Dosing of tranexamic acid in trauma.

PURPOSE OF REVIEW: Tranexamic acid is routinely used as part of the management of traumatic bleeding. The dose recommendation in trauma was extrapolated from other clinical settings and the results of pragmatic randomized trials rather than pharmaco-kinetic and -dynamic evaluations. The review addresses current evidence on dosing of tranexamic acid in traumatized patients with a focus on efficacy, safety and risk-benefit profile. RECENT FINDINGS: A majority, but not all, of existing randomized clinical trials reports a reduction in mortality and/or blood loss with tranexamic acid administration. Increasing dose above the general recommendation (1 g bolus + 1 g infusion/8 h intravenously) has not been shown to further increase efficacy and could potentially increase side effects. SUMMARY: The benefit of tranexamic acid as adjuvant therapy in the management of bleeding trauma patients on mortality and transfusion requirements is clear and well documented, being most effective if given early and to patients with clinical signs of hemorrhagic shock. Recent reports suggest that in some patients presenting with a shutdown of their fibrinolytic pathway the administration of tranexamic acid could be associated with an increased risk of thromboembolic events and poor outcomes. A more personalized approach based on bedside assessment of fibrinolytic activation and pharmacokinetic-based dose regimen should be developed moving forward.

Higher Cumulative Dose of Opioids and Other Sedatives are Associated with Extubation Failure in Norwood Patients.

BACKGROUND: The primary purpose of this study is to evaluate the relationship between sedation usage and extubation failure, and to control for the effects of hemodynamic, oximetric indices, clinical characteristics, ventilatory settings pre- and post-extubation, and echocardiographic (echo) findings in neonates with hypoplastic left heart syndrome (HLHS) post-Norwood procedure. METHODS: Single-center, retrospective analysis of Norwood patients during their first extubation post-surgery from January 2015 to July 2021. Extubation failure was defined as reintubation within 48 h of extubation. Demographics, clinical characteristics, ventilatory settings, echo findings (right ventricular function, tricuspid regurgitation), and cumulative dose of sedation medications before extubation were compared between patients with successful or failed extubation. RESULTS: The analysis included 130 patients who underwent the Norwood procedure with 121 (93%) successful and 9 (7%) failed extubations. Univariate analyses showed that vocal cord anomaly (p = 0.05), lower end-tidal CO2 (p < 0.01), lower pulse-to-respiratory quotient (p = 0.02), and ketamine administration (p = 0.04) were associated with extubation failure. The use of opioids, benzodiazepines, dexmedetomidine, and ketamine are mutually correlated in this cohort. On multivariable analysis, the vocal cord anomaly (OR = 7.31, 95% CI 1.25-42.78, p = 0.027), pre-extubation end-tidal CO2 (OR = 0.80, 95% CI 0.65-0.97, p = 0.025), and higher cumulative dose of opioids (OR = 10.16, 95% CI 1.25-82.43, p = 0.030) were independently associated with extubation failure while also controlling for post-extubation respiratory support (CPAP/BiPAP/HFNC vs NC), intubation length, and echo results. CONCLUSION: Higher cumulative opioid doses were associated with a greater incidence of extubation failure in infants post-Norwood procedure. Therefore, patients with higher cumulative doses of opioids should be more closely evaluated for extubation readiness in this population. Low end-tidal CO2 and low pulse-to-respiratory quotient were also associated with failed extubation. Consideration of the pulse-to-respiratory quotient in the extubation readiness assessment can be beneficial in the Norwood population.

Retrospective Comparison of Recombinant Activated Factor VII Versus 4-Factor Prothrombin Complex Concentrate in Cardiac Surgical Patients.

