Oncologic Emergencies
Oncologic Emergencies
Juanita Madison, RN, MN, AOCN
Franciscan Health System
Life-threatening medical
emergencies caused by:
Malignancy
Treatment of malignancy
When do they occur?
Initial manifestations of
malignancy
or
Late in disease process
Oncologic Emergencies
Metabolic Oncologic Emergencies
Tumor Lysis Syndrome (TLS)
Sepsis & Septic Shock
Disseminated Intravascular Coagulation (DIC)
Hypercalcemia
Inappropriate Antidiuretic Hormone Secretion (SIADH)
Anaphylaxis
Structural Oncologic Emergencies
Spinal Cord Compression
Superior Vena Cava Syndrome
Increased Intracranial Pressure (ICP)
Cardiac Tamponade
Tumor Lysis Syndrome (TLS)
Metabolic imbalance
Caused by breakdown of malignant cells
(spontaneous, or induced by chemotherapy,
biotherapy, or radiation therapy)
Large number of rapidly proliferating cells killed
Cell lysis, rupture of tumor cell membranes
Intracellular components released into blood
stream
Holmes Gobel, B. (2013). Tumor Lysis Syndrome. In Kaplan, M (Ed). Understanding and managing
oncologic emergencies: A resource for nurses .Oncology Nursing Society, Pittsburgh, PA. pp: 433-459.
1
TLS: Pathophysiology
Tumor Lysis Syndrome: Who’s At Risk?
K+
PO4PO4Nucleic Acids
K+
K+
K+ PO4-
Intracellular components
Potassium
Phosphorous
Nucleic acids (DNA, RNA)
Cell killed (lysed), cell
membrane ruptures
Nucleic acids released into blood
stream
Potassium & Phosphorous
released into blood stream
Results in:
PO4- PO4- PO4-
Ca++ Ca++ Ca++
K+
K+
K+
Most common in:
Nucleic
Acids
Hypoxanthine
Xanthine
Risk Factors:
Tumor-related
High-grade lymphomas
Hematologic malignancies (acute or chronic leukemia's with  WBC)
Tumors with high growth fractions (anticipated to be responsive to treatment)
Patient-related
Xanthine
Oxidase
(Liver)
Hyperuricemia
Hyperkalemia
Hyperphosphatemia
Hypocalcemia
Patients with large tumor burden that is highly responsive to
antineoplastic therapy (resulting in rapid cell kill)
Large tumor burden/bulky tumors
Elevated LDH
Pre-existing renal dysfunction
Uric Acid
Treatment-related
Chemotherapy & biologic agents
Radiation therapy
Urine
Tumor Lysis Syndrome:
Onset, Duration, Incidence
Onset:
Usually within 24-48 hrs after initiation of antineoplastic
therapy
Duration:
May persist for 5-7 days post-therapy
Incidence:
Exact incidence unknown
Occurs mostly in patients with
Hematologic malignancies with large proliferative growth fractions
Large bulky disease (acute leukemia's, high-grade lymphomas)
Clinical Manifestations
Often asymptomatic initially
Detected initial via abnormalities in blood
chemistries
Signs & symptoms patients exhibit depend
on extent of metabolic abnormalities
Hyperkalemia
Hyperuricemia
Hyperphosphatemia
Hypocalcemia
2
TLS: Signs & Symptoms
Hyperkalemia
Early cardiac:
• Tachycardia
• EKG Changes: Prolonged
QT and ST segment,
lowering and inversion of T
wave
Late cardiac:
• Bradycardia
• EKG Changes: Shortened
QT, elevated T wave, wide
QRS
• Ventricular tachycardia,
ventricular fibrillation,
cardiac arrest
• Nausea/vomiting
Hyperuricemia
• Oliguria, anuria, azotemia
• Malaise, weakness, fatigue
Serum uric acid >10 mg/dl
Severe = >20 mg/dl
• Edema, hypertension
• Nausea, vomiting
• Acute renal failure
• Flank pain, gout
• Chronic renal failure
• Pruritus
Serum K+ >6.5 mEq/L
TLS: Signs & Symptoms
• Diarrhea
• Increased bowel sounds
• Twitching
• Muscle cramps
• Weakness
Hyperphosphatemia
• Anuria
• Edema
Serum PO4 >5 mg/dl
• Oliguria
• Hypertension
• Azotemia
• Acute renal failure
Neurological/Neuromuscular
•Twitching, paresthesias
• Restlessness
• Muscle cramps & weakness
• Anxiety, depression
• Carpopedal spasms
• Seizures
• Confusion
• Hallucinations
Cardiac
• Tetany
• Ventricular arrhythmias
• Prolonged QT interval, inverted T
wave
• Heart block
• Cardiac arrest
• Paresthesias
• Lethargy
• Syncope
Gobel, B. H. (2013). In M. Kaplan (Ed.), Understanding an managing oncologic emergencies: A resource for nurses
2nd Edition (pp. 433 - 459). Pittsburgh, PA: ONS
Prevention TLS
Hydration
IV Normal saline or 5% dextrose
Begin 24 – 48 hours prior to therapy
Ensure urine output >150 – 200 ml/hr
Diuresis
If urine output no maintained by hydration
alone
Loop diuretics or osmotic diuretics
Holmes Gobel, B. (2013). Tumor Lysis Syndrome. In Kaplan, M (Ed). Understanding and managing oncologic emergencies:
A resource for nurses, 2nd ED. ONS, Pittsburgh, PA. pp: 433-459; McGraw, B. (2008). CJON 12 (4); 563-565.
