2 Cardiovascular system
2.7 Sympathomimetics
2.7.1 Inotropic sympathomimetics 2.7.2 Vasoconstrictor sympathomimetics 2.7.3 Cardiopulmonary resuscitation
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.
2.7.1
Inotropic sympathomimeticsThe cardiac stimulants dobutamine and dopamine act on beta1 receptors in cardiac muscle and increase contractility with little effect on rate.
Dopamine has a variable, unpredictable, and dose dependent impact on vascular tone. Low dose infusion (2 micrograms/kg/minute) normally causes vasodilata-tion, 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 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.
Isoprenaline injection is available from ‘special-order’ manufacturers or specia-list importing companies, see p. 943.
Shock Shock is a medical emergency associated with a high mortality. The underlying causes of shock such as haemorrhage, sepsis or myocardial insuffi-ciency should be corrected. Additional treatment is dependent on the type of shock.
Septic shock is associated with severe hypovolaemia (due to vasodilation and capillary leak) which should be corrected with crystalloids or colloids (section 9.2.2). If hypotension persists despite volume replacement,dopamine should be started. For shock refractory to treatment with dopamine, if cardiac output is high and peripheral vascular resistance is low (warm shock),noradrenaline (norepi-nephrine) (section 2.7.2) should be added or if cardiac output is low and peripheral vascular resistance is high (cold shock),adrenaline (epinephrine) (section 2.7.2) should be added. Additionally, in cold shock, a vasodilator such asmilrinone (section 2.1.2),glyceryl trinitrate (section 2.6.1), or sodium nitroprusside (on specialist advice only) (section 2.5.1.1) 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 (section 6.3.2) can 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 (section 6.5.2) can be added.
Neonatal septic shock can be complicated by the transition from fetal to neonatal circulation. Treatment to reverse right ventricular failure, by decreasing pulm-onary artery pressures, is commonly needed in neonates with fluid-refractory ILOPROST (continued)
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shock and persistent pulmonary hypertension of the newborn (section 2.5.1.2).
Rapid administration of fluid in neonates with patent ductus arteriosus may cause left-to-right shunting and congestive heart failure induced by ventricular overload.
In cardiogenic shock, the aim is to improve cardiac output and to reduce the afterload on the heart. If central venous pressure is low, cautious volume expan-sion with a colloid or crystalloid can be used. An inotrope such asadrenaline (epinephrine) (section 2.7.2) ordopamine should be given to increase cardiac output.Dobutamine is a peripheral vasodilator and is an alternative if hypo-tension is not significant.
Milrinone (section 2.1.2) has both inotropic and vasodilatory effects and can be used when vascular resistance is high. Alternatively,glyceryl trinitrate (2.6.1) or sodium nitroprusside (on specialist advice only) (section 2.5.1.1) can be used to reduce vasoconstriction.
Hypovolaemic shock should 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 haemody-namic monitoring.
For advice on the management of anaphylactic shock, see section 3.4.3.
DOBUTAMINE
Cautions hyperthyroidism; interactions: Appen-dix 1 (sympathomimetics)
Pregnancy no information available
Contra-indications marked obstruction of cardiac ejection, such as idiopathic hypertrophic subaor-tic stenosis
Side-effects tachycardia and marked increase in systolic blood pressure indicate overdosage;
phlebitis; rarely thrombocytopenia Licensed use not licensed for use in children Indication and dose
Inotropic support in low cardiac output states, after cardiac surgery, cardiomyopathies, shock . By continuous intravenous infusion
Neonateinitially 5 micrograms/kg/minute, adjusted according to response to 2–15 micr-ograms/kg/minute; max. 20 micrograms/kg/
minute
Child 1 month–18 yearsinitially 5 micrograms/
kg/minute adjusted according to response to 2–
20 micrograms/kg/minute
Administration for continuous intravenous infusion, using infusion pump, dilute to a concentration of 0.5–1 mg/mL (max. 5 mg/mL if fluid restricted) with Glucose 5% or Sodium Chloride 0.9%; infuse higher concentration solutions through central venous catheter only. Incompatible with bicarb-onate and other strong alkaline solutions.
