e3 86 Chait P, Dinyari M, Massicotte MP The sensitivity and specificity of lineograms and ultrasound compared to venography for the diag nosis of central venous line related thrombosis in symptomatic[.]
e3 86 Chait P, Dinyari M, Massicotte MP The sensitivity and specificity of lineograms and ultrasound compared to venography for the diagnosis of central venous line related thrombosis in symptomatic children: the LUV study Thromb Haemost 2001;(suppl):697 87 Shankar KR, Abernethy LJ, Das KS, et al Magnetic resonance venography in assessing venous patency after multiple venous catheters J Pediatr Surg 2002;37(2):175-179 88 Li S, Silva CT, Brudnicki AR, et al Diagnostic accuracy of pointof-care ultrasound for catheter-related thrombosis in children Pediatr Radiol 2016;46(2):219-228 89 Kanis J, Hall CL, Pike J, Kline JA Diagnostic accuracy of the D-dimer in children Arch Dis Child 2018;103(9):832-834 90 Kline JA, Ellison AM, Kanis J, Pike JW, Hall CL Evaluation of the pulmonary embolism rule out criteria (PERC rule) in children evaluated for suspected pulmonary embolism Thromb Res 2018;168:1-4 91 Van Ommen CH, Peters M Acute pulmonary embolism in childhood Thromb Res 2006;118(1):13-25 92 Andrew M, Monagle P, Brooker L Pulmonary embolism in childhood In: Andrew M, Monagle P, Brooker L, eds Thromboembolic Complications During Infancy and Childhood Hamilton, ON: BC Decker; 2000:147-164 93 Stümper O, Sutherland GR, Geuskens R, Roelandt JR, Bos E, Hess J Transesophageal echocardiography in evaluation and management after a Fontan procedure J Am Coll Cardiol 1991;17(5): 1152-1160 94 Fyfe DA, Kline CH, Sade RM, Gillette PC Transesophageal echocardiography detects thrombus formation not identified by transthoracic echocardiography after the Fontan operation J Am Coll Cardiol 1991;18(7):1733-1737 95 Balling G, Vogt M, Kaemmerer H, Eicken A, Meisner H, Hess J Intracardiac thrombus formation after the Fontan operation J Thorac Cardiovasc Surg 2000;119(4 Pt 1):745-752 96 Yang JY, Williams S, Brandão LR, Chan AK, Mondal T Neonatal and childhood right atrial thrombosis: critical clot size Blood Coagul Fibrinolysis 2013;24(4):458 97 Hanson SJ, Lawson KA, Brown AM, et al Current treatment practices of venous thromboembolism in children admitted to pediatric intensive care units Paediatr Anaesth 2011;21(10):1052-1057 98 Monagle P, Chan AK, Goldenberg NA, et al Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines Chest 2012;141(suppl 2):e737S-e801S 99 Monagle P, Cuello CA, Augustine C, et al American Society of Hematology 2018 Guidelines for management of venous thromboembolism: treatment of pediatric venous thromboembolism Blood Adv 2018;2(22):3292-3316 100 Hanson SJ, Lawson KA, Brown AM, et al Current treatment practices of venous thromboembolism in children admitted to pediatric intensive care units Paediatr Anaesth 2011;21(10):1052-1057 101 Peng C, Doan J, Monagle P, Newall F Compliance of antithrombotic management at a tertiary paediatric hospital with international guidelines: a 100-Day audit Thromb Res 2011;128(2):135-140 102 Zaleski KL, DiNardo JA, Nasr VG Bivalirudin for pediatric procedural anticoagulation: a narrative review Anesth Analg 2019; 128(1):43-55 103 Medar SS, Hsu DT, Lamour JM, Bansal N, Peek GJ Use of bivalirudin as a primary anticoagulant in a child during Berlin Heart EXCOR ventricular assist device support Perfusion 2020;35(2):172-176 104 Hasija S, Talwar S, Makhija N, et al Randomized controlled trial of heparin versus bivalirudin anticoagulation in acyanotic children undergoing open heart surgery J Cardiothorac Vasc Anesth 2018;32(6):2633-2640 105 von Vajna E, Alam R, So TY Current clinical trials on the use of direct oral anticoagulants in the pediatric population Cardiol Ther 2016;5(1):19-41 106 Randolph AG, Cook DJ, Gonzales CA, Andrew M Benefit of heparin in central venous and pulmonary artery catheters: a meta-analysis of randomized controlled trials Chest 1998;113(1): 165-171 107 Newall F, Johnston L, Ignjatovic V, Monagle P Unfractionated heparin therapy in infants and children Pediatrics 2009;123(3): e510-e518 108 Lane