Secondary
Hypocalcemia
Serum
Ca++
< 8.7 mg/dl
Gobel, B. H. (2013). In M. Kaplan (Ed.), Understanding an managing oncologic emergencies: A resource for nurses
2nd Edition (pp. 433 - 459). Pittsburgh, PA: ONS
Prevention TLS
Allopurinol (Oral or IV)
Begin 24 hour prior to therapy
Blocks uric acid production by inhibiting
xanthine oxidase (liver enzyme)
Prevents uric acid precursors from
converting to uric acid, ↓ risk uric acid
crystallization
Rasburicase IV
Converts uric acid into allantoin → very
soluble compound, excreted by kidneys
Holmes Gobel, B. (2013). Tumor Lysis Syndrome. In Kaplan, M (Ed). Understanding and managing oncologic emergencies:
A resource for nurses, 2nd ED. ONS, Pittsburgh, PA. pp: 433-459; McGraw, B. (2008). CJON 12 (4); 563-565.
3
Prevention TLS
Urinary Alkalinization
TLS Preventative Measures
Sodium bicarbonate added to IV fluid
(50-100 meq/liter)
Goal: urine pH level > 7.0
Monitor serial lab values
Use is controversial
Frequency of monitoring
Potential complications associated with
alkalinization
Metabolic alkalosis
Calcium phosphate precipitation
Holmes Gobel, B. (2013). Tumor Lysis Syndrome. In Kaplan, M (Ed). Understanding and managing oncologic emergencies:
A resource for nurses, 2nd ED. ONS, Pittsburgh, PA. pp: 433-459; McGraw, B. (2008). CJON 12 (4); 563-565.
Mr. J.: 63 Year-Old Male
diagnosed with High-Grade NHL
Past Medical History:
Noninsulin-dependent diabetes mellitus, supraventricular
arrhythmia
Scheduled to receive 1st cycle CHOP-R chemotherapy
in outpatient clinic
Cyclophosphamide (Cytoxan), doxorubicin (Adriamycin),
vincristine (Oncovin), prednisone, + Rituximab (Rituxan)
Started on oral allopurinol 300 mg daily
IV hydration pre & post chemotherapy in clinic
Instructed to increase oral intake to 8 glasses fluid
per day
Serum potassium, phosphorous, calcium, uric acid
Renal function studies – BUN & creatinine
Prior to initiation of therapy
Every 8 – 12 hours during the first 48 – 72 hours
of treatment
Holmes Gobel, B. (2013). Tumor Lysis Syndrome. In Kaplan, M (Ed). Understanding and managing oncologic emergencies:
A resource for nurses, 2nd ED. ONS, Pittsburgh, PA. pp: 433-459; McGraw, B. (2008). CJON 12 (4); 563-565.
Mr. J: Two Days Post 1st Chemo
Mr. J’s wife calls clinic and reports:
Weakness, muscle cramping, numbness & tingling
of extremities
Nausea/vomiting
Decreased urine output
Swelling both feet
What could be the cause of Mr. J’s
symptoms?
What should we advise Mrs. J. to do?
4
Treatment of TLS
Hyperuricemia • Hydration, urinary alkalinization
• Oral allopurinol or IV allopurinol
• Rasburicase
• Hemodialysis for significant renal compromise
Hyperkalemia
Mild (Potassium<6.5 mEq/L):
• Sodium polystyrene sulfonate orally or by retention enema
Potassium >6.5 mEq/L or cardiac changes:
• IV calcium gluconate or calcium carbonate
• IV sodium bicarbonate, hypertonic glucose & insulin
accompanied by sodium polystyrene sulfonate
• Loop diuretics & aggressive hydration
Holmes Gobel, B. (2013). Tumor Lysis Syndrome. In Kaplan, M (Ed). Understanding and managing oncologic emergencies:
A resource for nurses, 2nd ED. ONS, Pittsburgh, PA. pp: 433-459.
Treatment of TLS
Hyperphosphatemia • Phosphate-binding agents
• Aluminum-containing antacids
• Hypertonic glucose plus insulin
• Aggressive hydration
Hypocalcemia
• Appropriate management of hyperphosphatemia
• IV calcium gluconate or calcium chloride to treat
arrhythmias
Holmes Gobel, B. (2013). Tumor Lysis Syndrome. In Kaplan, M (Ed). Understanding and managing oncologic emergencies:
A resource for nurses, 2nd ED. ONS, Pittsburgh, PA. pp: 433-459.
Mr. J’s Labs in ER
(2 Days Post CHOP-R Chemotherapy)
Baseline Pre-Chemo
Labs
Hgb 11.1 g/dl
Platelets 245,000/mm3
Na++ 136
K+ 4.1
BUN 45 mg/dl
Creatinine 2.2 mg/dl
Uric acid 12.6 mg/dl
ER: 2 days postchemo
Hgb 11.2 g/dl
Platelets 200,00/mm3
Na++137 mmol/l
K+ 6.5 mmol/l
BUN 100
Creatinine 5.1 mg/dl
Uric acid 25 mg/dl
ED intake interview revealed Mr. J. had
not been able to tolerate oral
medications after his chemotherapy
Had not taken prescribed allopurinol
Had not taken in recommended 8 glasses
fluid per day
5
TLS: Nursing Interventions
Recognize patients at risk
Leukemia, lymphoma, small-cell lung cancer
Large tumors with large growth fractions or elevated LDH
Recent chemo or radiation therapy
High LDH, concurrent renal disease
Careful assessment of fluid balance
Patient teaching – strategies to reduce incidence or
severity of symptoms
Maintain adequate oral fluid intake
Take Allopurinol as ordered
Signs & symptoms to report to health care team
Written instructions
Mr. J. was treated with:
1 amp D50, 10 units regular insulin
D51/2 NS plus 100 mEq NaHCO3 at 250 cc/hr
Allopurinol 300 mg/day po
IV Lasix 40 mg
Transferred to inpatient telemetry unit with following
orders:
Strict I & O
Notify MD for urine output < 200 ml/hr
BID weights
Vital signs Q2 hrs
Repeat Laboratory tests in 1 hr, monitor Q4 hrs:
Electrolytes, Ca++, PO4-, BUN, Creatinine, Uric Acid
Holmes Gobel, B. (2013). Tumor Lysis Syndrome. In Kaplan, M (Ed). Understanding and managing oncologic emergencies:
A resource for nurses, 2nd ED. ONS, Pittsburgh, PA. pp: 433-459.