OBJECTIVES: To compare the incidences of postoperative thrombotic complications, transfusion of blood products, and chest tube output in congenital cardiac surgical patients who received either recombinant activated factor VII (rFVIIa) or 4-factor prothrombin complex concentrate (4F-PCC). DESIGN: We performed a retrospective study. SETTING: Patients who underwent surgery at a tertiary academic hospital. PARTICIPANTS: Pediatric patients who underwent cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were obtained from the Society of Thoracic Surgeons and the Pediatric Cardiac Critical Care Consortium databases, as well as from manual chart review. Adjusted p values were obtained from multivariate regression using age (days), surgeon (number), cardiopulmonary bypass time (minutes), and need for deep hypothermic circulatory arrest (yes/no). A total of 55 patients were included in the 4F-PCC group, and 89 in the rFVIIa group. The median dose of rFVIIa was 77 mcg/kg (46-88), and the median dose of 4F-PCC was 31 IU/kg (24-43). The incidences of thrombotic complications were 8% in the 4F-PCC group and 30% in the rFVIIa group (adjusted p = 0.023). No difference was reported between the groups regarding chest tube output on days 1 and 2 or transfusion of blood products. Using a sensitivity analysis with propensity matching, the incidence of thrombosis was 10% in the 4F-PCC group (n = 38), and 31% in the rFVIIa group (n = 39) (p = 0.036). No difference was reported in terms of bleeding or transfusion. CONCLUSIONS: This retrospective study suggested that the administration of rFVIIa was associated with a higher risk of thrombotic complications when compared to 4F-PCC, without benefits in terms of bleeding and transfusions.

Cardiac Arrest With or Without Need for Extracorporeal Life Support After Congenital Cardiac Surgery.

BACKGROUND: Postoperative cardiac arrest (CA) with or without need for extracorporeal cardiopulmonary resuscitation (ECPR) is one of the most significant complications in the early postoperative period after pediatric cardiac operation. The objective of this study was to develop and to validate a predictive model of postoperative CA with or without ECPR. METHODS: In this retrospective cohort study, we reviewed data from patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) between July 20, 2020, and December 31, 2021. Variables included demographic data, presence of preoperative risk factors, The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery mortality categories, perioperative data, residual lesion score (RLS), and vasoactive-inotropic score (VIS). We used multivariable logistic regression analysis to develop a predictive model. RESULTS: The incidence of CA with or without ECPR was 4.4% (n = 24/544). Patients who experienced postoperative CA with or without ECPR were younger (age, 130 [54-816.5] days vs 626 [127.5-2497.5] days; P < .050) and required longer CPB (253 [154-332.5] minutes vs 130 [87-186] minutes; P < .010) and cross-clamp (116.5 [75.5-143.5] minutes vs 64 [30-111] minutes; P < .020) times; 37.5% of patients with an outcome had at least 1 preoperative risk factor (vs 16.9%; P < .010). Our multivariable logistic regression determined that the presence of at least 1 preoperative risk factor (P = .005), CPB duration (P = .003), intraoperative residual lesion score (P = .009), and postsurgery vasoactive-inotropic score (P = .010) were predictors of the incidence of CA with or without ECPR. CONCLUSIONS: We developed a predictive model of postoperative CA with or without ECPR after congenital cardiac operation. Our model performed better than the individual scores and risk factors.

Development and validation of a multivariable prediction model in pediatric liver transplant patients for predicting intensive care unit length of stay.