D, Lindahl U Heparin: Chemical and Biological Properties, Clinical Applications Boca Raton FL: CRC Press; 1989 109 Rosenberg RD, Lam L Correlation between structure and function of heparin Proc Natl Acad Sci U S A 1979;76(3):1218-1222 110 Wu YI, Sheffield WP, Blajchman MA Defining the heparin-binding domain of antithrombin Blood Coagul Fibrinolysis 1994;5(1):83-95 111 Rosenberg RD, Lam L Correlation between structure and function of heparin Proc Natl Acad Sci U S A 1979;76(3):1218-1222 112 Wu Y, Sheffield WP, Blajchman MA Defining the heparin-binding domain of antithrombin Blood Coagul Fibrinolysis 1994;5:83-95 113 Pratt CW, Church FC Antithrombin: structure and function Semin Hematol 1991;28(1):3-9 114 Sandset PM Tissue factor pathway inhibitor (TFPI)–an update Haemostasis 1996;26(suppl 4):154-165 115 Andrew M, Marzinotto V, Massicotte P, et al Heparin therapy in pediatric patients: a prospective cohort study Pediatr Res 1994;31(1):78-83 116 Kuhle S A clinically significant incidence of bleeding in critically ill children receiving therapeutic doses of unfractionated heparin: a prospective cohort study Haematologica 2007;92(2):244-247 117 Monagle P, Studdert DM, Newall F Infant deaths due to heparin overdose: time for a concerted action on prevention J Paediatr Child Health 2012;48(5):380-381 118 Fareed J, Hoppensteadt DA, Ramacciotti E, Hull RD Contaminants in heparins: are all facts known? Clin Appl Thromb Hemost 2010;16(3):242-243 119 Mahajerin A, Petty JK, Hanson SJ, et al Prophylaxis against venous thromboembolism in pediatric trauma: a practice management guideline from the Eastern Association for the Surgery of Trauma and the Pediatric Trauma Society J Trauma Acute Care Surg 2017;82(3):627-636 120 Arlikar SJ, Atchison CM, Amankwah EK, et al Development of a new risk score for hospital-associated venous thromboembolism in critically-ill children not undergoing cardiothoracic surgery Thromb Res 2015;136(4):717-722 121 Hanson SJ, Faustino EV, Mahajerin A, et al Recommendations for venous thromboembolism prophylaxis in pediatric trauma patients: a national, multidisciplinary consensus study J Trauma Acute Care Surg 2016;80(5):695-701 122 Higgerson RA, Lawson KA, Christie LM, et al Incidence and risk factors associated with venous thrombotic events in pediatric intensive care unit patients Pediatr Crit Care Med 2011;12(6):628-634 123 Faustino EV, Hanson S, Spinella PC, et al A multinational study of thromboprophylaxis practice in critically ill children Crit Care Med 2014;42(5):1232-1240 124 Bigelow AM, Flynn-O’Brien KT, Simpson PM, Dasgupta M, Hanson SJ Multicenter review of current practices associated with venous thromboembolism prophylaxis in pediatric patients after trauma Pediatr Crit Care Med 2018;19(9):e448-e454 125 Landisch RM, Hanson SJ, Cassidy LD, Braun K, Punzalan RC, Gourlay DM Evaluation of guidelines for injured children at high risk for venous thromboembolism: a prospective observational study J Trauma Acute Care Surg 2017;82(5):836-844 126 Chima RS, Hanson SJ Venous thromboembolism in critical illness and trauma: pediatric perspectives Front Pediatr 2017;5:47 127 Onyeama SJ, Hanson SJ, Dasgupta M, et al Factors associated with continuous low-dose heparin infusion for central venous catheter patency in critically ill children worldwide Pediatr Crit Care Med 2016;17(8):e352-e361 128 Hanson S, Punzalan R, Arca M Effectiveness of clinical guidelines for deep vein thrombosis prophylaxis in reducing the incidence of venous thromboembolism in critically ill children after trauma J Trauma 2014;72(5):1292-7 e4 Abstract: Thrombosis is a common complication in critically ill children The epidemiology, optimal diagnosis, and management of thrombosis in children vary markedly from that used in adults and specific expertise is required There remains much to learn and much to to prevent thrombosis and improve the outcomes for affected children Key words: thrombosis, embolus, anticoagulation, heparin, developmental hemostasis 91 Transfusion Medicine JACQUES LACROIX, MARISA TUCCI, OLIVER KARAM, AND PHILIP C SPINELLA • • The