ICU & Drug therapy

Question 1

Is there any role for heparin in management of septic shock?

Answer 1

NO

Question 2

Is there more adrenaline (epinephrine) or noradrenaline (norepinephrine)
produced in shock? From where do these substances come from?

Answer 2

More adrenaline than noradrenaline is produced. Initially, this is from
increased sympathetic nervous activity but this is later augmented by
production of catecholamines from the adrenal medulla.

Question 3

I hear conflicting views as to whether activated protein C is useful in
shock.

Answer 3

Administration of recombinant
human activated protein C was shown to improve survival in patients
with sepsis-induced shock. A more recent study showed no benefit and
the view now is that it should be tried if all else fails.

Question 4

Why does both vasoconstriction and vasodilatation occur in shock?

Answer 4

The initial response in most forms of shock is release of catecholamines,
which cause vasoconstriction, increased myocardial contractility and a
tachycardia. There is later release of many vasoactive substances,
e.g. nitric oxide, which causes vasodilatation.

Question 5

Are pulmonary artery (PA) catheters dangerous?

Answer 5

No; not when used by experts. There is, however, some evidence that
PA catheters do not improve outcome and because of the complications
and cost; it has been suggested that pulmonary artery catheterization has
been overused.

Question 6

In most hospitals, what is the difference between a high-dependency
unit (HDU) and an intensive care unit (ITU) and what is ‘step down’
care?

Answer 6

ITU means ‘intensive’ care with facilities to deal with multi-organ failure.
The ratio between staff and patients is 1 : 1. In most hospitals, the ITU
is also where invasive ventilation is performed if necessary. HDUs are
often used postoperatively or when constant monitoring is required.
They are sometimes used as a ‘step down’ from ITU before the patient is
transferred to a ward.

Question 7

What is the difference between acute lung injury (ALI) and acute
respiratory distress syndrome (ARDS) from a practical point of view?

Answer 7

In ALI the PaO2/FIO2 ratio is 40 kPA (300 mmHg); in ARDS the ratio
is 26 kPa (200 mmHg). From a practical point of view, both are treated
in the same way; respiratory support and treatment of the underlying
condition.

Question 8

What is the role of inhaled nitric oxide (NO) in acute respiratory distress
syndrome (ARDS)?

Answer 8

Inhaled nitric oxide reduces pulmonary artery pressure and improves
V/Q mismatch. However it has not been shown to improve outcome.

Question 9

What is meant by ‘positive’ pressure ventilation?

Answer 9

Gas is delivered under positive pressure into the airways during
inspiration. It contrasts with negative pressure ventilation where the
chest or whole body is encased in a tank to produce a negative airway
pressure in inspiration.

Question 10

Why is an electroencephalogram (EEG) not used in all countries to
evaluate possible brain death.

Answer 10

An EEG looks only at cortical activity, and loss of brainstem reflexes
is necessary to confirm brain death. In the UK (but not the US) it is
considered that an experienced clinician’s examination of the patient
makes an EEG unnecessary

Question 11

How should the body surface area be calculated when giving drugs for
which doses are given per square metre of body surface area?

Answer 11

Body surface area is mainly used in children. The body surface area of a
70-kg man is 1.8m2. To calculate the dose in a child use the following
formula:
(Surface area of patient (m2) x adult dose) 1.8

Question 12

My question is concerned with the practical use of steroids. In
inflammatory bowel disease, what doses are used and when is the dose
reduced?

Answer 12

In moderate/severe inflammatory bowel
disease we start with 45 mg prednisolone as a single dose daily for
1 week, reducing this to 30 mg daily for 2 weeks and then by 5-mg
decrements, depending on the clinical condition of the patient and the
changes in inflammatory markers, e.g. erythrocyte sedimentation rate
and C-reactive protein.

Question 13

What is the safe dosage/length of treatment for the drug dexmethasone
so that its destructive effects are avoided

Answer 13

There is no safe dosage/length of treatment, particularly with a potent
steroid like dexmethasone. For example, ischaemic necrosis of bone has
been described after three doses of dexmethasone 4 mg. You must always
keep the dose as low as possible for as short a time as possible

Question 14

1. Please explain ‘odds ratio’ and ‘risk ratio’.
2. What is meant by saying that diabetics have a 3.3 risk ratio of
   developing dementia?

Answer 14

The odds ratio (OR) is the ratio of the probability of an event occurring
to the probability of an event not occurring.
OR = (a/b) divided (c/d)
RR ‘rate’ of the event occurring in the treated group = a/(a and b) DIVIDED c/(c and d)

A risk ratio of 3.3 means a 3.3 increased risk of developing dementia in
this case

Question 15

I have a question about the management of aspirin poisoning. Is it
reasonable to carry out a postalkaline diuresis in these patients?

