AbstractObjectivesNocturnal hypoventilation is a complication of neuromuscular disorders. There are various recommendations for measuring pCO2 during polysomnography and numerous national and international definitions of hypoventilation that could contribute to significant variations in clinical practice. We therefore aimed to determine clinical practices implemented by Australasian pediatric sleep physicians.
MethodsPediatric sleep physicians completed an electronic survey for information regarding pCO2 measurements and definitions of hypoventilation that are followed for children with neuromuscular disorders.
ResultsIt was found that transcutaneous measurement of pCO2 was performed in all centers, with 25% of the centers simultaneously performing capnography. Twelve definitions of hypoventilation were used, including published definitions from the American Academy of Sleep Medicine (AASM) manual and recommendations of the pediatric Australasian Sleep Association/Australasian Sleep Technologists Association. The most commonly used definition of hypoventilation (9/17, 53%) was the 2012 pediatric AASM definition (pCO2 >50 mmHg for >25% of the total sleep time). There was a discrepancy between centers and individuals within the same center when defining hypoventilation. Answers stating the use of the Australasian definitions (rise in pCO2 ≥10 mmHg from wake to sleep, average rise in pCO2 ≥3 mmHg from non rapid eye movement to rapid eye movement sleep) were more frequent when asked specifically via a checkbox (yes/no) compared to free text.
INTRODUCTIONNeuromuscular disorders (NMDs) can affect any part of the lower motor neurons, including the anterior horn cells, peripheral nerves, neuromuscular junctions, muscle fibers, and supporting structures of the muscle. Common NMD affecting children and adolescents include Duchenne muscular dystrophy, spinal muscular atrophy, congenital muscular dystrophies, congenital myopathies, and myotonic dystrophy. Many NMD cause respiratory muscle weakness that can lead to nocturnal hypoventilation. Hypoventilation first becomes apparent during rapid eye movement (REM) sleep because the normal physiological atonia of the accessory respiratory muscles in phasic REM is exaggerated by muscle weakness [1]. As nocturnal hypoventilation is usually the first sign of impending daytime respiratory failure in individuals with NMD, it is imperative that the onset of nocturnal hypoventilation be accurately identified in this population to allow timely institution of non-invasive ventilation [2,3].
Diagnosis of nocturnal hypoventilation requires the demonstration of hypercapnia during sleep. Continuous measurement of pCO2 during polysomnography (PSG) is recommended for assessing nocturnal gas exchange [4]. During PSG, pCO2 can be measured transcutaneously (TCO2) and/or end-tidally (ETCO2), which is also known as capnography. Both measurement methods are recommended in the American Academy of Sleep Medicine (AASM) manual and by the pediatric Australasian Sleep Association/Australasian Sleep Technologists Association (ASA/ASTA) as appropriate surrogate markers for alveolar pCO2 during pediatric PSG [4,5].
Although hypercapnia while awake is defined as an arterial pCO2 of >45 mmHg [6,7], there is no clear definition of what constitutes a clinically relevant change in pCO2 during sleep [8]. The threshold of hypercapnia associated with morbidity and mortality is unknown, the relationship between hypercapnia and end-organ damage has not been elucidated, and the impact of modulating factors such as peak pCO2, duration of hypercapnia, and age of the child is unclear [9]. Therefore, it is not surprising that the thresholds and values used to define significant hypercapnia and hence hypoventilation during sleep vary worldwide [10-20].
Defining hypoventilation is even more challenging in individuals with NMD, as the ‘normal range’ of pCO2 during sleep has not been defined and hypercapnia is often significant during sleep [21]. Some groups have proposed that individuals to define hypoventilation may be more sensitive to lower thresholds with NMD [13,14].
The most recent 2012 AASM manual defines hypoventilation in adults as an increase in arterial pCO2 or appropriate surrogate during sleep to >55 mmHg for ≥10 min [4] and/or a rise in arterial pCO2 or appropriate surrogate during sleep to ≥10 mmHg compared to awake supine value of >50 mmHg for ≥10 min [4]. Hypoventilation in children is defined as an increase in arterial pCO2 or an appropriate surrogate during sleep to >50 mmHg for >25% of the total sleep time (TST) [4]. The AASM manual states that pediatric scoring rules can be used up to the age of 18 years; however, for adolescents aged 13 years and above, adult scoring rules may be used if desired [4].
