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 METHODS: A comprehensive search of 11 databases was conducted to identify published and unpublished reviews up to March 2022.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.

Prognostic factors in epilepsy with eyelid myoclonia (Jeavons syndrome).

PURPOSE: To describe the prognostic factors of drug resistance in 40 patients with epilepsy with eyelid myoclonia or Jeavons syndrome. METHOD: Retrospective analysis from two French tertiary centers. RESULTS: Forty patients were enrolled (31 females and 9 males; mean age at epilepsy onset: 6.2±3.4 years [range: 1-15 years]). Half of the patients (20/40) achieved at least a one-year remission from all seizure types. In the responders, seizure freedom was achieved after a mean 13.85±13.43 years from the onset of epilepsy (range: 1-44). The presence of intellectual disability and an earlier onset of the disease (≤5 years) were the most powerful predictors of poor seizure control (P=0.003 and P=0.005, respectively). When considering the age of onset, patients with early-onset seizures (≤5 years) presented more frequently with intellectual disabilities, psychiatric comorbidities, absences, and a major risk of refractoriness (70% versus 30%, P=0.01) than patients with onset after 5 years. At the last follow-up, 15 patients (37.5%) were taking a single drug, 16 (40%) were taking two, and seven (17.5%) were taking more than two. The most frequent drugs were valproate (23/40, 57.7%), followed by levetiracetam (16/40, 40%), and lamotrigine (14/40, 35%). CONCLUSION: Patients with Jeavons syndrome present a high rate of pharmaco-resistance with the need for long-term treatment. Early onset of epilepsy and the presence of intellectual disability appeared to be the most relevant predictors of poor seizure control, suggesting the use of genetic tests to individualize specific etiologies and perhaps adapt the therapeutic strategy.

Early onset ataxia with comorbid myoclonus and epilepsy: A disease spectrum with shared molecular pathways and cortico-thalamo-cerebellar network involvement.

OBJECTIVES: Early onset ataxia (EOA) concerns a heterogeneous disease group, often presenting with other comorbid phenotypes such as myoclonus and epilepsy. Due to genetic and phenotypic heterogeneity, it can be difficult to identify the underlying gene defect from the clinical symptoms. The pathological mechanisms underlying comorbid EOA phenotypes remain largely unknown. The aim of this study is to investigate the key pathological mechanisms in EOA with myoclonus and/or epilepsy. METHODS: For 154 EOA-genes we investigated (1) the associated phenotype (2) reported anatomical neuroimaging abnormalities, and (3) functionally enriched biological pathways through in silico analysis. We assessed the validity of our in silico results by outcome comparison to a clinical EOA-cohort (80 patients, 31 genes). RESULTS: EOA associated gene mutations cause a spectrum of disorders, including myoclonic and epileptic phenotypes. Cerebellar imaging abnormalities were observed in 73-86% (cohort and in silico respectively) of EOA-genes independently of phenotypic comorbidity. EOA phenotypes with comorbid myoclonus and myoclonus/epilepsy were specifically associated with abnormalities in the cerebello-thalamo-cortical network. EOA, myoclonus and epilepsy genes shared enriched pathways involved in neurotransmission and neurodevelopment both in the in silico and clinical genes. EOA gene subgroups with myoclonus and epilepsy showed specific enrichment for lysosomal and lipid processes. CONCLUSIONS: The investigated EOA phenotypes revealed predominantly cerebellar abnormalities, with thalamo-cortical abnormalities in the mixed phenotypes, suggesting anatomical network involvement in EOA pathogenesis. The studied phenotypes exhibit a shared biomolecular pathogenesis, with some specific phenotype-dependent pathways. Mutations in EOA, epilepsy and myoclonus associated genes can all cause heterogeneous ataxia phenotypes, which supports exome sequencing with a movement disorder panel over conventional single gene panel testing in the clinical setting.

Sex-based electroclinical differences and prognostic factors in epilepsy with eyelid myoclonia.

