REVIEW

CURRENT
OPINION Total intravenous anaesthesia in ambulatory care
Edward I. McIlroy a and Kate Leslie a,b,c

Purpose of review
The purpose of this article is to review the use of total intravenous anaesthesia (TIVA) in ambulatory care.
Recent findings
The number of ambulatory surgery cases is likely to increase in coming years. Recent meta-analyses
suggest that TIVA offers decreased postoperative nausea and vomiting (PONV) and decreased pain scores
in the postanaesthesia care unit (PACU) in day case/ambulatory surgery patients when compared with
volatile anaesthesia. Particular improvements have also been shown in endoscopic nasal surgery in terms
of decreased blood loss. TIVA consistently scores higher than volatile techniques in patient satisfaction
surveys. Surveys of anesthetists suggest that TIVA is not in widespread use. This may be because of the
perceived lack of training or confidence in the technique, therefore, recent internationally agreed
guidelines aimed at formalizing its practice are welcome. There is also some recent evidence to suggest
that intraoperative dexmedetomidine is superior to remifentanil with respect to postoperative pain and
speed of recovery, and that intraoperative lignocaine infusion may reduce chronic pain incidence in breast
surgery.
Summary
Review of recent evidence of TIVA’s use in ambulatory surgery and summary of new international
guidelines on its use.
Keywords
ambulatory care, anaesthesia, intravenous, propofol, remifentanil

INTRODUCTION is timely to review recent literature about the use of

The first documented total intravenous anaesthetic TIVA for general anaesthesia in ambulatory care of
(TIVA) was administered to a dog at Oxford Univer- adult and paediatric patients.
sity in 1657, by injecting alcohol and opium via a
quill to induce ‘temporary stupefaction’ with a com-
SURVEYS
plete long-term recovery [1]. Although intravenous
anaesthetics ultimately became available in the 20th Several surveys about the use of propofol TIVA have
&&

century, it was not until the introduction of propo-
fol in the 1980s that TIVA became widespread as an
alternative to volatile-based general anaesthesia [2].
TIVA (defined as the exclusive use of intrave-
nous hypnotics and analgesics to induce and main-
tain anaesthesia) is a necessity for patients with a
history of malignant hyperthermia, however, it is
also relatively indicated in patients with potential
for postoperative nausea and vomiting (PONV). The
development of target-controlled infusion (TCI)
devices facilitated wider use of this technique,
smoothing the transition from induction to main-
tenance, and reducing the number of interventions
during the case [3]. As a result, TIVA became an
attractive technique for use in the ambulatory sur-
gery setting. With the rise of enhanced recovery
programs and an increased range of surgical proce-
dures being conducted on an ambulatory basis [4], it
been conducted recently. Wong et al. [5 ] surveyed
anaesthetists associated with specialist colleges and
societies around the world. Among the 763 respond-
ents, 42% were infrequent users, 42% were interme-
diate users and 16% were frequent users. Barriers
identified by infrequent users included the addi-
tional effort required to set up an infusion and lack
a
Department of Anaesthesia and Pain Management, Royal Melbourne
Hospital, bCentre for Integrated Critical Care, Melbourne Medical
School, and Department of Pharmacology and Therapeutics, University
of Melbourne and cDepartment of Epidemiology and Preventive Medi-
cine, Monash University, Melbourne, Australia
Correspondence to Professor Kate Leslie, AO, FAHMS, Department of
Anaesthesia and Pain Management, Parkville, VIC 3050, Australia.
Tel: +61 3 93427540; e-mail: kate.leslie@mh.org.au
Curr Opin Anesthesiol 2019, 32:703–707
DOI:10.1097/ACO.0000000000000786

