Age-Stratified Propofol Dosage for Pediatric Procedural Sedation and Analgesia.

BACKGROUND: Procedural sedation and analgesia (PSA) for diagnostic and minimally invasive therapeutic procedures has become common practice in children of all ages. Based on our clinical experience, we suspected an inverse relation between age and dosage. However, a schedule for age-stratified propofol induction and maintenance dosage for PSA was not available and could be helpful to many anesthesiologists as a reference. METHODS: We performed a retrospective cohort study of children who received procedural sedation at the Wilhelmina Children's Hospital (WKZ), a tertiary pediatric hospital part of the University Medical Center Utrecht (UMCU), between June 2007 and December 2020. We studied whether the induction (mg·kg -1 ) and maintenance (mg·kg -1 ·h -1 ) dosage is age-dependent using linear regression models. RESULTS: A total of 6438 pediatric procedures were retrieved from Anesthesia Information Management Systems (AIMS). A total of 5567 records were available for induction dose analysis and 5420 records for analysis of the maintenance dose. After adjustment for sex, American Society of Anesthesiologists (ASA) physical status classification, opioid administration, and diagnostic or interventional, we obtained a coefficient of -0.11 (95% confidence interval [CI], -0.12 to -0.11) for age (years) from a multivariable linear regression model for propofol induction dosage (mg·kg -1 ) and a coefficient of -0.36 (95% CI, -0.39 to -0.34) for age (years) for propofol maintenance dosage. CONCLUSIONS: We found a noteworthy inverse age-effect on propofol dosage for both induction and maintenance of pediatric procedural sedation. Furthermore, our study revealed that remarkably higher propofol sedation doses were needed for infants and toddlers than previously expected and reported.

Definitions of low cardiac output syndrome after cardiac surgery and their effect on the incidence of intraoperative LCOS: A literature review and cohort study.

Objectives: Low cardiac output syndrome (LCOS) is a serious complication after cardiac surgery. Despite scientific interest in LCOS, there is no uniform definition used in current research and clinicians cannot properly compare different study findings. We aimed to collect the LCOS definitions used in literature and subsequently applied the definitions obtained to existing data to estimate their effect on the intraoperative LCOS incidences in adults, children and infants. Design: This is a literature review, followed by a retrospective cohort study. Setting: This is a single-institutional study from a university hospital in the Netherlands. Participants: Patients from all ages undergoing cardiac surgery with cardiopulmonary bypass between June 2011 and August 2018. Interventions: We obtained different definitions of LCOS used in the literature and applied these to data obtained from an anesthesia information management system to estimate intraoperative incidences of LCOS. We compared intraoperative incidences of LCOS in different populations based on age (infants, children and adults). Measurements and main results: The literature search identified 262 LCOS definitions, that were applied to intraoperative data from 7,366 patients. Using the 10 most frequently published LCOS definitions, the obtained incidence estimates ranged from 0.4 to 82% in infants, from 0.6 to 56% in children and from 1.5 to 91% in adults. Conclusion: There is an important variety in definitions used to describe LCOS. When applied to data obtained from clinical care, these different definitions resulted in large distribution of intraoperative LCOS incidence rates. We therefore advocate for standardization of the LCOS definition to improve clinical understanding and enable adequate comparison of outcomes and treatment effects both in daily care and in research.

Early Determinants of Adverse Motor Outcomes in Preschool Children with a Critical Congenital Heart Defect.

Neurodevelopmental disabilities are common in infants with critical congenital heart disease (CCHD). A prospective, longitudinal cohort study was conducted to establish the prevalence and early determinants of adverse motor outcomes in infants who underwent cardiac surgery with cardiopulmonary bypass before six months of age. Motor development was assessed in 147 preschoolers using the Movement Assessment Battery for children-II. Although the majority displayed an average motor development, 22% of preschool children with CCHD deteriorated in their motor developmental score compared to their previous assessment at 18 months, especially in those with an aortic arch anomaly (AAA) (35%). Individual stability over time appeared to be moderate and the number of children with a motor delay increased, up to 20% in children with AAA. Motor development up to 42 months was best predicted by gestational age, cardio pulmonary bypass time, aortic cross clamp time, number of heart catheterizations up to 18 months and early motor outcomes. The increase in number of preschool children with a motor delay underlines the importance of longitudinal screening of motor skills in children with CCHD at risk for adverse motor outcomes. Offering early interventions may protect their current and future cardiovascular health as motor development is an independent predictor of exercise capacity, physical activity and participation in daily living.

