Dose Sympathomimetics
2.7 Dose Sympathomimetics
. By intravenous infusion , 2.5–10 micrograms/kg/ minute, adjusted according to response
2.7.1 Inotropic sympathomimetics
2.7.2 Vasoconstrictor sympathomimetics
Dobutamine (Non-proprietary) A Strong sterile solution , dobutamine (as hydro-
2.7.3 Cardiopulmonary resuscitation
chloride) 12.5 mg/mL. For dilution and use as an intravenous infusion. Net price 20-mL amp = £5.20
The properties of sympathomimetics vary according to whether they act on alpha or on beta adrenergic recep- tors. Adrenaline (epinephrine) (section 2.7.3) acts on
DOPAMINE HYDROCHLORIDE
both alpha and beta receptors and increases both Indications cardiogenic shock in infarction or cardiac heart rate and contractility (beta effects); it can cause
surgery
peripheral vasodilation (a beta effect) or vasoconstric- Cautions correct hypovolaemia; low dose in shock tion (an alpha effect).
due to acute myocardial infarction—see notes above; hyperthyroidism; pregnancy (Appendix 4); interac- tions: Appendix 1 (sympathomimetics)
Contra-indications
tachyarrhythmia, phaeochromo-
2.7.1 cytoma Inotropic
ardiov C
Side-effects
nausea and vomiting, peripheral vaso-
sympathomimetics
constriction, hypotension, hypertension, tachycardia Dose
ascular
The cardiac stimulants dobutamine and dopamine act . By intravenous infusion , 2–5 micrograms/kg/min- on beta receptors in cardiac muscle, and increase
ute initially (see notes above) contractility with little effect on rate.
Dopamine (Non-proprietary) A syst
Dopexamine acts on beta receptors in cardiac muscle Sterile concentrate , dopamine hydrochloride 40 mg/ mL, net price 5-mL amp = £3.88; 160 mg/mL, 5-mL
em
to produce its positive inotropic effect; and on periph- eral dopamine receptors to increase renal perfusion; it is
amp = £14.75. For dilution and use as an intravenous reported not to induce vasoconstriction.
infusion
Isoprenaline injection is available from ‘special-order’ Intravenous infusion , dopamine hydrochloride manufacturers or specialist-importing companies, see
1.6 mg/mL in glucose 5% intravenous infusion, net p. 939.
price 250-mL container (400 mg) = £11.69; 3.2 mg/ mL, 250-mL container (800 mg) = £22.93 (both hosp.
Shock Shock is a medical emergency associated with a
only)
high mortality. The underlying causes of shock such as Select-A-Jet c Dopamine (UCB Pharma) haemorrhage, sepsis, or myocardial insufficiency should
be corrected. The profound hypotension of shock must Strong sterile solution , dopamine hydrochloride
40 mg/mL, net price 5-mL vial = £5.01; 10-mL vial =
be treated promptly to prevent tissue hypoxia and organ £8.05. For dilution and use as an intravenous infusion failure. Volume replacement is essential to correct the
hypovolaemia associated with haemorrhage and sepsis but may be detrimental in cardiogenic shock. Depend-
DOPEXAMINE HYDROCHLORIDE
ing on haemodynamic status, cardiac output may be
improved by the use of sympathomimetic inotropes inotropic support and vasodilator in exacerbations of chronic heart failure and in heart such as adrenaline (epinephrine), dobutamine or
Indications
failure associated with cardiac surgery dopamine (see notes above). In septic shock, when fluid replacement and inotropic support fail to maintain
Cautions myocardial infarction, recent angina, hypo- blood pressure, the vasoconstrictor noradrenaline (nor-
kalaemia, hyperglycaemia; correct hypovolaemia epinephrine) (section 2.7.2) may be considered. In
before starting and during treatment, monitor blood cardiogenic shock peripheral resistance is frequently
pressure, pulse, plasma potassium, and blood glucose; high and to raise it further may worsen myocardial
avoid abrupt withdrawal; pregnancy; interactions: performance and exacerbate tissue ischaemia.