.
Sepsis & Septic Shock
Septicemia: Invasion of blood by microorganisms
Sepsis: Systemic response to infection
(vasodilation, displacement of intravascular volume)
Septic Shock: Vascular collapse caused by
vasodilation, leakage intravascular volume into
interstitial space
Continuum Septic Shock:
Infection  Septicemia  Sepsis  Septic Shock
Incidence and Mortality
Incidence in cancer patients
Bacteremia or sepsis: 10-20% of patients with febrile
neutropenia
Hematologic Malignancies have higher incidence than solid
tumors
Hematologic malignancies: 66.4 per 1,000 hospitalized
patients
Solid tumors: 7.6 per 1,000 hospitalized patients
Mortality in cancer patients
Approximately 28%, same mortality rates for hematologic
malignancies & solid tumors
Courtney, et al (2007). Oncologist, 12, 1019-1026; Shelton, B.K. (2011), in Yarbro et al (eds), Cancer Nursing: Principles and Practice
(7th ed., pp 713-744). Jones & Bartlett.; Williams, et al (2004).Critical Care 8, 291-298.
6
Septic Shock: Pathophysiology
Micro-organisms in blood stream release chemical
mediators & hormones
Endotoxins – released by gram negative bacteria
Exotoxins – released by gram positive bacteria
Profound systemic vasodilation
Hypotension
Tachycardia
Increased vascular permeability
Fluid leaks from vascular space to interstitial space
Decreases circulating blood volume
Hypoxic tissues
Metabolic acidosis
Holmes Gobel, et al (2013). Sepsis & septic shock. In Kaplan, M (Ed). Understanding and managing oncologic emergencies:
A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 287-335.
Clinical Presentation: Septic Shock
Early Phase
• Normal or elevated
•
•
•
•
temperature
Chills
Warm, flushed skin
Anorexia
Normal or low BP
Hyperdynamic Phase
(Warm)
• Normal or elevated
•
•
•
•
temperature
Chills and rigors
Changes in LOC
(anxiety, restlessness,
confusion)
Tachycardia, bounding
pulses, widening pulse
pressure
Decreased urine output
Hypodynamic Phase
(Cold)
• Subnormal temperature
• Pale, cool, and clammy
skin
• Disorientation, lethargy
• Tachycardia
• Weak, thready pulse
• Hypotension
• Anuria
Causes of Sepsis
Bacterial organisms (most common cause of sepsis)
Gram-negative bacteria (responsible for 50-60%
cases of septic shock)
Escherichia coli
Klebsiella pneumoniae
Pseudomonas aeruginosa
Gram-positive bacteria (increased incidence due to
use of vascular access devices)
Streptococcus pneumoniae
Staphylococcus aureus
Corynebavcterium
Other organisms
Invasive fungal infections, viruses
Lewis, et al (2011). CA: A Cancer Journal for Clinicians, 61, 287-314.
Mr. J.: Seven days post-3rd cycle
chemotherapy (CHOP-R)
Wife calls outpatient clinic at 5 pm on
Friday and reports husband has:
Fever
Dry cough
Discomfort with swallowing
Holmes Gobel, et al (2013). Sepsis & septic shock. In Kaplan, M (Ed). Understanding and managing oncologic emergencies:
A resource for nurses, 2nd ED. ONS, Pittsburgh, PA. pp: 287-335.
7
Mr. J & Wife arrive in ER at 7:30 pm:
Awake, alert, anxious
Skin warm, appears flushed
↓ breath sounds lower lobes bilaterally with rales in
right lung base
Oral cavity without erythema or lesions, skin intact
Dual-lumen Groshong® central venous catheter exit
site without redness or drainage; however, c/o slight
tenderness to area above catheter exit site
O2 sat 98% room air
Temp 1020F, HR irregular 96, RR 16, BP 126/84
Diagnostic Evaluation
CBC with differential
Complete metabolic panel
Serum lactate
Blood cultures X 2
Cultures of body fluids
Urine, stool, throat, wounds, sputum
Chest X-Ray
Holmes Gobel, et al (2013). Sepsis & septic shock. In Kaplan, M (Ed). Understanding and managing oncologic emergencies:
A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 287-335.
Treatment of
Sepsis/Septic Shock:
Immediate initiation IV
antibiotics (within 1
hour of fever onset)
Fluid resuscitation
Goals:
CVP: 8-12 mmHg
MAP: > 65 mmHg
Urine output: > 0.5
mg/kg/hr
Holmes Gobel, et al (2013). Sepsis & septic shock. In Kaplan, M (Ed). Understanding and managing oncologic emergencies:
A resource for nurses, 2nd ED. ONS, Pittsburgh, PA. pp: 287-335.
Treatment of
Sepsis/Septic Shock
Mean arterial pressure (MAP) < 65
Vasopressor and inotropic drugs
Norepinephrine, dopamine (first line)
Phenylephrine, dobutamine, etc (second
line)
Oxygen therapy
Antipyretics
Holmes Gobel, et al (2013). Sepsis & septic shock. In Kaplan, M (Ed). Understanding and managing oncologic emergencies:
A resource for nurses, 2nd ED. ONS, Pittsburgh, PA. pp: 287-335.
