Intensive Care Unit Analgosedation after Cardiac Surgery in Children with Williams Syndrome – a Matched Case-Control Study

doi:10.21203/rs.3.rs-3150158/v1

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Intensive Care Unit Analgosedation after Cardiac Surgery in Children with Williams Syndrome – a Matched Case-Control Study

https://doi.org/10.21203/rs.3.rs-3150158/v1

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published 26 Oct, 2023

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Objective: Cardiovascular abnormalities are common in patients with Williams syndrome (WS) and frequently require surgical intervention necessitating analgesia and sedation in a population with a unique neuropsychiatric profile, potentially increasing the risk of adverse cardiac events (ACE) during the perioperative period. Despite this risk, the overall postoperative analgosedative requirements in patients with WS in the cardiac intensive care unit (CICU) have not yet been investigated. Our primary aim was to examine the analgosedative requirement in patients with WS after cardiac surgery compared to a control group. Our secondary aim was to compare the risk of major ACE and mortality between the two groups.

Design: Matched case-control study.

Setting: Pediatric CICU at a Tertiary Children’s Hospital.

Patients: Patients with WS and age-matched controls who underwent cardiac surgery and were admitted to the CICU after cardiac surgery between July 2014 and January 2021.

Interventions: None

Measurements and Main Results: Postoperative outcomes and total doses of analgosedative medications were collected in the first six days after surgery for the study groups. Median age was 29.8 (12.4-70.8) months for WS and 23.5 (11.2-42.3) months for controls. Across all study intervals (48h and first 6 post-operative days), there were no differences between groups in total doses of morphine equivalents (5.0 mg/kg vs 5.6mg/kg, p=0.7 and 8.2mg/kg vs 10.0 mg/kg, p=0.7), midazolam equivalents (1.8mg/kg vs 1.5mg/kg, p=0.4 and 3.4 mg/kg vs 3.8mg/kg, p=0.4), or dexmedetomidine (20.5 mcg/kg vs 24.4 mcg/kg, p=0.5 and 42.3 mcg/kg vs 39.1 mcg/kg, p=0.3). There was no difference in major ACE or mortality.

Conclusions: Patients with WS received similar analgosedative medication doses compared with controls. There was no difference in the frequency of major ACE (including cardiac arrest, extracorporeal membrane oxygenation, and surgical reintervention) or mortality between the two groups. Patients with WS can receive similar analgosedation to controls without untoward cardiovascular events.

Williams Syndrome

Sedation

Analgesia

Cardiac Surgery

First described in the early 1960s, Williams syndrome (WS), also known as Williams-Beuren syndrome, is a multi-system disorder characterized by abnormal cardiovascular, connective tissue, and neurologic development resulting from a deletion of 26-to-28-genes on chromosome 7q11.23 [1–3]. The most well-described genotype-phenotype association is that of the ELN gene which results in an elastin deficiency and is responsible for the most threatening phenotypic manifestations, including supravalvar aortic stenosis, pulmonary arterial stenosis, coronary artery abnormalities, and other systemic arterial stenoses [4,5]. These cardiovascular abnormalities are present in about 80% of patients with WS and require intervention in up to 30% of those presenting during the first year of life [6,7].

The arterial pathology in patients with WS, including coronary artery stenosis, increases the risk of perioperative and periprocedural cardiac complications which are compounded by the risk of arterial hypotension with anesthesia and analgosedation [8,9]. Although the mechanism of cardiac compromise in patients with WS is not fully understood, the risk of sudden death in this group is estimated to be 25-to-100-fold higher than the general population [10]. The increased awareness of this perioperative risk has resulted in the development of risk stratification systems and management strategies [8,11]. These strategies have focused on the immediate perioperative period, but patients with WS remain at an increased risk of cardiovascular compromise beyond the operation, a risk that may be exacerbated by analgesia and sedation.

