Section 6: Home ventilation in children with chronic lung diseases

This article is related to:

Pediatric home mechanical ventilation: A Canadian Thoracic Society clinical practice guideline executive summary

Introduction

Some children with chronic lung diseases (CLD) may require home mechanical ventilation (HMV). This section will focus on bronchopulmonary dysplasia (BPD) and cystic fibrosis (CF), though other CLDs such as primary ciliary dyskinesia and those that may result in pulmonary hypertension are also addressed.^1,2 The goals of this section are: (1) to review the literature on the experience in using HMV (invasive and noninvasive) in children with chronic respiratory failure secondary to CLD such as BPD and CF; (2) to review the outcomes of HMV for these populations; (3) to provide Canadian-specific pediatric practice recommendations around long-term home ventilation for children with respiratory failure and hypoventilation secondary to CLD; and (4) to identify areas for further research.

Literature review: Methodology

A systematic search of the literature from 1946 to August 24, 2015 was conducted in the following databases: Medline, Embase, AMED, PsycINFO, Central, Cinahl. MeSH terms and keywords used captured the concepts “home” and “ventilation” as well as specified lung diseases, namely cystic fibrosis, bronchopulmonary dysplasia, interstitial lung diseases, chronic lung disease and tracheostomy. The search was limited to all children 0–18 years and English and French languages. A similar search was also performed in the gray literature to yield 1437 citations. A total of 153 articles with relevant titles or abstracts were reviewed by the authors in more detail. A scan of the reference lists in sentinel papers yielded an additional 35 articles that were also reviewed for this chapter. Results of this literature review are presented in the subsequent text and in Tables 1–3.

Table 1. Summary of studies evaluating outcomes in children with bronchopulmonary dysplasia and related chronic lung disease on HMV.

