Confusion For Medical Finals (based On Newcastle University Learning Outcomes)

Hospital Based Practice – Confusion.

Confusion. •

Can be: o

Acute or sub – acute. 

o

Delerium

Chronic and progressive. 

Dementia

•

Causes of delirium can also exacerbate dementia, to give a acute on chronic picture.

•

Confusion in the elderly is very common o

Can be exacerbated by admission to hospital.

Differential diagnosis of confusion. •

Dementia. o

o

Commonly. 

Alzheimer’s disease



Vascular dementia



Lewy body dementia



Fronto – temporal dementia

Rarer: 

Chronic alcohol abuse



Huntington’s chorea



CJD



Parkinson’s disease



Pick’s disease



HIV



Pellagra



Subacute sclerosing panencephalitis



Progressive multiple leukencephathy



Pellagra. •

Niacin deficiency

o

Treatable causes. 

Have to be excluded in all patients.



Deficiencies •

B12

•

Hypothyroidism

•

Thiamine



Subdural haematoma



Normal pressure hydrocephalus



Neurosyphilis



Resectable tumour



Depression •

•

Pseudodementia.

Delerium o

o

o

Infection. 

Any



Most commonly •

UTI

•

Pneumonia

•

Cellulitis

•

Meningitis

•

Encephalitis

Drug intoxication. 

Opiates



Anxiolytics



Steroids



Tricyclics



Anticonvulsants



Drugs of abuse.

Drug withdrawal. 

Alcohol



Benzodiazepines.

o

Metabolic. 



o

Failures. •

Liver

•

Kidney

•

Cardiorespiratory. Hypoxia

o

Hypercapnia

Electrolytes. •

Hypernatraemia

•

Hyponatraemia

•

Hypoglycaemia

•

Hypercalcaemia

Vitamin deficiencies. 

Thiamine. •

o

o

Wernicke – Korsakoff

Cerebral pathology. 

Abscess



Tumour



Haemorrhage



Infarction



Trauma



Epilepsy



Post - ictal

o

Pain

o

New surroundings. 

Hospital ward. •

Possibly without good hearing (missing/ forgotten hearing aid)

•

Possibly without good sight (missing/ forgotten glasses)

History in the confused patients. •

Establish whether patient has delirium or dementia. o

Good collateral history from: 

Relatives



Carers



Close friends

o

Review previous hospital notes.

o

Good social history is vital. 

Allows the problems to be put in context.

•

Try and identify possible causes for the confusion.

•

Pattern of confusion. o

Confusion developing 2 days after hospital admission could be due to alcohol withdrawl.

o

Delerium. 

Develops over hours – day.



Characterised by:



o

•

Clouding of consciousness

•

Fluctuating in severity. o

Worse at night.

o

May have lucid periods during the day.

•

Poor recent memory

•

Disorientation

•

Hallucinations

Patient may appear. •

Agitated

•

Uncooperative

•

Paranoid

Dementia. 

Gradual onset over months to years.



Characterised by: •

Global deterioration in higher cerebral functions.

o

o

•

No change in levels of consciousness

•

Deterioration tends to be progressive

•

Often exacerbated by removal from familiar environment.

•

Multi – infarct dementia progresses in a stepwise fashion.

More rapid onset occurs with: 

CJD



Hydrocephalus



Depression

Depression can be suggested by: 

Complaining of memory loss. •

Patients with dementia or delirium tend not to realise that their losing their memeory.

•

Poor effort at attempting tests.

•

Personal or family history of depression.

Possible underlying causes. •

Age. o

Dementia becomes increasingly common after 60 years.

o

In younger patients a thorough search for an underlying cause should be made.

•

Underlying infection

•

Raised ICP o

Headache worse on: 

Coughing



Sneezing



Leaning over

o

Headache worse in the morning.

o

Visual disturbances. 

•

Due to papilloedema

o

Nausea and vomiting

o

Diplopia. 

False localising



CN VI palsy

Risk factors or known vascular disease. o

Previous CVD, Stroke, TIA

•

•

o

Age

o

Sex

o

Smoking

o

Elevated Blood pressure

o

Diabetes

o

Exercise

o

Cholesterol

o

Genetics

Dietary history. o

Vitamin deficiency

o

Alcohol use

•

•

Chronic alcohol abuse



Folate and thiamine deficiency.

Previous head injury. o

•



Subdural haematoma

Drug history. o

Sedatives

o

Anticonvulsants

o

Steroids

Other neurological symptoms. o

Cerebrovascular disease

o

MS

o

Cerebral tumour

o

Cerebral abscess.

Past medical history. o

Renal disease. 

o

o

Malignancy. 

Brain metts



Hypercalcaemia



Paraneoplastic

Diabetes. 

•

Uraemia

Insulin overload

Family history. o

Wilson’s disease. 

o

Autosomal recessive

Huntingdon’s chorea.

 o

•

Autosomal dominant.

Depression

Brief psychiatric history. o

Particularly symptoms of depression. 

Poor sleep



Loss of interest in things



Guilt



Poor energy



Poor concentration



Anxiety



Psychomotor retardation



Suicidality

Examination of the confused patient. •

Since causes of confusion are so varied, a thorough clinical exam should be conducted.

•

Particular attention should be paid to. o

Glasgow Coma Scale.

Category Best motor response

Best verbal response

Response

Score

Moves on command

6

Localises to pain

5

Withdraws from pain

4

Flexes to pain

3

Extends to pain

2

No movement

1

Coherent words

5

Confused speech

4

Inappropriate speech

3

Grunting

2

No speech

1

Best eye opening response

o

o

To pain

2

No opening

1



Oxygen saturation should be performed.

Blood pressure. Hypotension. •

Overwhelming infection

•

Cardiac failure

Hypertension. •

Risk factor for cerebrovascular disease.

•

Can be caused by raised intracranial pressure.

Blood glucose. Hypoglycaemia.

Evidence of head injury. 

o

3

Hypoxia is a common cause of confusion in hospital



o

On command





o

4

Cyanosis.



o

Spontaneous

Subdural haematoma.