Neonatal intensive care, dilute 30 mg/kg body-weight to a final volume of 50 mL with infusion fluid; an intravenous infusion rate of 0.5 mL/hour provides a dose of 5 micrograms/kg/minute Dobutamine(Non-proprietary)A
Strong sterile solution, dobutamine (as hydro-chloride) 12.5 mg/mL. For dilution and use as an intravenous infusion. Net price 20-mL amp = £5.20
DOPAMINE HYDROCHLORIDE
Cautions correct hypovolaemia; hyperthyroidism;
interactions: Appendix 1 (sympathomimetics) Pregnancy manufacturer advises use only if potential benefit outweighs risk
Contra-indications tachyarrhythmia, phaeo-chromocytoma
Side-effects nausea and vomiting, peripheral vasoconstriction, hypotension, hypertension, tachycardia
Licensed use not licensed for use in children under 12 years
Indication and dose
To correct the haemodynamic imbalance due to acute hypotension, shock, cardiac failure, adjunct following cardiac surgery . By continuous intravenous infusion
Neonateinitially 3 micrograms/kg/minute, adjusted according to response (max. 20 micr-ograms/kg/minute)
Child 1 month–18 yearsinitially 5 micrograms/
kg/minute adjusted according to response (max. 20 micrograms/kg/minute)
Administration for continuous intravenous infusion, dilute to a max. concentration of 3.2 mg/mL with Glucose 5% or Sodium Chloride 0.9%. Infuse higher concentrations through central venous catheter using a syringe pump to avoid
extrava-BNFC 2009 2.7.1 Inotropic sympathomimetics
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sation and fluid overload. Incompatible with bicarbonate and other alkaline solutions.
Neonatal intensive care, dilute 30 mg/kg body-weight to a final volume of 50 mL with infusion fluid; an intravenous infusion rate of 0.3 mL/hour provides a dose of 3 micrograms/kg/minute Dopamine(Non-proprietary)A
Sterile concentrate, dopamine hydrochloride 40 mg/mL, net price 5-mL amp = £3.88; 160 mg/
mL, net price 5-mL amp = £14.75. For dilution and use as an intravenous infusion
Intravenous infusion, dopamine hydrochloride 1.6 mg/mL in glucose 5% intravenous infusion, net price 250-mL container (400 mg) = £11.69; 3.2 mg/
mL, 250-mL container (800 mg) = £22.93 (both hosp. only)
Select-A-JetcDopamine(UCB Pharma)A Strong sterile solution, dopamine hydrochloride 40 mg/mL. For dilution and use as an intravenous infusion. Net price 5-mL vial = £5.01; 10-mL vial =
£8.05
2.7.2
Vasoconstrictor sympathomimeticsVasoconstrictor 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 (see also section 2.7.1).
The danger of vasoconstrictors is that although they raise blood pressure they also reduce perfusion of vital organs such as the kidney.
Ephedrine is used to reverse hypotension caused by spinal and epidural anaes-thesia.
Metaraminol is used as a vasopressor during cardiopulmonary bypass.
Phenylephrine causes peripheral vasoconstriction and increases arterial pres-sure.
Ephedrine, metaraminol and phenylephrine 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 contrac-tility; high doses act predominantly on alpha receptors causing intense systemic vasoconstriction.
EPHEDRINE HYDROCHLORIDE
Cautions hyperthyroidism, diabetes mellitus, hypertension, susceptibility to angle-closure glaucoma,interactions: Appendix 1 (sympatho-mimetics)
Renal impairment use with caution Pregnancy increased fetal heart rate reported Contra-indications
Breast-feeding irritability and disturbed sleep reported in breast-fed infants
Side-effects nausea, vomiting, anorexia; tachy-cardia (sometimes bradytachy-cardia), arrhythmias, anginal pain, vasoconstriction with hypertension, vasodilation with hypotension, dizziness and flushing; dyspnoea; headache, anxiety, restless-ness, confusion, psychoses, insomnia, tremor;
difficulty in micturition, urine retention; sweating, hypersalivation; changes in blood-glucose con-centration
Indication and dose
Reversal of hypotension from epidural and spinal anaesthesia
. By slow intravenous injection of a solution containing ephedrine hydrochloride 3 mg/mL Child 1–12 years500–750 micrograms/kg or 17–25 mg/m2every 3–4 minutes according to response; max. 30 mg during episode Child 12–18 years3–7.5 mg (max. 9 mg) repeated every 3–4 minutes according to response, max. 30 mg during episode Nasal congestionsection 12.2.2
Administration By slow intravenous injection, via central line.
