112. Oncologic Emergencies Flashcards
Febrile neutropenia definition
ANC below: mild: 1000 to 1500, moderate 500 to 1000 less than 500 severe. current guidelines suggest that and see less than 500 or expected drop below the threshold within 48 hours
How to calculate the absolute neutrophil count
Percent granulocytes plus percent bands times total white blood cells divided by 100
Where are the most common sources of neutropenic fever?
Pneumonia, anorectal lesion, skin infection, pharyngitis, or urinary tract infection
Definition of fever in federal neutropenia
Single temp greater than 38.3 or a greater or sustained temperature of 38 for one hour or more
Diagnostic testing for neutropenia
Blood cultures from two sites, one can be done from the central line. Where is the other should be done properly, white blood differential, urine analysis and urine culture, chemistries and renal and hepatic function tests. VBG for lactate.
Consider CDiff, chest x-ray
When should patients were a febrile neutropenia receive antibiotics?
Prior to confirming infection given high mortality
Parental broad-spectrum, antibiotic, such as pip, Tazo or Carbapenem
Multinational Association of Supportive Care in Cancer: clinical features
age <60
onset of fever while outpatient
overall moderate sx burden
absence dehydration
no prior fungal infection or solid tumor tyoe
no copd hx
absence of hypotension
asx or overall mild symptom burden
score >/=21 suggests low risk complication; likely resolution fever <5d
Clinical features and corresponding point value of clinical index of stable febrile neutropenia:
eastern coop oncology group performance status >/=2
stress induced hyperglycemia
copd
chronic cardiovascular disease
mucositis of grade >/=2
monocyte coun <200 per microL
If pt with febrile neutropenia show signs of shock, what should they add to broad spectrum beta lactam with antipseudomonal coverage?
+ FQ or aminoglycoside
What abx for neutropenic pt with CAP?
levo 750mg IV a24h or azithro 500mg IV q24h and doxy 100mg BID
TMP for pcp if necessary
For neutropenic pt with GI sx, what abx to give?
cefepime 2g IV q8h and metronidazole 500mg PO q8h
What febrile neutropenia patients can be managed as outpt?
criteria:
- low risk criteria MASCC 21 or less
- no evidence of pneumonia, line infection, cellulitis or organ failure
- reliable daily f/u with oncology
- clinical stability in ER 4h or longer
- low suspicion of infection with drug R organism
Metastatic SC compression: where does lesion most often come from?
extradural
Metastatic SC compression: how does cord injury normally occur?
occlusion of epidural venous plexus leading to breakdown of BBB and vasgenic edema
if untx - arterial obstruction –> cord ischemia and infarct
less common direct compression
Metastatic SC compression: what cancers typically cause this?
prostate
breast
lung ca
RCC
nonHodgkin lymphoma
MM
Metastatic SC compression: where mc?
thoracic
lumobosacral
cervical
Metastatic SC compression: clinical features?
back pain (mc)
weakness (extremity often first pre. weakness)
sensory loss
autonomic function loss
Metastatic SC compression: diagnostic testing
MRI
Metastatic SC compression: tx in ED
CS: 10mg bolus IV then 16mg oral per d
if paraplegic consider first dose of 100mg IV then 96/day orally in divided doses
initiation of defin tx - surgery, rad therapy or both
Metastatic SC compression: how do steroids work?
temporize vasogenic cord edema but damage occurs without source control
Malignant pericardial disease: mc three?
pericarditis
neoplasm
effusion
Malignant pericardial disease: how can this occur as an effusion?
lymphatic flow becomes obstructed by proximal malignant LN
so mets spread to pericardial lining
mc cancers causing pericardial effusion?
lung
breast
heme
melanoma
Kussmaul sign
paradoxial incr in JVP with inspiration
Beck’s triad
hypotension
elevated JVP
muffled heart sounds
Malignant pericardial disease: ddx?
acs
hf or valve failure
pe
pleural effusion
pneumonia
ptx
Malignant pericardial disease: pericardial effusion work up?
cxr
ecg
tte
Malignant pericardial effusion findings on ecg?
nonsp st or t change
low amp qrs
electrical alternans
Malignant pericardial disease: management of pericardial effusion?
drainage by subxiphoid approach
likely will recur so needs LT f/u
fluid sampling for cytology or tumor marker analysis
Hypercalcemia: what two main hormones incr serum ca regulation?
what decr?
