Pharmacological interventions for reducing the incidence of myoclonus in patients receiving etomidate for induction of general anesthesia: an umbrella review.

OBJECTIVE: The objective of this umbrella review was to examine various pharmacologic interventions for their potential to reduce etomidate-induced myoclonus. A secondary objective was to compare the relative effectiveness of those medications in reducing the incidence of myoclonus when etomidate is utilized for the induction of general anesthesia. INTRODUCTION: Etomidate is the drug of choice when inducing general anesthesia in hemodynamically unstable patients. However, its use is limited among the general surgical population due to its ability to cause adrenal suppression, vomiting, and myoclonus. Myoclonus can lead to damage of muscle fibers, myalgias, and patient discomfort, and can also be detrimental in patients with low cardiac reserve. Several systematic reviews have reported on the effectiveness of various intravenous medications in reducing mild, moderate, and severe myoclonus; however, a more thorough examination of their influence was lacking. INCLUSION CRITERIA: This review included systematic reviews and meta-analyses of randomized controlled trials involving the use of pharmacologic interventions to reduce etomidate-induced myoclonus. Reviews in English and conducted after 1965 were considered for inclusion. METHODS: A comprehensive search of 11 databases was conducted to identify published and unpublished reviews up to March 2022. Critical appraisal was conducted by 2 independent reviewers using the standardized JBI appraisal tool. Quantitative findings were summarized according to the dose, timing of administration, and relative risk using a data matrix, and were synthesized in tabular format with supporting narrative text. Results were organized by severity of myoclonus (overall, mild, moderate, and severe) and by type of intervention. RESULTS: Eight systematic reviews were included in this umbrella review, which included 48 relevant studies, after removal of duplicates (3909 participants included in the primary studies). Five of the systematic reviews examined the effectiveness of various types of opioids in the prevention of myoclonus, and 3 systematic reviews examined the effectiveness of non-opioid interventions, such as lidocaine, midazolam, and dexmedetomidine. Seven reviews searched at least 4 databases for pertinent studies and specifically indicated that blinded reviewers appraised the articles. All reviews used a published and validated appraisal instrument. The overall quality of all included reviews was judged to be moderate to high. The absolute risk reduction indicating the effectiveness of the prophylactic medications ranged from 47% to 81% for mild, 52% to 92% for moderate, and 61% to 96% for severe myoclonus. Opioids demonstrated the most consistent and substantial effect on the reduction in myoclonus. CONCLUSIONS: All pharmacologic interventions identified in this review demonstrated a statistically significant reduction in the incidence of myoclonus. Future studies and reviews should focus on elucidating the particular dose range and timing that is most effective. Anesthesia providers should consider a pre-treatment dose of one of the medications described in this umbrella review as a means to reduce myoclonus and the untoward effects of that condition.

Efficacy of Granisetron versus Sufentanil on Reducing Myoclonic Movements Following Etomidate: Double-blind, randomised clinical trial.

Objectives: This study aimed to reduce the intensity of myoclonus movements by comparing the effectiveness of granisetron and sufentanil in reducing the intensity of etomidate-induced myoclonic movements. Etomidate-induced myoclonus occurs in up to 85% of patients under general anaesthesia. This type of myoclonus can induce significant clinical and economic problems in patients with special conditions. Methods: This double-blind randomised clinical trial study consisted of 96 adult patients recruited between January and July 2021 from Mashhad University of Medical Sciences, Mashhad, Iran. Using block randomisation, subjects were divided into three groups of 32 patients: the group receiving granisetron 40 µg/kg (group G), the group receiving sufentanil 0.2 µg/kg (group S) and the control group who did not receive the pretreatment (group C). Patients received these medications as pretreatments 120 seconds before induction with etomidate. After the injection of etomidate with a dose of 0.3 mg/kg, the incidence of myoclonus was evaluated. After evaluating the myoclonus, the full dose of narcotics (fentanyl 1 µg/kg) and muscle relaxants (atracurium 0.5 mg/kg) were administered to patients and a suitable airway was established for them. Results: The findings indicated that granisetron reduced the intensity and incidence of myoclonic movements more than sufentanil. In addition, myoclonic movements were observed at a significantly higher intensity in the control group (P = 0.001). Conclusion: The results obtained from the current study indicate that granisetron and sufentanil as pretreatments are effective for reducing myoclonus in patients.

Low-dose nalmefene pretreatment reduces etomidate-induced myoclonus: A randomized, double-blind controlled trial.

