Average volume-assured pressure support vs conventional bilevel pressure support in pediatric nocturnal hypoventilation: a case series

Abstract

Study Objectives:

Average volume-assured pressure support (AVAPS) is a modality of noninvasive ventilation that provides a targeted tidal volume by automatically adjusting the inspiratory pressure support within a set range. Pediatric studies evaluating the efficacy of AVAPS in treating nocturnal hypoventilation are confined to case reports. The aim of this study was to compare AVAPS to conventional bilevel positive airway pressure (BPAP) support in improving hypercarbia in a cohort of pediatric patients with nocturnal hypoventilation.

Methods:

Retrospective review of patient records at an established tertiary pediatric sleep laboratory over a 6-year period. Ventilatory and sleep study parameters from AVAPS and conventional BPAP titration studies were compared. AVAPS was used only if hypoventilation was not controlled using conventional BPAP. Inspiratory pressures, tidal volumes, and adherence were downloaded on final titrated ventilatory settings. Comparisons were made using paired t test.

Results:

A total of 19 patients (11 boys, 8 girls; median age 10.5 years, range 1 to 20 years) were identified. Diagnoses included neuromuscular disease (n = 9), obstructive hypoventilation (n = 5), parenchymal lung disease (n = 4), and congenital central hypoventilation syndrome (n = 2). AVAPS demonstrated significant improvement in peak (P = .009) and mean (P = .001). Transcutaneous CO₂ parameters compared to conventional bilevel. Oxygenation on AVAPS showed positive trend but did not reach statistical significance. AVAPS delivered higher tidal volumes (P = .04) using similar pressures. There was no statistically significant difference in obstructive apnea-hypopnea index, respiratory arousal index, sleep efficiency, and adherence between AVAPS and conventional BPAP.

Conclusions:

AVAPS was an effective alternative to conventional BPAP in improving hypercarbia in our selective cohort of pediatric patients. Prospective, longitudinal studies are needed to evaluate the benefits of AVAPS feature in the pediatric population.

Citation:

Saddi V, Thambipillay G, Pithers S, et al. Average volume-assured pressure support vs conventional bilevel pressure support in pediatric nocturnal hypoventilation: a case series. J Clin Sleep Med. 2021;17(5):925–930.

BRIEF SUMMARY

Current Knowledge/Study Rationale: The average volume-assured pressure support mode delivers a consistent tidal volume by automatically adjusting the inspiratory pressure support within a set limit. Pediatric data on its efficacy are lacking and confined to case reports.

Study Impact: Using average volume-assured pressure support, we demonstrate a better control of nocturnal hypoventilation compared to conventional bilevel positive airway pressure in a selective cohort of pediatric patients. The average volume-assured pressure support feature is an alternative to conventional bilevel positive airway pressure, especially in children with difficult to control nocturnal hypoventilation.

INTRODUCTION

The use of noninvasive ventilation (NIV) has increased substantially in children over the last few decades,¹ at least in part due to enhanced survival of children with chronic medical conditions.^2,3 Improvements in home ventilatory technology and provision of mask interface specifically designed for pediatric age groups have made home NIV more accessible for pediatric patients than ever before. When NIV is initiated, ventilatory parameters are generally determined based on clinical assessment followed by an in-laboratory polysomnography titration study where the parameters are adjusted throughout the recording period to determine optimal ventilatory settings for adequate gas exchange and upper airway patency.⁴

One of the limitations of conventional NIV is the inability to compensate for changes in tidal volume as a result of dynamic changes during sleep stages.⁵ In normal patients, during rapid eye movement (REM) sleep, breathing is mainly diaphragmatic, owing to physiologic inhibition of intercoastal muscles accompanied by decreases in tidal volume.^6,7 These effects are exaggerated in patients with underlying lung disease, leading to inconsistent ventilation during sleep.⁸ Although traditional NIV produces favorable results in many patients with hypoventilation during sleep, some patients may require very high inspiratory pressures to achieve acceptable gas exchange. Rarely, high ventilatory pressures can cause barotrauma.9 Patient discomfort from high inspiratory pressures may have a detrimental effect on adherence to NIV. A relatively newer feature on home NIV machines, termed average volume-assured pressure support (AVAPS), enables the machine to deliver a constant preset tidal volume by automatically adjusting the inspiratory pressure support within a set range. Fixed pressure support NIV is unable to compensate for the change in tidal volume that occurs with changes in the lung adherence or upper airway resistance, which may be positional in patients with morbid obesity. AVAPS ensures constant tidal volume delivery by fluctuating the pressure settings within a set limit. Data on its use in pediatric population are lacking and are confined to case reports of achieving more stable ventilation using this feature.^5,10–13 In this study, we present a case series of 19 pediatric patients with nocturnal hypoventilation, demonstrating improvements in gas exchange using lower inspiratory pressures with the AVAPS feature compared to conventional bilevel positive airway pressure (BPAP). To the best of our knowledge, this is the largest case series on the use of AVAPS in the pediatric population.

