Magnesium Sulfate: A Versatile Anesthetic Adjuvant
Hyun Jung Shin and Sang Hwan Do*
Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Korea
Submission: September 21, 2017; Published: December 13, 2017
*Corresponding author: Sang Hwan Do, Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea, Telephone: +82-31-787-7501, Fax: +82-31-787-4063, Email: shdo@snu.ac.kr
How to cite this article: Hyun Jung Shin, Sang Hwan Do. Magnesium Sulfate: A Versatile Anesthetic Adjuvant. J Anest & Inten Care Med. 2017; 4(5): 555646. DOI:10.19080/JAICM.2018.05.555646
Abstract
Magnesium sulfate has long been used to prevent seizures in parturients with preeclampsia. Additionally, it has been used in patients with status asthmaticus or Torsades de pointes arrhythmia. Recently, numerous clinical studies reported that magnesium sulfate may improve postoperative analgesia, neuromuscular relaxation, post anesthetic shivering, sore throat, back pain after surgery. If used appropriately, magnesium sulfate can be advantageous for patients recovering from surgery.
Keywords: Magnesium Sulfate; Postoperative Analgesia; Post Anesthetic Shivering.
Introduction
Magnesium sulfate has not been familiar to anesthesiologists until recently. However, magnesium plays a critical role in a variety of physiological processes of the human body. Recently, it has drawn much attention in the field of anesthesiology [1,2], resulting in numerous publications of clinical studies [3,6], review articles, and meta-analyses [7-12]. In this review article, clinical efficacies of magnesium sulfate are described.
Pharmacology and Physiology
As the 4th most common cation, magnesium plays a variety of key roles in the physiological processes of the human body [13]. The normal plasma concentration range of magnesium is around 0.7-1.3 mmol/L (1.4-2.6 mEq/L). Unless patient's renal function is compromised, hyper magnesemia is rare in clinical settings. Hypo magnesemia, on the other hand, is common in perioperative situations because magnesium, supplied through diet, is easily lost by enema, bleeding, and transfusion [13,14]. Magnesium depletion often occurs in patients just before surgery, which peaks immediately after surgery [13]. From a physiological perspective, magnesium is a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist and a calcium channel blocker
Magnesium sulfate-a drug with high therapeutic index—is a safe drug. Magnesium toxicity occurs when the level goes above 4 mM/L, which begins with a loss of deep tendon reflex and drowsiness [13]. When the level further increases, respiratory arrest (> 6 mM/L) or cardiac arrest (> 8 mM/L) may develop [16]. Calcium administration, supportive care with ventilatory/ circulatory support and/or excretion of magnesium (loop diuretics or hemodialysis) may be used to treat magnesium toxicity.
Post operative Analgesia
Adequate treatment of pain after surgery is important not only for the recovery from surgical operation but also for the prevention of chronic postsurgical pain [17]. Since magnesium sulfate was studied in surgical patients for the first time in 1996 [18], numerous clinical studies have been reported regarding its analgesia potentiation in surgical patients. Most previous studies suggest that perioperative intravenous administration of magnesium sulfate potentiates analgesia after surgery [9,10]. The usual dosage regimen of magnesium sulfate was as follows: a loading dose of 30-50 mg/kg followed by a maintenance dose of 6-20 mg/kg/h (continuous infusion), until the end of surgery [11]. Even a single bolus dose of magnesium sulfate without the maintenance dose was previously reported to provide effective postoperative analgesia [19].
In terms of potentiation of postoperative analgesia, magnesium sulfate may decrease not only opioid consumption after surgery, but also improve pain scores as well [20]. Decreased opioid consumption after surgery can be associated with less postoperative complications, such as nausea and vomiting [6,21]. Sometimes, magnesium sulfate decreased the requirement for anesthetics during surgery. Ryu et al. [22] made a comparison between magnesium sulfate and remifentanil as an agent for hypotensive anesthesia in patients undergoing middle ear surgery. Both drugs showed adequate level of controlled hypotension; however, the magnesium group showed more favorable postoperative courses with better analgesia.
