etomidate is a popular anesthetic agent since it is associated with hemodynamic stability , minimal respiratory depression , cerebral protection , and rapid recovery after either a single dose or a continuous infusion .
the mechanism of myoclonus is not clear and does not seem to be associated with seizure - like electroencephalographic activities .
however , myoclonus is believed to be the result of activities either in the brainstem or deep cerebral structures .
the incidence of myoclonus is highly variable ( 0 - 80% ) and can be problematic in patients with open globe injuries or those at high risk of aspiration . the incidence of myoclonus can be reduced after premedication with either opioid or benzodiazepine . among the evaluated medications , both midazolam , and sufentanil , as pretreatment agents , have been reported to effectively reduce the myoclonus .
however , a comparison between midazolam and sufentanil has not been made so far , and it is not clear which agent is a better option for reducing myoclonus after etomidate injection .
therefore , we conducted a prospective , randomized , double - blind , clinical trial to compare the efficacy of midazolam and sufentanil in reducing the incidence and severity of myoclonus after etomidate injection in patients , undergoing elective ophthalmic surgery with general anesthesia .
fifty adult patients with american society of anesthesiologists class ii or iii , who were scheduled for elective eye surgery under general anesthesia , were selected for the study .
the exclusion criteria were allergy to benzodiazepine or opioid , neuropsychological or neuromuscular diseases , adrenal dysfunction or epilepsy , addiction ; and analgesic or sedatives administration within 24 h before the procedure .
patients did not receive premedication and were randomly assigned to one of the two groups ( n = 25 per group ) group m consisted of patients receiving midazolam ( 0.015 mg / kg ) and group s consisted of patients receiving sufentanil ( 0.2 /kg ) .
an anesthesiologist , who was blinded to the study and was not involved in anesthesia induction , prepared and coded syringes containing a total volume of 4 ml of medications .
patient monitoring included electrocardiography , pulse oximetry , noninvasive blood pressure ( bp ) monitoring , and capnography .
patients received isotonic saline solution ( 5 ml / kg ) over 10 min at room temperature and were preoxygenated with 100% oxygen ; then , the medication was injected over 30 s. ninety seconds after pretreatment with the medication , etomidate ( 0.3 mg / kg ) was intravenously injected within 20 s. two minutes after intravenous ( iv ) administration of etomidate , anesthesia was completed by atracurium ( 0.5 mg / kg ) and fentanyl ( 2 /kg ) to guarantee adequate anesthetic induction .
patients were continuously monitored during anesthesia by one single physician , blinded to treatment procedures . heart rate ( hr ) , bp and mean arterial pressure ( map ) in pre- and post - induction ( 90 s after administration ) were recorded .
the intensity of myoclonus was clinically graded as follows : 0 = no myoclonus , 1 = mild myoclonus ( short movement of a body segment ) , 2 = moderate myoclonus ( mild movements of two different muscles ) , and 3 = severe myoclonus ( intense clonic movements in two or more muscle groups ) .
based on previous studies , a minimum number of 23 patients were required in each group ( with a significance level of 90% and a power of 80% ) . hence , 25 patients in each group were included in this study .
t - test and chi - square were performed to compare patients ' characteristics , and comparisons between the groups were performed by mann - whitney test .
based on previous studies , a minimum number of 23 patients were required in each group ( with a significance level of 90% and a power of 80% ) . hence , 25 patients in each group were included in this study .
t - test and chi - square were performed to compare patients ' characteristics , and comparisons between the groups were performed by mann - whitney test .
demographic information of the patients is shown in table 1 ; there was no significant difference between the two groups in terms of age , although they were different regarding sex distribution ( p = 0.047 ) [ table 1 ] .
demographic characteristics of the patients the incidence of myoclonus was significantly different between the two groups ; it was 28% ( 7 patients ) in the sufentanil group and 84% ( 21 patients ) in the midazolam group ( p = 0.001 ) .
the intensity of myoclonus was also significantly more severe in midazolam groups compare to sufentanil group [ table 2 ] .
severity of myoclonus in sufentanil and midazolam groups the mean duration of myoclonus was significantly less in sufentanil group than in midazolam group ( 5.8  13.2 s vs. 69  47.8 s ; p < 0.001 )
. there was a significant difference in hr pre- and post - anesthesia induction in the sufentanil group .
the mean hr was 83.96  18.1 before the induction and 71.8  15.2 after the induction in this group ( p < 0.001 ) .
however , the difference in hr before and after the induction in the midazolam group was not significant ( 77.24  15.1 vs. 76.2  13 ) ( p = 0.705 ) .
mean arterial pressure was significantly different before and after the induction in the sufentanil group ; it was 120.46  15.4 mmhg before the induction and 109.5  18.8 mmhg after the induction ( p = 0.0001 ) .
however , map was not significantly different before and after the induction in the midazolam group ; it was 123.12  19 mmhg before the induction and 116.2  25.5 mmhg after the induction ( p = 0.098 ) .