Ephedrine Hydrochloride(Non-proprietary)A Injection, ephedrine hydrochloride 3 mg/mL, net price 10-mL amp = £2.83; 30 mg/mL, net price 1-mL amp = £1.70
DOPAMINE HYDROCHLORIDE (continued)
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METARAMINOL
Cautions see under Noradrenaline; longer dura-tion of acdura-tion than noradrenaline (norepinephr-ine), see below; cirrhosis;interactions: Appendix 1 (sympathomimetics)
Hypertensive responseMetaraminol has a longer dura-tion of acdura-tion than noradrenaline, and an excessive vasopressor response may cause a prolonged rise in blood pressure
Breast-feeding manufacturer advises caution—
no information available
Contra-indications see under Noradrenaline Pregnancy may reduce placental prefusion—
manufacturer advises use only if potential benefit outweighs risk
Side-effects see under Noradrenaline; tachy-cardia; fatal ventricular arrhythmia reported in Laennec’s cirrhosis
Licensed use Not licensed for use in children
Indication and dose Acute hypotension . By intravenous infusion
Child 12–18 years15–100 mg adjusted according to response
Emergency treatment of acute hypotension . By intravenous administration
Child 12–18 yearsinitially by intravenous injection 0.5–5 mg, then by intravenous infusion 15–100 mg adjusted according to response Administration for intravenous infusion dilute to a
concentration of 30–200 micrograms/mL with Glucose 5% or Sodium Chloride 0.9% and give through a central venous catheter
Metaraminol(Non-proprietary)A
Injection, metaraminol 10 mg (as tartrate)/mL.
Available from ‘special-order’ manufacturers or specialist importing companies, see p. 943
NORADRENALINE/NOREPINEPHRINE
Cautions coronary, mesenteric, or peripheral vascular thrombosis; Prinzmetal’s variant angina, hyperthyroidism, diabetes mellitus; hypoxia or hypercapnia; uncorrected hypovolaemia; extra-vasation at injection site may cause necrosis;
interactions: Appendix 1 (sympathomimetics) Contra-indications hypertension (monitor blood
pressure and rate of flow frequently) Pregnancy avoid—may reduce placental perfu-sion
Side-effects hypertension, headache, brady-cardia, arrhythmias, peripheral ischaemia Licensed use not licensed for use in children Indication and dose
Acute hypotension (septic shock) or shock secondary to excessive vasodilation(as noradrenaline)
. By continuous intravenous infusion Neonate20–100 nanograms(base)/kg/minute adjusted according to response; max. 1 micr-ogram(base)/kg/minute
Child 1 month–18 years20–100 nan-ograms(base)/kg/minute adjusted according to response; max. 1 microgram(base)/kg/minute Note1 mg of noradrenaline acid tartrate is equivalent to 500 micrograms of the base. Dose expressed as the base Administration for continuous intravenous infusion, dilute to a max. concentration of noradrenaline (base) 40 micrograms/mL (higher concentrations can be used if fluid-restricted) with Glucose 5% or Sodium Chloride and Glucose. Infuse through central venous catheter; discard if discoloured.
Incompatible with bicarbonate or alkaline solu-tions.
Neonatal intensive care, dilute 600 micrograms (base)/kg body-weight to a final volume of 50 mL with infusion fluid; an intravenous infusion rate of 0.1 mL/hour provides a dose of 20 nanograms (base)/kg/minute
Noradrenaline/Norepinephrine(Non-proprietary)A Injection, noradrenaline acid tartrate 2 mg/mL (equivalent to noradrenaline base 1 mg/mL). For dilution before use. Net price 2-mL amp = £1.01, 4-mL amp = £1.50, 20-4-mL amp = £6.35
Excipientsmay include sodium metabisulphite
PHENYLEPHRINE HYDROCHLORIDE
Cautions see under Noradrenaline; longer dura-tion of acdura-tion than noradrenaline (norepinephr-ine), see below; coronary disease
Hypertensive responsePhenylephrine has a longer duration of action than noradrenaline, and an excessive vasopressor response may cause a prolonged rise in blood pressure
Contra-indications see under Noradrenaline;
severe hyperthyroidism
Pregnancy avoid if possible; malformations reported following use in first trimester; fetal hypoxia and bradycardia reported in late pregnancy and labour
Side-effects see under Noradrenaline; tachy-cardia or reflex bradytachy-cardia
Licensed use not licensed for use in children by intravenous infusion or injection
Indication and dose Acute hypotension
. By subcutaneous or intramuscular injection (but intravenous injection preferred, see below) Child 1–12 years100 micrograms/kg every 1–2 hours as needed (max. 5 mg)
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Child 12–18 years2–5 mg, followed if neces-sary by further doses of 1–10 mg (max. initial dose 5 mg)
. By slow intravenous injection
Child 1–12 years5–20 micrograms/kg (max.