Although a striking female preponderance has been consistently reported in epilepsy with eyelid myoclonia (EEM), no study has specifically explored the variability of clinical presentation according to sex in this syndrome. Here, we aimed to investigate sex-specific electroclinical differences and prognostic determinants in EEM. Data from 267 EEM patients were retrospectively analyzed by the EEM Study Group, and a dedicated multivariable logistic regression analysis was developed separately for each sex. We found that females with EEM showed a significantly higher rate of persistence of photosensitivity and eye closure sensitivity at the last visit, along with a higher prevalence of migraine with/without aura, whereas males with EEM presented a higher rate of borderline intellectual functioning/intellectual disability. In female patients, multivariable logistic regression analysis revealed age at epilepsy onset, eyelid myoclonia status epilepticus, psychiatric comorbidities, and catamenial seizures as significant predictors of drug resistance. In male patients, a history of febrile seizures was the only predictor of drug resistance. Hence, our study reveals sex-specific differences in terms of both electroclinical features and prognostic factors. Our findings support the importance of a sex-based personalized approach in epilepsy care and research, especially in genetic generalized epilepsies.

Etomidate-Induced Myoclonus in Sprague-Dawley Rats Involves Neocortical Glutamate Accumulation and N -Methyl- d -Aspartate Receptor Activity.

BACKGROUND: Etomidate-induced myoclonus, a seizure-like movement, is of interest to anesthetists. However, its origin in the brain and its underlying mechanism remain unclear. METHODS: Adult male Sprague-Dawley rats were anesthetized with etomidate, propofol, or lidocaine plus etomidate. We assessed the incidence of myoclonus, behavioral scores, and levels of glutamate and γ-aminobutyric acid (GABA) in the neocortex and hippocampus. To determine the origin and how N -methyl- d -aspartate receptors (NMDARs) modulate etomidate-induced neuroexcitability, the local field potential and muscular tension were monitored. Calcium imaging in vitro and immunoblotting in vivo were conducted to investigate the mechanisms underlying myoclonus. RESULTS: The incidence of etomidate (1.5 mg/kg in vivo)-induced myoclonus was higher than that of propofol (90% vs 10%, P = .0010) and lidocaine plus etomidate (90% vs 20%, P = .0050). Etomidate at doses of 3.75 and 6 mg/kg decreased the mean behavioral score at 1 (mean difference [MD]: 1.80, 95% confidence interval [CI], 0.58-3.02; P = .0058 for both), 2 (MD: 1.60, 95% CI, 0.43-2.77; P = .0084 and MD: 1.70, 95% CI, 0.54-2.86; P = .0060), 3 (MD: 1.60, 95% CI, 0.35-2.85; P = .0127 and MD: 1.70, 95% CI, 0.46-2.94; P = .0091) minutes after administration compared to etomidate at a dose of 1.5 mg/kg. In addition, 0.5 and 1 µM etomidate in vitro increased neocortical intracellular calcium signaling; this signaling decreased when the concentration increased to 5 and 10 µM. Etomidate increased the glutamate level compared to propofol (mean rank difference: 18.20; P = .003), and lidocaine plus etomidate (mean rank difference: 21.70; P = .0002). Etomidate in vivo activated neocortical ripple waves and was positively correlated with muscular tension amplitude (Spearman's r = 0.785, P < .0001). Etomidate at 1.5 mg/kg decreased the K-Cl cotransporter isoform 2 (KCC2) level compared with propofol (MD: -1.15, 95% CI, -1.47 to -0.83; P < .0001) and lidocaine plus etomidate (MD: -0.64, 95% CI, -0.96 to -0.32; P = .0002), DL-2-amino-5-phosphopentanoic acid (AP5) suppressed these effects, while NMDA enhanced them. CONCLUSIONS: Etomidate-induced myoclonus or neuroexcitability is concentration dependent. Etomidate-induced myoclonus originates in the neocortex. The underlying mechanism involves neocortical glutamate accumulation and NMDAR modulation and myoclonus correlates with NMDAR-induced downregulation of KCC2 protein expression.

