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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3612_Библиотеки_им_академика_М_И_Перельмана
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110
Key Questions in CONGENITAL CARDIAC SURGERY
18 What are the pharmacological properties of sildenafil?
Class of drug: phosphodiesterase inhibitor.
•
Mechanism of action: sildenafil relaxes the pulmonary arterial wall by
•
inhibiting the cyclic guanosine monophosphate specific
phosphodiesterase type 5 enzyme that promotes degradation of
cGMP.
Indications: pulmonary arterial hypertension.
•
Cautions: hepatic impairment, renal impairment, concurrent use of
•
nitric oxide donors, hypotension, hereditary degenerative retinal
disorders, left ventricular outflow obstruction, pulmonary venoocclusive disease.
Side effects: headache, flushing, dyspepsia, nasal congestion,
•
disturbances in colour vision and photophobia.
Dose:
•
a) neonate-1 year: initially 250-500µg/kg every 4-8 hours,
maximum 30mg/day;
b) child (1-18 years):
i) body weight <20kg: 10mg t.d.s;
ii) body weight over 20kg: 20mg t.d.s.
19 What are the pharmacological properties of
bosentan?
Class of drug: endothelin-1 competitive antagonist.
•
Mechanism of action: bosentan competitively binds to the endothelin-
•
1 receptor preventing endothelin-1 attachment and pulmonary
vasoconstriction.
Indications: primary pulmonary hypertension.
•
Cautions: hypotension, liver enzymes must be checked prior to
•
prescription as bosentan can be hepatotoxic, contraindicated in
acute porphyria.
Side effects: liver failure, peripheral oedema, pulmonary oedema,
•
anaemia
Dose (2-8 years) oral:
•
a) body-weight 10-20kg: 31.25mg o.d. for 4 weeks then b.d.;
b) body-weight 20-40-kg: 31.25mg o.d. for 4 weeks then 62.5mg
b.d.
3 Congenital cardiac pharmacology
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20 What are the pharmacological properties of
angiotensin-converting enzyme inhibitors?
Mechanism of action: angiotensin-converting enzyme inhibitors
•
inhibit the conversion of inactive angiotension I to active angiotensin
II and also diminish the rate of bradykinin inactivation. Vasodilatation
occurs as a result of the combined effects of lower vasoconstriction
caused by diminished levels of angiotensin II and the potent
vasodilating effect of increased bradykinin.
Indications: hypertension, severe left ventricular dysfunction,
•
secondary prevention of cardiovascular events.
Cautions: renal impairment, renal artery stenosis, severe aortic
•
stenosis, concurrent use of potassium-sparing diuretics, children
under 20kg weight (not licensed for use for hypertension).
Side effects: postural hypotension, renal insufficiency,
•
hyperkalaemia, persistent dry cough, angioedema.
Dose enalapril oral:
•
a) neonate: initially 10µg/kg o.d., increased based on the blood
pressure up to 500µg/kg daily in 1-3 divided doses;
b) child (1 month-12 years): initially 100µg/kg o.d., then
according to blood pressure may be increased up to 1mg/kg
daily o.d. or b.d.;
c) child (12-18 years): initially 2.5mg o.d., with a usual
maintenance dose of 10-20mg daily o.d. or b.d., maximum
40mg daily o.d. or b.d. if body weight over 50kg.
111
21 What are the pharmacological properties of beta-
blockers?
Mechanism of action: beta-blockers are β-adrenoreceptor blocking
•
agents that produce negative inotropic and chronotropic effects,
thereby reducing myocardial oxygen demand. They also have a
cardiomyocyte membrane stabilizing effect, thereby acting as an antiarrhythmic agent.
Indications: arrhythmias, hypertension, primary and secondary
•
prevention of cardiovascular events and heart failure; esmolol or
propranolol may be given intravenously for the initial management of
cyanotic spells in the tetralogy of Fallot.
Cautions: heart block, poor left ventricular function, asthma,
•
peripheral vascular disease.
Side effects: bradycardia, heart block, postural hypotension,
•
peripheral vasoconstriction, bronchospasm.
