Eur J Anaesthesiol 2020; 37:787–795

ORIGINAL ARTICLE

Effects of adding a combined femoral and sciatic nerve

block with levobupivacaine and clonidine to general
anaesthesia in femoropopliteal bypass surgery
A randomised, double-blind, controlled trial
Martin Charvin, François Longeras, Philippe Jouve, Anne-Laure Cherprenet, Emmanuel Futier,

Bruno Pereira and Christian Duale
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BACKGROUND Adding a regional block to general anaes-
thesia can prevent postoperative pain and improve peripheral
circulation.
OBJECTIVE To seek improved postoperative analgesia and
care due to a long-acting combined femoral and sciatic nerve
block in patients undergoing femoropopliteal bypass surgery.
DESIGN A randomised, double-blind, controlled trial.
SETTING Vascular surgery unit of a French university hospital.
PATIENTS Forty-four adults scheduled for bypass surgery
under general anaesthesia.
INTERVENTION Patients were allocated to receive either an
active nerve block with 20 ml of 0.375% levobupivacaine and
clonidine 0.5 mg kg –1, or a simulated (sham) block only, but
with local anaesthesia of the skin, before general anaesthe-
sia. General anaesthesia was standardised with propofol,
then sevoflurane and sufentanil adjusted according to clinical
need. Postoperative analgesia was standardised with para-
cetamol 1 g every 6 h, and intravenous morphine, initially
titrated in the postanaesthesia care unit and then patient-
controlled. Oral analgesics were repeated up to day 3.
MAIN OUTCOME MEASURES The primary outcome was
morphine consumption during the first 24 postoperative
hours. In a subgroup of postoperative patients distal tissue
oxygen saturation was recorded at the lateral side of the
blocked calf.
RESULTS Patients in the active group received less intra-
operative sufentanil (median dose 25 vs. 41 mg), needed less
morphine during the first 24 h (15 vs. 27 mg) and 72 (20 vs.
35 mg) postoperative hours, than in the control group. They
also had less pain on movement, but pain at rest, the tissue
oxygen saturation and other rehabilitation outcomes were
unaffected by the treatment. Tolerance outcomes were also
similar between groups.
CONCLUSION Combining the two regional blocks improves
the quality of postoperative care in this frail population,
probably by reducing the amount of peri-operative opioid.
TRIAL REGISTRATION ClinicalTrials.gov (ref.
NCT01785693).
Published online 7 July 2020

Introduction
Occlusive peripheral arterial disease affects nearly 2
million people in France;1 about 70% of the lesions are
located in the infra-inguinal area, for which a femoropo-
pliteal bypass is frequently required.2 The procedure
generally includes one proximal inguinal incision and
one distal incision, and postoperative morbidity is notice-
ably high3 due to the combination of the effects of
anaesthesia and immobilisation, in a frail population.
This procedure is currently conducted under either gen-
eral or regional anaesthesia,4 with protocols that aim to

From the CHU Clermont-Ferrand, M edecine Peri-Op

eratoire (MC, FL, PJ, A-LC, EF); Universit
e Clermont-Auvergne (EF); CHU Clermont-Ferrand, Unit
e de Biostatistiques,
Direction de la Recherche Clinique et des Innovations (BP); CHU Clermont-Ferrand, Centre de Pharmacologie Clinique (CD); and INSERM, CIC1405 & UMR1107,
Clermont-Ferrand, France (CD)
Correspondence to Christian Dual
e, Centre de Pharmacologie Clinique (INSERM CIC1405), CHU de Clermont-Ferrand, 58 Rue Montalembert, 63001 Clermont-
Ferrand, France
Tel: +33 473 178 418; fax: +33 473 178 412; e-mail: cduale@chu-clermontferrand.fr

0265-0215 Copyright ß 2020 European Society of Anaesthesiology. All rights reserved. DOI:10.1097/EJA.0000000000001263

Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.