In addition, sevoflurane was less required in the magnesium group, showing a sevoflurane-sparing effect of magnesium sulfate. The analgesia-potentiating effect of magnesium stabilized blood pressure and heart rate during recovery from anesthesia [22]. It is also conceivable that the use of magnesium sulfate during surgery may mitigate remifentanil-induced hyperalgesia in patients recovering from remifentanil-based anesthesia [23].
The usefulness of magnesium was also reported for postoperative analgesia in patients undergoing spinal anesthesia.Intravenous administration of magnesium sulfate improved postoperative analgesia in patients undergoing total hip replacement arthroplasty under spinal anesthesia [6]. A small dose of magnesium sulfate added to intrathecal administration of local anesthetic extended the duration of spinal anesthesia and improved postoperative analgesia [4,24-26]. Moreover, only postoperative intravenous administration of magnesium sulfate increased the time to analgesic need and the total consumption of analgesics after spinal anesthesia [6,27]. Unlike intrathecal magnesium sulfate administration, there are limited data on the effectiveness of epidural administration. Arcioni et al. [24] reported that combined intrathecal and epidural administration of magnesium sulfate reduced postoperative analgesic requirements. When mixed with local anesthetics, magnesium also showed beneficial effects in intravenous regional anesthesia (Bier block).
Turan et al. [28] reported that when magnesium sulfate was added to lidocaine for Bier block, the quality of anesthesia and analgesia was improved. However, they also reported that recovery was delayed from Bier block in the magnesium group. The mechanism of pain-reducing effect of magnesium seems to be the attenuating effect on central sensitization via NMDA antagonism [10]. In addition, calcium channel blockade by magnesium may also lead to better postoperative analgesia via augmentation of morphine-induced analgesia [29].
Muscle Relaxation
As a calcium channel blocker, magnesium decreases acetylcholine release at the presynaptic nerve terminals, which diminishes the excitability of muscle fiber and reduces the amplitude of endplate potential, resulting in the potentiation of neuromuscular blockade by nondepolarizing muscle relaxants [30]. Thus, one of the findings from magnesium studies in patients undergoing general anesthesia is that magnesium decreases the requirement for nondepolarizing muscle relaxants [21,31,32] and accelerates the onset of muscle relaxation [33-35].
Although some researchers have focused on the direct effects of magnesium on the neuromuscular blockade, others concluded that magnesium sulfate administration reduced the requirements for nondepolarizing neuromuscular blockers. Administration of magnesium sulfate—while potentiating the effect of muscle relaxants— has not been found to delay the recovery from general anesthesia [21,36,37]. In the operating room, some patients exhibit resistance to nondepolarizing muscle relaxants, which may result from either certain drugs (such as valproic acid) or diseases (such as cerebral palsy) [31,38]. Magnesium sulfate can be used efficaciously in such cases. Moreover, when used during anesthesia induction, magnesium sulfate can prevent cardiovascular responses (hypertension and tachycardia) from endotracheal intubation [39,40]. In addition, when combined with rocuronium priming, magnesium sulfate improved rapid- sequence intubating condition [35].
Magnesium sulfate was also reported to improve tracheal intubation using succinylcholine as it has shown to prevent hyperkalemia and fasciculation induced by succinylcholine [41]. However, it was also reported that the clinical course of malignant hyperthermia induced by succinylcholine was not influenced by magnesium sulfate administration [42]. Recently, intraoperative magnesium sulfate administration showed beneficial to postoperative pulmonary function in patients who underwent video-assisted thoracoscopic surgery [43]. This result seems tobe due to muscle relaxant sparing effect and analgesia potentiating effect of magnesium sulfate [44]. Because postoperative respiratory impairment may result from residual neuromuscular blockade and postoperative pain [45,46] magnesium sulfate use is worth being considered in terms of pulmonary function improvement after surgery.
Miscellaneous Effects
Based on its diverse roles in cellular functions, magnesium sulfate has been suggested to have neuroprotective effects [29]. In the clinical setting, intraoperative use of magnesium sulfate attenuated postoperative neurocognitive impairment [47,48]. Postoperative emergence agitation-related to alteration of cognitive perception-was also reduced in pediatric patients who received magnesium sulfate during adenotonsillectomy [3].
