Hypotension and shock

Sympathomimetics

Overview

The properties of sympathomimetics vary according to whether they act on alpha or on beta adrenergic receptors.

Response to sympathomimetics can also vary considerably in children, particularly neonates. It is important to titrate the dose to the desired effect and to monitor the child closely.

Inotropic sympathomimetics

Dopamine hydrochloride p.114has a variable,

unpredictable, and dose dependent impact on vascular tone.

Low dose infusion normally causes vasodilatation, but there is little evidence that this is clinically beneficial; moderate doses increase myocardial contractility and cardiac output in older children, but in neonates moderate doses may cause a reduction in cardiac output. High doses cause

vasoconstriction and increase vascular resistance, and should therefore be used with caution following cardiac

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surgery, or where there is co-existing neonatal pulmonary hypertension.

In neonates the response to inotropic sympathomimetics varies considerably, particularly in those born prematurely;

careful dose titration and monitoring are necessary.

Isoprenalineinjection is available from’special-order’ manufacturers or specialist importing companies.

Shock

Shock is a medical emergency associated with a high mortality. The underlying causes of shock such as haemorrhage, sepsis or myocardial insufficiency should be corrected. Additional treatment is dependent on the type of shock.

Septic shockis associated with severe hypovolaemia (due to vasodilation and capillary leak) which should be corrected with crystalloids or colloids. If hypotension persists despite volume replacement, dopamine hydrochloride should be started. For shock refractory to treatment with dopamine hydrochloride, if cardiac output is high and peripheral vascular resistance is low (warm shock),

noradrenaline/norepinephrine p.115should be addedorif cardiac output is low and peripheral vascular resistance is high (cold shock), adrenaline/epinephrine p.128^{should be} added. Additionally, in cold shock, a vasodilator such as milrinone p.118, glyceryl trinitrate p.127, or sodium nitroprusside p.109(on specialist advice only) can be used to reduce vascular resistance.

If the shock is resistant to volume expansion and catecholamines, and there is suspected or proven adrenal insufficiency, low dose hydrocortisone p.411can be used.

ACTH-stimulated plasma-cortisol concentration should be measured; however, hydrocortisone can be started without such information. Alternatively, if the child is resistant to catecholamines, and vascular resistance is low, vasopressin p.62can be added.

Neonatal septic shockcan be complicated by the transition from fetal to neonatal circulation. Treatment to reverse right ventricular failure, by decreasing pulmonary artery pressures, is commonly needed in neonates withfl uid-refractory shock and persistent pulmonary hypertension of the newborn. Rapid administration offluid in neonates with patent ductus arteriosus may cause left-to-right shunting and congestive heart failure induced by ventricular overload.

Incardiogenic shock, the aim is to improve cardiac output and to reduce the afterload on the heart. If central venous pressure is low, cautious volume expansion with a colloid or crystalloid can be used. An inotrope such as

adrenaline/epinephrine or dopamine hydrochloride should be given to increase cardiac output. Dobutamine below is a peripheral vasodilator and is an alternative if hypotension is not significant.

Milrinone has both inotropic and vasodilatory effects and can be used when vascular resistance is high. Alternatively, glyceryl trinitrate or sodium nitroprusside (on specialist advice only) can be used to reduce vasoconstriction.

Hypovolaemic shockshould be treated with a crystalloid or colloid solution (or whole or reconstituted blood if source of hypovolaemia is haemorrhage) and further steps to improve cardiac output and decrease vascular resistance can be taken, as in cardiogenic shock.

The use of sympathomimetic inotropes and vasoconstrictors should preferably be confined to the intensive care setting and undertaken with invasive haemodynamic monitoring.

See also advice on the management of anaphylactic shock in Antihistamines, allergen immunotherapy and allergic emergencies p.162^.

Vasoconstrictor sympathomimetics

Vasoconstrictor sympathomimetics raise blood pressure transiently by acting on alpha-adrenergic receptors to constrict peripheral vessels. They are sometimes used as an

emergency method of elevating blood pressure where other measures have failed.

The danger of vasoconstrictors is that although they raise blood pressure they also reduce perfusion of vital organs such as the kidney.

