Acute Hemodynamics in the Fontan Circulation: Open-Label Study of Vasopressin.

OBJECTIVE: To describe the acute hemodynamic effect of vasopressin on the Fontan circulation, including systemic and pulmonary pressures and resistances, left atrial pressure, and cardiac index. DESIGN: Prospective, open-label, nonrandomized study (NCT04463394). SETTING: Cardiac catheterization laboratory at Lucile Packard Children's Hospital, Stanford. PATIENTS: Patients 3-50 years old with a Fontan circulation who were referred to the cardiac catheterization laboratory for hemodynamic assessment and/or intervention. INTERVENTIONS: A 0.03 U/kg IV (maximum dose 1 unit) bolus of vasopressin was administered over 5 minutes, followed by a maintenance infusion of 0.3 mU/kg/min (maximum dose 0.03 U/min). MEASUREMENTS AND MAIN RESULTS: Comprehensive cardiac catheterization measurements before and after vasopressin administration. Measurements included pulmonary artery, atrial, and systemic arterial pressures, oxygen saturations, and systemic and pulmonary flows and resistances. There were 28 patients studied. Median age was 13.5 (9.1, 17) years, and 16 (57%) patients had a single or dominant right ventricle. Following vasopressin administration, systolic blood pressure and systemic vascular resistance (SVR) increased by 17.5 (13.0, 22.8) mm Hg ( Z value -4.6, p < 0.001) and 3.8 (1.8, 7.5) Wood Units ( Z value -4.6, p < 0.001), respectively. The pulmonary vascular resistance (PVR) decreased by 0.4 ± 0.4 WU ( t statistic 6.2, p < 0.001), and the left atrial pressure increased by 1.0 (0.0, 2.0) mm Hg ( Z value -3.5, p < 0.001). The PVR:SVR decreased by 0.04 ± 0.03 ( t statistic 8.1, p < 0.001). Neither the pulmonary artery pressure (median difference 0.0 [-1.0, 1.0], Z value -0.4, p = 0.69) nor cardiac index (0.1 ± 0.3, t statistic -1.4, p = 0.18) changed significantly. There were no adverse events. CONCLUSIONS: In Fontan patients undergoing cardiac catheterization, vasopressin administration resulted in a significant increase in systolic blood pressure, SVR, and left atrial pressure, decrease in PVR, and no change in cardiac index or pulmonary artery pressure. These findings suggest that in Fontan patients vasopressin may be an option for treating systemic hypotension during sedation or general anesthesia.

Clinical Study of Continuous Non-Invasive Blood Pressure Monitoring in Neonates.

The continuous monitoring of arterial blood pressure (BP) is vital for assessing and treating cardiovascular instability in a sick infant. Currently, invasive catheters are inserted into an artery to monitor critically-ill infants. Catheterization requires skill, is time consuming, prone to complications, and often painful. Herein, we report on the feasibility and accuracy of a non-invasive, wearable device that is easy to place and operate and continuously monitors BP without the need for external calibration. The device uses capacitive sensors to acquire pulse waveform measurements from the wrist and/or foot of preterm and term infants. Systolic, diastolic, and mean arterial pressures are inferred from the recorded pulse waveform data using algorithms trained using artificial neural network (ANN) techniques. The sensor-derived, continuous, non-invasive BP data were compared with corresponding invasive arterial line (IAL) data from 81 infants with a wide variety of pathologies to conclude that inferred BP values meet FDA-level accuracy requirements for these critically ill, yet normotensive term and preterm infants.

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.

Bronchopulmonary dysplasia.

Bronchopulmonary dysplasia is the most frequent adverse outcome of prematurity. Before implementation of antenatal steroids and surfactant therapy, bronchopulmonary dysplasia was mostly characterized by fibrotic, scarred, and hyper-inflated lungs due to pulmonary injury following mechanical ventilation and oxygen toxicity. With advances in neonatal medicine, this "old" bronchopulmonary dysplasia has changed to a "new" bronchopulmonary dysplasia characterized by an arrest in lung growth, leading to alveolar simplification and pulmonary vascular dysangiogenesis. While the old definition was based on the need for oxygen supplementation at a postnatal age of 28 days or at a corrected gestational age of 36 weeks, the newer definition looks at the mode of respiratory support required (eg, invasive versus noninvasive) and is then graded as mild, moderate, or severe. Patients with bronchopulmonary dysplasia may present with significantly impaired pulmonary function, reactive airway disease, or exercise intolerance. Over time, these patients may develop asthma or chronic obstructive pulmonary disease. The most serious long-term complication is the development of pulmonary vascular disease and pulmonary hypertension. Medical treatment often includes diuretics, steroids, bronchodilators, or oxygen supplementation and in the presence of pulmonary hypertension medication to decrease the pulmonary vascular resistance. Perioperative anesthetic risk is increased in children with pulmonary hypertension. These patients might require additional diagnostic imaging and plans for increased resource allocation such as postoperative intensive care admission.