Author (Year)	Study population /# of patients	Study type	Aim of study	Outcomes	Comments
El-Masri (2015)^1	N = 1 (out of 48 children with MRSA sepsis) on T + V	Retrospective cohort study	Describe outcomes of children with MRSA sepsis.	Patient survived
Reiterer (2015)^2	N = 1 on T + V (primary pulmonary lymphangiectasis and related CLD)	Case report	Describe outcome	Patient surviving as of 3 years, 7 months of age
Com (2013)^3	N = 91, 26 with CLD on T + V	Retrospective cohort study	Describe outcomes of T + V in children	Long-term outcomes of survival, decannulation/ventilator independence, and cognitive achievement were highest in the group with acquired chronic lung disease (100% survival), BPD without CNS insult (92% survival, 79% ventilator independence) than those with BPD with CNS insult (62% survival, 0% ventilator independence)
Cristea (2015)^4	N = 94 with BPD on T + V (overlap with cohort below)	Retrospective cohort study	Effect of living in a lower income neighborhood on mortality in BPD patients on T + V	15 patients died Median time to liberation from ventilation: 23–26 months Median time to decannulation: 34–39 months	Children from lower-income neighborhoods had a higher mortality rate. At least one death was due to accidental tracheostomy decannulation
Cristea (2013)^5	N = 102 with BPD	Retrospective cohort study	Program evaluation	81% alive, 19% deceased 67.6% weaned off ventilator (97.1% weaned before 5 years old) 58.8% decannulated (96.7% before 6 years old) Increase in rate of PPV for BPD from 1.23 per 100 000 live births in 1984 to 4.77 per 100 000 live births in 2010	No deaths were reported due to ventilator dysfunction, but the cause of 8/14 deaths was unknown.
Hsia (2012)^6	N = 139; 21 at home (remainder in “respiratory ward”), N = 10 with pulmonary disease (CLD, lung hypoplasia)	Retrospective cohort study	Examine status of children on long-term mechanical ventilation	(N = 21 at home, 19 invasive, 2 NIV, 6 with 24-hour support)
Downes (2007)^7	N = 1008; 454 with CLD	Retrospective cohort study	Program evaluation	44% long-term survival with continued ventilation, 34% weaned from ventilation, 18% mortality; ventilation rate for CLD increased from 36%–53%
Ramsey (2013)^8	N = 62; 38 with BPD on T + V	Retrospective chart review	Identify factors influencing wean from HMV	Weight gain (z-score) predicted decrease in weaning severity index score
Rane (2014)^9	N = 31 with BPD on T + V	Retrospective chart review	Comparison of early vs. late tracheostomy in neonates	Need for HMV significantly associated with gestational age, higher respiratory severity scores and late tracheostomy; shorter duration of ventilation in early tracheostomy group
Tofil (2013)^10	N = 15; 3 with CLD on T + V	Post intervention prospective survey	Evaluate simulator delivered caregiver education	Simulator training improved parents’ confidence
Aghamohammadi (2012)^11	N = 166; 29% with CLD	Retrospective cohort study	Program evaluation	71.5% discharged to home and 24.8% discharged to chronic care facility; 3.6% died before discharge
Kun (2012)^12	N = 109, 66 with CLD	Retrospective cohort study	Understand factors associated with re-admission	Incidence reason for re-admission; non-elective re-admission in 40%, half of those within 3 months of discharge	A change in medical management <1 week before discharge was associated with non-elective re-admission
Sovtic (2012)^13	N = 29, 4 with CF all treated with NIV (palliative treatment)	Retrospective cohort study	Program evaluation	2 CF patients died of progression of their disease 2 CF patients stopped NIV due to mask intolerance all 4 CF patients required O2 with NIV	HMV is feasible in developing countries
Reiter (2011)^14	N = 54, 4 with BPD, 3 restrictive lung disease, 1 with PAP, 1 with CF and CDH	Retrospective analysis using questionnaires/ interviews	Investigate incidence and safety of HMV	5/14 children with respiratory disease suffered an emergency situation, 2 severe enough to call for rescue 1 death due to disconnection of ventilator with pulse oximetry turned off	low incidence of severe complications independent of diagnosis, mode of ventilation interface and nursing coverage
Edwards (2010)^15	N = 228 T + V; 120 with CLD (BPD, pulmonary hypoplasia, congenital heart disease, recurrent pneumonitis)	Retrospective cohort study	Program evaluation	29.1% weaned; 51.7% alive on T + V; 19.2% died; CLD as reason for ventilation is independently associated with earlier weaning (HR =7.38; 95% CI 3.0–18.2, p < 0.001); median age of discharge on T + V = 8 months
Tibballs (2010)^16	N = 168; 8 with CLD, pulmonary hypoplasia	Retrospective cohort study	Program evaluation	2 recovered 2 stable on ventilation 1 transferred to other institution 3 died	Multi-disciplinary approach to early discharge with trained parents and laypersons is effective and economical
Paiva (2009)^17	N = 50 with NIV, 2 with lung disease	Prospective cohort study	Validation of combined SpO2/PtcCO2 probe	42% of patients were hypercapneic during sleep; nocturnal hypercapnia is observed in 1/3 of children treated at home with nocturnal NIV that is not associated with symptoms of sleep-disordered breathing, nocturnal desaturation or daytime hypercapnia on blood gases	Non-invasive monitoring of CO2 is possible and this probe is reliable in children
Oktem (2008)^18	N = 34, 21 with CLD and/or airway problems	Retrospective cohort study	Program evaluation	Higher rate of NIV use in younger age children than previously reported; 1 patient died of CVID end-stage lung disease
Downes (2007)^7	N = 77; 37% with CLD	Retrospective cohort study	Program evaluation	Advantages: child is at home with parents and has improved social and neurodevelopment, less healthcare costs, fewer infections Disadvantages: increased parental stress and fatigue, unanticipated expenses, negative impact on other children in the family