It is also worthy of note that magnesium sulfate has an anti-shivering effect [49]. Shivering is a frequent complication following general anesthesia, and the incidence has been reported to range from 10% to 66% [50]. Due to the undesirable effects of postoperative shivering, such as increased postoperative pain, increased intraocular pressure, interference with monitoring equipment, and increased oxygen consumption [51], it is important to appropriately control postoperative shivering. Kizilirmak et al. [52] reported that an intravenous administration of magnesium sulfate was effective in treating shivering after general anesthesia. Moreover, magnesium sulfate reduced the incidence of shivering after neuraxial blockade when administered intravenously or intrathecally [53,54].
Several studies suggested the effect of magnesium sulfate on postoperative sore throat (POST). Interestingly, various routes of magnesium administration have been shown to effectively control POST. Park et al. [55] described that an intravenous administration of magnesium sulfate appears to be non-inferior to dexamethasone in preventing POST after lumbar spinal surgery in prone position. Magnesium sulfates gargle could also decrease the incidence and severity of POST significantly compared with ketamine gargle [56]. Preoperative administration of oral magnesium lozenge was effective in reducing the incidence and severity of POST in the immediate postoperative period [57].
Since magnesium is an important cofactor of the blood coagulation cascade [58], it also has diverse effects on blood coagulation. Despite some clinical trials that suggested the lack of coagulation effect by magnesium [59,60] several studies have demonstrated an anti-thrombotic effect of magnesium sulfate. Na et al. [31] reported that an intraoperative administration of magnesium sulfate attenuated blood hypercoagulability in patients undergoing laparoscopic colorectal cancer surgery [61] and pelviscopic gynecological operations [62]. Because postoperative hypercoagulability could induce thromboembolic complications [63,64], magnesium sulfate administration may be useful for preventing such complications after surgery. Further studies regarding the effects of magnesium sulfate on perioperative blood coagulation are necessary.
Conclusion
Magnesium sulfate has been around for a long time, but only as of recently, its properties have been investigated and found to be useful in the field of anesthesia. If used appropriately, it would enhance smooth recovery and better postoperative outcome for surgical patients.
Conflict of Interest Statement
There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.
References
- Soave PM, Conti G, Costa R, Arcangeli A (2009) Magnesium and anaesthesia. Curr Drug Targets 10(8): 734-743.
- Barbosa FT, Barbosa LT, Juca MJ, Cunha RM (2010) Applications of magnesium sulfate in obstetrics and anesthesia. Rev Bras Anestesiol 60(1): 104-110.
- Abdulatif M, Ahmed A, Mukhtar A, Badawy S (2013) The effect of magnesium sulphate infusion on the incidence and severity of emergence agitation in children undergoing adenotonsillectomy using sevoflurane anaesthesia. Anaesthesia 68(10): 1045-1052.
- Buvanendran A, McCarthy RJ, Kroin JS, Leong W, Perry P, et al. (2002) Intrathecal magnesium prolongs fentanyl analgesia: a prospective, randomized, controlled trial. Anesth Analg 95(3): 661-666.
- Czarnetzki C, Lysakowski C, Elia N, Tramer MR (2010) Time course of rocuronium-induced neuromuscular block after pre-treatment with magnesium sulphate: a randomised study. Acta Anaesthesiol Scand 54(3): 299-306.
- Hwang JY, Na HS, Jeon YT, Ro YJ, Kim CS, et al. (2010) I.V. infusion of magnesium sulphate during spinal anaesthesia improves postoperative analgesia. Br J Anaesth 104(1): 89-93.
- Dube L, Granry JC (2003) The therapeutic use of magnesium in anesthesiology, intensive care and emergency medicine: a review. Can J Anaesth 50(7): 732-746.
- Lysakowski C, Suppan L, Czarnetzki C, Tassonyi E, Tramer MR (2007) Impact of the intubation model on the efficacy of rocuronium during rapid sequence intubation: systematic review of randomized trials. Acta Anaesthesiol Scand 51(7): 848-857.
- De Oliveira GS, Castro Alves LJ, Khan JH, McCarthy RJ (2013) Perioperative systemic magnesium to minimize postoperative pain: a meta-analysis of randomized controlled trials. Anesthesiology 119(1): 178-190.
