Retrospective observational study of chloral hydrate use in mechanically-ventilated pediatric intensive care unit (PICU) patients 2012-2017.

Introduction: Chloral hydrate (CH) has long been utilized as a pediatric procedural sedation agent. However, very little is published describing CH use in a pediatric intensive care unit (PICU) setting. The aim of this retrospective observational cohort study was to investigate and describe the use of CH in mechanically-ventilated, critically ill children at a large pediatric tertiary referral hospital. Methods: Data were extracted from the hospital electronic medical record and a locally maintained registry of all children admitted to the PICU between 2012 and 2017. Patients admitted to the cardiovascular ICU were not included in this review. The clinical and pharmacy data for 3806 consecutive PICU admissions of mechanically-ventilated, critically ill children were examined. Results: 283 admissions received CH during their first ICU stay. CH-exposed children were younger (16 months vs. 35 months, p < 0.001), the median total dose of CH (indexed to duration of ventilation) was 11 mg/kg/day, the median time to first CH dose was 3 days and more CH doses were administered at night (1112 vs. 958, p < 0.001). We constructed a propensity score to adjust for the differences in patients with and without CH exposure using logistic regression including variables of age, sex, diagnosis, and PRISM3 score. After adjustment, the median length of mechanical ventilation was 5 days longer in the CH-exposed group (95% Confidence Interval [CI] 4-6) compared to unexposed CH patients. Similarly, the median length of ICU duration was 9.4 days longer (95% CI 7.1-11.6) and median length of hospital admission duration was 13.2 days longer (95% CI 7.8-18.6) in CH-exposed patients compared to CH-non-exposed. After adjustment, CH-exposed patients had a 9% higher median exposure to HFOV (95% CI 3.9-14.6), but did not have higher median exposures to new tracheostomy (95% CI -0.4-2.2) or ECMO (95% CI -0.2-5.0). Discussion: As part of an extended sedation regimen in mechanically-ventilated and critically ill children, CH is associated with somewhat higher complexity of illness and longer ICU durations.

A survey of current practices in sedation, analgesia, withdrawal, and delirium management in paediatric cardiac ICUs.

OBJECTIVE: To characterise the current approach to sedation, analgesia, iatrogenic withdrawal syndrome and delirium in paediatric cardiac ICUs. DESIGN: A convenience sample survey of practitioners at institutions participating in the Pediatric Cardiac Critical Care Consortium conducted from September to December 2020. SETTING: Paediatric cardiac ICUs. MEASUREMENTS AND MAIN RESULTS: Survey responses were received from 33 of 42 institutions contacted. Screening for pain and agitation occurs commonly and frequently. A minority of responding centres (39%) have a written analgesia management protocol/guideline. A minority (42%) of centres have a written protocol for sedation. Screening for withdrawal occurs commonly, although triggers for withdrawal screening vary. Only 42% of respondents have written protocols for withdrawal management. Screening for delirium occurs "always" in 46% of responding centres, "sometimes" in 36% of centres and "never" 18%. Nine participating centres (27%) have written protocols for delirium management. CONCLUSIONS: Our survey identified that most responding paediatric cardiac ICUs lack a standardised approach to the management of analgesia, sedation, iatrogenic withdrawal, and delirium. Screening for pain and agitation occurs regularly, while screening for withdrawal occurs fairly frequently, and screening for delirium is notably less consistent. Only a minority of centres use written protocols or guidelines for the management of these problems. We believe that this represents an opportunity to significantly improve patient care within the paediatric cardiac ICU.

Analgesia, Sedation, and Anesthesia for Neonates With Cardiac Disease.

Analgesia, sedation, and anesthesia are a continuum. Diagnostic and/or therapeutic procedures in newborns often require analgesia, sedation, and/or anesthesia. Newborns, in general, and, particularly, those with heart disease, have an increased risk of serious adverse events, including mortality under anesthesia. In this section, we discuss the assessment and management of pain and discomfort during interventions, review the doses and side effects of commonly used medications, and provide recommendations for their use in newborns with heart disease. For procedures requiring deeper levels of sedation and anesthesia, airway and hemodynamic support might be necessary. Although associations of long-term deleterious neurocognitive effects of anesthetic agents have received considerable attention in both scientific and lay press, causality is not established. Nonetheless, an early multimodal, multidisciplinary approach is beneficial for safe management before, during, and after interventional procedures and surgery to avoid problems of tolerance and delirium, which can contribute to long-term cognitive dysfunction.

