|Year : 2014 | Volume
| Issue : 3 | Page : 460-464
Efficacy of lignocaine versus midazolam in controlling etomidate-induced myoclonus: a randomized placebo-controlled study
Kahlon A Singh, Gupta Ruchi, Aujla K Singh, Bindra T Kaur
Department of Anaesthesia and Critical Care, Sri Guru Ram Das Institute of Medical Science and Research, Vallah, Amritsar, Punjab, India
|Date of Submission||13-Dec-2013|
|Date of Acceptance||19-May-2014|
|Date of Web Publication||27-Aug-2014|
Kahlon A Singh
11-B Circular Road, Near KD Hospital, Amritsar - 143001, Punjab
Source of Support: None, Conflict of Interest: None
Etomidate has many desirable properties like rapid onset of profound hypnosis, short duration, hemodynamic stability, and minimal respiratory depression. Few side effects such as myoclonus, reduced cortisol secretion, and pain on injection abate its regular use.
The aim of this study was to evaluate the effect of pretreatment with lignocaine and midazolam on the incidence and severity of myoclonus due to etomidate.
Materials and methods
A prospective, randomized, double-blind, placebo-controlled study was conducted on 75 patients with American Society of Anesthesiology physical status I or II, undergoing general anesthesia for various elective surgical procedures. Patients were divided into three groups each comprising 25 patients: group I received 1 ml of normal saline, group II received 1 ml of 2% lignocaine and group III received 1 ml of midazolam (1 mg) as premedication 2 min before induction with 0.3 mg/kg etomidate. Myoclonus was assessed and graded on a four-point scale.
Statistical data analysis
Results were compiled and statistically analyzed using the χ2 -test for nonparametric data and analysis of variance test for parametric data. For all statistical analysis, P less than 0.05 was considered statistically significant.
The incidence of myoclonus in control group was 76%, whereas patients premedicated with midazolam or lignocaine showed 28 and 44% incidence, respectively. The severity of myoclonus was also decreased in both midazolam and lignocaine groups. The incidence of other side effects among the groups was similar (P > 0.05).
Premedication with both lignocaine and midazolam was effective in reducing the incidence and severity of myoclonus.
Keywords: etomidate, incidence, lignocaine, midazolam, myoclonus
|How to cite this article:|
Singh KA, Ruchi G, Singh AK, Kaur BT. Efficacy of lignocaine versus midazolam in controlling etomidate-induced myoclonus: a randomized placebo-controlled study. Ain-Shams J Anaesthesiol 2014;7:460-4
|How to cite this URL:|
Singh KA, Ruchi G, Singh AK, Kaur BT. Efficacy of lignocaine versus midazolam in controlling etomidate-induced myoclonus: a randomized placebo-controlled study. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2021 Oct 24];7:460-4. Available from: http://www.asja.eg.net/text.asp?2014/7/3/460/139597
| Introduction|| |
Choosing the induction agent is a very vital step in commencing general anesthesia. Etomidate was selected as an ideal induction agent because of its many desirable properties like rapid onset of profound hypnosis, minimal histamine release, hemodynamic stability, minimal respiratory depression, and favorable cerebral effects. Despite problems such as pain on injection, decreased cortisol secretion, and myoclonus, the positive pharmacologic attributes of etomidate have contributed toward its continued use. Pain on injection has been eliminated by the use of a lipid emulsion in this study [1,2]. There is transient adrenal suppression but it is not clinically significant after a single bolus injection; the absolute cortisol levels remain in the normal range following a brief use of etomidate .
Myoclonus has been described as the involuntary contracture of some muscle fibers, which involves a whole muscle or different muscles of one group, leading to short observable movements of the corresponding body parts. From 50 to 80% of unpremedicated patients develop myoclonic movements after an induction dose (0.3 mg/kg) of etomidate. Under emergency conditions, myoclonus may increase the risk for regurgitation and aspiration.
