Perioperative considerations in the paediatric patient with congenital and acquired coagulopathy.

Neonates, infants, and children undergoing major surgery or with trauma can develop severe coagulopathy perioperatively. Neonates and infants are at highest risk because their haemostatic system is not fully developed and underlying inherited bleeding disorders may not have been diagnosed before surgery. Historically, laboratory coagulation measurements have been used to diagnose and monitor coagulopathies. Contemporary dynamic monitoring strategies are evolving. Viscoelastic testing is increasingly being used to monitor coagulopathy, particularly in procedures with a high risk of bleeding. However, there is a lack of valid age-specific reference values for diagnosis and trigger or target values for appropriate therapeutic management. A promising screening tool of primary haemostasis that may be used to diagnose quantitative and qualitative platelet abnormalities is the in vitro closure time by platelet function analyser. Targeted individualised treatment strategies for haemostatic bleeding arising from inherited or acquired bleeding disorders may include measures such as tranexamic acid, administration of plasma, derived or recombinant factors such as fibrinogen concentrate, or allogeneic blood component transfusions (plasma, platelets, or cryoprecipitate). Herein we review current recommended perioperative guidelines, monitoring strategies, and treatment modalities for the paediatric patient with a coagulopathy. In the absence of data from adequately powered prospective studies, it is recommended that expert consensus be considered until additional research and validation of goal-directed perioperative bleeding management in paediatric patients is available.

Perioperative paediatric patient blood management: a narrative review.

Patient blood management (PBM) encompasses implementing multimodal evidence-based strategies to screen, diagnose, and properly treat anaemia and coagulopathies using goal-directed therapy while minimising bleeding. The aim of PBM is to improve clinical care and patient outcomes while managing patients with potential or ongoing critical anaemia, clinically significant bleeding, and coagulopathies. The focus of PBM is patient-centred rather than transfusion-centred. Multimodal PBM strategies are now recommended by international organisations, including the World Health Organization, as a new standard of care and a proven means to safely and effectively manage anaemia and blood loss while minimising unnecessary blood transfusion. Compared with adult PBM, paediatric PBM is currently not routinely accepted as a standard of care. This is partly because of the paucity of robust data on paediatric patient PBM. Managing paediatric bleeding and blood product transfusion presents unique challenges. Neonates, infants, children, and adolescents each have specific considerations based on age, weight, physiology, and pharmacology. This narrative review covers the latest updates for PBM in paediatric surgical populations including the benefits and principles of paediatric PBM, current expert consensus guidelines, and important universal multimodal therapeutic strategies emphasising clinical management of the anaemic, bleeding, or coagulopathic paediatric patient in the perioperative period. Practical paediatric rules for PBM in the perioperative period are highlighted, with review of specific PBM strategies including treatment of preoperative anaemia, restrictive transfusion thresholds, antifibrinolytic agents, cell salvage, standardised transfusion algorithms, and goal-directed therapy based on point-of-care and viscoelastic testing.

Trends in Gender of Authors of Patient Blood Management Publications.

BACKGROUND: Diverse representation in the field of patient blood management (PBM) may help bring varying perspectives to improve patient care. We assessed trends in gender of first and last authorship of recent PBM publications to evaluate diversity within the field. METHODS: Publications from 10 high-impact anesthesiology and blood transfusion medicine journals between 2017 and 2021 were reviewed using 19 keywords to identify PBM-related articles. Each publication title was reviewed independently to determine whether it met the inclusion criteria. A software program was used to identify the gender of each first and last author for the most common first names. Author gender that could not be identified through this process was determined by querying institutional websites and professional social networks (eg, ResearchGate). Any publication where the gender of the first and/or last author could not be reliably determined was excluded from the analysis. Trends over time were assessed using the Cochran-Armitage test. RESULTS: A total of 2467 publications met the inclusion criteria of the 2873 yielded by the initial search. Gender of the first and last author was identified for 2384 of these publications and included in the final analysis. Approximately 42.8% of publications featured a woman as the first author with the highest from the journals such as the Journal of the American Medical Association ( JAMA ) (48.7%) and Transfusion (48.1%) and the lowest from the journals such as the British Journal of Anaesthesia (24.1%) and Anesthesia & Analgesia (24.4%). Approximately 32.0% of the publications featured a woman as the last author with the highest being Transfusion (36.9%) and Anaesthesia (31.8%) and the lowest being Anesthesia and Analgesia (18.3%) and Anesthesiology (18.6%). Approximately 57.6% of publications had either a woman as the first or last author while 16.3% of the publications had women as both the first and last authors. Women authors comprised 32.6% of the publications with a single author. Women as the first or last authors did not change significantly over the study period ( P = .115 and P = .119, respectively). No significant difference was observed in the percentage of PBM articles with a woman as the first or last author, a woman as the first and last author, or a woman as a single author from 2017 to 2021 ( P = .089, P = .055, and P = .226, respectively). CONCLUSIONS: The percentage of women as the first and last authors in PBM publications from the 5-year period of 2017 to 2021 was <50%. Gender equity in PBM authorship was identified as an area for potential future improvement. International mentorship and sponsorship of women remain important in promoting gender equity in PBM authorship.