Signs of infection. 

Temperature.



Neck stiffness



Consolidation on CXR



Signs of endocarditis



Abdominal tenderness



Otitis media



Pressure sores



Cellulitis.

Mental state. 

AMT is used for •

Confirming confusion

• 



Monitoring progress.

MMSE is used for: •

Diagnosing dementia

•

Providing a baseline for monitoring of deterioration.

Abbreviated Mental Test.  Address for recall. 42 West Street.  Age  Date of birth  Time ( to the nearest hour)  Year  Name of this place  Recognition of 2 people  Year of WWI  Name of current monarch  Count backwards from 20

o

Focal neurological deficit. 

Pattern of signs may provide clues to the diagnosis.



Fundoscopy to look for •

Papilloedema. o

•

Optic atrophy. o

•

Raised ICP

Demylination

Subhyaloid bleeding o



Parkinsonism



CJD signs.

Subarachnoid haemorrhage

•

Myoclonus

•

Extrapyrimidal signs

• o

Aphasia.

Signs of chronic liver disease. 

Hepatic encephalopathy can cause confusion.



Chronic liver disease may also indicate:



•

Alcoholism

•

Wilson’s disease.

Malignancy. •

Breasts

•

PR

•

Lymph nodes

•

Skin

Investigating the confused patient. Blood •

FBC. o

o

•

Reactive picture in 

Malignancy



Infection



Inflammation

Anaemia, with raised MCV in deficiency of: 

B12



Folate

ESR. o

o

o

Raised in 

Malignancy



Infection



Inflammation

U&Es. 

Hyponatraemia



Hypernatraemia

LFT. 

Abnormal in liver disease.



γ – glutamyl transferase raised in alcohol consumption.

o

Thyroid function test. 

o

Low T4 in hypothyroidism

Serum calcium 

Hypocalcaemia



Hypercalcaemia

o

Serum glucose

o

Serum B12 and red blood cell folate.

o

Syphilis serology

o

ABG

o

Blood culture. 

If considering infection.

Urine •

MSU for: o

Microscopy

o

Culture

o

Sensitivity. Radiology

•

•

CXR may show: o

Pneumonia

o

Cardiac failure

o

Malignancy

CT of MRI of head may show: o

Tumour

o

Infarction

o

Haematoma

o

Hydrocephalus

o

Abscess.

Other tests •

When clinically indicated, consider: o

Malaria.



Thick & thin films.

o

HIV serology

o

Urine toxicology screen

o

Thiamine deficiency 

o

o

Wilson’s disease. 

Low serum copper



Low caeruloplasmin



Raised 24 – hour copper excretion.

Electroencephalogram. 

o

Red cell transketolase.

Typical changes in herpes simplex encephalitis.

Lumbar puncture & CSF examination. 

Protien



Glucose



Microscopy



Culture



Oligoclonal bands.

Pathway for managing confusion.

Confusion

History & Examination

CT Scan

Abscess Tumour Haemorrhage Haematoma Infarction

Alcohol withdrawl.

Acute/ subacute

Longstanding

FBC U&E Glucose LFT ABGs Sepsis screen Drug screen Consider CT

FBC U&E Biochemistry B12/ folate TFTs Syphilis serology Consider CT

Biochemistry ABGs

Failure of: Cardiac Respiratory Liver Renal

Drug history

Intoxication Withdrawl

Temperature Cultures

Sepsis

Untreatable

Alzheimers Vascular Lewy body Fronto – temporal

Treatable

B12/ folate deficiency Hypothyroidis Thiamine deficiency Subdural haematoma Hydrocephalus Syphilis Tumour Depression

•

•

•

Acute onset of confusion in the recently hospitalised is acute alcohol withdrawl/ delirium tremens until proven otherwise. o

Check serum phosphate.

o

Can be > 0.4 mmol/L in acute withdrawl.

If left untreated, risk of: o

Seizures.

o

Permanent neurological deficits.

o

Death

Minor symptoms can be managed at home by the GP. o

Often a short admission is more effective

o

Allows close observation for:

o

•



Complications



Psychosocial assessment



Rehabilitation.

Admission particularly important if: 

History of seizures



Signs of Delerium Tremens

Presentation. o

o

Initially. 

Anxiety



Tremor



Hyperactivity



Sweating



Nausea & retching



Tachycardia



Hypotension



Mild pyrexia.



Insomnia



Sweating

Symptoms normally peak at 12 – 30 hours, and subside by 48 hours.

o

•

May be complicated by generalised tonic – clonic seizures. 

“Rum Fits”



Rarely progress to status epilepticus.



Distinguished from epilepsy by EEG.



May be precipitated by flickering lights.



Particularly likely to occur in those with epilepsy

Delerium tremens. o

Occur in < 5% of acute withdrawl p[aitents.

o

Usually 3 – 4 days after abstinence.

o

Untreated, is associated with mortality of 15%.

o

Features include.  

Disorientation



Labile mood



Irritability



Coarse tremor



Agitation



Confusion



Delusion



Hallucinations



•

Visual

•

Auditory

Fever •

Occisionally severe



Sweating



Tachycardia



Acidosis.



•

Rare

•

Ketoacidotic

•

Lactic.

Also be aware of: •

Hypoglycaemia

•

Wernicke – Korsakoff psychosis

•

Subdural haematoma

•

Hepatic encephalopathy.

•

Management. o

General management. 

Nurse in a well lit room to prevent disorientation.



Rehydrate. •

IV fluids if needed

•

Avoid saline in patients with chronic liver disease.



Monitor urine output.



Vitamin supplements. •

Parbinex 2 – 3 ampulles

•

Treat for 5 days

•

Give as slow IV over 8 hours

•

Beware of anaphylaxis.

•

Oral therapy for 1 week. o

Thiamine 100 mg BD

o

Vitamin B 2 tablets TDS

o

Vitamin C 50 mg BD



Monitor and treat BM for hypoglycaemia.



