Pronounced QT Prolongation During General Anesthesia in a Child with Left Ventricular Noncompaction Cardiomyopathy: A Case Report.

We report the case of an 8-year-old boy with left ventricular noncompaction cardiomyopathy (LVNC) and QT prolongation who experienced further prolongation of the QTc during general anesthesia for extraction of a maxillary mesiodens. Pronounced prolongation of the QTc was observed after induction of general anesthesia with thiamylal and during emergence. No notable fluctuations in blood pressure, heart rate, and estimated continuous cardiac output were observed. We considered it likely that the QT prolongation was triggered by thiamylal and increased sympathetic nervous system activity. During general anesthesia for children with LVNC and QT prolongation, it is necessary to monitor intraoperative hemodynamic fluctuations and prepare for the possible occurrence of arrhythmias.

Administration of lipid emulsion reduced the hypnotic potency of propofol more than that of thiamylal in mice.

Administration in a lipid emulsion can modify the pharmacodynamics of drugs via a process known as lipid resuscitation. However, the detailed mechanism remains unclear. We studied the volume and another pharmacodynamic effect, the lipid sink, using propofol and thiamylal. Male adult mice (ddY) were intravenously administered 10 ml/kg propofol or thiamylal diluted with physiological saline, 10% soybean oil, or 20% soybean oil. The 50% effective dose (ED50) for achieving hypnosis was calculated using probit analysis. To investigate the volume effect, 0, 10, or 20 ml/kg of saline or soybean oil was administered, either simultaneously or beforehand. Next, a two- or three-fold dose of the anesthetics was administered and the durations of anesthesia were measured. Finally, at 30 s after the first injection, supplemental soybean oil was administered. The mean (± SE) ED50 values of propofol and thiamylal were 5.79 mg/kg (0.61) and 8.83 mg/kg (0.84), respectively. Lipid dilution increased the ED50 values of both anesthetics. After injection of a dose two-fold the ED50 value, the respective mean (± SD) durations of anesthesia were 125 ± 35 s and 102 ± 38 s. Supplemental administration of soybean oil significantly shortened the duration of anesthesia of propofol, but not that of thiamylal. The results indicate that administration of a lipid emulsion vitiated the anesthetic effect of propofol by reducing the non-emulsified free fraction in the aqueous phase, which may elucidate the lipid resuscitation likely caused by the lipid sink mechanism.

Quantitative analysis of thiamylal and its metabolite secobarbital using liquid chromatography-tandem mass spectrometry in adipose tissue, serum, and liver.

Thiamylal is an ultrashort-acting barbiturate used for intravenous administration or general anesthesia induction. However, some cases of poisoning and suicide with thiamylal administration have been reported. Additionally, there are few reports on its analysis in the organs and adipose tissue, which requires purification by column chromatography and evaporation. A rapid and sensitive method was developed for quantifying thiamylal and its metabolite, secobarbital, in the adipose tissue, serum, and liver using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Samples were prepared using modified QuEChERS extraction. For adipose tissue samples, an acetonitrile-hexane partitioning step was added to the extraction. This method was applied to investigate a suspected self-poisoning autopsy case. The quantitation accuracy for thiamylal added to porcine pericardial fat (0.18 µg/g), human serum (0.015 µg/mL), and porcine liver (0.18 µg/g) was 103%, 113%, and 95.3%, respectively. The quantitation limits calculated for porcine pericardial fat, human serum, and porcine liver at a signal-to-noise ratio of 10 were 0.06 µg/g, 0.005 µg/mL, and 0.06 µg/g, respectively. In addition, the thiamylal and secobarbital levels in the forensic autopsy case were 140 and 1.5 µg/g, respectively, in myocardial fat; 3.5-4.9 and 0.12-0.20 µg/mL, respectively, in serum; and 6.2-42 and 0.58-1.1 µg/g, respectively, in liver tissue. Thiamylal is especially distributed in the adipose tissue. The thiamylal-to-fat ratio may help estimate the time from administration to death. The developed modified QuEChERS extraction method with acetonitrile-hexane partitioning is suitable for analyzing hydrophobic compounds, such as thiamylal, in the adipose tissue.

Analgesic and cardiopulmonary effects of premedication with tramadol in calves anesthetized with the infusion of guaifenesin and thiamylal.