Implementation of an Enhanced Recovery after Surgery Pathway for Transgender and Gender-Diverse Individuals Undergoing Chest Reconstruction Surgery: An Observational Cohort Study.

Enhanced Recovery After Surgery (ERAS) protocols are associated with improved clinical outcomes in cisgender breast surgery patients. However, a paucity of research exists regarding transgender and gender-diverse individuals (TGD) in the ERAS framework. The primary objective of this observational cohort study is to describe the implementation of a gender-affirming ERAS protocol and its relationship to hospital length of stay (LOS) in TGD patients following chest reconstruction surgery. The secondary aim is to identify intraoperative predictors of LOS and define variables associated with adverse outcomes. We identified 362 patients in three epochs: a traditional group (n = 144), a partial ERAS implementation group (n = 92), and an ERAS group (n = 126). Exploratory multivariable median regression modeling was performed to identify independent predictors of LOS. We report that the traditional group's median hospital LOS was 1.1 days compared to 0.3 days in the ERAS group. Intraoperative tranexamic acid administration was associated with significantly shorter LOS (p < 0.001), reduced postoperative drainage (p < 0.001), and fewer returns to the operating room within 24 h (p = 0.047). Our data suggest that implementing a multimodal ERAS gender-affirming pathway was associated with improved patient-centered surgical outcomes such as decreased return to the operating room for hematoma evacuation, higher rates of discharge home, and reduced postoperative drainage output.

Tranexamic Acid Use in Pediatric Craniotomies at a Large Tertiary Care Pediatric Hospital: A Five Year Retrospective Study.

Tranexamic acid (TXA), a synthetic antifibrinolytic drug, has proven efficacy and is recommended for major pediatric surgery to decrease perioperative blood loss. Accumulating evidence suggests that TXA reduces bleeding and transfusion in a variety of adult neurosurgical settings. However, there is a paucity of research regarding TXA indications for pediatric neurosurgery and thus, there are currently no recommendations for its use with this specific population. The objective of this study is to evaluate the existing practice of TXA administration for pediatric neurosurgery at a U.S. tertiary care pediatric hospital over a five-year period. The authors conclude that TXA administration is feasible and should be considered for pediatric neurosurgical cases where potential blood loss is a concern.

Evaluation of a Pre-Filled Table and a Flowchart-Based Algorithm as Cognitive Aids to Reduce Deviations in Dose Calculation for Intraoperative Red Blood Cell Transfusions in Children-An International Web-Based Simulation.

