|Year : 2014 | Volume
| Issue : 2 | Page : 226-231
Effect of pre-emptive epidural low-dose magnesium sulfate on postoperative analgesic requirement after open abdominal hysterectomy Ramadan Shabana
Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain-Shams University, Cairo, Egypt
|Date of Submission||27-Feb-2013|
|Date of Acceptance||30-Sep-2013|
|Date of Web Publication||31-May-2014|
Department of Anesthesiology, Ain Shams University
Source of Support: None, Conflict of Interest: None
The aim of the study was to evaluate the efficacy of single-shot epidural injection of combined low-dose magnesium sulfate with levobupivacaine as a pre-emptive analgesic to decrease the postoperative analgesic requirement in female patients undergoing abdominal hysterectomy.
Patients and Methods
The study included 90 ASA I-II adult female patients assigned for open abdominal hysterectomy. Patients were randomly allocated into two equal groups: group L received single-shot epidural plain levobupivacaine 0.25% and group M received single-shot epidural levobupivacaine 0.25% mixed with 50 mg MgSO 4 . The intensity of postoperative pain was measured with 0-100 point visual analog scale (VAS). Rescue analgesia was given if patients had VAS scores of 40 or more and the duration of analgesia was determined. The degree of sedation was assessed 30 and 120 min after admission to the recovery room using the four-point Brussels Sedation Scale.
Cumulative pain VAS until the end of first postoperative 24 h was significantly lower in patients who received combined epidural therapy compared with those who received local anesthetic alone. Moreover, pain-free duration was significantly longer in group M compared with group L. Throughout 24 h after surgery, 31 patients requested rescue analgesia only once, 37 patients requested it twice, 16 patients requested it three times, and only six patients required rescue analgesia for more than three times. Patients who received combined therapy requested rescue analgesia at significantly lower frequency compared with those who received local anesthetic alone. Patients enrolled in group M showed a significantly lower mean sedation score at 30 min; however, at 120 min postoperatively, the score was nonsignificantly lower in comparison with group L.
Pre-emptive epidural bolus of magnesium sulfate and levobupivacaine provides postoperative analgesia superior to epidural levobupivacaine alone for patients undergoing open abdominal hysterectomy.
Keywords: Epidural, levobupivacaine, magnesium sulfate, pre-emptive analgesia
|How to cite this article:|
Shabana R. Effect of pre-emptive epidural low-dose magnesium sulfate on postoperative analgesic requirement after open abdominal hysterectomy Ramadan Shabana. Ain-Shams J Anaesthesiol 2014;7:226-31
|How to cite this URL:|
Shabana R. Effect of pre-emptive epidural low-dose magnesium sulfate on postoperative analgesic requirement after open abdominal hysterectomy Ramadan Shabana. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2021 Oct 27];7:226-31. Available from: http://www.asja.eg.net/text.asp?2014/7/2/226/133446
| Introduction|| |
Perioperative pain management is a crucial topic especially for patients undergoing major surgeries. Postoperative pain is multifactorial: first, surgery and tissue trauma with concomitant nerve sparing or scarification may be the most dominant nociceptive mechanism; second, acute inflammation induced by tissue injury with concomitant release of nociceptive cytokines and inflammatory mediators plays a role for induction and/or aggravation of pain; third, as a characteristic feature for open surgery conducted through laparotomy incision is associated with pain during respiration and motion ,,.
The N-methyl-d-aspartate receptors (NMDARs) are amino acid inotropic receptors (ligand-gated ion channels), and are unique in that channel activation requires binding of glutamate with glycine as an obligatory coagonist. NMDARs mediate neuronal signaling and regulate neuronal gene expression, and therefore perform critical roles in the central nervous system functioning. NMDA has been implicated in a number of physiological and pathological phenomena in the spinal cord dorsal horn, including activity-dependent synaptic plasticity ,,.
Central sensitization secondary to trauma or ischemia is associated with the development of hyperalgesia and neurotoxicity due to excessive stimulation of NMDARs, which can induce neuronal damage and death. Thus, the analgesic mechanism of NMDA antagonists is by preventing nociceptive central sensitization and/or by the reduction of catecholamine release with sympathetic stimulation, thereby decreasing peripheral nociceptor or the stress response to surgery .
