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REVIEW

Neurologic Deficits following Epidural or Spinal Anesthesia Robert E. Kane, MS, MBA

OUR CASES of prolonged neurologic deficit fol- F lowing attempted epidural block with chloropro- caine were recently reported (I, 2). Two patients received epidural chloroprocaine during labor; fol- lowing delivery, motor paralysis of the lower extrem- ities was noted. Complete recovery of function was seen by 72 hours after delivery in one case. The other patient showed gradual partial recovery after 4 weeks. In the two other patients, total spinal anesthesia oc- curred following administration of 27 ml of 2% or 28 ml of 3% chloroprocaine for postpartum tuba1 ligation. Artificial ventilation was instituted and the operation was completed, but motor paralysis of the lower extremities was noted following regression of anes- thesia in both patients, accompanied by urinary and fecal incontinence and partial sensory loss in one patient. Gradual return of function occurred over 72 hours in one case and over 4 weeks in the other, but tne latter patient developed symptoms of adhesive arachnoiditis 7 weeks following the operation.

As part of the evaluation of these cases, a literature search was conducted for previous reports of similar sequelae following epidural or spinal anesthesia. The search was begun by consulting Index Medicus and computerized files including Medline, Toxline, and Excerpta Medica. Its purpose was to establish whether or not paralysis had been reported following epidural or spinal anesthesia with local anesthetics other than chloroprocaine. Reports of large series of epidural or

Received from the Pennwalt Pharmaceutical Division, Rochester,

Reprint requests to Mr. Kane, Pennwalt Pharmaceutical Divi- New York. Accepted for publication October 31, 1980.

sion, PO Box 1710, Rochester, NY 14603.

spinal anesthetics were collected to give an indication of the incidence of neurologic sequelae. Discussions of causative factors in published case reports led to literature dealing with spinal paralysis unrelated to local anesthesia and to pertinent experimental studies.

This review summarizes the findings of published surveys of major regional anesthesia and lists case reports of severe neurologic sequelae in a series of tables. The signs and symptoms associated with known and suspected causes of neurologic deficit are described, and relevant experimental studies are dis- cussed. Finally, previously reported cases are com- pared to the recently reported chloroprocaine cases in an effort to determine the etiology of the latter.

Neurologic Deficits following Epidural Anesthesia

Seven articles, which report on large series of pa- tients undergoing epidural anesthesia, are summa- rized in Table 1. Local anesthetics included bupiva- caine, chloroprocaine, hexylcaine, and lidocaine. In these surveys, the incidence of serious neurologic sequelae was low. Only three patients suffered per- sistent paralysis or paresis of the lower extremities in more than 50,000 cases. An extensive review of the literature by Dawkins (10) also indicates that paralysis occurs infrequently following lumbar or thoracic ep- idural block. Transient paralysis was reported in 48 cases @.I%), whereas seven patients suffered perma- nent paralysis in this series of 32,718 cases (0.02%). In his own series of 4,000 epidural blocks, Dawkins had one case of permanent paraplegia; a second patient suffered paresis that improved over 2 months.

ANESTHESIA AND ANALGESIA Vol60, No 3, March 1981 1 50

KANE

In contrast to the above surveys, a number of individual case reports have been published in which serious neurologic deficit has followed epidural an- esthesia. Table 2 includes 30 cases of lower paralysis of undetermined etiology in addition to the four chloroprocaine cases cited above. Various local anes- thetics were used, including lidocaine, procaine, tri- mecaine, mepivacaine, and hexylcaine. Many of the

TABLE 1 Survey Reports of Epidural Anesthesia

solutions contained epinephrine. Six of the cases listed in Table 2 were unrelated to the anesthetic solution itself. Cord compression due to epidural hematoma occurred in four patients. All of these patients were receiving anticoagulant therapy. In one of the other cases, paralysis was due to unrecognized preexisting stenosis of the spinal canal. The patient reported by Craig et a1 (14) received a 40-mI epidural

~~

Anesthetics Procedures Neurologic sequelae No. of Reference patients

Bleyaert (3) 3,000 Bupivacaine, 0.1 25%. 1 :800,000 epineph- Obstetric None

Moore (4) 11,080 Bupivacaine, 0.25%, 0.5%, or 0.75%. with Surgical, obstetric, diag- None

Holdcroft (5) 1,000 Bupivacaine. 0.5% or lidocaine, 1.5% (32 Obstetric 1 foot drop; 1 paresthesia of thigh

Moore (6) 7,286 Lidocaine + tetracaine with epinephrine in Surgical, obstetric 1 bilateral paralysis of quadriceps muscles

rine

or without epinephrine nostic

patients)

6,270 patients, various agents in remain- ing cases

caine, 3% (700 patients), hexylcaine, 2% (200 patients)

Lund (7) 10,000 Lidocaine, 2% (8,000 patients). chloropro- Surgical, obstetric, diag- 1 paresis of 1 leg (subarachnoid hexyl- nostic caine); 4 paresthesias of thigh; 1 persist-

ent numbness; 3 bladder or rectal incon- tinence

paraplegia (one of 5,091 surgical cases)

nostic (subarachnoid lidocaine); 1 paresthesias.