BACKGROUND: Liver transplantation is the life-saving treatment for many end-stage pediatric liver diseases. The perioperative course, including surgical and anesthetic factors, have an important influence on the trajectory of this high-risk population. Given the complexity and variability of the immediate postoperative course, there would be utility in identifying risk factors that allow prediction of adverse outcomes and intensive care unit trajectories. AIMS: The aim of this study was to develop and validate a risk prediction model of prolonged intensive care unit length of stay in the pediatric liver transplant population. METHODS: This is a retrospective analysis of consecutive pediatric isolated liver transplant recipients at a single institution between April 1, 2013 and April 30, 2020. All patients under the age of 18 years receiving a liver transplant were included in the study (n = 186). The primary outcome was intensive care unit length of stay greater than 7 days. RESULTS: Recipient and donor characteristics were used to develop a multivariable logistic regression model. A total of 186 patients were included in the study. Using multivariable logistic regression, we found that age < 12 months (odds ratio 4.02, 95% confidence interval 1.20-13.51, p = .024), metabolic or cholestatic disease (odds ratio 2.66, 95% confidence interval 1.01-7.07, p = .049), 30-day pretransplant hospital admission (odds ratio 8.59, 95% confidence interval 2.27-32.54, p = .002), intraoperative red blood cells transfusion >40 mL/kg (odds ratio 3.32, 95% confidence interval 1.12-9.81, p = .030), posttransplant return to the operating room (odds ratio 11.45, 95% confidence interval 3.04-43.16, p = .004), and major postoperative respiratory event (odds ratio 32.14, 95% confidence interval 3.00-343.90, p < .001) were associated with prolonged intensive care unit length of stay. The model demonstrates a good discriminative ability with an area under the receiver operative curve of 0.888 (95% confidence interval, 0.824-0.951). CONCLUSIONS: We develop and validate a model to predict prolonged intensive care unit length of stay in pediatric liver transplant patients using risk factors from all phases of the perioperative period.

Selected 2022 Highlights in Congenital Cardiac Anesthesia.

This article is a review of the highlights of pertinent literature of interest to the congenital cardiac anesthesiologist, and was published in 2022. After a search of the United States National Library of Medicine PubMed database, several topics emerged in which significant contributions were made in 2022. The authors of this manuscript considered the following topics noteworthy to be included in this review-intensive care unit admission after congenital cardiac catheterization interventions, antifibrinolytics in pediatric cardiac surgery, the current status of the pediatric cardiac anesthesia workforce in the United States, and kidney injury and renal protection during congenital heart surgery.

Secondary impacts of the COVID-19 pandemic at a tertiary children's hospital in Canada: a mixed-methods study.

OBJECTIVES: Decisions to pause all non-essential paediatric hospital activities during the initial phase of the COVID-19 pandemic may have led to significant delays, deferrals and disruptions in medical care. This study explores clinical cases where the care of children was perceived by hospital clinicians to have been negatively impacted because of the changes in healthcare delivery attributing to the restrictions placed resulting from the COVID-19 pandemic. DESIGN AND SETTING: This study used a mixed-methods approach using the following: (1) a quantitative analysis of overall descriptive hospital activity between May and August 2020, and utilisation of data during the study period was performed, and (2) a qualitative multiple-case study design with descriptive thematic analysis of clinician-reported consequences of the COVID-19 pandemic on care provided at a tertiary children's hospital. RESULTS: Hospital-level utilisation and activity patterns revealed a substantial change to hospital activity including an initial reduction in emergency department attendance by 38% and an increase in ambulatory virtual care from 4% before COVID-19 to 67% between May and August 2020. Two hundred and twelve clinicians reported a total of 116 unique cases. Themes including (1) timeliness of care, (2) disruption of patient-centred care, (3) new pressures in the provision of safe and efficient care and (4) inequity in the experience of the COVID-19 pandemic emerged, each impacting patients, their families and healthcare providers. CONCLUSION: Being aware of the breadth of the impact of the COVID-19 pandemic across all of the identified themes is important to enable the delivery of timely, safe, high-quality, family-centred paediatric care moving forward.

Management of severe peri-operative bleeding: Guidelines from the European Society of Anaesthesiology and Intensive Care: Second update 2022.