BACKGROUND: This study compared the effectiveness of nalmefene and fentanyl in reducing the incidence and severity of etomidate-induced myoclonus. METHODS: One hundred fifty patients were randomized to receive 0.25ug/kg of nalmefene, 1ug/kg of fentanyl, or the same volume of normal saline 3 minutes prior to etomidate-induced anesthesia. The primary observational indexes were the severity level and incidence of etomidate-induced myoclonus, and the secondary observational index included blood pressure, heart rate, and the incidence of adverse effects from anesthesia induction to resuscitation, such as cough, chest wall rigidity, dizziness, nausea, pain after awakening, and intraoperative awareness. RESULTS: The incidence of myoclonus was significantly lower in the nalmefene group (8.0%) than in the fentanyl group (32.0%) (P = .003) and in the normal saline group (72.0%) (P = .000). The severity level of myoclonus in the nalmefene group was significantly lower than the fentanyl group (P = .001) and normal saline group (P = .000). Meanwhile, the incidences of cough and chest wall rigidity during anesthesia induction were significantly lower in the nalmefene group compared with the fentanyl group (P = .003, P = .027). There were no statistically significant differences in heart rate and mean arterial pressure among the 3 gruops (P > .05). There was no difference in the incidence of adverse effects among the 3 groups during recovery from anesthesia (P > .05). CONCLUSION: Intravenous injection of 0.25ug/kg of nalmefene 3 minutes prior to etomidate is more effective in preventing etomidate-induced myoclonus during general anesthesia than 1ug/kg of fentanyl.

Comparison of the influence of low dose etomidate and propofol as priming dose on the incidence of etomidate induced myoclonus: a randomised, double-blind clinical trial.

BACKGROUND: Though hemodynamically stable, etomidate is known for its myoclonus side effect following induction. The main aim of this study is an effective attempt to decrease the incidence of myoclonus with a priming agent. METHODS: A prospective, double-blind study was carried out on 50 adults posted for elective surgery. After premedication, priming was done with etomidate 0.03 mg.kg-1 (Group E) and propofol 0.2 mg.kg-1 (Group P), i.e., 1/10th of induction dose. After 60 seconds of priming, patients were induced with etomidate by titrating dose over 60 seconds until loss of verbal command and eyelash reflex. The grading of myoclonus, induction dosage, and hemodynamics for 10 minutes post induction were recorded. RESULTS: In the study, only 4 cases had myoclonus. Grade 1 myoclonus was encountered in three cases of etomidate group, while only one case in the propofol group had grade 2 myoclonus which was not statistically significant (p-value: 0.12). There was a significant reduction in the etomidate induction dosage in both groups. CONCLUSION: Priming with etomidate and propofol is equally effective in reducing myoclonus with the added benefit of hemodynamic stability and reduction of an induction dose of etomidate (> 50%).

Comparison of the efficacy and safety of remifentanil versus different pharmacological approaches on prevention of etomidate-induced myoclonus: a meta-analysis of randomized controlled trials.

Objective: Myoclonus was considered as one conundrum in etomidate induction, which led to multiple risks during clinical anesthesia. The present study was conducted to compare the efficacy of pretreatment with remifentanil to different pharmacological approaches on reducing etomidate-induced myoclonus. Methods: We searched PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure from the inception to October 2018. Randomized controlled trials comparing remifentanil versus other pharmacological approaches in reducing etomidate-induced myoclonus were eligible to be analyzed. Results: Overall, 13 trials with 1,392 patients met with the inclusion criteria. 1) Pretreatment with remifentanil could reduce the incidence of etomidate-induced myoclonus compared to placebo and fentanyl; few differences were found between the use of remifentanil and the use of midazolam: (incidence of myoclonus: 5.56% with remifentanil vs 71.65% with saline, RR=0.08, with 95% CI [0.05, 0.12], P<0.0001; 3.80% with remifentanil vs 13.33% with fentanyl, RR with 95% 0.31 [0.11, 0.86], P=0.02; 46.00% with remifentanil vs 55.45% with midazolam, RR=0.82, with 95% CI [0.64, 1.06], P=0.13). 2) Compared with placebo, pretreatment with remifentanil could reduce the incidence of mild, moderate, and severe myoclonus; compared with midazolam, patients receiving remifentanil experienced lower occurrence of severe myoclonus; compared with fentanyl, pretreatment with remifentanil associated with significant low occurrence of moderate and severe myoclonus. 3) The outcomes also indicated that pretreatment with remifentanil could prevent excessive hemodynamic changes after endotracheal intubation compared to fentanyl. Conclusions: Pretreatment with remifentanil could be considered as one operative option to reduce both incidence and severity of etomidate-induced myoclonus. Compared with fentanyl, it also provides efficacy in preventing excessive hemodynamic changes after endotracheal intubation. However, the best treatment and the proper prophylactic dosage calls for more high quality evidence with large sample size.