 788 Charvin et al.
avoid hypotensive events, and improve postoperative
analgesia and encourage early mobilisation. Neuraxial
anaesthetic techniques can block all sensory territories
of the lower limb, but they do not avoid hypotensive
events and might not improve postoperative outcomes
when compared with general anaesthesia.4,5 Their use is
further complicated by concomitant anticoagulation, and
the use of infusion catheters to prolong postoperative
nociceptive blockade can impair mobilisation.6
Blocking nociceptive afferents during the surgical pro-
cedure might reduce the resultant postoperative hyper-
algesia7 and also the need for intra-operative opioids: the
latter may have both hypotensive and hyperalgesic
effects.8 Trials in different surgical models have shown
a benefit from adding regional to general anaesthesia,
provided the block is effective for the whole surgical
procedure.9–11 In femoropopliteal bypass surgery an
additional benefit is that regional anaesthesia could, in
theory, improve postoperative circulation by peripheral
vasodilatation given that ischaemia is one of the major
postoperative issues.3 Such improvement of regional
tissue oxygen saturation (rSO2) as measured by near-
infrared spectroscopy (NIRS) has been found following
a variety of peripheral nerve blocks.12,13
Combined sciatic and femoral nerve blocks with bupi-
vacaine are a promising technique14 that we have intro-
duced into our unit, but with levobupivacaine, to which
we have added the a2 agonist clonidine. Clonidine
potentiates local anaesthetic effects and is known to
prolong postoperative analgesia.15–17 It is well tolerated
provided the dose does not exceed 1 mg kg –1.18,19 We
therefore, conducted this trial to validate the hypothesis
that this local anaesthesia protocol, when combined with
general anaesthesia, provides superior postoperative anal-
gesia for femoropopliteal bypass surgery compared with a
sham block as control. A secondary endpoint was to show
an improvement in postoperative rSO2.
Methods
Ethics
Ethical approval for this study (ref. AU 973) was provided
by the research ethics committee CPP Sud-Est VI, Cler-
mont-Ferrand, France, on 12 July 2012. The study was
also authorised by the competent French authority
(ANSM) and registered on Clinical-Trials.gov
(NCT01785693) and EudraCT (2012-002123-15). It
started on 30 January 2013.
The randomised, placebo-controlled, double-blind, sin-
gle-centre trial was conducted in the vascular surgery unit
of the University Hospital of Clermont-Ferrand (F). The
inclusion criteria were adults, aged 18 to 80 scheduled for
femoropopliteal bypass. The exclusion criteria were:
grade I or IV peripheral arterial disease, emergency
surgery, pregnancy or breastfeeding, respiratory insuffi-
ciency, uncontrolled coronary artery disease, renal
Eur J Anaesthesiol 2020; 37:787–795
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insufficiency defined as a creatinine clearance less than
30 ml min1 (estimated by the Modification of Diet in
Renal Disease study equation for a 1.73 m2 body surface),
hepatic insufficiency, diabetes mellitus with insulin treat-
ment or with peripheral neuropathy, chronic pain, WHO
level-III current opioid medication, drug addiction, any
relevant coagulation disorder such as platelet count less
than 80 000 ml1, prothrombin time less than 50% or factor
V less than 50%, allergy or other contra-indication to the
molecules used in the protocol, or any cognitive impairment
that might interfere with informed consent, or the collection
of data. Patients received a detailed explanation of the study
during a preoperative consultation. The day before surgery,
they gave their signed consent and were shown how to
report pain on an 11-point numerical rating scale (NRS)
from 0 (no pain) to 10 (worst possible pain).
Patients were randomised into one of the two study
groups, named ‘active block’ and ‘sham’. The drugs were
administered using a blinded procedure. Randomisation
was overseen by an independent research assistant of the
Clinical Investigation Centre. The anaesthetist caring for
each patient had to open the sealed envelope giving the
allocation group before surgery. On arrival at the operat-
ing theatre, standard monitoring with noninvasive blood
pressure (BP), 5-lead electrocardiography and pulse
oximetry was established, and a 16-gauge peripheral
venous cannula was inserted. In the active block group,
two 20-ml syringes of a local anaesthetic mixture were
prepared, one for each block. The mixture was made of
10 ml of 0.25% levobupivacaine (Chirocaı̈ne; Abbott
France SA, Rungis, France) and 10 ml of 0.5% levobu-
pivacaine and 0.5 mg kg –1 of clonidine (Catapressan;
Boehringer Ingelheim France, Paris, France), without
exceeding 75 mg. The total dose of levobupivacaine to
be administered was 150 mg. Both sciatic and femoral
nerve blocks were ultrasound-guided following an in-
plane approach, with the probe protected by a sterile
sheath and held perpendicular to the course of the nerve.
The skin was anaesthetised with 1% lidocaine, and the
needle was inserted 2 cm lateral to the probe and directed
towards the nerve following the ultrasound beam. The
femoral nerve block was performed in the supine posi-
tion, with the ipsilateral extremity abducted 10 to 208 and
slightly externally rotated with the lateral side of the foot
resting on the table. The probe was placed at the middle
of the inguinal crease. The sciatic nerve block was then
performed, according to a modification of Di Benedetto’s
subgluteal approach, with the patient lain on the contra-
lateral side with a slight forward tilt and a 608 flexion of
the upper hip. The landmarks were the greater trochanter
of the femur, the ischial tuberosity, and a line between
the two with the midpoint marked, in which the probe
was placed. For both femoral and sciatic nerve block, a
21-gauge, 9-cm needle (Stimuquick; Arrow, Kingston-
upon-Thames, UK) was used for injection. For patients of
the sham group, two 5-ml syringes of 0.9% saline were