Ephedrine hydrochloride p.114is used to reverse hypotension caused by spinal and epidural anaesthesia.

Metaraminol p.115is used as a vasopressor during cardiopulmonary bypass.

Phenylephrine hydrochloride p.116causes peripheral vasoconstriction and increases arterial pressure.

Ephedrine hydrochloride, metaraminol and phenylephrine hydrochloride are rarely needed in children and should be used under specialist supervision.

Noradrenaline/norepinephrine is reserved for children with low systemic vascular resistance that is unresponsive to fluid resuscitation following septic shock, spinal shock, and anaphylaxis.

Adrenaline/epinephrine is mainly used for its inotropic action. Low doses (acting on beta receptors) cause systemic and pulmonary vasodilation, with some increase in heart rate and stroke volume and also an increase in contractility;

high doses act predominantly on alpha receptors causing intense systemic vasoconstriction.

SYMPATHOMIMETICS

›

^INOTROPIC

Dobutamine

lDRUG ACTIONDobutamine is a cardiac stimulant which acts on beta₁receptors in cardiac muscle, and increases contractility with little effect on rate.

lINDICATIONS AND DOSE

Inotropic support in low cardiac output states, after cardiac surgery, cardiomyopathies, shock

▶BY CONTINUOUS INTRAVENOUS INFUSION

▶Neonate:Initially5micrograms/kg/minute, then adjusted according to response to

2–20micrograms/kg/minute, doses as low as 0^.5–1microgram/kg/minute have been used.

▶Child:Initially5micrograms/kg/minute, then adjusted according to response to2–20micrograms/kg/minute, doses as low as0^.5–1microgram/kg/minute have been used

lCONTRA-INDICATIONSPhaeochromocytoma

lCAUTIONSAcute heart failure

.

acute myocardial infarction

.

arrhythmias

.

correct hypercapnia before starting and during treatment

.

correct hypovolaemia before starting and during treatment

.

correct hypoxia before starting and during treatment

.

correct metabolic acidosis before starting and during treatment

.

diabetes mellitus

.

extravasation may cause tissue necrosis

.

extreme caution or avoid in marked obstruction of cardiac ejection (such as idiopathic hypertrophic subaortic stenosis)

.

hyperthyroidism

.

ischaemic heart disease

.

occlusive vascular disease

.

severe hypotension

.

susceptibility to angle-closure glaucoma

.

tachycardia

.

tolerance may develop with continuous infusions longer than 72 hours lINTERACTIONS→Appendix1(sympathomimetics).

lSIDE-EFFECTS

▶RarePsychosis

▶Very rareAngle-closure glaucoma

.

AV block

.

bradycardia

.

cardiac arrest

.

coronary artery spasm

.

hypokalaemia

.

myocardial infarction

.

petechial bleeding

▶Frequency not knownAnxiety

.

arrhythmias

.

bronchospasm

.

cerebral haemorrhage

.

chest pain

.

dyspnoea

.

eosinophilia

.

fever

.

headache

.

hypertension (marked increase in systolic blood pressure indicates overdose)

.

hypotension

.

increased urinary urgency

.

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Hypotension and shock 113

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myoclonic spasm

.

nausea

.

palpitation

.

paraesthesia

.

phlebitis

.

pruritus of scalp

.

pulmonary oedema

.

rash

.

reduced platelet aggregation (on prolonged use)

.

tachycardia

.

tremor

.

vomiting

lPREGNANCYNo evidence of harm inanimalstudies— manufacturers advise use only if potential benefit outweighs risk.

lBREAST FEEDINGManufacturers advise avoid—no information available.

lDIRECTIONS FOR ADMINISTRATIONDobutamine injection should be diluted before use or given undiluted with syringe pump. Dobutamine concentrate for intravenous infusion should be diluted before use.

Forcontinuous intravenous infusion, using infusion pump, dilute to a concentration of0^.5–1mg/mL (max.5^{mg/mL if} fluid restricted) with Glucose5^%orSodium Chloride0^.9^%;

infuse higher concentration solutions through central venous catheter only. Incompatible with bicarbonate and other strong alkaline solutions.

