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Anaesthetic agents in adult day case surgery

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

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European Journal of Anaesthesiology (EJA): January 2003 - Volume 20 - Issue 1 - p 1-9
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The numbers of patients undergoing surgery on an ambulatory care basis is increasing world wide. In the UK in 1992, the Royal College of Surgeons of England recommended that at least 50% of all surgical procedures should be undertaken on a day case basis [1]. This figure will inevitably rise as a greater proportion of day case surgery is performed in the future. This type of surgery is being facilitated by improved surgical techniques as well as a greater number of patients with various forms of co-morbidity being accepted for treatment on a day case basis. The costs of ambulatory surgery are also lower than those of comparable in patient treatment [2].

One of the cornerstones of ambulatory surgery is the drive towards a rapid return to 'street fitness' and therefore discharge from the ambulatory facility. This is governed by a number of factors, but one key factor is the choice of anaesthetic agent and technique. A considerable number of studies have been undertaken over many years, and yet there is still no general agreement on the most appropriate choice of agents and technique. We therefore undertook a review of all published studies of adult day case anaesthesia up to the end of 2000.

Although not a formal systematic review, the search strategy followed the guidelines of the National Health Service (NHS) Centre for Reviews and Dissemination in the UK [3]. The following databases were searched: Medline, NHS Centre for Reviews and Dissemination (Database of Abstracts of Research Evidence (DARE) and economic evaluation database), Bath Information and Dissemination Service (BIDS), Cinahl, Cochrane Library, Embase, PsycInfo, Econlit, and the Office of Health Economics database. The following keywords (and their various spellings and root expansions) were used: Anaesthesia, Surgery, Day Surgery, Day Case Surgery, Outpatient Surgery, Ambulatory Surgery, Strabismus Surgery, Isoflurane, Enflurane, Sevoflurane, Halothane, Nitrous Oxide, Propofol, Thiopental, Nausea, Vomiting and Postoperative. The search results were included up to December 2000 and the results limited to human comparative studies in the English language. A standardized method of data extraction, assessment and tabulation was used.

Measurements of recovery

The speed and quality of recovery were measured in very many ways and this makes direct comparison between studies very difficult in many cases. It may not matter if a patient opens their eyes 5 or 6 min after the anaesthesia was discontinued. However, the time taken for the patient to be transferred from stage one to stage two recovery, or discharge from the hospital, is of considerable importance. For the purpose of this review and to simplify the comparisons between the various studies, the measures of recovery have been grouped into five broad areas: early recovery, intermediate recovery, late recovery, psychomotor recovery and unwanted side-effects (Table 1). The examples in Table 1 are not exhaustive but give an indication of the variables included. Psychomotor recovery has also been regarded as a separate entity. Attempts have been made to correlate the various psychomotor tests with different phases of recovery, but there is currently no single individual test regarded as an accurate predictor of street fitness.

Table 1
Table 1:
Measurements of recovery.

Induction of anaesthesia

There are few studies that attempted a comparison between two induction agents when all other aspects of the process of anaesthesia remain constant. The equipotency of the dose was also not uniform. An intravenous agent may, for example, be given as a fixed dose or adjusted according to body weight. The direct comparison between intravenous and inhalational agents is also extremely difficult because they are administered in different ways. Some conclusions can, however, be drawn.

Propofol and thiopental

Seventeen studies included both propofol and thiopental groups for the induction of anaesthesia [4-19]. In only six of these was the remainder of the process of anaesthesia kept constant between the two groups. The conclusion remains the same, however, whether those six are examined as a subgroup or the whole taken together. Five studies found no difference between thiopental and propofol [11-13,17,18]. In the remainder, propofol was superior to thiopental. One study compared thiamylal with propofol [20] and found propofol to be associated with a more rapid recovery.

Propofol and etomidate

Two studies examined this combination [21,22]. In the first, a propofol infusion was compared with a technique using etomidate followed by isoflurane. In the second study, propofol and etomidate were compared using total intravenous infusions and also for induction of anaesthesia followed by isoflurane maintenance. In all cases, propofol was superior with respect to early and intermediate recovery.

Propofol and methohexital

Three studies compared propofol with methohexital for induction [23-25]. Cade and colleagues [25] showed early recovery to be more rapid with propofol 2.5 mg kg−1 compared with methohexital 1.5 mg kg−1, although there were no differences with respect to intermediate or late recovery. The studies could not demonstrate any differences between the two agents. Methohexital has recently been withdrawn from clinical use in the UK.

Isoflurane and sevoflurane

A single vital capacity breath of 5% isoflurane or 5% sevoflurane was compared by Sloan and colleagues [26]. Anaesthesia was continued using the same inhalational agent. No differences were found with respect to early, intermediate, late or psychomotor recoveries.

