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Anaesthetic agents in paediatric day case surgery: do they affect outcome?

Moore, E. W.*; Pollard, B. J.; Elliott, R. E.§

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European Journal of Anaesthesiology: January 2002 - Volume 19 - Issue 1 - p 9-17



The number of children undergoing surgery as day case patients is increasing [1]. In the UK the Royal College of Surgeons and the National Health Service Executive aim for more than 50% of all surgery to be performed as day case procedure [2]. Children make excellent candidates for day case surgery as they are usually healthy, free of systemic disease and typically require straightforward, minor or intermediate surgical procedures [3]. The benefits to the patient of outpatient surgery are the avoidance of a hospital admission and minimal disruption to their lifestyle; these advantages may be more important in the paediatric population [4]. The practice of day case surgery is predicted to grow rapidly because the comparative costs of surgical care in this setting are lower than in an inpatient setting [5]. The choice of anaesthetic agent and technique has been seen as critical in the avoidance of postoperative morbidity (e.g. pain or nausea or vomiting), and is therefore an important factor in achieving rapid patient discharge [6]. However, there is currently no general agreement as to the most appropriate choice of anaesthetic technique. We therefore undertook a review of anaesthetic agent usage in paediatric practice with particular emphasis on the outcome following surgery.

Outcome measures

When investigators compare anaesthetic agents, the outcome measures employed fall into two distinct types; these are quantitative or qualitative. Quantitative end-points, e.g. induction of anaesthesia or discharge from hospital are seen as important in their own right, in that a shorter time may be regarded as beneficial through possible cost savings (e.g. nursing hours). However, true cost savings through reduced patient contact times will only be achieved if patient throughput can be increased or if fewer healthcare professionals are needed [7]. Qualitative end-points can be described as measures of postoperative morbidity, e.g. postoperative nausea and vomiting (PONV) or patient satisfaction scores.

In an editorial in Anesthesiology, Fisher distinguishes between 'true end-points', which he defines as 'patient satisfaction, discharge times and unplanned admissions', and 'surrogate end-points', e.g. PONV, which may generate differences in the former [8]. Fisher explains that surrogate end-points are used for two reasons. Firstly, historical precedent and secondly, where the true end-point would require a massive sample. For example, desflurane is associated with a more rapid time to initial responsiveness [9]. Although it may not necessarily matter whether a patient opens his eyes 10 min after the completion of an operation, this outcome is a surrogate for the true outcome, which is the time when the patient's trachea can be extubated (thereby permitting transfer from the operating room) or the time at which the patient can be discharged from the hospital. This review considers the effects of anaesthetic technique on both quantitative and qualitative measures of anaesthetic induction and recovery, the cardiovascular system and PONV. TABLE

Table 1
Table 1:
Induction times in studies comparing halothane and nitrous oxide with sevoflurane and nitrous oxide.

Induction of anaesthesia

Speed of induction

The most frequent measure of induction is the time required to reach a defined end-point. Commonly, the time to loss of eyelash reflex or time to the pupils becoming central and constricted (Guedel stage III: plane I) are recorded. Less objective measures include time to loss of jaw tone or time until tracheal intubation is achieved. The introduction of sevoflurane has led many investigators to compare the time required for induction of anaesthesia with that for halothane. Walker, Piat and Naito compared induction times using sevoflurane and nitrous oxide with halothane and nitrous oxide [10-12]. Each used groups of less than 25 patients and each used a step-wise increase in concentration during induction. All three studies found a more rapid induction with sevoflurane than with halothane but statistical significance was not achieved. Greenspun and colleagues also compared induction times using sevoflurane and nitrous oxide with halothane and nitrous oxide, again using a stepwise increase in concentration during induction. Each measured the time to loss of eyelash response [13-16]. All of these studies showed a statistically significant, faster induction using sevoflurane; the times for sevoflurane being approximately two-thirds of those required for halothane. Traditionally during an inhalational induction, anaesthetists use a stepwise increase in the concentration of the volatile anaesthetic agent. It has been argued that for a pleasant, non-irritant agent such as sevoflurane, a gradual increase in concentration is not required [17]. Meretoja and colleagues studied 120 children, randomized to receive an induction with sevoflurane and nitrous oxide or halothane and nitrous oxide; he did not employ a stepwise increase in volatile concentration for either agent. In this study a more rapid induction was achieved with sevoflurane (P < 0.05). Unsurprisingly the induction times achieved in this study were much shorter than those in the studies which used a stepwise increase in volatile agent [18].

