Transient neurological symptoms after spinal anaesthesia with 4% mepivacaine and 0.5% bupivacaine

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1 British Journal of Anaesthesia 1997; 79: Transient neurological symptoms after spinal anaesthesia with 4% mepivacaine and 0.5% bupivacaine A. HILLER AND P. H. ROSENBERG Summary Several studies have reported transient neurological symptoms after spinal anaesthesia with 5% lignocaine. In order to evaluate the role of concentrated solutions of local anaesthetic in the development of transient neurological symptoms, 200 ASA I or II patients undergoing minor orthopaedic or rectal surgery under spinal anaesthesia were allocated randomly to receive 4% mepivacaine 80 mg or hyperbaric 0.5% bupivacaine 10 mg. All patients were interviewed by an anaesthetist approximately 24 h after spinal anaesthesia, and after 1 week patients were asked to return a written questionnaire. The incidence of transient neurological symptoms consisting of pain in the buttocks or pain radiating symmetrically to the lower extremities differed (P 0.001) between patients receiving mepivacaine (30%) and those receiving bupivacaine (3%). Hyperbaric 0.5% bupivacaine can be recommended for minor operations on the lower abdomen or lower extremities. (Br. J. Anaesth. 1997; 79: ). Key words Anaesthetic techniques, subarachnoid. Anaesthetics local, mepivacaine. Anaesthetics local, bupivacaine. Complications, neurological. The first report of transient neurological symptoms, termed initially transient neurological impairment or transient radicular irritation, after spinal anaesthesia with hyperbaric 5% lignocaine by Schneider and colleagues in was confirmed later by several other studies. 2 6 It is thought that a localized local anaesthetic toxic effect may be an important contributing factor in the development of transient neurological symptoms after spinal anaesthesia with concentrated solutions. 7 8 The occurrence of this complication is rare after the use of 0.5% bupivacaine for spinal anaesthesia Mepivacaine has been used for spinal anaesthesia since the beginning of the 1960s. 11 In the first large-scale report of mepivacaine spinal anaesthetics, outcome was favourable and no neurological complications were noted. 12 However, as with 5% hyperbaric lignocaine, the hyperbaric spinal anaesthetic solution of mepivacaine is also quite concentrated (4%) and post-spinal sequelae similar to those after hyperbaric lignocaine spinal anaesthesia should be expected. In this study, we examined the occurrence of transient neurological symptoms after spinal anaesthesia with either 4% hyperbaric mepivacaine or hyperbaric 0.5% bupivacaine. Patients and methods Two hundred ASA I or II patients undergoing minor orthopaedic, varicose vein, rectal or gynaecological operations were studied in a randomized, doubleblind manner (table 1). Patients with a pre-existing neurological disease or diabetes mellitus were excluded. The study was approved by the Ethics Committee of the hospital, and informed consent was obtained from the patients. All patients were premedicated with diazepam 5 15 mg orally. Patients were allocated randomly by sealed envelope to receive 4% mepivacaine 80 mg with glucose 95 mg ml 1 (Scandicain 40 mg ml 1, Astra, Wedel, Germany) or 0.5% hyperbaric bupivacaine 10 mg with glucose 80 mg ml 1 (Marcain spinal 5 mg ml 1, Tung, Astra, Södertälje, Sweden). An identical volume of 2 ml was drawn into a syringe by an independent anaesthesia nurse so that the anaesthetist (A. H.) performing the block was unaware of which drug was given. Although the doses are not equipotent from a theoretical point of view, similar spread and duration of spinal anaesthesia have been observed after a dose of 10 mg of 0.5 % hyperbaric bupivacaine and 80 mg of hyperbaric mepivacaine. A peripheral i.v. infusion with acetated Ringer s solution was started before operation. Thereafter spinal anaesthesia was performed at the L3 4 interspace with the patient in the lateral position using a 27-gauge Quincke needle. However, if the puncture was considered difficult, a higher interspace, larger needle or the sitting position was chosen to perform spinal anaesthesia. Free flow of cerebrospinal fluid was verified before and after injection of the local anaesthetic. Immediately after spinal puncture, the patient was turned to the supine position with the operating table in a slight head-up tilt position. A. HILLER, MD, PHD, Department of Anaesthesia, Kuusankoski District Hospital, FIN Sairaalamäki, Finland. P. H. ROSENBERG, MD, PHD, Department of Anaesthesiology, Helsinki University Central Hospital, FIN Helsinki, Finland. Accepted for publication: April 10, Correspondence to A. H.