PTH
calcitriol - incr serum ca
decr: calcitonin
Hypercalcemia: what are two places active vitamin D works on?
bone - osteoclast activation to release
GI - to incr dietary ca uptake and dietary phosphate
Inactive vit d to active by which enzyme?
1 alpha hydroxylase
To incr ca: PTH acts on what two organs
kidneys: incr ca reuptake, decr phos reuptake
bone: osteoclast
How do cancer patients experience Hypercalcemia: 4 methods
synthesis PTHrP
overproduction calcitriol
bone osteolysis due to direct tumor spread
less common ectopic production of PTH
PTHrP producing cancers?
squamous.- head and neck, lung, esophageal, cervical, ovarian, endometrial
Cacitriol overproduction in which cancers?
hodgkin and non lymphomas
Hypercalcemia: sx
weakness
lethargy
confusion
abdo pain
n/emesis
constipation
polyruia
polydipsia
kidney injury
Hypercalcemia: ecg
qt interval shortening
to dysr and heart block
Hypercalcemia: which ca measurement needed?
free ca as lots bound to albumin
Hypercalcemia: Tx ED
- fluids ++ as helps to incr removal: 1-2L bolus, then 200-250ml/hour
–>. +/- dialysis above if needed to support u/o - bisphosphonates: inhibit bone turn over: pamidtronade 90mg over 2-4 hours or zolendronate 4mg over 15-30 mins
*expect decr 3-4mg/dl but probably not for 7-10d - calcitonin SC 4-8 units/kg q6h (faster 12-24h onset)
- Denosumab to block RANK ligand * esp if renal clearance bad
Rosen’s indications for admission for Hypercalcemia:
Ca >14
acutely incr
TLS: why does this occur?
desctruction of malignant cells so rapid that body mechanism for unwanted products are overwhelmed
TLS: 4 abnormal electrolyte/lab values
Hyperuricemia
HyperK
Hyperphos
HYPOcalcemia
AKI often as well
TLS: what other organ affected often
kidney
TLS: typical cancers causing this?
Burkitt lymphoma
ALL
TLS: PT risk factors (aside from type of ca)
preexisting renal failure
hypovolemia
hyperuriciemia
TLS: sx/presentation
nausea/emesis
lethargy
confusion
edem
seizure
myalgias and tetany
dysrh –> cardiac arest
TLS: ecg
qt interval prolongation due to hypoca, p wave flattening, PR and QRS interval prolongation
T wave peaking due to hyperk
TLS: diagnostic testing
chem 10 - K, phosphate, ca (ionized), BUN, Cr
uric acid ON ICE if had rasburicase already
LDH
TLS: management ED
- 3L/m2/d (as high as 5-6L /d)
- DialysisCRRT if Cr really bad/oliguria at BL
- Limit dietary intake
- Don’t tx hypoca as secondary to excess phosphate
- shift K (insulin, bicarb, beta agonist), ca gluconate if needed, etc usual tx
- hyperuric: allopurinol, febuxostat or rasburicase
TLS: nephrotoxic compound of ca phosphate: how to hypocalcemia tx or when to?
don’t tx as higher risk for getting this
only time to tx is cardiac dysr, neurologic (seiz, coma), hyperK
TLS: mechanism allopurinol in hyperuriciemia
analog of uric acid precuros hypoxanthine to competitively inhibit enzymatic conversion of xanthine to uric acid
xanthine watch kidneys though!!
TLS: hyperuricemia with tx of feboxostat - how does this work?
noncompetitive inhib of xanthine oxidase enzyme
not as good as allopurinol
TLS: hyperuricemia - how does rasburicase work?
recombinant enzume of urate oxidase, turns uric cid into allantoin
TLS: rasburicase dose
0.05-0.15mg/kg x1 dose (adult typc 6mg)
What is a CI to rasburicase?