Thiopental and desflurane

These two agents were compared by Fletcher and colleagues [27]. In two of the groups studied, the only difference was the induction agent, the maintenance of anaesthesia being continued with desflurane. Thiopental was inferior to desflurane with respect to intermediate recovery and choice reaction time but not with respect to critical flicker fusion threshold. Early and late recovery were not measured.

Propofol and sevoflurane

In the six studies found, no two studies had identical methods. Fredman and colleagues [28] examined three groups of patients. Two groups received propofol 1.5-2.0 mg kg−1 for induction, followed by either propofol or sevoflurane for maintenance. The third group received sevoflurane 3-4% for induction followed by sevoflurane for maintenance. There was no difference between the groups with respect to early, intermediate or late recovery. Dashfield and colleagues [29] studied 40 patients, half of whom received propofol given to loss of consciousness (mean (SD) dose 3.2 (0.4) mg kg−1) and the remaining patients took a single vital capacity breath of 8% sevoflurane. Anaesthesia was continued with sevoflurane and nitrous oxide in all cases. There was no difference in early or psychomotor recovery. A total intravenous technique using propofol was compared with a totally inhalational technique using sevoflurane in three studies [30-32]. There are no differences between the groups with respect to analgesia (remifentanil, alfentanil, fentanyl, none) and nitrous oxide use. Ong and colleagues [31] and Fish and colleagues [32] found no difference between propofol and sevoflurane, but Smith and Thwaites [30] concluded that the quality of early, intermediate and later recovery was better with sevoflurane.

Propofol and desflurane

Apfelbaum and colleagues [33] studied 20 volunteers, each of whom received one of four different anaesthetic techniques on each of four separate occasions. Two of those techniques differed only in the induction of anaesthesia (propofol 2.5 mg kg−1 or desflurane 3%). Desflurane was used for maintenance in all cases. Volunteers in the desflurane induction group showed more rapid early and intermediate recovery, although later and psychomotor recovery were no different. Four of the five studies using patients [34-37] could not show any differences between the groups. The fifth study found early and intermediate recovery to be more rapid in the desflurane group, but there was no difference with respect to late or psychomotor recovery [38].

Thiopental and sevoflurane

The one study comparing these two agents [39] concluded that sevoflurane was superior to thiopental with respect to late recovery.

Maintenance of anaesthesia

Sevoflurane and desflurane

All three studies [40-42] comparing sevoflurane and desflurane for the maintenance of anaesthesia used propofol for induction. The first two studies also included fentanyl and nitrous oxide as a part of the technique of anaesthesia. The third study used alfentanil. Desflurane displayed more rapid early recovery in two studies [40,42], but in the other study there was no difference. There was no difference with respect to late recovery in any study. Psychomotor recovery after desflurane was more rapid in the absence of nitrous oxide, but in those patients who received nitrous oxide there was no difference.

Isoflurane and desflurane

Propofol was used for induction in three studies together with fentanyl [43], alfentanil [44] or no opioid [45]. Two further studies used thiopental for induction with no opioid [27] or fentanyl [46]. In all cases, desflurane was superior to isoflurane with respect to early and intermediate recovery, but there was no difference in late recovery. Psychomotor recovery was better after desflurane than after isoflurane in all studies using propofol for induction, but only in one when thiopental was used [46].

Isoflurane and sevoflurane

Propofol was used for induction and fentanyl for analgesia in two studies [47,48]. In both, sevoflurane was superior to isoflurane in early, intermediate and psychomotor recovery measurements, although there was no difference with respect to late recovery. There was no difference between isoflurane and sevoflurane in a third study [49] where thiopental was used for induction. The fourth study used the same inhalational agent for induction of anaesthesia as for maintenance given in a single vital capacity breath [26] was could not show any difference between the two agents.

Isoflurane and halothane

This combination was examined in two studies. Patients received methohexital [51] or propofol [50] for induction of anaesthesia. No differences were found between the groups.

Isoflurane and enflurane

When propofol was used for induction, those patients who had received enflurane showed more rapid recovery on psychomotor tests than those who had received isoflurane [50]. A second study used thiopental for induction of anaesthesia, but it could not show any differences with respect to early, intermediate or late recovery [52]. When methohexital was used for induction [51], intermediate recovery was more rapid with enflurane.

Enflurane and halothane

The first study used propofol for induction and found enflurane recovery to be superior, but it only used psychomotor tests [50]. The second study [51] used methohexital for induction and found no differences. Thiopental was used for induction of anaesthesia in the remaining study [53]. Those patients who had received enflurane demonstrated more rapid early and intermediate recovery, but no difference was found with respect to psychomotor recovery.