BACKGROUND: Transfusion of red blood cell concentrate can be life-saving, but requires accurate dose calculations in children. AIMS: We tested the hypothesis that cognitive aids would improve identification of the correct recommended volumes and products, according to the German National Transfusion guidelines, in pediatric transfusion scenarios. METHODS: Four online questionnaire-based scenarios, two with hemodynamically stable and two with hemodynamically unstable children, were sent to German and international pediatric anesthetists for completion. In the two stable scenarios, participants were given pre-filled tables that contained all required information. For the two emergency scenarios, existing algorithms were used and required calculation by the user. The results were classified into three categories of deviations from the recommended values (DRV): DRV120 (<80% or >120%), as the acceptable variation; DRV 300 (<33% or >300%), the deviation of concern for potential harm; and DRV 1000 (<10% or >1000%), the excessive deviation with a high probability of harm. RESULTS: A total of 1.458 pediatric anesthetists accessed this simulation questionnaire, and 402 completed questionnaires were available for analysis. A pre-filled tabular aid, avoiding calculations, led to a reduction in deviation rates in the category of DRV120 by 60% for each and of DRV300 by 17% and 20%, respectively. The use of algorithms as aids for unstable emergencies led to a reduction in the deviation rate only for DRV120 (20% and 15% respectively). In contrast, the deviation rates for DRV300 and DRV1000 rose by 37% and 16%, respectively. Participants used higher transfusion thresholds for the emergency case of a 2-year-old compromised child than for the stable case with a patient of the same age (on average, 8.6 g/dL, 95% CI 8.5-8.8 versus 7.1 g/dL, 95% CI 7.0-7.2, p < 0.001) if not supported by our aids. Participants also used a higher transfusion threshold for unstable children aged 3 months than for stable children of the same age (on average, 8.9 g/dL, 95% CI 8.7-9.0 versus 7.9 g/dL, 95% CI 7.7-8.0, p < 0.001). CONCLUSIONS: The use of cognitive aids with precalculated transfusion volumes for determining transfusion doses in children may lead to improved adherence to published recommendations, and could potentially reduce dosing deviations outside those recommended by the German national transfusion guidelines.

Error traps in Pediatric Patient Blood Management in the Perioperative Period.

Patient blood management is a patient-centered evidence-based approach to improve patient outcomes by harnessing the patient's own hematopoietic system to optimize blood health while promoting patient safety and empowerment. Perioperative patient blood management is a standard of care in adult medicine, yet it is not commonly accepted in pediatrics. Raising awareness may be the first step in improving perioperative care for the anemic and/or bleeding child. This article highlights five preventable perioperative blood conservation error traps for children. The goal is to provide practical clinical guidance to improve preoperative diagnosis and treatment of anemia, facilitate recognition and treatment of massive hemorrhage, reduce unnecessary allogeneic blood transfusions, and decrease associated complications of anemia and blood component transfusions utilizing a patient/family-centered informed consent and shared decision-making approach.

Large Vertex Encephaloceles: Management and Outcomes.

BACKGROUND: Complex vertex and posterior encephaloceles containing brain tissue have uncertain prognosis and high operative risk. Patients may not be offered operative intervention depending on local and regional specialist expertise. The authors present their experience treating 5 such pediatric patients. METHODS: This is a retrospective review of the surgical assessment, planning, and technique of cranial repairs, as well as surgical outcomes and developmental follow-up regarding adaptive functioning for patients presenting for second opinion for encephalocele of the cranial vertex after having been deemed too high risk at another institution. RESULTS: Five consecutive patients presented between January 2014 and June 2016. One patient was not offered repair. Of 4 patients who underwent reconstruction, average age at time of repair was 2.7 months (range, 0.9-6.7). One presented with ruptured encephalocele, whereas the remaining 3 underwent drainage of the encephalocele (average volume of 1200 mL) at time of surgical resection. Operative time averaged 3.7 hours (range, 2.2-5.3). There were no deaths. One patient had a single seizure postoperatively. Two patients required placement of permanent shunt for hydrocephalus. Two patients completed developmental evaluations, both of whom exhibited delays in adaptive functioning relative to same-aged peers. CONCLUSIONS: Patients with large, complex encephalocele warrant evaluation by an experienced high-volume tertiary care pediatric craniofacial center. The decision to proceed with surgical management should include an interdisciplinary team of surgeons, anesthesiologists, neurologists, and social work. Further study of developmental outcomes in both operated and unoperated patients is necessary to better understand risks and benefits of reconstruction.

Update on Applications and Limitations of Perioperative Tranexamic Acid.