8
Mr. J’s Labs in ER:
ER Orders for Mr. J.:
Stat CBC with differential, CXR, & cultures of
blood (peripheral blood and central lines),
urine, sputum, stool, CVC exit site
Stat Electrolytes, Blood Glucose, BUN, &
Creatinine
Meropenum 1 gm IV stat & Q8h
Vancomycin 1000 mg IV stat & Q12h
Admit to medical unit
Neutropenic precautions
Nursing Assessment on Admission
to Inpatient Unit: 9 PM
Extreme restlessness & anxiety
Shaking chills
Skin warm, flushed
Temp 102.40F
HR 120 irregular, bounding
RR 20, oxygen saturation 96% room air
BP 128/60
No urine output since early am
Stat IV antibiotics ordered in ER not yet given
• WBC 1,100/mm3
• ANC
450/mm3
• K+ 3.3 mEq/l
• Hgb 10 g/dl
• Plt
• Na++ 134 mEq/l
• BUN 12 mg/dl
30,000/mm3
• Creatinine 0.9 mg/dl
• Glucose 201 mg/dl
Clinical Presentation: Septic Shock
Early Phase
• Normal or elevated
temperature
Hyperdynamic Phase
(Warm)
• Normal or elevated
temperature
• Chills
• Chills and rigors
• Warm, flushed skin
• Changes in LOC
• Anorexia
• Normal or low BP
(anxiety, restlessness,
confusion)
Hypodynamic Phase
(Cold)
• Subnormal temperature
• Pale, cool, and clammy
skin
• Disorientation, lethargy
• Tachycardia
• Weak, thready pulse
• Tachycardia, bounding
• Hypotension
pulses, widening pulse
pressure
• Decreased urine output
• Anuria
Holmes Gobel, et al (2013). Sepsis & septic shock. In Kaplan, M (Ed). Understanding and managing oncologic emergencies:
A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 287-335.
9
Nursing Management Sepsis
Frequent vital signs & assessments
LOC, skin color & temp, lungs
Maintain oxygenation
Oxygen therapy & ventilatory support
Administer IV fluids,
Expand intravascular volume (fluid
resuscitation)
Monitor I & O
Antipyretics
Assess for fluid overload
Clinical Presentation: Septic Shock
Early Phase
• Normal or elevated
•
•
•
•
temperature
Chills
Warm, flushed skin
Anorexia
Normal or low BP
Hyperdynamic Phase
(Warm)
• Normal or elevated
•
•
•
•
temperature
Chills and rigors
Changes in LOC
(anxiety, restlessness,
confusion)
Tachycardia, bounding
pulses, widening pulse
pressure
Decreased urine output
Hypodynamic Phase
(Cold)
• Subnormal temperature
• Pale, cool, and clammy
•
•
•
•
•
skin
Disorientation, lethargy
Tachycardia
Weak, thready pulse
Hypotension
Anuria
Mr. J: Nursing Assessment 9:45 pm
Disoriented, lethargic
Skin pale, cool
↓ breath sounds lower lobes bilaterally with diffuse
bilateral rales, hemoptysis
Abdomen distended, rebound tenderness
No urine output
Oozing blood from venipuncture sites
HR 136 irregular, weak
RR 28 labored, oxygen saturation 88% room air
BP 88/50
Nursing Interventions
Neutropenic patients with fever
Must be assessed immediately
Started on broad spectrum antibiotics
Monitor for sequelae of septic shock
Frequent vital signs
Assess tissue perfusion (skin color, temperature, capillary refill)
Lung assessments
I & O – report urine output < 30cc/hr
Monitor for symptoms of DIC
Monitor response to medical treatment
Assess for fluid overload
Monitor lab values, especially renal function & culture reports
Infection control measures
Holmes Gobel, et al (2013). Sepsis & septic shock. In Kaplan, M (Ed). Understanding and managing oncologic emergencies:
A resource for nurses, 2nd ED. ONS, Pittsburgh, PA. pp: 287-335.
Holmes Gobel, et al (2013). Sepsis & septic shock. In Kaplan, M (Ed). Understanding and managing oncologic emergencies:
A resource for nurses, 2nd ED. ONS, Pittsburgh, PA. pp: 287-335.
10
Possible Complications of
Sepsis/Septic Shock
DIC
Multiple organ dysfunction syndrome
Death
Disseminated Intravascular
Coagulation (DIC)
Syndrome of:
Thrombus formation (clotting)
Simultaneous Hemorrhage
Caused by over stimulation of normal
coagulation processes
Kaplan, M. (2013). Disseminated Intravascular Coagulation. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 69 – 102.
Pathophysiology DIC
Paradox of DIC: bleeding & clotting
Triggered by:
Intrinsic coagulation system activation
(damage to blood vessels)
Transfusion reactions
Endotoxins/Septicemia
Sickle Cell Disease
Malignant hypothermia
Extrinsic coagulation system activation (tissue injury)
Obstetrical Conditions
Extensive surgery
Crush injuries
Malignancies
Kaplan, M. (2013). Disseminated Intravascular Coagulation. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 69 – 102.
DIC in the Oncology Population:
Malignancy Induced
Acute Promyelocytic Leukemia (APL)
Procoagulant material release by granules of the
immature promyelocyte  initiates clotting
cascade
Occurs in 85% patients with APL
Solid Tumors (adenocarcinomas)
Lung, pancreas, prostate, stomach, colon, ovary,
gall bladder, breast, kidney
Kaplan, M. (2013). Disseminated Intravascular Coagulation. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 69 – 102.
