# # Pediatric Critical Care Review Hasan Pappas

1. Despite great advances in the treatment of childhood diseases, malignancy remains an ominous threat. All of the following statements regarding malignant diseases in children are true except: A. Neoplastic disease is the leading cause of death in the 1-15 year old population B. The leukemias are the most common malignancies of childhood C. Brain tumor is the most common solid tumor in childhood D. Ectodermal and endodermal carcinomas are rarely seen in children Click here for answer 2. With regard to the association of infection related to long-term catheter insertion in the pediatric population, which one of the following is the most accurate: A. Infus-a-port carries a lower rate of infection than Broviac single lumen catheters B. Infus-a-port has a lower rate of infection than both single lumen Broviac and double lumen Hickman catheters C. Double lumen catheters have a higher rate of infection compared to single lumen catheters D. There is no significant difference in infection rate between the externalized and the subcutaneously implanted catheters Click here for answer 3. A 4-year old boy with leukemia is being evaluated for fevers. Physical examination does not reveal any focus of infection. The white blood cell count is 1235 cells/mm3 with 12% neutrophils, 2% band forms, and 86% lymphocytes. The platelet count is 32,000/mm3. Which of the following statements is most accurate regarding this clinical scenario: A. Fifty to seventy percent of febrile episodes in oncology patients are non-infectious B. The blood culture is positive in greater than 75% of disseminated fungal infections C. The degree of neutropenia does not correlate with the morbidity and mortality due to bacterial infections D. Bronchoscopy should be done at this point to evaluate for pneumocystis E. Candida and aspergillus species are the two most common fungal agents causing fungal infections in pediatric oncology patients Click here for answer 4. All of the following statements regarding the child with malignant disease are true except: A. P. carnii will be identified in 15% of patients despite previous prophylaxis with trimethoprim-sulfamethoxazole. B. Granulocyte transfusions may be beneficial in the setting of neutropenia and culture proven sepsis C. The minor complications resulting from granulocyte transfusions can usually be avoided with appropriate pre-medication D. The half-life of transfused platelets is greater than 4 weeks E. Spontaneous bleeding may occur when the platelet count is less than 20,000/mm3 Click here for answer 5. Match the following chemotherapeutic drug with its most likely hematologic effect: A. Actinomycin D B. Anthracycline C. L-Asparaginase D. Methotrexate E. Vincristine F. Glucocorticoids ____ 1. Antithrombin III deficiency ____ 2. Chronic hepatic dysfunction ____ 3. Hypofibrinoginemia ____ 4. Increases fibrinolysis ____ 5. Increases factors II, VII, VIII, X ____ 6. Decreases Vitamin K dependent factors Click here for answer 6. All of the following statements are true regarding pulmonary parenchymal disease in children with malignancies except: A. The pulmonary parenchyma is commonly involved in leukemia B. The initial lesion from radiation exposure occurs within 6 hours of radiation therapy and involves capillary endothelial damage C. Bleomycin and Busulfan associated pulmonary fibrosis is dose dependent D. Cyclophosphamide and methotrexate have been associated with pulmonary fibrosis Click here for answer 7. Select whether the following statements regarding malignancies and chemotherapy in children are true or false: ____ Cyclophosphamide is associated with hemorrhagic cardiac necrosis ____ Anthracycline induced cardiomyopathy manifests itself as myofibrillar loss and cytoplasmic vacuolization ____ Cardiomyopathy is unrelated to radiotherapy ____ Vincristine may induce SIADH ____ Intrathecal chemotherapy may cause seizures ____ When P. carinii infection occurs after bone marrow transplant, it is most commonly seen at 2-4 weeks Click here for answer 8. Match the following chemotherapeutic drug with its most closely associated adverse neurologic effect: A. Methotrexate B. Cisplatin C. Vincristine D. 5-FU ____ 1. Ototoxicity ____ 2. Acute cerebellar ataxia ____ 3. Aseptic meningitis ____ 4. SIADH Click here for answer 9. Match the following chemotherapeutic drug with its most commonly associated complication: A. Methotrexate (high-dose) B. Cisplatin C. L-Aspariginase D. Cyclophosphamide ____ 