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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Ambulatory anesthesia
KEY POINTS
 TIVA may offer some benefit over volatile techniques in
PONV and pain scores over volatile techniques, and
consistently scores higher in quality of recovery studies.
 TIVA may offer better intraoperative surgical conditions
in nasal surgery, and in cancer patients receiving
surgery, TIVA may confer a survival advantage.
 Surveys suggest TIVA is not widely practiced,
particularly in paediatric anaesthesia.
 Newly published international guidelines for the safe
practice of TIVA provide recommendation for target
controlled infusion (TCI) maintenance and processed
electroencephalographic (pEEG) monitoring.
 New studies on intraoperative dexmedetomidine
suggest that it may be superior to remifentanil in
postoperative recovery and pain scores, and in
children it may offer a better safety profile.
of real-time monitoring of propofol concentration,
and by frequent users included difficult intravenous
access and unavailability of infusion pumps and
depth of anaesthesia monitors. These factors
may be particularly important in ambulatory care
patients.
Results of a recent survey of Australasian anaes-
thetists were similar. Lim et al. [6] found that 18% of
275 respondents used TIVA for most of their cases,
with 46% of respondents using TIVA infrequently.
Reasons for selecting TIVA included high risk of
PONV, neurosurgery and malignant hyperthermia.
Respondents stated that if enough evidence sug-
gested a benefit of TIVA over volatile anaesthesia
with respect to cancer surgery, they would be happy
to use it, and did not see lack of equipment, lack of
education or cost as barriers. As cancer surgery is
increasingly conducted on an ambulatory basis,
these results are significant.
Finally, Goh et al. [7] surveyed paediatric anaes-
thetists in the United Kingdom. TIVA was the
default maintenance technique for only 8% of the
291 respondents, but 46% used TIVA at least one a
month and use had increased in the last year in 53%
of respondents. Most administered propofol in com-
bination with remifentanil using TCI devices. Pro-
pofol-related infusion syndrome in children was a
significant concern, but the authors did not explore
whether anaesthetists were concerned about the
small numbers of children who contributed data
to paediatric infusion algorithms. TIVA was com-
monly administered for paediatric ear, nose and
throat (ENT) surgery, which is usually conducted
on an ambulatory basis.
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SYSTEMATIC REVIEWS
There have been three recent reviews into propofol
&&
TIVA in ambulatory surgery. Schraag et al. [8 ]
looked at TIVA versus volatile anaesthesia in 229
RCTs including 20 991 adult patients. They looked
for PONV as the primary outcome, but postoperative
pain, emergence agitation, time to recovery, hospi-
tal length of stay, postoperative shivering and hae-
modynamic instability were secondary outcomes.
The studies had a moderate risk of bias and were
across a heterogenous group of surgical procedures
and patient demographics. As with previous studies,
PONV was less frequent with propofol than with
volatile agents [relative risk (RR) 0.61; 95% confi-
dence interval (CI) 0.53, 0.69; P < 0.001]. However,
they also found that propofol significantly reduced
pain scores after extubation (mean difference 0.51;
95% CI 0.81 to 0.21; P ¼ 0.001) and time spent in
the PACU (mean difference 2.91 min; 95% CI
5.47 to 0.35; P ¼ 0.03). However, times to return
of respiratory function and extubation were longer
in the propofol group. Further research is required
into propofol’s potential analgesic properties and
whether this effect is significant beyond the PACU.
Hong et al. [9] performed a meta-analysis into
the use of propofol TIVA versus other anaesthetics in
children younger than 3 years of age. Two hundred
and forty-nine patients were identified from six
studies. Propofol was compared for induction of
anaesthesia versus thiopentone and halothane,
and for maintenance of anaesthesia versus volatile
techniques and dexmedomindine/sufentanil infu-
sions. Hypotension was observed significantly more
often in the propofol groups both when used for
induction and maintenance. Slightly faster times
to extubation, eye opening, and emergence were
observed in the propofol groups. The incidence of
adverse events (hypotension, desaturation, apnoea
and PONV) was not significantly different in the
propofol maintenance group versus comparator
groups, however, propofol significantly reduced
the incidence of emergence agitation versus sevo-
flurane (RR 0.60; 95% CI 0.39–0.94; I2 ¼ 0.0%).
TIVA has been postulated to offer improvements
long beyond the operating room, possibly prolong-
&
ing cancer survival. Recently Yap et al. [10 ] per-
formed a systematic review and meta-analysis of
studies comparing propofol TIVA with volatile-
based general anaesthesia. Ten studies [one random-
ized controlled trial (RCT) and nine cohort studies]
were included. These studies are relevant to our
review because they included breast cancer surgery.
Their analysis suggested that TIVA may be associ-
ated with improved recurrence free survival and
overall survival in patients having cancer surgery
Volume 32  Number 6  December 2019

