Original research

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Impact of varying degrees of peripheral nerve
blockade on experimental pressure and ischemic
pain: adductor canal and sciatic nerve blocks in a
human model of compartment syndrome pain
Yun-­Yun Kathy Chen,1 Philipp Lirk,1 K Mikayla Flowers,1 Carin A Colebaugh,1
Jenna M Wilson,1 Jose Zeballos,1 Arvind Von Keudell,2,3 Karyn E Barrett,1
Kamen Vlassakov ‍ ‍,1 Kristin L Schreiber ‍ ‍1

► Additional supplemental ABSTRACT

material is published online Introduction Early diagnosis of acute extremity WHAT IS ALREADY KNOWN ON THIS TOPIC
only. To view, please visit the ⇒ The use of regional anesthesia after lower
compartment syndrome is crucial to timely surgical
journal online (http://d​ x.​doi.​org/​
10.​1136/​rapm-2​ 022-​103671). management. Pain is commonly used as an early extremity fracture and surgery has been
1 diagnostic sign for acute extremity compartment controversial due to the concern of masking
Department of Anesthesiology, acute extremity compartment syndrome (AECS).
Perioperative and Pain Medicine, syndrome, making regional anesthesia after lower
Brigham and Women’s Hospital, extremity surgery controversial. This randomized
Harvard Medical School, Boston, study tested whether different concentrations of local WHAT THIS STUDY ADDS
Massachusetts, USA anesthetics, or combinations of nerve blocks, would ⇒ This randomized, controlled study modeling
2
Department of Orthopedic
differentially impact the perception of acute extremity AECS pain in healthy volunteers provided
Surgery, Brigham and Women’s
Hospital, Boston, Massachusetts, compartment syndrome-­like pressure and ischemic pain. evidence that pressure and ischemic pain
USA Methods Healthy volunteers underwent quantitative induced by a leg cuff is differently impacted by
3
Department of Orthopedic sensory testing, including determination of pressure pain adductor canal nerve block (ACB) alone or ACB
Surgery, Rigshospitalet, thresholds and prolonged pressure/ischemic pain in the with different concentrations of sciatic nerve
Kobenhavn, Denmark
leg using a variable cuff inflation system. Subjects were block.
randomized to receive (1) adductor canal block alone
Correspondence to
Dr Kristin L Schreiber, (ACB), (2) ACB with low-­concentration sciatic nerve HOW THIS STUDY MIGHT AFFECT RESEARCH,
Anesthesiology, Perioperative, block (ACB +LC SNB), or (3) ACB with high-­concentration PRACTICE, OR POLICY
and Pain Medicine, Brigham and SNB (ACB +HC SNB). For the primary outcome, we ⇒ Clinical provision of analgesia by application
Women’s Hospital, Boston, MA assessed block-­induced increases in pressure threshold
02115, USA; of partial or lower concentration blockade may
k​ lschreiber@​bwh.​harvard.​edu to reach 6/10 pain, and compared the degree of increase represent a more nuanced approach in patients
between the three groups. The main secondary outcome after lower extremity surgery, when there is
Received 29 March 2022 was a comparison of average pain score during a 5 min concern for AECS, and allow less reliance on
Accepted 7 July 2022 hold at the 6/10 pressure pain threshold between the opioid-­based analgesia.
Published Online First
three groups.
20 July 2022
Results All blocks raised pressure pain threshold
and decreased ischemic pain, but to variable extents.
