Abstract
Objective:
Individuals with Down syndrome (DS) have been reported to have lower systemic blood pressure compared to individuals without DS. This study sought to retrospectively evaluate biomedical parameters in patients with DS undergoing procedural sedation compared to non-DS controls.
Methods:
A retrospective observational study was performed comparing children and young adults with DS (n = 150) and age-matched non-DS patients (n = 146) who underwent procedural sedation. Demographics, comorbidities, and diagnostic studies were assessed, along with preprocedural baseline, median procedural, and procedural nadir systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP). The average rate of change in SBP and DBP from baseline to nadir was also examined between the two groups.
Results:
Although baseline SBP, DBP, and PP were comparable between the two groups, individuals with DS showed lower median procedural SBP and DBP (P < 0.001) as well as lower procedural nadir SBP, DBP, and PP (P < 0.001). Consistent results were found for median SBP (P = 0.006) and nadir SBP (P = 0.006) percentiles. Notably, the reduction from baseline to nadir during sedation was larger in individuals with DS for both SBP (mean difference [95% CI]: −12.3 [−16.1, −8.6]) and DBP (−10.2 [−13.3, −7.0]) compared to the non-DS controls. These differences remained consistent even after adjusting for demographic factors.
Conclusions:
Children and young adults with DS exhibited significantly larger blood pressure drops during procedural sedation. Additional research is warranted to investigate the clinical significance of these findings, including the potential for decreased cerebral blood flow in this population during sedation.
Keywords: blood pressure, down syndrome, hypotension, sedation, volatility
INTRODUCTION
Down syndrome (DS) is the most common genetic cause of intellectual disability [1]. The incidence of DS in the United States is approximately 1 in every 700 live births, with increasing rates in Black and Hispanic populations [2,3]. DS is associated with a variety of medical conditions which affect the cardiovascular, gastrointestinal, musculoskeletal, endocrine, ophthalmic, hematological, auditory, respiratory, and neurological organ systems [4].
Due to the abundance of clinical comorbidities, individuals with DS experience higher rates of anesthesia-induced surgery than individuals without DS [5]. The high prevalence of cardiac and autonomic dysfunction in patients with DS also increases the risk of perioperative and postoperative complications [6–10]. Additionally, previous studies suggest that patients with DS are more likely to experience bradycardia in response to sevoflurane and dexmedetomidine during surgery [11,12]. These unique features complicate sedation and anesthesia administration in individuals with DS.
Previous research has established that patients with DS tend to have lower baseline blood pressure compared to individuals without DS [13]. However, blood pressure changes during procedural sedation have never been studied extensively in individuals with DS. This retrospective study sought to compare the demographics, comorbidities, and baseline systolic blood pressures (SBP), diastolic blood pressures (DBP), and pulse pressure (PP) of patients with DS undergoing procedural sedation as compared to non-DS controls; and analyze the changes in SBP and DBP from baseline to nadir when these two groups undergo procedural sedation.
METHODS
Approval and data availability
This study was approved by the Children's Hospital Los Angeles institutional review board (IRB, CHLA-20-00105). As this study was retrospective in nature, assent and consent were waived. Anonymized data from this study is available to qualified investigators pending study team and IRB approval.
Study design and population
This retrospective study identified individuals undergoing outpatient procedural sedation for any purpose between July 1, 2022, and July 1, 2024. Medical charts were reviewed to collect relevant data. The study included two unique cohorts: individuals with DS and those without DS (non-DS controls), both of whom had procedural sedation at the home institution. Individuals with DS who had undergone procedural sedation were identified through ICD-10 code Q90.9, assigned during any clinical encounter at our institution. Non-DS controls were matched 1 : 1 with the DS group based on age and sex to ensure comparability.
Inclusion and exclusion criteria
For the DS cohort, individuals were included if they met the following criteria: a genetic analysis confirming trisomy of chromosome 21, age between 1 and 21 years at the time of procedure, and receipt of at least one procedural sedation at our institution for any reason. For the control cohort, inclusion criteria were as follows: age between 1 and 21 years at the time of procedure, and receipt of at least one procedural sedation at our institution for any reason.
