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Pediatric Critical Care and Neurotrauma Recovery Program, Oregon Health and Science University, Portland, OregonDivision of Pediatric Critical Care, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon
Division of Critical Care Medicine, Department of Pediatrics, St Louis Children's Hospital, Washington University School of Medicine, St. Louis, Missouri
Pediatric Critical Care and Neurotrauma Recovery Program, Oregon Health and Science University, Portland, OregonDivision of Pediatric Psychology, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Oregon Health and Science University, Portland, OregonDepartment of Neurology, Oregon Health and Science University, Portland, OregonDepartment of Behavioral Neuroscience, Oregon Health and Science University, Portland, OregonOregon Institute of Occupational Health Sciences, Oregon Health and Science University, Portland, OregonVA Portland Health Care System, Portland, Oregon
Division of Critical Care Medicine, Department of Pediatrics, St Louis Children's Hospital, Washington University School of Medicine, St. Louis, MissouriDivision of Pediatric and Developmental Neurology, Department of Neurology, St Louis Children's Hospital, Washington University School of Medicine, St. Louis, Missouri
Division of Pediatric and Developmental Neurology, Department of Neurology, St Louis Children's Hospital, Washington University School of Medicine, St. Louis, Missouri
Pediatric Critical Care and Neurotrauma Recovery Program, Oregon Health and Science University, Portland, OregonDivision of Pediatric Neurology, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon
Sleep-wake disturbances are underevaluated among children with acquired brain injury surviving critical care. We aimed to quantify severity, phenotypes, and risk factors for sleep-wake disturbances.
Methods
We performed a prospective cohort study of 78 children aged ≥3 years with acquired brain injury within three months of critical care hospitalization. Diagnoses included traumatic brain injury (n = 40), stroke (n = 11), infectious or inflammatory disease (n = 10), hypoxic-ischemic injury (n = 9), and other (n = 8). Sleep Disturbances Scale for Children standardized T scores measured sleep-wake disturbances. Overall sleep-wake disturbances were dichotomized as any total or subscale T score ≥60. Any T score ≥70 defined severe sleep-wake disturbances. Subscale T scores ≥60 identified sleep-wake disturbance phenotypes.
Results
Sleep-wake disturbances were identified in 44 (56%) children and were classified as severe in 36 (46%). Sleep-wake disturbances affected ≥33% of patients within each diagnosis and were not associated with severity of illness measures. The most common phenotype was disturbance in initiation and maintenance of sleep (47%), although 68% had multiple concurrent sleep-wake disturbance phenotypes. One third of all patients had preadmission chronic conditions, and this increased risk for sleep-wake disturbances overall (43% vs 21%, P = 0.04) and in the traumatic brain injury subgroup (52% vs 5%, P = 0.001).
Conclusions
Over half of children surviving critical care with acquired brain injury have sleep-wake disturbances. Most of these children have severe sleep-wake disturbances independent of severity of illness measures. Many sleep-wake disturbances phenotypes were identified, but most children had disturbance in initiation and maintenance of sleep. Our study underscores the importance of evaluating sleep-wake disturbances after acquired brain injury.
Building a pediatric neurocritical care program: a multidisciplinary approach to clinical practice and education from the intensive care unit to the outpatient clinic.
Each year tens of thousands of children require specialized pediatric neurocritical care (PNCC) to treat the primary neurological insult and minimize secondary brain injury in an effort to improve outcomes.
International survey of critically ill children with acute neurologic insults: the prevalence of acute critical neurological disease in children: a global Epidemiological Assessment Study.
Healthy sleep is vital for brain maturation and normal development, and is likely even more important after neurological injury or illness given that sleep facilitates neuronal healing and reduces inflammation.
Sleep-wake disturbances (SWDs) in otherwise healthy children are known to impair quality of life, reduce participation in social activities, and impair cognitive function.