Specifically, Ca2+ entry through NMDARs plays an important role in NMDAR-mediated plasticity and neurotoxicity. NMDA-gated channels are both Ca 2+ permeable and strong voltage-dependent block by extracellular Mg 2+ , which is relieved by sustained depolarization and glutamate binding and which is central to the function of the NMDARs in synaptic plasticity. Rapid membrane depolarization during agonist application reveals a slow unblock of NMDAR, which has important functional implications, for example in the generation of NMDAR spikes and in determining the narrow time window for spike-timing-dependent plasticity ,.
This prospective comparative study aimed to evaluate the effect of single-shot combined low-dose magnesium sulfate with levobupivacaine through the epidural route as a pre-emptive analgesic to decrease the postoperative analgesic requirement in women undergoing abdominal hysterectomy.
| Patients and Methods|| |
This study was conducted at King Abdul-Aziz Navel Base Hospital, KSA from June 2010 to October 2012. After approval of the study protocol by the Local Ethical Committee and obtaining patients' fully informed written consent, 90 ASA I-II adult female patients assigned for open abdominal hysterectomy for dysfunctional uterine bleeding through Pfannenstiel incision were enrolled in the study. Patients with chronic pain, severe cardiac, pulmonary, liver, or neurological disease, or allergy to the study drugs were excluded from the study.
Patients were randomly allocated (using sealed envelopes) into two equal groups (n = 45): group L included patients assigned to receive single-shot of plain levobupivacaine 10 ml 0.25% and 1 ml isotonic saline and group M included patients assigned to receive single-shot of combination of levobupivacaine 10 ml 0.25% mixed with 50 mg MgSO 4 diluted in 1 ml.
Patients were taken into the operating room unpremedicated. Standard monitoring with noninvasive blood pressure, ECG, and arterial oxygen saturation (SpO 2 ) were applied, and administration of lactated Ringer's solution was started. Patients were positioned in the lateral decubitus and after identification of the epidural space (L3-L4) using an 18-G Tuohy needle with loss of resistance technique, a 20-G epidural catheter was inserted and advanced 3-5 cm into the epidural space. Three milliliters of 2% xylocaine with epinephrine 1 : 200 000 was injected through the epidural catheter as a test dose for proper catheter positioning, then the catheter was fixed and the patient was repositioned supine. All epidural study medications were injected after induction of general anesthesia, and the catheter was removed at the end of surgery.
General anesthesia was induced with propofol (1-2 mg/kg), fentanyl (1-2 μg/kg), xylocaine (1 mg/kg), and atracurium (0.5 mg/kg) followed by endotracheal intubation. Anesthesia was maintained with O 2 /N 2 O/sevoflurane and atracurium intermittent doses. Ventilation was controlled with a tidal volume of 6-8 ml/kg, and the ventilatory rate was adjusted to maintain end-tidal CO 2 between 35 and 40 mmHg.
At the end of surgery, muscle relaxation was reversed by neostigmine and atropine. After extubation, patients were transferred to postanesthetic care unit and were monitored for respiratory rate, SpO 2 , heart rate, and systolic arterial blood pressure. Postoperative rescue analgesia was provided in the form of pethidine 50 mg intramuscular as required.
The intensity of postoperative pain was measured with the visual analog scale (VAS) (a 100-mm scale, with '0' indicating no pain and '100' indicating worst pain ever) . The duration of analgesia or pain-free duration is defined as the time elapsed since the epidural injection until the first request of rescue analgesia. Rescue analgesia was given when the patient had a VAS score of 40 during 24 h postoperative. The total cumulative dose of rescue analgesia was determined. VAS pain scores were assessed every 30 min for 2 h and then every 2 h for 12 h, and every 4 h thereafter.
The degree of sedation was assessed 30 and 120 min after admission to the recovery room using the Brussels Sedation Scale , where 1 = sedated and unarousable, 2 = sedated but responds to painful not auditory stimuli, 3 = sedated but responds to auditory stimuli, and 4 = awake and calm. The time to first postoperative ambulation and time to oral resumption were defined as well.
To establish the sample size, we selected heart rate and systolic blood pressure as relevant clinical variables , and an effect size of 0.6 was considered to represent a clinically relevant difference between the means. From a standard nomogram, a sample size of 45 patients per group was determined to be sufficient to give the trial 80% power to detect a difference at the 5% significance level . A series of mixed models were fitted to examine the effect of levobupivacaine on the hemodynamic and pain variables, at least four estimations so as to evaluate the effect of adding magnesium sulfate. Statistical analysis was conducted using the SPSS (version 15, 2006) for Windows statistical package.
| Results|| |
Ninety patients completed the study and all surgeries were completed uneventfully without intraoperative complications within a mean operative time of 92.5 ± 10.2 min. There were no significant (P > 0.05) differences among the study groups with respect to age, weight, height, BMI, ASA grade, and duration of surgery [Table 1]. No patient experienced motor or sensory block during postoperative period.
