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Background: The COVID-19 pandemic has yielded an unprecedented quantity of new publications, contributing to an overwhelming quantity of information and leading to the rapid dissemination of less stringently validated information. Yet, a formal analysis of how the medical literature has changed during the pandemic is lacking. In this analysis, we aimed to quantify how scientific publications changed at the outset of the COVID-19 pandemic., Methods: We performed a cross-sectional bibliometric study of published studies in four high-impact medical journals to identify differences in the characteristics of COVID-19 related publications compared to non-pandemic studies. Original investigations related to SARS-CoV-2 and COVID-19 published in March and April 2020 were identified and compared to non-COVID-19 research publications over the same two-month period in 2019 and 2020. Extracted data included publication characteristics, study characteristics, author characteristics, and impact metrics. Our primary measure was principal component analysis (PCA) of publication characteristics and impact metrics across groups., Results: We identified 402 publications that met inclusion criteria: 76 were related to COVID-19; 154 and 172 were non-COVID publications over the same period in 2020 and 2019, respectively. PCA utilizing the collected bibliometric data revealed segregation of the COVID-19 literature subset from both groups of non-COVID literature (2019 and 2020). COVID-19 publications were more likely to describe prospective observational (31.6%) or case series (41.8%) studies without industry funding as compared with non-COVID articles, which were represented primarily by randomized controlled trials (32.5% and 36.6% in the non-COVID literature from 2020 and 2019, respectively)., Conclusions: In this cross-sectional study of publications in four general medical journals, COVID-related articles were significantly different from non-COVID articles based on article characteristics and impact metrics. COVID-related studies were generally shorter articles reporting observational studies with less literature cited and fewer study sites, suggestive of more limited scientific support. They nevertheless had much higher dissemination., Competing Interests: The authors have declared that no competing interests exist.

Advances made in pediatric cardiology, cardiac surgery and critical care have significantly improved the survival rate of patients with congenital heart disease (CHD) leading to an increase in children with CHD presenting for noncardiac surgical procedures. This study aims (1) to describe the trend and perioperative mortality rates in patients with CHD undergoing noncardiac surgical procedures at children's hospitals over the past 5 years and (2) to describe the patient characteristics and the most common type of surgical procedures. The Pediatric Health Information System (PHIS) is an administrative database that contains inpatient, observation, and outpatient surgical data from 52 freestanding children's hospitals. Thirty-nine of the 52 hospitals submitted data on all types of patient encounters for the duration of the study from 2015 to 2019. The total numbers of non-cardiac surgical encounters among patients with history of a CHD diagnosis significantly increased each year from 38,272 in 2015 to 45,993 in 2019 (P < 0.001). Despite the increase in case numbers, there has been a significant decline in mortality rates to the most recent incidence of 1.06% in 2019. Careful patient selection and medical optimization of patients aligned with specific expertise at dedicated children's hospitals may lead to improvement in mortality rate. Future studies comparing the outcomes of patients with cardiac disease based on hospital type and volume as well as type of providers may help determine the future of care including potential need for regionalization of noncardiac care for this vulnerable patient population.

Purpose: Under times of supply chain stress, the availability of some medical equipment and supplies may become limited. The current pandemic involving severe acute respiratory syndrome coronavirus 2 has highlighted limitations to the ordinary provision of personal protective equipment (PPE). For perioperative healthcare workers, N95 masks provide a stark example of PPE in short supply necessitating the creation of scientifically valid protocols for their decontamination and reuse., Methods: We performed a systematic literature search of MEDLINE, Embase, Cochrane CENTRAL databases, and ClinicalTrials.gov to identify peer-reviewed articles related to N95 mask decontamination and subsequent testing for the integrity of mask filtration and facial seal. To expand this search, we additionally surveyed the official statements from key health agencies, organizations, and societies for relevant citations., Results: Our initial database search resulted in five articles that met inclusion criteria, with 26 articles added from the expanded search. Our search did not reveal any relevant randomized clinical trials or cohort studies. We found that moist mask heating (65-80°C at 50-85% relative humidity for 20-30 min) and vaporous hydrogen peroxide treatment were supported by the literature to provide consistent viral decontamination without compromising mask seal and filtration efficiency. Other investigated decontamination methods lacked comprehensive scientific evidence for all three of these key criteria., Conclusions: N95 mask reprocessing using either moist heat or vaporous hydrogen peroxide is recommended to ensure healthcare worker safety.

Background: Utilizing the intrinsic surgical risk (ISR) and the patient's chronic and acute conditions, this study aims to develop and validate a comprehensive predictive model of perioperative morbidity in children undergoing noncardiac surgery., Methods: Following institutional review board (IRB) approval at a tertiary care children's hospital, data for all noncardiac surgical encounters for a derivation dataset from July 2017 to December 2018 including 16,724 cases and for a validation dataset from January 2019 to December 2019 including 9043 cases were collected retrospectively. The primary outcome was a composite morbidity score defined by unplanned transfer to an intensive care unit (ICU), acute respiratory failure requiring intubation, postoperative need for noninvasive or invasive positive pressure ventilation, or cardiac arrest. Internal model validation was performed using 1000 bootstrap resamples, and external validation was performed using the 2019 validation cohort., Results: A total of 1519 surgical cases (9.1%) experienced the defined composite morbidity. Using multivariable logistic regression, the Risk Assessment of Morbidity in Pediatric Surgery (RAMPS) score was developed with very good predictive ability in the derivation cohort (area under the curve [AUC] = 0.805; 95% confidence interval [CI], 0.795-0.816), very good internal validity using 1000 bootstrap resamples (bias-corrected Nagelkerke R = 0.21 and Brier score = 0.07), and good external validity (AUC = 0.783; 95% CI, 0.770-0.797). The included variables are age <5 years, critically ill, chronic condition indicator (CCI) ≥3, significant CCI ≥2, and ISR quartile ≥3. The RAMPS score ranges from 0 to 10, with the risk of composite morbidity ranging from 1.8% to 42.7%., Conclusions: The RAMPS score provides the ability to identify a high-risk cohort of pediatric patients using a 5-component tool, and it demonstrated good internal and external validity and generalizability. It also provides an opportunity to improve perioperative planning with the intent of improving both individual-patient outcomes and the appropriate allocation of health care resources.

