Computer-aided drug design (CADD) has emerged as a highly effective and indispensable tool for streamlining the drug discovery process, leading to significant reductions in cost and time. The integration of CADD with machine learning (ML) and deep learning (DL) technologies further enhances its potential and promises novel advancements in the field. In this article, we provide a review of the computational methods employed in the development of novel anesthetics, outlining their respective advantages and limitations. These techniques have demonstrated their utility across various stages of drug discovery, encompassing the exploration of target-ligand interactions, identification and validation of new binding sites, de novo drug design, evaluation and optimization of absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties in lead compounds, as well as prediction of adverse effects. Through an in-depth exploration of computational approaches and their applications, this article aims to help relevant researchers develop safer and more effective anesthetic drugs.
The current study was designed to investigate the analgesic effect of esketamine on patients underwent thoracoscopic surgery and the underlying mechanism.
In this randomized, double blind, placebo-controlled study, 60 patients scheduled to undergo thoracoscopic lobectomy or segmentectomy were randomized to two groups to receive esketamine (group ESK) or saline (group SAL), respectively. 0.25 mg·kg−1 esketamine was given in group ESK for induction of anesthesia, and 0.12 mg·kg−1·h−1 esketamine for intraoperative maintenance. Group SAL received an equal volume of saline. The primary outcomes were the visual analogue scale (VAS) pain scores at rest and deep cough state which evaluated at departure from post-anesthesia care unit (PACU) (T1), 6 h, 24 h and 48 h after surgery (T2–T4). The secondary outcomes included the levels of white blood cell (WBC) count, absolute neutrophil count (ANC), interleukin-6 (IL-6), procalcitonin (PCT), anxiety/depression scores at T3, oxygen saturation (SpO2), and adverse reactions.
Esketamine significantly decreased both rest and cough VAS pain scores at T1, and rest pain scores at T1, T2 and T4. Patients in ESK group had significantly lower WBC and ANC levels than SAL group, while the alteration of IL-6 and PCT levels between groups showed no significance. The anxiety scores of patients in both groups were significantly decreased after surgery. However, the depression scores of patients in ESK group did not decrease after surgery when compared with the preoperation. The postoperative SpO2 and the incidence of adverse reaction including postoperative nausea, vomiting, dizziness and dissociative symptom showed no significant difference between two groups (p > 0.05).
Esketamine can alleviate the acute postoperative pain of patients undergoing thoracoscopic surgery without increasing adverse reactions, and the underlying mechanism may be associated with the reduction of postoperative inflammation.
Registered at Chinese Clinical Trial Registry on February 7, 2022 (ChiCTR 2200056524).
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most people infected with the virus experience mild to moderate respiratory illness. However, some might become seriously ill and may develop acute respiratory distress syndrome (ARDS), thus requiring non-invasive or invasive mechanical ventilation. Furthermore, COVID-19 disease can involve also other organs and systems, causing several extra-pulmonary manifestations and, thus, negatively influencing the patient’s outcome. Imaging studies play a pivotal role in the monitoring of severely ill patients, especially those admitted to the intensive care unit (ICU), who can develop several potentially life-threatening complications, both from the infection itself and the mechanical supporting system. This widespread utility of imaging modalities calls for a deeper understanding of potential radiologic findings in this disease and the need for multidisciplinary collaboration between radiologists and anesthesiologists to provide actionable guidance to appropriate interventions under such conditions.
We investigated the effects of a surgical mask and an N95 mask on speech intelligibility using explicit and ambiguous sentences in Japanese. In addition, the effects of background noise specific to an operating room environment on the speech intelligibility of these sentences were also investigated.
We created 20 sets of five sentences; 10 sets consisting of explicit words, and 10 containing ambiguous words. Each set was recorded by a speaker while wearing a surgical mask or an N95 mask, combined with a face shield. A total of four combinations of speech data were created. Each subject was asked to listen to one set from each of the four combinations and write down the speech. The test was performed in normal background noise as well as in noise levels of 50, 60, and 70 dB.
Twenty-eight volunteers were included in this study. In the tests for explicit sentences, intelligibility of speech with an N95 mask was significantly lower than that with a surgical mask in the presence of 60 dB noise. As for explicit sentences produced with a surgical mask, intelligibility was significantly decreased in the presence of 70 dB noise. Regarding explicit sentences produced with an N95 mask, intelligibility was significantly decreased in the presence of 60 and 70 dB noise. In the tests for ambiguous sentences, intelligibility of speech produced with an N95 mask was not significantly lower than that with a surgical mask at all noise levels. As for ambiguous sentences produced with a surgical mask, no significant decrease in intelligibility was observed at any noise level. Regarding ambiguous sentences produced with an N95 mask, intelligibility was significantly decreased in the presence of 60 and 70 dB noise.
