British Journal of Anaesthesia, 121 (5): 1059e1064 (2018)

doi: 10.1016/j.bja.2018.06.019
Advance Access Publication Date: 1 August 2018
Clinical Practice

Intravenous infusion of lidocaine significantly

reduces propofol dose for colonoscopy: a randomised
placebo-controlled study
C. Forster1, A. Vanhaudenhuyse2,3, P. Gast4, E. Louis4, G. Hick1,
J.-F. Brichant1 and J. Joris1,*
1
Department of Anaesthesiology, CHU Lie ge, University of Lie
ge, Domaine du Sart Tilman, Lie ge,
Belgium, 2Department of Algology and Palliative Care, CHU Lie ge, University Hospital of Lie
ge, Domaine du
Sart Tilman, Liege, Belgium, 3GIGA Consciousness, Sensation and Perception Research Group, University of
ge, Lie
Lie ge, Belgium and 4Department of Gastroenterology, CHU Lie ge, University of Lie
ge, Domaine du
Sart Tilman, Liege, Belgium

*Corresponding author. E-mail: jean.joris@chu.ulg.ac.be

Abstract
Background: Propofol use during sedation for colonoscopy can result in cardiopulmonary complications. Intravenous
lidocaine can alleviate visceral pain and decrease propofol requirements during surgery. We tested the hypothesis that
i.v. lidocaine reduces propofol requirements during colonoscopy and improves post-colonoscopy recovery.
Methods: Forty patients undergoing colonoscopy were included in this randomised placebo-controlled study. After
titration of propofol to produce unconsciousness, patients were given i.v. lidocaine (1.5 mg kg
1 then 4 mg kg
1 h
1) or
the same volume of saline. Sedation was standardised and combined propofol and ketamine. The primary endpoint was
propofol requirements. Secondary endpoints were: number of oxygen desaturation episodes, endoscopists’ working
conditions, discharge time to the recovery room, post-colonoscopy pain, fatigue.
Results: Lidocaine infusion resulted in a significant reduction in propofol requirements: 58 (47) vs 121 (109) mg (P¼0.02).
Doses of ketamine were similar in the two groups: 19 (2) vs 20 (3) mg in the lidocaine and saline groups, respectively.
Number of episodes of oxygen desaturation, endoscopists’ comfort, and times for discharge to the recovery room were
similar in both groups. Post-colonoscopy pain (P<0.01) and fatigue (P¼0.03) were significantly lower in the lidocaine
group.
Conclusions: Intravenous infusion of lidocaine resulted in a 50% reduction in propofol dose requirements during colo-
noscopy. Immediate post-colonoscopy pain and fatigue were also improved by lidocaine.
Clinical trial registration: NCT 02784860.

Keywords: anaesthetic i.v.; adverse effects; pain, postoperative; outcomes; local anaesthetic

Editorial decision: 1 July 2018; Accepted: 1 July 2018

© 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
For Permissions, please email: permissions@elsevier.com

1059
 1060 - Forster et al.