Effect of butorphanol on etomidate-induced myoclonus: a systematic review and meta-analysis.

Objective: To evaluate the effect of butorphanol on the prevention of myoclonus induced by etomidate. Materials and methods: We searched the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure databases to collect relevant randomized controlled trials (RCTs) evaluating the effect of butorphanol on etomidate-induced myoclonus in January 2019 without any language restrictions. The primary outcome was the incidence of etomidate-induced myoclonus. Secondary outcomes included the incidence of myoclonus at various degrees and the incidence of adverse effects. Risk ratios (RRs) were calculated for binary outcomes. All statistical analysis were performed by using RevMan 5.3 software. Results: We identified 6 RCTs involving a total of 608 patients who reported the incidence of etomidate-induced myoclonus. In pooled analyses, the incidence of etomidate-induced myoclonus in the butorphanol group was significantly lower than that in the control group (RR =0.15, 95% CI [0.10, 0.22], P<0.00001). Subgroup analyses showed that butorphanol significantly decreased the numbers of patients with mild myoclonus (RR =0.41, 95% CI [0.25, 0.68], P=0.0005), moderate myoclonus (RR =0.18, 95% CI [0.09, 0.34], P<0.00001), and severe myoclonus (RR =0.04, 95% CI [0.01, 0.10], P<0.00001). Additionally, butorphanol did not increase the incidence of postoperative nausea/vomiting (RR =3.0, 95% CI [0.32, 28.42], P=0.34) or dizziness (RR =6.79, 95% CI [0.84, 54.84], P=0.07) associated with etomidate. Conclusion: Our findings suggest that butorphanol can effectively prevent the incidence of etomidate-induced myoclonus and alleviate the intensity of etomidate-induced myoclonus, without inducing postoperative nausea/vomiting and dizziness.

Intrathecal morphine combined with ropivacaine induces spinal myoclonus in cancer patients with an implanted intrathecal drug delivery system: Three case reports.

RATIONALE: Although intrathecal opioid infusion has been used for decades for the treatment of severe pain, myoclonus as one of the complications of this therapeutic modality is now beginning to be recognized more. PATIENTS CONCERNS: Here, we report three patients who developed myoclonus after dose adjustment in intrathecal drug delivery system for the treatment of refractory cancer pain. DIAGNOSIS: Spinal myoclonus is a sudden, brief, shock-like muscle contractions originating from the central nervous system. In our cases, it occurred after opioid administration via intrathecal delivery system with no abnormality found in laboratory or imaging examinations. INTERVENTIONS: Spinal myoclonus can be treated effectively by reducing the dose or infusion rate as described in case 1, or changing from an intrathecal to systemic administration in case 2, or correcting infusion and bolus parameters mistakes in case 3. OUTCOMES: All patients recovered quickly after stopping or decreasing the intrathecal drug infusion. LESSONS: Prevention is more important than treatment as for spinal myoclonus. Pain management teams should be aware of this distressing complication. Dose of intrathecal drugs should not exceed the recommended maximal daily doses by guidelines and patient education is important for successful intrathecal analgesic therapy.

Aptamer Efficacies for In Vitro and In Vivo Modulation of αC-Conotoxin PrXA Pharmacology.

The medical staff is often powerless to treat patients affected by drug abuse or misuse and poisoning. In the case of envenomation, the treatment of choice remains horse sera administration that poses a wealth of other medical conditions and threats. Previously, we have demonstrated that DNA-based aptamers represent powerful neutralizing tools for lethal animal toxins of venomous origin. Herein, we further pursued our investigations in order to understand whether all toxin-interacting aptamers possessed equivalent potencies to neutralize αC-conotoxin PrXA in vitro and in vivo. We confirmed the high lethality in mice produced by αC-conotoxin PrXA regardless of the mode of injection and further characterized myoclonus produced by the toxin. We used high-throughput patch-clamp technology to assess the effect of αC-conotoxin PrXA on ACh-mediated responses in TE671 cells, responses that are carried by muscle-type nicotinic receptors. We show that 2 out of 4 aptamers reduce the affinity of the toxin for its receptor, most likely by interfering with the pharmacophore. In vivo, more complex responses on myoclonus and mice lethality are observed depending on the type of aptamer and mode of administration (concomitant or differed). Concomitant administration always works better than differed administration indicating the stability of the complex in vivo. The most remarkable conclusion is that an aptamer that has no or a limited efficacy in vitro may nevertheless be functional in vivo probably owing to an impact on the biodistribution or pharmacokinetics of the toxin in vivo. Overall, the results highlight that a blind selection of aptamers against toxins leads to efficient neutralizing compounds in vivo regardless of the mode of action. This opens the door to the use of aptamer mixtures as substitutes to horse sera for the neutralization of life-threatening animal venoms, an important WHO concern in tropical areas.