BACKGROUND: Management of peri-operative bleeding is complex and involves multiple assessment tools and strategies to ensure optimal patient care with the goal of reducing morbidity and mortality. These updated guidelines from the European Society of Anaesthesiology and Intensive Care (ESAIC) aim to provide an evidence-based set of recommendations for healthcare professionals to help ensure improved clinical management. DESIGN: A systematic literature search from 2015 to 2021 of several electronic databases was performed without language restrictions. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to assess the methodological quality of the included studies and to formulate recommendations. A Delphi methodology was used to prepare a clinical practice guideline. RESULTS: These searches identified 137 999 articles. All articles were assessed, and the existing 2017 guidelines were revised to incorporate new evidence. Sixteen recommendations derived from the systematic literature search, and four clinical guidances retained from previous ESAIC guidelines were formulated. Using the Delphi process on 253 sentences of guidance, strong consensus (>90% agreement) was achieved in 97% and consensus (75 to 90% agreement) in 3%. DISCUSSION: Peri-operative bleeding management encompasses the patient's journey from the pre-operative state through the postoperative period. Along this journey, many features of the patient's pre-operative coagulation status, underlying comorbidities, general health and the procedures that they are undergoing need to be taken into account. Due to the many important aspects in peri-operative nontrauma bleeding management, guidance as to how best approach and treat each individual patient are key. Understanding which therapeutic approaches are most valuable at each timepoint can only enhance patient care, ensuring the best outcomes by reducing blood loss and, therefore, overall morbidity and mortality. CONCLUSION: All healthcare professionals involved in the management of patients at risk for surgical bleeding should be aware of the current therapeutic options and approaches that are available to them. These guidelines aim to provide specific guidance for bleeding management in a variety of clinical situations.

Perioperative Considerations in Management of the Severely Bleeding Coagulopathic Patient.

Inherited and acquired coagulopathy are frequently associated with major bleeding in severe trauma, cardiac surgery with cardiopulmonary bypass, and postpartum hemorrhage. Perioperative management is multifactorial and includes preoperative optimization and discontinuation of anticoagulants and antiplatelet therapy in elective procedures. Prophylactic or therapeutic use of antifibrinolytic agents is strongly recommended in guidelines and has been shown to reduce bleeding and need for allogeneic blood administration. In the context of bleeding induced by anticoagulants and/or antiplatelet therapy, reversal strategies should be considered when available. Targeted goal-directed therapy using viscoelastic point-of-care monitoring is increasingly used to guide the administration of coagulation factors and allogenic blood products. In addition, damage control surgery, which includes tamponade of large wound areas, leaving surgical fields open, and other temporary maneuvers, should be considered when bleeding is refractory to hemostatic measures.

Validation of Automated Data Extraction From the Electronic Medical Record to Provide a Pediatric Risk Assessment Score.

BACKGROUND: Although the rate of pediatric postoperative mortality is low, the development and validation of perioperative risk assessment models have allowed for the stratification of those at highest risk, including the Pediatric Risk Assessment (PRAm) score. The clinical application of such tools requires manual data entry, which may be inaccurate or incomplete, compromise efficiency, and increase physicians' clerical obligations. We aimed to create an electronically derived, automated PRAm score and to evaluate its agreement with the original American College of Surgery National Surgical Quality Improvement Program (ACS NSQIP)-derived and validated score. METHODS: We performed a retrospective observational study of children <18 years who underwent noncardiac surgery from 2017 through 2021 at Boston Children's Hospital (BCH). An automated PRAm score was developed via electronic derivation of International Classification of Disease (ICD) -9 and -10 codes. The primary outcome was agreement and correlation among PRAm scores obtained via automation, NSQIP data, and manual physician entry from the same BCH cohort. The secondary outcome was discriminatory ability of the 3 PRAm versions. Fleiss Kappa, Spearman correlation (rho), and intraclass correlation coefficient (ICC) and receiver operating characteristic (ROC) curve analyses with area under the curve (AUC) were applied accordingly. RESULTS: Of the 6014 patients with NSQIP and automated PRAm scores (manual scores: n = 5267), the rate of 30-day mortality was 0.18% (n = 11). Agreement and correlation were greater between the NSQIP and automated scores (rho = 0.78; 95% confidence interval [CI], 0.76-0.79; P <.001; ICC = 0.80; 95% CI, 0.79-0.81; Fleiss kappa = 0.66; 95% CI, 0.65-0.67) versus the NSQIP and manual scores (rho = 0.73; 95% CI, 0.71-0.74; P < .001; ICC = 0.78; 95% CI, 0.77-0.79; Fleiss kappa = 0.56; 95% CI, 0.54-0.57). ROC analysis with AUC showed the manual score to have the greatest discrimination (AUC = 0.976; 95% CI, 0.959,0.993) compared to the NSQIP (AUC = 0.904; 95% CI, 0.792-0.999) and automated (AUC = 0.880; 95% CI, 0.769-0.999) scores. CONCLUSIONS: Development of an electronically derived, automated PRAm score that maintains good discrimination for 30-day mortality in neonates, infants, and children after noncardiac surgery is feasible. The automated PRAm score may reduce the preoperative clerical workload and provide an efficient and accurate means by which to risk stratify neonatal and pediatric surgical patients with the goal of improving clinical outcomes and resource utilization.