11
Pathophysiology of DIC
Other Causes DIC
(Oncology Population)
UNDERLYING
DISEASE OR
CONDITION
Chemotherapy
May induce DIC by damaging tumor, normal cells, or
endothelium  causes release procoagulant material
Large tumor burden/large cell kill  release granule
procoagulant from dead cells into systemic circulation
Infection/sepsis
Especially gram negative bacteria sepsis (release
of endotoxin)
STIMULATION OF
COAGULATION
CASCADE
WIDESPREAD FIBRIN
CLOT FORMATION
MICROTHROMBI
DEPOSITS
THROUGHOUT
MICROCIRCULATION
ACTIVATION OF
FIBRINOLYSIS
CONSUMPTION OF:

PLATELETS

FIBRINOGEN

PROTHROMBIN
PRODUCTION OF:

FIBRIN SPLIT
PRODUCTS

tPA
Hemolytic transfusion reactions
Rupture of RBC’s  platelet aggregation, release
platelet factors that initiate clotting cascade
Kaplan, M. (2013). Disseminated Intravascular Coagulation. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 69 – 102.
ISCHEMIC TISSUE
DAMAGE
SYMPTOMS OF ORGAN
DYSFUNCTION
Laboratory Values in DIC
Types of DIC
Acute DIC
Medical emergency
Chronic DIC
Produces coagulation abnormalities, with
or without clinical manifestations, that can
be medically managed
Most cases of chronic DIC due to
underlying malignancy
BLEEDING
Laboratory Test
Result
Comments or Cause
Prothrombin Time (PT)
Prolonged
Nonspecific in DIC
Activated Partial Thromboplastin
time (APPT)
Prolonged
Nonspecific in DIC
International normalized ratio
(INR)
Prolonged
Nonspecific in DIC
Fibrin Degradation Products
D-Dimer
Elevated
Indicates breakdown of
fibrin & fibrinogen
Elevated
Indicates hyperfibrinolysis
Platelet Count
Decreased
Platelets consumed
Fibrinogen
Decreased
Fibrinolysis; decreases very
slowly only in severe DIC
Antithrombin
Decreased
Anticoagulant activity
inhibited
Accelerated coagulation
Kaplan, M. (2013). Disseminated Intravascular Coagulation. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2nd ED. ONS, Pittsburgh, PA. pp: 69 – 102.
12
DIC Clinical Presentation
Mr. J: Nursing Assessment 9:45 pm
Disoriented, lethargic
Skin pale, cool
↓ breath sounds lower lobes bilaterally with
diffuse bilateral rales, hemoptysis
Abdomen distended, rebound tenderness
No urine output
Oozing blood from venipuncture sites
HR 136 irregular, weak
RR 28 labored, oxygen saturation 88% room air
BP 88/50
Decreased tissue/organ perfusion
Brain, CV, Lungs, Kidney, GI Tract, Skin
Decreased platelet count
Petechiae, ecchymosis
Hemorrhage
Tachycardia, hypotension
Tachypnea
Overt bleeding
Occult bleeding
Kaplan, M. (2013). Disseminated Intravascular Coagulation. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 69 – 102.
Mr. J’s Labs at 10:00 pm
Lab
7:30 pm
10:00 pm
Hemoglobin
10 g/dl
8.9 g/dl
Platelets
30,000/mm3 12,000/mm3
Normal
14-18 g/dl male
96 mg/dl
150,000 –
400,000/mm3
170 – 410 mg/dl
PT
15.8 sec
11.3 – 13.1 sec
Fibrin
Degradation
Products
60 mcg/ml
Fibrinogen
<10 mcg/mL
Treatment of DIC
Early recognition & treatment of underlying
disorder
Chemotherapy for malignancy
Antibiotics for infection
Correct hypoxia
Oxygen to maintain saturation >95%
Correct hypovolemia, hypotension, &
acidosis
NS until type & cross match completed & blood
available
Kaplan, M. (2013). Disseminated Intravascular Coagulation. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 69 – 102.
13
Treatment of DIC
Stop the micro clotting to
maintain perfusion & protect vital
function
IV Heparin
Antithrombin III (inhibits action
of thrombin)
Stop the bleeding
Pressure to active sites of
bleeding
Blood products (FFP,
cryoprecipitate, platelets, red
blood cells)
Antifibrinolytic agents (EACA)
Kaplan, M. (2013). Disseminated Intravascular Coagulation. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 69 – 102.
Hypercalcemia of
Malignancy (HCM)
Metabolic disorder, in cancer patients,
results from increased bone resorption
Serum calcium level >12-14 mg/dl
(normal serum calcium 9-11 mg/dl)
Nursing Interventions
Prevent severity of symptoms
Direct pressure sites of bleeding, pressure dressings, sand bags
Monitor for progression DIC
Worsening vital signs, hypotension, anuria, ’s LOC
Monitor response to therapy
Sites & amounts of bleeding
Changes in lab values
Assess tissue perfusion parameters – color, temperature, peripheral
pulses
Patient Teaching
Avoid ASA or NSAID’s (effects on platelet aggregation)
Signs and symptoms of DIC (bleeding and/or clotting)
Kaplan, M. (2013). Disseminated Intravascular Coagulation. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 69 – 102.
Normal Physiology
Normal levels Ca++ regulated by:
Parathyroid gland (production of parathyroid hormone)
GI tract (absorption of Vitamin D)
Kidneys (excretion)
Ca++ levels  below normal:
Parathyroid stimulated to produce parathyroid hormone
Acts on bone  release of calcium (bone resorption)
into circulation
Ca++ levels  above normal:
Kidneys  excretion of calcium
Kaplan, M. (2013) Hypercalcemia of malignancy. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 103 – 155.
Kaplan, M. (2013) Hypercalcemia of malignancy. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 103 – 155.