Exclusion criteria were consistent across both cohorts and included the following: active oncologic diagnosis, active cardiac disease (defined as taking cardiac medications), restrictive pulmonary disease, active renal disease or hepatic disease, use of antihypertensive therapies (e.g., beta blockers, alpha-2 agonists, diuretics, etc.), and untreated systemic disorder that could affect blood pressure (e.g., untreated hypothyroidism). In addition, in the DS cohort, individuals could not have a co-morbid genetic diagnosis. In the control cohort, individuals could have a neurodevelopmental disorder, autism spectrum disorder (ASD), or another genetic condition, provided they did not meet any of the exclusion criteria listed above.
For patients who had received multiple procedures under sedation, only the three most recent procedures were included in the analysis. Biometric variables in these circumstances were averaged across all sedation events to yield a single output for each demographic and clinical data point for individuals where this occurred.
Demographic characteristics and clinical data
Demographic data, including age (years), sex at birth, race/ethnicity, and biometric measurements, such as weight (kg), height (cm), and BMI (kg/m2), were collected for all patients. Additionally, procedure-related data were gathered, including the primary diagnosis leading to the procedure, procedure type, and total time of sedation. Blood pressure measurements (SBP and DBP, mmHg) were taken preprocedure and at five-minute intervals throughout the entire duration of the sedation, and then PP (mmHg) was calculated subtracting SBP from DBP. One outpatient preprocedure and one outpatient postprocedure BP were obtained for all patients to compare against baseline BP on the day of procedure.
Statistical analysis
Demographics, comorbidities, and blood pressure measurements (preprocedural baseline, median procedural, and procedural nadir) were compared between patients with DS and non-DS controls, using chi-square or Fisher's exact tests for categorical variables and Wilcoxon rank-sum test for continuous variables. Blood pressure metrics, including SBP, DBP, and PP, were visualized at five-minute intervals throughout the procedural sedation to highlight individual patterns and overall trends in both groups. In addition, distributions of mean percentage change in SBP and DBP were visualized for every 5% change from baseline for the duration of procedural sedation to compare the two groups. To estimate the average rate of change in SBP and DBP from baseline to the nadir, repeated measures analyses were performed via restricted maximum likelihood estimation. The models included fixed effects for Group (DS vs. Non-DS controls) and Time (Nadir vs. Baseline), with a Group × Time interaction term, and a random effect for subjects (Model A). Group-specific analyses were performed due to strong evidence of interactions with Group. We further examined the adjusted models by including potential covariates such as sex, age, weight, and height, BMI, total time of sedation. To explore potential effect modification, interaction terms between Group, Time, and the covariates were included in separate models (Model B), and their impact was evaluated using information criteria including Akaike information criterion and Bayesian Information Criterion. Statistical significance was defined a priori at two-sided P < 0.05. All analyses were conducted in Stata/MP release 18.0 (StataCorp LLC: College Station, TX; 2023)
RESULTS
Sample characteristics
A total of 1891 unique individuals underwent a procedural sedation for any purpose at our institution during the study timeframe. Among them, 150 individuals with DS (7.9%) met the inclusion criteria and were free of any exclusion criteria. These were matched to 146 non-DS controls. The most common reasons for exclusion from the control cohort included oncologic diagnosis (n = 846, 44.7%), use of antihypertensive medications (n = 239, 12.6%), active renal disease (n = 203, 10.7%), and active/untreated cardiac and/or pulmonary disease (n = 183, 9.6%).
Demographics and clinical characteristics, including comorbidities and procedure-related information, are reported in Table 1. Among the 296 individuals included, the median age was 14.2 years (25th, 75th percentiles: [6.8, 17.4]), with 54.1% assigned male at birth. The majority identified as Hispanic/Latino (n = 149, 61%), followed by White (n = 57, 23%). Median weight was 46.7 kg [22.8, 62.0], height was 144 cm [113.5, 157.6], and BMI was 22.0 kg/m2 [18.2, 27.6]. Comorbid conditions included congenital cardiac abnormalities in 26% (n = 76), thyroid dysfunction in 17.2% (n = 51), autism in 13.9% (n = 41), diabetes in 4.7% (n = 14), and hypertension in 1.4% (n = 4). The median duration of procedural sedation was 73.0 min [56.0, 103.0]. The most common procedures were lumbar puncture (n = 69, 23.3%) and imaging studies such as CT, MRI, CT angiogram, MAG3 scan (n = 63, 21.3%). Primary diagnoses included epilepsy or other neurologic disorders (n = 79, 26.7%), Down Syndrome Regression Disorder (DSRD, n = 66, 22.3%), and a range of other diagnoses, including ophthalmic, audiologic, diagnostic biopsy, and miscellaneous conditions (n = 122, 41.2%). Of the total participants, 51% (n = 150) were individuals with DS, while the remaining 49% (n = 146) comprised non-DS controls. As individuals with DSRD receive first line therapy with benzodiazepines in many cases, additional analysis for use of these therapies at the time of procedural sedation in both groups. A total of 19 (12.6%) individuals with DS and 14 (9.6%) non-DS controls were receiving benzodiazepines at the time of sedation which was not statistically significant between groups (P = 0.40, 95% CI: 0.67–2.84)
TABLE 1.
