14.4.5 Anaesthetic agents

Volatile and halogenated agents

Extensive research has been conducted on halothane (Fluothane^®), a substance that has since been withdrawn from the clinical market. While halothane is the most cardiodepressant halogenated agent, it exhibits an effective β-blocker effect in cases of dynamic stenosis of the outflow tract. At MAC, the ejection fraction (EF) is reduced by 25 to 38% in normal children [10]. This effect is amplified in infants due to their immature hearts (50% reduction in EF). It may become catastrophic in neonates who have no functional reserve given their high metabolic requirements [9].

In myocardial cells, halogenated agents inhibit Ca²⁺ flows in the slow channels of the membrane and the sarcoplasmic reticulum (L-type calcium channels), and in the Na⁺-Ca²⁺ exchanger channels. This means there is less free Ca²⁺ to bind with the tropomyosin complex and the contractile force is reduced [1]. Until the age of approximately 6 months, young children exhibit excessive reduction in contractility under all halogenated agents due to the immaturity of their Ca²⁺ release and uptake system. The same phenomenon occurs in the musculature of the arterioles, causing arterial vasodilation. Isoflurane and sevoflurane lower SVR by 22% and 15% respectively [15]. Desflurane prompts sympathetic stimulation, tachycardia and hypertension. It causes SVR and PVR to rise [18]. There is a higher risk of junctional bradycardia and a prolonged QTc interval with sevoflurane than with isoflurane, and the latter exhibits the least cardiodepressant effect of all the halogenated agents [1].

Sevoflurane is well-suited to mask induction, while isoflurane is a poor induction agent due to its repugnant odour and the upper respiratory tract irritation that it causes. The systemic vasodilation associated with isoflurane may exacerbate “pulmonary steal” caused by R-to-L shunting or pulmonary obstructions, but reduce “systemic steal” in cases of truncus arteriosus or single ventricle defects. Desflurane is not indicated for infant cardiac surgery due to the risk of raised PVR and pulmonary hypertensive crises.

N₂O is not used in paediatric cardiac anaesthesia, except in some simple cases where ventricular function is normal and CPB is not used. It is prohibited in all open-heart procedures due to the risk of increased air bubble size [7].

Intravenous agents

Due to its central sympathetic stimulation, ketamine maintains vascular resistance and myocardial contractility. Since it increases SVR in relation to PVR, it is a popular agent for forcing a bidirectional shunt to switch to L-to-R and reducing cyanosis, provided that PaO₂ and PaCO₂ are kept at normal levels [22]. PVR may rise in adults, but not in normoventilated children [2]. However, sympathetic stimulation due to ketamine may occasionally trigger pulmonary vasospastic crises in PAH-prone infants, exacerbate a dynamic muscular obstruction, and cause myocardial ischaemia in cases of aortic stenosis or hypoplasia. With the exception of these situations, it is a safe and rapid induction agent (1-2 mg/kg IV), even in haemodynamically compromised children. However, ketamine has a major negative inotropic effect on isolated myocardial fibres and its maintenance of haemodynamic stability is due only to the central sympathetic stimulation that it prompts [17]. Consequently, it is contraindicated for children with ventricular failure whose cardiac output is dependent on this sympathetic stimulation, whose neurohumoral system is exhausted by myocardial failure, or whose β-stimulant treatment has reduced their number of β1 receptors. In this case, its direct inotropic effect is no longer counterbalanced by sympathetic stimulation and may trigger circulatory collapse.

Midazolam (0.1 mg/kg IV) is an excellent induction agent, even in children aged under 3 years. Although the peak serum concentrations achieved by intravenous administration significantly lower preload and SVR (22% reduction in cardiac output), they do not compromise contractility [15]. These adjustments to loading conditions destabilise haemodynamics in delicately balanced cases and may exacerbate cyanotic R-to-L shunts. Central sympathicolysis particularly affects children who are dependent on catecholamine secretion for keeping their haemodynamic balance.

Etomidate (0.3 mg/kg) provides major haemodynamic stability, has no cardiodepressant effect, and does not cause bradycardia. Its duration of action is short [16]. Although it is not routinely used in paediatric anaesthesia due to induction discomfort (pain on injection, myoclonus, nausea), it is the only agent that guarantees haemodynamic stability in the most compromised children. As in adults, it reversibly inhibits 11-β-hydroxylase and temporarily blocks cortisol synthesis, which is not without risk when dealing with young children [4].