Propofol and sevoflurane

Seven studies compared sevoflurane by inhalation with propofol by infusion for the maintenance of anaesthesia [28,30-32,54-56]. In three studies, sevoflurane was used for induction in the sevoflurane group; propofol was used for induction of anaesthesia in all the others. Early recovery was more rapid with sevoflurane in four studies, while three showed no difference. With respect to intermediate recovery, three studies showed sevoflurane to be superior, while four showed no difference. Only five studies examined late recovery: one found sevoflurane to be superior, one found propofol to be superior and the others showed no difference. Only three studies examined psychomotor recovery and two found sevoflurane to be superior over propofol.

Propofol and desflurane

Twelve studies compared these two agents for the maintenance of anaesthesia [33-38,56-61] and used propofol for induction. Desflurane was superior to propofol for early and intermediate recovery in three studies and with respect to psychomotor recovery in one. Propofol was better with respect to late recovery in two. In all other cases there was no difference.

Propofol and enflurane

Three studies considered this comparison [13,50,52]. In two studies, propofol was used for induction and there was no difference with respect to all recovery parameters. The third study [13] included a group that received thiopental for induction followed by enflurane and showed this group to be inferior to propofol enflurane or to propofol alone.

Propofol and halothane

This comparison was examined in two studies [50,62]. Patients received propofol for induction of anaesthesia. In the first study, only psychomotor recovery was measured and the propofol group showed better recovery than the halothane group. The second study found no difference between the groups.

Propofol and isoflurane

There were 20 studies that included a comparison between these two agents [8,9,19,21,25,45,50,52,58,63-73]. In every case, propofol was used for induction in the propofol group, but in only 15 studies was it used for induction in the isoflurane group [19,44,50,52,58,63-71,73]. In the majority of cases there was no difference between the groups. In four studies [19,64,69,70], propofol was superior to isoflurane and in two [65,73] isoflurane was superior to propofol with respect to early and intermediate recovery. There was only one study that demonstrated a difference with respect to late recovery [64], finding propofol superior. When psychomotor recovery was examined, three studies showed propofol to be superior [50,64,71] and one isoflurane to be superior [68]. In the isoflurane group in the remaining five studies, thiopental was used as the induction agent in three [8,9,72], methohexital in one [25] and etomidate in the last [21]. When an agent other than propofol was used for induction, the isoflurane group always showed an inferior recovery profile.

Nitrous oxide

Most of the above studies used nitrous oxide as a part of the anaesthetic technique, although a few used oxygen-enriched air. There were nine studies in which the only difference in technique between the two groups was the presence or absence of nitrous oxide. In four studies, desflurane was the maintenance agent following a desflurane [36-38] or thiopental [27] induction. No difference was seen concerning any aspect of recovery. Two studies used isoflurane with or without nitrous oxide [74,75] and found no difference. The remaining studies used a propofol total intravenous technique in two groups with or without nitrous oxide [76-79]. Early and intermediate recovery was either faster in the absence of nitrous oxide [76,77] or there was no difference. Late recovery showed no difference in any group. In one study, the propofol consumption for the maintenance of anaesthesia was noted to be lower in the presence of nitrous oxide [76].

Opioid techniques

Alfentanil maintenance was compared with either halothane or enflurane by Apfelbaum and colleagues [33]. Patients in the alfentanil group demonstrated a more rapid early recovery. When alfentanil, fentanyl and enflurane were examined [80], alfentanil was better than fentanyl, and both opioids were better than enflurane with respect to early, intermediate or late recovery. Remifentanil was no better or worse than alfentanil for early, intermediate or late recovery [81], although the patients in the remifentanil group performed better on psychomotor testing. Alfentanil with nitrous oxide was associated with a more rapid early recovery than isoflurane with nitrous oxide, but there was no difference with psychomotor recovery [75]. Finally, a comparison between fentanyl and low-dose ketamine showed early recovery to be better in the ketamine group, but no other differences were found [82].

Postoperative nausea and vomiting (PONV)

Fifty-eight studies considered PONV [4,8,9,11,14,15,18,20,22,24-26,28-32,34-38,41-44,47,48,52,55,57-68,72,74,76-79,83-93]. The variety of comparisons of induction agents and maintenance agents used makes firm conclusions difficult. There were 48 studies that used propofol by total intravenous anaesthesia (TIVA) as one group, and in only two studies did the comparator group show less PONV than the TIVA group. In 21 studies the TIVA group was better and the remainder showed no difference. It would appear that the least PONV is achieved using propofol administered by TIVA. Induction of anaesthesia using propofol was superior to the use of any other agent. Patients who received desflurane for induction of anaesthesia were the most likely to suffer from PONV. Only four studies examined the effect of nitrous oxide on PONV. Three found no difference and one found nitrous oxide to be associated with more PONV.