Perioperative Management of an Adolescent Fontan Patient with Narrowing of the Aortopulmonary Space for Posterior Scoliosis Surgery.

Congenital cardiac patients who received neonatal reconstructive aortic arch surgery are at risk of aortopulmonary space narrowing with compression of the left pulmonary artery and left main bronchus (LMB) later in life. We discuss a challenging adolescent single ventricle patient who presented for surgical treatment of a non-idiopathic thoracic scoliosis (posterior spinal fusion) with severe stenosis of the LMB and left pulmonary artery due to a narrow aortopulmonary space. Careful preoperative imaging, evaluation, and decision making resulted in successful surgical treatment and uneventful perioperative course.

Effect of Nitric Oxide via Cardiopulmonary Bypass on Ventilator-Free Days in Young Children Undergoing Congenital Heart Disease Surgery: The NITRIC Randomized Clinical Trial.

Importance: In children undergoing heart surgery, nitric oxide administered into the gas flow of the cardiopulmonary bypass oxygenator may reduce postoperative low cardiac output syndrome, leading to improved recovery and shorter duration of respiratory support. It remains uncertain whether nitric oxide administered into the cardiopulmonary bypass oxygenator improves ventilator-free days (days alive and free from mechanical ventilation). Objective: To determine the effect of nitric oxide applied into the cardiopulmonary bypass oxygenator vs standard care on ventilator-free days in children undergoing surgery for congenital heart disease. Design, Setting, and Participants: Double-blind, multicenter, randomized clinical trial in 6 pediatric cardiac surgical centers in Australia, New Zealand, and the Netherlands. A total of 1371 children younger than 2 years undergoing congenital heart surgery were randomized between July 2017 and April 2021, with 28-day follow-up of the last participant completed on May 24, 2021. Interventions: Patients were assigned to receive nitric oxide at 20 ppm delivered into the cardiopulmonary bypass oxygenator (n = 679) or standard care cardiopulmonary bypass without nitric oxide (n = 685). Main Outcomes and Measures: The primary end point was the number of ventilator-free days from commencement of bypass until day 28. There were 4 secondary end points including a composite of low cardiac output syndrome, extracorporeal life support, or death; length of stay in the intensive care unit; length of stay in the hospital; and postoperative troponin levels. Results: Among 1371 patients who were randomized (mean [SD] age, 21.2 [23.5] weeks; 587 girls [42.8%]), 1364 (99.5%) completed the trial. The number of ventilator-free days did not differ significantly between the nitric oxide and standard care groups, with a median of 26.6 days (IQR, 24.4 to 27.4) vs 26.4 days (IQR, 24.0 to 27.2), respectively, for an absolute difference of -0.01 days (95% CI, -0.25 to 0.22; P = .92). A total of 22.5% of the nitric oxide group and 20.9% of the standard care group developed low cardiac output syndrome within 48 hours, needed extracorporeal support within 48 hours, or died by day 28, for an adjusted odds ratio of 1.12 (95% CI, 0.85 to 1.47). Other secondary outcomes were not significantly different between the groups. Conclusions and Relevance: In children younger than 2 years undergoing cardiopulmonary bypass surgery for congenital heart disease, the use of nitric oxide via cardiopulmonary bypass did not significantly affect the number of ventilator-free days. These findings do not support the use of nitric oxide delivered into the cardiopulmonary bypass oxygenator during heart surgery. Trial Registration: anzctr.org.au Identifier: ACTRN12617000821392.