Butorphanol effectively prevents etomidate-induced myoclonus: a pooled analysis of 788 patients.

OBJECTIVE: To evaluate the efficacy of pre-injection of butorphanol on etomidate-induced myoclonus during anesthesia induction. METHODS: Randomized controlled trials (RCTs) of the ability of butorphanol to prevent etomidate-induced myoclonus were collected by searching PubMed, Cochrane Library, CNKI, and WanFang databases, from the day of database establishment until May 2017. The literature was screened independently by two evaluators, and the data were then extracted and independently evaluated. Finally, meta-analysis was performed by using RevMan 5.2 software. RESULTS: Eight RCTs were analyzed. The results of meta-analysis showed that: 1. compared with the control group, butorphanol was effective in preventing etomidate-induced myoclonus [RR = 0.15, 95% CI: 0.11, 0.21]; 2. butorphanol was effective in preventing mild, moderate, and severe etomidate-induced myoclonus [RR = 0.40, 95% CI: 0.25, 0.63; RR = 0.15, 95% CI: 0.08, 0.27; and RR = 0.04, 95% CI: 0.01, 0.09]; 3. butorphanol did not increase the incidence of dizziness and nausea associated with etomidate. CONCLUSIONS: Butorphanol could reduce the incidence and degree of etomidate-induced myoclonus. Notably, it did not increase the incidence of dizziness and nausea associated with etomidate.

Pretreatment with lidocaine reduces both incidence and severity of etomidate-induced myoclonus: a meta-analysis of randomized controlled trials.

OBJECTIVE: One conundrum that frequently occurs during clinical anesthesia is etomidate-induced myoclonus, which results in multiple risks. The aim of the study was to evaluate systematically the effect of pretreatment with lidocaine on preventing etomidate-induced myoclonus. MATERIALS AND METHODS: The literature search was performed from the inception to April 2018 in PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure. All randomized controlled trials that used lidocaine to prevent etomidate-induced myoclonus were enrolled. The primary outcome included the incidence and severity of etomidate-induced myoclonus. The data were combined to calculate the risk ratio and relevant 95% CI. A meta-analysis was performed following the guidelines of the Cochrane Reviewer's Handbook and the Preferred Reporting Items for Systematic Reviews and Meta Analyses statement. RESULTS: A total of eight studies were enrolled, and the existing evidence indicated that 1) pretreatment with lidocaine can reduce the incidence of etomidate-induced myoclonus (the incidence of myoclonus: 37.6% in lidocaine vs 73.6% in saline, risk ratio =0.46, with 95% CI [0.34, 0.63], P<0.0001); 2) the pretreatment with lidocaine can reduce the incidence of mild, moderate, and severe myoclonus; 3) a dose of pretreatment with lidocaine cannot significantly decrease the duration of myoclonus compared to placebo; 4) the administration of lidocaine produced no effect on the stable hemodynamic parameters and no more additional adverse effects. CONCLUSION: Pretreatment with lidocaine could be served as one effective approach to decrease both the incidence and the severity of etomidate-induced myoclonus, with limited influence on the hemodynamic stability of patients. However, to confirm precise safety and efficacy of such intervention, more high-quality evidence is necessary.

Effects of transcutaneous acupoint electrical stimulation combined with low-dose sufentanil pretreatment on the incidence and severity of etomidate-induced myoclonus: A randomized controlled trial.