Spectrum of Movement Disorders Among Children With Subacute Sclerosing Panencephalitis: A Cross-Sectional Study.

Background: Subacute sclerosing panencephalitis is a progressive devastating condition due to persistence of mutant measles virus, affecting children and adolescents, characterised by myoclonus, seizures, and neuropsychiatric issues. Movement disorders apart from myoclonus are reportedly uncommon. We aimed to describe frequency and proportion of movement disorders among children with subacute sclerosing panencephalitis, hypothesizing that these occur more frequently than previously reported. Methods: In this cross-sectional study, we enrolled children with subacute sclerosing panencephalitis between 1 month and 18 years of age who fulfilled the diagnosis of subacute sclerosing panencephalitis as per modified Dyken criteria, and examined them for movement disorders. We also assessed their clinical profile and disease severity via Jabbour staging and modified Rankin Scale score. We compared demographic, clinical, and laboratory features of children with and without movement disorders. Results: We enrolled 50 children (36 males; 72%) (age range 1.5-14 years). Of these, 28 (56%) had movement disorders. Among movement disorders, the most frequent was myoclonus (92%), followed by ataxia (9; 18%), chorea-athetosis (7; 14%), dystonia (6; 12%), tremor (4; 8%), repetitive behavior (4; 8%), and parkinsonism (3; 6%). Movement disorders were the presenting feature of subacute sclerosing panencephalitis among 7 children. There were no significant differences in clinical or laboratory features among children with and without movement disorders. Conclusions: Movement disorders were frequent in subacute sclerosing panencephalitis. Hyperkinetic disorders were dominant. Dystonia and chorea-athetosis occurred more commonly among nonmyoclonus movement disorders. Movement disorders may manifest even in earlier stages of subacute sclerosing panencephalitis and may be the heralding feature. Recognition of these features is important to plan management and reduce morbidity.

Molecular epidemiology of enteroviruses associated with severe hand, foot and mouth disease in Shenzhen, China, 2014-2018.

In this study, we investigated the epidemiology and molecular characteristics of enteroviruses associated with severe hand, foot and mouth disease (HFMD) in Shenzhen, China, during 2014-2018. A total of 137 fecal specimens from patients with severe HFMD were collected. Enterovirus (EV) types were determined using real-time reverse transcription polymerase chain reaction (RT-PCR), RT nested PCR, and sequencing. Sequences were analyzed using bioinformatics programs. Of 137 specimens tested, 97 (70.8%), 12 (8.8%), and 10 (7.3%) were positive for EV-A71, coxsackievirus A6 (CVA6), and CVA16, respectively. Other pathogens detected included CVA2 (2.9%, 4/137), CVA10 (2.9%, 4/137), CVA5 (0.7%, 1/137), echovirus 6 (E6) (0.7%, 1/137) and E18 (0.7%, 1/137). The most frequent complication in patients with proven EV infections was myoclonic jerk, followed by aseptic encephalitis, tachypnea, and vomiting. The frequencies of vomiting and abnormal eye movements were higher in EV-A71-infected patients than that in CVA6-infected or CVA16-infected patients. Molecular phylogeny based on the complete VP1 gene revealed no association between the subgenotype of the virus and disease severity. Nevertheless, 12 significant mutations that were likely to be associated with virulence or the clinical phenotype were observed in the 5'UTR, 2Apro, 2C, 3A, 3Dpol and 3'UTR of CVA6. Eight significant mutations were observed in the 5'UTR, 2B, 3A, 3Dpol and 3'UTR of CVA16, and 10 significant mutations were observed in the 5'UTR, VP1, 3A and 3Cpro of CVA10. In conclusion, EV-A71 is still the main pathogen causing severe HFMD, although other EV types can also cause severe complications. Potential virulence or phenotype-associated sites were identified in the genomes of CVA6, CVA16, and CVA10.

