Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3612_Библиотеки_им_академика_М_И_Перельмана
.pdf
100
Key Questions in CONGENITAL CARDIAC SURGERY
Hence, to calculate the amount of oxygen per volume of blood:
•
Oxygen content = (oxygen-binding capacity x O2saturation) +
dissolved oxygen
Oxygen content = (1.34 x Hb [g/dL] x O2saturation) + (0.003 x PO2)
Acknowledgement
We would like to thank Soha Romeih for her help with the cardiac imaging.
Recommended reading
1. Kappanayil M, Kannan R, Kumar RK. Understanding the physiology of complex
congenital heart disease using cardiac magnetic resonance imaging.
`~кЗбзд
2011; 4(2): 177-82.
2. Sommer RJ, Hijazi ZM, Rhodes JF. Pathophysiology of congenital heart disease in the
adult: part III: complex congenital heart disease.
3. Rhodes JF, Hijazi ZM, Sommer RJ. Pathophysiology of congenital heart disease in the
adult, part II. Simple obstructive lesions.
4. Sommer RJ, Hijazi ZM, Rhodes JF Jr. Pathophysiology of congenital heart disease in
the adult: part I: Shunt lesions.
5. Chowdhury D. Pathophysiology of congenital heart diseases.
2007; 10(1): 19-26.
`бкЕмд~нбзе
`бкЕмд~нбзе
`бкЕмд~нбзе
2008; 117(8): 1090-9.
2008; 117(9): 1228-37.
2008; 117(10): 1340-50.
^åå= mÉÇá~íê
^åå= `~êÇ= ^å~ÉëíÜ
Chapter 3
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Congenital cardiac pharmacology
Shakil Farid, Kasra Shaikhrezai, Narain Moorjani
1 What are the pharmacological properties of aspirin?
Class of drug: cyclo-oxygenase inhibitor.
•
Mechanism of action: aspirin irreversibly inhibits thromboxane A2
•
production in platelets via acetylation of cyclo-oxygenase and
inhibiting it. Inhibition of thromboxane A2 production reduces the
adhesiveness of platelets.
Indications: prophylaxis against clot formation after cardiac surgery,
•
prophylaxis of stroke in children with high risk, Kawasaki syndrome.
Cautions: asthma, peptic ulcer disease, renal impairment,
•
concomitant use of a non-steroidal anti-inflammatory drug or
anticoagulant (warfarin).
Side effects: gastrointestinal effects, such as nausea, vomiting,
•
bleeding, epigastric distress, bronchospasm, respiratory depression
and hyperthermia in toxic doses, hypersensitivity, Reye syndrome
(which can happen in children under 16 years of age, characterised
by fulminant hepatitis with cerebral oedema).
Dose p.o.:
•
101
a) neonate: 1-5mg/kg o.d.;
b) child (1 month-12 years): 1-5mg/kg (usual maximum dose
75mg) o.d.;
c) child (12-18 years): 75mg o.d.
2 What are the pharmacological properties of clopidogrel?
Class of drug: platelet ADP (adenosine diphosphate) receptor
•
antagonist.
Mechanism of action: clopidogrel irreversibly modifies the platelet
•
ADP receptor thereby directly inhibiting the binding of ADP and
subsequent ADP-mediated activation of the glycoprotein IIb/IIIa
complex. Platelets exposed to clopidogrel are ineffective for the
remainder of their lifetime (5-7 days).
102
Key Questions in CONGENITAL CARDIAC SURGERY
Indications: primary and secondary prevention of cardiovascular and
•
cerebrovascular disease (CAPRIE trial). It is also used as dual
therapy in combination with aspirin for acute coronary syndrome
(CURE trial) and long-term anti-thrombotic prophylaxis for drugeluting stents.
Cautions: active bleeding.
•
Side effects: haemorrhage, neutropenia.
•
Dose:
•
a) child (0-24 months): 0.2mg/kg/day (maximum 75mg per dose);
b) child (2-17 years): 0.2-1mg/kg/day (maximum 75mg per dose).