Severe hypophosphataemia may complicate alcohol withdrawl. •





Give IV polyfusor phosphate if serum phosphate < 0.6 mM

Exclude intercurrent infection. •

Pneumonia

•

Urine

•

Skin

Beta – blockers may be useful for hypertension.

o

Sedation. 

Long – acting benzodiazepines are often used. •

Commonly used. o

o •

•



30 mg QDS for 2 days.



20 mg daily for 2 days



10 mg daily for 2 days



5 mg daily for 2 days



Women should be started on 20 mg and tapered down



Reduce dose if: •

Liver disease

•

Elderly

•

Thinness

Diazepam (Valium)

Lorazepam is metabolised by the liver o

•

Chlordiazepoxide (Librium)

Contraindicated in liver disease.

Chlormethiazole is no longer used regularly. o

Highly dependency inducing

o

Dangerous if combined with alcohol.

Carbamazepine. o

Effective as benzodiazepines.

o

Use limited by side effect profile. 

Drowsiness



Headache



Migraine



Motor co – ordination impairment



Upset stomach



Less commonly. •

Arrythmias

•

Blurred vision

•

Pancytopaenia

•

Aplastic anaemia

•

•

Start with 200 mg daily as divided does

o

Increase to 400 mg daily over next 2 -3 days

o

Taper off by day 8.

Haliperidol. o

For severe agitation

o

10 mg IM

Wernicke – Korsakoff syndrome. o

Wernicke disease consists of a triad of: 

o

Ophthalmoplegia. •

Nystagmus

•

Nerve VI palsy



Cerebellar ataxia



Confusion

In Korsakoff syndrome. 

Confusion predominates



Often presence of: •

Psychosis

•

Amnesia.

• 

•

o

o

Retrograde

o

Antegrade

Confabulation.

Causes permenant neurological damage.

o

Diagnosis by reduced red – cell transketolase activity.

o

Treat with IV thiamine on clinical suspicion.

Seizures. o

Withdrawl symptoms are typically self limiting.

o

If needed, give IV diazepam. 

o

Give chlordiazepoxide. 

o

10 mg over 5 minutes.

Not chlormethiazole or carbemazipine.

Phynetoin. 

Less effective.



Added if history of epilepsy or recurrent seizures.

•

Follow up o

Referral to alcohol abuse team.

o

Maintain vitamin supplementation

o

Screen for residual cognitive impairment

o

Involve Occupational therapy before discharge.

Diabetic ketoacidosis. •

Predominantly occurs in Type I diabetics.

•

Increasingly being recognised in some Type II diabetics. o

Afro – Caribbean patients. Presentation

•

Polyuria & polydypsia. o

Increasing dehydration over a few days.

•

Weight loss

•

Weakness

•

Hyperventilation or dyspnoea. o

Due to acidosis

o

Kussmaul’s breathing 

•

Abdominal pain. o

•

Exacerbates dehydration

Confusion. o

•

Have to be excluded in an acute abdomen.,

Vomiting. o

•

Deep sighing respiration.

10% develop coma.

On examination assess for: o

Hydration status.

o

Ventilation rate

o

Smell of ketones.

Investigations. •

Blood glucose. o

Not always high.

o

Patient can be severely acidotic at values as low as 10 mM. 

•

ABGs.

Eg. if patient has recently taken insulin.

o •

Assess degree of acidosis.

U&Es. o

Sodium will need to be corrected. Corrected Sodium = [Na+] +

•

•

o

Assess Potassium

o

Assess renal function.

Ketones strongly positive.

o

Starvation can cause mild ketones in normal patients.

o

Sulphydryldrugs, like captopril, can cause false positive for ketones.

FBC.

o

WCC will be raised

Leukaemoid reaction can occur in absence of infection.

o

Blood culture.

o

Urine culture.

Plasma ketones. Many labs do not regularly perform, so need to be specifically asked for

CXR. o

•

Mainly neutrophiles.

Septic screen.

o •

Look for signs of infection

Amylase. o

May be high with abdominal pain ± vomiting in absence of pancreatitis.

o

Acute pancreatitis will occur in 10% of patients with DKA.

Common precipitants of DKA. •

Infection. o

•

30%

Non – compliance with treatment. o

•

– 1.6

o



•

5.5

Urinalysis.

o

•

1.6 x [Glucose]

20%

First presentation of diabetes. o

25%

Poor prognostic factors in DKA.

•

pH < 7.

•

Oliguria

•

Serum osmolality > 320 o

•

Serum osmolality = 2([Na] + [K]) + [urea] + [glucose]

Newly diagnosed diabetes.

Notes. •

Diagnosis of DKA requires: o

Positive urine or plasma ketones 

Some labs don’t record plasma ketones.



Can be estimated on the ward by diluting plasma to 1:1 with normal saline and testing with urine diptix. •

o •

•

Result of +++ corresponds to plasma ketone of 5 mmol/L

Arterial pH < 7.3 and/ or serum bicarbonate > 15 mmol/L

Elderly patients may present as hyperglycaemic and ketotic, but with a relatively normal acid – base balance. However, they are: o

Not in DKA

o

Not necessarily insulin dependant.

Always consider other causes of hyperglycaemia and acidosis. o

Aspirin overdose

o

Lactic acidosis. 

Particularly in elderly.

Management. •

•

Consider arterial line to monitor: o

ABGs

o

Potassium.

Make patient Nil by mouth for at least 6 hours. o

•

Insert NG tube if GCS is reduced. o

•

•

Gastroparesis is common.

Aspirate stomach contents due to risk of aspiration.

Insert urinary catheter. o

Oliguria

o

High serum creatinine

Broad spectrum antibiotics if infection suspected.

•

•

LMWH should be given as DVT prophylaxis. o

Good idea.

o

Not yet standard clinical practice.

Half life of insulin is short. o

•

Continued replacement by IV or SC is essential.

General methods. o

Mainstays of treatment. 

Rehydration •

Site the IV cannula for rehydration well away from any major wrist veins. o

•

This large vein may be needed for AV fistula if patient develops diabetic neuropathy.