Ideally, a pretreatment drug for preventing myoclonic movements should be short-acting, should not have significant effects on respiration and hemodynamics, and should not prolong recovery from anesthesia . Various drugs that have been used as pretreatment to reduce myoclonic movement have been used concomitantly with other inducing agents, benzodiazepines, opioids, rocuronium, lignocaine, etc.; however, the drug of choice for short-term procedures has yet to be identified.
Thus, we conducted a placebo-controlled study to compare the effect of pretreatment with midazolam and lignocaine on the incidence and severity of myoclonus due to etomidate.
| Materials and methods|| |
After obtaining approval from the hospital ethics committee, written informed consent was obtained from all 75 patients with American Society of Anesthesiology physical statuses of I or II, undergoing general anesthesia for various elective surgical procedures. Patients with clinical adrenal cortex dysfunction, neurologic disease, psychiatric disorders, drug allergy, morbid obesity, and active gastro-oesophageal reflux, as well as pregnant patients and patients who had received sedatives, analgesics, or opioids within the previous 24 h were excluded from the study.
On arrival at the operating room, a standard monitor was attached, a 20 G cannula was inserted into a vein, and an intravenous line was started with 0.9% saline. Vitals such as pulse rate, blood pressure, respiratory rate, and oxygen saturation were recorded and taken as baseline readings. All patients were then preoxygenated with 100% oxygen for 3 min. Patients were divided into three groups of 25 each using a computer program, in a randomized double-blind manner. Group I received 1 ml of normal saline, group II received 1 ml of 2% lignocaine, and group III received 1 ml of midazolam (1 mg). The test solutions were prepared in coded syringes by the supervisor and were administered 2 min before induction with 0.3 mg/kg etomidate (B-Braun, Melsungen, Germany). The time to the loss of eyelash reflex was recorded as the onset of induction, and an additional dose of etomidate was administered if necessary.
The patients were observed continuously for myoclonic movements. The time of onset and the duration of myoclonus were observed, along with the intensity of myoclonus, which was graded on a four-point scale validated by Holdcroft et al. : grade 1, no movement; grade 2, mild (involuntary movement at a small unit of the muscle group); grade 3, moderate (movement in large or two muscle groups or a mild generalized response); and grade 4, severe (generalized response or intense movement in two or more muscle groups).
One minute after administration of etomidate and the evaluation of myoclonus, 0.5 mg/kg pentazocine and 0.5 mg/kg succinylcholine were administered to facilitate laryngeal mask airway insertion. The vitals were observed after administration of test solution, after induction, and after laryngeal mask airway insertion every minute for 5 min, then every 5 min for 15 min, and then every 15 min until the end of surgery. Anesthesia was maintained with isoflurane (0.5-1%) in a mixture of nitrous oxide in oxygen (60 : 40) with vecuronium.
After completion of the study, the drugs were decoded and the results were compiled and statistically analyzed using χ2 -test for nonparametric data and analysis of variance for parametric data. For all statistical analysis, P less than 0.05 was considered statistically significant. On the basis of previous studies, the minimum number of patients required to obtain 90% power for the study was 24 patients/group; hence, we decided to induct 25 patients in each group.
| Results|| |
Patient characteristics were comparable in all groups [Table 1]. Parameters such as mean dose requirement and time for loss of consciousness were also comparable [Table 2].
|Table 2: Mean dose required, time for LOC, and mean duration of myoclonus in all groups|
Click here to view
The incidence of myoclonus in group I was 76%; the difference was statistically significant when compared with that in group II (lignocaine group: 44%, P < 0.05) and group III (midazolam group: 28%, P < 0.05), as shown in [Figure 1]. The intensity of myoclonus was also reduced in groups II and III as compared with group I [Table 3]. The mean duration was comparable in all groups. The changes in heart rate and blood pressure did not differ among the three groups [Figure 2] and [Figure 3]. The incidence of postoperative nausea and vomiting, myalgia, and headache was comparable in all three groups [Figure 4].
|Figure 3: Mean systolic blood pressure of the patients in all the three groups.|
Click here to view
|Figure 4: Major adverse effects observed in the patients of all the three groups.|
Click here to view
| Discussion|| |
Myoclonus is as such harmless to the patient as it occurs when the patient is already in a hypnotic state; however, it may interfere with the clinical evaluation of the depth of anesthesia. It is assumed to be due to a disinhibition mechanism, where a large dose of etomidate depresses cortical activity before it depress subcortical activity [6-8].
