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1.  Randomised, controlled trial of nasal continuous positive airway pressure in the extubation of infants weighing 600 to 1250 g 
AIM—To determine whether extubation to nasal continuous airway pressure (NCPAP) results in a greater proportion of infants remaining free of additional ventilatory support for one week after extubation compared with those extubated directly to headbox oxygen.
METHODS—A randomised, controlled, clinical trial was conducted at the neonatal intensive care unit of the Royal Women's Hospital, Melbourne, of infants with birthweights between 600 and 1250 g, ventilated via an endotracheal tube for more than 12 hours, requiring less than 50% oxygen, a ventilator rate ⩽ 20/minute, considered by the clinical management team to be ready for extubation. Infants were randomly allocated either to NCPAP or to oxygen administered via a headbox. Success was defined by no requirement for additional ventilatory support over the week following extubation. Failure criteria were (i) apnoea; (ii) absolute increase in oxygen requirement greater than 15% above that required before extubation; or (iii) respiratory acidosis (pH<7.25 with pCO2 >6.67 kPa).
RESULTS—Thirty one of 47 (66%) infants were successfully extubated to NCPAP compared with 18 of 45 (40%) for headbox oxygen. The increase in failure rate in the headbox group was due primarily to increased oxygen requirements in this group. Of the 27 who failed headbox oxygen, 26 were given a trial of NCPAP and 13 did not require endotracheal reintubation. There was no significant difference between the groups in the total number of days of assisted ventilation or the duration of inpatient stay.
CONCLUSIONS—NCPAP applied prophylactically after endotracheal extubation reduces the incidence of adverse clinical events that lead to failure of extubation in the seven days after extubation. This reduction is clinically important. The benefits of NCPAP do not seem to be associated with an increased incidence of unwanted side effects.

PMCID: PMC1720820  PMID: 9797626
2.  Prophylactic nasal continuous positive airways pressure in newborns of 28–31 weeks gestation: multicentre randomised controlled clinical trial 
Background: The role of nasal continuous positive airways pressure (nCPAP) in the management of respiratory distress syndrome in preterm infants is not completely defined.
Objective: To evaluate the benefits and risks of prophylactic nCPAP in infants of 28–31 weeks gestation.
Design: Multicentre randomised controlled clinical trial.
Setting: Seventeen Italian neonatal intensive care units.
Patients: A total of 230 newborns of 28–31 weeks gestation, not intubated in the delivery room and without major malformations, were randomly assigned to prophylactic or rescue nCPAP.
Interventions: Prophylactic nCPAP was started within 30 minutes of birth, irrespective of oxygen requirement and clinical status. Rescue nCPAP was started when FIO2 requirement was > 0.4, for more than 30 minutes, to maintain transcutaneous oxygen saturation between 93% and 96%. Exogenous surfactant was given when FIO2 requirement was > 0.4 in nCPAP in the presence of radiological signs of respiratory distress syndrome.
Main outcome measures: Primary end point: need for exogenous surfactant. Secondary end points: need for mechanical ventilation and incidence of air leaks.
Results: Surfactant was needed by 22.6% in the prophylaxis group and 21.7% in the rescue group. Mechanical ventilation was required by 12.2% in both the prophylaxis and rescue group. The incidence of air leaks was 2.6% in both groups. More than 80% of both groups had received prenatal steroids.
Conclusions: In newborns of 28–31 weeks gestation, there is no greater benefit in giving prophylactic nCPAP than in starting nCPAP when the oxygen requirement increases to a FIO2 > 0.4.
PMCID: PMC1721765  PMID: 15321956
3.  Sustainable use of continuous positive airway pressure in extremely preterm infants during the first week after delivery 
Early use of nasal continuous positive airway pressure (nCPAP) may reduce lung damage, but it is not clear how many extremely preterm infants can be cared for without mechanical ventilation on the first days after delivery.
To describe our experience of nCPAP in infants born at <27 weeks' gestation and to determine the chance of reintubation of this group of extremely preterm infants.
A retrospective, observational study examined the period from November 2002 to October 2003, when efforts were made to extubate infants to nCPAP at the earliest opportunity. Data were collected on all infants born at <27 weeks' and gestation admitted to The Neonatal Intensive Care Unit, Queen Charlotte's and Chelsea Hospital, London, UK. The chance of an individual infant requiring reintubation within 48 h of delivery was estimated, calculating the predictive probability using a Bayesian approach, and oxygen requirements at 36 weeks' postmenstrual age were examined.
60 infants, 34 inborn and 26 ex utero transfers, were admitted; 7 infants admitted 24 h after birth were excluded and 5 died within 48 h. The mean birth weight was 788 g and the gestational age was 25.3 weeks. Extubation was attempted on day 1 in 21 of 52 infants on ventilators and was successful in 14; and on day 2 in 14 of 35 and successful in 10 of infants extubated within 48 h of delivery survived to discharge. 5 of 23 infants on mechanical ventilation at 48 h of age were on air at 36 weeks postmenstrual age, and 12 of 26 of those were on nCPAP at 48 h of age. The probability of an individual baby remaining on nCPAP was 66% (95% CI 46% to 86%) on day 1 and 80% (95% CI 60% to 99%) on day 2. The smallest infant to be successfully extubated was 660 g and the youngest gestational age was 23.8 weeks.
Extremely preterm infants can be extubated to nCPAP soon after delivery, with a reasonable probability of not requiring immediate reintubation.
PMCID: PMC2672749  PMID: 16820391
Pediatrics  2009;124(2):517-526.
Current literature suggests that use of synchronized nasal intermittent positive pressure ventilation (SNIPPV), following extubation, reduces the rate of reintubation compared to nasal continuous positive airway pressure (NCPAP). However, there is limited information available on the outcomes of infants managed with SNIPPV.