Eisen (8) 9,532 Lidocaine Obstetric 16 paresthesias; 9 numbness of thigh; 1

Bonica (9) 3.885 Various, mostly lidocaine Surgical, obstetric. diag- 1 hypalgesia of trunk, weakness of leg

numbness weakness of leg

TABLE 2 Severe Neurologic Deficit following Epidural Block: Case Reports

Reference ::;:is Anesthetics Neurologic sequelae Etiologic factors

Braham (1 1) 1

1

Catterberg (1 2) 11

Chaudhari (13) 1

Craig (1 4) 1

Davies (1 5) 1

Oawkins (1 0) 1

1

2 Gingrich (1 6) 1 Harrison (1 7) 1

Hellmann (1 8 ) 1 Helperin (1 9) 1

lagudin (20) 1

Lund (7) 1 Moore (6) 1 Urquhart-Hay (21) 1

Usubiaga (22) a

Procaine, 2%

Procaine. 2%

Lidocaine with epinephrine

Lidocaine. 1.5%, 1:200.000

Lidocaine. 1.5%. 1 :200,000

Lidocaine, 1.75% 1:

Lidocaine, 2%

Lidocaine, 2%. 1 :80.000 epinephrine

Not reported Lidocaine. 1 % Lidocaine, 1.5%. 1 :200.000

epinephrine Not stated Lidocaine. 2%, 1 :200,000

epinephrine Trimecaine. 2.5%

Hexylcaine, 2% Not stated Lidocaine, 1.5%. and 1 :

200,000 epinephrine Lidocaine or mepivacaine

epinephrine

epinephrine

300,000 epinephrine

Permanent paraplegia, adhesive arach-

Paralysis of iliopsoas and quadriceps

Paraplegia

Paraplegia

Severe paraparesis. very slow return of

Paraplegia, cellular degeneration of ante-

Permanent paraplegia, gross T6-12 de-

Partial sensory and motor loss of legs,

Temporary or permanent paralysis Paralysis of legs, sensory loss to T-I 0 Partial sensory and motor paralysis of

lower limbs, incomplete recovery. Paraplegia Moderate-severe weakness of legs, sen-

Severe weakness of lower limbs, partial

Partial paralysis of one leg Bilateral paralysis of quadriceps muscles Paraplegia, incomplete recovery, is-

chemic necrosis of lumbar spinal cord Paraplegia. loss of sphincter control

noiditis

muscles bilaterally

function over 2 years.

rior spinal cord T-I 0 downward

struction of spinal cord

full recovery after 2 mo

sory deficit

recovery over 2 mo

Possible subarachonid injection

Unknown

High concentrations of epinephrine or

Stenosis of lumbar spinal canal

Epidural injection of saline containing

Hypotension

Unknown

Hypotension

Epidural hematoma (anticoagulants) Epidural hematoma (anticoagulants) Hypotension

Unknown Epidural hematoma (anticoagulants)

Unknown

Subarachnoid injection Unknown Hypotension

Unknown

circulatory deficit

1.5% of benzyl alcohol

151 ANESTHESIA AND ANALGESIA Vol 60, No 3. March 1981

NEUROLOGIC DEFICITS

injection of saline containing the preservative benzyl alcohol. This was administered several hours after an inadvertent dural puncture and the authors speculate that the preservative may have caused the neurologic sequelae.

In the remaining cases, the cause of residual paral- ysis was unknown or was considered to be related to the epidural anesthetic solution or procedure. Severe or prolonged hypotension resulting from the epidural anesthesia occurred in at least four patients, and may have resulted in cord ischemia or infarct. In the 11 cases reported by Catterberg and Insauti (14, the addition of epinephrine to the local anesthetic was suggested as being responsible for localized vasocon- striction and resulting spinal cord lesions. Inadvertent subarachnoid injection of local anesthetic was sus- pected in two cases. In one patient, 25 to 30 ml of 2% procaine was intended for epidural administration. Subarachnoid injection was suspected because of headache following the procedure. Weakness pro- gressing to complete paralysis of the lower limbs developed over a period of weeks; laminectomy re- vealed arachnoiditis. The second patient experienced persistent partial paralysis of one leg following inad- vertent subarachnoid block with 2% hexylcaine.

In a monograph by Usubiaga (24 , 65 cases of neurologic complications following epidural anesthe- sia are presented. Many of these were previously unpublished. Probable causes included trauma, in- jected material, infection, vascular lesions, or preex- isting pathology. In eight patients, the cause of para- plegia was unknown or undetermined.

Neurologic Deficits following Spinal Anesthesia

Seven survey reports of spinal anesthesia are listed in Table 3. Results of spinal anesthesia in more than 65,000 patients were reviewed in these studies. Var- ious local anesthetics were used, including bupiva- caine, dibucaine, lidocaine, mepivacaine, procaine, and tetracaine. Vasoconstrictors were added to the solutions in at least 10,000 cases. From these reports, it appears that severe neurologic deficits following spinal anesthesia are rare, although several papers report only sequelae clearly related to the spinal anesthesia. As shown in Table 4, a number of indi- vidual case reports have appeared in which partial or, complete paralysis occurred following spinal anesthe- sia. Three types of syndromes appear to be repre- sented by these cases. The most benign is aseptic meningitis characterized by high fever, headache, nu- chal rigidity, and photophobia. The cerebral spinal fluid (CSF) pressure is increased, and CSF smears show high counts of polymorphonuclear cells; cul- tures of CSF are negative. Symptoms usually appear within 24 hours of spinal anesthesia and recovery occurs spontaneously within several days to a week (38).

