Preoperative Midazolam and Patient-Centered Outcomes of Older Patients: The I-PROMOTE Randomized Clinical Trial.

Importance: The effect of oral midazolam premedication on patient satisfaction in older patients undergoing surgery is unclear, despite its widespread use. Objective: To determine the differences in global perioperative satisfaction in patients with preoperative administration of oral midazolam compared with placebo. Design, Setting, and Participants: This double-blind, parallel-group, placebo-controlled randomized clinical trial was conducted in 9 German hospitals between October 2017 and May 2019 (last follow-up, June 24, 2019). Eligible patients aged 65 to 80 years who were scheduled for elective inpatient surgery for at least 30 minutes under general anesthesia and with planned extubation were enrolled. Data were analyzed from November 2019 to December 2020. Interventions: Patients were randomized to receive oral midazolam, 3.75 mg (n = 309), or placebo (n = 307) 30 to 45 minutes prior to anesthesia induction. Main Outcomes and Measures: The primary outcome was global patient satisfaction evaluated using the self-reported Evaluation du Vécu de l'Anesthésie Generale (EVAN-G) questionnaire on the first postoperative day. Key secondary outcomes included sensitivity and subgroup analyses of the primary outcome, perioperative patient vital data, adverse events, serious complications, and cognitive and functional recovery up to 30 days postoperatively. Results: Among 616 randomized patients, 607 were included in the primary analysis. Of these, 377 (62.1%) were male, and the mean (SD) age was 71.9 (4.4) years. The mean (SD) global index of patient satisfaction did not differ between the midazolam and placebo groups (69.5 [10.7] vs 69.6 [10.8], respectively; mean difference, -0.2; 95% CI, -1.9 to 1.6; P = .85). Sensitivity (per-protocol population, multiple imputation) and subgroup analyses (anxiety, frailty, sex, and previous surgical experience) did not alter the primary results. Secondary outcomes did not differ, except for a higher proportion of patients with hypertension (systolic blood pressure ≥160 mm Hg) at anesthesia induction in the placebo group. Conclusion and Relevance: A single low dose of oral midazolam premedication did not alter the global perioperative patient satisfaction of older patients undergoing surgery or that of patients with anxiety. These results may be affected by the low dose of oral midazolam. Further trials-including a wider population with commonplace low-dose intravenous midazolam and plasma level measurements-are needed. Trial Registration: ClinicalTrials.gov Identifier: NCT03052660.

Sugammadex: a selective relaxant-binding agent providing rapid reversal.

PURPOSE OF REVIEW: Sugammadex is a new reversal agent with a unique mechanism of action in anaesthesia. Because of its rapid onset of action and its efficacy in determining neuromuscular blockade at any time, it opens up new perspectives in anaesthesia. RECENT FINDINGS: During the last few years, a lot of phase II and III studies have been published, investigating various groups of patients and clinical situations. Sugammadex has been shown to be a well tolerated drug, which appears to meet every challenge it is presented with in daily clinical practice. SUMMARY: Sugammadex binds amino-steroidal muscle relaxants by encapsulation. It enables rapid reversal of neuromuscular blockade at any time point and at any depth of block. Its effects are predictable and very reliable, in contrast to cholinesterase inhibitors. This opens up new perspectives in anaesthesia. Even an emergency reversal of high-dose rocuronium-induced neuromuscular blockade is possible with sugammadex and times to full recovery (TOF 0.9) are faster than after spontaneous recovery from suxamethonium.

[Sugammadex--a new era in the antagonsim of muscle relaxants]. / Sugammadex: Eine neue Ara in der Antagonisierung von Muskelrelaxanzien.

Cyclodextrins consist of rings of sugar molecules with a lipophilic core and a hydrophilic periphery. Thus they are well soluble in water and possess the ability to bind (encapsulate) steroid molecules. Cyclodextrins have now been modified (sugammadex) in such a way a perfect complex formation with rocuronium results. In this way an alternative to the classical indirect antagonists has been discovered. It is now possible to terminate a neuromuscular blockade via an intravasal encapsulation of rocuronium far distant from the neuromuscular endplates and avoiding the side effects associated with acetylcholinestase inhibitors instead of by an intervention in the acetylcholine system. Furthermore, it has been found that even deep neuromuscular blockades can be reversed within 2 minutes by means of this novel mechanism.

Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points: an international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial.

BACKGROUND: Sugammadex (Org 25969), a novel, selective relaxant binding agent, was specifically designed to rapidly reverse rocuronium-induced neuromuscular blockade. The efficacy and safety of sugammadex for the reversal of profound, high-dose rocuronium-induced neuromuscular blockade was evaluated. METHODS: A total of 176 adult patients were randomly assigned to receive sugammadex (2, 4, 8, 12, or 16 mg/kg) or placebo at 3 or 15 min after high-dose rocuronium (1.0 or 1.2 mg/kg) during propofol anesthesia. The primary endpoint was time to recovery of the train-of-four ratio to 0.9. Neuromuscular monitoring was performed using acceleromyography. RESULTS: Sugammadex administered 3 or 15 min after injection of 1 mg/kg rocuronium decreased the median recovery time of the train-of-four ratio to 0.9 in a dose-dependent manner from 111.1 min and 91.0 min (placebo) to 1.6 min and 0.9 min (16 mg/kg sugammadex), respectively. After 1.2 mg/kg rocuronium, sugammadex decreased time to recovery of train-of-four from 124.3 min (3-min group) and 94.2 min (15-min group) to 1.3 min and 1.9 min with 16 mg/kg sugammadex, respectively. There was no clinical evidence of reoccurrence of neuromuscular blockade or residual neuromuscular blockade. Exploratory analysis revealed that prolongation of the corrected QT interval considered as possibly related to sugammadex occurred in one patient. Another two patients developed markedly abnormal arterial blood pressure after sugammadex that lasted approximately 15 min. CONCLUSION: Sugammadex provides a rapid and dose-dependent reversal of profound neuromuscular blockade induced by high-dose rocuronium (1.0 or 1.2 mg/kg) in adult surgical patients.