Appendix 1 (sympathomimetics) Contra-indications left ventricular outlet obstruction The use of sympathomimetic inotropes and vaso-
such as hypertrophic cardiomyopathy or aortic ste- constrictors should preferably be confined to the inten-
nosis; phaeochromocytoma, thrombocytopenia sive care setting and undertaken with invasive haemo-
dynamic monitoring. Side-effects nausea, vomiting; tachycardia, brady- cardia, arrhythmias, angina, myocardial infarction; For advice on the management of anaphylactic shock,
tremor, headache; dyspnoea; reversible thrombocy- see section 3.4.3.
topenia; sweating
2.7.2 Vasoconstrictor sympathomimetics BNF 57 Dose
Ephedrine Hydrochloride (Non-proprietary) A . By intravenous infusion into central or large per-
Injection , ephedrine hydrochloride 3 mg/mL, net ipheral vein, 500 nanograms/kg/minute, may be
price 10-mL amp = £2.83; 30 mg/mL, net price 1-mL increased to 1 microgram/kg/minute and further
amp = £1.70
increased up to 6 micrograms/kg/minute in incre- ments of 0.5–1 microgram/kg/minute at intervals of not less than 15 minutes
METARAMINOL
Dopacard c (Cephalon) A Indications acute hypotension (see notes above); Strong sterile solution , dopexamine hydrochloride
priapism (section 7.4.5) [unlicensed indication]
10 mg/mL (1%). For dilution and use as an intra- venous infusion. Net price 5-mL amp = £21.00 Cautions see under Noradrenaline Acid Tartrate; Note Contact with metal in infusion apparatus should be mini-
longer duration of action than noradrenaline (norepi- mised
nephrine), see below; cirrhosis; pregnancy (Appendix 4); breast-feeding (Appendix 5) Hypertensive response Metaraminol has a longer duration of action than noradrenaline, and an excessive vasopressor response may cause a prolonged rise in blood pressure
tem
Contra-indications see under Noradrenaline Acid
sys
2.7.2 Vasoconstrictor
Tartrate
sympathomimetics Side-effects see under Noradrenaline Acid Tartrate;
tachycardia; fatal ventricular arrhythmia reported in
ascular
Laennec’s cirrhosis Vasoconstrictor sympathomimetics raise blood pres-
Dose
diov sure transiently by acting on alpha-adrenergic receptors . By intravenous infusion , 15–100 mg, adjusted
C ar to constrict peripheral vessels. They are sometimes used as an emergency method of elevating blood pres- according to response sure where other measures have failed (see also section
. In emergency, by intravenous injection , 0.5–5 mg
then by intravenous infusion , 15–100 mg, adjusted according to response
The danger of vasoconstrictors is that although they raise blood pressure they also reduce perfusion of vital
Metaraminol (Non-proprietary) A organs such as the kidney.
Injection , metaraminol 10 mg (as tartrate)/mL Available from ‘special-order’ manufacturers or specialist-
Spinal and epidural anaesthesia may result in sympa- importing companies, see p. 939 thetic block with resultant hypotension. Management may include intravenous fluids (which are usually given prophylactically), oxygen (section 3.6), elevation of the legs, and injection of a pressor drug such as ephedrine.
NORADRENALINE ACID TARTRATE/
As well as constricting peripheral vessels ephedrine
NOREPINEPHRINE BITARTRATE
also accelerates the heart rate (by acting on beta recep- Indications see under dose tors). Use is made of this dual action of ephedrine to
manage associated bradycardia (although intravenous coronary, mesenteric, or peripheral vascular injection of atropine sulphate 400 to 600 micrograms
Cautions
thrombosis; following myocardial infarction, Prinz- may also be required if bradycardia persists).
