Post on 11-Apr-2017
Emergencias Oncológicas
Diplomado de cuidado paliativo, UnRemington, Medellín, 2017
Mauricio Lema Medina
Clínica de Oncología Astorga, Clínica SOMA, Medellín
YOUR LOGO
@onconerd
Urgencia
InesperadoRequiere atención
inmediata
Emergencia
InesperadoRequiere atención
inmediata
Peligrosa
Page 6
Emergencias oncológicas
S. Vena cava superior Compresión epidural Taponamiento cardíaco Obstrucción de víscera
Aérea S. Pilórico Intestinal Biliar Urinaria
Hipertensión endocraneana
Mecánicas
Hipercalcemia asociada a malignidad
Sindrome de secreción inapropiada de hormona antidiurética
Acidosis láctica Hipoglicemia Insuficiencia adrenal
Metabólicas
Neutropenia febril Sindrome de lisis tumoral Reacciones infusionales S. Hemolítico-urémico Colitis neutropénica Cistitis hemorrágica
Asociadas al tratamiento
Reto diagnóstico y terapéutico
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Temario
Hipercalcemia asociada a cáncer
Neutropenia febril
Sindrome de lisis tumoral
Compresión medular neoplásica
S. Vena cava superior
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Febrile Neutropenia
Neutropenia
Frecuente entre el día 7 y 14 después de la administración de quimioterapia citotóxica
20-30% requiere de hospitalización por neutropenia febril
Mortalidad en paciente neutropénico hospitalizado: 10%
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Neutropenia Febril
DEFINICIÓN
- Fiebre mayor de 38 grados centígrados durante 1 hora o más o fiebre mayor de 38.3 grados centígrados en 1 ocasión.
- Recuento absoluto de granulocitos menor de 500/mm3 o recuento de leucocitos < 1000/mm3 cuando se espera que el recuento de granulocitos es menor de 500/mm3.
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Recuento de granulocitos después de quimioterapia citotóxica
Día 1 Día 8 Día 15 Día 22
Inicio de ciclo de quimioterapia Inicio de ciclo de quimioterapia
ANC<500/mm3
Etiologìa infecciosa neutropenia febril - Clínica SOMA
Page 12 Carlos Betancur, 2017
Gérmenes resistentes en neutropenia febril – tips clínicos
Factores de riesgo para resistencia de los bacilos gramnegativos- Haber recibido un betalactamico en los tres meses precedentes, - Haber tenido uno de estos gérmenes previamente,- Hospitalización reciente, - Presencia de sondas o instrumentación.
Factores de riesgo para Pseudomona- Haber estado intubado por más de 72 horas, - Úlceras crónicas y - Pneumopatías crónicamente infectadas.
Factores de riesgo para Staphylococcus meticilinoresistentes (SAMR)- Tener catéter, - Haber recibido antibiótico betalactamico en los últimos tres meses - Tener historia previa de haber tenido este germen antes.
Page 13 Carlos Betancur, 2017
Neutropenia febril
Infección identificada Sin Factor de Riesgo Con factor de riesgo
InestableEstable
Imipenem + VancomicinaCefepime*Piperacilina/TazobactamRx apropiado
GNR: Gram Negativos resistentes / MRSA: Staphylococcus aureus resistentes a meticilina* + Vancomicina si factor de riesgo para MRSA
Factores de riesgoPara GNR: Hospitalización reciente; betalactámicos en los últimos 3 meses; historia de GNR
Para MRSA: Catéter; betalactámicos en los últimos 3 meses; historia de MRSAPara Pseudomona: Intubación >72 horas; úlceras crónicas; pneumopatía crónicamente infectada
Neutropenia febril: Selección antibiótico empírico
Febrile neutropenia
Time to treatment
Resistance to antibiotics
Empiric antifungals
Prophylactic antibiotics
Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was
initiated in the emergency department.
Gaieski DF, Mikkelsen ME, Band RA, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department*. Crit Care Med. 2010;38(4):1045-1053. doi:10.1097/CCM.0b013e3181cc4824.