BACKGROUND: Myoclonus is an undesirable phenomenon that occurs after induction of general anesthesia using etomidate. Opioids such as sufentanil are considered effective pretreatment drugs for myoclonus inhibition, although high doses are required. Transcutaneous acupoint electrical stimulation (TAES), a noninvasive technique involving electrical stimulation of the skin at the acupuncture points, exhibits analgesic effects, promotes anesthetic effects, decreases the dose of anesthetic drugs, and increases endogenous opioid peptide levels. In the present study, we investigated the effects of TAES combined with low-dose sufentanil pretreatment on the incidence and severity of etomidate-induced myoclonus in patients undergoing elective hysteroscopy. METHODS: In a double-blind manner, 172 patients (American Society of Anesthesiologists class I-II; age, 20-55 years) scheduled to undergo elective hysteroscopy were randomized into the following groups (n = 43 each): control (false TAES followed by saline injection after 30 min), TAES (TAES followed by saline injection after 30 minutes), sufentanil [false TAES followed by low-dose sufentanil (0.1 µg/kg) injection after 30 minutes], and sufentanil plus TAES (TAES followed by low-dose sufentanil injection after 30 minutes). In all groups, general anesthesia was induced by etomidate 0.3 mg/kg after sufentanil or saline injection. The incidence and severity of myoclonus were assessed for 2 minutes after etomidate administration. The visual analogue scale (VAS) scores for pain at 1 hour after surgery were recorded. The heart rate (HR), mean arterial pressure (MAP), and peripheral capillary oxygen saturation (SPO2) were recorded before premedication, after etomidate injection, after uterus expansion, and after recovery from anesthesia. RESULTS: The incidence of myoclonus was highest in the control group (88.3%), followed by TAES (74.4%), sufentanil (60.4%), and TAES plus sufentanil (48.8%) groups. Thus, the incidence was significantly higher in the control and TAES groups than in the sufentanil and TAES plus sufentanil groups. Grade 3 myoclonus occurred in 30.2%, 9.3%, 11.6%, and 9.3% patients in the control, TAES, sufentanil, and TAES plus sufentanil groups, respectively, with significant differences between the control group and the other 3 groups. Furthermore, the postoperative VAS scores for pain were significantly lower in the TAES, sufentanil, and TAES plus sufentanil groups compared with those in the control group. There were no significant differences in any other parameters among groups. CONCLUSION: Our results suggest that TAES combined with low-dose opioids such as sufentanil can decrease the incidence and severity of etomidate-induced myoclonus.

Efficacy and Safety of Opioids for the Prevention of Etomidate-Induced Myoclonus: A Meta-Analysis.

Etomidate is a widely used hypnotic drug for induction of general anesthesia and sedation, especially in elderly patients and hemodynamically unstable patients. Myoclonus, however, is the most prominent problem during induction of anesthesia with etomidate. Many agents have been used to prevent it and opioid is one of them. This meta-analysis was to evaluate effects of opioids pretreatment for preventing etomidate-induced myoclonus. We searched the PubMed, EMBASE, and the Cochrane Library databases and published studies in English updated to September 2015. Randomized controlled trials of opioids versus placebo/control in patients were included. We evaluated the prophylactic effect of opioids on etomidate-induced myoclonus. All statistical analysis was performed using RevMan 5.2 software. Nine randomized controlled trials involving 604 participants were included. The results indicated that compared with placebo/control, opioids allow more patients to experience no myoclonic movements after etomidate injection [risk ratio (RR) 2.76, 95% confidence interval (CI) 1.75-4.37, P < 0.0001]. The numbers of patients with mild myoclonus [(RR) 0.53, 95% (CI) 0.36-0.78, P = 0.001], moderate myoclonus [(RR) 0.36, 95% (CI) 0.23-0.55, P < 0.00001], and severe myoclonus [(RR) 0.20, 95% (CI) 0.08-0.52, P = 0.0009] after etomidate injection were significantly decreased with the pretreatment of opioids. This meta-analysis suggests that pretreatment with opioids before injecting etomidate was effective for preventing etomidate-induced myoclonus and can reduce the intensity of myoclonus without any adverse effects.

Propofol decreases etomidate-related myoclonus in gastroscopy.