▶In neonatesNeonatal intensive care, dilute30mg/kg body-weight to afinal volume of50mL with infusionfluid; an intravenous infusion rate of0^.5mL/hour provides a dose of 5micrograms/kg/minute; max. concentration of5^mg/mL;

infuse higher concentration solutions through central venous catheter only. Incompatible with bicarbonate and other strong alkaline solutions.

lMEDICINAL FORMS

There can be variation in the licensing of different medicines containing the same drug.

Solution for infusion EXCIPIENTS:May contain Sulfites

▶Dobutamine (Non-proprietary)

Dobutamine (as Dobutamine hydrochloride) 5 mg per 1 mlDobutamine250mg/50ml solution for infusion vials| 1vial^P£7.50

Dobutamine (as Dobutamine hydrochloride) 12.5 mg per 1 mlDobutamine250mg/20ml concentrate for solution for infusion ampoules|5ampoule^P£26.00–£26.25

Dopamine hydrochloride

lDRUG ACTIONDopamine is a cardiac stimulant which acts on beta1receptors in cardiac muscle, and increases contractility with little effect on rate.

lINDICATIONS AND DOSE

To correct the haemodynamic imbalance due to acute hypotension, shock, cardiac failure, adjunct following cardiac surgery

▶BY CONTINUOUS INTRAVENOUS INFUSION

▶Neonate:Initially3micrograms/kg/minute (max. per dose20micrograms/kg/minute), adjusted according to response.

▶Child:Initially5micrograms/kg/minute (max. per dose 20micrograms/kg/minute), adjusted according to response

lUNLICENSED USENot licensed for use in children under 12^years.

lCONTRA-INDICATIONSPhaeochromocytoma

.

tachyarrhythmia

lCAUTIONSCorrect hypovolaemia

.

hyperthyroidism lINTERACTIONS→Appendix1(sympathomimetics).

lSIDE-EFFECTS

▶Common or very commonChest pain

.

dyspnoea

.

headache

.

hypotension

.

nausea

.

palpitation

.

tachycardia

.

vasoconstriction

.

vomiting

▶UncommonBradycardia

.

gangrene

.

hypertension

.

mydriasis

▶RareFatal ventricular arrhythmias

lPREGNANCYNo evidence of harm inanimalstudies— manufacturer advises use only if potential benefit outweighs risk.

lBREAST FEEDINGMay suppress lactation—not known to be harmful.

lDIRECTIONS FOR ADMINISTRATIONDopamine concentrate for intravenous infusion to be diluted before use.

Forcontinuous intravenous infusion, dilute to a max.

concentration of3^.2mg/mL with Glucose5^%orSodium Chloride0^.9%. Infuse higher concentrations through central venous catheter using a syringe pump to avoid extravasation andfluid overload. Incompatible with bicarbonate and other alkaline solutions.

▶In neonatesNeonatal intensive care, dilute30mg/kg body-weight to afinal volume of50mL with infusionfluid; an intravenous infusion rate of0^.3mL/hour provides a dose of 3micrograms/kg/minute; max. concentration of 3^.2mg/mL; infuse higher concentrations through central venous catheter. Incompatible with bicarbonate and other alkaline solutions.

lMEDICINAL FORMS

There can be variation in the licensing of different medicines containing the same drug. Forms available from special-order manufacturers include: solution for infusion

Solution for infusion

▶Dopamine hydrochloride (Non-proprietary)

Dopamine hydrochloride 40 mg per 1 mlDopamine200mg/5ml solution for infusion ampoules|5ampoule^P£19.42–£20.00| 10ampoule^P £9.04

Dopamine200mg/5ml concentrate for solution for infusion ampoules

|10ampoule^P no price available

Dopamine hydrochloride 160 mg per 1 mlDopamine800mg/5ml solution for infusion ampoules|10ampoule^P £34.00 SYMPATHOMIMETICS

›

VASOCONSTRICTOR

Ephedrine hydrochloride

lINDICATIONS AND DOSE

Reversal of hypotension from spinal or epidural anaesthesia

▶BY SLOW INTRAVENOUS INJECTION

▶Child 1–11 years: 500–750micrograms/kg every 3–4minutes, adjusted according to response, alternatively17–25^mg/m2every3–4^minutes, adjusted according to response, injection solution to contain ephedrine hydrochloride3mg/ml; maximum 30mg per course