HR: 0.3 (Less vs More than 1 h)
Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was
initiated in the emergency department.
Gaieski DF, Mikkelsen ME, Band RA, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department*. Crit Care Med. 2010;38(4):1045-1053. doi:10.1097/CCM.0b013e3181cc4824.
HR: 0.5 (Less vs More than 1 h)
Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American
Society of Clinical Oncology clinical practice guideline.
Flowers CR, Seidenfeld J, Bow EJ, et al. Antimicrobial Prophylaxis and Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2013;31(6):794-810. doi:10.1200/JCO.2012.45.8661
Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American
Society of Clinical Oncology clinical practice guideline.
• Assess risk for medical complications in patients with FN using the Multinational Association for Supportive Care in Cancer (MASCC) score ≥ 21 with no other risk factors defines low risk
• An oral fluoroquinolone plus amoxicillin/clavulanate (or plus clindamycin for those with penicillin allergy) is recommended for initial empiric therapy, unless fluoroquinolone prophylaxis was used before fever developed (see text for alternatives)
Flowers CR, Seidenfeld J, Bow EJ, et al. Antimicrobial Prophylaxis and Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2013;31(6):794-810. doi:10.1200/JCO.2012.45.8661
MRSA, VRE, ESBL-producing gram-negatives, and carbapenemase-producing microorganisms,including Klebsiella
pneumoniae carbapenemase (KPC)
MRSA: vancomycin, teicoplanin, linezolid, or daptomycin.
VRE: linezolid or daptomycin.
ESBL-producing Enterobacteriaceae: carbapenems.
KPC-producing gram-negative bacteria: colistin or tigecycline. Akova M, Alp S. Management of febrile neutropenia in the era
of bacterial resistance. Ther Adv Infect Dis. 2013;1(1):37-43. doi:10.1177/2049936113475610.
Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the
Infectious Diseases Society of America
Empiric antifungal therapy is recommended in high-risk patients for IFD who have persistent fever after 4–7 days of broad-spectrum antibacterials and no identified infection source
Patterson TF, Thompson GR, Denning DW, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1-e60. doi:10.1093/cid/ciw326.
Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the
Infectious Diseases Society of America
• 1. Hospitalized allogeneic HSCT recipients should be placed in a protected environment to reduce mold exposure (strong recommendation; low-quality evidence) .
• 2. These precautions can be reasonably applied to other highly immunocompromised patients at increased risk for IA, such as patients receiving induction/reinduction regimens for acute leukemia (strong recommendation; low-quality evidence) .
• 3. In hospitals in which a protected environment is not available, we recommend admission to a private room, no connection to construction sites, and not allowing plants or cut flowers to be brought into the patient's room (strong recommendation; low-quality evidence) .
• 4. We recommend reasonable precautions to reduce mold exposure among outpatients at high risk for IA, including avoidance of gardening, spreading mulch (compost), or close exposure to construction or renovation (strong recommendation; low-quality evidence) .
Patterson TF, Thompson GR, Denning DW, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1-e60. doi:10.1093/cid/ciw326.
Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the
Infectious Diseases Society of America
Prolonged neutropenia, Allogeneic hematopoietic stem cell transplant (HSCT), Solid organ transplant (SOT),Inherited or acquired immunodeficiencies, Corticosteroid use
Patterson TF, Thompson GR, Denning DW, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1-e60. doi:10.1093/cid/ciw326.
Herbrecht R et al. N Engl J Med 2002;347:408-415.
Survival Curves for the Modified Intention-to-Treat Population According to Treatment Group.
Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the
Infectious Diseases Society of America
• We recommend primary treatment with voriconazole ( strong recommendation; high-quality evidence ).
• Early initiation of antifungal therapy in patients with strongly suspected IPA is warranted while a diagnostic evaluation is conducted (strong recommendation; high-quality evidence ).
• Alternative therapies include liposomal AmB ( strong recommendation; moderate-quality evidence ), isavuconazole ( strong recommendation; moderate-quality evidence ), or other lipid formulations of AmB ( weak recommendation; low-quality evidence ).