3 What are the pharmacological properties of heparin?
Mechanism of action: heparin is a mucopolysaccharide that:
•
a) inactivates activated factor X;
b) inhibits conversion of prothrombin to thrombin;
c) prevents fibrin formation from fibrinogen.
Indications: treatment and prophylaxis of deep venous thrombosis
•
and pulmonary embolism; unstable angina; anticoagulation during
cardiopulmonary bypass; temporary anticoagulation for prosthetic
valve patients
Cautions: active bleeding.
•
Side effects: haemorrhage, hyperkalaemia, osteoporosis,
•
thrombocytopaenia and hypersensitivity.
Dose:
•
a) prophylactic — 100 units/kg b.d. (maximum per dose 5000U)
by subcutaneous injection;
b) therapeutic:
i) neonate (up to 35 weeks corrected gestational age):
initially 50 units/kg, then 25 units/kg/hour continuous IV
infusion, adjusted according to APTT;
ii) neonate: initially 75 units/kg, then 25 units/kg/hour
continuous IV infusion, adjusted according to APTT;
iii) child (1-11 months): initially 75 units/kg, then 25
units/kg/hour continuous IV infusion, adjusted according
to APTT;
iv) child (1-17 years): initially 75 units/kg, then 20
units/kg/hour continuous IV infusion, adjusted according
to APTT;
3 Congenital cardiac pharmacology
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
c) full cardiopulmonary bypass — 300U/kg bolus; minimal
extracorporeal circulation (MECC) — 200U/kg.
Heparin can be reversed with protamine sulphate.
•
4 What are the pharmacological properties of
protamine?
Mechanism of action: protamine antagonises the anticoagulant
•
effects of heparin.
Indications: reversal of the effects of overdose with intravenous
•
unfractionated or low-molecular-weight heparin.
Cautions: excessive doses can have an anticoagulant effect,
•
increased risk of allergic reaction to protamine (previous treatment
with protamine or protamine insulin, allergy to fish, adolescent males
who are infertile).
Side effects: hypersensitivity (including angioedema, anaphylaxis),
•
dyspnoea due to pulmonary oedema, flushing, bradycardia and
hypotension.
Dose:
•
103
a) child (1 month-18 years): by intravenous injection (rate not
exceeding 5mg/minute) to neutralise each 100 units of
unfractionated heparin 1mg if less than 30 minutes has lapsed
since overdose, 500-750µg if 30-60 minutes has lapsed, 375500µg if 60-120 minutes has lapsed, 250-375µg if over 120
minutes has lapsed (maximum 50mg).
5 What are the pharmacological properties of low-
molecular-weight heparins (LWMHs)?
Mechanism of action: LMWH has a similar action to heparin except:
•
a) LWMH has a longer half-life than heparin;
b) LWMH does not require monitoring (APTTR is unaffected);
c) LMWH has a greater anti-factor Xa activity;
d) LMWH has a lower incidence of thrombocytopaenia and
osteoporosis.
Indications: acute coronary syndrome (FRISC trial, TIMI IIB trial) and
•
prophylaxis for deep vein thrombosis.
Cautions: active bleeding.
•
Side effects: haemorrhage, hyperkalaemia, osteoporosis,
•
thrombocytopaenia and hypersensitivity.
104
Key Questions in CONGENITAL CARDIAC SURGERY
Dose:
•
a) Dalteparin (Fragmin®):
i) therapeutic dose:
- neonate: 100 units/kg twice daily;
- child (1 month-11 years): 100 units/kg b.d.;
- child (12-17 years): 200 units/kg o.d. (maximum
18,000 units);
ii) prophylactic dose:
- neonate: 100 units/kg o.d.;
- child (1 month-11 years): 100 units/kg o.d.;
- child (12-17 years): 2500-5000 units o.d.;
b) Enoxaparin (Clexane®):
i) therapeutic dose:
- neonate: 1.5-2mg/kg b.d.;
- child (1-2 months): 1.5mg/kg b.d.;
- child (2 months-17 years): 1mg/kg b.d.;
ii) prophylactic dose:
- neonate: 750µg/kg b.d.;
- child (1-2 months): 750µg/kg b.d.;
- child (2 months-17 years): 500µg/kg b.d.