A second type of neurologic deficit following spinal anesthesia has been called the “cauda equina syn- drome.” The cases presented by Ferguson and Wat- kins (36) are characterized by urinary and fecal incon- tinence, localized sensory loss in the perineal area, and varying degrees of leg weakness. These symp-

TABLE 3 Survey Reports of Spinal Anesthesia

Anesthetics Procedure Neurologic sequelae No. of

patients Reference

Kortum (23) Bergman (24)

Phillips (25)

2,592 Bupivacaine, 0.5% 10.000 Lidocaine, mepivacaine, bu-

10,440 Lidocaine pivacaine

Moore (26) 11,574 Tetracaine, dibucaine; with epinephrine or phenyleph- rine in 8,852

Sadov (27) 20,000 Tetracaine, procaine, dibu- caine

Dripps (28); Vandam (29-31 ) 10,098 Tetracaine. procaine, dibu- caine; with epinephrine in 2,000

Brown (32) 600 Tetracaine

Surgical 1 lumbar plexus injury Various None

Obstetric, surgical

Surgical, obstetric

8 persistent peripheral neurop- athy

1 persistent muscular weak- ness of legs, impotence

Various

Surgical

1 paraplegia due to spinal tu- mor; 3 meningitis

No major neurologic sequelae; 2 foot drop; 1 leg weakness (trauma); 12 exacerbation of previous neurologic disease

2 peroneal paresis. unilateral

ANESTHESIA AND ANALGESIA Vol60, No 3. March 1981 1 52

KANE

TABLE 4

Case Reports: Severe Neurologic Deficits following Spinal Anesthesia

Anesthetics Neurologic sequelae Etiologic factors No. of Reference patients

Bergner (33)

Courville (34)

Desnoyers (35)

Ferguson (36)

Finch (37)

Goldman (38)

Guttman (39)

Kennedy (40)

Nicholson (41)

Paddison (42)

Payne (43)

Seigne (44)

Winkelman (45)

Williams (46)

4

2 1 2

1

1

14

I

5

1

5

2

1

2

1

1 1 3

2 1

1

f

1

3

8

1

8

Tetracaine, 10 mg, in glucose, with 5 mg of ephedrine in 2 patients

Dibucaine. 2.5 mg. in glucose Not stated Not stated

Not stated

Tetracaine. 1 % in 10% dextrose

"Heavy" durocaine (1 0% procaine in 15% ethanol + glycerine and gliadin or gum acacia)

Tetracaine, 10 mg, phenylephrine, 4 mg in dextrose solution

Tetracaine. 4 mg (4 patients) or procaine, 3.3% (1 patient)

Procaine, 25 mg. ammonium sul- fate, 400 mg. in 5 ml of sterile water

Procaine

Dibucaine. 1 :1,500

Piperocaine, 10%

Tetracaine

Procaine

Not stated Tetracaine-dextrose Tetracaine-dextrose

Procaine in CSF Tetracaine

Tetracaine in dextrose

Dibucaine. 0.2%

Tetracaine. 0.1 %

Not stated

Not stated

Procaine

Not stated

Radiculitis, ascending myelitis, adhe- sive arachnoiditis. meningo encepha- litis, death in 4 patients

Incontinence of bladder and rectum Numbness, weakness, pain of lower ex-

tremities, adhesive arachnoiditis Quadraplegia. death, necrosis of cen-

tral gray matter of cord Paraplegia developed 2-3 days after

spinal anesthesia Urinary and fecal incontinence, sensory

loss in saddle area, leg weakness of varying degree (cauda equina syn- drome)

Weakness of right quadriceps femoris muscle group

Aseptic meningitis (fever, nuchal rigid- ity. headache, photophobia). recov- ery over several days to 1 week

Flaccid paralysis of lower extremities, urinary retention, degenerative le- sions in lower spinal cord

Weakness of lower limbs progressing to paraplegia, adhesive arachnoiditis

Flaccid paresis or paralysis of lower limbs, urinary incontinence, constipa- tion

constipation

marked weakness of legs, numbness, impotence in one patient

sensory loss

Leg weakness, perianal numbness,

Bladder and bowel incontinence,

Progressive weakness of legs, partial

Incontinence. paresis of one leg Permanent paraplegia Paralysis of lower limbs

Paresis of lower limbs Paralysis of legs, incontinence

Progressive adhesive arachnoiditis. leading to hydrocephalis and death

Progressive weakness of legs, bladder incontinence, constipation: adhesive arachnoiditis

Fever, headache, nuchal rigidity, photo- phobia, aseptic meningitis

Weakness progressing to paraplegia, progressive arachnoiditis, death

Weakness or paralysis of legs: gradual partial recovery

Progressive weakness and sensory loss leading to complete paraplegia, ad- hesive arachnoiditis

Transverse myelitis appearing 3 mo to 2% yr after spinal, constrictive arach- noiditis

Unknown, undetected chemical con- tamination of the spinal solutions suspected

Unknown Unknown

Shock during operation

Metastatic peridural tumor

Authors consider high concentration of procaine as cause of the syn- drome

Unknown

Problem attributed to soaking sy- ringes with a phenolic disinfectant

Vasospasm induced by ammonium sulfate or procaine suggested by pathology

Unknown

Unknown

Unknown

Unknown

Unknown

Unknown Unknown Metastatic carcinoma to cord, dura

Unknown Possible contamination of local anes-

thetic with formaldehyde Authors postulate that detergent (Al-

konox) used to wash syringes was responsible

and vertebrae

Unknown

Unknown

Sequelae attributed to inadequate rinsing of detergent solution from syringes

Patient received spinal anesthesia with procaine 3 times over 2 mo

Unknown

toms usually had their onset immediately after the effects of the spinal anesthesia had worn off, and may be permanent or show gradual regression over periods of weeks or months.

Adhesive arachnoiditis is probably the most serious sequela of spinal anesthesia. Typical cases are de-

scribed by Bergner et a1 (33), Kennedy et a1 (40), and Winkelmen (45). Usually, gradual progressive weak- ness and sensory loss of the lower extremities occurs beginning several weeks to several months after spinal anesthesia. This may lead to complete paraplegia, and, in severe cases, to death. Laminectomy or au-

153 ANESTHESIA AND ANALGESIA Vol 60, No 3, March 1981

NEUROLOGIC DEFICITS

topsy reveals a proliferative reaction of the meninges with adhesive arachnoiditis and constriction of the spinal cord.