In our study, we found a significant decrease in the incidence of myoclonus in the lignocaine group (P < 0.05), as well as the midazolam (P < 0.01) group, compared with the control group. The incidence of myoclonus was lowest in the midazolam group (28%), followed by the lignocaine group (44%) and the saline group (76%). We waited for 2 min before administering etomidate to allow enough time for the pretreatment drug to act. Similar results were obtained by Hόter et al. , who found 20% incidence of myoclonus in the group pretreated with 0.015 mg/kg midazolam.
Khteishat and colleagues [4,9], in their studies, showed a decrease in the incidence of myoclonus to ˜10% with 0.015 mg/kg midazolam. This variation compared with our study could be due to ethnic variations or selection of a younger age group. The factors known to affect the incidence of myoclonus are age (the higher the age, the lesser the chances of development of myoclonus), sex of the patient (incidence is higher among male individuals), and the dose of etomidate [10,11]. However, in the study by Hόter and colleagues, patients were also on magnesium sulfate therapy, which itself leads to a decrease in myoclonus .
Yang and colleagues [13,14] could not demonstrate a significant reduction in the incidence of myoclonus with midazolam. The difference from our study could be because of age group selection (38 years in our study vs. 62 years in their study) or the difference in timing of administration of midazolam (5 min in their study vs. 2 min in our study).
Similar to our study, Gultop et al.  studied the effect of pretreatment with 2% lignocaine (1 ml) and saline, administered 30 s before induction with etomidate, and observed 56.6% incidence of myoclonus in the lignocaine group compared with 83% in the saline group.
Myoclonus could be due to suppression of g-amino butyric acid receptors in the central nervous reticular activating system, causing subcortical disinhibition or depression of the inhibitory circuits earlier than that of excitatory neuronal circuits after etomidate administration, and it is not caused by an epileptic focus [16-18]. The various effects of benzodiazepines on the different g-amino butyric acid receptors may reduce the incidence of myoclonus. The mechanism by which lignocaine works is unclear; however, Nyman and colleagues speculated that lignocaine reduces the excitability of the central nervous system, which is the cause of myoclonic movements, as discussed earlier .
We found a significant decrease in the severity of myoclonus in midazolam and lignocaine groups. The reduction in the grade of myoclonus has been proven in most of the studies that used midazolam [2, 4, 7, 13, 19, 20] and lignocaine  as pretreatment drugs.
The hemodynamic parameters were statistically comparable in all the three groups. All patients showed hemodynamic stability; the mean fall in blood pressure after induction with etomidate was less than 5%. These results are supported by those of Hόter et al.  and Lee et al. .
The incidence of postoperative nausea and vomiting was around 30% and was comparable in all the groups. Giese and colleagues [21,22] found the incidence of postoperative nausea and vomiting to be 36 and 38%, respectively, when they used etomidate in their study.
| Conclusion|| |
Thus, our study demonstrated that 1 mg midazolam and 1 ml of 2% lignocaine decrease the incidence and severity of myoclonus due to etomidate. However, midazolam was more effective than lignocaine. The hemodynamic stability of etomidate was not affected by these pretreatment drugs.