Specifically, the amount the block increased pressure often the first symptom of compartment syndrome,
pain threshold was significantly different among ACB, even though it has a low positive predictive value
ACB+LC SNB, and ACB+HC SNB groups (mean±SD: (11%–15%),2 and compartment syndrome can
24±32 mm Hg, 120±103 mm Hg, 159±93 mm Hg; occur in the absence of pain.3 Well-­timed regional
p=0.002), with post hoc testing revealing ACB as less anesthesia (RA) has the potential to decrease acute
than the other two groups. Similarly, average pain scores postoperative pain and opioid consumption after
during a prolonged/ischemic cuff hold differed among fracture surgery,4–6 but there is concern that this
the groups (4.2±1.4, 1.4±1.7, 0.4±0.7; p<0.001), with may also mask developing AECS and delay diag-
post hoc testing revealing ACB as significantly higher. nosis.7 The debate regarding whether nerve blocks
Discussion This study suggests the possible utility of should be avoided to facilitate AECS diagnosis has
titrating regional anesthesia, to provide some analgesia been long-­standing.7 8
while still allowing acute extremity compartment A suggested middle ground is the idea of less
syndrome detection. dense peripheral nerve blockade, either by blocking
© American Society of Regional
Anesthesia & Pain Medicine Trial registration number NCT04113954. only some of the nerves to an area (eg, saphenous
2022. No commercial re-­use. nerve using an adductor canal block (ACB) for tibial
See rights and permissions. plateau fracture), or by using lower concentrations
Published by BMJ. of local anesthetics without adjuncts.8 The degree
To cite: Chen Y-­YK, INTRODUCTION to which such variations may provide analgesia has
Lirk P, Flowers KM, et al. Acute extremity compartment syndrome (AECS) not been systematically tested.
Reg Anesth Pain Med is a surgical emergency, where time to diagnosis is The goal of this study was to investigate whether
2022;47:630–636. crucial to avoid morbidity and mortality.1 Pain is varying the concentration of local anesthetics, or
630    Chen Y-­YK, et al. Reg Anesth Pain Med 2022;47:630–636. doi:10.1136/rapm-2022-103671

Figure 1 Study flow diagram. ACB, adductor canal block; BL, baseline; BMI, body mass index; HC, high concentration; LC, low concentration; PPT,
pressure pain threshold; SNB,sciatic nerve block; SPCS, situational pain catastrophizing.
specific constellations of nerve blocks, would decrease pain
perception in a human model of early AECS using admin-
istration of cuff pressure to the leg. Specifically, we aimed to
determine whether ACB alone, or the use of a lower concen-
tration in a sciatic nerve block (ACB +LC SNB) would impact
pressure and ischemic pain less than higher concentration SNB
(ACB +HC SNB). The primary outcome examined was the
block-­induced increase in pressure pain threshold, compared
between the three block groups. The main secondary outcome
was average pain score during a 5 min cuff hold (ischemic pain),
compared between the three groups. We hypothesized that both
ACB alone, or addition of a lower concentration sciatic block
(ACB +LC SNB), would impact leg pain to a lesser degree than
addition of a ACB +HC SNB.
METHODS
Patient selection and recruitment
Participants were recruited using online advertisements and
underwent a video-­based informed consent process with demon-
stration of study procedures prior to being scheduled for the
study. Inclusion criteria were 18–65 years of age and body mass
index <35 kg/m2. Exclusion criteria included chronic pain and/
or opioid use, neuropathy, diabetes, peripheral artery disease
or limb loss, coagulation disorder, skin breakdown in lower
extremities, pregnancy, smoking/vaping, or illicit substance use.
Subjects who received at least one nerve block received financial
compensation for their participation in the study.
Baseline assessment
In order to characterize baseline differences in factors known to
modulate pain, participants used an encrypted iPad to complete
self-­reported, validated questionnaires. These included a survey
of baseline pain (Brief Pain Inventory 9), widespread pain
(Fibromyalgianess questionnaire,10 and catastrophic thinking
about pain (Pain Catastrophizing Scale11), which assesses trait
catastrophizing.
Quantitative sensory testing of pain in absence and presence
of blocks
General pain sensitivity
Using a subset of previously validated quantitative sensory tests
(QST),12 psychophysical sensitivity to standardized painful
stimuli were performed to assess baseline differences in pain
sensitivity between groups. A handheld algometer assessed
Chen Y-­YK, et al. Reg Anesth Pain Med 2022;47:630–636. doi:10.1136/rapm-2022-103671
Original research
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general pressure pain threshold and tolerance at extremity
(forearm) and truncal (trapezius) sites, and weighted pinprick
probes assessed temporal summation of pain and painful after
sensations after repeated pain stimuli, measures of pain central-
ization.12 13 A verbal Numeric Rating Scale (from 0 to 10) was
used by participants to rate pain scores during testing procedures.
