In Reply:

We thank all the authors who commented on our study regarding the intraneural local anesthetic injection.1  Although the general concern regarding this approach is understandable, the conclusions in the received comments apparently do not stem from scientific evidence. Allocating resources to avoid intraneural local anesthetic injection should not be based on common sense but on clear evidence that it could be worse than the extraneural injection.

Jiang et al. suggested that the axonal damage could be attributable to a higher concentration/volume of the local anesthetic deposited around the nerve fascicles after injection within the epineurium. Furthermore, the injection pressure below 15 psi used in our study could be too high for sciatic nerve causing ischemia. Although the hypothesis of nerve fascicle ischemia as the cause of axonal damage is plausible, the possible mechanism described by Jiang et al. is not supported by evidence. A previous animal study demonstrated that nerve fascicle damage ensued only when the intraneural injection pressure was greater than 25 psi.2  Moreover, in our previous study,3  we found that the amplitude reduction seen after injection out of the epineurium was comparable with that observed after intraneural injection. When the sciatic nerve, with an intact epineurium, was exposed to a clinically relevant concentration of lidocaine, the epineurium contained 30% of the “total neural local anesthetic” when the equilibrium was reached.4  Unfortunately, this drop in concentration caused by the epineurium seems to reduce the block effectiveness but not to prevent axonal damage.3 

In our 2016 work, we directly compared the intraneural injection with the extraneural one (named as subparaneural), hoping to demonstrate that intraneural injection was as safe as the subparaneural at the electrophysiogic test. Surprisingly, we found that both techniques resulted in 100% of axonal nerve damage 5 weeks after surgery.3  As highlighted by both the Swenson et al. and Lai and Rosenblatt letters, the study was underpowered for this secondary outcome; nevertheless, our result is worth considering. Swenson et al. underlined that in our trial a blind radiologist found that 22% of extraneural injection (named subparaneural) were actually inadvertent intraneural. We had also found that 16% of the intraneural injections were actually subparaneural. Data were reanalyzed after recoding group allocation, and the results were comparable with those of the intention-to-treat analysis.3 

Inadvertent intraneural injection was frequent before ultrasound technique introduction.5  Reported neurologic complications were rare but, worryingly, they did not diminish with the use of ultrasounds.6  In our previous studies1,3  no patient reported clinically evident neurologic symptoms. In their letter, Swenson et al. correctly pointed out that a phone call is not equivalent to a clinical visit. Nevertheless, a routine clinical visit after peripheral nerve block, as well as an electrophysiologic test, is hardly performed regardless of the approach used.

New insights on the different layers enveloping the sciatic nerve7  have allowed new approaches to the sciatic block, but peripheral nerve block safety did not develop at a similar rate. Our knowledge regarding possible nerve damage after peripheral nerve block does not consider the actual structure of the sciatic nerve. Animal studies are dated or have investigated only the intraneural injection effects.8,9  No study addressed the effects of the purportedly safer extraneural injection (in or out of the paraneural sheath).

Common experience would suggest avoiding intraneural injection, taking for granted that local anesthetic injection outside of the epineurium is safer and effective at the same time. Instead, our previous3  and present1  findings raise doubt about whether the axonal damage after peripheral nerve block was related to the site of local anesthetic injection or to local anesthetic itself.

In conclusion, we do not propose that the intraneural local anesthetic injection could be better than extraneural, because we agree with Lai and Rosenblatt that systemic local anesthetic toxicity after peripheral nerve blocks is rare, and the increased effectiveness of intraneural injection may have a clinical impact only in case of sciatic nerve block as a sole anesthetic technique. Instead of spreading unjustified alarm, we would rather stimulate further investigation to verify to what extent the struggle to avoid intraneural injection is justifiable. It is evident how this is an ethically, economically, and scientifically grounded issue.

Competing Interests

The authors declare no competing interests.

References

1.
Cappelleri
G
,
Ambrosoli
AL
,
Gemma
M
,
Cedrati
VLE
,
Bizzarri
F
,
Danelli
GF
:
Intraneural ultrasound-guided sciatic nerve block: Minimum effective volume and electrophysiologic effects.
Anesthesiology
2018
;
129
:
241
8
.
2.
Hadzic
A
,
Dilberovic
F
,
Shah
S
,
Kulenovic
A
,
Kapur
E
,
Zaciragic
A
,
Cosovic
E
,
Vuckovic
I
,
Divanovic
KA
,
Mornjakovic
Z
,
Thys
DM
,
Santos
AC
:
Combination of intraneural injection and high injection pressure leads to fascicular injury and neurologic deficits in dogs.
Reg Anesth Pain Med
2004
;
29
:
417
23
.
3.
Cappelleri
G
,
Cedrati
VL
,
Fedele
LL
,
Gemma
M
,
Camici
L
,
Loiero
M
,
Gallazzi
MB
,
Cornaggia
G
:
Effects of the intraneural and subparaneural ultrasound-guided popliteal sciatic nerve block: A prospective, randomized, double-blind clinical and electrophysiological comparison.
Reg Anesth Pain Med
2016
;
41
:
430
7
.
4.
Leeson
S
,
Strichartz
G
:
Kinetics of uptake and washout of lidocaine in rat sciatic nerve in vitro.
Anesth Analg
2013
;
116
:
694
702
.
5.
Robards
C
,
Hadzic
A
,
Somasundaram
L
,
Iwata
T
,
Gadsden
J
,
Xu
D
,
Sala-Blanch
X
:
Intraneural injection with low-current stimulation during popliteal sciatic nerve block.
Anesth Analg
2009
;
109
:
673
7
.
6.
Munirama
S
,
McLeod
G
:
A systematic review and meta-analysis of ultrasound versus electrical stimulation for peripheral nerve location and blockade.
Anaesthesia
2015
;
70
:
1084
91
.
7.
Andersen
HL
,
Andersen
SL
,
Tranum-Jensen
J
:
Injection inside the paraneural sheath of the sciatic nerve: Direct comparison among ultrasound imaging, macroscopic anatomy, and histologic analysis.
Reg Anesth Pain Med
2012
;
37
:
410
4
.
8.
Kirchmair
L
,
Ströhle
M
,
Löscher
WN
,
Kreutziger
J
,
Voelckel
WG
,
Lirk
P
:
Neurophysiological effects of needle trauma and intraneural injection in a porcine model: A pilot study.
Acta Anaesthesiol Scand
2016
;
60
:
393
9
.
9.
Wiesmann
T
,
Steinfeldt
T
,
Exner
M
,
Nimphius
W
,
De Andres
J
,
Wulf
H
,
Schwemmer
U
:
Intraneural injection of a test dose of local anesthetic in peripheral nerves: Does it induce histological changes in nerve tissue?
Acta Anaesthesiol Scand
2017
;
61
:
91
8
.