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An anatomical study of the intradural space.

We have recently published details of 10 parturients who experienced epidural blocks that were inadequate, at least initially (1-3), with several unusual features. Subsequent radiological examination showed restricted spread of injected contrast quite unlike that seen following epidural, subdural or subarachnoid catheter placement (Figure 1). We postulated that the catheters had accidentally entered a fourth space, within the dura mater, which we termed the 'intradural space'. We wished to ascertain whether this novel concept was an anatomical possibility.

Our earlier work involved several studies of the electron microscopic structure of human dura mater (4-7). The aim of the present laboratory investigation was to determine whether it would be possible to separate the laminae that compose the dura, allowing the formation of this 'new space'. Our aim was then to place an epidural catheter within the dura. Further, using electron microscopy, we wished to observe any resulting damage to the dura and determine whether such damage persisted after catheter removal.



Following approval from the Ethics Committee of Clinical Research (CEIC del Grupo Hospital de Madrid, Spain), the dural sac and its contents at thoraco-lumbar levels were extracted from six human cadavers between 61 and 72 years of age. Those with a history of spinal surgery, disc prolapse and lesions of the spinal cord, nerve roots or meninges were excluded. The time elapsed from death to the fixing of samples was less than 36 hours and the bodies were refrigerated prior to dissection. Laminectomies were performed on all subjects, with the dural sac and its contents being isolated. 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 labelled with sutures to identify their orientation within the spinal canal. Longitudinal and transverse sections were performed. The samples were fixed by immersion for four 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%, 95% until a concentration of 100% was reached. The acetone from the samples was exchanged with carbon dioxide in a closed pressurised chamber (Balzers CPD 030-Critical Point Dryer, Bal Tec AG, Furstentum, Lichtenstein) at 31[degrees]C until the critical pressure of 73.8 bar was attained.

Tissue samples with a length of 10 to 20 mm were placed over slides of 25 mm diameter. A carbon layer was then deposited on the samples to a thickness of less than 200 Amstrong 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 10-5 millibars. The specimens were covered with a gold microfilm by circulating a 20 amp current through a gold electrode within a vaporisation chamber (SCD 004 Balzers Sputter Coater) regulated to 0.1 millibars vacuum. Afterwards, the specimens were studied with a JEOL JSM 6400 Scanning Electron Microscope (JEOL Corporation Ltd, Tokyo, Japan).

We examined the scanning electron microscopy (SEM) images of our 54 samples of the dural sac, beginning with observation of the dural laminar structures in some detail, in order to ascertain whether the laminae had been damaged during the preparation process, creating artefactual intradural spaces. The laminae were studied to see if they could become separated without deformation or damage, while maintaining their structural integrity. In some cases the separation could also be seen clearly under optical microscopy. Furthermore, the factors that may cause separation of laminae 'in vivo' needed to be considered, particularly those related to the presence of an epidural catheter of a type commonly used in clinical practice. Of the 54 specimens examined under the scanning electron microscope, 32 exhibited some separation of the dural laminae and these were selected as being optimal for trials of catheter placement.

Placement of catheters within the dura

In the 32 selected specimens, attempts were made to place a 20 gauge epidural catheter with an external diameter of 0.85 mm through an 18 gauge Tuohy epidural needle (diameter 1.3 mm, B. Braun, Melsungen AG, Germany). We observed under optical microscopy whether the laminae of the dura could be separated to allow the entry of a catheter into the substance of the membrane. Samples were mounted over a metallic support and were kept fixed by a synthetic adhesive sheet on both sides. The dehydrated samples from the dural sac and their contents had a length of 10 to 20 mm. We tried to insert the bevel of the Tuohy needle in several different areas of our specimens and at varying depths within the dura. The catheters were directed through the Tuohy needle and the degree of resistance to insertion noted. Once an epidural catheter had been successfully introduced inside the laminae to a distance of approximately 5 to 8 mm, the catheter was divided with a surgical blade. The samples and the inserted catheters were coated in gold prior to re-examination by SEM. Finally, the catheters were removed and the tissues inspected again under SEM, searching for signs of residual damage.


The observed thickness of the dura in our specimens ranged from 250 to 400 [micro]m. Samples of dura mater at the level of the dural sac showed it was composed of approximately 80 bundles of fibres with a well-defined morphology. These bundles, which were arranged in concentric rings or laminae (Figure 2), were approximately 4 to 6 [micro]m in diameter and were composed of 10 to 12 collagen fibres and a few elastic fibres (Figure 3). Each lamina extended along the entire circumference of the sac (Figure 2). Variations in lamina thickness were caused by the number of collagen fibres constituting each lamina. Collagen fibres were seen interposing in axial and longitudinal planes, orientated in varying directions, with a smaller number of fibres crossing between laminae (Figure 3). Some dural laminae became detached from one another, keeping their shape unaltered while allowing an artefactual intradural space to develop (Figure 3). The intradural space was concentric and parallel to the dural layers.