In 2010, the ASA/ASTA published an addendum to the 2007 AASM manual as it felt that some recommendations were not applicable to the circumstances, population, and equipment available in Australia and New Zealand [22]. A further addendum was published specifically for pediatrics in 2011 [5] which recommends using the AASM pediatric definition of hypoventilation; however, an increase in pCO2 ≥10 mmHg from wake to sleep [5] and/or an average rise in pCO2 ≥3 mmHg from nonrapid eye movement (NREM) to REM sleep [5] were offered as alternative definitions of hypoventilation and REM related hypoventilation, respectively. Other published definitions of hypoventilation are listed in Table 1.
Although an accurate diagnosis of nocturnal hypoventilation in individuals with NMD is imperative to guide treatment decisions, the authors hypothesized that the existence of numerous definitions of hypoventilation and the lack of agreement between sleep physicians are likely to lead to significant variation in methods of measuring pCO2 during PSG and defining hypoventilation in this vulnerable group. Therefore, this study surveyed pediatric sleep physicians in Australia and New Zealand to assess the usual clinical practice of diagnosing nocturnal hypoventilation in children and adolescents with NMD.
METHODSThis study was registered on the Child and Adolescent Health Services Governance Evidence Knowledge Outcomes (GEKO) platform, which is a low- and negligible-risk pathway for audits of clinical practice and quality improvement (QA 6245, Accreditation Standard EQuIP 12 Provision of Care). Publication approval was granted via GEKO.
All pediatric sleep physicians in Australia and New Zealand who worked in a hospital setting with access to a sleep laboratory were invited to participate. A fourteen-question electronic survey (SurveyMonkey, www.momentive.ai; Momentive Inc. San Mateo, CA, USA) was emailed via an electronic weblink and a QR code. Responses were anonymous, although potentially identifying information was included to allow grouping of responses by center (such as state of practice and name of the hospital). When the responses were grouped by center, the results were presented ensuring that the individuals could not be identified.
Survey questions were worded to ensure that the information collected pertained only to children and adolescents with NMD. The collected data included methods of measuring pCO2 during PSG for a child or adolescent with NMD and the criteria used to define hypoventilation in children and adolescents with NMD. Definitions of hypoventilation were entered as free text in response to the question, ‘What parameters or rules do you use to decide whether hypoventilation is present or absent?’ After providing free-text definitions of hypoventilation, physicians were asked about the use of pediatric ASA/ASTA definitions via a checkbox (yes/no).
The frequencies, frequency distributions, and calculations were performed using Microsoft Excel (version 2110, Microsoft, Redmond, WA, USA). The free-text responses were coded into published and unpublished definitions of hypoventilation. Unpublished definitions/criteria were further categorized into descriptive pCO2 trends, pCO2 criteria with threshold values, and PSG features. Free text comments were grouped into two categories: the potential for pCO2 measurement to be affected by artifacts and how to best define hypoventilation.
RESULTSThe survey was sent to 58 pediatric sleep physicians, and 17 responses were returned (response rate: 30%). All the physicians who responded worked in dedicated pediatric sleep laboratories in hospital-based settings. Fourteen of the responses came from seven centers in Australia, with three responses from one center in New Zealand. Each of the seven tertiary pediatric centers in Australia had at least one response, with responses per center ranging from to 1–4.
Measurement of pCO2 was performed using TCO2 only in six of eight centers (75%), and simultaneously with TCO2 and ETCO2 in two of eight (25%) centers. None of the centers used ETCO2 alone.
Supplementary Material (in the online-only Data Supplement) lists 12 definitions of hypoventilation that were provided. The number of definitions provided by each physician ranged from to 1–5. The coded responses are presented in Table 2. As seen in the Table 2, some definitions included specific thresholds (for example, ‘a rise in pCO2 of >3 mmHg from NREM to REM’) and others were purely descriptive (‘a rise in pCO2 during REM’). The most commonly used definition (9/17, 53%) was the 2012 AASM pediatric definition: an increase in arterial pCO2 or an appropriate surrogate during sleep to >50 mmHg for >25% of the TST.