Treatment and challenges with antiepileptic drugs in patients with juvenile myoclonic epilepsy.

BACKGROUND: Patients with juvenile myoclonic epilepsy (JME) may have uncontrolled seizures. The purpose of this study was to investigate the use and challenges with antiepileptic drugs (AEDs) and the patients' view of these challenges. METHOD: A questionnaire about the use of AEDs, adherence to therapy, and quality of life was given to patients with JME recruited from Drammen Hospital. Data regarding AEDs were confirmed from medical records at Drammen Hospital, Norway (2007-2018). Additional clinical interviews were performed, and a mixed method approach was applied. RESULTS: Ninety patients with defined JME diagnosis, 54/36 women/men aged 14-39 (mean: 25) years, were included. Only 29 (33%) were seizure-free. Within the last year, 21% experienced generalized tonic-clonic seizures (GTCS), and 68% had myoclonic jerks. Seventy-six (84%) used AEDs, 78% in monotherapy. A total of 10 AEDs were used;: most commonly valproate (n = 33), lamotrigine (n = 27), and levetiracetam (n = 21). Two-thirds of valproate users were men while all other AEDs were used more in females than in men. Valproate and levetiracetam displayed better efficacy against GTCS than lamotrigine. One-third often/sometimes forgot their medication nonintentionally while 14% had intentional poor adherence. The majority reported good quality of life (76%). No significant correlations between the use of AEDs, use of valproate, poor adherence, quality of life score, and seizure freedom were demonstrated. Half of the patients had serum concentrations measured every year, and two-thirds thought this was important. Qualitative interviews elucidated treatment challenges in JME;, adverse effect burden, adherence, and activities of daily life. CONCLUSION: Despite the use of AEDs in the majority of patients, only one-third were seizure-free. Other challenges included polypharmacy, the use of valproate in women, and variable adherence. This points to a need for closer follow-up in patients with JME.

Jeavons Syndrome: Clinical Features and Response to Treatment.

BACKGROUND: Jeavons syndrome is an underreported epileptic syndrome characterized by eyelid myoclonia, eyelid closure-induced seizures or electroencephalography paroxysms, and photosensitivity. Drug-resistant epilepsy is common, but the prognostic factors and clinical course leading to drug resistance have not been well characterized. METHODS: We identified 30 patients who met the diagnostic criteria of Jeavons syndrome at a single institution between January 1, 2000 and December 15, 2016. Criteria for Jeavons syndrome included all of the following: (1) eyelid myoclonia with or without absences, (2) eye-closure-induced seizures or electroencephalography paroxysms, and (3) seizure onset after 12 months of age. We reviewed and described the epilepsy history, antiepileptic drug trials, and response to treatments. RESULTS: Mean age at seizure onset was 7.3 years, and 80% were female. Absence seizures (63%) and generalized tonic-clonic seizures (23%) were most common at onset. Diagnosis was delayed by an average of 9.6 years. After a median follow-up of two years, 80% of patients had drug resistant epilepsy and 70% experienced generalized tonic-clonic seizures. Generalized tonic-clonic seizures and seizure types other than absence seizures increased the risk of drug-resistant epilepsy (P values 0.049 and 0.03, respectively). Valproic acid, lamotrigine, ethosuximide, and levetiracetam were the most effective in reducing seizures by more than 50%. CONCLUSIONS: The diagnosis of Jeavons syndrome is often delayed. Generalized tonic-clonic seizures and seizure types other than absence seizures may be predictors of drug-resistant epilepsy among patients with Jeavons syndrome.

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.

Oxycodone for prevention of etomidate-induced myoclonus: a randomized double-blind controlled trial.