| Acknowledgements|| |
| References|| |
|1.||Sarkar M, Laussen PC, Zurakowski D, Shukla A, Kussman B. Haemodynamic responses to etomidate on induction of anesthesia in pediatric patients. Anesth Analg 2005; 101:645-650. |
|2.|| Doenicke AW, Roizen MF, Kugler J, Kroll H, Ostwald P. Reducing myoclonus after etomidate. Anesthesiology 1999; 90:113-119. |
|3.|| Duthie DJ, Fraser R, Nimmo WS. Effect of induction of anaesthesia with etomidate on corticosteroid synthesis in man. Br J Anaesth 1985; 57:156-159. |
|4.|| Khteishat B, Salaytah W, Qatawneh T, Alsagheer M. The effect of preinduction with midazolam, fentanyl and ketamine on etomidate induced myoclonic muscle movements. J Res Med Sci 2011; 18:38-41. |
|5.|| Holdcroft A, Morgan M, Whitwam JG, Lumley J. Effect of dose and premedication on induction complications with etomidate. Br J Anaesth 1976; 48:199-205. |
|6.|| Helmers JH, Adam AA, Giezen J. Pain and myoclonus during induction with etomidate. A double-blind, controlled evaluation of the influence of droperidol and fentanyl. Acta Anaesthesiol Belg 1981; 32:141-147. |
|7.|| Schwarzkopf KR, Huter L, Simon M, Fritz HB. Midazolam pretreatment reduces etomidate-induced myoclonic movements. Anaesth Intensive Care 2003; 31:18-20. |
|8.|| Van Keulen, SG,Burton JH. Myoclonus associated with etomidate for ED procedural sedation and analgesia. Am J Emerg Med 2003; 21:556-558. |
|9.|| Hüter L, Schreiber T, Gugel M, Schwarzkopf K. Low-dose intravenous midazolam reduces etomidate-induced myoclonus: a prospective randomized study in patients undergoing elective cardioversion. Anesth Analg 2007; 105:1298-1302. |
|10.||Lee SW, Gill HJ, Park SC, Kim JY, Lee JY. The effect of remifentanyl for reducing myoclonus during induction of anesthesia with etomidate. Korean J Anesthesiol 2009; 574:438-443. |
|11.||Kelsaka E, Karakaya D, Sarihasan B, Baris S. Remifentanyl pretreatment reduces myoclonus after etomidate. J Clin Anesth 2006; 18:83-86. |
|12.||Un B, Ceyhan D, Yelken B. Prevention of etomidate-related myoclonus in anesthetic induction by pretreatment with magnesium. J Res Med Sci 2011; 16:1490-1494. |
|13.||Yang YY, Choi SJ, Kim HJ, Son SC. The effect of midazolam, fentanyl and a small dose of etomidate for prevention of myoclonus during induction of anesthesia with etomidate. Korean J Anesthesiol 2000; 39:166-171. |
|14.||Hodgson RE, Burrows RC. Midazolam and etomidate for induction of anesthesia in ophthalmic surgery. South Afr J Anaesth Analg 2002; 8:23-26. |
|15.||Gultop A, Akkaya T, Bedirli N, Gumus H. Lidocaine pretreatment reduces the frequency and severity of myoclonus induced by etomidate. J Anesth 2010; 24:300-302. |
|16.||Kugler J, Doenicke A, Laub M. The EEG after etomidate. Anaesthesiol Resusc 1977; 106:31-48. |
|17.||Gancher S, Laxer KD, Krieger W. Activation of epileptogenic activity by etomidate. Anesthesiology 1984; 61:616-618. |
|18.||Nyman Y, von Hofsten K, Ritzmo C, Eksborg S. Effect of a small priming dose on myoclonic movements after intravenous anaesthesia induction with etomidate-lipuro in children. Br J Anaesth 2011; 107:225-228. |
|19.||Hwang JY, Kim JH, Oh AY, Do SH, Jeon YT. A comparison of midazolam with remifentanil for the prevention of myoclonic movements following etomidate injection. J Int Med Res 2008; 36:17-22. |
|20.||Kwon MS, Kim JH, Baik HJ. The effect of midazolam for reducing myoclonus after etomidate. Korean J Anesthesiol 2002; 43:395-400. |
|21.||Giese JL, Stockham RJ, Stanley TH. Etomidate versus thiopental for induction of anesthesia. Anesth Analg 1985; 64:871-876. |
|22.||St Pierre M, Dunkel M, Rutherford A, Hering W. Does etomidate increase postoperative nausea? A double-blind controlled comparison of etomidate in lipid emulsion with propofol for balanced anaesthesia. Eur J Anaesthesiol 2000; 17:634-641. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]