High-volume surfactant administration using a minimally invasive technique: Experience from a Canadian Neonatal Intensive Care Unit

Abstract

Background

Surfactant delivery via a thin endotracheal catheter during spontaneous breathing, a technique called minimally invasive surfactant therapy (MIST), is an alternative to intubation and surfactant administration. There is paucity of data regarding the administration of high-volume surfactant using this technique.

Methods

We conducted a retrospective cohort study to review the safety, efficacy, and procedural details pertaining to the delivery of 5 mL/kg of BLES® via MIST approach. In 2016, our centre initiated a practice change allowing the use of MIST as an alternative method of surfactant delivery in infants born at ≥28 weeks and/or with a birth weight ≥ 1,000 g with respiratory distress syndrome. In this study, we identified all neonates who received surfactant via MIST between May 1, 2016 and July 30, 2018 and collected relevant procedural data.

Results

Since this practice change, MIST technique was attempted in 43 neonates with successful instillation of surfactant in 41 (95.3%) of the neonates. Intubation and positive pressure ventilation was avoided in 35 neonates (85.3%). No serious adverse effect was noted.

Conclusions

Our study reports successful use of higher volume surfactant via MIST. This should encourage other similar centres to consider this technique, in order to avoid unnecessary intubation and positive pressure ventilation.

Respiratory distress syndrome (RDS) is a common morbidity in premature neonates admitted to the intensive care unit. Surfactant replacement therapy has been the cornerstone of treatment of RDS and has resulted in significant reduction in mortality and morbidity (1). The usual method of surfactant delivery involves placing an endotracheal tube followed by intra-tracheal administration of exogenous surfactant followed by the removal of the endotracheal tube (INSURE technique) (2). This procedure is often preceded by premedication (atropine, opioid, and muscle relaxant) and utilizes positive pressure ventilation (PPV) to ensure effective instillation of the surfactant. While this is an effective way for intra-tracheal delivery of surfactant, this process does not always allow for immediate extubation, necessitating invasive mechanical ventilation of variable duration (3,4). The past few decades have witnessed the growing popularity and effective use of noninvasive ventilation in neonates (5). The new ‘mantra’ is to avoid intubation and PPV as much as possible, in order to protect the fragile lungs. In this new ‘noninvasive’ era of respiratory care, the method of delivering surfactant has garnered new attention. Alternative techniques of surfactant delivery that would eliminate the need of intubation and PPV have been explored. Intra-tracheal surfactant administration via a thin catheter in spontaneously breathing neonates is one such technique, often referred to as Minimally Invasive Surfactant therapy (MIST) or Less Invasive Surfactant Administration (LISA) (6). There is robust evidence to suggest that this technique is feasible, safe, and results in decreased need for intubation, mechanical ventilation, and improved short-term respiratory outcomes (6–13). There is also some preliminary evidence suggesting that such a method in comparison to intubation for surfactant delivery may lead to a reduction in incidence of bronchopulmonary dysplasia (7). While used extensively in Europe, widespread use of the MIST technique is yet to occur in Canada. This could be because most of the MIST literature describes higher concentration and lower volume surfactant (10,13,14) with a scarcity of data regarding the use of lower concentration (and therefore higher volume) surfactant. An example of the latter is Bovine Lipid Extract Surfactant (BLES®), which is manufactured locally in Canada and used widely in the neonatal intensive care units across the country (15). Additional controversies exist surrounding use of premedication and ideal catheter type (16). Our centre, following a practice change initiative in 2016, has been using MIST to deliver 5 mL/kg dose of Bovine Lipid Extract Surfactant (BLES®) to select neonates with RDS. Given the scarcity of data pertaining to higher volume surfactant use via minimally invasive technique, we designed this present study to generate safety, efficacy, and procedural data regarding this modality of surfactant administration.

METHODS

This was a retrospective analysis of prospectively collected data. The study was approved by institutional ethics board (HSREB 112609).

Study eligibility criteria

We included all neonates from May 1, 2016 to July 30, 2018 in whom MIST technique was performed as a primary method of surfactant delivery. We excluded neonates with RDS given surfactant via INSURE technique, neonates already on invasive mechanical ventilation and neonates with known or suspected chromosomal/congenital anomaly.