To compare the outcomes of infants managed with SNIPPV (postextubation or for apnea) to infants not treated with SNIPPV at 2 sites.
Clinical retrospective data was used to evaluate the use of SNIPPV in infants ≤1250 g birth weight (BW); and 3 BW subgroups (500 –750, 751–1000, and 1001–1250 g, decided a priori). SNIPPV was not assigned randomly. Bronchopulmonary dysplasia (BPD) was defined as treatment with supplemental oxygen at 36 weeks’ postmenstrual age.
Overall, infants who were treated with SNIPPV had significantly lower mean BW (863g vs. 964g) and gestational age (26.4 weeks vs. 27.9 weeks), more frequently received surfactant (85% vs. 68%), and had a higher incidence of BPD or death (39% vs. 27%) (all p<0.01), compared to infants treated with NCPAP. In the subgroup analysis, SNIPPV was associated with lower rates of BPD (43% vs 67%, P = .03) and BPD/death (51% vs 76%, P = .02) in the 500- to 750g infants, with no significant differences in the other BW groups. Logistic regression analysis, adjusting for significant covariates, revealed infants with 500 –700-g BW who received SNIPPV were significantly less likely to have the outcomes of BPD (OR: 0.29 [95% CI: 0.11– 0.77]; P = .01), BPD/death (OR: 0.30 [95% CI: 0.11– 0.79]; P = .01), neurodevelopmental impairment (NDI) (OR: 0.29 [95% CI: 0.09–0.94]; P = .04), and NDI/death (OR: 0.18 [95% CI: 0.05– 0.62]; P = .006).
SNIPPV use in infants at greatest risk of BPD or death (500-750g) was associated with decreased BPD, BPD/death, NDI, and NDI/death when compared to infants managed with NCPAP.
PMCID: PMC2924622  PMID: 19651577
premature newborn; respiratory distress syndrome; non-invasive ventilation
5.  Incidence of nasal trauma associated with nasal prong versus nasal mask during continuous positive airway pressure treatment in very low birthweight infants: a randomised control study 
Objective: To compare the incidence of nasal trauma associated with the use of prong or mask during nasal continuous positive airway pressure (nCPAP) support in very low birthweight (<1501 g) infants.
Design: Randomised controlled clinical trial.
Setting: Tertiary care university hospital, Department of Paediatrics, Kuala Lumpur, Malaysia.
Methods: All very low birthweight infants admitted to the neonatal intensive care unit between July 2001 and December 2003 who received nCPAP through the Infant Flow Driver were randomised to the use of either nasal prong or mask. The nasal cavity of these infants was inspected daily during the first week and then weekly until they were weaned off nCPAP.
Results: Of the 89 infants recruited, 41 were randomised to the mask group and 48 to the prong group. There was no significant difference in the incidence of nasal trauma between the two groups (p = 0.5). The primary site of trauma was at the junction between the nasal septum and the philtrum in infants in the mask group and the walls of the nasal septum in the prong group. Logistic regression analysis showed that duration of nCPAP was the only significant risk factor associated with development of nasal injury, after birth weight, gestational age, and nasal device used had been controlled for (adjusted odds ratio 1.04; 95% confidence interval 1.01 to 1.07; p = 0.003).
Conclusion: Irrespective of the type of nasal device used, nasal trauma is common during nCPAP treatment, which should therefore be terminated as soon as possible.
PMCID: PMC1721971  PMID: 15941825
6.  Sustained lung inflation in the delivery room in preterm infants at high risk of respiratory distress syndrome (SLI STUDY): study protocol for a randomized controlled trial 
Trials  2013;14:67.
Some studies have suggested that the early sustained lung inflation (SLI) procedure is effective in decreasing the need for mechanical ventilation (MV) and improving respiratory outcome in preterm infants. We planned the present randomized controlled trial to confirm or refute these findings.
In this study, 276 infants born at 25+0 to 28+6 weeks’ gestation at high risk of respiratory distress syndrome (RDS) will be randomized to receive the SLI maneuver (25 cmH2O for 15 seconds) followed by nasal continuous positive airway pressure (NCPAP) or NCPAP alone in the delivery room. SLI and NCPAP will be delivered using a neonatal mask and a T-piece ventilator.
The primary endpoint is the need for MV in the first 72 hours of life. The secondary endpoints include the need and duration of respiratory support (NCPAP, MV and surfactant), and the occurrence of bronchopulmonary dysplasia (BPD).
Trial registration
Trial registration number: NCT01440868
PMCID: PMC3599289  PMID: 23497495
Sustained lung inflation; Preterm infants, Resuscitation; Delivery room; Mechanical ventilation
7.  A randomised control study comparing the Infant Flow Driver with nasal continuous positive airway pressure in preterm infants 
OBJECTIVE—To compare the effectiveness of the Infant Flow Driver (IFD) with single prong nasal continuous positive airway pressure (nCPAP) in preterm neonates affected by respiratory distress syndrome.
DESIGN—Randomised controlled study.
PATIENTS—Between September 1997 and March 1999, 36 preterm infants who were eligible for CPAP treatment were randomly selected for either nCPAP or IFD and studied prospectively for changes in oxygen requirement and/or respiratory rate. The requirement for mechanical ventilation, complications of treatment, and effects on mid-term outcome were also evaluated.