When specifically asked about the pediatric ASA/ASTA definitions with a check-box (yes/no), 12 (70%) agreed that a rise from awake to asleep pCO2 of ≥10 mmHg and 10 (59%) claimed that an average rise in pCO2 ≥ 3 mmHg from NREM to REM indicates hypoventilation. In centers with more than one responding physician, there was occasionally a discrepancy between individuals. For example, in one center, 100% of the responders stated using a rise from awake to asleep pCO2 of ≥10 mmHg from NREM to REM to define hypoventilation, but only 75% used a rise in pCO2 of >3 mmHg.
Several physicians commented about the potential for TCO2 measurement to be affected by artifact and thus be inaccurate, such as the following statements: ‘if you have ETCO2 tracing, it is useful to recheck whether the rise in TCO2 was not artifactual’ and ‘our TCO2 leads tend to over-read, which is why we do not rely on them as a baseline measurement; whereas, a rise in REM is more accurate in our setting.’ Two comments reinforced that the pediatric ASA/ASTA recommendations are not always used in Australasian centers, as follows: ‘we use AASM guidelines solely without the ASA/ASTA recommendations’ and ‘ASA/ASTA recommendations are better characterized as ‘recommended’ rather than ‘recommend’ given the age of that commentary.’ Two physicians commented that they would never use adult rules for pediatric patients, regardless of their age.
DISCUSSIONAlthough accurate diagnosis of hypoventilation in children with NMD requires consistency when measuring pCO2 during PSG as well as standardized definitions of hypoventilation, results of this survey confirm the heterogeneity in clinical practice and lack of standardization that exists within Australasia.
Measurement of ETCO2 during pediatric PSG is desirable to aid the identification of upper airway obstruction [4,23]. However, reliance on ETCO2 only may be unsuitable in children, as it has been shown to have variable accuracy [4,24], particularly in those with NMD [25], is often poorly tolerated, and artifacts are common due to nasal obstruction [5]. Although TCO2 is unaffected by nasal obstruction, it cannot measure breath-to-breath changes in pCO2, has a lag time of approximately two minutes [4,26,27], and artifacts in children are frequent. The potential for TCO2 values to be affected by artifacts was reinforced by the comments of several physicians in this survey.
Given that both ETCO2 and TCO2 have benefits and limitations, simultaneous measurement is desirable to identify artifacts and increase the likelihood that the measured pCO2 values accurately reflect alveolar pCO2. In this study, the measurement of ETCO2 was only reported by 25% of the centers, likely because the equipment and consumables for ETCO2 measurement are expensive. Perhaps, given the challenges in children and the expense required to measure ETCO2, this could be reserved for children at a high risk of hypoventilation, such as those with NMD or obesity.
A wide variety of published and unpublished definitions of hypoventilation were used in this study, highlighting the inconsistent application of criteria and the frequent use of parameters or definitions that are not in line with published recommendations. The pediatric AASM definition of hypoventilation was most frequently used, which is unsurprising given that the AASM manual is generally accepted as the definitive reference for PSG scoring [28]. However, despite the AASM manual stating that adult rules can be used for adolescents aged 13 years and above [4], no physicians reported practicing such, and two specifically commented that they would never use adult rules regardless of the patient’s age. This finding could be explained by the fact that all physicians worked in dedicated pediatric sleep centers; therefore, exposure to adult scoring rules may be limited, and the data required to apply adult definitions (for example, pCO2 >55 mmHg) may not be easily available to pediatric physicians. However, the most likely explanation is that adult scoring rules have been shown to underestimate the presence of sleep-related pathologies in adolescents, as they are not sufficiently sensitive [29]; hence, pediatric sleep physicians are reluctant to use adult rules.
