia and primary pulmonary hypertension in the differential diagnosis. Most panellists agreed on the need for studies that determine the benefit/harm balance, clinical profile and methods of surfactant administration in moderate/late preterm neonates. All respondents would use the MIST approach with devices specifically designed for surfactant administration. Regarding sedation measures during MIST, most participants agreed on the use of nonpharmacological interventions and, if these proved ineffective, an opioid. All respondents agreed that moderate/late preterm neonates are at increased risk of neonatal morbidity and mortality, particularly respiratory problems, and considered the need for more specialised monitoring in hospital follow-up visits in neonates with associated risk factors or a history of complications in the neonatal period. Finally, all respondents agreed that there is a lack of studies identifying risk factors and medium-term adverse outcomes in moderate/late preterm neonates. CONCLUSION: This expert consensus will help with the diagnosis and management of RDS and guide decision-making about surfactant administration in moderate/late preterm neonates.

Comparison of minimally invasive surfactant therapy with intubation surfactant administration and extubation for treating preterm infants with respiratory distress syndrome: a randomized clinical trial.

BACKGROUND: Respiratory distress syndrome (RDS) is a common cause of hospitalization and death in preterm infants who require surfactant treatment and respiratory support. PURPOSE: This study aimed to compare the clinical outcomes of minimally invasive surfactant therapy (MIST) and the INtubation, SURfactant administration, and Extubation (INSURE) technique in preterm infants with RDS. METHODS: In this clinical trial, 112 preterm infants born at 28-36 weeks of gestation and diagnosed with RDS randomly received 200-mg/kg surfactant by MIST or the INSURE method. In the MIST group, surfactant was administered using a thin catheter (5F feeding tube); in the INSURE group, surfactant was administered after intubation using a feeding tube and the tracheal tube was removed after positive pressure ventilation was started. Nasal continuous positive airway pressure was applied in both groups for respiratory support and the postprocedure clinical outcomes were compared. RESULTS: The mean hospitalization time was shorter for infants in the MIST group than for those in the INSURE group (9.19± 1.72 days vs. 10.21±2.15 days, P=0.006). Patent ductus arteriosus was less frequent in the MIST group (14.3% vs. 30.4%, P=0.041). Desaturation during surfactant administration occurred less commonly in the MIST group (19.6% vs. 39.3%, P=0.023). There were no significant intergroup differences in other early or late complications. CONCLUSION: These results suggest that surfactant administration using MIST could be a good replacement for INSURE in preterm infants with RDS since its use reduced the hospitalization time and the number of side effects.

Minimally invasive surfactant therapy versus intubation for surfactant delivery in preterm infant with RDS: evaluation of safety and efficacy.

BACKGROUND: Minimally invasive surfactant therapy (MIST) is a promising mode of administration that offers the potential to limit barotrauma and prevent lung injury in preterm infants with respiratory distress syndrome (RDS). OBJECTIVE: This study assessed the effects of the implementation of MIST on safety and efficacy in infants who met criteria for surfactant administration and were treated by MIST as compared with a historical control group treated with surfactant via an endotracheal tube during mechanical ventilation. METHODS: This retrospective study included infants born between 2012 and 2017 who met the following inclusion criteria: gestational age 23-36 + 6 weeks, a diagnosis of RDS requiring at least 30% oxygen with or without nasal continuous positive airway pressure (nCPAP). MIST was introduced in 2014 and a comparison was made between the study group who received MIST and the control group who met similar criteria and received surfactant via an endotracheal tube during mechanical ventilation. RESULTS: No significant differences were found between the groups in baseline and demographic data. Severity of initial disease, assessed by the CRIB II score, was similar in the two groups (control 4.6 ± 2.8, MIST 4.4 ± 2.4, p=.995). The requirement for oxygen during the first 3 d of life was significantly lower (area under the curve [AUC]: p=.001) in the MIST group as assessed by the AUC. Likewise, the mean days of oxygen requirement were significantly lower in the MIST group (Control: 10.3 d, MIST: 5.9 d, p=.04). Only six infants in the MIST group (13%) subsequently required intubation for mechanical ventilation, only one of whom adjacent to the procedure. A modest reduction in duration of ventilation was also noted. Duration of admission was 32 ± 23 d in the control group and 26 ± 21 d in the MIST group, p=.061. No significant differences were found between the groups in the incidence of major morbidities or mortality. No major adverse events related to the procedure were observed. CONCLUSIONS: Transition to MIST was associated with significantly reduced need for oxygen, mechanical ventilation and surfactant, and a borderline shortened NICU admission.

Introducing Less-Invasive Surfactant Administration into a Level IV NICU: A Quality Improvement Initiative.