Neurosurgical intervention in children with ventricular assist devices: A single-center case series review.

BACKGROUND: The incidence of neurological complications related to ventricular assist devices (VAD) remains high and includes life-threatening conditions such as intracranial hemorrhage or ischemic stroke. Although no definitive management guidelines exist, operative interventions may be required for major neurological injuries. AIMS: This case series describes the perioperative management of children at a single center who underwent neurosurgical procedures for major intracranial bleeds or ischemic strokes while on VAD support. METHODS: A database review identified all pediatric VAD patients who underwent a neurosurgical procedure for an intracranial hemorrhage or ischemic stroke from April 2014 to January 2020. Data regarding patient characteristics, preoperative medical management, intraoperative anesthetic management, and postoperative outcomes were collected using retrospective chart review. RESULTS: Ninety VADs were implanted in 78 patients. Five neurosurgical interventions were performed: four for intracranial hemorrhages and one for an ischemic stroke. All four patients with hemorrhages were receiving anticoagulation at the time of their event and the three patients on warfarin received emergent reversal with prothrombin concentrate complex and vitamin K. Three patients also received pre-procedural platelet transfusions. Two of the five procedures were emergent bedside external ventricular drain placements, and three were surgical operations. All three patients who underwent operative procedures received invasive hemodynamic monitoring and were supported with a combination of inotropes and afterload reduction. One patient required a massive blood product transfusion. The two patients who underwent external ventricular drain placement had no further surgical interventions and died from the severity of their neurological injuries. All three patients who underwent operative procedures survived to transplantation and discharge home. CONCLUSIONS: Perioperative concerns for the anesthesiologist include VAD hemodynamic management, bleeding, VAD thrombosis, and prevention of secondary brain injury. A systematic, multidisciplinary approach to management is paramount to attain favorable outcomes.

Impact of Modified Anesthesia Management for Pediatric Patients With Williams Syndrome.

OBJECTIVE: This study compared the percent change in systolic blood pressure and the incidence of adverse cardiac events (ACEs; defined as cardiac arrest, cardiopulmonary resuscitation, arrhythmias, or ST-segment changes) during anesthesia induction in patients with Williams syndrome (WS) before and after implementation of a perioperative management strategy. DESIGN: Retrospective observational cohort study. SETTING: Single quaternary academic referral center. PARTICIPANTS: The authors reviewed the records of all children with WS at the authors' institution who underwent general anesthesia for cardiac catheterization, diagnostic imaging, or any type of surgery between November 2008 and August 2019. The authors identified 142 patients with WS, 48 of whom underwent 118 general anesthesia administrations. A historic group (HG) was compared with the intervention group (IG). INTERVENTIONS: Change in perioperative management (three-stage risk stratification: preoperative intravenous hydration, intravenous anesthesia induction, and early use of vasoactives). MEASUREMENTS AND MAIN RESULTS: The authors determined event rates within 60 minutes of anesthesia induction. Standardized mean difference (SMD) was calculated (SMD >0.2 suggests clinically meaningful difference). Sixty-seven general anesthesia encounters were recorded in the HG (mean age, 4.8 years; mean weight, 16.3 kg) and 51 in the IG (mean age, 6.0 years; mean weight, 18.2 kg). The change in systolic blood pressure was -17.5% (-30.0, -5.0) in the HG versus -9% (-18.0, 5.0) in the IG (p = 0.015; SMD = 0.419), and the incidence of ACEs was 6% in the HG and 2% in the IG (p = 0.542; SMD = 0.207). CONCLUSIONS: Preoperative risk stratification, preoperative intravenous hydration, intravenous induction, and early use of continuous vasoactives resulted in greater hemodynamic stability, with a 2% incidence of ACEs.

