BACKGROUND AND OBJECTIVES

Many preterm infants stabilized on continuous positive airway pressure (CPAP) at birth require mechanical ventilation (MV) during the first 72 hours of life, which is defined as CPAP failure. Our objective was to decrease CPAP failure in infants ≤29 weeks’ gestational age (GA).

METHODS

A quality improvement bundle named OPTISURF was implemented for infants ≤29 weeks’ GA admitted on CPAP, consisting of stepwise escalation of CPAP and less invasive surfactant administration guided by fractional inspired oxygen concentration ≥0.3. The CPAP failure rate was tracked by using control charts. We compared practice and outcomes of a pre–OPTISURF cohort (January 2017 to September 2018) to a post-OPTISURF cohort (October 2018 to December 2019).

RESULTS

Of the 216 infants ≤29 weeks’ GA admitted to NICU on CPAP, 125 infants belonged to the pre-OPTISURF cohort (OSC) and 91 to the post-OSC. Compared with the pre-OSC, a higher proportion of infants in the post-OSC received CPAP 7 cm H2O within 4 hours of life (7% vs 32%; P < .01). The post-OSC also had lower rates of CPAP failure (54% vs 11%; P < .01), pneumothoraces (8% vs 1%; P < .03), need for MV (58% vs 31%; P < .01), and patent ductus arteriosus treatment (21% vs 9%; P = .02). Additionally, in a subgroup analysis, CPAP failure was lower in the post-OSC among infants 23 to 26 weeks (79% vs 27%; P < .01) and 27 to 29 weeks’ GA (46% vs 3%; P < .01).

CONCLUSIONS

Implementation of a quality improvement bundle including CPAP optimization and less invasive surfactant administration decreased CPAP failure and need for MV in preterm infants.

The harmful effects of mechanical ventilation (MV) on the developing lung are well established.1,2  Avoiding intubation in the delivery room (DR) decreases the composite outcome of death or bronchopulmonary dysplasia (BPD).35  Infants are increasingly being admitted to the NICU on continuous positive airway pressure (CPAP).6,7  However, 40% to 50% of infants admitted on CPAP require MV during the first 72 hours of life (HOLs), which is defined as CPAP failure.810  Infants failing CPAP have worse outcomes compared with those managed successfully on CPAP.1014 

Although CPAP is widely used for the respiratory support of preterm infants, significant center differences exist in the CPAP failure rate.10,11,13  The effectiveness of CPAP therapy depends on an optimal device,15,16  staff acceptance, and the strategies employed.17,18  Use of the bubble CPAP respiratory support system improves oxygenation19  and ventilation.20,21  A stepwise increase of CPAP improves functional residual capacity and oxygenation.2224 

Traditionally, surfactant is administered via an endotracheal tube (ETT), then continued MV. To decrease exposure to MV, a strategy of intubation, surfactant administration, and extubation (InSurE) was adopted by some hospitals.2527  However, in large randomized controlled trials (RCTs), researchers have reported a higher reintubation rate (30%–40%) after InSurE.28,29  Over the last decade, less invasive surfactant administration (LISA) using a thin tracheal catheter, thereby avoiding exposure to positive pressure ventilation (PPV) altogether, has been evaluated.3038  In meta-analyses of studies comparing LISA with either InSurE or continued MV, researchers report a reduction in the need for MV and a decrease in death or BPD.39 

The DR intubation rate at Parkland Health and Hospital System (PHHS) decreased after implementation of a resuscitation guideline focused on improving facemask PPV.7  However, nearly 50% of infants born ≤29 weeks’ gestational age (GA) failed CPAP after admission to the NICU.10  Our specific aim with this quality improvement (QI) project was to decrease CPAP failure in preterm infants ≤29 weeks’ GA admitted to the NICU on CPAP. We hypothesized that a QI bundle combining optimization of CPAP and LISA would decrease CPAP failure and improve outcomes.

PHHS is a large public hospital with >12 000 deliveries annually. DR resuscitation is conducted per Neonatal Resuscitation Program guidelines, as previously described.7  Infants not requiring intubation in the DR are maintained on CPAP through binasal prongs (Hudson prongs; Teleflex, Wayne, PA) connected to a positive end-expiratory pressure valve. All infants admitted to the NICU on CPAP are started on bubble CPAP (Fisher and Paykel, Auckland, New Zealand).

As previously reported,10  at the start of this project, a unit-specific CPAP guideline was in place based on published CPAP guidelines.4042  Regular training of nurses and respiratory therapists (RTs) together with bedside auditing of guideline compliance was conducted. Before the initiation of the new bundle, there was no set algorithm for the escalation of CPAP. Infants were intubated in the NICU for surfactant therapy if they required 0.45 to 0.5 fraction of inspired oxygen (Fio2) at CPAP 5 to 7 cm H2O and were continued on MV. InSurE was used in a select group of infants per physician discretion. The pulse oximeter oxygen saturation target limits in the PHHS NICU are maintained between 88% and 94%.10  Infants born ≤29 weeks’ GA received caffeine on admission.

The Institutional Review Board of University of Texas Southwestern Medical Center considered this QI project exempt from review. The PHHS Office of Research Administration approved the project.

Our retrospective study of infants ≤29 weeks’ GA revealed variation in the threshold for intubation (median [25th, 75th] Fio2 0.49 [0.4, 0.54]) and CPAP 6 cm H2O (5, 6). Importantly, Fio2 was >0.3 within 2 HOLs and severe respiratory distress syndrome on initial chest radiograph predicted CPAP failure.10  In addition, only 11% of infants received CPAP 7 cm H2O before intubation. In addition, one of the authors (H.H.) worked with the QI team to create process mapping and a fishbone diagram to define the processes involved in CPAP delivery. These activities helped us identify opportunities for improvement.