Background: The objective of this study is to estimate the surgical risk of noncardiac procedures on the incidence of 30-day mortality in children with congenital heart disease., Methods: Children with congenital heart disease undergoing noncardiac surgery from 2012 to 2016 and included in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Pediatric database were included in the derivation cohort, while the 2017 database was used as a validation cohort. Intrinsic surgical risk quartiles were built utilizing 30-day mortality rates for each Current Procedural Terminology code and relative value units to create 2 groups defined as low surgical risk (quartiles 1-3) and high surgical risk procedures (quartile 4). We used multivariable logistic regression to determine the predictors for 30-day mortality including patient comorbidities and intrinsic surgical risk. A partially external validation of the model was performed using the 2017 version of the database., Results: We included 37,658 children with congenital heart disease undergoing noncardiac surgery with an incidence of overall 30-day mortality of 1.7% in the derivation cohort and 1.5% in the validation cohort (n = 13,129). Intrinsic surgical risk of procedures represented by Current Procedural Terminology procedural codes and relative value units risk quartiles was significantly associated with 30-day mortality (unadjusted P < .001). Predicted probability of 30-day mortality ranges from 0.2% (95% confidence interval [CI], 0.2-0.2) with no comorbidities to 39.6% (95% CI, 23.2-56.0) when all comorbidities were present among high surgical risk procedures and from 0.3% (95% CI, 0.3-0.3) to 54.8% (95% CI, 39.4-70.1) among low surgical risk procedures. An excellent discrimination was reported for the multivariable model with area under the curve (AUC) of 0.86 (95% CI, 0.85-0.88). High surgical risk was not associated with increased odds of 30-day mortality after adjustment for all other predictors (adjusted odds ratio [OR]: 0.75, 95% CI, 0.62-0.91). We also estimated the discriminative ability of a model that does not include the surgical risk (0.86 [95% CI, 0.84-0.88], with P value for the direct comparison of the AUC of the 2 models = 0.831). The multivariable model obtained from an external validation cohort reported an optimism corrected AUC of 0.88 (95% CI, 0.85-0.91)., Conclusions: Our study demonstrates that integration of intrinsic surgical risk to comorbidities and severity of cardiac disease does not improve prediction of 30-day mortality in children undergoing noncardiac surgery. In children with congenital heart disease, patient comorbidities, and severity of the cardiac lesion are the predominant predictors of 30-day mortality.

Purpose: Motor-evoked potentials (MEPs) are frequently used in pediatric posterior spinal fusion surgery (PSFS) to detect spinal cord ischemia. Dexmedetomidine is increasingly being used as an adjunct to total intravenous anesthesia, but its effect on MEP amplitude has been variably reported. The purpose of this study was to evaluate the effect of an infusion of dexmedetomidine on the amplitude of MEPs., Methods: We performed a retrospective case-control study of 30 pediatric patients who received a 0.5 µg·kg -1 ·hr -1 infusion of dexmedetomidine, ten patients who received 0.3 µg·kg -1 ·hr -1 dexmedetomidine, and 30 control patients who did not receive dexmedetomidine during PSFS. Two neurophysiologists reviewed the MEP amplitudes in six muscle groups at three time points: when the patient was turned prone (baseline; T1), one hour after incision (T2), and after exposure of the spine but before insertion of the first screw (T3)., Results: In all muscles tested, the mean MEP amplitude was reduced by T3 when dexmedetomidine was infused at 0.5 µg·kg -1 ·hr -1 . The greatest reduction from baseline MEP amplitude was 829 µV (95% confidence interval, 352 to 1230; P < 0.001) seen in first right dorsus interosseous. When dexmedetomidine was infused at 0.3 µg·kg -1 ·hr -1 , there was a significant reduction in MEP amplitude in four of the six muscles tested at T3 compared with the control group., Conclusions: Dexmedetomidine at commonly used infusion rates of 0.3 µg·kg -1 ·hr -1 or 0.5 µg·kg -1 ·hr -1 causes a significant decrease in MEP amplitude during pediatric PSFS. We suggest that dexmedetomidine should be avoided in children undergoing PSFS so as not to confuse the interpretation of this important neurophysiological monitor.