Less-invasive surfactant administration (LISA), a newer technique of delivering surfactant via a thin catheter, avoids mechanical ventilation. LISA has been widely adopted in Europe but less so in the US. Our goal was to increase the percentage of surfactant delivered via LISA from 0% to 51% by 12/2020. Project planning and literature review started 12/2019, and included a standardized equipment kit and simulation training sessions. We began Plan-Do-Study-Act (PDSA) cycles in 6/2020. Initial exclusions for LISA were gestational age (GA) <28 weeks (w) or ≥36 w, intubation in the delivery room, or PCO2 >70 if known; GA exclusion is now <25 w. From 6 to 12/2020, 97 patients received surfactant, 35 (36%) via LISA. When non-LISA-eligible patients were excluded, 35/42 (83%) received LISA successfully. There were only 2/37 patients for whom LISA was not able to be performed. Three LISA infants required mechanical ventilation in the first week of life. Sedation remained an initial challenge but improved when sucrose was used routinely. LISA was safely and successfully introduced in our NICU.

Minimally invasive surfactant therapy versus intubation for surfactant administration in very low birth weight infants with respiratory distress syndrome.

BACKGROUND: Minimally invasive surfactant therapy (MIST) is a new mode of surfactant administration without intubation to spontaneously breathing preterm infants with respiratory distress syndrome (RDS). The aims of this study were to assess the feasibility, efficacy and safety of using MIST to give surfactant for very low birth weight (VLBW) infants with RDS. METHODS: In total, 53 VLBW infants who were born before 32 gestational weeks with spontaneous breathing, respiratory distress, and requiring surfactant therapy were divided into two groups. The infants in group A (n = 29) were intubated and received surfactant replacement therapy via endotracheal tube, followed by mechanical ventilation (MV). The infants in group B (n = 24) received tracheal instillation of surfactant via a semirigid vascular catheter during spontaneous breathing under nasal continuous positive airway pressure (nCPAP). After surfactant instillation, the infants in group B were still placed on nCPAP. RESULTS: Our data showed that infants in group B (MIST group) had significantly lower rate (P < 0.05) of composite outcome of death or bronchopulmonary dysplasia (BPD), duration of intermittent positive airway pressure ventilation (IPPV) or MV, drug treatment of patent ductus arteriosus (PDA), and surgical ligation of PDA than group A. CONCLUSION: MIST is feasible, safe and it may reduce the composite outcome of death or BPD for VLBW infants with RDS requiring surfactant replacement therapy.

A national survey on use of less invasive surfactant administration in Turkey.

BACKGROUND: The aim of the study was to assess the rate of utilization, policy of premedication, technique, equipment, experience on safety and efficacy for less invasive surfactant administration or minimally invasive surfactant therapy (LISA/MIST) use in Turkey. METHODS: An online survey was designed and distributed via Google Forms tool to 350 neonatologists from 173 units through NICU-Turk mailing list of the Turkish Neonatal Society. Participants were asked to answer the survey for their own neonatal intensive care unit (NICU). RESULTS: LISA/MIST use rate was 81.6% among 87 NICUs which responded (response rate was 50.2%). LISA was used regularly in 23 of the units (26.4%), occasionally in 35 (40.2%), rarely in 12 (13.8%), and only for clinical trials in 1 (1.1%). LISA/MIST has been never applied in 16 units (18.4%). CONCLUSIONS: LISA/MIST is widely used in Turkey similar to several regions in Europe but unlike the USA. Future studies are expected to further clarify some questions about LISA/MIST procedure, especially on its efficacy and safety.

Minimally Invasive Surfactant Therapy: An Analytical Report of Our Prospective Dubai Cohort.

INTRODUCTION:  Type 2 pneumocytes of the respiratory epithelium secrete the endogenous surfactant, a detergent-like substance that lines the alveolar sacs of the lungs. The surfactant facilitates the gas exchange process across the alveolar membrane by preventing the collapse of the alveoli and thereby maintaining their distended state. Respiratory distress syndrome of the premature neonates is characterized by quantitative and/or qualitative defects of endogenous surfactant metabolic pathways. The advent of exogenous surfactant therapy is rightly hailed as the major milestone in advancement of the care of the babies with surfactant-deficient lung disease. The administration of exogenous surfactant traditionally involves endotracheal intubation and mechanical ventilation. Minimally invasive surfactant therapy (MIST) is the technique of delivering surfactant without intubation whilst continuing the baby on noninvasive respiratory support. This author introduced MIST as the default way of administering surfactant in his neonatal units in Dubai and has to his credit the first published report on MIST from the United Arab Emirates in this journal in 2018.  Objective: To analyze prospectively all our babies in Dubai who received surfactant by MIST. DESIGN:  Prospective descriptive study of all babies receiving surfactant by MIST starting from January 2018. SETTING:  Three tertiary care neonatal centers in Dubai. PATIENTS AND METHODS:  Thirteen babies (gestation 27-36 weeks and birth weight 0.95-2.81 kg) were treated with MIST on 15 occasions. Catheterization techniques were by infant feeding tube in 10 babies, LISA (less invasive surfactant administration) catheter in one baby, and 2.0 size endotracheal tube (ETT) with surfactant filled syringe directly attached to its hub two times each in two babies. Curosurf the porcine surfactant at 200 mg/kg was used on nine occasions and Survanta the bovine surfactant at 4 mL/kg on six occasions. MAIN OUTCOME MEASURES:  MIST success defined as the baby not needing intubation and ventilation within 72 hours post MIST. Outcome measures with respect to the different modalities of MIST procedure and surfactant preparations used in this prospective cohort. RESULTS:  Only one of the 13 babies (7.7%) in this cohort needed escalation of support with mechanical ventilation and high frequency oscillation (HFO). MIST using semi-rigid catheters like the LISA catheter or the smallest size ETT was technically easier to perform. No differences were observed with regard to the surfactant preparation used. None had an abnormal neurosonogram and there were no instances of sepsis and necrotizing enterocolitis either. The baby that had an unsuccessful MIST had retinopathy of prematurity that was effectively treated with Laser post discharge from neonatal unit. All the babies in this cohort had age appropriate developmental milestones on subsequent follow up visits ranging from three months to two years. CONCLUSIONS:  MIST can be easily mastered and adapted in our neonatal units. MIST by any of the three variations of techniques as described in our cohort at FiO2 thresholds not exceeding 0.4 results in quicker resolution of the surfactant deficient lung disease, reduces the oxygen days in these babies and perhaps thereby insures intact survival of these babies.