500 micrograms) repeated as necessary after at least 15 minutes
Child 12–18 years100–500 micrograms repeated as necessary after at least 15 minutes . By intravenous infusion
Child 1–16 years100–500 nanograms/kg/
minute, adjusted according to response
Child 16–18 yearsinitially up to 180 micr-ograms/minute reduced to 30–60 micrograms/
minute according to response
Administration for intravenous injection dilute to a concentration of 1 mg/mL with Water for Injec-tions and administer slowly.
For intravenous infusion dilute to a concentration of 20 micrograms/mL with Glucose 5% or Sod-ium Chloride 0.9% and administer as a continu-ous infusion via a central vencontinu-ous catheter using a controlled infusion device
Phenylephrine(Sovereign)A
Injection, phenylephrine hydrochloride 10 mg/mL (1%), net price 1-mL amp = £5.50
ADRENALINE/EPINEPHRINE
Cautions diabetes mellitus, hyperthyroidism, hypertension, arrhythmias, cerebrovascular dis-ease, avoid extravasation, monitor urine output, limb perfusion (especially at higher doses), cen-tral venous pressures and ECG;interactions:
Appendix 1 (sympathomimetics)
Side-effects nausea, vomiting, sweating, tachy-cardia, dyspnoea, anxiety, tremor, headache, weakness, dizziness and hyperglycaemia , cold extremities; in overdosage hypertension, arrhy-thmias, cerebral haemorrhage, pulmonary oedema
Indication and dose Acute hypotension
. By continuous intravenous infusion Neonateinitially 100 nanograms/kg/minute adjusted according to response; higher doses up to 1.5 micrograms/kg/minute have been used in acute hypotension
Child 1 month–18 yearsinitially 100 nan-ograms/kg/minute adjusted according to
response; higher doses up to 1.5 micrograms/
kg/minute have been used in acute hypotension Anaphylaxissection 3.4.3
Administration for continuous intravenous infusion dilute with Glucose 5% or Sodium Chloride 0.9%
and give through a central venous catheter.
Incompatible with bicarbonate and alkaline solutions.
Neonatal intensive care, dilute 3 mg/kg body-weight to a final volume of 50 mL with infusion fluid; an intravenous infusion rate of 0.1 mL/hour provides a dose of 100 nanograms/kg/minute NoteThese infusions are usually made up with adrenaline 1 in 1000 (1 mg/mL) solution; this concentration of adr-enaline is not licensed for intravenous administration
Preparations Section 3.4.3
2.7.3
Cardiopulmonary resuscitationThe algorithms for cardiopulmonary resuscitation (see inside back cover) reflect the recommendations of the Resuscitation Council (UK); they cover paediatric basic life support, paediatric advanced life support, and newborn life support. The guidelines are available atwww.resus.org.uk.
Paediatric advanced life support Cardiopulmonary (cardiac) arrest in children is rare and frequently represents the terminal event of progressive shock or respiratory failure.
During cardiopulmonary arrest in children without intravenous access, the intraosseous route is chosen because it provides rapid and effective response; if circulatory access cannot be gained, the endotracheal tube can be used. When the endotracheal route is used ten times the intravenous dose should be used; the drug should be injected quickly down a narrow bore suction catheter beyond the tracheal end of the tube and then flushed in with 1 or 2 mL of sodium chloride 0.9%. The endotracheal route is useful for lipid-soluble drugs, including lidocaine, adrenaline, atropine, and naloxone. Drugs that are not lipid-soluble (e.g. sodium bicarbonate and calcium chloride) should not be administered by this route because they will injure the airways.
For the management of acute anaphylaxis see section 3.4.3.
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