Recommendations From the International Consensus Conference on Anemia Management in Surgical Patients (ICCAMS).

BACKGROUND: Perioperative anemia has been associated with increased risk of red blood cell transfusion and increased morbidity and mortality after surgery. The optimal approach to the diagnosis and management of perioperative anemia is not fully established. OBJECTIVE: To develop consensus recommendations for anemia management in surgical patients. METHODS: An international expert panel reviewed the current evidence and developed recommendations using modified RAND Delphi methodology. RESULTS: The panel recommends that all patients except those undergoing minor procedures be screened for anemia before surgery. Appropriate therapy for anemia should be guided by an accurate diagnosis of the etiology. The need to proceed with surgery in some patients with anemia is expected to persist. However, early identification and effective treatment of anemia has the potential to reduce the risks associated with surgery and improve clinical outcomes. As with preoperative anemia, postoperative anemia should be treated in the perioperative period. CONCLUSIONS: Early identification and effective treatment of anemia has the potential to improve clinical outcomes in surgical patients.

Perioperative Considerations for Pediatric Patients With Congenital Heart Disease Presenting for Noncardiac Procedures: A Scientific Statement From the American Heart Association.

Continuous advances in pediatric cardiology, surgery, and critical care have significantly improved survival rates for children and adults with congenital heart disease. Paradoxically, the resulting increase in longevity has expanded the prevalence of both repaired and unrepaired congenital heart disease and has escalated the need for diagnostic and interventional procedures. Because of this expansion in prevalence, anesthesiologists, pediatricians, and other health care professionals increasingly encounter patients with congenital heart disease or other pediatric cardiac diseases who are presenting for surgical treatment of unrelated, noncardiac disease. Patients with congenital heart disease are at high risk for mortality, complications, and reoperation after noncardiac procedures. Rigorous study of risk factors and outcomes has identified subsets of patients with minor, major, and severe congenital heart disease who may have higher-than-baseline risk when undergoing noncardiac procedures, and this has led to the development of risk prediction scores specific to this population. This scientific statement reviews contemporary data on risk from noncardiac procedures, focusing on pediatric patients with congenital heart disease and describing current knowledge on the subject. This scientific statement also addresses preoperative evaluation and testing, perioperative considerations, and postoperative care in this unique patient population and highlights relevant aspects of the pathophysiology of selected conditions that can influence perioperative care and patient management.

Tranexamic acid dose-response relationship for antifibrinolysis in postpartum haemorrhage during Caesarean delivery: TRACES, a double-blind, placebo-controlled, multicentre, dose-ranging biomarker study.

