Intravenous induction versus gaseous induction in paediatric patients

Intravenous induction versus gaseous induction in paediatric patients

Intravenous induction versus gaseous induction in paediatric patients

Operating department practitioner Arwinder Singh provides an overview of intravenous versus gaseous induction in paediatric patients to assist the anaesthetic team in practice

Paediatric anaesthesia takes into account the unique physiology and technical challenges associated with induction in the child compared with the adult. The aim of this paper is to provide an overview of intravenous versus gaseous induction in paediatric patients to assist the anaesthetic team in practice.


Ideal induction characteristics

Induction agents need to fulfil a certain amount of criteria in order to be considered useful in the clinical setting, in addition to their ability to achieve clinical anaesthesia (Zielinska, Holtby and Wolf, 2011). Ideally, induction should be a smooth, painless process that is rapid and easily accepted by the child, parent and operating room staff (Moore, et al., 2003). Above all, the induction process should be safe, in that it does not result in direct harm to the child nor interfere with metabolic or physiological processes in such a way that harm might ensue (Rappaport, et al., 2011). This includes an agent that does not alter haemodynamic or respiratory stability and one that is safe in the postoperative period (Rappaport, et al., 2011). Postoperative pain, nausea and vomiting and altered mental states are outcomes that should be avoided but can be precipitated by some induction agents (Zielinska, Holtby and Wolf, 2011).

In addition to these concerns, the anaesthetist should select the correct induction agent based on the nature of the procedure and specific patient factors. For instance, difficult airways, stomach contents and the difficulty in establishing venous access may all influence the choice of agent – specifically gaseous or intravenous (Zielinska, Holtby and Wolf, 2011). Therefore, a number of factors need to be considered when selecting the induction agent of choice in paediatric medicine. Furthermore, this choice should be based on the best available evidence for the patient and procedure being performed, where such evidence is available (Cravero and Blike, 2004).

The remainder of this review will focus on these specific ideals of an induction agent in order to determine how the most commonly used gaseous (sevoflurane) and intravenous (propofol) agents meet these criteria, in order to compare their importance for paediatric practice.


Relative advantages of gaseous and intravenous induction

Gaseous agents

The main advantages of gaseous induction include the ease with which the technique can be applied, the speed of induction and the avoidance of intravenous techniques in the child, which may be a source of anxiety and technically challenging (Mellon, Simone and Rappaport, 2007). Gaseous induction agents rely on a high level of solubility between air and blood and fat in order to produce their anaesthetic effect rapidly in the brain (Nolan, 2013). Consequently, agents such as sevoflurane act very rapidly due to their solubility characteristics, and are also relatively short-lived in the body, with unchanged exhalation after a matter of minutes (FRCA, 2004). This suggests that two major advantages to gaseous induction are apparent: firstly, the rapid onset and rapid clearance from tissues indicates that induction will be quick and recovery also quick, and secondly the lack of extensive metabolism of the gaseous agent, as it is exhaled unchanged, would suggest few metabolic side effects (FRCA, 2004).

The primary benefit of gaseous induction agents is considered to be in the administration of anaesthesia in children who are afraid of needles (Nolan, 2013). The process is pain-free and less stressful than needle use in children, particularly those who are agitated or who are moving during the induction process (Lonnqvist and Morton, 2006). Such movement can make intravenous access technically demanding and potentially painful (Beule, et al., 2007). Indeed, pain has been noted in up to 60 per cent of cases of intravenous induction (Mellon, Simone and Rappaport, 2007). Sevoflurane and associated compounds have been shown to reduce anxiety associated with anaesthesia in children and might therefore result in a more refined and effective clinical pathway for the patient and practitioners present (Beule, et al., 2007).

In addition, the use of ventilatory measurements to ascertain the effectiveness of anaesthesia induced by gaseous agents is considered a significant benefit (Breschan and Likar, 2006). The alveolar ventilation characteristics can be monitored during the procedure and constant adjustments made to ensure that the patient remains under anaesthesia throughout the operation (Ahn, et al., 2008). Furthermore, the responses to doses of gaseous induction agents are highly predictable, which is not often the case with propofol and other intravenous agents, where individual variation in response is common and may preclude optimal anaesthesia (Pieters, et al., 2010). Therefore, response to changes in physiology can be anticipated and, in principle, managed more effectively with gaseous agents.

