Acta Anaesthesiol Scand 2003; 47: 3–12 Printed in Denmark. All rights reserved

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Review Article

Neurologic deficits and arachnoiditis following neuroaxial anesthesia J. A. ALDRETE University of South Florida, Tampa, and the Aldrete Pain Center, Santa Rosa Beach, Florida, FL, USA

Of late, regional anesthesia has enjoyed unprecedented popularity; this increase in cases has brought a higher frequency of instances of neurological deficit and arachnoiditis that may appear as transient nerve root irritation, cauda equina, and conus medullaris syndromes, and later as radiculitis, clumped nerve roots, fibrosis, scarring dural sac deformities, pachymeningitis, pseudomeningocele, and syringomyelia, etc., all associated with arachnoiditis. Arachnoiditis may be caused by infections, myelograms (mostly from oil-based dyes), blood in the intrathecal space, neuroirritant, neurotoxic and/or neurolytic substances, surgical interventions in the spine, intrathecal corticosteroids, and trauma. Regarding regional anesthesia in the neuroaxis, arachnoiditis has resulted from epidural abscesses, traumatic punctures (blood), local anesthetics, detergents, antiseptics or other substances unintentionally injected into the spinal canal. Direct trauma to nerve roots or the spinal cord may be manifested as paraesthesia that has not been considered an injurious event; however, it usually implies dural penetration, as there are no nerve roots in the epidural space posteriorly. Sudden severe

headache while or shortly after an epidural block using the loss of resistance to air approach usually suggests pneumocephalus from an intradural injection of air. Burning severe pain in the lower back and lower extremities, dysesthesia and numbness not following the usual dermatome distribution, along with bladder, bowel and/or sexual dysfunction, are the most common symptoms of direct trauma to the spinal cord. Such patients should be subjected to a neurological examination followed by an MRI of the effected area. Further spinal procedures are best avoided and the prompt administration of IV corticosteroids and NSAIDs need to be considered in the hope of preventing the inflammatory response from evolving into the proliferative phase of arachnoiditis.

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also be influenced by the immune responsiveness of the individual patient and the neural tissue predisposition to evolve into a late proliferative phase characterized by fibrosis, adhesions and scarring (4). This process has been termed arachnoiditis (ARC) because it is the arachnoid layer, of the meningeal sac, that contains small vessels appearing to be immune reactive and more susceptible to undergo an initial inflammatory and edematous reaction and later generate fibroblast proliferation. However, not uncommonly the pia is also involved, as well as the adjacent neural tissue (spinal cord, ganglia, nerve roots, brain, and/or cranial nerves). It would be presumptive to assume that these events occurred only in anatomically topographic structures; however, more devastating is the physiological disruption that may be elicited by aberrant nociceptive stimuli of such magnitude that manifests itself by severe burning pain, stabbing and throbbing sensations and dysesthesia, frequently not following the classic dermatome

20 years regional anesthesia and pain relief procedures have become more frequently practiced. This trend has been welcomed by the medical community in general and anesthesia organizations in particular. However, these invasive procedures do have risks (1–3) and such risks have become more apparent as the manipulations of the spine and its delicate contents seem to be more daring, resulting in a number of injuries that appear to be related to the medications injected, their dosage, trauma produced by needle punctures or some of the manipulations aimed at damaging neural tissue (neurolytics, freezing, coagulation, etc.) Usually the injurious events result in an acute local and regional tissue reaction of the inflammatory type, which depends on the dose of medication injected, its concentration in reference to the diluent (saline solutions, local anesthetics or CSF), the number of attempts, and into what compartment the drugs were injected (peridural, subdural, or intradural). It may N THE LAST

Key words: arachnoiditis; CSF; epidural anesthesia; neurological deficit; radiculitis; regional anesthesia; spinal anesthesia; spinal cord. c Acta Anaesthesiologica Scandinavica 47 (2003)

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J. A. Aldrete Table 1 Various forms of arachnoiditis. Temporary nerve root irritation* Cauda equina syndrome* Clumped nerve roots Nerve roots adhered to thecal sac wall Deformed thecal sac Pseudomeningocele Intrathecal calcifications Pachymeningitis Arachnoiditis ossificants Optochiasmatic arachnoiditis Cerebral arachnoiditis *Considered functional only because of our limitations in demonstrating fine anatomical lesions.