Moyamoya disease in children and its anesthetic implications: A review.

Moyamoya disease is a rare, progressive cerebral vasculopathy which most commonly presents in the first and fourth decades of life. The mainstay of treatment is surgical revascularization; without treatment, most patients experience ischemic or hemorrhagic strokes. This report reviews moyamoya disease, its associated conditions, surgical treatment techniques, and anesthetic management of patients with moyamoya disease.

Accuracy of a portable pulse oximeter in monitoring hypoxemic infants with cyanotic heart disease.

OBJECTIVE: Infants with single ventricle physiology have arterial oxygen saturations between 75 and 85%. Home monitoring with daily pulse oximetry is associated with improved interstage survival. They are typically sent home with expensive, bulky, hospital-grade pulse oximeters. This study evaluates the accuracy of both the currently used Masimo LNCS and a relatively inexpensive, portable, and equipped with Bluetooth technology study device, by comparing with the gold standard co-oximeter. DESIGN: Prospective, observational study. SETTING: Single institution, paediatric cardiac critical care unit, and neonatal ICU. INTERVENTIONS: none. PATIENTS: Twenty-four infants under 12 months of age with baseline oxygen saturation less than 90% due to cyanotic CHD. MEASUREMENTS AND RESULTS: Pulse oximetry with WristOx2 3150 with infant sensors 8008 J (study device) and Masimo LCNS saturation sensor connected to a Philips monitor (hospital device) were measured simultaneously and compared to arterial oxy-haemoglobin saturation measured by co-oximetry. Statistical analysis evaluated the performances of each and compared to co-oximetry with Schuirmann's TOST equivalence tests, with equivalence defined as an absolute difference of 5% saturation or less. Neither the study nor the hospital device met the predefined standard for equivalence when compared with co-oximetry. The study device reading was on average 4.0% higher than the co-oximeter, failing to show statistical equivalence (p = 0.16). The hospital device was 7.4% higher than the co-oximeter and also did not meet the predefined standard for equivalence (p = 0.97). CONCLUSION: Both devices tended to overestimate oxygen saturation in this patient population when compared to the gold standard, co-oximetry. The study device is at least as accurate as the hospital device and offers the advantage of being more portable with Bluetooth technology that allows reliable, efficient data transmission. Currently FDA-approved, smaller portable pulse oximeters can be considered for use in home monitoring programmes.

Pharmacokinetics of Cefazolin and Vancomycin in Infants Undergoing Open-Heart Surgery With Cardiopulmonary Bypass.

BACKGROUND: Gram-positive bacteria account for nearly three-quarters of all surgical site infections. Antibiotic prophylaxis against these bacteria with cephalosporins or, in select circumstances, with vancomycin is considered standard of care for prevention of surgical site infections. There is little evidence to describe the optimal dosing regimen for surgical site infection prophylaxis in infants undergoing cardiac surgery, and a great deal of institutional variability exists in dosing prophylactic antibiotics. We designed this study to describe an optimal dose regimen for cephalosporin and vancomycin based on pharmacokinetic evidence for infant open-heart surgery on cardiopulmonary bypass. METHODS: Two separate cohorts of infants undergoing cardiac surgery with cardiopulmonary bypass were evaluated. Plasma concentrations of vancomycin (cohort 1, N = 10) and cefazolin (cohort 2, N = 10) were measured, and mixed-effects pharmacokinetic models were constructed for each drug. Simulations of various dosing regimens were performed to describe an appropriate dosing regimen necessary to maintain antibiotic concentrations above the susceptibility cutoff for staphylococci. RESULTS: Both cefazolin and vancomycin plasma concentration versus time profiles were characterized by a 2-compartment model. Subject weight was a significant covariate for V1 for vancomycin. Subject age was a significant covariate for V1 for cefazolin. Cardiopulmonary bypass did not influence concentration versus time profiles. Simulations demonstrated that a 1-hour vancomycin infusion (15 mg·kg), repeated every 12 hours and a 10-minute infusion of cefazolin (30 mg·kg), repeated every 4 hours maintained plasma concentrations above 4 µg·mL and 16 µg·mL, for vancomycin and cefazolin, respectively. Both concentrations are above the minimum inhibitory concentration 90 for most susceptible staphylococci. CONCLUSIONS: Prophylactic treatment of vancomycin 15 mg·kg infused >1 hour with 12-hour redosing and cefazolin 30 mg·kg infused >10 minutes with 4-hour redosing will maintain serum levels of each antibiotic above the susceptibility cut-offs for susceptible staphylococci in infants undergoing cardiac surgery. Cefazolin levels may be adequate for some, but not all, Gram-negative bacteria. The effect of cardiopulmonary bypass on pharmacokinetics is negligible.