Many of the impairments found in children with SWD overlap with those of children with postintensive care syndrome. SWDs including insomnia, somnolence, and sleep-related breathing disorders are reported in survivors of brain injury, but to date have been poorly quantified in children after critical care hospitalization.
Our prior work showed SWDs were a common subjective complaint in children with various neurological diagnoses treated in a critical care follow-up clinic.
Most research has focused on traumatic brain injury (TBI), and very few studies have reported SWD outcomes in children with injuries more severe than concussion.
Therefore the severity of SWDs and phenotypes of the SWDs are largely underevaluated and under-reported in prior studies limiting the ability to adequately identify risk factors and design targeted intervention studies.
To address these important knowledge gaps surrounding SWDs in survivors with acquired brain injury, we evaluated SWDs at two institutions with longitudinal critical care programs treating children in specialized multidisciplinary clinics. On the basis of our clinical experience, we hypothesized SWDs would be prevalent and severe after acquired brain injury. We aimed to quantify overall SWDs, severity and phenotypes of SWDs, and risk factors for SWDs after PNCC hospital discharge using a multidimensional sleep questionnaire.
Materials and Methods
Study design
We evaluated SWDs one to three months after hospital discharge (December 2017 to October 2018) in a prospective cohort study of children aged three to 18 years with acquired brain injury. Evaluations were performed as part of routine clinical care in each institution's coordinated follow-up clinic. More than two thirds of all PNCC survivors complete a clinic visit and referral patterns and follow-up rates at each program have been previously described.
The Institutional Review Board at each institution approved the study under a waiver of informed consent.
Population characteristics
Both institutions are tertiary children's hospitals and accredited level I pediatric trauma centers with multidisciplinary critical care follow-up programs that include pediatric critical care, pediatric neurology, and pediatric neuropsychology faculty. Consecutive children who completed a follow-up visit were included. For the analysis, diagnoses were grouped into five unique subgroups: TBI; stroke (hemorrhagic and ischemic); infectious or inflammatory (meningitis, encephalitis, and demyelinating); hypoxic-ischemic (cardiac arrest and extracorporeal life support); and other (carbon monoxide, hemolytic uremic syndrome, severe sepsis, hippocampal necrosis after polypharmacy ingestion, and refractory status epilepticus). The primary diagnosis was used in patients with multiple diagnoses (e.g., patients with seizures because of meningitis were classified as infectious).
Demographic and clinical characteristics were collected from electronic medical records. Preadmission chronic conditions were grouped into system categories given the large number of individual diagnoses (Supplemental Table 1). The presence of any chronic condition was dichotomized for analysis. Pediatric Index of Mortality-2 score and critical care interventions (intubation, noninvasive ventilation, central venous catheterization, arterial catheter placement, intracranial pressure monitoring, continuous antiepileptic infusion, neurosurgical intervention, hemodynamic resuscitation or vasopressor use, and in-hospital cardiopulmonary resuscitation) were evaluated as markers of illness severity. Interventions were not counted if only used during operative management and were discontinued before return or admission to the pediatric intensive care unit (e.g., intubation during operation only). Functional assessments were made by attending physicians using the Functional Status Scale (FSS).
Glasgow Coma Scale measured TBI severity (mild complicated 13 to 15, moderate 9 to 12, and severe 3 to 8). Location and type of TBI and concurrent non–brain traumatic injuries were identified from radiology reports.
Outcomes
Sleep outcomes were measured at follow-up visits using the Sleep Disturbances Scale for Children (SDSC), a parent-reported 26-item validated multidimensional questionnaire for use in children aged 3 to 18 years.
The Sleep Disturbance Scale for Children (SDSC). Construction and validation of an instrument to evaluate sleep disturbances in childhood and adolescence.
Each question is scored 1 to 5 with higher scores reflecting more disturbance. The SDSC provides six subscale scores and a total composite score that can each be converted to T scores to reflect risk of clinical sleep disorders.