Leg pain testing
Pressure pain (primary outcome) and ischemic pain (secondary
outcome) were induced using a Hokanson rapid cuff inflator
with a pneumatic cuff centered around the largest diameter of
the gastrocnemius muscle, approximately 2 cm below the tibial
tuberosity, with marking between trials to ensure consistency of
placement. This cuff inflation system applies a carefully titrated
amount of pressure pain to the leg and has been used by our
group in previous studies with chronic pain patients.14 15 Addi-
tionally, previous studies using a leg cuff have demonstrated
measured ischemia under these conditions.16 Participants were
blinded to pressure readings.
To determine cuff pressure pain threshold, the cuff was grad-
ually inflated (~20 mm Hg/second) until the subject reported
that the pressure first turned to pain (1/10 pain). The cuff pres-
sure was then released. The cuff was then gradually reinflated
(~20 mm Hg/second), and cuff pressures were noted when the
subject reported pain reaching levels of 4/10, 6/10, 8/10 and
10/10. Once the participant indicated pain level was 10/10, the
cuff pressure was released. This pressure ramp was applied three
times on each leg, with a 1 min break between each round of
testing. Pressure values to achieve each target pain level (4, 6, 8,
10/10 pain) were measured in three trials and averaged for each
individual participant. Pressure threshold testing was repeated
on the leg 20 min after ACB placement and 40 min after SNB
(figure 1). We then assessed the amount of increase in pressure
needed to achieve the same targeted pain threshold, compared
with the baseline pressure values. To avoid any possible tissue
damage, we limited cuff pressures to 400 mm Hg.
For the prolonged pressure/ischemic pain assessment, each
participant’s averaged pressures to achieve 4, 6, 8 and 10/10
pain at baseline were applied to the leg. The leg cuff was rapidly
inflated to the target pressure and then held for 5 min. Pain ratings
(numeric rating scale, 0–10) were verbally gathered every 30 s.
This procedure was performed four times, using pressures that
induced 4, 6, 8 and 10/10 pain, with a 1 min break between each
test. Subjects were repeatedly reminded that they could choose
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Table 1 Baseline demographic, psychosocial and pain sensitivity characteristics
All
(n=42) ACB only (n=14) ACB+LC SNB (n=14) ACB+HC SNB (n=14) P value
Demographics
 Mean age in years (SD) 34.1±11.9 36.6±12.3 31.4±10.6 34.4±13.0 0.334*
 Gender 0.530
 Male (n, %) 19 (45.2%) 6 (42.9%) 8 (57.1%) 5 (35.7%)
 Female (n, %) 23 (54.8%) 8 (57.1%) 6 (42.9%) 9 (64.3%)
 BMI 25.4±4.1 26.3±4.4 25.2±3.9 24.7±4.2 0.417*
 Race/ethnicity 0.472†
 African American (n, %) 3 (7.1%) 2 (14.3%) 1 (7.1%) 0 (0%)
 Caucasian (n, %) 28 (66.7%) 11 (78.6%) 8 (57.1%) 9 (64.3%)
 Hispanic/Latina (n, %) 4 (9.5%) 0 (0%) 4 (28.6%) 0 (0%)
 Asian (n, %) 2 (4.8%) 0 (0%) 0 (0%) 2 (14.3%)
