INTRODUCTION Etomidate is an imidazole derivative with potent hypnotic properties and better haemodynamic stability as compared to other induction agents.[1] However, the most certain and undesirable side effect of etomidate is myoclonus; the incidence of which has been reported as much as 50%–80% after induction.[2] We designed this study to compare the influence of dexmedetomidine with magnesium sulphate on incidence and severity of etomidate induced myoclonus. The secondary outcome was to compare the incidence of pain on etomidate injection and study the haemodynamic response during intubation. METHODS This randomised, double-blind clinical study was conducted from July to December 2019 on 100 patients posted for surgery under general anaesthesia after approval of the Institutional Ethics Committee. The study population consisted of 90 patients who consented for the study; of both the genders aged 18–50 years, with body mass index <25 kg/m2, classified as American Society of Anesthesiologists (ASA) physical status I or II. The patients were randomly allocated into three groups using simple randomisation and closed envelope method based upon a computer-generated list and received pre-treatment of either normal saline, dexmedetomidine (0.5 μg/kg) or magnesium sulphate (30 mg/kg) 10 min before etomidate induction [Figure 1].Figure 1: CONSORT chartAll patients received injection midazolam 0.03 mg/kg intravenously. Study drugs were prepared and coded in 10 ml syringes by an anaesthesiologist not involved in the study. Group C received 10-mL normal saline that acted as control group, group D received dexmedetomidine 0.5 μg/kg and group M received magnesium 30 mg/kg; both diluted up to 10 ml with normal saline and infused over 10 minutes. All patients were preoxygenated with 100% oxygen via face mask for 3 min and induction was carried out with intravenous etomidate 0.3 mg/kg administered over 60 s. After evaluation of myoclonus, all patients received fentanyl 2 μg/kg and intubation was facilitated with injection vecuronium 0.1 mg/kg and further maintenance of anaesthesia carried out in the conventional manner. Myoclonus was defined as involuntary, short muscle contractions, of a whole muscle, or of different muscles of one group leading to short observable movements of the corresponding body parts. The severity of myoclonus was graded as follows: 0––no myoclonus, 1––mild myoclonus (short movements of a body segment e.g., a finger or wrist), 2––moderate myoclonus (contraction of different groups of muscles, e.g., face and leg), 3––severe myoclonus (intense clonic movement in two or more muscle groups, e.g., fast adduction of a limb).[3] The secondary objective was to study the incidence and intensity of pain on etomidate injection. The assessment of pain was done after 25% of total etomidate dose was administered and severity was graded using a 4-grade scale (McCrirrick and Hunter scale)[4] as 0––no pain, 1––mild (pain reported only when asked), 2––moderate (pain reported without being asked or reported when asked and there were associated behavioural symptoms), and 3––severe (verbal response, grimacing, pulling the arm, tearing in the eyes). Haemodynamic parameters were monitored as baseline, after study drug, before induction, immediately after intubation and 5 min after intubation. Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 16.0 (SPSS, Chicago, Illinois). A value of P < 0.05 was considered as significant. RESULTS Demographic data represented in Table 1 show no significant difference between the three groups. The evaluation of myoclonus in the three groups is shown in Table 2. Myoclonus was observed in 20 patients in group C, 12 patients in group D and 8 patients in group M and the difference was of statistical significance (P = 0.023). More number of patients in group C had moderate i.e., grade 2 myoclonus and the difference was statistically significant (P < 0.05). Additionally, the severity level in group M was significantly lower as compared to other 2 groups, the median intensity of grade 2 myoclonus being one patient in group M as compared to six patients in group D (P = 0.028).Table 1: Comparison of demographic profile between the three groupsTable 2: Comparison of incidence and intensity of myoclonus among the 3 groupsRegarding the pain on etomidate injection, we found a statistically significant difference (P = 0.002) in its incidence between the three groups [Table 3]. Between the study drugs, we observed that a smaller number of patients in group M (n = 3) had