20 Handbook of Drugs in Intensive Care

Aminophylline
Aminophylline is the ethylenediamine salt of theophylline. It is a non-specific
inhibitor of phosphodiesterase, producing increased levels of cAMP. Increased
cAMP levels result in:
• bronchodilation
• CNS stimulation
• positive inotropic and chronotropic effects
• diuresis
Theophylline has been claimed to reduce fatigue of diaphragmatic muscles

Uses
Prevention and treatment of bronchospasm

Contraindications
Uncontrolled arrhythmias
Hyperthyroidism

Administration
• Loading dose: 5 mg/kg IV, diluted in 100 ml sodium chloride 0.9% or glucose
5%, given over 30 minutes, followed by maintenance dose 0.1–0.8 mg/kg/h
Dilute 500 mg (20 ml) aminophylline (25 mg/ml) in 480 ml sodium
chloride 9% or glucose 5% to give a concentration of 1 mg/ml
No loading dose if already on oral theophylline preparations (toxicity)
Reduce maintenance dose (0.1–0.3 mg/kg/h) in the elderly and patients
with congestive heart failure and liver disease
Increase maintenance dose (0.8–1 mg/kg/h) in children (6 months to 16
years) and young adult smokers
Monitor plasma level (p. 309)
Therapeutic range 55–110 μmol/l or 10–20 mg/l. Take first level 4–6 hours
after starting treatment
The injection can be administered nasogastrically (unlicensed). This may be
useful as there is no liquid preparation of aminophylline or theophylline. To
convert from IV to NG, keep the total daily dose the same, but divide into four
equal doses. Aminophylline modified-release tablets are taken by mouth twice
daily. Alternatively, if these are crushed up to go down a nasogastric tube then
they will lose their slow-release characteristic and will need to be administered
four times per day, keeping the total daily dose the same.
Downloaded from https://www.cambridge.org/core. University of Edinburgh Library, on 22 Aug 2019 at 20:14:50,
subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
https://doi.org/10.1017/9781108349550.001
 Drugs: An A–Z Guide 21

Unlicensed indication: Methotrexate toxicity: aminophylline 25 mg/kg, 6

hourly IV (methotrexate increases adenosine, which is inhibited by
aminophylline)

Dosage chart (ml/h)

Weight (kg) Dose (mg/kg/h)

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

50 5 10 15 20 25 30 35 40 45 50

60 6 12 18 24 30 36 42 48 54 60

70 7 14 21 28 35 42 49 56 63 70

80 8 16 24 32 40 48 56 64 72 80

90 9 18 27 36 45 54 63 72 81 90

100 10 20 30 40 50 60 70 80 90 100

110 11 22 33 44 55 66 77 88 99 110

120 12 24 36 48 60 72 84 96 108 120

• Elderly • Usual adult • Children

• Congestive maintenance • Young adult
heart failure smokers
• Liver disease

How not to use aminophylline

Rapid IV administration (hypotension, arrhythmias)

Adverse effects
Tachycardia
Arrhythmias
Convulsions

Cautions
Subject to enzyme inducers and inhibitors (p. 307)
Concurrent use of erythromycin and ciprofloxacin: reduce dose

Organ failure
Cardiac: prolonged half-life (reduce dose)
DownloadedHepatic: prolonged half-life (reduce
from https://www.cambridge.org/core. dose)of Edinburgh Library, on 22 Aug 2019 at 20:14:50,
University
subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
https://doi.org/10.1017/9781108349550.001
 22 Handbook of Drugs in Intensive Care

Amiodarone
Amiodarone has a broad spectrum of activity on the heart. In addition to having
an anti-arrhythmic activity, it also has anti-anginal effects. This may result from its
α- and β-adrenoceptor-blocking properties as well as from its calcium-channel-
blocking effect in the coronary vessels. It causes minimal myocardial depression. It
is therefore often a first-line drug in critical care situations. It has an extremely
long half-life (15–105 days). Unlike oral amiodarone, IV administration usually acts
relatively rapidly (20–30 minutes). Oral bioavailability is 50%, therefore 600 mg
PO/NG is equivalent to 300 mg IV. Overlap the initial oral and IV therapy for 16 to
24 hours. An oral loading dose regimen is necessary even when the patient has
been adequately ‘loaded’ intravenously. This is because amiodarone has a large
volume of distribution (4,000 l) and a long half-life. The high initial plasma levels
quickly dissipate as the drug binds to the peripheral lipophilic tissues. Thus a
prolonged loading regimen is required. When the cause of the arrhythmia has
resolved, e.g. sepsis, then amiodarone treatment can be stopped abruptly.

