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).