RESULTS—Use of the IFD had a significantly beneficial effect on both oxygen requirement and respiratory rate (p < 0.0001) when compared with nCPAP. Moreover, O2 requirement and respiratory rate were significantly decreased by four hours (p < 0.001 and p < 0.03 respectively). The probability of remaining supplementary oxygen free over the first 48 hours of treatment was significantly higher in patients treated with the IFD than with nCPAP (p < 0.02). IFD treated patients had a higher success (weaning) rate (94% v 72%) and shorter duration of treatment (49.3 (31) v 56 (29.7) hours respectively; mean (SD)), although the difference was not significant.
CONCLUSIONS—IFD appears to be a feasible device for managing respiratory distress syndrome in preterm infants, and benefits may be had with regard to oxygen requirement and respiratory rate when compared with nCPAP. The trend towards reduced requirement for mechanical ventilation, shorter clinical recovery time, and shorter duration of treatment requires further evaluation in a multicentre randomised clinical trial.

PMCID: PMC1721298  PMID: 11517199
8.  Flow-Synchronized Nasal Intermittent Positive Pressure Ventilation for Infants <32 Weeks' Gestation with Respiratory Distress Syndrome 
Aim. To evaluate whether synchronized-NIPPV (SNIPPV) used after the INSURE procedure can reduce mechanical ventilation (MV) need in preterm infants with RDS more effectively than NCPAP and to compare the clinical course and the incidence of short-term outcomes of infants managed with SNIPPV or NCPAP. Methods. Chart data of inborn infants <32 weeks undergoing INSURE approach in the period January 2009–December 2010 were reviewed. After INSURE, newborns born January –December 2009 received NCPAP, whereas those born January–December 2010 received SNIPPV. INSURE failure was defined as FiO2 need >0.4, respiratory acidosis, or intractable apnoea that occurred within 72 hours of surfactant administration. Results. Eleven out of 31 (35.5%) infants in the NCPAP group and 2 out of 33 (6.1%) infants in the SNIPPV group failed the INSURE approach and underwent MV (P < 0.004). Fewer infants in the INSURE/SNIPPV group needed a second dose of surfactant, a high caffeine maintenance dose, and pharmacological treatment for PDA. Differences in O2 dependency at 28 days and 36 weeks of postmenstrual age were at the limit of significance in favor of SNIPPV treated infants. Conclusions. SNIPPV use after INSURE technique in our NICU reduced MV need and favorably affected short-term morbidities of our premature infants.
PMCID: PMC3514808  PMID: 23227317
9.  Automatic nasal continuous positive airway pressure titration in the laboratory: patient outcomes 
Thorax  1997;52(1):72-75.
BACKGROUND: Manual titration of nasal continuous positive airway pressure (NCPAP) treatment for obstructive sleep apnoea (OSA) is time consuming and expensive. There are now "intelligent" NCPAP machines that try to find the ideal pressure for a patient by monitoring a combination of apnoeas, hypopnoeas, inspiratory flow limitation, and snoring. Although these machines usually find similar pressures to skilled technicians, it is not clear if their use in the sleep laboratory influences subsequent acceptance by patients. This study addresses this question. METHODS: One hundred and twenty two patients undergoing a trial of NCPAP were randomly allocated to either manual or automatic (Horizon, DeVilbiss) titration of pressure during their first night on NCPAP in a hospital sleep laboratory. The primary outcome (available on 112 patients) was the acceptance of NCPAP or otherwise six weeks following the initial titration night. Baseline indicators of severity were compared between the groups, as were the pressures selected and the subsequent improvement in the sleepiness of the patients. RESULTS: The initial severity of OSA was not significantly different in the two groups and the mean (SD) NCPAP pressures were similar (manual 8.7 (2.5) cm H2O, automatic 8.2 (2.1) cm H2O). The percentage of patients successfully established on CPAP at six weeks was 64% and 73% for the manual and automatic groups, respectively; 13% and 2%, respectively, in the manual and automatic groups had given up completely (p < 0.05), and there were about equal numbers (23% versus 25%) in the two groups who were still undecided. CONCLUSIONS: The substitution of automatic NCPAP titration for manual titration during the first night of NCPAP in patients with OSA does not reduce the number accepting the treatment at six weeks and may slightly improve it. This has important cost saving potential. 

PMCID: PMC1758408  PMID: 9039254
10.  Nasal continuous positive airway pressure and outcomes in preterm infants: A retrospective analysis 
Paediatrics & Child Health  2008;13(2):99-103.
The aim of the present retrospective study was to describe the use of nasal continuous positive airway pressure (NCPAP) and the prevalence of bronchopulmonary dysplasia (BPD).
Data from 1526 neonates with gestational age less than 32 weeks, admitted to Children’s and Women’s Health Centre of British Columbia (Vancouver, British Columbia) between period 1 (1996 to 2000) and period 2 (2000 to 2004) were analyzed. The use of respiratory therapies and outcomes were retrospectively compared before and after the introduction of a NCPAP approach to respiratory support.
A significant increase in the use of NCPAP was noted between periods 1 and 2 (60% versus 71%), as well as a significant reduction in the use of surfactant (50% versus 41%), postnatal steroids (30% versus 10%) and the need for mechanical ventilation (77% versus 64%). In period 2, there was a significant reduction in the prevalence of BPD at 28 days (33% versus 26%), higher prevalence of severe retinopathy of prematurity (3% versus 6%) and less periventricular leukomalacia (4% versus 2%).
A significant increase in the use of NCPAP therapy in the neonatal unit has been associated with a decrease in the use of more invasive therapies. The incidence of BPD has decreased if defined as need for supplemental oxygen at 28 days of age, but not when the 36 weeks’ postconceptional age criterion was used. NCPAP therapy may decrease the use of more invasive therapies and may improve respiratory outcomes. The impact of this intervention on nonrespiratory outcomes warrants further investigation.