Throughout the postoperative period, there was nonsignificant (P > 0.05) difference between the study groups with respect to blood pressure, heart rate, respiratory rate, and SpO 2 , with nonsignificant (P > 0.05) difference compared with their corresponding baseline data [Table 2].
Cumulative pain VAS until the end of first postoperative 24 h was significantly (P = 0.001) lower in patients who received combined epidural therapy compared with those who received local anesthetic alone. Moreover, pain-free duration was significantly (P < 0.001) longer in group M compared with group L [Figure 1]. Throughout 24 h after surgery, 31 patients requested rescue analgesia only once, 37 patients requested it twice, 16 patients requested it three times, and only six patients required rescue analgesia for more than three times. Patients who received combined therapy requested rescue analgesia at significantly (c2 = 3.402, P<0.05) lower frequency compared with those who received local anesthetic alone. Moreover, the cumulative dose of rescue analgesia used was significantly (Z = 3.873, P < 0.001) lower in group M compared with group L [Table 3], [Figure 2].
|Table 2: Patients' vital data recorded at the end of first 24 h after surgery|
Click here to view
Patients who received magnesium showed lower sedation scores at 30 and 120 min postoperatively, with significantly higher frequency of patients with high sedation scores at 30 min but nonsignificant at 120 min in comparison with group L [Table 4], [Figure 3]. Patients of group L could ambulate and take oral fluids earlier than those of group M, despite the difference being nonsignificant [Table 5].
|Table 4: Sedation score of patients within each group at 30 and 120 min postoperatively|
Click here to view
|Table 5: Postoperative time until first ambulation and until first oral intake for both studied groups|
Click here to view
| Discussion|| |
The current study reported improved outcome of the study patients with the use of pre-emptive epidural analgesia, irrespective of the medication used, manifested as a low request for rescue analgesia throughout the postoperative 24 h, despite the invasiveness of the surgical procedure undertaken. These data indicated the applicability for the epidural route for the provision of postoperative analgesia, and are in agreement with the study by Lin et al.  who compared epidural patient-controlled analgesia with a mixture of levobupivacaine and fentanyl with intravenous patient-controlled analgesia and reported that pain scores with epidural patient-controlled analgesia were significantly lower than those with intravenous route. In accordance with pre-emptive analgesia using magnesium sulfate as adjuvant, Farouk  reported that continuous epidural magnesium started before anesthesia provided pre-emptive, preventive analgesia and an analgesic-sparing effect that improved postoperative analgesia without increasing the incidence of side effects.
The use of adjuvant medication in combination with local anesthetic provided superior postoperative analgesia compared with local anesthetic alone and is manifested as significantly lower pain VAS scores and lower consumption of rescue analgesia with significantly lower numbers of requests. These data indicated the additive analgesic effects of epidural magnesium sulfate and coincided with that reported in the literature.
Bilir et al.  found no significant difference between epidural fentanyl alone versus fentanyl and magnesium with respect to time to first analgesic requirement, but significantly higher pain scores were reported with fentanyl alone; patients who received combination therapy required significantly smaller doses of rescue analgesia with significantly smaller cumulative analgesic consumption during the postoperative 24 h. Ghrab et al.  found that the addition of intrathecal magnesium sulfate (100 mg) to morphine 100 μg improved the quality and the duration of postoperative analgesia without increasing the incidence of adverse effects in patients undergoing cesarean section under spinal anesthesia.
Yousef and Amr  reported that the addition of magnesium sulfate to epidural bupivacaine and fentanyl in elective cesarean section using combined spinal-epidural anesthesia improved intraoperative conditions and the quality of postoperative analgesia. Ghatak et al.  compared magnesium sulfate or clonidine along with epidural bupivacaine for surgical anesthesia in patients undergoing lower abdominal and lower limb surgeries and reported that magnesium sulfate is a predictable and safe adjunct to epidural bupivacaine for rapid onset of anesthesia, whereas clonidine provided prolonged duration of anesthesia with sedation.