112
Key Questions in CONGENITAL CARDIAC SURGERY
Dose:
•
a) atenolol:
i) neonate: 0.5-2mg/kg once daily; may be given in two
divided doses;
ii) child (1 month-12 years): 0.5-2mg/kg once daily; may be
given in two divided doses;
iii) child (12-18 years): 25-50mg once daily; may be given in
two divided doses. In arrhythmias, 50-100mg may be
given in two divided doses;
b) carvedilol (predominantly used for heart failure) by mouth:
i) child (2-18 years): initially 50µg/kg (maximum 3.125mg)
b.d., double dose at intervals of at least 2 weeks up to
350µg/kg (maximum 25mg) b.d.;
c) esmolol, in tetralogy of Fallot:
i) neonate: initially intravenous injection over 1-2 minutes
600µg/kg, then, if necessary, by intravenous infusion
300-900µg/kg/min.
22 What are the pharmacological properties of sotalol?
Mechanism of action: sotalol is a potent class III anti-arrhythmic
•
agent that prolongs phase 3 repolarisation in ventricular muscle
fibres by blocking outward potassium current but it also has potent
non-selective β-blocker activity. It widens the action potential leading
to a prolonged QT interval on the electrocardiogram.
Indications: arrhythmias, preventing recurrence of arrhythmias.
•
Cautions: heart block, poor left ventricular function, asthma,
•
peripheral vascular disease.
Side effects: prolongs QT interval (may cause torsade de pointes),
•
bradycardia, heart block, postural hypotension.
Dose:
•
a) neonate: initially 1mg/kg b.d., increased as necessary every 3-
4 days to maximum 4mg/kg bd orally;
b) child (1 month-12 years): initially 1mg/kg b.d., increased as
necessary every 2-3 days to a maximum of 4mg/kg b.d. orally
(maximum 80mg b.d.);
c) child (12-18 years): initially 80mg o.d. or 40mg b.d., increased
gradually to 80-160mg b.d.; higher dose of 480-640mg daily
for life-threatening ventricular arrhythmias.
3 Congenital cardiac pharmacology
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23 What are the pharmacological properties of calcium
gluconate?
Mechanism of action: calcium gluconate increases the threshold
•
potential of cardiac myocytes and therefore restores the normal
gradient with the resting membrane potential, which is abnormally
elevated in hyperkalaemia.
Indications: cardioprotective agent in hyperkalaemia, hypocalcaemia.
•
Cautions: rapid injections may cause vasodilatation, cardiac
•
arrhythmias, hypotension.
Side effects: nausea, constipation, with rapid injections cardiac
•
arrhythmias, hypotension and bradycardia.
Dose:
•
a) acute hypocalcaemia, hyperkalaemia (prevention of
arrhythmias): 0.11mmol/kg (0.5mL/kg of calcium gluconate
10%) as a single dose.
24 What are the pharmacological properties of
amiodarone?
Mechanism of action: amiodarone is a class III anti-arrhythmic agent
•
that increases the duration of the action potential and refractory
period throughout the cardiac conduction system. It diminishes
outward potassium current during repolarisation of the cardiac cells
by blocking the potassium channels.
Indications: supraventricular and ventricular tachyarrhythmias.
•
Cautions: hepatic impairment, thyroid dysfunction, hypokalaemia,
•
bradycardia, drug interactions with digoxin and warfarin.
Side effects: interstitial pulmonary fibrosis, gastrointestinal tract
•
intolerance, hypotension (with intravenous administration),
photosensitivity, slate-grey skin, hypothyroidism or hyperthyroidism,
neuropathy, hepatic dysfunction, muscle weakness, tremor, ataxia.
Dose:
•
a) by mouth:
i) neonate: initially 5-10mg/kg b.d. for 7-10 days, then
reduced to a maintenance dose of 5-10mg/kg o.d.;
ii) child (1 month-12 years): initially 5-10mg/kg (maximum
200mg) b.d. for 7-10 days, then reduced to a
maintenance dose of 5-10mg/kg o.d. (maximum 200mg
daily);
113
114
Key Questions in CONGENITAL CARDIAC SURGERY
iii) child (12-18 years): 200mg t.d.s. for 1 week, then
200mg b.d. for 1 week, then usually 200mg o.d.
adjusted according to dose;
b) intravenous infusion:
i) neonate: initially 5mg/kg over 30 minutes, then 5mg/kg
over 30 minutes every 12-24 hours;
ii) child (1 month-18 years): initially 5-10mg/kg over 20
minutes-2 hours, then by continuous infusion
300µg/kg/hour (maximum dose 1.2g/24 hours).
