E  The Open Mind
Regional Anesthesia and Compartment Syndrome
Peter Marhofer, MD,* Jens Halm, MD,† Georg C. Feigl, MD,‡ Tim Schepers, MD,† and
Markus W. Hollmann, MD, PhD§
GLOSSARY
ACS-NSQIP = American College of Surgeons National Surgical Quality Improvement Project; ASRA
= American Society of Regional Anesthesia; ATP = adenosine triphosphate; ESRA = European
Society of Regional Anaesthesia
M
any surgeons express concerns against the
use of regional anesthetic blocks for limb
surgery after trauma. This controversial dis-
cussion between surgeons and anesthesiologists does
not always rely on a solid evidence-based background
and is more based on emotional grounds or on possi-
ble forensic consequences. The main argument against
regional anesthesia for limb surgery is based on the
delayed diagnosis and subsequent delayed treatment
of compartment syndrome. To phrase it more provoc-
ative, regional blocks are suspected to cause damage.
From the anesthesiologist’s perspective, regional
anesthesia has become an important role in the spe-
cialty of anesthesia. The implementation of ultraso-
nographic guidance for the detection of neuronal and
adjacent anatomical structures led to high success
rates with extreme low block-related side effects or
complications. Thus, regional blocks can be consid-
ered as reliable means to provide adequate analgesia
for many surgical procedures.
Conversely, unwanted effects such as the decep-
tion of trauma- or surgery-related nerve damage or
a prolonged motor block need to be seriously consid-
ered. In particular, delayed diagnosis of compartment
syndrome warrants a balanced discussion that should
lead to a sustainable consensus between surgeons and
From the *Department of Anesthesiology Intensive Care Medicine, Orthopedic
Hospital Speising, Vienna, Austria; †Department of Surgery, Amsterdam
University Medical Center, Amsterdam, the Netherlands; ‡Institute of
Anatomy and Clinical Morphology, University Witten/Herdecke, Witten,
Germany; and §Department of Anesthesiology, Amsterdam University
Medical Center, Amsterdam, the Netherlands.
Accepted for publication June 7, 2021.
Funding: Financial support was provided solely from institutional and/or
departmental sources.
The authors declare no conflicts of interest.
Reprints will not be available from the authors.
Address correspondence to Markus W. Hollmann, MD, PhD, Department
of Anesthesiology, DEAA Amsterdam University Medical Center, Location
AMC, Meibergdreef 9 1105 DD, Amsterdam, the Netherlands. Address
e-mail to m.w.hollmann@amsterdamumc.nl.
Copyright © 2021 International Anesthesia Research Society
DOI: 10.1213/ANE.0000000000005661
1348 www.anesthesia-analgesia.org
Copyright © 2021 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
anesthesiologists. The present article aims to provide
state-of-the-art and anatomical-based knowledge
regarding the relationship between compartment
syndrome and regional anesthesia to facilitate clinical
decisions.
ANATOMICAL CONSIDERATIONS
From an anatomical point of view, the extensor com-
partment of the forearm and the fibular and extensor
compartments of the lower leg are the most critical
compartments for the development of acute com-
partment syndrome. Tibial diaphyseal and forearm
(mainly distal radius and diaphyseal forearm) frac-
tures seem to be the most common injuries that are
associated with acute posttraumatic compartment
syndromes. Any increase in pressure in such a com-
partment causes a risk of damage to neurovascular
structures by compression with a subsequent initia-
tion of a toxic cascade.
The extensor compartment of the forearm is
bounded by the antebrachial fascia and in the depth
by the radius, the ulna, and the interosseous mem-
brane. The deep and superficial extensor muscles, as
well as the deep branch of the radial nerve, the pos-
terior interosseous nerve, and posterior interosseous
vessels are located inside this compartment. This
compartment is extremely narrow and therefore the
deep branch of the radial nerve is per se constricted.