Gowans (2007)^19	N = 77; 19 with CLD (BPD and other diseases)	Retrospective comparative cross-sectional study	Assess prevalence of HMV use	Prevalence of HMV did not change much over time (9 children in 1996 and 9 in 2004) 15 were weaned off HMV Progression of underlying disease was most common cause of death
Graham (2007)^20	N = 197 (up to age 21), 138 cared for at home, only 14 with BPD, 12 with “other” CLD	Cross sectional survey	Program evaluation	3 fold overall increase in prevalence of children ventilated over 15 years with higher proportion of children with neuro/neuromuscular disease (vs CLD) in more recent years
Zaidi (2005)^21	N = 1 (severe BPD and PH on T + V and iv epoprostenol)	Case report	Effect of epoprostenol in child with BPD	Weaned from both ventilator and vasodilator after age 5
Edwards (2005)^22	N = 39 on 24 hour T + V; 12 with BPD	Retrospective cohort study	Program evaluation	1 child with BPD died at home. Death was not secondary to failure of ventilator. All children >1.2 years old have been decannulated.
Appierto (2002)^23	34 children on T + V; 3 (6.5%) with BPD	Retrospective cohort study	Program evaluation	Discharged between 5 and18 months of age  - 1 died after 7 months at home from medical deterioration - 2 improved and were decannulated and still alive after >4 years  - caregivers expressed satisfaction after initial 6 months of anxieties
Schweitzer (2002)^24	N = 16;2 with CLD (1 on T + V, 1 on NIV)	Retrospective cohort	Program evaluation	No deaths
Kamm (2001)^25	N = 32, 1 of which had “other” lung disease	Cross sectional survey	Identify and establish family history of children HMV	CCHS and NMD far outnumbered those children with “other” diagnosis
Nakamura (2000)^26	N = 57, 13 with CLD	Prospective cohort study	Prevalence of latex allergy in children on HMV	4/13 patients with CLD had positive RAST tests for latex, though overall latex sensitivity for all 57 patients was 29.8% (17 patients) (prevalence in general population is 0.1–1%) length of mechanical ventilation and underlying disorder do not correlate with frequency of latex allergy
Jardine (1999)^27	N = 136, 6 with BPD, 8 “other”	Cross sectional survey	Identify and establish family history and vent needs	Number of children requiring support has increased substantially Majority of children ventilated lived at home and were able to attend mainstream schools
Dhillon (1996)^28	N = 82, 4 with BPD, 11 “miscellaneous”	Cross sectional survey	Outcomes of children on chronic ventilation	45 of 82 received ventilation at home, remainder in PICU, intermediate care unit or general community hospital setting
Sakakihara (1996)^29	N = 434; 19 with CLD	Retrospective cohort study	Program evaluation	Average duration of HMV: 3.9 years
Goldberg (1994)^30	N =1 with BPD	Case series	Describe healthcare costs and outcomes of children on HMV	Significantly decreased cost of care Decannulation by age 3
Wheeler (2014)^31	N = 100; 50 with CLD, 50 with CHD on T + V	Retrospective cohort study	Program evaluation	98% survival in CLD group vs 74% in CHD group (p = 0.01), 6.6 re-admissions days/patient in CLD group vs 25.9 days/patient in CHD group (p = 0.01), 96% decannulation rate in CLD vs 63% in CHD (p = 0.0001), mean decannulation age 19.5–21.3 months (CLD and CHD)	Overall morbidity concluded to be higher in children with CHD and T + V HMV, versus children with CLD alone.
Wheeler (1994)^32	N = 55; 16 with CLD (most with BPD on T + V)	Retrospective cohort study	Program evaluation	95% survival 71% weaned off ventilator in <1 year of home use 0.8 respiratory hospitalizations/year
Nelson (1996)^33	N = 68, though included patients up to age 29; 7 with BPD, 19 with “other”	Retrospective cohort study	Program evaluation of stressors/complications of home care	Younger children had greatest numbers of hospitalizations and required longest initial hospital stay 3 patients died of ventilator malfunction/disconnection 1 patient with BPD was weaned from ventilator no correlation of death or weaning with any parameter measured
Fields (1991)^34	N = 23 ventilator-dependent children, 8 of whom had primary respiratory disease (6 had BPD, 1 with interstitial pneumonia, 1 with tracheomalacia)	Prospective descriptive study	Program review of community-based care management as alternative to hospital-based	Outcomes of community-based care similar to hospital-based 2 children with BPD, 1 with tracheomalacia, and 1 with IP became technology-independent by 33 months; no deaths in those with primary respiratory disease, all 5 deaths occurred in neurologic dysfunction group (overall mortality rate 18%)
Robinson (1990)^35	N = 10; 3 with CLD on T + V (2 = BPD, 1 = other)	National retrospective survey	Prevalence and outcomes of children on HMV	Increase prevalence of children on long-term ventilation over time
Rodriguez (1990)^36	N = 35 with BPD; 5 on T + V;	Retrospective cohort study	Program evaluation	Reduced healthcare cost to third-party payers
Schreiner (1987)^37	N = 19 with BPD	Retrospective cohort study	Program evaluation	Increased prevalence over time of CLD among children discharged on home T + V; no deaths so home T + V is safe and weaning is possible in many by age 1 year; 4 children with restrictive lung disease not weaned
Burr (1983)^38	N = 6; 1 with CLD on T + V	Case series	Describe outcomes of children on HMV	HMV is safe and results in > $166,000 USD reduction in healthcare costs per year; negative aspects include loss of privacy, disruption of sleeping patterns and schedules of families, limitation on social activities of parents/siblings

