Regional Anesthesia Unintentional Subdural Placement of Epidural Catheters by mandeepgoma


									Regional Anesthesia & Pain Medicine:
November/December 2011 - Volume 36 - Issue 6 - pp 537-541
doi: 10.1097/AAP.0b013e31822e0e8c
Original Articles

Unintentional Subdural Placement of Epidural
Catheters During Attempted Epidural Anesthesia:
An Anatomic Study of Spinal Subdural
Reina, Miguel Angel MD, PhD*†; Collier, Clive B. MD‡; Prats-Galino,
Alberto MD, PhD§; Puigdellívol-Sánchez, Anna MD, PhD§; Machés,
Fabiola MD*†; De Andrés, José Antonio MD, PhD∥
Free Access
Article Outline

Author Information

From the *Department of Clinical Medical Sciences and Applied Molecular Medicine Institute, CEU
San Pablo University School of Medicine; †Department of Anesthesiology, Madrid-Montepríncipe
University Hospital, Madrid, Spain; ‡Anaesthesia, Prince of Wales Private Hospital, Sydney, Australia;
§Laboratory of Surgical NeuroAnatomy, Human Anatomy and Embryology Unit, Faculty of Medicine,
Universitat de Barcelona, Barcelona; and ∥Anesthesia, Critical Care and Multidisciplinary Pain
Management Department, General University Hospital, Valencia, Spain.

Accepted for publication July 12, 2011.

Address correspondence to: Miguel Angel Reina, MD, PhD, Department of Clinical Medical Sciences
and Applied Molecular Medicine Institute, CEU San Pablo University School of Medicine; and
Department of Anesthesiology, Madrid-Montepríncipe University Hospital, Madrid, Spain. c/Valmojado
95 1° B 28047 Madrid, Spain (e-mail:

The authors have no conflict of interest to declare.


Background: Although infrequent, subdural block is a complication of epidural anesthesia with obvious
implications. Knowledge of the spinal subdural compartment (dura-arachnoid interface) may help
elucidate controversies arising from evidence that subdural catheter placement is feasible and may be
difficult to identify clinically.

Methods: Samples of arachnoid lamina obtained during in vivo lumbosacral surgery (n = 4) and from
cadavers (n = 6) were obtained and prepared for transmission electron microscopy and scanning
electron microscopy. Subdural spaces were artificially produced in suitable samples, and an epidural
catheter was inserted between the arachnoid and dura to compare the dimensions of meninges in
relation to epidural catheters.

Results: Scanning electron microscopy of the dural sac showed areas of continuity between the
arachnoid lamina and dura mater and other parts with both membranes separated by a subdural
space. Transmission electron microscopy allowed the study of such border zones, where alternating
cellular and collagen layers could be seen. A layer rich in collagen fibers and some fibroblasts
separated arachnoid and neurothelial cells (dural border cells). Few specialized membrane junctions
were found among cells adjacent to collagen fibers.

Dura mater had an average thickness of 260 to 400 μm, with a dural lamina of approximately 4 to 6
μm. In areas where the arachnoid appeared separated from the dural lamina, its thickness measured
35 to 45 μm. Catheters with a diameter of 700 μm were successfully inserted inside the subdural
space, between the dura mater and the arachnoid lamina.

Conclusions: Dura mater and arachnoid layers act as a single unit but may be pulled apart by traction
forces during cadaver processing of the dural sac or in vivo placement of catheters. This generates
subdural spaces, either parallel or concentric, because of the minimal resistance offered by the tissue,
which may be explained by its few specialized membrane junctions.

There are 4 possible sites into which an epidural needle or catheter may be unintentionally placed:
                                       1,2                      3,4                                 1
intravascular, subarachnoid, subdural, and intradural spaces. Subdural blocks are rare. Dawkins
reported a 0.1% incidence of "massive subdurals" in 16,644 epidural cases. Lubenow et al reported a
0.82% incidence of subdural injections in 2182 cases and defined a subdural block as having
occurred when there was an extensive neural block in the absence of subarachnoid puncture.
Subdural blocks occur more frequently in parturients with an approximate incidence of 1 in 3000
attempted epidural blocks. However, this incidence is probably higher in clinical practice.