Objective This study was performed compare the effectiveness of oxycodone and fentanyl in reducing the incidence and severity of etomidate-induced myoclonus. Methods In total, 162 patients with an American Society of Anesthesiologists physical status of I or II were assigned at random to three groups. Patients assigned to Group O received 0.1 mg/kg of oxycodone (n = 54), those assigned to Group F were given 1 µg/kg of fentanyl (n = 54), and those assigned to Group S were given an equal volume of saline intravenously 2 minutes prior to administration of 0.3 mg/kg of etomidate (n = 54). The incidence and severity of myoclonus was evaluated 2 minutes after etomidate administration. The patients' vital signs, coughing, nausea, dizziness, and other related adverse reactions were also recorded. Results The incidence of myoclonus was significantly lower in Group O (0.0%) than in Group F (31.5%) and Group S (72.2%); the intensity was also lowest in Group O. All patients in each group had stable cardiovascular profiles. Conclusions Intravenous injection of 0.1 mg/kg of oxycodone 2 minutes prior to etomidate is more effective in preventing etomidate-induced myoclonus during general anesthesia than is 1 µg/kg of fentanyl.

Relative Incidence of Seizures and Myoclonus in Alzheimer's Disease, Dementia with Lewy Bodies, and Frontotemporal Dementia.

BACKGROUND: Patients with Alzheimer's disease (AD) are more prone to seizures and myoclonus, but relative risk of these symptoms among other dementia types is unknown. OBJECTIVE: To determine incidence of seizures and myoclonus in the three most common neurodegenerative dementias: AD, dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). METHODS: Our institution's medical records were reviewed for new-onset unprovoked seizures and myoclonus in patients meeting criteria for AD (n = 1,320), DLB (n = 178), and FTD (n = 348). Cumulative probabilities of developing seizures and myoclonus were compared between diagnostic groups, whereas age-stratified incidence rates were determined relative to control populations. RESULTS: The cumulative probability of developing seizures after disease onset was 11.5% overall, highest in AD (13.4%) and DLB (14.7%) and lowest in FTD (3.0%). The cumulative probability of developing myoclonus was 42.1% overall, highest in DLB (58.1%). The seizure incidence rates, relative to control populations, were nearly 10-fold in AD and DLB, and 6-fold in FTD. Relative seizure rates increased with earlier age-at-onset in AD (age <50, 127-fold; 50-69, 21-fold; 70+, 2-fold) and FTD (age <50, 53-fold; 50-69, 9-fold), and relative myoclonus rates increased with earlier age-at-onset in all groups. Seizures began an average of 3.9 years after the onset of cognitive or motor decline, and myoclonus began 5.4 years after onset. CONCLUSIONS: Seizures and myoclonus occur with greater incidence in patients with AD, DLB, and FTD than in the general population, but rates vary with diagnosis, suggesting varied pathomechanisms of network hyperexcitability. Patients often experience these symptoms early in disease, suggesting hyperexcitability could be an important target for interventions.

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.

Etomidate versus propofol sedation for complex upper endoscopic procedures: a prospective double-blinded randomized controlled trial.

BACKGROUND AND AIMS: Although a growing body of evidence demonstrates that propofol-induced deep sedation can be effective and performed safely, cardiopulmonary adverse events have been observed frequently. Etomidate is a new emerging drug that provides hemodynamic and respiratory stability, even in high-risk patient groups. The objective of this study was to compare safety and efficacy profiles of etomidate and propofol for endoscopic sedation. METHODS: A total of 128 patients undergoing EUS were randomized to receive either etomidate or propofol blinded administered by a registered nurse. The primary outcome was the proportion of patients with any cardiopulmonary adverse events. RESULTS: Overall cardiopulmonary adverse events were identified in 22 patients (34.38%) of the etomidate group and 33 patients (51.56%) of the propofol group, without significant difference (P = .074). However, the incidence of oxygen desaturation (4/64 [6.25%] vs 20/64 [31.25%]; P =.001) and respiratory depression (5/64 [7.81%] vs 21/64 [32.81%]; P =.001) was significantly lower in the etomidate group than in the propofol group. The frequency of myoclonus was significantly higher in the etomidate group (22/64 [34.37%]) compared with the propofol group (8/64 [12.50%]) (P =.012). Repeated measure analysis of variance revealed significant effects of sedation group and time on systolic blood pressure (etomidate group greater than propofol group). Physician satisfaction was greater in the etomidate group than in the propofol group. CONCLUSIONS: Etomidate administration resulted in fewer respiratory depression events and had a better sedative efficacy than propofol; however, it was more frequently associated with myoclonus and increased blood pressure during endoscopic procedures. (Clinical trial registration number: KCT0001701.).

