22nd Annual Northeast Regional Nurse Practitioner Conference – May 6-8, 2015

Oncologic EmergenciesJill Burke, NP

D I S C L O S U R E S

• There has been no commercial support or sponsorship for this program.

• The planners and presenters have declared that no conflicts of interest exist.

• The program co-sponsors do not endorse any products in conjunction with any educational activity.

A C C R E D I TAT I O N

Boston College Connell School of Nursing Continuing Education Program is accredited as a provider of continuing nursing education by the American Nurses Association Massachusetts, an accredited approver by the American Nurses Credentialing Center’s Commission on Accreditation.

22nd Annual Northeast Regional Nurse Practitioner Conference – May 6-8, 2015

S E S S I O N O B J E C T I V E S

• Define oncologic emergency.• Identify patients at risk for oncologic

emergency.• Classify types of oncologic emergencies

into 3 groups.• Describe measures to prevent oncologic

emergencies.

Oncologic Emergencies

Jill N. Burke APRN,BC Center for Multiple Myeloma Massachusetts General Hospital Cancer Center

May 8, 2015

Overview

• Definition of oncologic emergency

• Identify patients at risk

• Classification of emergencies in cancer patients, three different groups:

1. structural or obstructive emergencies caused by

space – occupying tumor.

2. due to metabolic or hormonal problems.

3. secondary to complications arising from treatment.

• Preventive measures

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Structural and obstructive oncological emergencies:

• Superior vena cava syndrome

• Cardiac tamponade

• Spinal cord compression

• Increased intracranial pressure

• Urinary obstruction

• Hemoptysis and airway obstruction

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Superior vena cava syndrome

• Results from the partial or complete obstruction of blood flow through the superior cava vein to the right atrium, causing severe reduction in venous return to the right atrium, causing severe reduction in venous return from head, neck and upper extremities.

• Obstruction may be due to compression, invasion, thombosis or fibrosis of this vessel.

• Malignant tumors, such as lung cancer, lymphoma and metastatic tumors are responsible for > 90% of all SVCS cases. Lung cancer, particularly small-cell and squamous-cell, accounts for almost 85% of all cases.

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Superior vena cava syndrome

• As a result of a venous obstruction, there is a rise in the intra-venous-pressure and collateral circulation often flows through the azygoud system.

• SVCS most often develops insidiously over several weeks, allowing some mechanisma of compensation.

• Patients often present with: facial-swelling, particularly around eyes, dyspnea, cough, head fullness and pressure sensation are common.

• Diagnosis is SVCS is mainly clinical. CT scan is the most usual radiographic study for imaging the mediastinum and for diagnosing SVC obstruction. CT may reveal the site of the obstruction and collateral flow and is also able to differentiate extrinsic compression of the vein by tumor from intravascular thrombosis.

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SVC Syndrome

Superior vena cava syndrome

• More than 50% of patients with SVCS become symptomatic before the diagnosis of cancer is made. SVCS is rarely life-threatening by itself.

• Prognosis of patients with SVCS depends very much on the prognosis of the underlying disease.

• SVCS management is diagnostic: initial measure of oxygen, diuretics, head elevation, and corticoids may be useful in relieving symptoms.

• Emergency radiation before biopsy may preclude proper interpretation of the biopsy sample in >50% of cases. The only exception to this may be those cases with impending airway obstruction or severe increase in intracranial pressure.

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Superior vena cava syndrome

• Chemotherapy is the preferred treatment of malignant lymphoma or small-cell lung cancer.

• Most patients will experience a significant response with disappearance of all clinical manifestations of SVCS within 1-2 weeks.

• Radiation is the main option for patients having SVCS due to tumors insensitive to chemotherapy, such as recurrent non-small cell lung cancer

• When SVCS is related to central venous catheters, catheter removal should be combined with anticoagulation to prevent embolization.