In Table 4 are listed several cases in which paraple- gia or paralysis following spinal anesthesia was due to preexisting pathology, such as metastatic lesions to the cord or meninges. These cases illustrate the po- tential ability for spinal anesthesia to precipitate neu- rologic deficits in patients with central nervous system pathology, or for spinal anesthesia to be temporally, but purely coincidentally, related to the onset of neurologic deficits due to other causes.

Possible Causes of Spinal Cord Injury

Spinal Cord Ischemia

Four cases of lower limb paralysis following pro- longed hypotension during surgery are summarized in Table 5. All patients received epidural anesthesia with lidocaine plus epinephrine, and systolic blood pressure remained below 100 mm Hg during surgery. After the effects of the anesthesia had worn off, a flaccid paralysis or paresis of the lower extremities was noted, with loss of bladder or rectal function in two cases. Neurologic examination revealed the ab-

sence of knee and/or ankle jerks. Sensation was impaired in two patients, and the outcome in these cases ranged from no change in neurologic signs to a gradual moderate return of motor function. In the two patients who died from intercurrent illness, autopsy revealed degenerative changes of the lower spinal cord indicative of ischemic necrosis.

It has been suggested that the spinal cord infarction in these cases was associated with prolonged arterial hypotension during surgery (47). Other factors must have been involved, however, as epidural anesthesia is frequently employed to produce controlled hypo- tension during surgery without producing neurologic damage. In the above cases, factors such as posture, caval compression, and use of epinephrine may have contributed to a compromise of blood flow to the lumbosacral cord (47). Whatever the exact causes, partial or complete vascular occlusion may be respon- sible for spinal cord ischemia or infarct. The blood supply to the areas of the cord between adjacent radicular vessels is precarious (21). Individual ana- tomic differences may be important as well; a defi- ciency in segmental supplements of the anterior spinal artery may make some people especially vulnerable to spinal cord ischemia (48).

TABLE 5 Cases of Spinal Cord infarction Due to Arterial Hypotension during Epidural Anesthesia

Davies (1 5) Harrison (1 7) Urquhart-Hay (21) Usubiaga (22): case 35

Epidural at L1-2 with 27 ml of Epidural at L4-5 with 30 ml of Epidural at L3-4 with 36 ml of Epidural at L3-4 with 25 ml Anesthesia

Operative sys-

Onset of paral-

Paralysis sites

tolic BP

ysis

Reflexes

Sensation

Outcome

Postmortem findings

1.75% lidocaine, 1 : 300,000 epinephrine

80-90 mm Hg. 45 min

1 st day after surgery

Both legs paralyzed; very slight movement of right foot, left toes; loss of blad- der and rectal function

Knee and ankle jerks absent; no plantar responses

Loss to pinprick to level of umbilicus: fine and course touch intact; Posture and vi- bration senses intact

Very slight improvement; re- turn of bladder control at 5 weeks; death from intercur- rent disease nine months after surgery

Bilateral degeneration of spinal cord from T-10 downwards, confined to distribution of anterior spinal artery; no evidence of arachnoiditis

1.5% lidocaine, 1 :200,000 epinephrine

55-65 mm Hg, falling to 50 mm Hg after surgery

Immediately after surgery

Severe motor weakness of legs, hips and ankles, more oronounced on left

Knee and ankle jerks absent: plantar responses flexor

Loss to pinprick L4-5 seg- ments; relative sparing be- low S-1 , paraesthesia of feet 1st day, pain in mid- lumbar region 7th day after surgery

Gradual partial return of mo- tor power over 4 weeks, no change m sensory deficit; motor weakness present at 2% yr

1.5% lidocaine, 1 :200.000 epinephrine

80-90 mm Hg

Immediately after surgery

Severe symmetrical motor weakness affecting cord segments Li-S1 with less involvement of L3-4 level, loss of bladder function

Knee jerks brisk, ankle jerks absent, plantar responses absent

Sensation to light touch and pinprick normal

Return of bladder control after 8 days; no change in neuro- logic signs in legs; death 14 mo later from intercurrent disease

Bilateral necrosis of anterior and posterior horns and nerve roots of lower lumbar cord. degenerative changes of white matter; appearance of ischemic necrosis

of 1.5% lidocaine. 1 : 200,000 epinephrine

60-85 mm Hg

Immediately after surgery

Both legs paralyzed: slight movement remained in left foot

Loss of deep tenden re- flexes

No sensory deficit

Slight improvement in the left leg with physical ther- apy; permanent complete paralysis of right leg; par- tial paralysis the left

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KANE

Ditzler and McIlver (49) described a case of flaccid paraplegia following hypotension during general an- esthesia. Neurologic examination led to a diagnosis of anterior spinal artery thrombosis. It was believed that preexisting arteriosclerosis of the anterior spinal ar- tery and the period of serious hypotension during surgery permitted the thrombosis.

Many cases of paralysis due to occlusion of the anterior spinal artery have been reported in addition to cases associated with hypotension during regional or general anesthesia. Various causes have been cited including vascular spasm, trauma, arteriosclerosis, syphilitic thrombosis, or interference with aortic blood flow (21). Steegman (50) has described six cases of anterior spinal artery syndrome in which throm- bosis of the anterior spinal artery was due to syphilitic arteritis, spinal arteriosclerosis, or infection. Clinical signs varied with the level of the lesion. With lumbar cord involvement, a flaccid paralysis of the lower extremities with sphincter disturbance was seen, and pain and temperature sense was lost below the seg- mental level of the lesion. The usual outcome was the return of rectal and bladder control within a few days to months. Partial return of sensation and gradual recovery of motor power may occur.