decision to prescribe the transfusion of any blood product must be based on individualized indications and must take into account specific health problems Acute severe anemia (hemoglobin concentration ,5 g/dL) increases the risk of death in critically ill patients There is no evidence that a red cell transfusion improves outcomes in stable critically ill children if their hemoglobin concentration is greater than 7.0 g/dL A hemoglobin concentration greater than 7.0 g/dL may be required in unstable critically ill children and in pediatric intensive care patients with heart • • • • PEARLS disease, particularly those with cyanotic heart disease, but the best threshold is unknown in such patients Plasma can be useful to treat severe coagulopathy in bleeding patients Platelets can be useful to treat bleeding caused by low platelet counts and/or platelet dysfunction In pediatric intensive care units, most transfusion-related adverse events are linked to immune-mediated effects of blood products rather than to transfusion-transmitted infectious diseases This chapter reviews the rationale for the transfusion of red blood cells (RBCs), plasma, platelets, whole blood, and cryoprecipitate in pediatric intensive care units (PICUs) Red Blood Cell Transfusion: Why and Why Not Red Blood Cells Oxygen Delivery in the Critically Ill Variables related to oxygen delivery and consumption, and hemodynamic adaptive mechanisms related to anemia, are explained in more detail in Chapters 23, 28, and 34 Anemia decreases the capacity of blood to deliver O2 because of lower Hb content Systemic (global) Do2 is dependent on cardiac output and the arterial concentration of O2 (Cao2): Do cardiac output (stroke volume heart rate) Cao Native RBCs contain hemoglobin (Hb), which carries oxygen (O2) to cells, thus facilitating efficient adenosine triphosphate (ATP) production and cell survival Because energy expenditure is high in critically ill patients, an adequate Hb is necessary to deliver enough oxygen to meet metabolic demand Anemia is observed in up to 74% of critically ill children.1 The transfusion of RBC units is the only effective way to rapidly increase the Hb level However, the efficacy and safety of transfused RBCs has been questioned for decades Infections transmitted by blood products were the most important concern in the 1980s In the 1990s, noninfectious serious hazards of transfusion (NISHOT), such as transfusion-related immune modulation (TRIM),2 transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and multiple-organ dysfunction syndrome (MODS)4–6 have become significant concerns This section discusses anemia, O2 delivery (Do2), and O2 consumption (Vo2); reviews evidence on the effectiveness of RBC transfusion in the intensive care setting; discusses the recommendations found in guidelines on RBC transfusion in critically ill children; and reviews the most frequent transfusion reactions and transfusion-related complications 1082 Anemia and Oxygen Delivery Cao2 (mL O2/100 mL) is defined by the formula: (Hb Sao 1.34) (0.003 Pao ) where Sao2 is arterial oxygen saturation and Pao2 is partial pressure of arterial oxygen Because systemic Do2 is directly linked to Hb concentration, the most rapid and effective way of increasing Do2 (within minutes) in anemic patients is by giving an RBC transfusion The ultimate goal of RBC transfusion is to improve cellular energy production, that is, ATP production, which translates into Vo2 An adequate O2 delivery to cells does not imply necessarily that Vo2 is adequate and that cells produce enough energy Vo2 depends on substrate availability and metabolic demands; it can be amplified by increasing cellular O2 extraction rate (O2ER), or by increasing Do2 if there is Vo2/Do2 dependence CHAPTER 91 Transfusion Medicine The relationship between O2 delivery and consumption is characterized by two phases: a directly linear relationship between Vo2 and Do2 up to a “critical threshold” (often referred to as the critical Do2) and a flat section above this threshold (eFig 91.1) Above this threshold, a fall in Do2 does not cause a drop