The acute influence of vasopressin on hemodynamic status and tissue oxygenation following the Norwood procedure.

Objectives: Arginine vasopressin (AVP) is used to treat hypotension. Because AVP increases blood pressure by increasing systemic vascular resistance, it may have an adverse effect on tissue oxygenation following the Norwood procedure. Methods: Retrospective analysis of continuously captured hemodynamic data of neonates receiving AVP following the Norwood procedure. Results: We studied 64 neonates exposed to AVP within 7 days after the Norwood procedure. For the entire group, AVP significantly increased mean blood pressure (2.5 ± 6.3) and cerebral and renal oxygen extraction ratios (4.1% ± 9.6% and 2.0% ± 4.7%, respectively; P < .001 for all values). In the right ventricle to pulmonary artery shunt cohort, AVP significantly increased blood pressure, arterial oxygen saturation (1.4% ± 3.8%; P = .011), pulmonary to systemic perfusion ratio (0.2 ± 0.4; P = .017), and cerebral and renal oxygen extraction ratios (4.6% ± 8.7%; P = .010% and 4.7% ± 9.4%; P = .014, respectively). The Blalock-Taussig shunt cohort experienced a less significant vasopressor response and no change in arterial oxygen saturation, pulmonary to systemic perfusion ratio, or cerebral and renal oxygen extraction ratios. Conclusions: The right ventricle to pulmonary artery shunt cohort experienced a significant vasopressor response to AVP that was associated with a significant increase in pulmonary perfusion and decrease in cerebral and renal perfusion, whereas the Blalock-Taussig shunt cohort experienced a less significant vasopressor response and no change in pulmonary or systemic perfusion. The influence of AVP on tissue oxygenation following the Norwood procedure may have clinical implications that require further study.

Sedation Practices in the PICU: An Unexpected Casualty of COVID-19.

Pediatric intensivists often use an "analgosedation" approach in mechanically ventilated children. By prioritizing analgesia and minimizing sedation, patients experience less delirium. However, when COVID-19 surged, our pediatric intensive care unit providers were tasked with caring for adults with severe acute hypoxemic respiratory failure (AHRF). As documented in the literature, adults with COVID-19-AHRF received significantly higher doses of sedatives than matched cohorts with non-COVID-19 AHRF. Surprisingly, when the pediatric intensive care unit returned to caring for children, a quality review showed that we were unintentionally using far more sedatives than that prior to COVID-19. This experience is not unique to our institution, or to COVID-19. Lingering effects of crisis care can persist beyond the event itself. We seek to share our experience in order to extend the conversation regarding the unexpected effects of crises on best practices and to stress the need for high-quality research on interventions to support mental health and resilience in frontline healthcare providers.

Neurodevelopmental Outcomes in Infants With Cardiac Surgery Associated Acute Kidney Injury.

BACKGROUND: Infants who undergo surgery for congenital heart disease are at risk of neurodevelopmental delay. Cardiac surgery-associated acute kidney injury (CS-AKI) is common but its association with neurodevelopment has not been explored. METHODS: This was a single-center retrospective observational study of infants who underwent cardiac surgery in the first year of life who had neurodevelopmental testing using the Bayley Scale for Infant Development, third edition. Single and recurrent episodes of stages 2 and 3 CS-AKI were determined. RESULTS: Of 203 children with median age at first surgery of 12 days, 31% had one or more episodes of severe CS-AKI; of those, 16% had recurrent CS-AKI. Median age at neurodevelopmental assessment was 20 months. The incidence of delay was similar for patients with and patients without CS-AKI but all children with recurrent CS-AKI had a delay in one or more domains and had significantly lower scores in all three domains, namely, cognitive, language, and motor. CONCLUSIONS: This study has assessed the association of CS-AKI with neurodevelopmental delay after surgery for congenital heart disease in infancy. Infants who have recurrent CS-AKI in the first year of life are more likely to be delayed and have lower neurodevelopmental scores.

