The effect of adding intrathecal magnesium sulphate to bupivacaine���fentanyl spinal anaesthesia M. OZALEVLI, �� T. O. CETIN, H. UNLUGENC, T. GULER and G. ISIK Department of Anaesthesiology, Faculty of Medicine, Cukurova University, Adana, Turkey Background: The addition of intrathecal (IT) magnesium to spinal fentanyl prolongs the duration of spinal analgesia for vaginal delivery. In this prospective, randomized, double- blind, controlled study, we investigated the effect of adding IT magnesium sulphate to bupivacaine���fentanyl spinal anaesthesia. Methods: One hundred and two ASA I or II adult patients undergoing lower extremity surgery were recruited. They were randomly allocated to receive 1.0 ml of preservative-free 0.9% sodium chloride (group S) or 50 mg of magnesium sulphate 5% (1.0 ml) (group M) following 10 mg of bupivacaine 0.5% plus 25 mg of fentanyl intrathecally. We recorded the following: onset and duration of sensory block, the highest level of sensory block, the time to reach the highest dermatomal level of sensory block and to complete motor block recovery and the duration of spinal anaesthesia. Results: Magnesium caused a delay in the onset of both sensory and motor blockade. The highest level of sensory block was significantly lower in group M than in group S at 5, 10 and 15 min (P 0.001). The median time to reach the highest der- matomal level of sensory block was 17 min in group M and 13 min in group S (P 0.05). The mean degree of motor block was also lower in group M at 5, 10 and 15 min (P 0.001). The median duration of spinal anaesthesia was longer in group M (P 0.001). Conclusion: In patients undergoing lower extremity surgery, the addition of IT magnesium sulphate (50 mg) to spinal anaes- thesia induced by bupivacaine and fentanyl significantly delayed the onset of both sensory and motor blockade, but also prolonged the period of anaesthesia without additional side- effects. Accepted for publication 7 April 2005 Key words: analgesic bupivacaine fentanyl inorganic chem- icals local anaesthetics magnesium sulphate opioids spinal anaesthesia. # Acta Anaesthesiologica Scandinavica 49 (2005) O PIOIDS such as fentanyl and sufentanil are com- monly added to local anaesthetics to produce spinal anaesthesia. However, significant adverse effects, such as pruritus, urinary retention, respira- tory depression, haemodynamic instability and, occasionally, severe nausea and vomiting, may limit their use (1���3). Adding magnesium may also improve the quality and increase the duration of spinal anaesthesia (4). Magnesium blocks the N- methyl-D-aspartate (NMDA) channels in a voltage- dependent way, producing a dramatic reduction in NMDA-induced currents (5). In experimental stud- ies, intrathecal (IT) administration of magnesium sulphate (MgSO4) significantly potentiated opioid antinociception in rats during spinal anaesthesia in an acute incisional model (6). Although systemic MgSO4 decreases post-operative opioid requirements in surgical patients, its IT use has not been extensively evaluated clinically (7). However, it has been used safely intrathecally in humans, and its safety profile has been documented by histopathological analysis in experimental stud- ies (8). Magnesium prolongs the duration of spinal opioid analgesia given during labour (4). This prospective, randomized, double-blind, con- trolled study was designed to test the hypothesis that, in patients undergoing lower extremity surgery under bupivacaine���fentanyl spinal anaesthesia, the duration of anaesthesia would be prolonged by IT MgSO4 (50 mg). Methods Following Ethics Committee approval and informed patient consent, 102 ASA physical status I or II patients undergoing lower extremity surgery were recruited. Exclusion criteria included significant coexisting disease, including hepatorenal, any con- traindication to regional anaesthesia, such as local infection or bleeding disorders, long-term opioid Acta Anaesthesiol Scand 2005 49: 1514���1519 Copyright # Acta Anaesthesiol Scand 2005 Printed in UK. All rights reserved ACTA ANAESTHESIOLOGICA SCANDINAVICA doi: 10.1111/j.1399-6576.2005.00793.x 1514