Induction adverse events

Several studies have investigated the incidence of adverse events during induction, comparing halothane and nitrous oxide with sevoflurane and nitrous oxide. The incidences of coughing, laryngospasm, breath holding and excitatory movement have been recorded most commonly [10-12,15,19]. An increased incidence of laryngospasm [10,11,19] and coughing [10,15] has been recorded for halothane and nitrous oxide when compared with sevoflurane and nitrous oxide, although it did not reach statistical significance in any study. Two studies have documented increased excitatory movements during sevoflurane and nitrous oxide induction compared to halothane and nitrous oxide, again without statistical significance in any one study [10,15]. It remains to be seen if larger studies will find these differences to be significant.

When Meretoja and colleagues approached the 120 patients, who were >2 yr old in his study, and asked them to describe their induction as pleasant or unpleasant, 77% of those in the sevoflurane and nitrous oxide group chose pleasant against 26% of those in the halothane and nitrous oxide group (P = 0.0001). When asked if they would choose a similar induction technique for future anaesthesia, 85% said yes to sevoflurane and nitrous oxide, compared to 43% for halothane and nitrous oxide (P = 0.0001) [18].

When Martin and colleagues compared induction using propofol with halothane and nitrous oxide in 156 paediatric outpatients, the time from commencing induction to tracheal intubation was the same in both groups. However 34% of the children in the halothane group had episodes of airway obstruction prior to intubation compared to 10% in the propofol group (P < 0.001) [20].

Viitanen compared two groups of 26 children (aged 1-3 yr). One group was given propofol 3 mg kg−1 followed by increments of 0.5 mg kg−1, the other group received up to 8% sevoflurane with 70% nitrous oxide until the child had 'fallen asleep' (pupils small and midline). Each was then given mivacurium 0.2 mg kg−1 and the trachea intubated 2 min later. Movement related to tracheal intubation occurred in seven (31%) of the propofol group compared with two (9%) in the sevoflurane group (P = 0.06) [21].

Effects on the cardiovascular system

When assessing cardiovascular stability in day case patients, investigators tend to study two specific outcomes. Firstly, changes from the baseline in the blood pressure (BP) (mean or systolic) and the heart rate (HR) are measured, and secondly, the incidences of any cardiovascular adverse events (bradycardia or other dysrhythmia) are noted. Changes in BP and HR are important in their own right in that such changes may impact upon organ perfusion. Perhaps more importantly, such changes in uncompromised American Society of Anesthesiologists grade I and II patients in response to anaesthetic agents may act as a proxy for their effects in unstable patients. The propensity of halothane to cause dysrhythmias when used to anaesthetize patients for outpatient dental surgery has been postulated to be linked to unexplained cardiac arrest during such minor procedures [22]. The incidence of dysrhythmias is therefore often measured in studies investigating new anaesthetic agents.

Four authors have measured the effects on the HR and BP of inducing and maintaining anaesthesia with sevoflurane and nitrous oxide or halothane and nitrous oxide [10,11,13,14]. All have found that halothane is associated with a statistically significantly greater reduction in BP and HR than sevoflurane in the first minutes after induction and before commencement of surgery. However, none of these patients required any specific treatment for hypotension. Piat and colleagues attribute the smaller reduction in systolic BP with sevoflurane when compared with halothane to the greater myocardial contractility depressant effect with the latter [11]. The incidence of cardiac dysrhythmias during sevoflurane and nitrous oxide anaesthesia has been found to be much lower than that during halothane and nitrous oxide anaesthesia in four studies [10,14,15,18]. Meretoja and colleagues found a significantly higher incidence of ventricular ectopic beats with halothane whilst Lerman and colleagues [15] found a significantly higher incidence of dysrhythmias in general and of bradycardia (rate <60 beats min−1) with halothane. This may prove a persuasive argument against the routine use of halothane in modern practice, despite lack of direct evidence of any morbidity associated with halothane induced arrhythmias.

Martin and colleagues compared 143 children aged 1-7 yr who were randomized to receive either halothane with nitrous oxide or propofol with nitrous oxide for anaesthetic induction and maintenance. The patients in the halothane group recorded a greater decrease in systolic and diastolic BPs than the propofol group (P < 0.01) [20]. These authors comment that the lower BP in the halothane group is not associated with a lower HR, although all those patients received atropine 0.02 mg kg−1 as premedication.