in Vo2 because it is compensated by mechanisms such as an increase in O2ER These mechanisms are limited, though, and there is a critical threshold of Do2 under which O2ER cannot increase any further, and below which Vo2 diminishes if Do2 decreases The stress of critical illness increases metabolic rate and Vo2, which shifts the critical level of Do2 to the right and upward However, compensatory mechanisms are limited in anemic critically ill patients Adaptive Mechanisms With Anemia Anemia significantly decreases blood O2-carrying capacity However, in the normal host, the amount of O2 delivered to tissues exceeds resting O2 requirements by a twofold to fourfold factor While the Hb concentration is dropping, several adaptive processes maintain Vo2 These processes include (1) increased O2ER; (2) increased heart rate and stroke volume, which increase cardiac output; (3) redistribution of blood flow from nonvital organs toward the heart and brain at the expense of O2 delivery to less important vascular beds, such as the splanchnic vasculature; and (4) left shift of the oxy-Hb-dissociation curve, which decreases affinity between Hb and O2, thereby increasing the amount of O2 released to cells Moreover, anemia decreases blood viscosity, which, in turn, decreases cardiac afterload and increases cardiac output.7 Increasing O2ER is an important way to adapt to anemia The upper range of normal O2ER is 30%; O2ER increases if O2 requirements are not met Higher O2ER is frequently observed in severely ill patients, which translates into low central venous O2 saturation (Scvo2) When maximal O2ER is attained and other adaptive mechanisms are overwhelmed, Vo2/Do2 dependence appears and may result in O2 debt, which is associated with mortality O2 requirements are increased in patients with sepsis and MODS Impaired left ventricular function and abnormal regulation of vascular tone can restrict Do2 and disturb redistribution of regional blood flow Moreover, the mitochondria of patients with severe sepsis and MODS are dysfunctional and cannot adequately produce ATP.8 A severe cellular energy crisis may result A number of host characteristics specific to children and infants may also impair their adaptive mechanisms While an increase in cardiac output generally compensates for anemia, this may not occur in the first few weeks of life due to lower myocardial compliance during this period and a significant impairment in diastolic filling, which limits stroke volume increase In addition, an elevated resting heart rate in newborns also limits their ability to increase cardiac output Greater energy requirements in young infants and children mostly attributable to growth imply a greater need for substrates, including O2 Issues affecting O2 transport and release in children also include a higher proportion of fetal Hb during the first months of life, which causes a left shift of the oxy-Hb saturation curve, and a physiologic anemia Oxygen Kinetics in the Critically Ill Tissue hypoxia from low Do2 may be due to low Hb concentration (anemic hypoxia), low cardiac output (stagnant hypoxia), or low Hb saturation (hypoxic hypoxia) or some intoxications (e.g., toxic hypoxia caused by carbon monoxide) RBC transfusions are 1083 typically administered to increase Do2 in critically ill children.9 RBC transfusion increases Do2 in the central circulation, but it does not always increase tissue Do2 and global Vo2 in ICU patients.10,11 Several mechanisms may explain this.12 Mitochondrial dysfunction can impede O2 utilization in critically ill patients.8 Moreover, peripheral Do2 is impaired in ICU patients, and there is some evidence that RBC transfusion may worsen this problem.13 Regulation by Red Blood Cells of Oxygen Delivery to Tissue While RBC transfusion certainly increases systemic Do2 in the central circulation, this does not imply that regional Do2 is improved There is evidence that RBC transfusion may disturb local Do2.14 However, data on regional Do2 are inconsistent, their clinical significance remains to be determined, and the underlying mechanisms, which may involve