Insert central line in patients who have a history of: o

Cardiac disease.

o

Autonomic neuropathy

o

Elderly.

•

Use normal saline ± potassium until BM < 12 mmol/L.

•

Average fluid loss in DKA is 3 – 6 L. o

•

Aim to restore this over 24 hours.

If hypotensive and oliguric (and no history of heart disease), give following regime: o

IV colloids ± N saline to restore BP.

o

1 L saline over 30 minutes.

o

1 L saline every 2 hours, for 8 hours. 

Add potassium based on current serum potassium.

Plasma potassium (mmol/L)

Potassium added to each litre (mmol)

< 3.0

40

< 4.0

30

< 5.0

20

o



Potassium can be depleted by 1000 mmol.



Plasma potassium can rapidly fall as potassium shifts into cells under action of insulin.



Use less potassium in patients with:

Oliguria.

Until fully rehydrated.

If pH < 7 give isotonic (1.26%) bicarbonate at 500 ml/h.. 

Faster rates cause paradoxical intracellular acidosis.

o

Add 10 – 20 mEq Potassium per 500 ml.

o

There is no evidence that use of bicarbonate improves outcome in DKA.

When BM < 12 mmol/L start o

5% dextrose infusion

o

Continuous insulin infusion. 



•

Use of bicarbonate is controversial. o

•

Renal impairment

1 L saline every 4 hour, with potassium added as above. 

•

•

Continuous insulin is required to inhibit ketoacid production.

Insulin therapy. •

Dilute 50 units of actrapid insulin in 50 ml 0.9% saline, and administer by IV infusion.

•

Start off infusing at 0.1U/kg/h. o

This is 7 units/hour for a 70kg patient.

•

If BM falls by 5 mmol in one hour, halve rate to 0.05 U/kg/h.

•

When BM < 12 mmol/h, change the infusion for one diluted in 5% dextrose rather than saline. o

•

Infuse according to the sliding scale below.

BM should be checked hourly, and rate altered.

Blood glucose (mmol/L)

Insulin infusion (units/hour)

0.0 – 2.0

Stop insulin – call specialist

2.1 – 4.0

Call specialist

4.1 – 7.0

0.5 – 1

7.1 – 11.0

2

11.1 – 20.0

4

> 20.

7 – call specialist

•

This sliding scale is a guide, and should be tailored to the patient and response to therapy

•

Aim for fall in BM of 5 mmol/h, with correction of acidosis and plasma bicarbonate levels.

•

If glucose or acidosis not changing, increase insulin rate accordingly.

•

Keep BM = 10 – 14 mmol for the first 24 hours.

•

o

Or until ketoacidosis resolves.

o

Use 5% dextrose infusion to do this.

Maintain IV insulin until 4 hours after regular SC insulin is restarted.

Complications •

Assessment during treatment. o

Rapid normalisation of biochemistry can be detrimental in all patients.

o

Better to be cautious and less than perfect, than be enthusiastric and dangerous.

o

Check ward BM hourly. 

o

Check lab BM 4 hourly.

Check electrolytes every 2 hours, reducing to 4 hours when patient consistently improving. 

Main risk is hypokalaemia.

o

Do ABGs every 4 hours, until persistent improvement or normalised.

o

Check plasma osmolality every 4 hours.

o

Consider need for regular/ continuous ECG monitoring for T – wave changes

o

Check phosphate daily.

o

•



Falls due to treatment.



Moved intracellular with potassium.



If phosphate drops to < 0.4 mmol/L. •

Monobasic potassium phosphate IV infusion

•

Don’t exceed rate of 0.75 mmol/h.

•

Check preparation with pharmacist.

Check magnesium levels daily. 

May fall during insulin therapy.



If levels fall < 0.6 mmol/L •

4 – 8 mmol in 50 ml 0.9% saline over 15 – 30 minutes.

•

Repeat as necessary.

Complications. o

Main complications. 

Hypokalaemia



Hypophosphataemia



Hypoglycaemia •



Hyperchloraemic acidosis •

A high anion gap acidosis in a well – hydrated patient.

•

May be seen in:

• 

Due to over zealous insulin replacement.

o

Excessive administration of saline.

o

Increased consumption of bicarbonate.

No specific treatment is required, just correct acidosis.

Cerebral oedema. •

Mainly in children o

May be precipitated by sudden shifts in plasma osmolality.

o

Symptoms include: 

Drowsiness

o



Severe headache



Confusion

Management. 

Open airway.



Give oxygen



Consider invasive ventilation. •



Correct hypotension



Treat seizures



Give IV mannitol at 0.5 g/kg body weight. •





Enforced hyperventilation can blow off carbon dioxide and reduce ICP.

Repeat as necessary.

Transfer to ITU.

o

Mortality of 70%

o

Full recovery of normal function about 7 – 14 %

Thromboembolism. •

Tissue hypoperfusion due to dehydration can trigger coagulation cascade.

•

Consider LMWH prophylaxis for those at risk.

Hyperosmolar Non – Ketotic Coma (HONC) •

Occurs in elderly patients with non – insulin dependant diabetes.

•

Large risk of venous and arterial thrombi

•

Much higher mortality than DKA

•

Presentation. o

Elderly

o

Previously unknown diabetic.

o

Insideous onset of polyuria and polydypsia.

o

Severe dehydration

o

Reduced GCS. 

Degree correlates with increase in plasma osmolality.



Osmolality > 440 associated with coma.

•

o

Respiration typically normal

o

May present with: 

CVA



Seizures



MI

Investigations. o

BM. 

o

U&E. 





o

o

o

•

Greater rise in urea than creatinine.

•

If units are ignored (as urea is in mmol/L and creatinine is in μmol/L), ratio of Cr:U is about 20:1.

Significant hypernatraemia. •

Can be obscured by a high glucose.

•

Corrected sodium concentration can be calculated.

•

Before relying on corrected results, check that lab doesn’t already measure ionic sodium.

•

As glucose falls, hypernatraemia may appear to worsen.