A tailored transfusion algorithm based on viscoelastic testing in the perioperative period or in trauma patients is recommended by guidelines for bleeding management. Bleeding management strategies in neonates and children are mostly extrapolated from the adult experience, as published evidence in the youngest age group is scarce. This manuscript is intended to give a structured overview of what has been published on the use of viscoelastic testing to guide bleeding management in neonates and children. Several devices that use either the traditional viscoelastic method or resonance viscoelastography technology are on the market. Reference ranges for children have been evaluated in only some of them. As most of the hemostasis maturation processes can be observed during the first year of life, adult reference ranges for viscoelastic testing could be applied over the age of 1 year. The majority of the published trials in children are based on retrospective analyses describing the correlation between viscoelastic testing and standard laboratory testing or focusing on the prediction of bleeding. Clinically more relevant studies in pediatric patients undergoing cardiac surgery have demonstrated that the implementation of a transfusion algorithm based on viscoelastic testing has significantly reduced transfusion requirements and that this approach has enabled a rapid detection of coagulation disorders in the presence of excessive bleeding. Although further studies are urgently needed, experts have reviewed the use of a transfusion algorithm based on viscoelastic testing in children as a feasible approach, as it has been shown to improve bleeding management and rationalize blood product transfusion., (© 2020 AABB.)

Background and Aims: In this study, we assessed the association between preoperative hemoglobin and red blood cell transfusion in children undergoing spine surgery after the implementation of our preoperative iron supplementation protocol., Method: We performed a retrospective analysis of patients who underwent posterior spinal fusion surgery between January 2013 and December 2017 and received preoperative iron supplementation. We used uni- and multivariable logistic regression to determine the association between preoperative hemoglobin level and red blood cell transfusion in patients receiving iron supplementation., Results: A total of 382 patients treated with preoperative oral iron were included. Of these, 175 (45.5%) patients were transfused intraoperatively. Multivariable logistic regression analysis revealed nonidiopathic etiology of the scoliosis (OR 4.178 [95% CI: 2.277-7.668], P < .001), the Cobb angle (OR 1.025 [95% CI: 1.010-1.040], P = .001), and number of vertebrae fused (OR 1.169 [95% CI: 1.042-1.312], P = .008) were associated with red blood cell transfusion. In addition, patients with a preoperative hemoglobin ≥ 140 g/L (OR 0.157 [95% CI: 0.046-0.540], P = .003), and hemoglobin between 130 and 140 g/L (OR 0.195 [95% CI: 0.057-0.669], P = .009) were less likely to be transfused compared with patients with preoperative hemoglobin between 120 and 130 g/L (OR 0.294 [95% CI: 0.780-1.082], P = .066) or <120 g/L (reference)., Conclusion: Our study suggests that higher preoperative hemoglobin levels (>130 g/L) are associated with a reduced need for red blood cell transfusion in pediatric patients who have received iron supplementation before undergoing posterior spinal fusion in our institution. The effect of iron supplementation, the optimal dosing, and duration of supplemental iron therapy remains unclear at this time., (© 2020 John Wiley & Sons Ltd.)

The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. Global health care now faces unprecedented challenges with widespread and rapid human-to-human transmission of SARS-CoV-2 and high morbidity and mortality with COVID-19 worldwide. Across the world, medical care is hampered by a critical shortage of not only hand sanitizers, personal protective equipment, ventilators, and hospital beds, but also impediments to the blood supply. Blood donation centers in many areas around the globe have mostly closed. Donors, practicing social distancing, some either with illness or undergoing self-quarantine, are quickly diminishing. Drastic public health initiatives have focused on containment and "flattening the curve" while invaluable resources are being depleted. In some countries, the point has been reached at which the demand for such resources, including donor blood, outstrips the supply. Questions as to the safety of blood persist. Although it does not appear very likely that the virus can be transmitted through allogeneic blood transfusion, this still remains to be fully determined. As options dwindle, we must enact regional and national shortage plans worldwide and more vitally disseminate the knowledge of and immediately implement patient blood management (PBM). PBM is an evidence-based bundle of care to optimize medical and surgical patient outcomes by clinically managing and preserving a patient's own blood. This multinational and diverse group of authors issue this "Call to Action" underscoring "The Essential Role of Patient Blood Management in the Management of Pandemics" and urging all stakeholders and providers to implement the practical and commonsense principles of PBM and its multiprofessional and multimodality approaches.