distribution but characteristic of neuropathic pain (5, 6). In addition, there is also suggestive evidence that the sympathetic nervous system is affected with regional and tissular vascular dysfunction, profuse diaphoresis, migraine-like headaches, low-grade fever and others (7, 8). In cases of lumbosacral nerve root involvement, asymmetric perineal numbness, vesical, rectal and/or sexual dysfunction are common (9, 10). Analogous events may occur intracranially in cerebral arachnoiditis manifested by severe, intractable facial pain, aberrant headaches, painful tics, and visual and hearing deficits (11, 12). Readers are referred to other publications (5, 6, 9, 10, 13) for a detailed discussion of the presumed mechanisms of pain transmission involved in ARC. Depending on the degree and extent of the injurious event, whether chemical, infectious or mechanical, one or more of the forms of arachnoiditis may occur (Table 1). It should also be pointed out that most of them can be identified by radiological imaging at MRI; however, when contraindicated because of the presence of metal artifacts, a myelogram followed by a CAT scan would allow the identification of most of the lesions listed in Table 1 (2,14).

sociation, the origins of regional anesthesia coincided with these events. Apparently, Corning (18) first injected 110 mg of cocaine into the epidural space in 1885, and in 1895 A. Bier (19) performed the first spinal anesthesia by injecting 15 mg of the same drug into the subarachnoid space. By 1905 Konig (20) had published the first description of what appeared to be a neurological deficit after a spinal anesthetic. From there on, cases of ARC appeared to relate to the introduction of new diagnostic or therapeutic trends. At least four waves of cases of ARC have been related to technical advances or fashionable trends. Although myelography was first performed with lipiodol by Siccard and Forestier in 1922 (21), the use of this technique was carried out with caution because it was soon noted to produced severe reactions (22), even when more refined water soluble dyes such as Abradil, Dimer X, Thorotrast, and others were tried (23). Pantopaque (ethyliodophenylundecilate) was introduced by Ramsey et al. (24) in 1944, acquiring popularity for its good visualization and supposedly slow absorption into the circulation. Nevertheless, by 1945 reports of neurological damage had been published (25, 26) and confirmed in experimental observations (27) (Fig. 1). A water-soluble agent, metrizamide, became available in 1973 (28), but it proved also to be hazardous (29); nevertheless it was used for some time. Iohexol and iopamidol are also waterbased dyes that appear to be safer, though they have been known to cause ARC, especially if blood is present in the CSF, patients are dehydrated or paraesthesia is elicited during needle puncture (27, 30–32). Other possible causes of ARC are listed in Table 2.

Background Records indicate that the first report of ARC appeared in 1869, when Charcot and Joffroy (15) described two cases of progressive muscular atrophy with lesions in the anterolaterolateral fascicles of the spinal cord. It is said that Quinke (16) recognized the two main phases of the disease: the acute inflammatory and chronic prolipherative phases. Horsely (17) in 1909 gave a detailed description of the symptoms of this disease and named it ‘chronic spinal meningitis’; up to that time, most of the cases were neurological syndromes secondary to tuberculosis or syphilitic infections. By as-

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Fig. 1. Lumbar spine CAT scan. Clumped nerve roots below L2 distributed in a ‘circle’ contour, 12 years after a pantopaque myelogram.

Neurodeficit following neuroaxial anesthesia

It has been has been suspected that blood in the subarachnoid space may facilitate the clumping of nerve roots (33, 34). This same phenomenon can occur when small vessels are injured during the performance of spinal or epidural blocks (35), or even a simple spinal tap (36) can trigger ARC. This has also occurred in a few cases when autologous blood has been injected purposely into the epidural space to seal a dural hole (37) and incidentally in the subarachnoid compartment (38) (Fig. 1). The potential threat from the insertion of an epidural or intrathecal catheter into the spine of patients who are receiving or will receive anticoagulants (39, 40) as a possible cause of perioperative epidural and intrathecal bleeds cannot be ignored, even when the specific instructions as to when to insert or remove the catheter in reference to the time of giving the anticoagulants are observed precisely (41). The realization that degenerative disc disease was a common cause of sciatica (42) was followed by an exponentially larger number of patients undergoing myelogram with pantopaque, then a discectomy through a partial laminectomy (43). Recurrence usually prompted a second laminectomy and some type of fusion with a bone graft (44). When pain persisted and either a pseudoarthrois or spondylolysthesis were suspected, repeated fusion with hardware was recommended (45). After all resources have been exhausted, patients are declared as having ‘failed back syndrome’, as if the spine of the patient had failed, rather than to accept that it was the therapeutic regimen that failed to relieve the patients’ pain (43–45). Arachnoiditis may occur in these cases from either diagnostic myelograms (27, 29), blood entering the CSF through dural rents (43, 46, 47) during one of the operations or as direct injury while attempting to relieve the pain experienced during the interludes between the surgical procedures (48), and worse yet as a result of so-called ‘neuromodulation interventions’ (49–51 52). Not surprisingly, Deyo (52) has questioned the need for this aggressive interventional trend in the U.S. and the excessive utilization of helpcare resources; while Davies (53) has shown an apparent unexplainable disparity of cervical and lumbar Table 2 Etiology of arachnoiditis. Infections Myelography Blood in the intrathecal space Anesthetic and other substances in the spine Spinal surgical interventions Corticosteroids Trauma