•

If glucose is high enough, patients may present with a pseudohyponatraemia.

Plasma osmolality •

Calculated as 2([Na+]+[K+]) + [urea]+[glucose]

•

Should be > 350 mosm/kg for diagnosis.



Relatively normal.



Compare with DKA



Coexistant lactic acidosis significantly worsens prognosis.

FBC. 

Polycythemia may indicate dehydration



Leukocytosis may indicate infection.

ECG. Look for signs of ischemia.

CXR 

o

Dehydration.

ABGs.

 o

Usually > 50 mmol/L

Urine

Look for signs of infection.



Dipstix •

Ketones may be due to simple starvation.

•

Requires levels of > 5 mM for DKA



Microscopy



Culture & Sensitivity



UTI suggested by urinalysis showing. •

Blood

•

Protein.

Management. •

Rehydration and insulin are mainstay.

•

Give oxygen if hypoxic on air.

•

Nil by mouth for 6 hours. o

•

•

Insert urinary catheter if: o

Oligouria

o

High creatinine.

Anticoagulate with LMWH. o

•

Aspirate with an NG tube if reduced GCS to prevent reflux and aspiration.

Enoxaparin 40 mg SC OD

Fluid replacement. o

Be cautious in the elderly.

o

To avoid fluid overload monitor CVP

o

Average fluid loss is 8 – 10 L. 

Replace cautiously.

o

1 L saline over first hour

o

1 L saline over 2 hours

o



Add potassium as per DKA protocol.



Continue for 4 hours.

1 L saline with potassium (as per DKA protocol) QDS until rehydrated. 

Should take about 48 hours in total.

o

o

•

If corrected sodium is > 160 mmol/.L, use 0.45% saline for first 3 litres. 

Otherwise use 0.9% saline.



Remember artificial lowering effect of hyperglycaemia.

When BM < 12 mmol/L, commence 5% dextrose infusion. 

Consider stopping insulin therapy.



Consider starting oral hypoglycaemics.



Consider using diet control alone.

Insulin regimen. o

Similar to DKA protocol.

o

With HONK, stopping insulin completely is less dangerous in the short term than in DKA.

Hypoglycaemic coma. •

•

All comatose patients are hypoglycaemic until proven otherwise. o

Check with a BM

o

Confirm with a lab BM.

Most common cause of coma in a diabetic is hypoglycaemia due to drugs. o

•

Hypoglycaemic patients who are not known to have diabetes should have a lab BM saved for insulin and C – peptide determination. o

o •

Long acting sulphonyureas (eg. Glibenclamide) are more prone to do this than short acting ones.

Differential diagnoses. 

Insulinoma



Facticious drug administration.

Take these blolods before glucose is given.

Presentation. o

o

Sympathetic overactivity ( BM < 3.6 mM) 

Tachycardia



Palpatations



Sweating



Anxiety



Pallor



Tremor



Cold extremeties.

Neuroglycopaenia ( BM < 2.6 mM) 

Confusion



Slurred speech



Focal neurological deficits.

•  o

o

o

Coma

Patients with well controlled diabetes are at increased risk of hypoglycaemia. 

Can be desensitised to sympathetic sctivation.



Can develop neuroglycopaenia without warning signs.

β – blockers blunt the symptoms of sympathetic activation. 

o

Stroke – like syndrome

Patients on these drugs lose early warning symptoms.

Patients with poor diabetes control become hypersensitised to sympathetic activation. 

Develop warning signs early.



May present complaining of “going hypo” with a normal blood sugar.



Need reassurance and better diabetes control, not glucose.

Patients with diabetes post – total pancreotomy have more frequent and severe attacks of hypoglycaemia (“brittle diabetes”) 

Due to lack of glucagons producing α cells, as well as insulin producing β cells.

Causes. •

Drugs. o

Insulin

o

Sulphonyureas 

o

Particular risk in patients who have a stroke or other pathology that decreases their food intake.

Alcohol 

Acute injestion can suppress hepatic gluconeogenesis.

o

Salicylates

o

Prescription errors.

 o

•

Others. 

Disopyramide



β – blockers



Pentamidine



Quinine

.Organ failure. o

Hypopituitarism. 

•

•

Eg. chlopropamide instead of chlorpromazine

Especially acute pituitary necrosis

o

Acute liver failure

o

Myxoedmea

o

Rarely. 

Congestive cardiac failure



Chronic renal failure

Infections. o

Sepsis syndrome

o

Malaria

Tumours. o

Insulinoma

o Retroperitoneal sarcoma

Investigations. •

•

Blood glucose. o

Check with ward BM

o

Confirm with lab BM.

U&Es. o

•

Hypoglycaemia is more common in diabetic nephropathy.

Save serum prior to giving glucose. o

Insulin

•

o

C – peptide.

o

Send 20 ml to lab for immediate centrifuge if indicated.

Notes. o

Lab glucose < 2.2 mmol/L is defined as a severe attack.

o

Coma normally occurs if BM < 1.5 mmol/.L

o

Low C – peptide and high insulin. 

o

Exogenous insulin

High C – peptide and high insulin. 

Endogenous insulin. •

Sulphonyurea ingestion

•

Insulinoma.

Management. •

Acute measures. o

Take blood prior to glucose administration.

o

If history of alcohol abuse or malnutrition.

o

o



Give IV thiamine 1 – 2 mg/kg prior to beginning glucose therapy.



Risk of precipitating Wernike’s encephalopathy.

If patient is conscious and co – operative. 

50g oral glucose.



Eg. lucozade



Eg. milk and sugar

If patient unable to take oral fluids. 

o

50 ml of 50% dextrose IV

If IV access impossible. 

1 mg glucagons IM •



o

Less effective if hypoglycaemia due to alcohol.

Oral glucose to prevent recurrent hypoglycaemia.

If cause is long – acting sulphonyurea/ long – acting insulin. 

Admit patient.



Commence continuous infusion of 10% dextrose at 125 ml/h.



Check B< every 1 – 2 hours.

•

Further management. o

o

Patients should regain consciousness, or become coherent, within 10 minutes of therapy starting. 