Tranexamic acid (TXA) is a potent antifibrinolytic with documented efficacy in reducing blood loss and allogeneic red blood cell transfusion in several clinical settings. With a growing emphasis on patient blood management, TXA has become an integral aspect of perioperative blood conservation strategies. While clinical applications of TXA in the perioperative period are expanding, routine use in select clinical scenarios should be supported by evidence for efficacy. Furthermore, questions regarding optimal dosing without increased risk of adverse events such as thrombosis or seizures should be answered. Therefore, ongoing investigations into TXA utilization in cardiac surgery, obstetrics, acute trauma, orthopedic surgery, neurosurgery, pediatric surgery, and other perioperative settings continue. The aim of this review is to provide an update on the current applications and limitations of TXA use in the perioperative period.

Transfusion Strategies for Hemostatic Blood Products in Critically Ill Children: A Narrative Review and Update on Expert Consensus Guidelines.

Critically ill children commonly receive coagulant products (plasma and/or platelet transfusions) to prevent or treat hemorrhage or correct coagulopathy. Unique aspects of pediatric developmental physiology, and the complex pathophysiology of critical illness must be considered and balanced against known transfusion risks. Transfusion practices vary greatly within and across institutions, and high-quality evidence is needed to support transfusion decision-making. We present recent recommendations and expert consensus statements to direct clinicians in the decision to transfuse or not to transfuse hemostatic blood products, including plasma, platelets, cryoprecipitate, and recombinant products to critically ill children.

Safety of antifibrinolytics in 6583 pediatric patients having craniosynostosis surgery: A decade of data reported from the multicenter Pediatric Craniofacial Collaborative Group.

BACKGROUND: Antifibrinolytics such as tranexamic acid and epsilon-aminocaproic acid are effective at reducing blood loss and transfusion in pediatric patients having craniofacial surgery. The Pediatric Craniofacial Collaborative Group has previously reported low rates of seizures and thromboembolic events (equal to no antifibrinolytic given) in open craniofacial surgery. AIMS: To query the Pediatric Craniofacial Collaborative Group database to provide an updated antifibrinolytic safety profile in children given that antifibrinolytics have become recommended standard of care in this surgical population. Additionally, we include the population of younger infants having minimally invasive procedures. METHODS: Patients in the Pediatric Craniofacial Collaborative Group registry between June 2012 and March 2021 having open craniofacial surgery (fronto-orbital advancement, mid and posterior vault, total cranial vault remodeling, intracranial LeFort III monobloc), endoscopic cranial suture release, and spring mediated cranioplasty were included. The primary outcome is the rate of postoperative complications possibly attributable to antifibrinolytic use (seizures, seizure-like activity, and thromboembolic events) in infants and children undergoing craniosynostosis surgery who did or did not receive antifibrinolytics. RESULTS: Forty-five institutions reporting 6583 patients were included. The overall seizure rate was 0.24% (95% CI: 0.14, 0.39%), with 0.20% in the no Antifibrinolytic group and 0.26% in the combined Antifibrinolytic group, with no statistically reported difference. Comparing seizure rates between tranexamic acid (0.22%) and epsilon-aminocaproic acid (0.44%), there was no statistically significant difference (odds ratio = 2.0; 95% CI: 0.6, 6.7; p = .257). Seizure rate was higher in patients greater than 6 months (0.30% vs. 0.18%; p = .327), patients undergoing open procedures (0.30% vs. 0.06%; p = .141), and syndromic patients (0.70% vs. 0.19%; p = .009). CONCLUSIONS: This multicenter international experience of pediatric craniofacial surgery reports no increase in seizures or thromboembolic events in those that received antifibrinolytics (tranexamic acid and epsilon-aminocaproic acid) versus those that did not. This report provides further evidence of antifibrinolytic safety. We recommend following pharmacokinetic-based dosing guidelines for administration.

Tranexamic acid administered during cesarean delivery in high-risk patients: maternal pharmacokinetics, pharmacodynamics, and coagulation status.