Opioid Weaning Protocol Using Morphine Compared With Nonprotocolized Methadone Associated With Decreased Dose and Duration of Opioid After Norwood Procedure.

OBJECTIVES: Opioids are used to manage pain, comfort, maintain devices, and decrease oxygen consumption around Norwood palliation (NP), but in high dose and prolonged exposure, they increase risk of tolerance and iatrogenic withdrawal syndrome (IAWS). Variability in practice for IAWS prevention potentially increases opioid dose and duration. We hypothesize that protocolized weaning with morphine (MOR) versus nonprotocolized methadone (MTD) is associated with reduction in opioid exposure. DESIGN: A before-versus-after study of outcomes of patients weaned with protocolized MOR versus nonprotocolized MTD including subset analysis for those patients with complications postoperatively. Primary endpoints include daily, wean phase, and total morphine milligram equivalent (MMEq) dose, duration, and, secondarily, length of stay (LOS). SETTING: Quaternary-care pediatric cardiac ICU. PATIENTS: Neonates undergoing single-ventricle palliation. INTERVENTIONS: Introduction of IAWS prevention protocol. MEASUREMENTS AND MAIN RESULTS: Analysis included 54 patients who underwent the NP in 2017-2018 including the subset analysis of 34 who had a complicated postoperative course. The total and wean phase opioid doses for the MTD group were significantly higher than that for the MOR group: 258 versus 22 and 115 versus 6 MMEq/kg; p < 0.001. Duration of opioid exposure was 63 days in the MTD group and 12 days in MOR group (p < 0.001). Subanalysis of the complicated subset also identifies higher total and wean dose for MTD group (293 vs 41 and 116 vs 7 MMEq/kg; p < 0.001) with a longer duration (65 vs 22 days; p = 0.001). Within the subset, LOS was 55% longer in the MTD group than that in the MOR group (150 vs 67 d; p = 0.01) and not different in the uncomplicated group. CONCLUSIONS: After complex NP, a protocolized opioid weaning using MOR versus MTD is associated with 65% shorter opioid duration, 10-fold decreased dose, and shortened LOS.

Redefining the Relationship: Palliative Care in Critical Perinatal and Neonatal Cardiac Patients.

Patients with perinatal and neonatal congenital heart disease (CHD) represent a unique population with higher morbidity and mortality compared to other neonatal patient groups. Despite an overall improvement in long-term survival, they often require chronic care of complex medical illnesses after hospital discharge, placing a high burden of responsibility on their families. Emerging literature reflects high levels of depression and anxiety which plague parents, starting as early as the time of prenatal diagnosis. In the current era of the global COVID-19 pandemic, the additive nature of significant stressors for both medical providers and families can have catastrophic consequences on communication and coping. Due to the high prognostic uncertainty of CHD, data suggests that early pediatric palliative care (PC) consultation may improve shared decision-making, communication, and coping, while minimizing unnecessary medical interventions. However, barriers to pediatric PC persist largely due to the perception that PC consultation is indicative of "giving up." This review serves to highlight the evolving landscape of perinatal and neonatal CHD and the need for earlier and longitudinal integration of pediatric PC in order to provide high-quality, interdisciplinary care to patients and families.

Pediatric Palliative Care in the Heart Failure, Ventricular Assist Device and Transplant Populations: Supporting Patients, Families and Their Clinical Teams.