The Sleep Disturbance Scale for Children (SDSC). Construction and validation of an instrument to evaluate sleep disturbances in childhood and adolescence.
In our study, SWDs were defined as a T score ≥60 in any of the SDSC total or subscale scores, corresponding to moderate or greater risk of clinical sleep disorders and ≥1 standard deviation (S.D.) from healthy population means.
The Sleep Disturbance Scale for Children (SDSC). Construction and validation of an instrument to evaluate sleep disturbances in childhood and adolescence.
SWD group was used to compare demographic and clinical characteristics. Severe SWDs were defined as T scores ≥70 (≥2 S.D. from normal). Phenotypes of SWDs were identified by the six SDSC subscales: disorders of initiation and maintenance of sleep (e.g., insomnia); sleep breathing disorders (e.g., sleep apnea); disorders of arousal (e.g., nightmares); sleep-wake transition disorders (e.g., sleep talking, bruxism); disorders of excessive somnolence (e.g., daytime sleepiness); and sleep hyperhidrosis (e.g., night sweats).
Statistical analysis
Descriptive statistics were used to describe the population including percent for categorical variables and median with interquartile range for continuous variables as data were not normally distributed in our sample. SDSC total and subscale score mean and S.D. for our cohort were compared with unpaired t tests to prior published data on SDSC total and subscale means among healthy children (historical control subjects).
The Sleep Disturbance Scale for Children (SDSC). Construction and validation of an instrument to evaluate sleep disturbances in childhood and adolescence.
Demographic and clinical characteristics were compared between dichotomized SWD groups. We used χ2 tests for categorical variables and Mann-Whitney U tests to compare continuous variables. Multiple logistic regression was used to identify variables associated with SWDs among the overall cohort and results reported as adjusted odds ratio with 95% confidence interval. We controlled for diagnosis subgroup (“other” as reference diagnosis category), gender, age, Medicaid, non–White race, Hispanic ethnicity, and the presence of any preadmission chronic condition based on the significance in the bivariate analysis (P < 0.05) and prior reports of risk factors for SWDs in children.
The full model results are reported (Supplemental Table 2) as it showed good calibration (Hosmer-Lemeshow P = 0.9) and discrimination (area under the curve = 0.80) and outperformed reduced models (using area under the curve) derived from stepwise regression.
A descriptive analysis evaluated SWD phenotypes using SDSC subscales and SWDs by diagnosis subgroup. A secondary analysis was performed to explore demographic and clinical variables by SWD group with the same tests as mentioned previously for the TBI subgroup. Analyses were conducted using SPSS (version 24.0; IBM Corporation, Armonk, NY). All tests were two-tailed and significance defined as P < 0.05. When multiple pairwise comparisons were made within variable groups, a Bonferroni adjustment was used to define significance level.
Results
A total of 78 children were evaluated in clinic a median of 1.8 months (interquartile range 1.3, 2.8) postinjury. Most patients had TBI (n = 40) followed by stroke (n = 11), infectious or inflammatory disease (n = 10), hypoxic-ischemic injury (n = 9), and other diagnoses (n = 8). Table 1 shows demographic and clinical characteristics. Preadmission chronic conditions were found in 26 (33%) patients and varied by diagnosis subgroup (Supplemental Table 1). Severity of illness and length of stay were variable, but two thirds required at least one critical care intervention and half were intubated (Table 1). No significant differences were found between institutions in diagnosis, severity, or any interventions. Average SDSC total score was 39.4 (S.D. 10.4) for the overall cohort and was significantly higher than the average for healthy children in published cohorts
The Sleep Disturbance Scale for Children (SDSC). Construction and validation of an instrument to evaluate sleep disturbances in childhood and adolescence.
(35.1, S.D. 7.7; P < 0.001; Table 2). The distribution of standardized T scores for the SDSC total score is shown in Fig 1.