PMCID: PMC2528745  PMID: 19183712
Bronchopulmonary dysplasia; CPAP; Neonatology; Premature infants; Retinopathy of prematurity
11.  The use of nasal continuous positive airway pressure to treat obstructive sleep apnoea 
Archives of Disease in Childhood  2002;87(5):438-443.
Aim: To review 66 children with obstructive sleep apnoea (OSA) for whom a trial of nasal continuous positive airway pressure (nCPAP) was proposed.
Methods: Baseline sleep studies were performed to assess OSA severity; a trial of nCPAP was performed where moderate to severe OSA, not relieved by adenotonsillectomy, was found. The nCPAP trial was considered either technically successful (ST), if the child accepted the mask for sufficient time to determine nCPAP efficacy, or a technical failure (FT) if otherwise. Patients with an initial FT were offered a period of home acclimatisation to familiarise them with wearing the mask during sleep. ST patients in whom nCPAP was effective were established on long term therapy.
Results: Nasal CPAP trials were successful (ST) in 49/66 (74%) patients. Nasal CPAP efficacy could not be determined in the remaining 17 FT patients (26%), generally because of their poor nCPAP tolerance. These patients were subsequently considered for other treatment. A total of 42/49 (86%) ST patients were established on long term nCPAP therapy, 2/49 (4%) derived no benefit from nCPAP, while 5/49 (10%) refused long term nCPAP therapy. Of patients on long term nCPAP, the most frequently reported side effects were skin irritation and nasal dryness; however, these were not serious enough to require any patients to discontinue therapy. A period of home acclimatisation was found to be effective in increasing nCPAP acceptance, with 26% of FT children being subsequently successfully reassessed for nCPAP.
Conclusion: The use of nCPAP was feasible in a significant proportion of a paediatric OSA population. Failure was usually because of the child's intolerance of the nCPAP equipment. Nasal CPAP was an effective treatment in the majority of patients where it could be assessed, and was adopted as a long term therapy in most cases. We have successfully used nCPAP to treat OSA across a wide range of ages. Motivated parents and skilled support staff have proved essential for the success of nCPAP in a paediatric setting.
PMCID: PMC1763069  PMID: 12390928
12.  Early Surfactant Therapy With Nasal Continuous Positive Airway Pressure or Continued Mechanical Ventilation in Very Low Birth Weight Neonates With Respiratory Distress Syndrome 
Various strategies have been suggested for the treatment of respiratory distress syndrome (RDS).
The aim of this study was to compare the efficacies of two common methods of RDS management among neonates with low birth weight.
Patients and Methods:
A cohort study was conducted on 98 neonates with definite diagnosis of RDS during 2008-2009. The neonates were divided into two groups by a blinded supervisor using simple randomization (odd and even numbers). Forty-five cases in the first group were treated with intubation, surfactant therapy, extubation (INSURE method) followed by nasal continuous positive airway pressure (N.CPAP) and 53 cases in the second group underwent intubation, surfactant therapy followed by mechanical ventilation (MV).
Five (11.1%) cases in the first group and 23 (43%) cases in the second group expired during the study. The rates of MV dependency among cases with INSURE failure and cases in the MV group were 37% and 83%, respectively (P < 0.001). Birth weight (BW) (P = 0.017), presence of retinopathy of prematurity (P = 0.022), C/S delivery (P = 0.029) and presence of lung bleeding (P = 0.010) could significantly predict mortality in the second group, although only BW (P = 0.029) had a significant impact on the mortality rate in the first group. Moreover, BW was significantly related to the success rate in the first group (P = 0.001).
Our findings demonstrated that INSURE plus NCPAP was more effective than the routine method (permanent intubation after surfactant prescription). In addition, the lower rates of mortality, MV dependency, duration of hospitalization, and complications were observed in cases treated with the INSURE method compared to the routine one.
PMCID: PMC4028758  PMID: 24910785
Respiration, Artificial; Infant, Newborn; Respiratory Distress Syndrome, Newborn
13.  Continuous positive airway pressure and ventilation are more effective with a nasal mask than a full face mask in unconscious subjects: a randomized controlled trial 
Critical Care  2013;17(6):R300.
Upper airway obstruction (UAO) is a major problem in unconscious subjects, making full face mask ventilation difficult. The mechanism of UAO in unconscious subjects shares many similarities with that of obstructive sleep apnea (OSA), especially the hypotonic upper airway seen during rapid eye movement sleep. Continuous positive airway pressure (CPAP) via nasal mask is more effective at maintaining airway patency than a full face mask in patients with OSA. We hypothesized that CPAP via nasal mask and ventilation (nCPAP) would be more effective than full face mask CPAP and ventilation (FmCPAP) for unconscious subjects, and we tested our hypothesis during induction of general anesthesia for elective surgery.
In total, 73 adult subjects requiring general anesthesia were randomly assigned to one of four groups: nCPAP P0, nCPAP P5, FmCPAP P0, and FmCPAP P5, where P0 and P5 represent positive end-expiratory pressure (PEEP) 0 and 5 cm H2O applied prior to induction. After apnea, ventilation was initiated with pressure control ventilation at a peak inspiratory pressure over PEEP (PIP/PEEP) of 20/0, then 20/5, and finally 20/10 cm H2O, each applied for 1 min. At each pressure setting, expired tidal volume (Vte) was calculated by using a plethysmograph device.
The rate of effective tidal volume (Vte > estimated anatomical dead space) was higher (87.9% vs. 21.9%; P<0.01) and the median Vte was larger (6.9 vs. 0 mL/kg; P<0.01) with nCPAP than with FmCPAP. Application of CPAP prior to induction of general anesthesia did not affect Vte in either approach (nCPAP pre- vs. post-; 7.9 vs. 5.8 mL/kg, P = 0.07) (FmCPAP pre- vs. post-; 0 vs. 0 mL/kg, P = 0.11).
nCPAP produced more effective tidal volume than FmCPAP in unconscious subjects.