2 302 British Journal of Anaesthesia Patients were monitored with electrocardiography, automated arterial pressure and pulse oximetry. Hypotension (systolic arterial pressure 90 mm Hg or 30% decrease from baseline) was treated with 5-mg increments of ephedrine or 200- g increments of phenylephrine. Bradycardia (heart rate 50 beat min 1 was treated with atropine 0.5 mg or glycopyrronium 0.2 mg. Testing of pinprick analgesia and motor block was performed at 5, 10, 15, 60 min, and thereafter at 30-min intervals. A modified Bromage scale was used for testing motor block: 0 no paralysis (full flexion of the knees and feet), 1 inability to flex the extended leg (just able to move the knees), 2 inability to flex the knee (able to move the feet only), 3 inability to flex the ankle joint (unable to move the feet or knees). Patients were discharged from the recovery room when recovery of motor block was complete. Nurses on the ward recorded the time when patients reported that they had normal sensation in the buttocks and feet. All patients were interviewed by the investigator on the first postoperative morning. They were asked if they had experienced any of the symptoms on the following standardized symptom checklist: headache, backache, pain not associated with surgery, sensory disturbances, change in muscle strength, or difficulties in voiding or in hearing. Special attention was paid to lower extremity symptoms, type of pain and radiation of pain. 3 One week after spinal anaesthesia, patients were asked to return a mailed questionnaire. They were asked to mention symptoms which they particularly associated with spinal anaesthesia. Enquiries concerning symptoms and their duration included headache, backache, pain in the operation area and pain in the thighs, buttocks, calves or elsewhere. Patients were also asked to assess the degree of satisfaction with their spinal anaesthesia. Transient neurological symptoms were defined as symmetrical bilateral pain in the back or buttocks or pain radiating to the lower extremities after recovery from spinal anaesthesia. Student s t test and Fisher s exact test were used to compare differences. P 0.05 was considered significant. Results The characteristics of the patients and details of the operations and spinal anaesthetic procedures are summarized in tables 1 and 2. Motor block was complete in 96% of patients in the mepivacaine group and in 81% of patients in the bupivacaine group (P 0.001). Details of motor block are presented in table 3. In one case, bupivacaine provided inadequate surgical anaesthesia although free flow of cerebrospinal fluid was verified before and after injection of the drug. Eighty-nine of 99 (90%) patients in the mepivacaine group and 88 of 99 (89%) patients in the bupivacaine group returned the questionnaire. Twelve patients in the mepivacaine group and two patients in the bupivacaine group were not satisfied with their spinal anaesthesia (P 0.05). Two patients who had received mepivacaine spinal anaesthesia had headache at home, one for 3 days and the other for 1 week. Neither needed an extradural blood patch. Two patients who had received bupivacaine spinal anaesthesia reported transient deterioration in hearing. The incidence of transient neurological symptoms differed (P 0.001) between patients who received Table 1 Characteristics of patients and variables of spinal anaesthesia (median (range) or number) Characteristic/variable 4% Mepivacaine 0.5% Bupivacaine n Sex (M/F) 45/55 47/53 Age (yr) 41 (21 68) 44 (20 70) Height (cm) 170 ( ) 171 ( ) Weight (kg) 76 (49 115) 75 (50 116) Needle size 25-gauge gauge Patient position during injection Sitting 4 3 Lateral Duration of operation (min) 32 (9 115) 32 (7 87) Patient position during operation Supine Lithotomy 2 4 Prone 3 2 Table 2 Details of the spinal anaesthetic procedures. ***P<0.001 All patients Patients with transient neurological symptoms 4% Mepivacaine 0.5% Bupivacaine 4% Mepivacaine 0.5% Bupivacaine n *** 3 Sex (M/F) 45/55 47/53 14/16 1/2 Surgery Arthroscopy of knee Other orthopaedic Varicose veins Rectal or gynaecological Attempts at dural puncture > Paraesthesia during dural puncture Median maximum height of block (range) T6 (T3 12) T7 (T3 L4) T6 (T3 12) T8 (T8 12)