(maximum 40mg per day).
6 What are the pharmacological properties of warfarin?
Mechanism of action: warfarin is a coumarin derivative that interferes
•
with vitamin K metabolism. Vitamin K is a cofactor in the hepatic
production of numerous proteins including coagulation factors II, VII,
IX and X.
Indications: prophylaxis and treatment for thromboembolism with
•
deep vein thrombosis, pulmonary embolism, atrial fibrillation,
mechanical prosthetic valves, left ventricular thrombus and transient
ischaemic attacks.
Cautions: hepatic impairment; peptic ulcer disease; warfarin
•
interacts with numerous drugs including amiodarone, antibiotics
(such as rifampicin), anticonvulsants, non-steroidal anti-inflammatory
drugs and statins.
Side effects: haemorrhage.
•
Dose (induction):
•
a) neonate: initially 200µg/kg for 1 dose on day 1; then reduced
to 100µg/kg once daily for 3 days; subsequent doses are
dependent upon INR levels; if the INR is above 3.5, a dose
should be omitted;
3 Congenital cardiac pharmacology
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
b) child: initially 200µg/kg (maximum per dose 10mg) for 1 dose
on day 1; then reduced to 100µg/kg once daily (maximum per
dose 5mg) for the following 3 days; subsequent doses are
adjusted according to the INR levels; if the INR is above 3.5, a
dose should be omitted.
Warfarin can be reversed with vitamin K, fresh frozen plasma or
•
Beriplex®(human prothrombin complex concentrate).
7 What are the pharmacological properties of vitamin K?
Mechanism of action: vitamin K acts as a cofactor in the hepatic
•
production of several protein coagulation factors including II, VII, IX
and X.
Indications: bleeding in neonates and infants due to blood clotting
•
factors and vitamin K deficiency, warfarin-induced bleeding.
Cautions: allergic reactions, risk of vascular collapse (should be
•
given very slowly).
Side effects: allergic reactions, haemolytic anaemia and cytotoxicity
•
in liver cells.
Dose:
•
105
a) neonatal hypoprothrombinaemia or vitamin K deficiency
bleeding: by intravenous injection 1mg, repeated 8-hourly if
necessary;
b) for reversal of coumarin anticoagulation when continued
anticoagulation is required or if no significant bleeding in a
child (1 month-18 years): 15-30µg/kg (maximum 1mg) as a
single-dose intravenous injection, repeated as necessary;
c) for reversal of coumarin anticoagulation when continued
anticoagulation is not required or if significant bleeding;
treatment of haemorrhage associated with vitamin K deficiency
in a child (1 month-18 years): 250-300µg/kg (maximum 10mg)
as a single-dose intravenous injection.
8 What are the pharmacological properties of
tranexamic acid?
Class of drug: lysine analogue antifibrinolytic agent.
•
Mechanism of action: tranexamic acid binds to plasminogen, thereby
•
inhibiting fibrinolysis.
Indications: prophylaxis to reduce bleeding and the use of blood
•
products following cardiac surgery. Tranexamic acid is also used
following massive haemoptysis and in haemophiliacs.
106
Key Questions in CONGENITAL CARDIAC SURGERY
Cautions: renal impairment, disseminated intravascular coagulation,
•
thromboembolic disease.
Side effects: renal function, graft patency.
•
Dose: 30mg/kg/5 minutes loading bolus (maximum 2g) followed by
•
a 5-10mg/kg/hr maintenance IV infusion; 30mg/kg added to the
prime volume of the cardiopulmonary bypass circuit.