BPD = bronchopulmonary dysplasia; T + V = tracheostomy + ventilator; MRSA = Methicillin Resistant Staphylococcus Aureus; NIV = noninvasive positive pressure ventilation; CLD = chronic lung disease; CF = cystic fibrosis; PCD = primary ciliary dyskinesia; CNS = central nervous system; USA = United States of America; vs. = versus; BO = bronchiolitis obliterans; IP = interstitial pneumonia; PPV = positive pressure ventilation; PAP = pulmonary alveolar proteinosis; CDH = congenital diaphragmatic hernia; HR = hazard ratio; CI = confidence interval; CVID = common variable immunodeficiency; PICU = pediatric intensive care unit; CCHS = congenital central hypoventilation syndrome; NMD = neuromuscular disorder; USD = US dollars; CHD = congenital heart disease.

Table 2. Summary of studies evaluating outcomes in children with cystic fibrosis on HMV.

Authors (Year)	Study population/# of patients	Study type	Aim of study	Outcomes	Comments
Mallory (2014)^39	N = 150; CF children <10 years old, post lung transplantation	Retrospective cohort study	Determine outcomes post transplant	6 patients were on NIV at the time of lung transplantation and all survived	Evidence for NIV as a bridge to transplant in children
Collins (2011)^40	N = 23 CF pediatric patients using NIV	Cross sectional survey	Establish factor for NIV initial and extent of use	Median age of NIV initiation was 14 years Reasons for initiation of NIV included acute exacerbation, bridge to transplant and adjunct to physiotherapy	1 report of pneumothorax
Busa (2010)^41	N = 52, 6 with CF	Pilot study of mask contamination	Investigate hygiene of nasal mask	Masks of 6 patients with CF using NIV were tested, one found contaminated with S. aureus, rest were sterile or grew polymicrobial flora
Ottonello (2007)^42	Total N = 20, 1 with CF NIV, 1 with pulmonary hypertension on T + V	Retrospective cohort study	Program evaluation	Ventilation initiated electively after polysomnography showing hypoventilation Both required <24 hour support Overall home costs were lower than hospital costs
Fauroux (2008)^43	N = 2078 CF patients, pediatric only	Cross sectional survey	Evaluation of NIV use in CF	Most common indications for starting were respiratory exacerbations and stable persistent diurnal hypercapnia
Fauroux (2005)^44	N = 40, 10 pediatric CF patients	Cross sectional study	Quantify side effects of NIV	Global facial flattening was less common in children with CF (OR 18, 95% CI 1.6–200, p = 0.007) on NIV but skin injury more common
Fauroux (2004)^45	N = 10 with CF (5 already on home NIV)	Prospective trial	Comparison of invasive vs noninvasive methods to initiate NIV	Clinical noninvasive approach to initiating NIV is as effective as a more invasive technique
Fauroux (2003)^46	N = 102 on NIV; 17 with VF	Cross sectional national survey	Determine prevalence of HMV use	NIV used successfully in CF patients ages 6–18
Fauroux (2001)^47	N = 8 CF patients with PaO2 < 60, PaCO2 > 45	Randomized crossover trial	Comparison of 2 ventilators/modes	NIV sessions of 20 min awake improved blood gases, increased tidal volume, reduced respiratory effort in both modes
Gozal (1997)^48	N = 6, 3 were pediatric patients with CF	Randomized cross-over trial	Compare respiratory and sleep benefits of NIV or low-flow oxygen	NIV as effective as supplemental oxygen in improving REM and NREM sleep-related hypoxemia, though NIV improved alveolar ventilation as well 4/6 patients preferred oxygen to NIV despite morning headache in 2 patients
Padman (1994)^49	N = 15 patients age 4–21 years, 4 with CF	Retrospective case review	Evaluate NIV use in severe CF	4 patients with CF survived to lung transplantation

CF = cystic fibrosis; NIV = noninvasive positive pressure ventilation; T + V = tracheostomy + ventilator; UK = United Kingdom; REM = rapid eye movement sleep; NREM = non-rapid eye movement sleep.

Table 3. Summary of studies evaluating outcomes in children with bronchopulmonary dysplasia, cystic fibrosis or other causes of chronic lung disease on HMV.

Authors (Year)	Study population/# of patients	Study type	Aim of study	Outcomes	Comments
Nasilowski (2015)^50	N = 187 children (total study N = 928) from 9 centers across Poland	Retrospective cohort study	Program evaluation	Increase in rate of HMV use among children between 2000 and 2010 (7 in 2000 to 187 in 2010) and overall (children and adults) increase over time of 21% in proportion of patients with lung disease (CF, CLD, other) rather than neuromuscular disease as indication for HMV
Amin (2013)^51	N = 257; 10 with BPD (4 on NIV, 6 on T + V); 14 CF/PCD on NIV	Retrospective cohort study	Program evaluation	Overall mortality rate = 0.73%/year
Racca (2011)^52	N = 378, 20 with CLD (CF, BPD, other)	Cross sectional multi-center national survey	Assess prevalence of HMV use and patient characteristics	Invasive ventilation correlated with younger age; 81% of those invasively ventilated spent >12 hours on ventilator
Edwards (2005)^22	N = 160, 2 with CF, 5 with bronchiectasis, 2 with BPD	Retrospective cohort study	Program evaluation	Chronic lung disease specific outcomes not highlighted
Fauroux (1995)^53	N = 158 on home vent; 8 with CF, 18 with BPD, 1 with ARDS, 1 with pulmonary fibrosis	Cross sectional survey	Program evaluation	Most children attended school Overall good prognosis (total of 9 deaths)
Canlas-Yamsuan, (1993)^54	N = 22, 8 of whom had primary pulmonary disease	Retrospective cohort study	Program evaluation	4/8 have died from progression of underlying disease (CF, chronic interstitial fibrosis, asphyxiating thoracic dystrophy); 2 patients with BPD were weaned; no effect of type of family, home location, age at start of mechanical ventilation
Goldberg (1984)^55	N = 18; 2 with CLD on home T + V (1 with post-radiation fibrosis and 1 with pulmonary hypoplasia)	Case series	Describe healthcare costs and outcomes of children on HMV	Home T + V allows improvement in medical condition and psychosocial development; 70% initial cost savings; child with pulmonary fibrosis died; child with pulmonary hypoplasia alive and well at 3.5 years; attends school
Wallis (2011)^56	N = 933; 18 with CLD (9 on T + V, 9 on NIV), 5 with CF on NIV, 14 with BPD (9 on T + V, 5 on NIV)	Assess prevalence of HMV use and patient characteristics	Cross sectional multi-center national survey	Overall increase in prevalence of HMV among children (141children in 1998 to 933 children in 2007)	Steepest increase in rate of HMV is among children with neuromuscular diseases

BPD = bronchopulmonary dysplasia; CF = cystic fibrosis; NIV = noninvasive positive pressure ventilation; T + V = tracheostomy plus ventilator; UK = United Kingdom; ARDS = acute respiratory distress syndrome.

