Up until relatively recently, the concept of pre-treatment medications for rapid sequence intubation has remained uncontested. The acronym “LOAD” has often been proposed as a simple way to remember and apply this concept in clinical practice – lidocaine, opioids, atropine, and defasciculating doses of neuromuscular blocking agents. While most of these (classes) of agents have sparked controversy in the literature in recent years regarding their (f)utility as pre-treatment measures in rapid sequence intubation, it may be worth exploring other agents that may replace some of the letters of this acronym.
One agent that has had a surprisingly long and interesting history in the world of anesthesia is one that many that may not even consider for use in this setting for airway management. The agent? Magnesium…yes, magnesium.
Some of the effects of magnesium in this clinical setting, largely derived from the anesthesia literature, are described below:
1 – Catecholamine Blunting Effect
Magnesium is thought to attenuate the release of catecholamine associated with the process of intubation through its action on the adrenal medulla and nerve terminals of the adrenergic system. It has been hypothesized that magnesium competes with the actions of calcium at the ion channels within these systems, which ultimately prevents the response of catecholamine release induced by calcium in the first place (1-3). One of the earliest studies conducted in human subjects that tested this premise occurred in patients undergoing intubation who were randomized to receive an intravenous bolus of magnesium sulfate at a dose 60 mg/kg or placebo solution of 0.9% sodium chloride placebo with the administration of thiopental and succinylcholine. After intubation, the investigators found that heart rate remained unchanged in patients treated with magnesium and the rate of increase in systolic blood pressure was less in those patients treated with magnesium relative to placebo (p < 0.05). In addition, in those patients treated with magnesium sulfate, measured plasma concentrations of epinephrine and norepinephrine were also found to be significantly lower post-intubation relative to placebo (4). Several other studies have demonstrated similar results in attenuation an increase in heart rate, systolic blood pressure, and mean arterial pressure following administration of magnesium pre-intubation with significant decrease in measured plasma concentrations of catecholamines (5-8).
2 – Minimization of Fasciculation Associated with Administration of Succinylcholine
In terms of preference of paralytic for the purposes of intubation, some clinicians are of the camp that “succ(inylcholine) sucks and roc(uronium) rocks.” Nonetheless, whether some folks like it or not, succinylcholine still continues to utilized to facilitate intubation in daily practice. Investigators of a few studies have suggested that magnesium may minimize the number and degree of muscle fasciculation associated with the administration of succinylcholine (9-13). There is conflicting evidence related to the downstream effects of this effect, such as reduction in the increase in potassium associated with the administration of succinylcholine and myalgia occurring as a result of fasciculation (14).
3 – Shorter Onset and Prolonged Effect of Non-Depolarizing Neuromuscular Blocking Agents
It has been proposed that magnesium may mitigate the release of acetylcholine from presynaptic nerve terminals at the neuromuscular junction as a result of its actions in antagonizing the action of calcium in mediating this reaction (15). In addition, other mechanisms that have been suggested leading to the effect of shorter onset and prolonged effect of non-depolarizing neuromuscular blocking agents includes reduced sensitivity of the neuronal endplate to acetylcholine and modification of the electrical excitability threshold of the muscle membrane (16-17). Again, the evidence related to this concept is somewhat conflicting, as depending on the study evaluated, the specific neuromuscular blocking agent utilized, and associated outcomes, there may or may not be a demonstrated difference on onset and duration of action of the agent with concomitant administration of magnesium. For some, this practice is certainly not without concern or controversy due to the unpredictability at which this may occur in terms of the potential danger associated with prolonged paralysis as well as the very idea of exploiting the use of a drug-drug interaction in such a critical setting as airway management.
With these purported effects, is it worth administering magnesium as a pre-treatment adjunct for the purposes of intubation? Some may argue that this concept has yet to be evaluated in the setting of the emergency department, and as a result, the clinical applicability is minimal at best, especially as the evidence associated with the outcomes of the effects described above are conflicting and the dose of magnesium evaluated in many of these trials varies (but generally, doses have fallen within 10 mg/kg of 50 mg/kg/dose of intravenous magnesium sulfate). For some who may be interested in thinking outside of the box when it comes to airway management and novel measures of application in the emergency department, this path may be worth future pursuit.Peer reviewed by: Craig Cocchio, PharmD, BCPS (@iEMPharmD)
- Douglas WW, Rubin RP. The mechanism of catecholamine release from the adrenal medulla and the role of calcium in stimulus-secretion coupling. J Physiol 1963; 167:288-310.