3 Neurological symptoms after hyperbaric spinal anaesthesia 303 Table 3 Characteristics of the motor block (median (range)). Motor block 3 unable to move the feet or knees, 2 able to move the feet only, 1 just able to move the knees. ***P<0.001 All patients Patients with transient neurological symptoms 4% Mepivacaine 0.5% Bupivacaine 4% Mepivacaine 0.5% Bupivacaine n *** 3 Motor block 3 96*** No paralysis Time to maximum motor block (min) 8 (5 60)*** 17 (5 60) 8 (5 60) 13 (5 60) Time to total recovery of motor block (min) 135 (90 210) 127 (60 240) 130 (90 210) 100 (60 120) Table 4 Nature of pain and analgesic requirement in patients with transient neurological symptoms (NSAID non-steroidal anti-inflammatory drug). ***P % Mepivacaine 0.5% Bupivacaine n 30*** 3 Location of pain Buttocks 13 0 Buttocks and thighs 13 1 Thighs 0 1 Buttocks, thighs and legs 4 1 Severity of pain Mild or moderate 20 3 Severe 10 0 Onset of pain after recovery of block (h) Duration of pain (h) < Needed analgesia Yes 23 2 NSAID 14 1 Opioids 1 0 Both NSAID and opioids 8 1 No 7 1 mepivacaine (30%) and those who had received bupivacaine (3%). The mean age of patients with transient neurological symptoms in the mepivacaine group was 44 (range 21 68) yr and in the bupivacaine group 51 (47 54) yr. Mean weight was 77 (56 105) kg in the mepivacaine group and 77 (75 80) kg in the bupivacaine group. There was no association between the incidence of transient neurological symptoms and patient sex, weight or age. All patients who experienced transient neurological symptoms had been in the supine position during operation, except for one who was in the lithotomy position. Furthermore, in all patients with transient neurological symptoms the spinal puncture had been performed in the lateral position. There was no association between transient neurological symptoms and difficulty of block placement or paraesthesia. In all three patients in the bupivacaine group and in 26 of 30 patients with symptoms in the mepivacaine group, pain occurred within the first 24 h. In one patient who had both pain and dysaesthesia in the buttocks, symptoms lasted for 5 days. In 14 patients in the mepivacaine group and in one patient in the bupivacaine group, pain was relieved by non-steroidal anti-inflammatory drugs; nine patients also needed opioids. Five patients reported that the pain was worse in the supine position and it was relieved when they stood up and started to walk (table 4). No patient had sensory disturbances, change in muscle strength or difficulties in voiding on the first postoperative morning. Three patients who had transient neurological symptoms after mepivacaine spinal anaesthesia had experienced similar symptoms before, one after 5% hyperbaric lignocaine spinal anaesthesia and two after 4% hyperbaric mepivacaine anaesthesia. All three patients who had transient neurological symptoms in the bupivacaine group returned the questionnaire and were satisfied with the spinal anaesthesia. In the mepivacaine group, 27 of 30 patients returned the questionnaire and 20% were not satisfied with spinal anaesthesia; four because of transient neurological symptoms, one because of painful puncture and one patient complained of difficulty in breathing because of the maximum height of block (T4) during operation. All complaints were transient and had disappeared by the time the patients mailed the questionnaire. Discussion In this study, transient neurological symptoms occurred in 30% of patients who received spinal anaesthesia with mepivacaine but also in 3% of patients who received spinal anaesthesia with hyperbaric bupivacaine. However, duration of symptoms after bupivacaine spinal anaesthesia was less than 12 h compared with h after mepivacaine spinal anaesthesia. In 1993, Schneider and colleagues published the first case reports of transient neurological symptoms after spinal anaesthesia with 5% hyperbaric lignocaine. 1 Other later studies have shown similar symptoms, termed transient radicular irritation (TRI) after 5% hyperbaric lignocaine spinal anaesthesia in 10 37% of patients. 2 5 Thus the incidence of transient neurological symptoms or TRI after concentrated solutions of 4% mepivacaine and 5% lignocaine is similar. In the study of Pollock and colleagues the incidence of TRI was 16% after both