G6PD deficiency as hydrogen peroxide is a byproduct of drug and can trigger hemolytic crisis
Complications of rasburicase
methemoglobinemia
hemolytic crisis of G6PD deficient
Leukostasis level
CLL 500 vs AML <100 (really depends on ca)
Leukostasis: complications
retinal hemorrhage
CNS typical
MI
acute limb ischemia
priapism
Renal vein thrombosis
renal infarction
Leukostasis: what might you see on VBG o2 if it waits to be sent?
leukocytes will eat o2 so it looks falsely low
Leukostasis: ED management
- reduction of blood viscosity via IV fluids
- avoid RBC as will incr viscosity
- leukaphresis
and or - dose of hydroxyurea (works 24-48 hr)
and or - chemo agents per oncology, but watch for TLS
SVC syndrome: when is flow compromised?
20-40mmhg
SVC syndrome: mc malignancies causing?
lung ca
lymphoma
SVC syndrome: outside of neoplasm, what is second mc cause?
thrombus
SVC syndrome: hx symptoms
upper extreimity, chest or face edema or erythema
-possible sobm dysphagia, cp, cough
SVC syndrome: signs on PE
elevated JVD
edema, flushing or cyanosis of the face, arms, upper trunk
vc paralysis blurred vision, horner sydrome are possible
pleural effusion
SVC syndrome: dx
cellulits or deep tissue infection of face neck (ludwig angina)
thoracic inlet syndrome
obstruction of -DVT in IJ or subclavian vein)
SVC syndrome: diagnostics
thoracic and contract enh CT
typically like to know what ca prior - may ned bronch/bx
SVC syndrome: tx
Elevated HOB, supplemental o2, anticoag if b thrombus
know the cancer
+/- rads if appropriate
+/- endovascular stenting
Monoclonal antibody therapies: mc ca?
lymphmas
colon
lung
h+N
Breast
Monoclonal antibody therapies: basic physiology
nonconjugated antibodies bind to tumor target, marking tumor for kill by antibody depn cell mediated cytoxicity and compliment dependent
Monoclonal antibody therapies: typical infusion reaction for alemtuzumab, ibritumomab, trastuzumab
type I anaphylaxis like
Monoclonal antibody therapies: which one causes sudden cardiac death?
cetuximab
colon/lung/H+N
Monoclonal antibody therapies: which specifically causes cardiomyopathy?
trastuzumab
Monoclonal antibody therapies: which specifically causes hepatotoxicity?
inotuzumab
Monoclonal antibody therapies: how to work up
if looks like sepsis, infectious w/u
if cardiac - usual
neuro - brain imaging
Monoclonal antibody therapies: management
Largely supportive
High temp - antipyretics, mild infction - histamine blocker
HD sypport as needed
if worried about anaphylaxis tx it
Monoclonal antibody therapies: which can cause PML?
brentuximab
ofatumumab
rituximab
Monoclonal antibody therapies: rituximab notable complications?
severe infusion reaction
TLS
severe mucocutaneous reactions
PML
T lymphocyte checkpoint inhibitor therapies and complications: how do these work?
reduce T cell tolerance to allow T cell immune response against tumor specific antigen bearing cancer cells (as these attack T cells normally)
T lymphocyte checkpoint inhibitor therapies and complications: which 2 checkpoints is self tolerance achieved by?
prevent mature t cells into peripheral tissues from attacking self antigen bearing cells (inhibit these) –> TLA-4, PD-1
T lymphocyte checkpoint inhibitor therapies and complications: most feared complication?
hypophysitis - immune mediated pitu disease which can cause shock due to GC deficiency and colitis
T lymphocyte checkpoint inhibitor therapies and complications: cardiac issues
pericardial effusion
myocarditis
T lymphocyte checkpoint inhibitor therapies and complications: endocrine
hypophysitis: anorexia, fatigue, headache, nausea, diplopia, confusion, temp intol… 6-12 weeks post starting
thyroid dysfunc
T lymphocyte checkpoint inhibitor therapies and complications: GI
colitis
diarrhea
hepatotoxicity
T lymphocyte checkpoint inhibitor therapies and complications: hematologic
neutropenia
anemia
ITP
T lymphocyte checkpoint inhibitor therapies and complications: skin
intraoral lesion
skin toxicity
T lymphocyte checkpoint inhibitor therapies and complications: neurologic
MG
GBS
T lymphocyte checkpoint inhibitor therapies and complications: pulmonary
pneumonitis
T lymphocyte checkpoint inhibitor therapies and complications: renal
AKI
T lymphocyte checkpoint inhibitor therapies and complications: rheum
vasculitis
myalgias
arthralgias
T lymphocyte checkpoint inhibitor therapies and complications: general management
supportive, specific to presentation
if sp to qol - consider taking to oncology: prednisolone, methylpred if hypophysitis
T lymphocyte checkpoint inhibitor therapies and complications: diagnosing and treating hypophysitis
visual field test, MRI brain, pitu function test
meythlpred 1-2mg/kg/d IV
T lymphocyte checkpoint inhibitor therapies and complications: colitis dx and tx
ct imaging abdo pelvis, test for cdiff, colonoscopy/endoscopy considerations
consider predn and if severe, infliximab
Adoptive cell transfer therapy and complications/Chimeric Antigen Rector (CAR) - T cell therapy: what is this?