Intravenous agents

Intravenous induction agents have the potential to produce a more stable anaesthesia, can be used in more complex scenarios (e.g. upper airway surgery), do not rely on alveolar ventilation to take effect and are relatively easy to monitor and adjust during the procedure, without producing operating room pollution (Eyres, 2004). Propofol in particular is commonly used in children and is able to produce anaesthesia as rapidly as gaseous agents, although distribution throughout the bodily compartments is more extensive (Zielinska, Holtby and Wolf, 2011). Initially, the brain, kidneys, liver and heart receive the drug (due to the high blood flow in these regions) and then slow absorption is seen in muscles and fat tissue (Beule, et al., 2007). Liver-based metabolism of the drug is most common, with water-soluble products excreted in the urine (Mellon, Simone and Rappaport, 2007). Despite these processes, propofol metabolites are not associated with significant clinical effects in the majority of cases (see next section) and clearance from the body is relatively fast (Zielinska, Holtby and Wolf, 2011).

It has been argued in the literature, that while gaseous agents are considered advantageous for induction, as they avoid the use of needles during waking periods, the use of masks during gaseous induction may also be associated with anxiety and stress in the child (Zielinska, Holtby and Wolf, 2011). This is particularly evident when the mask is placed onto the child and held there against their will. In addition, the pungency of some inhalation agents is such that they can be upsetting to the child and may irritate the respiratory tract to some degree (Brown, 2013). These negative associations are avoided in intravenous induction and therefore may benefit the child who is upset by the mask or the smell of the volatile anaesthetic (Zielinska, Holtby and Wolf, 2011).

Other advantages of intravenous induction are seen in the rapid induction produced compared with gaseous induction, which is particularly important in emergency anaesthesia situations (FRCA, 2004). Furthermore, a child with a full stomach or with a notable degree of gastro-oesophageal reflux may pose a relative contraindication to gaseous induction and this would preferentially support the use of agents such as propofol (Zielinska, Holtby and Wolf, 2011). Similarly, in neurosurgical procedures, where the risk of central nervous system ischaemia is high, intravenous techniques may be more useful due to the enhanced benefits of neuroprotection (Engelhard, et al., 2004).

Potential complications

Gaseous agents

Several complications or side-effects have been consistently noted with both types of induction agent. In general, gaseous induction is more likely to be associated with movement during induction (though this is reduced with isoflurane and halothane compared with sevoflurane) (TerRiet, et al., 2000). This excitation movement may be problematic in larger patients, where restraint may be necessary (Zielinska, Holtby and Wolf, 2011). Emergence agitation may be common in preschool age children (up to 80 per cent), and postoperative nausea and vomiting is also common (approximately 20 per cent of patients) (Zielinska, Holtby and Wolf, 2011). Gaseous induction agents may also be associated with liver toxicity if used for prolonged periods, due to a small proportion of the agent being metabolised by the liver into harmful compounds (FRCA, 2004). While this is a rare complication, liver toxicity has been demonstrated in children and should be considered in paediatric patients with poor hepatic function (Zielinksa, Holtby and Wolf, 2011).

Malignant hyperthermia is a condition that affects one in 10,000 anaesthetic episodes in children, and is characterised by disordered skeletal muscle calcium regulation and is precipitated by volatile anaesthetics, including halothane, isoflurane, sevoflurane and enflurane (Brady, Sun and Rosenburg, 2009). The condition is characterised by excessive muscle contracture, heat generation and metabolic disturbances that may lead to death (Hopkins, 2011). Where a family history of malignant hyperthermia is noted, gaseous induction is absolutely contraindicated and therefore intravenous induction (propofol) is advisable (Brislin and Theroux, 2013).

It has also been noted that during anaesthetic procedures where sevoflurane and associated agents are used there is a relatively high frequency of epileptiform changes noted on electroencephalography (EEG) (Constant, Seeman and Murat, 2005). Although it is prudent to assess for a history of epilepsy prior to the use of many anaesthetic agents, the significance of these EEG findings are not clear for patients with a history of epilepsy (Constant, Seeman and Murat, 2005). However, it is generally advisable to avoid the use of gaseous agents in children with severe epilepsy or in those with a history of adverse reactions or strange behaviour following the use of sevoflurane in other contexts (Zielinska, Holtby and Wolf, 2011).