Chairperson: Prof. V. Seutin, No 2016-36) and registered with

Editor’s key points Clinical Trials (ref: NCT02784860). After obtaining written
informed consent, 40 ASA 1e2 patients undergoing colonoscopy
 Propofol is commonly used for sedation during colo-
under sedation were included in this randomised placebo-
noscopy, but this is associated with haemodynamic
controlled double blind study (see Fig. 1 for CONsolidated Stan-
and respiratory adverse effects.
dards Of Reporting Trials (CONSORT) trial profile). Exclusion
 Propofol is commonly used in combination with an
criteria were: age <18 and >70 yr, renal failure, liver insufficiency,
opioid, analgesic adjunct, or both.
epilepsy, major cardiac arrhythmia, and allergy to lidocaine.
 Intravenous lidocaine, which is known to alleviate
visceral pain, reduced propofol requirements by 50%
and reduced postprocedural pain and fatigue. Study protocol
Intravenous sedation was standardised and performed in all
patients by the same anaesthetist (C.F.) unaware of patient
Anaesthesia providers are increasingly involved in providing
allocation group. An i.v. bolus injection of propofol 0.5 mg kg
1
procedural sedation and analgesia (PSA) for gastrointestinal
was given to all patients. Propofol was then titrated if neces-
endoscopy. In Europe, tens of millions of people undergo
sary to produce unconsciousness during the introduction of
endoscopic procedures every year.1 In 2010, colonoscopy for
the endoscope. A dose of ketamine 0.3 mg kg
1 was adminis-
colon cancer screening had been performed at least once in
tered i.v. after loss of consciousness. Then, patients were
more than 50% of Americans during the past 10 yr.2 The most
randomly and double blindly assigned to one of two groups
commonly used medications for PSA are midazolam, propofol,
using sealed envelopes. Patients were given either an i.v. bolus
and opioid. Each of these drugs, however, causes respiratory
of lidocaine 1.5 mg kg
1 followed by a continuous infusion of
depression3 and combining midazolam or propofol with opioid
4 mg kg
1 h
1 or the same volume of saline. This dose of
further increases the risk for hypoxemia and apnoea.4,5 A 2006
lidocaine given for 30 min does not result in toxic plasma
review of closed malpractice claims in the ASA closed claim
levels.20 Study medications were prepared by an anaesthetist
database found that respiratory depression secondary to over-
(G.H.) involved neither in patient care nor in collection of the
sedation played a pivotal role in patients’ injuries during PSA.6
study variables. As the initial bolus of lidocaine can result in
Nowadays, propofol use for PSA is one of the most popular
side-effects, study medications were infused after loss of
techniques because of its short onset time and quicker re-
consciousness to avoid interference with blinding. During
covery profile.7 Propofol also improves patient satisfaction.7
colonoscopy, patients were allowed to recover a level of con-
However, the risk of respiratory and hemodynamic compli-
sciousness to answer simple questions. I.V. boluses of propo-
cations when using propofol or midazolam for PSA was re-
fol 20e30 mg were given in response to abdominal discomfort
ported to be similar (10e14.5%).7,8 Nevertheless, during
expressed by the patient or evidenced by grimaces or hae-
colonoscopy, propofol sedation results in fewer cardiopul-
modynamic changes (increase in HR 20 beats min
1 or in
monary complications than midazolam.8
MAP 10 mm Hg). If propofol was insufficiently effective, ke-
Different strategies have been tried to reduce the incidence
tamine 10 mg was added. During sedation, all patients
and frequency of complications during PSA. Dexmedetomi-
breathed spontaneously and received oxygen 4 L min
1
dine, which possesses anxiolytic and sedative properties
through a nasal catheter.
without respiratory side-effects, has been assessed in diges-
tive endoscopy.9,10 Unfortunately, dexmedetomidine causes
prolonged hypotension and bradycardia. It also results in less Measurements
patient satisfaction than propofol, which precludes its use as
The primary endpoint was propofol requirements. Secondary
sole sedative medication.10 Another strategy consists of
endpoints were: oxygen desaturation episodes [defined as pe-
combining propofol with an adjunct medication to reduce the
ripheral capillary oxygen desaturation (SpO2) less than 95% and
needs for propofol and the incidence of propofol-induced
90%), time for discharge to the recovery room (time between end
adverse effects. Low doses of ketamine have propofol-
of exam and ability for the patient to provide his date of birth),
sparing effects, and so propofol-ketamine combinations are
post-colonoscopy pain, and fatigue assessed on a 0e10 cm VAS.
associated with fewer cardiopulmonary adverse effects than
Pain scores were recorded on admission to the recovery room,
with propofol alone.11e13 I.V. lidocaine is another potentially
15 and 30 min later; postoperative fatigue was assessed on
interesting adjunct to propofol sedation. Benefits of i.v. lido-
admission to the recovery room and 30 min later. Endoscopists
caine were reported mainly in cases of visceral surgery.14
were also asked to rate the conditions of the examination on a
Indeed, i.v. lidocaine can reduce visceral pain in experi-
0e10 cm VAS. Personnel involved in the assessment of these
mental animal models14e16 and alleviate abdominal pain in
variables were unaware of patient allocation group.
patients.17,18 Colonic distension and traction during colonos-
copy result in abdominal discomfort and visceral pain poten-
tially amenable to i.v. lidocaine. Furthermore, lidocaine Statistics
infusion increases the ventilatory response to CO2 in
A local pilot study determined propofol requirements during
humans.19 We therefore tested the hypothesis that i.v. lido-
colonoscopy: 442 (143) mg per 30 min. We estimated that a
caine reduces propofol requirements during colonoscopy and
sample size of 18 patients per group would provide an 80%
improves post-colonoscopy recovery.
power for detecting a 30% difference in propofol needs be-
tween groups at an alpha level of 0.05. A total of 40 patients
were finally included.
Methods Data were analysed using GraphPad Software (GraphPad
This study was approved by the Institutional Ethics Committee Prism® version 5.0a, La Jolla, CA, USA). Data expressed as mean
of Centre Hospitalier Universitaire de Lie ge (Lie
ge, Belgium, (standard deviation) and as mean (range) for age were
 I.V. lidocaine and colonoscopy - 1061