 Mixed race (n, %) 5 (11.9%) 1 (7.1%) 1 (7.1%) 3 (21.4%)
Block leg
 Left (n, %) 21 (50%) 7 (50%) 7 (50%) 7 (50%)
 Right (n, %) 21 (50%) 7 (50%) 7 (50%) 7 (50%)
Baseline Pain Questionnaires
 Mean BPI mean pain (SD) 0.3±0.5 0.3±0.4 0.3±0.7 0.3±0.4 0.818*
 Mean fibromyalgianess (SD) 1.3±1.3 1.6±1.5 1.1±1.1 0.9±1.3 0.420*
Baseline Psychosocial Questionnaires
 Mean Pain Catastrophizing Scale (SD) 5.5±7.6 3.7±7.0 5.5±5.7 7.3±9.6 0.312*
Baseline General Pain Sensitivity
 Mean Forearm PPT-­algometer (SD) 5.3±3.1 5.9±2.0 5.8±4.8 4.0±1.3 0.035*
 Mean Trapezius PPT-a­ lgometer (SD) 8.8±3.7 9.5±2.8 8.5±4.6 8.5±3.6 0.713
 Mean Forearm PPTol-­algometer (SD) 10.1±4.8 11.5±3.8 10.6±6.1 8.1±3.9 0.164
 Mean Trapezius PPTol-a­ lgometer (SD) 14.1±5.2 15.0±4.2 13.3±6.0 13.9±5.5 0.815*
 Mean Finger TSP-p­ inprick (SD) 2.1±1.6 2.3±1.3 1.6±1.2 2.5±2.0 0.164*
 Mean Foot TSP-p­ inprick (SD) 2.3±1.8 2.1±1.6 1.8±1.6 3.0±2.2 0.428*
 Mean Finger PAS (SD) 0.3±0.5 0.1±0.3 0.2±0.6 0.4±0.7 0.369*
 Mean Foot PAS (SD) 0.2±0.4 0.2±0.3 0.0±0.1 0.4±0.6 0.125*
Baseline cuff pressure needed to produce targeted
pain (0–400 mm Hg)
 Mean 4/10 target pain (SD) 149.3±66.6 154.6±45.6 158.6±87.9 134.9±61.9 0.613
 Mean 6/10 target pain (SD) 192.4±80.8 199.8±59.2 208.6±103.9 168.7±73.2 0.403
 Mean 8/10 target pain (SD) 227.3±91.9 237.2±74.1 248.1±112.0 196.7±83.9 0.304
 Mean 10/10 target pain (SD) 263.2±97.9 273.9±79.2 285.4±110.8 230.2±99.2 0.296
Average ischemic pain in control leg during hold
at target pain level (0–10)
 Mean 4/10 target ischemic hold pain (SD) 3.4±1.5 3.8±1.0 3.4±1.7 2.9±1.6 0.256*
 Mean 6/10 target ischemic hold pain (SD) 5.0±1.8 5.3±0.9 5.1±2.0 4.6±2.3 0.467*
 Mean 8/10 target ischemic hold pain (SD) 6.1±1.9 6.6±1.3 6.0±1.7 5.6±2.6 0.444
 Mean 10/10 target ischemic hold pain (SD) 7.3±2.2 7.7±1.9 7.3±2.0 6.9±2.6 0.769*
*Data not normally distributed, non-­parametric assessment used.
†χ2 performed for white/non-­white across participant groups.
ACB+HC-­SNB, Adductor canal nerve block with high-­concentration sciatic nerve block; ACB+LC-­SNB, ACB with low-­concentration sciatic nerve block; ACB only, Adductor canal
nerve block alone; BMI, body mass index; BPI, Brief Pain Inventory; PAS, painful after sensations after pinprick train; PPT, pressure pain threshold; PPTol, pressure pain tolerance;
TSP, temporal summation of pain.

to have the cuff deflated prior to the end of the 5 min hold at any
point. If the subject could not complete the 5 min hold, a pain
score of ‘10’ was recorded for any time point between time of
cuff deflation to the end of 5 min. Prolonged pressure/ischemic
pain assessment were conducted first on the unblocked, then on
the blocked leg. All QST procedures were completed by one of
three trained behavioral testers (KLS, KMF, CAC). The order of
cuff pressure pain testing and prolonged/ischemic pain testing in
relation to block placement is depicted in figure 1.