There are reports, predominantly based on animal models, that long-term use of gaseous agents, in particular sevoflurane, may be associated with neurodegeneration and therefore may present a risk to paediatric patients (Khan, Hayes and Buggy, 2013). While these findings have not been confirmed in practice in humans, there is compelling laboratory evidence to suggest these agents may have a detrimental effect on central nervous system function if used in high doses over long periods of time (Khan, Hayes and Buggy, 2013). Therefore, further research is advised to assess the risk to paediatric patients.

Intravenous agents

One of the main disadvantages of intravenous induction is the necessity of vein catheterisation, which can be painful in a number of cases and may be off-putting for children (Zielinska, Holtby and Wolf, 2011). In addition, the pain associated with the injection can be present even where the skin is anaesthetised beforehand (Pieters, et al., 2010). Even when the skin is correctly anaesthetised in order to remove the pain of the injection, it may be the case that psychological fear of the needle results in patient discomfort regardless, emphasising the need for the anaesthetist to be aware of the anxiety levels of the patient prior to the procedure (Eyres, 2004). Finally, the actual agent may be responsible for a reduction in heart rate (bradycardia) and hypotension during the injection process, and therefore careful monitoring is needed at this early stage (Zielinska, Holtby and Wolf, 2011).

Propofol infusion syndrome (PIS) is a potentially fatal complication of extended use of high doses of propofol in paediatric patients (Vasile, et al., 2003). The condition is characterised by cardiac failure, rhabdomyolysis, metabolic acidosis and renal failure (Kam and Cardone, 2007). More than twenty-one paediatric cases have been described in the literature; but while the condition is relatively rare it may have a devastating effect on the child (Kam and Cardone, 2007); however, the association of PIS with propofol use for induction in short operations (under 6 hours) is unclear and therefore the risk to the child may be minimal in these circumstances (Vasile, et al., 2003).

There has been concern raised over the lack of data on propofol use in neonates during the induction process, particularly following the emergence of several cases of sudden cardiac arrest in the literature (Zielinksa, Holtby and Wolf, 2011). The precise mechanism underlying this reaction is not clear, although it was noted that no infants had underlying congenital anomalies and that the dosing protocols of propofol in each case were within reasonable limits (Veyckemans, 2001). Therefore, further exploration of this reaction is warranted in neonates (Zielinska, Holtby and Wolf, 2011).

Comparisons of agents: clinical data

The use of nitrous oxide with either halothane or propofol for the induction and maintenance of anaesthesia in children during day surgery was reviewed in one study, which found that the only relative advantage of propofol was a reduction in post-operative nausea and vomiting, otherwise the agents were comparable in their efficacy and side-effect profile (Ved et al., 1996). More recent data focused on comparing propofol induction with sevoflurane induction in 322 children attending for day surgery (Moore, et al., 2003). The authors found that excitatory movements were more commonly associated with sevoflurane induction, while the average time for induction with sevoflurane was five minutes, compared with 3.1 minutes in the propofol group. Recovery times were longer in the propofol group compared with the sevoflurane group (26.4 minutes versus 23.2 minutes; P < 0.002), although time spent in postoperative wards was the same. Delirium during recovery was greater in the sevoflurane group, while postoperative nausea and vomiting was also significantly higher than in patients managed with propofol (Moore, et al., 2003).

Additional data supports the observation that side-effects and postoperative nausea and vomiting may be increased when using gaseous induction in children, while it has also been reported that the relative cost of sevoflurane induction exceeds that of propofol due to the occurrence of these side effects (Elliott, et al., 2003); however, clinical outcomes in patient groups managed with either propofol or sevoflurane in this study did not differ at seven days following surgery (Elliott, et al., 2003).

While the increased risk of side-effects, including nausea and vomiting and induction-related excitatory movements would suggest that sevoflurane is a less suitable induction agent than propofol in this setting (paediatric day care), the differences between the two groups were small from a clinical perspective, despite exhibiting statistical significance. Therefore, further studies of this nature are warranted to extend recommendations on induction techniques beyond anecdotal observations and practitioner preferences based on experience (Mani and Morton, 2010).