Assessment of Ketamine Adult Anesthetic Doses in Pediatrics Using Pharmacokinetic Modeling and Simulations.

BACKGROUND: Although few studies have used ketamine for induction and maintenance of pediatric anesthesia, official dosage recommendations are lacking. This study evaluates the outcomes of adult anesthetic doses in a pediatric population through pharmacokinetic modeling and computer simulations in an attempt to recommend an adequate ketamine dosing regimen. METHODS: Ketamine plasma concentration-time data in 19 children (age 8 months to 16 years; weight 5.5 to 67 kg) were analyzed according to a non-compartmental pharmacokinetic approach. The relationship between pharmacokinetic parameters and demographic covariates was mathematically characterized. A one-compartment open model was implemented to simulate the plasma profile following administration of 1-4.5 mg/kg IV bolus dose and 0.1-0.5 mg/kg/min continuous infusion of ketamine and to predict anesthesia onset and offset. KEY RESULTS: Pharmacokinetic parameters determined were clearance 0.025 ± 0.008 L/kg/min; distribution volume 3.3 ± 1.3 L/kg; half-life 2.6 ± 1 h; and mean residence time 2.3 ± 0.64 h. Body weight was the best predictor of clearance and distribution volume according to a 0.75-power model. Using weight to scale doses was associated with limited variability in simulated concentrations. Ketamine administered as 2.25 mg/kg IV bolus dose, followed by 0.1 mg/kg/min continuous IV infusion enables anesthesia initiation within 3 minutes and maintains it for 3 hours. CONCLUSIONS & INFERENCES: Weight-based dosing minimizes age-dependent variation in the plasma concentration of ketamine. Low-to-intermediate adult doses are suitable for induction and maintenance of safe anesthesia in children undergoing short-term surgical operations. However, this finding requires validation in controlled clinical trials before it is adopted into surgical standard practices.

Safety of ferumoxytol in children undergoing cardiac MRI under general anaesthesia.

BACKGROUND: Ferumoxytol, an "off-label" contrast agent, allows for better cardiac MRI quality as compared with gadolinium-based contrast agents. However, hypotension has been reported with the use of ferumoxytol for indications other than cardiac MRI. The purpose of our investigation was to evaluate the safety of ferumoxytol in children undergoing general anaesthesia for cardiac MRI. METHODS: Medical records of children undergoing general anaesthesia for cardiac MRI were reviewed. Baseline demographic and medical characteristics, as well as imaging and anaesthetic duration and technique, were collected. The incidence of hypotension or other adverse events', need for vasoactive support, or airway intervention throughout the anaesthetic, was recorded. RESULTS: A total of 95 patients were identified, 61 received ferumoxytol and 34 received gadolinium. There were no significant differences between groups with respect to age, weight, or baseline blood pressure. The incidence of low blood pressure - systolic or mean - after contrast administration did not differ between groups, and there was no difference in sustained hypotension or use of vasopressors between groups. One patient who received ferumoxytol had possible anaphylaxis. The image acquisition time (45 versus 68 min, p=0.002) and anaesthesia duration (100 versus 132 min, p=0.02) were shorter in the ferumoxytol group. CONCLUSION: Transient low blood pressure was common in children undergoing cardiac MRI with anaesthesia, but the incidence of hypotension did not differ between ferumoxytol and gadolinium groups. The use of ferumoxytol was associated with significantly shorter scan time and anaesthesia duration, as well as a decreased need for airway intervention.

Applying Lessons from an Inaugural Clinical Pathway to Establish a Clinical Effectiveness Program.