14
Incidence of Hypercalcemia
of Malignancy
HCM: Etiology
Tumor-induced bone breakdown
releasing Ca++ into bloodstream
Occurs in approximately 30% of cancer
patients
Solid tumors of squamous cell
origin – potential to produce
parathyroid hormone-related
protein that stimulates Ca++
release from bone
Most often in advanced stages of disease
50% of patients die within 30 days of
diagnosis
Survival beyond 6 months is rare
Lung, breast, prostate, head & neck,
esophagus, kidney
Decreased ability of kidneys to
clear calcium from the blood
Kaplan, M. (2013) Hypercalcemia of malignancy. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 103 – 155.
Incidence of Hypercalcemia
of Malignancy
Malignancy
Breast cancer with metastasis
Multiple myeloma
Incidence of
Hypercalcemia
Incidence of Bone
Metastasis
30% - 40%
65% - 75%
20% - 40%
70% - 90%
Squamous cell carcinoma of lung
12.5% - 35%
30% - 40%
Squamous cell carcinoma of head
& neck
2.9% - 25%
Uncommon
Renal cell carcinoma
3% - 17%
20% - 25%
Non-Hodgkin’s Lymphoma
14% - 33%
Rare
50%
Rare
T-Cell Lymphoma
Kaplan, M. (2013) Hypercalcemia of malignancy. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 103 – 155.
Hypercalcemia:
Clinical Presentation
Clinical signs & symptoms related to rapidity
of onset & serum calcium level
Corrected total serum calcium (TSC) needs
to be calculated if albumin is low
Corrected Serum Calcium (mg/dl)=
Measured serum Ca++ + (4.0 – serum albumin g/dl) X 0.8
**Normal Serum Ca++ = 8.5 – 10.5 ml/dl
Kaplan, M. (2013) Hypercalcemia of malignancy. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 103 – 155.
15
Signs and Symptoms of
Hypercalcemia of Malignancy
System
Early
Late
Seizures
Stupor
Coma
Hypercalcemia: Treatment
Neurologic
Drowsiness, lethargy, weakness,
restlessness, irritability, confusion,
cognitive dysfunction, disorientation
Renal
Polyuria, polydipsia, nocturia, dehydration, Renal failure
kidney stones, renal insufficiency
GI
Anorexia, nausea, vomiting, constipation,
vague abdominal pain, weight loss, peptic
ulcers
Atonic ileus
Obstipation
Ca++ 12-15 ml/dl & asymptomatic
Cardiovascular
EKG changes (slowed conduction,
Prolonged PR, wide QRS, short QT, short
ST), sinus bradycardia
Heart block
Cardiac arrest
Ca++ >15 ml/dl & symptomatic
Musculoskeletal
Muscle weakness, fatigue, hypotonia,
bone pain
Ataxia
Pathologic fractures
Depends on serum calcium level &
patient symptoms:
Ca++ <12 ml/dl & asymptomatic
observe carefully & treat as outpatient
requires specific but non-urgent treatment
requires emergent treatment
Kaplan, M. (2013) Hypercalcemia of malignancy. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 103 – 155.
Hypercalcemia: Treatment
Treat the cancer – tumor control or
reduction is the only long-term measure for
reversing hypercalcemia
Hydration & forced diuresis
Oral fluids (3-4 L/day)
IV Saline
Initial: NS 100-300 ml/hr
Maintenance: 2.5 – 5L/day
Loop diuretics (furosemide)
Mobilization
Kaplan, M. (2013) Hypercalcemia of malignancy. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 103 – 155.
Agents to Inhibit Bone Resorption
Agent
Mechanism of Action
Dosing
Bisphosphonates
• Pamidronate (Aredia)
• Inhibits osteoclast activity IV: 60-90 mg over 2 hrs
May repeat after 7 days
• Zoledronate (Zometa)
• Inhibits osteoclast activity IV: 4 mg over 15 minutes
May repeat after 7 days
Calcitonin
• Direct inhibition of
osteoclast receptors
• Increases renal calcium
excretion
Gallium nitrate (Ganite)
• Used when HCM resistant IV: 200 mg/m2/day
to bisphosphonates
continuous for 5 days
• Inhibits osteoclast activity
SC or IM: 4-8 IU/kg every
6-12 hours for 2 days
Kaplan, M. (2013) Hypercalcemia of malignancy. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 103 – 155.
16
Hypercalcemia Treatment
Dietary recommendations
Maintain salt intake
Dietary calcium restrictions not necessary
Medications to avoid
Thiazide diuretics
NSAIDS, H2 receptor antagonists
Vitamins A & D
Parenteral/enteral solutions with calcium
Corticosteroids
Therapy of choice multiple myeloma or lymphomas
Inhibits vitamin D conversion to calcitriol
Kaplan, M. (2013) Hypercalcemia of malignancy. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 103 – 155.
Mr. C: Hypercalcemia
62-year-old male diagnosed with stage IV
squamous cell cancer of lung
CT of spine showed metastatic disease in
thoracic & lumbar spine at T1 & L3 vertebrae
Based on extent of disease & poor pulmonary
function, Mr. C. was not a surgical candidate.
Scheduled for second course of palliative
chemotherapy
Also receiving concurrent radiation for the
spinal metastasis
Nursing Interventions
Recognize early signs & symptoms
Careful monitoring of patients taking:
Thiazide diuretics (inhibits calcium excretion)
Digitalis preparations (action potentiated in hypercalcemic
states)
Measures to decrease calcium removal from bone:
Ambulation, weight bearing, ROM, isometric exercises
Careful assessment & monitoring
Fluid balance & renal function
GI motility
Cardiac Status
Mental status
Kaplan, M. (2013) Hypercalcemia of malignancy. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 103 – 155.