- Albrecht E, Kirkham KR, Liu SS, Brull R (2013) Peri-operative intravenous administration of magnesium sulphate and postoperative pain: a meta-analysis. Anaesthesia 68(1): 79-90.
- Do SH (2013) Magnesium: a versatile drug for anesthesiologists. Korean J Anesthesiol 65(1): 4-8.
- Eizaga Rebollar R, Garcia Palacios MV, Morales Guerrero J, Torres LM (2017) Magnesium sulfate in pediatric anesthesia: the Super Adjuvant. Paediatr Anaesth 27(5): 480-489.
- Fawcett WJ, Haxby EJ, Male DA (1999) Magnesium: physiology and pharmacology. Br J Anaesth 83(2): 302-320.
- Sharma P, Chung C, Vizcaychipi M (2014) Magnesium: The Neglected Electrolyte? A Clinical Review. Pharmacology & Pharmacy 5: 762-772.
- Aglio LS, Stanford GG, Maddi R, Boyd JL 3rd, Nussbaum S, et al. (1991) Hypomagnesemia is common following cardiac surgery. J Cardiothorac Vasc Anesth 5(3): 201-208.
- Sugiyama M, Kusumoto E, Ota M, Kimura Y, Tsutsumi N, et al. (2016) Induction of potentially lethal hypermagnesemia, ischemic colitis, and toxic megacolon by a preoperative mechanical bowel preparation: report of a case. Surg Case Rep 2(1): 18.
- Rashiq S, Dick BD (2014) Post-surgical pain syndromes: a review for the non-pain specialist. Can J Anaesth 61(2): 123-130.
- Tramer MR, Schneider J, Marti RA, Rifat K (1996) Role of magnesium sulfate in postoperative analgesia. Anesthesiology 84(2): 340-347.
- Taheri A, Haryalchi K, Mansour Ghanaie M, Habibi Arejan N (2015) Effect of low-dose (single-dose) magnesium sulfate on postoperative analgesia in hysterectomy patients receiving balanced general anesthesia. Anesthesiol Res Pract 2015: 306145.
- Bujalska Zadrozny M, Tatarkiewicz J, Kulik K, Filip M, Naruszewicz M (2017) Magnesium enhances opioid-induced analgesia - What we have learnt in the past decades? Eur J Pharm Sci 99: 113-127.
- Ryu JH, Kang MH, Park KS, Do SH (2008) Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia. Br J Anaesth 100(3): 397-403.
- Ryu JH, Sohn IS, Do SH (2009) Controlled hypotension for middle ear surgery: a comparison between remifentanil and magnesium sulphate. Br J Anaesth 103(4): 490-495.
- Song JW, Lee YW, Yoon KB, Park SJ, Shim YH (2011) Magnesium sulfate prevents remifentanil-induced postoperative hyperalgesia in patients undergoing thyroidectomy. Anesth Analg 113(2): 390-397.
- Arcioni R, Palmisani S, Tigano S, Santorsola C, Sauli V, et al. (2007) Combined intrathecal and epidural magnesium sulfate supplementation of spinal anesthesia to reduce post-operative analgesic requirements: a prospective, randomized, double-blind, controlled trial in patients undergoing major orthopedic surgery. Acta Anaesthesiol Scand 51(4): 482-489.
- Kathuria B, Luthra N, Gupta A, Grewal A, Sood D (2014) Comparative efficacy of two different dosages of intrathecal magnesium sulphate supplementation in subarachnoid block. J Clin Diagn Res 8(6): GC01- GC05.
- Ozalevli M, Cetin TO, Unlugenc H, Guler T, Isik G (2005) The effect of adding intrathecal magnesium sulphate to bupivacaine-fentanyl spinal anaesthesia. Acta Anaesthesiol Scand 49(10): 1514-1519.
- Kahraman F, Eroglu A (2014) The effect of intravenous magnesium sulfate infusion on sensory spinal block and postoperative pain score in abdominal hysterectomy. Biomed Res Int 2014:236024.
- Turan A, Memis D, Karamanlioglu B, Guler T, Pamukcu Z (2005) Intravenous regional anesthesia using lidocaine and magnesium. Anesth Analg 100(4): 1189-1192.