Statistical analysis plan for the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) trial.

Background: The NITric oxide during cardiopulmonary bypass (CPB) to improve Recovery in Infants with Congenital heart defects (NITRIC) trial, a 1320-patient, multicentre, randomised controlled trial, is aiming to improve survival free of ventilation after CPB by using nitric oxide delivered into the oxygenator of the CPB. Objective: To provide a statistical analysis plan before completion of patient recruitment and data monitoring. Final analyses for this study will adhere to this statistical analysis plan, which details all key pre-planned analyses. Stata scripts for analyses have been prepared alongside this statistical analysis plan. Methods: The statistical analysis plan was designed collaboratively by the chief investigators and trial statistician and builds on the previously published study protocol. All authors remain blinded to treatment allocation. Detail is provided on statistical analyses including cohort description, analysis of primary and secondary outcomes and adverse events. Statistical methods to compare outcomes are planned in detail to ensure methods are verifiable and reproducible. Results: The statistical analysis plan developed provides the trial outline, list of mock tables, and analysis scripts. The plan describes statistical analyses on cohort and baseline description, primary and secondary outcome analyses, process of care measures, physiological descriptors, and safety and adverse event reporting. We define the pre-specified subgroup analyses and the respective statistical tests used to compare subgroups. Conclusion: The statistical analysis plan for the NITRIC trial establishes detailed pre-planned analyses alongside Stata scripts to analyse the largest trial in the field of neonatal and paediatric heart surgery. The plan ensures standards for trial analysis validity aiming to minimise bias of analyses. Trial registration: ACTRN12617000821392.

Vital Signs Monitoring with Wearable Sensors in High-risk Surgical Patients: A Clinical Validation Study.

BACKGROUND: Vital signs are usually recorded once every 8 h in patients at the hospital ward. Early signs of deterioration may therefore be missed. Wireless sensors have been developed that may capture patient deterioration earlier. The objective of this study was to determine whether two wearable patch sensors (SensiumVitals [Sensium Healthcare Ltd., United Kingdom] and HealthPatch [VitalConnect, USA]), a bed-based system (EarlySense [EarlySense Ltd., Israel]), and a patient-worn monitor (Masimo Radius-7 [Masimo Corporation, USA]) can reliably measure heart rate (HR) and respiratory rate (RR) continuously in patients recovering from major surgery. METHODS: In an observational method comparison study, HR and RR of high-risk surgical patients admitted to a step-down unit were simultaneously recorded with the devices under test and compared with an intensive care unit-grade monitoring system (XPREZZON [Spacelabs Healthcare, USA]) until transition to the ward. Outcome measures were 95% limits of agreement and bias. Clarke Error Grid analysis was performed to assess the ability to assist with correct treatment decisions. In addition, data loss and duration of data gaps were analyzed. RESULTS: Twenty-five high-risk surgical patients were included. More than 700 h of data were available for analysis. For HR, bias and limits of agreement were 1.0 (-6.3, 8.4), 1.3 (-0.5, 3.3), -1.4 (-5.1, 2.3), and -0.4 (-4.0, 3.1) for SensiumVitals, HealthPatch, EarlySense, and Masimo, respectively. For RR, these values were -0.8 (-7.4, 5.6), 0.4 (-3.9, 4.7), and 0.2 (-4.7, 4.4) respectively. HealthPatch overestimated RR, with a bias of 4.4 (limits: -4.4 to 13.3) breaths/minute. Data loss from wireless transmission varied from 13% (83 of 633 h) to 34% (122 of 360 h) for RR and 6% (47 of 727 h) to 27% (182 of 664 h) for HR. CONCLUSIONS: All sensors were highly accurate for HR. For RR, the EarlySense, SensiumVitals sensor, and Masimo Radius-7 were reasonably accurate for RR. The accuracy for RR of the HealthPatch sensor was outside acceptable limits. Trend monitoring with wearable sensors could be valuable to timely detect patient deterioration.