Demographic, comorbidities, and procedure characteristics by DS and non-DS control groups
| DS (n = 150) | Non-DS control (n = 146) | Total (n = 296) | P | |
|---|---|---|---|---|
| Demographics | ||||
| Age at procedure (years)* | 15.0 [5.0, 18.0] | 13.0 [8.0, 16.0] | 14.0 [6.0, 17.0] | 0.012 |
| Weight (kg) | 48.0 [20.8, 60.4] | 46.0 [25.6, 65.5] | 46.7 [22.8, 62.0] | 0.417 |
| Height (cm)* | 138.1 [104.9, 149.0] | 151.8 [120.0, 161.0] | 144.0 [113.5, 157.6] | <0.001 |
| BMI (kg/m2)* | 23.0 [18.8, 28.1] | 20.2 [17.6, 26.9] | 22.0 [18.2, 27.6] | 0.033 |
| Sex at birth | 0.560 | |||
| Male | 84 (56.0%) | 76 (52.1%) | 160 (54.1%) | |
| Female | 66 (44.0%) | 70 (47.9%) | 136 (45.9%) | |
| Race/ethnicity* | <0.001 | |||
| Hispanic/Latino | 74 (62.2%) | 75 (59.5%) | 149 (60.8%) | |
| White | 38 (31.9%) | 19 (15.1%) | 57 (23.3%) | |
| Black/African American | 5 (4.2%) | 11 (8.7%) | 16 (6.5%) | |
| Asian | 2 (1.7%) | 10 (7.9%) | 12 (4.9%) | |
| Other | 0 (0.0%) | 11 (8.7%) | 11 (4.5%) | |
| Comorbidities | ||||
| Autism* | <0.001 | |||
| No | 114 (76.0%) | 141 (96.6%) | 255 (86.1%) | |
| Yes | 36 (24.0%) | 5 (3.4%) | 41 (13.9%) | |
| Thyroid function* | <0.001 | |||
| Not present | 101 (67.3%) | 144 (98.6%) | 245 (82.8%) | |
| Treated | 28 (18.7%) | 0 (0.0%) | 28 (9.5%) | |
| Untreated | 21 (14.0%) | 2 (1.4%) | 23 (7.8%) | |
| Diabetes | 0.170 | |||
| No | 140 (93.3%) | 142 (97.3%) | 282 (95.3%) | |
| Yes | 10 (6.7%) | 4 (2.7%) | 14 (4.7%) | |
| Cardiac condition* | <0.001 | |||
| Not present | 76 (50.7%) | 144 (98.6%) | 220 (74.3%) | |
| Congenital, no surgery | 35 (23.3%) | 2 (1.4%) | 37 (12.5%) | |
| Congenital, surgery done | 39 (26.0%) | 0 (0.0%) | 39 (13.2%) | |
| History of hypertension | 0.060 | |||
| No | 148 (100.0%) | 142 (97.3%) | 290 (98.6%) | |
| Yes | 0 (0.0%) | 4 (2.7%) | 4 (1.4%) | |
| Procedure details | ||||
| Total time of sedation (minutes)* | 82.5 [58.0, 114.0] | 68.0 [53.0, 87.0] | 73.0 [56.0, 103.0] | <0.001 |
| Procedure type* | ||||
| Lumbar puncture | 44 (29.3%) | 25 (17.1%) | 69 (23.3%) | |
| Imaging (CT, MRI, CT angiogram, MAG3 scan) | 50 (33.3%) | 13 (8.9%) | 63 (21.3%) | |
| Renal biopsy | 5 (3.3%) | 26 (17.8%) | 31 (10.5%) | |
| Wound cleaning/Abscess drainage | 1 (0.7%) | 17 (11.6%) | 18 (6.1%) | |
| Auditory brainstem test | 3 (2.0%) | 12 (8.2%) | 15 (5.1%) | |
| Other | 47 (31.3%) | 53 (36.3%) | 100 (33.8%) | |
| Primary diagnosis* | ||||
| DSRD | 66 (44.0%) | 0 (0.0%) | 66 (22.3%) | |
| Neurologic disorder (epilepsy/other neurologic disorder) | 39 (26.0%) | 40 (27.4%) | 79 (26.7%) | |
| GI | 3 (2.0%) | 15 (10.3%) | 18 (6.1%) | |
| Neoplastic | 5 (3.3%) | 6 (4.1%) | 11 (3.7%) | |
| Diagnostic testing (ophthalmology/hearing/biopsy) | 37 (24.7%) | 85 (58.2%) | 122 (41.2%) | |
Data are frequency (%) or median [25th, 75th percentiles].
