7 Drug dosing guidelines
Pearls and pitfalls
Introduction
• These drug profile notes are intended to serve as guidelines for the treatment of children under emergency conditions by trained and appropriately qualified medical professionals – they can never replace sound clinical judgement.
• All doses, unless otherwise specified, must be calculated according to each patient’s individual requirements, risks and special circumstances, notwithstanding the dosage that is presented in this material.
• Tracheal drug administration is not recommended other than as a last resort route of administration, and should only be used if intravenous or intraosseous routes are unavailable (and there is seldom a reason not to establish an IO line).
• The general principle of drug administration is that of titrating the minimum dose to the desired effect or response.
• This section should not be considered to be absolute information on the pharmacology of the drugs listed. The science supporting pharmacological management of seriously ill or injured children is dynamic, and currently very limited, with advances being published continually. Readers are advised to check for changes in recommended doses, indications and contraindications in current reliable sources, including the product information sheets; furthermore, drug use should be guided by local protocol and practice – familiarity with current local and national protocols is strongly advocated.
• The drug dose that is used in this book is reflected in this chapter. Where there is a range of doses that are in general use then this is given as well.
• Hypersensitivity is not always mentioned as a contraindication for any drug, although this is an obvious contraindication. In true emergencies, however, if a previous reaction to a drug has not been severe and if there is no alternative agent to use, then that drug or one in the same class may be used with due caution. This is not advised unless the patient’s life depends on the intervention.
• Some contraindications are absolute and some relative – ensure that you know the difference. This book won’t teach you everything you need to know but will be a useful reminder in times of need.
• Please see Chapter 4 to see what adjustments need to be made for obese children.
Adenosine
Indications
• Stable patients with narrow-complex SVT, to terminate arrhythmia. Does not convert atrial fibrillation, atrial flutter or VT, but may transiently slow the ventricular rate – which may be useful diagnostically – without terminating the arrhythmia or controlling the rate in the long term.
• May consider for unstable narrow-complex tachycardia while preparations are made for electrical cardioversion.
• In a stable patient with a regular, narrow-complex or wide complex tachycardia (not known to be a result of WPW syndrome), adenosine is the first-line treatment.
Pharmacological action
• Adenosine decreases automaticity and rate of discharge in SA and AV node cells.
• Adenosine interrupts and terminates supraventricular arrhythmias due to re-entry pathways involving the AV node (i.e. most SVTs).
• SVTs that do not involve the AV node (e.g. WPW syndrome) are usually not terminated by adenosine; this is particularly true for atrial flutter and atrial fibrillation.
Precautions
• Constant ECG monitoring with the patient connected to the monitor-defibrillator.
• WPW – there is a possibility of initiating atrial fibrillation with rapid ventricular responses.
• Avoid in patients taking dipyridamole or carbamazepine (may need to halve dose if required) as co-administration with carbamazepine may produce higher degrees of heart block; dipyridamole may potentiate effects.
• Reduce initial dose in patients with transplanted hearts, or if given by central venous catheter.
• Methylxanthines may antagonize effects of adenosine – it is therefore less effective in patients taking theophylline or caffeine – the usual dose may need to be doubled.
• May cause bronchospasm in asthmatics.
• Patient should be supine or even slightly head-down during administration.
Miscellaneous notes
• Adenosine is administered by an extremely rapid IV push followed immediately by 5–10 mL NS rapid IV push into a large vein.
• Use the two syringe with four hands technique. One person presses the two syringe plungers one after the other, while continuing to maintain pressure on both syringes until they are empty. The other person simultaneously stabilizes the injection port and 3-way stopcock.
• Record rhythm strip during administration – may serve a diagnostic purpose.
• Adenosine should only be used when monitoring, resuscitation equipment and expertise are available.
• Side effects are generally short-lived and last for less than 1 minute.
• If the patient does not experience side-effect symptoms such as flushing and chest discomfort then the dose may not have been effective – increase the dose or rate of administration.
Adrenaline (epinephrine)
Indications
• Cardiac arrest (IV/IO) – bolus doses.
• Haemodynamically unstable bradycardia – bolus doses or low dose infusion.
• Anaphylaxis (IM or IV under certain circumstances) for patients with signs of systemic reaction: hypotension, laryngeal oedema or definite difficulty in breathing.
• Impending upper airway obstruction (nebulized) due to inflammation e.g. upper airway infection, inhalational burns.
• Life-threatening severe asthma – SQ or IM.
• Severe hypotension not due to hypovolaemia – as an infusion.
Pharmacological action
• Adrenaline acts on both α and β receptors: it increases both heart rate and contractility (β1 effects) and it causes dose-dependent peripheral vasodilation (β2 effect) or vasoconstriction (α effect).