Study protocol: NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC trial): a randomised controlled trial.

INTRODUCTION: Congenital heart disease (CHD) is a major cause of infant mortality. Many infants with CHD require corrective surgery with most operations requiring cardiopulmonary bypass (CPB). CPB triggers a systemic inflammatory response which is associated with low cardiac output syndrome (LCOS), postoperative morbidity and mortality. Delivery of nitric oxide (NO) into CPB circuits can provide myocardial protection and reduce bypass-induced inflammation, leading to less LCOS and improved recovery. We hypothesised that using NO during CPB increases ventilator-free days (VFD) (the number of days patients spend alive and free from invasive mechanical ventilation up until day 28) compared with standard care. Here, we describe the NITRIC trial protocol. METHODS AND ANALYSIS: The NITRIC trial is a randomised, double-blind, controlled, parallel-group, two-sided superiority trial to be conducted in six paediatric cardiac surgical centres. One thousand three-hundred and twenty infants <2 years of age undergoing cardiac surgery with CPB will be randomly assigned to NO at 20 ppm administered into the CPB oxygenator for the duration of CPB or standard care (no NO) in a 1:1 ratio with stratification by age (<6 and ≥6 weeks), single ventricle physiology (Y/N) and study centre. The primary outcome will be VFD to day 28. Secondary outcomes include a composite of LCOS, need for extracorporeal membrane oxygenation or death within 28 days of surgery; length of stay in intensive care and in hospital; and, healthcare costs. Analyses will be conducted on an intention-to-treat basis. Preplanned secondary analyses will investigate the impact of NO on host inflammatory profiles postsurgery. ETHICS AND DISSEMINATION: The study has ethical approval (HREC/17/QRCH/43, dated 26 April 2017), is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617000821392) and commenced recruitment in July 2017. The primary manuscript will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ACTRN12617000821392.

Postoperative cerebral oxygenation was not associated with new brain injury in infants with congenital heart disease.

OBJECTIVE: The aim of this study was to evaluate postoperative indices of cerebral oxygenation and autoregulation in infants with critical congenital heart disease in relation to new postoperative ischemic brain injury. METHODS: This prospective, clinical cohort included 77 infants with transposition of the great arteries (N = 19), left ventricular outflow tract obstruction (N = 30), and single ventricle physiology (N = 28) undergoing surgery at 30 days or less of life. Postoperative near-infrared spectroscopy and physiologic monitoring were applied to extract mean arterial blood pressure, regional cerebral oxygen saturation, fractional tissue oxygen extraction, and regional cerebral oxygen saturation mean arterial blood pressure correlation coefficient (≥0.5 considered sign of impaired cerebral autoregulation). New postoperative ischemic injury was defined as moderate-severe white matter injury or focal infarction on magnetic resonance imaging. Low cardiac output syndrome was measured as lactate greater than 4 mmol/L with pH less than 7.30. RESULTS: After surgery, regional cerebral oxygen saturation was decreased in all congenital heart disease groups with a notable increase in regional cerebral oxygen saturation between 6 and 12 hours after surgery, on average with a factor of 1.4 (range, 1.1-2.4). Both single ventricle physiology and postoperative low cardiac output syndrome were associated with lower regional cerebral oxygen saturation and increased time with correlation coefficient of 0.5 or greater. New postoperative ischemic injury was seen in 39 patients (53%) and equally distributed across congenital heart disease groups. Postoperative regional cerebral oxygen saturation, fractional tissue oxygen extraction, and correlation coefficient were not independently associated with new postoperative white matter injury or focal infarction (mixed-model analysis, all F > 0.12). CONCLUSIONS: Postoperative indices of cerebral oxygenation and cerebral autoregulation are not independent predictors of new ischemic brain injury in infants with critical congenital heart disease. Further exploration of the complex interplay among low regional cerebral oxygen saturation, low cardiac output syndrome, and heart defect is required to identify potential biomarkers enabling early intervention for ischemic brain injury.