P < 0.05 (in bold font).
DS: Down syndrome. The frequency and percentage of incomplete variables: race/ethnicity (n = 51, 17.23%); history of hypertension (n = 2, 0.68%).
Differences in demographics and clinical characteristics
At the time of the procedure, individuals with DS had a slightly higher median age at the time of the procedure (15.4 years [5.7, 18.6] vs. 13.2 years [8.3, 16.2], P = 0.012) and BMI (23.0 kg/m2 [18.8, 28.1] vs. 20.2 kg/m2 [17.6, 26.9], P = 0.033), but a lower median height (138.1 cm [104.9, 149.0] vs. 151.8 cm [120.0, 161.0], P < 0.001) compared to non-DS controls (Table 1). Differences in race/ethnicity were observed, with higher proportions of Hispanic/Latino and White individuals in the DS group (P < 0.001). Further, individuals with DS were more likely to have autism (P < 0.001), thyroid dysfunction (P < 0.001), and congenital cardiac conditions (P < 0.001) than those in the control group. Finally, individuals with DS had a longer median duration of procedural sedation (82.5 min [58.0, 114.0] vs. 68.0 min [53.0, 87.0], P < 0.001). This latter effect was driven by a higher quantity of very short procedures such as wound cleaning/abscess draining and renal biopsy in the non-DS control group (P = 0.004, 95%CI: 0.01–0.39 and P = 0.003, 95% CI: 0.06–0.43, respectively). In addition, individuals with DS were also noted to have longer neuroimaging studies (e.g., MRI with and without contrast compared to CT head) than individuals non-DS controls.
Comparison of blood pressure measurements
Table 2 summarizes the comparison of blood pressure metrics between individuals with DS and non-DS controls. While baseline SBP, DBP, and PP were comparable between the two groups, individuals with DS showed lower median procedural SBP (86.0 mmHg [79.0, 94.0] vs. 96.5 mmHg [87.0, 105.0], P < 0.001) and DBP (45.0 mmHg [38.0, 54.0] vs. 53.8 mmHg [46.0, 62.0], P < 0.001). Additionally, procedural nadir values were lower for individuals with DS, including SBP (74.0 mmHg [68.0, 81.0] vs. 84.0 mmHg [76.0, 95.0], P < 0.001), DBP (35.5 mmHg [30.0, 41.0] vs. 45.5 mmHg [38.0, 53.0], P < 0.001), and PP (31.5 mmHg [25.0, 38.0] vs. 26.5 mmHg [18.0, 33.0], P < 0.001). Consistent results were found when analyzing percentiles for baseline SBP (P = 0.666), median SBP (P = 0.006), and nadir SBP (P = 0.006).
TABLE 2.