Objective: Children with congenital heart defects are at increased risk for perioperative bleeding and postoperative thrombosis. In this study, the authors sought to develop a predictive model for postoperative thrombotic complications that integrates intraoperative bleeding and the requirement for allogenic blood products in addition to known patient and surgical characteristics., Design: Retrospective cohort., Setting: Pediatric hospital., Participants: Neonates and children who underwent surgery with cardiopulmonary bypass (CPB)., Interventions: None MEASUREMENTS AND MAIN RESULTS: Demographic, laboratory, point-of-care coagulation, surgical, and perioperative transfusion data were collected. Among the 369 participants included in the study, 67 (18%) developed postoperative thrombotic complications. From multivariable logistic regression analyses, preoperative oxygen saturation <85% (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.10-3.85; p = 0.024), surgery in the neonatal period (OR 2.16, 95% CI 1.02-4.55; p = 0.044), use of preoperative antiplatelet or anticoagulation therapy (OR 3.34, 95% CI 1.61-6.96; p = 0.001), and the volume of blood product transfused post-CPB (>80 mL/kg [OR 5.72, 95% CI 1.73-18.91; p = 0.004] and 15-80 mL/kg [OR 3.06, 95% CI 1.24-7.53; p = 0.015]) were independently associated with an increased incidence of thrombotic complications. No statistical differences were observed in available preoperative coagulation tests between children who developed postoperative thrombosis and those who did not., Conclusion: This observational cohort study found that cyanosis, surgery in neonates, preoperative anticoagulation or antiplatelet therapy, and the volume of post-CPB transfusion are important predictors of postoperative thrombotic complications in children undergoing cardiac surgery. Additional studies are required to explore the relationship between hypoxia, coagulopathy, and postoperative thrombosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Pediatric cardiac surgery is associated with a substantial risk of bleeding, frequently requiring the administration of allogeneic blood products. Efforts to optimize preoperative hemoglobin, limit blood sampling, improve hemostasis, reduce bleeding, correct coagulopathy, and incorporate blood sparing techniques (including restrictive transfusion practices) are key elements of patient blood management (PBM) programs, and should be applied to the pediatric cardiac surgical population as across other disciplines. Many guidelines for implementation of PBM in adults undergoing cardiac surgery are available, but evidence regarding the implementation of PBM in children is limited to systematic reviews and specific guidelines for the pediatric cardiac population are missing. The objective of the task force from the Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis (NATA, www.nataonline.com) is to provide evidence-based recommendations regarding anemia management and blood transfusion practices in the perioperative care of neonates and children undergoing cardiac surgery, and to highlight potential areas where additional research is urgently required., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Early identification of children at high risk for perioperative mortality could lead to improved outcomes; however, there is a lack of well-validated risk prediction tools. The Pediatric Risk Assessment (PRAm) score is a new model to prognosticate perioperative risk of mortality in pediatric patients undergoing noncardiac surgery. It was derived from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) Pediatric database. In this study, we aimed to externally validate the PRAm score at 1 large institution., Methods: A PRAm score was prospectively assigned by the primary anesthesia team to children ≤18 years of age undergoing noncardiac surgery between July 2017 and July 2018 at a tertiary care pediatric hospital. The primary outcome was the PRAm score's ability to predict 30-day mortality. The area under the receiver operating characteristic (ROC) curve was utilized to determine discriminative ability. Sensitivity and specificity at varying cutoffs were considered. Youden J index and the gray zone approach were applied to determine the optimal PRAm cutoff for predicting 30-day mortality., Results: Among the 13,530 cases included in the external validation cohort, the incidence of 30-day mortality was 0.21% (29/13,530). The PRAm score was found to predict 30-day mortality with an area under the curve (AUC) of 0.956 (95% confidence interval [CI], 0.938-0.974; P < .001). Youden J index determined the optimal PRAm score threshold to be ≥5 with a sensitivity of 86% and a specificity of 91%. The gray zone identified an inconclusive risk of mortality in 6.93% (938/13,530) of patients who had PRAm scores of 4 or 5 (sensitivity or specificity <90%, respectively), therefore refining the optimal cutoff point to be a PRAm score of ≥6. The incidence of mortality for patients with an American Society of Anesthesiologists Physical Status (ASA PS) ≤3 (0.06%, 8/13,530) increased 8-fold for those with an ASA PS of ≤3 and a PRAm score of ≥6., Conclusions: The PRAm score is a simple and objective tool that has excellent ability to predict perioperative risk of mortality in pediatric patients undergoing noncardiac surgery and can be easily used by clinicians. The application of the PRAm score could have important implications on the safety and quality of care delivered to infants and children and on the resource utilization in the pediatric health care system.

Purpose: Viscoelastic tests (VETs), thromboelastography (TEG ® ) and thromboelastometry (ROTEM ® ) are global tests of coagulation performed on whole blood. They evaluate the mechanical strength of a clot as it builds and develops after coagulation itself. The time required to obtain haemostasis results remains a major problem for clinicians dealing with bleeding, although some teams have developed a rapid laboratory response strategy. Indeed, the value of rapid point-of-care diagnostic devices such as VETs has increased over the years. However, VETs are not standardised and there are few recommendations from the learned societies regarding their use. In 2014, the recommendations of the International Society of Thrombosis and Haemostasis (ISTH) only concerned haemophilia. The French Working Group on Perioperative haemostasis (GIHP) therefore proposes to summarise knowledge on the clinical use of these techniques in the setting of emergency and perioperative medicine., Methods: A review of the literature., Principal Findings: The role of the VETs seems established in the management of severe trauma and in cardiac surgery, both adult and paediatric. In other situations, their role remains to be defined: hepatic transplantation, postpartum haemorrhage, and non-cardiac surgery. They must be part of the global management of haemostasis based on algorithms defined in each centre and for each population of patients. Their position at the bedside or in the laboratory is a matter of discussion between clinicians and biologists., Conclusion: VETs must be included in algorithms. In consultation with the biology laboratory, these devices should be situated according to the way each centre functions., (Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose of Review: Perioperative bleeding and blood product transfusion are associated with significant morbidity and mortality. Prevention and optimal management of bleeding decreases risk and lowers costs. Tranexamic acid (TXA) is an antifibrinolytic agent that reduces bleeding and transfusion in a broad number of adult and pediatric surgeries, as well as in trauma and obstetrics. This review highlights the current pediatric indications and contraindications of TXA. The efficacy and safety profile, given current and evolving research, will be covered., Recent Findings: Based on the published evidence, prophylactic or therapeutic TXA administration is a well-tolerated and effective strategy to reduce bleeding, decrease allogeneic blood product transfusion, and improve pediatric patients' outcomes. TXA is now recommended in recent guidelines as an important part of pediatric blood management protocols., Summary: Based on TXA pharmacokinetics, the authors recommend a dosing regimen of between 10 to 30 mg/kg loading dose followed by 5 to 10 mg/kg/h maintenance infusion rate for pediatric trauma and surgery. Maximal efficacy and minimal side-effects with this dosage regime will have to be determined in larger prospective trials including high-risk groups. Furthermore, future research should focus on determining the ideal TXA plasma therapeutic concentration for maximum efficacy and minimal side-effects.