This review has uncovered a considerable number of studies examining the techniques of anaesthesia available for day case procedures. The remit was not to consider inpatient surgery, but to limit the searches to day case work, and studies not specific to day case work have therefore been excluded.

The quality of the studies reported varied considerably. There were few truly convincing randomized controlled trials. The majority were randomized or pseudo-randomized, but very few were fully blinded. A common model was where the recovery assessments were blinded but the original group allocations were otherwise open. A large proportion of the studies only examined small numbers of patients, often less than 50 overall.

The variety of techniques and range of doses and concentrations of anaesthetic agents used as considerable and it made it difficult to compare results. The same drug may be used as a fixed dose, or according to body weight in different studies. This was further confounded by the different adjuncts to anaesthesia that may have an unknown effect on the findings, but which made it very difficult to control, e.g. opioid analgesics, non-steroidal agents, muscle relaxants, antibiotics, cardiovascular agents, vagolytics. The onset of anaesthesia, the quality of surgical conditions, cardiovascular effects and respiratory effects were among those measured.

Postoperatively, the measures of outcome were quite diverse. We grouped them arbitrarily for the purpose of this review, but there may be subtle differences in the same apparent measurement of recovery between studies. For example, it was assumed that the measure of 'intermediate recovery' would include the time to give the correct date of birth, correct name, orientation in place, time, etc. These are all nevertheless separate measurements and combining them is certain to reduce sensitivity across the studies as a whole. They cannot all be considered individually, however, as comparisons would then prove to be impossible. Psychomotor tests were the most difficult with respect to this issue. There are upwards of 20 different tests, each with possible variants. This makes combining them very difficult, but probably equally as valid (or invalid) as attempting to compare them separately. They have been developed as surrogate markers for later recovery, not early or intermediate as a patient would not be capable of any such test at that phase of recovery. The ultimate goal of many tests of recovery is to quantify the time at which the patient is 'street fit' and can leave the day stay facility. It may be that the opinion of a senior nurse or a simple test such as the ability to walk unaided in a straight line may actually be all that is required, although the latter, of course, may be difficult occasionally, e.g. following lower limb surgery.


A number of aspects of recovery from anaesthesia have been addressed in nine meta-analyses [93-101]. Many of the studies that we examined also appear as a part of those meta-analyses. All except one of the meta-analyses include inpatients in addition to day stay patients and, therefore, include data that we have not addressed here. Nevertheless, the conclusions are not dissimilar to ours. A meta-analysis of PONV in day surgery has compared propofol with other anaesthetics for induction and maintenance [97]. The results were presented in graphical form only. The study appears to suggest that the use of propofol can reduce PONV rates in day surgery, although the actual reduction cannot be determined. This apparently beneficial effect of propofol was also confirmed by Joo and Perks [96], Sneyd and colleagues [98] and Tramèr and colleagues [100], although the latter commented that the effect was short-lived and only significant when propofol was used as the maintenance agent and when the baseline PONV rate without prophylaxis was high. Omission of nitrous oxide was found to reduce the risk of PONV by 28% [94], a rate that was not confirmed in the other studies. Tramèr and colleagues [99] found the reduction of PONV from omitting nitrous oxide only to be important if the baseline risk of vomiting was high. This group also concluded that the benefit of omitting nitrous oxide on PONV equated to using propofol for maintenance [101]. Dexter and Tinker [93] found only minor clinically important differences between desflurane, isoflurane and propofol with respect to the time of discharge; desflurane was superior to isoflurane with respect to early recovery, but propofol was not. The times to early recovery with sevoflurane or propofol were significantly shorter when compared with isoflurane, but later recovery times showed no difference [95].


The overall conclusion from this review has to be tempered with the diversity of the data presented. A summary is presented in Table 2. Propofol was the induction agent of choice in day case patients and may help to reduce PONV. If an inhalational agent was required, then either sevoflurane or desflurane would be suitable (on quality of recovery criteria). With respect to the maintenance of anaesthesia, isoflurane and halothane would seem to be the least useful. Any of the other four - propofol, desflurane, sevoflurane, enflurane - would seem to be appropriate, but propofol may have merit if it helps to minimize PONV. It seems the jury is still out with respect to the supposed benefits of nitrous oxide on recovery, although its use may be associated with more PONV in certain patients.

Table 2
Table 2:
Summary of results.


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ANAESTHESIA; ANAESTHETICS INHALATIONAL, halothane, isoflurane, enflurane, desflurane, sevoflurane, nitrous oxide; ANAESTHETICS INTRAVENOUS, propofol; SURGICAL PROCEDURES, OPERATIVE, ambulatory surgical procedures

© 2003 European Academy of Anaesthesiology