May take 30 – 45 minutes for full cognition to return.



Don’t give further glucose boluses without rechecking BM.

If patient doesn’t regain consciousness in this time. 

Recheck BM



Consider an alternative cause. •

•

Eg. head injury due to fall while hypoglycaemic.

o

Prolonged severe hypoglycaemia (> 4 hours at < 2.s mmol) may bresult in permanent cerebral dysfunction.

o

Recurrent hypoglycaemia may induce diabetic nephropathy. 

Adaptive process to reduce insulin demand.



Insulin partly degraded by the kidney.

o

Review patient’s medication and inspect all tablets from home for a possible cause.

o

Consider psychiatric review if self – inflicted.

Liver dysfunction and recurrent hypoglycaemia. o

Hypoglycaemia is common in acute liver failure. 

o

Coma may occur due to hepatic encephalopathy rather than hypoglycaemia.

Hypoglycaemia is rare in chronic liver disease.

Hyponatraemia. •

Presentation. o

Mild hyponatraemia (Na = 130 – 135 mmol/L) 

Common. •

Especially in patients on thiazide diuretics.

 o

o

Moderate hyponatraemia (Na = 120 – 129 mmol/L) 

Usually asymptomatic.



Unless it has developed quickly.

Severe hypotension (Na < 120 mmol/L) 

 •

•

Usually asymptomatic

May be associated with: •

Disturbed mental state.

•

Restlessness

•

Confusion

•

Irritability.

Seizures and coma prevail as Na < 110 mmol/L

History. o

Drugs

o

Fluid losses. 

Diarrhoea



Frequency



Sweating

o

Symptoms of Addison’s

o

Cardiac disease

o

Lung disease

o

Liver disease

o

Renal disease.

Examination. o

Focus on careful assessment of volume status. 

Hypovolemic or Normovolemic

• 

•

Patients who are hyponatraemic and hypovolemic are salt depleted.

Oedema

o

Lying and standing BP

o

Heart rate

o

JVP ± CVP

o

Skin turgor

o

Oedema & Ascites

Investigations. o

Tests should be aimed at excluding other causes of hyponatraemia. 

Assessment of fluid status. •

Capillary refill

•

Engorged neck veins

•

Orthostatic hypotension

•

Ascites

•

Skin turgor



BM



Serum osmolality •

Compare calculated osmolality with measured osmolalaity o

•

Hypovolaemic

Correct sodium if BM is high.

Osmolar gap increased when having: o

Hyperlgycaemia

o

Ethelyne glycol

o

Mannitol



Urine osmolality



Urine sodium

Normovolaemic (normal or slightly raised ECV) SIADH: urine osm > 100, serum osm < 260, unine Na > 40 mmol/L

Oedematous states

Renal losses (uNa > 20 mmol/L)

Non – renal losses

CNS disorders

Malignancy

Pulmonary disease

Drugs

Others

Lung (oat cell)

Pneumonia

Opiates

Vasculitis

CCF

TB

Haloperidol

(eg. SLE)

Lung abscess

Amitriptyline

Abscess

Cirrhosis with ascites

Cystic fibrosis

Cyclophoshamide

Meningioencephalitis

Vasopressin

Severe myxoedema

Thiodizine

Psychogenic polydipsia

(uNa < 20 mmol/L)

Diuretics

Vomiting

Trauma

Adrenal insufficiency (Addison’s disease)

Diarrhoea

Stroke

Intrinsic renal disease.

Burns 3rd space fluid losses

Pancreas

Sub – arachnoid bleed

Lymphoma Leukaemia

Malignancy o

Prostate

o

(1 or 2 )

Hypothyroidism

Urinary tract

Lung vasculitis

Carbamazepine Clofibrate Oxytocin Chlopropramide Thiazides Vincristine

•

Management o

General principles. 

Mild asymptomatic hyponatraemia will normally resolve with treatment of underlying condition.



Correction of hyponatraemia should be gradual to avoid.



•

Fluid overload

•

Central pontine myelinolysis o

May be delayed 2 – 5 days.

o

Often irreversible or only partially reversible.

o

Dysarthrai

o

Dysphasia

o

Parparesis or quadriparesis

o

Lethargy

o

Coma

o

Seizures.

Aim to actively get [Na] = 125 mmol/L with IV fluids, then allow gradual rise as underlying cause is treated. •

Do not increase sodium by > 12 mmol./day.



Seek expert help if [Na] < 120 mmol/L, or severely symptomatic.



Patients with cirrhosis, ascites and severe hyponatraemia.

SIADH

Severe renal failure Nephrotic syndrome



o

o

•

Stop diuretics

•

Give volume expansion.

SIADH, and other conditions associated with plasma volume expansion, can cuase hypouricaemia due to increased renal clearance.

Exclude psuedohyponatraemia. 

Lipaemic serum will be obvious.



Calculate osmolar gap to check for hidden osmoles



Exclude possibility of artificially lowered [Na] by not taking blood proximal to an IV infusion.

Symptomatic hyponatraemia. 

Ie. Seizures or Coma



Aggressively increase [Na] by 6 mmol/L over 3 – 4 hours.



Then increase [Na] more slowly, so total increase is by 12 mmol/L over 24 hours.



Seek expert help.



Start IV 0.9% saline at 250 – 500 ml/h. •

o



As a rule, if 1 tire of 0.9% saline was instantly infused, it would raise serum sodium by 4 – 5 mmol/L.



Alternatively, infuse 5% saline at 50 – 850 ml/h until [Na] increases significantly

If dehydrated. 

Start infusion of 0.9% saline.



Insert central venous line if indicated.



Monitor fluid output. •

 o

Watch out for fluid overload.

Catheterise bladder if renal impairment.

Watch out for heart failure.

If not dehydrated. 

For patients with moderate SIADH, restrict fluid intake to 500 ml/24 hours.



Seek expert help.

Hypernatraemia. •

As with low sodium, hypernatraemia is normally associated with disorders of water, not of salt.