Patterson TF, Thompson GR, Denning DW, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1-e60. doi:10.1093/cid/ciw326.
Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American
Society of Clinical Oncology clinical practice guideline.
Flowers CR, Seidenfeld J, Bow EJ, et al. Antimicrobial Prophylaxis and Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2013;31(6):794-810. doi:10.1200/JCO.2012.45.8661
Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American
Society of Clinical Oncology clinical practice guideline.
Antibacterial and antifungal prophylaxis are only recommended for patients expected to have < 100 neutrophils/μL for > 7 days,
An oral fluoroquinolone is preferred for antibacterial prophylaxis and an oral triazole for antifungal prophylaxis
Flowers CR, Seidenfeld J, Bow EJ, et al. Antimicrobial Prophylaxis and Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2013;31(6):794-810. doi:10.1200/JCO.2012.45.8661
Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American
Society of Clinical Oncology clinical practice guideline.
Antibacterial and antifungal prophylaxis are only recommended for patients expected to have < 100 neutrophils/μL for > 7 days,
An oral fluoroquinolone is preferred for antibacterial prophylaxis and an oral triazole for antifungal prophylaxis
Interventions such as footwear exchange, protected environments, respiratory or surgical masks, neutropenic diet, or nutritional supplements are not recommended because evidence is lacking of clinical benefits to patients from their use
Flowers CR, Seidenfeld J, Bow EJ, et al. Antimicrobial Prophylaxis and Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2013;31(6):794-810. doi:10.1200/JCO.2012.45.8661
Hipercalcemia asociada a malignidad
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Page 33
Hipercalcemia asociada a malignidad
Ca broncogénico Ca mama Ca próstata Mieloma múltiple Ca cabeza y cuello Ca renal Linfomas
Tumores
Astenia / Fatiga Letargo / Confusión Anorexia Constipación Polidipsia / Poliuria Náusea / Vómito Debilidad muscular Arritmias
Clínica
Ca corregido(mg/dL) = Ca medido(mg/dL) + 0.8 (4 - Albúmina(gr/dL) )
Ca (mMol/L) = Ca sangre (mg/dL) * 0.25
Calcio sérico
Generalidades
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Hipercalcemia asociada a cáncer
Tipos de hipercalcemia asociada a cáncerTipo Frecuencia Metástasis
óseasAgente causal
Tipo de tumor
Hipercalcemia humoral asociada a malignidad
80% Rara PTHrP Escamocelulares, renales, ovario, endometrio, mama
Osteolítica 20% Universal Citokinas Mama, mieloma, linfoma
Vitamina D <1% Rara Vitamina D Linfoma
Hiperparatiroidismo ectópico
<1% Variable PTH Variable
Wagner J, Arora S. Oncologic Metabolic Emergencies. Emerg Med Clin North Am. 2014;32(3):509-525. doi:10.1016/j.emc.2014.04.003.
Page 35
Hipercalcemia asociada a malignidad
Anorexia, náuseas, pérdida de peso, debilidad, constipación y alteraciones en el estado mental
Calcificación metastásica (en
órganos)
Coma
Arritmias
Severidad (calcio sérico)
Náuseas y vómito severos, deshidratación, disfunción renal, estado confusional severo con pérdida de la conciencia
. Wagner J, Arora S. Oncologic Metabolic Emergencies. Emerg Med Clin North Am. 2014;32(3):509-525. doi:10.1016/j.emc.2014.04.003.
Short QT interval
J-wave
EKG of hypercalcemia
Hypercalcemia
Ionized-calcium Serum PTH levels
Hypercalcemia confirmedLow PTH
Humoral hypercalcemia of malignancy
To treat or not to treat
“Most patients who experience hypercalcemia of malignancy are in the last few weeks of their lives, as shown by a median survival of 35 days
and a 2- year mortality of 72% in those with aerodigestive squamous cancer, and it is also
predictive of early death in patients presenting with multiple myeloma”
Wagner J, Arora S. Oncologic Metabolic Emergencies. Emerg Med Clin North Am. 2014;32(3):509-525. doi:10.1016/j.emc.2014.04.003.