Specific clinical signs and symptoms are predictive of clinical course in sporadic Creutzfeldt-Jakob disease.

BACKGROUND AND PURPOSE: Akinetic mutism is thought to be an appropriate therapeutic end-point in patients with sporadic Creutzfeldt-Jakob disease (sCJD). However, prognostic factors for akinetic mutism are unclear and clinical signs or symptoms that precede this condition have not been defined. The goal of this study was to identify prognostic factors for akinetic mutism and to clarify the order of clinical sign and symptom development prior to its onset. METHODS: The cumulative incidence of akinetic mutism and other clinical signs and symptoms was estimated based on Japanese CJD surveillance data (455 cases) collected from 2003 to 2008. A proportional hazards model was used to identify prognostic factors for the time to onset of akinetic mutism and other clinical signs and symptoms. RESULTS: Periodic synchronous discharges on electroencephalography were present in the majority of cases (93.5%). The presence of psychiatric symptoms or cerebellar disturbance at sCJD diagnosis was associated with the development of akinetic mutism [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.14-1.99, and HR 2.15, 95% CI1.61-2.87, respectively]. The clinical course from cerebellar disturbance to myoclonus or akinetic mutism was classified into three types: (i) direct path, (ii) path via pyramidal or extrapyramidal dysfunction and (iii) path via psychiatric symptoms or visual disturbance. CONCLUSIONS: The presence of psychiatric symptoms or cerebellar disturbance increased the risk of akinetic mutism of sCJD cases with probable MM/MV subtypes. Also, there appear to be sequential associations in the development of certain clinical signs and symptoms of this disease.

Psychiatric comorbidities in patients from seven families with autosomal dominant cortical tremor, myoclonus, and epilepsy.

OBJECTIVE: The objective of this report was to assess the psychiatric comorbidity in a group of patients affected by autosomal dominant cortical tremor, myoclonus, and epilepsy (ADCME). METHODS: Reliable and validated psychodiagnostic scales including the BDI (Beck Depression Inventory), STAI-Y1 and 2 (State-Trait Anxiety Inventory - Y; 1 and 2), MMPI-2 (Minnesota Multiphasic Personality Inventory - 2), and QoLIE-31 (Quality of Life in Epilepsy Inventory - 31) were administered to 20 patients with ADCME, 20 patients with juvenile myoclonic epilepsy (JME), and 20 healthy controls. RESULTS: There was a higher prevalence of mood disorders in patients with ADCME compared to patients with JME and healthy controls, particularly depression (p=0.035 and p=0.017, respectively) and state anxiety (p=0.024 and p=0.019, respectively). Trait anxiety was not different from JME (p=0.102) but higher than healthy controls (p=0.017). The myoclonus score positively correlated with both state (rho: 0.58, p=0.042) and trait anxiety (rho: 0.65, p=0.011). These psychiatric features were also often associated with pathological traits of personality: paranoid (OR: 25.7, p=0.003), psychasthenia (OR: 7.0, p=0.023), schizophrenia (OR: 8.5, p=0.011), and hypomania (OR: 5.5, p=0.022). Finally, in patients with ADCME, decreased quality of life correlated with these psychiatric symptoms. SIGNIFICANCE: Patients with ADCME show a significant psychiatric burden that impairs their quality of life. A comprehensive psychiatric evaluation should be offered at the time of diagnosis to detect these comorbidities and to treat them.

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.

Adverse events associated with poor neurological outcome during targeted temperature management and advanced critical care after out-of-hospital cardiac arrest.