The fibular compartment is bounded by the lateral
surface of the fibular, the anterior and posterior inter-
muscular septa, and the crural fascia and contains the
fibularis longus and fibularis brevis muscles, as well
as the common fibular, the deep and the superficial
fibular nerves. There are no relevant vessels in this
compartment, but small arteries originate from the
peroneal artery that enter the compartment by pierc-
ing the posterior intermuscular septum. The extensor
compartment is bounded by the lateral surface of the
tibia, the interosseous membrane, the medial surface
of the fibula, the anterior intermuscular septum, and
November 2021 • Volume 133 • Number 5
 E  The Open Mind
the crural fascia. It is filled with the extensor muscle
group: the tibialis anterior, the extensor digitorum
longus, and the extensor hallucis longus muscles.
The blood supply is provided by the anterior tibial
artery, which enters the compartment via a gap in the
most proximal part of the interosseous membrane.
Innervation is provided by the deep peroneal nerve,
which enters the compartment by piercing the ante-
rior intermuscular septum.
INCIDENCE, PATHOPHYSIOLOGY, CLINICAL
SYMPTOMS, AND DIAGNOSIS OF EXTREMITY
COMPARTMENT SYNDROME
The incidence of compartment syndrome of the
extremities is sex-dependent and reported to range
between 7.3 per 100,000 in men and 0.7 per 100,000
in women.1 Fractures and soft-tissue injuries are the
main causes for the development of compartment
syndrome. The risk of developing acute compartment
syndrome increases with age and a higher degree of
fracture comminution and/or segmental fractures
after high-energy trauma mechanisms. Nevertheless,
about 30% of acute compartment syndromes occur
without a fracture.1 Worth mentioning, delays in diag-
nosis (87%) and treatment (37%) were the most com-
mon causes of acute compartment syndrome–related
claims.2
The pathophysiology of acute compartment syn-
drome is complex and based on several mechanisms.
Various traumatic and nontraumatic causes lead to
tissue injury with subsequent tissue ischemia and
reperfusion. Precapillary vasodilation in the arteriole
system, collapsing venules, and increased permeabil-
ity of the capillary bed are the predominant micro-
vascular mechanisms underlying an increased net
filtration with an elevated interstitial pressure (which
is normally lower than 10 mm Hg) in traumatized
Figure. The simplified pathophysiological mechanisms of compart-
ment syndrome.
November 2021 • Volume 133 • Number 5
Copyright © 2021 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
tissues. Once the interstitial pressure increases, suf-
ficient perfusion to tissues decreases with subsequent
tissue hypoxemia. Hypoxia, oxidant stress, and local
hypoglycemia cause cell edema. In addition, the cel-
lular osmotic balance is disturbed due to a deficiency
of adenosine triphosphate (ATP) and shutdown of
the sodium-potassium ATPase channels with a sub-
sequent influx of chloride ions causing cell swelling
and cell necrosis. The next pathophysiological step
of compartment syndrome is reperfusion injury with
the production of oxygen radicals, lipid peroxida-
tion, and calcium influx, whereby the intracellular
homeostasis is disturbed. All cellular mechanisms
lead to hyperkalemia and acidosis facilitating sys-
temic organ failure.3 The Figure illustrates the simpli-
fied pathophysiological mechanisms of compartment
syndrome.
The time from the cause to clinical symptoms
of compartment syndrome varies from minutes to
hours, and the longer the anerobic situation persists,
the more severe are the long-term consequences.
Irreversible changes of functional outcomes (axo-
notmesis of peripheral nerves, muscle contractures)
occur after a maximum time of 6 hours.3
In the 1960s, Sir Herbert Seddon described
Volkmann’s ischemia in the lower limb.4 Based on
these papers, the P’s commonly quoted in the diag-
nosis of acute compartment syndrome have been
introduced: Pain, Paralysis, Pallor, and Pulselessness.
Likelihood ratio calculations by Ulmer5 revealed that
the probability of acute compartment syndrome with
a single clinical finding was approximately 25%, and
93% with 3 symptoms present.