Discussion

Indications for home ventilation in children with chronic lung disease

The indication to consider long-term home ventilation in children with CLD is when respiratory insufficiency appears to be chronic, usually after 6–8 weeks of ventilation support.⁴² As it is not standard practice to implement HMV for children with BPD in Canada, most commonly, infants with more severe pulmonary involvement require prolonged hospitalization in a critical care unit well beyond term gestational age, until they can be successfully weaned off ventilation and discharged on home oxygen. However, in other countries, there is consensus that home ventilation may be considered if the child with BPD demonstrates persisting need for long-term ventilation for survival (see Section 2 for eligibility criteria).

Bronchopulmonary dysplasia

While the majority of infants with BPD can be discharged home without supplemental oxygen or with low concentrations of supplemental oxygen, some infants may require assisted ventilation for months or even years. Infants with BPD who have concomitant pulmonary hypertension are more likely to require longer-term ventilation.⁵⁷ In many countries, there is high economic pressure to discharge children with BPD as early as possible, and some studies indicate a rise in the number of children with BPD receiving HMV.^5,19,50,58 However there is significant international and institutional variability, largely due to lack of rigorous studies to determine the optimal timing for consideration of tracheostomy and HMV in this group.⁹ There is no recognized standard timing for tracheostomy placement in children undergoing prolonged mechanical ventilation.^59,60 It has been shown that pediatric tracheostomy carries about twice the morbidity and mortality risk of that in adults,⁶¹ so it is often delayed in comparison to the timing of tracheostomy in adults.

Outcomes of children with BPD on HMV

1. Safety of HMV: While HMV is uncommon in Canadian children with BPD, there is growing recognition it can be safely accomplished in this population. Available data come from the published experience of centers with HMV programs over the last few decades. A study by Cristea in the US spanning 1984 to 2010 demonstrated a survival rate of 81% among 102 children with BPD who were sent home on tracheostomy plus ventilation. Of the 14 children who died in this retrospective cohort review, the cause of death was unknown in 8, and at least 1 was related to accidental decannulation.⁵ It was observed that most of these deaths occurred among children living in neighborhoods with a lower median income, suggesting that factors related to socioeconomic status may impact outcome for children on HMV.⁴ Two thirds of children were eventually weaned off ventilation prior to age five,⁵ with a median time to liberation from ventilation of 23–26 months and time to decannulation of 34–39 months.⁴ Another study by Wheeler showed similar results with 95% survival among children discharged on HMV, with 71% being weaned off within one year of home use and the average number of respiratory hospitalizations per child being 0.8/year.³² The same authors noted that children with congenital heart disease sent home on ventilation experienced more morbidity in the form of repeat hospitalizations than children with chronic lung disease alone.³¹ Com et al. noted that of 26 children with BPD discharged on HMV between 1987–2006, survival was 92%, with success rates for weaning off ventilation of 79%. The authors noted that outcomes were best among children with BPD without additional central nervous system insults.³

2. Social and neurodevelopment: While one of the perceived advantages of discharging infants with BPD on HMV is improvements in “normal socialization,” neurodevelopment and bonding with the family, no studies have rigorously studied this. An observational study by Downes et al. of 770 children observed between 1980 and 2006 with chronic respiratory failure, including 37% with CLD, found that long-term ventilation at home enhanced normal development and social relationships by uniting children with their families.⁷ Other HMV programs reported that many of the children on a ventilator for CLD are able to attend school.⁵³

3. Cost savings: The development of HMV programs has allowed patients to transition to home care more quickly and decrease the length of stay in critical care units,¹¹ which can result in significant cost savings.³⁶ Burr et al. reported in 1983 that the annual cost of treating a child with CLD with HMV was 69% less than treating the child in hospital.³⁸ More recent Canadian cost analyses are not available.

Types of ventilators and modes of ventilation for children with BPD

Children with BPD who require long-term ventilation are usually discharged home on positive pressure ventilation through a tracheostomy tube, rather than noninvasive ventilation (NIV). For most children, this mode of ventilation is optimal as it ensures a secure airway, facilitates neurological and social development and is feasible, given the young age of these children who often need for 24-hour ventilation.⁶² In this age group, an uncuffed tracheostomy tube is preferred⁶³ as the leak around a properly fitted tube in an infant or young child is minimal⁶⁴ and the lack of cuff minimizes potential injury to the tracheal wall.