Minimally Invasive Surfactant Therapy Using a 2.0 mm Uncuffed Endotracheal Tube as the Conduit: An Easily Adaptable Technique.

Minimally invasive surfactant therapy (MIST) is the accepted way of surfactant administration in Europe, and in 2018, we reported its successful outcome with three babies in Dubai. Although this procedure minimizes the barotrauma associated with intubation for surfactants, threading the fine infant-feeding tube is perceived to be technically difficult. Semi-rigid catheters like the angiocath and the less invasive surfactant administration (LISA) catheter simplify the procedure. We have used successfully the smallest size of endotracheal tube available (2.0 mm) as a surrogate LISA catheter in our neonatal unit in Dubai. We present herein the simplicity and ease of this procedure versus the conventional LISA or MIST technique.

Should Minimally Invasive Surfactant Therapy be a Must in Neonatal Intensive Care Units? Pilot Report of Initial Cases in Dubai.

Minimally invasive surfactant therapy (MIST) in neonates without intubation has in recent times become an accepted standard in the neonatal intensive care units (NICU) especially in Europe. We have adapted this novel technique in our clinical practice in the neonatal intensive care units in Dubai since 2018. Herein we report the successful outcome of implementation of this technique in three of our neonates of gestation/weight, 28/1.03 kg, 34/2.0 kg and 28/1.18 kg respectively in our NICU in Dubai, United Arab Emirates.

Minimally Invasive Surfactant Therapy and Noninvasive Respiratory Support.

Respiratory distress syndrome (RDS) caused by surfactant deficiency is major cause for neonatal mortality and short- and long-term morbidity of preterm infants. Continuous positive airway pressure and other modes of noninvasive respiratory support and intubation and positive pressure ventilation with surfactant therapy are efficient therapies for RDS. Because continuous positive airway pressure can fail in severe surfactant deficiency, and because traditional surfactant therapy requires intubation and positive pressure ventilation, this entails a risk of lung injury. Several strategies to combine noninvasive respiratory therapy with minimally invasive surfactant therapy have been described. Available data suggest that those strategies may improve outcome of premature infants with RDS.

Nasal continuous positive airway pressure versus nasal intermittent positive-pressure ventilation within the minimally invasive surfactant therapy approach in preterm infants: a randomised controlled trial.

OBJECTIVE: To compare the effectiveness of nasal continuous positive airway pressure (NCPAP) and nasal intermittent positive-pressure ventilation (NIPPV) as the initial respiratory support within the minimally invasive surfactant therapy (MIST) approach in preterm infants with respiratory distress syndrome. DESIGN: Prospective, randomised controlled study. SETTING: Tertiary neonatal intensive care unit. PATIENTS AND INTERVENTIONS: This study enrolled 200 preterm infants with a gestational age of 26-32 weeks who showed signs of respiratory distress but did not require intubation in the delivery room. Surfactant therapy was performed using the MIST approach in the patients who met the criteria for surfactant administration. MAIN OUTCOME MEASURES: The primary outcomes were a need for intubation within the first 72 h of life and a surfactant requirement. RESULTS: The infants in the study displayed similar characteristics at birth. Fewer infants in the NIPPV group required surfactant therapy (38% vs 60%; p=0.002) or invasive ventilation during the first 72 h of life (13% vs 29%; p=0.005), and NIPPV reduced the rate of moderate-to-severe bronchopulmonary dysplasia (BPD) (7% vs 16%; p=0.046). Multivariate logistic regression analysis showed that NIPPV support (OR: 0.36, 95% CI 0.17 to 0.76; p=0.008) and higher gestational age (OR: 0.76, 95% CI 0.59 to 0.98; p=0.041) reduced the need for invasive ventilation within the first 72 h of life. Surfactant requirement was also decreased with NIPPV support (OR: 0.39, 95% CI 0.22 to 0.71; p=0.002). However, there was no impact on BPD, based on the multivariate analysis. CONCLUSIONS: In infants born at 26-32 weeks' gestation, NIPPV reduced the need for invasive ventilation and the surfactant requirement within the MIST approach. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov under identifier NCT01741129.