spine surgery in American hospitals in comparison with other industrialized countries. The answer is still not known. The popularity of neuroaxial regional anesthesia in the last 25 years has been unprecedented, with definite advantages over general anesthesia as shown in traumatized, pediatric, obstetric and geriatric patients, as well as, in some cases of ambulatory surgery, limb reimplantation, renal transplants, major vascular surgery and others. This success has not come without a rise in complications (2, 3, 54, 55), those involving neurological deficit are the subject of this review.

Regional anesthesia as a cause of arachnoiditis As reluctant as we may be to admit to this feasibility, we are obligated to recognize that this otherwise noble form to produce insensibility and pain alleviation, may be in itself a possible cause of morbidity. To avoid the early causes of paresis and neurologic deficit (56, 57) from spinal anesthesia, a variety of approaches have been applied, among them remarkable improvements in needle technology (58). Consistent sterility has been obtained without the threat of detergents (59) and antiseptics (60, 61) by the simple measure of introducing disposable trays, syringes and needles, as well as the universal acceptance of preservative-free medications. These measures have been effective in reducing some of the complications from regional anesthesia; however, as the recognition that morphine injected epidurally could reduce postoperative pain, the traditional ‘sanctity’ of the epidural and subarachnoid spaces has been lost (62). It is the purpose of this review to identify the events that may lead to the development of ARC, so they may be prevented. In addition the diagnostic tests recommended and the typical symptoms that may appear upon occurrence of the injurious event will be listed, mentioning the therapeutic approach that may be beneficial in the acute inflammatory phase.

Incidence Attempts to identify the frequency with which neurological deficits occur after regional anesthesia have been met with certain skepticism, as a result of the lack of standardized data, on the consistency of the individuals performing the procedures (trainees vs. experienced) and/or recognition of pre-existent neurological diseases. Similarly, the patient population has been diverse, the follow up of patients to determine if in fact there was neurological deficit has

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J. A. Aldrete Table 3 Incidence of neurologic complications from neuroaxial anesthesia. Authors

Countries

Year

Incidence Spinal

Epidural

Dahlgren & Törnebrand (67) Auroy et al. (66) Aromaa et al. (68) Moen et al. (69)

Sweden France Finland Sweden

1995 1997 1997 2000

1 : 2834 6 : 10000 0.45 : 10000 1 : 13000

1 : 923 2 : 10000 0.52 : 10000 1 : 4000

been lax, and in most cases, no determination has been made as to the actual cause of the complication. Some authors (54, 55, 63–65) have identified factors that make patients more susceptible to complications (pre-existing neurological disease, obesity, paraesthesia, etc.) but no attempts have been made to define their incidence. Of late, efforts to standardize a population of patients, such as from a whole country (66) or province (67), have been made. Considerably different ratios have been reported from reviews of injury claims in Finland (68) and Sweden (69) (Table 3). Fitzgibbon (70) reported on the analysis of an ASA closed claims project originated by anesthesia-based chronic pain procedures occurring between 1970 and 1988. Out of 5480 claims 245 (4.4%) were related to pain management with a progressive increase from 1.95% in the 1970s and 2.76% in the 1980s to 8% in the 1990s; 120 claims were because of neurological blocks, 78% of which were related to the injection of steroids and associated agents. The injuries relating from these mishaps were paralysis and nerve injury 23%, pneumothorax 19%, death or brain damage 10%, meningitis 6%, and postdural puncture headache (PDPH) 11%. The remainder were catheter fractures, abscess, and infections, etc. It is likely that the liability caused by these procedures will continue to increase.

Local anesthetics The old adage ‘all local anesthetics are neurotoxic’ (71) has been debated. Nevertheless clarification is in order before this premise is taken as dogma or is discarded. In the first half of the 20th century a number of local anesthetics (LA) were introduced and discarded. Some were long lasting and neurotoxic, but procaine and tetracaine prevailed with relative consistency, efficacy and safety, as long as certain limitations (dosage, duration of action and indication) were followed. Attempts to use larger doses (72, 73) or to prolong their efficacy by mixing them with preservatives such as glycerin, polyethylene glycol, strychnine or methylparaben usually resulted in disastrous consequences (64, 74, 75). Just when everyone thought that the newly intro-