Comparison of blood pressure metrics between individuals with DS and non-DS controls
| DS (n = 150) | Non-DS control (n = 146) | Total (n = 296) | P | |
|---|---|---|---|---|
| Systolic blood pressure (SBP) | ||||
| Baseline | 112.0 [100.0, 121.0] | 109.8 [101.0, 117.3] | 110.1 [100.5, 120.0] | 0.293 |
| Baseline percentile | 59.0 [42.0, 86.0] | 60.0 [38.0, 84.0] | 60.0 [40.0, 85.0] | 0.666 |
| Median* | 86.0 [79.0, 94.0] | 96.5 [87.0, 105.0] | 91.0 [82.2, 100.0] | <0.001 |
| Median percentile* | 14.0 [4.0, 38.0] | 29.0 [8.0, 50.0] | 20.5 [5.0, 48.0] | 0.006 |
| Nadir* | 74.0 [68.0, 81.0] | 84.0 [76.0, 95.0] | 79.0 [72.0, 89.0] | <0.001 |
| Nadir percentile* | 2.0 [1.0, 12.0] | 10.5 [1.0, 32.0] | 4.0 [1.0, 23.0] | 0.006 |
| Diastolic blood pressure (DBP) | ||||
| Baseline | 68.2 [61.0, 79.0] | 68.0 [60.0, 74.5] | 68.0 [60.0, 77.0] | 0.302 |
| Median* | 45.0 [38.0, 54.0] | 53.8 [46.0, 62.0] | 49.0 [41.0, 58.0] | <0.001 |
| Nadir* | 35.5 [30.0, 41.0] | 45.5 [38.0, 53.0] | 40.0 [32.5, 48.0] | <0.001 |
| Pulse pressure | ||||
| Baseline | 41.2 [35.0, 47.3] | 41.0 [31.5, 51.0] | 41.0 [32.8, 49.0] | 0.633 |
| Median | 40.2 [36.0, 48.0] | 41.0 [35.0, 47.0] | 41.0 [35.0, 47.5] | 0.353 |
| Nadir* | 31.5 [25.0, 38.0] | 26.5 [18.0, 33.0] | 29.0 [19.5, 35.5] | <0.001 |
Data are frequency and percentage or median [25th, 75th percentiles].
P < 0.05 (in bold font).
Pulse Pressure (PP = SBP – DBP); DS: Down syndrome.
Figure 1 illustrates individual trajectories and overall trends in SBP, DBP, and PP at five-minute intervals during the procedural sedation for both groups. Panels (a) and (b) show that both groups begin with a similar preprocedure (baseline) SBP and DBP, though individuals with DS exhibit greater variability in these measures. As time progresses, during sedation, SBP and DBP decline in both groups, with individuals with DS experiencing a more rapid decrease, reaching a lower nadir compared to non-DS controls. Although both groups gradually recover, individuals with DS exhibit a slower recovery in SBP and DBP. These findings suggest that individuals with DS may experience greater fluctuations in SBP and DBP during sedation and may recover more slowly toward baseline values than non-DS controls. Panel (c) presents that PP is similar for both groups before sedation, with slight fluctuations. While PP decreases in both groups during sedation, individuals with DS show a more pronounced increase in PP starting around 40 min into the procedure, particularly toward the later stages. This suggests that individuals with DS experience greater fluctuations in PP and a less predictable response to sedation compared to non-DS controls.
FIGURE 1.
Change in systolic blood pressure (SBP, panel a); diastolic blood pressure (DBP, panel b), and pulse pressure (SBP – DBP, panel c) during sedation between individuals with Down syndrome (DS) and non-DS controls. Note, y-axis is different for the three panels to best demonstrate differences between groups.
Figure 2 shows the distribution of mean percentage changes in SBP and DBP from baseline during procedural sedation for individuals with DS and non-DS controls. The distribution of non-DS controls is centered closer to 0, reflecting smaller and more consistent reductions in SBP and DBP. In contrast, the DS group shows a broader, left-shifted distribution, indicating greater reductions and increased variability. Despite some overlap between the two groups, these findings further support that individuals with DS may experience more substantial and variable decline in blood pressure during sedation compared to non-DS controls.
FIGURE 2.
Distribution of mean percentage changes in systolic blood pressure (SBP, panel a) and diastolic blood pressure (DBP, panel b) from baseline during procedural sedation between individuals with Down syndrome (DS) and non-DS controls, shown in 5% intervals.
Table 3 summarizes the average rate of change in SBP and DBP from baseline to nadir in individuals with DS compared to non-DS controls. The DS group exhibited significantly greater reduction in both SBP (mean difference [95% CI]: −12.3 mmHg [−16.1, −8.6], P < 0.001) and DBP (−10.2 mmHg [−13.3, −7.0], P < 0.001) compared to the non-DS controls (Model A). These differences are visually represented in Fig. 3, which illustrates group-specific blood pressure reductions from baseline to nadir. These group differences remained significant after adjusting for covariates including sex, age, weight, height, BMI, and total time of sedation. Further analysis (Model B) indicates that age, weight, and height modified the mean blood pressure changes from baseline to nadir. Specifically, for every additional year in age, the mean SBP in the DS group decreased by −0.8 mmHg [−1.4, −0.2], and the mean DBP decreased by −1.0 mmHg [−1.5, −0.5] compared to non-DS controls. Similarly, each 1-kg increase in weight was associated with a mean SBP decrease of −0.2 mmHg [−0.3, −0.04] and a DBP decrease of −0.2 mmHg [−0.3, −0.1]. For every 1-cm increase in height, the corresponding decrease was −0.2 mmHg [−0.3, −0.04] for SBP and −0.2 mmHg [−0.3, −0.1] for DBP.