(pooled hazard ratio 0.76; 95% CI 0.63–0.92;
P < 0.01). However, this benefit was most evident
in patients having major cancer surgery and may
not be as relevant to the ambulatory surgery cancer
population. These authors alerted readers to at least
four large randomized controlled trials that are now
in progress.
ENDOSCOPIC SINUS SURGERY
Several recent RCTs have compared propofol TIVA
and volatile anaesthesia in ambulatory endoscopic
sinus surgery (ESS). For example, Liu et al. [11]
recently compared TIVA with desflurane-based
anaesthesia in 80 ESS patients and found signifi-
cantly less intraoperative blood loss and signifi-
cantly improved quality of recovery scores at 6
hours in the TIVA group. However, they did not
conduct further follow-up. Little et al. [12] compared
TIVA with desflurane with respect to the quality of
the surgical field in 30 patients having ESS and
found that TIVA gave a statistically improved surgi-
cal field, even though mean arterial pressure (MAP)
was significantly higher [mean 68 (standard devia-
tion 5) mmHg versus 63 mmHg [6], P ¼ 0.015] and
blood loss was similar (245 versus 285 ml; P ¼ 0.45).
Similarly, Brunner et al. [13] compared TIVA and
sevoflurane in 72 ESS patients and found that TIVA
was associated with better surgical field visualiza-
tion. There was significantly less blood loss in the
TIVA group compared with the sevoflurane group
[median 200 ml (interquartile range 100–450)
versus 300 ml (200–500), P ¼ 0.046]. Unfortunately,
MAP was not recorded in this study. Lu et al. [14]
recently published a meta-analysis, which con-
cluded that overall, TIVA was associated with
superior visibility, less bleeding and stable haemo-
dynamics. However, they suggested that caution
should be exercised when interpreting these results
as there was significant heterogeneity among
the studies.
GUIDELINES FOR TOTAL INTRAVENOUS
ANAESTHESIA
Recent guidelines from the Association of Anaesthe-
tists of Great Britain and Ireland [4] on day surgery
have been updated as it was recognized that the case
mix and range of surgical specialities that can be
performed as day cases has markedly increased in
the last decade, and there is an aim that 75% of
elective surgery should be as day case/ambulatory
procedures. The guidelines suggest that TIVA might
offer benefits in improving surgical conditions and
recovery and may be indicated for several patient
populations, including nasal surgery.
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TIVA in ambulatory care McIlroy and Leslie
Despite being in widespread use for over
25 years, it is perhaps surprising that until recently
there were no robust guidelines for TIVA. In 2019,
the Association of Anaesthetists of Great Britain and
Ireland and Society for Intravenous Anaesthesia
&&
published their guidelines [15 ] for the safe practice
of TIVA. This was in-part driven by the fact that
training in TIVA anaesthesia is currently inconsis-
tent and inadequate, and many anaesthetists do not
feel confident in its use. The increased incidence of
self-reported awareness in TIVA patients in the
NAP5 audit into accidental awareness under general
anaesthesia (a majority of which were avoidable)
also inspired a drive for guidance [16].
The guideline states that ‘all anaesthetists
should be able to deliver TIVA competently and
&&
safely’ [15 ]. The guidelines identified four key
knowledge domains were identified for anaesthetists
to be aware of to deliver TIVA: principles of achieving
and maintaining appropriate concentrations, factors
determining appropriate dosing, practical aspects of
drug delivery and monitoring of drug effect. The
guideline also makes 10 recommendations about
the need for training and continuing education,
the superiority of TCI over manually controlled infu-
sions, the need to target appropriate concentrations
especially in the elderly, the importance to stocking
and preparing standard concentrations of drugs, the
primacy of careful preparation of equipment and
intravenous access, the advantages of processed
electroencephalographic monitoring (pEEG) when
using TIVA and the requirement for similar standards
inside and outside the operating suite, including in
the ambulatory care centre. In an accompanying
editorial, Irwin and Wong [17] commented that
the guidelines ‘are timely and apposite as they clarify
a number of important safety issues and should help
clinicians feel more confident in their practice’.
ADJUVANT DRUGS
Remifentanil is commonly used in combination
with propofol or a volatile agent for maintenance
of anaesthesia [18]. Remifentanil may be useful in
the ambulatory setting to give rapid, titratable hae-
&&
modynamic and nociceptive control [19 ]. How-
ever, it has been implicated in hypotension,
bradycardia and increased postoperative opioid con-
sumption, and there has been a growing body of
research comparing it with dexmedetomidine.
&&
Grape et al. [19 ] performed a meta-analysis
directly comparing remifentanil and dexmedetomi-
dine, both in combination with propofol and volatile
anaesthetics. The surgical specialities were heteroge-
nous, however, many studies were in ENT surgeries
and ambulatory laparoscopic procedures. They found
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Ambulatory anesthesia
that pain scores 2 h postoperatively were lower in the
dexmedetomidine group (mean difference 0.7; 95%
CI 1.2 to 0.2; P ¼ 0.004), with moderate evidence
that pain control in the first 24 h was superior to