pt own t cell is reprogrammed to attack ca cell after harvest from leukophoresis
Chimeric Antigen Rector (CAR) - T cell therapy: what CD are these 2 (tisagenleleucel and axicabtagene ciloleucel) designed to attack?
CD-19, B cell sp
Chimeric Antigen Rector (CAR) - T cell therapy: 2 major complications
cytokine release syndrome
immune effector cell associated neurotoxicity syndrome
Chimeric Antigen Rector (CAR) - T cell therapy: Cytokine release syndrome - what is this?
uncontrolle ck release leading to life thr inflamm (60% pt so ++ prevalent) –> end organ dysfun and looks like spesis as fever, malaise, fatigue, rash, hypotension
Chimeric Antigen Rector (CAR) - T cell therapy: Cytokine release syndrome onset from therapy?
~3d
Chimeric Antigen Rector (CAR) - T cell therapy: immune effector cell-associated neurotoxicty syndrome -what is this?
cns undergo immune cell mediated damage (50% CAR-T)
Chimeric Antigen Receptor (CAR) - T cell therapy: Immune effector cell associate neurotoxicity syndrome: symptoms
confusion, aphagsia, headach,e tremor, behaviour change, peripheral numbness
**expressive aphasia
Chimeric Antigen Receptor (CAR) - T cell therapy: Immune effector cell associate neurotoxicity syndrome: which type of aphasia is very sn and sp to this?
expressive
Chimeric Antigen Receptor (CAR) - T cell therapy: Immune effector cell associate neurotoxicity syndrome: median onset post tx
4d
Chimeric Antigen Receptor (CAR) - T cell therapy: Immune effector cell associate neurotoxicity syndrome: how to work up in ED
- tx as sepsis until provden otherwise and or stroke if necessary: image, septic work up, +/- eeg/ +/- LP
MRI may show t2 hyperinensity in wm and thalami, csf can show elevated levels of pro nad leykocytes (needs cultures to r/o meningitis)
Chimeric Antigen Receptor (CAR) - T cell therapy: Immune effector cell associate neurotoxicity syndrome: management in the ED (once know not sepsis, stroke, etc):
Low grade CRS: tx symptomatically
More severe: Tocilizumab and CS following this if no response
Supportive: IVF, vasopressors, respiratory support
Chimeric Antigen Receptor (CAR) - T cell therapy: Immune effector cell associate neurotoxicity syndrome: how does tocilizumab work for this?
anti IL 6 receptor antibody for Cytokine release syndrome
What antibiotics have antipseudomonal coverage
with imipenem, meropenem, ceftazidime, or cefepime is as effective as traditional dual therapy with an antipseudo- monal penicillin (piptazo) and aminoglycoside
When should vancomycin be included for febrile neutropenia pt?
Hypotension or cardiac involvement
suspected cath infection
+ blood cultures of a + organism
known colonization with MRSA or cephalosporin R pneumococcus
Cairo Bishop score for TLS
Meet more than 2/4 of lab in same 24h criteria:
lab TLS: uric acid >8
K >/=6
Phos >/=4.6
Ca </=7
(greater than 25% incr)
Clinical:
AKI as Cr >/=1.5 x ULN N
cardiac arrh
seizure tetany or other symp
Which cancers cause hypercalemia
Hem: leuk, lymphoma, MM
Head and neck
Breast
Lung
ovarian
renal
endometrial