In addition to their complex cardiovascular profile and hemodynamic derangements, patients with WS have a unique neurocognitive profile that is particularly relevant to the postoperative analgosedation requirements. Specifically, WS is not only typified by mild to moderate intellectual deficits, but perhaps more germanely, they frequently have generalized and specific anxieties, phobias, difficulties with sensory modulation, and hyperactivity, all of which have significant implications for analgosedation [12–26].

Our anecdotal experience suggests patients with WS may be less responsive to postoperative analgosedation than other non-syndromic patients, which can have direct implications on their management in the intensive care unit. Therefore, we aimed to test the hypothesis that patients with WS have a greater analgosedative use compared to matched controls.

Study Cohort and Data Source: Following approval from the Stanford University School of Medicine Institutional Review Board (Protocol 43206, approval date 9/28/2017) and in accordance with ethical standards of the responsible committee on human experimentation and the Helinski Declaration of 1975, we performed a retrospective study of all patients with WS who underwent cardiothoracic surgery at Lucile Packard Children’s Hospital Stanford from June 2014 to January 2021. Given the retrospective study design, the requirement for informed consent was waived. We used our institutional cardiothoracic surgical database to identify a control group of non-syndromic subjects. We sought to employ a 2:1 matching scheme using an age within 6 months of the age of each matched WS subject and a cardiothoracic surgical operation of similar complexity (i.e., complex pulmonary artery reconstruction, repair of SVAS, and coronary artery repair). Our numbers were insufficient to match 2 control subjects for each WS subject, as described by Yokota et al [27]. The presence or absence of a genetic syndrome was based on genetic testing available or the assessment of the clinicians caring for the patients.

Data Collection: The collected study data included demographic and anthropometric data, preoperative clinical data, surgical procedure data, and postoperative clinical data. Cardiothoracic surgical data included the surgical procedure, total bypass time, cross-clamp time, and any complications. Postoperative clinical data included duration of mechanical ventilation, duration of chest tubes, days to chest closure (when delayed sternal closure was employed), cardiac intensive care unit (CICU) and hospital length of stay (LOS), occurrence of cardiac arrest, need for extracorporeal membranous oxygenation (ECMO), occurrence of a cerebrovascular accident, and surgical re-intervention during the hospitalization. Postoperative pharmacologic therapy data included hourly doses of analgesics, sedatives, and neuromuscular blocking agents. The analgesic medications included morphine, hydromorphone, and fentanyl (which were converted to morphine equivalents). The sedative medications included midazolam and lorazepam (converted to midazolam equivalents), and dexmedetomidine.

Institutional Protocol: In our institution, we employ a pre-procedural risk stratification and management algorithm for all patients with WS, which has been associated with greater periprocedural hemodynamic stability and a lower incidence of adverse cardiac events [28,29]. This algorithm allows for collection of routine preoperative laboratory studies and pre-procedural intravenous hydration to maintain euvolemia and mitigate the risk of hypotension, decreased preload, and compromised coronary perfusion pressure during anesthesia and analgosedation. The goal post-operative level of sedation for patients in both groups was the same with a goal State Behavioral Scale score of -1 to 0 for the first 24 hours [30].

Statistical Analysis: We described continuous variables with nonparametric distributions with median and interquartile range (IQR), and categorical variables with count (%). We compared clinical and outcome variables between patients with WS and controls using Wilcoxon rank-sum test for continuous variables and Fisher’s exact test for categorical variables. Univariate and multivariable regression modeling was used to determine variables associated with morphine and versed equivalent doses over the first 48-hours and 6 days postoperatively. The final regression models were adjusted for number of prior surgeries, age at surgery, and aortic cross-clamp time. The primary aim was to compare the amount of analgosedation between the WS cohort and controls. Secondarily, we analyzed the frequency of individual major adverse cardiac events, as well as the risk of a composite adverse cardiac event (ACE) endpoint (death, cardiac arrest, ECMO, and surgical reintervention during the inpatient period) between patients with WS and controls. Findings were presented as beta coefficient or odds ratio (OR) with a 95% confidence interval (CI), as appropriate. A p value of < 0.05 was used to define statistical significance. Statistical analyses were performed using Stata (Version 15.1; College Station, TX).