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Cardiac Tamponade

• Life threatening complication of cancer

• Excess accumulation of fluid in the pericardial space

• Results in decreased cardiac output and compromised cardiac function

• Pericardial cavity

– Space between the two-layered sac surrounding the heart

– Normally filled with 50 mg of fluid and allows the heart to move without friction

Cardiac Tamponade

• Risk factures

– Cancer in the chest, mediastinum, pleural effusions

– Direct tumor invasion to the pericardial sac- primary tumor or mets

– Fibrosis of the pericardial sac related to radiation therapy (more than 4000 Cgy)

• Pathophysiology

– Left ventricular filling decreases

– Ability of the heart to pump decreases

– Cardiac output decreases

– Impaired systemic perfusion occurs

Cardiac Tamponade

• Diagnosis

– Chest xray- enlarged pericardial silhouette

– CT scan- pleural effusion, masses, or pericardial thickening

– Echocardiography- (2D) Right atrium collapse at diastole

– Electrocardiography- tachycardia, premature contractions, atrial fibrillation, and electrical alternans

– Pericardiocentesis and cytology

• Bloody fluid with positive cytology

• Significant false negative

Cardiac Tamponade

• Assessment- ROS

– Retrosternal chest pain relieved by leaning forward and intensified when lying supine

– Dyspnea

– Cough

– Anxiety and agitation, altered levels of consciousness

– Hiccups

Cardiac Tamponade

• Assessment- Physical Exam

– Muffled heart sounds

– Weak or absent apical pulse

– Tachycardiac

– Tachypnea

– Decreased systolic pressure and rising diastolic pressure

– Pulsus paradoxus greater then 10 mm Hg

– Peripheral edema

– Diaphoresis

– Cyanosis

Cardiac Tamponade

• Treatment

• Pericardiocentesis- temporary removal of excess pericardial fluid

• Pericardial window- surgical opening of the pericardium to allow fluid drainage

• Total pericardectomy- removal of the pericardial sec

• Radiation- for radiosensitive tumors

Cardiac Tamponade

• Pericardial sclerosis- installation of chemicals which cause inflammation and fibrosis through a pericardial catheter

• Systemic antineoplastic therapy for chemotherapy- sensitive maligancies

• Corticosteriods- used in mild cases to reduce inflammation of contrictive pericarditis

Chest CT

Spinal Cord Compression

• Spinal cord compression remains a true oncological emergency requiring immediate intervention, the effects may be devastating if unrecognized.

• Metastatic cord compression is estimated to effect from 5-10% of all cancer patients

• Thoracic spine is the largest percentage of cases (70%). (adult- prostate, lung, breast & pedi-sarcoma, neuroblastoma)

• Spinal cord compression is seen in 2.7-5% of children with cancer at diagnosis, progression, or recurrence of disease

• Localized back pain and tenderness due to vertebral metastases are the most common and earliest symptom of spinal cord compression.

Spinal Cord Compression

Intradural: Intramedullary (leptomeningeal) &

Extramedullary, almost all metastasis to the vertebrae (85%) or epidural space (15%)

Biphosphonates reduce pathological fractures and bone pain with patients with multiple myeloma and breast cance

Spinal Cord Compression

• Primary tumors (15%) • The resulting cord dysfunction

results, regardless of the histology.

• Spinal cord compression is rarely fatal but can increase morbidity & mortality as a result of irreversible loss of function.

Spinal Compromise

Lower extremity weakness, paresthesias, reflex asymmetry, spinal pain, and loss of bladder and bowel function. Additionally, neoplasms may compromise the vascular supply, causing edema or ischemia

Spinal cord compression symptoms:

• Early: nonspecific, pain or weakness. Gradually worsening pain preceded other signs of cord compression

• Discomfort may be radicular, localized to the back, generally bilateral, worse with movement or straining.

• There is thoracic localization and percussion tenderness. • Pain from vertebral metastasis may worsen with a

recumbent position in contrast to back pain from other sources.