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duced local anesthetics could be trusted, experience with two of them was surprising: after using 2-chloroprocaine for over 14 years, cases of neurologic deficit and arachnoiditis after intrathecal and epidural injections were reported (35, 76). Eventually it was determined that the addition of Na bisulfite as a preservative into the anesthetic solutions was the cause of these deplorable complications (75, 77, 78). Unexpectedly, similar cases were noted after 5% lidocaine with dextrose was used as a spinal anesthetic for over 40 years. Lesions noted ranged from transient nerve root irritation, cauda equinoid syndrome, and even arachnoiditis accompanied by dysesthesia, radicular pain, and even paresis and sphincter dysfunction (79, 80). Amazingly, less severe but still neurotoxic symptoms have been reported from intrathecal 2% lidocaine (81) and bupivacaine 0.75% (82), so the prediction made by Pizzolatto (71) that all local anesthetics are neurotoxic has been proven ominously correct. In a more realistic form, we may accept that prolongation of the depolarization of the axon, usually considered an innocuous and reversible phenomenon, may under certain circumstances, such as high doses (83), high concentration, low CSF volume as in dehydration (32, 84–86) or when local anesthetics are weighted with dextrose loculated in dural cuff sheaths, certain positioning (87), or when vasoconstrictors are used (49, 88), may be irreversible when chemically irritant substances are in prolonged contact with nerve roots, spinal cord and the leptomeninges.

Table 4 Traumatic injuries from neuroaxial procedures that may result in arachnoiditis. Incidental dural puncture or rent Trauma to nerve roots or spinal cord nerve root paraesthesia Laceration of myelin sheath herniation of axons Blood in the cerebrospinal fluid*: tinged; serousanguinolent; flow volumetric solution drop Injection of neurotoxic or neuroirritant substances into subarachnoid or epidural spaces *Frequently more than one injury coincides *May be caused by trauma, but the injurious agent is blood.

Neurodeficit following neuroaxial anesthesia

Other factors There is also need to re-evaluate, in cases of non-cancer pain, the administration of neurolytic substances into the epidural space; contrary to earlier belief, they have been shown to cross the meningeal barrier (41, 89–92) or, as in some other instances, they may accidentally be injected intradurally (51); either way, the meningeal barrier is vulnerable to puncture or osmosis and neither of these phenomena can be controlled or guaranteed not to occur. The appearance of bloody, serosanguinolent or blood-tinged free-flowing CSF are ominous signs, as they may indicate vascular injury with a certain amount of blood present in the subarachnoid compartment. In contrast, finding only a small drop of blood-tinged clear oily fluid, without free flow, usually heralds that the bevel of the needle is in the subdural space (93). Accepting that these injurious events may produce one or more of the forms of ARC (Table 1) would be the first step in preventing such calamities, as the risk/benefit ratio can be established and possibly evaluated objectively to delete some of these techniques in patients at high risk or to stop a procedure when warning signs appear (Table 4).

Paraesthesia There has been a gradual change in attitude regarding the earlier concept of ‘no paraesthesia, no anesthesia’, meaning the need to intentionally elicit paraesthesia (94, 95) in order to assure the proximity of the needle tip to the peripheral nerve. By recognizing that this practice may be hazardous (96) this concept has evolved, as it has been realized that paraesthesia provoked in peripheral nerve trunks not only implies nerve contact but frequently represents a puncture. When similar results can be obtained with battery operated nerve stimulators, the procurement of paraesthesia seems unnecessary because there is the possibility of nerve injury and subsequent neuropathy (96– 98). Eliciting paraesthesia while performing a lumbar spinal or epidural anesthesia and even a spinal tap has far more serious consequences. If the mid-line is to be used for needle insertion, the aim is to enter the ligamentum flavum mediad. As there are no nerve roots in the posterior peridural space, paraesthesia implies that perforation of the dural sac has occurred, as at this point all nerve roots are intrathecal, or that the needle tip has deviated away from the midline sufficiently that the needle tip has made contact with the exciting nerve root, which is usually approximate-