632
Nerve blocks
Subjects were randomized into equal groups receiving ACB,
ACB+LC SNB or ACB+HC SNB. Within each group, nerve
blocks were randomized to the left or right leg, using the
randomization function in REDCap. Prior to nerve block place-
ment, a 20-­gage intravenous catheter was placed in the hand, and
continuous pulse oximetry, 5-­lead EKG, and intermittent (5 min)
non-­invasive blood pressure cuff monitoring was applied. Nerve
blocks were performed by specialty-­trained experienced regional
Chen Y-­YK, et al. Reg Anesth Pain Med 2022;47:630–636. doi:10.1136/rapm-2022-103671

Figure 2 Impact of blocks on pressure pain threshold. Pain threshold
pressures were compared before and after ACB, ACB +LC SNB, and
ACB +HC SNB in the same leg, allowing calculation of the increase in
cuff pressure to reach 6/10 pain. (A) Comparison of increase in pressure
pain thresholds between groups. Each circle represents an individual
participant, with bar height showing group mean and error bars SD.
(B) Kruskal-­Wallis test was used to compare the extent of increase in
pressure pain threshold between groups. ACB, Adductor canal nerve
block; ACB +LC-­SNB, Adductor canal nerve block with low-­concentration
sciatic nerve block; ACB +HC-­SNB, Adductor canal nerve block with
high-­concentration sciatic nerve block.
anesthesiologists (KLS, PL). The subject, QST tester, and anes-
thesiologist placing the nerve block were blinded to the SNB
local anesthetic concentration. Nerve blocks were placed under
sterile technique with chlorhexidine after the skin was anes-
thetized with 1 cc of 1% lidocaine, and a 21-­gage 10 cm block
needle (SonoPlex II Facet, PAJUNK) under ultrasound guidance
(Sonosite Edge) using a HFL50x Linear Transducer Probe. Base-
line strength and sensory testing was performed before and after
blocks to ascertain successful nerve block placement.
For the ACB, the needle was advanced under ultrasound
guidance at mid-­thigh in-­plane toward the saphenous nerve in
the adductor canal, lateral to the superficial femoral artery, as
previously described.17 After negative aspiration for blood, 1 cc
of 0.9% normal saline was injected to confirm correct needle tip
location, after which 10 cc of 1.5% mepivacaine was deposited
around the saphenous nerve.
For the SNB, beginning in the popliteal fossa, ultrasound
scanning was performed to identify the point of bifurcation of
sciatic into common peroneal and tibial nerves. The needle was
advanced in-­plane toward the site of bifurcation. After negative
aspiration for blood, 1 cc of 0.9% normal saline was injected to
confirm correct needle tip location, after which 15 cc of either
0.375% mepivacaine (low-­concentration) or 1.5% mepivacaine
Chen Y-­YK, et al. Reg Anesth Pain Med 2022;47:630–636. doi:10.1136/rapm-2022-103671
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(high concentration) was deposited around the sciatic nerve.
The order of nerve block placement in relation to pressure pain
testing and ischemic pain testing can be seen in figure 1.
Outcomes
The primary outcome was the impact of block on pressure pain;
specifically, block-­induced increase in pressure pain threshold
(mm Hg) to achieve 6/10 pain, compared between the three
block groups (ACB, ACB +LC SNB, ACB +HC SNB). The main
secondary outcome was the average pain score reported during
the 5 min prolonged pressure/ischemic pain-­ induced hold at
the 6/10 targeted pressure, compared between the three block
groups. Other secondary/supplementary outcomes included the
assessment of impact of blocks on other pressure pain thresholds
and pain scores during prolonged/ischemic holds at other (4, 8,
and 10/10) targeted pain levels.