prepared. The preparation was similar to the above with
regard to position, skin preparation and anaesthesia,
ultrasound probe application and injection site. The
patient was left unaware of the syringes used, and the
solutions were subcutaneously injected.
The patient was then laid supine and moved to the
operating room. The monitoring set up for general anaes-
thesia was complemented by neuromuscular monitoring,
and capnometry. Induction of general anaesthesia was
performed with 2 to 3 mg kg –1 of propofol, 0.3 to
0.3 mg kg –1 of sufentanil and 0.15 mg kg –1 of cisatracur-
ium. After tracheal intubation, anaesthesia was maintained
with sevoflurane set at the age-adjusted minimal alveolar
concentration (range 0.5 to 3%), and subsequently both
anaesthesia and analgesia were adjusted according to an
algorithm based on the pressure, rate, sweating, tears
(PRST ) score.20 If the PRST score exceeded three, the
initial intervention was an age-adapted bolus of intrave-
nous sufentanil (15 mg under 45 years, 10 mg for 45 to 75
years, and 5 mg over 75 years); the second intervention was
a 1% increase in sevoflurane concentration. Myorelaxation
was maintained with boluses of 0.15 mg kg –1 of cisatracur-
ium if necessary, according to the train-of-four response at
the orbicular muscle. Mechanical ventilation set to target a
PETCO2 in the range of 3.6 to 4.3 kPa and SpO2 more than
95%. The baseline inspiratory gas was a 50/50 mixture of
oxygen and air. End-expiratory pressure was set to
5 cmH2O. Hypothermia was prevented by forced-air skin
surface warming. Systematic fluid loading was performed
with 8 ml kg –1 h –1 of lactated Ringer’s solution. If hypo-
tension occurred, as defined by a mean BP under 70% of
the baseline value, the concentration of sevoflurane was
lowered by 1% and a treatment was administered depend-
ing on heart rate (HR) (fluid loading if more than 90 bpm,
0.5 mg of intravenous atropine if <45 bpm, 6 mg of intra-
venous ephedrine otherwise or if hypotension was persis-
tent). If hypertension occurred, as defined by a mean BP
over 130% of the baseline value with no sign of insufficient
anaesthesia or analgesia, a treatment was administered
depending on HR (esmolol if >100 bpm, urapidil other-
wise). At wound closure, 1 g paracetamol and 20 mg nefo-
pam were administered intravenously. No information
about the study drugs was given to the staff in charge of
the patient after surgery. On the patient’s anaesthetic file
only the protocol was mentioned, and the administration of
‘either levobupivacaine þ clonidine or not’. The study
outcomes were collected by the nursing staff responsible
for postoperative care. This team was independent from
the staff responsible for intra-operative care. Intra-opera-
tive variables such as duration of surgery, and total dose of
sufentanil administered, were noted. Patients were trans-
ferred to the postanaesthesia care unit (PACU) and extu-
bated as soon as possible, once SpO2 was more than 95%.
T0 was given as the time of extubation.
To prevent postoperative pain, 1 g of intravenous paracet-
amol was administered every 6 h over a 48 h period. Pain
Eur J Anaesthesiol 2020; 37:787–795
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Bitruncal nerve block for femoropopliteal bypass 789
was assessed on a NRS ranging from 0 (no pain) to 10 (the
worst pain possible). A score of spontaneous pain above 3/
10 prompted intravenous administration of 1 mg ml –1
titrated morphine chlorhydrate (Morphine Aguettant;
Aguettant, Lyon, France), following a written protocol.
The initial bolus was 3 mg (or 2 mg if weight <60 kg), then
boluses of 2 mg were administered every 5 min until the
pain score was 3/10 or less, unless excessive sedation or any
sign of overdose noted. Morphine was then delivered via a
PCA device, in which 2.5 ml of droperidol were added to
the 50-ml-syringe containing 50 mg of morphine; the PCA
regimen was: bolus ¼ 1 ml, refractory period ¼ 7 min, max-
imal dose per 4 h ¼ 30 mg, no continuous infusion. Pain
score at rest and vital signs were then recorded at T0 þ 30,
T0 þ 60 min, T0 þ 90 min, T0 þ 120 min and at discharge
from the PACU. In the case of nausea or vomiting, 4 mg of
intravenous ondansetron were administered.
Distal tissue oxygen saturation (rSO2) of the blocked limb
was continuously recorded by NIRS through an Equanox
Model 7600 (Nonin, Plymouth, Minnesota, USA) with a
skin sensor (Equanox Classic Plus model 8003CA) set at
the lateral side of the calf. The rSO2 data were extracted
through an electronic file (Microsoft Excel 2010; Micro-
soft, Redmond, Washington, USA).
Patients were transferred from the PACU to the surgical
unit under the guidance of the anaesthetist when all the
following conditions were reached: modified Aldrete score
greater or equal to 8, no nausea or vomiting, pain score
under 3/10, no surgical or neurological complications. An
infusion of isotonic glucose was maintained at 1 to
1.5 ml kg –1 h –1 until first oral intake, usually the morning
after surgery. Pain scores at rest and on movement (sitting/
coughing) were recorded every 4 h during the 24 first
postoperative hours, then every 8 h during the following
48 h. After discontinuation of the PCA at T0 þ 72 h, rescue
analgesia was delivered by 10 mg oral morphine, with a
maximal dose of 20 mg every 8 h. Morphine consumption
was recorded at T0 þ 24 h, T0 þ 48 h and T0 þ 72 h.
Sedation was assessed every 30 min until discharge from
PACU, then every 8 h until T0 þ 24 h according to the
Observer’s Assessment of Alertness/Sedation scale,
which quotes alertness from 5 (normal) to 1 (none) to
assess four domains – responsiveness, speech, facial
expression, and aspect of the eyes.21 At discharge from
PACU and at H0 þ 24 h and H0 þ 48 h, nausea/vomiting,
hypotension/malaise, constipation, oxygen desaturation
and urinary retention were recorded. Time to first ambu-
lation and the length of stay in the surgical ward were also
treated as outcomes. Finally, any other adverse event was
also noted, as well as any severe adverse event until the
30th postoperative day.
The primary outcome was morphine consumption during
the first 24 postoperative hours. Morphine consumption
during the first 48 and 72 postoperative hours were
treated as secondary outcomes, as well as rSO2, and
 790 Charvin et al.
the other efficacy and tolerance outcomes. The postop-
erative opioid consumption was standardised as milli-
grams of intravenous morphine, so the doses of oral
morphine were divided by three. If oral oxycodone or
tramadol was given instead of oral morphine, a calculation
was based on a conversion table.22 Two different treat-
ments were conducted for pain scores; in one, the raw
values were kept and missing data were not replaced to
conduct analyses with a linear mixed model (see below);
in the other, missing data were replaced by multiple
imputation processes and an area under the curve
(AUC) was calculated as the sum of the values [(pain
at tn þ 1 þ pain at tn)/2]  [time (h) between tn and tn þ 1]
for each interval between observations. AUCs could
therefore, be directly compared, and give more precise
information on the size of the treatment effect.
The sample size was estimated on the basis of a prelimi-
nary report of the morphine-sparing effect of a continuous
femoral nerve block,6 with a consumption at 33 mg
24 h1  11 mg in the control group and a between-groups
difference of 29 mg 24 h1. However, we estimated a
smaller consumption (14 mg) in our control group
due to co-analgesia, and a lower difference (14 mg)
due to the single shot administration. With type-I and
type-II errors of 5%, the sample size was estimated at 17
patients per group, which was set at 24 to compensate
for attrition.
Fig. 1
Enrolled in the trial; N = 47
Major deviations; n = 3
Wrong selection criteria a
id,a & unplanned glucocorticoid treatment b
Early reoperation c
Principal analysis
(per protocol)
a: current opioid medication
b: preoperative opioid and intraoperative dexamethasone, l0mg
c: thrombectomy before T0+24hrs
CONSORT 2010 flow diagram of the trial.
Eur J Anaesthesiol 2020; 37:787–795
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Statistical analysis
Analyses were performed using Stata 13 (StataCorp,
College Station, Texas, USA). The tests were two-sided,
with type-I error at 0.05. Numerical data were expressed
as mean  SD for normal distribution and otherwise as
median [IQR]. The normality of the distribution was
checked using a Shapiro–Wilk test. Categorical data were
expressed as number of patients/events and percentage.
Comparisons between groups for nonrepeated data were
conducted using the Student’s t test or the Mann–Whit-
ney test for numerical variables, and the x2 or Fisher’s
exact test for categorical variables. For comparison of
repeatedly measured pain scores, data were analysed
using random-effects regression models (linear mixed
model) to evaluate the following fixed effects: group,
time-points evaluation and their interaction, taking into
account between and within patient variability (subject as
random-effect). The normality of residuals was checked.
The principal analysis was done according to protocol.
Results
The CONSORT flow chart is shown in Fig. 1. The baseline
characteristics of the groups were similar (Table 1), as were
the intra-operative variables uninfluenced by the allocated
treatment (Table 2).
Table 3 shows the effects of the studied treatments on the
outcomes related to the analgesic efficacy, either directly or
Randomised; N = 47
Sham block Active block
n = 23 n = 24
n=1
n=1
n=1
n = 20 n = 24
 Bitruncal nerve block for femoropopliteal bypass 791