• Back discomfort that is unrelieved with rest or recumbency may also be a symptom of destructive lesions

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C2: Breathing, vent depend C3-4C4-6: Shoulder Flexion &Extension: Spontaneous breathing, Trapezius function

C5: Deltoid Abduction at Shoulder C6: Biceps Flexion at Forearm C6: Wrist Extension C7: Wrist Flexion, can be independent with devices C7: Elbow Extension (Triceps) C7: Finger Extension C8: Fingers Flexion middle finger

Common Motor Levels

T1: Small finger abductors

L2: Hip flexors

L3: Knee Extension (Quadriceps)

L4: Ankle dorsiflexion

L4: Anterior Tibial, Foot Inversion

L5: Long toe extension

L5: Foot dorsiflexion

L5: Weak heel walking, foot drop

S1: Ankle plantar flexors

S1: Weak toe walking

Common Motor Levels

Common Sensory Levels

C5: Deltoid, Lateral Upper Arm & Forearm

C6: Thumb (Radial Nerve)

C7: Middle Finger (Median Nerve)

C8: Ring

C8: Little Finger (Ulnar Nerve)

T4: Nipple

T8: Xiphoid

T10: Umbilicus

T12: Symphysis

Common Sensory Levels

L4: Medial Low Leg and foot

L5: Space between 1st and second toes

S1: Lateral Foot

S3: Ischial tuberosity area

S4-5: Perianal region

Spinal cord compression

• Neoplastic epidural spinal cord compression (ESCC) is a common complication of cancer that can cause pain and potentially irreversible loss of neurologic function.

Spinal cord compression

• The single most important prognostic factor for regaining ambulation after treatment of an ESCC is pretreatment neurologic status

• Management of patients with ESCC includes the immediate administration of glucocorticoids in all patients, followed by surgery, external beam radiation therapy (EBRT), or stereotactic body radiotherapy (SBRT). Systemic therapy may be beneficial in patients with chemosensitive tumors.

Treatment of Spinal Cord Tumors

• Control pain & preserve function • Immediate steroids, bolus 4-100mg decadron,

then divided doses with tapering (Flaherty, 2000)

• Radiation therapy, epidural metastasis, 2 – 4 K cGy in 5-20 fractions/ 2-4 weeks (Ratiff & Cooper, 2004)

• Surgery for decompression or stabilization, usually within 24-48 hours.

Increased intracranial pressure

• Increased intracranial pressure may be caused by brain metastases. 25 % of cancer patients will die with intra-cranial metastases

• Lung, breast and melanoma are the most common tumors to the brain

• Clinical manifestations: headache, nausea, vomiting, seizures, behavioral changes and sometimes focal neurological changes.

• The tumor mass together with its surrounding edma may produce hydrocephalus and as the mass enlarges various herniation syndromes may occur depending on the location of the tumors within the cranium.

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Emergency treatment of increased intracranial pressure • Prepare for intubation, target PCO2- 35, avoid aggressive hyperventilation

• IV access & 20-100gms of Mannitol 20% with fluid resuscitation

• Prepare for CT scan (MRI is best radiographic exam, but in emergent situation CT is quicker and easier to obtain)

• Possible steroids

• Consider decompressive craniotomy, or ventriculostomy

• Once herniation has been controlled, a decision on the treatment of the brain metastases should be made. If multiple nodules, whole - brain irradiation is considered standard.

• Single brain noduules, surgery followed by radiation. Radiosurgery may be indicated in patients having fewer than three metastases, each measuring <2cm

Urinary Obstruction

• May occur in patients with gynecological or urological tumors particularly cervical and prostatic carcinoma.

• Urinary obstruction may lead to bilateral hydronephrosis and renal failure.

• Flank pain with sudden anuria, sometimes alternating with polyuria and a progressive rise in serum creatinine may indicate urinary obstruction.

• Renal US is the easiest was to detect bilateral hydronephrosis

• CT is helpful in detecting the exact location of the obstruction, particularly if there is a retroperitoneal or pelvic mass.

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Urinary obstruction

• Urinary obstruction associated with pain, infection or renal failure requires intervention.

• Urinary stents may be placed with local anesthesia and may relieve obstruction. If not possible, percutaneous nephrostomy is an alternative approach.

• After relief, polyuria may follow, increasing the risk of dehydration and electrolyte disturbances, particularly hypokalemia. Careful replacement of fluid and electrolytes is required.

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Hemoptysis and airway obstruction

• Massive hemoptysis is defined as the expectoration of volumes ranging from one single episode of 100 ml to > 600 ml of blood during 24-48 h.

• When respiratory difficulty occurs, hemoptysis should be treated immediately.

• Airway bleeding leading to life-threatening airway obstruction, aspiration, anemia or hypovolemic shock is also considered massive hemoptysis.