The main clinical symptom of and the only early
sign of acute compartment syndrome is pain, whereby
the incidence of pain alone is reported to be 20% with
a specificity of 97%.5 Acute compartment syndrome–
related pain is disproportional to the injury or other
causes of the tissue trauma. Paresthesia and paresis
are later clinical signs of nerve ischemia. In particular,
motor nerves show a notable resistance to ischemia,6
which is due to differences in ion channel composi-
tion between motor and sensory axons. Therefore,
onset of motor paralysis is a late sign of compartment
syndrome and should not be relied on for prompt
diagnosis of compartment syndrome.
On the other hand, swelling and distension of
affected compartments are clear clinical signs of
acute compartment syndrome, but it should be
highlighted that the degree of swelling and disten-
sion of the affected compartment is not related to
tissue trauma. Pulselessness is definitively not a
clinical sign of compartment syndrome. It should
be emphasized that peripheral pulses can still be
detected in compartments with critically high pres-
sures. Thus, pain and paresthesia/paresis are the
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 Regional Anesthesia and Compartment Syndrome
widely accepted and useful clinical signs of acute
compartment syndrome with a low sensitivity and
high specificity.
The main diagnostic tool is the measurement of
pressure in the affected compartment. The physi-
ological pressures vary between 8 mm Hg in adults
to 10 to 15 mm Hg in children.7,8 It seems obvious that
pressures need to be measured in the affected com-
partment, and therefore an exact knowledge of the
specific anatomy (as described earlier) is required.
The threshold for a critical tissue delta pressure (dia-
stolic blood pressure minus compartment pressure) is
widely accepted to be 30 mm Hg. This threshold can
be considered as indication for fasciotomy. Invasive
monitoring of the partial pressure of oxygen is
another method to diagnose compartment syndrome.
A cutoff value of less than 30 mm Hg is associated
with a 100% sensitivity and specificity.9 Alternatively,
oxygen saturation could also be monitored noninva-
sively via near-infrared spectroscopy, which is based
on the physiological fact that a reduced local blood
flow causes a reduction in local oxygen saturation
and muscle oxygen tension. Despite the plausible
pathophysiological background, near-infrared spec-
troscopy showed controversial results in its clinical
application.10 The monitoring of localized perfusion
via pulsed phased-locked loop ultrasound, photople-
thysmography, laser Doppler flowmetry, and scintig-
raphy did also not find its way into clinical practice
until today. Conversely, intramuscular glucose and
pH monitoring seem to be promising methods for the
detection of compartment syndrome,11 but is also not
used clinically. Serum biomarkers such as creatinine
kinase, myoglobin, or ischemia-modified albumin are
useful in the assessment of systemic consequences of
compartment syndrome, but cannot be used for acute
diagnosis.
WHAT DO WE REALLY KNOW?
In an effort to find what is most suitable, intravenous
morphine is generally ruled out as it may mask acute
compartment syndrome by affecting the sympathetic
pathway (partially responsible for conduction of isch-
emic pain).
Quite honestly, our knowledge regarding the
impact of regional anesthetic blocks on delayed
diagnosis of compartment syndromes is limited.
The low incidence of compartment syndrome may
explain the weak evidence in literature, given
that performing well-designed clinical studies is
extremely difficult.
The specific literature is mainly based on small
case series or case reports. Interestingly, orthopedic
surgeons mainly report cases of delayed diagnosis of
compartment syndrome, when regional anesthesia
was performed. On the other hand, anesthesiologists
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primarily describe the harmless use of regional anes-
thesia in the context of compartment syndrome.
(Loco)regional anesthesia overall has shown prom-
ising results. Only a very few cases of acute compart-
ment syndrome have been reported during the last
30 years where ischemic pain was not masked by
locoregional anesthesia (ie, peripheral nerve blocks)
resulting in breakthrough pain (ischemic pain) as a
symptom of acute compartment syndrome alerting
the treating physicians.
Two exemplary cases should illustrate the predom-
inant problem with timely detection of a compartment
syndrome, namely the use of a too high concentration
of the local anesthetic used for nerve block and the
second the lack of rigid vigilance.