The reported beneficial effects of adding magnesium to local anesthetic for postoperative analgesia could be attributed to the more analgesic effect of magnesium sulfate during the phase 2 of pain mechanism , to attenuation of spinal release of amino acids acting as agonists for NMDARs , or to direct block of NMDA glutamate channel . However, a supposed local analgesic effect of magnesium was proposed depending on the findings recorded by Narang et al.  who found that magnesium sulfate when added as an adjuvant to lignocaine during intravenous regional anesthesia hastens the onset of sensory and motor block and decreases tourniquet pain.
Patients who received magnesium showed lower sedation scores at 30 and 120 min postoperatively with significantly higher frequency of patients with high sedation scores at 30 min but nonsignificant at 120 min compared with those who received plain local anesthetic; this effect could be attributed to the fact that magnesium is widely regarded as a central nervous system depressant . However, such minimal effect supported the fact that serum magnesium concentrations near to the upper limits of normal range are not related to sedation but only provide better quality of sleep, and less discomfort occurs in magnesium-treated patients during the postoperative period .
No significant hemodynamic changes were reported in both groups, apart from the effect of epidural analgesia on blood pressure with nonsignificant difference between both study groups. In agreement with such data, Kara et al.  reported that the hypotensive effect of magnesium explained by its direct vasodilating effect through a calcium channel blockade is rarely observed when magnesium is administered either as a bolus or as a continuous intravenous infusion.
The reported minimal adverse effects of epidural magnesium may be attributed to the slow systemic absorption of magnesium from the epidural space, modulating its sedative and hypotensive effects, and also to the small dose used and the administration as a bolus not as continuous infusion. In accordance with these assumptions, Bilir et al.  reported no difference with respect to hemodynamic and respiratory variables, sedation, pruritus, and nausea between epidural fentanyl versus epidural fentanyl and magnesium sulfate for 24 h epidural analgesia. El-Kerdawy  reported that, for lower extremity orthopedic procedure, supplementation of spinal anesthesia with combined intrathecally injected and epidurally infused Mg considerably reduced the perioperative analgesic requirements without any side effects. In addition, Benhaj Amor et al.  compared intravenous magnesium given as a bolus followed by infusion versus placebo and reported that the frequency of side effects was similar in the two groups.
| Conclusion|| |
Pre-emptive epidural bolus of levobupivacaine and magnesium sulfate provides postoperative analgesia superior to epidural levobupivacaine for patients undergoing open abdominal hysterectomy.
| Acknowledgements|| |
Conflicts of interest
| References|| |
|1.||Lu YL, Wang XD, Lai RC. Correlation of acute pain treatment to occurrence of chronic pain in tumor patients after thoracotomy. Ai Zheng 2008; 27:206-209. |
|2.|| Imasogie NN, Singh S, Watson JT, Hurley D, Morley-Forster P. Ultra low-dose naloxone and tramadol/acetaminophen in elderly patients undergoing joint replacement surgery: a pilot study. Pain Res Manag 2009; 14:103-108. |
|3.|| Senard M, Deflandre EP, Ledoux D, Roediger L, Hubert BM, Radermecker M, et al. Effect of celecoxib combined with thoracic epidural analgesia on pain after thoracotomy. Br J Anaesth 2010; 105:196-200. |
|4.|| Cui C, Xu M, Atzori M. Voltage-dependent block of N-methyl-d-aspartate receptors by dopamine D1 receptor ligands. Mol Pharmacol 2006; 70:1761-1770. |
|5.|| Magazanik LG, Tikhonov DB, Tikhonova TB, Lukomskaya NY. Mechanisms of the blockade of glutamate channel receptors: significance for structural and physiological investigations. Neurosci Behav Physiol 2007; 37:277-284. |