Trial registration identifier: NCT01524614.
PMCID: PMC4056076  PMID: 24365207
14.  Impact of Changes in Perinatal Care on Neonatal Respiratory Outcome and Survival of Preterm Newborns: An Overview of 15 Years 
Survival and outcomes for preterm infants with respiratory distress syndrome (RDS) have improved over the past 30 years. We conducted a study to assess the changes in perinatal care and delivery room management and their impact on respiratory outcome of very low birth weight newborns, over the last 15 years. A comparison between two epochs was performed, the periods before and after 2005, when early nasal continuous positive airway pressure (NCPAP) and Intubation-SURfactant-Extubation (INSURE) were introduced in our center. Three hundred ninety-five clinical records were assessed, 198 (50.1%) females, gestational age 29.1 weeks (22–36), and birth weight 1130 g (360–1498). RDS was diagnosed in 247 (62.5%) newborns and exogenous surfactant was administered to 217 (54.9%). Thirty-three (8.4%) developed bronchopulmonary dysplasia (BPD), and 92 (23%) were deceased. With the introduction of early NCPAP and INSURE, there was a decrease on the endotracheal intubation need and invasive ventilation (P < 0.0001), oxygen therapy (P = 0.002), and mortality (P < 0.0001). The multivariate model revealed a nonsignificant reduction in BPD between the two epochs (OR = 0.86; 95% CI 0.074–9.95; P = 0.9). The changes in perinatal care over the last 15 years were associated to an improvement of respiratory outcome and survival, despite a nonsignificant decrease in BPD rate.
PMCID: PMC3539442  PMID: 23320153
15.  Aerosol delivery of synthetic lung surfactant 
PeerJ  2014;2:e403.
Background. Nasal continuous positive airway pressure (nCPAP) is a widely accepted technique of non-invasive respiratory support in premature infants with respiratory distress syndrome due to lack of lung surfactant. If this approach fails, the next step is often intubation, mechanical ventilation (MV) and intratracheal instillation of clinical lung surfactant.
Objective. To investigate whether aerosol delivery of advanced synthetic lung surfactant, consisting of peptide mimics of surfactant proteins B and C (SP-B and SP-C) and synthetic lipids, during nCPAP improves lung function in surfactant-deficient rabbits.
Methods. Experimental synthetic lung surfactants were produced by formulating 3% Super Mini-B peptide (SMB surfactant), a highly surface active SP-B mimic, and a combination of 1.5% SMB and 1.5% of the SP-C mimic SP-Css ion-lock 1 (BC surfactant), with a synthetic lipid mixture. After testing aerosol generation using a vibrating membrane nebulizer and aerosol conditioning (particle size, surfactant composition and surface activity), we investigated the effects of aerosol delivery of synthetic SMB and BC surfactant preparations on oxygenation and lung compliance in saline-lavaged, surfactant-deficient rabbits, supported with either nCPAP or MV.
Results. Particle size distribution of the surfactant aerosols was within the 1–3 µm distribution range and surfactant activity was not affected by aerosolization. At a dose equivalent to clinical surfactant therapy in premature infants (100 mg/kg), aerosol delivery of both synthetic surfactant preparations led to a quick and clinically relevant improvement in oxygenation and lung compliance in the rabbits. Lung function recovered to a greater extent in rabbits supported with MV than with nCPAP. BC surfactant outperformed SMB surfactant in improving lung function and was associated with higher phospholipid values in bronchoalveolar lavage fluid; these findings were irrespective of the type of ventilatory support (nCPAP or MV) used.
Conclusions. Aerosol delivery of synthetic lung surfactant with a combination of highly active second generation SP-B and SP-C mimics was effective as a therapeutic approach towards relieving surfactant deficiency in spontaneously breathing rabbits supported with nCPAP. To obtain similar results with nCPAP as with intratracheal instillation, higher dosage of synthetic surfactant and reduction of its retention by the delivery circuit will be needed to increase the lung dose.
PMCID: PMC4045332  PMID: 24918030
Aerosol delivery; Synthetic lung surfactant; Captive bubble surfactometry; Surfactant-deficient rabbits; Lung function; Mechanical ventilation; Surfactant protein B; Surfactant protein C; Nasal continuous positive airway pressure
16.  A study of the effect of nasal modes of ventilation on the incidence of gastro-oesophageal reflux in preterm neonates 
Nasal modes of respiratory support cause variable amounts of gastric dilatation which may increase gastro-oesophageal reflux (GER) in preterms. To compare the incidence of GER in nasally ventilated, preterm babies with controls (babies not on ventilation). Type of study: A prospective, observational comparative study.
Twenty-three preterm babies of gestational age 28–36 weeks and weight ranging between 1,000 g and < 2,500 g on either nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure venti-lation (nIPPV) were assessed for GER. They were compared with controls not on ventilation some of who were test babies when off ventilation (subgroup A) and some were unrelated babies not on ventilator but matched for gestational age and weight with test babies (subgroup B). All babies were subjected to continuous, oesophageal pH monitoring with dual sensor (upper and lower oesophageal) catheters. Reflux index (RI) was calculated as the percentage of study time the lower oesophageal pH was < 4. Primary outcome was the RI in the test and controls groups. Secondary outcome was the temporal relation of the reflux with symptoms if any. Numerical data were shown as mean with standard deviation and statistical comparisons were done using the χ2-test, Fischer test, and t-test wherever applicable.