A similar pattern of flaccid paraplegia or quadra- plegia, incontinence, and sensory loss was seen in the cases of anterior spinal artery thrombosis reported by Wells (51). Cross-clamping of the aorta above the renal arteries for prolonged periods during surgery can also produce spinal cord injury due to ischemia (22). Symptoms appear immediately after surgery and may be severe and permanent. These include flaccid paralysis, abolition of segmental reflexes, anesthesia, and sphincter incontinence. Similar symptoms have been reported following abdominal aortography (52, 53), shock due to cardiac arrest or coronary infarction (54), and damage to intercostal vessels by surgery, trauma, or diseases of the spine (55).

Studies in animals have corroborated the propen- sity of cord ischemia for production of paralysis or paresis. In rabbits, compression of the abdominal aorta for 20 to 25 minutes produced flaccid paralysis of the hind limbs in some animals and paresis in others (56), ligation of the intercostal arteries led to paraplegia in dogs (57), and obstruction of blood flow to the surface vessels of the cervical cord in dogs produced myelopathy and hemiparesis (58). In a re- view of studies in various animal species, Heymans (59) noted that paralysis can be induced by interrup- tion of blood flow to the spinal cord for periods ranging from 1 to 20 minutes. Histologically, the

anterior horn cells were the most severely damaged, as in human cases. On the other hand, restoration of function occurred in some species after interruption of circulation for as long as 40 minutes.

Trauma

Traumatic injury to the spinal cord or nerve roots during spinal or epidural anesthesia is an infrequent cause of neurologic disease. Vandam and Dripps (31) report one case in which paresthesias in legs, thighs, and feet occurred during multiple attempts at lumbar puncture. After surgery the patient developed leg weakness, loss of position sense, and backache. Symptoms improved over 3 months. In the same series of 10,098 patients given spinal anesthesia, there were 17 cases of minor sequelae after paresthesias was elicited during lumbar puncture. Symptoms in- cluded pain, paresthesias, or localized numbness of the feet or legs persisting for 1 day to 1 year.

The occurrence of numbness, weakness, or pain in the legs following forceps delivery has been reported (60, 61). Symptoms are often in the distribution of the sciatic nerve and foot drop is common. Recovery is seen within several months. The most likely cause is said to be lumbosacral cord trauma by obstetric for- ceps (60). Murray (62) reviewed 201 published cases of postpartum paralysis of the lower extremities caused by injury to the sacral plexus. Bilateral lesions were rare, but did occur. Foot drop associated with nerve injury to the sacral plexus can be distinguished from the more frequent paralysis caused by compres- sion of the common peroneal nerve between the head of the fibula and the stirrup used for maintenance of the lithotomy position (62). Pain is rare in the latter cases and motor loss is limited to the peripheral distribution of the peroneal nerve.

Cases of nerve trauma due to the epidural catheter (63) or to abdominal retractors (64) have also been reported. Signs of localized weakness and hypoes- thesia are seen, usually with complete recovery over a period of several weeks or months.

Chemical Contamination of Local Anesthetic Solutions

Contamination of local anesthetic solutions with detergents or other chemicals has often been blamed for production of neurologic sequelae to spinal anes- thesia. The cases of aseptic meningitis reported by Goldman and Sanford (38) were attributed to soaking syringes with a phenolic disinfectant. A similar case reported by Seigne (44) was believed to be due to

ANESTHESIA AND ANALGESIA Vol 60, No 3, March 1981 155

NEUROLOGIC DEFICITS

contamination with detergent, although no real evi- dence for this was presented.

The irritant effect of contaminants in local anes- thetic solutions can produce a progressive prolifera- tive reaction of the meninges leading to adhesive arachnoiditis (65). Winkelman (45) reported 11 cases of progressive weakness following spinal anesthesia. These cases attributed to incomplete rinsing of deter- gent solutions from syringes. In these cases, symp- toms usually were first noted within 1 or 2 weeks following spinal anesthesia. The milder cases resem- bled cauda equina syndrome, but others showed pro- gressive severe impairment of function. Four patients died following ascending involvement of the cord and its membranes, eventually producing a fluid block over the vertex of the brain and internal hydroceph- alus. Pathologic examination in one case showed hy- perplasia of the pia mater with compression of nerve roots along the entire cord.

Further cases of paraplegia due to adhesive arach- noiditis, sometimes resulting in death, have been reported. Bergner et a1 (33) suspected the cause in their six cases to have been an undetected chemical contaminant of the spinal solutions. The case reported by Paddison and Alper (42) was attributed to a deter- gent solution. Kennedy et a1 (40) and Williams (46) on the other hand, believed that the local anesthetic solutions were responsible for the sequelae, and Payne and Bergentz (43) recommended that large volumes or continuous injections of local anesthetics should not be used for spinal anesthesia.

Local Anesthetic Solutions

Central nervous system injury following spinal an- esthesia has been attributed to a direct neurotoxic effect of local anesthetic agents or their vehicles. Ferguson and Watkins (36) reported 14 cases of cauda equina syndrome following spinal anesthesia with heavy Durocaine, a preparation in use in the 1930s that contained 10% procaine hydrochloride in 15% ethanol, glycerine, and gum acacia or gliadin. Onset of symptoms followed immediately after regression of the spinal anesthesia. The most constant finding was sphincter disturbances, but muscle weakness, usually of the lower legs, was sometimes present. Localized impairment of light touch, pinprick, and temperature sense was seen, mainly in the buttocks, but extending to the thighs in some cases. Knee and ankle jerk reflexes were diminished or absent. Most patients recovered bladder and rectal function over a period of weeks, as well as return of motor strength.

The sensory loss was permanent in 13 of the 14 cases. The incidence of cauda equina syndrome with spinal Durocaine was estimated to be between one in 90 and one in 155.