93 patients were screened for eligibility

• 10 patients did not consent

• 15 patients had exclusion

criteria (5 renal insuf iciency, 2
hepatic insuf iciency, 4 epilepsy,
4 major cardiac arrhythmia)

68 patients included for randomisation

• 26 patients withdrawn because

gastroscopy combined with
colonoscopy

42 patients underwent randomisation

21 were included in the placebo 21 were included in the lidocaine

group group

• 1 excluded because propofol • 1 excluded because propofol

data missing data missing
• 20 patients included for inal • 20 patients included for inal
analysis analysis

Fig 1. CONSORT trial profile.

compared using Student’s t-test. Categorical variables and
gender were compared using c2 test. Endoscopists’ working
conditions [median (inter-quartile range)] were compared us-
ing the ManneWhitney test. Mixed model analysis of variance
(ANOVA) was used to compare postoperative pain score and
fatigue. A P-value less than 0.05 was considered as statistically
significant.
Results
Subject’ characteristics and duration of colonoscopy are pre-
sented in Table 1. Subjects from the lidocaine group were
significantly older as compared with the saline group (P¼0.03).
The other characteristics were similar in the two groups.
Lidocaine infusion [188 (34) mg] allowed a significant 50%
reduction in propofol consumption (P¼0.02; Table 2). A similar
dose of ketamine was administered in the two groups
(Table 2). The numbers of subjects who experienced oxygen
desaturation below 95% (five patients in each group) and below
90% (four vs five subjects in the lidocaine and saline groups,
respectively) were similar in the two groups. The times for
readiness to be discharged to the recovery room were 3 (1) min
in both groups. The conditions of colonoscopy assessed by the
colonoscopists on 0e10 VAS were not different in the two
groups [9.0 (1) vs 9.7 (1) in the saline and lidocaine, respec-
tively). Pain scores after colonoscopy were significantly lower
in the lidocaine group [ANOVA: drug effect (df¼1, F¼5.3):
P¼0.023; time effect (df¼2, F¼5.02): P¼0.008; interaction (df¼2,
 1062 - Forster et al.

Table 1 Subject characteristic data and duration of colonos-

copy. Data are mean (range), mean (standard deviation), or Pain score after colonoscopy
number. *significantly different (P<0.05)
5
Saline Lidocaine

VAS (0-10 cm)

Age (yr) 53 (25e65) 59 (41e69)*
Gender (M/F) 8/12 8/12
Weight (kg) 78 (15) 72 (16)
Height (cm) 168 (9) 166 (9) 3
BMI (kg m
2) 27.4 (4.6) 25.7 (3)
ASA physical status (1/2/3)
Duration of colonoscopy (min)
8/12/0
21 (5)
6/13/1
25.7 (3)
2