What We Already Know About This Topic: Risk stratification models to predict perioperative mortality in pediatric surgical populations are based on patient comorbidities, but do not take into consideration the intrinsic risk of the surgical procedures., What This Article Tells Us That Is New: Surgical procedures identified by specialty are not independent risk factors for perioperative mortality in pediatric patients. However, in multivariable predictive algorithms, the interaction of patient comorbidities with the intrinsic risk of the surgical procedure strongly predicts 30-day mortality., Background: Recently developed risk stratification models for perioperative mortality incorporate patient comorbidities as predictors but fail to consider the intrinsic risk of surgical procedures. In this study, the authors used the American College of Surgeons National Surgical Quality Improvement Program Pediatric database to demonstrate the relationship between the intrinsic surgical risk and 30-day mortality and develop and validate an accessible risk stratification model that includes the surgical procedures in addition to the patient comorbidities and physical status., Methods: A retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program Pediatric database was performed. The incidence of 30-day mortality was the primary outcome. Surgical Current Procedural Terminology codes with at least 25 occurrences were included. Multivariable logistic regression model was used to determine the predictors for mortality including patient comorbidities and intrinsic surgical risk. An internal validation using bootstrap resampling, and an external validation of the model were performed., Results: The authors analyzed 367,065 surgical cases encompassing 659 unique Current Procedural Terminology codes with an incidence of overall 30-day mortality of 0.34%. Intrinsic risk of surgical procedures represented by Current Procedural Terminology risk quartiles instead of broad categorization was significantly associated with 30-day mortality (P < 0.001). Predicted risk of 30-day mortality ranges from 0% with no comorbidities to 4.7% when all comorbidities are present among low-risk surgical procedures and from 0.07 to 46.7% among high-risk surgical procedures. Using an external validation cohort of 110,474 observations, the multivariable predictive risk model displayed good calibration and excellent discrimination with area under curve (c-index) equals 0.95 (95% CI, 0.94 to 0.96; P < 0.001)., Conclusions: Understanding and accurately estimating perioperative risk by accounting for the intrinsic risk of surgical procedures and patient comorbidities will lead to a more comprehensive discussion between patients, families, and providers and could potentially be used to conduct cost analysis and allocate resources.

Fibrinolytic activation is a major and preventable source of bleeding in neonates and children undergoing cardiac surgery with cardiopulmonary bypass. Based on the existing literature (adult and pediatric; cardiac and noncardiac), prophylactic administration of antifibrinolytic agents can help reduce fibrinolytic activation, and consequently reduces perioperative bleeding and the requirement for blood product transfusion. Due to the increased risk of renal failure and mortality reported in adults undergoing cardiac surgery, aprotinin should not be considered as a safe option in neonates and children. Further well-designed studies would be required before the prophylactic administration of aprotinin could be considered in pediatric cardiac surgery. The lysine analogs, tranexamic acid and ϵ-aminocaproic acid,, should be considered as safe and effective antifibrinolytic agents. Although no major side effects have been reported following the administration of lysine analogs in children undergoing cardiac surgery, high-dose tranexamic acid should not be recommended in order to avoid the increased risk of clinical seizures. Despite the recent advances made in our understanding of the pharmacokinetics of tranexamic acid and ϵ-aminocaproic acid,, the optimal plasmatic concentration to be targeted remains unknown. Further studies are therefore urgently needed to better define the optimal dose regimen to be used in neonates and children. In the meantime, the dose regimen published in the most recent pharmacokinetic studies can be used. Although no studies have assessed the effect of massive bleeding and transfusion on the plasmatic concentrations of the lysine analogs, additional boluses might be considered in the presence of bleeding and/or when signs of fibrinolytic activations are observed on viscoelastic hemostatic assays., (© 2018 John Wiley & Sons Ltd.)

Background: Preoperative anemia is an important modifiable risk factor for red blood cell (RBC) transfusion in a variety of surgical populations. The primary objective of this study was to examine the association between preoperative anemia and i) transfusion of RBCs within 72 hours of surgery and ii) postoperative clinical outcomes in children undergoing spine arthrodesis surgery., Study Design and Methods: We assembled a retrospective cohort of children included in the American College of Surgeons National Quality Improvement Program Pediatric database who underwent spine arthrodesis surgery from 2012 to 2016. Anemia was defined using age- and sex-specific hematocrit thresholds. Data collected included demographic and surgical characteristics, RBC transfusion within 72 hours, and 30-day postoperative outcomes (postoperative mechanical ventilation, infection, readmission, hospital length of stay, mortality). Multivariable logistic regression analyses were used to identify independent predictors of RBC transfusion and postoperative outcomes., Results: We included 9,095 patients in the analysis. Preoperative anemia was present in 14% (n = 1,233) of the population and 67% (n = 6,135) of patients were transfused. Our multivariable logistic regression showed anemia, surgical time > 350 minutes, > 7 vertebral levels fused, neuromuscular disease, and cerebral palsy were all independent predictors of RBC transfusion. Preoperative anemia was also associated with prolonged hospital LOS (adjusted OR: 1.31, 95%CI: 1.11-1.54, p = 0.002)., Conclusions: In this study of 9,095 children undergoing spine surgery, preoperative anemia was associated with an increased risk of RBC transfusion and prolonged LOS. Further studies are needed to determine if treatment of preoperative anemia can effectively reduce intraoperative RBC transfusion., (© 2018 AABB.)