METHODS

Data were collected retrospectively from pediatric patients aged 1 to 20 years undergoing NIV titration polysomnography between 2013 and 2019 at an established tertiary pediatric sleep laboratory. All patients who underwent NIV titration during the study period and had data available for both conventional and AVAPS titration were included in the study. No patients were excluded. AVAPS was commenced only in patients where conventional BPAP failed to adequately control hypoventilation (defined as transcutaneous CO₂ [TcCO₂] of more than 50 mmHg for at least 25% of the study period). All reported patients underwent titration with conventional BPAP first followed by AVAPS. None of the patients underwent upper airway surgery between BPAP and AVAPS titration study. A total of 19 patients with data available for both conventional NIV titration and titration with AVAPS feature were identified. Data extracted from patient records included descriptive demographics, polysomnogram derivatives, final ventilatory parameters and diagnosis. Machine downloads for the last 30 days, which are routinely performed as part of titration studies, were reviewed to assess delivered inspiratory pressures, tidal volumes, and adherence to treatment.

Sleep studies were performed using the Compumedics (Compumedics, Melbourne, Australia) computerized polysomnographic system. Six channels of electroencephalograph electro-oculography (right outer canthus/A1, left outer canthus/A2) were employed for sleep staging. Submental electromyography was used to detect masticatory muscle activity. Respiratory variables were measured using thoracic and abdominal electromyography, chest and abdominal inductance plethysmography, and nasal airflow detected by nasal prongs attached to a pressure transducer. Hemoglobin oxygen saturation was recorded by pulse oximetry on a finger (Masimo, Irvine, CA). TcCO₂ was continuously measured (SenTec, Therwil, Switzerland). Infrared audio-visual monitoring and recording was employed. The attending sleep physician provided maximum and minimum range of ventilatory parameter settings prior to the commencement of the titration study. Adjustments to pressure settings were made to improve gas exchange within the set parameters by an experienced sleep scientist. The American Academy of Sleep Medicine scoring criteria were used for scoring. Titration of NIV was performed as per the American Academy of Sleep Medicine clinical guidelines for titration of positive airway pressure.

Data were extracted to an Excel spreadsheet and analyzed using Stata version 13 (StataCorp LP, College Station, TX). Comparisons were made using a paired t test. The significance level was set at P ≤ .05 for all analyses.

RESULTS

A total of 19 patients with titration study data from both conventional NIV and NIV with AVAPS were analyzed. Demographic features were listed in Table 1. The mean age of all patients was 10.5 years. Diagnoses included neuromuscular disease (n = 9), obstructive hypoventilation (n = 5), parenchymal lung disease (n = 4), and congenital central hypoventilation syndrome (n = 2). No patient was acutely unwell at the time of their titration study. Only 1 patient with Prader–Willi syndrome was obese, with a body mass index over the 95th percentile for age. All patients used a nasal mask. AVAPS demonstrated significant improvement in peak (P = .009) mean (P = .001), total sleep time with TcCO₂ above 50 mmHg (P = .02), and mean TcCO₂ (P = .02) in REM sleep parameters compared to conventional bilevel. Oxygenation on AVAPS showed a trend to improvement but did not reach statistical significance. AVAPS delivered higher tidal volumes (P = .04) using similar pressures (Figure 1). All patients, except for one, achieved delivered tidal volumes equivalent to or greater than their set tidal volumes (see Table S1 ^{(5.1KB, pdf)} ). There was no statistically significant difference in obstructive apnea index, respiratory arousal index, sleep efficiency, and adherence between AVAPS and conventional BPAP (Table 2). The backup respiratory rates used for conventional BPAP and AVAPS have been included in Table S2 ^{(5.1KB, pdf)} .