2nd Cycle Chemotherapy
Wife consults with nursing staff &
reports:
Concern re: husband’s ↑ forgetfulness,
wonders if confusion is because of recent
change in pain medication (oxycodone)
Husband experiencing more fatigue than
usual (4-5 naps per day)
17
Mr. C’s Labs: 2nd Cycle
Chemotherapy
Corrected Serum Ca++
Mr. C’s :
4,500/mm3
WBC
Hgb 11.2 g/dl
Hct 35%
Platelets
119,000/mm3
Serum Ca++ 10.4
Creatinine 1.1 mg/dl
BUN 19 mg/dl
Albumin 2.3 g/dl
Albumin 2.3
Corrected Serum Calcium =
Measured serum Ca++ + (4.0 – serum albumin) X 0.8
= 10.4 + (4.0 – 2.3) X 0.8
= 10.4 + 1.7 X 0.8
= 10.4 + 1.36
= 11.78 (rounded up to 11.8)
Mr. C’s Lab Trends
Mr. C’s 3rd Cycle Chemotherapy
Wife reports confusion improved for 1st
two weeks following last chemotherapy
Past week, he has been increasingly
forgetful, depressed, and fatigued
(stayed in bed last 2 days)
Ca++ 10.4
2nd Chemo Visit
3rd Chemo Visit
WBC
Lab Test
4,500/mm3
2,200/mm3
Hgb
11.2 d/dl
10.4 g/dl
Hct
35%
29%
119,000/mm3
102,000 mm/3
Platelet count
BUN
19 mg/dl
28 mg/dl
Creatinine
1.1 mg/dl
1.5 mg/dl
Serum calcium
10.4 mg/dl
12.8 mg/dl
2.3 g/dl
2.1 g/dl
Albumin
18
Corrected Serum Ca++
Mr. C’s :
Ca++ 12.8
The best immediate treatment to correct
Mr. C’s calcium & symptoms is:
Albumin 2.1
Corrected Serum Calcium =
Measured serum Ca++ + (4.0 – serum albumin) X 0.8
= 12.8 + (4.0 – 2.1) X 0.8
= 12.8 + 1.9 X 0.8
= 12.8 + 1.52
= 14.32 (rounded to 14.3)
The best immediate treatment to
correct Mr. C’s calcium & symptoms is:
a. Hydration & Bisphosphonate (anti-
Resorptive therapy) infusion
b. Chemotherapy administration &
corticosteroids
c. Growth factor to improve fatigue and
minimize myelosuppression
d. Hydration & observation
Structural Oncologic
Emergencies
a. Hydration & Bisphosphonate (anti-
Spinal Cord Compression
Superior Vena Cava Syndrome (SVCS)
b. Chemotherapy administration &
Increased Intracranial Pressure (ICP)
Cardiac Tamponade
Resorptive therapy) infusion
corticosteroids
c. Growth factor to improve fatigue and
minimize myelosuppression
d. Hydration & observation
Kaplan, M. (2013). Spinal Cord Compression. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 337 – 383.
19
Spinal Cord Compression
Compression of spinal cord
Direct tumor pressure on cord
Tumor invasion of the vertebral column causing collapse
& pressure on cord
Compression causes:
Edema
Inflammation
Mechanical compression
Leads to:
Direct neural injury to cord
Vascular Damage
Kaplan, M. (2013). Spinal Cord Compression. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 337 – 383.
Cancers Associated with Risk of
Spinal Cord Compression
Frequency
Cancer Type
Most Common
•
•
•
•
•
•
•
•
Breast (15% - 20%)
Lung (15% - 20%)
Prostate (15% - 20%)
Multiple Myeloma (10% - 15%)
Unknown primary (10%)
Renal cell carcinoma (5% - 10%)
Non-Hodgkin lymphoma 5% - 10%)
Hodgkin disease (5%)
Less Common
•
•
•
•
GI malignancies
Soft Tissue sarcoma
Thyroid cancer
Neuroblastoma
Uncommon
•
•
•
Melanoma
Uterine, cervical, bladder cancers
Leukemia
Rare
•
Head and neck cancer, brain, pancreatic,
liver, ovarian, testicular, esophageal
cancer
Incidence
Occurs in approximately 5-14% of general
cancer population
Highest incidence in solid tumors that
metastasize via hematogenous routes to bone
in the spine
Most common:
Breast
Lung
Prostate
Lymphoma
Kaplan, M. (2013). Spinal Cord Compression. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 337 – 383.
Clinical Presentation:
Back Pain
Most common presenting symptom
Occurs in 90% of patients
Precedes other signs and symptoms (e.g. neurological)
by weeks to months
Median time from onset to pain to diagnosis of spinal cord
compression: 2 months
Kaplan, M. (2013). Spinal Cord Compression. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 337 – 383.
20
Back Pain Associated with
Spinal Cord Compression
Progression of Symptoms
Time Frame
Early
Can occur at any level of the spine
Can take several forms:
Local (near the site of compression)
Radicular (distributed along dermatones)
Referred (in a non-radicular distribution)
May be a combination of all 3 types
Kaplan, M. (2013). Spinal Cord Compression. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 337 – 383.
Diagnostic Tests
MRI
Gold standard for diagnosis
Accurate, sensitive, and specific diagnostic
tool for spinal cord compression
Other Diagnostic Tests
Spinal x-rays
CT scan
Myelography – reserved for patient’s who
can’t undergo MRI
Bone Scan and/or PET Scan
Kaplan, M. (2013). Spinal Cord Compression. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 337 – 383.
Signs & Symptoms
• Pain
• Motor weakness or gait changes
• Sensory Loss
•
Numbness, tingling, sensory changes
• Autonomic Dysfunction
Late
•
•
Constipation and/or bladder retention
Bowel and/or bladder incontinence
• Paralysis
Kaplan, M. (2013). Spinal Cord Compression. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 337 – 383.