remifentanil with reduced postoperative morphine
and rescue analgesia use. Postoperative hypotension,
shivering, and nausea and vomiting were at least twice
as frequent in the remifentanil group compared with
the dexmedetomidine group. However, the dexmede-
tomidine group had significantly increased time to
extubation and time spent in recovery compared with
remifentanil (mean difference 4.9 min; 95% CI 0.8–
9.1 min; I2 ¼ 99%; P ¼ 0.02 and 8.9 min; 95% CI 4.4–
13.4 min; I2 ¼ 97%; P < 0.0001, respectively).
&
In addition to this, Ter Brugen et al. [20 ] per-
formed a meta-analysis of dexmedetomidine as sole
sedative agent for small diagnostic and therapeutic
procedures in comparison with other commonly
used sedatives (propofol/midazolam/short acting
opioid). In adults, dexmedetomidine yielded 31%
lower pain scores than other sedatives and 68% more
patient satisfaction. Heart rate and mean arterial
blood pressure were significantly lower in dexmede-
tomidine groups compared with placebo, propofol,
midazolam and opioid; however, these differences
were not deemed clinically significant. In children,
dexmedetomidine gave more favourable results con-
cerning respiratory safety and adequacy of sedation,
and reduction in emergence delirium. To date, dex-
medetomidine’s use has been limited in the ambula-
tory setting partly because of its slow time to effect (as
an infusion) and variable context sensitive half time,
however, the above studies suggest more familiarity
with the drug may be required to optimize its use in
&&
ambulatory surgery. However, Grape et al. [19 ] have
confirmed previous findings of prolonged extubation
times and recovery stay, which may limit its use.
Lignocaine is already used extensively in ambu-
latory surgery in local anaesthetic infiltration and
regional blockade [21]. Its use as an intravenous
infusion has been described in major abdominal
&
and thoracic surgery; however, Chang et al. s [22 ]
meta-analysis of lignocaine infusions in breast sur-
gery may have some relevance the ambulatory pop-
ulation. There was no benefit to acute postoperative
pain, but a significantly lower risk of development
of chronic pain in the lignocaine group (RR, 0.332;
95% CI 0.141–0.781; P ¼ 0.012). However, the stud-
ies analysed were small and may be insufficient to
extrapolate a proved benefit.
THE FUTURE OF TOTAL INTRAVENOUS
ANAESTHESIA
Currently, TIVA is delivered by a human, titrating
to effect, physiological response to clinical signs
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and sometimes processed electroencephalographic
(pEEG) values. However, a substantial amount of
research has been done into computer-controlled
feedback loops (closed-loop delivery systems) that
interpret physiological feedback and titrate drug
&
delivery accordingly. In Pasin et al. s [23 ] meta-
analysis computer programs were unequivocally
better than their human counterparts at maintain-
ing a constant pEEG value across a variety of surgical
procedures. Closed loop delivery systems used less
drug for induction and had a significant reduction
in recovery time compared with manual delivery.
Limitations of their use seems to be the lack of
significantly improved patient outcomes, no protec-
tion from human error (e.g. extravasation of drug,
pump programming errors) and cost-effectiveness.
However, this research is in progress.
CONCLUSION
There is a drive to increase to number ambulatory/
day surgery, and there will be a need to improve
efficiency of operating room turnover and recovery
discharge. TIVA offers a short-lived benefit in PONV
over volatile anaesthesia, and may offer some intra-
operative additive analgesic effect. TIVA increases
speed of discharge from recovery, and as a result
TIVA scores are significantly better than volatile
anaesthesia in numerous quality of recovery studies.
Certain ambulatory surgeries may benefit from pro-
pofol anaesthesia; with better surgical conditions
(with less blood loss) in endoscopic ENT surgery
and potentially reduced recurrence rates in cancer
surgery patients receiving versus volatile techni-
ques. In children less than 3 years of age TIVA offers
a reduction in emergence delirium, without a sig-
nificant increase in adverse events.
Surveys into anaesthetists use and comfort with
TIVA suggest it is not widely practiced. It is, therefore,
timely that guidance on key knowledge in TIVA has
become available, with strong recommendation for
the use of TCI programs for anaesthesia delivery and
monitoring depth of anaesthesia via pEEG.
There is some recent evidence to suggest dex-
medetomidine may be superior to remifentanil in
reducing postoperative pain, shivering and hypo-
tension, and that is has a better side effect profile in
children. However, prolonged time to extubation
and time in recovery may hinder its uptake in the
ambulatory setting. There is some evidence to sug-
gest that lignocaine infusions in breast surgery
may reduce chronic pain incidence. The future of
TIVA may lie in closed-loop computer-delivered
TIVA, in that it is better than manual administration
at maintaining physiological parameters and speed
of wake up; however, the evidence to prove
Volume 32  Number 6  December 2019

improved patient outcome and safety is not
yet forthcoming.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED
READING
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been highlighted as:
& of special interest
&& of outstanding interest
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