MIST procedural details

Based on the growing body of literature supporting the efficacy of MIST, our centre (a 42 bed tertiary care neonatal intensive care unit) approved a practice change in May, 2016. This new practice guideline recommended the use of MIST in neonates ≥ 28 weeks and/or ≥1,000 g, who did not require intubation, had RDS, and met the criteria for surfactant administration (oxygen requirement of >0.40 on optimal noninvasive respiratory support) (6). Presence of experienced operators (neonatologist, senior respiratory therapists, and fellows) was a necessary prerequisite. In the absence of experienced operators, conventional method of surfactant delivery was chosen (surfactant delivered via endotracheal tube after premedication and paralysis). Neonates with poor respiratory drive (defined as >3 apneic episodes in the hour preceding surfactant delivery), hemodynamic instability (hypotension), birth asphyxia, and major congenital anomalies, were not considered suitable candidates for MIST. BLES® at a dose of 5 mL/kg/dose was used. The local Quality Improved (QI) committee was involved to monitor and ensure safe and effective implementation of the new practice. Predesigned forms were used to collect procedural data. Use of atropine and sucrose as premedications was recommended but not mandatory. We used the 5Fr Kim Vent Multi Access catheter ® (MAC) to deliver the surfactant. Neonates were kept on NCPAP using nasal prongs or masks using the Drager VN 500® for the entire procedure. Using a laryngoscope and Magill’s forceps, the MAC was guided across the vocal cords under direct vision. The depth of insertion was 6 cm + weight in kilogram as measured from the lip, which was marked by an adhesive tape. BLES® was administered slowly over 1 to 3 minutes, synchronizing instillation with the neonate’s inspiration. After successful catheter placement, the laryngoscope was withdrawn and attempts were made to keep the infant’s mouth closed in order to facilitate continued delivery of positive airway pressure. Postprocedure, stomach contents were aspirated via a nasogastric/orogastric tube to check for accidental instillation in the esophagus and to assess for substantial pharyngeal reflux. As per the institutional protocol, attempts were limited to no more than three times. Additionally, the clinical practice change protocol specified that if the neonate qualified for a second dose of surfactant, it would be delivered using the standard INSURE technique.

Data collection and analysis

Neonates who received surfactant via MIST were identified from the Neonatal Respiratory Therapy Database and QI committee data. Baseline demographic characteristics such as gestational age, weight, antenatal steroids, and respiratory support prior to procedure were collected from the patient’s chart. Data regarding the procedure was extracted from the completed procedural forms. This included premeditations used, number of attempts, successful delivery of surfactant, oxygen requirement postsurfactant, subsequent need of mechanical ventilation, and/or need of second dose of surfactant.

Attempt was defined as successful when full intended dose of surfactant was delivered intra-tracheally without immediate need of intubation for the purpose.

Data regarding complications including apneas, desaturations (oxygen saturation below 85%, bradycardia (heart rate <100 beats/minute), need to use PPV/need to intubate during procedure were also collected. Data regarding reflux of surfactant was not collected as the mouth was kept closed during the procedure and ongoing visualization of the catheter during instillation was not attempted.

Our data was analyzed using descriptive statistics such as frequency, proportions, means, and standard deviations (SD) as appropriate.

RESULTS

On analysis of our data, we found that in the period May 2016 to July 2018, MIST technique was attempted in 43 neonates (Study flow diagram – Figure 1). The gestational age in this cohort was 32.1 ± 2.7 weeks (mean ± SD) with a birth weight of weight of 2,038.2 ± 746 g (mean ± SD). The MIST technique was successful in 41 out of 43 neonates. The procedure failed in two neonates due to inability to place the MAC. Surfactant delivery in these two cases was completed via INSURE. Procedural data are summarized in Table 1. Procedural data were incomplete/missing in 3 out of the 41 patients who completed MIST. Success in first attempt was recorded in 23 out of 38 neonates (60.5%). Of the 41 neonates who received MIST, 35 (85.3%) did not require subsequent intubation or mechanical ventilation. The other six required intubation for further surfactant delivery (n = 4) or for poor respiratory drive and hypercarbia (n = 2). Apnea, desaturations, and bradycardia occurred during MIST (Table 2), but only one infant needed PPV or intubation.

Figure 1.

Study flow diagram. *Either ineligible for MIST as per clinical protocol/ already intubated and mechanically ventilated/operator unavailable/physician preference.

Table 1.

MIST procedure details

	n/N**	%
MIST with BLES® successful procedure	41/43	95.3
Single Attempt*	23/38	60.5
Atropine Use	27/41	65.8
Sucrose Use*	26/39	66.7
Successful weaning to room air within 24 h	35/41	85.3
Second Dose of Surfactant	4/41	9.8
Intubation and/ Mechanical Ventilation within 72 h	6/41	14.6
Surfactant delivery	4
Poor drive/Hypercapnia	2

*Missing data; **N = total number of neonates, n = number of neonates with the particular attribute.

BLES Bovine Lipid Extract Surfactant; MIST Minimally invasive surfactant therapy.

Table 2.

Adverse effects related to BLES administration via MIST

	n/N**	%
Apnea*	9/38	23.6
Bradycardia*	5/38	13.2
Desaturations*	20/38	52.6
Need for PPV/Intubation during procedure*	1/38	2.6
Other complications:	3/41	7.3
Emesis	1/41
Bleeding Gum	1/41
Air leak	1/41

*Missing data; **N = total number of neonates, n = number of neonates with the particular attribute.