This study examined the analgesic and cardiopulmonary effects of intravenous (IV) tramadol during general intravenous anesthesia in calves. Calves were premedicated with diazepam (0.2 mg/kg, IV) with tramadol (2 mg/kg, IV) (group T) or saline (group S). Anesthesia was induced by thiamylal sodium (4 mg/kg, IV) and maintained with an infusion (2 ml/kg/hr) of 5% guaifenesin containing thiamylal sodium (2 mg/ml). Additional thiamylal sodium (1-2 mg/kg, IV) was administered when interference from the calves was observed during surgery. The total counts of additional thiamylal sodium administration, analgesia score using a visual analog scale, recovery time, and cardiopulmonary function in the different groups were assessed and compared. Group T showed significantly fewer counts of additional drug administration and a significantly higher analgesia score. Tramadol may provide adequate analgesia with minimal cardiopulmonary changes in calves during general anesthesia.

A novel step-down infusion method of barbiturate therapy: Its safety and effectiveness for intracranial pressure control.

Intracranial pressure (ICP) has to be maintained quite constant, because increased ICP caused by cerebrovascular disease and head trauma is fatal. Although controlling ICP is clinically critical, only few therapeutic methods are currently available. Barbiturates, a group of sedative-hypnotic drugs, are recognized as secondary treatment for controlling ICP. We proposed a novel "step-down infusion" method, administrating barbiturate (thiamylal) after different time point from the start of treatment under normothermia, at doses of 3.0 (0-24 h), 2.0 (24-48 h), 1.5 (48-72 h), and 1.0 mg/kg/h (72-96 h), and evaluated its safety and effectiveness in clinical. In 22 patients with severe traumatic brain injury or severe cerebrovascular disease (Glasgow coma scale ≤8), thiamylal concentrations and ICP were monitored. The step-down infusion method under normothermia maintained stable thiamylal concentrations (<26.1 µg/ml) without any abnormal accumulation/elevation, and could successfully keep ICP <20 mmHg (targeted management value: ICP <20 mmHg) in all patients. Moreover the mean value of cerebral perfusion pressure (CPP) was also maintained over 65 mmHg during all time course (targeted management value: CPP >65 mmHg), and no threatening changes in serum potassium or any hemodynamic instability were observed. Our novel "step-down infusion" method under normothermia enabled to maintain stable, safe thiamylal concentrations to ensure both ICP reduction and CPP maintenance without any serious side effects, may provide a novel and clinically effective treatment option for patients with increased ICP.

Possible Role of High-Dose Barbiturates and Early Administration of Parenteral Ketogenic Diet for Reducing Development of Chronic Epilepsy in Febrile Infection-Related Epilepsy Syndrome: A Case Report.

We describe the efficacy of high-dose barbiturates and early administration of a parenteral ketogenic diet (KD) as initial treatments for acute status epilepticus (SE) in an 8-year-old girl with febrile infection-related epilepsy syndrome (FIRES). The patient was admitted to our hospital with refractory focal SE. Abundant epileptic discharges over the left frontal region were observed on electroencephalogram (EEG). Treatment with continuous infusion of thiamylal for 4 hours, increased incrementally to 40 mg/kg/h, successfully ended the clinical SE, and induced a burst-suppression coma. The infusion rate was then gradually decreased to 4 mg/kg/h over the next 12 hours. Parenteral KD was administered from days 6 to 21 of illness. Continuous infusion of thiamylal was switched to midazolam on day 10 without causing seizures or EEG exacerbations. The patient has remained seizure free in the 15 months since hospital discharge. The effectiveness of KD for the treatment of FIRES has attracted attention amongst clinicians, but KD treatment may need to last for 2 to 4 days before it can stop SE, a time period that could cause irreversible brain damage. Considering the severity of SE in our patient and the dose of barbiturates needed to treat it, we consider this case to have had a good clinical outcome. The results suggest that rapid termination of seizure using high-dose barbiturates in conjunction with early administration of parenteral KD could reduce the development of chronic epilepsy in patients with FIRES.

Thiamylal anaesthetic therapy for febrile refractory status epilepticus in children.

