Download 18- OncoEmergencies Hypercalc HyperUric

Oncologic Emergencies
Prof. Dr. Khaled Abouelkhair, PhD
Medical Oncology SCE, Royal College, UK
Ass. Professor of Clinical Oncology
Mansoura University, Egypt
• Hypercalcemia
• Hyperuricaemia / TLS
• A patient admitted in the medical floor, known
case of lung cancer metastatic to bone, the
nurse reporting that the patient is Lethargic,
stupor, as well as Fatigue, Dehydration and
constipation. ECG was requested which
revealed Cardiac bradycardia, and short QT
interval
• What would it be?
• Metabolic or Neurologic?
The calcium ion
cellular function
signaling, cardiac
and
plays a critical role in normal
and signaling (neuromuscular
contractility, hormone secretion,
blood
coagulation).
• Feedback mechanisms maintaining extracellular
calcium concentrations within a narrow,
physiologic range.
• Normal Ca level (8.9 – 10.1 mg/dl).
• Corrected Ca mg/dl = (4- albumin in g/dl) x 0.8 + serum Ca.
• Commonest Cancer NSCLC, SCLC, Breast, M.M,
RCC, and NHL (T-cell).
• Causes of Hypercalcemia:
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Direct bone destruction
Immobilization
Parathormone like hormones
Medications e.g. Thiazides, Antiestrogens, Vit A
Excessive calcium intake, milk alkali syndrome
Management
• First be sure it is true hypercalcemia?
• The second most important laboratory test in
the diagnostic evaluation is a PTH level.
• Serum creatinine should be measured to assess
renal function.
Mild Hypercalcemia: asymptomatic patients with
minimally elevated calcium levels (< 12.0 mg/dL)
…Encouragement of oral hydration, mobilization, and
elimination of drugs that contribute to hypercalcemia
are essential. 2-3 L of intravenous fluid may be required
over the first 24 h
• Moderate Hypercalcemia: 12 -14 mg/dl
symptomatic directed therapy.
• Severe Hypercalcemia: ≥ 14 mg/dl. Emergency
– Hydration 3-6 L/24h.
– Loop diuretics. Furosemide, 20 to 40 mg IV, may
be initiated after volume expansion is achieved,
with subsequent doses given when urine output is
< 150 to 200 mL/h. Thiazides are contraindicated.
– Bisphosphonates. Onset of action 2-4 days.
– Calcitonin. Rapid onset 2-4 Hours, peak effect in
48 hours, short lived effect. Dose 4-8 IU/Kg S.C
Q12h. Works through inhibiting the effects of
parathyroid hormones.
– Corticosteroids: only in steroid responsive tumors
– Phosphate: rarely used for fear of soft tissue
precipitations.
– Cyclo - Oxygenase inhibitor: Indomethacin, rarely
used if other drugs fail.
– Dialysis: if renal failure is not improving with
hydration and emerging volume overload.
• Prevents bone resorption.
• Side Effects: Flu like symptoms, Nausea and vomiting
46%, Fatigue 39%, Fever 32%, Diarrhea 24%,
Arthralgia/ myalgia 23%, and deterioration of renal
function.
• Delayed onset of action 48 – 72h.
• 4mg IV infusion over 15 minutes following
rehydration. May repeat after 7 days if not normocalcemic and can tolerate hydration.
• Remember dose reduction based on creatinine
clearance.
• No Diuretics without Hydration in Hypercalcemia.
• Always check creatinine clearance and adjust
doses.
• Be aware about renal toxicity of Bisphosphnates
and renal doses.
• Calcitonin lost its effect after 2-3 days.
• Review medications and stop agents, if feasible,
that may cause hypercalcemia and/or renal
impairment.
• It’s a rapid development of metabolic
abnormalities accompanying the release of
intracellular contents into the bloodstream due
to tumor cells death.
• Rapid release of intracellular contents can
happen spontaneously with high tumor burden or
from cell lysis due to cytotoxic agents (even
steroids!), cytokine or hormonal therapy .
Aetiology:
 A–Diseases:
a –Leukemia
- Acute and CLL
b–Lymphoma
- Burkitt’s
- T- Cell
- Lymphoblastic
c –Solid tumor
- Neuroblastoma
- SCLC - Breast Cancer
 B - Large tumor burden:
- Stage IV extensive rapidly dividing tumors
Precipitating Factors:
- Spontaneous
- Commencing treatment
Co-factors:
- Pre-existing renal insufficiency
- hyperuricemia
Metabolic Abnormalities:
• Tumor cells contain a high concentration of
potassium and phosphate. Their rapid
breakdown will release these electrolytes into
the blood resulting in:
Hyperkalemia, Hyperuricaemia,
Hyperphosphatemia and hypocalcaemia
• Soft tissue calcium phosphate deposition and
hypocalcaemia occur as a result of calcium downregulation secondary to Hyperphosphatemia
• Renal failure is a common complication.
Presentation:
• Many are asymptomatic
• Symptoms’ severity reflects the underlying
metabolic abnormalities.
1- Hyperkalemia: life-threatening, ventricular
dysrhythmias, paresthesia and weakness.
2- Hyperuricaemia: may lead to arthralgia and
renal colic, urate nephropathy, fatigue,
weakness etc… the worst ARF.
3- Hypocalcaemia: Neuromuscular instability with
muscle cramps, tetany, anxiety, carpopedal
spasms, bronchospasm, confusion and
convulsions.
ARF in TLS
Management
Prevention
Once occurred ARF is a major problem with serious
consequences. A good physician is not the one who treats it
efficiently but the one who can prevent it.
 Fix conditions that will make effects worse . NSAIDs
 Get baseline labs: K, Ca, Phos, Uric Acid, LDH, Cr.
 Preventing renal failure and severe electrolyte imbalances.
 Increase urine production with proper hydration.
 Decrease uric acid concentrations using Allopurinol
(Competitive inhibitor of xanthine oxidase) which decrease
uric acid synthesis from Purines but limited efficacy.
 Alkalinize urine keeping PH above 6.5 as …………
If occurred….
• Continue the same measures Plus.
• K+..Resoniums, Diuretics, Ca ++…….
• Manage ARF…..Dialysis.
• Magic Drug RASBURICASE (recombinant urate oxidase)
promotes catabolism of uric acid  Allantoins (10x more
soluble than uric acid).
What are the differences between
Allopurinol and Rasburicase
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Oral versus IV
Prevention and treatment
Nephrotoxic
Needs dose adjustment
Fast action
Drug - drug interactions
Inhibits Enzymatic reactions or an enzyme
Readily revert metabolic abnormaliti es including ARF
Needs alkalinization