Over time, there have been changes in the types of ventilators available for home use, as well as their sensitivity and ability to synchronize with respiratory efforts of small children. As such, there is no consensus on the best type of ventilator to use in infants with BPD for home use, though the goal is to reduce the child’s work of breathing while providing optimal respiratory support. It is suggested that a respiratory rate of 20–35 breaths per minute, an inspiratory time of 0.5–1 seconds and an inspiration to expiration ratio of 1:1 to 1:265 to achieve tidal volumes of 6–8 ml/kg51 is generally appropriate for infants; however, further patient-specific adjustments to ventilator parameters should be made based on work of breathing and gas-exchange parameters as measured through capillary blood gases and end tidal CO₂ monitoring.⁶⁶ Some suggest that neonates are usually best treated by time-cycled pressure controlled/limited ventilation as this ensures that excessive airway pressures do not develop and allows for consistent tidal volumes delivered as long as there are no changes in compliance, resistance and air leak.³² However the disadvantage of this mode is that there can be significant variation in tidal volume, which may lead to hypoventilation if not monitored frequently. Another recommended option is to use volume-cycled, pressure-oriented ventilators that allow adjustments in tidal volumes to maintain peak airway pressures within a certain range.⁶⁵ Both pressure⁶⁷ and flow⁶⁸ triggering have been reported to reduce the work of breathing in different scenarios. Regardless of the ventilator used, the infant should be transitioned to the home ventilator weeks before discharge to ensure stability, synchrony and appropriate triggering without significant work of breathing. Hospital re-admission soon after discharge has been observed to be associated with a change in medical management within 1 week of discharge,¹² so examination of discharge readiness should occur whenever a change is made in the child’s clinical management.

Weaning HMV in children with BPD

In contrast to most children on long-term HMV for neuromuscular conditions, it is expected that respiratory sufficiency in children with BPD should improve over time, such that most children can be successfully weaned from the ventilator before the age of 3.^32,69 There is very little published on specific techniques for weaning of home mechanical ventilation;⁷⁰ however, a general approach would be to consider weaning once CO₂ levels are maintained below 50 mm Hg while asleep for more than 75% of the night, oxygen saturation is consistently >95% on an FiO2 < 0.35–0.4 and the infant has demonstrated consistent growth and a period of health stability.⁶⁶ Weaning should focus on reducing dependence on mechanical ventilation before reducing supplemental oxygen. One technique to do this would involve slowly reducing intermittent mandatory ventilation rates, then pressures, until the infant is triggering all breaths spontaneously on minimal pressure settings. Short periods off positive pressure support with supplemental oxygen just delivered by tracheostomy mask in short sprints can then be introduced. The duration of these ‘sprints’ can be gradually increased until the infant is off ventilation during all waking hours, before discontinuing nocturnal ventilation. Throughout the weaning phase, infants should be monitored periodically with oxygen saturation, end tidal CO₂, capillary blood gases and, when necessary, polysomnograms. In addition to adequacy of ventilation, maintenance of growth and activity during weaning should also be monitored.^36,66 Children with BPD and chronic hypoxemia can develop pulmonary hypertension so regular monitoring for pulmonary hypertension, especially during weaning of ventilation, should also be considered. An American survey of 38 children with BPD demonstrated that weight gain was the only factor predictive of decreasing Weaning Severity Index.⁸ The Weaning Severity Index rates the severity of ventilatory support on a five-point scale based on ventilator mode, PEEP, respiratory rate and pressure support level.⁸

Research questions

1. What is the optimal timing for tracheostomy insertion in children with BPD and consideration for HMV?

2. What are the optimal modes of ventilation to use in children with different types of chronic lung disease?

3. What are the optimal methods for weaning HMV in children with BPD?

4. What is the impact of long-term ventilation and different modes of HMV on subsequent lung growth and health?

Cystic fibrosis

Cystic fibrosis (CF) is a genetic disease where progressive loss of lung function is caused by chronic infection and inflammation, leading to bronchiectasis and, ultimately, end-stage respiratory failure. Patients with end-stage lung disease present a dilemma, as there is evidence that endotracheal intubation and mechanical ventilation have been associated with a high degree of morbidity and mortality in this population, and therefore intubation is rarely employed unless warranted by exceptional circumstances.⁷¹ However, noninvasive ventilation has been used to improve quality of life, prevent deterioration and bridge to lung transplantation,^72,73 without the morbidity associated with endotracheal intubation or tracheostomy. It also offers the advantage of intermittent use to facilitate speaking. There is evidence that NIV improves sleep-related hypoxemia and hypercapnia,⁴⁸ reduces respiratory load and work of breathing⁴⁷ and can be used in an acute exacerbation.⁴⁹ In a survey of both pediatric and adult CF centers in France, it was found that only 1.2% of pediatric patients were being treated with NIV vs. 7.6% in adult centers.⁴³ Lack of NIV use in children likely reflects the slowing of the progressive lung function decline in CF due to medical advances, with the majority of pediatric patients now surviving well into adulthood. While there are several theoretical benefits to the use of NIV, there is a lack of pediatric evidence.