ly 1.5–2.0-cm anterior from the ligamentum flavum and would require a 20-degree angle from the midline. Once this anatomical fact is realized the occurrence of paraesthesia while performing a lumbar puncture below the Tuffier line (L2–3) can not be considered irrelevant, as it implies that not only has a nerve root been touched or punctured, but most likely that the dural sac has been perforated and the nerve root has been touched or punctured. This event is usually manifested by a tingling sensation or by a sudden electric shock-like painful sensation, usually transmitted centrifugally and leaving a feeling of soreness around the puncture site. Considering that in 90% of adults the epidural space can be reached in less than 6 cm in depth from the skin to the ligamentum flavum, the epidural space ought to be reached in less than 6 cm and the subarachnoid space in no more than 7.5 cm in most patients (99, 100). For single-shot epidural injections, shorter (⬍ 9 cm) epidural needles may prevent some incidental dural punctures (101). Producing paraesthesia in the upper lumbar, thoracic and cervical spine regions may mean intrathecal contact with the spinal nerve roots located laterally to the spinal cord, extradurally with an exiting nerve root, or worse yet, by direct contact with or puncture of the spinal cord (102). As Selander (103) reported a 2.8% incidence of neurological complications in patients in whom painful paraesthesia was intentionally sought, controversy concerning peripheral nerve blocks has been on-going (94, 95, 104). There is however, evidence that paraesthesia encountered when performing neuroaxial blocks is an ominous sign (3, 87, 102). If in fact the integrity of the perineurium is violated, allowing for herniation, loculation and eventual scarring of the intraneural contents (72, 87, 102), it may be reasonable to expect that in the nerve roots similar or worse lesions may result. Furthermore, the persistent pursuit of the anesthetic technique by injecting the local anesthetic upon and around a nerve root with a perforated myelin sheath (64, 105, 106) may turn an otherwise usually innocuous concentration of LA (81– 86) into a neurotoxic agent (Table 4). Though this contention remains to be confirmed, a number of clinical observations (106–111) have suggested its validity. Reynolds’ (112) report of seven cases of neurological deficit syndromes occurring in obstetric patients who had spinal anesthetics performed with pencil-tip needles, which appear to produce paraesthesia more frequently as the distal tip of these needles has to penetrate further into the dural sac for the whole bevel to be in the subarachnoid space in order to obtain CSF to confirm location and

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Fig. 2. MRI of the thoracic spine, axial view. Syringomyelia in the thoracic spinal cord after a thoracic epidural catheter insertion with injection of anesthetic into the cord.

also to be able to inject the anesthetic into the intrathecal compartment, appears to support this premise. If the spinal cord is injured by an epidural needle puncture (3, 109, 110), advancement of a catheter may create a syrinx (111) (Fig. 2). Depending on the site of injury, patients may experience paralysis and or numbness, sphincter dysfunction and in some instances segmental numbness and weakness. Reassessment of the impact of paraesthesia as generator of a potential neurological deficit when LA is injected into or around it, includes the consideration to immediately discontinue the procedure rather than to attempt another puncture at a different intervertebral space, as a hole in the dura has already been made. A related controversy needs mentioning: the trend of performing neuroaxial blocks in anesthetized and paralyzed patients was questioned by Bromage and Benumof (109) who warned that paraesthesia if elicited under these circumstances could not be perceived because the patients would not move or complain. This proposal was rebuffed by a large number of pediatric anesthesiologists who practiced this very approach in infants and children (113). Since then two other cases, one in a child (111) and one in an adult (3), have been reported. Moreover, Horlocker and Caplan (114) have advised careful consideration of whatever benefits may be obtained, as there is ‘risk for a rare catastrophic, but potentially preventable outcome’ if that trend is followed.

Recommendations The need for reassessment of the impact of traumatic taps, blood in the CSF or paraesthesia as originators

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of potential neurological deficit when a local anesthetic or any other irritant substance is injected into or around a recent nerve root penetration was discussed, implying the need for deferment of the procedure rather than to attempt puncture at a higher or lower level as has been customary (115, 116). Similarly the occurrence of sudden, severe headache during or shortly after attempts at performing an epidural anesthetic by the loss of resistance technique with air, suggests a dural puncture with pneumoencephalus (117– 119). Headache appearing 12–23 h after any of these procedures, implies dural puncture and sufficient CSF leakage as to produce the headache. The presence of blood in the CSF indicates vessel injury and as such it should be considered as a possible cause of complication, as blood in itself can cause ARC or facilitate the neurotoxicity of other agents (dyes or local anesthetics). It must be recognized that while performing major plexus blocks the spinal cord can be injured also (120, 121). If after a suspected injurious event, symptoms such as burning, gnawing pain, dysesthesia, prolonged numbness or weakness without dermatome distribution appear with or without sphincter dysfunction, a complete neurological examination is in order followed by a magnetic resonance imaging study of the effected area in order to determine if a medullary, cauda equina or radicular lesion is present (2, 14, 55). The more common radiological finding is clumping of the nerve roots below L2 in the lumbosacral region (Fig. 1); other less frequent findings include nerve roots adhered to the dural sac arranged in circle or in a ‘string of pearls’ (Fig. 3) distribution, dural sac de-

Fig. 3. Lumbar spine MRI, axial view. Swollen nerve roots clumped in a ‘chain of pearls’ fashion 7 months after an epidural blood patch for PDPH after paraesthesia was elicited during an epidural anesthetic placement.