Uses
Good results with both ventricular and supraventricular arrhythmias,
including those associated with WPW syndrome

Contraindications
Iodine sensitivity (amiodarone contains iodine)
Sinus bradycardia (risk of asystole)
Heart block (unless pacemaker fitted)

Administration
• Loading: 300 mg in 25–250 ml glucose 5% IV over 20–120 minutes,
followed by 900 mg in 50–500 ml glucose 5% over 24 hours. If fluid-
restricted, up to 900 mg can be diluted in 50 ml glucose 5% and
administered centrally
• Maintenance: 600 mg IV daily for 7 days, then 400 mg IV daily for 7 days,
then 200 mg IV daily
Administer IV via central line. A volumetric pump should be used as the
droplet size of amiodarone may be reduced.
Must be diluted in glucose 5% (do not dilute in sodium chloride 0.9%)
Because phlebitis may occur, the drug should be given through a central
venous line when possible. If peripheral administration is necessary, dilute
dose in 500 ml glucose 5%. Concentrations >2 mg/ml must be given
centrally
Downloaded from https://www.cambridge.org/core. University of Edinburgh Library, on 22 Aug 2019 at 20:14:50,
subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
https://doi.org/10.1017/9781108349550.001
 Drugs: An A–Z Guide 23

Dilution to a concentration of less than 600 µg /ml is unstable. Solutions of

<300 mg/500 ml glucose 5% should not be used
Continuous cardiac monitoring
• Oral: 200 mg 8 hourly for 7 days, then 200 mg 12 hourly for 7 days, then
200 mg daily

How not to use amiodarone

Incompatible with sodium chloride 0.9%
Avoid the use of peripheral vein (thrombophlebitis) unless well diluted

Adverse effects
Short-term
• Skin reactions common
• Vasodilation and hypotension or bradycardia after rapid infusion
• Corneal microdeposits (reversible on stopping)
Long-term
• Pulmonary fibrosis, alveolitis and pneumonitis (usually reversible on
stopping)
• Liver dysfunction (asymptomatic ↑ in LFT common)
• Hypo- or hyperthyroidism (check TFT before starting drug)
• Peripheral neuropathy, myopathy and cerebellar dysfunction (reversible
on stopping)

Cautions
Increased risk of bradycardia, AV block and myocardial depression with
beta-blockers and calcium-channel antagonists
Potentiates the effect of digoxin, theophylline and warfarin – reduce dose

Organ failure
Hepatic: worsens
Renal: accumulation of iodine may ↑ risk of thyroid dysfunction

Downloaded from https://www.cambridge.org/core. University of Edinburgh Library, on 22 Aug 2019 at 20:14:50,

subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
https://doi.org/10.1017/9781108349550.001
 Drugs: An A–Z Guide 33

Atropine
The influence of atropine is most noticeable in healthy young adults in whom
vagal tone is considerable. In infancy and old age, even large doses may fail to
accelerate the heart.

Uses
Sinus bradycardia – will increase BP as a result
Reversal of muscarinic effects of anticholinesterases (neostigmine)
Organophosphate poisoning
Hypersalivation

Contraindications
Complete heart block
Tachycardia

Administration
Bradycardia: 0.3–1 mg IV bolus, up to 3 mg (total vagolytic dose), may be
diluted with WFI
Reversal of muscarinic effects of anticholinesterase: 1.2 mg for every 2.5 mg
neostigmine
Organophosphate poisoning: 1–2 mg initially, then further 1–2 mg every
30 min PRN
Hypersalivation: 1% atropine eye drops 1–2 drops sublingually twice to four
times a day (unlicensed indication) – can cause hallucinations

How not to use atropine

Slow IV injection of doses <0.3 mg (bradycardia caused by medullary vagal
stimulation)

Adverse effects
Drowsiness, confusion
Dry mouth
Blurred vision
Urinary retention

Downloaded from https://www.cambridge.org/core. University of Edinburgh Library, on 22 Aug 2019 at 20:14:50,

subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
https://doi.org/10.1017/9781108349550.001
 34 Handbook of Drugs in Intensive Care

Tachycardia
Pyrexia (suppression of sweating)
Atrial arrhythmias and atrioventricular dissociation (without significant
cardiovascular symptoms)
Dose >5 mg results in restlessness and excitation, hallucinations, delirium
and coma

Cautions
Elderly (↑ CNS side effects)
Child with pyrexia (further ↑ temperature)
Acute myocardial ischaemia (tachycardia may cause worsening)
Prostatic hypertrophy–urinary retention (unless patient’s bladder
catheterized)
Paradoxically, bradycardia may occur at low doses (<0.3 mg)
Acute-angle glaucoma (further ↑ IOP)
Pregnancy (fetal tachycardia)

Downloaded from https://www.cambridge.org/core. University of Edinburgh Library, on 22 Aug 2019 at 20:14:50,

subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
https://doi.org/10.1017/9781108349550.001