OBJECTIVE: Myoclonus, a common complication during intravenous induction with etomidate, is bothersome to both anesthesiologists and patients. This study explored the preventive effect of pretreatment with propofol on etomidate-related myoclonus. METHODS: This was a prospective, double-blind, clinical, randomized controlled study. Totally, 363 patients who were scheduled for a short-duration, painless gastrointestinal endoscopy were divided into 5 groups. Four groups received 0 mg/kg (E group), 0.25 mg/kg (LPE group), 0.50 mg/kg (MPE group), or 0.75 mg/kg (HPE group) propofol pretreatment before etomidate anesthesia. Another group only received 1 to 2 mg/kg of propofol (P group) as anesthesia. The incidence and severity of myoclonus, patient circulation and respiratory status, and intraoperative and postoperative complications were recorded. RESULTS: The incidence of myoclonus in the LPE group (26.8%), MPE group (16.4%), HPE group (14.9%), and P group (0) was lower than the E group (48.6%, P < .05). The incidence of grade 1, 2, and 3 of myoclonus in the LPE group, MPE group, HPE group, and P group was significantly lower than the E group, and that in the P group was lower than the LPE group (P < .05). The incidence of hypoxemia in the P group was higher than the E group, and the incidence of adverse events in the HPE group and P group was lower than the E group (P < .05). DISCUSSION: Pretreatment with propofol was feasible for preventing etomidate-related myoclonus. Furthermore, as propofol dosage increased, its effect on reducing the incidence and severity of myoclonic movements induced by etomidate increased.

Effect of pretreatment with midazolam on etomidate-induced myoclonus: A meta-analysis.

Objective To investigate the effect of pretreatment with midazolam on myoclonus induced by etomidate injection. Methods A meta-analysis was performed using Review Manager software, version 5.2. Two researchers independently searched PubMed, Cochrane Library, and Embase® databases for randomized controlled trials involving patients who underwent etomidate induced general anaesthesia with or without midazolam pretreatment, published between 1990 and 2016. Outcome measures comprised overall myoclonus incidence rate and incidence rate classified by degree of myoclonus following etomidate injection. Data were assessed using a fixed effects model. Results Five studies, comprising 302 patients, were included for analysis. Overall incidence rate of etomidate injection-induced myoclonus was significantly lower in the pooled midazolam group versus controls (relative risk [RR] 0.34, 95% confidence interval [CI] 0.26, 0.44); Results subgrouped by degree of myoclonus showed significantly lower incidence in midazolam groups versus control groups for mild myoclonus (RR 0.56, 95% CI 0.39, 0.80); moderate myoclonus (RR 0.20, 95% CI 0.10, 0.41); and severe myoclonus (RR 0.12, 95% CI 0.04, 0.39). Conclusion Midazolam can effectively prevent etomidate-induced myoclonus, and alleviate the degree of etomidate-induced myoclonus.

Dimethyl fumarate ameliorates myoclonus stemming from protein misfolding in oligodendrocytes.

Multiple sclerosis (MS) is considered a primary autoimmune disease; however, this view is increasingly being challenged in basic and clinical science arenas because of the growing body of clinical trials' data showing that exclusion of immune cells from the CNS only modestly slows disease progression to disability. Accordingly, there is significant need for expanding the scope of potential disease mechanisms to understand the etiology of MS. Concomitantly, the use of a broader range of pre-clinical animal models for characterizing existing efficacious clinical treatments may elucidate additional or unexpected mechanisms of action for these drugs that augment insight into MS etiology. Herein, we explore the in vivo mechanism of action of dimethyl fumarate, which has been shown to suppress oxidative stress and immune cell responses in psoriasis and MS. Rather than studying this compound in the context of an experimental autoimmune-induced attack on the CNS, we have used a genetic model of hypomyelination, male rumpshaker (rsh) mice, which exhibit oligodendrocyte metabolic stress and startle-induced subcortical myoclonus during development and into adulthood. We find that myoclonus is reduced 30-50% in treated mutants but we do not detect substantial changes in metabolic or oxidative stress response pathways, cytokine modulation, or myelin thickness (assessed by anova). All procedures involving vertebrate animals in this study were reviewed and approved by the IACUC committee at Wayne State University.

Parecoxib sodium pretreatment reduces myoclonus after etomidate: A prospective, double-blind, randomized clinical trial
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OBJECTIVE: Myoclonus induced by etomidate during induction of general anesthesia is a common phenomenon. This prospective, randomized, saline-controlled clinical study was performed to evaluate the effect of parecoxib sodium pretreatment on the incidence and severity of etomidate-induced myoclonus. METHODS: 60 patients, American Society of Anesthesiologists (ASA) physical status I or II, aged 20 to 60 years, who were scheduled to undergo elective laparoscopic cholecystectomy under general anesthesia, were allocated randomly into one of two groups to receive parecoxib sodium 40 mg intravenous (group P, n = 30) or the same volume of saline (group S, n = 30) 30 minutes before administration of etomidate (0.3 mg/kg). Myoclonus was assessed on a scale of 0 - 3. Postoperative side effects were recorded. RESULTS: The two groups were comparable with regard to baseline characteristics. The incidence of myoclonus was significantly lower in the parecoxib sodium group (11/30; 37%) than in the saline group (21/30; 70%) (p < 0.05). The severity of myoclonic movements was also significantly reduced by parecoxib sodium (p < 0.05). There were no significant differences between the two groups with respect to postoperative side effects. CONCLUSIONS: Pretreatment with intravenous injection of parecoxib sodium 40 mg significantly reduced the incidence and severity of etomidate-induced myoclonus without significant side effects.
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Effect of dexmedetomidine in preventing etomidate-induced myoclonus: a meta-analysis.