IV Fluids
Bisphosphonates
Steroids (in myeloma/lymphoma)
Consider off-label denosumab
LeGrand SB, Leskuski D, Zama I. Narrative Review: Furosemide for Hypercalcemia: An Unproven yet Common Practice. Ann Intern Med. 2008;149(4):259. doi:10.7326/0003-4819-149-4-200808190-00007.
Narrative Review: Furosemide for Hypercalcemia: An Unproven yet Common Practice
• Additional volume depletion• Hypokalemia• Worsening hypercalcemia• Need for intensive monitoring of urine output and
electrolytes in an ICU.
Furosemide should only be used to reverse overaggressive fluid replacement or in patients who show signs of volume overload.
(1) Major P, et al. J Clin Oncol 2001; 19: 558-567
RHipercalcemia(>3 mMol/L)
Pamidronato 90 mg IV (4h)
Ácido zoledrónico
Variable Pamidronato ZoledronatoNormocalcemia @10d 70% 87% p=0.02
Duración de normocalcemia (mediana) 18 días >30 días
n=287
Pamidronato vs Zoledronato en hipercalcemia asociada a malignidad(1)
4 mg y 8 mg: similar eficacia.8 mg: mayor nefrotoxicidad
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Denosumab for treatment of hypercalcemia of malignancy
CONTEXT:Hypercalcemia of malignancy (HCM) in patients with advanced cancer is often caused by excessive osteoclast-mediated bone resorption. Patients may not respond to or may relapse after iv bisphosphonate therapy.
OBJECTIVE:We investigated whether denosumab, a potent inhibitor of osteoclast-mediated bone resorption, reduces serum calcium in patients with bisphosphonate-refractory HCM.
DESIGN, SETTING, AND PARTICIPANTS:In this single-arm international study, participants had serum calcium levels corrected for albumin (CSC) >12.5 mg/dL (3.1 mmol/L) despite bisphosphonates given >7 and ≤30 days before screening.
INTERVENTION:Patients received 120 mg sc denosumab on days 1, 8, 15, and 29 and then every 4 weeks.
CONCLUSIONS:In patients with HCM despite recent iv bisphosphonate treatment, denosumab lowered serum calcium in 64% of patients within 10 days, inducing durable responses. Denosumab may offer a new treatment option for HCM.
Hu MI, Glezerman IG, Leboulleux S, et al. Denosumab for Treatment of Hypercalcemia of Malignancy. J Clin Endocrinol Metab. 2014;99(9):3144-3152. doi:10.1210/jc.2014-1001.
Denosumab for treatment of hypercalcemia of malignancy
Hu MI, Glezerman IG, Leboulleux S, et al. Denosumab for Treatment of Hypercalcemia of Malignancy. J Clin Endocrinol Metab. 2014;99(9):3144-3152. doi:10.1210/jc.2014-1001.
Major P, et al. J Clin Oncol 2001;19:558-567Stewart AF. N Engl J Med 2005;352:373-9
Medir calcio, albúmina, fósforo y creatinina
Establecer severidad
Establecer severidad, si se va a tratar. Ingreso a UCI o no
SSN @ 200-500 mL/hora
Considerar furosemida
Corregir fosfato (si <3 mg/dL)
Ácido zoledrónico 4 mg IV – 15 minPrednisolona: puede ser eficaz en linfoma y mieloma
Tratar la enfermedad de base
Hipercalcemia asociada a cáncer
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Sindrome de lisis tumoral
Page 47Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Sindrome de lisis tumoral
HiperKalemia
Eflujo de potasio Hiperfosfatemia
Catabolismo de purinas
Arritmias
Imbalance calcio / fósforo
Depleción de volumen
Liberación ácido nucleico
Hiperuricemia
Precipitación de cristales de urato
Insuficiencia renal aguda
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Sindrome de lisis tumoral
Coiffier B. J Clin Oncol 2008; 26:2767-2778