- Herroeder S, Schonherr ME, De Hert SG, Hollmann MW (2011) Magnesium--essentials for anesthesiologists. Anesthesiology 114(4): 971-993.
- Fisher DM (1999) Clinical pharmacology of neuromuscular blocking agents. Am J Health Syst Pharm 56(11 Suppl 1): S4-S9.
- Na HS, Lee JH, Hwang JY, Ryu JH, Han SH, et al. (2010) Effects of magnesium sulphate on intraoperative neuromuscular blocking agent requirements and postoperative analgesia in children with cerebral palsy. Br J Anaesth 104(3): 344-350.
- Ryu JH, Koo BW, Kim BG, Oh AY, Kim HH, et al. (2016) Prospective, randomized and controlled trial on magnesium sulfate administration during laparoscopic gastrectomy: effects on surgical space conditions and recovery profiles. Surg Endosc 30(11): 4976-4984.
- Choi ES, Jeong WJ, Ahn SH, Oh AY, Jeon YT, et al. (2017) Magnesium sulfate accelerates the onset of low-dose rocuronium in patients undergoing laryngeal microsurgery. J Clin Anesth 36: 102-106.
- Park SJ, Cho YJ, Oh JH, Hwang JW, Do SH, et al. (2013) Pretreatment of magnesium sulphate improves intubating conditions of rapid sequence tracheal intubation using alfentanil, propofol, and rocuronium - a randomized trial. Korean J Anesthesiol 65(3): 221-227.
- Kim MH, Oh AY, Jeon YT, Hwang JW, Do SH (2012) A randomised controlled trial comparing rocuronium priming, magnesium pretreatment and a combination of the two methods. Anaesthesia 67(7): 748-754.
- Lee DH, Kwon IC (2009) Magnesium sulphate has beneficial effects as an adjuvant during general anaesthesia for Caesarean section. Br J Anaesth 103(6): 861-866.
- Ozcan PE, Tugrul S, Senturk NM, Uludag E, Cakar N, et al. (2007) Role of magnesium sulfate in postoperative pain management for patients undergoing thoracotomy. J Cardiothorac Vasc Anesth 21(6): 827-831.
- Kim MH, Hwang JW, Jeon YT, Do SH (2012) Effects of valproic acid and magnesium sulphate on rocuronium requirement in patients undergoing craniotomy for cerebrovascular surgery. Br J Anaesth 109(3): 407-412.
- Panda NB, Bharti N, Prasad S (2013) Minimal effective dose of magnesium sulfate for attenuation of intubation response in hypertensive patients. J Clin Anesth 25(2): 92-97.
- Shin YH, Choi SJ, Jeong HY, Kim MH (2011) Evaluation of dose effects of magnesium sulfate on rocuronium injection pain and hemodynamic changes by laryngoscopy and endotracheal intubation. Korean J Anesthesiol 60(5): 329-333.
- Yap LC, Ho RT, Jawan B, Lee JH (1994) Effects of magnesium sulfate pretreatment on succinylcholine-facilitated tracheal intubation. Acta Anaesthesiol Sin 32(1): 45-50.
- Metterlein T, Schuster F, Kranke P, Hager M, Roewer N, et al. (2011) Magnesium does not influence the clinical course of succinylcholine- induced malignant hyperthermia. Anesth Analg 112(5): 1174-1178.
- Sohn HM, Jheon SH, Nam S, Do SH (2017) Magnesium sulphate improves pulmonary function after video-assisted thoracoscopic surgery: A randomised double-blind placebo-controlled study. Eur J Anaesthesiol 34(8): 508-514.
- Rodriguez Rubio L, Nava E, Del Pozo JSG, Jordan J (2017) Influence of the perioperative administration of magnesium sulfate on the total dose of anesthetics during general anesthesia. A systematic review and meta-analysis. J Clin Anesth 39: 129-138.
- Tiefenthaler W, Pehboeck D, Hammerle E, Kavakebi P, Benzer A (2011) Lung function after total intravenous anaesthesia or balanced anaesthesia with sevoflurane. Br J Anaesth 106(2):272-276.