Heart failure is a life-changing diagnosis for a child and their family. Pediatric patients with heart failure experience significant morbidity and frequent hospitalizations, and many require advanced therapies such as mechanical circulatory support and/or heart transplantation. Pediatric palliative care is an integral resource for the care of patients with heart failure along its continuum. This includes support during the grief of a new diagnosis in a child critically ill with decompensated heart failure, discussion of goals of care and the complexities of mechanical circulatory support, the pensive wait for heart transplantation, and symptom management and psychosocial support throughout the journey. In this article, we discuss the scope of pediatric palliative care in the realm of pediatric heart failure, ventricular assist device (VAD) support, and heart transplantation. We review the limited, albeit growing, literature in this field, with an added focus on difficult conversation and decision support surrounding re-transplantation, HF in young adults with congenital heart disease, the possibility of destination therapy VAD, and the grimmest decision of VAD de-activation.

RBC Transfusion Induced ST Segment Variability Following the Norwood Procedure.

The transfusion of stored RBCs decreases nitric oxide bioavailability, which may have an adverse effect on vascular function. We assessed the effects of RBC transfusion on coronary vascular function by evaluating the relationship between myocardial oxygen delivery and demand as evidenced by ST segment variability. DESIGN: Retrospective case-control study. SETTING: Nine-hundred seventy-three-bed pediatric hospital with a 54-bed cardiovascular ICU. PATIENTS: Seventy-three neonates with hypoplastic left heart syndrome following the Norwood procedure, 38 with a Blalock-Taussig shunt and 35 with a right ventricle to pulmonary artery shunt. INTERVENTIONS: RBC transfusion. MATERIALS AND MAIN RESULTS: High-frequency physiologic data were captured 30 minutes prior to the initiation of (baseline) and during the 120 minutes of the transfusion. A rate pressure product was calculated for each subject and used as an indicator of myocardial oxygen demand. Electrocardiogram leads (aVL, V1, II) were used to construct a 3D ST segment vector to assess ST segment variability and functioned as a surrogate indicator of myocardial ischemia. One-hundred thirty-eight transfusions occurred in the Blalock-Taussig shunt group and 139 in the right ventricle to pulmonary artery shunt group. There was no significant change in the rate pressure product for either group; however, ST segment variability progressively increased for the entire cohort during the transfusion, becoming statistically significant by the end of the transfusion. Upon subgroup analysis, this finding was noted with statistical significance in the Blalock-Taussig shunt group and trending toward significance in the right ventricle to pulmonary artery shunt group. CONCLUSIONS: We found a significant increase in the ST segment variability and evidence of myocardial ischemia temporally associated with RBC transfusions in neonates following the Norwood procedure, specifically among those in the Blalock-Taussig shunt group, which may impact immediate and long-term outcomes.

Postoperative Pain Management in Pediatric Patients Undergoing Cardiac Surgery: Where Are We Heading?

OBJECTIVES: Adequate postoperative pain management is crucial in pediatric patients undergoing cardiac surgery because pain can lead to devastating short- and long-term consequences. This review discusses the limitations of current postoperative pain assessment and management in children after cardiac surgery, the obstacles to providing optimal treatment, and concepts to consider that may overcome these barriers. DATA SOURCE: MEDLINE and PubMed. CONCLUSIONS: Effective pain management in infants and young children undergoing cardiac surgery continues to evolve with innovative methods of both assessment and therapy using newer drugs or novel routes of administration. Artificial intelligence- and machine learning-based pain assessment and patient-tailored management in both pain measurement and prevention are already being integrated into the routine of current practice.

Hypotensive Response to IV Acetaminophen in Pediatric Cardiac Patients.