Gürkan and colleagues looked specifically at the incidence of the oculocardiac reflex during strabismus surgery [6]. Traction on the extraocular muscles during strabismus surgery can produce dysrhythmias via the trigeminal-vagal reflex: the most common effect is sinus bradycardia. Other dysrhythmias, including junctional rhythms, ectopic atrial rhythm, bigeminy and multifocal premature ventricular contractions, have been reported [23]. Gürkan compared children aged 3-15 yr randomized to receive either propofol with nitrous oxide or sevoflurane and nitrous oxide anaesthesia, and found a significantly higher incidence of oculocardiac reflex events in the propofol group. Forty-five percent of the patients in the propofol group required treatment with atropine, compared to 20% of the sevoflurane group, as a treatment for cardiac dysrhythmias.

Viitanen and colleagues compared two groups of children, all of whom had anaesthesia maintained with sevoflurane and nitrous oxide, but in whom the induction was either sevoflurane and nitrous oxide or propofol. Significant differences were found in HR during induction and tracheal intubation, and in mean arterial pressure during intubation, between the two anaesthetic techniques [21]. They suggested that the lower HR seen after induction with propofol rather than with sevoflurane, may reflect the impairment of the baroreflex caused by propofol described by Aun and colleagues [24], and attributed the lower BP observed at tracheal intubation following sevoflurane induction to a greater attenuation of the pressor response by sevoflurane [21].

Recovery from anaesthesia

Speed of recovery

As with induction of anaesthesia, many authors have studied the times required for various stages of the recovery process to take place. The time from discontinuing anaesthetic agents to eye opening, or first movement, is often used; this is usually referred to as the emergence time and is used to record earliest signs of recovery. Later stages include time to obeying commands or verbal communication. The time taken for the patient to be able to leave the post-anaesthetic care unit (recovery room) and the time until ready for discharge to home are usually dependent on meeting predefined criteria. The most common research tools for assessing recovery room discharge readiness are the Aldrete and the Stewart scoring systems (Table 2)[25,26]. Discharge to the ward is recommended with a score of eight out of a possible ten using the Aldrete score, or with a full six points using the Stewart method. Home discharge is commonly allowed when the patient has had stable vital signs for 30 min, no signs or symptoms of excessive bleeding or pain, tolerance of clear fluids and ability to ambulate appropriately for their age [13].

Table 2
Table 2:
The Aldrete[25] and Stewart [26] scoring systems for assessing discharge from the postanaesthetic recovery room.

As with induction of anaesthesia, comparisons between halothane and nitrous oxide and sevoflurane and nitrous oxide are frequently made (Table 3). Nine studies investigated the recovery times observed following anaesthesia using halothane and nitrous oxide compared with those following sevoflurane and nitrous oxide [10-16,19,27]. Eight of these studies found the first stages of recovery (eye opening or response to verbal commands) and the time until ready to be discharged from the postanaesthetic care unit (recovery room) to be shorter after sevoflurane and nitrous oxide than after halothane and nitrous oxide. Seven reached statistical significance [10-13,15,19,27] and one did not [14]. Of interest is the study by Ariffin and colleagues who investigated the difference between emergence time in two groups of 40 children, one group anaesthetized with sevoflurane and nitrous oxide and the other with halothane and nitrous oxide [16]. They observed a shorter time to eye opening after halothane and nitrous oxide which was statistically significant (P < 0.05). They also recorded a shorter time to standing and walking after halothane and nitrous oxide, although these results did not achieve statistical significance. Ariffin and colleagues point out that the total anaesthesia time in their patients was < 5 min whilst the total anaesthesia time in the eight studies above ranged from approximately 30 min to 1 h. Although sevoflurane wash-out curves and the above studies suggest a more rapid recovery with sevoflurane than with halothane, these workers explain that at the end of 5 min the children receiving sevoflurane were nearer the stage of full saturation than those who received halothane. Consequently, when the surgery finished and sevoflurane was discontinued, serum sevoflurane concentration decreased mainly by excretion, whereas for those receiving halothane, considerable scope was available for serum halothane concentration to decrease by redistribution, in addition to excretion through the lungs [16].

Table 3
Table 3:
Measures of first emergence in studies comparing sevoflurane and nitrous oxide with halothane and nitrous oxide.

Table 4 details the comparisons for halothane and nitrous oxide with sevoflurane and nitrous oxide with respect to time when considered ready for discharge home [13-16,19]. None of these studies demonstrated any difference between anaesthetic techniques.

Table 4
Table 4:
Time to readiness for discharge home in studies comparing sevoflurane and nitrous oxide with halothane and nitrous oxide.

