BNF for Children 2011-2012

BNFC 2011–2012 2.5.1 Vasodilator antihypertensive drugs 95Hepatic impairment use with caution; avoid inhepatic failure—cyanide or thiocyanate metabolitesmay accumulateRenal impairment avoid prolonged use—cyanide orthiocyanate metabolites may accumulatePregnancy avoid prolonged use—potential for accumulationof cyanide in fetusBreast-feeding no information available; cautionadvised due to thiocyanate metaboliteSide-effects associated with over rapid reduction inblood pressure (reduce infusion rate): headache, dizziness,nausea, retching, abdominal pain, perspiration,palpitation, anxiety, retrosternal discomfort; occasionallyreduced platelet count, acute transient phlebitisCyanide Side-effects caused by excessive plasma concentrationof the cyanide metabolite include tachycardia,sweating, hyperventilation, arrhythmias, marked metabolicacidosis (discontinue and give antidote, see p. 32)Licensed use not licensed for use in the UKIndication and doseHypertensive emergencies. By continuous infusionNeonate 500 nanograms/kg/minute thenincreased in steps of 200 nanograms/kg/minute asnecessary to max. 8 micrograms/kg/minute (max.4 micrograms/kg/minute if used for longer than24 hours)Child 1 month–18 years 500 nanograms/kg/minute then increased in steps of 200 nanograms/kg/minute as necessary to max. 8 micrograms/kg/minute (max. 4 micrograms/kg/minute if usedfor longer than 24 hours)Administration for continuous intravenous infusion inGlucose 5%, infuse via infusion device to allow precisecontrol; protect infusion from light. For furtherdetails, consult product literatureSodium Nitroprusside (Non-proprietary) AIntravenous infusion, powder for reconstitution,sodium nitroprusside 10 mg/mL. For dilution and useas an infusion. Available from ‘special-order’ manufacturersor specialist importing companies, seep. 8092.5.1.2 Pulmonary hypertensionOnly pulmonary arterial hypertension is currently suitablefor drug treatment. Pulmonary arterial hypertensionincludes persistent pulmonary hypertension ofthe newborn, idiopathic pulmonary arterial hypertensionin children, and pulmonary hypertension relatedto congenital heart disease and cardiac surgery.Some types of pulmonary hypertension are treated withvasodilator antihypertensive therapy and oxygen. Diuretics(section 2.2) may also have a role in children withright-sided heart failure.Initial treatment of persistent pulmonary hypertensionof the newborn involves the administration of nitricoxide; epoprostenol can be used until nitric oxide isavailable. Oral sildenafil may be helpful in less severecases. Epoprostenol and sildenafil can cause profoundsystemic hypotension. In rare circumstances eithertolazoline or magnesium sulphate can be given byintravenous infusion when nitric oxide and epoprostenolhave failed.Treatment of idiopathic pulmonary arterial hypertensionis determined by acute vasodilator testing;drugs used for treatment include calcium-channelblockers (usually nifedipine, section 2.6.2), long-termintravenous epoprostenol, nebulised iloprost, bosentan,or sildenafil. Anticoagulation (usually with warfarin)may also be required to prevent secondarythrombosis.Inhaled nitric oxide is a potent and selective pulmonaryvasodilator. It acts on cyclic guanosine monophosphate(cGMP) resulting in smooth muscle relaxation.Inhaled nitric oxide is used in the treatment of persistentpulmonary hypertension of the newborn, and may alsobe useful in other forms of arterial pulmonary hypertension.Dependency can occur with high doses andprolonged use; to avoid rebound pulmonary hypertensionthe drug should be withdrawn gradually, oftenwith the aid of sildenafil.Excess nitric oxide can cause methaemoglobinaemia;therefore, methaemoglobin concentration should bemeasured regularly, particularly in neonates.Nitric oxide increases the risk of haemorrhage by inhibitingplatelet aggregation, but it does not usually causebleeding.Epoprostenol (prostacyclin) is a prostaglandin and apotent vasodilator. It is used in the treatment of persistentpulmonary hypertension of the newborn, idiopathicpulmonary arterial hypertension, and in the acute phasefollowing cardiac surgery. It is given by continuous 24-hour intravenous infusion.Epoprostenol is a powerful inhibitor of platelet aggregationand there is a possible risk of haemorrhage. It issometimes used as an antiplatelet in renal dialysis whenheparins are unsuitable or contra-indicated. It can alsocause serious systemic hypotension and, if withdrawnsuddenly, can cause pulmonary hypertensive crisis.Children on prolonged treatment can become tolerantto epoprostenol, and therefore require an increase indose.Iloprost is a synthetic analogue of epoprostenol and isefficacious when nebulised in adults with pulmonaryarterial hypertension, but experience in children is limited.It is more stable than epoprostenol and has alonger half-life.Bosentan is a dual endothelin receptor antagonist usedorally in the treatment of idiopathic pulmonary arterialhypertension. The concentration of endothelin, a potentvasoconstrictor, is raised in sustained pulmonary hypertension.Sildenafil, a vasodilator developed for the treatment oferectile dysfunction, is also used for pulmonary arterialhypertension. It is used either alone or as an adjunct toother drugs and has relatively few side-effects.Sildenafil is a selective phosphodiesterase type-5 inhibitor.Inhibition of this enzyme in the lungs enhances thevasodilatory effects of nitric oxide and promotes relaxationof vascular smooth muscle.Sildenafil has also been used in pulmonary hypertensionfor weaning children off inhaled nitric oxide followingcardiac surgery, and less successfully in idiopathic pulmonaryarterial hypertension.Tolazoline is now rarely used to correct pulmonaryartery vasospasm in pulmonary hypertension of thenewborn as better alternatives are available (see2 Cardiovascular system