|6.|| Dravid SM, Erreger K, Yuan H, Nicholson K, Le P, Lyuboslavsky P, et al. Subunit-specific mechanisms and proton sensitivity of NMDA receptor channel block. J Physiol 2007; 581:107-128. |
|7.|| Coderre TJ, Katz J, Vaccariono AL, Melzack R. Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence. Pain 1993; 52:259-285. |
|8.|| Kim NK, Robinson HP. Effects of divalent cations on slow unblock of native NMDA receptors in mouse neocortical pyramidal neurons. Eur J Neurosci 2011; 34:199-212. |
|9.|| Nikolaev MV, Magazanik LG, Tikhonov DB. Influence of external magnesium ions on the NMDA receptor channel block by different types of organic cations. Neuropharmacology 2012; 62:2078-2085. |
|10.||1Huskisson EC. Measurement of pain. Lancet 1974; 2:1127-1131. |
|11.||1Detriche O, Berre J, Massaut J, Vincent JL. The Brussels sedation scale: use of a simple clinical sedation scale can avoid excessive sedation in patients undergoing mechanical ventilation in the intensive care units. Br J Anaesth 1999; 83:698-701. |
|12.||1Wolf AR, Hughes D. Pain relief for infants undergoing abdominal surgery: comparison of infusions of IV morphine and extradural bupivacaine. Br J Anaesth 1993; 70:10-16. |
|13.||1Day SJ, Graham DF. Sample size and power for comparing two or more treatment groups in clinical trials. BMJ 1989; 299:663-665. |
|14.||1Lin MC, Huang JY, Lao HC, Tsai PS, Huang CJ. Epidural analgesia with low-concentration levobupivacaine combined with fentanyl provides satisfactory postoperative analgesia for colorectal surgery patients. Acta Anaesthesiol Taiwan 2010; 48:68-74. |
|15.||1Farouk S. Pre-incisional epidural magnesium provides pre-emptive and preventive analgesia in patients undergoing abdominal hysterectomy. Br J Anaesth 2008; 101:694-699. |
|16.||1Bilir A, Gulec S, Erkan A, Ozcelik A. Epidural magnesium reduces postoperative analgesic requirement. Br J Anaesth 2007; 98:519-523. |
|17.||1Ghrab BE, Maatoug M, Kallel N, Khemakhem K, Chaari M, Kolsi K, Karoui A. Does combination of intrathecal magnesium sulfate and morphine improve postcaesarean section analgesia?. Ann Fr Anesth Reanim 2009; 28:454-459. |
|18.||1Yousef AA, Amr YM. The effect of adding magnesium sulphate to epidural bupivacaine and fentanyl in elective caesarean section using combined spinal-epidural anaesthesia: a prospective double blind randomised study. Int J Obstet Anesth 2010; 19:401-404. |
|19.||1Ghatak T, Chandra G, Malik A, Singh D, Bhatia VK. Evaluation of the effect of magnesium sulphate vs. clonidine as adjunct to epidural bupivacaine. Indian J Anaesth 2010; 54:308-313. |
|20.||2Takano Y, Sato E, Kaneko T, Sato I. Antihyperalgesic effects of intrathecally administered magnesium sulfate in rats. ? 2000; ?:?-?. |
|21.||2Tsai P, Cheng J, Marsala M, Lin C, Wen G, Yang L. Intrathecal magnesium sulfate attenuates algogenic behavior and spinal amino acids release after kainic acid receptor activation in rats. Neuroscience 2001; 301:115-118. |
|22.||2Buvanendran A, McCarthy RJ, Kroin JS, Leong W, Perry P, Tuman KJ. Intrathecal magnesium prolongs fentanyl analgesia: a prospective, randomized, controlled trial. Anesth Analg 2002; 95:661-666. |
|23.||2Narang S, Dali JS, Agarwal M, Garg R. Evaluation of the efficacy of magnesium sulphate as an adjuvant to lignocaine for intravenous regional anaesthesia for upper limb surgery. Anaesth Intensive Care 2008; 36:840-844. |
|24.||2MacLean RM. Magnesium and its therapeutic uses: a review. Am J Med 1993; 96:63-74. |
|25.||2Tramèr MR, Schneider J, Marti RA, Rifat K. Role of magnesium sulfate in postoperative analgesia. Anesthesiology 1996; 84:340-347. |
|26.||2Kara H, Sahin N, Ulusan V, Aydogdu I. Magnesium infusion reduces perioperative pain. Eur J Anaesthesiol 2002; 19:52-56. |
|27.||2El-Kerdawy H. Analgesic requirements for patients undergoing lower extremity orthopedic surgery - the effect of combined spinal and epidural magnesium. Middle East J Anesthesiol 2008; 19:1013-1025. |
|28.||2Benhaj Amor M, Barakette M, Dhahri S, Ouezini R, Lamine K, Jebali A, Ferjani M. Effect of intra and postoperative magnesium sulphate infusion on postoperative pain. Tunis Med 2008; 86:550-555. |
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]