Hyder et al12 describe a case of a 28-year-old patient
with a tibial shaft fracture, who received a triple nerve
block postoperatively (femoral, obturator, and lateral
cutaneous femoral) with bupivacaine 0.5%. The first
compartment pressure measurement was performed
48 hours after surgery, where the patient reported per-
sistent paresthesia and inability to actively extend his
big toe. The pressure in the compartment at that time
was 108 mm Hg. This case illustrates the importance
of diligently interpreting and considering all possible
etiologies of prolonged postoperative sensory and
motor blockade. The use of blocks with dilute concen-
tration of local anesthetic is recommended in high-
risk scenarios such as tibial shaft fractures.
A similar case is reported by Ganeshan et al.13 A
75-year-old patient with a complicated forearm frac-
ture underwent ambulatory surgical revision using
axillary brachial plexus blockade (without a descrip-
tion of the type, volume, and concentration of the local
anesthetic solution). Subsequently, the patient devel-
oped a compartment syndrome during the next 24
hours and was readmitted after 24 hours with severe
pain. These cases illustrate the importance of clinical
vigilance and a high level of suspicion regarding the
potential occurrence of compartment syndrome.
The 2 case reports described earlier were included
in a recent systematic review on the effect of regional
anesthesia on diagnosis and management of acute
compartment syndrome following long bone frac-
tures.14 Only 6 single-patient case reports could be
included in this study, where only 2 case reports (see
above) describe a delayed diagnosis of acute compart-
ment syndrome by regional anesthesia. The authors
expressed their concerns that a consensus regarding
regional anesthesia and delayed recognition of com-
partment syndrome is still lacking.
Conversely, various cases were published where the
use of peripheral nerve blocks did not mask or delay
the diagnosis of compartment syndrome. Cometa et
al15 described the use of femoral and sciatic nerve
blocks for pain management during and after distal
ANESTHESIA & ANALGESIA
 E  The Open Mind
femur and proximal tibia osteotomy with subsequent
compartment syndrome, where adequate diagnosis
and management was not delayed. A compartment
syndrome after knee arthroplasty, which was also not
masked by the regional anesthetic technique (adduc-
tor canal catheter), was described by Torrie et al.16 In
both case reports, ropivacaine 0.2% was used.
Most publications report on the use of peripheral,
and not central, nerve blocks and their possible delay
in the diagnosis of compartment syndrome. This
emphasis is in accordance with a more general trend
toward peripheral regional anesthesia. Neuraxial
anesthesia (ie, epidural), on the other hand, has been
associated with masking acute compartment syn-
drome in at least 23 reported cases in the literature.17
Single-shot spinal anesthesia is of minor importance
in this context because of the short-lasting anesthetic
and analgesic effect of subarachnoidally administered
local anesthetics. Spinal catheters are hardly used
regional techniques in daily clinical practice, and no
literature exists regarding spinal catheters and com-
partment syndrome. Epidural anesthesia and analge-
sia was predominantly reported to mask compartment
syndrome. However, the use of ropivacaine 0.1% to
0.2% should not influence motor or sensory function
to an extent, that diagnosis of compartment syndrome
is delayed. Mar et al17 reviewed 23 case reports where
epidural anesthesia and analgesia was associated
with compartment syndrome. In 90% of these cases,
the classical signs of compartment syndrome were
detected. Thus, low concentrated epidural ropivacaine
will unlikely mask compartment syndrome.
REGIONAL ANESTHESIA DOES NOT DELAY
DETECTION OF COMPARTMENT SYNDROME
Both the European and the American Societies of
Regional Anesthesia (ESRA, ASRA) clearly acknowl-
edge a lack of current evidence-based data supporting
that the use of regional anesthesia increases the risk
of acute compartment syndrome or a delay in diag-
nosis in children.18 Data from the American College
of Surgeons National Surgical Quality Improvement
Project (ACS-NSQIP) indicate also no differences
in postoperative complications after lower extrem-
ity traumatic fractures between regional or general
anesthesia.19 Large case series where regional blocks
were used for pain therapy during extremity trauma
surgery did not show 1 single case of compartment
syndrome.20
Regional anesthesia provides optimal pain man-
agement and is associated with improved func-
tional outcome.21 Optimal pain treatment should
not be used as an argument to impede a technique.