Table 1 Baseline characteristics Table 3 Efficacy outcomes (per protocol analysis)

Sham block, Active block, Sham block, Active block,

nU20 nU24 P value nU20 nU24 P value
Age (years) 63.7  7.7 64.8  8.3 0.650 Intra-operative outcomes
Male sex 17 (85) 19 (79.2) 0.710 Intra-operative sufentanil: 41 [35 to 50] 25 [20 to 35] <0.0001
Weight (kg) 79.7  15.8 79.8  13.1 0.976 total dose (mg)
Height (cm) 172  8 172  8 0.900 Postoperative opioid consumption (mg of intravenous morphine)a
BMI (kg m –2) 26.7  4.2 26.9  3.6 0.878 From T0 to T0 þ 24 h 27 [18 to 41] 15 [6 to 21] 0.004
Overweight (BMI > 25 kg m – 2) 14 (70.0) 15 (62.5) 0.601 From T0 þ 24 h to T0 þ 48 h 0 [0 to 6] 0 [0 to 4] 0.874
Obesity (BMI > 30 kg m – 2) 3 (15.0) 6 (25.0) 0.477 From T0 þ 48 h to T0 þ 72 h 0 [0 to 2] 0 [0 to 0] 0.344
Active smoking 4 (20.0) 5 (20.8) 1.000 From T0 to T0 þ 72 h 35 [23 to 56] 20 [8 to 330] 0.010
Chronic alcohol abuse 1 (5.0) 2 (8.3) 1.000 Cumulative pain score (area-under-curve, from T0 to T0 þ 72 h)a
Diabetes 5 (25.0) 7 (29.2) 0.757 Pain at rest 165 [120 to 208] 103 [32 to 175] 0.056
Dyslipaemia 8 (40.0) 13 (54.2) 0.349 Pain on movement 294 [206 to 372] 185 [99 to 251] 0.006
Hypertension 13 (65.0) 17 (70.8) 0.679 Other postoperative outcomes
Hypothyroidism 2 (10.0) 2 (8.3) 1.000 Mean rSO2 84.2  6.2b 82.4  3.7c 0.267
Coronary disease 7 (35.0) 12 (50.0) 0.317 Time to first ambulation 2 [1 to 2] 2 [1 to 2] 0.750
Rhythm/Conduction trouble 2 (10.0) 3 (12.5) 1.000 (days)
Valvular heart disease 3 (15.0) 2 (8.3) 0.646 Length of stay (days) 7 [6 to 8] 7 [6 to 8] 0.548
Chronic heart failure 0 (0.0) 2 (8.3) 0.493
Thromboembolism 1 (5.0) 3 (12.5) 0.614 Efficacy outcomes according to the group of randomisation. The numerical data
Stroke (even transient) 1 (5.0) 3 (12.5) 0.614 are expressed as median [interquartile range] or median  SD. rSO2, regional
(blocked limb) oxygen saturation. a See Methods’ section for details. b Data
Other arterial disease 5 (25.0) 4 (16.7) 0.710
available for eight patients only. c Data available for 12 patients only.
Previous surgery for PAD 9 (45.0) 8 (33.3) 0.429
Obstructive pulmonary disease 4 (20.0) 4 (16.7) 1.000
Chronic renal failure 2 (10.0) 1 (4.2) 0.583
Chronic hepatic failure 1 (5.0) 0 (0.0) 0.455 groups, with a trend for a greater effect in the early observa-
Allergy 4 (20.0) 1 (4.2) 0.160 tions. Conversely, no effect could be identified, either on
Gastritis 1 (5.0) 2 (8.3) 1.000
History of cancer 1 (5.0) 1 (4.2) 1.000
distal oxygenation or on discharge outcomes.