Placement of catheters within the dura

In eight of the 32 samples it was possible, under optical microscopy, to introduce the catheter intradurally, following successful placement of the bevel of the Tuohy needle within the substance of the dura. In other cases the dural specimen was irreparably damaged by the bevel. Because dehydrated tissues lack elasticity there was some resistance to catheter insertion in all eight cases. The resistance was least if the catheter tip entered a space between adjacent laminae and opened up the space, as later confirmed on SEM. If the tip was not at this location, more insertion force was required and this often destroyed the specimen. If the laminae separated easily, there was minimal damage to surrounding tissues (Figure 4). In a few cases, the tip of the catheter pierced and exited the dura to reach the subdural or subarachnoid space (Figure 5). The external diameter of the 20 gauge epidural catheter was measured using an electronic microscopy length scale (X25 to X50 augmentation), and was approximately 770 to 800 [micro]m (Figure 4). After insertion of the epidural catheter, the combined thickness of the dura and catheter measured 1300 to 1400 [micro]m (Figure 4).






Following removal of the catheters, re-examination with SEM revealed a persisting cavity within the dura (Figure 6). Microscopically, some damage to the dural laminae that had been in direct contact with the epidural catheter was observed, however, these alterations did not affect the complete structure of the lamina, but just a few of the cellular strata in most cases (Figure 6).


Based on these laboratory investigations, we conclude that an epidural catheter can be placed inside the dura through a Tuohy needle, albeit in dehydrated specimens. If the results of the cadaver studies on elderly subjects also apply to healthy parturients, then it is feasible that such an event could happen accidentally during the attempted performance of epidural block. Accidental intradural catheter placement has until now only been a hypothesis and there are already some who dispute this concept (8,9). Researchers may be reluctant to accept that the dura mater, which has a thickness of up to 0.5 mm (500 [micro]m), can accommodate an epidural catheter of almost twice its diameter within its thickness. However, the nature of its structure with concentric laminae containing collagen fibres in specific proportions and orientation (Figures 2 and 3) allows us to suggest that dural laminar detachment, or 'delamination', is the major factor in the formation of an intradural space. Delamination follows the application of pressure or traction to the dura and does not result in significant structural damage. It should be stressed that the use of dehydrated samples undoubtedly favours the separation of the dural laminae in the laboratory, but we do not believe that this reduces the validity of our study which was designed to determine if it would be possible to insert epidural catheters into the dura, as we believe may happen clinically on rare occasions. No-one, to our knowledge, has previously suggested such a possibility and it seemed unlikely, given the relative dimensions of an epidural catheter and intact dura. We are now contemplating employing fresh specimens but a problem, yet to be overcome, is that the fresh tissue specimens with inserted catheters handle processing and dehydration poorly prior to SEM, because the catheters tend to move and valid images are not obtained.

The mechanism underlying intradural catheter placement may be considered as a 'tenting effect' during advancement of the epidural needle once the dura is reached. If enough pressure is exerted, the tip of the needle may partially pierce some of the dural layers, allowing the passage of the catheter between these layers, creating an intradural space. Injection of air, saline, contrast or other solutions would encourage laminar detachment, thus expanding this space within the thickness of the dura, as we have observed on radiographic screening, being represented by a dense swelling mass of contrast (Figure 1) (2,3,10). Intradural injection may be painful. We cannot yet predict which regions within the dura, or which particular laminae, are most vulnerable to detachment.

In clinical practice, the loss of resistance felt when an epidural needle reaches the epidural space might be expected to differ from that felt if the tip of the needle is placed in the intradural space, but this was not noticed in any of the 10 patients we previously reported1-3. We believe that intradural catheterisation is infrequent, probably occurring in about one in 500 obstetric epidurals in our hands, based on clinical and radiographic findings. The increased incidence in term-pregnancy patients may be related to the high circulating levels of progesterone acting on the many progesterone receptors located in the arachnoid mater and surrounding structures11, which might alter the consistency of the tissues.