The RI was higher in ventilated babies as compared to the control group, particularly in the subgroup A, where test babies formed their own controls. Grade IV reflux (7 cases) was seen only in the ventilated babies. There was no difference in the incidence of GER in babies on nCPAP as compared with nIPPV. Grade IV reflux could not be reliably predicted by RI alone. No definite temporal relation between episodes of reflux and symptoms could be determined in this study.
There is an increase in GER in preterms on nasal modes of ventilation. A combination of upper (pharyngeal) and lower oesophageal sensors are preferred to a single lower oesophageal sensor when assessing GER by oesophageal pHmetry in neonates.
PMCID: PMC3862922  PMID: 24669032
CPAP; gastro-oesophageal reflux; nasal ventilation; preterm
17.  Determinants of survival in very low birth weight neonates in a public sector hospital in Johannesburg 
BMC Pediatrics  2010;10:30.
Audit of disease and mortality patterns provides essential information for health budgeting and planning, as well as a benchmark for comparison. Neonatal mortality accounts for about 1/3 of deaths < 5 years of age and very low birth weight (VLBW) mortality for approximately 1/3 of neonatal mortality. Intervention programs must be based on reliable statistics applicable to the local setting; First World data cannot be used in a Third World setting. Many neonatal units participate in the Vermont Oxford Network (VON); limited resources prevent a significant number of large neonatal units from developing countries taking part, hence data from such units is lacking. The purpose of this study was to provide reliable, recent statistics relevant to a developing African country, useful for guiding neonatal interventions in that setting.
This was a retrospective chart review of 474 VLBW infants admitted within 24 hours of birth, between 1 July 2006 and 30 June 2007, to the neonatal unit of Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in Johannesburg, South Africa. Binary outcome logistic regression on individual variables and multiple logistic regression was done to identify those factors determining survival.
Overall survival was 70.5%. Survival of infants below 1001 grams birth weight was 34.9% compared to 85.8% for those between 1001 and 1500 grams at birth. The main determinant of survival was birth weight with an adjusted survival odds ratio of 23.44 (95% CI: 11.22 - 49.00) for babies weighing between 1001 and 1500 grams compared to those weighing below 1001 grams. Other predictors of survival were gender (OR 3. 21; 95% CI 1.6 - 6.3), birth before arrival at the hospital (BBA) (OR 0.23; 95% CI: 0.08 - 0.69), necrotising enterocolitis (NEC) (OR 0.06; 95% CI: 0.02 - 0.20), hypotension (OR 0.05; 95% CI 0.01 - 0.21) and nasal continuous positive airways pressure (NCPAP) (OR 4.58; 95% CI 1.58 - 13.31).
Survival rates compare favourably with other developing countries, but can be improved; especially in infants < 1001 grams birth weight. Resources need to be allocated to preventing the birth of VLBW babies outside hospital, early neonatal resuscitation, provision of NCPAP and prevention of NEC.
PMCID: PMC2885379  PMID: 20444296
18.  Can mandibular advancement devices be a satisfactory substitute for short term use in patients on nasal continuous positive airway pressure? 
Thorax  2002;57(4):305-308.
Background: Mandibular advancement devices (MADs) can successfully control both snoring and obstructive sleep apnoea (OSA). Many patients on nasal continuous positive airway pressure (NCPAP) for OSA would like a more portable alternative, even if only temporarily. This study assesses what proportion of patients with OSA already on NCPAP can successfully use a MAD for short periods (up to 1 month) as a temporary alternative to NCPAP.
Methods: Fifty patients with OSA, already on NCPAP for at least 3 months, were recruited by invitation. They were provided with a simple fixed MAD estimated to provide 75% of maximum mandibular protrusion. Sleep studies using a portable home recorder were performed on and after three nights without NCPAP to provide control data. Following acclimatisation to the MAD, sleep studies were also planned after 3, 7, and 28 days while using the MAD. If their overnight >4% SaO2 dips per hour deteriorated to >20 or the Epworth sleepiness score (ESS) rose to >9 (or increased by >4 over baseline) on nights 3 or 7, they were then deemed to have failed the trial and were withdrawn.
Results: Of the 50 patients entered, one had inadequate teeth for a MAD and 31 gave up trying to use the device during the acclimatisation period because of side effects. Of the 18 prepared to use the device, two patients failed at night 3, five at night 7, and two at night 28. Thus, nine patients remained controlled by our criteria at night 28. On average, sleep study indices while using the MAD were poor compared with the night on NCPAP.
Conclusions: Simple MADs are poorly tolerated by patients with OSA already on NCPAP. OSA was adequately controlled by our criteria in 32% of those recruited for the equivalent of a weekend, in 22% for 1 week, and in 18% for up to 1 month. Better tolerated devices would be likely to improve on these figures.
PMCID: PMC1746287  PMID: 11923547
19.  Randomised prospective parallel trial of therapeutic versus subtherapeutic nasal continuous positive airway pressure on simulated steering performance in patients with obstructive sleep apnoea 
Thorax  2000;55(3):224-231.
BACKGROUND—Obstructive sleep apnoea (OSA) impairs vigilance and may lead to an increased rate of driving accidents. In uncontrolled studies accident rates and simulated steering performance improve following treatment with nasal continuous positive airway pressure (NCPAP). This study seeks to confirm the improvement in steering performance in a randomised controlled trial using subtherapeutic NCPAP as a control treatment.
METHODS—Fifty nine men with OSA (Epworth Sleepiness Score (ESS) of ⩾10, and ⩾10/h dips in SaO2 of >4% due to OSA) received therapeutic or subtherapeutic NCPAP (≈1 cm H2O) for one month. Simulated steering performance over three 30-minute "drives" was quantified as: standard deviation (SD) of road position, deterioration in SD across the drive, length of drive before "crashing", and number of off-road events. The reaction times to peripheral target stimuli during the drive were also measured.