PURPOSE: To evaluate barbiturate anaesthetic therapy using thiamylal for febrile refractory status epilepticus (fRSE) in children. METHODS: This was a review of a prospectively-collected database between April 2012-March 2016 for fRSE cases treated with thiamylal anaesthetic therapy in a single paediatric hospital in Japan. The sample comprised 23 children (median age, 23 months) with fRSE that underwent thiamylal anaesthetic therapy for convulsive seizures lasting longer than 60 min, sustained after intravenous administration of benzodiazepine and non-benzodiazepine anticonvulsants. The intervention comprised protocol-based thiamylal anaesthetic therapy with bolus administration. We measured the dose and time required to achieve the burst suppression pattern (BSP) on electroencephalography, seizure recurrence, death, neurological sequelae, and complications. RESULTS: All patients except one reached the BSP. The thiamylal median dose until reaching the BSP was 27.5 mg/kg, and the median time from thiamylal administration to reaching the BSP was 109.5 min. There was one case of immediate treatment failure and one of withdrawal seizure, but no breakthrough seizure. No deaths occurred during treatment, and neurological sequelae occurred in four cases (17%). Vasopressors were administered in all cases. Other complications included 11 cases of pneumonia and one of enterocolitis. CONCLUSION: We revealed the time and dose required to reach the BSP with thiamylal anaesthetic therapy using bolus administration in children. Our results suggested that reaching the BSP with bolus administration requires markedly less time than without bolus administration, rarely causes seizure recurrence in paediatric fRSE, and causes haemodynamic dysfunction and infections as often as observed without bolus administration.

Pediatric procedural sedation in Japan: A single-facility study of 1,436 cases.

BACKGROUND: Pediatric procedural sedation (PPS) has been established worldwide as standard practice for several decades. However, there are no comprehensive guidelines or multi-facility databases of PPS in Japan, and the current status of PPS and PPS-related adverse events is unclear. The objectives of this study were to investigate the status of PPS in Japan and clarify the adverse events and risk factors. METHODS: This study was a single-facility, database survey performed at Oita University Hospital from September 2016 to March 2019. Children under 18 years of age who had been kept sedated for medical procedures with intravenous sedatives were enrolled in this study. Adverse events were recorded and defined according to the Quebec Guideline. RESULTS: During the study period, PPS was performed for 1,436 consecutive cases. The majority (94%) of the sedatives used were thiamylal alone or thiamylal combined with ketamine. There were a total of 253 adverse events in 233 cases (16.2%), including oxygen desaturation, airway hypersensitivity, and vomiting. Patients recovered from respiratory-related adverse events immediately with simple intervention. No patient required endotracheal intubation and no severe adverse event occurred. Four risk factors (a higher American Society of Anesthesiologists classification, longer procedure time, non-compliance of nil per os status, and no Pediatric Advanced Life Support certification for sedation personnel) were associated with the occurrence of adverse events. CONCLUSIONS: Adverse events occurred in 16.2% of all PPS cases. Further studies are needed to analyze the serious adverse events and risk factors for PPS in Japan.

Efficacy and safety of intravenous thiamylal in pediatric procedural sedation for magnetic resonance imaging.

OBJECTIVE: To evaluate the efficacy and safety of intravenous (i.v.) thiamylal in pediatric magnetic resonance imaging (MRI) sedation. METHODS: Infants and children from 1 month up to 8 years of age who underwent MRI in our hospital between April 2017 and March 2019 were included in this prospective observational study. Initial dose of 2 mg/kg thiamylal was given intravenously; however, additional doses were administered as needed. MRI was performed after adequate sedation was achieved. The primary endpoint was the success rate of MRI, while secondary endpoints were adverse events related to sedation, time to sedate, recovery time, and the dose of thiamylal. RESULTS: A total of 118 patients were included in the analysis with median age and weight of 31.5 months (14.0-56.8 months) and 12.6 kg (9.5-15.7 kg), respectively. The success rate of MRI was 96.6% (114/118), and the median dose of thiamylal per body weight was 3.6 (2.8-4.0) mg/kg. The median time from the first dose of thiamylal to MRI was 7 min (4-10 min) and that from the end of MRI scanning to the confirmation of emergence was 8 min (5-25 min). Adverse events encountered included respiratory arrests (n = 3) and reduction in oxygen saturation (SpO2; n = 9). There were no significant differences in the age, dose of thiamylal, sex, body weight, the American Society of Anesthesiologists physical status, and neurological abnormalities between the groups with and without respiratory complications. CONCLUSION: This study demonstrated an adequate efficacy and safety of i.v. thiamylal, with rapid sedation and patient recovery.