NIV in CF

There is only one isolated case report of NIV use in a pediatric CF patient; this patient was an infant.⁷⁴ Much of the evidence about outcomes of NIV use in CF includes a mix of adult and pediatric data. Such studies have demonstrated that nocturnal nasal bilevel intermittent positive pressure ventilation is well tolerated and improves respiratory acidosis and dyspnea.^48,75,76 NIV is also associated with a reduction in respiratory rate, improved quality of sleep and an increased capacity to perform activities of daily living.⁴⁹ Through the reduction of spontaneous inspiratory effort, improvements in respiratory muscle strength, respiratory muscle energy expenditure, work of breathing and lung function have also been reported in CF patients on NIV.⁷⁵ Despite these positive studies, there still remains some controversy as to the efficacy of NIV in CF patients, as the evidence is mixed.⁷⁷ Whether earlier use will attenuate the early effects of CF or slow the progression of respiratory failure has yet to be proven. In addition to the lack of data on long-term benefits, there are currently no validated criteria for starting NIV.

Outcome studies of CF patients on NIV

Survival: There are no pediatric studies that report mortality after starting NIV. Case reports and series describe the use of NIV in adult CF patients in chronic respiratory failure as a bridge to transplant, thereby improving survival once lung transplantation occurs,^72,73,75 but few studies are available for children. One case series of 150 children who underwent lung transplantation between 2002 and 2015 identified 6 patients who used NIV just prior to transplant and survived post-transplant.³⁹ Furthermore, the effect on long-term survival of starting NIV at an earlier stage of the disease has not been studied in pediatric patients. In contrast, invasive ventilation showed an unweighted average mortality of 67% for children, with the rate increasing with advancing age such that in adults, 3 of 4 patients invasively ventilated would perish.⁷⁸ As such, any decision to invasively ventilate a child with CF for respiratory failure requires careful consideration.

Gas exchange: While ventilation/perfusion mismatch from chronic lung disease is the major source of hypoxemia in those with CF,⁷⁹ hypoventilation may also play a role. Potential mechanisms responsible for this may include respiratory muscle weakness, poor chest wall elasticity, central nervous system depression secondary to the use of narcotics for pain and sleep-disordered breathing.⁸⁰ During sleep, Tepper et al. found that there were significant gas exchange abnormalities with hypoxemia and hypercarbia in 6 adolescents with moderate to severe CF. These abnormalities were most pronounced during REM sleep, associated with a 26% decrease in tidal volume. The authors hypothesize that tonic inhibition of the respiratory muscles during sleep prevents patients from maintaining the extra work of breathing they would usually employ to maintain gas exchange while they are awake.^79–81 Another study of overnight gas exchange in pediatric patients maintained on nocturnal NIV showed that 42% of patients, without evidence of sleep-disordered breathing, were hypercapneic during sleep, as measured by a transcutaneous PCO₂ device. This nocturnal hypercapnia was not associated with nocturnal hypoxemia or abnormal daytime blood gases in one third of the patients.¹⁷ NIV unloads the respiratory muscles in CF patients with a comparable level of lung function,⁴⁷ which supports its use even in patients with only moderate hypercapnia. Patient comfort in using NIV has been shown to correlate with unloading of the respiratory muscles.⁴³ A recent Cochrane review on the topic of NIV for those with CF concluded that, in patients with moderate to severe disease, noninvasive ventilation, in addition to oxygen, may improve gas exchange more than oxygen alone.⁸²

Airway clearance: Recent guidelines suggest that NIV should be used for airway clearance if the patient has respiratory muscle weakness or fatigue, if desaturations happen during airway clearance maneuvers or if the patient has difficulty clearing secretions with other techniques.⁸³ A more extensive discussion of airway clearance for children on HMV is provided elsewhere in this guideline. (See Section 4: Airway Clearance)

Quality of life, symptoms and function: There are no pediatric studies that specifically address quality of life after initiation of NIV in patients with CF. One trial in adults demonstrated no change in daytime Epworth sleepiness scores, but there was improvement in dyspnea scores relative to being on room air alone.⁷⁶ With respect to symptoms and function, a case series of 7 children and young adults with end-stage CF (age 9–30 years) showed that nocturnal nasal bilevel intermittent positive pressure ventilation improved sleep quality and the capacity to perform activities of daily living.⁴⁹

Pulmonary Function: There are conflicting reports regarding the pulmonary function outcome of CF patients treated with NIV. Efrati et al. reported on NIV used in 9 CF patients (age range 15–40) with end-stage lung disease for a mean duration of 8 months and demonstrated positive effects on BMI, blood pH, PaCO₂, and bicarbonate levels, but no effect on pulmonary function.⁸⁴ No significant change in lung function was observed after 6 weeks of NIV in a randomized controlled trial of 8 adult patients with CF.⁷⁶ However, a study using the French national registry compared the decline of lung function in patients who were started on NIV against a group who were not and demonstrated a significantly greater decline in lung function among patients during the year prior to the start of NIV than in the matched control group. The reduction in lung function was not different between the 2 groups 1 year after the start of NIV, suggesting that NIV may stabilize lung function decline.⁴³ More recently, Flight et al. studied 48 patients, most of whom were adults, who were treated with long-term NIV at a single center over the past 2 decades. Seventy-three percent of patients displayed either an improvement in Forced Expiratory Volume in 1 second (FEV₁) following initiation of NIV or a reduction in the rate of decline in FEV_1. “Responders” were more likely to be male and have a significantly lower FEV₁% predicted at NIV initiation and had an increased rate of FEV₁ decline prior to starting NIV.⁸⁵ This lung function “maintenance” effect appeared to be preserved up to 3 years post-NIV initiation.

