Pretreatment with Dexmedetomidine or Thiopental Decreases Myoclonus after Etomidate: A Randomized, Double-Blind Controlled Trial

Background

Myoclonic movements are common problems during induction of anesthesia with etomidate. The aim of this study was to compare the effect of pretreatment with dexmedetomidine (0.5 μg/kg) and thiopental (1 mg/kg) on the incidence of etomidate- induced myoclonus and postoperative pain.

Materials and Methods

A prospective double-blind study was conducted at a university hospital. Ninety patients (ASA physical status I-II) were randomly assigned to one of three groups: patients were pretreated with either dexmedetomidine (0.5 μg/kg), thiopental (1mg/kg), or saline before induction of anesthesia with etomidate. One minute after the injection of study drugs, etomidate, 0.3mg/kg was given. Myoclonus was assessed on a scale of 0 to 3. Recovery time, postoperative pain score, and hemodynamic variables were recorded during the intraoperative and postoperative period. Headache, nausea, vomiting, and coughing were noted during the study.

Results

The incidence and the intensity of myoclonus was significantly lower in the dexmedetomidine and thiopental groups (34%, 36%) than in the control group (64%) (P<0.05). The postoperative pain score at 30min in the thiopental group was significantly higher than in the dexmedetomidine and control groups (63%) (P<0.05).

Conclusions

We concluded that pretreatment with dexmedetomidine or thiopental is effective in reducing the incidence and severity of etomidate-induced myoclonic muscle movements and pretreatment with thiopental increases the postoperative pain.

Introduction

Etomidate was introduced in 1973 and was described as a new induction agent with very rare cardiopulmonary side effects but several disturbing side effects, such as pain on injection, myoclonus, postoperative nausea and vomiting, and adrenal suppression. Even though pain on injection has been successfully addressed by a new fat formulation of etomidate (Etomidate-Lipuro) [1], myoclonus is still a common problem; 50% to 80% of unpremedicated patients may develop myoclonic movements after induction of anesthesia with etomidate. Myoclonic movement may lead to patient discomfort [2] and increase the risk of prolapse of vitreous content because of high intraocular pressure. Therefore, in patients with open globe injury, myoclonus might also be a problem [3]. Myoclonus also may be detrimental in those who have limited cardiovascular reserves 4, 5, and in emergency nonfasting conditions [6].

Different kinds of drugs have been investigated as pretreatment drugs before induction of anesthesia with etomidate as a means of preventing myoclonic movements. It was shown that various opioid agents, including sufentanyl [2], fentanyl [7], and remifentanyl [6] reduced the incidence of myoclonus. It was reported that midazolam pretreatment reduced etomidate-induced myoclonic movements 4, 6. Magnesium sulfate pretreatment and benzodiazepines have shown some effect in reducing myoclonus 4, 5 but, even with these drugs, myoclonus was still observed at a rate of 7%–50%.

Although the mechanism is not clear, Yang et al. reported that myoclonus after treatment with etomidate was a phenomenon of subcortical disinhibition, like the phenomenon of restless legs during normal human sleep, and is not generated by an epileptic focus 3, 8. It was hypothesized that the reason for the excitatory phenomenon of myoclonus was a disequilibrium of the drug at the various effect sites in the central nervous system (CNS) 9, 10. Tanaka et al. showed that dexmedetomidine administered for sedation reduced the convulsive potency of bupivacaine and levobupivacaine in awake, spontaneously breathing rats, probably by α₂-adrenoceptor agonism [11]. Although myoclonus is thought not to be generated by an epileptic focus, dexmedetomidine, which acts to reduce the severity of convulsions, has not been previously investigated for myoclonus induced by etomidate.

In mammals, pyramidal neurons are the main excitatory cells in the prefrontal cortex (PFC), which is representative of 70% of all neurons [12]. The excitability of the PFC and the excitatory output from the PFC is basically dependent upon the function of NMDA receptors [13]. In a previous study, NMDA-gated currents were reduced by thiopental sodium in the PFC pyramidal neurons, which may reduce the excitability of the PFC. Neural transmission mediated by the other transmitters in both the PFC and the other brain regions may be influenced by thiopental sodium [14]. The effectiveness of pretreatment with thiopental in myoclonic activity has not been previously investigated.

Therefore, the aim of the present study was to show and compare the effect of pretreatment with dexmedetomidine and thiopental on the incidence and severity of myoclonus during induction of anesthesia with etomidate and to determine postoperative pain scores.