The anatomy of the spinal subdural region has been the subject of controversy. In recent years, the
concept of a subdural space has been redefined by authors such as Vandenabeele et al and Reina
et al, who reported that the human spinal subdural space is not an anatomic cavity, as had been
previously thought, but an acquired one. An acquired subdural space is formed when traction forces,
caused by epidural needles, catheters, or fluid injections, tear neurothelial cells apart. Unintentional
intradural or subdural placement of epidural catheters has been documented in radiographic studies
where such spaces were filled by contrast solutions. One of the sites exposed to unintentional
formation of subdural spaces is the dura-arachnoid interface, which is located between the spinal
dura mater and the arachnoid membrane. Other authors have previously described this area as the
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"medial border of the spinal dura mater," the dural border cell layer, the subdural mesothelium, or
the subdural compartment.

The present study was designed to describe the inner layers of the dura-arachnoid lamina, where
epidural catheters could be placed unintentionally, and to compare the diameters of catheters with
those of the meningeal layers after in vitro subdural placement and microscopic analysis.

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After approval from our research ethics committee (Comité Etico de Investigaciones Clínicas del
Grupo de Hospitales Madrid), samples from spinal meninges were obtained during surgical
procedures at Madrid-Montepríncipe University Hospital and also from samples of cadavers at the
Human Anatomy and Embryology Unit, Faculty of Medicine, Barcelona University. Selected images
from the dura-arachnoid interface obtained for previous studies         were reexamined to compare
with actual samples.

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Transmission Electron Microscopy

Informed consent was obtained for anesthetic purposes and to obtain arachnoid samples from
surgical patients (n = 4), aged between 37 and 59 years and undergoing dural sac opening to treat a
neurinoma of the cauda equina. After careful opening of the dura mater, the arachnoid lamina was
separated and identified as a thin and translucent membrane containing cerebrospinal fluid within the
subarachnoid space. Cauda equina roots were visualized through the transparent arachnoid
membrane in the lumbosacral region. Samples of arachnoid membrane were collected after partial
dissection of the membrane.

Fresh samples (n = 8) were cut immediately with a sharp knife in 1 × 2-mm longitudinal fragments and
immersed in 2.5% glutaraldehyde in phosphate buffer (pH 7.2-7.3) for 4 hours. The samples were
processed for transmission electron microscopy immediately after surgery. These samples were later
fixed with a solution of 1% osmium tetroxide and 1% ferrocyanide for 1 hour. The specimens were
dehydrated with increasing concentrations of acetone in water and soaked in epoxy resin (Epon 812,
Merck, Darmstadt, Germany). The resin was polymerized at 60°C for 24 hours. Thin slides, 0.5 μm
thick, were dyed with Richardson methylene blue and observed by light microscopy. Ultrathin slides,
70 nm thick, were cut with an ultramicrotome (Reichert Jung ultracut E, Vienna, Austria) and treated
with Reynold lead citrate solution during 3 minutes. The specimens were then observed under a Jeol
1010 Transmission Electron Microscope (JEOL Corp Ltd, Tokyo, Japan).

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Scanning Electron Microscopy

The dural sac (dura mater, arachnoid membrane) and its contents at the thoracic and lumbar levels
were extracted from 6 human cadavers between 61 and 72 years. The elapsed time from death to the
fixing of samples was less than 36 hours, and the bodies were refrigerated before dissection.

Laminectomies were performed in all subjects to isolate the dural sac and its contents. Samples were
cut to include portions of the dural sac and the nerve roots with their cuffs. Anterior attachments of the
dura to the spinal canal wall at the level of the discs were surgically dissected to avoid damage to the
dural laminae. Samples were labeled with sutures to identify their orientation within the spinal canal.
Samples were immersed in buffered 10% formaldehyde for a week and then immersed in saline
solution during 24 hours. Later, 10-mm-thick slices of the dural sac and their content were cut with a
surgical blade. Some samples (n = 6) were processed for transmission electron microscopy as
described previously and others (n = 32) were processed for scanning electron microscopy.