In practice, we believe that intradural injection presents as an inadequate neuraxial block because the spread of local anaesthetic is restricted by the dural laminae and adjacent tissues, which have limited elasticity, but which allow the space to expand to an unknown degree (2,3). A repeat volume of local anaesthetic appears to become effective by further raising the pressure in the intradural space (which may cause transient pain) and then escaping, most commonly in a retrograde flow around the catheter, into the epidural space, leading to development of a reasonable block (2). However, as we have seen, delayed subarachnoid or subdural spread with extensive, life-threatening blocks can also occur (2). This may result from the eventual rupture of the attenuated laminae or alternatively, as seen in the laboratory, the catheter itself may migrate out of the intradural space into the subarachnoid or subdural spaces. We do not know how long an intradural space persists following removal of the epidural catheter, but it is interesting to note that one of the 10 patients developed intradural blocks on two occasions, three years apart.

In conclusion, in this study we examined the ultrastructural morphology of the dura mater in an attempt to explain the origin of a fourth or intradural space. Such a space could account for the 10 clinical cases of atypical neuraxial block and characteristic radiographic findings we observed. We were able to insert epidural catheters into the substance of the dura and observe the intradural space persisting after their removal. Definitive proof that this can happen in individual patients awaits the introduction of higher definition imaging techniques (magnetic resonance imaging, computed tomography or ultrasound) than are currently available.


(1.) Collier CB. Accidental subdural injection during attempted lumbar epidural block may present as a failed or inadequate block; radiographic evidence. Reg Anesth Pain Med 2004; 29:45-51.

(2.) Collier CB. The intradural space: the fourth place to go astray during epidural block. Int J Obstet Anesth 2010; 19:133-141.

(3.) Collier CB. Most cases of subdural injection are not in the subdural space: they are intradural! Reg Anesth Pain Med 2009; 34:613-615.

(4.) Reina MA, Dittmann M, Lopez A, van Zundert A. New perspectives in the microscopic structure of human dura mater in the dorso lumbar region. Reg Anesth 1997; 22:161-166.

(5.) Reina MA, De Leon Casasola OA, Lopez A, De Andres JA, Mora M, Fernandez A. The origin of the spinal subdural space. Ultrastructure findings. Anesth Analg 2002; 94:991-995.

(6.) Reina MA, De Leon Casasola O, Villanueva MC, Lopez A, Maches F, De Andres JA. Ultrastructural findings in human spinal pia mater in relation to subarachnoid anesthesia. Anesth Analg 2004; 98:1479-1485.

(7.) Reina MA, Villanueva MC, Maches F, Carrera A, Lopez A, De Andres JA. Ultrastructure of human spinal nerve root cuff in lumbar spine. Anesth Analg 2008; 106:339-344.

(8.) Hogan QH. In reply to Collier CB ; Most reported "subdural injections" are not in the subdural space, they are intradural! Reg Anesth Pain Med 2010; 35:117.

(9.) Feigl G, Dorn C, Bornemann-Cimenti H. Does an intradural space really exist? Int J Obstet Anesth 2011; 20:89.

(10.) Collier CB. In, Epidural Anaesthesia: Images, Problems and Solutions. London, UK: Hodder Arnold 2011.

(11.) Go KG, Blankenstein MA, Vroom TM, Blaauw EH, Dijk F, Hollema H et al. Progesterone receptors in arachnoid cysts. An immunocytochemical study in 2 cases. Acta Neurochir (Wien) 1997; 139:349-354.

C. B. COLLIER *, M. A. REINA ([dagger]), A. PRATS-GALINO ([double dagger]), F. MACHES ([section]) Department of Clinical Medical Sciences and Applied Molecular Medicine Institute, CEU San Pablo University School of Medicine, Madrid and Human Anatomy and Embryology Unit, Barcelona University School of Medicine, Barcelona, Spain

* M.D., M.R.C.P., F.R.C.A., F.A.N.Z.C.A., Clinical Researcher, Obstetric Anaesthesia. Prince of Wales Private Hospital.

([dagger]) M.D., Professor, Department of Clinical Medical Sciences and Applied Molecular Medicine Institute.

([double dagger]) M.D., Professor, Human Anatomy and Embryology Unit, Faculty of Medicine, Barcelona University.

([section]) M.D., Clinical Researcher.

Address for correspondence: Dr C. Collier, Obstetric Anaesthesia, Prince of Wales Private Hospital, Barker Street, Sydney, NSW 2031. Email: nfi1@

Accepted for publication on June 19, 2011.
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Article Details
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Author:Collier, C.B.; Reina, M.A.; Prats-Galino, A.; Maches, F.
Publication:Anaesthesia and Intensive Care
Article Type:Clinical report
Date:Nov 1, 2011
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