Propofol specifically reduces PMA-induced neutrophil extracellular trap formation through inhibition of p-ERK and HOCl.

Neutrophil extracellular traps (NETs) are net-like chromatin fibers that can trap and kill microorganisms. Although several anti-inflammatory effects of intravenous anesthetics have been reported, it has not been investigated whether intravenous anesthetics influence NET formation. AIMS: To compare the effects of four intravenous anesthetics (propofol, thiamylal sodium, midazolam, and ketamine) on phorbol myristate acetate (PMA)-induced NET formation and analyze the associated signaling pathways. MATERIALS AND METHODS: PMA-stimulated NETs formed in the absence or presence of intravenous anesthetics were stained with SYTOX Green and then quantified. Inhibitors were applied to investigate the related mechanism, which was confirmed by western blotting, and ROS were detected. KEY FINDINGS: The neutrophils incubated with propofol showed the lowest degree of NET formation compared with those incubated with the other intravenous anesthetics. Propofol significantly reduced the level of myeloperoxidase (MPO)-derived HOCl but not that of superoxide. Aminopyrine, an MPO inhibitor, markedly decreased the number of PMA-induced NETs, indicating the involvement of HOCl in the inhibitory effect of propofol on NET formation. According to western blotting results, the level of p-ERK was reduced by propofol during PMA-induced NET formation. The ERK inhibitor PD98059 decreased NET formation but did not inhibit PMA-induced HOCl generation, and aminopyrine did not reduce ERK phosphorylation. SIGNIFICANCE: Through this study, we define a new anti-inflammatory effect of intravenous anesthetics. Of the four intravenous anesthetics tested, propofol was the most potent inhibitor of NET formation. Moreover, propofol resulted in a decrease in PMA-induced NET formation by two independent mechanisms: inhibition of HOCl and p-ERK.

Thiamylal Plus Pentazocine Shows Similar Efficacy as Ketamine Plus Midazolam for Painful Procedures in Children With Leukemia.

This retrospective study compared the use of thiamylal plus pentazocine (TP) to ketamine plus midazolam (KM) in children with leukemia who were undergoing bone marrow aspiration and/or intrathecal chemotherapy. A total of 268 procedures in 35 children with leukemia were retrospectively analyzed for efficacy and adverse events. All procedures were successfully completed without severe adverse events. TP induced significantly faster sedation. The incidents of desaturation were significantly greater in the TP group, but were transient and recovered by oxygen supplementation alone. Therefore, TP can be a useful combination with a similar efficacy as KM for painful procedures in children.

Comparison of the effect of intravenous anesthetics used for anesthesia during electroconvulsive therapy on the hemodynamic safety and the course of ECT. / Porównanie wplywu anestetyków dozylnych stosowanych do znieczulenia w trakcie leczenia elektrowstrzasowego na bezpieczenstwo hemodynamiczne i przebieg zabiegów elektrowstrzasowych.

Electroconvulsive therapy (ECT) is the treatment method widely used in psychiatric disorders such as depression, bipolar disorder, schizophrenia and schizoaffective disorder. The advantage of ECT is therapeutic response that occurs significantly earlier than during pharmacotherapy. Initially ECTwas used without anesthesia. Then, in the 1950s procedures with general anesthesia were introduced to reduce the complications that may occur during a seizure caused by ECT, such as broken bones, teeth, tendon rupture, muscle damage. Currently, in general anesthesia for ECTseveral medications are used interchangeably: thiopental, propofol, etomidate and ketamine. In different resorts and different countries different anestethics are used, the choice is determined mainly by the experience of each resort and a kind of tradition. The authors provide an overview of objective data showing how various anesthetics affect the quality of ECT and the presence of any hemodynamic complications after ETC. Selection of articles included in this paper was made by searching Medline and PubMed databases using specific keywords: electroconvulsive therapy, general anesthesia, the risks and benefits of thiopental, ketamine, propofol and etomidate. The results of this review are inconclusive when it comes to the effect of intravenous anesthetics on the quality of the ECT treatment and side effects relating to respiratory and cardiovascular system. On this basis it is impossible to determine which of intravenous anesthetics is most advantageous from the point of view of the patient. To develop the optimum scheme of anesthesia for ECT, it is necessary to conduct further, methodologically correct studies.

General Anesthesia for a Patient With Pelizaeus-Merzbacher Disease.