Statistical analysis
All outcomes were assessed for normality of distribution and
parametric or non-­ parametric testing used accordingly. Anal-
ysis of variance or Kruskal-­Wallis tests were used to determine
whether there was a difference among the ACB, ACB+LC SNB,
and ACB+HC SNB groups for demographic information,
psychosocial and pain profiles, block-­induced increase in pres-
sure threshold to reach pain thresholds, and average pain score
during a 5 min cuff pressure holds. When significant, post hoc
pairwise comparisons were performed. Paired t-­tests were used
to compare blocked and unblocked conditions within partici-
pants. Data analysis was conducted using SPSS (V.27). A p<0.05
was considered significant. Based on preliminary testing in a
pool of volunteer test subjects, a sample size estimation was
calculated using a mean of 160 mm Hg and SD of 70 mm Hg,
which showed that to detect a 50% difference in cuff pressure
pain thresholds at the 6/10 pain level, with 80% power and
alpha 0.05, a sample size of 13 subjects per group was required.
RESULTS
Participants (n=14 in each group) included 23 women and 19
men. Participants’ characteristics, including demographics, base-
line pain sensitivity, and pain catastrophizing, were generally
balanced between groups (table 1). Details of screening, enrol-
ment, and study visit flow and testing procedures are shown in
figure 1.
Effect of nerve blocks on cuff pressure pain threshold
The cuff pressure needed to produce 6/10 pain (6/10 pres-
sure pain threshold) was tested before and after block(s), and
shown to increase after all three nerve block combinations,
but to varying degrees (ACB alone: increase of 24±32 mm
Hg, ACB+LC SNB: increase of 120±103 mm Hg, and
ACB+HD-­ SNB: increase of 159±93 mm Hg (figure 2,
see also online supplemental appendix table A for paired
testing results). For our primary outcome, we compared
the amount of increase in 6/10 pressure pain threshold
between the three groups (ie, change in pressure pain sensi-
tivity), which revealed a significant overall group difference
(p=0.004). Post hoc pairwise comparisons showed that the
ACB group had significantly less increase in pressure pain
threshold (ie, was more pain sensitive) compared with the
ACB+LC SNB group (p=0.028) and the ACB+HC SNB group
(p=0.001). There was no significant difference in increase
of pressure pain threshold between the ACB+LC SNB and
ACB+HC SNB groups (p=0.306). Supplemental findings of
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Figure 3 Pain scores during prolonged cuff pressure/ischemic holds. Participants rated pain during 5 min sustained leg cuff pressure holds at the
pressure needed to induce 4,6,8, and 10/10 pain at baseline, and rated pain every 30 s. Graphs show group mean and SD. Average difference between
blocked and unblocked condition, and results of within subject paired t-­test are shown for each block type and targeted pain level. ACB, Adductor
canal nerve block; ACB +LC-­SNB, ACB with low-­concentration sciatic nerve block; ACB +HC-­SNB, ACB with high-­concentration sciatic nerve block.

group comparisons of block-­induced increase in pressure to
produce 4, 8, and 10/10 pain are reported in online supple-
mental appendix table B.
Effect of nerve blocks on prolonged pressure ischemic pain
In all three block groups, decreased pain scores were reported
in the block leg compared with the control leg during
prolonged/ischemic pain holds (figure 3). Our main secondary
outcome was a comparison between the three groups on the
average pressure pain reported during the 6/10 pressure hold
634
in the presence of a block. We observed significant between-­
block-­group differences in the average pain scores (4.2±1.4,
1.4±1.7, 0.4±0.7, p<0.001) (figure 4). Post hoc pairwise
comparisons showed a significant difference in average pain
scores between the ACB and ACB +LC SNB (p<0.001), and
the ACB and ACB +HC SNB (p=0.001), but not between the
ACB +LC SNB and ACB +HC SNB (p=0.21). Supplemental
findings of group comparisons of pain scores at the 4, 8, and
10/10 holds are reported in online supplemental appendix
table C.