The numerical data are expressed as mean  SD; the binary data are expressed
as number of observations (percentage). PAD, peripheral arterial disease.
indirectly. Compared with the sham block, the active
bitruncal nerve block reduced the intra-operative consump-
tion of sufentanil, and opioid consumption during both the
first 24 postoperative hours, and the first 72 postoperative
hours. There was no significant effect between the 24th and
the 72nd postoperative hours. For pain at rest, whereas no
treatment effect was shown on the AUCs (despite a trend in
less pain with active block), the linear mixed model on raw
data showed both a time (P < 0.0001) and a treatment effect
(P < 0.001). Pain on movement, was reduced by the active
block, either with direct comparison of AUCs, or with the
linear mixed model on raw data which showed both a time
(P ¼ 0.004) and a treatment effect (P < 0.0001). Fig. 2 shows
the time course of pain at rest and at movement in both
Table 2 Intra-operative events
Table 4 shows the effects of the studied treatments on
tolerance outcomes. No effect could be identified by the
per-protocol analysis.
Discussion
We have shown that adding a combined femoral and
sciatic nerve block with levobupivacaine and clonidine to
general anaesthesia in femoropopliteal bypass surgery
improved pain control and reduced postoperative analge-
sic consumption, and pain on movement. However, these
benefits could not be converted into hard health outcomes
such as the time to first ambulation or the duration of stay.
The better effect observed on pain on movement, com-
pared with pain at rest, can be explained by the analgesic
protocol, which included opioids on request, probably
blunting pain at rest in both groups, while pain on move-
ment is usually less sensitive to opioids. We reported a
similar observation in a previous trial of regional anaesthe-
sia to treat pain after sternotomy.23

Sham block, Active block,

Considering general and regional anaesthesia as exclusive
nU20 nU24 P value options tends to be challenged by the combination of the
Side of operation: left 10 (50.0) 14 (58.3) 0.580 two. First, some patients are reluctant to be operated on
Premedication 9 (45.0) 10 (41.7) 0.824 under regional anaesthesia alone, and would prefer a
Sufentanil: induction 16.8  4.0 15.6  3.2 0.327
dose (mg)
variable level of sedation. Second, the intra-operative
Level of bypass: higha 9 (45.0) 5 (20.8) 0.112 blockade of nociceptive afferents might prevent postop-
Venous graftb 8 (40.0) 16 (66.7) 0.077 erative pain, something found more than twenty years
Duration of clamping (min) 65 [47.5 to 92] 67.5 [50 to 82] 0.883 ago in a trial of intra-operative inferior alveolar blockade
Duration of surgery (min) 163 [124 to 207] 171 [143 to 229] 0.199
for molar extraction, where both intervention and control
Description of the surgical and anaesthetic variables independent of randomisa- groups included general anaesthesia.24 Similar observa-
tion, per protocol analysis (Fig. 1 for details). The numerical data are expressed as tions have been made, for example with intra-operative
mean  SD or median [interquartile range]; the nominal data are expressed as
number of observations (percentage). a The other cases had a low bypass. b The epidural blockade in major abdominal surgery, even
other cases had a prosthetic graft. including late postoperative pain outcomes.25 In women

Eur J Anaesthesiol 2020; 37:787–795

Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
 792 Charvin et al.

undergoing modified radical mastectomy, intra-operative infraclavicular brachial plexus block with ropivacaine
pectoral nerve blockade improved a number of postop- for fixation of a fractured radius, all patients also receiving
erative analgesia and comfort outcomes,9 and in patients general anaesthesia with remifentanil and propofol10; an
undergoing total hip arthroplasty, intra-operative lumbo- unintended effect was that postoperative analgesia was
sacral plexus block reduced postoperative pain.11 much improved following a pre-operative block that had
Another trial compared pre to postoperative a much longer action than anticipated.

Fig. 2

10
Pain at rest
* * * * * *

8
Pain score (out of 10)

10
* * * * * *
Pain at movement

8
Pain score (out of 10)

0
h0 + 30 min

h0 + 1h

h0 + 1h30

h0 + 2h

h0 + 4h

h0 + 8h

h0 + 12h

h0 + 16h

h0 + 20h

h0 + 24h

h0 + 32h

h0 + 40h

h0 + 48h

h0 + 56h

h0 + 64h

h0 + 72h

Active block Sham block Time

Time course of pain scores at rest (top) and standardised mobilisation (bottom) during the first 72 h after the end of surgery, measured by numerical
rating scale (out of 10). The limits of the boxes represent the interquartile range, the limits of the whiskers represent the range and the inner line
represents the median value, for each group at each time of measurement. The grey and the white boxes represent the active and the sham block
group, respectively. The statistically significant time  group interactions (P < 0.05) are indicated by an asterisk.