▶Child 12–17 years:3–7^.5^{mg every}3–4minutes (max. per dose9mg), adjusted according to response, injection solution to contain ephedrine hydrochloride3^mg/ml;

maximum30mg per course

lCAUTIONSDiabetes mellitus

.

hypertension

.

hyperthyroidism

.

susceptibilityto angle-closure glaucoma lINTERACTIONS→Appendix1(sympathomimetics).

lSIDE-EFFECTS

▶Common or very commonAnginal pain

.

anorexia

.

anxiety

.

arrhythmias

.

changes in blood-glucose concentration

.

confusion

.

difficulty in micturition

.

dizziness

.

dyspnoea

.

flushing

.

headache

.

hypersalivation

.

insomnia

.

nausea

.

psychoses

.

restlessness

.

sweating

.

tachycardia

.

tremor

.

urine retention

.

vasoconstriction with hypertension

.

vasodilation with hypotension

.

vomiting

▶Very rareAngle-closure glaucoma

▶Frequency not knownBradycardia

.

Increased lacrimation (can have adverse effects on contact lens wear) lPREGNANCYIncreased fetal heart rate reported with

parenteral ephedrine.

lBREAST FEEDINGPresent in milk; manufacturer advises avoid—irritability and disturbed sleep reported.

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lRENAL IMPAIRMENTUse with caution.

lDIRECTIONS FOR ADMINISTRATIONForslow intravenous injection, give via central venous catheter using a solution containing ephedrine hydrochloride3^mg/ml.

lMEDICINAL FORMS

There can be variation in the licensing of different medicines containing the same drug. Forms available from special-order manufacturers include: solution for injection

Solution for injection

▶Ephedrine hydrochloride (Non-proprietary)

Ephedrine hydrochloride 3 mg per 1 mlEphedrine30mg/10ml solution for injection ampoules|10ampoule^P £73.21 Ephedrine30mg/10ml solution for injection pre-filled syringes|1 pre-filled disposable injection^P£7.59–£9.50|12pre-filled disposable injection^P£114.00

Ephedrine hydrochloride 30 mg per 1 mlEphedrine30mg/1ml solution for injection ampoules|10ampoule^P £4.31–£4.74

Metaraminol

lINDICATIONS AND DOSE Acute hypotension

▶BY INTRAVENOUS INFUSION

▶Child 12–17 years:15–100mg, adjusted according to response

Emergency treatment of acute hypotension

▶INITIALLY BY INTRAVENOUS INJECTION

▶Child 12–17 years:Initially0^.5–5mg, then (by intravenous infusion)15–100mg, adjusted according to response

lUNLICENSED USENot licensed for use in children.

lCONTRA-INDICATIONSHypertension

lCAUTIONSCirrhosis

.

coronary vascular thrombosis

.

diabetes mellitus

.

extravasation at injection site may cause necrosis

.

following myocardial infarction

.

hypercapnia

.

hyperthyroidism

.

hypoxia

.

mesenteric vascular thrombosis

.

peripheral vascular thrombosis

.

Prinzmetal’s variant angina

.

susceptibility to angle-closure glaucoma

.

uncorrected hypovolaemia CAUTIONS, FURTHER INFORMATION

▶Hypertensive response

Metaraminol has a longer duration of action than noradrenaline, and an excessive vasopressor response may cause a prolonged rise in blood pressure.

lINTERACTIONS→Appendix1(sympathomimetics).

lSIDE-EFFECTSAngle-closure glaucoma

.

anorexia

.

anxiety

.

arrhythmias

.

bradycardia

.

confusion

.

dyspnoea

.

fatal ventricular arrhythmia reported in Laennec’s cirrhosis

.

headache

.

hypertension

.

hypoxia

.

insomnia

.

nausea

.

palpitation

.

peripheral ischaemia

.

psychosis

.

tachycardia

.

tremor

.

urinary retention

.

vomiting

.

weakness lPREGNANCYMay reduce placental perfusion—

manufacturer advises use only if potential benefit outweighs risk.

lBREAST FEEDINGManufacturer advises caution—no information available.