Patient sedation and analgesia on extracorporeal membrane oxygenation (ECMO) is vital for safety and comfort. However, adsorption to the circuit may alter drug pharmacokinetics and remains poorly characterized. This study characterizes drug adsorption of morphine, fentanyl, midazolam, and dexmedetomidine in an ex vivo infant ECMO circuit utilizing polymethylpentene (PMP) membrane oxygenator (MO) with protein-bounded polyvinylchloride (PVC) tubing. Twelve closed-loop ex vivo ECMO circuits were prepared using P.h.i.s.i.o (phosphorylcholine)-coated PVC tubing (Sorin Group USA, Inc.) and a Quadrox-iD pediatric polymethylpentene MO (Maquet Cardiopulmonary AG). Once the circuits were primed and running, a single medication was injected as a bolus into the circuit with three circuits per drug. Drug samples were drawn following injection, at 2, 5, 15, 30, 60, 120 minutes and at 4, 12, 24, 36, and 48 hours and analyzed using ultra high-performance liquid chromatography with mass spectrometry. Compared with morphine, the other drugs are highly sequestered with fentanyl 68.5%, dexmedetomidine 50.8%, and midazolam 26.2% affecting the availability of free drug in the circuit. Sequestration of fentanyl, midazolam, and dexmedetomidine in an ECMO circuit with P.h.i.s.i.o-coated PVC tubing and PMP MO may limit drug delivery to infants. Future in vivo studies are needed to determine the clinical impact of sequestration.

Importance: Substantial preclinical evidence suggests that the developing brain is susceptible to injury from anesthetic drugs. Findings from clinical studies of the neurotoxic effects of anesthesia are mixed, but these effects can be influenced by unmeasured confounding from biological and environmental risk and protective factors on child development., Objective: To examine the association between surgical procedures that require general anesthesia before primary school entry and child development in biological siblings., Design, Setting, and Participants: This retrospective sibling-matched cohort study included sibling pairs aged 5 to 6 years with the same birth mother who had Early Development Instrument (EDI) data completed. The EDI is a population-based measure of child development that assesses children's readiness to learn in 5 major domains (physical health and well-being, social knowledge and competence, emotional health and maturity, language and cognitive development, and communication skills and general knowledge). All eligible children in public and Catholic schools in Ontario, Canada, from 2004 through 2012 were included. Data were analyzed from December 13, 2017, through July 27, 2018., Exposures: Surgical procedures that require general anesthesia from the date of birth to EDI completion., Main Outcomes and Measures: Early developmental vulnerability, defined as any major domain of the EDI in the lowest 10th percentile of the Ontario population., Results: Of the 187 226 eligible children for whom the EDI was completed, a total of 10 897 sibling pairs (21 794 children; 53.8% female; mean [SD] age, 5.7 [0.3] years) were subsequently identified, including 2346 with only 1 child exposed to surgery. No significant differences were found between exposed and unexposed children in early developmental vulnerability (697 of 3080 [22.6%] vs 3739 of 18 714 [20.0%]; adjusted odds ratio [aOR], 1.03; 95% CI, 0.98-1.14; P = .58) or for each of the 5 major EDI domains (aOR for language and cognitive development, 0.96 [95% CI, 0.80-1.14]; aOR for physical health and well-being, 1.09 [95% CI, 0.96-1.24]; aOR for social knowledge and competence, 0.98 [95% CI, 0.84-1.14]; aOR for emotional health and maturity, 0.98 [95% CI, 0.84-1.14]; and aOR for communication skills and general knowledge, 0.90 [95% CI, 0.77-1.05]), after adjusting for confounding factors (age at EDI completion, sex, mother's age at birth, and eldest sibling status)., Conclusions and Relevance: In this provincial cohort study, children who had surgical procedures that require general anesthesia before primary school entry were not found to be at increased risk of adverse child development outcomes compared with their biological siblings who did not have surgery. These findings further support that anesthesia exposure in early childhood is not associated with detectable adverse child development outcomes.

: We evaluated clinical and laboratory biomarkers of disseminated intravascular coagulation (DIC) following cardiac surgery in the cardiothoracic surgical ICU (CTICU) to predict mortality. We retrospectively analyzed CTICU patients with suspected DIC identified from the hospital laboratory database, and calculated International Society on Thrombosis and Haemostasis (ISTH) and the Japanese Association for Acute Medicine (JAAM) DIC scores to predict DIC-related mortality. The predictive accuracy of the JAAM and ISTH DIC scoring system were then assessed by logistic regression analysis and receiver operative characteristics analysis, and compared to other potential predictors of mortality (e.g., Acute Physiology and Chronic Health Evaluation II, systemic inflammatory response syndrome criteria, laboratory variables). Our study showed a 30-day mortality rate of 71% in CTICU patients with DIC. The JAAM DIC score offered the best predictive accuracy [area under the curve (AUC): 0.723, 95% % confidence interval (CI): 0.638-0.947, P = 0.021], when compared with ISTH DIC score (AUC: 0.707, 95% CI: 0.491-0.923, P = 0.066) and Acute Physiology and Chronic Health Evaluation II (AUC: 0.687, 95% CI: 0.483-0.891, P = 0.110). A JAAM DIC score at least 6 was reported in 89% of the nonsurvivors and 46% of survivors (P = 0.010), and predicted mortality [odds ratio: 9.33 (1.50-58.20)] with a 73% sensitivity and a 78% specificity. Our results also show a strong relationship between acid-base derangement and mortality. This initial evaluation of DIC-related mortality in the CTICU found the standardized JAAM DIC scoring system in combination with acid-base laboratory values were most useful to predict mortality in postcardiac surgery patients with DIC. Additional prospective studies are needed to further validate our findings.