RESULTS—Subtherapeutic NCPAP did not improve overnight >4% SaO2 dips/h compared with baseline values, thus acting as a control. The SD of the steering position improved from 0.36 to 0.21 on therapeutic NCPAP, and from 0.35 to 0.30 on subtherapeutic NCPAP (p = 0.03). Deterioration in SD of the steering position improved from 0.18to 0.06 SD/h with therapeutic NCPAP and worsened from 0.18 to 0.24 with subtherapeutic NCPAP (p = 0.04). The reaction time to target stimuli was quicker after therapeutic than after subtherapeutic NCPAP (2.3 versus 2.7 seconds, p = 0.04).
CONCLUSIONS—Therapeutic NCPAP improves steering performance and reaction time to target stimuli in patients with OSA, lending further support to the hypothesis that OSA impairs driving, increases driving accident rates, and that these improve following treatment with NCPAP.

PMCID: PMC1745705  PMID: 10679542
20.  In vitro comparison of nasal continuous positive airway pressure devices for neonates 
Objective: To compare the resistance in vitro of different devices used for the delivery of nasal continuous positive airway pressure (NCPAP) in neonates.
Design: Flows of 4–8 litres/min were passed through a selection of neonatal NCPAP devices (single prong, Duotube, Argyle prong, Hudson prong, Infant Flow Driver), and the resultant fall in pressure measured using a calibrated pressure transducer.
Results: The decrease in pressure (cm H2O) for each device (size in parentheses) at a constant flow of 6 litres/min was: Duotube: (2.5), 21; (3.0), 6.2; (3.5), 2.3; single prong: (2.5), 4.4; (3.0), 2.1; (3.5), 1.2; Argyle prong: (XS), 3.6; (S), 1.9; (L), 1.5; Hudson prong: (0), 3.1; (1), 1.8; (2), 0.6; (3), 0.4; (4), 0.3; Infant Flow Driver: (small), 0.3; (medium), -0.3; (large), -0.5.
Conclusions: A large variation in the potential fall in pressure may occur in the clinical setting. Devices with short double prongs had the lowest resistance to flow. These results have implications in the selection of the optimal device/s for clinical application and for future comparisons in randomised trials of NCPAP in neonates.
PMCID: PMC1721427  PMID: 12091290
21.  Changes in snoring characteristics after 30 days of nasal continuous positive airway pressure in patients with non-apnoeic snoring: a controlled trial. 
Thorax  1994;49(6):562-566.
BACKGROUND--A study was performed to evaluate the effect of discontinuation of nasal continuous positive airway pressure (NCPAP) treatment on snoring characteristics. METHODS--Eighteen non-apnoeic snoring subjects were randomly allocated to either a no treatment control group or an NCPAP treatment group. The control group was studied twice (baseline and day 30 of follow up). In the NCPAP group the level of NCPAP that abolished snoring was determined and part abolished snoring was determined and patients were placed on NCPAP every night for one month. A sleep study was performed on the first night without NCPAP after completing 30 days of treatment (follow up 1). A fourth polysomnographic study was performed 8-10 days after NCPAP was stopped (follow up 2) in six subjects. RESULTS--In both groups total sleep time (TST) and sleep architecture remained unchanged at the different visits. Baseline snoring characteristics in the two groups were similar. In the control group the mean (SE) number of snoring episodes/hour of sleep (snoring index) and the percentage of TST > 60 decibels (dB) were 380 (36)/h and 11.1 (2.0)% TST respectively at baseline, and was unchanged at follow up. In the NCPAP group the snoring index decreased from 387 (50)/h to 320 (57)/h after NCPAP therapy, but the % TSTS > 60 dB decreased from 10.3 (1.8)% to 7.4 (1.5)%. The snoring index and intensity returned to baseline values at follow up 2 (374 (74)/h, 9.8 (2.1)% TST). Changes in snoring characteristics could not be explained by changes in body position between the different sleep studies. CONCLUSIONS--NCPAP improves snoring but this effect is lost soon after stopping treatment.
PMCID: PMC474945  PMID: 8016794
22.  The Danish neonatal clinical database is valuable for epidemiologic research in respiratory disease in preterm infants 
BMC Pediatrics  2014;14:47.
We examined the quality of the information on the use of surfactant and the use of and duration of nasal continuous positive airway pressure (nCPAP), oxygen supplementation, and mechanical ventilation in the Danish Neonatal Clinical Database (NeoBase).
We included all neonates born with a gestational age < 32 weeks admitted to a Neonatal Intensive Care Unit (NICU) at two university hospitals in 2005. On discharge, the clinicians complete a structured form with information related to the delivery and course of stay in the NICU. These forms were entered into the NeoBase. The nurses’ daily bedside documentation was used as reference standard. Concordance was used as a measure of agreement between the NeoBase and the reference standard. For the dichotomous variables the concordance was defined as the sensitivity of the information registered in the NeoBase. For the continuous variables, it was based on the discrepancy in days between the NeoBase and the reference standard. The percentage of concordance was described as high (> 90), moderate (70–90) or low (< 70).
Overall, 153 infants participated in the study. Concordance was high for all dichotomous variables. The NeoBase slightly underestimated the duration of nCPAP and mechanical ventilation. The duration of oxygen therapy was neither over- nor underestimated in the NeoBase. Concordance was low for all continuous variables if we assumed that the registered information was identical. It was 100% for duration of mechanical ventilation and moderate for nCPAP and oxygen supplementation if we allowed for a discrepancy of 1 day.