lMONITORING REQUIREMENTSMonitor blood pressure and rate offlow frequently.

lDIRECTIONS FOR ADMINISTRATIONForintravenous infusion, dilute to a concentration of

30–200micrograms/mL with Glucose5% or Sodium Chloride0^.9% and give through a central venous catheter.

lMEDICINAL FORMS

There can be variation in the licensing of different medicines containing the same drug. Forms available from special-order manufacturers include: solution for injection

Solution for injection

▶Metaraminol (Non-proprietary)

Metaraminol (as Metaraminol tartrate) 10 mg per 1 mlMetaraminol10mg/1ml solution for injection ampoules| 10ampoule^P £31.97

Noradrenaline/norepinephrine

lINDICATIONS AND DOSE

Acute hypotension (septic shock)|Shock secondary to excessive vasodilation (as noradrenaline)

▶BY CONTINUOUS INTRAVENOUS INFUSION

▶Neonate:20–100nanograms/kg/minute (max. per dose 1microgram/kg/minute), adjusted according to response.

▶Child:20–100nanograms/kg/minute (max. per dose 1microgram/kg/minute), adjusted according to response

DOSE EQUIVALENCE AND CONVERSION 1mg of noradrenaline base is equivalent to2^{mg of} noradrenaline acid tartrate.Doses expressed as the base.

lUNLICENSED USENot licensed for use in children.

lCONTRA-INDICATIONSHypertension

lCAUTIONSCoronary vascular thrombosis

.

diabetes mellitus

.

extravasation at injection site may cause necrosis

.

following myocardial infarction

.

hypercapnia

.

hyperthyroidism

.

hypoxia

.

mesenteric vascular thrombosis

.

peripheral vascular thrombosis

.

Prinzmetal’s variant angina

.

susceptibility to angle-closure glaucoma

.

uncorrected hypovolaemia

lINTERACTIONS→Appendix1(sympathomimetics).

lSIDE-EFFECTSAngle-closure glaucoma

.

anorexia

.

anxiety

.

arrhythmias

.

bradycardia

.

confusion

.

dyspnoea

.

headache

.

hypertension

.

hypoxia

.

insomnia

.

nausea

.

palpitation

.

peripheral ischaemia

.

psychosis

.

tachycardia

.

tremor

.

urinary retention

.

vomiting

.

weakness lPREGNANCYAvoid—may reduce placental perfusion.

lMONITORING REQUIREMENTSMonitor blood pressure and rate offlow frequently.

lDIRECTIONS FOR ADMINISTRATIONForcontinuous intravenous infusion, dilute to a max. concentration of noradrenaline (base)40micrograms/mL (higher concentrations can be used iffluid-restricted) with Glucose5% or Sodium Chloride and Glucose. Infuse through central venous catheter; discard if discoloured.

Incompatible with bicarbonate or alkaline solutions.

▶In neonatesNeonatal intensive care, dilute600^micrograms (base)/kg body-weight to afinal volume of50^{mL with} infusionfluid; an intravenous infusion rate of0^.1^mL/hour provides a dose of20nanograms(base)/kg/minute; infuse through central venous catheter; max. concentration of noradrenaline (base)40micrograms/mL (higher concentrations can be used iffluid-restricted). Discard if discoloured. Incompatible with bicarbonate or alkaline solutions.

lPRESCRIBING AND DISPENSING INFORMATIONFor a period of time, preparations on the UK market may be described as either noradrenaline base or noradrenaline acid tartrate; doses in the BNF are expressed as the base.

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Hypotension and shock 115

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lMEDICINAL FORMS

There can be variation in the licensing of different medicines containing the same drug. Forms available from special-order manufacturers include: infusion, solution for infusion Solution for infusion

▶Noradrenaline/norepinephrine (Non-proprietary) Noradrenaline (as Noradrenaline acid tartrate) 1 mg per 1 mlNoradrenaline (Norepinephrine)4mg/4ml concentrate for solution for infusion ampoules|10ampoule^P £44.00 Noradrenaline (base)8mg/8ml concentrate for solution for infusion ampoules|10ampoule^P £116.00

Noradrenaline (base)2mg/2ml solution for infusion ampoules| 5ampoule^P £12.00(Hospital only)