Plan Do Study Act 1 (May 2018 to February 2019)

Our findings in the retrospective study and the control chart of CPAP failure rate were presented to the faculty and variations in practice were highlighted (Table 1). A critical appraisal was conducted to evaluate the safety and effectiveness of LISA.43  These discussions helped us develop the key drivers of change (Fig 1).

FIGURE 1

Key drivers of change. RN, registered nurse.

FIGURE 1

Key drivers of change. RN, registered nurse.

Close modal
TABLE 1

Details of PDSA Cycles

Details
PDSA 1: development and implementation of OPTISURF bundle (May 2018 to February 2019) 
 Divisional conference presentation (May to June 2018) 
  Control chart of CPAP failure, retrospective review highlighting variations in practice 
  Critical appraisal of LISA evidence presented to the division, nurses, RTs 
  Identified key drivers of change including optimization of CPAP and LISA 
 Finalization of the components of the OPTISURF bundle (July 2018) 
 Discussions with nurses and RTs to identify barriers to implementation (August 2018) 
 Creation of a training module and defining of responsibilities for staff, fellows, and APPs (August 2018) 
 Identification of a core group of nurses and RTs to lead the training: training the trainers (August 2018) 
 Peer-to-peer training of nurses and RTs (September 2018) 
 Simulation training of fellows, attending physicians, and APPs focused on the LISA procedure (September 2018) 
 Development of a video with detailed description of the OPTISURF bundle (October 2018) 
 Guidelines made available in NeoSource (October 2018) 
 LISA kit was developed to include all necessary items in 1 bag for performing LISA (October 2018) 
 Creation of bedside display of the OPTISURF bundle algorithm (October 2018) 
 First patient was treated per the OPTISURF bundle (October 15, 2018) 
 LISA procedures by attending physicians, fellows, and experienced APPs 
PDSA 2: revised bundle (March to May 2019) 
 Monthly QI team meetings to evaluate progress and monitor safety especially for infants failing CPAP 
 Reviewed data and identified changes needed 
 Revised the bundle to decrease CPAP pressure after LISA when FiO2 <0.25 ± CXR (March 2019) 
PDSA 3: residents perform LISA (June to September 2019) 
 Residents trained in LISA procedure after mastering intubation skills 
 Monitored processes after revised bundle implemented to ensure safety with new learners 
PDSA 4: retraining of nurses and RTs (October to December 2019) 
 Retraining sessions were held for nurses and RTs to ensure compliance with the OPTISURF bundle 
 Monthly QI team meetings to monitor processes 
Details
PDSA 1: development and implementation of OPTISURF bundle (May 2018 to February 2019) 
 Divisional conference presentation (May to June 2018) 
  Control chart of CPAP failure, retrospective review highlighting variations in practice 
  Critical appraisal of LISA evidence presented to the division, nurses, RTs 
  Identified key drivers of change including optimization of CPAP and LISA 
 Finalization of the components of the OPTISURF bundle (July 2018) 
 Discussions with nurses and RTs to identify barriers to implementation (August 2018) 
 Creation of a training module and defining of responsibilities for staff, fellows, and APPs (August 2018) 
 Identification of a core group of nurses and RTs to lead the training: training the trainers (August 2018) 
 Peer-to-peer training of nurses and RTs (September 2018) 
 Simulation training of fellows, attending physicians, and APPs focused on the LISA procedure (September 2018) 
 Development of a video with detailed description of the OPTISURF bundle (October 2018) 
 Guidelines made available in NeoSource (October 2018) 
 LISA kit was developed to include all necessary items in 1 bag for performing LISA (October 2018) 
 Creation of bedside display of the OPTISURF bundle algorithm (October 2018) 
 First patient was treated per the OPTISURF bundle (October 15, 2018) 
 LISA procedures by attending physicians, fellows, and experienced APPs 
PDSA 2: revised bundle (March to May 2019) 
 Monthly QI team meetings to evaluate progress and monitor safety especially for infants failing CPAP 
 Reviewed data and identified changes needed 
 Revised the bundle to decrease CPAP pressure after LISA when FiO2 <0.25 ± CXR (March 2019) 
PDSA 3: residents perform LISA (June to September 2019) 
 Residents trained in LISA procedure after mastering intubation skills 
 Monitored processes after revised bundle implemented to ensure safety with new learners 
PDSA 4: retraining of nurses and RTs (October to December 2019) 
 Retraining sessions were held for nurses and RTs to ensure compliance with the OPTISURF bundle 
 Monthly QI team meetings to monitor processes 

NeoSource is a decision-support tool. CXR, chest radiograph; PDSA, plan do study act.

A series of conferences were held with key stakeholders to develop a QI bundle incorporating optimization of CPAP and LISA, named OPTISURF (Fig 2), for infants admitted to NICU on CPAP. The OPTISURF bundle included stepwise escalation of CPAP at 30-minute intervals from 5 to 7 cm H2O for Fio2 ≥0.3. Infants with Fio2 ≥0.3 on CPAP 7 cm H2O for ≥30 minutes would qualify for LISA. In addition, the bundle included the intubation criteria for infants admitted to the NICU on CPAP.