•

Presentation. o

•

Symptoms of severe volume depletion. 

Weakness



Malaise



Fatigue



Altered mental state



Confusion



Delirium



Coma

Investigations o

Assess ECV. 

Neck vein engorgement



Supine and standing BP



Cardiac signs of fluid overload.

 o

Third heart sound

•

Oedema

Skin turgor.

Assess urine and serum osmolality. 

•

•

Serum sodium > 145 mmol/L is always associated with hyperosmolality.

Causes. o

Normal or low ECV 

Renal water losses. •

Urine osmolality inappropriately low.

•

Diabetes insipidus.

•

o

Central

o

Nephrogenic

Osmotic diuresis with water replacement only. o



Eg, Diabetes Mellitus.

Non – renal water losses. •

Urinary osmolality > 400 mosmo/L

•

Hypotonic GI losses.

o •

• o

•

Eg. diarrhoea

Cutaneous losses. o

Burns

o

Heat shock

o

Sweating

o

High fever

Chest infections with prolonged hyperventilation.

Salt overload (normally iatrogenic) 

Overdose with sodium bicarbonate.



Post – operatively if huge fluid volumes used.



In ITU, when volume loaded with saline.



Concentrated infant formula.



Conn’s syndrome. •

Hypertension

•

Hypokalaemia

•

Alkalosis

Management. o

Avoid rapid and extreme changes in [Na]. 

o

Safer to cautiously change [Na]

If there is hypovolaemia. 

Start fluid replacement.



Use 0.9% NaCl to correct hypovolaemia.



Use 5% dextrose to replace water and gradually reduce [Na]

o

If patient haemodynamically stable, encourage oral fluids.

o

Check U&Es twice daily.

Hypocalcaemia. •

Presentation. o

Abnormal neurological sensations & neuromuscular excitability.

o

Numbness around mouth

o

Parasthesia of the distal limbs

o

Hyperreflexia

o

Carpopedal spasm

o

Tetanic contractions. 

May include laryngospasm

o

Focal or generalised seizures.

o

Hypotension

o

Bradycardia

o

Arrythmias

o

CCF

o

Chvostek’s sign

o



Tap facial nerve anterior to the ear.



Causes contraction of facial muscles



Seen in 10% of normal patients.

Trousseau’s sign. 

Inflate a BP cuff to 10 – 20 mmHg above SBP for 3 – 5 minutes.



The mild ischaemia will unmask latent neuromuscular hyperexcitability.



Carpal spasm is observed. •

o

•

Dd for carpospasm is respiratory alkalosis induced by hyperventilation.

Rarely. 

Papilloedema



Extra – pyramidal effects.

Causes. o

o

Vitamin D deficiency. 

Asians



Chronic renal failure

Loss of calcium from circulation. 

Extra – vascular deposition. •

Hyperphosphataemia. o

Renal failure

o

Tuumour lysis

•

Acute pancreatits

•

Osteoblastic metastases. o



Eg. prostate.

Intra – vascular binding. •

Citrate

•

Blood products

•

Foscarnet. o

•

o



Post – thyroid, parathyroid or other neck surgery.



Idiopathic



Pseudo – hypoparathyroidism

Infiltration



HIV infection

Disorders of Magnesium metabolism. Magnesium deficiency.

Other 

Sepsis



Burns



Floride intoxication



Chemotherapy. •

•

Eg. cisplatin.

Investigations. o

o

Bloods. 

Calcium



Phosphate



Albumin



Magnesium



Parathyroid hormone

ECG. 

o

•

PTH receptors stop responding.



 o

Acute respiratory alkalosis.

Hypoparathyroidism.

•

o

Anti – CMV drug.

Prolonged QT time

Skull X – ray. 

Intercranial calcification.



Seen especially in hypoparathyroidism.

Management. o

If hypocalcaemia is difficult to correct, check for magnesium deficiency.

o

Aim of acute management is to reduce the effects of low calcium, not necessarily to return calcium to normal.

o

For frank tetany. 

10ml of 10% calcium gluconate (2.25 mmol) IV over 10 minutes •

NB: Calcium chloride has 4 times more calcium than calcium gluconate.

•

Don’t muddle the two drugs up.

•

Generally gluconate is preferred as reduced risk of:

• 

o

o

o

Tissue necrosis on extravasation

o

Arrythmias.

Do not give at a higher rate, as risk of arrythmias.

Next, start calcium infusion at 0.025 – 0.05 mmol/kg/h. •

For 70 kg add 50 ml 10% calcium gluconate, or 10 ml 10% calcium carbonate to 200 ml 0.9% saline.

•

Infuse 50 – 80 ml/h.

Post parathyroidectomy. 

Mild hypocalcaemia is normal.



Requires simple monitoring and observation.



For patients who have parathyroid bone disease (“hungry bones”). •

Profound hypocalcaemia may occur when parathyroids are removed.

•

May become prolonged, and requiring treatment.

Chronic hypocalcaemia is best managed with: 

Oral calcium



Vitamin D. •



If cause is simply low calcium intake/ high excretion.

Hydroxylated Vitamin D. •

Hypoparathyroidism.

•

Problem with vitamin D metabolism.

• o

Eg. Alfacalcidol, Calcitriol.

If magnesium deficient. 

Take 20 ml (40 mmol) of 50% magnesium sulphate.



Make it up to 250 ml with 0.9% saline.



Infuse 50 ml (8 mmol) over 10 minutes.



Continuing infusing at 25ml/h.

Hypercalcaemia. •

•

.Free (ionic) calcium is dependent on arterial pH and plasma albumin. o

Increased calcium in acidosis

o

Increased calcium in low albumin.

Ionized calcium = [Ca] + 0.02(40 – [Albumin]) o

•

Most ITU departments now measure ionized calcium.

Presentation. o

Routine biochemical screen in asymptomatic patients.

o

General. 

Depression •



Weakness •

o

o

30 – 40%

30%



Tiredness



Malaise.



Constipation



Anorexia



Nausea & Vomiting



Weight loss

GI.

Renal. 