BACKGROUND: The optimal dose of tranexamic acid to inhibit hyperfibrinolysis in postpartum haemorrhage is unclear. Tranexamic Acid to Reduce Blood Loss in Hemorrhagic Cesarean Delivery (TRACES) was a double-blind, placebo-controlled, randomised, multicentre dose-ranging study to determine the dose-effect relationship for two regimens of intravenous tranexamic acid vs placebo. METHODS: Women experiencing postpartum haemorrhage during Caesarean delivery were randomised to receive placebo (n=60), tranexamic acid 0.5 g (n=57), or tranexamic acid 1 g i.v. (n=58). Biomarkers of fibrinolytic activation were assayed at five time points, with inhibition of hyperfibrinolysis defined as reductions in the increase over baseline in D-dimer and plasmin-antiplasmin levels and in the plasmin peak time. RESULTS: In the placebo group, hyperfibrinolysis was evidenced by a mean increase over baseline [95% confidence interval] of 93% [68-118] for D-dimer level at 120 min and 56% [25-87] for the plasmin-antiplasmin level at 30 min. A dose of tranexamic acid 1 g was associated with smaller increases over baseline (D-dimers: 38% [13-63] [P=0.003 vs placebo]; plasmin-antiplasmin: -2% [-32 to 28] [P=0.009 vs placebo]). A dose of tranexamic acid 0.5 g was less potent, with non-significant reductions (D-dimers: 58% [32-84] [P=0.06 vs placebo]; plasmin-antiplasmin: 13% [18-43] [P=0.051]). Although both tranexamic acid doses reduced the plasmin peak, reduction in plasmin peak time was significant only for the 1 g dose of tranexamic acid. CONCLUSIONS: Fibrinolytic activation was significantly inhibited by a dose of intravenous tranexamic acid 1 g but not 0.5 g. Pharmacokinetic-pharmacodynamic modelling of these data might identify the best pharmacodynamic monitoring criteria and the optimal tranexamic acid dosing regimen for treatment of postpartum haemorrhage. CLINICAL TRIAL REGISTRATION: NCT02797119.

Prophylactic Use of Antifibrinolytics During Pediatric Cardiac Surgery With Cardiopulmonary Bypass on Postoperative Bleeding and Transfusion: A Systematic Review and Meta-Analysis.

OBJECTIVES: To determine the effect of intraoperative antifibrinolytics, including tranexamic acid (TXA), aminocaproic acid (EACA), or aprotinin, on bleeding in children undergoing cardiac surgery with cardiopulmonary bypass (CPB). DATA SOURCES: Relevant articles were systematically searched from Ovid MEDLINE, Ovid EMBASE, CINAHL, Cochrane Library, and Web of Science to November 15, 2021. STUDY SELECTION: Abstracts were screened, and full texts were reviewed using predetermined inclusion and exclusion criteria using the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. DATA EXTRACTION: A standardized data extraction tool was used. DATA SYNTHESIS: Sixty-eight studies including 28,735 patients were analyzed. TXA compared with placebo resulted in a mean decrease in chest tube output of 9.1 mL/kg (95% CI, 6.0-12.3 mL/kg), I2 equals to 65.2%, p value of less than 0.001, platelet requirement of 2.9 mL/kg (95% CI, 0.1-5.8 mL/kg), I2 =72.5%, p value less than 0.001 and plasma requirement of 4.0 mL/kg (95% CI, 0.6-7.2 mL/kg), I2 equals to 94.5%, p value less than0.001. Aprotinin compared with placebo resulted in a mean decrease in chest tube output of 4.3 mL/kg (2.4-6.2 mL/kg), I2 equals to 66.3%, p value of less than 0.001, platelet transfusion of 4.6 mL/kg (95% CI, 0.6-8.6 mL/kg), I2 equals to 93.6%, p value of less than 0.001, and plasma transfusion of 7.7 mL/kg (95% CI, 2.1-13.2 mL/kg), I2 equals to 95.3%, p value of less than 0.001. EACA compared with placebo resulted in a mean decrease in chest tube output of 9.2 mL/kg (2.3-21.0 mL/kg), I2 equals to 96.4%, p value of less than 0.001, RBC transfusion of 7.2 mL/kg (95% CI, 2.4-12.1 mL/kg), I2 equals to 94.5%, p value equals to 0.002, and platelet transfusion of 10.7 mL/kg (95% CI, 2.9-18.5 mL/kg), I2 equals to 0%, p value of less than 0.001. No statistical difference was observed in chest tube output when TXA was compared with aprotinin. Subgroup analysis of cyanotic patients showed a significant decrease in chest tube output, platelet requirement, and plasma requirement for patients receiving aprotinin. Overall, the quality of evidence was moderate. CONCLUSIONS: Antifibrinolytics are effective at decreasing blood loss and blood product requirement in children undergoing cardiac surgery with CPB although the quality of evidence is only moderate.