Neurodeficit following neuroaxial anesthesia

with confirmation of arachnoiditis by MRI usually imply that injury to one of the neural structures located intrathecally has taken place. There is need to determine its incidence and all other factors that may render a patient a susceptible candidate for this complication. Considerable thought needs to be given to the fashionable approach of performing neuroaxial blocks in anesthetized, paralyzed patients in whom no warning could be perceived in case of paraesthesia. New medications and procedures need to be shown as safe before wide acceptance. The apparent growing frequency of these neurological complications seem to have a multifactorial origin:

Fig. 4. Computerised axial tomography scan of the lumbar spine. Oval shape dural sac deformity with clumped nerve roots after bilateral laminotomy. The dural sac is partly out of the vertebral canal.

1. More operations are being carried out under regional anesthesia; 2. Adverse outcomes are being reported more frequently; 3. Patients seem to be better informed by Internet sources;

formities (Fig. 4), intrathecal calcification, partial or complete obstruction of the dural sac (Fig. 5), syringomyelia (Fig. 2), pseudomeningocele and/or pachymeningitis, which may represent ARC (2, 14). Acceptance of the occurrence of some of the injurious events as potential originators of ARC (122), would allow us to use them as determinants of whether to continue or to stop the procedure, obtain neurological or radiological consultations, and eventually to initiate treatment during the early phase of the inflammatory stage of ARC when aggressive therapy with methylprednisolone IV and anti-inflammatories may better act during the ‘window of opportunity’ to reduce or abolish the evolution into a more permanent proliferative phase. If an incidental dural puncture is performed and later an epidural catheter is inserted for the surgical procedure, the catheter may be left there for two or three days for the administration of 0.9% saline or dextran 40 solutions, either in boluses and/or by infusion, to treat the PDPH (123, 124). The injection of blood through the catheter is not recommended (38).

Conclusion The earlier remarks should by no means be taken as condemnation of regional anesthesia of the neruroaxis. The author is and has been an enthusiastic advocate of these techniques. The symptomatology mentioned and the presence of neurologic deficit along

Fig. 5. Lumbar spine myelogram revealing obliteration of the dural sac at L3 after multiple spine surgeries and myelograms (arachnoiditis ossificants).

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4. While performing paraspinal nerve blocks, spinal cord injury may occur; 5. Some anesthesiologists may find themselves having to carry out a procedure to which they are unfamiliar; and 6. The epidural of intrathecal injection of neurotoxic, neurolytic and even neuroirritant substances may produce ARC. Although rare, in some cases the risks outweigh the alleged benefits of regional anesthetic techniques, making the catastrophic outcome markedly obvious. The aim of this review was to present the elements of thought and the possible odds used in the decisionmaking processes that may lead to the prevention of neurologic deficit and ARC from neuroaxial blocks. Recognizing that some of these concepts question practices that have been considered acceptable for decades, means that debate is in order. However, as evidence gradually mounts, this contention deserves the most serious of considerations.