BLES Bovine Lipid Extract Surfactant; MIST Minimally invasive surfactant therapy; PPV Positive pressure ventilation.

DISCUSSIONS

In the current era of neonatal practice, noninvasive or minimally invasive techniques of surfactant delivery that preclude the need for endotracheal intubation and PPV are increasingly being sought after. There is a growing body of literature regarding intra-tracheal instillation of surfactant using a thin catheter in spontaneously breathing neonates (11,14–18). Most of the evidence pertains to higher concentration lower volume surfactant (14,17–20). There are limited data regarding higher volume surfactant (10,11,21) and none regarding BLES at 5 mL/kg. Our study is the first to demonstrate that BLES can be administered successfully via MIST in neonates between 28 and 37 weeks with RDS. Surfactant was instilled successfully in 95.3% of the eligible patients. The two unsuccessful cases were related to difficulty in catheter placement and the pre-existing directive in our clinical protocol to limit the number of attempts to no more than 3. Need for two or more attempts were around 39.5% in our cohort, slightly higher than reports ranging from 5 to 32% by other authors (10,11,14,17,20,22). The higher number of attempts is possibly related to operator experience. In the first year of practice change (2016 to 2017), the procedure was performed only by neonatologists and rate of success in first attempt was higher (70%). In the second year (2017 to 2018) of the practice change, the operator pool was expanded to include respiratory therapists as well as junior staff/fellows and we witnessed a parallel increase in the number of attempts. We believe that there is a critical learning curve and experienced intubators are integral to success. We predict stabilization of proportion of failed attempts with continued practice of this method.

Second dose of surfactant, a surrogate marker of successful intra-tracheal instillation of first dose, was needed in 9.8% of our cohort. This is comparable to the rates (9 to 35%) reported in studies using lower volume surfactant (17,19,20,22). Intubation, PPV, or mechanical ventilation of any duration in the first 72 hours could be avoided in 85.3% of our cohort. This is similar to the reports from studies (66 to 88%) using lower volume surfactant (10–12,14,19,20,22). Adverse effects such as apnea, bradycardia, and desaturations were seen with this technique but only one neonate required PPV during the procedure. Rates of desaturation were around 52% in our study; this is similar to 58% reported by Olivier et al. (21). The rates of bradycardia and need for PPV in our study were less than the 30 to 43% reported by Dargaville et al, but similar to rates described by Kribs et al (17%) and Kanmaz et al (12%) (11,14,17). The lower rates of bradycardia are possibly related to the use of atropine in the majority of our infants. The only five infants in our cohort with bradycardia did not receive Atropine prior to MIST.

Ideal catheter type for intra-tracheal delivery of surfactant remains a matter of controversy. Selection of catheter depends on local availability, cost, operator comfort and experience. Thin catheters such as 4 to 5 FG feeding tubes (11–13,19) or 16G vascular catheter (17,18) have been successfully used to deliver intra-tracheal surfactant in neonates born between 23 and 34 weeks. We used a MAC to deliver the surfactant. This is a widely available catheter, designed for intra-tracheal use in neonates for in-line suctioning and often used to deliver surfactant during INSURE technique. We found that the multi-access catheter by itself can be gently guided across the vocal cords using a Magill’s forceps and it did not interfere with spontaneous breathing. This represents a novel adaptation of the MIST technique. The graduated markings on the MAC catheter, its diameter of 5Fr, its pliability, and the ease of attaching a syringe at the proximal end were perceived as added advantages. Manoeuvring the catheter across the vocal cord in an un-sedated infant is difficult, especially in the more mature neonates. Hence, potential use of analgesics and short acting sedatives need to be explored. The use of video laryngoscopy to aid and confirm correct catheter placement is an interesting idea that is being considered at our centre. There are ongoing efforts at our institution to develop a graduated, semi-rigid 5Fr catheter specifically designed for MIST that can be placed intra-tracheally without using Magill’s forceps.

While a completely noninvasive method of surfactant delivery such as use of nebulized surfactant would be ideal, until that is available, reduction of intubation and mechanical ventilation in preterm neonates with RDS can be achieved by MIST. Our study is limited by its retrospective nature and relatively small sample size. However, our procedural data were prospectively collected and confirm that even higher volume surfactant can be safely administered via MIST. Data from our experience and details regarding our unique, local adaptations are a valuable addition to the present body of literature and can help guide practice patterns across Canada.

Funding information: There are no funders to report for this submission.

Potential Conflicts of Interest: OS has received professional consulting fees from Bles Biochemical Inc. in the past. BLES Biochemical Inc. did not fund the study nor have any influence in the design, data collection, and interpretation of the results. The surfactant maker did not review or revised the manuscript submitted for publication. Other authors have no conflicts of interest to declare. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.