Patients With Congenital Heart Disease Undergoing Noncardiac Procedures at Hospitals With and Without a Cardiac Surgical Program.

Background The type and location of hospitals where patients with congenital heart disease (CHD) undergo noncardiac procedures have not been investigated. This study aimed to describe (1) the characteristics of these patients, (2) the distribution of procedures among hospitals with and without a cardiac surgical program and travel distances, (3) the characteristics determining the distribution, and (4) mortality rates. Methods and Results This is a retrospective cohort analysis of inpatient data from the Center for Healthcare Information and Analysis of the Commonwealth of Massachusetts, Texas Healthcare Information Collection, and Health Care Cost and Utilization Project State Inpatient Database. Children <18 years old with CHD who underwent noncardiac procedures were included. Distances were calculated using the Haversine formula. Logistic regression was performed to evaluate the odds of a procedure at a hospital with a cardiac program. There were 7435 encounters at 235 hospitals analyzed. Most procedures (87.8%) occurred at hospitals with a cardiac program. Patients at a hospital without a cardiac program had simple CHD (72.4%) with <1% with single ventricle disease. At hospitals with a cardiac program, 56.8% had simple CHD, 35.4% complex CHD, and 7.8% single ventricle disease. The median distance traveled was 25.2 miles (interquartile range, 10.3-73.8 miles) to a hospital with a cardiac program and 14.6 miles (interquartile range, 6.2-37.4 miles) to a hospital without a cardiac program (P<0.001). Single ventricle disease (adjusted odds ratio [aOR], 16.25 [95% CI, 7.22-36.61]) and ≥6 chronic conditions (aOR, 1.81 [95% CI, 1.57-2.09]) were associated with performance at a hospital with a cardiac program. Mortality rate was 3.8%. Conclusions Patients with CHD are more likely to travel to a hospital with a cardiac program for noncardiac procedures than to a hospital without; especially patients with single ventricle disease, other complex CHD, and with ≥6 chronic conditions.

Alternative routes to intravenous tranexamic acid for postpartum hemorrhage: A systematic search and narrative review.

OBJECTIVE: To review available data on tranexamic acid (TXA) plasma concentration needed to inhibit fibrinolysis and the time to achieve this concentration when giving TXA by different routes in humans. To identify ongoing trials assessing alternatives to intravenous TXA administration. METHODS: We updated two previous systematic reviews by searching MEDLINE, EMBASE, OviSP, and ISI Web of Science from database inception to July 2021. We also searched the WHO International Clinical Trials Registry Platform for ongoing trials to July 2021. Titles and abstracts were screened for relevant trials. Two reviewers independently reviewed and agreed the trials to be included. RESULTS: Plasma TXA concentrations over 10 mg/L provide near maximal inhibition of fibrinolysis, with concentrations over 5 mg/L providing partial inhibition. Oral TXA tablets take about 1 h to reach a plasma concentration of 5 mg/L in postpartum women. Studies in healthy volunteers and shocked trauma patients show that intramuscular TXA achieves a plasma level of over 10 mg/L within 15 min. One trial is ongoing to determine the pharmacokinetics of intramuscular and oral solution TXA in pregnant women. CONCLUSION: Intramuscular TXA in healthy volunteers and shocked trauma patients reaches therapeutic concentration rapidly. Oral TXA tablets take too long to reach the minimum therapeutic concentration in postpartum women.