During the study period, 41 patients with WS and 54 controls (68% vs 54% male, p= 0.2) were identified. As shown in Table 1, demographic and baseline variables were similar between the WS and control groups. The median age for the WS group was 29.8 months compared to 23.5 months for controls (p=0.1). The median weight was 10.8 kg and 11.9 kg for WS and non-WS, respectively (p=0.8). There were no significant differences between cardiopulmonary bypass time (CPB), although patients with WS had significantly more aortic cross-clamp time in conjunction with a greater frequency of surgery involving systemic arterial structures, including the aorta, aortic valve, and coronary arteries (Table 2).

As shown in supplemental Table 1, there was no difference between the two groups in total doses of morphine equivalents, midazolam equivalents, or dexmedetomidine in the first 48 postoperative hours. Similarly, there was no difference between the two groups over the total six-day post operative time frame in morphine equivalents, midazolam equivalents , or dexmedetomidine. There was a difference in vecuronium use in the first 48 hours between WS and non-WS patients but no difference over the first 6 days. There were also no differences between the groups in either interval on adjusted analyses (Table 3) among postoperative doses of morphine equivalents, midazolam equivalents, dexmedetomidine, or vecuronium.

There were no significant differences between the two groups in length of stay, duration of mechanical ventilation, major ACE, or mortality. The odds of composite major ACE were similar between the two groups when adjusted for total midazolam equivalents (OR 0.9, 95% CI 0.3, 3.2, p=0.9) or total morphine equivalents (OR 1.3, 95% CI 0.4, 4.6, p=0.7).

When analyzing those who received total doses of morphine equivalents in the upper tertile (>16mg/kg over 6 days) for each group (WS vs non-WS), there was no difference between the groups in the incidence of death (8% vs 0%, p>0.99), cardiac arrest (8% vs 0%, p>0.99), ECMO (42% vs 36%, p=0.2), chest exploration (0% vs 9%. p=0.5) or surgical reintervention (17% vs 36%, p=0.4). Similarly, when comparing those who received total doses of versed equivalents in the upper tertile (>6mg/kg over 6 days) there was no difference between the two groups in frequency of death (8% vs 0%, p=0.5), cardiac arrest (zero events), ECMO (33% vs 23%, p=0.7), chest exploration (0% vs 8%, p>0.99) or surgical reintervention (8% vs 23%, p=0.6).

This study was designed to assess the postoperative analgosedation requirement in patients with WS after cardiac surgery compared to a matched control population. The main finding was that there were no significant differences in the doses of morphine equivalents, midazolam equivalents, dexmedetomidine, or neuromuscular blocking agents. Secondly, we found that there was no increased frequency or risk of postoperative major ACE in WS, even amongst the patients who received the most analgosedation in both groups. This represents the first report of the analgosedation requirements and outcomes in the WS population beyond the immediate perioperative period.

Disproving our initial hypothesis, we found no differences in the analgosedation management between the WS and control groups, both in the first 48 hours and across the first six postoperative days. We can envisage several potential reasons for this result. It is possible there is an intrinsic difference between the groups but owing to our relatively large experience with WS and high level of vigilance of their hemodynamic state, we have been able to mitigate the risks. Given the known periprocedural risks in WS and our work in this area, especially as it pertains to avoidance of hypotension, decreased preload, and poor coronary artery perfusion, this seems plausible [11,29,31]. Conversely, it is possible there is an intrinsic difference, but due to the complexity of the interventions of the matched controls, some of the postoperative management philosophy we typically employ in WS were also used in controls. Further, it is possible that any avoidance of analgosedation in the WS group is counteracted by the potential increased need resulting from the neuropsychiatric associations previously described. It is also possible there is no intrinsic difference between the two groups. At face value, our data seem to support that conclusion, but it does not mesh well with what has been previously demonstrated in WS. It may also be there is an intrinsic difference, but our study was underpowered to detect it. The distributions of the confidence intervals in our analyses hint this could be a possibility. A future, multicenter study would be helpful to further explore the question of what impact variations in perioperative management may play in adverse cardiovascular events in WS.