Noradrenaline (base)4mg/4ml solution for infusion ampoules| 5ampoule^P £22.00(Hospital only)

Noradrenaline (base)4mg/4ml concentrate for solution for infusion ampoules|10ampoule^P £58.00

Noradrenaline (Norepinephrine)2mg/2ml concentrate for solution for Infusion ampoules|5ampoule^P £11.00

Phenylephrine hydrochloride

lINDICATIONS AND DOSE Acute hypotension

▶BY SUBCUTANEOUS INJECTION, OR BY INTRAMUSCULAR INJECTION

▶Child 1–11 years:100micrograms/kg every1–2^hours (max. per dose5mg) as required

▶Child 12–17 years:Initially2–5mg (max. per dose5^mg), followed by1–10mg, after at least15^{minutes if} required

▶BY SLOW INTRAVENOUS INJECTION

▶Child 1–11 years:Initially5–20micrograms/kg (max. per dose500micrograms), repeated as necessary after at least15^minutes

▶Child 12–17 years:100–500micrograms, repeated as necessary after at least15^minutes

▶BY INTRAVENOUS INFUSION

▶Child 1–15 years:Initially

100–500nanograms/kg/minute, adjusted according to response

▶Child 16–17 years:Initially up to 180micrograms/minute, reduced to

30–60micrograms/minute, adjusted according to response

lUNLICENSED USENot licensed for use in children by intravenous infusion or injection.

lCONTRA-INDICATIONSHypertension

.

severe hyperthyroidism

lCAUTIONSCoronary disease

.

coronary vascular thrombosis

.

diabetes

.

extravasation at injection site may cause necrosis

.

following myocardial infarction

.

hypercapnia

.

hyperthyroidism

.

hypoxia

.

mesenteric vascular thrombosis

.

peripheral vascular thrombosis

.

Prinzmetal’s variant angina

.

susceptibility to angle-closure glaucoma

.

uncorrected hypovolaemia CAUTIONS, FURTHER INFORMATION

▶Hypertensive responsePhenylephrine has a longer duration of action than noradrenaline (norepinephrine), and an excessive vasopressor response may cause a prolonged rise in blood pressure.

lINTERACTIONS→Appendix1(sympathomimetics).

Phenylephrine may interact with systemically administered monoamine-oxidase inhibitors.

lSIDE-EFFECTSAngle-closure glaucoma

.

anorexia

.

anxiety

.

arrhythmias

.

bradycardia (also reflex bradycardia)

.

confusion

.

dyspnoea

.

headache

.

hypertension

.

hypoxia

.

insomnia

.

nausea

.

palpitation

.

peripheral ischaemia

.

psychosis

.

tachycardia

.

tremor

.

urinary retention

.

vomiting

.

weakness

lPREGNANCYAvoid if possible; malformations reported following use infirst trimester; fetal hypoxia and bradycardia reported in late pregnancy and labour.

lMONITORING REQUIREMENTS

▶Contra-indicated in hypertension—monitor blood pressure and rate offlow frequently.

lDIRECTIONS FOR ADMINISTRATIONForintravenous injection, dilute to a concentration of1mg/mL with Water for Injections and administer slowly. Forintravenous infusion, dilute to a concentration of20micrograms/mL with Glucose5% or Sodium Chloride0^.9% and administer as a continuous infusion via a central venous catheter using a controlled infusion device.

lPRESCRIBING AND DISPENSING INFORMATIONIntravenous administration preferred when managing acute hypotension in children.

lMEDICINAL FORMS

There can be variation in the licensing of different medicines containing the same drug. Forms available from special-order manufacturers include: solution for injection

Solution for injection

▶Phenylephrine hydrochloride (Non-proprietary)

Phenylephrine (as Phenylephrine hydrochloride) 50 microgram per 1 mlPhenylephrine500micrograms/10ml solution for injection pre-filled syringes|1pre-filled disposable injection^P£15.00| 10pre-filled disposable injection^P £150.00

Phenylephrine hydrochloride 100 microgram per 1 mlPhenylephrine1mg/10ml solution for injection ampoules| 10ampoule^P £40.00

Phenylephrine hydrochloride 10 mg per 1 mlPhenylephrine 10mg/1ml solution for injection ampoules|10ampoule^P£99.12

5 Heart failure

Drugs used for Heart failure not listed below Bendroflumethiazide, p.102

.