INTRODUCTION: Clinical effectiveness (CE) programs promote standardization to reduce unnecessary variation and improve healthcare value. Best practices for successful and sustainable CE programs remain in question. We developed and implemented our inaugural clinical pathway with the aim of incorporating lessons learned in the build of a CE program at our academic children's hospital. METHODS: The Lucile Packard Children's Hospital Stanford Heart Center and Center for Quality and Clinical Effectiveness partnered to develop and implement an inaugural clinical pathway. Project phases included team assembly, pathway development, implementation, monitoring and evaluation, and improvement. We ascertained Critical CE program elements by focus group discussion among a multidisciplinary panel of experts and key affected groups. Pre and postintervention compared outcomes included mechanical ventilation duration, cardiovascular intensive care unit, and total postoperative length of stay. RESULTS: Twenty-seven of the 30 enrolled patients (90%) completed the pathway. There was a reduction in ventilator days (mean 1.0 + 0.5 versus 1.9 + 1.3 days; P < 0.001), cardiovascular intensive care unit (mean 2.3 + 1.1 versus 4.6 + 2.1 days; P < 0.001) and postoperative length of stay (mean 5.9 + 1.6 versus 7.9 + 2.7 days; P < 0.001) compared with the preintervention period. Elements deemed critical included (1) project prioritization for maximal return on investment; (2) multidisciplinary involvement; (3) pathway focus on best practices, critical outcomes, and rate-limiting steps; (4) active and flexible implementation; and (5) continuous data-driven and transparent pathway iteration. CONCLUSIONS: We identified multiple elements of successful pathway implementation, that we believe to be critical foundational elements of our CE program.

LVOT-VTI is a Useful Indicator of Low Ventricular Function in Young Patients.

Left ventricular outflow tract velocity time integral (LVOT-VTI), a Doppler-derived measure of stroke distance, is used as a surrogate marker of cardiac function in adults. LVOT-VTI is easily obtained, independent of ventricular geometry and wall motion abnormalities. We investigated the relationship between LVOT-VTI and conventional measures of function in young patients by comparing controls to children with dilated cardiomyopathy (DCM). Sixty-two healthy and 52 DCM patients over 1 year were studied retrospectively. The average pulsed (PW) and continuous wave (CW) LVOT-VTIs from apical views were measured from three cycles. Body surface area (BSA) and Ejection fraction (EF) were obtained. We compared LVOT-VTIs between study and control groups and assessed BSA's impact on LVOT-VTI. The entire cohort was classified into three levels of LV function which were compared. We determined LVOT-VTI cutoff values that indicated an EF <50%. The mean PW-LVOT-VTI in the DCM group was significantly lower than that of the normal group (0.15 vs. 0.18 m; p < 0.0012). The mean CW-LVOT-VTI was significantly lower in DCM (0.20 vs. 0.24 m; p < 0.0001). There was no impact of BSA on LVOT-VTI except when comparing BSA and CW-LVOT-VTI in the normal group. There was a positive relationship between LVOT-VTI and EF for PW (Rs = 0.29, p = 0.0022) and CW (Rs = 0.22, p = 0.0364) and a difference in mean LVOT-VTI between EF groups (p < 0.0001). ROC analysis demonstrated that PW-LVOT-VTI <0.17 m (AUC = 0.73; p < 0.0001) and CW-LVOT-VTI <0.22 m (AUC = 0.76; p < 0.0001) was associated with EF <50%. This study indicates that LVOT-VTI can be a useful alternative measure of LV performance in children over 1 year.

Perioperative management of pediatric en-bloc combined heart-liver transplants: a case series review.