Initiation of noninvasive ventilation

Criteria for initiating NIV in CF patients are variable and currently there are no consensus recommendations. In the absence of high-level evidence, NIV in patients with stable CF is therefore approached on an individual basis. Severe hypercapnia during an acute exacerbation, persistent hypercapnia, stable diurnal hypercapnia, FEV₁ < 25–30% of predicted, clinical symptoms of sleep disturbance and nocturnal desaturation were all considerations in the survey conducted by Fauroux et al. in France.⁴³ Pulmonary exacerbation was the most common criterion to initiate NIV, followed by stable persistent diurnal hypercapnia.⁴³ Bridging to lung transplantation is not a universal indication for the start of NIV, though in 1994, Padman reported on their single center’s experience in starting NIV in 4 CF patients (age 4–21) during an acute deterioration of their chronic respiratory failure and all 4 patients survived to lung transplantation.⁴⁹

Mode of ventilation

Both pressure-controlled and volume-controlled modes are used equally in pediatrics. Pressure-targeted, pressure support, volume-targeted and volume support modes are now all available options on contemporary ventilators. Fauroux et al.⁴⁷ found that both pressure- and volume-controlled modes resulted in greater patient comfort, decreased inspiratory muscle effort and work of breathing, as well as gas exchange in awake patients with CF and chronic respiratory failure. Initial studies in CF used volume-targeted devices, but this can result in high inspiratory airway pressures that lead to discomfort, and some suggest pressure support is the more preferred “physiologic” mode. Fauroux et al. also compared a clinical noninvasive method (pulse oximetry, respiratory rate, patient comfort) of titrating noninvasive pressure support ventilation with a more invasive method (electro-myogram, gastro-esophageal pressure catheter measurements) in 10 pediatric patients with CF, and found that the noninvasive method was as effective at unloading the respiratory muscles and improving gas exchange as a more invasive approach. Adjustments to the ventilator made based on invasive measurements were, however, found to improve patient-ventilator synchrony and comfort.⁴⁵

Research questions

1. What are the indications, or best physiologic indicators or tests to predict the need for initiation of NIV in CF?

2. What are the long-term outcomes of NIV in CF patients?

3. What follow-up (i.e., overnight monitoring, polysomnogram, measurement of gas exchange, invasive vs. noninvasive measures) is required to ensure adequacy and efficacy?

Recommendations for long-term mechanical ventilation at home in chronic lung disease

1. Consider tracheostomy and HMV in children with bronchopulmonary dysplasia with stable pressure settings that are achievable with a home ventilator, an FiO2 < 0.4 and children who are otherwise medically stable, demonstrating stable growth, and can be safely transported. (Grade 1C)

2. Children with bronchopulmonary dysplasia who are being considered for home ventilation should be discharged with a tracheostomy + ventilator (rather than NIV). Adequacy of ventilation should be determined before discharge based on work of breathing and optimal gas exchange as measured through capillary blood gase, pulse oximetry and end tidal CO₂ monitoring. (Grade 1C)

3. Weaning of home ventilation should be considered once oxygen saturations are consistently >95% and the child is demonstrating growth and health stability. (Grade 1C)

4. Home NIV should be considered in cystic fibrosis patients who have evidence of any of the following: sleep-disordered breathing (SDB), hypercapnia, nocturnal desaturations, increased work of breathing, poor exercise tolerance, and a decline in FEV₁ to below <30% predicted. (Grade 1C)

5. Efficacy of NIV in a cystic fibrosis patient can be evaluated by blood gases, nocturnal oximetry, PSG, exercise tolerance, patient comfort and quality of life. (Grade 1C)

6. Consider tracheostomy and HMV in children with bronchopulmonary dysplasia with stable pressure settings that are achievable with a home ventilator, an FiO2 < 0.4 and children who are otherwise medically stable, demonstrating stable growth, and can be safely transported. (Grade 1C)

7. Children with bronchopulmonary dysplasia who are being considered for home ventilation should be discharged with a tracheostomy + ventilator (rather than NIV). Adequacy of ventilation should be determined before discharge based on work of breathing and optimal gas exchange as measured through capillary blood gase, pulse oximetry, and end tidal CO₂ monitoring. (Grade 1C)

8. Weaning of home ventilation should be cosidered once oxygen saturations are consistently >95% and the child is demonstrating growth and health stability. (Grade 1C)

9. Home NIV should be considered in cystic fibrosis patients who have evidence of any of the following: sleep-disordered breathing (SDB), hypercapnia, nocturnal desaturations, increased work of breathing, poor exercise tolerance and a decline in FEV₁ to below <30% predicted. (Grade 1C)

10. Efficacy of NIV in a cystic fibrosis patient can be evaluated by blood gases, nocturnal oximetry, PSG, exercise tolerance, patient comfort and quality of life. (Grade 1C)