TABLE 1.Demographic and Clinical Characteristics by Sleep-Wake Disturbance Group
Characteristics
All, N = 78 (%)
No SWD, n = 34 (%)
SWD+, n = 44 (%)
P Value
Age in years, median (IQR)
9.9 (6.8, 14.1)
8 (6, 11)
10.7 (7.6, 15)
0.03
Male gender
47 (60)
18 (53)
29 (66)
0.35
Preadmission chronic condition
26 (33)
7 (21)
19 (43)
0.04
Race
0.61
White
63 (81)
26 (77)
37 (84)
Black
6 (8)
4 (12)
2 (5)
Other, multiple races, or unknown
9 (12)
4 (12)
5 (11)
Hispanic ethnicity
13 (17)
4 (12)
9 (21)
0.38
Medicaid insurance
35 (45)
17 (50)
18 (41)
0.42
Diagnosis category
0.13
Traumatic brain injury
40 (51)
19 (56)
21 (48)
Stroke
11 (14)
4 (12)
7 (16)
Infectious and inflammatory disease
10 (13)
1 (3)
9 (21)
Hypoxic-ischemic injury
9 (12)
6 (18)
3 (7)
Other
8 (10)
4 (12)
4 (9)
Pediatric Index Mortality-2; median (IQR)
−3.7(−4.1, −3)
−3.1(−4.1, −3)
−4 (−4, −3.1)
0.49
Intensive care interventions
Monitoring only
27 (35)
8 (24)
19 (43)
0.07
Intubation
39 (50)
19 (56)
20 (46)
0.36
Noninvasive ventilation
10 (13)
7 (21)
3 (7)
0.07
Central venous line
29 (37)
15 (44)
14 (32)
0.27
Arterial line
31 (40)
14 (41)
17 (39)
0.82
Bolt
5 (6)
1(3)
4 (9)
0.27
External ventricular drain
6 (8)
2 (6)
4 (9)
0.60
Infusion for seizure control
12 (15)
4 (12)
8 (18)
0.44
Neurosurgical intervention
21 (27)
11 (32)
10 (23)
0.34
Hemodynamic resuscitation or vasopressor
25 (32)
12 (35)
13 (30)
0.59
Cardiopulmonary resuscitation in-hospital
8 (10)
5 (15)
3 (7)
0.26
Inpatient nutrition
0.43
Any parenteral
5 (6)
3 (9)
2 (5)
Any nasogastric or nasojejunal
17 (22)
10 (29)
7 (15)
Oral only
56 (72)
21 (62)
35 (80)
Inpatient consults
Physical therapy
52 (67)
20 (59)
32 (73)
0.20
Occupational therapy
47 (60)
19 (56)
28 (64)
0.49
Speech therapy
20 (26)
9 (27)
11 (25)
0.88
Psychology
26 (33)
7 (21)
19 (43)
0.05
Inpatient rehabilitation discharge
11 (14)
7 (21)
4 (9)
0.15
New tracheostomy
6 (8)
3 (9)
3 (7)
>0.99
New gastrostomy
3 (4)
2 (6)
1 (2)
0.41
Hours of mechanical ventilation, median (IQR) n = 39
16.7 (4, 37.2)
17.4 (6.3, 28)
15.5 (3.1, 35.8)
0.68
Hospital length of stay in days, median (IQR)
7.4 (2.1, 20.8)
6.8 (1.8, 29.6)
7.4 (2.8, 16.7)
0.61
PICU length of stay in days, median (IQR)
2.8 (1.4, 11.9)
2.8 (1.0, 13.0)
2.5 (1.5, 7.9)
0.78
Clinic Functional Status Scale, median (IQR)
6 (6, 7)
6 (6, 6)
6 (6, 7)
0.30
Abbreviations:
IQR = interquartile range
PICU = pediatric intensive care unit
SWD = sleep-wake disturbance
Values are prevalence or median when stated. Values in the parentheses represent group percentage or IQR when stated. Mann-Whitney U tests were used for continuous variables and χ2 tests for categorical variables.