Table 2 Propofol, ketamine, and lidocaine consumption. Data 0

are mean (standard deviation). *significantly different 0 15 30
(P¼0.02), **significantly different (P¼0.01)
Time after arrival in RR (min)
Saline Lidocaine

Propofol: total dose (mg) 200 (109) 128 (53)**
Propofol: induction of sedation (mg) 79 (16) 71 (14)
Propofol: during infusion 121 (109) 58 (47)*
of study medications (mg)
Ketamine (mg) 20 (2) 19 (3)
Lidocaine (mg) e 188 (37)
Fig 2. Pain score after colonoscopy. Data are mean (SD). Pain
was measured on a 0e10 VAS at arrival in the recovery room
(RR), 15 and 30 min later. Pain scores in the lidocaine group
(white bars) were significantly lower than in the saline group
(black bars) (analysis of variance: P¼0.02).

F¼1.56): P¼0.2] (Fig. 2). Postoperative fatigue was also signifi-

cantly lower in the lidocaine group [ANOVA: drug effect (df¼1,
F¼7.64): P¼0.007; time effect (df¼1, F¼7.98): P¼0.006; interac-
tion (df¼1, F¼0.36): P¼0.55] (Fig. 3).

Discussion
This study demonstrates that adding i.v. lidocaine to propofol-
ketamine PSA results in a 50% reduction in propofol needs for
colonoscopy without affecting endoscopists’ working condi-
tions. Intravenous lidocaine also improves post-colonoscopy
pain and fatigue.
Discomfort associated to colonoscopy results mainly from
visceral nociception secondary to colonic distension and
tractions. Yet, experimental studies demonstrate i.v. lidocaine
is efficient in alleviating visceral pain.15,16 Accordingly, during
visceral surgery, i.v. lidocaine allows for a 30e40% reduction in
requirements of intraoperative volatile anaesthetics.18,21 I.V.
lidocaine decreases also intraoperative propofol requirements
during surgery under total i.v. anaesthesia.20,22 These sparing
effects are only observed during surgical stimulation, which Fig 3. Postoperative fatigue after colonoscopy. Data are mean
suggests a property mediated by an antinociceptive ac- (SD). Fatigue was assessed on a 0e10 VAS at arrival in the re-
tion.20,22,23 We therefore extend these observations to propofol covery room (RR), and 30 min later. Fatigue in the lidocaine
PSA used to relieve visceral nociception during digestive group (white bars) was significantly lower than in the saline
endoscopy. We do not believe that the significant age differ- group (black bars) (analysis of variance: P¼0.007).
ence between the two groups explains the propofol-sparing
effect of lidocaine. Indeed, if we discard the one patient aged
25 yr in the saline group and the two patients aged 69 yr in the
lidocaine group, no significant age difference persists, whereas of ketamine were similar in both groups. Indeed ketamine was
propofol requirement in the lidocaine group still remains administered per-protocol as a dose per kilo, and therefore not
significantly less [lidocaine¼127 (55) mg vs saline¼195 (105) titrated, at the beginning of the PSA. Thereafter, additional
mg, P¼0.012]. It should be noted that this decrease in propofol boluses of ketamine were rarely needed in both groups.
administration was not at the expense of working conditions Postoperative pain after colorectal surgery is less in the
as endoscopists’ satisfaction was similar in both groups. Doses case of perioperative administration of i.v. lidocaine.14