The definitions of hypoventilation in this survey included PSG findings that are not part of any currently published definitions, such as the presence of central apnea, hypopnea, sleepdisordered breathing, and oxygen desaturation. Although older definitions of nocturnal hypoventilation often included oxygen desaturation [30], this was prior to the ability to easily measure pCO2 continuously during PSG. Currently, hypoventilation is defined as hypercapnia during sleep, rather than oxygen desaturation. Although oxygen desaturation can be associated with hypoventilation, it is important to recognize that oxygen desaturation without hypercapnia is not associated with hypoventilation and is likely secondary to parenchymal lung disease or obstructive sleep apnea [1,2]. Similarly, the presence of central apnea and/or hypopnea can be associated with hypoventilation, but may be physiologic in children due to the instability of the respiratory drive [11] and is also seen in NMD, secondary to reduced respiratory drive, diaphragmatic weakness, and cardiomyopathy [1]. The presence of central hypopnea and/or sub-criterion central events without associated hypercapnia is often a precursor to hypoventilation. Therefore, although PSG features, such as central apnea, hypopnea, sleep-disordered breathing, and oxygen desaturation, may be associated with hypoventilation, a diagnosis of hypoventilation requires the demonstration of significant hypercapnia during sleep and should not be based on these PSG findings.
Despite the pediatric ASA/ASTA addendum being developed specifically by Australasian physicians to better reflect their clinical environment, when asked which definitions were used via free text, only 18% used a rise from awake to asleep pCO2 >10 mmHg and 12% claimed the use of an average increase in pCO2 ≥3 mmHg from NREM to REM. There was also a discrepancy between individual physicians working in the same center when using these definitions. This variation in clinical practice and infrequent use of these definitions could be explained by comments that imply that some pediatric sleep physicians felt that the addendum was irrelevant and/or outdated, which justifies a comprehensive review of the definition of hypoventilation.
Of interest, when later asked about the ASA/ASTA definitions via checkbox (yes/no), 70% of physicians agreed that a rise from awake to asleep pCO2 >10 mmHg and 59% that an average increase in pCO2 ≥3 mmHg from NREM to REM indicated hypoventilation. This discrepancy could be explained by the excessive cognitive load associated with remembering multiple definitions of specific values. Further support for the notion of excess cognitive loading is the fact that, when asked to enter definitions via free text, answers including specific thresholds or values were much less frequent than descriptive phrases. As excessive cognitive load on physicians is known to have implications in performance and patient safety [31], this study presents an exciting opportunity to summarize and collate the most clinically useful definitions into a user-friendly reference guideline.
This study has several limitations. The response rate of 30% was low; however, many sleep units operate with a model in which not all physicians who practice sleep medicine are involved in reporting or scoring PSGs for children with NMD. The survey was sent to pediatric sleep physicians working solely in private practices, where exposure to children with NMD is likely to be limited. Therefore, it is likely that many physicians invited to participate in this survey did not respond because the survey was not relevant to their clinical practice.
Although the survey responses included at least one physician from each tertiary pediatric sleep center in Australia and New Zealand, the number of physician responses per center (range 1–4) was not necessarily proportional to the patient load. This reduces the representation of all practices and the likely outcome is an underestimation of heterogeneity.
Data regarding the number of years of experience in reporting and interpreting PSGs were not collected. Although sleep physicians with all levels of experience were invited to participate, a range of experience should have been captured. The use of free text may have underestimated the use of definitions with specific values, because some respondents might have preferentially entered a descriptive response.
In conclusion, this study confirms that despite the accurate diagnosis of nocturnal hypoventilation being of utmost importance in children with NMD to guide clinical decision-making, there is significant variation in normal clinical practice and a lack of standardization when defining hypoventilation in this group. The ability to examine the factors that contribute to this variation, particularly the impact of pediatric sleep physicians’ level of experience, warrants further investigation. The lack of a standardized definition of hypoventilation in children and adolescents with NMD hampers future research collaboration, as well as the comparison and benchmarking of clinical practice between centers. Therefore, a standardized definition of hypoventilation in individuals with NMD that is evidence-based and related to clinical outcomes is urgently required.
Supplementary MaterialsThe online-only Data Supplement is available with this article at https://doi.org/10.13078/jsm.230005.
NotesAuthor Contributions
Conceptualization: Adelaide L Withers, Andrew C Wilson, Graham Hall. Data curation: Adelaide L Withers. Formal analysis: Adelaide L Withers. Investigation: Adelaide L Withers. Methodology: all authors. Project administration: Adelaide L Withers. Supervision: Jenny Downs, Andrew C Wilson, Graham Hall. Writing—original draft: Adelaide L Withers. Writing— review & editing: all authors.
AcknowledgmentsThe authors would like to thank all the pediatric sleep physicians who participated in the survey.
Table 1.
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