9 What are the pharmacological properties of
dopamine?
Mechanism of action: dopamine can activate α- and β-adrenergic
•
receptors:
a) very high doses — can cause vasoconstriction by activating α1
receptors;
b) moderate doses — stimulates β1 receptors of the heart having
both inotropic and chronotropic effects. With this moderate
dose in older children, there is an increase in myocardial
contractility and cardiac output; however, in neonates, this
moderate dose causes a reduction in cardiac output;
c) low doses — dilates renal and splanchnic arterioles by
activating dopaminergic receptors, thereby increasing blood
flow to the kidneys and other viscera.
Indications: cardiogenic shock and septic shock.
•
Cautions: tachyarrythmias, neonatal pulmonary hypertension,
•
phaeochromocytoma, patients on mono-amine oxidase inhibitors.
Side effects: tachycardia, vasoconstriction, hypotension, rarely
•
hypertension, dyspnoea.
Dose:
•
a) neonate: initially 3µg/kg/min, adjusted according to response
(maximum 20µg/kg/min);
b) child (1 month-18 years): initially 5µg/kg/min, adjusted
according to response (maximum 20µg/kg/min).
10 What are the pharmacological properties of
dobutamine?
Mechanism of action: dobutamine is a direct-acting catecholamine
•
that acts as a β1 receptor agonist. One of the stereoisomers has a
stimulatory effect and increases the cardiac rate and output.
Indications: inotropic support after cardiac surgery, increase cardiac
•
output in acute congestive heart failure.
3 Congenital cardiac pharmacology
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Cautions: tachyarrhythmias, phaeochromocytoma, marked
•
obstruction of cardiac ejection (such as idiopathic hypertrophic
subaortic stenosis).
Side effects: tachyarrhythmias, bronchospasm, nausea,
•
hypertension.
Dose: initially 5µg/kg/min, adjusted according to response to 2-
•
20µg/kg/minute by intravenous infusion.
11 What are the pharmacological properties of
adrenaline?
Mechanism of action: adrenaline increases the contractility of the
•
myocardium (positive inotropic β1 action) and increases its rate of
contraction (positive chronotropic β1 action). At low doses, it causes
systemic vasodilatation and bronchodilation by β2 effects but at
higher doses its α-adrenergic vasoconstriction effects predominate.
Indications: low cardiac output syndrome, cardiopulmonary
•
resuscitation, anaphylaxis, acute hypotension, bradycardia
(unresponsive to atropine).
Cautions: obstructive cardiomyopathy, aortic stenosis, occlusive
•
vascular disease, arrhythmias, hypertension, phaeochromocytoma,
glaucoma, diabetes mellitus, arrhythmias.
Side effects: tachycardia, arrhythmias, hypertension, metabolic
•
acidosis, central nervous system disturbances, such as anxiety, fear,
tension, headache, tremor.
Dose: initially 100ng/kg/min adjusted according to response, higher
•
doses up to 1.5µg/kg/min can be used.
107
12 What are the pharmacological properties of
noradrenaline?
Mechanism of action: noradrenaline is a potent α1-adrenergic
•
agonist, causing a rise in peripheral resistance due to intense
vasoconstriction of most vascular beds. It is also a β1-adrenergic
agonist producing increased myocardial contractility and increased
heart rate, although it has minimal effects
the drug is given in therapeutic doses in humans, the α-adrenergic
receptor is most affected.
Indications: shock or low systemic vascular resistance due to sepsis,
•
vasodilatation or anaphylaxis, low cardiac output following cardiac
surgery.
Cautions: peripheral vascular thrombosis, hyperthyroidism, diabetes
•
mellitus, extravasation at the injection site causing necrosis,
susceptibility to angle-closure glaucoma, uncorrected hypovolaemia.
áå=îáîç
. In practice, when
108
Key Questions in CONGENITAL CARDIAC SURGERY
Side effects: hypertension, tachyarrhythmias, anorexia, nausea,
•
vomiting, tremor, psychosis.