• The primary effect of adrenaline in cardiac arrest is due to its potent α effects which include peripheral vasoconstriction, improved coronary and cerebral blood flow and rendering ventricular fibrillation more susceptible to defibrillation.
Precautions
Intravenous administration should always be carefully infused in patients not in cardiac arrest.
Packaging
• Adrenaline acid tartrate 1 mg/1 mL (1 : 1000).
• A pre-filled syringe may be available, containing 1 mg/10 mL (1 : 10 000). This is a convenient dilution for paediatrics but can also easily be made up by diluting a 1 mg/mL ampoule with 9 mL of NS or WFI.
• Adrenaline auto-injectors may also be available – this delivers an adult dose of 0.3 mg (0.3 mL adrenaline 1 : 1000), allowing for immediate self-administration. The paediatric form delivers a dose of 0.15 mg (0.15 mL of 1 : 1000), and should be used in the anterolateral thigh.
Dosage and administration
Cardiac arrest
• Adrenaline administration, when injected through a peripheral line, should be flushed with at least 5 mL NS to aid entry into the central circulation.
• Tracheal: 0.1 mg/kg, diluted to 3 mL with WFI; tracheal administration is the last resort route of choice – IV/IO definitely preferred.
Anaphylaxis
• 0.01 mg/kg IM (use undiluted 1 : 1000 with a 1 mL syringe).
• Repeat every 5 minutes if no clinical improvement.
• IV (only if life-threatening or unresponsive to IM).
Life-threatening severe asthma (near fatal asthma)
Croup/laryngeal oedema
• For severe croup, nebulized adrenaline solution 1 : 1000 (1 mg/mL) should be given with close clinical monitoring in a dose of 0.4 mg/kg (maximum 5 mg), repeated after 30 minutes if necessary. The effects of nebulized adrenaline last 2–3 hours and the child needs to be monitored carefully for recurrence of obstruction.
• Racemic adrenaline is preferred for nebulization whenever possible.
• Nebulization: Initiate with 1 mL of 1 : 1000 + 4 mL NS. If necessary increase to 2–4 mg adrenaline per nebulization.
Miscellaneous notes
• The use of adrenaline in cardiac arrest has not demonstrated any long-term survival.
• High dose adrenaline should not be used in cardiac arrest as it has been shown to worsen the outcome compared to standard dose adrenaline.
• In children suffering from hypothermia and cardiac arrest, the doses of adrenaline should be spaced at longer intervals (8 to 12 minutes rather than 4 minutes).
• The efficacy of adrenaline is greatly diminished in a severely acidotic patient – consider correcting the acidosis if the adrenaline is not having the expected effect.
• The adrenaline dose for anaphylaxis is to some degree dependent on weight, but a dose of 0.3 mg (0.3 mL of a 1 : 1000 solution) can safely be used for any size child.
• IM adrenaline should be administered in the anterolateral thigh into the vastus lateralis muscle.
Amiodarone
Indications
• For defibrillation-refractory VF and pulseless VT.
• For cardioversion of haemodynamically stable monomorphic wide-complex (>0.09 second) tachycardia.
• Polymorphic ventricular tachycardia with normal QTc interval, (i.e. EXCLUDING torsades de pointes).
• Stable narrow-complex re-entry tachycardias if the rhythm remains uncontrolled by adenosine and vagal manoeuvres, or when these are contraindicated.
• To control rapid ventricular rate due to accessory pathway conduction in pre-excited atrial dysrhythmias.
Pharmacological action
• Amiodarone (an iodine-containing agent) is a class III anti-arrhythmic medication that prolongs phase 3 of the cardiac action potential. It also has a profound effect on the sodium, potassium and calcium channels of the cardiac cells whilst simultaneously blocking both α- and β-adrenergic receptors.
Miscellaneous notes
• The surface tension properties of solutions containing injectable amiodarone are altered such that the drop size may be reduced. This reduction may lead to under dosage of the patient by up to 30% if drop counter infusion sets are used. Amiodarone IV must be delivered by a volumetric infusion pump.
• Amiodarone in D5W is incompatible with sodium bicarbonate.
• Amiodarone that is diluted in D5W at concentrations less than 150 mg/250 mL (or <0.6 mg/mL) may be unstable and should ideally not be used for an infusion.
Atropine
Pharmacological action
• Atropine acts as a competitive antagonist at muscarinic (cholinergic) receptor sites, blocking the stimulation of parasympathetic nerve fibres.