TABLE 3.
The average rate of change in SBP and DBP from baseline to the nadir during procedural sedation, stratified by DS and non-DS control groups and demographics
| Nadir vs. baseline | ||||
|---|---|---|---|---|
| Coef. | SE | [95% CI] | P | |
| SBP Model A: Group × Time | ||||
| DS vs. non-DS control | −12.34 | 1.92 | [−16.10, −8.58] | <0.001 |
| Group-specific estimates | ||||
| Non-DS control | −22.82 | 1.37 | [−25.49, −20.14] | <0.001 |
| DS | −35.16 | 1.35 | [−37.80, −32.52] | <0.001 |
| SBP Model B: Group × Time × Covariate | ||||
| Age (years) | ||||
| DS vs. non-DS control | −0.8 | 0.30 | [−1.39, −0.21] | 0.007 |
| Weight (kg) | ||||
| DS vs. Non-DS control | −0.19 | 0.08 | [−0.34, −0.04] | 0.012 |
| Height (cm) | ||||
| DS vs. non-DS control | −0.16 | 0.06 | [−0.27, −0.04] | 0.007 |
| DBP Model A: Group × Time | ||||
| DS vs. non-DS control | −10.15 | 1.63 | [−13.34, −6.96] | <0.001 |
| Group-specific estimates | ||||
| Non-DS control | −21.85 | 1.16 | [−24.12, −19.58] | <0.001 |
| DS | −32.00 | 1.14 | [−34.24, −29.76] | <0.001 |
| DBP Model B: Group × Time × Covariate | ||||
| Age (years) | ||||
| DS vs. Non-DS control | −0.96 | 0.26 | [−1.47, −0.46] | <0.001 |
| Weight (kg) | ||||
| DS vs. Non-DS control | −0.21 | 0.07 | [−0.34, −0.09] | 0.001 |
| Height (cm) | ||||
| DS vs. non-DS control | −0.19 | 0.05 | [−0.28, −0.09] | <0.001 |
DBP, diastolic blood pressure; DS, Down syndrome; SBP, systolic blood pressure.
*P < 0.05 (in bold font).
FIGURE 3.
Average change in systolic blood pressure (SBP, panel a) and diastolic blood pressure (DBP, panel b) from baseline to the nadir (lowest recorded level) during procedural sedation between individuals with Down syndrome (DS) and non-DS controls.
The baseline SBP and DBP for all individuals in this study were compared to the average of a preprocedural and postprocedural BP recording. Individuals with DS had no statistically significant differences on SBP (average percentile: 44, P = 0.19, 95% CI: 0.67–2.31) or DBP (P = 0.41, 95% CI: 0.33–1.49). A similar, nonstatistically significant, theme was present in non-DS controls for SBP (average percentile: 53, P = 0.69, 95% CI: 0.89–1.73) and DBP (P = 0.53, 95% CI: 0.55–1.42).
DISCUSSION
This study found that children and young adults with DS undergoing procedural sedation experienced greater reductions in both SBP and DBP compared to non-DS controls. This pattern was demonstrated at nearly all time points, particularly from baseline to nadir, and was consistent regardless of sedation duration. Importantly, these blood pressure differences were present after adjusting for demographic factors such as age, weight, and height. To our knowledge, this is the first study to identify blood pressure differences in children and young adults with DS specifically during procedural sedation.
Although previous studies have reported lower baseline blood pressure in patients with DS compared to non-DS controls [13,14], we did not observe baseline differences in our study sample. This may be because our baseline measurements were taken immediately preceding a procedure and it is possible that children and young adults with DS may be more anxious in these settings than the control cohort [15,16]. There were notable differences between the baseline SBP percentiles and pre/post procedural SBP percentiles for the DS cohort appreciated (15 percentile points difference), but this was not statistically significant. While repeated measures were utilized in this study as part of clinical standard of care, all individuals knew they were having a procedure performed which may have impacted the assessment. As BP is fluctuant and can be influenced by a variety of factors, including stress, this could be an explanation for this finding and is supported by the observed percentile differences in the pre/post cohort although these were not statistically significant [16,17]. Additionally, the DS group in our study was slightly older than the non-DS control cohort, which may have contributed to the higher reported baseline blood pressure measurement [18].