1. Tubular necrosis ____ 2. Hemorrhagic cystitis ____ 3. Tubular precipitation Click here for answer 10. All of the following statements regarding bone marrow transplantation are true except: A. The most common indications are acute myelogenous leukemia and acute lymphoblastic leukemia in remission B. In patients who receive allogeneic bone marrow transplantation, the mortality rate is 20-35% C. The risk periods for pneumonitis and pulmonary insufficiency are 2 weeks, 6-12 weeks, and 3-6 months after bone marrow transplantation D. Cytomegalovirus infection is most common 6 months after a bone marrow transplant E. Cyclosporin may prevent acute rejection Click here for answer 11. Match the chemotherapy drug with its mechanism of action: A. Methotrexate B. Vincristine C. Doxorubicin D. Cyclophosphamide E. Glucocorticoids ____ 1. Antimetabolite ____ 2. Breaks DNA strands ____ 3. Inhibits microtubule function ____ 4. Antibiotic ____ 5. Lymphocytotoxic Click here for answer 12. A 5-year old girl has prolonged bleeding after her dentist pulls a tooth. Additionally, her 16-year old sister has protracted monthly menses of 7-9 days. You suspect von Willebrand’s disease. Which of the following statements regarding the coagulation system is/are true: A. The prothrombin time measures the extrinsic and common pathways B. The activated partial thromboplastin time measures the intrinsic and common pathways C. The thrombin time measures the coagulation cascade from prothrombin to stable fibrin D. Factors XII, XI, IX, and X comprise the intrinsic system E. All of the above Click here for answer 13. Select whether the following statements regarding the clotting system and blood products are true or false: ____ The only source for factors V and XI is fresh frozen plasma ____ The preferred source for factors II, VII, X, and antithrombin III is cryoprecipitate ____ Cryoprecipitate contains fibrinogen, factor VIII, and von Willebrand’s factor ____ The main components of the anti-thrombotic system include antithrombin III, protein C and protein S. ____ Protein C induces proteolysis of factors V and VIII and neutralizes plasminogen activator inhibitor ____ Vitamin K dependent factors include II, VII, IX, and X ____ Vitamin K is a vitamin that is stored in the body and therefore no exogenous supplementation is necessary Click here for answer 14. All of the following are the main components of the anti-thrombotic system except: A. Anti-thrombin III B. Protein C C. Protein S D. Protein B Click here for answer 15. An 11-month old male with a history of biliary atresia has developed fulminant hepatic failure with gastrointestinal bleeding and bleeding from his central line site. You suspect a hepatic coagulopathy. Which one of the following statements regarding this situation is/are true: A. Dietary inadequacy and total parenteral nutrition are causes of Vitamin K deficiency B. Fibrinogen, factors V, VIII, and proteins C and S are depleted during disseminated intravascular coagulopathy C. In hepatic coagulopathy, a prolonged PT indicates decreased synthesis of Vitamin K dependent factors D. Factor V synthesis is independent of Vitamin K availability E. All of the above Click here for answer 16. Which of the following is a true statement regarding coagulopathy associated with cardiopulmonary bypass: A. Protamine is used to potentiate heparinization B. Hyperfibrinolysis causing significant bleeding can be treated with epsilon-aminocaproic acid intravenously C. Vitamin K deficiency is a rarely noted event D. D-dimers are frequently elevated Click here for answer 17. Which of the following is/are true statements regarding the coagulopathy associated massive transfusion: A. Hemolysis always occurs B. Platelet destruction occurs, necessitating platelet transfusion to maintain a platelet count of 80,000 to 100, 000 /mm3 C. Changing the transfusion circuit may temporarily reduce the activity of the coagulation cascade D. A, B, and C E. B and C only Click here for answer 18. Which of the following biochemical changes is least likely to be associated with massive transfusion: A. Disseminated intravascular coagulopathy B. Abnormal platelet function C. An increase in 2,3,-DPG D. Hyperkalemia E. Hypothermia and metabolic acidosis Click here for answer 19. Which of the following regarding Antithrombin III and heparin is/are true: A. Antithrombin III is synthesized in the liver and inhibits thrombin and factor Xa B. Acquired Antithrombin III deficiency is more common than the autosomal