Emergencies in Oncology

Transcription

1 Emergencies in Oncology Peter Kabos, MD University of Colorado Denver Outline Neutropenic fever Spinal cord compression Tumor lysis syndrome Hypercalcemia Superior vena cava syndrome Other Brain mets SIADH Uncontrolled pain Pericardial tamponade SBO Urinary obstruction Hyperviscosity Leukostasis Fever and Neutropenia

2 Fever & Neutropenia Extremely common emergency in oncology Up to 70% mortality rate at 48 hours Now able to use aggressive cytotoxic therapy as induction chemotherapy for leukemia with use of broad-spectrum antibiotics Definitions Neutropenic: ANC (polys and bands) < 500 ANC <1000 and expected to fall to <500 Fever: One reading of (38.3) (38) for more than one hour Elderly, steroids, sick, hypotension even in the absence of fever Sources of infection 60% of patients with F+N are actually infected 16-20% with counts <100 are bacteremic Endogenous (80%): translocation from GI tract due to mucosal damage from chemotherapy Catheter-related Environmental: food, water, air

3 Sepkowitz, Clin Infect Dis 2005 Neutropenic fever: evaluation H/P: sinus, fundi, peri-anal, lines Lab: CBC, LFTs, lipase LP not necessary without symptoms Cultures BC through each port and peripheral blood X-rays: CXR HR ct may show pneumonia Diagnostic algorithm for radiologic chest procedures Heussel, C. P. et al. J Clin Oncol; 17: Copyright American Society of Clinical Oncology

4 Multinational Association of Supportive Care in Cancer ID subcommittee (2000) Prediction of low-risk neutropenic patients with fever: Burden of illness No or mild symptoms 5 Moderate symptoms 3 No hypotension 5 No COPD 4 Solid tumor or no previous fungal infection 4 Outpatient status 3 No dehydration 3 Age <60 years 2 Score of 21 _ predictive of <5% risk for severe complications Klastersky J et al., J Clin Oncol 18(2000), Treatment Begin therapy within 4 hours of fever spike Monotherapy cheaper, safer equaly effective as dual therapy in uncomplicated neutropenic fever (Cefepime, Imipenem, Meropenem) Dual therapy offers synergy against GNR and may be preferred in sicker patients or those with focal infections requiring broader coverage (pneumonia). Regimen must always include anti-pseudomonal coverage Risk stratification Need for vancomycin Cellulitis, severe mucositis Infected catheter Hypotension, signs of sepsis Known MRSA colonization Prior quinolone prophylaxis Need for anaerobic coverage Gingivitis Bowel involvement/rectal abscess?remove catheter How long will you treat

5 Clinical Infectious Diseases 2002, 34: ; Freifeld NEJM; 341:305 Mullen Cancer 1999;86:126 Addition of antifungal Incidence rises after 7 days of antibiotics with persistent fever and neutropenia Antifungal added at 5-7 days of persistent F+N+ patients without other source Liposomal ampho as effective as ampho, less toxic, fewer breakthrough fungal infections Voriconazole vs ampho: same mortality, other endpoints difficult to interpret Caspofungin vs ampho: better mortality and fewer SE Intraconazole (avoid in renal insufficiency and for longer than 14 days) Duration of therapy If pathogen identified: treat as indicated If ANC rises and F stops: can stop A If F resolves but N persists: less clear Consider stopping with early signs of hematologic recovery, but watch closely

6 Growth factors (CSFs) for febrile neutropenia Several trials, placebo controlled, blinded Minor clinical benefit documented Shorter duration of neutropenia (3 v 4 days) Quicker resolution of fever (5 v 6 days) Shorter hospital stay No difference in mortality May be more effective in high risk (ASCO Guidelines JCO 2000;18:3558) Antibiotic prophylaxis National Comprehensive Cancer Network 2007 Spinal Cord Compression

