Remimazolam and Its Place in the Current Landscape of Procedural Sedation and General Anesthesia.

Remimazolam was derived from its parent compound by adding an ester linkage into its structure so that the drug becomes a substrate for ester metabolism. As a result, it undergoes organ-independent ester hydrolysis, although the clinical benefits in terms of shorter recovery are not uniformly observed in clinical practice. Remimazolam is mainly tested in procedural sedation. In comparison to propofol, the current gold standard for procedural sedation, its proposed attractiveness is shorter wake-up times and a clear-headed recovery. Its clear advantages over propofol are better hemodynamic stability, lack of pain on injection and availability of a reversal agent in the form of flumazenil. Data on patient and proceduralist satisfaction are lacking. Remimazolam is also used for induction and maintenance of general anesthesia in Japan (where it is approved for this purpose). In this scenario, it is not clear if it can achieve the same degree of lack of recall as propofol. The use of remimazolam in obstetrics, pediatrics and high-risk populations is an emerging area.

A novel ultrasound software system for lumbar level identification in obstetric patients.

PURPOSE: Using machine learning, we developed a proprietary ultrasound software called the Spine Level Identification (SLIDE) system, which automatically identifies lumbar landmarks in real time as the operator slides the transducer over the lumber spine. Here, we assessed the agreement between SLIDE and manual palpation and traditional lumbar ultrasound (LUS) for determining the primary target L3-4 interspace. METHODS: Upon institutional ethics approval and informed consent, 76 healthy term parturients scheduled for elective Caesarean delivery were recruited. The L3-4 interspace was identified by manual palpation and then by the SLIDE method. The reference standard was located using traditional LUS by an experienced operator. The primary outcome was the L3-4 interspace identification agreement of manual palpation and SLIDE with the reference standard, as percentage agreement and Gwet's agreement coefficient (AC1). RESULTS: The raw agreement was 70% with Gwet's agreement coefficient (AC1) = 0.59 (95% confidence interval [CI], 0.41 to 0.77) for manual palpation and 84% with Gwet's AC1 = 0.82 (95% CI, 0.70 to 0.93) for SLIDE. When the levels differ from the reference, the manual palpation method identified L2-3 more often than L4-5 while the SLIDE method identified equally above or below L3-4. The SLIDE system had greater agreement than palpation in locating L3-4 and all other lumber interspaces after controlling for body mass index (adjusted odds ratio, 2.99; 95% CI, 1.21 to 8.7; P = 0.02). CONCLUSION: The SLIDE system had higher agreement with traditional ultrasound than manual palpation did in identifying L3-4 and all other lumber interspaces after adjusting for BMI in healthy term obstetric patients. Future studies should examine factors that affect agreement and ways to improve SLIDE for clinical integration. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT02982317); registered 5 December 2016.

RéSUMé: OBJECTIF: À l'aide de l'apprentissage automatique, nous avons développé un logiciel d'échographie propriétaire appelé SLIDE (pour Spine Level Identification, c.-à-d. système d'identification du niveau vertébral), qui identifie automatiquement les points de repère lombaires en temps réel lorsque l'opérateur fait passer le transducteur sur la colonne lombaire. Ici, nous avons évalué l'agrément entre le SLIDE et la palpation manuelle et l'échographie lombaire traditionnelle pour déterminer l'espace intervertébral cible principal L3­L4. MéTHODE: Après avoir obtenu l'approbation du comité d'éthique de l'établissement et le consentement éclairé, 76 parturientes en bonne santé et à terme devant bénéficier d'un accouchement par césarienne programmée ont été recrutées. L'espace intervertébral L3­L4 a été identifié par palpation manuelle puis avec le logiciel SLIDE. L'étalon de référence a été localisé à l'aide d'une échographie lombaire traditionnelle par un opérateur expérimenté. Le critère d'évaluation principal était l'agrément entre l'identification de l'espace intervertébral L3­L4 par palpation manuelle et par logiciel SLIDE avec l'étalon de référence, en pourcentage d'agrément et coefficient d'agrément de Gwet (CA1). RéSULTATS: L'agrément brut était de 70 % avec le coefficient d'agrément de Gwet (CA1) = 0,59 (intervalle de confiance [IC] à 95 %, 0,41 à 0,77) pour la palpation manuelle et de 84 % avec le CA1 de Gwet = 0,82 (IC 95 %, 0,70 à 0,93) pour le logiciel SLIDE. Lorsque les niveaux lombaires différaient de la référence, la méthode de palpation manuelle a identifié L2­L3 plus souvent que L4­L5, tandis que la méthode SLIDE a identifié les vertèbres supérieures ou inférieures à L3­L4 de manière égale. Le système SLIDE a affiché un agrément plus important que la palpation pour localiser L3­L4 et tous les autres espaces intervertébraux lombaires après ajustement pour tenir compte de l'indice de masse corporelle (rapport de cotes ajusté, 2,99; IC 95 %, 1,21 à 8,7; P = 0,02). CONCLUSION: Le système SLIDE avait affiché un agrément plus élevé avec l'échographie traditionnelle que la palpation manuelle pour identifier le niveau L3­L4 et tous les autres espaces intervertébraux lombaires après ajustement pour tenir compte de l'IMC chez les patientes obstétricales à terme en bonne santé. Une étude future devrait examiner les facteurs qui affectent l'agrément et les moyens d'améliorer le logiciel SLIDE pour une intégration clinique. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT02982317); enregistrée le 5 décembre 2016.