the mean hr before and after the induction was significantly different between the two groups ( p = 0.002 ) .
the mean difference in hr before and after the induction was 12.16  10.3 in the sufentanil group and 1.04  13.5 in the midazolam group .
the mean of map before and after the induction was not significantly different between the two groups ( p = 0.406 ) .
the mean difference in map before and after the induction was 10.09  12.6 mmhg in the sufentanil group and 6.9  20 mmhg in the midazolam group .
the current study showed that pretreatment with sufentanil 0.2 g / kg significantly prevents the occurrence and reduces the severity of myoclonus during anesthesia induction with etomidate .
the mean duration of myoclonus in the sufentanil group was significantly less than that of the midazolam group .
the mean of variations in hr before and after the induction between the two groups was significantly different , but the mean of map before and after the induction was not significantly different between the two groups .
application of different medications , as pretreatment agents , has been investigated for the reduction of myoclonus after etomidate injection .
. however , diazepam ( 0.0625 - 0.0125 mg / kg iv ) or flunitrazepam ( 0.01 mg / kg iv ) failed to reduce myoclonic movements . on the other hand , doenicke et al . reported a significant reduction in the incidence of myoclonus when 0.1 mg / kg of diazepam was administrated 5 min before etomidate .
reported that the incidence of myoclonic movements was significantly lower in patients , who were pretreated with midazolam 0.015 mg / kg ( 20% ) , compared to the placebo group ( 90% ) . in this study
, all patients in the study groups were premeditated with oral midazolam ; however , in our study , patients did not receive premedication . in the study by hwang et al .
, iv administration of midazolam 2 min before etomidate injection reduced the incidence of myoclonus up to 17% . in the current study ,
the incidence of myoclonus in the midazolam - treated group was 84% , which was significantly higher than that observed in the study by hwang . in the study by hwang , etomidate
was administered 2 min after midazolam ( 0.05 mg / kg ) ; the higher dosage and longer interval in the study by hwang may account for the lower incidence of myoclonus , following midazolam administration in their study , compared to ours .
use of higher fentanyl doses ( 500 g ) significantly reduced myoclonic movements ; however , the incidence of apnea increased during induction . in a study by fassoulaki et al .
, they found no change in myoclonic occurrence when fentanyl 100 g was administered before anesthesia induction with etomidate .
remifentanil ( 1 g / kg ) , administered 2 min before etomidate injection , was reported to reduce the incidence of myoclonus to 7% , without any clinically relevant side - effects . in another study ,
pretreatment with remifentanil ( with the same dose ) was associated with a 17% incidence of myoclonus , which was higher than that observed in the study by kelsaka et al .
furthermore , 10% of the remifentanil - treated patients experienced clinically relevant side - effects such as chest muscle rigidity and bradycardia . therefore , their results suggested that remifentanil may not be a good option for routine pretreatment during etomidate injection .
other investigators have recommended sufentanil ( 0.3 g / kg ) as a pretreatment agent before anesthesia induction with etomidate .
in fact , this medication has been shown to completely prevent myoclonus without causing any side - effects .
studies with other opioids such as alfentanil and buprenorphine have not shown higher efficiencies . in our study ,
pretreatment with sufentanil ( 0.2 g / kg ) was associated with a significantly reduced incidence and severity of myoclonus ; however , pretreatment with midazolam resulted in a higher incidence and severity of myoclonus ( including moderate and severe grades of myoclonus ) .
the duration of myoclonus in the sufentanil group was also less than that of the midazolam group . due to the findings of the current study , in the sufentanil group , hr reduced after induction , but the mean difference in map was not clinically significant after sufentanil administration .
the sample of our study was small so further studies are required for comparing different doses of opioids ( e.g. , sufentanil ) and determining other adverse effects .
the sample of our study was small so further studies are required for comparing different doses of opioids ( e.g. , sufentanil ) and determining other adverse effects .
according to the results of this study , it seems using sufentanil as a pretherapeutic agent might reduce the risk of development of etomidate - induced myoclonus .
 background and aims : myoclonus is a major side - effect following etomidate injection requiring use of medical intervention.material and methods : in this double - blinded clinical trial , 50 consecutive patients , randomly received sufentanil 0.2 g / kg or midazolam 0.015 mg / kg , 90 s before induction of anesthesia with etomidate ( 0.3 mg / kg ) . 
 then , the patients were monitored for any myoclonic movements during anesthesia.results:the incidence of myoclonus was 28% in the sufentanil group and 84% in the midazolam group . 
 the frequency and intensity of myoclonus were significantly higher in the midazolam group , compared to the sufentanil group ( p < 0.001 ) . 
 myoclonus duration in the sufentanil and midazolam groups were 5.8  13.2 and 69  47.8 s , respectively ( p < 0.0010).conclusion : the frequency , intensity and duration of myoclonus in the midazolam group , were significantly more prevalent than the sufentanil group . 
Introduction
Material and Methods
Statistical considerations
Results
Discussion
Limitations
Conclusion