Definición de laboratorio de SLT – Cairo-BishopVariable Valor Δ del basal
Ácido úrico > 8 mg/dL ↑ 25%
Potasio > 6 mg/L ↑ 25%
Fósforo > 1.45 mMol/L ↑ 25%
Calcio < 1.75 mMol/L ↓ 25%
NOTA: 2 o más cambios de laboratorio que dentro de 3 días antes o 7 días después de quimioterapia citotóxica
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Sindrome de lisis tumoral
Coiffier B. J Clin Oncol 2008; 26:2767-2778
Cánceres asociados a SLT en adultosLinfoma no Hodgkin 28%
Leucemia mieloide aguda 27%
Leucemia linfoide aguda 19%
Leucemia linfoide crónica 10%
Mieloma múltiple 3.9%
Enfermedad de Hodgkin 1.6%
Tumores sólidos 1%
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Sindrome de lisis tumoral
Coiffier B. J Clin Oncol 2008; 26:2767-2778
Factores de riesgo para SLTTipo de tumor Linfoma de Burkitt
Linfoma linfoblásticoLinfoma difuso de células grandesLeucemia linfoide agudaTumores sólidos (alta proliferación y respuesta rápida a tratamiento)
Masa tumoral Enfermedad voluminosa (>10 cm)Incremento LDH (> 2 x LSN)Leucocitos > 25000/uL
Función renal Falla renal pre-existenteOliguria
Ácido úrico basal >7.5 mg/dL
Terapia eficaz citorreductiva Variable
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Sindrome de lisis tumoral
Coiffier B. J Clin Oncol 2008; 26:2767-2778
Estratificación de riesgo de SLTTipo de tumor Alto riesgo Riesgo Intermedio Bajo RiesgoLinfoma No Hodgkin Burkitt, linfoblástico,
Leucemia linfoide aguda
Linfoma difuso de células grandes
Linfoma indolente
Leucemia linfoide aguda
>100k/mm3 50-100k/mm3 <50k/mm3
Leucemia linfoide aguda
>50k/mm3Monoblástica
10-50k/mm3 <10k/mm3
Leucemia linfoide crónica
10-100k/mm3Fludarabina
Demás
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Definición y gradación clínica del SLT – Criterios de Cairo-BishopGrado
Complicación 1 2 3 4 5Creatinina <1.5 x LSN 1.5-3 x LSN 3-6 x LSN >6 x LSN Muerte
Arritmias No requiere tratamiento
Tratamiento no urgente
Sintomática o requiere de dispositivo
Con peligro para la vida
Muerte
Convulsiones Ninguna Una generalizada, controlada con anticonvulsivante; hasta varias focales, infrecuentes, que no afecten las actividades diarias
Convulsiones con alteración de la consciencia. Convulsiones pobremente controladas. Convulsiones con pobre respuesta al tratamiento
Status epilepticus, convulsiones de difícil control - prolongadas
Muerte
LSN: Límite superior de lo normal
Coiffier B. J Clin Oncol 2008; 26:2767-2778 Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Catabolismo de purinas
Hipoxantina
Xantina
Ácido úrico
Alantoína
Xantina oxidasa
Xantina oxidasa
Urato oxidasa / Rasburicase
Alopurinol
Alopurinol
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
TLS
Prophylacxis of TLS
Single-dose raseburicase
Treatment of TLS
Prophylactic rasbiricase
Prevención•Si tiene riesgo intermedio o alto.•Hidratación: - 2 – 3 Lt/m2/día - Vigilar gasto urinario (>2 ml/kg/h)
•Alcalinización de la orina: - Previene deposición de cristales de urato. - Precipita deposicón de cristales de fosfato de calcio. - HCO3: Sólo si hay acidosis metabólica.
Coiffier B, Altman A, Pui CH, et al. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol 2008
Prevención• Alopurinol: - No degrada el ácido úrico ya formado. - 100 mg/m2 tid (max 800 mg/d). - Iniciar 24 – 48 h antes de la QT y 7 días depsués.
• Rasburicasa: - Degrada el AU ya formado a un compuesto más soluble. - Ideal en pacientes con hiperuricemia de base. - 0.2 mg/kg qd por 2 – 7 días.