OBJECTIVE: To investigate the effect of dexmedetomidine in the prevention of etomidate-induced myoclonus. METHODS: We searched for randomized controlled trials (RCTs) regarding the use of dexmedetomidine in preventing etomidate-induced myoclonus in the databases PubMed, EMBASE, the Cochrane Library, and CNKI. We extracted data and assessed the quality of the literature and adopted RevMan 5.2 to conduct meta-analysis on each effective index and employed funnel plot to test publication bias. RESULTS: The results showed that the incidence of etomidate-induced myoclonus in the dexmedetomidine treated groups was significantly lower than that of the control groups (risk ratio [RR]=0.27, 95% confidence interval [CI] [0.15, 0.47], P<0.00001). With regard to the severity of etomidate-induced myoclonus, incidences of etomidate-induced myoclonus in the dexmedetomidine treated groups resulting in mild myoclonus (RR=0.37, 95% CI [0.19, 0.75], P=0.006), moderate myoclonus (RR=0.21, 95% CI [0.12, 0.37], P<0.00001), or severe myoclonus (RR=0.18, 95% CI [0.08, 0.38], P<0.00001) were significantly lower than those of the control groups. No statistically significant difference was found (RR=0.70, 95% CI [0.47, 1.04], P=0.08) between etomidate-induced myoclonus in the dexmedetomidine treated groups and that of the midazolam treated groups. CONCLUSION: Dexmedetomidine can effectively prevent the incidence of etomidate-induced myoclonus and reduce the severity of etomidate-induced myoclonus. In addition, there were no significant differences between the effects of dexmedetomidine and midazolam in preventing etomidate-induced myoclonus.

Effect of gabapentin pretreatment on myoclonus after etomidate: a randomized, double-blind, placebo-controlled study / Efeito do pré-tratamento com gabapentina sobre a mioclonia após etomidato: um estudo randômico, duplo-cego e controlado por placebo

Abstract Aim: To evaluate the effects of three different doses of gabapentin pretreatment on the incidence and severity of myoclonic movements linked to etomidate injection. Method: One hundered patients, between 18 and 60 years of age and risk category American Society of Anesthesiologists I-II, with planned elective surgery under general anesthetic were included in the study. The patients were randomly divided into four groups and 2 h before the operation were given oral capsules of placebo (Group P, n = 25), 400 mg gabapentin (Group G400, n = 25), 800 mg gabapentin (Group G800, n = 25) or 1200 mg gabapentin (Group G1200, n = 25). Side effects before the operation were recorded. After preoxygenation for anesthesia induction 0.3 mg kg−1 etomidate was administered for 10 s. A single anesthetist with no knowledge of the study medication evaluated sedation and myoclonic movements on a scale between 0 and 3. Two minutes after induction, 2 µg kg−1 fentanyl and 0.8 mg kg−1 rocuronium were administered for tracheal intubation. Results: Demographic data were similar. Incidence and severity of myoclonus in Group G1200 and Group G800 were significantly lower than in Group P; sedation incidence and level were appreciably higher compared to Group P and Group G400. While there was no difference in the incidence of myoclonus between Group P and Group G400, the severity of myoclonus in Group G400 was lower than in the placebo group. In the two-hour period before induction other than sedation none of the side effects related to gabapentin were observed in any patient. Conclusion: Pretreatment with 800 mg and 1200 mg gabapentin 2 h before the operation increased the level of sedation and reduced the incidence and severity of myoclonic movements due to etomidate.

