Andrew Grouse MBBS FACEM

Department of Emergency Medicine

Nepean Hospital
NSW
Australia

A 64 year old man BIBA with a behavioural disturbance.

B/G
Type 2 NIDDM
Squamous cell carcinoma lung with metastatic disease, diagnosed 2
yrs ago, chemoRx ceased six weeks ago
Hypertension
PVD
HPI
Four day Hx progressive confusion and drowsiness. Drinking but not
eating. Several falls but no significant injury.
Medications
Metformin, oxycontin, fentanyl patch, amlodipine
Habits: Smoked 35 pack years ceased 3 yrs ago, EtOH light

Examination
Cachectic, drowsy
BP 145/90, P 102, T 37.5, RR 20, SaO2 93% RA Glucose
7.8
Opens his eyes to voice, disorientated T&P, uses appropriate
words
Clinically dehydrated, neck veins flat
Chest: Reduced breath sounds on the R side
Abdomen: No masses or organomegally
No lateralising neurological signs

Problem:
Confusion in a patient with metastatic squamous cell carcinoma of the
lung
DDx
Factors related to malignancy:
Cerebral metastases
Metabolic causes: Hyponatraemia (SIADH common with small cell
carcinoma) Hypercalcaemia
Sepsis
Complication of therapy: Medications
Cause unrelated to malignancy

Na
144 mmol/L (136-148)
K
4.3 mmol/L (3.8-5.0)
Cl
110 mmol/L (95-110)
CO2 28 mmol/L (24-31)
Urea
10.1 mmol/L (2.5-6.4)
Creat
102 mol/L (55-105)
Bilirubin 18 mol/L (5-20)
AST 39 U/L (5-52)
ALT 55 U/L (4-35)
ALP 567 U/L (18-116)
Alb
30 g/L (33-50)
T Protein 67 g/L (66-82)
Ca
3.6 mmol/L (2.2-2.6)
Mg
0.7 mmol/L (0.7-1.1)
Phosp
0.6 mmol/L (0.8-1.5)

WCC
12.1X 109/L
Hb 102 g/L
Platelets 450 X 109/L
MCV

82 fL

Total calcium changes with serum albumin

concentration. Thus the measured calcium
must be corrected for hypoalbuminaemia
Serum Ca = measured Ca + 0.2*(normal albumin
measured albumin)
Ca = 3.6 + 0.2*(44 30)
= 3.88 mmol/l
CT brain normal
Explanation for altered mental state assumed to
be hypercalcaemia

Normal
Calcium
Homeostasis

feedback

Hypercalcaemia
in Malignancy

Tumour
1,25(OH)2D

feedback

PGs ILs
GM-CSF
RANKL

Solid

Breast (almost always
bone mets)

Lung (SCC commonly,
small cell rarely)

Head & neck (often
without bone mets)

Others: urological,
bowel, prostate (rare)
and many others (up to
20% of all pts with
cancer)

Haematological

Multiple myeloma

NHL

Other causes
Refer to the books!
Long tourniquet time
Hyperparathyroidism
Granulomatous diseases
Drugs (thiazides, Li)

KIDNEY
Polyuria
Polydipsia
Electrolyte &
water loss

CNS
Confusion to
Coma

(Stones)
Moans
Bones
Groans
GUT
Constipation
Anorexia
Nausea
PUD

CVS
Short QTc
Prolonged QTc
Dysrhythmias
Hypertenstion

Aims

Restore circulating volume

Replace electrolytes

Reduce serum calcium

Prevent recurrence of hypercalcaemia

Consider

NOT treating!

50% one month mortality


Restores

circulating volume, increases Ca

filtration and is calciuric

No randomised trials supporting its use

Reduction of 0.5 0.75 mmol/l in 36 hours

Beware of hypernatraemia and fluid
overload

Remember to replace K, Mg, Phosphate
as necessary


Inhibit

osteoclastic activity and bone

reabsorbtion

Pamidronate and Zoledronate most
efficacious (response rate about 90%)

Pamidronate cheaper

Serum Ca usually falls in 48 hours,
normalisation in 4/7

Side effects generally minor
Osteonecrosis of the jaw?
GI side effects
Possibly renal dysfunction. No change in dose

required with Creatinine < 250 mol/L


Loop

diuretics

No randomised trials to support their use

Risk of significant electrolyte and fluid

balance disturbances
Should be consigned to history

Corticosteroids

Inhibit osteoclastic activity

Increase calcuria
Mostly used for haematological

malignancy and breast cancer


Calcitonin

Inhibits osteoclasts
Inhibits renal reabsorption of calcium
No serious side effects
Rapid onset of action (2 4 hours)
Mild reduction only
May have a role when used in

combination with bisphosphonates when

a rapid reduction of Ca level is required


Gallium

nitrate

Developed as an anticancer agent

Unclear how it lowers calcium levels
Very long infusion time
Safe and effective
Slow onset of action
Limited role


Dialysis
HD and PD both very

effective
Normalisation of Ca
within 2 to 3 hours
Suitable for patients in
renal failure

Treat the cancer
The cancer needs to be

treated to prevent
recurrence of
hypercalcaemia

A 42 year old man with a history of lymphoma. Treated with

chemotherapy until 9 months ago. In remission since

Recent Weight loss 4 Kg and night sweats

Last three days
Cough, dyspnoea, mild chest discomfort
Dizzyness
Todays attendance precipitated by an episode of syncope when he
stood up from a chair
PH Nil relevant
Meds Nil

o/e
BP 75/40 PR 128 RR 28 Sa02 92% RA
Chest equal breath sounds
Heart sounds audible
Abdomen mild epigastric tenderness
Pitting oedema to the midcalf

HYPOVOLAEMIC
Haemorrhage
Fluid loss

DISTRIBUTIVE
Sepsis

Malignancy
with
Shock

CARDIOGENIC
Drugs
Ischaemia

OBSTRUCTIVE
Pulmonary
embolism
Pericardial
tamponade

What other clinical sign is most useful in

stratifying patients into one of these
groups?

Low
JVP

Jugular Venous
Pressure

High JVP

HYPOVOLAEMIC
Haemorrhage
Fluid loss

CARDIOGENIC
Drugs
Ischaemia

DISTRIBUTIVE
Sepsis

OBSTRUCTIVE
Pulmonary
embolism
Pericardial
tamponade

JVP elevated and rises on

expiration (Kussmals
sign)
Heart sounds difficult to
hear
Pulsus paradoxus 50
mmHg
Becks triad
Hypotension
Jugular venous distention
Muffled heart sounds

What is the most appropriate next step?


Malignancy

most common cause in

medical patients

Malignancies with cardiac involvement at
autopsy:
15 35% lung cancer
60% melanoma
15% lymphoma


Malignancy

Lung
Breast
Lymphoma (Hodgekins, NHL)
Leukaemia
Almost any malignancy

Radiation

Drugs

(anthracyclines, ATRA)

Graft v Host reaction

Infections (NB immunosuppression)


Direct spread from lung and oesophagus

Impaired lymphatic drainage with mediastinal

lymphatic involvement

Haematogenous spread

Fluid accumulation

Insideous with radiation and drugs

Rapid with haemorrhagic effusion eg

leukaemias with thrombocytopenia,

sarcomas, mesothelioma erode pericardial
blood vessels


Pericardial

aspiration

Pericardial window

Prognosis

Mean survival 4 months

25% one year survival
Better prognosis with breast than lung cancer