Chen Y-­YK, et al. Reg Anesth Pain Med 2022;47:630–636. doi:10.1136/rapm-2022-103671

Figure 4 Impact of Blocks on Prolonged Pressure/Ischemic Pain:
Group comparisons. Participants rated pain every 30 s during a 5 min
hold at the pressure needed to induce 6/10 pain at baseline, and
average pain across 5 min was calculated.(A) Comparison of average
pain in the blocked leg during a prolonged pressure/ischemic hold
between groups. Each circle represents an individual participant, with
bar height showing group mean and error bars SD. (B) Kruskal-­Wallis
was used to compare pain scores between groups. ACB, Adductor
canal nerve block; ACB +LC-­SNB, Adductor canal nerve block with low-­
concentration sciatic nerve block; ACB +HC-­SNB, Adductor canal nerve
block with high-­concentration sciatic nerve block.
DISCUSSION
In this human volunteer study, we sought to assess the influence
of varying peripheral nerve block types and local anesthetic
concentrations on pressure and ischemic pain in the leg. Our
results suggest that ACB alone results in a small increase in the
pressure pain threshold and decrease in ischemic pain. The addi-
tion of a low-­concentration sciatic block further increased pres-
sure pain threshold and decreased ischemic pain substantially
more than ACB alone, as did addition of a high-­concentration
(full-­strength/surgical) sciatic block.
The systematic investigation of these various block combi-
nations allowed quantitative distinction of the analgesic effect
of ACB (pain scores decreasing by about one point compared
with baseline, which may be considered clinically significant),18
supporting the hypothesis that ACB alone provides mild pain
relief in the lower leg. Since AECS is difficult to study in a clinical
setting, and literature about AECS pain breaking through RA is
limited to case reports, we believe that these findings in a human
experimental model provide insight into the variable effects of
different applications of RA on pressure and ischemic pain. In
the case of AECS, most commonly occurring in the anterior
compartment (de facto anterolateral), innervation is provided
predominantly by the sciatic nerve. In addition, however, the
saphenous nerve provides sensory innervation to the skin and
Chen Y-­YK, et al. Reg Anesth Pain Med 2022;47:630–636. doi:10.1136/rapm-2022-103671
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subcutaneous tissues of the anteromedial aspect of the leg down
to the ankle and foot, including partial innervation of the peri-
osteum in the area of the medial malleolus. Therefore, while a
dense SNB may significantly alter the clinical presentation of
AECS, blocking the saphenous nerve should provide analgesia
without altering AECS presentation. Although there appeared to
be a graphical trend toward relatively larger impact on both pres-
sure pain threshold and prolonged pressure/ischemic pain in the
HC-­SNB than the LC SNB, these were not statistically different.
These differences appeared greater at the highest tested pain
levels (pressure to induce 10/10 and ischemic holds at this pres-
sure, online supplemental appendix tables B and C), potentially
suggesting that the most severe pain, as would occur with AECS,
would in fact break through a milder, low-­concentration SNB
faster than through a high-­concentration SNB, but future studies
with a larger sample size and broader range of local anesthetic
concentrations are needed to explore this. The clinical relevance
of these findings is that low-­concentration nerve block is less
likely to obscure AECS than a high-­concentration nerve block,
while still providing relief from pressure and ischemic pain.
The mechanism of ischemic pain remains poorly understood,
although it is thought to be more similar to visceral pain than
cutaneous incisional pain.19 Afferent fibers that detect isch-
emic metabolites in muscle tissue20 also carry deep tissue pres-
sure sensation and have been shown to be poorly blocked with
conventional peripheral nerve blocks,21 especially in the case of
acidosis.20 22 While it is unlikely to completely block ischemic
pain, RA is an effective tool to reduce acute pain and opioid
administration after lower extremity fracture and surgery4 23 24
and may also impact the development of chronic postsurgical
pain.25 26 Despite the drawbacks of frequent clinical examination
or compartment pressure measurement in at risk patients,7 their
use is likely superior to a reliance on pain as a clinical sign. Taken
together, clinical practice guidelines and case reports suggest that
vigilance and possibly using other methods of diagnosing AECS,
rather than avoidance of a certain type of analgesia, is required
to protect patients. A risk–benefit discussion about use of RA
between the surgical and anesthesia team should be employed in
patients with lower extremity fractures and high clinical suspi-
cion for AECS.27
Limitations
Ethical and practical considerations limited us to a relatively
brief, external application of high pressure to induce pressure
and ischemic pain, and thus, the stimuli used in this experi-
mental model of AECS are different in nature, timing, and sense
of control to the insidious onset of pressure experienced clini-
cally with AECS. As a healthy volunteer study, self-­selection bias
was likely present in our volunteer subjects, given that they were
willing to receive a nerve block, potentially representing a group
of individuals who were less anxious and more pain tolerant.