In fact, only a very few cases were published where
diagnosis of compartment syndrome was delayed
in the presence of regional anesthesia.13 These
November 2021 • Volume 133 • Number 5
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cases should rather emphasize that our manage-
ment to detect compartment syndromes should
be improved. Optimal pain management is the
anesthesiologist’s responsibility, detection of com-
partment syndrome mainly that of the surgeons.
However, anesthesiologists should facilitate sur-
geons by providing optimal circumstances for early
diagnosis of compartment syndrome. Pain man-
agement should be achieved by the lowest pos-
sible dose/concentration of the local anesthetic
required for sensory blockade but avoiding motor
blockade. Consequently, sudden increase in pain
(breakthrough pain) should always be seen as com-
partment syndrome unless proven otherwise.
For adequate early detection of compartment syn-
drome, 7 pillars should be highlighted:
• Pain and paresthesia/paresis have low sensitivity
and high specificity.
• All pathologies (trauma, spontaneous bleeding) in
compartments, which are of particular risk for com-
partment syndromes (see above), require particu-
lar attention. Tibial diaphyseal, distal radius, and
diaphyseal forearm fractures are the most common
pathologies that are associated with acute compart-
ment syndromes.
• The minimal concentration/dose of a local anes-
thetic should be used for peripheral nerve blocks.
We specifically recommend the use of dilute concen-
tration of local anesthetics, for example, ropivacaine
0.2% for either epidural or peripheral nerve block-
ade in scenarios here there is concern regarding
delayed diagnosis of compartment syndrome.15,16
• Any disproportionate pain requires immediate
diagnostic steps (see pillar no. 5).
• Diagnosis of compartment syndromes need to be
based on the clinical examination, at times pressure
monitoring or monitoring of the partial pressure of
oxygen in the affected compartment.
• Additional comorbidities, for example, blood
coagulation disorders, need to be considered and
those patients should be monitored even more
intensively.
• The indication for fasciotomy should be liberal.
To simplify the above described “seven-pillars-con-
cept” for early detection of compartment syndrome
in the presence of regional anesthesia, we could break
it down to 3 crucial points: vigilance, vigilance, vigi-
lance. All reported severe consequences of compart-
ment syndromes in the presence of peripheral nerve
blocks would have easily been detected by an ade-
quate level of vigilance.
Finally, we want to emphasize the importance of
an appreciative relationship and respectful coopera-
tion between surgeons and anesthesiologists. Both
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 Regional Anesthesia and Compartment Syndrome
specialties have a joint responsibility toward patients
with the common goal of treating patients in an opti-
mal manner. The time of eminence or emotional-based
medicine, defined as “making the same mistakes with
increasing confidence over an impressive number of
years” has definitively passed.22 E
DISCLOSURES
Name: Peter Marhofer, MD.
Contribution: This author helped write the manuscript.
Name: Jens Halm, MD.
Contribution: This author helped write the manuscript.
Name: Georg C. Feigl, MD.
Contribution: This author helped write the manuscript.
Name: Tim Schepers, MD.
Contribution: This author helped write the manuscript.
Name: Markus W. Hollmann, MD, PhD.
Contribution: This author helped write the manuscript.
This manuscript was handled by: Michael J. Barrington,
MBBS, FANZCA, PhD.
REFERENCES
1. McQueen MM, Gaston P, Court-Brown CM. Acute com-
partment syndrome. Who is at risk? J Bone Joint Surg Br.
2000;82:200–203.
2. DePasse JM, Sargent R, Fantry AJ, Bokshan SL, Palumbo
MA, Daniels AH. Assessment of malpractice claims associ-
ated with acute compartment syndrome. J Am Acad Orthop
Surg. 2017;25:e109–e113.
3. von Keudell AG, Weaver MJ, Appleton PT, et al. Diagnosis
and treatment of acute extremity compartment syndrome.
Lancet. 2015;386:1299–1310.
4. Seddon HJ. Volkmann’s ischaemia in the lower limb. J Bone
Joint Surg Br. 1966;48:627–636.
5. Ulmer T. The clinical diagnosis of compartment syndrome
of the lower leg: are clinical findings predictive of the disor-
der? J Orthop Trauma. 2002;16:572–577.