• Fatal hemorrhage may present in one-third of patients with massive hemoptysis and the risk of death is directly associated with the amount of blood expectorated.

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Hemoptysis and airway obstruction

• The rate of hemoptysis, the amount of blood retained in the lungs and the underlying pulmonary reserve are risk factors.

• 20% of cases of lung cancer patient will have hemoptysis at any time during its disease course

• Endobronchial metastases from carcinoid tumors, breast, colon or kidney cancer, melanoma or sarcoma may also cause hemoptysis.

• Hemoptysis in cancer patients may also be caused by non-malignant conditions: fungal infections, thrombocytopenia or other coagulation disorders.

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Hemoptysis and airway obstruction

• Airway should be protected and intubation is recommended in patients with hemodynamic instability, severe dyspnea or hypoxia.

• Patients may require: volume supplementation, oxygen, sough suppressants and correction of any coagulation disorder.

• Site of bleeding must be identified. The lesion should generally be treated with a surgical procedure, bronchial artery embolization or radiotherapy. Radiotherapy may inhibit hemoptysis by causing vascular thrombosis and necrosis of contributing vessels.

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Airway obstruction

• Acute airway obstruction involves the upper airways and may be caused by malignant or non-malignant conditions.

• It may result from intraluminal tumor growth or from extrinsic compression of the airway.

• Tumors that obstruct the upper airway by direct extension are primary tumors of the head and neck and lung.

• Non-malignant causes of airway obstruction are food or foreign body aspiration, airway edema or hemorrhage, tracheal stenosis and infections.

• Angioedema may also cause severe and life-threatening airway obstruction.

• Primary tumors. of the lung are the most common cause of lower airway obstruction

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Airway obstruction

• Dyspnea is frequently the only early symptom of airway obstruction.

• If dyspnea occurs on exercise, the airway is decreased to 8mm, but if dyspnea occurs at rest, the airway diameter is usually < 5mm and is related to the appearance of stridor.

• Treat depends on cause, may involve tracheostomy, radiation and/ or stenting.

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Metabolic or hormonal problems

• Hypercalcemia

• SIADH

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Hypercalcemia of Malignancy

• Sometimes called Tumor-induced hypercalcemia (TIH) or Cancer-induced hypercalcemia (CIH)

• Most common metabolic oncologic emergency • Estimated to occur in 10-20% of adults with cancer • Under diagnosed and under treated

The General Skeleton

• Consists of 206 bones • Support • Protection • Movement • Serves as a storage area for

minerals (e.g. calcium and phosphorus)

Gray, Henry. Anatomy of the Human Body. Philadelphia: Lea & Febiger, 1918; Bartleby.com, 2000. www.bartleby.com/107/.

Bone Composition: Two tissue types

Compact (cortical bone) • dense, hard, and forms the

protective exterior portion of all bones

• designed to nourish and regulate bone cells and bone matrix.

Spongy (cancellous bone) • exists inside the compact bone • very porous • contains trabeculae (spaces

between are filled with bone marrow) and bone cells (osteocytes)

OC = osteocytes http://www.cytochemistry.net/microanatomy/bone/compact_bone_histology.htm

www.anatomy.dal.ca/Human%Histology/Lab6/220DL.html

Bone Cells: Osteoclasts (bone-resorbing cells)

• Large and multinucleated • Derived from

monocyte/macrophage cells

• Dissolve mineral and degrade matrix proteins

• Function regulated by hormones, growth factors, and cytokines

Osteoclasts and Howship’s Lacunae

Marcus R, Feldman D, Kelsey J (eds). Osteoporosis. San Diego, CA: Academic Press; 1996:14.

Bone Cells: Osteoblasts (Bone-forming cells)

• Derived from stem cells in bone marrow

• Produce collagen and other proteins which become mineralized to form bone in bone matrix

• Function is regulated by hormones and growth factors

• Secrete local factors that influence other bone cells

Marcus R, Feldman D, Kelsey J (eds). Osteoporosis. San Diego, CA: Academic Press; 1996:13.