Table 1.

Patient demographics.

Patient	Agea (y)	Ethnicity	Diagnosis	BMI (kg/m2)	Days Between BPAP and AVAPS Titration	Mode
						BPAP	AVAPS
1	12	Caucasian	Prader Willi syndrome	52.6	0b	PC	PC
2	12	Asian	Nemaline myopathy	13	584	ST	ST
3	15	Middle Eastern	Moebius syndrome	21.6	53	ST	ST
4	7	Polynesian	CCHSc	17.5	547	ST	ST
5	6	Asian	Congenital myopathy	14.2	586	ST	ST
6	13	Caucasian	Cerebral palsy	14.2	216	ST	ST
7	11	Caucasian	Scimitar syndrome, single lung, left bronchial stenosis	16.5	140	ST	ST
8	2	Caucasian	CCHS	16.5	211	ST	PC
9	19	Caucasian	Neurodegenerative disorder	16.1	244	ST	ST
10	2	Greek	Trisomy 21	15.6	0b	ST	ST
11	15	Asian	Collagen VI related myopathyc	16.7	429	ST	ST
12	2	Caucasian	Undiagnosed syndrome, GDD	20.9	117	ST	ST
13	12	Caucasian	Multiminicore myopathy	12.7	252	ST	ST
14	2	Caucasian	Undiagnosed syndrome	16.5	379	ST	ST
15	19	Middle Eastern	Dyggve Melchior Clausen syndrome	26.8	443	ST	ST
16	9	Caucasian	Multiminicore myopathy	14.5	5	ST	ST
17	20	Caucasian	Muscular dystrophy	10	478	ST	ST
18	1	Asian	Chronic lung disease		50	PC	PC
19	20	Asian	Chromosome 16p deletion	26.7	53	ST	ST

AVAPS = average volume-assured pressure support, BMI = body mass index, calculated for patients aged 2 years and above, BPAP = bilevel positive airway pressure, CCHS = congenital central hypoventilation syndrome, GDD = global developmental delay, PC = pressure control, ST = spontaneous timed. ^aAge at the time of study on conventional BPAP. ^bVentilated through tracheostomy. ^cSplit titration study on conventional BPAP and AVAPS on the same night.

Figure 1. Comparison of gas exchange and pressure parameters: conventional BPAP vs AVAPS.

AVAPS = average volume-assured pressure support, BPAP = bilevel positive airway pressure, TcCO₂ = transcutaneous CO₂.

Table 2.

Comparison of clinical variables: conventional BPAP vs AVAPS.

Variable	Conventional BPAP (Mean ± SD)	AVAPS (Mean ± SD)	P Value
Peak TcCO2 (mm Hg)	63 ± 14	57 ± 9	.009
Mean TcCO2 (mm Hg)	55 ± 10	49 ± 7	.001
TST with TcCO2 above 50 mm Hg (%)	47 ± 9	26.7 ± 8	.02
TcCO2 in REM (mm Hg)	54 ± 2	47 ± 1	.02
Baseline oxygenation (%)	95 ± 3	96 ± 2	.07
Mean IPAP (cm H2O)	15 ± 3	16 ± 2	.15
Mean EPAP (cm H2O)	5 ± 2	5 ± 1	.27
Tidal volume (mL)	135 ± 104	165 ± 100	.04
Sleep efficiency (%)	80 ± 16	86 ± 10	.15
Respiratory arousal index (events/h)	0.1 ± 0.4	0.2 ± O.8	.43
Compliance (% of use for >4 h/30 days)	82 ± 30	81 ± 30	.89
OAHI (events/h)	0.9 ± 3	0.6 ± 2	.26
REM sleep (%)	21.2 ± 7.8	18.9 ± 5.4	.26

Values represent entire titration period for both BPAP and AVAPS. AVAPS = average volume-assured pressure support, BPAP = bilevel positive airway pressure, EPAP = expiratory positive airway pressure, IPAP = inspiratory positive airway pressure, OAHI = obstructive apnea-hypopnea index, REM = rapid eye movement, TcCO₂ = transcutaneous CO₂, TST = total sleep time.