use or a history of chronic pain. Patients were instructed pre-operatively in the use of the verbal rating scale (VRS) for pain assessment. All patients were fasted for 6 h pre-operatively and pre- medicated with intravenous diazepam, 0.2 mg/kg, 2 h before operation. Intraoperative monitoring included pulse oximetry, automated blood pressure cuff and lead II electrocardiogram. All patients received an intravenous pre-load of 15 ml/kg lac- tated Ringer���s solution before subarachnoid block. The patients were randomly allocated to one of two groups of 50 each. Group S, the saline group, received 10 mg of isobaric bupivacaine 0.5% (2 ml), 25 mg of fentanyl (0.5 ml) and 1.0 ml of preservative- free 0.9% sodium chloride intrathecally. Group M received 10 mg of isobaric bupivacaine 0.5% (2 ml), 25 mg of fentanyl (0.5 ml) and 50 mg of MgSO4 5% (1.0 ml) intrathecally. Subjects were allocated to the study groups by computer-generated random num- ber assignment, kept in sealed envelopes, before the start of the study. The envelopes were opened just before entry into the study. Both patients and anaes- thetists were blind to the treatment. Lumbar puncture was performed in the sitting position. A 25-gauge Quincke spinal needle was introduced into the subarachnoid space at the L2 3 or L3 4 vertebral level via a midline approach. With the needle orifice cephalad, cerebrospinal fluid was aspirated, and the pre-mixed solution, 10 mg of iso- baric bupivacaine 0.5% (2 ml) and 25 mg of fentanyl (0.5 ml), was injected through the spinal needle over a period of 10 s with no barbotage. The study solution described above, prepared by another researcher not involved in patient care, was then injected intrathecally immediately afterwards. The spinal needle was withdrawn and patients were repositioned supine with slight elevation of the head (15���20 ) for comfort. No additional analgesic was administered unless requested by the patient. Surgery was permitted 20 min after IT injection. Sensory and motor block, systolic and diastolic blood pressures (SBP, DBP), heart rate (HR) and peripheral oxygen saturation (SpO2) were recorded by an anaesthetist blind to the patient group, 5 min before IT injection, 5, 10, 15, 20 and 25 min after IT injection and subsequently every 15 min until the patient complained of pain. Pain scores were recorded 5 min before IT injection, after the start of surgery and subsequently every 15 min until sur- gery was complete. The onset and duration of sensory block, highest level of sensory block, time to reach the highest dermatomal level of sensory block, time to complete motor block recovery and duration of spinal anaes- thesia were also recorded. The onset of sensory block was defined as the time between injection of the IT anaesthetic and the absence of pain at the T10 dermatome, assessed by pinprick the duration was defined as the time for regression of two segments in the maximum block height, evaluated by pin- prick. The highest level of sensory block was eval- uated by pinprick every 5 min for 25 min after injection. Motor block was assessed by modified Bromage score (0, no motor loss 1, inability to flex the hip 2, inability to flex the knee 3, inability to flex the ankle) complete motor block recovery was assumed when the modified Bromage score was zero. The duration of spinal anaesthesia was defined as the period from spinal injection to the first occasion when the patient complained of pain in the post-operative period. Pain was assessed using a VRS from 0 to 10 (0, no pain at all 10, maximum imaginable pain) by an anaesthetist blind to the treatment group. If the VRS exceeded 3, tramadol HCl, 1 mg/kg, was given intravenously for pain relief. An intravenous bolus of 500 ml lactated Ringer���s solution was given to maintain the blood pressure. If SBP was 20% below baseline or 90 mmHg, intravenous (i.v.) ephedrine, 10 mg, was given repeatedly. If HR was less than 50 beats/min, 0.5 mg of atropine sulphate was administered intra- venously. The incidence of hypotension (mean arterial pressure, 20% of baseline), bradycardia (HR, 50 beats/min), hypoxaemia and excessive sedation, pruritus, dizziness, nausea and vomiting was recorded. Patients were discharged from the recovery room when the motor block was completely resolved. The discharge criteria for the ward were stable vital signs, no nausea or vomiting and no severe pain or bleeding. Patients were also assessed for the pre- sence of motor or sensory complications on the day after surgery by an observer blind to the treat- ment group. Using data from a previous investigation in a similar clinical setting (4), the primary endpoint was defined as a 15-min difference in the median duration of anaesthesia between groups. Power ana- lysis showed that, with a power of 0.8 and signifi- cance level of 0.05, 50 subjects per study group were required. Statistical analyses were performed using the statistical package SPSS version 10.0. Normality was checked for each continuous variable, and nor- mally distributed values were expressed as the mean (standard deviation, SD) and others as the Intrathecal magnesium in spinal anaesthesia 1515