BNF for Children 2011-2012

120 2.8.3 Protamine sulphate BNFC 2011–20122 Cardiovascular system2.8.3 Protamine sulphateProtamine sulphate is used to treat overdosage ofunfractionated or low molecular weight heparin. Thelong half-life of low molecular weight heparins shouldbe taken into consideration when determining the doseof protamine sulphate; the effects of low molecularweight heparins can persist for up to 24 hours afteradministration. Excessive doses of protamine sulphatecan have an anticoagulant effect.PROTAMINE SULPHATE(Protamine Sulfate)Cautions see above; also monitor activated partialthromboplastin time or other appropriate blood clottingparameters; if increased risk of allergic reaction toprotamine (includes previous treatment with protamineor protamine insulin, allergy to fish, and adolescentmales who are infertile)Side-effects nausea, vomiting, lassitude, flushing,hypotension, hypertension, bradycardia, dyspnoea,rebound bleeding, back pain; hypersensitivity reactions(including angioedema, anaphylaxis) and pulmonaryoedema reportedIndication and doseOverdosage with intravenous injection orintravenous infusion of unfractionated heparin. By intravenous injection (rate not exceeding5 mg/minute)Child 1 month–18 years to neutralise each100 units of unfractionated heparin, 1 mg if lessthan 30 minutes lapsed since overdose, 500–750 micrograms if 30–60 minutes lapsed, 375–500 micrograms if 60–120 minutes lapsed, 250–375 micrograms if over 120 minutes lapsed; max.50 mgOverdosage with subcutaneous injection ofunfractionated heparin. By intravenous injection and intravenous infusionChild 1 month–18 years 1 mg neutralises approx.100 units of unfractionated heparin; give 50–100%of the total dose by intravenous injection (rate notexceeding 5 mg/minute), then give any remainderof dose by intravenous infusion over 8–16 hours;max. total dose 50 mgOverdosage with subcutaneous injection of lowmolecular weight heparin. By intermittent intravenous injection (rate notexceeding 5 mg/minute) or by continuousintravenous infusionChild 1 month–18 years 1 mg neutralises approx.100 units low molecular weight heparin (consultproduct literature of low molecular weight heparinfor details); max. 50 mgAdministration may be diluted if necessary withSodium Chloride 0.9%Protamine Sulphate (Non-proprietary) AInjection, protamine sulphate 10 mg/mL, net price 5-mL amp = £1.43, 10-mL amp = £4.152.9 Antiplatelet drugsAntiplatelet drugs decrease platelet aggregation andinhibit thrombus formation in the arterial circulation,because in faster-flowing vessels, thrombi are composedmainly of platelets with little fibrin.Aspirin has limited use in children because it has beenassociated with Reye’s syndrome. Aspirin-containingpreparations should not be given to children and adolescentsunder 16 years, unless specifically indicated,such as for Kawasaki syndrome (see below), for prophylaxisof clot formation after cardiac surgery, or forprophylaxis of stroke in children at high risk.If aspirin causes dyspepsia, or if the child is at a high riskof gastro-intestinal bleeding, a proton pump inhibitor(section 1.3.5) or a H 2 -receptor antagonist (section1.3.1) can be added.Dipyridamole is also used as an antiplatelet drug toprevent clot formation after cardiac surgery and may beused with specialist advice for treatment of persistentcoronary artery aneurysms in Kawasaki syndrome.Kawasaki syndrome Initial treatment is with highdoseaspirin and a single dose of intravenous normalimmunoglobulin (p. 622); this combination has an additiveanti-inflammatory effect resulting in faster resolutionof fever and a decreased incidence of coronaryartery complications. After the acute phase, when thepatient is afebrile, aspirin is continued at a lower dose toprevent coronary artery abnormalities.ASPIRIN (antiplatelet)(Acetylsalicylic Acid)Cautions asthma; uncontrolled hypertension; previouspeptic ulceration (but manufacturers may adviseavoidance of low-dose aspirin in history of pepticulceration); concomitant use of drugs that increaserisk of bleeding; G6PD deficiency (section 9.1.5);interactions: Appendix 1 (aspirin)Contra-indications children under 16 years (risk ofReye’s syndrome) unless for indications below; activepeptic ulceration; haemophilia and other bleedingdisordersHypersensitivity Aspirin and other NSAIDs are contraindicatedin history of hypersensitivity to aspirin or anyother NSAID—which includes those in whom attacks ofasthma, angioedema, urticaria, or rhinitis have been precipitatedby aspirin or any other NSAIDHepatic impairment avoid in severe impairment—increased risk of gastro-intestinal bleedingRenal impairment use with caution (avoid in severeimpairment); sodium and water retention; deteriorationin renal function; increased risk of gastro-intestinalbleedingPregnancy use with caution during third trimester;impaired platelet function and risk of haemorrhage;delayed onset and increased duration of labour withincreased blood loss; avoid analgesic doses if possiblein last few weeks (low doses probably not harmful);with high doses, closure of fetal ductus arteriosus inutero and possibly persistent pulmonary hypertensionof newborn; kernicterus in jaundiced neonatesBreast-feeding avoid—possible risk of Reye’ssyndrome; regular use of high doses could impairplatelet function and produce hypoprothrombinaemiain infant if neonatal vitamin K stores low