Propofol is suitable for brief periods of anaesthesia and continuous infusions. Unfortunately, it cannot be recommended for unrestricted use with neonates and children aged under two years, except for short procedures [11]. Induction doses are high in paediatrics – infants are given double the adult dose (3-4 mg/kg) and the dose for children is 50% higher (2-3 mg/kg) [11,21]. This amplifies haemodynamic effects (10-25% reduction in preload, SVR, and arterial pressure), especially in the event of R-to-L shunting. These amplified requirements can be explained by pharmacokinetic factors: high cardiac index (lower peak concentrations after injection), presence of intracardiac shunting, highly vascularised compartment, and higher total water volume in relation to body weight [21]. Continuous infusions require 25-50% higher doses than in adults (10-25 mg/kg/hour) and are also followed by a fall in pressure (-25%) and stroke volume (-23%) [12]. Moreover, they incur specific risks in young children: major lipid overload, delayed clearance due to low hepatic hydroxylation and glucuronidation capacity, impaired protein binding, severe acidosis [11]. They are not indicated for postoperative sedation. In practice, propofol can be used for induction and maintenance of anaesthesia in children aged over 6 months with non-cynanotic heart diseases and unimpaired myocardial function. When performing simple procedures (e.g. ASD correction), it allows rapid recovery and early extubation 1-2 hours after arrival in intensive care.

Barbiturates are direct cardiodepressants – thiopental reduces contractility by 20-25%, inhibits the baroreceptors and causes venodilation, which lowers preload [1]. With the exception of simple cases where haemodynamics are normal, barbiturates are not suitable for anaesthetising children with congenital heart diseases.

Dexmedetomidine (Precedex^®) is an excellent sedative that lowers sympathetic response, potentiates anaesthesia, and limits analgesic requirements. It tends to alleviate pulmonary hypertensive crises and tachyarrhythmias like the junctional ectopic tachycardia (JET). It shortens the length of ventilation, makes early extubation easier and drops the incidence of cardiac complications [14]. It has little depressant effect on respiration and does not incur the hypercapnic risk linked to common sedatives. However, it causes hypotension and bradycardia. The latter effect is useful in cases of atrial tachycardia. The recommended dosage is a 0.7 mcg/kg in 10 minutes followed by an infusion of 0.2-0.7 mcg/kg/h [8,13]. Its elimination half-life is 2.6 hours, although this is longer for subjects aged under 6 months [19], but shorter in case of R-L shunt [8]. When combined with ketamine (bolus 1 mg/kg, infusion 1 mg/kg/h), it offers the benefit of balancing the two substances’ side effects, with ketamine's sympathetic stimulation compensating for dexmedetomidine's inhibition [20]. For sedation or premedication, dexmedetomidine can be administered by nasal route (0.5 mcg/kg < 6 months, 1-2 mcg/kg > 6 months) instead of chloral hydrate; ketamine is also used by nasal route (1 mg/kg) [8,13].

Opiates

Fentanyl offers by far the greatest haemodynamic stability and the least myocardial depression. At moderate doses (≤ 25 mcg/kg in total), it enables extubation at the table, in the same way as sufentanil (0.5-2.5 mcg/kg). Haemodynamic stability is well maintained at high doses (≥ 50 mcg/kg). When combined with the vagolytic effect of pancuronium bromide, heart rate remains stable. Moreover, high doses reduce pulmonary resistance reactivity to pain, intubation, and surgical or tracheal procedures [6] – they limit the hormonal stress response. There is no significant difference between fentanil (50-100 mcg/kg) and sufentanil (5-10 mcg/kg) [1].

Remifentanil (0.1-0.2 mcg/kg/min) is useful for brief procedures such as cardiac catheterisation [5]. It allows rapid recovery, even post-CPB as its clearance does not change and it is not absorbed in the plastic tubings [3]. However, at induction doses, it prompts severe bradycardia and hypotension, which may dangerously compromise young children's haemodynamic balance. It is advisable to prevent bradycardia by simultaneously administering glycopyrrolate (6 mcg/kg IV).
 

 

 

© BETTEX D, BOEGLI Y, CHASSOT PG, June 2008, last update February 2020