Eur J Anaesthesiol 2020; 37:787–795

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 Bitruncal nerve block for femoropopliteal bypass 793

Table 4 Tolerance outcomes (per protocol analysis) any advantage on any tolerance outcome, probably
Sham block, Active block,
because of the sample size, but our cohort, mostly male
nU20 nU24 P value smokers, was at low risk for nausea and vomiting.31
Sedation during the first 0.167
24 postoperative hours In addition to a reduction in intra-operative opioids, adding
No event 11 (55) 19 (79.2) a block to general anaesthesia could also allow a lighter
Brief 6 (30) 3 (12.5) narcosis, therefore, minimising the haemodynamic impact.
Sustained 0 (0.0) 1 (4.2)
Not reported 3 (15) 1 (4.2)
As a consequence, there are benefits in postoperative
Constipation 3 (15.0) 4 (16.7) 1.000 morbidity, both in terms of life-threatening events,32 and
Hypotension/Malaise 3 (15.0) 2 (8.3) 0.646 also rehabilitation. In the study of total hip arthroplasty,
Nausea/Vomiting 3 (15.0) 3 (12.5) 1.000 patients having the intra-operative block had either light or
Oxygen desaturation 2 (10.0) 0 (0.0) 0.201
Hyperthermia 1 (5) 1 (4.2) 1.000
deep intra-operative sedation11; those having deep seda-
Transfusion 1 (5) 0 (0.0) 0.455 tion had more interventions for hypotension, and higher
Distal complication 1 (5) 2 (8.3) 1.000 postoperative cognitive disturbances. Our design, by
Any event imputable to treatment 7 (35) 7 (29.2) 0.679
controlling equal narcosis in both groups, did not allow
Serious adverse event 0 (0.0) 0 (0.0) n/c
such a finding, but we must note that hypotension and
Tolerance outcomes according to the randomisation group. The nominal data are sedation were similar in both groups, despite the inclu-
expressed as number of observations (percentage). n/c, not calculated.
sion of clonidine in the block which was likely to favour
such effects.19
Our negative results on rSO2 are hard to interpret, mostly
A prolonged analgesic effect can be explained by the
because it could be measured in only 20 patients. An
properties of local anaesthetic agents such as bupivacaine,
increase in distal oxygenation following peripheral nerve
ropivacaine or levobupivacaine, with sensory blocks lasting
block (of either upper or lower limb) had been shown in a
up to 20 h26,27 providing analgesia for a large part of the first
before-and-after study including 40 patients, a much
postoperative day. Also, depending on the type of surgery,
greater statistical power.12 This effect was not observed
pain can appear before complete resolution of the sensory
between postoperative interventions, and the possibility
block. In the study on radial fixation reported above, in the
of stress-induced vasoconstriction before anaesthesia
group having the block at the end of surgery the mean time
should be taken into account.
to first rescue analgesic was about 6 h after recovery from
general anaesthesia,10 but, in the group having the block at The benefits of adding peripheral blockade to general
the initiation of surgery this mean time was about 9 h. anaesthesia can be offset by some limitations of the
Therefore, a genuine pre-emptive analgesia, one not technique. Although low, there is some risk of neurologi-
explained by pharmacokinetics, is a strong hypothesis, cal complications with peripheral nerve blocks,33 to
although two mechanisms are possible: first, avoiding which diabetic patients are particularly exposed.34 Epi-
central sensitisation by blocking the nociceptive afferents dural block, as an alternative, has an associated risk of
during surgical stimulation,7 and second, limiting the epidural haematoma during anticoagulant therapy.35 It
hyperalgesic effects of intra-operative opioids.8 The first may induce more hypotensive events and less satisfac-
mechanism is supported by the study in dental surgery tion when compared with a peripheral nerve block after
reported above, as in both groups, general anaesthesia was major knee surgery, for similar analgesia.36 Perhaps the
opioid-free.24 However, the second mechanism cannot be chief benefit of epidural block would be its prolonged
excluded, as in other trials intra-operative blockade was action if maintained with the help of a catheter. Finally,
associated with less intra-operative opioids, either because insufficient training or confidence are barriers to the
it was dictated by the protocol,25 or because the perceived practice of regional blocks,37 and those patients who
clinical need was less.9 are reluctant to submit to additional needle punctures,
would hardly accept having one in addition to general
Blocking the femoral or sciatic nerve could have motor
anaesthesia.
effects with negative impact on postoperative rehabilita-
tion.28,29 We did not observe such a trend, although time As regards the limitations of our study, we tested only one
to first ambulation, the only related outcome we mea- regional anaesthesia protocol, which we designed for a
sured, was poorly sensitive, compared with outcomes maximal efficacy: a sciatic nerve block that included the
such as quadriceps strength. But we did see positive posterior cutaneous nerve of the thigh to cover incisions
effects of the block on pain on movement, a relevant in popliteal fossa, and a long-lasting anaesthetic agent at
indicator for postoperative analgesia,30 although this was the maximal dose according to the drug label, potentiated
not converted into better rehabilitation. One explanation by clonidine. Protocols using less anaesthetics and
for this could be a too passive attitude of our unit, and also favouring motor function should also be tested.38 Poten-
because the effects on pain and opioid consumption were tiation of the block by a corticosteroid could also be
mostly apparent during the first 24 postoperative hours, considered,39 and the a2 agonist dexmedetomidine is
when rehabilitation is not yet initiated. We could not find another new alternative to clonidine40; however, none