25 What are the pharmacological properties of
flecainide?
Mechanism of action: flecainide is a class Ic anti-arrhythmic drug that
•
markedly slows phase 0 depolarisation by blocking the sodium
channels in the Purkinje and ventricular muscle fibres. This causes
slowing of conduction in all cardiac tissues. The automaticity is also
reduced.
Indications: tachyarrythmias, including paroxysmal atrial
•
fibrillation/flutter, paroxysmal supraventricular tachycardia, ventricular
tachycardia, resistant re-entry supraventricular tachycardia,
arrhythmias associated with accessory pathways (Wolff-ParkinsonWhite syndrome).
Cautions: can aggravate congestive heart failure due to negative
•
inotropic effects.
Side effects: dizziness, blurred vision, headache, nausea, can rarely
•
aggravate pre-existing arrhythmias or induce life-threatening
ventricular tachycardias resistant to treatment.
Dose:
•
a) neonate: 2mg/kg b.d. or t.d.s., adjusted according to response
and plasma flecainide concentration;
b) child (1 month-12 years): 2mg/kg b.d. or t.d.s., adjusted
according to response and plasma flecainide concentration
(maximum 8mg/kg/day or 300mg daily);
c) child (12-18 years): initially 50-100mg b.d.; maximum 300mg
daily (with a maximum of 400mg daily for ventricular
arrhythmias in heavily built children).
26 What are the pharmacological properties of
lidocaine?
Mechanism of action: lidocaine is a class Ib anti-arrhythmic drug. It
•
shortens phase 3 repolarisation in ventricular muscle fibres by
3 Congenital cardiac pharmacology
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blocking the sodium channel. This drug has little effect on atrial or
atrioventricular junction arrhythmias and does not markedly slow
conduction.
Indications: ventricular arrhythmias, digoxin toxicity.
•
Cautions: heart block (second or third degree), severe sinoatrial
•
block, serious adverse effects to local anaesthetics, Wolff-ParkinsonWhite syndrome, acute porphyria, severe myocardial depression.
Side effects: bradycardia, arrhythmias, hypotension, central nervous
•
system effects, such as drowsiness, slurred speech, paraesthesia,
agitation, confusion, convulsions, respiratory depression.
Dose:
•
a) neonate: 0.5-1mg by injection, followed by infusion of 0.6-
3mg/kg/hour;
b) child (1 month-12 years): 0.5-1mg by injection, followed by an
infusion of 0.6-3mg/kg/hour;
c) child (12-18 years): 50-100mg by injection, followed by an
infusion of 120mg over 30 minutes, then 240mg over 2 hours,
then 60mg/hour; reduce dose further if the infusion is
continued beyond 24 hours.
115
27 What are the pharmacological properties of
procainamide?
Mechanism of action: procainamide is a class Ia anti-arrhythmic drug.
•
It slows phase 0 depolarisation in ventricular muscle fibres by
blocking sodium channels. It slows conduction that may result in
widening of the QRS complex on an electrocardiogram.
Indications: supraventricular and ventricular arrhythmias, Wolff-
•
Parkinson-White syndrome.
Cautions: renal failure.
•
Side effects: reversible lupus erythematosus-like syndrome that
•
develops with chronic use, asystole, induction of ventricular
arrhythmias (such as torsades de pointes), central nervous system
effects (such as depression, hallucination, psychosis),
hypersensitivity reactions (such as fever, agranulocytosis).
Dose:
•
a) IM: 20mg/kg/day divided in four doses; maximum 4g/day;
b) IV: loading: 3-6mg/kg in 5 minutes, maximum 15mg/kg/dose;
maintenance: 0.02-0.08mg/kg/min, maximum 2g/24 hour.
