Description of the condition
Endotracheal intubation in paediatric patients is a fundamental skill required for the practice of medicine in a multitude of settings, from the emergency department (ED) to the operating room. The goal of endotracheal intubation is to place a temporary but secure airway within the trachea, thus allowing for establishment or protection of the airway and to provide manual or mechanically assisted ventilation. In paediatric patients, intubation may be considered for any number of reasons that include elective or emergency surgical procedures, medical management of respiratory illness, altered level of consciousness, or to simply decrease metabolic demand. Regardless of the indication, endotracheal intubation is a high-risk procedure requiring that the physician assume control of the respiratory system by attempting visualization of the glottis and successfully passing a tube into the trachea via the mouth or nose.
Assuming control of a patient's airway can result in undesirable physiologic responses in the patient. Hypoxaemia, bradycardia, and hypotension are potential physiologic responses to intubation that have been reported in paediatric studies (Fastle 2004; McAllister 1999; Nishisaki 2013). In one study of paediatric intubations in an intensive care unit setting, in nearly 2000 intubation events, the rate of hypotension requiring intervention was as high as 3.4% (Nishisaki 2013). In addition, more than one intubation attempt in a single encounter has been associated with higher rates of undesirable physiologic responses (Nishisaki 2013).
The reported incidence of bradycardia in paediatric intubation varies. In a commonly referenced retrospective cohort study of all paediatric intubations in an urban children’s hospital over the course of four years, there were only six instances (4%) of bradycardia out of a total of 143 intubations (Fastle 2004). In a randomized controlled trial (RCT) examining paediatric intubation facilitated by sevoflurane versus no medication, the incidence of bradycardia in the awake group was as high as 44.4% (Hassid 2007). Bradycardia is thought to occur for several reasons, secondary to vagal stimulation from the intubation equipment, laryngoscopy blade, or endotracheal tube; secondary to hypoxia resulting from the removal of the patient’s drive to breathe with sedative agents; or as a result of adverse effects from other commonly used premedication agents (mainly succinylcholine).
In a study of preterm infants, Marshall (Marshall 1984) proposed that the bradycardia observed during endotracheal intubation was the result of parasympathetic stimulation involving the vagal nerve. Basic physiology supports this theory as the vagus nerve plays a role in lowering the intrinsic heart rate in normal individuals. The pharynx, oesophagus, and respiratory tract contain afferent vagal fibres that may come in contact with the laryngoscope blade or endotracheal tube resulting in an increased parasympathetic tone. To compound this effect, infants and children may have a more sensitive or pronounced vagal response to intubation than adults (Fastle 2004).
Sedative agents used in premedication often completely remove the patient’s ability to drive respiration. Oxygen is required for normal neuronal and electrical conduction through the cardiac conduction system (Guyton 2006). Apnoeic conditions that cause hypoxia result in stimulation of peripheral chemoreceptors and subsequent bradycardia (Alboni 2011). As a study by Wennergren suggests, bradycardia induced by the aforementioned vagal reflex may be more pronounced in the presence of underlying hypoxia (Wennergren 1989). In this way, the bradycardic response to physical instrumentation of the airway may be compounded if the patient becomes hypoxic during the intubation sequence.
The use of paralytic agents is a fundamental aspect of premedication. A popular agent for this purpose is succinylcholine. Succinylcholine is a depolarising paralytic agent, formed from two molecules of acetylcholine linked together. In addition to direct stimulation of cholinergic receptors at the neuromuscular junction, it also stimulates muscarinic and nicotinic receptors in the autonomic nervous system thus enhancing the parasympathetic drive. It is through the latter mechanism that succinylcholine is thought to precipitate sinus bradycardia and other bradycardic cardiac rhythms (Miller 2010).
Description of the intervention
The pre-emptive administration of atropine is commonly employed in order to avoid bradycardia associated with intubation. Atropine sulfate, given for the indication of premedication for intubation, is typically given intravenously in a dose of 0.02 mg/kg per dose to a maximum of 0.5 mg/dose (American Heart Association 2011). Atropine may also be administered to reduce airway secretions.