Eur J Anaesthesiol 2020; 37:787–795

Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
 794 Charvin et al.
of these adjuvants could be used here according to their
drug label.
In conclusion, the protocol of intra-operative regional
anaesthesia appears to offer sensible postoperative
advantages in femoropopliteal bypass surgery, and could
be easily implemented into current practice to improve
postoperative rehabilitation. Further studies aiming at
lowering the level of narcosis associated with the block to
improve haemodynamic tolerance would be useful.
Acknowledgements relating to this article
Assistance with the study: The authors would like to thank:
Jugurtha Aliane, Philippe Barrau, Veronica Balaceanu, Antoine
Brandely, Sylvia Colomb, Sophiano A. V. Radji (CHU Clermont-
Ferrand, Medecine P eri-Op
eratoire, Clermont-Ferrand, France) for
data collection; C
eline Lambert (CHU Clermont-Ferrand, Unit e de
Biostatistiques, Direction de la Recherche Clinique et des Inno-
vations, Clermont-Ferrand, France) for building the graphs; Sylvie
Sonneville (CHU Clermont-Ferrand, Centre de Pharmacologie
Clinique, Clermont-Ferrand, France) for quality control; Eugenio
Rosset (Universit e Clermont-Auvergne, France) and Caroline
Carrieres-Couchet, Geoffroy Couchet, Edouard Warein, and
the nursing staff of the vascular surgery unit (CHU Clermont-
Ferrand, Chirurgie Thoracique et Vasculaire, Clermont-Ferrand,
France).
Financial support and sponsorship: none.
Conflicts of interest: none.
Presentation: preliminary data for this study were presented as a
poster presentation at the annual meeting of the Societe Française
d’Anesthesie et de Reanimation, September 2018, Paris.
References
1 Haute Autorite de Sant e. Prise en charge de l’art
eriopathie chronique
oblit
erante ath
erosclereuse des membres inf erieurs (indications
medicamenteuses, de revascularisation et de r eeducation). April 2006.
http://www.has-sante.fr/portail/upload/docs/application/pdf/
AOMI_recos.pdf [accessed March 2, 2018].
2 Norgren L, Hiatt WR, Dormandy JA, et al. Inter-society consensus for the
management of peripheral arterial disease (TASC II). J Vasc Surg 2007;
45 (Suppl S):S5–S67; doi: 10.1016/j.ejvs.2006.09.024.
3 van de Weijer MA, Kruse RR, Schamp K, et al. Morbidity of femoropopliteal
bypass surgery. Semin Vasc Surg 2015; 28:112–121.
4 Ghanami RJ, Hurie J, Andrews JS, et al. Anesthesia-based evaluation of
outcomes of lower-extremity vascular bypass procedures. Ann Vasc Surg
2013; 27:199–207.
5 Singh N, Sidawy AN, Dezee K, et al. The effects of the type of anesthesia on
outcomes of lower extremity infrainguinal bypass. J Vasc Surg 2006;
44:964–968.
6 Griffith JP, Whiteley S, Gough MJ. Prospective randomized study of a new
method of providing postoperative pain relief following femoropopliteal
bypass. Br J Surg 1996; 83:1735–1738.
7 Wilder-Smith OH, Arendt-Nielsen L. Postoperative hyperalgesia: its clinical
importance and relevance. Anesthesiology 2006; 104:601–607.
8 Fletcher D, Martinez V. Opioid-induced hyperalgesia in patients after
surgery: a systematic review and a meta-analysis. Br J Anaesth 2014;
112:991–1004.
9 Bashandy GM, Abbas DN. Pectoral nerves I and II blocks in multimodal
analgesia for breast cancer surgery: a randomized clinical trial. Reg Anesth
Pain Med 2015; 40:68–74.
10 Holmberg A, Sauter AR, Klaastad O, et al. Preoperative brachial plexus
block compared with an identical block performed at the end of surgery: a
prospective, double-blind, randomised clinical trial. Anaesthesia 2017;
72:967–977.
11 Mei B, Zha H, Lu X, et al. Peripheral nerve block as a supplement to light or
deep general anesthesia in elderly patients receiving total hip arthroplasty:
a prospective randomized study. Clin J Pain 2017; 33:1053–1059.
Eur J Anaesthesiol 2020; 37:787–795
Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
12 Tighe PJ, Elliott CE, Lucas SD, et al. Noninvasive tissue oxygen saturation
determined by near-infrared spectroscopy following peripheral nerve block.
Acta Anaesthesiol Scand 2011; 55:1239–1246.
13 Keuler J, Weiss C, Klemm K, et al. Assessing changes in tissue oxygenation
by near-infrared spectroscopy following brachial plexus block for
arteriovenous fistula surgery: a prospective observational pilot study. Eur J
Anaesthesiol 2018; 35:759–765.
14 Yazigi A, Madi-Gebara S, Haddad F, et al. Combined sciatic and femoral
nerve blocks for infrainguinal arterial bypass surgery: a case series. J
Cardiothorac Vasc Anesth 2005; 19:220–221.
15 Gentili M, Juhel A, Bonnet F. Peripheral analgesic effect of intra-articular
clonidine. Pain 1996; 64:593–596.
16 Kroin JS, Buvanendran A, Beck DR, et al. Clonidine prolongation of
lidocaine analgesia after sciatic nerve block in rats Is mediated via the