- Siafakas NM, Mitrouska I, Bouros D, Georgopoulos D (1999) Surgery and the respiratory muscles. Thorax 54(5): 458-465.
- Mack WJ, Kellner CP, Sahlein DH, Ducruet AF, Kim GH, et al. (2009) Intraoperative magnesium infusion during carotid endarterectomy: a double-blind placebo-controlled trial. J Neurosurg 110(5): 961-967.
- Bilotta F, Gelb AW, Stazi E, Titi L, Paoloni FP, et al. (2013). Br J Anaesth 110 Suppl 1: i113-i1120.
- Park SM, Mangat HS, Berger K, Rosengart AJ (2012) Efficacy spectrum of antishivering medications: meta-analysis of randomized controlled trials. Crit Care Med 40(11): 3070-3082.
- Lewis SR, Nicholson A, Smith AF, Alderson P (2015) Alpha-2 adrenergic agonists for the prevention of shivering following general anaesthesia. Cochrane Database Syst Rev 8: CD011107.
- Alfonsi P (2003) Postanaesthetic shivering. Epidemiology, pathophysiology and approaches to prevention and management. Minerva Anestesiol 69(5): 438-442.
- Kizilirmak S, Karakas SE, Akca O, Ozkan T, Yavru A, et al. (1997) Magnesium sulfate stops postanesthetic shivering. Ann N Y Acad Sci 813: 799-806.
- Ibrahim IT, Megalla SA, Khalifa OM (2014) Prophylactic vs. therapeutic magnesium sulfate for shivering during spinal anesthesia. Egyptian Journal of Anaesthesia 30(1): 31-37.
- Faiz SH, Rahimzadeh P, Imani F, Bakhtiari A (2013) Intrathecal injection of magnesium sulfate: shivering prevention during cesarean section: a randomized, double-blinded, controlled study. Korean J Anesthesiol 65(4): 293-298.
- Park JH, Shim JK, Song JW, Jang J, Kim JH, et al. (2015) A Randomized, Double-blind, Non-inferiority Trial of Magnesium Sulphate versus Dexamethasone for Prevention of Postoperative Sore Throat after Lumbar Spinal Surgery in the Prone Position. Int J Med Sci 12(10): 797-804.
- Teymourian H, Mohajerani SA, Farahbod A (2015) Magnesium and ketamine gargle and postoperative sore throat. Anesth Pain Med 5(3): e22367.
- Borazan H, Kececioglu A, Okesli S, Otelcioglu S (2012) Oral magnesium lozenge reduces postoperative sore throat: a randomized, prospective, placebo-controlled study. Anesthesiology 117(3): 512-518.
- Sekiya F, Yoshida M, Yamashita T, Morita T (1996) Magnesium (II) is a crucial constituent of the blood coagulation cascade. Potentiation of coagulant activities of factor IX by Mg2+ ions. J Biol Chem 271(15): 8541-8544.
- Ravn HB, Lassen JF, Bergenhem N, Kristensen AT (2001) Intravenous magnesium does not influence the activity of the coagulation cascade. Blood Coagul Fibrinolysis 12(4): 223-228.
- Ames WA, McDonnell N, Potter D (1999) The effect of ionised magnesium on coagulation using thromboelastography. Anaesthesia 54(10): 999-1001.
- Na HS, Shin HJ, Kang SB, Hwang JW, Do SH (2014) Effects of magnesium sulphate on coagulation after laparoscopic colorectal cancer surgery, measured by rotational thromboelastometry (ROTEM®). Anaesthesia 69(12): 1314-1321.
- Na HS, Chung YH, Hwang JW, Do SH (2012) Effects of magnesium sulphate on postoperative coagulation, measured by rotational thromboelastometry (ROTEM®). Anaesthesia 67(8): 862-869.
- Kashuk JL, Moore EE (2009) The emerging role of rapid thromboelastography in trauma care. J Trauma 67(2): 417-418.
- Mc Crath DJ, Cerboni E, Frumento RJ, Hirsh AL, Bennett Guerrero E (2005) Thromboelastography maximum amplitude predicts postoperative thrombotic complications including myocardial infarction. Anesth Analg 100(6): 1576-1583.