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59. Smith RA Corner EH. Experimental study of intrathecal detergents. Anesthesiology 1962: 23: 5–14. 60. Ericsson NO. frequency of complications, especially those of long duration after spinal anesthesia. Acta Chir Scand 1947: 95: 167. 61. Cope RW. Wooley and Roe case. Anesthesia 1954: 9: 249. 62. Wang JK Nauss LA Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology 1979: 50: 149–151. 63. Vandam LD Dripps RD. exacerbation of pre-existing neurologic disease after spinal anesthesia. New Engl J Med 1956: 255: 843. 64. Green NM. Neurological sequelae of spinal anesthesia. Anesthesiology 1961: 22: 682–698. 65. Usubiaga JE. Neurologic complications from Epidural Anesthesia. Int Anesth Clin 1975: 1: 1–123. 66. Auroy Y Narch P Messiah A et al. Serious complications related to regional anesthesia. Result of a prospective study in France. Anesthesiology 1997: 87: 479–486. 67. Dahlgren N, Törnebrandt K. Neurological complications after anaesthesia. A follow-up of 18,000 spinal and epidural anaesthesia performed over three years. Acta Anaesthesiol Scand 1995: 39: 872–880. 68. Aromaa V, Lahdensuv M. Cozanitis DA. Severe complications with epidural and spinal anesthesia in Finland. A study based on patient insurance claims. Acta Anaesthesiol Scand 1995: 41: 445–452. 69. Moen V, Irestedt L, Räf L. Ryggbedömning inte helt kompolikationsfri. Läkartidingien 2000: 97: 5769–5774. 70. Fitzgibbon DR. Liability arising from anaesthesiology based pain management in the non-operative setting. ASA News 2001: 61: 12–15. 71. Pizzolato P, Renegar OJ. Hispathological effects of long exposure to local anesthetics on the spinal cord on peripheral nerves. Anesth Analg 1959: 38: 138–141. 72. Selander D. Neurotoxicity of local anesthetics. Animal data. Reg Anesth 1993: 18: 461–468. 73. Basra J, Batra M, Fink BR et al. A comparative in vivo study of local neurotoxicity of lidocaine, bupivacaine, 2-chloroprocaine, and a mixture of 2-chloriprocaine and bupivacaine. Anesth Analg 1982: 61: 961–967. 74. Jurgens PE. A study of effocaine. Anesthesiology 1955: 16: 615–622. 75. Reisner LS, Hachman BN, Plumer MH. Persistent neurologic and adhesive arachnoiditis following intrathecal 2-Chloroprocaine injection. Anesth Analg 1980: 59: 452–454. 76. Wang BC, Hillman DE, Spielholz NI, Turndorf H. Chronic neurological deficits and Nesacaine-CE- and effect of the anesthetic, 2-chloroprocaine, or the antioxidant, sodium bisulfite? Anesth Analg 1984: 63: 445–447. 77. Kalichman MW, Powell HC, Reisner LS et al. The role of 2chloroprocaine and sodium bisulfite in rat sciatic nerve edema. J Neuropathol Exp Neurol 1986: 45: 566–575. 78. Tapia DP, Waxler BJ, Hursh D, Aldrete JA. Effects of sodium bisulfite on Sprague-Dawley rat sciatic nerve. A preliminary report. Reg Anesth 1990: 15: 90. 79. Huhtala J, Tarkkila P, Tuominen M. transient radicular irritation after anaesthesia with hyperbaric 5% lidocaine. Acta Anaesthsiol Scand 1995: 39: 426. 80. Panadero A, Monedero P, Fernandez-Liesa A et al. Repeated transient neurological symptoms after spinal anaesthsia with hyperonic 5% lidocaine. Br J Anaesth 1998: 81: 471–472. 81. Ramasamy D, Eadie R. transient radicular irritation after spinal anaesthesia with 2% isobaric lignocaine. Br J Anaesth 1997: 79: 394–395. 82. Tarkkila P, Huhtala J, Tuominem M et al. Transient radicular irritation after bupivacaine spinal anesthesia. Reg Anesth 1996: 21: 26–29.

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J. A. Aldrete 83. Meyers RR, Kalichman MW, Reisner LS et al. Neurotoxicity of local anesthetics; altered perineural permeability, edema and nerve fiber injury. Anesthesiology 1986: 64: 29–35. 84. Bainton CR, Strichartz GR. Concentration dependence of lidocaine-induced irreversible conduction loss in frog nerve. Anesthesiology 1994: 81: 657–667. 85. Lambert LA, Lambert DH, Strchartz GR. Irreversible conduction block in isolated nerve by high concentrations of local anesthetics. Anesthesiology 1994: 80: 1082–1094. 86. Carpenter RL, Hogan QH, Liu SS, Crane B, Moore J. Lumbosacral cerebrospinal fluid Volume is the primary determinant of sensory block extent and duration during spinal anesthesia. Anesthesiology 1998: 89: 24–29. 87. Bromage PR. Nerve injury and paralysis related to spinal and epidural anesthesia. Reg Anesth 1993: 18: 481–484. 88. Rowlingson JC. Transient neurological symptoms now with phenylephrine? (edtorial). Anesthesiology 1997: 87: 737–738. 89. Coombs DW. Potential hazards of transcatheter serial epidural phenol – neurolysis. Anesth Analg 1985: 64: 1205–1207. 90. Barnards CM, Hill HF. Morphine and alfentanil permeability through the spinal dura, arachnoid and pia matter of dogs and monkeys. Anesthesiology 1990: 73: 1214– 1219. 91. Kim RC, Porter RN, Choi BH, Kim SW. Myelopathy after the intrathecal administration of hypertonic saline. Neurosurgery 1988: 22: 942–945. 92. Katz JA, Sehlhorst S, Blisard KS. Histopathologic changes in primate spinal cord after single and repeated epidural phenol administration. Reg Anesth 1995: 20: 283–290. 93. Reynolds F, Speedy HM. The subdural space: the third place to go astray. Anaesthesia 1990: 45: 120–123. 94. Moore DC, Thompson GE. Commentary: neurotoxicity of local anesthetics – an issue or a scapegoat. Reg Anesth Pain Med 1998: 23: 605–610. 95. Moore DC. ‘No paresthesias – no anesthesia’, the nerve stimulator or neither. Reg Anesth 1997: 22: 388–390. 96. Winchell SW, Wolfe R. The incidence of neuropathy following upper extremity nerve blocks. Reg Anesth 1985: 10: 12– 15. 97. Groh GI, Gainor BJ, Jeffries JT et al. Pseudoaneurysm of axillary artery with median nerve deficit after axillary block anesthesia. J Bone Joint Surg 1990: 72: 14071408. 98. Ben-David B, Stahl S. Axillary block complicated by hematoma and radial nerve injury. Reg Anesth Pain Med 1999: 24: 264–266. 99. Aldrete JA, Gabriel-Velasco A, Moshin AU, Roztoczynska H, Brown T. skin to lumbar epidural space distances as determined by magnetic resonance imaging. Pain Clinic 1997: 10: 101–106. 100. Aldrete JA, Moshin AU, Zapata JC, Ghaly RF. Skin to cervical epidural space distances as determined by MRI. consideration of the Hump pad. J Clin Anesth 1998: 10: 309–313. 101. Aldrete JA. Experience with a 25 gauge epidural needle. Pain Digest 1998: 8: 260–263. 102. Klemm H. De Perinerium al Diffusionbarriere gegenüber Peroxydase bel epi und endoneuralerApplikation. Z Zellforsch Mikronsk Anat 1970: 108: 431–445. 103. Selander D, Dhune´r KG, Lundborg G. peripheral nerve injury due to injection needles used for regional anesthesia. Acta Anaesthesiol Scand 1977: 21: 182–186. 104. Selander D, Edshage S, Wolff T. Paraesthesiae or no paresthesiae? Acta Anaesthesiol Scand 1979: 23: 27–33. 105. Gentili F, Hudson AR, Hunter D, Kline DG. Nerve injection injury with local anesthetic agents. a light and electrons microscopic and horseradish perofidase study. Neurosurgery 1980: 6: 263–272.