7 Spinal Cord Compression Prevalence: 5-10% of cancer patients and in 10% of these it is the presenting complaint Most common sites: thoracic spine (70%) LS spine (20%) cervical (10%) Multiple sites common in breast, prostate; lung almost always a single site Presentation 96% have pain as first symptom Precedes other findings by average 7 weeks Severe, local, increasing Worse with recumbency Radicular pain more common in lumbar region Bilateral in thoracic region

8 Back pain 87 patients with cancer and back pain Epidural metastases in Myelopathy 78% Radiculopathy 61% Normal PE 36% Rodichok et a. Am J Med 1981;70:1181 Examination Palpate vertebrae, flex and extend cervical/lumbar spine Thorough neurologic examination including rectal tone and perineal sensation may localize lesion Can check post-void residual If > 150cc = bladder dysfunction Spinal cord compression: findings Motor findings in 60-85% at presentation LE flexors, UE extensors, hyper-reflexia below In most series, most patients are not ambulatory at presentation Weakness most prominent in T-spine Sensory findings less common Sensory findings usually 3-4 levels below Saddle parasthesias common in CE Bowel/bladder dysfunction usually late Usually urinary retention and rarely the only sx

9 Delay in diagnosis 301 patients with ESCC Median time to treatment 2 months from onset of pain 10 days from onset of SCC 3 due to patient 4 due to physician Majority deteriorated in function Husband BMJ 1998;317:18-21 Spinal cord compression: evaluation MRI of entire spine recommended 1/3 have multiple levels 21% miss rate if only T or L spine is imaged Physical exam/ plain x-rays inadequate Vertebral collapse or pedicle erosion in right region is 80% predictive 15-20% false negative rate Neurologists miss level in 25% cases Degree of urgency Radicular pain and normal exam: 24 hour Pain and radiculopathy: 24 hour and admit XRT within 24 hours; Steroids not necessary if <50% narrowing Plexopathy: MRI today and admit Steroids and XRT within 24 hours Myelopathy: MRI today, steroids and admit Steroids and XRT (surgery) today (tonight)

10 Spinal cord compression: treatment Pain control Steroids decrease pain usually in hours Most will require narcotics Bed rest not necessary Consider prophylactic heparin Treat constipation aggressively Braces not well-studied Spinal cord compression: treatment Steroids One randomized trial (Sorenson Eur J Ca 1994;30A:22) 57 patients (most with breast) No dex vs 96 mg IV followed by 24 qid x 3 days then tapered Ambulatory rate was 80% vs 60% at end of Rx 56% vs 33% at 6 months TOXIC Subsequent studies of 16 mg/day had similar outcome and no significant serious side effects 10 mg IV bolus vs 100 mg bolus then 4mg po qid, taper over 2 wk: no difference?pain without myelopathy may not need steroids Spinal cord compression: radiation therapy 70-85% response rate for pain control Predictors of response: ambulation, tumor type, degree of subarachnoid block If ambulatory at presentation: 90% remain If paraplegic at presentation: 10% regain

11 Surgery versus radiation therapy Patchell. Lancet 2005;366:643 Prognosis Depends on primary tumor type If patients treated while still ambulatory, there is an 89-94% chance of remaining ambulatory If paraplegic, 10% Hypercalcemia

12 Hypercalcemia Most common paraneoplastic syndrome Prevalence is 10% in patients with advanced cancer Responsible for 40% of all hypercalcemia Lung, breast, head and neck, renal and multiple myeloma most common causes Etiology Humoral hypercalcemia of malignancy - 80% of cases Squamous cell lung ca, H+N ca, renal cell PTH-related protein produced by tumor has homology with parathyroid hormone Local osteolytic hypercalcemia - 20% of cases Myeloma, leukemia, lymphoma, breast and other solid tumors Bone resorbtion by osteoclasts Lymphoma can rarely produce vitamin D Presentation Malaise, fatigue, confusion, anorexia, bone pain, polyuria, polydipsia, weakness, constipation, nausea, vomiting Severe hypercalcemia: confusion, lethargy, coma, death