Most Common Cancers with Bone Metastases

Cancer Breast

Prostate

Myeloma

Thyroid

Lung

Kidney

Frequency

65%-75%

65%-75%

70%-95%

60%

30%-40%

20%-25%

Coleman RE. Cancer Treatment Reviews. 2001;27:165-176.

Plasmacytoma, on flat plate xray

Hypercalcemia of Malignancy

Tumor Type Percentage of Patients who develop HCM

LUNG 27.3

BREAST 25.7

MULTIPLE MYELOMA 7.3

HEAD AND NECK 6.9

UNKNOWN PRIMARY 4.7

LYMPHOMA/LEUKEMIA 4.3

RENAL 4.3

GASTROINTESTINAL 4.1

1. Lang-Kummer J(1997): Hypercalcemia In Groenwald SL et al. Cancer Nursing: Principles and Practice pg684-701).

2. Pearson KE (2009). Tumor induced hypercalcemia . In Acute Care Oncology Nursing. Saunders. Pg 286.

Types of HCM

1. Humoral Hypercalcemia

– 80% of cases

– Via release of parathyroid related protein ( PTHrP) which increases osteoclast activity

– Associated with squamous cell cancer, renal, breast, ovarian, and endometrial cancer.

– PTH and phosphate levels usually low

– Should be suspected in any case of HCM in the absence of bone mets

Types of HCM cont’d

2. Osteolytic Hypercalcemia - 20% of cases - Usually due to breast cancer, myeloma, or

lymphoma in the presence of bony disease - Release of osteoclast activating factors including

lymphotoxin, IL 6, IL-1 alpha and others have been identified

- Phosphate level usually normal, PTH low

Harrison’s Manual of Oncology 2008

Pathogenesis of HCM

• Increased bone destruction

• Increased tubular reabsorption of calcium by the kidney

• Decreased urinary calcium excretion

• Decrease in bone formation

Fleisch H. In: Bisphosphonates in Bone Disease. San Diego, California: Academic Press; 2000;90-92.

Signs and Symptoms of HCM

CNS Personality change; lethargy; somnolence; coma; confusion; depression; increased sensitivity to pain

Neuromuscular Muscle weakness; hypotonia

CV Hypertension; arrhythmia

Renal Kidney stones; decreased glomerular filtration; polyuria; polydipsia, renal failure

GI Nausea; vomiting; constipation; anorexia

Skeletal Bone pain

Ralston SH. Treatment of tumor-induced hypercalcemia. In: Body JJ (ed). Tumor Bone Diseases and Osteoporosis in Cancer Patients. New York, NY: Marcel Dekker; 2000;393-407.

Mundy GR, Martin TJ. Metabolism.1982;31:1247-1277.

Serum Calcium Levels

• Confirm by measuring corrected serum calcium

• Why calculation is necessary

– Calcium binds to albumin in the blood2,3

– Hypoalbuminemia or hyperalbuminemia distorts serum calcium measurements3

– Hypoalbuminemia is common in cachectic patients (eg, cancer patients)1

1. Iqbal SJ, Giles M, Ledger S, Nanji N, Howl T. Lancet. 1988;ii:1477-1478. 2. Mundy GR, Martin TJ. Metabolism.1982;31:1247-1277. 3. Payne RB, Little AJ, Williams RB, Milner JR. BMJ. 1973;4:643.

Calculating Corrected Serum Calcium

Corrected serum calcium = serum calcium mg/dL + 0.8 (4.0 - serum albumin, g/dL)

– Example: Serum Calcium = 12.1 mg/dL Serum albumin = 2.0 g/dL Corrected Ca = 12.1 mg/dL + 0.8 x (4.0 - 2.0 g/dL) Corrected Ca = 12.1 mg/dL + 1.6 mg/dL Corrected Ca = 13.7 mg/dL

Mundy GR, Martin TJ. Metabolism.1982;31:1247-1277.