MacDonald and Watkins (66) reported a study of spinal anesthesia in cats using heavy Durocaine. The vehicle components, alcohol and glycerine, did not cause paralysis, whereas 10% procaine or heavy Dur- ocaine produced symptoms similar to cauda equina syndrome in some animals. Lower concentrations of procaine did not produce paralysis. Based on this study, Ferguson and Watkins (36) concluded that procaine itself was the causative agent in the produc- tion of the cauda equina syndrome, with paralysis of nerve roots exposed to the greatest concentration of the drug, and function of the smaller autonomic fibers being most impaired.

Cauda equina syndrome has been reported follow- ing spinal anesthesia with drugs other than procaine. Ferguson and Watkins (36) cited seven cases pub- lished between 1907 and 1927 in which the anesthetic agent was Stovaine (amylocaine). Kennedy et a1 (40) and Nicholson and Eversole (41) reported cases in the 1940s in which cauda equina syndrome followed spinal anesthesia with piperocaine or tetracaine. Symptoms resembled those reported by Ferguson and Watson (36). Courville (34) in 1955 reported cases with similar symptoms, but the spinal anesthetic was not identified.

In contrast to the above reports, the low incidence of complications following spinal anesthesia in the surveys listed in Table 3 is not strongly indicative of a direct neurotoxic effect of local anesthetic agents. Chloroprocaine appears to be similar to other agents in this respect. Foldes and McNall (67) administered 3.3% chloroprocaine intrathecally to 214 patients for various surgical procedures without evidence of neu- rologic sequelae. Greene (65) indicates that the inci- dence of complications due to spinal anesthesia has decreased since the 1940s, probably due to the use of lower concentrations of local anesthetics, and the fact that solutions containing such substances as alcohol, acacia, and strychnine are no longer used.

The report of prolonged spinal anesthesia by Ans- bro et a1 (68) supports the conclusion that local an- esthetics in concentrations normally used in clinical practice produce no direct toxic effects on the cord. Continuous spinal anesthesia for ?,11, or 14 days was maintained with injections of procaine or dibucaine every 4 hours through a catheter. The only sequelae were transient fever, back pain, and stiff neck on day 14 in one patient; all symptoms cleared upon with-

ANESTHESCA AND ANALGESIA Vol60, No 3, March 1981 1 56

KANE

drawal of the catheter. Kamsler (69) found no in- creases in spinal fluid cell counts following single administrations of procaine, tetracaine, or hexylcaine, with or without dextrose, ephedrine, or epinephrine. However, catheter techniques produced large in- creases in spinal fluid leukocyte counts. These changes occurred in some cases in which no local anesthetic was injected, confirming that the catheter and not the local anesthetic was the causative factor. The lack of histologic changes in human spinal cords after spinal anesthesia with procaine (70) supports a similar conclusion. In another study (71), no histologic changes were seen in the spinal cord of a patient who had received 81 spinal anesthetics in 24 years.

Animal Studies

A number of animal studies have been conducted to investigate the possible neurotoxic effects of local anesthetics. Davis et a1 (72) in 1931 reported a study in which dogs were given intrathecal injections of Spinocaine, Gravocaine, and Scurocaine, three pro- caine preparations in use at that time. Dose-related but reversible histologic changes were seen, including an inflammatory meningeal reaction and secondary degenerative changes in the spinal cord.

In contrast to the above results, Lundy et a1 (73) showed that the central nervous system of the dog is able to withstand large doses of procaine. Intradural injection of 5 ml of 25% or 50% procaine produced permanent paralysis of the hind limbs and degener- ative changes of the myelin sheath. Lower concentra- tions or smaller volumes of the high concentrations had no permanent effects. The pia mater and arach- noid were not thickened in any animal, nor was inflammation observed in the subarachnoid space. Tui et a1 (74) did a similar study in cats and rabbits using various concentrations of procaine, monocaine, and dibucaine. All animals that survived the anes- thetic recovered full sensory and motor function. Minimum anesthetic concentrations of the drugs pro- duced no histologic changes of the cord or meninges. Reversible inflammatory and degenerative changes were seen following minimal lethal concentrations or half of minimal lethal concentrations. All changes were absent by 14 days after injection.

Several animal studies have looked at the effects of possible contaminants of spinal solutions. Denson et a1 (75,76) soaked syringes in 1% or 5% tribasic sodium phosphate or various detergent solutions, then auto- claved them without rinsing before giving spinal an- esthesia with 1% tetracaine to monkeys. Experimental

animals and control animals given spinal anesthesia without contaminants were observed for 3 to 14 months, then sacrificed. Examination of the spinal cord showed adhesive arachnoiditis in 12 of the 14 experimental monkeys, one of which became clini- cally paraplegic after 4 months. No gross or micro- scopic evidence of neuropathology was seen in the control animals.

Hurst (77) studied the effects of various detergents and antiseptics injected into the cisterna magna of monkeys. There were no or few immediate symp- toms, but progressive, severe neurologic signs oc- curred after a latent period. Histologically, the various agents damaged the superficial structures and elicited a cellular proliferation of the pia-arachnoid with con- sequent obstruction of CSF. Necrosis of meningeal arteries leading to obstruction of the lumen and re- striction of blood supply to nervous tissues was also seen. Similar histologic changes have been reported in dogs given subarachnoid injections of anionic or cationic detergents (78).

Neurologic Deficit following Epidural or Subarachnoid Administration of

Chloroprocaine

Clinical descriptions of the cases recently reported by Reisner et a1 (1) and Ravindran et a1 (2) are presented in Table 6. Chloroprocaine was adminis- tered for epidural anesthesia in all four patients, but inadvertent subarachnoid injection resulting in total spinal block occurred in two patients. In the case reported by Reisner et a1 (I), mechanical ventilation was required for 5% hours following administration of 25 ml of 3% chloroprocaine. In case 3 of Ravindran et a1 (2) artificial ventilation was continued for 2% hours after injection of 23 ml of 2% chloroprocaine. In the other two cases reported by Ravindran et al, total spinal anesthesia did not occur. The only indi- cation of subarachnoid administration was very rapid onset of perineaI anesthesia foilowing injection of 10 to 12 ml of 3% chloroprocaine.