A second important finding was that there was no difference in risk of major adverse events between patients with WS and the control group. Given the known increased risk in WS of cardiovascular compromise leading to significant morbidity and mortality, this is a finding that was unexpected. Like the prior discussion on the finding of analgosedation, we can see four potential explanations for this result. First, our low rate of major adverse cardiovascular events could be a result of a WS population in which there is no increased intrinsic risk. Given the work of Hornik et al that showed such events are common in WS and are related to complexity of the operative procedure, our result would seem to be opposed to that prior work [31]. Conversely, there could be an intrinsic difference between the groups, but our study was insufficiently powered to detect it. Finally, it is possible that at a certain level of surgical complexity, the role of WS may not be particularly contributory to the risk of adverse events. That is, when severe disease requiring complex surgical interventions is present, which it was in both of our study groups, the impact of the presence of WS is less important [32,33]. This possibility could certainly fit with prior work on WS, as Hornik and colleagues did not employ a matched control group in their study. It is important to appreciate that despite the significant progress in the understanding of the role of genetics in the pathogenesis of congenital heart disease over the past 15 years, elucidating the extent to which genetic abnormalities contribute to morbidity and mortality in complex cardiac disease is challenging due to extracardiac manifestations and genetic heterogeneity among patients [34].

Limitations: This report is subject to the inherent limitations of a single-center retrospective analysis. Further, the population sample size may be robust by comparison to other reports, but it remains small, nonetheless. It is possible that our conclusions could be altered with a larger, multi-centered analysis. As such, these conclusions are not generalizable to the broader population, and analgosedation in the WS population must be carefully titrated to each patient’s specific needs. Additional limitations include the fact that nursing assessments of the degree of sedation were not routinely recorded. Therefore, it is possible that while there were no differences in the pharmacologic interventions between the two groups, the adequacy of sedation may have been inferior for the WS group, despite the fact that the goal level of sedation between the two is similar and fluctuates only with patient specific factors.

We found patients with WS receive similar amounts of analgosedation compared to matched controls in our center without any evidence of increased risk of morbidity or mortality. Amongst patients with similar complex surgical repairs, the postoperative management of pain and sedation in WS might not have to be different based on the presence of WS alone.

The authors have no relevant financial or non-financial interests to disclose. The authors did not receive any support from any organizations for the submitted work.

Financial Disclosure: No financial support was required for this study.