Samples were then fixed by immersion for 4 hours in 2.5% glutaraldehyde with a phosphate solution
buffered at a pH of 7.28 to 7.32 and then dehydrated through repeated immersion in acetone 50%,
70%, 80%, 90%, and 95% until a concentration of 100% was reached. The acetone from the samples
was exchanged with carbon dioxide in a closed pressurized chamber (Balzers CPD 030-Critical Point
Dryer; Bal Tec AG, Fürstentum, Lichtenstein) at 31°C until the critical pressure of 73.8 bar was

Tissue samples were mounted on metal sample holders 25 mm in diameter. A carbon layer less than
200 Å in width was deposited over the samples with a Balzers MED 010 Mini Deposition System. The
carbon layer evaporated on passing an electrical current through a graphite electrode within a
vacuum chamber regulated to 10 mbar. The specimens were covered with a gold microfilm, by
circulating a 20-A current through a gold electrode within a vaporization chamber SCD 004 Balzers
Sputter Coater regulated to a 0.1-mbar vacuum. Afterward, specimens were studied with a JEOL JSM
6400 scanning electron microscope.

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Epidural Catheters in the Subdural Space

An operating stereoscopic microscope Zeiss S 21 OPMI 111 (Carl Zeiss, Oberkochen, Germany) was
used during the introduction of an epidural catheter in the subdural spaces within the samples. At the
time of catheter insertion, there were already areas in the samples where subdural spaces appeared
as they had been partly produced during the process of dissection. Attempts were made at placing
20-gauge epidural catheters inside these subdural spaces. Catheters, with an external diameter of
0.85 mm (B.Braun Melsungen AG, Germany), were passed through 18-gauge epidural needles to
direct their tips across the thickness of the dura mater. Once the catheters had been successfully
introduced up to a depth of 5 to 8 mm, they were cut with a surgical blade. The resulting samples
were coated in gold microfilm, by circulating a 20-A current through a gold electrode within a
vaporization chamber SCD 004 Balzers Sputter Coater regulated to a 0.1-mbar vacuum before
microscopic examination with a JEOL JSM 6400 scanning electron microscope.

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Transmission Electron Microscopy

The subdural compartment was found between the inner part of the dura mater and the external part
of the arachnoid lamina. Both areas had to be examined separately because the subdural space
generated during processing exceeded the extent of the microscope's image field. Approximately 2 to
6 layers were found below the dura and approximately 10 to 14 layers were found adjacent to the
arachnoid lamina in different samples from both sides (Figs. 1 and 2).

Figure 1   Figure 2
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Few specialized membrane junctions (desmosomes and tight junctions) were found among
neighboring cells, whereas other samples showed neither junctions nor substances in the
surroundings, even when cells were close to each other. In other cases, abundant collagen matrix
layers were distributed between cellular layers. Branched cells were often seen in these samples.

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Scanning Electron Microscopy

Epidural catheters, dural laminae, arachnoid laminae, and secondary subdural spaces were studied.
Fixation of the dural sac with paraformaldehyde allowed good conservation of the arachnoid
membrane. In some areas, the dural sac showed continuity between the arachnoid membrane and
the dural laminae, whereas in other areas, there was either partial continuity or both layers appeared
completely separated from each other (Figs. 3 and 4). The dura mater had a thickness ranging from
260 to 400 μm among studied samples. The dura mater was formed by successive 4- to 6-μm-thick
dural laminae. Within the same cadaver, the dural thickness varied between 50 and 80 μm in different
zones depending on the number of dural laminae and the amount of collagen fibers. In areas where
the arachnoid membrane was found separated from the dural lamina, it had a thickness of 35 to 45

Figure 3   Figure 4
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Close to the ligaments (dentate, posticum, posterolateral, and anterior), the predominant feature was
the continuity between dural laminae and arachnoid membrane.