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106. Faccenda KA, Finucane BT. Complications of regional anaesthesia. Incidence and prevention. Drug Saff 2001: 24: 413–442. 107. Paech MJ. Unexplained neurological deficit after uneventful combined spinal epidural anesthetisa for cesarean section delivery. Reg Anesth 1997: 22: 479–482. 108. Selander D, Braddsand R, Lundborg G et al. Local anesthetics: importance of mode of application, concentration and adrenaline for the appearance of nerve lesion. Acta Anaesthesiol Scand 1979: 23: 127–136. 109. Bromage PR, Benumof JL. Paraplegia following intracord injections during attempted epidural anesthesia. Reg Anesth Pain Med 1998: 23: 104–107. 110. Toussirout E, Benayoun P, Despaux J, Vieille J, Kremer P, Wendling D. Proximal paraparesis following spinal anesthesia. Rev Rheum Engl Ed 1996: 63: 450–452. 111. Aldrete JA, Ferrari HA. Myolopathy after thoracic epidural anesthesia. Anesth Analg (in press). 112. Reynolds F. Damage to the conus medullaris following spinal anaesthesia. Anaesthesia 2001: 56: 238–247. 113. Krane EJ, Dalens BJ, Murat I et al. The safety of epidurals placed during general anesthesia. Reg Anesth Pain Med 1998: 23: 433–438. 114. Horlocker TT, Caplan RA. Should regional blockade be performed in anesthetized patients? ASA Newsl 2001: 65: 5–6. 115. Okell RW, Sprigge JS. Unintentional dural puncture, a survey of recognition and management. Anesthesia 1987: 42: 1110–1113. 116. Renck h. neurological complications of central nerve blocks. Acta Anaesthesiol Scand 1995: 39: 859–868. 117. Katz Y, Morkovitz R, Rosenberg B. Pneumocephalus after inadvertent intrathecal air injection during epidural block. Anesthesiology 1990: 73: 1277–1279. 118. Saberski LR, Kondamiuri S, Omorvonmi VO et al. Identification of the epidural space. Is loss of resistance to air a safe technique? Reg Anesth 1997: 22: 3–15. 119. Aldrete JA. Identification of the epidural space: is loss of resistance to air a safe technique? Reg Anesth 1997: 22: 590– 591. 120. Passamante AN. Spinal anesthesia and permanent neurologic deficit after interscale block. Anesth Analg 1996: 82: 873–874. 121. Benumoff JL. Permanent loss of cervical spinal cord function associated with interscalene block performed under general anesthesia. Anesthesiology 2000: 93: 154–156. 122. Yuen EC, Layzer RB, Weitz S. Neurological complications of lumbar epidural anesthesia and analgesia. Neurology 1995: 45: 1795–1801. 123. Usubiaga JE, Usubiaga LE, Brea L. Effect of saline injections on epidural and subarachnoid space pressures and relation to postspinal anesthesia headache. Anesth Analg 1967: 46: 293–296. 124. Aldrete JA. Persistent postdural puncture headache treated with epidural infusion of dextran. Headache 1994: 34: 265– 267.

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