Coiffier B, Altman A, Pui CH, et al. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol 2008
Control of plasma uric acid in adults at risk for tumor Lysis syndrome: efficacy and safety of rasburicasealone and rasburicase followed by
allopurinol compared with allopurinol alone--results of a multicenter phase III study.
PATIENTS AND METHODS:Adults with hematologic malignancies at risk for hyperuricemia and tumor lysis syndrome (TLS) were randomly assigned to rasburicase (0.20 mg/kg/d intravenously days 1-5), rasburicase plus allopurinol (rasburicase 0.20 mg/kg/d days 1 to 3 followed by oral allopurinol 300 mg/d days 3 to 5), or allopurinol (300 mg/d orally days 1 to 5).
Primary efficacy variable was plasma uric acid response rate defined as percentage of patients achieving or maintaining plasma uric acid ≤ 7.5 mg/dL during days 3 to 7.
RESULTS:Ninety-two patients received rasburicase, 92 rasburicase plus allopurinol, and 91 allopurinol.
Plasma uric acid response rate was 87% with rasburicase, 78% with rasburicase plus allopurinol, and 66% with allopurinol.
It was significantly greater for rasburicase than for allopurinol (P = .001) in the overall study population, in patients at high risk for TLS (89% v 68%; P = .012), and in those with baseline hyperuricemia (90% v 53%; P = .015).
Time to plasma uric acid control in hyperuricemic patients was 4 hours for rasburicase, 4 hours for rasburicase plus allopurinol, and 27 hours for allopurinol.
Cortes J, Moore JO, Maziarz RT, et al. Control of Plasma Uric Acid in Adults at Risk for Tumor Lysis Syndrome: Efficacy and Safety of Rasburicase Alone and Rasburicase Followed by Allopurinol Compared With Allopurinol Alone—Results of a Multicenter Phase III Study. J Clin Oncol. 2010;28(27):4207-4213. doi:10.1200/JCO.2009.26.8896.
Control of plasma uric acid in adults at risk for tumor Lysis syndrome: efficacy and safety of rasburicasealone and rasburicase followed by
allopurinol compared with allopurinol alone--results of a multicenter phase III study.
Cortes J, Moore JO, Maziarz RT, et al. Control of Plasma Uric Acid in Adults at Risk for Tumor Lysis Syndrome: Efficacy and Safety of Rasburicase Alone and Rasburicase Followed by Allopurinol Compared With Allopurinol Alone—Results of a Multicenter Phase III Study. J Clin Oncol. 2010;28(27):4207-4213. doi:10.1200/JCO.2009.26.8896.
Control of plasma uric acid in adults at risk for tumor Lysis syndrome: efficacy and safety of rasburicasealone and rasburicase followed by
allopurinol compared with allopurinol alone--results of a multicenter phase III study.
CONCLUSION:In adults with hyperuricemia or at high risk for TLS, rasburicase provided control of plasma uric acid more rapidly than allopurinol.
Rasburicase was well tolerated as a single agent and in sequential combination with allopurinol.
Cortes J, Moore JO, Maziarz RT, et al. Control of Plasma Uric Acid in Adults at Risk for Tumor Lysis Syndrome: Efficacy and Safety of Rasburicase Alone and Rasburicase Followed by Allopurinol Compared With Allopurinol Alone—Results of a Multicenter Phase III Study. J Clin Oncol. 2010;28(27):4207-4213. doi:10.1200/JCO.2009.26.8896.
A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis
syndrome PATIENTS AND METHODS:We evaluated the efficacy of rasburicase (0.15 mg/kg) administered as single dose followed by as needed dosing (maximum five doses) versus daily dosing for 5 days in adult patients at risk for TLS.
RESULTS:Eighty of the 82 patients enrolled received rasburicase;
40 high risk [median uric acid (UA) 8.5 mg/dl; range, 1.5-19.7] and 40 potential risk (UA = 5.6 mg/dl; range, 2.4-7.4).
Seventy-nine patients (99%) experienced normalization in their UA within 4 h after the first dose; 84% to an undetectable level (<0.7 mg/dl).