metal’s variant angina, hyperthyroidism, diabetes mellitus; hypoxia or hypercapnia; uncorrected hypo- volaemia; elderly; extravasation at injection site may
cause necrosis; interactions: Appendix 1 Indications
EPHEDRINE HYDROCHLORIDE
(sympathomimetics) see under Dose
Contra-indications Cautions
hypertension (monitor blood hyperthyroidism, diabetes mellitus,
pressure and rate of flow frequently); pregnancy ischaemic heart disease, hypertension, susceptibility
(Appendix 4)
to angle-closure glaucoma, elderly, pregnancy (Appendix 4); may cause acute urine retention in Side-effects hypertension, headache, bradycardia, prostatic hypertrophy; interactions: Appendix 1
arrhythmias, peripheral ischaemia (sympathomimetics)
Dose
Contra-indications breast-feeding (Appendix 5) . Acute hypotension, by intravenous infusion , via Side-effects nausea, vomiting, anorexia; tachycardia
central venous catheter, of a solution containing (sometimes bradycardia), arrhythmias, anginal pain,
noradrenaline acid tartrate 80 micrograms/mL vasoconstriction with hypertension, vasodilation with
(equivalent to noradrenaline base 40 micrograms/ hypotension, dizziness and flushing; dyspnoea; head-
mL) at an initial rate of 0.16–0.33 mL/minute, ache, anxiety, restlessness, confusion, psychoses,
adjusted according to response insomnia, tremor; difficulty in micturition, urine
. Cardiac arrest, by rapid intravenous or intracardiac retention; sweating, hypersalivation; changes in
injection , 0.5–0.75 mL of a solution containing blood-glucose concentration; very rarely angle-closure
noradrenaline acid tartrate 200 micrograms/mL glaucoma
(equivalent to noradrenaline base 100 micrograms/ Dose
mL)
. Reversal of hypotension from spinal or epidural Noradrenaline/Norepinephrine (Non-proprietary) A anaesthesia, by slow intravenous injection of a
Injection , noradrenaline acid tartrate 2 mg/mL solution containing ephedrine hydrochloride 3 mg/
(equivalent to noradrenaline base 1 mg/mL). For mL, 3–6 mg (max. 9 mg) repeated every 3–4 min-
dilution before use. Net price 2-mL amp = £1.01, 4-mL utes according to response to max. 30 mg
amp = £1.50, 20-mL amp = £6.35
BNF 57
2.7.3 Cardiopulmonary resuscitation 123
all, the endotracheal route can be considered for some Indications
PHENYLEPHRINE HYDROCHLORIDE
drugs.
For the management of acute anaphylaxis see section Cautions see under Noradrenaline Acid Tartrate;
acute hypotension (see notes above); priapism (section 7.4.5) [unlicensed indication]
longer duration of action than noradrenaline (norepi- nephrine), see below; coronary disease
ADRENALINE/EPINEPHRINE
Hypertensive response Phenylephrine has a longer dura- tion of action than noradrenaline, and an excessive vaso- Indications see notes above pressor response may cause a prolonged rise in blood
Cautions heart disease, hypertension, arrhythmias, pressure
cerebrovascular disease, phaeochromocytoma; dia- Contra-indications see under Noradrenaline Acid
betes mellitus, hyperthyroidism; susceptibility to Tartrate; severe hyperthyroidism; pregnancy (Appen-
angle-closure glaucoma; elderly; interactions: dix 4)
Appendix 1 (sympathomimetics) Side-effects see under Noradrenaline Acid Tartrate;
Side-effects nausea, vomiting; tachycardia, arrhyth- tachycardia or reflex bradycardia
mias, palpitation, cold extremities, hypertension (risk Dose
of cerebral haemorrhage); dyspnoea, pulmonary . By subcutaneous or intramuscular injection , 2–
oedema (on excessive dosage or extreme sensitivity);
5 mg, followed if necessary by further doses of 1– anxiety, tremor, restlessness, headache, weakness,
10 mg dizziness; hyperglycaemia; urinary retention; sweat- . By slow intravenous injection of a 1 mg/mL solu-
ing; tissue necrosis at injection site and angle-closure tion, 100–500 micrograms repeated as necessary
glaucoma also reported after at least 15 minutes
Dose
. By intravenous infusion , initial rate up to 180 micr-
. See notes above
ograms/minute reduced to 30–60 micrograms/ Adrenaline/Epinephrine 1 in 10 000, Dilute minute according to response (Non-
proprietary) A
Phenylephrine (Sovereign) A Injection , adrenaline (as acid tartrate) 100 micr- Injection , phenylephrine hydrochloride 10 mg/mL
ograms/mL. 10-mL amp.
(1%), net price 1-mL amp = £5.50
Brands include Minijet
Adrenaline
C ardiov
ascular
2.8 Anticoagulants and
2.7.3 Cardiopulmonary
resuscitation protamine
syst
2.8.1 Parenteral anticoagulants em
The algorithm for cardiopulmonary resuscitation (see
inside back cover) reflects the most recent recommen-
2.8.2 Oral anticoagulants
dations of the Resuscitation Council (UK). These guide-
2.8.3 Protamine sulphate
lines are available at www.resus.org.uk . Cardiac arrest can be associated with ventricular fibril-
The main use of anticoagulants is to prevent thrombus lation, pulseless ventricular tachycardia, asystole, and
formation or extension of an existing thrombus in the electromechanical dissociation (pulseless electrical
slower-moving venous side of the circulation, where the activity).