BACKGROUND: Combined heart and liver transplantation (CHLT) in the pediatric population involves a complex group of patients, many of whom have palliated congenital heart disease (CHD) involving single ventricle physiology. OBJECTIVE: The purpose of this study was to describe the perioperative management of pediatric patients undergoing CHLT at a single institution and to identify management strategies that may be used to optimize perioperative care. METHODS: We did a retrospective database review of all patients receiving CHLT at a children's hospital between 2006 and 2014. Information collected included preoperative characteristics, intraoperative management, blood transfusions, and postoperative morbidity and mortality. RESULTS: Five pediatric CHLTs were performed over an 8-year period. All patients had a history of complex CHD with multiple sternotomies, three of whom had failing Fontan physiology. Patient age ranged from 7 to 23 years and weight from 29.5 to 68.5 kg. All CHLTs were performed using an en-bloc technique where both the donor heart and liver were implanted together on cardiopulmonary bypass (CPB). The median operating room time was 14.25 h, median CPB time was 3.58 h, and median donor ischemia time was 4.13 h. Patients separated from CPB on dopamine, epinephrine, and milrinone infusions and two required inhaled nitric oxide. All patients received a massive intraoperative blood transfusion post CPB with amounts ranging from one to three times the patient's estimated blood volume. The patient who required the most transfusions was in decompensated heart and liver failure preoperatively. Four of the five patients received an antifibrinolytic agent as well as a procoagulant (prothrombin complex concentrate or recombinant activated Factor VII) to assist with hemostasis. There were no 30-day thromboembolic events detected. Postoperatively the median length of mechanical ventilation, ICU stay and stay to hospital discharge was 4, 8, and 37 days, respectively. All patients are alive and free from allograft rejection at this time. CONCLUSION: Combined heart and liver transplantation in the pediatric population involves a complex group of patients with unique perioperative challenges. Successful management starts with thorough preoperative planning and communication and involves strategies to deal with massive intraoperative hemorrhage and coagulopathy in addition to protecting and supporting the transplanted heart and liver and meticulous surgical technique. An integrated multidisciplinary team approach is the cornerstone for successful outcomes.

Hemodynamic Effects of Phenylephrine, Vasopressin, and Epinephrine in Children With Pulmonary Hypertension: A Pilot Study.

OBJECTIVES: During a pulmonary hypertensive crisis, the marked increase in pulmonary vascular resistance can result in acute right ventricular failure and death. Currently, there are no therapeutic guidelines for managing an acute crisis. This pilot study examined the hemodynamic effects of phenylephrine, arginine vasopressin, and epinephrine in pediatric patients with pulmonary hypertension. DESIGN: In this prospective, open-label, nonrandomized pilot study, we enrolled pediatric patients previously diagnosed with pulmonary hypertensive who were scheduled electively for cardiac catheterization. Primary outcome was a change in the ratio of pulmonary-to-systemic vascular resistance. Baseline hemodynamic data were collected before and after the study drug was administered. PATIENTS: Eleven of 15 participants were women, median age was 9.2 years (range, 1.7-14.9 yr), and median weight was 26.8 kg (range, 8.5-55.2 kg). Baseline mean pulmonary artery pressure was 49 ± 19 mm Hg, and mean indexed pulmonary vascular resistance was 10 ± 5.4 Wood units. Etiology of pulmonary hypertensive varied, and all were on systemic pulmonary hypertensive medications. INTERVENTIONS: Patients 1-5 received phenylephrine 1 µg/kg; patients 6-10 received arginine vasopressin 0.03 U/kg; and patients 11-15 received epinephrine 1 µg/kg. Hemodynamics was measured continuously for up to 10 minutes following study drug administration. MEASUREMENTS AND MAIN RESULTS: After study drug administration, the ratio of pulmonary-to-systemic vascular resistance decreased in three of five patients receiving phenylephrine, five of five patients receiving arginine vasopressin, and three of five patients receiving epinephrine. Although all three medications resulted in an increase in aortic pressure, only arginine vasopressin consistently resulted in a decrease in the ratio of systolic pulmonary artery-to-aortic pressure. CONCLUSIONS: This prospective pilot study of phenylephrine, arginine vasopressin, and epinephrine in pediatric patients with pulmonary hypertensive showed an increase in aortic pressure with all drugs although only vasopressin resulted in a consistent decrease in the ratio of pulmonary-to-systemic vascular resistance. Studies with more subjects are warranted to define optimal dosing strategies of these medications in an acute pulmonary hypertensive crisis.

Cognitive Dysfunction in Children with Heart Disease: The Role of Anesthesia and Sedation.