- Lishajko F. Releasing effect of calcium and phosphate on catecholamines, ATP, and protein from chromaffin cell granules. Acta Physiol Scand 1970; 79:575-85.
- Sasaki R, Hirota K, Roth SH, Yamazaki M: Extracellular magnesium ion modifies the actions of volatile anesthetics in area CA1 of rat hippocampus in vitro. Anesthesiology 2002; 96:681-7.
- James MFM, Beer RE, Esser JD. Intravenous magnesium sulfate inhibits catecholamine release associated with tracheal intubation. Anesth Analg 1989; 68:772-6.
- Puri GD, Marudhachalam KS, Chari P, Suri RK. The effect of magnesium sulphate on hemodynamics and its efficacy in attenuating the response to endotracheal intubation in patients with coronary artery disease. Anesth Analg 1998; 87:808-11.
- Durmus M, But AK, Erdem TB, Ozpolat Z, Ersoy MO: The effects of magnesium sulphate on sevoflurane minimum alveolar concentrations and haemodynamic responses. Eur J Anaesthesiol 2006; 23:54-9.
- Yap LC, Ho RT, Jawan B, Lee JH. Effects of magnesium sulfate pretreatment on succinylcholine-facilitated tracheal intubation. Acta Anaesthesiol Sin 1994; 32:45-50.
- Ashton WB, James MFM, Janicki P, Uys PC. Attenuation of the pressor response to tracheal intubation by magnesium sulphate with and without alfentanil in hypertensive proteinuric patients undergoing caesarean section. Br J Anaesth 1991; 67:741-7.
- Stacey MR, Barclay K, Asai T, Vaughan RS. Effects of magnesium sulphate on suxamethonium-induced complications during rapid-sequence induction of anaesthesia. Anaesthesia 1995; 50:933-6.
- Sakuraba S, Serita R, Kosugi S, Eriksson LI, Lindahl SG, Takeda J. Pretreatment with magnesium sulphate is associated with less succinylcholine-induced fasciculation and subsequent tracheal intubation-induced hemodynamic changes than precurarization with vecuronium during rapid sequence induction. Acta anaesthesiologica Belgica 2006; 57:253-7.
- Danladi KY, Sotunmbi PT, Eyelade OR. The effects of magnesium sulphate-pretreatment on suxamethonium-induced complications during induction of general endotracheal anaesthesia. Afr J Med Med Sci 2007; 36:43-7.
- Kumar M, Talwar N, Goyal R, Shukla U, Sethi A. Effect of magnesium sulfate with propofol induction of anesthesia on succinylcholine-induced fasciculations and myalgia. J Anesthesiol Clin Pharmacol 2012; 28:81-5.
- Ahsan B, Rahimi E, Moradi A, Rashadmanesh N. The effects of magnesium sulphate on succinylcholine-induced fasciculation during induction of general anaesthesia. J Pak Med Assoc 2014; 64:1151-3.
- Schreiber JU, Lysakowski C, Fuchs-Buder T, Tramèr MR. Prevention of succinylcholine-induced fasciculation and myalgia: a meta-analysis of randomized trials. Anesthesiology 2005; 103:877-84.
- Ghoneim MM, Long JP. The interaction between magnesium and other neuromuscular blocking agents. Anesthesiology 1970; 32:23-7.
- Sinatra RS, Philip BK, Naulty JS, Ostheimer GW. Prolonged neuromuscular blockade with vecuronium in a patient treated with magnesium sulfate. Anesth Analg. 1985;64:1220-2.
- Fuchs-Buder T, Wilder-Smith OH, Borgeat A, Tassonyi E. Interaction of magnesium sulphate with vecuronium-induced neuromuscular block. Br J Anaesth. 1995;74:405-9.