Another limitation of the study was that only two concentra-
tions of the shorter-­acting mepivacaine were tested, again for
practical reasons. We extrapolate that these doses are the equiv-
alent of 0.375% and 0.1% bupivacaine,28 but future testing of
local anesthetics that are more commonly used (bupivacaine),
as well as lower concentrations of LA, is needed to explore an
optimal balance of provision of analgesia and retention of isch-
emia detection.
CONCLUSION
Experimentally induced pressure and ischemic pain were
inhibited by all block types, but the degree of block of ACB
635
 Original research
alone was significantly less than when either the low- or high-­
concentration SNB was added. At higher levels of induced
pain, a trend toward greater separation of analgesic effect was
observed between the low and high-­concentration sciatic block
conditions, but this was not statistically significant. The extent to
which either of these block modifications could reduce delay in
detecting a rapid AECS-­related increase in pain in clinical prac-
tice remains unknown. Future clinical studies employing graded
degree of neural blockade in patients with lower extremity frac-
tures, occurring over the longer period (days) of clinical care, are
needed to assess the clinical utility of such block modifications.
Twitter Jose Zeballos @Jose_L_Zeballos
Acknowledgements James Gosnell and Svetlana Gorbatov contributed to initial
screening of participants.
Contributors Y-­YKC: funding acquisition, study conception and design,
investigation, data collection, data curation, analysis and interpretation of results,
draft manuscript preparation (writing—original draft and writing—review and
editing), data visualization. PL: study conception and design, data collection,
investigation, manuscript preparation (writing—original draft and writing—review
and editing). KMF: study conception and design, data collection, data curation,
analysis and interpretation of results, draft manuscript contribution (writing—
original draft and writing—review and editing), data visualization. CAC: study
conception and design, data collection, data curation, draft manuscript preparation
(writing—review and editing). JMW: draft manuscript preparation (writing—
original draft and writing—review and editing). JZ: study conception and design,
draft manuscript preparation (writing—review and editing). AVK: draft manuscript
preparation (writing—original draft and writing—review and editing). KEB: draft
manuscript preparation (writing—review and Editing). KV: study conception and
design, draft manuscript preparation (writing—original draft and writing—review
and editing). KLS: study conception and design, investigation, data collection,
analysis and interpretation of results, draft manuscript preparation (writing—original
draft and writing—review and editing), supervision, guarantor.
Funding This study was supported by Brigham and Women’s Hospital Department
of Anesthesiology, Perioperative and Pain Medicine Seed Grant.
Competing interests None declared.
Patient consent for publication Consent obtained directly from patient(s).
Ethics approval Written and informed consent were obtained from each
participant. This study was conducted between October 2020 and April 2021 at
Brigham and Women’s Hospital in Boston, Massachusetts, USA.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request.
Supplemental material This content has been supplied by the author(s). It
has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have
been peer-­reviewed. Any opinions or recommendations discussed are solely those
of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and
responsibility arising from any reliance placed on the content. Where the content
includes any translated material, BMJ does not warrant the accuracy and reliability
of the translations (including but not limited to local regulations, clinical guidelines,
terminology, drug names and drug dosages), and is not responsible for any error
and/or omissions arising from translation and adaptation or otherwise.
ORCID iDs
Kamen Vlassakov http://orcid.org/0000-0002-7704-3709
Kristin L Schreiber http://orcid.org/0000-0002-7361-2214
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