FIGURE 2

OPTISURF bundle. a Place head of the infant at the foot end of the incubator on admission to allow for LISA during line placement. b If no umbilical arterial catheter (UAC), obtain capillary blood gas (CBG). c Intubate if requiring Fio2 ≥0.7 or having frequent apnea (≥3 in one hour needing stimulation or any needing PPV). d If requiring Fio2 ≥0.5, intervene at 20-minute intervals. e Wean CPAP to 6 if Fio2 <0.25 after surfactant and obtain CXR within 2 hours status post-LISA and wean for hyper-expansion. Avoid rapid wean of pressure in <26 weeks’ GA infants and those without antenatal steroids. f Intubate if needing Fio2 >0.45 on CPAP ≥7 cm H2O for >1 hour after LISA, or if not due for next dose. g Keep head midline. Do not change infant’s position while administering LISA. ABG, arterial blood gas; CL, control line; UCL, upper control limit; UVC, umbilical venous catheter.

FIGURE 2

OPTISURF bundle. a Place head of the infant at the foot end of the incubator on admission to allow for LISA during line placement. b If no umbilical arterial catheter (UAC), obtain capillary blood gas (CBG). c Intubate if requiring Fio2 ≥0.7 or having frequent apnea (≥3 in one hour needing stimulation or any needing PPV). d If requiring Fio2 ≥0.5, intervene at 20-minute intervals. e Wean CPAP to 6 if Fio2 <0.25 after surfactant and obtain CXR within 2 hours status post-LISA and wean for hyper-expansion. Avoid rapid wean of pressure in <26 weeks’ GA infants and those without antenatal steroids. f Intubate if needing Fio2 >0.45 on CPAP ≥7 cm H2O for >1 hour after LISA, or if not due for next dose. g Keep head midline. Do not change infant’s position while administering LISA. ABG, arterial blood gas; CL, control line; UCL, upper control limit; UVC, umbilical venous catheter.

Close modal

We adopted the Hobart method of LISA described by Dargaville et al44  as part of the bundle. Briefly, the catheter (Angiocath 16G; BD, Sandy, Utah) was marked to the desired depth32,44  by using sterile precautions and inserted below the vocal cords by using direct laryngoscopy while maintaining the infant on CPAP via Hudson prongs. Poractant alfa, 200 mg/kg, was injected slowly in 4 aliquots, each aliquot administered over 15 to 20 seconds with a 10-second interval in between each aliquot. An orogastric tube was placed soon after instillation to check for reflux of surfactant, but the surfactant dose was not repeated, even if there was significant reflux (≥0.5 mL). Repeat LISA was performed at 12 hourly intervals if the infant required Fio2 0.4 or greater at CPAP 7 cm H2O (Fig 2).

A teaching module for the OPTISURF bundle was developed, and a group of trainers conducted peer-to-peer education for nurses, RTs, and advanced practice providers (APPs). The individual responsibilities of each team member were defined. A simulation-based training of the LISA procedure was conducted for faculty, fellows, and APPs. A video detailing the LISA procedure was developed. Both the bundle and video were made available on our intranet-based decision-support tool (NeoSource).

Implementation of the OPTISURF bundle started on October 15, 2018. The OPTISURF bundle was displayed at the bedside of every infant ≤29 weeks’ GA on admission to the NICU on CPAP. Nurses and RTs alerted the primary provider about the need for escalation of CPAP and LISA the basis of the Fio2. Initially, the LISA procedure was performed by attending physicians or fellows, and subsequently it was expanded to APPs. Each catheter insertion attempt was limited to 30 seconds, and, at most, 2 attempts per provider were allowed.

Plan Do Study Act 2 (March 2019 to May 2019)

The QI team prospectively evaluated the safety and effectiveness of the OPTISURF bundle (Table 1). Starting March 2019, a change to the bundle was made to include a recommendation to obtain a chest radiograph 30 minutes after LISA and decrease CPAP for any hyper-expansion noted on the chest radiograph or when the Fio2 <0.25 after LISA.

Plan Do Study Act 3 (June 2019 to September 2019)

After a period of time with experienced providers performing LISA, residents who had mastered intubation skills were allowed to perform LISA (Table 1).

Plan Do Study Act 4 (October 2019 to December 2019)

A group of trainers conducted retraining sessions to nurses and RTs on the OPTISURF bundle to ensure continued compliance with the bundle (Table 1).

Infants admitted after birth to the NICU on CPAP between January 2017 and September 2018 constituted the pre–OPTISURF cohort (OSC), and those admitted between October 2018 and December 2019 were included as the post-OSC. CPAP and Fio2 before surfactant and the details of each LISA procedure were recorded in real time by RTs. Two team members retrospectively collected other relevant data from the electronic health record. The baseline patient characteristics and outcome data were obtained from an existing NICU database.

The primary outcome of interest was the CPAP failure rate, defined as need for MV within 72 HOLs for infants admitted to the NICU on CPAP. Process measures included the proportion of infants receiving CPAP 7 cm H2O within 4 HOLs, CPAP level, and Fio2 before surfactant therapy. Secondary outcomes included need for any MV during the first 7 days of life (DOLs), MV, high-frequency ventilation, and patent ductus arteriosus (PDA) treatment during the hospital stay. Secondary outcomes also included the incidence of BPD, defined as the need for supplemental oxygen at 36 weeks’ postmenstrual age, further confirmed with a timed oxygen reduction test,4547  severe (grade ≥3) intraventricular hemorrhage (IVH),48  necrotizing enterocolitis stage ≥2,49  severe retinopathy of prematurity,50  mortality, and length of hospital stay. Balancing measures included the incidence of pneumothorax, the number of LISA attempts, the proportion of infants having surfactant reflux, desaturation and bradycardia events during LISA, and the need for repeat surfactant doses.