4 304 British Journal of Anaesthesia 5% hyperbaric lignocaine and 2% lignocaine without glucose, but 0% after 0.75% hyperbaric bupivacaine. 5 In the study by Tarkkila, Huhtala and Tuominen, only one of 110 patients had TRI after 0.5% hyperbaric bupivacaine. 10 The neurot oxic potential of 5% hyperbaric lignocaine and 0.75% bupivacaine has been evaluated. 7 Exposure of amphibian nerves to 0.75% isobaric bupivacaine produced partially reversible conduction block, whereas 5% lignocaine with or without glucose caused irreversible block of impulses. 7 Furthermore, it has been shown in an in vitro study that lignocaine 80 mmol, which is equivalent to a concentration of 2% lignocaine, caused complete ablation of impulse activity. 8 In clinical studies, decreasing the concentration of lignocaine from 5% to 2% did not prevent the development of TRI The doses of mepivacaine and bupivacaine in our study were based on the clinical study of Pitkänen, Kalso and Rosenberg, where 80 mg (2 ml) of 4% hyperbaric mepivacaine resulted in spinal anaesthesia similar to that after a dose of 0.5% hyperbaric bupivacaine 10 mg (2 ml) or 0.5% hyperbaric lignocaine 100 mg (2 ml). 14 Also, spinal anaesthesia with mepivacaine 60 mg produced analgesia and motor block of good quality but of short duration compared with spinal anaesthesia with 0.5% hyperbaric bupivacaine 15 mg. 16 Decreasing the dose of mepivacaine from 80 to 60 mg may diminish the development of transient neurological symptoms and still provide adequate anaesthesia for operations on the lower extremities. Lambert, Lambert and Strichartz demonstrated synergistic neurotoxic effects of lignocaine and glucose in vitro, in frog sciatic nerve. 7 The loss of neural activity was not found to correlate with the glucose concentration and inhibition could not be induced without local anaesthetic. The hyperbaric mepivacaine solution has a higher concentration of glucose (95 mg ml 1 ) compared with hyperbaric lignocaine (62.5 mg ml 1 ) or hyperbaric bupivacaine (80 mg ml 1 ). The great er t he baricit y of t he solution the greater the chance of gravitydetermined spread restriction. This, together with the use of small gauge pencil-point needles with one side hole near the tip, could result in pooling of the concentrated local anaesthetic solution. Repeated injections through thin intrathecal catheters may, therefore, result in cauda equina syndrome. 17 Beardsley and colleagues showed that sacral direction of the needle orifice and a slow injection rate with a Whitacre needle may be predisposing factors to transient neurological complications with 5% hyperbaric lignocaine. 18 However, other studies have failed to confirm this In contrast, in this study we injected via Quincke-type needles (orifice at the bevelled tip) and initial directional pooling of the local anaesthetic in the sacral region was unlikely. In addition to a toxic effect of the local anaesthetic, the lithotomy position during surgery has been thought to be a possible cause of transient neurological symptoms The lithotomy position may contribute to transient neurological symptoms by stretching the cauda equina and sciatic nerves, thus decreasing the vascular supply and increasing vulnerability to injury. In our study, four patients in the bupivacaine group and two in the mepivacaine group were in the lithotomy position during surgery. Only one patient in the mepivacaine group had transient neurological symptoms starting h after anaesthesia. However, transient neurological symptoms occurred in 22 patients undergoing arthroscopy of the knee. In our hospital, arthroscopy patients have both legs straight at the hip, and flexed 90 at the knee. The operative leg position is varied throughout surgery. The position and manipulation may contribute to neural stretching and thus to the development of transient neurological symptoms. Also, Pollock and colleagues found a higher incidence of transient neurological symptoms in patients undergoing arthroscopy than in those having inguinal hernia repair. 5 Individual physical characteristics of patients may predispose to the development of transient neurological symptoms after spinal anaesthesia. Interestingly, in this study three patients who had transient neurological symptoms after mepivacaine spinal anaesthesia had experienced similar symptoms before, one after 5% hyperbaric lignocaine and two after 4% hyperbaric mepivacaine spinal anaesthesia. It has been shown that the anatomical configuration of the spinal column affects the spread of subarachnoid anaesthetic solutions that move under the influence of gravity Both lumbar lordosis and thoracic kyphosis differ between individuals, particularly with respect to the lowest point of the thoracic spinal canal. 