Uezono and colleagues compared patients aged 1-5 yr who had anaesthesia induced with 5% sevoflurane in oxygen and then maintained with either sevoflurane or propofol. Neither group received nitrous oxide. The time to first eye opening and time to discharge from the recovery room was shorter in the sevoflurane maintenance group than in the propofol maintenance group (P < 0.05) [28]. Viitanen and colleagues compared children aged 1-3 yr who received maintenance anaesthesia with sevoflurane and nitrous oxide but were randomly allocated to either a propofol or sevoflurane and nitrous oxide induction. The children who received only sevoflurane and nitrous oxide had the shortest time to first eye opening [21].

Davis and colleagues compared 22 patients, who had their anaesthesia maintained with desflurane and nitrous oxide, with 23 patients who had their anaesthesia maintained with halothane and nitrous oxide. All received induction with halothane and nitrous oxide [29]. The children who received desflurane had a shorter mean time to first eye opening; 9.5 min compared to 20.9 min in the halothane group (P < 0.05) [29]. Although desflurane was also associated with a shorter time to recovery discharge (Aldrete score > 8), the times to hospital discharge between the groups were the same.

Recovery adverse events

When authors compare the incidence of adverse events during recovery in a paediatric population, common variables recorded are coughing, breath holding, laryngospasm, excessive secretions and the presence of emergence delirium. Seven authors have specifically compared the quality of recovery from anaesthesia with halothane and nitrous oxide or sevoflurane and nitrous oxide [10,12,14-16,18,19]. The most frequently reported disadvantage of a sevoflurane and nitrous oxide anaesthetic is the experience of emergence delirium in the early recovery period. Six authors reported that emergence delirium was observed more frequently after sevoflurane and nitrous oxide than halothane and nitrous oxide, two of these studies reaching statistical significance [10,12,14-16,19]. Johannesson and colleagues explains that the low blood/gas solubility coefficient of sevoflurane should cause us to expect a more rapid and turbulent awakening [14]. Fourteen of the 22 patients who underwent ear, nose or throat (ENT) surgery with a sevoflurane anaesthetic in this trial displayed excitation in the early postoperative period - far higher than the number in the halothane group. When they changed their analgesic regimen from rectal paracetamol (acetaminophen) at induction to oral paracetamol 30 min preoperatively, there was a prompt reduction in the incidence of postoperative excitement [14]. The number of excited children upon awakening from sevoflurane anaesthesia implies that analgesics ought to be administered early enough in order to allow enough time to achieve effect before emergence. This is especially relevant for surgery that does not easily allow the use of local anaesthetic techniques, e.g. ENT surgery.

Investigators have noted increased laryngospasm, coughing, shivering and breath holding during recovery from sevoflurane and nitrous oxide compared to halothane and nitrous oxide, however none of the studies have shown statistical significance for these elements of recovery [10,12,15,16,19].

When Davis and colleagues compared desflurane and nitrous oxide with halothane and nitrous oxide, after induction with halothane and nitrous oxide [29] 50% of the children in the desflurane group displayed postanaesthetic delirium compared to 20% in the halothane group; however, this difference was not statistically significant. Davis and colleagues also commented on the apparent lack of airway irritability observed during the maintenance and emergence periods in the desflurane group. This contrasts sharply with the airway irritability observed when desflurane is used as an induction agent [30].

Viitanen and colleagues studied 52 children, aged 1-3 yr, who had anaesthesia maintained with sevoflurane and nitrous oxide after randomization to induction with either propofol or sevoflurane and nitrous oxide. Twice as many patients exhibited emergence delirium in the sevoflurane induction group as the propofol induction group [21]. When Uezono and colleagues compared the incidence of emergence delirium in patients who had anaesthesia induced with sevoflurane and nitrous oxide, and were then randomized to receive either sevoflurane and nitrous oxide, or propofol and nitrous oxide maintenance, they found a higher incidence of emergence delirium in the sevoflurane group (P < 0.05) [28]. Uezono and colleagues also recorded significantly higher parent satisfaction scores from the parents of those children who received propofol. Although the patients who did not receive propofol had a shorter recovery time, parents seemed to prefer the slower, but smoother postoperative course provided by propofol. Uezono feels that the satisfaction scores for sevoflurane would have been even lower if the parents had been present in the recovery room and had seen their children whilst agitated. He postulated that the low satisfaction scores for the sevoflurane group were mediated by poor behaviour (e.g. bad moods, crying) in this group of children.