Thirty-nine of 40 (98%) patients in the daily-dose arm and 34 of 40 (85%) patients in single-dose arm showed sustained UA response.
Vadhan-Raj S, Fayad LE, Fanale MA, et al. A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis syndrome. Ann Oncol. 2012;23(6):1640-1645. doi:10.1093/annonc/mdr490.
A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis
syndrome
Vadhan-Raj S, Fayad LE, Fanale MA, et al. A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis syndrome. Ann Oncol. 2012;23(6):1640-1645. doi:10.1093/annonc/mdr490.
A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis
syndrome
CONCLUSIONS:Rasburicase is highly effective for prevention and management of hyperuricemia in adults at risk for TLS. Single-doserasburicase was effective in most patients; only a subset of high-risk patients required a second dose.
Vadhan-Raj S, Fayad LE, Fanale MA, et al. A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis syndrome. Ann Oncol. 2012;23(6):1640-1645. doi:10.1093/annonc/mdr490.
S. Lisis tumoral
Hidratación
Alcalinización orina Alopurinol/Rasburicase Cr / Ca / P / K, etc
HemodiálisisAntiarrítmicos Anticonvulsivantes
Coiffier B. J Clin Oncol 2008; 26:2767-2778Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Tratamiento•UCI / monitoreo cardíaco.•Líquidos.•Trastornos hidroelectrolíticos: - Hiperkalemia - Hipocalcemia sintomática.•Rasburicasa (si no la recibía).•Diálisis: oliguria / anuria Hiper K persisntente. Hipo Ca sintomática por hiperfosfatemia
The tumor lysis syndrome. Howard SC et al. New England Journal of Medicine. 2001. May;364(19):1844-54
Compresión epidural metastásica
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
Page 68
Compresión epidural
Ocurre en 5-10% de los cánceres metastásicos
Presentación inicial de hasta 10% de los cánceres metastásicos
Consecuencias devastadoras si no es tratada a tiempo
Cuadri/para-plejía “total care”
Epidemiología
Cuerpo vertebral que comprime saco dural
Metástasis epidurales Tumor paraespinal que
invade por los forámenes vertebrales
Mecanismos
70% - Torácico 20% - Lumbar 10% - Central
Ubicación
Generalidades
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Ca pulmón Ca mama Ca próstata Mieloma Linfoma Melanoma
Etiología
Dolor de espalda Transtornos esfínteres Debilidad miembros con
nivel Hipoestesia con nivel
Clínica
Loblaw A. J Clin Oncol 23:2028-2037
Esteroides en compresión medular Resultados Comentarios
Dexametasona 96 mg IV x1, 24 mg VO q6h x3 día…(1)
81% ambulatorios @3m
Toxicidad severa: 11%
Nada(1) 61% ambulatorios @3m
NS (n=57)
Dexametasona 100 mg IV(2) Mejoría en la fuerza 25%
NS
Dexametasona 10 mg IV(2) Mejoría en la fuerza 8%
NS (n=37)
Dexametasona 100 mg(3) Efectos adversos serios: 14.2%
Casos y controles
Dexametasona 10 mg, seguido 4 mg IV q6h…(3)
Efectos adversos serios: 0%
Casos y controles
No esteroides en ambulatorios(4) 20/20 ambulatorios @3m post RT
(1) Sorensen et al, (2) Vecht et al, (3) Heimdal et al, (4) Maranzano et al.
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Esteroides en compresión medular metastásica
Parecen eficaces (junto con RT) Dosis demasiado altas, demasiado
tóxicas Dosis demasiado bajas, menos
eficaces En pacientes Ambulatorios, RT
suficiente
Recomendación (Soft) Dexametasona 16 mg IV qd hasta
que se defina el manejo definitivo
White BD et al. NICE Guidance. BMJ 2008; 337:a2538 Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Cirugía en compresión medular metastásica
Indicaciones- Inestabilidad vertebral
- Descompresión posterior- Considerar laminectomía si no hay
inestabilidad vertebral
- Área preirradiada- Expectativa de vida >3
meses- No diagnóstico
Limitaciones- Ineficaz si paraplejía o
cuadriplejía >24 horas- No recomendada si
expectativa de vida <3 meses
- Mortalidad 0-13%- Complicación severa
- Laminectomía: 0-10%- Resección de cuerpo vertebral:
10-54%Loblaw A. J Clin Oncol 23:2028-2037White BD et al. NICE Guidance. BMJ 2008; 337:a2538
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Radioterapia
Indicaciones:
- No candidato a cirugía.