Dose: 20-100ng/kg/minute intravenous infusion adjusted according
•
to response, maximum 1µg/kg/minute.
13 What are the pharmacological properties of
vasopressin?
Mechanism of action: vasopressin has both antidiuretic and
•
vasopressor effects. In the kidney, it binds to the V2 receptor to
increase water permeability and reabsorption in the collecting
tubules. The vasoconstrictor effect is mediated by the V1 receptor
that is located in vascular smooth muscle; it also remains in liver and
other tissues.
Indications: diabetes insipidus, bleeding from oesophageal varices or
•
colonic diverticula.
Cautions: coronary artery disease, epilepsy, asthma, heart failure,
•
conditions that might be aggravated by water retention.
Side effects: vascular disease, chronic nephritis, fluid retention,
•
peripheral ischaemia, hypersensitivity reactions.
Dose: for acute massive haemorrhage of the gastrointestinal tract:
•
a) child (1 month-18 years): initially 0.3 units/kg (maximum 20
units) over 20-30 minutes, then 0.3 units/kg/hour, adjusted
according to response (maximum 1 unit/kg/hour).
14 What are the pharmacological properties of
phenylephrine?
Mechanism of action: phenylephrine is a selective α1-adrenergic
•
receptor agonist, which produces systemic vasoconstriction.
Indications: acute hypotension; to maintain systemic blood pressure
•
whilst on cardiopulmonary bypass.
Cautions: severe hyperthyroidism.
•
Side effects: hypertension, peripheral ischaemia, headache.
•
Dose: 500µg-1mg IV boluses whilst on cardiopulmonary bypass.
•
15 What are the pharmacological properties of
levosimendan?
Class of drug: calcium sensitizer.
•
Mechanism of action: myocytes become more sensitive to calcium,
•
hence increasing contractility.
3 Congenital cardiac pharmacology
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Indications: severe congestive heart failure.
•
Cautions: hepatic and renal impairment.
•
Side effects: dysrrhythmia, hypokalaemia, myocardial ischaemia.
•
Dose: 0.05-0.2µg/kg/min intravenous infusion.
•
16 What are the pharmacological properties of
enoximone?
Class of drug: phosphodiesterase inhibitor.
•
Mechanism of action: enoximone is a type 3 phosphodiesterase
•
inhibitor that acts as an inodilator by reducing systemic and
pulmonary vascular resistance, as well as having moderate positive
inotropic effects. They increase intracellular calcium by increasing
the intracellular concentration of cyclic AMP, thereby improving
cardiac contractility.
Indications: low cardiac output following cardiac surgery, especially
•
in the presence of pulmonary hypertension or right ventricular failure.
Cautions: hypertrophic cardiomyopathy, stenotic or obstructive
•
valvular disease, or other outlet obstruction (such as aortic stenosis),
hypotension.
Side effects: tachyarrhythmias, hypotension, thrombocytopaenia,
•
ectopic beats, ventricular tachycardia, supraventricular arrhythmias.
Dose: initial loading dose of 500µg/kg by slow intravenous injection,
•
followed by 5-20µg/kg/min by continuous intravenous infusion over
24 hours adjusted according to the response; maximum 24mg/kg
over 24 hours.
109
17 What are the pharmacological properties of nitric
oxide?
Mechanism of action: nitric oxide is a potent and selective pulmonary
•
vasodilator, which causes relaxation of pulmonary artery smooth
muscle by acting on cyclic guanosine monophosphate (cGMP).
Indications: persistent neonatal pulmonary hypertension and other
•
forms of arterial pulmonary hypertension.
Cautions: methaemoglobin should be measured regularly,
•
particularly in neonates.
Side effects: risk of haemorrhage by inhibiting platelet aggregation,
•
methaemoglobinaemia.
Dose: 20 ppm.
•
Соседние файлы в папке Библиотека им академика М.И. Перельмана