As physicians and caregivers of children with congenital heart disease, we are aware of the increasing need for procedures requiring anesthesia. While these procedures may be ideal for medical and cardiac surgical management, the risks and benefits must be assessed carefully. There are well known risks of cardiovascular and respiratory complications from anesthesia and sedation and a potentially under-appreciated risk of neurocognitive dysfunction. Both animal and human studies support the detrimental effects of repeated anesthetic exposure on the developing brain. Although the studies in humans are less convincing of this risk, the Society of Pediatric Anesthesia jointly with SmartTots provided a consensus statement on the use of anesthetic and sedative drugs in infants and toddlers when speaking to families. (www.pedsanesthesia.org; http://smarttots.org/wp-content/uploads/2015/10/ConsensusStatementV910.5.2015.pdf). An excerpt of the statement is "Concerns regarding the unknown risk of anesthetic exposure to your child's brain development must be weighed against the potential harm associated with cancelling or delaying a needed procedure. Each child's care must be evaluated individually based on age, type, and urgency of the procedure and other health factors. This review provides a summary of the current evidence regarding anesthesia-induced neurotoxicity and the developing brain and its implications for children with congenital heart disease.

Accuracy of Pulse Oximeters Intended for Hypoxemic Pediatric Patients.

OBJECTIVES: Prior studies have shown inaccuracies in pulse oximetry readings at saturations less than 85%; however, no large studies have evaluated new sensors marketed for these low saturations. This study's purpose was to evaluate two sensors with claims of improved accuracy in children with saturations less than 85%. DESIGN: Prospective observational study. SETTING: Single institution; cardiac catheterization laboratory, and operating room. PATIENTS: Fifty patients weighing 3-20 kg with baseline saturations less than 90% undergoing surgical or catheterization procedure. MEASUREMENTS AND MAIN RESULTS: Data collected included demographics, diagnosis, continuous saturations from three different pulse oximeters (Masimo LNCS [Masimo, Irvine, CA], Masimo Blue [Masimo], and Nellcor Max-I [Medtronic, Dublin, Ireland]) and up to four blood samples for co-oximetry as the gold-standard arterial oxygen saturation. Analysis included scatter plots, smoothed regression estimates of mean continuous saturation levels plotted against corresponding arterial oxygen saturation values, and Bland-Altman plots. Bland-Altman analysis indicated increasing levels of bias and variability for decreasing arterial oxygen saturation levels for all three sensors, with a statistically significant increase in mean difference observed for decreasing arterial oxygen saturation level. The Masimo Blue sensor had the lowest mean difference, SD and Bland-Altman limits in patients with saturations less than or equal to 85%. At saturation range of less than or equal to 85% and greater than 75%, 14% of the samples obtained from Masimo Blue, 24% of the readings from the Nellcor, and 31% from the Masimo Standard sensors were greater than or equal to 5% points difference. All three sensors had a further increase in these differences for arterial oxygen saturation values less than 75%. CONCLUSIONS: The Masimo Blue sensor has improved accuracy at saturations 75-85% versus the Nellcor and Masimo Standard sensors. The accuracy of peripheral capillary oxygen saturation of the Masimo Blue sensor was within 5% points of the arterial oxygen saturation the majority of the time. Currently, at saturations less than or equal to 85%, pulse oximetry alone should not be relied on in making clinical decisions.

Population pharmacokinetics of ketamine in children with heart disease.

This study aims at developing a population pharmacokinetic model for ketamine in children with cardiac diseases in order to rationalize an effective 2-h anesthetic medication, personalized based on cardiac function and age. Twenty-one children (6 months to 18 years old) were enrolled in this prospective, open label study. Ketamine 2mg/kg IV was administered and blood samples were then collected over 8h for ketamine assay. Pharmacokinetic data analysis using NONMEM, was undertaken. Ketamine pharmacokinetics was adequately described by a two-compartment linear disposition model. Typical population parameters were: total clearance: 60.6 ×(weight/70)(0.75)L/h, intercompartmental clearance: 73.2 ×(weight/70)(0.75)L/h, central distribution volume: 57.3 ×(weight/70)L, and peripheral distribution volume: 152 ×(weight/70)L. Ketamine clearance in children with pre-existing congenital heart disease was comparable to values reported in healthy subjects. Computer simulations indicated that an initial loading dose of ketamine 2mg/kg IV over 1 min followed by a constant rate infusion of 6.3mg/kg/h for 29 min, 4.5mg/kg/h from 30 to 80 min, and 3.9 mg/kg/h from 80 to 120 min achieves and maintains anesthetic plasma level for 2h in children 1 year or older (weight ≥ 10 kg).