- Después de cirugía. Objetivo:
- Control del dolor.
- Control local del tumor.
Dosis: Variable.
- Generalmente pocas sesiones, altas dosis.
- 8 Gy (1 o 2 veces).
- MM: 30 Gy (10 sesiones).
Radiosensible Radioresistente
Linfoma. Melanoma.
Mieloma. RCC.
SCLC. NSCLC.
Ca próstata. Sarcomas.
Ca de mama.
Seminoma.
Short-course versus split-course radiotherapy in metastatic spinal cord compression: results of a phase III, randomized, multicenter trial. J Clin Oncol. 2005;23(15):3358.
Loblaw A. J Clin Oncol 23:2028-2037
Estado a la presentación % ambulatorio después de radioterapia
IC 95%
Ambulatorio 92% 89% - 95%
Ambulatoria con asistencia 65% 56% - 74%
Paraparético 43% 38% - 48%
Parapléjico 14% 10% - 17%
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Radioterapia estereotáxica Cyberknife. Tumores pequeños. Ventajas:
- Menos daño a tejido adyacente.
- Efectiva en tumores radio resistentes. Dosis: Dosis única alta.
- 26 – 24 Gy.
Local disease control after decompressive surgery and adjuvant high-dose single-fraction radiosurgery for spine metastases. J Neurosurg Spine. 2010;13(1):87
Sindrome de vena cava superior
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
Page 76
Sindrome de vena cava superior
Neoplásica (90%) Ca pulmón – 85% Linfoma – 8% Células germinales Carcinoma de mama
No neoplásico (10%) T. Benignos / bocio Trombosis Aneurisma de aorta Mediastinitis
fibrosante
Causas
Insidiosa Disnea Sensación de peso en
cabeza y cuello Edema de cara, cuello y
miembros superiores Distensión venosa de
cuello Circulación colateral Plétora / cianosis
Clínica
Rayos X de tórax Normal Ensanchamiento
mediastinal Derrame pleural
TAC de tórax Colapso de vena
cava superior Edema de tejidos
blandos Circulación colateral Masa
Imágenes
Emergencia oncológica
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Sindrome de Vena Cava Superior
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2004
Sindrome de vena cava superior – Clasificación de Yu
Grado %
0 – Asintomático 10 Dx radiológico.
1 – Leve 25 Edema / cianosis
2 – Moderado 50 Disfaga / tos / alteración movimiento cabeza u ojos / alteración visual.
3 – Severo 10 Edema cerebral (Cefalea / mareo)Edema laríngeo leve / moderado.Disminución reserva cardíaca (síncope con movimiento)
4 – Amenaza vida 5 Edema cerebral severo (confusión)Edema laríngeo severo (estridor).Compromiso hemodinámico (síncope, hipotensión)
5 - Fatal <1 Muerte.
Page 80
Sindrome de vena cava superior
Diuréticos Cabeza elevada Oxígeno
Paliativo
Tratamiento de la neoplasia
NSCLC: Radioterapia
SCLC: Quimioterapia
Linfoma: Quimioterapia
No neoplásico Trombosis:
anticoagulación / fibrinolisis +/- retirar el catéteter
Específico
Obstrucción traqueal
Peligro inminente
Manejo
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
Stent vena cava superior.
Restaura flujo venoso. Percutáneo por yugular,
subclavia o femoral. Indicaciones:
- Severo.
- Paliación. Antiplaquetarios.
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2011
RT
Plétora, edema facial y de cuello
Ingurgitación venosa, circulación colateral
Ensanchamiento mediastinal
Colapso vena cava superior, masa - NSCLC
Sindrome de vena cava superior