thrombus consists of a fibrin web enmeshed with plate- (100 micrograms/mL) is recommended in a dose of
Adrenaline (epinephrine)
1 in 10 000
lets and red cells. They are therefore widely used in the
1 mg (10 mL) by intravenous injection repeated every prevention and treatment of deep-vein thrombosis in 3–5 minutes if necessary. Administration through a
the legs.
central line is preferred, however if adrenaline is Anticoagulants are of less use in preventing thrombus injected through a peripheral line, it must be flushed
formation in arteries, for in faster-flowing vessels throm- with at least 20 mL Sodium Chloride 0.9% injection to
bi are composed mainly of platelets with little fibrin. aid entry into the central circulation. Intravenous injec-
They are used to prevent thrombi forming on prosthetic tion of amiodarone 300 mg or 5 mg/kg (from a prefilled
heart valves.
syringe or diluted in 20 mL Glucose 5%) should be considered after adrenaline to treat ventricular fibrilla- tion or pulseless ventricular tachycardia in cardiac arrest refractory to defibrillation. An additional dose of
2.8.1 Parenteral anticoagulants
amiodarone 150 mg (or 2.5 mg/kg) can be given by intravenous injection if necessary, followed by an intra- venous infusion of amiodarone 900 mg over 24 hours.
Heparin
Lidocaine, in a dose of 1 mg/kg, is an alternative if Heparin initiates anticoagulation rapidly but has a short amiodarone is not available; a total dose of 3 mg/kg
duration of action. It is often referred to as ‘standard’ or should not be exceeded during the first hour. Atropine
‘unfractionated heparin’ to distinguish it from the low
3 mg by intravenous injection (section 15.1.3) as a single molecular weight heparins (see p. 125), which have a dose is also used in non-shockable cardiopulmonary
longer duration of action. Although a low molecular resuscitation to block vagal activity.
weight heparin is generally preferred for routine use, During cardiopulmonary arrest if intravenous access
heparin can be used in those at high risk of bleeding cannot be obtained, the intraosseous route can be
because its effect can be terminated rapidly by stopping considered; if circulatory access cannot be obtained at
the infusion.
Treatment For the initial treatment of deep-vein thrombosis and pulmonary embolism a low molecular weight heparin is used; alternatively, heparin is given as an intravenous loading dose, followed by continuous intravenous infusion (using an infusion pump) or by intermittent subcutaneous injection. Intermittent intra- venous injection of heparin is no longer recommended. An oral anticoagulant (usually warfarin, section 2.8.2) is started at the same time as the heparin (the heparin needs to be continued for at least 5 days and until the INR has been in the therapeutic range for 2 consecutive days). Laboratory monitoring, preferably on a daily basis, is essential; determination of the activated partial thromboplastin time (APTT) is the most widely used measure. A low molecular weight heparin or, in some circumstances, heparin is also used in regimens for the management of myocardial infarction (section 2.10.1) and unstable angina (section 2.6).
Prophylaxis In patients undergoing general surgery, a low molecular weight heparin is effective for the pre- vention of postoperative deep-vein thrombosis and pulmonary embolism in ‘high-risk’ patients (i.e. those with obesity, malignant disease, history of deep-vein thrombosis or pulmonary embolism, patients over 40 years, or those with an established thrombophilic dis- order or who are undergoing major or complicated surgery). Subcutaneous injection of low-dose heparin is an alternative; this regimen does not require labora- tory monitoring.
To combat the increased risk in major orthopaedic surgery an adjusted dose regimen of heparin (with monitoring), low molecular weight heparin (p. 125) or fondaparinux (p. 128) can be used—a low molecular weight heparin is probably more effective.
Pregnancy Heparins are used for the management of venous thromboembolism in pregnancy because they do not cross the placenta. Low molecular weight hepar- ins are preferred because they have a lower risk of osteoporosis and of heparin-induced thrombocytopenia. Low molecular weight heparins are eliminated more rapidly in pregnancy, requiring alteration of the dosage regimen for drugs such as dalteparin, enoxaparin, and tinzaparin. Treatment should be stopped at the onset of labour and advice sought from a specialist on continuing therapy after birth.
Extracorporeal circuits Heparin is also used in the maintenance of extracorporeal circuits in cardiopulmo- nary bypass and haemodialysis.
Haemorrhage If haemorrhage occurs it is usually sufficient to withdraw heparin, but if rapid reversal of the effects of heparin is required, protamine sulphate (section 2.8.3) is a specific antidote (but only partially reverses the effects of low molecular weight heparins).