Two patients underwent a split titration study: conventional BPAP followed by AVAPS titration on the same night. The titration study for patient 1 was commenced on conventional BPAP and recorded 57 minutes of non-REM (NREM) and 0 minutes of REM sleep on conventional BPAP before switching over to AVAPS and recording 285 minutes of NREM and 92 minutes of REM. The split study for patient 10 recorded 27 minutes of NREM and 12 minutes of NREM before switching over to AVAPS and recording 190 minutes of NREM and 90 minutes of REM.

DISCUSSION

To the best of our knowledge, this is the largest case series of children comparing use of AVAPS feature to conventional BPAP. Over a period of 6 years, we identified 19 children with nocturnal hypoventilation who had comparatively better gas exchange using the AVAPS compared to conventional BPAP.

To date, research on use of AVAPS in children has been confined to case reports of more stable ventilation using AVAPS compared to conventional BPAP. One case report described its use in a 10-month-old infant with congenital central hypoventilation syndrome.⁵ In this patient, the use of AVAPS enabled a more consistent transcutaneous carbon dioxide profile compared to conventional nasal noninvasive BPAP. Another center reported successful transition of a 16-year-old girl with congenital central hypoventilation syndrome from being ventilated through tracheostomy using conventional BPAP to nasally delivered BPAP using the AVAPS feature.¹² One center described its use in treating a morbidly obese child with severe obstructive sleep apnea refractory to continuous positive airway pressure treatment, thereby preventing tracheostomy along with delivering significant improvements in apnea-hypopnea index, oxygenation, ventilation, and sleep quality.¹³ A case report described use of AVAPS in a 11-year-old child with rapid‐onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation resulting in improved control of hypoventilation, adherence, and pulmonary hypertension compared to conventional BPAP.¹⁰ Another case report demonstrated significant improvement in nocturnal hypoventilation using the AVAPS in a child with congenital myopathy.¹¹ These case reports highlight the potential benefits of using AVAPS in managing nocturnal hypoventilation in pediatric patients. In all cases, traditional approaches of managing sleep-disordered breathing using either continuous positive airway pressure or BPAP were utilized before switching over to the AVAPS. At our center, we employed a similar strategy of using conventional BPAP for nocturnal hypoventilation and reserving the AVAPS only for challenging cases with difficult to control hypercarbia.

We found significant decreases in TcCO₂ using AVAPS in our cohort compared to conventional BPAP without significant changes in sleep efficiency, obstructive apnea-hypopnea index, respiratory arousal index, or adherence with treatment. Oxygenation was better on AVAPS but not statistically significant when compared to conventional BPAP. The improvements in gas exchange observed in our cohort, especially hypercarbia, were secondary to the ability of AVAPS to maintain delivery of a constant tidal volume in the setting of altered patient effort in different sleep stages or altered lung compliance secondary to parenchymal lung disease. The AVAPS feature targets average tidal volume over several breaths. For our patients, we used the recommended range of a tidal volume of 6 to 10 ml/kg of ideal body weight.¹⁴ The device uses a built-in algorithm to calculate the average inspiratory pressure over the prior 2 minutes to achieve the set tidal volume. If the desired tidal volume is not achieved, the inspiratory pressure for the next breath is increased within the set limit. The AVAPS rate setting allows adjustments to the rate at which the inspiratory pressure changes to achieve desired tidal volume. The AVAPS feature is particularly useful for conditions leading to hypoventilation during REM sleep or neuromuscular patients with variable respiratory effort during sleep. In these patients, conventional BPAP with fixed pressure support may lead to higher pressures during NREM sleep or lower pressures during REM sleep, consequently leading to intolerance or inconsistent ventilation during sleep. Thus, we observed better control of hypoventilation in our cohort of patients.