HCM: Assessment & Diagnostic Evaluation Symptoms: • Anorexia • Nausea/Vomiting • Confusion • Polydipsia • Polyuria • constipation • Weakness “Bones, Moans and

Abdominal Groans”

Labs: • Serum calcium • Ionized calcium > 5 mg/dL

(most accurate) • PTH, PTHrP • Lytes, BUN, CR • HCM may be associated

with: – Decreased phosphate – Metabolic alkalosis – Hypochloremia – Decreased serum parathyroid

hormone (PTH)

1. Mundy GR, Martin TJ. Metabolism.1982;31:1247-1277. 2. Carroll MF, Schade DS. Am Fam Physician.2003;67:1959-1966. 3. Uptodate.com, 2012

HCM Treatment -

• Aggressive saline rehydration (5-8 liters in first 24 hours): decreases calcium levels through dilution and increases excretion.

• Loop diuretics (furosemide): BEGIN DAY 2! 40-80 mg/day orally or IV: used in conjunction with hydration to increase calcium excretion.

• Bisphosphonates (pamidronate, zoledronic acid): inhibits osteoclast activity for up to one month. Need to give with fluid and renally dose.

HCM treatment cont’d

• Other antihypercalcemic agents: Calcitonin, Plicamycin, Gallium Nitrate

• Reducing underlying tumor burden (if effective treatment is available)

**If patient is in renal failure, dialysis may be only option for

treatment. Also, best supportive care can be discussed.

Bisphosphonates- Mechanism of Action

• Attach to bone mineral surface by physio-chemical properties

• During resorption, osteoclasts release bisphosphonate embedded in bone matrix

• Bisphosphonates are taken up by osteoclasts and inhibit bone resorption

Coleman RE. Cancer Treat Rev. 2001;27:165-176.

Zoledronic acid

• Potential for longer duration of response (as opposed to pamidronate) due to higher potency

• Recommended dose of Zoledronic acid is 4 mg administered as an IV infusion in 100 mL of sterile 0.9% Sodium Chloride, USP or 5% Dextrose Injection, USP over 15 minutes*

• Requires serum Cr prior to dosing, use modified CG to calculate CrCl

• Risks:

– Osteonecrosis of the Jaw (ONJ)

– Renal toxicity (dose and time dependent)

– Infusion reaction (pain, flu like symptoms)

*ZOMETA [Package Insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2003.

Osteonecrosis of the Jaw (ONJ)

• Observed among cancer patients receiving intravenous bisphosphonates and denosumab

• Less frequent among patients receiving oral bisphosphonates

• Bone under the teeth is exposed, often painfully

• Swelling and loosening of teeth may be seen

Definition of SIADH

• Syndrome of inappropriate antidiuretic hormone (SIADH) is a disorder of water intoxication.

• SIADH describes the inappropriate production and secretion of ADH that causes increased water reabsorption in the renal tubules and leads to increased water retention and dilutional hyponatremia.

Pathophysiology of SIADH

• Vasopressin, is the biologically active form of ADH in humans.

• Vasopressin is synthesized in the hypothalamus.

• After synthesis, Vasopressin is transported down to the posterior pituitary gland.

Pathophysiology

• Vasopressin is stored there until appropriate reflexes signal release into the bloodstream.

• A major physiologic action of vasopressin is to regulate water reabsorption in the renal tubules.

• ADH specifically acts on the tubular segments of the collecting duct system.

• With high plasma concentrations of vasopressin, the collecting duct becomes highly permeable to water; thus, water is retained with the excretion of a small volume of concentrated urine.

To Sum It Up

• SIADH is characterized by a primary water excess that predisposes to hyponatremia and hypoosmolality.

• When renal excretion of water is decreased, due to high plasma concentration of ADH, water is reabsorbed

• Because the total body water is increased, distribution between ICF and ECF compartments is 2:1.

• Plasma sodium levels reflect dilutional hyponatremia.

• Patients with SIADH lack the ability to stop the thirst mechanism.

Signs and Symptoms

• General

– Weakness, fatigue

• Neurologic

– Altered mental status, headache, lethargy, irritability, delirium, psychosis, personality changes

• Cardiovascular

-Normotensive, regular rate, rhythm

• Gastrointestinal

– Anorexia, nausea, vomiting, diarrhea, excessive thirst, abdominal cramping.

• Renal

– Oliguria (<400 cc/24 hours), weight gain, incontinence.