TABLE 2.Comparison of the Overall Acquired Brain Injury and Traumatic Brain Injury Cohorts to Healthy Control Subjects Reported for the Sleep Disturbances Scale for Children
The Sleep Disturbance Scale for Children (SDSC). Construction and validation of an instrument to evaluate sleep disturbances in childhood and adolescence.
The Sleep Disturbance Scale for Children (SDSC). Construction and validation of an instrument to evaluate sleep disturbances in childhood and adolescence.
SWDs were identified in 44 (56%) patients with acquired brain injury and were severe in 36 (46%) patients. Table 1 shows demographic and clinical characteristics compared by SWD group. FSS at follow-up ranged from 6 to 12, and ≥75% had good functional outcomes (FSS, 6 to 7). Older median age and the presence of preadmission chronic conditions were significantly associated with SWDs. There was no association in bivariate analyses between SWDs and institution or other demographic and clinical characteristics. Using multiple logistic regression controlling for demographic characteristics and diagnosis, the presence of a preadmission chronic condition was the only variable significantly associated with SWDs, portending fivefold increased odds of SWDs among the overall cohort (adjusted odds ratio, 5.4; 95% confidence interval, 1.3 to 21.9).
SWD phenotypes
All SWD phenotypes measured by the SDSC were identified. Multiple SWD phenotypes were found in 30 (68%) of the 44 patients with SWDs. Table 2 shows the overall cohort had significantly higher average scores in the total score and several subscales when compared with healthy children. Overall, the disorders of initiation and maintenance of sleep phenotype was most common with 37 (47%) patients having disturbance and 26 (33%) having severe disturbance (Fig 2). Sleep-wake transition disorders (n = 18, 23%) and somnolence (n = 15, 19%) were also prevalent phenotypes in the overall cohort. Sleep breathing disorder (n = 8, 10%), arousal disorder (n = 8, 10%), and hyperhidrosis (n = 5, 6%) phenotypes were less common. Among patients with any SWD, 37 (84%) showed disturbance in the disorders of initiation and maintenance of sleep subscale.
FIGURE 2Distribution of standardized T scores for the Disorders of Initiation and Maintenance of Sleep subscale is shown separated by primary diagnosis.
Prevalence of SWDs varied by diagnosis, but SWDs were found in ≥33% in each subgroup. SWDs were found in nine (90%) patients with infectious and inflammatory diseases, seven (64%) patients with stroke, 21 (53%) patients with TBI, four (50%) patients with other diagnoses, and three (33%) patients with hypoxic-ischemic injury. The disorders of initiation and maintenance of sleep phenotype was most commonly disturbed among all diagnosis groups (Table 3).
TABLE 3.Sleep-Wake Disturbance Phenotypes by Diagnosis Group
Phenotype
All, N = 78
TBI, n = 40
Stroke, n = 11
Infectious or Inflammatory, n = 10
Hypoxic-Ischemic, n = 9
Other, n = 8
Total score
Median (IQR)
36.5 (32, 46)
34 (30.5, 45)
42 (32.5, 46)
41.5 (37, 47)
32 (32, 37)
37 (33, 46.5)
N (%) disturbance
28 (36)
15 (38)
4 (36)
4 (40)
2 (22)
3 (38)
N (%) severe
8 (10)
5 (13)
0
2 (20)
1 (11)
0
Disorders of Initiation and Maintenance of Sleep
Median (IQR)
12 (9, 16)
11 (8.5, 16.5)
14 (10, 17)
16 (13, 18)
11 (8, 12)
11.5(9, 13.5)
N (%) disturbance
37 (47)
17 (43)
6 (55)
9 (90)
2 (22)
3 (38)
N (%) severe
26 (33)
13 (33)