OBJECTIVES: Acetaminophen is ubiquitously used as antipyretic/analgesic administered IV to patients undergoing surgery and to critically ill patients when enteral routes are not possible. Widely believed to be safe and free of adverse side effects, concerns have developed in adult literature regarding the association of IV acetaminophen and transient hypotension. We hypothesize that there are hemodynamic effects after IV acetaminophen in the PICU and assess the prevalence of such in a large pediatric cardiovascular ICU population using high-fidelity data. DESIGN: Observational study analyzing an enormous set of continuous physiologic data including millions of beat to beat blood pressures surrounding medication administration. SETTING: Quaternary pediatric cardiovascular ICU between January 1, 2013, and November 13, 2017. PATIENTS: All patients less than or equal to 18 years old who received IV acetaminophen. Mechanical support devices excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Physiologic vital sign data were analyzed in 5-minute intervals starting 60 minutes before through 180 minutes after completion. Hypotension defined as mean arterial pressure -15% from baseline and relative hypotension defined -10%. Only doses where patients received no other medications, including vasopressors, within the previous hour were included. t test and a correlation matrix were used to eliminate correlated factors before a logistic regression analysis was performed. Six-hundred eight patients received 777 IV acetaminophen doses. Median age was 8.8 months (interquartile range, 2-62 mo) with a dose of 12.5 mg/kg (interquartile range, 10-15 mg/kg). Data were normalized for age and reference values. One in 20 doses (5%) were associated with hypotension, and one in five (20%) associated with relative hypotension. Univariate analysis revealed hypotension associated with age, baseline mean arterial pressure, and skin temperature (p = 0.05, 0.01, and 0.09). Logistic regression revealed mean arterial pressure (p = 0.01) and age (p = 0.05) remained predictive for hypotension. CONCLUSIONS: In isolation of other medication, a hemodynamic response to IV acetaminophen has a higher prevalence in critically ill children with cardiac disease than previously thought and justifies controlled studies in the perioperative and critical care setting. The added impact on individual patient hemodynamics and physiologic instability will require further study.

Risk factors for mortality in paediatric cardiac ICU patients managed with extracorporeal membrane oxygenation.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation is frequently used in patients with cardiac disease. We evaluated short-term outcomes and identified factors associated with hospital mortality in cardiac patients supported with veno-arterial extracorporeal membrane oxygenation. METHODS: A retrospective review of patients supported with veno-arterial extracorporeal membrane oxygenation at a university-affiliated children's hospital was performed. RESULTS: A total of 253 patients with cardiac disease managed with extracorporeal membrane oxygenation were identified; survival to discharge was 48%, which significantly improved from 39% in an earlier era (1995-2001) (p=0.01). Patients were categorised into surgical versus non-surgical groups on the basis of whether they had undergone cardiac surgery before or not, respectively. The most common indication for extracorporeal membrane oxygenation was extracorporeal cardiopulmonary resuscitation: 96 (51%) in the surgical group and 45 (68%) in the non-surgical group. In a multiple covariate analysis, single-ventricle physiology (p=0.01), duration of extracorporeal membrane oxygenation (p<0.01), and length of hospital stay (p=0.03) were associated with hospital mortality. Weekend or night shift cannulation was associated with mortality in non-surgical patients (p=0.05). CONCLUSION: We report improvement in survival compared with an earlier era in cardiac patients supported with extracorporeal membrane oxygenation. Single-ventricle physiology continues to negatively impact survival, along with evidence of organ dysfunction during extracorporeal membrane oxygenation, duration of extracorporeal membrane oxygenation, and length of stay.

Epinephrine syringe exchange events in a paediatric cardiovascular ICU: analysing the storm.

Introduction Haemodynamically unstable patients can experience potentially hazardous changes in vital signs related to the exchange of depleted syringes of epinephrine to full syringes. The purpose was to determine the measured effects of epinephrine syringe exchanges on the magnitude, duration, and frequency of haemodynamic disturbances in the hour after an exchange event (study) relative to the hours before (control). Materials and methods Beat-to-beat vital signs recorded every 2 seconds from bedside monitors for patients admitted to the paediatric cardiovascular ICU of Texas Children's Hospital were collected between 1 January, 2013 and 30 June, 2015. Epinephrine syringe exchanges without dose/flow change were obtained from electronic records. Time, magnitude, and duration of changes in systolic blood pressure and heart rate were characterised using Matlab. Significant haemodynamic events were identified and compared with control data. RESULTS: In all, 1042 syringe exchange events were found and 850 (81.6%) had uncorrupted data for analysis. A total of 744 (87.5%) exchanges had at least 1 associated haemodynamic perturbation including 2958 systolic blood pressure and 1747 heart-rate changes. Heart-rate perturbations occurred 37% before exchange and 63% after exchange, and 37% of systolic blood pressure perturbations happened before syringe exchange, whereas 63% occurred after syringe exchange with significant differences found in systolic blood pressure frequency (p<0.001), duration (p<0.001), and amplitude (p<0.001) compared with control data. CONCLUSIONS: This novel data collection and signal processing analysis showed a significant increase in frequency, duration, and magnitude of systolic blood pressure perturbations surrounding epinephrine syringe exchange events.