Collins RT (2018) Cardiovascular disease in Williams syndrome. Curr Opin Pediatr 30(5):609–615. 10.1097/MOP.0000000000000664
Beuren AJ, Apitz J, Harmjanz D (1962) Supravalvular aortic stenosis in association with mental retardation and a certain facial appearance. Circulation 26:1235–1240. 10.1161/01.cir.26.6.1235
Williams JC, Barratt-Boyes BG, Lowe JB (1961) Supravalvular aortic stenosis. Circulation 24:1311–1318. 10.1161/01.cir.24.6.1311
Keating MT (1995) Genetic approaches to cardiovascular disease. Supravalvular aortic stenosis, Williams syndrome, and long-QT syndrome. Circulation 92(1):142–147. 10.1161/01.cir.92.1.142
Pober BR, Johnson M, Urban Z (2008) Mechanisms and treatment of cardiovascular disease in Williams-Beuren syndrome. J Clin Invest 118(5):1606–1615. 10.1172/JCI35309
Collins RT, Kaplan P, Somes GW, Rome JJ (2010) Long-term outcomes of patients with cardiovascular abnormalities and williams syndrome. Am J Cardiol 105(6):874–878. 10.1016/j.amjcard.2009.10.069
Collins RT (2013) Cardiovascular disease in Williams syndrome. Circulation 127(21):2125–2134. 10.1161/CIRCULATIONAHA.112.000064
Matisoff AJ, Olivieri L, Schwartz JM, Deutsch N (2015) Risk assessment and anesthetic management of patients with Williams syndrome: a comprehensive review. Paediatr Anaesth 25(12):1207–1215. 10.1111/pan.12775
Staudt GE, Eagle SS (2021) Anesthetic Considerations for Patients With Williams Syndrome. J Cardiothorac Vasc Anesth 35(1):176–186. 10.1053/j.jvca.2020.01.022
Wessel A, Gravenhorst V, Buchhorn R, Gosch A, Partsch CJ, Pankau R (2004) Risk of sudden death in the Williams-Beuren syndrome. Am J Med Genet A 127A(3):234–237. 10.1002/ajmg.a.30012
Collins Ii RT, Collins MG, Schmitz ML, Hamrick JT (2017) Peri-procedural risk stratification and management of patients with Williams syndrome. Congenit Heart Dis 12(2):133–142. 10.1111/chd.12447
Atkinson J, Braddick O (2011) From genes to brain development to phenotypic behavior: “dorsal-stream vulnerability” in relation to spatial cognition, attention, and planning of actions in Williams syndrome (WS) and other developmental disorders. Prog Brain Res 189:261–283. 10.1016/B978-0-444-53884-0.00029-4
Atkinson J, Braddick O, Anker S et al (2003) Neurobiological models of visuospatial cognition in children with Williams syndrome: measures of dorsal-stream and frontal function. Dev Neuropsychol 23(1–2):139–172. 10.1080/87565641.2003.9651890
Bellugi U, Lichtenberger L, Jones W, Lai Z, St George MI (2000) The neurocognitive profile of Williams Syndrome: a complex pattern of strengths and weaknesses. J Cogn Neurosci 12(Suppl 1):7–29. 10.1162/089892900561959
Doyle TF, Bellugi U, Korenberg JR, Graham J (2004) Everybody in the world is my friend” hypersociability in young children with Williams syndrome. Am J Med Genet A 124A(3):263–273. 10.1002/ajmg.a.20416
Dykens EM (2003) Anxiety, fears, and phobias in persons with Williams syndrome. Dev Neuropsychol 23(1–2):291–316. 10.1080/87565641.2003.9651896
Järvinen-Pasley A, Bellugi U, Reilly J et al (2008) Defining the social phenotype in Williams syndrome: a model for linking gene, the brain, and behavior. Dev Psychopathol 20(1):1–35. 10.1017/S0954579408000011
Jones W, Bellugi U, Lai Z et al (2000) II. Hypersociability in Williams Syndrome. J Cogn Neurosci 12(Suppl 1):30–46. 10.1162/089892900561968
Kirchner RM, Martens MA, Andridge RR (2016) Adaptive Behavior and Development of Infants and Toddlers with Williams Syndrome. Front Psychol 7:598. 10.3389/fpsyg.2016.00598
Klein-Tasman BP, Li-Barber KT, Magargee ET (2011) Honing in on the social phenotype in Williams syndrome using multiple measures and multiple raters. J Autism Dev Disord 41(3):341–351. 10.1007/s10803-010-1060-5
Leyfer OT, Woodruff-Borden J, Klein-Tasman BP, Fricke JS, Mervis CB (2006) Prevalence of psychiatric disorders in 4 to 16-year-olds with Williams syndrome. Am J Med Genet Part B Neuropsychiatr Genet Off Publ Int Soc Psychiatr Genet 141B(6):615–622. 10.1002/ajmg.b.30344
Martens MA, Wilson SJ, Reutens DC, Research Review (2008) Williams syndrome: a critical review of the cognitive, behavioral, and neuroanatomical phenotype. J Child Psychol Psychiatry 49(6):576–608. 10.1111/j.1469-7610.2008.01887.x
Mervis CB, John AE (2010) Cognitive and behavioral characteristics of children with Williams syndrome: implications for intervention approaches. Am J Med Genet C Semin Med Genet 154C(2):229–248. 10.1002/ajmg.c.30263
Mervis CB, Kistler DJ, John AE, Morris CA (2012) Longitudinal assessment of intellectual abilities of children with Williams syndrome: multilevel modeling of performance on the Kaufman Brief Intelligence Test-Second Edition. Am J Intellect Dev Disabil 117(2):134–155. 10.1352/1944-7558-117.2.134
Morris CA (2010) The behavioral phenotype of Williams syndrome: A recognizable pattern of neurodevelopment. Am J Med Genet C Semin Med Genet 154C(4):427–431. 10.1002/ajmg.c.30286
Woodruff-Borden J, Kistler DJ, Henderson DR, Crawford NA, Mervis CB (2010) Longitudinal course of anxiety in children and adolescents with Williams syndrome. Am J Med Genet C Semin Med Genet 154C(2):277–290. 10.1002/ajmg.c.30259
Yokota R, Kwiatkowski DM, Journel C et al (2022) Postoperative Acute Kidney Injury in Williams Syndrome Compared With Matched Controls. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc 23(3):e162–e170. 10.1097/PCC.0000000000002872
Collins RT (2018) Cardiovascular disease in Williams syndrome. Curr Opin Pediatr 30(5):609–615. 10.1097/MOP.0000000000000664
Schmidt AR, Collins RT, Adusumelli Y et al (2021) Impact of Modified Anesthesia Management for Pediatric Patients With Williams Syndrome. J Cardiothorac Vasc Anesth 35(12):3667–3674. 10.1053/j.jvca.2021.04.019
Curley MAQ, Harris SK, Fraser KA, Johnson RA, Arnold JH (2006) State Behavioral Scale (SBS) A Sedation Assessment Instrument for Infants and Young Children Supported on Mechanical Ventilation. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc 7(2):107–114. 10.1097/01.PCC.0000200955.40962.38
Hornik CP, Collins RT, Jaquiss RDB et al (2015) Adverse cardiac events in children with Williams syndrome undergoing cardiovascular surgery: An analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database. J Thorac Cardiovasc Surg 149(6):1516–1522e1. 10.1016/j.jtcvs.2015.02.016
Berger JT, Holubkov R, Reeder R et al (2017) Morbidity and Mortality Prediction in Pediatric Heart Surgery: Physiological Profiles and Surgical Complexity. J Thorac Cardiovasc Surg 154(2):620–628e6. 10.1016/j.jtcvs.2017.01.050
Kumar SR, Gaynor JW, Jones LA et al (2023) The Society of Thoracic Surgeons Congenital Heart Surgery Database: 2022 Update on Outcomes and Research. Ann Thorac Surg 115(4):807–819. 10.1016/j.athoracsur.2022.12.040
Pierpont ME, Brueckner M, Chung WK et al (2018) Genetic Basis for Congenital Heart Disease: Revisited: A Scientific Statement From the American Heart Association. Circulation 138(21):e653–e711. 10.1161/CIR.0000000000000606