21 Musculoskeletal disturbances in the back and leg symptoms cannot be totally excluded. We speculate that profound relaxation of the supportive muscles of the lumbar spine may result in straightening of the lordotic curve, and even transient spondylolisthesis, when the patient is lying on the operating table. This may be responsible in part for the radiating back symptoms which occurred after the intense motor block, observed during mepivacaine spinal block in particular. In summary, the incidence of transient neurological symptoms was greater after spinal anaesthesia with 4% hyperbaric mepivacaine than after 0.5% hyperbaric bupivacaine. Patients were more satisfied with bupivacaine spinal anaesthesia. Except for a greater number of complete motor blocks after mepivacaine, spinal anaesthesia and recovery were similar after both agents. Therefore, hyperbaric 0.5% bupivacaine 10 mg can be recommended for minor operations on the lower extremities or lower abdomen lasting less than 90 min. References 1. Schneider M, Ettlin T, Kaufmann M, Schumacher P, Urwyler A, Hampl K, von Hochstetter A. Transient neurologic toxicity after hyperbaric subarachnoid anesthesia with 5% lidocaine. 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5 Neurological symptoms after hyperbaric spinal anaesthesia Salmela L, Aromaa U, Cozanitis DA. Leg and back pain after spinal anaesthesia involving hyperbaric 5% lignocaine. Anaesthesia 1996; 51: Pollock JE, Neal JM, Stephenson CA, Wiley CE. Prospective study of the incidence of transient radicular irritation in patients undergoing spinal anesthesia. Anesthesiology 1966; 84: Rodríquez-Chinchilla R, Rodríquez-Pont A, Pintanel T, Vidal-López F. Bilateral severe pain at L3 4 after spinal anaesthesia with hyperbaric 5% lignocaine. British Journal of Anaesthesia 1996; 76: Lambert LA, Lambert DH, Strichartz GR. Irreversible conduction block in isolated nerve by high concentrations of local anesthetics. Anesthesiology 1994; 80: Bainton C, Strichartz G. Concentration dependence of lidocaine-induced irreversible conduction loss in frog nerve. Anesthesiology 1994; 81: Hampl K, Schneider M, Ummenhofer W, Drewe J. Transient neurologic symptoms after spinal anesthesia. Anesthesia and Analgesia 1993; 81: Tarkkila P, Huhtala J, Tuominen M. Transient radicular irritation after bupivacaine spinal anesthesia. Regional Anesthesia 1996; 21: Knox PR, North WC, Stepher CS. Pharmacologic and clinical observations with mepivacaine. Anesthesiology 1961; 22: El-Shirbing AM, Rasheed MH, Elmaghraby A, Motahew M. Experiences with carbocaine in spinal anaesthesia. Report of cases. Acta Anaesthesiologica Scandinavica 1966; 10 (Suppl. 23): Covino BG, Vassallo HG. Local Anesthetics: Mechanisms of Action and Clinical Use. New York: Grune and Stratton, 1976; 49, Pitkänen MT, Kalso EA, Rosenberg PH. Comparison of hyperbaric bupivacaine, lidocaine and mepivacaine in spinal anesthesia. Regional Anesthesia 1984; 9: Hampl KF, Schneider MC, Pargger H, Gut I, Drewe J, Drasner K. A similar incidence of transient neurologic symptoms after spinal anesthesia with 2% and 5% lidocaine. Anesthesia and Analgesia 1996; 83: Bengtsson M, Edström HH, Löfström JB. Spinal analgesia with bupivacaine, mepivacaine and tetracaine. Acta Anaesthesiologica Scandinavica 1983; 27: Rigler ML, Drasner K, Krejcic TC, Yelich SJ, Schelnick FT, DeFontes J, Bohner D. Cauda equina syndrome after continuous spinal anesthesia. Anesthesia and Analgesia 1991; 72: Beardsley D, Holman S, Gantt R, Robinson RA, Lindsey J, Bazaral M, Stewart SFC. Transient neurologic deficit after spinal anesthesia: local anesthetic maldistribution with pencil point needles? Anesthesia and Analgesia 1995; 81: Greene N. Distribution of local anesthetic solutions within the subarachnoid space. Anesthesia and Analgesia 1985; 64: Wildsmith J. Baricity and spinal anesthesia: What solution when? Anesthesiology Clinics of North America 1992; 10: Hirabayashi Y, Shimizu R, Saitoh K, Fukuda H, Furuse M. Anatomical configuration of the spinal column in the supine position. I. A study using magnetic resonance imaging. British Journal of Anaesthesia 1995; 75: 3 5.