Postoperative nausea and vomiting

Postoperative vomiting is a major factor limiting hospital discharge [31], and may result in unanticipated overnight admission [8]. Persistent PONV may result in dehydration, electrolyte imbalance and delayed discharge, particularly after outpatient surgery [6]. Several factors influence the incidence of PONV in paediatric patients undergoing surgery: the site and nature of the surgery, the use of opioid analgesia, pain, antiemetic administration, ambulation, mandatory oral intake regimens, patient age and anaesthetic agent have all been implicated [31-33]. For outpatient anaesthesia, the ideal anaesthetic agent should provide not only favourable induction and recovery characteristics, but also minimal postoperative emesis both in the hospital and at home. None of the studies included in this review employed prophylactic antiemetics. This approach is advocated by those who claim that treatment of established PONV is a more cost-effective and safer option than prophylaxis [34,35].

Investigations into the choice of anaesthetic agent on PONV have concentrated on the following permutations: sevoflurane vs. halothane, propofol vs. sevoflurane or halothane, and the presence or absence of nitrous oxide. Eight authors have measured PONV rates with sevoflurane and nitrous oxide compared with halothane and nitrous oxide [10,13-16,18,19,27]. All have recorded an increased incidence of nausea and vomiting with the use of halothane compared to sevoflurane, in five of these studies the difference was significant [14-16,18,19]. The incidence of nausea and vomiting in these studies ranged from 10-30% in the sevoflurane groups and 15-40% in the halothane groups. The large ranges are probably accounted for by the different types of surgery, differences in the age group of the patients and different analgesic regimes.

Nitrous oxide has been proposed as a possible factor in the causation of postoperative nausea and vomiting. A possible mechanism states that nitrous oxide could stimulate the vestibular system by traction caused by negative middle ear pressure, as nitrous oxide is lost during recovery, thus causing nausea. Two studies compared the effect on PONV of the addition of nitrous oxide [31,36]. Pandit studied 60 children aged 4-12 yr after tonsillectomy [36], Splinter studied 230 children aged 1-13 yr after myringotomy [31]. Both randomized those taking part to halothane in oxygen with or without nitrous oxide. Neither study demonstrated any effect of nitrous oxide on nausea and vomiting rates, however it is interesting to compare the nausea and vomiting rates in each study: 60% after tonsillectomy and 13% after myringotomy.

Propofol is associated with less PONV in adult patients [37]. Three studies have compared the nausea and vomiting rates after sevoflurane and propofol; all patients received nitrous oxide [6,21,28]. In each of these studies the incidence of nausea and vomiting was lower in those patient groups who received propofol; however, in only one study were the differences significant [6]. Four authors have compared propofol and nitrous oxide induction and maintenance with halothane and nitrous oxide induction and maintenance. Each found a reduced incidence of PONV in the patients who received propofol. In each study this difference was significant (P < 0.05) [20,32,33,38]. Two studies also included a group of patients who had anaesthesia induced with propofol, but maintained with halothane and nitrous oxide. The incidence of PONV in each of these groups was intermediate between the low incidence propofol and nitrous oxide group and the higher incidence halothane and nitrous oxide group [33,38].

Both Reimer and Hamunen and their colleagues have specifically studied postoperative emesis associated with the use of propofol anaesthesia for strabismus surgery [39,40]. Reimer's group compared propofol with and without nitrous oxide with a thiopental induction and halothane-nitrous oxide maintenance, and found a lower incidence of emesis in the two propofol groups which was significant only in the first 12 h postoperatively, supporting the concept of a short-acting, specific antiemetic effect of propofol [39]. Hamunen and colleagues compared propofol anaesthesia with thiopental induction and isoflurane maintenance. Although they found a reduction in PONV in the propofol group this was not significant [40].


Sevoflurane provides a more rapid induction of anaesthesia than halothane, when a stepwise increase in sevoflurane concentration is not used induction is even more rapid. During anaesthesia with sevoflurane, less bradycardia and hypotension are seen than with halothane. Emergence from anaesthesia is faster after sevoflurane anaesthesia than halothane or propofol anaesthesia; however, the incidence of emergence delirium after sevoflurane detracts from the quality of the recovery. The incidence of PONV is less following sevoflurane than halothane. Desflurane is also associated with a more rapid emergence than halothane; however, as with sevoflurane, an increased incidence of emergence delirium may negate any advantage.

Propofol anaesthesia is associated with less PONV than halothane or sevoflurane anaesthesia; however, this reduction is significant only in the first 12h and has not impacted upon admission rates in any study.

It seems unlikely that any one agent will provide all the properties required for ideal day case anaesthesia, however that is not to say that the newer agents do not provide advantages: they do.


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ANAESTHESIA, paediatric; SURGERY, day case; ANAESTHETICS VOLATILE, sevoflurane, halothane, desflurane; ANAESTHETICS, INTRAVENOUS, propofol; ANAESTHETIC GASES, nitrous oxide

© 2002 European Academy of Anaesthesiology