Dexmedetomidine Use in Intensive Care Unit Sedation and Postoperative Recovery in Elderly Patients Post-Cardiac Surgery (DIRECT).

OBJECTIVE: This study examined recovery, delirium, and neurocognitive outcome in elderly patients receiving dexmedetomidine or propofol sedation after undergoing cardiac surgery. DESIGN: Open-label randomized trial. SETTING: Single center. PARTICIPANTS: A total of 70 patients older than 75 years without English language limitations and Mini Mental State Examination scores >20. INTERVENTIONS: Patients received either propofol (group P) or dexmedetomidine (group D) postoperatively until normothermic and hemodynamically stable. MEASUREMENTS AND MAIN RESULTS: Quality of recovery (QoR) was measured by the QoR-40 questionnaire on postoperative day (POD) three. Secondary outcomes were incidence and duration of delirium, time to extubation, length of hospital stay, hospital mortality rate, postoperative quality of life (QoL; measured by SF-36 performed at baseline and six months postoperatively), and neurocognitive disorder (measured by Minnesota Cognitive Acuity Screen [MCAS] performed at baseline, POD5, and six months postoperatively). A total of sixty-seven patients completed the trial. There was no significant difference in QoR-40 scores (95% confidence interval [CI], -7.6081-to-10.9781; p = 1.000), incidence of delirium (group P, 42%; group D, 24%; p = 0.191), mean hospital stay (95% CI, -5.4838-to-1.5444; p = 0.297), mean time to extubation (95% CI, -19.2513-to-7.5561; p = 0.866), or mean duration of delirium (95% CI, -4.3065-to-1.067; p = 0.206) between groups. No patients died in the hospital. There were no significant differences in changes in SF-36 or MCAS scores over time between groups. There was a decline in MCAS score from preoperatively to POD5 in group P (95% CI, -8.95725-to- -2.61775; p = 0.0005), which was greater than that observed in group D. CONCLUSIONS: The authors' findings demonstrated that the use of dexmedetomidine compared with propofol in elderly patients undergoing cardiac surgery was unlikely to improve QoR/postoperative QoL. Although the study was underpowered to detect secondary outcomes, the results suggested no reductions in delirium, time to extubation, and hospital stay, but a potential decrease in delayed neurocognitive recovery.

The Role of GABA Receptor Agonists in Anesthesia and Sedation.

GABA (γ-aminobutyric acid) receptors, of which there are two types, are involved in inhibitory synapses within the central nervous system. The GABAA receptor (GABAAR) has a central role in modern anesthesia and sedation practice, which is evident from the high proportion of agents that target the GABAAR. Many GABAAR agonists are used in anesthesia practice and sedation, including propofol, etomidate, methohexital, thiopental, isoflurane, sevoflurane, and desflurane. There are advantages and disadvantages to each GABAAR agonist currently in clinical use. With increasing knowledge regarding the pharmacology of GABAAR agonists, however, newer sedative agents have been developed which employ 'soft pharmacology', a term used to describe the pharmacology of agents whereby their chemical configuration allows rapid metabolism into inactive metabolites after the desired therapeutic effect(s) has occurred. These newer 'soft' GABAAR agonists may well approach ideal sedative agents, as they can offer well-controlled, titratable activity and ultrashort action. This review provides an overview of the role that GABAAR agonists currently play in sedation and anesthesia, in addition to discussing the future role of novel GABAAR agonists in anesthesia and sedation.