116
Key Questions in CONGENITAL CARDIAC SURGERY
28 What are the pharmacological properties of
adenosine?
Mechanism of action: adenosine is a naturally occurring nucleoside
•
but at high doses it causes a reduction in conduction velocity,
prolongs the refractory period and decreases automaticity in the
atrioventricular node.
Indications: intravenous use for abolishing acute supraventricular
•
tachycardia.
Cautions: second or third degree heart block, sick sinus syndrome,
•
decompensated heart failure, long QT syndrome and severe
hypotension.
Side effects: arrhythmia (asystole, bradycardia), flushing, chest pain,
•
hypotension, metallic taste, light-headedness.
Dose: by rapid intravenous injection:
•
a) neonates: 150µg/kg; if necessary, repeat injection every 1-2
minutes increasing the dose by 50-100µg/kg until the
tachycardia terminates or a maximum single dose of 300µg/kg
has been given;
b) child (1 month-1 year): 150µg/kg; if necessary, repeat injection
every 1-2 minutes, increasing the dose by 50-100µg/kg until
tachycardia terminates or a maximum single dose of 500µg/kg
has been given;
c) child (1 year-12 years): 100µg/kg; if necessary, repeat injection
every 1-2 minutes, increasing the dose by 50-100µg/kg until
the tachycardia terminates or a maximum single dose of
500µg/kg (maximum 12mg) has been given;
d) child (12-18 years): initially 3mg; if necessary, followed by 6mg
after 1-2 minutes and then by 12mg after a further 1-2 minutes.
29 What are the pharmacological properties of atropine?
Mechanism of action: atropine is a competitive muscarinic
•
acetylcholine receptor blocker, with effects on the cardiovascular
system, including at:
a) low dose — bradycardia due to blockade of M1 receptors on
the inhibitory pre-junctional (or presynaptic) neurons;
b) higher dose — blockade of the M2 receptors on the sinoatrial
node, associated with a modest increase in the cardiac rate.
Indications: bradycardia, anti-secretory agent prior to surgery.
•
3 Congenital cardiac pharmacology
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Cautions: tachyarrhythmia.
•
Side effects: supraventricular or ventricular tachycardia, dry mouth,
•
blurred vision, dilated pupils, urinary retention, constipation, nausea,
dizziness, restlessness, confusion, high temperature.
Dose:
•
a) for bradycardia by intravenous infusion:
i) neonate 10-20µg/kg;
ii) child (1 month-12 years): 10-20µg/kg;
iii) child (12-18 years): 300-600µg (larger doses in
emergency);
b) as a premedication:
i) neonate 10-20µg/kg;
ii) child (1 month-18 years): 20-40µg/kg (maximum 900µg).
30 What are the pharmacological properties of
furosemide?
Mechanism of action: furosemide inhibits the reabsorption of sodium,
•
potassium, chloride and water in the ascending limb of the loop of
Henle by inhibiting the Na+/K+/2Cl−cotransporter.
Indications: pulmonary oedema, heart failure, hyperkalaemia,
•
peripheral oedema and oliguria associated with renal impairment,
hypercalcaemia.
Cautions: hypovolaemia, hypotension, hepatorenal syndrome, and
•
some liquid preparations contain alcohol, caution especially in
neonates.
Side effects: electrolyte disturbances (hypokalaemia,
•
hyponatraemia), pancreatitis, hepatic encephalopathy, postural
hypotension, bone marrow suppression, visual disturbances.
Dose:
•
117
a) neonate: 0.5-2mg/kg every 12-24 hours orally or 0.5-1mg/kg
every 12-24 hours intravenously;
b) child (1 month-12 years): 0.5-2mg/kg b.d. or t.d.s., maximum
12mg/kg daily orally or intravenously 0.5-1mg/kg repeated
every 8 hours, as necessary;
c) child (12-18 years): 20-40mg o.d., increased in resistant
oedema to 80-120mg orally, intravenously 20-40mg t.d.s.;
d) by continuous infusion child (1 month-18 years): 0.1-
2mg/kg/hour (following cardiac surgery, initially
100µg/kg/hour, doubled every 2 hours until urine output
exceeds 1mL/kg/hour).