Table 1. Baseline Preoperative Characteristics of Study Population.
Characteristics	Total (n=95)	Non-WS (n=54)	^aWS (n=41)	p value
Age (months)	26.1 (11.8, 52.6)	23.5 (11.2, 42.3)	29.8 (12.4, 70.8)	0.1
Male	57 (60.0)	29 (53.7)	28 (68.3)	0.2
Weight (kilograms)	11.4 (7.9, 15.8)	11.9 (7.9, 15.0)	10.8 (8.1, 18.5)	0.8
Race/ethnicity Non-Hispanic White Non-Hispanic Black Hispanic Asian Other/Unknown	33 (39.3) 6 (7.1) 12 (14.3) 8 (9.5) 9 (10.7)	24 (50.0) 4 (8.3) 8 (16.7) 5 (10.4) 8 (16.7)	9 (25.0) 2 (5.6) 4 (11.1) 3 (8.3) 1 (2.8)	0.03 0.7 0.5 >0.99 0.07
Number of prior surgeries	1 (0, 2)	1 (0, 2)	1 (0, 1)	0.02
Months from last surgery	15.1 (6.9, 44.6)	13.3 (6.8, 42.3)	25.0 (6.9, 59.1)	0.2
Intubated preoperatively	4 (4.2)	3 (5.6)	1 (2.4)	0.6