4 (36)
6 (60)
2 (22)
1 (13)
Sleep breathing disorders
Median (IQR)
3 (3, 4)
3 (3, 4)
3 (3, 5)
3.5 (3, 6)
3 (3, 4)
3.5 (3, 4.5)
N (%) disturbance
8 (10)
2 (5)
1 (9)
3 (30)
1 (11)
1 (13)
N (%) severe
4 (5)
1 (3)
1 (9)
1 (10)
1 (11)
0
Disorders of arousal
Median (IQR)
3 (3, 3)
3 (3, 3)
3 (3, 3)
3 (3, 5)
3 (3, 4)
3 (3, 4.5)
N (%) disturbance
8 (10)
2 (5)
0
3 (30)
1 (11)
2 (25)
N (%) severe
8 (10)
2 (5)
0
3 (30)
1 (11)
2 (25)
Sleep-wake transition disorders
Median (IQR)
8 (7, 10)
7 (6, 10.5)
7 (6.5, 8)
9 (7, 11)
8 (7, 10)
9 (7, 10)
N (%) disturbance
18 (23)
10 (25)
1 (9)
4 (40)
2 (22)
1 (13)
N (%) severe
6 (8)
5 (13)
0
0
1 (11)
0
Hypersomnolence
Median (IQR)
7 (5, 9)
7 (5, 9)
7 (6.5, 7.5)
7.5 (5, 9)
6 (5, 8)
6 (5.5, 9.5)
N (%) disturbance
15 (19)
8 (20)
1 (9)
2 (20)
2 (22)
2 (25)
N (%) severe
7 (9)
6 (15)
0
1 (10)
0
0
Sleep hyperhidrosis
Median (IQR)
2 (2, 3)
2 (2, 3)
2 (2, 3.5)
2 (2, 2)
2 (2, 2)
2 (2, 3)
N (%) disturbance
5 (6)
3 (8)
1 (9)
0
0
1 (13)
N (%) severe
1 (1)
0
1 (9)
0
0
0
Abbreviations:
IQR = interquartile range
TBI = traumatic brain injury
Total and subscale scores from the Sleep Disturbances Scale for Children; disturbance defined as T score ≥60; severe defined as T score ≥70.
The Sleep Disturbance Scale for Children (SDSC). Construction and validation of an instrument to evaluate sleep disturbances in childhood and adolescence.
No association between SWDs and severity, mechanism, or location of TBI was found (Table 4). Type of intracranial injury was not statistically different between SWD groups. Preadmission chronic conditions were strongly associated with SWDs in the TBI population (52% with SWDs versus 5% without SWDs, P = 0.001). The most prevalent preadmission conditions identified in TBI were attention deficit hyperactivity disorder (ADHD) and behavioral disorders (n = 5), but this was not statistically different between SWD groups. The disorders of initiation and maintenance of sleep subscale was disturbed in 17 (43%) patients with TBI and severely disturbed in 13 (33%) patients. Sleep-wake transition disorders (25%) and somnolence (20%) phenotypes were also common. Phenotypes did not vary between mild complicated, moderate, and severe patients with TBI.
TABLE 4.Clinical Characteristics by Sleep-Wake Disturbance Group Among Patients with Traumatic Brain Injury
Among children with acquired brain injury treated in critical care follow-up clinics after discharge, SWDs are highly prevalent and often severe. Risk of SWDs was increased in children with preadmission chronic conditions, but SWDs were not associated with severity of injury measures. Many SWD phenotypes were found, some varying by diagnosis, and multiple SWD phenotypes coexisted in most patients. The disorders of initiation and maintenance of sleep phenotype was most common and nearly universally identified in patients with SWDs. These disturbances were also frequently severe and may serve as a target for future intervention studies seeking to improve outcomes in critical care survivors with acquired brain injury.
Our study adds to the literature showing that SWDs are important outcomes in survivors of critical care and brain injury. This study is the first to describe SWDs after many PNCC diagnoses. Case reports of SWDs in children with stroke, meningitis, and hypoxic-ischemic injury are reported, although SWDs have not been systematically evaluated in these populations after critical care.