Calculi. •



If long standing

Nephrogenic diabetes insipidus. •

20%



Pre – renal failure



Chronic hypercalcaemic nephropathy

o

o

•



Polyuria



Polydipsia



Dehydration

Neuopsychiatric. 

Depression



Cognitive dysfunction



Coma



Obtundation.

Cardiac. 

Hypertension



Cardiac dysrhythmias.

Causes. o

Primary (or tertiary) hyperparathyroidism. 

o

o

Malignancy. 

Humoral hypercalcaemia.



Local osteolytic hypercalcaemia.

o

•

Metasteses

15 – 20% of patients.

Sarcoidosis

Drug related. 

Vitamin D intoxication



Theophylline toxicity



“Milk – alkali” syndrome



Thiazide diuretics



Lithium. •

Mild

•

Present in 50% of patients on long – term lithium.

Immobilization. 

o

Myeloma

Granulomatous disorders. 

o

•

Hyperthyroidism. 

o

85% of cases.

Paget’s disease

Benign familial hypocalcuric hypercalcaemia. 

High serum calcium



Normal 24 hour urinary calcium





Causes mild symptoms. •

Mild fatigue

•

Lethargy

PTH may be raised. •

o

HTLV – 1 infection. 

o

Phaeochromocytoma. 

Part of MEA Type II



Also acromegaly.

Adrenal failure

o

Rhabdomyolysis 

•

May cause hypo – or hypercalcaemia.

Congential lactase deficiency.

Investigations. o

•

May present with sever hypercalcaemia.

o

o

Patients don’t respond to parathyroidectomy.

Bloods. 

Calcium



Phosphate



Magnesium



U&Es



LFTs



PTH levels

o

CXR

o

Urine. 

24 hour urinary calcium



Urinary cAMP.

Management. o

o

Urgent treatment required if. 

[Ca] < 3.5 mmol/L



Clouding of conciousness



Confusion



Hypotension



Severe dehydration, causing pre – renal failure.

Rehydrate with 0.9% saline. 

Aim for 3 – 6L/24 hours.



Monitor fluid status with urine output.

•

o

o

If patient doesn’t pass urine for 4 hours, monitor fluid status with o

Central venous line

o

Urinary catheter.

Once patient is rehydrated. 

Continue saline infusion.



Give 40 mg frusemide every 2 – 4 hours.



Continue monitoring CVP to prevent fluid overload or dehydration.



Monitor U&Es, particularly potassium and magnesium •

Diuretics and rehydration can cause electrolytes to rapidly fall.

•

Replace potassium as 20 – 40 mmol in each litre of saline.

•

Replace magnesium as up to 2 mmol in each litre of saline.

If these measures fail to reduce calcium fully (Ca > 2.8 mM), then consider. 



Salmon calcitoninc 400 IU TDS. •

Rapid onset of action (within hours)

•

Effects will only last 2 – 3 days (tachyphylaxis)

Bisphosphonates. •

Inhibit osteoclast activity, causing fall in plasma Ca.

•

Pamidronate at 30 – 60 mg IV over 4 – 6 hours. o

Give 30 mg over 4 hours if 

[Ca] < 3 mmol/L



Significant renal impairment.

o

Give 60 mg over 8 hours if.[Ca] = 3 – 4 mmol/L

o

Calcium levels begin to fall after 48 hours. 

•



Remain suppressed for up to 14 days.

Zolendronate is drug of choice. o

Can infuse over 15 minutes.

o

More effective

o

Longer duration of action.

Prednisolone 30 – 60 mg PO OD. •

Most effective in hypercalcaemia due to: o

Sarcoidosis

o

Myeloma

o

Vitamin D intoxication.

Hypophosphataemia. •

Plasma phosphate is normally 0.8 – 1.4 mmol/L.

•

Hypophosphataemia is:

•

o

Common

o

Often unrecognised by clinicians.

Most intracellular phosphate is present as: o

Creatine phosphates

o

Adenosine phosphates

o

2.3 – diphosphoglycerate. 

•

Hypophosphataemia doesn’t always indicate phosphate deficiency. o

•

In Red Blood Cells.

Phosphate deficiency may present with normal or high plasma phosphate.

Causes. o

Modest (0.4 – 0.75 mmol/L) 

Decreased dietary intake



Vitamin D deficiency



Chronic liver disease



Hyperparathyroidism



Decreased absorption.



o

•

Vitamin D deficiency

•

Steatorrhoea

•

Phosphate binding antacids.

Hungry bones syndrome. •

Post parathyroidectomy

•

Acute leukaemia



Lymphoma



Leukamias



Hyperaldosteronism



Diuretics



Fanconi syndrome

Severe (<0.4 mmol/L) 

Respiratory alkalosis



Treatment of DKA



Alcohol withdrawal. •



Acute liver failure



Hyperalimentation. •

•

Eg. refeeding syndrome.



Ventilation of chronic severe respiratory failure.



Neuroleptic malignant effects.

Presentation. o

Most cases of severe hypophosphataemia occur in very sick patients. 

o

Often in ITU.

Manifestation of severe hypophosphataemia. 

Myopathy. •

Skeletal muscle

•

Diaphragm



Rhabdomyolysis



Cardiomyopathy



Erythrocyte dysfunction



Leukocyte dysfunction



Metabolic acidosis



CNS dysfunction. •

Encephalopathy

•

Irritability

•

Seizures

•

Parasthesia

•

Coma



Respiratory failure



Reduced platelet half – life.



Mineral mobilization.

o

Occasionally seen in asymptomatic patients.

o

Modest hypophosphataemia has no effects. 

•

Especially with ketoacidosis

Warrants investigation

Treatment. o

Phosphate repletion should be reserved for sustained hypophosphataemia with either. 

Oral effervescent Phosphate Sandoz.

• 

IV potassium phosphate. •

o

2 tablets TDS

9 – 18 mmol/day.

Excessive phosphate replacement may cause hypocalcaemia and metastatic calcification. 

Monitor calcium, phosphate and other electrolytes.