Long-Term Outcomes of Pediatric Cardiac Patients Supported by Extracorporeal Membrane Oxygenation.

OBJECTIVE: Extracorporeal membrane oxygenation is an important form of short-term mechanical support in children with cardiac disease, but information on long-term outcomes and quality of life is limited. The primary objective of this study was to determine the long-term outcomes of children previously supported by extracorporeal membrane oxygenation for cardiac etiologies. DESIGN: A retrospective analysis was performed on patients with cardiac disease managed with extracorporeal membrane oxygenation between January 1, 1995, and December 31, 2012, at the Children's Hospital of Philadelphia. Survivors completed patient- and parent-reported verbal and written surveys, and univariate analyses assessed risk factors for long-term outcomes. SETTING: Tertiary-care children's hospital. PATIENTS: Patients with cardiac disease managed with extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Over 18 years, 396 patients were managed with extracorporeal membrane oxygenation with 43% survival to discharge. The median age at cannulation was 78 days. The majority had congenital heart disease (86%), surgery prior to extracorporeal membrane oxygenation (71%), and cardiopulmonary arrest as the primary extracorporeal membrane oxygenation indication (53%). With 6-year median follow-up, 66% are known to be deceased, including 38 deaths after hospital discharge. Among survivors at discharge, 65 (38%) completed the phone survey, and 33 (19%) completed the written survey. Negative clinical outcomes, defined as having at least significant physical limitations or "fair" or "poor" health, were present in 18% of patients. No patient- or extracorporeal membrane oxygenation-related variables were associated with negative outcomes in univariate analyses. There were significantly lower self-reported and parent-reported written Pediatric Quality of Life Inventory quality of life scores in children compared with healthy individual normative data but no differences in adolescents. CONCLUSIONS: In this series of pediatric cardiac patients supported by extracorporeal membrane oxygenation, mortality was 66% with 6-year median follow-up. The majority reported positive outcomes with respect to health and physical limitations, but children reported lower quality of life compared with healthy individuals.

Intraoperative dexmedetomidine reduces postoperative mechanical ventilation in infants after open heart surgery.

OBJECTIVE: The inclusion of dexmedetomidine in the operative and postoperative management of infants with congenital heart defects has lessened the need for opioids that may cause respiratory depression. Our objective was to show that a dexmedetomidine bolus at or about the time of sternal closure is associated with a decrease in the use of mechanical ventilation in the immediate postoperative period. DESIGN: Retrospective cohort study. SETTING: Single pediatric tertiary cardiac center. PATIENTS: Infants undergoing surgical intervention for congenital heart defects requiring cardiopulmonary bypass, age 30-365 days in a 5-year time period from June 1, 2008, to December 31, 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1,057 total encounters, 441 met inclusion criteria and were evenly distributed over the 5-year time period. Dexmedetomidine had been given at or about the time of sternal closure in 57% of patients. When the exposed and unexposed groups were compared in terms of mechanical ventilation immediately postoperative, there was a statistically significant effect of using dexmedetomidine on the odds of receiving mechanical ventilation (p = 0.0019). This difference remained significant after adjusting for covariates affecting the decision for mechanical ventilation, including year of the procedure, age and weight of subject, cardiopulmonary bypass time, the use of deep hypothermic circulatory arrest, intraoperative fentanyl dose, and the Risk Adjustment for Congenital Heart Surgery Score 1 (p = 0.0317). The odds of receiving mechanical ventilation are estimated to be two times higher for patients who did not receive dexmedetomidine than for patients who received dexmedetomidine after adjusting for variables. CONCLUSION: The use of dexmedetomidine bolus in the operating room at the time of sternal closure in infants undergoing open heart surgery is associated with reduced need for mechanical ventilation in the immediate postoperative period.