The NeoBase is a valuable tool for clinical and epidemiologic research and quality assurance regarding neonatal respiratory disease.
PMCID: PMC3930301  PMID: 24528529
Respiratory variables; Very preterm infants; Validation; Epidemiology; Quality assurance
23.  Factors Affecting the Weaning from Nasal CPAP in Preterm Neonates 
Objective. Identification of the weight and postmenstrual age (PMA) at successful weaning of NCPAP in preterm neonates and the factors influencing the successful wean. Study Design. Retrospective review of 454 neonates ≤32 weeks of gestational age (GA) who were placed on NCPAP and successfully weaned to room air was performed. Results. Neonates had a mean birth weight (BW) of 1357 ± 392 grams with a mean GA of 29.3 ± 2.2 weeks. Neonates were weaned off NCPAP at mean weight of 1611 ± 432 grams and mean PMA of 32.9 ± 2.4 weeks. Univariate analysis showed that chorioamnionitis, intubation, surfactant use, PDA, sepsis/NEC, anemia, apnea, GER and IVH were significantly associated with the time to NCPAP wean. On multivariate analysis, among neonates that were intubated, BW was the only significant factor (P < 0.001) that was inversely related to time to successful NCPAP wean. Amongst non-intubated neonates, along with BW (P < 0.01), chorioamnionitis (P < 0.01), anemia (P < 0.0001), and GER (P < 0.02) played a significant role in weaning from NCPAP. Conclusion. Neonates were weaned off NCPAP at mean weight of 1611 ± 432 grams and mean PMA of 32.9 ± 2.4 weeks. BW significantly affects weaning among intubated and non-intubated neonates, though in neonates who were never intubated chorioamnionitis, anemia and GER also significantly affected the duration on NCPAP.
PMCID: PMC3236475  PMID: 22187570
24.  Plasma leptin levels and cardiac sympathetic function in patients with obstructive sleep apnoea-hypopnoea syndrome 
Thorax  2002;57(5):429-434.
Background: The control of body weight and cardiac sympathetic function in patients with obstructive sleep apnoea-hypopnoea syndrome (OSAHS) are important because both factors have significant effects on the mortality of these patients. It has recently been reported that OSAHS has a significant effect on the secretion of leptin, a hormone involved in the control of body weight and sympathetic nerve activity. In addition to the circadian rhythm of leptin secretion, the effects of one night of treatment with nasal continuous positive airway pressure (nCPAP) and the mechanism of the effects of nCPAP on nocturnal leptin secretion in patients with OSAHS has not yet been elucidated.
Methods: Blood samples were obtained at 21.00 hours, 00.00 hours, 03.00 hours, and 06.30 hours from 21 subjects with OSAHS (mean apnoea and hypopnoea index 52.4/h), with and without nCPAP treatment. Iodine-123 (I123)-meta-iodobenzylguanidine (MIBG) imaging was used to evaluate myocardial sympathetic function before nCPAP treatment.
Results: Plasma leptin reached a peak level at 00:00 hours (p<0.01) in patients with OSAHS, both with and without nCPAP treatment. The first night of nCPAP treatment significantly decreased the plasma leptin levels at 03.00 hours (without nCPAP: mean (SE) 21.6 (4.7) ng/ml; with nCPAP: 19.3 (4.1) ng/ml, p<0.02) and at 06.30 hours (without nCPAP: 17.6 (3.8) ng/ml; with nCPAP: 15.2 (3.2) ng/ml, p<0.01). The magnitude of the decrease in leptin levels after nCPAP treatment was significantly correlated with cardiac sympathetic function measured before nCPAP treatment (p<0.03).
Conclusions: Patients with OSAHS undergo nocturnal increases in leptin levels in spite of interruption of sleep due to apnoea and hypopnoea, a trend seen in normal subjects. Plasma leptin levels in patients with OSAHS decreased significantly after the first night of nCPAP treatment. Enhanced cardiac sympathetic function in these patients may contribute to the leptin levels before nCPAP treatment and vice versa.
PMCID: PMC1746321  PMID: 11978920
25.  Efficacy of nasal continuous positive airway pressure therapy in chronic heart failure: importance of underlying cardiac rhythm 
Thorax  1998;53(11):957-962.
BACKGROUND—Some previous reports have indicated beneficial cardiac effects of nasal continuous positive airway pressure (NCPAP) in patients with severe congestive heart failure (CHF), but others have reported deleterious cardiac effects, particularly among patients in atrial fibrillation (AF). The aim of this study was to determine if differences in cardiac rhythm influence the acute cardiac response to NCPAP.
METHODS—Eleven consecutive patients with CHF were recruited, six in atrial fibrillation (AF) and five with sinus rhythm (SR). Cardiac index was measured during awake NCPAP application by the thermodilution technique during cardiac catheterisation. NCPAP was applied in a randomised sequence at pressures of 0, 5, and 10 cm H2O with three 30 minute applications separated by 20 minute recovery periods without NCPAP.
RESULTS—Significant differences were found between the AF and SR groups for cardiac index responses to NCPAP (p = 0.004, ANOVA) with a fall in cardiac index in the AF group (p = 0.02) and a trend towards an increase in the SR group (p = 0.10). Similar differences were seen between the groups in stroke volume index responses but not in heart rate responses. Changes in systemic vascular resistance were also significantly different between the two groups (p< 0.005, ANOVA), rising in the AF group but falling in the SR group. 
CONCLUSIONS—These data indicate an important effect of underlying cardiac rhythm on the awake haemodynamic effects of NCPAP in patients with CHF.

PMCID: PMC1745106  PMID: 10193395

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