Answer 15

Plasma salicylate levels should be performed in all patients suspected of
aspirin overdosage.
Plasma salicylate levels of 500–700 mg/L (3.62–5.07 mmol/L) at
2 hours, 4 hours (or later) after aspirin ingestion should have urine
alkalinization (see K&C 7e, p. 938) with 225 mL of an 8.4% bicarbonate
infused over 1 hour. Forced alkaline diuresis should no longer be used

Question 16

What is meant by intermediate syndrome in organophosphorus

poisoning?

Answer 16

The intermediate syndrome consists of cranial nerve and brainstem
lesions with a proximal neuropathy, which starts 1–4 days after acute
intoxication and lasts 2–3 weeks. Respiratory failure due to muscle
weakness can occur. The aetiology is uncertain but is probably due to
inadequate treatment.

Question 17

What are the pulmonary manifestations of Pink’s disease and how
common are they relative to the usual cerebral, skin and renal
effects?

Answer 17

Pink’s disease is due to mercury ingestion in the old teething powders
and therefore infants were affected. You will need to check with a
paediatric specialist. The disease does not now occur in many countries
because the compounds are no longer available.

Question 18

Is it necessary to administer antivenom to a person bitten by a snake
6 hours previously, presenting only with local leg swelling over the bitten
site and so far no other systemic feature of poisoning?

Answer 18

Antivenoms are not usually required unless signs of systemic
envenoming are present. There are, however, exceptions to this rule and rapid progression of swelling is one. If systemic signs are present
it is never too late to give antivenom. You must get expert local
advice.

Question 19

What is the ideal management for scorpion bite?

Answer 19

Pain from the sting can be helped by local anaesthetic (local infiltration
or ring block). Parenteral analgesia is also required frequently. The use of
antivenom is controversial

Question 20

In acute anaphylaxis, you recommend IM adrenaline (epinephrine).
Surely in such an acute situation intravenous adrenaline would
be better?

Answer 20

Adrenaline has a rapid onset of action. It is well absorbed from the IM
route, even in shocked patients. For these reasons it is a much safer
option than IV adrenaline, which can be dangerous.

Question 21

Why should patients avoid grapefruit juice if they are taking
terfenadine?

Answer 21

Grapefruit juice inhibits the P450 enzyme CYP3A4. This is due to the
interaction between flavinoids and other chemicals that are found in
grapefruit. Interaction between the antihistamine terfenadine means
that the two should never be given together. However, this is academic
because terfenadine has been withdrawn because of its cardiac
effects.

Question 22

Please explain why some drugs are teratogenic in the first trimester and
some in the second?

Answer 22

Teratogenicity only occurs in the first trimester (particularly 3rd–11th
weeks), causing congenital malformation. Following this, drugs can
affect growth and functional development of the fetus but this is not
teratogenic.

Question 23

What is the difference between compliance and concordance?

Answer 23

Compliance simply means that patients are not taking the drug
prescribed. Concordance is a more general term implying an implicit
agreement between the doctor and the patient on the value of taking
therapy.

Question 24

The rates of paracetamol (acetaminophen) self-poisoning have decreased
in the UK. Why is this?

Answer 24

There are many reasons; one being the education about the dangers of
the drug. In addition, you cannot buy more than 16 tablets at any one
time from drug outlets in the UK. Foil-wrapped drugs are also less likely
to be taken for self-harm.

Question 25

Is N-acetylcysteine of any use in a case of paracetamol overdosage taken
16 hours previously?

Answer 25

Yes there is evidence that continued infusion of N-acetylcysteine
improves the morbidity and mortality of liver problems, even after
16 hours

Question 26

What is meant by primary end point and secondary end point?

Answer 26

The main result is measured at the end of the study to see if the treatment
has worked, e.g. mortality in the treatment group versus the placebo
group. This primary end point should be clear before the study starts.
The secondary end point refers to other variables, such as side-effects in
the treatment group, which might affect the overall results

Question 27

Can chronic exposure to organophosphorus compounds (in farmers)
cause axonal radiculoneuropathy persisting for years? Is this disease
reversible?

Answer 27

Chronic low exposure might cause
neurological lesions, but these changes are subtle. Acute exposure does
cause axonal damage to roots and peripheral nerves.

Question 28

Antidote regimens for paracetamol poisoning

N-acetylcysteine (intravenously in 5% glucose)

Answer 28

● 150 mg/kg in 200 mL over 15 min, then 50 mg/kg in 500 mL over the
next 4 hours and 100 mg/kg in 1000 mL of 5% glucose over the ensuing
16 hours
● Total dose: 300 mg/kg over 20.15 hours

Note: A 48-hour regimen is used in some US centres: patients receive a
loading dose of 140 mg/kg, followed by 70 mg/kg every 4 hours for
12 doses, all infused over 1 hour

Question 29

Antidote regimens for paracetamol poisoning

N-acetylcysteine (orally)

Answer 29

● 140 mg/kg initially, then 60 mg/kg every 4 hours for 17 additional doses
● Total dose: 1300 mg/kg over 72 hours

Question 30

Antidote regimens for paracetamol poisoning

Methionine

Answer 30

● Oral 2.5 g followed by three similar doses every 4 hours if unable to give
N-acetylcysteine