Speech intelligibility was impaired both with a surgical mask and an N95 mask in the normal background noise specific in an operating room during surgery, even if the speech consisted of explicit words. The impairment of speech intelligibility was significantly exacerbated with the use of ambiguous language and in the background noise typical in an operating room environment. Speech intelligibility was further reduced with the use of an N95 mask.
Registered at the University Hospital Medical Information Network Clinical Trials Registry on March 7, 2023 (UMIN R000050373).
Disposcope is a novel fibreoptic intubation device that allows visualization of the glottis without aligning the oral, pharyngeal, and tracheal axes. This device may offer advantages in improving glottis exposure, or reducing hemodynamic disturbance, and minimizing movement of the upper cervical spine (C-spine). In this study, we aimed to evaluate laryngoscopy using Disposcope compared to Macintosh laryngoscope.
This study enrolled 60 adult patients (American Society of Anesthesiologists physical status 1 and 2), both male and female, underwent lumbar spine surgery, scheduled for general anesthesia with endotracheal intubation. We compared the Cormack and Lehane grade, hemodynamic response, and the maximal change in the angle between adjacent cervical vertebrae and cumulative upper C-spine movement between Disposcope and Macintosh laryngoscope. A crossover trial design was employed, with half of the patients being exposed to the glottis using the Macintosh laryngoscope first, followed by the Disposcope, and vice versa for the other half.
The intubation time in the Disposcope group was significantly lower than that in the Macintosh laryngoscope group (P < 0.01). Using the Disposcope resulted in improved views of the glottis (Z = −4.82, P < 0.01). Cormack and Lehane grade I views were achieved with the Disposcope in more patients than the Macintosh laryngoscope (36.7% versus 13.3%, P < 0.01). Grade II views were obtained in 58.3% of patients with the Disposcope, whereas a lower percentage (43.3%) was observed with the Macintosh laryngoscope. The incidence of grade III views was significantly lower with the Disposcope than with the Macintosh laryngoscope (5% versus 33.3%, P < 0.01). Additionally, there was significantly less hemodynamic disturbance (mean arterial pressure and heart rate) with the Disposcope compared to the Macintosh laryngoscope (P < 0.01). Finally, the median cumulative upper C-spine movement was greater with the Macintosh laryngoscope than with the Disposcope (26.9° versus 9.4°, P < 0.01).
In comparison to the Macintosh laryngoscope, the Disposcope provided improved views of the glottis and resulted in less hemodynamic disturbance and movement of the upper C-spine during laryngoscopy in patients.
Dexmedetomidine (Dexmed) is a highly selective alpha 2 adrenoceptor (α2-AR) agonist with excellent sedation and analgesic effects and is frequently used in breast cancer surgery. However, the exact impact of Dexmed on breast cancer prognosis is still unclear. The primary objective of this pilot study was to explore study feasibility (recruitment and dropout rates) for future large-scale randomized controlled trial (RCT) to test the hypothesis that intraoperative Dexmed reduced recurrence-free survival (RFS) and overall survival (OS) in patients after breast cancer surgery.
Interviews with patients were performed during the anesthetic preoperative visit for informed consent. Adult females scheduled for a mastectomy due to primary breast cancer were 1:1 randomised to saline (Group Control) or Dexmed (Group Dexmed) treatment groups. The primary outcomes were descriptions of study feasibility (recruitment and dropout rates). We also performed a preliminary analysis of RFS (time from surgery to the earliest date of recurrence/metastasis) and OS (time from surgery to the date of all-cause death) and collected data on percentages/numbers of circulating immune cells at pre- and 24 h post-operation.
A total of 964 patients were screened; 40% (385/964) met the inclusion criteria, among which 39% (150/385) were enrolled and randomly assigned to either Group Control (n = 75) or Group Dexmed (n = 75). The median follow-up duration was 49 months (interquartile range (IQR): 34–58 months) for Group Control and 48 months (IQR: 33–60 months) for Group Dexmed. Five percent (5%, 8/150) patients were lost to follow-up and 1% (2/150) died. There was no significant difference in RFS and OS. The percentage/number of natural killer (NK), B and T-cell subsets and the CD4+/CD8+ ratio were similar between groups at 24 h post-operation.
The pilot study was feasible to deliver. In a future definitive trial, the lower recruitment rate may be improved by increasing the number of anesthesiologists involved in the study. The study about the effects of Dexmed on long-term prognoses of breast cancer patients that is planned to follow this pilot study is a large-scaled randomized control study with the aim of providing evidence-based guidelines for rational use of Dexmed in patients undergoing breast cancer surgery.
Registered at ClinicalTrials.gov on October 20, 2016 (ID: NCT03109990).
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