INTRODUCTION: The aim of this study was to investigate the association of adverse events (AEs) during targeted temperature management (TTM) and other AEs and concomitant treatments during the advanced critical care period with poor neurological outcome at hospital discharge in adult out-of-hospital cardiac arrest (OHCA) patients. METHODS: This was a retrospective study using Korean Hypothermia Network registry data of adult OHCA patients treated with TTM in 24 teaching hospitals throughout South Korea from 2007 to 2012. Demographic characteristics, resuscitation and post-resuscitation variables, AEs, and concomitant treatments during TTM and the advanced critical care were collected. The primary outcome was poor neurological outcome, defined as a cerebral performance category (CPC) score of 3-5 at hospital discharge. The AEs and concomitant treatments were individually entered into the best multivariable predictive model of poor neurological outcome to evaluate the associations between each variable and outcome. RESULTS: A total of 930 patients, including 704 for whom a complete dataset of AEs and covariates was available for multivariable modeling, were included in the analysis; 476 of these patients exhibited poor neurological outcome [CPC 3 = 50 (7.1%), CPC 4 = 214 (30.4%), and CPC 5 = 212 (30.1%)]. Common AEs included hyperglycemia (45.6%), hypokalemia (31.3%), arrhythmia (21.3%) and hypotension (29%) during cooling, and hypotension (21.6%) during rewarming. Bleeding (5%) during TTM was a rare AE. Common AEs during the advanced critical care included pneumonia (39.6%), myoclonus (21.9%), seizures (21.7%) and hypoglycemia within 72 hours (23%). After adjusting for independent predictors of outcome, cooling- and rewarming-related AEs were not significantly associated with poor neurological outcome. However, sepsis, myoclonus, seizure, hypoglycemia within 72 hours and anticonvulsant use during the advanced critical care were associated with poor neurological outcome [adjusted odds ratios (95% confidence intervals) of 3.12 (1.40-6.97), 3.72 (1.93-7.16), 4.02 (2.04-7.91), 2.03 (1.09-3.78), and 1.69 (1.03-2.77), respectively]. Alternatively, neuromuscular blocker use was inversely associated with poor neurological outcome (0.48 [0.28-0.84]). CONCLUSIONS: Cooling- and rewarming-related AEs were not associated with poor neurological outcome at hospital discharge. Sepsis, myoclonus, seizure, hypoglycemia within 72 hours and anticonvulsant use during the advanced critical care period were associated with poor neurological outcome at hospital discharge in our study.

Prevention of etomidate-induced myoclonus during anesthetic induction by pretreatment with dexmedetomidine

Myoclonus induced by etomidate during induction of general anesthesia is undesirable. This study evaluated the effect of dexmedetomidine (DEX) pretreatment on the incidence and severity of etomidate-induced myoclonus. Ninety patients undergoing elective surgical procedures were randomly allocated to three groups (n=30 each) for intravenous administration of 10 mL isotonic saline (group I), 0.5 µg/kg DEX in 10 mL isotonic saline (group II), or 1.0 µg/kg DEX in 10 mL isotonic saline (group III) over 10 min. All groups subsequently received 0.3 mg/kg etomidate by intravenous push injection. The incidence and severity of myoclonus were recorded for 1 min after etomidate administration and the incidence of cardiovascular adverse events that occurred between the administration of the DEX infusion and 1 min after tracheal intubation was recorded. The incidence of myoclonus was significantly reduced in groups II and III (30.0 and 36.7%), compared with group I (63.3%). The incidence of severe sinus bradycardia was significantly increased in group III compared with group I (P<0.05), but there was no significant difference in heart rate in groups I and II. There were no significant differences in the incidence of low blood pressure among the 3 groups. Pretreatment with 0.5 and 1.0 µg/kg DEX significantly reduced the incidence of etomidate-induced myoclonus during anesthetic induction; however, 0.5 µg/kg DEX is recommended because it had fewer side effects.