Analyses were performed by using SAS version 9.2 (SAS Institute, Inc, Cary, NC.). Categorical variables were analyzed by using Pearson’s χ2 or Fisher’s exact test, as applicable. Continuous variables were analyzed by Student’s t test or Mann-Whitney U test. A 2-sided 0.05 level of significance was used for all analyses. The CPAP failure rate was tracked by using statistical process control charts (QI Macros; KnowWare International, Inc, Denver, CO) using quarterly intervals, applying Montgomery standard rules of special cause variation.51 

Of the 333 infants actively resuscitated, 125 of 198 infants in the pre-OSC and 91 of 135 in the post-OSC were admitted to the NICU on CPAP (Fig 3). There were no differences in the baseline characteristics between the 2 cohorts (Table 2).

FIGURE 3

Flow diagram of study population.

FIGURE 3

Flow diagram of study population.

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TABLE 2

Comparison of Maternal and Infant Characteristics

CharacteristicsPre-OSC (n = 125)Post-OSC (n = 91)P
Maternal age, ya 29 (22, 34) 29 (25, 35) NS 
Hispanic, n (%) 73 (58) 56 (62) NS 
PIH, n (%) 59 (47) 44 (48) NS 
Antenatal steroids, n (%) 116 (93) 83 (91) NS 
Antenatal magnesium, n (%) 89 (71) 61 (67) NS 
Multiple birth, n (%) 25 (20) 12 (13) NS 
Chorioamnionitis, n (%) 2 (2) 12 (13) NS 
Diabetes, n (%) 23 (18) 14 (15) NS 
Cesarean delivery, n (%) 101 (81) 62 (78) NS 
Prolonged ROM, n (>18 h) 17 (14) 7 (8) NS 
Male sex, n (%) 57 (46) 48 (53) NS 
GA, wka 28 (26, 29) 28 (26, 29) NS 
 23, n (%) 3 (2) 2 (2) — 
 24, n (%) 6 (5) 5 (6) — 
 25, n (%) 5 (4) 13 (14) — 
 26, n (%) 19 (15) 8 (9) — 
 27, n (%) 24 (19) 14 (15) — 
 28, n (%) 25 (20) 21 (23) — 
 29, n (%) 43 (34) 28 (31) — 
Birth wt, ga 1010 (790, 1285) 1090 (840, 1290) NS 
Apgar score: 1 mina 5 (3, 7) 4 (3, 6) NS 
Apgar score: 5 mina 8 (7, 8) 7 (7, 8) NS 
Cord blood gas pHa 7.28 (7.24, 7.31) 7.27 (7.21, 7.32) NS 
Cord blood gas base deficita −4.7 (−6.3, −2.7) −5.2 (−7.6, −3.0) NS 
CharacteristicsPre-OSC (n = 125)Post-OSC (n = 91)P
Maternal age, ya 29 (22, 34) 29 (25, 35) NS 
Hispanic, n (%) 73 (58) 56 (62) NS 
PIH, n (%) 59 (47) 44 (48) NS 
Antenatal steroids, n (%) 116 (93) 83 (91) NS 
Antenatal magnesium, n (%) 89 (71) 61 (67) NS 
Multiple birth, n (%) 25 (20) 12 (13) NS 
Chorioamnionitis, n (%) 2 (2) 12 (13) NS 
Diabetes, n (%) 23 (18) 14 (15) NS 
Cesarean delivery, n (%) 101 (81) 62 (78) NS 
Prolonged ROM, n (>18 h) 17 (14) 7 (8) NS 
Male sex, n (%) 57 (46) 48 (53) NS 
GA, wka 28 (26, 29) 28 (26, 29) NS 
 23, n (%) 3 (2) 2 (2) — 
 24, n (%) 6 (5) 5 (6) — 
 25, n (%) 5 (4) 13 (14) — 
 26, n (%) 19 (15) 8 (9) — 
 27, n (%) 24 (19) 14 (15) — 
 28, n (%) 25 (20) 21 (23) — 
 29, n (%) 43 (34) 28 (31) — 
Birth wt, ga 1010 (790, 1285) 1090 (840, 1290) NS 
Apgar score: 1 mina 5 (3, 7) 4 (3, 6) NS 
Apgar score: 5 mina 8 (7, 8) 7 (7, 8) NS 
Cord blood gas pHa 7.28 (7.24, 7.31) 7.27 (7.21, 7.32) NS 
Cord blood gas base deficita −4.7 (−6.3, −2.7) −5.2 (−7.6, −3.0) NS 

NS, not significant; PIH, pregnancy-induced hypertension; ROM, rupture of membrane; —, not applicable.

a

Median (25th percentile, 75th percentile).

A control chart for CPAP failure revealed a special cause variation in the fourth quarter of 2018. The central line (CL) representing the mean was lowered at that point per standard rules (Fig 4).

FIGURE 4

CPAP failure rate. Numbers in the parentheses represent infants ≤29 weeks’ GA admitted to the NICU on CPAP each quarter. CL, control line; CXR, chest radiograph; LCL, lower control limit; PDSA, plan do study act; UCL, upper control limit.

FIGURE 4

CPAP failure rate. Numbers in the parentheses represent infants ≤29 weeks’ GA admitted to the NICU on CPAP each quarter. CL, control line; CXR, chest radiograph; LCL, lower control limit; PDSA, plan do study act; UCL, upper control limit.

Close modal

Of the process measures, compared with the pre-OSC, a higher proportion of infants received CPAP 7 cm H2O within 4 HOLs and before surfactant therapy in the post-OSC. Similarly, maximum Fio2 was lower before surfactant therapy in the post-OSC compared with the pre-OSC (Table 3).