118
Key Questions in CONGENITAL CARDIAC SURGERY
31 What are the pharmacological properties of
spironolactone?
Mechanism of action: spironolactone is an aldosterone antagonist
•
that inhibits the aldosterone-mediated reabsorption of sodium and
secretion of potassium in the distal collecting tubule and duct;
thereby it promotes the loss of sodium and water, whilst preserving
potassium.
Indications: oedema and ascites caused by cardiac failure, liver
•
cirrhosis, nephrotic syndrome, Conn’s syndrome, reduction of
hypokalaemia induced by diuretics and amphotericin.
Cautions: potassium supplementations, concurrent use of ACEI,
•
acute porphyria, Addison’s disease.
Side effects: electrolyte disturbances (hyperkalaemia,
•
hyponatraemia), postural hypotension, acute renal failure,
hepatotoxicity, agranulocytosis.
Dose:
•
a) neonate: 1-2mg/kg daily in 1-2 divided doses, up to 7mg/kg in
resistant ascites;
b) child (1 month-12 years): 1-3mg/kg daily in 1-2 divided doses,
up to 9mg/kg daily in resistant ascites;
c) child (12-18 years): 50-100mg daily in 1-2 divided doses, up to
9mg/kg daily (maximum 400mg daily) in resistant ascites.
32 What are the pharmacological properties of
alprostadil?
Class of drug: prostaglandin E1(PGE1).
•
Mechanism of action: vasodilatation of the ductus arteriosus.
•
Indications: maintain patency of the ductus arteriosus.
•
Cautions: history of haemorrhage, weakening of the duct wall
•
following prolonged usage.
Side effects: apnoea (be prepared for intubation), disseminated
•
intravascular coagulation, hypokalaemia.
Dose: 5-100ng/kg/min intravenous infusion.
•
33 What are the pharmacological properties of
indomethacin?
Mechanism of action: indomethacin is a non-steroidal anti-
•
inflammatory drug (NSAID) that acts by reversibly inhibiting cyclooxygenase. It has anti-inflammatory, analgesic and anti-pyretic
activity.
3 Congenital cardiac pharmacology
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Indications: to close a patent ductus arteriosus in neonates, potent
•
anti-inflammatory agent, juvenile arthritis, pericarditis.
Cautions: concurrent use of warfarin and other NSAIDs, liver and
•
renal impairment, thrombocytopaenia, coagulation defects.
Side effects: serious gastrointestinal event, such as bleeding,
•
ulceration and perforation.
Dose:
•
a) for symptomatic ductus arteriosus by intravenous infusion over
20-30 minutes. Neonate: initially 100-200µg/kg as a single
dose followed by two doses of 100µg/kg at 2-hour intervals; if
residual patency is present then 100µg/kg for a further three
doses at 24-hour intervals;
b) for pain relief and anti-inflammatory effect (1 month-18 years):
0.5mg/kg twice daily; higher doses may be used under
specialist supervision.
34 What are the pharmacological properties of
prednisolone?
Class of drug: steroid with predominantly glucocorticoid activity.
•
Mechanism of action: anti-inflammatory, immunosuppressant.
•
Indications: autoimmune inflammatory disorders, corticosteroid
•
replacement therapy, infantile therapy, idiopathic thrombocytopaenic
purpura.
Cautions: may hamper growth (frequent monitoring required).
•
Side effects: adrenal suppression, infection (such as chickenpox,
•
measles), behavioural change.
Dose: varies as per pathology.
•
35 What are the pharmacological properties of propofol?
Mechanism of action: propofol is a short-acting intravenous sedative
•
and hypnotic anaesthetic agent, which potentiates GABAAreceptor
activity and also acts as a sodium channel blocker. Induction of
anaesthesia using propofol occurs within 30-40 seconds of
administration.
Indications: induction and maintenance of anaesthesia, sedation of
•
ventilated patients.
Cautions: respiratory depression (when used with other respiratory
•
depressants, such as benzodiazepines), hypotension.
Side effects: pain at the injection site, vasodilatation causing
•
hypotension, transient apnoea, dystonia, propofol infusion syndrome,
119
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