Abdominal discomfort is particularly improved by i.v. lido-
caine.18 We report significantly less pain in the lidocaine
group. This analgesic effect is weak and probably not clinically
relevant. However, pain scores were low in the control group.
This is secondary in part to ketamine administration.12 In the
absence of ketamine, pain would have probably been more
elevated and the analgesic effect of i.v. lidocaine could have
been more relevant as reported by others after endoscopic
submucosal dissection for gastric neoplasm.24
Fatigue after colonoscopy was improved in the lidocaine
group. Similarly, i.v. lidocaine is reported to reduce post-
operative fatigue and improve quality of recovery after sur-
gery.18,25 This reduction in post-procedural fatigue might be
secondary to the propofol-sparing effect.
Hypoxia and apnoea secondary to respiratory depression
and airway obstruction are the most frequent cardiopulmonary
complications of PSA for endoscopy.26 One of the aims to
administer an adjunct to propofol is to reduce its needs and
consequently the incidence of its adverse effects. Accordingly
ketamine in combination with propofol is associated with less
respiratory depression and fewer adverse respiratory events as
compared with propofol alone.12,13 Despite a significant
propofol-sparing effect and the potentially increased ventila-
tory response to CO2 produced by lidocaine,19 we did not
observe any reduction in the number of patients with oxygen
desaturation in the lidocaine group. The percentage of patients
who experienced episodes of oxygen desaturation could appear
elevated (25%). These numbers are certainly greater than those
reported in large databases.27 However, the latter frequently
underestimate the actual frequency of acute complications
because of missing data and underreporting. Nevertheless, our
results are in the range of those reported by others during
sedation when hypoxaemia is prospectively searched for.28 We
decided to administer only 4 L min
1 of oxygen through a nasal
catheter and not a greater flow via a facemask to make SpO2
more sensitive to potential respiratory depression and airway
obstruction, and to detect possibly between-groups differences
more easily. Our patient management may have contributed,
therefore, to the high number of oxygen desaturation. One
limitation of our study was that we did not measure the dura-
tion of the episodes of oxygen desaturation, which could have
allowed us to detect beneficial effects of lidocaine.
Our study has some limitations. It was powered and
designed to detect a significant propofol-sparing effect, but not
to ascertain the potential benefits of this reduction on
propofol-induced adverse events, which can be significant
with this procedure.29 As mentioned earlier, recording of the
duration of oxygen desaturation (maybe without supple-
mental oxygen) might help detect differences in the magni-
tude of respiratory depression. Finally, the doses of ketamine
we administered seem to have precluded demonstration of
benefits potentially associated with the propofol-sparing ef-
fects. Repeating the study without ketamine, which some
anaesthetists might be reluctant to use for outpatient pro-
cedures, should be useful to ascertain potential post-
procedural benefits of lidocaine.
In conclusion, i.v. lidocaine allows for a 50% reduction in
propofol needs when combined with ketamine during PSA for
colonoscopy, without impacting working conditions for the
endoscopists. Lidocaine also improves post-colonoscopy pain
and fatigue. Our protocol and the power of the study calcu-
lated to detect a difference in propofol need did not allow us to
detect reduction in the incidence of oxygen desaturation
despite this propofol-sparing effect.
I.V. lidocaine and colonoscopy - 1063
Authors’ contributions
Study design: C.F., A.V., P.G., E.L., J.-F.B., J.J.
Patient recruitment: C.F., P.G., E.L., G.H.
Data collection: C.F., A.V., J.J.
Analysis and interpretation of results: C.F., A.V., J.F.B.
Manuscript reviewing: C.F., P.G., E.L., G.H., J.-F.B.
Writing up of the manuscript: A.V., J.J.
Statistical analyses: J.J.
Gave final approval of the version to be published: all authors.
Declaration of interest
E.L. has received fees for: research grant from Takeda, Pfizer;
educational grant from Abbvie, MSD, Takeda; speaker fees
from Abbott, Abbvie, AstraZeneca, Ferring, MSD, Chiesi, Falk,
Takeda, Hospira, Janssen, Pfizer; advisory board from Abbott,
Abbvie, Ferring, MSD, Mitsubishi Pharma, Takeda, Celltrion,
Celgene, Hospira, Janssen; consultancy from Abbvie. J-F.B. has
received an honorarium from Abbvie, AstraZeneca, and MSD.
J.J. has received an honorarium from Abbvie and MSD. None
declared by the other authors.
Funding
Supported solely by departmental resources.
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Handling editor: A.R. Absalom