We report the successful management of general anesthesia for a patient with Pelizaeus-Merzbacher disease (PMD). PMD is one of a group of progressive, degenerative disorders of the cerebral white matter. The typical clinical manifestations of PMD include psychomotor retardation, nystagmus, abnormal muscle tone, seizures, and cognitive impairment. General anesthesia for a patient with PMD may be difficult mainly because of seizures and airway complications related to poor pharyngeal muscle control. In addition, the possibility of exacerbation of spasticity should be considered. A 20-year-old man with PMD required removal of impacted wisdom teeth under general anesthesia. General anesthesia was induced with thiamylal, fentanyl, and desflurane. Anesthesia was maintained with desflurane and continuous intravenous remifentanil under bispectral index and train-of-4 monitoring. Anesthesia lasted 1 hour 20 minutes and was completed uneventfully. Airway complications, seizures, and exacerbation of spasticity did not occur postoperatively. Preoperatively, our patient had no history of epilepsy attacks or aspiration pneumonia, and no clinical symptoms of gastroesophageal reflux disease. Therefore, exacerbation of spasticity was one of the most likely potential complications. Identification of these associated conditions and evaluation of risk factors during preoperative examination is important for performing safe anesthesia in these patients.

Thiamylal sodium increased inflammation and the proliferation of vascular smooth muscle cells / 대한마취과학회지

BACKGROUND: Thiamylal sodium is a common anesthetic barbiturate prepared in alkaline solution for clinical use. There is no previously reported study on the effects of barbiturates on the inflammation and proliferation of vascular smooth muscle cells (VSMCs). Here, we examined the effects of clinical-grade thiamylal sodium solution (TSS) on the inflammation and proliferation of rat VSMCs. METHODS: Expression levels of interleukin (IL)-1α, IL-1β, IL-6, and toll-like receptors in rat VSMCs were detected by quantitative reverse transcription-polymerase chain reaction and microarray analyses. The production of IL-6 by cultured VSMCs or ex vivo-cultured rat aortic segments was detected in supernatants by enzyme-linked immunosorbent assay. VSMC proliferation and viability were determined by the water-soluble tetrazolium-1 assay and trypan blue staining, respectively. RESULTS: TSS increased expression of IL-1α, IL-6, and TLR4 in VSMCs in a dose-dependent manner, and reduced IL-1β expression. Ex vivo TSS stimulation of rat aorta also increased IL-6. Low concentrations of TSS enhanced VSMC proliferation, while high concentrations reduced both cell proliferation and viability. Expression of IL-1 receptor antagonist, which regulates cell proliferation, was not increased by TSS stimulation. Exposure of cells to the TSS additive, sodium carbonate, resulted in significant upregulation of IL-1α and IL-6 mRNA levels, to a greater extent than TSS. CONCLUSIONS: TSS-induced proinflammatory cytokine production by VSMCs is caused by sodium carbonate. However, pure thiamylal sodium has an anti-inflammatory effect in VSMCs. TSS exposure to VSMCs may promote vascular inflammation, leading to the progression of atherosclerosis or in-stent restenosis, resulting in vessel bypass graft failure.

Intravenous ketogenic diet therapy for treatment of the acute stage of super-refractory status epilepticus in a pediatric patient.

BACKGROUND: A ketogenic diet has been used successfully to treat intractable epilepsy. However, the role of early intravenous initiation of ketogenic diet in the acute phase of super-refractory status epilepticus is not well-described. METHODS: An intravenous ketogenic diet was administered to a boy with super-refractory status epilepticus. At 24 hours after intravenous ketogenic diet, moderate ketosis appeared, and thiamylal was successfully weaned at 70 hours after admission. RESULTS: An intravenous ketogenic regimen led to subsequent ketosis and seizure control in a child with super-refractory status epilepticus. CONCLUSION: Early induction of ketosis may be a novel strategy to effectively treat super-refractory status epilepticus. Although there are few data regarding the early use of intravenous ketogenic diet in the treatment of super-refractory status epilepticus, it may be considered an alternative option.

Influence of intravenous anesthetics on neuromonitoring of the recurrent laryngeal nerve during thyroid surgery.