13 Diagnosis Check Ca, albumin, renal function, PO4, alk phos, EKG R/o bony mets Normal PTH and low PO4 suggest HHM Normal PTHrP, normal PO4 in presence of bone mets suggests LOH Treatment Moderate ( mg/dl) IV NS for hydration-at least 2-4 liters/day Once euvolemic begin lasix to prevent volume overload Pamidronate 60-90mg IV over 2 hours or (Zolendronate-more effective, more expensive) If LOH, glucocorticoids may inhibit bone resorption and cytokine production NEJM 2005;352:373 Treatment Severe (>13.5 mg/dl) In addition to treatment for moderate, add calcitonin 4-8 U/kg SQ qid If refractory, gallium 200mg/meter squared in 1 liter IV QD x 5 days (can t use in renal failure) Mithramycin can be considered (toxic to kidney, BM)

14 Prognosis Median survival of patients with hypercalcemia only 1-3 months Treatment may not be indicated if patient has endstage disease unless it will improve quality of life Tumor Lysis Syndrome Tumor lysis: definition Cairo-Bishop Lab: 2 or more Uric acid >8 K >6 Phos >4.5 Calcium <7 Clinical Lab + creat > 1.5 x ULN Cardiac arrhythmia/sudden death Seizure

15 Major dangers Acute renal failure which can be caused by uric acid nephropathy or nephrocalcinosis Prior to allopurinol, 10% of patients treated for acute leukemia got uric acid nephropathy Now hyperphosphatemia causing calciumphosphate uropathy is more common Cardiac arrythmias from hyperkalemia or hypocalcemia Management Prophylaxis Pre-treat for at least 2 days before chemotherapy with: Allopurinol Aggressive hydration (with NS) to maintain urine output > 2.5L/day Alkalinization is no longer recommended as it can enhance calcium/phosphate deposition Do not begin therapy until Cr <1.6 Once therapy has begun Check lytes, Ca, Mg, Po4 BID until stable Use PRN: Phosphate binders: lower serum phos either with calcium carbonate (taken with meals) or aluminum based binders (amphogel, alternagel) if calciumphosphorus product >60 Kayexalate prn hyperkalemia Dialysis when required

16 Allopurinol vs Rasburicase Purine catabolism Hypoxanthine Xanthine Xanthine Oxidase Urate Oxidase RASBURICASE Uric Acid Allantoin ALLOPURINOL Superior Vena Cava Syndrome

17 Superior Vena Cava Syndrome Invasion or external compression of SVC Malignant tumors account for 85% 60% have known cancers Lung cancer Lymphoma Thrombosis Fibrosis SVC: evaluation Contrast enhanced CT Histologic diagnosis Minimally invasive if possible Sputum, pleural fluid cytology, FNA node Bronchoscopy, mediastinoscopy, thoracotomy General anesthesia safe Watch for tracheal obstruction, pericardial effusion

18 SVC: treatment Control of underlying disease Chemo for sensitive tumors Consider combined chemo/xrt with NSCLC Urgent if stridor or laryngeal edema Endovascular stents? Quicker resolution of symptoms Anticoagulation? Brain Metastasis 25% of patients with cancer die with intracranial mets Lung, breast, melanoma most common Melanoma, germ cell, renal cell most likely to hemorrhage Treatment If symptomatic, treat with corticosteroids to lessen brain edema (see section on cord compression) If multiple mets: whole brain radiation If a single met and controlled extra cranial disease can consider surgical excision prior to whole-brain radiation. Selected patients with hydrocephalus may benefit from a shunt No data supporting prophylactic anticonvulsants

19 SIADH Definition: Euvolemic, hypotonic hyponatremia (Na <135, osm<280 with urine Na >20 and urine osm >100) Presentation Usually asymptomatic Occasionally anorexia, lethargy, confusion, personality change Rarely seizures/coma/death SIADH: etiology Inappropriate or ectopic secretion of ADH Tumors 40% of small cell lung cancer pt (poor prognosis) Cytotoxic agents Vincristine, cyclophosphamide, cisplatin High-dose cyclophosphamide Drug, fluids to prevent cystitis, nausea Pain, surgery, brain lesions, narcotics