Efforts to reduce blood product transfusions and adopt blood conservation strategies for infants and children undergoing cardiac surgical procedures are ongoing. Children typically receive red blood cell and coagulant blood products perioperatively for many reasons, including developmental alterations of their hemostatic system, and hemodilution and hypothermia with cardiopulmonary bypass that incites inflammation and coagulopathy and requires systemic anticoagulation. The complexity of their surgical procedures, complex cardiopulmonary interactions, and risk for inadequate oxygen delivery and postoperative bleeding further contribute to blood product utilization in this vulnerable population. Despite these challenges, safe conservative blood management practices spanning the pre-, intra-, and postoperative periods are being developed and are associated with reduced blood product transfusions. This review summarizes the available evidence regarding anemia management and blood transfusion practices in the perioperative care of these critically ill children. The evidence suggests that adoption of a comprehensive blood management approach decreases blood transfusions, but the impact on clinical outcomes is less well studied and represents an area that deserves further investigation.

Background: Perioperative bleeding is a common complication in pediatric patients undergoing cardiac operation. Although thromboelastography (TEG) has been used in patients undergoing adult cardiac operation, limited data are available in pediatric patients. We hypothesize that TEG variables may be associated with surrogate end points for postoperative bleeding in pediatric patients undergoing complex cardiac operation., Methods: In a retrospective study, TEG was obtained after protamine administration and on admission to the intensive care unit (ICU) in pediatric patients (≤18 years) undergoing cardiac operation that required cardiopulmonary bypass. A composite end point of extended blood product transfusion or surgical re-exploration for bleeding was used as a surrogate for perioperative bleeding. TEG variables were compared between patients who did or did not reach the composite end point., Results: The study included 511 pediatric patients undergoing complex cardiac operation. The composite end point was reached in 52% of patients with maximum amplitude (MA) less than 45 mm compared with 31% with MA of 45 mm or more (p < 0.001). With the use of multivariable regression analysis, MA less than 45 mm was independently associated with the composite end point (p < 0.001). Patients with MA less than 45 mm who received platelet transfusion in the operating room (OR) were less likely to reach the composite end point within the subsequent 24 hours (8%) compared with patients who did not receive intraoperative platelet transfusion (24%) (p = 0.02)., Conclusions: Intraoperative TEG MA less than 45 mm is associated with a surrogate end point for intraoperative bleeding in pediatric patients undergoing complex cardiac operation. In patients with MA less than 45 mm, prophylactic platelet transfusion in the OR may be associated with reduction in bleeding end points in the ICU., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary hypertension (PHTN) is associated with increased post-procedure morbidity and mortality. Pre-procedure echocardiography (ECHO) is a widely used tool for evaluation of these patients, but its accuracy in predicting post-procedure outcomes is unproven. Self-reported exercise tolerance has not been evaluated for operative risk stratification of PHTN patients., Objective: We analyzed whether self-reported exercise tolerance predicts outcomes (hospital length-of-stay [LOS], mortality and morbidity) in PHTN patients (WHO Class I-V) undergoing anesthesia and surgery., Methods and Findings: We reviewed 550 non-cardiac, non-obstetric procedures performed on 370 PHTN patients at a single institution between 2007 and 2013. All patients had cardiac ECHO documented within 1 year prior to the procedure. Pre-procedure comorbidities and ECHO data were collected. Functional status (< or ≥ 4 metabolic equivalents of task [METs]) was assigned based on responses to standard patient interview questions during the pre-anesthesia clinic visit. Multiple logistic regression was used to develop a risk score model (Pulmonary Hypertension Outcome Risk Score; PHORS) and determine its value in predicting post-procedure outcomes. In an adjusted model, functional status <4 METs was independently associated with a LOS >7 days (p < .003), as were higher ASA class (p < .002), open surgical approach (p < .002), procedure duration > 2 hours (p < .001), and the absence of systemic hypertension (p = .012). PHORS Score ≥2 was associated with an increased 30-day major complication rate (28.7% vs. 19.2%; p < 0.001) and ICU admission rate (8.6% s 2.8%; p = .007), but no statistical difference in hospital readmissions rate (17.6% vs. 14.0%; p = .29), or mortality (3.5% vs. 1.4%; p = .75). Similar ECHO findings did not further improve outcome prediction., Conclusions: Poor functional status is associated with severe PHTN and predicts increased LOS and post-procedure complications in patients with moderate to severe pulmonary hypertension with different etiologies. A risk assessment model predicts increased LOS with fair accuracy. A thorough evaluation of underlying etiologies of PHTN should be undertaken in every patient., Competing Interests: I certify that there is no actual or potential conflict of interest in relation to this article. Gail Van Norman, MD, receives funding from the Journal of the American College of Cardiology for work unrelated to this study or the creation of this manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: To describe the demographic and thromboelastographic characteristics of patients with congenital heart disease presenting with decreased heparin response before cardiac surgery., Design: Retrospective, observational study., Setting: Single institution, tertiary, academic, university hospital., Participants: The study comprised 496 pediatric and adult patients undergoing cardiac surgery for congenital heart disease., Interventions: Retrospective review of medical records., Measurements and Main Results: Data on preoperative thromboelastography (TEG), demographics, and response to heparin were collected retrospectively. Logistic regression analysis was used to study the association between TEG and response to heparin. Decreased heparin response (defined as activated clotting time <480 s initial bolus of 300 U/kg heparin) was observed in 23.6% of patients presenting for surgery. Age distribution and preoperative coagulation profiles were similar for both nonresponders and responders to heparin. Preoperatively, nonresponders demonstrated all thromboelastrographic characteristics consistent with a hypercoagulable profile (shorter reaction time, K value, wider angle, and maximum amplitude). Univariate logistic regression identified all TEG variables significantly associated with decreased heparin response. After adjustment for age, procedure type, and the presence of cyanosis, a multivariate logistic regression model identified the TEG variable K (≤1.3 min) as being significantly associated with decreased heparin response (odds ratio 3.7; confidence interval 2.3-5.8; p < 0.0001)., Conclusions: Decreased response to heparin before cardiac surgery in patients with congenital heart disease is associated with preoperative hypercoagulability identified using a viscoelastic test. Additional studies are needed to better understand the etiology of decreased heparin response and potential clinical strategies to improve anticoagulation management., (Copyright © 2017 Elsevier Inc. All rights reserved.)