Data are presented as median (interquartile range) or count (percent). A p-value of 0.05 is considered significant.^aWilliams Syndrome (WS)

Table 2. Operative Data and Postoperative Outcomes.
Characteristics	Total (n=95)	Non-WS^a (n=54)	WS^a (n=41)	p value
Cardiopulmonary bypass time (min)	309 (178, 459)	294 (135, 422)	324 (190, 492)	0.3
Cross clamp time (min)	0 (0, 65)	0 (0, 26)	55 (0, 100)	<0.001
Left-sided surgery^b	36 (37.9)	8 (14.8)	28 (68.3)	<0.001
Pulmonary artery reconstruction,	80 (84.2)	52 (96.3)	28 (68.3)	<0.001
Bilateral surgery^b,	26 (27.4)	11 (20.4)	15 (36.6)	0.1
Postoperative ICU^c LOS^d (d)	6.0 (4.1, 13.2)	5.8 (3.0, 13.8)	7.0 (4.9, 10.0)	0.3
Postoperative hospital LOS (d)	11.0 (7.0, 17.5)	8.5 (6.0, 17.0)	12.0 (8.0, 22.0)	0.2
Duration of mechanical ventilation (d)	3.3 (2.0, 7.0)	3.3 (2.0, 7.0)	4.0 (1.2, 7.0)	0.2
Chest tube duration (d)	5.0 (3.0, 9.0)	4.5 (3.0, 9.0)	5.0 (3.0, 9.0)	1 (1.4)
Cardiac arrest	1 (1.1)	0 (0)	1 (2.4)	0.4
ECMO^e	11 (11.6)	4 (7.4)	7 (17.1)	0.2
Delayed sternal closure	0 (0, 0)	0 (0, 0)	0 (0, 0)	0.4
Surgical re-intervention	8 (8.4)	6 (11.1)	2 (4.9)	0.5
Death	2 (2.1)	0 (0)	2 (4.9)	0.2
Data are presented as median (interquartile range) or count (percent). A p-value of 0.05 is considered significant.^aWilliams Syndrome (WS),^bIncludes surgery on the aortic valve, aortic arch, and/or coronary arteries. ^cIntensive Care Unit (ICU), ^dLength of stay (LOS), ^eExtracorporeal Membrane Oxygenation.

Table 3. Cumulative postoperative analgesic, sedative, and neuromuscular blockade dosages in patients with Williams syndrome compared to controls from adjusted analysis^a.
Medication	First 48 hours			Total over 6 days
Medication	β coefficient	95% CI^b	p- Value	β coefficient	95% CI	p- Value
Morphine equivalents (mg/kg)	-0.01	-1.8, 1.8	>0.99	1.0	-6.7, 8.8	0.8
Midazolam equivalents (mg/kg)	1.1	-0.5, 2.7	0.2	4.3	0.01, 8.7	0.049
Dexmedetomidine (mcg/kg)	-2.4	-11.4, 6.7	0.6	20.6	-10.6, 51.9	0.2
Vecuronium (mg/kg)	0.3	-0.4, 1.0	0.4	1.1	-0.8, 2.9	0.2
^aAdjusted analysis was performed with multivariable linear regression models with adjustment For age at surgery, number of prior surgeries, and aortic cross clamp time. ^bConfidence Interval (CI). A p-value of 0.05 is considered significant.

No competing interests reported.

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Intensive Care Unit Analgosedation after Cardiac Surgery in Children with Williams Syndrome – a Matched Case-Control Study

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