Several larger studies, including several randomised trials, have been conducted, specifically focusing on the use of propofol versus sevoflurane, two common agents used in paediatric anaesthesia (Pieters, et al., 2010). A randomised, double-blind study was conducted in 42 patients following induction with either sevoflurane or propofol (including continued maintenance with that agent) during ear, nose and throat surgery to assess the impact of the drugs on emergence agitation (Pieters, et al., 2010). The results suggested that propofol did not have a superior effect on agitation compared with sevoflurane during adenotonsillectomy procedures, although propofol was associated with reduced nausea and vomiting, as well as reduced postoperative pain levels. Recovery time, nursing satisfaction and parental happiness were equal with both techniques.

The finding that pain may be enhanced in patients following sevoflurane use was also noted in a double-blind, randomised study of 88 children aged 3–6 years undergoing hernia repair surgery (Hasani, et al., 2013). Pain was more likely to be an issue when sevoflurane induction was used (24.3 per cent) compared with propofol induction (4.5 per cent), although recovery time was shorter in the sevoflurane group (10.1 minutes versus 16.5 minutes, P<0.001). Similarly, the incidence of emergence agitation or delirium and the incidence of postoperative pain was reduced following induction with propofol compared with sevoflurane in a randomised controlled trial of 112 children undergoing strabismus repair (Chandler, et al., 2013). In conclusion to the association of sevoflurane and associated gaseous anaesthetic induction agents with emergence agitation, a recent meta-analysis of 14 studies demonstrated a statistically significant reduction in agitation with propofol use in a variety of surgical contexts (P<0.0001) (Kanaya, et al., 2014).

A recent study has highlighted the importance of context during the surgical approach, as the authors explored the use of sevoflurane induction in children under three years of age undergoing spontaneous breathing rigid bronchoscopy (Liao, Li and Liu, 2010). Sixty-four children were included in the analysis, with random allocation to either sevoflurane or propofol. The results demonstrated that haemodynamic data and respiration were more stable in sevoflurane-managed patients, while induction speed, recovery rate and excitement were all increased with sevoflurane compared with propofol. The only negative feature is the increased level of excitement therefore, but otherwise in this context sevoflurane was superior to propofol from a technical and symptomatic perspective (Liao, Li and Liu, 2010).

A recent Cochrane summary provides an overview of the comparability of gaseous versus intravenous anaesthetic agents for use in paediatric anaesthesia (Ortiz, et al., 2014). A total of 16 studies were identified and evaluated in order to explore the impact of either type of agent on specific outcomes, including postoperative nausea and vomiting, pain, delirium and other mental disturbances. The authors found that propofol use was generally associated with lower rates of postoperative nausea and vomiting and the risk of behavioural problems resulting from postoperative pain or mental state disturbance compared with sevoflurane; data on other variables was weak due to the heterogeneous and methodologically variable approaches used by studies and therefore further research is recommended for other agents. However, as noted by Moore et al. (2003), this review also finds that hospital discharge and recovery time are comparable with both sevoflurane and propofol use (Ortiz, et al., 2014).


Overall, it is apparent that clinicians have specific preferences for either gaseous or intravenous induction techniques in practice, although the comparable efficacy of these agents limits constructive critical analysis. Consequently, both types of induction agent are in common use and may be selected on their basis of pre-operative child anxiety levels (favouring gaseous induction) or specific technical elements of the procedure (for instance, airway surgery may demand intravenous induction). While side-effects are noted for both types of induction agent, these are generally rare, although nausea and vomiting may be unpleasant for the child and disorientating confusion following the operation may persist with gaseous agents. In practice it may be useful to consider specific situations in which each type of anaesthetic induction method is most useful and base clinical decision on this data, rather than a predilection for one agent over the other.

Key practice points:

  • Gaseous induction agents may be best used in children with needle phobia.
  • Gaseous agents can be associated with post-operative adverse events, including nausea and vomiting, and delirium.
  • Intravenous agents (typically propofol) may be best for specific technical procedures, including airways or sinus surgery.
  • Specific contraindications to gaseous induction agents, including malignant hyperthermia, should be noted.
  • Gaseous induction followed by total intravenous anaesthesia for the procedure is an emerging trend maximising the advantages of both types of agent.



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