moderate to severe pain as compared to group D (n = 7) and the difference was statistically significant (P = 0.036). Without pre-treatment as in group C, the number of patients with moderate to severe pain was statistically high (n = 17).Table 3: Comparison of incidence and severity of pain among the 3 groupsThe haemodynamic variables between the three groups during and after intubation were comparable. [Figures 2 and 3].Figure 2: Comparison of heart rate (per minute) in the three groupsFigure 3: Comparison of mean arterial pressure (mm Hg) in three groupsDISCUSSION Our present study demonstrates that pre-treatment with both dexmedetomidine and magnesium reduces the incidence of myoclonus induced by etomidate. However, magnesium appears to be more effective than dexmedetomidine in not only decreasing the incidence but also reducing the intensity of myoclonus. The study also shows that pain on etomidate injection is reduced more efficiently by magnesium when compared to dexmedetomidine. Etomidate because of its beneficial effects is widely used induction agent in clinical practice.[12] Pain on injection and myoclonus remain the consistent and most undesirable effects of etomidate. Many studies have demonstrated that etomidate-induced myoclonus might be associated with a seizure-like activity.[5] Opioids like nalbuphine and fentanyl have been studied either alone or in combination with benzodiazepines.[6] Choi et al.[7] reported pre-treatment with rocuronium significantly decreased the myoclonus; however, it was accompanied with disadvantages of muscle relaxants (airway obstruction, regurgitation and aspiration). Drugs like lignocaine, and small priming doses of either thiopental or etomidate have been tried with variable results.[89] Dexmedetomidine, a highly selective α2 agonist is widely used in anaesthesia as an anaesthetic adjuvant. The effect of dexmedetomidine in relieving myoclonus may be related to the analgesic effects.[3] Dexmedetomidine has been found to be more effective than midazolam for decreasing the etomidate-induced myoclonus.[10] Dexmedetomidine has been evaluated in the doses of 0.5-1 μg/kg as a pre-treatment to reduce etomidate induced myoclonus. In our study no incidence of significant haemodynamic instability warranting treatment was observed in group D. These findings are in concordance with results of study by Luan et al.[3] Magnesium on the other hand is an antagonist of N-methyl D- aspartate (NMDA) receptor. Activation of NMDA receptor leads to calcium influx and also catalyses the production of nitric oxide which is associated with nociception.[11] Thus blocking these receptors imparts magnesium it's analgesic property. Magnesium has been shown to prevent etomidate-related myoclonus when compared to normal saline.[12] Magnesium has been compared with ketamine, another NMDA antagonist and has been proven to be more efficient in decreasing the myoclonus. This may be because magnesium in addition also blocks inositol 1, 4, 5-triphosphate (IP3) mediated calcium channels which are responsible for preventing pain of etomidate injection.[1112] The incidence of myoclonus is highly dependent upon the dosage and speed of injection. A slower rate of infusion was found to be effective in reducing the myoclonic jerks in a study by Sang Hwan Do et al.[13] Therefore, we kept the etomidate dose fixed with slow rate of injection in all our cases. The major advantage of etomidate is its stable cardiovascular profile that aids in counteracting the sympathetic stress response during laryngoscopy and intubation.[1] In our study we observed that both dexmedetomidine and magnesium preserved this haemodynamic stability and there were no incidences of either bradycardia or hypotension. There are certain limitations of our study. Firstly, we only studied the incidence and severity of etomidate induced myoclonus and not the duration of myoclonus which may also have an adverse effect. Secondly, infusing the drug slowly over 10 minutes using infusion pump maybe time-consuming and not suitable under some emergency situations. Other measures like bolus injection of lignocaine may be convenient and need to be compared with these study drugs. CONCLUSION In conclusion, both dexmedetomidine and magnesium pre-treatment before etomidate administration significantly prevents the myoclonus without adverse side effects. Magnesium, however, is superior to dexmedetomidine in decreasing not only the incidence but also the severity of myoclonus. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.