Physical exam

Hypovolemia • Orthostatic

hypotension • Poor skin turgor • Dry mucous

membranes • Tachycardia

Hypervolemia • Edema • Increased jugular

distension • Changes in breath

sounds

Diagnostic Studies

• Serum sodium (norm range 135-147 mEq/l) • Plasma osmolality (decreased in SIADH)

• Urine sodium concentration is usually below 25 meq/L in hypovolemia, unless there is renal salt-wasting, due most often to diuretic therapy and infrequently to adrenal insufficiency or cerebral salt-wasting)

• . The urine sodium concentration is usually above 40 meq/L in patients with the SIADH who are normovolemic and whose rate of sodium excretion is determined by sodium intake, as it is in normal subjects

• Urine osmolality (increased in SIADH)

Diagnostics Studies

• Electrolytes, BUN, creatinine, albumin and uric acid should be checked as they can also be lower in the setting of SIADH.

• Studies to r/o cardiac, hepatic, adrenal and thyroid causes of hyponatremia should be completed.

Laboratory Values

• Serum sodium <130 mEq/L

• Serum osmolality <280 mOsm/kg

• Urine osmolality >500 mOsm/kg

• Urine sodium >20 mEq/L

Medical Management if SIADH

• Directed at treating the underlying pathology.

• Treatment with chemotherapy or radiation causes regression of tumor and usually results in resolution of SIADH.

• Treatment for mild hyponatremia (serum Na >125 mEq/l) includes fluid restriction of 800-1000 ml/day.

• Fluid restriction often increases Na within 3-10 days.

Complications arising from treatment:

• Tumor lysis syndrome

• Sepsis

• Anaphylatic reaction related to chemotherapeutic agents.

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TLS: Tumor Lysis Syndrome

• TLS is a metabolic oncologic emergency caused by rapid cell lysis.

• Intracellular components potassium, phosphorus, and uric acid are released into the vascular system.

Incidence

• Exact Incidence Unknown

• Estimated Incidence 5%-25%

Causes of Tumor Lysis

• Spontaneous • Chemotherapy • Biotherapy • Radiation Therapy • Surgery

Risk Factors • High Grade Lymphomas • Acute Leukemias • Large, Bulky, Treatment- Sensitive, Solid Tumors • Preexisting Renal Dysfunction • Volume Depletion • Elevated Lactate Dehydrogenase • Elevated Uric Acid Level

Pathophysiology

1. Malignancy is Treated 2. Malignant Cells Undergo Rapid

Death 3. Intracellular Components are

Released Into the Vascular Circulation

Clinical Assessment

Directed toward the expected signs and symptoms of

• Hyperkalemia • Hyperphosphatemia • Hypocalcemia • Hyperuricemia

Allopurinol • Prevents Hypoxanthine From Becoming

Uric Acid • Not Helpful if Uric Acid is Already Formed,

or in Renal FailureGiven PO/IV • Interaction with 6-MP • Rash is Common Side Effect • Cost/day: <$3

Rasburicase • Converts Uric Acid into Allantoin Which

Can Be Excreted By the Urine • May Cause Severe Hemolysis in

Patients with G6PD (glucose-6-phosphate dehydrogenase) Deficiency

• Given IV: recombinant product, needs close monitoring

• Cost: ~ $13,000 for an adult dose

Hyperkalemia

• Hydration with a Lasix chaser • Sodium Polystyrene Sulfonate

(Kayexelate, now used with caution) • Sodium Bicarbonate • Insulin/Dextrose 50 • Calcium Gluconate • Dialysis

Hyperphosphatemia

• Dietary Restrictions: carbonated drinks, milk, meat, chocolate, eggs, fish, nuts, bread, poultry

• Diuretics • Aluminum Hydroxide Antacids

Hypocalcemia

• Only Treat with Severe Symptoms

• Calcium May Bind with Phosphate and Result in Calcium/Phosphate Crystal Formation

Nursing Management of TLS

• Identify Patients at Risk – Type of malignancy – Tumor burden – Lab values-

• Elevated WBC • Elevated uric acid • Hyperphosphatemia • Hyperkalemia • Hypocalcemia • Elevated LDH • Elevated creatinine

Sepsis

• 10-50% of Solid Tumor and 80% of Liquid Tumor cancer patients experience fever

• Oncology patients are at HIGH RISK for sepsis

– #11 leading cause of death in US

– Severe sepsis 20% mortality

– Septic shock 50% mortality

Sepsis in Cancer

• Complex interaction between an infectious organism and a person’s immune, inflammatory, and coagulation response.