Adult studies have reported the use of AVAPS in acute and chronic settings with mixed success. Piesiak et al¹⁵ compared the effectiveness of AVAPS to conventional BPAP in patients with advanced kyphoscoliosis complicated with severe respiratory failure and found significant improvement of diurnal partial pressure of O₂ and partial pressure of CO₂ on the fifth day of AVAPS use and after 1 year along, with improvements in forced vital capacity. In a prospective interventional matched study conducted in the emergency intensive care unit setting on patients with chronic obstructive pulmonary diseases and hypercapnic encephalopathy, AVAPS facilitated rapid recovery of consciousness compared to traditional BPAP.¹⁶ In a 2-center prospective single-blind randomized controlled trial of AVAPS vs fixed-level BPAP in patients with stable obesity hypoventilation syndrome, there were no differences between AVAPS and conventional BPAP using a strict protocolized setup in patients who were morbidly obese.¹⁷ In a single-blind, randomized, crossover study in patients with stable hypercapnic chronic obstructive pulmonary diseases, AVAPS resulted in better sleep efficiency, although no significant differences were found in reduction of respiratory acidosis when compared to conventional BPAP.¹⁸ In a prospective randomized crossover trial in patients with obesity hypoventilation syndrome, Storre et al¹⁹ found that sleep quality and gas exchange improved during BPAP therapy, but patients remained hypercapnic overnight. The addition of AVAPS significantly decreased PaCO₂, but it did not improve sleep quality. In another study, Ambrogio et al²⁰ compared sleep efficiency and sleep architecture in patients with chronic respiratory failure and found that neither BPAP nor AVAPS significantly modified sleep architecture, quality, or quantity. There was improvement in minute ventilation of uncertain clinical significance using the AVAPS feature. Despite limitations of small sample sizes and difficulty blinding patients to treatment, adult studies indicate that AVAPS provides better ventilation resulting in more efficient decrease of partial pressure of CO₂. The clinical benefits on sleep quality, sleep architecture, quality of life, and long-term mortality, however, are uncertain.

Our study has several limitations. This was a retrospective review of patient records from a single center and is subject to bias by the nature of such a study design. The treating clinician, patients, and investigators were not blinded to the modality of ventilation that was used. We did not use a standardized protocol, rather the patients were switched to AVAPS based on assessment of gas exchange and ventilatory parameters by the admitting clinician. This is a major limitation of our study. Ideally, we would need to conduct a blinded randomized controlled trial with patients receiving either AVAPS or conventional BPAP to draw firm conclusions. We were unable to control for respiratory rate and inspiratory time between the 2 comparison groups. Both play an important role in gas exchange. It is conceivable that our results may simply reflect a poor choice of ventilatory settings on conventional BPAP. During the titration study, several changes were made to the inspiratory pressures, respiratory rate, and inspiratory time along efforts to reduce air leak and maintain patient machine synchrony to achieve acceptable gas exchange. It must be highlighted that the titration studies were performed by a scientist experienced in NIV titration in an established tertiary pediatric sleep laboratory and reflect real world data in a clinical setting. The time interval between conventional BPAP and studies was long in some patients, making direct comparison difficult. However, as AVAPS was used after conventional BPAP, the patients likely had more advanced disease on AVAPS. The long time interval between studies precludes direct comparison of certain variables such as respiratory rate that may significantly impact gas exchange. A minimum tidal volume of 50 mL and high trigger sensitivity limits use of AVAPS in very young infants. Finally, we did not report data on long term outcomes on AVAPS. Despite these limitations, we believe that this study provides valuable information, as it confirms the usefulness of AVAPS feature in pediatric patients with nocturnal hypoventilation where conventional BPAP fails to provide consistent ventilation.

In summary, in a retrospective single center study, we observe that AVAPS was more effective than conventional BPAP in reducing hypercarbia in a cohort of pediatric patients with nocturnal hypoventilation. Future multicenter, adequately powered randomized controlled trials in pediatric patients are needed to confirm increased efficacy of AVAPS over conventional BPAP in treating nocturnal hypoventilation.

DISCLOSURE STATEMENT

All authors have seen and approved this manuscript. Work for this study was performed at Sydney Children’s Hospital. The authors report no conflicts of interest.

ABBREVIATIONS

AVAPS

average volume-assured pressure support

BPAP

bilevel positive airway pressure

NIV

noninvasive ventilation

NREM

non-rapid eye movement

REM

rapid eye movement

TcCO₂

transcutaneous CO₂