Captopril, p.103

.

Chlorothiazide, p.103

.

Chlortalidone, p.134

.

Digoxin, p.75

.

Enalapril maleate, p.105

.

Glyceryl trinitrate, p.127

.

Lisinopril, p.106

.

Prazosin, p.92

BETA-ADRENOCEPTOR BLOCKERS

›

ALPHA- AND BETA-ADRENOCEPTOR BLOCKERS

eiii^F95 i

Carvedilol

lINDICATIONS AND DOSE

Adjunct in heart failure (limited information available)

▶BY MOUTH

▶Child 2–17 years:Initially50micrograms/kg twice daily (max. per dose3^.125mg) for at least2weeks, then increased to100micrograms/kg twice daily for at least 2weeks, then increased to200micrograms/kg twice daily, then increased if necessary up to

350micrograms/kg twice daily (max. per dose25^mg)

lUNLICENSED USENot licensed for use in children under 18^years.

lCONTRA-INDICATIONSAcute or decompensated heart failure requiring intravenous inotropes

lSIDE-EFFECTSAllergic skin reactions

.

angina

.

AV block

.

changes in liver enzymes

.

depressed mood

.

disturbances of micturition

.

influenza-like symptoms

.

leucopenia

.

nasal stuffiness

.

postural hypotension

.

thrombocytopenia

.

wheezing

lPREGNANCYInformation on the safety of carvedilol during pregnancy is lacking. If carvedilol is used close to delivery,

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infants should be monitored for signs of alpha-blockade (as well as beta-blockade).

lBREAST FEEDINGInfants should be monitored as there is a risk of possible toxicity due to alpha-blockade (in addition to beta-blockade).

lHEPATIC IMPAIRMENTAvoid in hepatic impairment.

lMONITORING REQUIREMENTSMonitor renal function during dose titration in patients with heart failure who also have renal impairment, low blood pressure, ischaemic heart disease, or diffuse vascular disease.

lPATIENT AND CARER ADVICE

Medicines for Children leaflet: Carvedilol for heart failure www.medicinesforchildren.org.uk/carvedilol-heart-failure-0

lMEDICINAL FORMS

There can be variation in the licensing of different medicines containing the same drug. Forms available from special-order manufacturers include: oral suspension

Tablet

CAUTIONARY AND ADVISORY LABELS8

▶Carvedilol (Non-proprietary)

Carvedilol 3.125 mgCarvedilol3.125mg tablets|28tablet^P

£8.00DT price = £0.89

Carvedilol 6.25 mgCarvedilol6.25mg tablets|28tablet^P

£8.99DT price = £0.98

Carvedilol 12.5 mgCarvedilol12.5mg tablets|28tablet^P £9.99 DT price = £0.99

Carvedilol 25 mgCarvedilol25mg tablets|28tablet^P£12.50 DT price = £1.15

DIURETICS

›

POTASSIUM-SPARING DIURETICS

›

ALDOSTERONE ANTAGONISTS

Potassium canrenoate

lINDICATIONS AND DOSE

Short-term diuresis for oedema in heart failure and in ascites

▶BY INTRAVENOUS INJECTION, OR BY INTRAVENOUS INFUSION

▶Neonate:1–2mg/kg twice daily.

▶Child 1 month–11 years:1–2mg/kg twice daily

▶Child 12–17 years:1–2mg/kg twice daily (max. per dose 200^mg)

DOSE EQUIVALENCE AND CONVERSION To convert to equivalent oral spironolactone dose, multiply potassium canrenoate dose by0^.7^.

lUNLICENSED USENot licensed for use in the UK.

lCONTRA-INDICATIONSHyperkalaemia

.

hyponatraemia lCAUTIONSAcute porphyrias p.562

.

hypotension

.

potential metabolic products carcinogenic inrodents lINTERACTIONS→Appendix1(diuretics).

lSIDE-EFFECTS

▶Common or very commonAtaxia

.

drowsiness

.

headache

.