• IMMEDIATE treatment is necessary to avoid a rapid progression to death

Sepsis Defined

Septic shock is characterized by hemodynamic instability which results in alterations in cellular metabolism and abnormal coagulation

Septic shock results when the body fails to initiate an adequate immune response

Risk Factors for Sepsis

Comorbid Conditions

Diabetes

Renal disease

Hepatic disease

Cardiovascular disease

Gastrointestinal disease

Pulmonary disease

Hospital and ICU stays

Loss of skin or mucosal integrity

Asplenic: Spleen produces IgM antibodies, which is required to encapsulate pathogens.

Endogenous Flora

Sites of Origin

Endogenous flora: Pulmonary Cutaneous Renal/GU (Urosepsis) GI (translocation of GI flora)

Indwelling devices: Port, PICC, Foley, Chest Tube, Drain, Gtube

SIRS Criteria Defined

SYSTEMIC INFLAMMITORY RESPONSE

developed to describe the hemodynamic impairment seen with severe infections

Immune Defense Mechanisms

Granulocytes phagocytize and kill bacteria Cell-mediated immunity activates monocytes,

macrophages and T lymphocytes which eliminate pathogens, viruses and malignant cells

Humoral immunity activates B lymphocytes which produce antibodies to specific foreign bodies or antigens.

Normal Physiology

Inflammation includes vasodialation, increased microvascular permeability

Lymphocytes release cytokines Tumor necrosis factor Interleukins

Cytokines cause increased vascular permeability in order to assist with phagocytosis of bacteria

Septic Shock

Systemic host response to infection with SIRS plus a documented infection

End-organ dysfunction or distal hypoperfusion

Sepsis can cause blood clots to form in your organs and limbs

Hypotension, despite fluid resuscitation

Evidence of inadequate tissue perfusion

ICU level of support is needed if reversible and in line with goals of care

Bacterial Organisms

40% gram-negative bacteria: consider this if GI/GU/Pulmonary source: E-coli, Klebsiella pneumoniae, Pseudomonas

aeruginosa ESBL enzymes that mediate resistance to

extended-spectrum (third generation) cephalosporins

5%-10% gram-positive bacteria:consider if has a indwelling line or skin compromise

Staph aureas, Strep pneumoniae

Speciation of Organisms

Fungi (associated with prolonged suppression) Candida

Aspergillus

Viruses Herpes simplex (HSV)

Cytomeglovirus (CMV)

Respiratory Synctal virus (RSV)

BK virus

Adeno virus

Endogenous Flora 20%-30% of these organisms are not identified

Pathophysiology of Sepsis

Microbes enter the circulatory system and tissue and create an UNCONTROLLED inflammatory response

Exotoxins (gram positive bacteria) and Endotoxins

(gram negative bacteria) stimulate release of macrophages, monocytes, neutrophils, and plasma cells

Tumor necrosis factor and cytokines are released,

causing a cascade of inflammation

Pathophysiology of Sepsis

Widespread tissue inflammation and vasodilatation

Decreased arterial and venous tone

Activation of clotting mechanisms

Capillary leak syndrome, third-spacing

Hypoperfusion

Organ Ischemia

Coagulapathy

Anaphylactic reactions related to chemotherapeutic agents

• May create medical emergencies

• Angioedema and urticaria are the most common manifestations of anaphylaxis and make up >90% of allergic reactions.

• Other frequent manifestations: abdominal pain, chest tightness, upper airway obstruction, bronchospasm and hypotension.

• Laryngeal edema followed by hypotension is the most frequent cause of death related to allergic reactions.

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main issues in treating anaphylactic reactions:

• Removing the drug considered to be responsible • Immediate assessment of the airway and

administration of epinephrine subcutaneously, depending on the severity,

• Intravenous fluids should be given, particularly in the case of hypotension.

• Glucocorticoids and antihistamines may also be administered.

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Preventative measures:

• Have an understanding of disease extent

• What co-morbidities may contribute to risks

• Lab values

• Patient and support system education

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