hyperpolarization-activated cation current, not by alpha-adrenoreceptors.
Anesthesiology 2004; 101:488–494.
17 Ouchi K, Sugiyama K. Dexmedetomidine dose dependently enhances the
local anesthetic action of lidocaine in inferior alveolar nerve block: a
randomized double-blind study. Reg Anesth Pain Med 2016; 41:348–355.
18 Casati A, Magistris L, Fanelli G, et al. Small-dose clonidine
prolongs postoperative analgesia after sciatic-femoral nerve block
with 0.75% ropivacaine for foot surgery. Anesth Analg 2000; 91:388 –
392.
19 P€opping DM, Elia N, Marret E, et al. Clonidine as an adjuvant to local
anesthetics for peripheral nerve and plexus blocks: a meta-analysis of
randomized trials. Anesthesiology 2009; 111:406–415.
20 Evans JM, Bithell JF, Vlachonikolis IG. Relationship between lower
oesophageal contractility, clinical signs and halothane concentration
during general anaesthesia and surgery in man. Br J Anaesth 1987;
59:1346–1355.
21 Chernik DA, Gillings D, Laine H, et al. Validity and reliability of the
Observer’s Assessment of Alertness/Sedation Scale: study with
intravenous midazolam. J Clin Psychopharmacol 1990; 10:244–251.
22 Wikipedia. Equianalgesic. Updated March 2018. https://en.wikipedia.org/
wiki/Equianalgesic [accessed March 2, 2018].
23 Eljezi V, Duale C, Azarnoush K, et al. The analgesic effects of a bilateral
sternal infusion of ropivacaine after cardiac surgery. Reg Anesth Pain Med
2012; 37:166–174.
24 Gordon SM, Dionne RA, Brahim J, et al. Blockade of peripheral neuronal
barrage reduces postoperative pain. Pain 1997; 70:209–215.
25 Lavand’homme PM, De Kock M, Waterloos H. Intraoperative epidural
analgesia combined with ketamine provides effective preventive analgesia
in patients undergoing major digestive surgery. Anesthesiology 2005;
103:813–820.
26 Foster RH, Markham A. Levobupivacaine: a review of its pharmacology and
use as a local anaesthetic. Drugs 2000; 59:551–579.
27 Cuvillon P, Nouvellon E, Ripart J, et al. A comparison of the
pharmacodynamics and pharmacokinetics of bupivacaine, ropivacaine
(with epinephrine) and their equal volume mixtures with lidocaine used for
femoral and sciatic nerve blocks: a double-blind randomized study. Anesth
Analg 2009; 108:641–649.
28 Muraskin SI, Conrad B, Zheng N, et al. Falls associated with lower-
extremity-nerve blocks: a pilot investigation of mechanisms. Reg Anesth
Pain Med 2007; 32:67–72.
29 Luo TD, Ashraf A, Dahm DL, et al. Femoral nerve block is associated with
persistent strength deficits at 6 months after anterior cruciate ligament
reconstruction in pediatric and adolescent patients. Am J Sports Med
2015; 43:331–336.
30 Farrar JT, Portenoy RK, Berlin JA, et al. Defining the clinically important
difference in pain outcome measures. Pain 2000; 88:287–294.
31 Apfel CC, Heidrich FM, Jukar-Rao S, et al. Evidence-based analysis of risk
factors for postoperative nausea and vomiting. Br J Anaesth 2012;
109:742–753.
32 Botto F, Alonso-Coello P, Chan MT, et al. Myocardial injury after noncardiac
surgery: a large, international, prospective cohort study establishing
diagnostic criteria, characteristics, predictors, and 30-day outcomes.
Anesthesiology 2014; 120:564–578.
33 Sondekoppam RV, Tsui BC. Factors associated with risk of neurologic
complications after peripheral nerve blocks: a systematic review. Anesth
Analg 2017; 124:645–660.
34 ten Hoope W, Looije M, Lirk P. Regional anesthesia in diabetic peripheral
neuropathy. Curr Opin Anaesthesiol 2017; 30:627–631.
35 Svircevic V, van Dijk D, Nierich AP, et al. Meta-analysis of thoracic epidural
anesthesia versus general anesthesia for cardiac surgery. Anesthesiology
2011; 114:271–282.
36 Fowler SJ, Symons J, Sabato S, et al. Epidural analgesia compared with
peripheral nerve blockade after major knee surgery: a systematic review
and meta-analysis of randomized trials. Br J Anaesth 2008; 100:154–164.
 Bitruncal nerve block for femoropopliteal bypass 795

37 Dual
e C, Gayraud G, Taheri H, et al. A French nationwide survey on
anesthesiologist-perceived barriers to the use of epidural and paravertebral
block in thoracic surgery. J Cardiothorac Vasc Anesth 2015; 29:942–949.
38 Taha AM, Abd-Elmaksoud AM. Ropivacaine in ultrasound-guided femoral
nerve block: what is the minimal effective anaesthetic concentration
(EC90)? Anaesthesia 2014; 69:678–682.
39 Baeriswyl M, Kirkham KR, Jacot-Guillarmod A, et al. Efficacy of perineural vs
systemic dexamethasone to prolong analgesia after peripheral nerve block:
a systematic review and meta-analysis. Br J Anaesth 2017; 119:183–191.
40 Sun Q, Liu S, Wu H, et al. Dexmedetomidine as an adjuvant to local
anesthetics in transversus abdominis plane block: a systematic review and
meta-analysis. Clin J Pain 2019; 35:375–384.

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