Summary Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus. Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894. Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus. Funding National Institute for Health Research Health Technology Assessment programme.

Our large series of propofol sedations performed by emergency physicians supports the safety of this practice. The sentinel adverse event rate of 1% that we identify prompts review: we will in future emphasize adherence to the reduced 0.5 mg kg(-1) propofol dose in the elderly, and reconsider our use of metaraminol. We believe that our application of the World SIVA adverse event tool sets a benchmark for further studies.

BackgroundThe Valsalva manoeuvre (VM) is used to treat supraventricular tachycardia (SVT) by inducing a vagal response (drop in HR). There is debate as to the best position in which to carry out the VM and how the strain should be delivered in practice. We aimed to compare vagal responses induced with supine and modified VMs using strains delivered with a standardised manometer or novel Valsalva Assist Device (VAD), a simple device to provide resistance to exhalation.MethodsWe conducted a repeated measures randomised trial of four VMs (two supine VM and two modified VMs), in healthy adult volunteers, with strains delivered using an adapted sphygmomanometer (manometer) or a VAD. Changes in HR, pressure and duration of strain and adverse events were monitored and compared between the techniques and devices. The trial was approved by the University of Exeter Medical School Research ethics committee.Results75 healthy participants aged 19–55 years were recruited over a 4-month period. A mixed-effects linear regression showed the modified VM resulted in a 3.8 beats per min (bpm) greater drop in HR compared with the supine VM (p=0.002, 95% CI 2.2 to 5.4). VM strains produced by the VAD were of a similar pressure but of slightly shorter duration and resulted in a 1.9 bpm smaller drop in HR compared with the manometer (p=0.01, 95% CI 0.4 to 3.4). There were no differences in adverse events.ConclusionsModified VM was associated with a greater drop in HR than a supine VM with no increase in adverse events in healthy volunteers. The VAD can be used to safely generate the recommended VM strain pressure, but produced a smaller drop in HR compared with a manometer and requires modification to enable the recommended strain duration to be achieved consistently.Trial registration numberNCT03298880.

were available on 1766 patients (999 and 767 patients in phases 1 and 3, respectively). The majority of the procedures were colonoscopies, upper gastrointestinal endoscopies, examinations under anesthesia, endoscopic retrograde cholangiopancreatographies, and central venous catheter placements. There was no difference in demographics between the 2 groups. The RSS was inversely associated with the BIS value r = 0.16 (95% confidence interval, −0.19 to −0.12). An RSS of 2 to 3 was maintained in 94% of patients in phase 1 and 96% of patients in phase 3. The mean BIS values were 80.9 (SD, 6.8) in phase 1 and 80.4 (SD, 6.5) in phase 3.The number of sedation-related adverse events was lower in the sample when BIS was used, with an odds ratio of 0.41 (95% confidence interval, 0.28-0.62), and patients with restlessness had a lower BIS value than those without. No serious adverse events or deaths were reported. Moderate sedation administered by nurses using midazolam and fentanyl was usually related to appropriate levels of sedation, as assessed by both the RSS and BIS with a low overall incidence of adverse events. The use of BIS did not change the mean level of sedation, although the number of sedation-related adverse events seems to be lower when BIS was used. COMMENTThese investigators from Duke University Medical Center found that sedation provided by trained nurses was generally associated with appropriate levels of sedation (moderate sedation), as reflected by RSS and BIS values. Use of BIS monitoring to guide anesthetic drug administration did not appreciably change sedation levels. Moreover, the investigators identified that RSS and BIS had a statistically significant inverse correlation, suggesting that BIS is a reliable monitor for assessing sedation for moderate sedation with midazolam, fentanyl, and hydromorphone. Although there were fewer adverse events when BIS values were made visible to sedation nurses, the overall incidence of adverse events was too low to establish a relationship. This is an important and germane study, given that the use of intravenous sedation by nonanesthesia providers has grown enormously, largely as a result of the explosive growth in out-ofoperating room invasive diagnostic and therapeutic procedures. Midazolam-opioid sedation was administered, because propofol was not permitted to be given by nurses at Duke during the time of the study. The cases included gastrointestinal endoscopies, bronchoscopies, examinations under sedation, and central line placement. The goal was to provide moderate, rather than deep, sedation, because in the hands of nonanesthesiologists, deep sedation and moderate sedation are associated with notably different levels of risk. Importantly, no supplemental oxygen was administered. The cases were brief, and the nurses were well trained. There were insufficient numbers of adverse events to identify any important advantage of BIS monitoring. Forty-five of the 999 patients developed hypoxemia, but only 3 of these patients became apneic. As underscored in an acco...

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