blood viscosity, microcirculatory flow, local Do2, and cellular respiration, are not well characterized Resistance to blood flow increases rapidly if the hematocrit level exceeds 0.45, which corresponds to an Hb of 15 g/dL.15 RBC transfusion increases blood viscosity, which can lead to microcirculatory stasis and impaired Do2 to tissues.16 Activation of white blood cells (WBCs) in RBC units and cytokine generation in the supernatant of transfused RBC units may also have a microcirculatory effect: some cytokines can mediate vasoconstriction or thrombosis of small vessels and cause local ischemia Most RBC units are now prestorage leukocyte reduced, which significantly decreases cytokine levels in the supernatant The clinical impact of cytokines on regional Do2 remains to be determined There is evidence that RBC transfusion can cause vasoconstriction of microvasculature via an interaction between intracellular Hb and uptake by RBCs of nitric oxide released by blood vessels With local tissue hypoxia, Hb in the microvasculature releases nitric oxide and triggers local vasodilation Conversely, if there is sufficient O2 in the microvasculature, Hb traps nitric oxide and causes vasoconstriction This regulatory mechanism is almost immediately lost once RBCs are stored: it has been shown that in vitro exposure of blood vessels to RBC units stored hours or more causes vasoconstriction.16 The clinical significance of these observations is not clear; nonetheless, they suggest that regional Do2 can be disturbed by RBC transfusion (see also Chapter 87) RBC units undergo several changes during storage, which are generally referred to as storage lesions.12,17 For example, the concentration of 2,3-diphosphoglycerate (2,3-DPG) in stored RBCs decreases over time and can induce a left shift in the oxy-Hb dissociation curve, which impedes O2 release to tissues even if systemic Do2 is increased.18 In addition, RBC deformability decreases after or weeks of storage, which may alter their capacity to pass through the capillary bed Furthermore, hemolysis in older RBC units releases substantial amounts of free Hb, ranging from 0.5 mg/dL in 1-day-old RBC units to 250 mg/dL in 25-day-old units.19 Moreover, microparticles are released by RBCs stored more than or weeks Free intravascular Hb and microparticles tightly bind nitric oxide and therefore cause vasoconstriction.20 Thus, while RBC transfusions certainly increase systemic Do2, some evidence suggests that impaired microcirculatory flow and O2 availability can occur, which may have adverse effects on tissue oxygenation and cellular respiration Oxygen consumption (VO2) 1083.e1 Critical threshold Oxygen delivery (DO2) • eFig 91.1 Relationship between oxygen delivery (Do2) and O2 consumption (Vo2) in normal patients (black line), between Do2 and blood lactate level in normal patients (blue dashed line), and between Do2 and Vo2 in septic critically ill patients (red dotted line) Under the critical threshold Do2 (arrow), Vo2 diminishes and blood lactate level increases Over this threshold, a fall in Do2 does not cause a drop in Vo2 because it is compensated for by an increase in O2 extraction and/or an increased cardiac index In critically ill patients, Vo2 is frequently higher than normal Then, the level of the Do2/Vo2 curve (red dotted line) is shifted upward; the critical threshold may also be shifted to the right, which may explain why pathologic O2 supply dependence is reported in some critically ill patients ... “critical threshold” (often referred to as the critical Do2) and a flat section above this threshold (eFig 91.1) Above this threshold, a fall in Do2 does not cause a drop in Vo2 because it is compensated... cardiac output generally compensates for anemia, this may not occur in the first few weeks of life due to lower myocardial compliance during this period and a significant impairment in diastolic... transfusion may worsen this problem.13 Regulation by Red Blood Cells of Oxygen Delivery to Tissue While RBC transfusion certainly increases systemic Do2 in the central circulation, this does not imply