BACKGROUND: Tranexamic acid is frequently administered for postpartum hemorrhage. The World Health Organization recommends 1 g intravenous dosing, repeated once after 30 minutes for ongoing bleeding. Understanding the pharmacokinetics and pharmacodynamics of tranexamic acid in patients at high risk of postpartum hemorrhage may enable dosage tailoring for optimal antifibrinolysis with minimal adverse events, such as thrombosis or renal cortical necrosis. OBJECTIVE: This study aimed to report tranexamic acid pharmacokinetics and pharmacodynamics after 1 g intravenous dosing during cesarean delivery in patients at risk of hemorrhage. The primary endpoint was tranexamic acid plasma concentration of >10 µg/mL, known to inhibit 80% of fibrinolysis. In addition, the correlation between patient demographics and rotational thromboelastometry coagulation changes were analyzed. STUDY DESIGN: In this prospective study, 20 women aged 18 to 50 years, ≥23 weeks of gestation undergoing cesarean delivery with at least 1 major (placenta previa, suspected placenta accreta spectrum, or active bleeding) or 2 minor (≥2 previous cesarean deliveries, previous postpartum hemorrhage, chorioamnionitis, polyhydramnios, macrosomia, obesity, or suspected placental abruption) risk factors for postpartum hemorrhage were recruited. The exclusion criteria were allergy to tranexamic acid, inherited thrombophilia, previous or current thrombosis, seizure history, renal or liver dysfunction, anticoagulation, or category III fetal heart tracing. Tranexamic acid 1 g was administered after umbilical cord clamping. Blood samples were drawn at 3, 7, 15, and 30 minutes and then at 30-minute intervals up to 5 hours. Plasma concentrations were evaluated as mean (standard error). Serial rotational thromboelastometry was performed and correlated with tranexamic acid plasma concentrations. RESULTS: The median age of participants was 37.5 years (interquartile range, 35.0-39.5), and the median body mass index was 28.6 kg/m2 (interquartile range, 24.9-35.0). The median blood loss (estimated or quantitative) was 1500 mL (interquartile range, 898.5-2076.0). Of note, 9 of 20 (45%) received a transfusion of packed red blood cells. The mean peak tranexamic acid plasma concentration at 3 minutes was 59.8±4.7 µg/mL. All patients had a plasma concentration >10 µg/mL for 1 hour after infusion. Plasma concentration was >10 µg/mL in more than half of the patients at 3 hours and fell <10 µg/mL in all patients at 5 hours. There was a moderate negative correlation between body mass index and the plasma concentration area under the curve (r=-0.49; 95% confidence interval, -0.77 to -0.07; P=.026). Rotational thromboelastometry EXTEM maximum clot firmness had a weak positive correlation with longitudinal plasma concentration (r=0.32; 95% confidence interval, 0.21-0.46; P<.001). EXTEM maximum clot lysis was 0% after infusion in 18 patients (90%), and no patient in the study demonstrated a maximum lysis of >15% at any interval from 3 minutes to 5 hours. There was no significant correlation between EXTEM clot lysis at 30 minutes and longitudinal tranexamic acid plasma concentrations (r=0.10; 95% confidence interval, -0.20 to 0.19; P=.252). CONCLUSION: After standard 1 g intravenous dosing of tranexamic acid during cesarean delivery in patients at high risk of hemorrhage, a plasma concentration of ≥10 µg/mL was sustained for at least 60 minutes. Plasma tranexamic acid levels correlated inversely with body mass index. The concurrent use of rotational thromboelastometry may demonstrate tranexamic acid's impact on clot firmness but not a hyperfibrinolysis-derived trigger for therapy.

Plasma and Platelet Transfusion Strategies in Critically Ill Children Following Severe Trauma, Traumatic Brain Injury, and/or Intracranial Hemorrhage: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.

OBJECTIVES: To present consensus statements and supporting literature for plasma and platelet transfusions in critically ill children with severe trauma, traumatic brain injury, and/or intracranial hemorrhage from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding. DESIGN: Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children. SETTING: Not applicable. PATIENTS: Critically ill neonates and children with severe trauma, traumatic brain injury, and/or intracranial hemorrhage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A panel of eight experts developed expert-based statements for plasma and platelet transfusions in critically ill neonates and children with severe trauma, traumatic brain injury, and/or intracranial hemorrhage. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed one good practice statement and six expert consensus statements. CONCLUSIONS: The lack of evidence precludes proposing recommendations on monitoring of the coagulation system and on plasma and platelets transfusion in critically ill pediatric patients with severe trauma, severe traumatic brain injury, or nontraumatic intracranial hemorrhage.