Our rates of SWDs among children with TBI are similar to prior reports showing high rates of somnolence, insomnia, and overall disturbances after pediatric TBI when compared with control subjects.
One prior study used the SDSC in a PNCC population, showing significantly worse SWDs in children after TBI compared with healthy control subjects, and reported similar total SDSC scores to our population.
SWDs are also reported in broader populations of children surviving critical care, with high rates similar to our study, and much higher than healthy children.
Taken together, results highlight the importance of evaluating SWDs in all PNCC survivors.
Our study additionally evaluated SWD phenotypes, showing the disorders of initiation and maintenance of sleep subscale was abnormal in most children with SWD after acquired brain injury. This subscale suggests insomnia or circadian rhythm disturbances are contributing to SWDs in children surviving PNCC. Insomnia has been described in up to 60% of adults with TBI and after concussion.
Poor sleep efficiency and impaired onset and maintenance were reported using actigraphy in 15 children with moderate and severe TBI consistent with insomnia.
although none of our patients had complete blindness or cortical visual impairment at follow-up. Hospitalized patients do have altered levels of melatonin and circadian rhythms while inpatient due to cares, medications, and persistently high ambient light levels,
It is possible that children in our cohort have acquired circadian rhythm disturbance from brain injury compounded by the hospital environment, but more research is needed to distinguish these phenotypes and investigate the relative contribution of brain injury and the therapeutic environment. Both insomnia and circadian rhythm disturbances have been treated successfully in pediatric populations,
It remains unknown if interventions during or after hospitalization to improve sleep could augment recovery after discharge for pediatric acquired brain injury.
Risk of SWDs was significantly increased with preadmission chronic conditions in our cohort. We found similar rates of chronic conditions in PNCC patients in prior studies.
We did not measure baseline SWDs to determine effects of preinjury SWD or potential association with preadmission chronic conditions. A small number of our patients had any one of these individual chronic conditions limiting our ability to determine if specific preadmission conditions were associated with SWD. One prior study did show children with TBI and concurrent ADHD had worse SWDs than ADHD control subjects 1 to 4 years after injury.
The acquired brain injury may compound preinjury SWDs or increase risk of SWDs among those with pre-existing chronic conditions. However, most children in our study were previously healthy and prevalence of SWDs was higher than reports in healthy children, which suggests the acquired brain injury and hospital course, rather than solely preadmission conditions, explain our findings.
Older age was associated with SWDs in bivariate analysis. Adolescents and teens are reported to have high rates of baseline SWDs, which may explain the trend for increased SWDs with older age in our study. Estimates show 30% to 40% of teenagers may have clinically important SWDs at baseline, whereas estimates are lower in preschool to adolescence.
Older children may have more insight into sleeping problems, more effectively communicate problems to caregivers, or have behavioral differences in screen-time, caffeine intake, and sleep schedules contributing to these findings. Prior studies in TBI show inconsistent results with respect to age and SWDs, and our analysis did not find age to be an independent risk factor when controlling for confounders in multivariable analysis. In addition, most prior studies focus on narrower age ranges and have small sample sizes, thereby limiting direct comparison to our study.
We found overall SWDs were not associated with measures of severity of illness, including need for critical care interventions, functional outcome, or discharge to inpatient rehabilitation. Prior studies of heterogeneous pediatric critical care cohorts also failed to show associations between SWDs and severity of illness markers or length of stay.
Although not associated with SWDs in our study, some of the markers we used for severity of illness (e.g., critical care interventions) have been associated with delusional memories, delirium, and risk for post-traumatic stress,
all of which may impact sleep. Evaluation of these important outcomes as mediators of SWDs after discharge should be evaluated in future studies.
In the TBI subgroup, our study also found overall SWDs were not associated with Glasgow Coma Scale on admission, loss of consciousness, or type or location of intracranial injury, and is consistent with prior work showing SWDs are pervasive after all severities of TBI.
evaluated young children and found no difference in daytime sleepiness based on severity of TBI, but did show increased bedtime resistance in patients with severe TBI. Daytime fatigue was also similar in children by TBI severity in other studies.