TABLE 3

Resuscitation and Respiratory Support Details

CharacteristicsPre-OSC (n = 125)Post-OSC (n = 91)P
Needs PPV in DR, n (%) 86 (69) 64 (70) .81 
Maximum PIP in DR, cm H2Oa 25 (25, 30) 25 (25, 30) .41 
Maximum CPAP in DR, cm H2Oa 5 (5, 5) 5 (5, 6) .34 
Maximum Fio2 in DRa 70 (60, 90) 75 (60, 100) .53 
Maximum Fio2 within 4 HOLsa 35 (25, 47) 25 (21, 35) <.01 
Maximum CPAP within 4 HOLs 5 (5, 6) 6 (5, 7) .02 
CPAP 7 cm H2O within 4 HOLs, n (%) 9 (7) 23 (32) <.01 
Alveolar-arterial gradienta 112 (77, 153) 54.2 (22, 104) <.01 
Arterial or alveolar Pao2a 0.29 (0.23, 0.40) 0.34 (0.26, 0.48) <.01 
Surfactant administration, n (%) 71 (57) 48 (53) .55 
Requiring >1 dose of surfactant, n (%) 20/71 (28) 9/48 (19) .24 
Time to surfactant from birth, ha 5.5 (2:51, 20.34) 5.27 (2.54, 22.15) .74 
CPAP before surfactanta,b 6 (6, 6) 7 (7,7) <.01 
CPAP 7 cm H2O before surfactant, n (%)b 13 (20) 36 (95) <.01 
Fio2 before surfactanta,b 50 (42, 60) 40 (30, 50) <.01 
CharacteristicsPre-OSC (n = 125)Post-OSC (n = 91)P
Needs PPV in DR, n (%) 86 (69) 64 (70) .81 
Maximum PIP in DR, cm H2Oa 25 (25, 30) 25 (25, 30) .41 
Maximum CPAP in DR, cm H2Oa 5 (5, 5) 5 (5, 6) .34 
Maximum Fio2 in DRa 70 (60, 90) 75 (60, 100) .53 
Maximum Fio2 within 4 HOLsa 35 (25, 47) 25 (21, 35) <.01 
Maximum CPAP within 4 HOLs 5 (5, 6) 6 (5, 7) .02 
CPAP 7 cm H2O within 4 HOLs, n (%) 9 (7) 23 (32) <.01 
Alveolar-arterial gradienta 112 (77, 153) 54.2 (22, 104) <.01 
Arterial or alveolar Pao2a 0.29 (0.23, 0.40) 0.34 (0.26, 0.48) <.01 
Surfactant administration, n (%) 71 (57) 48 (53) .55 
Requiring >1 dose of surfactant, n (%) 20/71 (28) 9/48 (19) .24 
Time to surfactant from birth, ha 5.5 (2:51, 20.34) 5.27 (2.54, 22.15) .74 
CPAP before surfactanta,b 6 (6, 6) 7 (7,7) <.01 
CPAP 7 cm H2O before surfactant, n (%)b 13 (20) 36 (95) <.01 
Fio2 before surfactanta,b 50 (42, 60) 40 (30, 50) <.01 

PIP, peak inspiratory pressure.

a

Median (25th percentile, 75th percentile).

b

Values are determined before intubation and initiation of MV in the pre-OSC and before LISA in the post-OSC.

Compared with pre-OSC, the CPAP failure rate, the primary outcome of the study, decreased in the post-OSC. Similarly, MV during the first 7 DOLs, need for MV, high-frequency ventilation, and PDA treatment during hospital stay also decreased in the post-OSC compared with the pre-OSC. There were no differences in BPD, mortality, composite death or BPD, severe IVH, and severe retinopathy of prematurity between the 2 groups (Table 4).

TABLE 4

Comparison of Respiratory Care and Neonatal Outcomes of all Infants in Pre- Versus Post-OSC and in the Subgroups of Infants Born 23–26 Weeks’ GA and 27–29 Weeks’ GA