Motor weakness was seen in all four patients, sen- sory loss was reported in three patients, and sphincter disturbances occurred in two. Recovery from anesthe- sia was very slow in cases 2 and 3 of Ravindran et a1 (4, with a gradual return of motor function over 3 days. These two cases resemble previous reports of delayed recovery after epidural block with bupiva- caine. Six patients reported by Cuerden et a1 (79), Maycock (BO), and Pathy and Rosen (81) experienced sensory and motor deficit for between 11 and 60

ANESTHESIA AND ANALGESIA Vol 60, No 3, March 1981 157

NEUROLOGIC DEFICITS

TABLE 6 Neurologic Deficit following Epidural or Inadvertent Subarachnoid Block with Chloroprocaine

Reisner et al (I) Ravindran et al , (2): case 1 Ravindran et al(2): case 2 Ravindran et al(2): case 3

Anesthesia

Procedure Operative

course

Onset of se- quelae

Motor func- tion

Reflexes

Sensation

Outcome

3% chloroprocaine with 1 : 200,000 epinephrine, 3 4 test dose, then 25-ml single injection

Postpartum tubal ligation Respiratory arrest shortly after

injection; mechanical ventila- tion for 5% hr, blood pressure stable; operation completed under ketamine, nitrous oxide

Immediately following proce- dure

Marked weakness of the lower extremities, urinary retention, fecal incontinence

3% chloroprocaine, total of 16 ml over 90 min by cath- eter

Labor and vaginal delivery Minimal dyspnea; given sup-

plemental oxygen; blood pressure at 100/70 to 11 0/80, patient conscious throughout delivery

Immediately following regres- sion of anesthesia

Paralysis of lower extremities

Loss of pinprick senses below T-12 level at 20 hr. below 5-2 at 25 hr after anesthesia: vi- bratory and position sense in- tact

Gradual return of muscle power over 4 weeks; return of bowel function at 3 wk; 7 wk after surgery, patient developed back pain, marked paresis of lower extremities and patchy sensory loss to T-12; urinary and fecal incontinence; diag- nosis of adhesive arachnoidi- tis or arachnoid cyst by mye- lography

Knee and plantar reflexes ab- sent bilaterally

Intact pressure, touch, vibra- tion and position sense; tactile discrimination and temperature senses absent below L-1

Gradual partial return of mo- tor function; walking with aid of crutches and brace on left leg at 4 wk

0.5% bupivicaine with 1 : 200.000 epinephrine, 11 ml for labor, then 12 ml of 3% chloroprocaine

Labor and vaginal delivery Systolic blood pressure fell to

90 mm Hg; quickly con- trolled with fluids and uter- ine displacement

Immediately following delivery

Paresis of lower extremities 3 hr after delivery; inconti- nence

Knee and ankle jerks absent

Intact touch, vibration, pres- sure, position senses

2% chloroprocaine, 4 4 test dose followed by 23 ml

Postpartum tubal ligation Dyspnea progressing to ap-

nea; mechanical ventila- tion for 2% hr

Immediately following pro- cedure

Paralysis of lower extremi- ties 7% hr after epidural injection

Tingling sensation in right lower extremity

Complete recovery of neuro- logic function by 72 hr after delivery

Recovery of motor function by 72 hr after surgery; re- sidual numbness of heels and buttocks subsided over 6 mo

hours after epidural injection of 10 to 36 ml of 0.375% or 0.5% bupivacaine, with or without epinephrine. In case 2 of Ravindran et a1 (2) 11 ml of 0.5% bupivacaine with 1:200,000 epinephrine was used for relief of labor pains before injection of chloroprocaine for perineal analgesia. It is possible that the epidural bupivacaine played a role in prolonging anesthesia in this patient.

The case reported by Reisner et a1 (1) and case 1 of Ravindran et a1 (2) also showed early onset of sensory and motor deficit. Gradual recovery was seen over a period of several weeks, but after 4 weeks, leg weak- ness persisted in case 1 of Ravindran et al, and Reisner’s patient required intermittent bladder cath- eterization and had loss of pinprick sensation to 5-4. This patient returned to the hospital 7 weeks after surgery with back pain, marked paresis of the lower extremities, and patchy sensory loss to T-12. A my- elogram was consistent with a diagnosis of adhesive arachnoidosis or an arachnoidal cyst. Some return of sensory and motor function was seen, but after 9 weeks the patient remained markedly paretic, incon- tinent of feces, and unable to void. At this time there was some return of sensation to legs and buttocks.

158 ANESTHESIA AND ANALGESIA Vol60, No 3. March 1981

Etiology of Neurologic Deficit

Comparison of the clinical findings in the two cases of prolonged sequelae following injection of chloro- procaine to those of the previously described syn- dromes may provide clues to the etiology of the former. The immediate onset of neurologic sequelae most closely resembles cases of paralysis due to hy- potension during surgery, following either epidural anesthesia (Table 5) or general anesthesia. The pattern of motor and sensory loss with gradual recovery over a period of weeks is similar to that seen in cases of cord infarction due to hypotension or anterior spinal artery thrombosis. Cauda equina syndrome following spinal anesthesia is also usually characterized by im- mediate onset and gradual recovery of sphincter con- trol. However, sensory loss was said to be permanent in the cases reported by Ferguson et a1 (36). In Reis- ner’s (1) patient, the paresis and incontinence that developed after 7 weeks is consistent with the delayed onset seen in adhesive arachnoiditis, but the early symptoms could not have been produced by arach- noiditis.