Treatment of Spinal Cord Compression
IMMEDIATE & aggressive
Corticosteroids – initial supportive treatment
High-dose steroids to  spinal cord edema &
inflammation
High-dose loading with Dexamethasone (up to
100 mg IV loading dose) followed by tapering
doses over several days
Radiation therapy (radiosensitive tumors)
In general, a course of radiation with a total of 30
Gy in 10 fractions
Kaplan, M. (2013). Spinal Cord Compression. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 337 – 383.
21
Treatment of Spinal Cord Compression
Surgery
Laminectomy (no longer typically used)
Anterior vertebral body resection with stabilization
Vertebroplasty
Kyphoplasty
Chemotherapy
Rarely used in acute management
Response to treatment slow & unpredictable
Bisphosphonates
Can effectively reduce pain and other skeletal
complications of vertebral metastasis
Kaplan, M. (2013). Spinal Cord Compression. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 337 – 383.
Superior Vena Cava Syndrome
Obstruction of superior vena cava that
impairs venous drainage (above the
obstruction)
Obstruction  venous return from head,
neck, upper arms, upper thorax impaired
Venous pressure increases
Cardiac output decreases
Nursing Interventions
Early recognition
Thorough assessment of neck &
back pain in high risk patients
Neurological assessments
Mental status
Cranial nerves
Motor & sensory system
Reflexes
Pain Management
Mobility and safety issues
Skin care
Bowel and Bladder function
Rehabilitation & palliative care
Kaplan, M. (2013). Spinal Cord Compression. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 337 – 383.
Incidence
Occurs in 3 – 4% of Oncology Population
Malignant conditions: Majority of cases (70% 95%) related to underlying malignancy
Most common:
Small cell & non-small cell lung cancers
Non-Hodgkin lymphoma (high-grade)
Less common:
Esophageal cancer
Thyroid cancer
Breast cancer, thymoma, mesothelioma, leukemia
Non-Malignant conditions:
Intraluminal thrombus formation
Mediastinal fibrosis or benign mass
Shelton, B. K. (2013). Superior Vena Cava Syndrome. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 385 – 410.
Shelton, B. K. (2013). Superior Vena Cava Syndrome. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 385 – 410.
22
Clinical Presentation
Gradual onset (rarely occurs rapidly)
Symptoms vary depending on extent of
obstruction, location, collateral
circulation
Shelton, B. K. (2013). Superior Vena Cava Syndrome. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 385 – 410.
Late Physical
Signs & Symptoms
Cyanosis of face &
upper torso
Decreased or absent
peripheral pulses
CHF
Decreased BP
Chest pain
Mental status changes
Tachypnea
Tachycardia
Engorged conjunctivae
Visual disturbances
Syncope
Hoarseness
Stridor
Early/Common Physical
Signs & Symptoms
Dyspnea
Facial and neck swelling (occurs when supine,
subside after arising)
Sensation of fullness in head
Cough
Arm Swelling
Chest pain
Venous distention of neck & chest wall
Cyanosis
Shelton, B. K. (2013). Superior Vena Cava Syndrome. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 385 – 410.
Diagnostic Evaluation
Chest X-ray
MRI
Contrast-enhanced CT
Tissue diagnosis
Shelton, B. K. (2013). Superior Vena Cava Syndrome. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 385 – 410.
23
Nursing Interventions
Treatment SVCS
Assess for signs & symptoms in patients at risk
Based on etiology, severity of symptoms
Relieve obstruction & control underlying disease
Radiation therapy
Non-small cell lung cancer, small cell lung cancer, non-Hodkin
lymphoma
Central venous catheter access devices
Interventions to relieve symptoms
Elevate HOB, avoid supine position & elevation of lower
extremities
Avoid venipuncture, BP, IV therapy upper extremities
Monitoring response to treatment
Gold standard for non-small cell lung cancer
Chemotherapy
Primary treatment for chemo-sensitive malignancies
Small cell lung cancer
Non-Hodgkin Lymphoma
Surgical Intervention
Assess for progressive respiratory distress or edema
Monitor tolerance of activities
Monitor fluid status(over hydration exacerbates symptoms)
Assess CNS (LOC, mental status change, visual changes, headache)
Stent placement or SVC bypass
Chronic or recurrent SVCS
Thrombolytic therapy
SVCS caused by intraluminal thrombus)
Shelton, B. K. (2013). Superior Vena Cava Syndrome. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 385 – 410.
Sepsis is a common cause of disseminated
intravascular coagulation (DIC). Which of the
following conditions most accurately describes how
sepsis causes DIC?
a. Sepsis causes viruses to thrive, and viruses cause DIC
b. Endotoxins released from bacteria activate the
coagulation cascade
c. Sepsis and bleeding occur simultaneously in patients who
are immunosuppressed
d. Antiangiogenesis factors are released during periods of
sepsis, which leads to DIC
Shelton, B. K. (2013). Superior Vena Cava Syndrome. In Kaplan, M (Ed). Understanding and managing oncologic
emergencies: A resource for nurses, 2 nd ED. ONS, Pittsburgh, PA. pp: 385 – 410.
Which of the these statements is not true in regards
to hypercalcemia in malignancy?
It is a rare complication
Early manifestations of the syndrome are insidious
including fatigue, muscle weakness, and depression and
easily overlooked as manifestations of the disease.
c. Bisphosphonates are frequently used in the treatment of
malignancy induced hypercalcemia because of their
ability to interfere with osteoclastic activity
d. A complication of malignancy induced hypercalcemia
include decreased GFR and acute kidney failure,
neuropsychiatric disturbances, and cardiovascular
complications.
a.
b.
24