hyperuricaemia

.

menstrual irregularities

.

pain at injection site on rapid administration

▶UncommonEosinophilia

.

hyperkalaemia

.

thrombocytopenia

▶RareAgranulocytosis

.

alopecia

.

deepening of voice

.

erythema

.

hepatotoxicity

.

hoarseness

.

hypersensitivity reactions

.

osteomalacia

.

urticaria

▶Frequency not knownGastro-intestinal disturbances

.

gynaecomastia

.

hirsutism

.

hypochloraemic acidosis

.

hyponatraemia

.

hypotension

.

mastalgia

.

transient confusion with high doses

lPREGNANCYCrosses placenta. Feminisation and undescended testes in male fetus inanimalstudies— manufacturer advises avoid.

lBREAST FEEDINGPresent in breast milk—manufacturer advises avoid.

lRENAL IMPAIRMENTUse with caution if estimated glomerularfiltration rate30–60^mL/minute/1^.73^{m2. Avoid} if estimated glomerularfiltration rate less than

30^mL/minute/1^.73^m2. Monitor plasma-potassium concentration if estimated glomerularfiltration rate 30–60^mL/minute/1^.73^m2.

lMONITORING REQUIREMENTSMonitor electrolytes (discontinue if hyperkalaemia occurs).

lDIRECTIONS FOR ADMINISTRATIONConsult product literature. Intravenous injection to be given over at least 3^minutes.

lPRESCRIBING AND DISPENSING INFORMATIONPotassium canrenoate injection is available from‘special-order’ manufacturers or specialist importing companies.

lMEDICINAL FORMS

There can be variation in the licensing of different medicines containing the same drug.

Solution for injection

▶Potassium canrenoate (Non-proprietary)

Potassium canrenoate 20 mg per 1 mlAldactone200mg/10ml solution for injection ampoules|10ampoule^P no price available

Spironolactone

lINDICATIONS AND DOSE

Oedema in heart failure and in ascites|Nephrotic syndrome|Reduction of hypokalaemia induced by diuretics or amphotericin

▶BY MOUTH

▶Neonate:Initially1–2mg/kg daily in1–2divided doses;

increased if necessary up to7mg/kg daily, in resistant ascites.

▶Child 1 month–11 years: Initially1–3mg/kg daily in 1–2divided doses; increased if necessary up to9^mg/kg daily, in resistant ascites

▶Child 12–17 years:Initially50–100mg daily in 1–2divided doses; increased if necessary up to9^mg/kg daily, in resistant ascites; maximum400^{mg per day}

lUNLICENSED USENot licensed for reduction of hypokalaemia induced by diuretics or amphotericin.

lCONTRA-INDICATIONSAddison’s disease

.

anuria

.

hyperkalaemia

lCAUTIONSAcute porphyrias p.562

.

potential metabolic products carcinogenic inrodents

lINTERACTIONS→Appendix1(diuretics).

Potassium supplements mustnotbe given with potassium-sparing diuretics.

Administration of a potassium-sparing diuretic to a patient receiving an ACE inhibitor or an angiotensin-II receptor antagonist can also cause severe hyperkalaemia.

lSIDE-EFFECTSAcute renal failure

.

agranulocytosis

.

alopecia

.

benign breast tumour

.

breast pain

.

changes in libido

.

confusion

.

dizziness

.

drowsiness

.

electrolyte disturbances

.

gastro-intestinal disturbances

.

gynaecomastia

.

hepatotoxicity

.

hyperkalaemia (discontinue)

.

hypertrichosis

.

hyperuricaemia

.

hyponatraemia

.

leg cramps

.

leucopenia

.

malaise

.

menstrual disturbances

.

rash

.

Stevens-Johnson syndrome

.

thrombocytopenia

lPREGNANCYUse only if potential benefit outweighs risk— feminisation of male fetus inanimalstudies.

lBREAST FEEDINGMetabolites present in milk, but amount probably too small to be harmful.

lRENAL IMPAIRMENTAvoid in acute renal insufficiency or severe impairment. Monitor plasma-potassium concentration (high risk of hyperkalaemia in renal impairment).

BNFC2016–2017

Heart failure 117

Cardiovascularsystem

2

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