CharacteristicsAll Infants23–26 Wk’ GA27–29 Wk’ GA
Pre-OSC, n = 125Post-OSC, n = 91Pre-OSC, n = 33Post-OSC, n = 28Pre-OSC, n = 92Post-OSC, n = 63
CPAP failure, n (%) 68 (54) 10 (11)* 26 (79) 8 (27)* 42 (46) 2 (3)* 
MV within 7 d 70 (56) 12 (13)* 27 (82) 10 (36)* 43 (47) 2 (3)* 
Any MV, n (%) 72 (58) 28 (31)* 25 (76) 16 (57) 47 (51) 12 (19)* 
HFV, n (%) 30 (24) 5 (6)* 21 (64) 4 (14)* 9 (10) 1 (2)**** 
MV daysa 4 (1, 11) 2 (0, 12) 10 (3, 25) 5 (2, 27) 1 (1, 7) 1 (0, 2)* 
 CV days 4 (1,8) 4 (1, 17) 3 (2, 10) 9 (2, 20) 4 (1, 7) 2 (1, 4) 
 HFV days 7 (2, 14) 4 (3, 23) 6 (2, 18) 9 (3, 28) 8 (3, 9) 
NIPPV, n (%) 15 (12) 15 (17) 8 (24) 12 (43)6 7 (8) 3 (5) 
NIPPV daysa 3 (1, 13) 6 (4, 10) 8 (1, 14) 7 (5, 12) 2 (1, 7) 5 (4, 6) 
CPAP daysa 18 (9, 33) 21 (9, 35) 34 (11, 46) 38 (22, 43) 16 (9, 28) 14 (9, 28) 
Oxygen daysa 38 (12, 66) 31 (8, 55) 75 (43, 99) 57 (19, 92) 32 (9, 60) 27 (7, 42) 
Pneumothorax, n (%) 10 (8) 1 (1)** 5 (15) 0**** 5 (5) 1 (2) 
Pulmonary hemorrhage, n (%) 4 (3) 4 (4) 2 (6) 4 (14) 2 (2) 0 (0) 
PDA treatment, n (%) 26 (21) 8 (9)** 15 (46) 6 (22)** 11 (12) 2 (3)*** 
Postnatal steroids, n (%) 6 (5) 2 (2) 6 (18) 2 (7) 
NEC, n (%) 10 (8) 7 (8) 5 (15) 5 (5) 7 (11) 
Severe IVH, n (%) 5 (4) 4 (4) 2 (6) 4 (14) 3 (3) 
Severe ROP, n (%) 8 (6) 3 (3) 5 (15) 3 (11) 3 (3) 
Supplemental oxygen at 28 DOLs, n (%) 22 (18) 12 (13) 11 (33) 6 (21) 11 (12) 6 (10) 
BPD, n (%) 20 (16) 8 (9) 12 (36) 7 (25) 8 (9) 1 (2)***** 
Home oxygen, n (%) 4 (3) 4 (5) 3 (9) 4 (14) 1 (1) 
Mortality, n (%) 9 (7) 8 (9) 6 (18) 7 (25) 3 (3) 1 (2) 
Death or BPD, n (%) 29 (23) 16 (17) 18 (55) 14 (50) 11 (12) 2 (3)*** 
Length of staya 80 (62, 105) 72 (59, 96) 105 (87, 136) 96 (60, 123) 72 (59, 90) 70 (59, 85) 
CharacteristicsAll Infants23–26 Wk’ GA27–29 Wk’ GA
Pre-OSC, n = 125Post-OSC, n = 91Pre-OSC, n = 33Post-OSC, n = 28Pre-OSC, n = 92Post-OSC, n = 63
CPAP failure, n (%) 68 (54) 10 (11)* 26 (79) 8 (27)* 42 (46) 2 (3)* 
MV within 7 d 70 (56) 12 (13)* 27 (82) 10 (36)* 43 (47) 2 (3)* 
Any MV, n (%) 72 (58) 28 (31)* 25 (76) 16 (57) 47 (51) 12 (19)* 
HFV, n (%) 30 (24) 5 (6)* 21 (64) 4 (14)* 9 (10) 1 (2)**** 
MV daysa 4 (1, 11) 2 (0, 12) 10 (3, 25) 5 (2, 27) 1 (1, 7) 1 (0, 2)* 
 CV days 4 (1,8) 4 (1, 17) 3 (2, 10) 9 (2, 20) 4 (1, 7) 2 (1, 4) 
 HFV days 7 (2, 14) 4 (3, 23) 6 (2, 18) 9 (3, 28) 8 (3, 9) 
NIPPV, n (%) 15 (12) 15 (17) 8 (24) 12 (43)6 7 (8) 3 (5) 
NIPPV daysa 3 (1, 13) 6 (4, 10) 8 (1, 14) 7 (5, 12) 2 (1, 7) 5 (4, 6) 
CPAP daysa 18 (9, 33) 21 (9, 35) 34 (11, 46) 38 (22, 43) 16 (9, 28) 14 (9, 28) 
Oxygen daysa 38 (12, 66) 31 (8, 55) 75 (43, 99) 57 (19, 92) 32 (9, 60) 27 (7, 42) 
Pneumothorax, n (%) 10 (8) 1 (1)** 5 (15) 0**** 5 (5) 1 (2) 
Pulmonary hemorrhage, n (%) 4 (3) 4 (4) 2 (6) 4 (14) 2 (2) 0 (0) 
PDA treatment, n (%) 26 (21) 8 (9)** 15 (46) 6 (22)** 11 (12) 2 (3)*** 
Postnatal steroids, n (%) 6 (5) 2 (2) 6 (18) 2 (7) 
NEC, n (%) 10 (8) 7 (8) 5 (15) 5 (5) 7 (11) 
Severe IVH, n (%) 5 (4) 4 (4) 2 (6) 4 (14) 3 (3) 
Severe ROP, n (%) 8 (6) 3 (3) 5 (15) 3 (11) 3 (3) 
Supplemental oxygen at 28 DOLs, n (%) 22 (18) 12 (13) 11 (33) 6 (21) 11 (12) 6 (10) 
BPD, n (%) 20 (16) 8 (9) 12 (36) 7 (25) 8 (9) 1 (2)***** 
Home oxygen, n (%) 4 (3) 4 (5) 3 (9) 4 (14) 1 (1) 
Mortality, n (%) 9 (7) 8 (9) 6 (18) 7 (25) 3 (3) 1 (2) 
Death or BPD, n (%) 29 (23) 16 (17) 18 (55) 14 (50) 11 (12) 2 (3)*** 
Length of staya 80 (62, 105) 72 (59, 96) 105 (87, 136) 96 (60, 123) 72 (59, 90) 70 (59, 85) 

CV, conventional ventilation; HFV, high-frequency ventilation; NEC, necrotizing enterocolitis; NIPPV, noninvasive positive pressure ventilation; ROP, retinopathy of prematurity.

a

Median (25th percentile, 75th percentile).

*

P ≤ .01;

**

P < .05;

***

P = .053;

****

P = .06;

*****

P = .08.

In a post-hoc subgroup analysis (Table 4), CPAP failure decreased in the post-OSC in both 23 to 26 weeks’ and 27 to 29 weeks’ GA infants. In addition, the post-OSC had a decreased need for MV and fewer MV days in the 27 to 29 weeks’ GA infants. Interestingly, in the post-OSC, the need to treat PDA and use high-frequency ventilation decreased in 23 to 26 weeks’ GA infants. There were no differences in any other outcomes between the 2 cohorts in either GA group.