• Atropine (anticholinergic) effects: positive chronotrope, positive dromotrope, mydriasis, decreased sweat, tears, salivary and pancreatic secretions, reduction in bronchial secretions, bronchodilation, decreased peristalsis, bladder relaxation, sphincter constriction.
Precautions
• Always rule out important causes of bradycardia: hypoxia, hypothermia, raised ICP, hyperkalaemia.
• 2° type II and 3° AV heart blocks with wide QRS complexes (indicating a possible point of origin below the supraventricular conductive tissue) – atropine may induce a paradoxical slowing of the heart rate.
• Paradoxical bradycardia may occur in reaction to small dosages (<0.1 mg).
Miscellaneous notes
• Atropine is one of those drugs that should always be close at hand in the ED, especially when administering drugs that might cause bradycardias. The routine use of atropine prior to RSI or with ketamine PSA is no longer recommended.
• Atropine should, however, be used as a premedication agent before a second dose of suxamethonium is administered during RSI.
Blood bolus
Miscellaneous notes
• Blood boluses at 10 mL/kg may need to be administered after 2 to 3 crystalloid boluses to manage haemorrhagic shock.
• The rate of infusion depends on the clinical scenario, but blood products must always be completely warmed before administration. Repeat as needed.
• If unmatched blood is required, use O-negative blood for females and either O-positive or O-negative blood for males. Consider FFP, platelets and cryoprecipitate if multiple blood boluses (>40 mL/kg) are needed.
• Fresh blood (<5 days old) should be used as it results in a higher survival rate in children requiring resuscitation from major haemorrhage.
Blood packed cells transfusion
Miscellaneous notes
Calcium chloride/calcium gluconate
Pharmacological action
• Calcium is essential for the initiation and maintenance of normal muscular contractions.
• Has a positive inotropic effect on cardiac muscle and mediates general vasoconstriction (vascular smooth muscle).
• Calcium is also required to maintain enzymatic reactions and blood coagulation.
• Roughly 40% of plasma calcium is bound to albumin. In hypoalbuminaemia, calcium levels need to be corrected as the level falls by 0.2 mmol/L for every 10g/L decline in plasma albumin.
• Calcium gluconate 10% contains about 9 mg/mL elemental calcium while calcium chloride 10% contains 27 mg/mL elemental calcium.
Precautions
• Rapid administration may cause bradycardia or asystole – administer over 5 minutes when a pulse is present.
• AVOID in patients receiving digoxin even if they are hyperkalaemic as it may induce arrhythmias.
• Never combine with sodium bicarbonate in the same infusion as calcium carbonate will precipitate.
• A well-placed and free flowing IV line is mandatory as subcutaneously extravasated calcium causes tissue necrosis.
Miscellaneous notes
• Calcium chloride should only be used for acute or urgent indications for IV calcium administration. Calcium gluconate should be used for less urgent conditions because of the greater safety of this solution.
• In significant hyperkalaemia, IV calcium chloride should be the first drug to be administered. It is possible to tell when a sufficient dose has been given because the widened QRS complex narrows into the normal range again (it is broad as a result of the hyperkalaemia).
Cardioversion/defibrillation
Indications
• Cardioversion is used for children suffering from tachyarrhythmias with adverse clinical features (the unstable patient) or medication unresponsive conditions. Cardioversion is synchronized – the ‘sync’ button must be on and the machine recognizing each R wave of each QRS complex.
• Defibrillation is for children who have suffered an arrythmogenic cardiac arrest (VF or VT). Defibrillation is unsynchronized – the ‘sync’ button must be off.
Miscellaneous notes
• The single best way of defining an unstable patient is arguably by assessing the level of consciousness – an agitated or lethargic child is showing signs of cerebral hypoperfusion and should be managed aggressively.
• If the exact dosage level is not available on your machine, use the closest higher setting.
• A synchronized shock should be used for perfusing arrhythmias except for polymorphic ventricular tachycardias – here an unsynchronized shock will work better.
• There is no evidence on what energy levels should be used with biphasic-waveform cardioversion and the recommendation is to use the same as for monophasic machines.
• It is better to use a manual defibrillator than an AED in children, whenever possible.
• Sedation before cardioversion is desirable as long as it does not unduly delay the procedure: propofol, etomidate and midazolam are good agents if used carefully.
• NOTE: Make sure the ‘sync’ button is switched on before each cardioversion shock, as many machines will reset to defibrillation mode to allow an immediate defibrillation shock if VF develops.
• Ensure that when the monitor is set to leads the leads are on the patient, and when the monitor is set to paddles/pads that those are being used to conduct the ECG from the patient to the machine. Beware of artefact that might mimic VF. Always check the patient! Don’t treat the monitor!
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