Limited reports are available in the literature on the impact of intravenous administration of anesthetics on laryngeal electromyographic (EMG) activity. The purpose of this study was to determine the influence of the two commonly used intravenous anesthetics (propofol and thiamylal) on EMG amplitude evoked from the recurrent laryngeal nerve (RLN) during thyroid surgery. A total of 40 patients were randomized to receive a bolus of propofol (0.5 mg/kg; n = 20) or thiamylal (1.5 mg/kg; n = 20) to increase anesthetic depth when the surgeon found patient movement intraoperatively. Evoked potentials were obtained before and every 1 minute after the administration of each agent for up to 5 minutes by stimulating the RLN. The magnitude of evoked potentials at each time point and hemodynamic response were compared within groups. The mean amplitude of evoked potentials did not change significantly after administration of either propofol or thiamylal (p > 0.05 within groups). Mean arterial pressure measured from 1 minute to 5 minutes was significantly lower in the propofol group than in the thiamylal group (p < 0.05). Heart rate measured within 5 minutes did not differ significantly within groups. Low dose of propofol (0.5 mg/kg) or thiamylal (1.5 mg/kg) did not affect EMG readings during neuromonitoring of the RLN in thyroid surgery. Our results show that thiamylal provides better hemodynamic stability than propofol, and is therefore a preferable agent to increase anesthesia depth and prevent further patient movement during intraoperative neuromonitoring.

Appropriate head position for nasotracheal intubation by using lightwand device (Trachlight).

The purpose of this study was to determine the relationship between the head position and the subsequent ease of nasotracheal intubation by using the lightwand device Trachlight (TL). Patients requiring nasotracheal intubation were subdivided into 3 groups according to the intubated head position (group S: sniffing position; group E: extension position; and group N: neutral position). The number of attempts, the total intubation time, and the failures of the TL intubation were recorded. Intubation difficulty by means of TL was assessed by the ordinal 6-point scale. Of the 300 patients enrolled in the study, TL intubation was successful in 91.3% of them. There was no significant difference in the success rate of the first attempt between the groups. No correlation between the ordinal scale and the head position was observed. The total intubation time and the ratio of "unsuccessful" cases were not significantly different among the 3 groups. TL is an effective alternative for patients who require nasotracheal intubation. Our study did not determine the most favorable head position for nasotracheal intubation with the TL, so we recommend that nasotracheal intubation with TL be started with the head in the neutral position and then changed to a more appropriate position, if necessary, on an individual basis.

The influence of glucose load on metabolism during minor surgery using remifentanil-induced anesthesia.

BACKGROUND: During perioperative fasting, lipid metabolism gradually increases, resulting in free fatty acids (FFA) and/or ketone bodies. Suppression of surgical stress by remifentanil may allow the safe administration of glucose infusions, avoiding both hyperglycemia and ketogenesis. The effects of glucose infusion on glucose and lipid metabolism were therefore investigated in patients undergoing minor surgery with remifentanil anesthesia. METHODS: Thirty-four patients were randomized 1 : 1 to receive no glucose (0G group) or low-dose glucose (0.1 g/kg/h for 1 h followed by 0.05 g/kg/h for 1 h; LG group). The concentrations of glucose, adrenocorticotropic hormone (ACTH), 3-methylhistidine (3-MH), insulin, cortisol, FFA, creatinine (Cr), and ketone bodies were measured before anesthetic induction, 1 and 2 h after glucose infusion, at the end of surgery, and the next morning. RESULTS: The concentrations of cortisol and ACTH decreased during surgery in both groups when compared with the concentrations before anesthesia and at the end of surgery (P < 0.05). Glucose and insulin concentrations were significantly higher in the LG than in the 0G group at 1 and 2 h after infusion. No patient experienced hyperglycemia. The concentrations of FFA and ketone bodies were lower in the LG than in the 0G group during surgery, but there were no significant between group differences in 3-MH/Cr. CONCLUSION: Infusion of low-dose glucose attenuated fat catabolism without causing hyperglycemia, indicating that infusion of low-dose glucose during remifentanil-induced anesthesia may be safe for patients.

Different regimens of intravenous sedatives or hypnotics for electroconvulsive therapy (ECT) in adult patients with depression.