A standard intubation procedure consists of pre-oxygenation and preparation of the patient, administration of anaesthesia, administration of neuromuscular blockade, direct laryngoscopy, and passage of an endotracheal or nasotracheal tube (hereafter named 'intubation sequence'). Other scenarios require alternate approaches to intubation; in cardiac arrest anaesthesia is often omitted. In rapid sequence induction, the patient is believed to be at higher risk for aspiration of gastric contents, and the patient is therefore administered neuromuscular blockade at the time of induction of anaesthesia. Finally, patients may be intubated in an awake fashion with subdissociative doses of anaesthetic agents or topical anaesthesia. When atropine is administered in any intubation it is typically given prior to neuromuscular blockade and prior to direct laryngoscopy (that is prior to anticipated bradycardia from the mechanisms mentioned above, and prior to direct laryngoscopy that could be obscured by airway secretions).
How the intervention might work
Atropine sulfate, a competitive antagonist of muscarinic acetylcholine receptors, is classified as an anticholinergic agent (Lucking 2012). Anticholinergic agents, by definition, reduce the effect of the parasympathetic nervous system and, in doing so, block the effects of the vagus nerve. By blocking vagal activity, atropine allows for increased stimulation of the sinoatrial node and conduction through the cardiac electrical system resulting in contraction of the cardiac muscle. Because bradycardia is associated with anaesthesia, paralysis and direct laryngoscopy is thought to be predominantly vagally mediated, atropine is a natural choice for counteracting these effects. In addition to increasing heart rate, atropine also plays a role in reducing respiratory secretions, effectively 'drying out' the airway and facilitating visualization of the glottis.
Why it is important to do this review
Evidence of bradycardia during paediatric intubation dates back to the 1950s (Leigh 1957). While these studies raised the initial question of bradycardia during the intubation procedure, most are small, non-randomized, and often report atypical conditions; such as multiple doses of succinylcholine (Lupprian 1960). As recent as this year, the routine use of atropine has been supported in published literature (Jones 2013), "atropine reduces the prevalence of arrhythmias and conduction disturbances during intubations, which may contribute to the safety of the procedure...". Accordingly, current guidelines recommend that all children under one year of age, any child aged one to five years who will also receive the paralytic succinylcholine, and any child over the age of five years who receives a second dose of succinylcholine should also receive a dose of intravenous atropine sulfate (American Heart Association 2011). This recommendation is pervasive in the paediatric literature (American Heart Association 2011; Fleisher 2010; Gerardi 1996) and is the standard practice amongst physicians intubating children and infants.
Despite this climate, the practice has several times been called into question (McAuliffe 1995; Mirakhur 1978). These early studies are small and predominantly anaesthesia based, but in some countries surveys from the 1990s suggested that the pendulum was swinging and routine use of atropine was not common practice (Parnis 1994; Warde 1995). Despite this, national guidelines recommended the routine use of atropine in specific paediatric populations. Prompted by this resistance to change, a narrative review was completed by Fleming. The review examined the previous literature and proposed that: “atropine premedication for emergency department rapid sequence intubation is unnecessary and should not be viewed as ‘standard of care’” (Fleming 2005). A retrospective cohort study, published in 2004, also concluded that pretreatment with atropine did not always prevent bradycardia (Fastle 2004). This study was included in a “BestBET” on the topic and published in 2007 examining the effectiveness of atropine to reduce reflex bradycardia during rapid sequence induction. The authors went on to conclude that the incidence of bradycardia was less frequent than previously reported, that hypoxia was likely to be the main contributing factor to bradycardia, and that there was evidence suggesting the use of atropine was unnecessary (Bean 2007).
Reflective of the contradictory climate, some paediatric texts acknowledge the lack of evidence surrounding the issue but maintain the recommendation (Fleisher 2010), while others no longer recommend routine use of atropine in the paediatric intubation sequence (Walls 2008). While recent publications raise the issue, the authors of this paper believe that a more rigorous look at the literature is warranted. Therefore, the current contradictory recommendation regarding the role of atropine in endotracheal intubation of children demands a formalized systematic review to synthesize the existing evidence.