dominant inherited congenital type C. Antithrombin III concentrations < 70% are associated with thromboses D. Heparin-induced anti-platelet antibodies occur in approximately 5% of patients receiving heparin E. All of the above Click here for answer 20. Which of the following statements is/are true regarding heparin-induced antiplatelet antibodies: A. Typically occurs 4-15 days after first exposure to heparin B. Typically occurs 1-9 days following the second exposure to heparin C. Are associated with thromboses D. All of the above Click here for answer 21. Which of the following statements is/are true regarding Protein C and Protein S anticoagulant systems: A. Protein C is a Vitamin K dependent protease which is produced by the liver B. Protein C is deactivated by thrombin C. Protein C is catalyzed by thrombomodulin D. Protein C deficiency is most commonly an acquired abnormality, rather than a congenital one E. A, C, and D only Click here for answer 22. Which of the following statements regarding fibrinolytic therapy is/are true: A. Streptokinase is produced by b-streptococci; it attaches to plasminogen and is rapidly inactivated by naturally occurring antibodies with a half life of 30 minutes B. Urokinase can be produced from human urine; it hydrolyzes plasminogen to plasmin with a half life of 30 minutes C. Tissue plasminogen activator (t-PA) is produced in vascular endothelium; it converts plasminogen to plasmin D. Absolute contraindications to fibrinolytic therapy included acute hemorrhage, recent cerebral vascular accident, and aneurysm. E. All of the above Click here for answer 23. A 1-week-old infant undergoes a cardiac catheterization for a diagnosis of a cardiac defect. His right femoral artery is cannulated. After the procedure, his right leg is cold and his femoral pulse is barely palpable. You suspect a thrombus. Which of the following statements are true regarding thrombolytic therapy: A. Heparinzation is standard management until recannulation or vascular integrity improves B. PTT should be 2.5-3.0 times normal during heparin therapy C. Streptokinase and t-PA are contraindicated for femoral artery spasm after catheterization D. Indications for surgical intervention of pulmonary emboli include pulmonary artery cross-sectional obstruction > 50%, right ventricular failure, or shock Click here for answer 24. Which of the following statements is/are true regarding chronic anti-coagulation therapy: A. Warfarin inhibits synthesis of factors II, VII, IX, X, Protein C, and Protein S B. Platelet aggregation is decreased by blocking the synthesis of thromboxane A2 with cyclo-oxygenase inhibitors C. Sulfinpyrazone or aspirin may be used D. Platelet aggregation is decreased by administration of a phosphodiesterase inhibitor E. All of the above Click here for answer 25. Match the following drug with its site of action A. Aspirin B. Sulfinpyrazone C. Both D. Neither ____ 1. Cyclooxygenase inhibition ____ 2. Phosphodiesterase inhibition ____ 3. Irreversibly bound to thromboxane A2 Click here for answer 26. All of the following regarding thrombosis of prosthetic valves are true except: A. Biologic valves are less thromboembolic than mechanical valves B. Mitral valves are more thromboembolic than aortic valves C. Recommendations by the National Heart, Lung and Blood Institute for mechanical valves include long term anticoagulation D. Thromboprophylaxis for prosthetic valves in pediatric patients does not decrease the occurrence of acute thromboembolic effects Click here for answer Answers 1. A Trauma is the leading cause of death in the 1 – 15 year old population. Neoplastic disease is second. The other responses are true. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1433-1434) 2. D Infection is higher in patients with central lines than those without. Recent retrospective data suggests that there are no differences in infection rates between subcutaneously implanted, versus externalized catheters. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1438) 3. E Fifty five to seventy percent of febrile episodes in oncology patients are of infectious origin. Blood cultures are positive in less than 50% of cases of serious disseminated fungal infections. Candida albicans and Aspergillus species are the most common fungal organisms. Neutropenia is closely correlated with morbidity and mortality. Pneumocystis is unlikely in this clinical scenario, however, Pneumocystis is responsible for up to 50% of nonbacterial pneumonitis in oncology patients. Chest radiographs demonstrate bilateral infiltrates radiating from the hilum. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1438–1445; Table 42.6) 4. D The half life of transfused platelets is 7 days; with significant alloimmunization, it can be hours. All of the other statements are correct. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1442–1443) 5. D, E, C, B, F, A Chemotherapy may promote the development of a coagulopathy associated with an increased risk of hemorrhage or thrombosis. Actinomycin D and other antibiotics decrease the vitamin K dependent clotting factors. Anthracycline increases fibrinolysis. L-asparaginase may cause hypofibrinogenemia. Methotrexate can cause an antithrombin III deficiency. Vincristine may cause chronic hepatic dysfunction. Glucocorticoids increase the levels of factors II, VII, VIII and X. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1442-1457) 6. A Primary pulmonary parenchymal involvement with leukemia is very rare. Parenchymal involvement is occasionally seen with histiocytosis X and metastatic disease (eg. Osteogenic and Ewings sarcoma, and Wilms tumor). All other statements are correct. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1445–1447, Table 42.8) 7. T, T, F, T, T, F A variety of chemotherapeutics as well as radiotherapy can cause cardiomyopathy. Effects appear to be dose related. Radiotherapy may cause pericarditis with a chronic effusion. Histologically, interstitial fibrosis with vascular narrowing is seen. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1447–1448) The onset of pneumocystis carinii infection typically occurs 3–6 months after bone marrow transplantation. Bacterial or fungal infection can occur within the first 2 weeks. CMV infection occurs 6–12 weeks after bone marrow transplantation. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1454–1455) 8. B, D, A, C The child with neoplastic disease may acquire a variety of neurologic deficits related to the neoplasm, the therapy or a combination of both. Methotrexate is associated with aseptic meningitis, arachnoiditis, demyelinization, somnolence and chronic leukoencaphalopathy. Cisplatin may cause ototoxicity, cerebral edema and seizures. Vincristine is associated with SIADH. 5-FU may cause acute cerebellar ataxia. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1449–1452; Table 42.17) 9. B, D, A Chemotherapy is commonly associated with renal injury. High dose methotrexate is associated with renal tubular injury. Cisplatin may cause tubular necrosis; Cyclophosphamide and Ifosfamide are both associated with hemorrhagic cystitis. L-Aparaginase is not associated with renal injury. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1452–1453; Table 42.18) 10. D CMV infection occurs most commonly 6–12 weeks after bone marrow transplantation. All of the other statements are correct. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1454–1455) 11. A, D, B, C, E Chemotherpeutic agents form the mainstay of treatment for childhood neoplasms. All agents act by disrupting some aspect of normal cell growth or division. Antimetabolites interact with various cell enzymes (eg. Methotrexate inhibits the activity of dihydrofolate reductase). Vincristine, a vinca alkaloid, inhibits microtubule function within the cell. This prevents the formation of the spindle apparatus during metaphase, thus inhibiting cell division. The anthracyclines (daunorubicin and doxorubicin) and Actinomycin D inhibit the synthesis of DNA in tumor cells. Alkylating agents like cyclophosphamide cause breaks in the DNA strands. The glucocorticoids are directly lymphocytotoxic to lymphoid leukemia and lymphoma cells. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1456 –1458; Tables 42.23, 42.24, 42.26 and 42.27) 12. E Von Willebrand’s Disease is the most common inherited bleeding disorder. One percent of the population have detectable abnormalities in the VWD protein. All of the statements are correct. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1414–1416; Figure 41.2) 13. T, F, T, T, T, F The preferred source for factors II, VII, X and antithrombin III is fresh frozen plasma. Vitamin K is not a stored vitamin. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1415–1416) 14. D Anti-thrombin III, Protein C and Protein S are the main components of the anti-thrombotic system. Thrombomodulin and heparin cofactor II, among others, are also included as endogenous anticoagulants. Protein B is not included among these components. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1421; Figure 41.3) 15. E When the liver itself is diseased, abnormal coagulation results. The liver synthesizes fibrinogen, pro-thrombin, protein C, protein S, antithrombin III, plasminogen, and factors V, VII, IX, X, XI and XII. All of the above statements are correct. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1408 – 1409 and 1415 – 1416) 16. B Epsilon-aminocaproic acid prevents the breakdown of the fibrin clot by complexing with plasmin to prevent its fibrinolytic activity. Protamine is used to reverse the effects of heparin. Vitamin K deficiency generally occurs within 2-3 days following cardiopulmonary bypass. D-dimers are rarely elevated. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1405–1406; Table 41.11; Chang, AC, et al. Pediatric Cardiac Intensive Care; pp 397–399) 17. D Massive transfusion is defined as the replacement of at least one blood volume; estimated as 75 mL/kg for children less than 1 year of age and burn victims, and 70 mL/kg for all others. All of the above statements are true. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1403-1408) 18. C A variety of metabolic abnormalities can be induced by massive transfusion. 2,3-diphosphoglycerate is decreased in transfused red cells, which increases red cell affinity for oxygen. Thus, oxygen unloading to tissues may be impaired. All other statements are correct. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edtion; pp 1421–1422; Gilman, AG, et al. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 8th Edition; pp 1316) 19. E Antithrombin III primarily inhibits the vitamin K dependent procoagulant factors (II, VII, IX, and X). Deficiency will lead to recurrent thrombosis. Heparin induced anti-platelet antibodies occur in approximately 5% of patients receiving heparin therapy. Most cases are mild with platelet counts above 100,000/uL. All of the above statements are correct. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1406–1407) 20. D Two forms of acute, heparin induced thrombocytopenia occur. The mild form occurs in approximately 5% of patients, 4 – 15 days after initiation of full-dose heparin therapy (platelet counts above 100,000/uL). Severe thrombocytopenia occurs less frequently. The more severe form is associated with thrombotic complications. All of the above statements are correct. (Gilman, AG, et al. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 8th Edition; pp 1316) 21. E Protein C activation is controlled by several different mechanisms, including by thrombomodulin. Protein C activation and thrombin generation are tightly coupled. Acquired and hereditary deficiencies are the primary cause of thrombophila. (Nathan, DG, et al. Nathan and Oski’s Hematology of Infancy and Childhood, 5th Edition; pp 1545–1547) 22. E In contrast to heparin, which acts as a cofactor with antithrombin III to prevent coagulation, the plasminogen activators, urokinase, streptokinase and tPA increase fibrinolysis, thereby lysing the clot. Plasminogen is cleaved into plasmin by these activators. Plasmin lyses clot directly. All of the above statements are correct. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edtion; pp 1415–1416, 1423-1424) 23. E Both heparin and plasminogen activators (streptokinase, t-PA) may be used to treat arterial thrombosis. The PTT should be kept 1.5–2.0 times normal during heparin therapy. Note, younger neonates may be resistant to thrombolytic therapy, possibly due to lower levels of plasminogen. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp 1424) 24. E Disorders in children that are treated with chronic anticoagulants include cardiac disorders (prosthetic valves, Blalock-Taussig shunts, endovascular shunts), some cerebrovascular events, Kawasaki’s disease. All of the above statements are correct. (Nathan, DG, et al. Nathan and Oski’s Hematology of Infancy and Childhood, 5th Edition; pp 1704) 25. C, D, A Aspirin is a potent and irreversible inhibitor of cyclooxygenase and thromboxane A2. Sulfinpyrazone like aspirin is also a nonsteroidal anti-inflammatory agent that reversibly inhibits cyclooxygenase. (Gilman, AG, et al. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 8th Edition; pp 652, 1524) 26. D Thromboprophylaxis for prosthetic heart valves has reduced the occurrence of thromboemolic events from approximately 6% to under 2%. The other statements are true. (Michelson, AD, et al. Antithrombotic Therapy in Children, Chest1998; 114 (5 Suppl): 748S–769S)