BACKGROUND: Depression is a common mental disorder. It affects millions of people worldwide and is considered by the World Health Organization (WHO) to be one of the leading causes of disability. Electroconvulsive therapy (ECT) is a well-established treatment for severe depression. Intravenous anaesthetic medication is used to minimize subjective unpleasantness and adverse side effects of the induced tonic-clonic seizure. The influence of different anaesthetic medications on the successful reduction of depressive symptoms and adverse effects is unclear. OBJECTIVES: This review evaluated the effects of different regimens of intravenous sedatives and hypnotics on anti-depression efficacy, recovery and seizure duration in depressed adults undergoing ECT. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12); MEDLINE via Ovid SP (from 1966 to 31 December 2012); and EMBASE via Ovid SP (from 1966 to 31 December 2012). We handsearched related journals and applied no language restrictions. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and cross-over trials evaluating the effects of different intravenous sedatives and hypnotics for ECT. We excluded studies and trials using placebo or inhalational anaesthetics and studies that used no anaesthetic. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. When possible, data were pooled and risk ratios (RRs) and mean differences (MDs), each with 95% confidence intervals (CIs), were computed using the Cochrane Review Manager statistical package (RevMan). MAIN RESULTS: We included in the review 18 RCTs (599 participants; published between 1994 and 2012). Most of the included trials were at high risk of bias.We analysed the results of studies comparing six different intravenous anaesthetics.Only a few studies comparing propofol with methohexital (four studies) and with thiopental (three studies) could be pooled.No difference was noted in the reduction of depression scores observed in participants treated with propofol compared with methohexital (low-quality evidence). These four studies were not designed to detect differences in depression scores.The duration of electroencephalograph (EEG) and of motor seizures was shorter in the propofol group compared with the methohexital group (low-quality evidence). No difference was seen in EEG seizure duration when propofol was compared with thiopental (low-quality evidence).Time to recovery (following commands) was longer among participants after anaesthesia with thiopental compared with propofol (low-quality evidence).For the remaining comparisons of anaesthetics, only single studies or insufficient data were available. Adverse events were inadequately reported in eligible trials, and none of the included trials reported anaesthesia-related mortality. AUTHORS' CONCLUSIONS: Most of the included studies were at high risk of bias, and the quality of evidence was generally low. The studies were not designed to detect clinically relevant differences in depression scores. Anaesthetic agents should be chosen on the basis of adverse effect profile, emergence and how these medications affect seizure duration. If it is difficult to elicit an adequately long seizure, methohexital may be superior to propofol (low-quality evidence). If a patient is slow to recover from anaesthesia, propofol may allow a faster time to follow commands than thiopental (low-quality evidence). A factor of clinical concern that was not addressed by any study was adrenal suppression from etomidate. Optimal dosages of intravenous sedatives or hypnotics have not yet been determined.Larger well-designed randomized studies are needed to determine which intravenous anaesthetic medication leads to the greatest improvement in depression scores with minimal adverse effects.

Procedural sedation with dexmedetomidine during ablation of atrial fibrillation: a randomized controlled trial.

AIMS: Procedural sedation by non-anaesthesiologists with GABAergic anaesthetics has the potential risk of fatal respiratory depression. Dexmedetomidine works its sedative action via α2-adrenergic receptors, and is less associated with respiratory depression. We tested the usability of dexmedetomidine as a procedural sedative during ablation of atrial fibrillation (AF). METHODS AND RESULTS: Consecutive patients were randomized to be treated with dexmedetomidine (n = 43) or thiamylal (n = 44) as sedatives during AF ablation. Apnoeic and body movement events were monitored using a novel portable respiratory monitor, the SD-101, during the procedure. Although the majority of the patients receiving dexmedetomidine required rescue sedations with thiamylal, the respiratory disturbance index (RDI) defined as the total number of sleep-disordered breathing events divided by the recording time (10.4 ± 5.1 vs. 18.2 ± 8.1 events/h; P < 0.0001) and movement index defined as the number of body movement events per hour (7.6 ± 6.1 vs. 11.0 ± 5.5 events/h; P = 0.0098) were both significantly lower in the dexmedetomidine arm than in the thiamylal arm. A multivariate linear regression analysis including potential factors revealed that dexmedetomidine vs. thiamylal was solely and independently associated with the RDI (ß = -0.62; P = 0.0031). The occurrence of hypotension [9 (21%) vs. 4 (9%); P = 0.14] and bradycardia [4 (9%) vs. 4 (9%); P = 1.0] were similar in the patients with dexmedetomidine and thiamylal. CONCLUSION: Procedural sedation with dexmedetomidine may assure safety and patient immobility during AF ablation, and therefore may be a potential alternative for that with GABAergic anaesthetics.