The etiology of individuals with DS having more dramatic declines in SBP and DBP are unknown although multiple hypotheses exist. Multiple studies have shown that individuals with DS have poor end-vascular resistance, which is thought to be related to autonomic dysfunction [6,7,10,13,19,20]. Additionally, previous studies suggest that individuals with DS are more likely to exhibit chronotropic incompetence in response to sympathetic stimuli [8,9] and are more likely to exhibit bradycardia during sedation [11,12,21].
The impact of these findings may be clinically significant. Prior literature has suggested a higher rate of postoperative cognitive dysfunction and demonstrated higher rates of delayed awakening after anesthesia in individuals with DS [22,23]. This could potentially be explained by poor perfusion of the central nervous system as a secondary phenomenon in the setting of systemic hypotension. This hypothesis would need to be validated by assessment of cerebral blood flow during procedural sedation, which can be investigated using noninvasive methods such as transcranial Doppler ultrasound (TCD) and therefore may be a feasible next step in this study [24,25]. In addition, there is potential for therapeutic intervention on this systemic (and potentially central) phenomenon using blood pressure raising therapies such as steroids/mineralocorticoid compounds or other vasoactive agents should cerebral blood flow match systemic blood flow in this population.
This study is not without limitations. As a retrospective study based on clinically acquired data, it lacked a standardized research protocol for data collection. Instead, data were collected according to institutional clinical protocols, which may have introduced variability. Although the study included a weight- and sex-matched control cohort of individuals without DS, the small sample size for both groups – due to multiple exclusion criteria – limited the statistical power to detect differences between groups throughout the procedural sedation. Similarly, due to the lower sample size, individuals with other neurodevelopmental disorders (including autism spectrum disorder) were permitted in the non-DS control group. Although inclusion/exclusion criteria were rigid, which would limit many neurodevelopmental disorders that affect cardiopulmonary function from being included, this broader inclusion into the control group may limit generalizability. Future, larger, studies would benefit from sub-analyzing individuals with neurodevelopmental disorders against individuals with DS. Particularly, our analysis focused on the changes in blood pressure from baseline to nadir. While this approach provided valuable insight into the hemodynamic changes after beginning procedural sedation, increasing the sample size in both groups could facilitate more thorough longitudinal analyses, estimating the average rate of blood pressure change for every unit increase in sedation time and allowing for exploration of within-individuals fluctuations over time. This study was conducted at a single center, which introduces ascertainment and severity bias, particularly in the DS group. For example, we observed a higher-than-typical rate of procedural sedation among individuals suffering from DSRD, which may not be representative of the broader DS population. Furthermore, the generalizability of our findings may be restricted by a limited number of procedural sedation physicians administering treatment. In addition, while oxygen saturation is available to clinicians during procedural sedation, it is not logged in the electronic medical record system for short procedures and as such this was not available to the study team. Lastly, the variety of procedures received by individuals in both groups may introduce potential heterogeneity in the data, as different procedures may impact sedation duration, stress level, and physiological responses differently. Future research with larger, multicenter cohorts and standardized sedation protocols is needed to confirm and expand upon our findings.
CONCLUSION AND FUTURE DIRECTIONS
This study identified significantly larger declines in SBP and DBP during procedural sedation in children and young adults with DS compared to non-DS controls. Future research should investigate the clinical implication of these observed blood pressure changes in children and young adults with DS undergoing procedural sedation, including the potential for decreased cerebral blood flow in this population during sedation.
ACKNOWLEDGEMENTS
The authors wish to thank the Byrne family and AGAPE foundation for their generous philanthropy to research in individuals with Down syndrome.
Previously presented: no.
Sources of funding: National Heart, Lung and Blood Institute (NHLBI) at the National Institutes of Health (K23HL155898).
Conflicts of interest
There are no conflicts of interest.
Footnotes
Abbreviations: BMI, body mass index; DBP, diastolic blood pressure; DS, Down syndrome; PP, pulse pressure; SBP, systolic blood pressure
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