Differences between available studies and our findings are likely explained by different populations, measurement tools, and limited sample sizes. Associations between sleep phenotypes and injury characteristics should be assessed in future studies with larger populations using validated measures of SWDs to inform targeted intervention studies.
Given known associations between SWDs and poor academic achievement, depression, and obesity in otherwise healthy children, SWDs represent a substantial problem.
a function even more critical in the developing brain and after injury. SWDs offer a potentially modifiable target to improve recovery after acquired brain injury, and our results underscore the importance of systematically evaluating sleep in these children.
Although our study includes data from two centers, our centers are unique in the presence of coordinated critical care follow-up programs. Most institutions do not have similar programs,
International survey of critically ill children with acute neurologic insults: the prevalence of acute critical neurological disease in children: a global Epidemiological Assessment Study.
and care of children with morbidities after brain injury is often left to general practitioners and subspecialists. Our unique clinical population limits generalizability, but our results show a need for increased awareness of SWDs after acquired brain injury in PNCC survivors. Our study has several other limitations to consider including lack of preinjury sleep measures, parent-reported questionnaires to define sleep outcomes, short-term follow-up, and lack of objective measures of SWDs to supplement the questionnaire data. Prevalence of SWDs in our study was high suggesting a large increase in prevalence even if baseline disturbances are present. In addition, questionnaires may not capture the true prevalence of SWDs relying on recall and estimation of events. The SDSC represents one of the only validated multidimensional tools to measure sleep in pediatric patients,
but future studies should use objective measures like actigraphy and polysomnography to supplement patient and parent report. Our follow-up evaluations were limited to 1 to 3 months after discharge, so the trajectory of SWD after PNCC remains largely unknown, although studies in TBI have documented persistence of SWDs several years after injury.
Despite these limitations, our study highlights an important problem in survivors with acquired brain injury for which future research is needed.
Conclusions
SWDs are an important morbidity affecting more than 50% of children surviving critical care with acquired brain injury in the months after discharge, and are frequently severe. Phenotypes consistent with insomnia or circadian rhythm disturbances were most common, but all SWD phenotypes were found in our cohort. SWDs can impair physical, cognitive, and psychosocial functions, and our study showed SWDs were pervasive in all diagnoses and regardless of severity of acute injury, which underscores the importance of evaluating SWDs after discharge. More research is needed to identify effective interventions to prevent and treat SWDs and determine if treating SWDs can also augment recovery from acquired brain injury in other important domains.
Acknowledgments
This research was made possible with support from the Oregon Clinical and Translational Research Institute (OCTRI), grant number UL1RR024140 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Funding: C.N.W. is supported by the Agency for Healthcare Research and Quality, grant number K12HS022981. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality. C.T.M. is supported by the National Heart, Lung and Blood Institute, R01 HL105447 with cofunding from the Office of Dietary Supplement, R01H L129060 and UG3OD023288. M.M.L. is supported with resources and the use of facilities at the VA Portland Health Care System and VA Career Development Award #IK2 BX002712. Interpretations and conclusions are those of the authors and do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. S.A.S. is supported by the National Institutes of Health, grant numbers R01-HL125893, R01-HL125893-03S1, R01-HL142064, and R01 HL140577, as well as the Oregon Institute of Occupational Health Sciences via funds from the Division of Consumer and Business Services of the State of Oregon (ORS 656.630). K.P.G. is supported by the National Institute of Neurological Disorders and Stroke, grant number K23NS099472. J.A.P. is supported by the National Heart, Lung and Blood Institute, grant number K12HL133115.
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Conflict of interest and source of funding statement: The authors declare no conflict of interest or financial disclosures concerning the materials or methods used in this study or the findings specified in this article.
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