Of the balancing measures, the post-OSC had a lower incidence of pneumothorax compared with the pre-OSC. Of the 48 infants who received surfactant in the post-OSC, 42 received LISA. Four infants were intubated in the period before initiation of the OPTISURF bundle. One infant was intubated for apnea, and 1 required emergency intubation for hypoxia. Information was available for 38 of the 42 LISA procedures (Table 5). Procedures were either directly performed or supervised by fellows. Overall, 39% of infants required >1 attempt. Four infants (10%) required a second provider to complete the procedure. Overall, 92% of infants had desaturation or bradycardia during the procedure. Of those, 51% resolved with increase in Fio2 alone and another 34% required both higher Fio2 and tactile stimulation. Two infants required bag and/or mask PPV, 1 requiring PPV for 1 minute and the other for 30 seconds, both events occurring during laryngoscopy. In addition, 3 infants had surfactant reflux varying between 15% and 50% of the surfactant dose (Table 5).

TABLE 5

Details of LISA Procedure

LISA DetailsPost-OSC (n = 38)
Requiring ≥2 attempts, n (%) 15 (39) 
Provider, n (%)a  
 Attending 1 (3) 
 Fellow 19 (50) 
 Nurse practitioner 13 (34) 
 Resident physician 5 (13) 
Desaturation (≤80) and bradycardia (<100) events, n (%) 21 (55) 
 Increased Fio2 10/21 (48) 
 Increased Fio2 and tactile stimulation 10/21 (48) 
 Increased Fio2, tactile stimulation and PPV 1/21 (5) 
Desaturation without bradycardia, n (%) 9 (24) 
 Increased Fio2 8/9 (89) 
 Increased Fio2, tactile stimulation and PPV 1/9 (11) 
Bradycardia (<100) without desaturation, n (%) 5 (13) 
 Self-resolving 3/5 (60) 
 Increased Fio2 and tactile stimulation 2/5 (40) 
Surfactant reflux (≥0.5 mL from gastric aspirate) 3 (8) 
LISA DetailsPost-OSC (n = 38)
Requiring ≥2 attempts, n (%) 15 (39) 
Provider, n (%)a  
 Attending 1 (3) 
 Fellow 19 (50) 
 Nurse practitioner 13 (34) 
 Resident physician 5 (13) 
Desaturation (≤80) and bradycardia (<100) events, n (%) 21 (55) 
 Increased Fio2 10/21 (48) 
 Increased Fio2 and tactile stimulation 10/21 (48) 
 Increased Fio2, tactile stimulation and PPV 1/21 (5) 
Desaturation without bradycardia, n (%) 9 (24) 
 Increased Fio2 8/9 (89) 
 Increased Fio2, tactile stimulation and PPV 1/9 (11) 
Bradycardia (<100) without desaturation, n (%) 5 (13) 
 Self-resolving 3/5 (60) 
 Increased Fio2 and tactile stimulation 2/5 (40) 
Surfactant reflux (≥0.5 mL from gastric aspirate) 3 (8) 
a

Provider attempting the procedure for the first time.

This single-center study reveals that implementation of the OPTISURF bundle decreased CPAP failure, pneumothorax, and the need for MV and PDA treatment in preterm infants ≤29 weeks’ GA. To the best of our knowledge, this is the first QI project to systematically evaluate a bundle combining optimization of CPAP and LISA to decrease CPAP failure rate.

As preterm infants are increasingly being admitted to the NICU on CPAP, it is essential to develop strategies to decrease CPAP failure. The baseline CPAP failure rate in our center between 2016 to 2018 third quarter was similar to the experience from large RCTs.9,29  The CPAP failure rate remained unchanged despite our efforts to standardize the CPAP care guideline, regular team training, and monitoring compliance. In our retrospective study, we identified variations in the threshold used for intubation and surfactant therapy.7  Large RCTs have safely used CPAP 5 to 7 cm H2O.9,29  Our center, as well as others, has reported that Fio2 ≥0.3 within 2 HOLs predicts CPAP failure.10,13,52  Therefore, optimizing CPAP and LISA by using a threshold that predicted the CPAP failure became the cornerstones of our QI interventions. Increased use of higher CPAP within 4 HOLs and before LISA suggests compliance with the OPTISURF bundle. Similarly, a lower maximum Fio2 within 4 HOLs and before LISA in the post-OSC suggests the positive impact of escalation of CPAP and surfactant therapy using a standardized Fio2 threshold. In addition, the similar proportion of surfactant use between the 2 cohorts suggests that the guideline helped target surfactant administration to infants who were at risk for failing CPAP.

The CPAP failure rate in our project is comparable to large RCTs that used LISA after initially stabilizing infants on CPAP. Göpel et al30  compared LISA for Fio2 ≥0.3 versus rescue ETT surfactant therapy in 26 to 28 weeks’ GA infants (n = 220). Using LISA decreased CPAP failure (43% vs 22%) and the need for MV (47% vs 27%). Kribs et al31  compared LISA versus elective intubation and surfactant administered between 10 and 120 minutes of life in 23 to 26 weeks’ GA infants that met a Fio2 threshold ≥0.3 and/or Silverman score ≥5 (n = 211). In their study, in the LISA arm, 47% of the infants failed CPAP and 75% required MV. CPAP failure also decreased in the subgroup of 23 to 26 weeks’ GA infants in our study. However, the incidence of BPD was not different between the 2 cohorts in our study, possibly related to a small sample size not adequately powered to detect the difference in the outcome of a disease that has multifactorial etiology.