6. Hofmeijer J, Franssen H, van Schelven LJ, van Putten MJ.
Why are sensory axons more vulnerable for ischemia than
motor axons? PLoS One. 2013;8:e67113.
7. Shadgan B, Menon M, O’Brien PJ, Reid WD. Diagnostic
techniques in acute compartment syndrome of the leg. J
Orthop Trauma. 2008;22:581–587.
8. Staudt JM, Smeulders MJ, van der Horst CM. Normal com-
partment pressures of the lower leg in children. J Bone Joint
Surg Br. 2008;90:215–219.
9. Hansen EN, Manzano G, Kandemir U, Mok JM. Comparison
of tissue oxygenation and compartment pressure following
tibia fracture. Injury. 2013;44:1076–1080.
1352   
www.anesthesia-analgesia.org
Copyright © 2021 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
10. Schmidt AH, Bosse MJ, Obremskey WT, et al; Major
Extremity Trauma Research Consortium (METRC).
Continuous near-infrared spectroscopy demonstrates limi-
tations in monitoring the development of acute compart-
ment syndrome in patients with leg injuries. J Bone Joint
Surg Am. 2018;100:1645–1652.
11. Doro CJ, Sitzman TJ, O’Toole RV. Can intramuscular glu-
cose levels diagnose compartment syndrome? J Trauma
Acute Care Surg. 2014;76:474–478.
12. Hyder N, Kessler S, Jennings AG, De Boer PG. Compartment
syndrome in tibial shaft fracture missed because of a local
nerve block. J Bone Joint Surg Br. 1996;78:499–500.
13. Ganeshan RM, Mamoowala N, Ward M, Sochart D. Acute
compartment syndrome risk in fracture fixation with
regional blocks. BMJ Case Rep. 2015;2015:bcr2015210499.
14. Tran AA, Lee D, Fassihi SC, Smith E, Lee R, Siram G. A
systematic review of the effect of regional anesthesia on
diagnosis and management of acute compartment syn-
drome in long bone fractures. Eur J Trauma Emerg Surg.
2020;46:1281–1290.
15. Cometa MA, Esch AT, Boezaart AP. Did continuous femo-
ral and sciatic nerve block obscure the diagnosis or delay
the treatment of acute lower leg compartment syndrome? A
case report. Pain Med. 2011;12:823–828.
16. Torrie A, Sharma J, Mason M, Cruz Eng H. Regional anes-
thesia did not delay diagnosis of compartment syndrome: a
case report of anterior compartment syndrome in the thigh
not masked by an adductor canal catheter. Am J Case Rep.
2017;18:444–447.
17. Mar GJ, Barrington MJ, McGuirk BR. Acute compartment
syndrome of the lower limb and the effect of postoperative
analgesia on diagnosis. Br J Anaesth. 2009;102:3–11.
18. Ivani G, Suresh S, Ecoffey C, et al. The European Society of
Regional Anaesthesia and Pain Therapy and the American
Society of Regional Anesthesia and Pain Medicine Joint
Committee Practice Advisory on Controversial Topics
in Pediatric Regional Anesthesia. Reg Anesth Pain Med.
2015;40:526–532.
19. Brovman EY, Wallace FC, Weaver MJ, Beutler SS, Urman
RD. Anesthesia type is not associated with postoperative
complications in the care of patients with lower extremity
traumatic fractures. Anesth Analg. 2019;129:1034–1042.
20. Zadrazil M, Opfermann P, Marhofer P, Westerlund AI,
Haider T. Brachial plexus block with ultrasound guidance
for upper-limb trauma surgery in children: a retrospective
cohort study of 565 cases. Br J Anaesth. 2020;125:104–109.
21. Atchabahian A, Schwartz G, Hall CB, Lajam CM, Andreae
MH. Regional analgesia for improvement of long-term
functional outcome after elective large joint replacement.
Cochrane Database Syst Rev. 2015:CD010278.
22. Isaacs D, Fitzgerald D. Seven alternatives to evidence based
medicine. BMJ. 1999;319:1618.
ANESTHESIA & ANALGESIA