: Although there are numerous publications addressing venous thromboembolism and its prevention in neurosurgery, there are relatively few high-quality studies to guide decisions regarding thromboprophylaxis. In patients undergoing craniotomy, we recommend that if intermittent pneumatic compression (IPC) is used, it should be applied before the surgical procedure or on admission (Grade 1C). In craniotomy patients at particularly high risk for venous thromboembolism, we suggest considering the initiation of mechanical thromboprophylaxis with IPC preoperatively with addition of low molecular weight heparin (LMWH) postoperatively when the risk of bleeding is presumed to be decreased (Grade 2C). In patients with non-traumatic intracranial haemorrhage, we suggest thromboprophylaxis with IPC (Grade 2C). For patients who have had non-traumatic intracranial haemorrhage, we suggest giving consideration to commencement of LMWH or low-dose unfractionated heparin when the risk of bleeding is presumed to be low (Grade 2C). We suggest continuing thromboprophylaxis until full mobilisation of the patient (Grade 2C). For patients undergoing spinal surgery with no additional risk factors, we suggest no active thromboprophylaxis intervention apart from early mobilisation (Grade 2C). For patients undergoing spinal surgery with additional risk factors, we recommend starting mechanical thromboprophylaxis with IPC (Grade 1C), and we suggest the addition of LMWH postoperatively when the risk of bleeding is presumed to be decreased (Grade 2C).

: None of the predictive models for venous thromboembolism (VTE) prophylaxis have been designed for and validated in patients undergoing cardiothoracic and vascular surgery. The presence of one or more risk factors [age over 70 years old, transfusion of more than 4 U of red blood cells/fresh frozen plasma/cryoprecipitate, mechanical ventilation lasting more than 24 h, postoperative complication (e.g. acute kidney injury, infection/sepsis, neurological complication)] should place the cardiac population at high risk for VTE. In this context, we suggest the use of pharmacological prophylaxis as soon as satisfactory haemostasis has been achieved, in addition to intermittent pneumatic compression (IPC) (Grade 2C). In patients undergoing abdominal aortic aneurysm repair, particularly when an open surgical approach is used, the risk for VTE is high and the bleeding risk is high. In this context, we suggest the use of pharmacological prophylaxis as soon as satisfactory haemostasis is achieved (Grade 2C). Patients undergoing thoracic surgery in the absence of cancer could be considered at low risk for VTE. Patients undergoing thoracic surgery with a diagnosis of primary or metastatic cancer should be considered at high risk for VTE. In low-risk patients, we suggest the use of mechanical prophylaxis using IPC (Grade 2C). In high-risk patients, we suggest the use of pharmacological prophylaxis in addition to IPC (Grade 2B).

Background: Hospital readmissions are being used as a quality metric for hospital reimbursement without a clear understanding of the factors that contribute to readmission., Objective: The objective of this study was to report the incidence of 30-day postsurgical readmission in children, identify the predictors for readmission, and create an algorithm to identify high-risk children., Methods: Data from the 2012-2014 Pediatric database of the American College of Surgeons National Surgical Quality Improvement Program were analyzed using univariable and multivariable logistical regression analysis., Results: Among 182 589 children included in the 2012-2014 American College of Surgeons National Surgical Quality Improvement Program Pediatric database, 4.8% (8815/182 589) experienced a readmission within 30 days. Four significant predictors were retained in the multivariable logistic regression model: American Society of Anesthesiologists physical status ≥ 3 (OR: 1.9, 95% CI: 1.8-2.0), presence of congenital heart disease (OR: 1.66, 95% CI: 1.31-2.11), inpatient status at time of surgery (OR: 3.5, 95% CI: 3.3-3.7), and at least 1 postoperative complication (neurologic, renal, wound, cardiac, bleeding, or pulmonary) (OR: 3.14, 95% CI: 2.92-3.34). The multivariable logistic regression model showed reasonably good discrimination in predicting 30-day readmissions with receiver operating characteristic area under the curve of 0.747 (95% CI: 0.73-0.75) and good calibration (Brier score: 0.044). We created a predictive algorithm of 30-day readmission based on the 4 significant predictors., Conclusion: Children with congenital heart disease, high American Society of Anesthesiologist physical class, inpatient status, and at least 1 postoperative complication of any kind are at high risk for postsurgical readmissions. We provide an algorithm for quantifying this risk with the goal of reducing the number of readmissions, improving the care of patients with complex chronic illnesses, and reducing hospital costs., (© 2017 John Wiley & Sons Ltd.)