Resumo Objetivo: Avaliar os efeitos de três doses diferentes de gabapentina como pré-tratamento sobre a incidência e a gravidade dos movimentos mioclônicos associados à injeção de etomidato. Método: Cem pacientes, entre 18-60 anos, estado físico ASA I-II, programados para cirurgia eletiva sob anestesia geral, foram incluídos no estudo. Os pacientes foram randomicamente divididos em quatro grupos e duas horas antes da operação receberam cápsulas orais de placebo (Grupo P, n = 25), 400 mg de gabapentina (Grupo G400, n = 25), 800 mg de gabapentina (Grupo G800, n = 25) e 1.200 mg de gabapentina (Grupo G1.200, n = 25). Os efeitos colaterais antes da cirurgia foram registados. Após pré-oxigenação para a indução da anestesia, etomidate (0,3 mg.kg−1) foi administrado por 10 segundos. Um único anestesista, cego para a medicação do estudo, avaliou a sedação e os movimentos mioclônicos com uma escala de 0 a 3. Dois minutos após a indução, fentanil (2 µgr.kg−1) e rocurônio (0,8 mg.kg−1) foram administrados para a intubação traqueal. Resultados: Os dados demográficos foram semelhantes. A incidência e a gravidade da mioclonia nos grupos G1.200 e G800 foram significativamente menores do que no Grupo P; a incidência e o nível de sedação foram consideravelmente maiores comparados com o Grupo P e o Grupo G400. Enquanto não houve diferença na incidência de mioclonia entre os grupos P e G400, a gravidade da mioclonia no Grupo G400 foi menor do que no grupo placebo. No período de duas horas antes da indução, nenhum dos efeitos colaterais relacionados à gabapentina, exceto sedação, foi observado em qualquer paciente. Conclusão: O pré-tratamento com 800 mg e 1.200 mg de gabapentina duas horas antes da operação aumentou o nível de sedação e reduziu a incidência e a gravidade dos movimentos mioclônicos associados ao etomidato.

Effect of gabapentin pretreatment on myoclonus after etomidate: a randomized, double-blind, placebo-controlled study.

AIM: To evaluate the effects of three different doses of gabapentin pretreatment on the incidence and severity of myoclonic movements linked to etomidate injection. METHOD: One hundered patients, between 18 and 60 years of age and risk category American Society of Anesthesiologists I-II, with planned elective surgery under general anesthetic were included in the study. The patients were randomly divided into four groups and 2h before the operation were given oral capsules of placebo (Group P, n=25), 400mg gabapentin (Group G400, n=25), 800mg gabapentin (Group G800, n=25) or 1200mg gabapentin (Group G1200, n=25). Side effects before the operation were recorded. After preoxygenation for anesthesia induction 0.3mgkg(-1) etomidate was administered for 10s. A single anesthetist with no knowledge of the study medication evaluated sedation and myoclonic movements on a scale between 0 and 3. Two minutes after induction, 2µgkg(-1) fentanyl and 0.8mgkg(-1) rocuronium were administered for tracheal intubation. RESULTS: Demographic data were similar. Incidence and severity of myoclonus in Group G1200 and Group G800 were significantly lower than in Group P; sedation incidence and level were appreciably higher compared to Group P and Group G400. While there was no difference in the incidence of myoclonus between Group P and Group G400, the severity of myoclonus in Group G400 was lower than in the placebo group. In the two-hour period before induction other than sedation none of the side effects related to gabapentin were observed in any patient. CONCLUSION: Pretreatment with 800mg and 1200mg gabapentin 2h before the operation increased the level of sedation and reduced the incidence and severity of myoclonic movements due to etomidate.

Low-Dose Ketamine Pretreatment Reduces the Incidence and Severity of Myoclonus Induced by Etomidate: A Randomized, Double-Blinded, Controlled Clinical Trial.

Myoclonic movement induced by etomidate is a common but undesirable problem during general anesthesia induction. To investigate the influence of pretreatment with low-dose ketamine on the incidence and severity of myoclonus induced by etomidate, 104 patients were randomized allocated to 1 of 2 equally sized groups (n = 52) to receive either intravenous low-dose ketamine 0.5 mg/kg (group K) or an equal volume of normal saline (group S) 1 minute before induction of anesthesia with 0.3-mg/kg etomidate. The incidence and severity of myoclonus were assessed for 2 minutes after administration of etomidate. Here, we found that the incidence and intensity of myoclonus were both significantly reduced in low-dose ketamine-treated group compared with saline-treated group. The incidence of adverse effects was low and similar between groups. These results demonstrate that intravenous infusion of low-dose ketamine 0.5 mg/kg 1 minute prior to etomidate administration is effective in relieving etomidate-induced myoclonic movements during general anesthesia induction.