PDA treatment was significantly lower in the post-OSC. The decision to treat the PDA in our unit is dependent on the severity of respiratory illness and the inability to de-escalate support.53  Therefore, reduction in the need for MV might have directly affected the decision to treat PDA. This is consistent with the retrospective study by Kribs et al54  comparing pre- and post-LISA cohorts. Furthermore, increased pulmonary vascular resistance from higher CPAP might also have contributed to this outcome.55,56 

The occurrence of pneumothorax was followed as a balancing measure because of concerns of air leak with higher CPAP.8  One infant developed pneumothorax in the first 2 quarters after starting the OPTISURF bundle. Therefore, the bundle was modified to decrease CPAP after surfactant administration in plan do study act 2. Decreased pneumothorax in the post-OSC is consistent with the 2 center retrospective study by Dargaville et al57  that employed similar techniques and thresholds, (Fio2 >0.35, CPAP ≥7 cm H2O), in 29 to 32 weeks’ GA infants.

We employed the Hobart method for LISA because of its semirigid structure, which permits easy insertion.44,58  In our study, no serious adverse events were observed, with the majority of infants only developing transient desaturation and/or bradycardia. These findings are consistent with the RCTs that revealed higher transient hypoxia and bradycardia events with LISA compared with ETT surfactant.3032  The proportion of infants who required >1 attempt for successful insertion of the catheter is comparable to studies using a thin catheter31  or ETT.59,60  We did not use analgesia, sedation, or premedication during LISA. Although preprocedural analgesia is recommended for elective intubations in neonates,61  large RCTs of LISA did not routinely use sedatives or analgesics30,31  because LISA relies on a spontaneously breathing neonate. Kribs et al,31  reported lower IVH with LISA compared with ETT surfactant. The 2 year neurodevelopmental outcome revealed a decreased incidence of low Bailey II psychomotor developmental index in the LISA group compared with the intubation group, further supporting the safety of LISA using thin catheter without sedation.62 

Our study has several strengths. First, we systematically employed QI methodology to implement a consensus bundle to optimize CPAP and LISA.63  Second, our study reveals a safe strategy to escalate the CPAP by using a Fio2 threshold. The uniform bedside bundle helped decrease variation in escalation of CPAP and delay in surfactant therapy. Third, we demonstrated the safety of thin catheter insertion for LISA in an academic tertiary care center with multiple levels of providers. A readily available video and simulation-based training played a key role in achieving competence with the procedure.

Our study has some limitations. First, both optimization of CPAP and LISA were introduced simultaneously as a bundle, thereby making the contribution of each intervention in decreasing CPAP failure difficult to ascertain. Although escalation of CPAP was part of the routine our clinical practice, it was variable and not standardized. The stepwise and timely escalation of CPAP on the basis of the Fio2 threshold before LISA was the next logical step to decrease variation in surfactant administration and prevent CPAP failure, precluding a staggered approach. Similarly, a chest radiograph to evaluate the severity of respiratory distress syndrome was not included in the guideline to avoid delay in surfactant therapy. Second, this is a single-center prospective study with retrospective collection of outcome data between 2 epochs over 3 years. Other confounding factors and co-interventions could have had an effect on the study outcomes. However, to the best of our knowledge, no major changes were made to our respiratory care practices during this period. The antenatal steroid administration and DR intubation rate remained stable during the study period.

Our QI study reveals that a combined approach of optimizing CPAP and LISA decreased CPAP failure, pneumothorax, PDA treatment, and need for MV during hospital stay. Larger studies should be conducted in a variety of settings to confirm the effectiveness of this bundle.

We thank Dr. Charles Rosenfeld and Myra Wyckoff for their input throughout this project. We thank Patti Jeannette Burchfield, RN, for her help with extraction of data from the Parkland NICU database. We also thank Dr. Dalibor Kurepa for participating in the design of the study and reviewing the article. We thank Augustin Martinez, RRT; Arnulfo Niego, RRT; Erica Wilson, RRT; Jane S. Tuason, RNC; Joshua Hart, RNC; Rokiatu Kabba, RNC; and Susan Harville, RNC, for providing valuable input for the implementation of the project and participating in team training and data collection.

Dr Kakkilaya conceptualized and designed the study, analyzed and interpreted the data, and drafted the initial manuscript; Drs Weydig, Smithhart, Kapadia, Savani, and Jaleel participated in the conceptualization of the study design and interpretation of results; Dr Wagner, Ms Garcia, Ms Renfro, Ms Brown, Mr Metoyer, and Dr He participated in the prospective collection of data and interpretation of results; Mr Brown participated in the design of the study, conducted the analysis of data and interpretation of results, and participated in the preparation of the initial draft; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

FUNDING: Dr Savani holds the William Buchanan chair in Pediatrics at The University of Texas Southwestern Medical Center. Dr Kapadia acknowledges support from a K23HD083511 grant by the National Institutes of Health.

APP

advanced practice provider

BPD

bronchopulmonary dysplasia

CPAP

continuous positive airway pressure

DOL

day of life

DR

delivery room

ETT

endotracheal tube

Fio2

fraction of inspired oxygen

GA

gestational age

HOL

hour of life

InSurE

intubation, surfactant administration, and extubation

IVH

intraventricular hemorrhage

LISA

less invasive surfactant administration

MV

mechanical ventilation

OSC

OPTISURF cohort

PDA

patent ductus arteriosus

PHHS

Parkland Health and Hospital System

PPV

positive pressure ventilation

QI

quality improvement

RCT

randomized controlled trial

RT

respiratory therapist

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Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.