Catheters had a diameter of 700 μm, and despite having larger diameters than the arachnoid lamina
and dura mater, it was feasible to introduce them inside the subdural space (Fig. 5). Catheters were
introduced besides nerve roots in the cauda equina, which showed diameters of 980 to 1930 μm (1-
1.9 mm) (Fig. 6). Introduction of a Tuohy needle inside the dural sac during sectioning and before
paraformaldehyde immersion leads to difficulties such as unintentional puncture of the dura or
damage to the arachnoid laminae.
Figure 5
Image ToolsFigure 6
           Image Tools
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Scanning electron microscopic images suggest a continuity of dural and arachnoid layers in some
areas, whereas a subdural space, probably generated during sample processing, appears between
layers in others. Transmission electron microscopy allows the study of the characteristics of areas
where the inner layers of the dura mater become separated from the outer layers of the arachnoid
membrane. The reduced number of specialized junctions among neurothelial cells explains the
possibility of subdural spaces originating in these areas under specific circumstances. Successive
collagen and cell layers, visible on both sides of the subdural space, suggest the possibility of
producing such subdural spaces between different layers of the dura-arachnoid interface, known as
the subdural compartment. Furthermore, with the aid of scanning microscopy, it is possible to assess
the location of catheters inside spaces that had been previously described using radiographic
techniques. Here, comparisons between the diameters of catheters, dura mater, and arachnoid
laminae have been undertaken.

Although aged cadaver samples were used for scanning microscopy, these allowed the identification
of dural and arachnoid laminae, subdural spaces, and their relationship with catheter size, at low
magnification. Furthermore, most transmission electron microscopy samples came from surgical
patients, thereby avoiding postmortem changes affecting samples and allowing a good visualization of
neurothelial cells and their specialized membrane junctions. Inner dural laminae and the dura-
arachnoid interface were also visible in cadaver samples. The difficulties that we encountered during
perforation of the dura mater and our attempts at needle placement replicate those from previous
studies. Furthermore, the characteristics of the thin and fragile arachnoid laminae help explain
unintentional subdural catheter placement, probably during the process of needle introduction. The
use of techniques such as electron microscopy represents new research tools in anesthesia because,
in the past, anesthetists had to rely mainly on clinical signs, such as the absence of cerebrospinal
fluid through the epidural catheter, to predict correct epidural catheter placement.        The use of
electron microscopy also seems promising in more speculative areas, such as hypotheses that
explain the possibility of epidural catheter migration into the subdural space.

Mehta and Salmon used radiographic contrast to show the sites of Tuohy needle orifices with
intentional epidural placement and found that the Tuohy needle bevel was sited partly in the epidural
space and partly in the subdural space in 7% of cases. Furthermore, the symptoms of an
unintentional subdural block may differ among patients, probably because the size and location of the
acquired subdural space may depend on the anesthetic volumes being injected at the time of block. A
typical feature of high subdural blocks is the presence of only mild hypotension, rarely requiring
treatment. However, it also has been described that the subdural space may extend as far as
intracranial level, possibly reaching the floor of the third ventricle. Extensive spread of local anesthetic
may induce respiratory depression, followed shortly afterward by apnea and unconsciousness, which
                                                                    20                        16
may persist for several hours, together with pupillary dilatation. Hoftman and Ferrante, in a recent
literature review, reported significant cardiorespiratory depression in almost half of their 70 collected
cases of subdural block. However, scrutiny of these cases suggests that the subdural diagnosis may
well have been questionable in many, despite claims that the block was "radiologically confirmed."

Although our images suggest the events that may take place in the subdural region during attempted
epidural blockade, which up to now could only be hypothesized, final definitive evidence of catheter
misplacement in individual patients will only be forthcoming in the future, when much higher definition
imaging techniques (magnetic resonance imaging, computed tomography, or ultrasound) become

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The authors thank Prof. Anna Carrera and Prof. Anna Oliva, from the Anatomy and Embryology Unit,
Faculty of Medicine, Girona University, for their collaboration in cadaver dissection in the Human
Anatomy and Embryology Unit of the Faculty of Medicine, Barcelona University; and Prof. Rafael
García de Sola and Dr. Paloma Pulido, from the Neurosurgery Department from La Princesa
University Hospital for their collaboration obtaining samples during surgery in the Madrid-
Montepríncipe University Hospital, Madrid.

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