Trauma cannot be completely ruled out in the

KANE

chloroprocaine cases, although paresthesias were not elicited, and the distribution of motor and sensory loss was not localized. With regard to the possible direct neurotoxic effect of chloroprocaine, solutions of this agent have been used for spinal anesthesia without adverse effects (67). Moreover, prolonged exposure of the sciatic nerve in rats to 1% chloropro- caine produced no evidence of nerve injury (82). The low pH of chloroprocaine solutions (pH 2.7 to 4.0) has been suggested as a possible causative factor (83). Other local anesthetic solutions are also acidic. For example, the pH of lidocaine solutions containing epinephrine is in the range of 3.5 to 4.0 (84). Intrathe- cal injections of solutions with pH less than 4.0 pro- duced no residual effects in monkeys (85).

The fact that large volumes of local anesthetic are sometimes used for epidural anesthesia may contrib- ute to neurologic damage following inadvertent sub- arachnoid injection. In the two cases of total spinal block following chloroprocaine, more than 20 ml was administered. If all of this volume was injected in- trathecally, the local anesthetic would escape the di- lutional and buffering effects to be expected with the small volumes normally employed in spinal anesthe- sia. Thus the lumbar cord would be exposed to a high concentration of chloroprocaine at a low pH. Another possibility involves ischemic injury to the cord. As noted above, the early symptoms in the cases reported by Reisner (1) and Ravindran et a1 (2) resemble those of anterior spinal artery syndrome or paresis caused by hypotension during surgery. The administration of a large volume of solution into the subarachnoid space may have produced spasm of the spinal arteries with resulting ischemia or infarct. The effects of local anesthetics on the spinal vasculature are unknown. Certain agents including chloroprocaine and bupiva- caine have been shown to cause vasoconstriction in gravid uterine blood vessels (86). The presence of epinephrine in the anesthetic solution in the patient reported by Reisner (1) may have contributed to a vasospastic reaction.

A vascular mechanism for the spinal cord injury is an attractive hypothesis for several reasons. The lower spinal cord is vulnerable to ischemic injury because of the anatomy of its blood supply (55). A deficiency in segmental supplements to the anterior spinal artery may make some people more prone to ischemic injury to the spinal cord than others (46). The fact that all of the cases were obstetric may also be significant in that hemodynamic changes due to pregnancy may have compromised circulation to the spinal cord. Pedersen and Finster (87) report that diversion of venous blood

via the intervertebral venous plexus and azygos vein to the superior vena cava occurs in late pregnancy and results in engorgement of the intervertebral plexus and reduction in the size of the epidural and subarachnoid spaces. In addition, the lower aorta may be compressed in the supine position.

The coincidental occurrence of paralysis folIowing spinal anesthesia has been reported (88). In an eval- uation of the electromyelogram, Marinacci and Cour- ville (89) found that of 482 patients whose neurologic complaints seemed to be related to spinal anesthesia, 478 turned out to be caused by concurrent and un- related conditions. Thus the possibility that a preex- isting condition played a role in one or more of the chloroprocaine cases cannot be excluded.

Conclusions

Four cases of prolonged neurologic deficit following the use of chloroprocaine for epidural block have been reported. Inadvertent subarachnoid administra- tion occurred in at least two of these patients. The literature on neurologic sequelae following epidural or spinal anesthesia has been reviewed. Clinical de- scriptions and possible etiologic factors are presented for cases resembling the four recent cases.

Most survey reports indicate that the incidence of severe neurologic deficit following epidural or spinal block is very low; however numerous published case reports describing temporary or permanent paralysis following these procedures have appeared. Paraplegia may be due to cord ischemia or infarct caused by arterial hypotension during surgery, or compromise of blood supply to the cord by the procedure or condition of the patient, or by production of an epidural or subdural hematoma. Injury to the spinal cord or the nerve roots has also occurred following inadvertent subarachnoid administration of toxic chemicals or chemical contamination of anesthetic solutions. Chemical contaminants such as detergents or antiseptics act as irritants and induce a meningeal reaction which may progress to constrictive adhesive arachnoiditis.

The pattern of symptoms and the timing of their onset in the recently reported cases appears to resem- ble most closely cases of cord ischemia following spinal or epidural anesthesia. Symptoms are also sim- ilar to cord ischemia produced by other causes, such as shock or aortography. Anterior spinal artery spasm may have been produced by one or more of the following factors: subarachnoid administration of a large volume of anesthetic solution, the vasoconstric-

159 ANESTHESIA AND ANALGESIA Vol 60, No 3. March 1981

NEUROLOGIC DEFICITS

tive effects of chloroprocaine, the possible vasocon- strictive effect of the vehicle or its pH, and the addi- tion of epinephrine to the anesthetic solution. Special susceptibility to cord ischemia may have been present due to hernodynamic changes during pregnancy.

In view of the fact that causation of adverse reac- tions to inadvertent subarachnoid introduction of lo- cal anesthetics is conjectural, the precautions iterated by Covino et a1 (83) should be kept in mind when using any of these agents epidurally. These precau- tions include use of an adequate test dose to rule out inadvertent intrathecal placement of the catheter, in- jection of repeated fractional doses rather than large single doses, and, in the case of intrathecal injection of a full anesthetizing dose, withdrawal of a similar volume of CSF.

Clearly, further work is needed in order to deter- mine the factors associated with the fortunately rare but severe neurologic complications associated with epidural or spinal anesthesia. It is especially desirable that animal studies be conducted to explore the pos- sible role of local anesthetics, vehicle components, injection volume, and intraoperative blood pressure in producing prolonged neurologic sequelae.

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