Ageing is the process generated by senescent cells, free radicals, inflammation and other relevant factors. Ageing contributes to age-related diseases that affect the quality of life. People are interested in anti-ageing intervention and many scientists attempt to search for anti-ageing medicines. This review focused on describing in vivo anti-ageing activity of US-FDA-approved drugs and found that alogliptin, canagliflozin and metformin might produce anti-ageing activity via AMPK activation. Rapamycin and canagliflozin are capable to inhibit mTOR to promote lifespan. Atracurium, carnitine and statins act as DAF-16 activators, which potentially contribute to anti-ageing activity. Hydralazine, lisinopril, rosiglitazone and zidovudine may help stabilize genomic integrity to prolong life expectancy. Other indirect mechanisms, including insulin-lowering effect by acarbose and calcium channel blocking activity by verapamil may also promote longevity. Interestingly, some drugs (i.e., canagliflozin, metformin, rapamycin and acarbose) are likely to demonstrate a lifespan-promoting effect predominantly in male animals. These pre-clinical data might provide mechanistic and phenotypic perspectives to better understand the targets of anti-ageing interventions.

Objective: One of the most common complications in general anesthesia is the Emergence delirium (ED). Many agents have been studied for prevention of ED, among which propofol has been successfully used. However, there is no information about the optimal dosage of this agent considering the ultimate outcome and the adverse effects; therefore, aimed to assess in this study. Method : 70 children undergoing general anesthesia using propofol, fentanyl, and atracurium were assessed. Participants were allocated randomly to treatment with either propofol 1 mg/kg (n = 35) or 0.5 mg/kg (n = 35) by the end of the anesthesia. The Pediatric Anesthesia Emergence Delirium (PAED) Scale, Face, Legs, Activity, Cry, Consolability (FLACC) scale, and the University of Michigan Sedation Scale (UMSS) were assessed by 10-minute intervals. Post-anesthesia care unit (PACU) stay and adverse effects were registered and compared as well. Results: Duration of PACU stay (P < 0.001), PAED (P = 0.001), and UMSS (P = 0.003) were remarkably lower among low-dose propofol-treated children in the assessment at the 30th minute, while there were no significant differences in FLACC scores between the groups (P > 0.05). Apnea was found in a patient (2.85%) treated with high-dose propofol and decreased oxygen saturation was demonstrated in 5 (14.28%) and 2 (5.71%) participants in high- versus low-dose propofol. None of the patients experienced postoperative nausea and vomiting. Conclusion: Based on the current study, propofol 0.5 mg/kg by the end of anesthesia could efficiently prevent ED incidence and reduce time of PACU stay and adverse effects compared to a high dose of 1 mg/kg.

No information is available on the use of atracurium during breastfeeding. Because it is short acting, highly polar and poorly absorbed orally, it is not likely to reach the breastmilk in high concentration or to reach the bloodstream of the infant.[1,2] When a combination of anesthetic agents is used for a procedure, follow the recommendations for the most problematic medication used during the procedure.

Neuromuscular blockade is frequently used in anesthesia to facilitate endotracheal intubation, optimize surgical conditions, and assist with mechanical ventilation in patients who have reduced lung compliance. Neuromuscular blocking agents (NMBAs) come in two forms: depolarizing neuromuscular blocking agents (e.g., succinylcholine) and nondepolarizing neuromuscular blocking agents (e.g., rocuronium, vecuronium, atracurium, cisatracurium, mivacurium). The class of NMBAs used for achieving neuromuscular blockade must be selected carefully based on patient factors, the type of procedure being performed, and clinical indication.

Non-depolarizing neuromuscular blockers (nNMBs) are administered as primary therapy in facilitating endotracheal intubations and adjuvant therapy in the perioperative maintenance of anesthesia and care of the critically ill patient. Primarily nNMBs (rocuronium, vecuronium, pancuronium, atracurium, cisatracurium, mivacurium) are used to facilitate airway management and decrease the risk of laryngeal injury during regular and emergent intubations. This activity outlines the indications, mechanism of action, methods of administration, significant adverse effects, contraindications, monitoring, and toxicity of nNMBs, so providers can direct patient therapy to optimal outcomes in anesthesia and other conditions where nNMBs have therapeutic benefit.

Data in the literature are still scarce to establish any recommendations on the use of quantitative monitoring during tracheal intubation.

Atracurium is indicated as an addition to general anesthesia to facilitate endotracheal intubation and provide skeletal muscle relaxation during surgery or mechanical ventilation. Atracurium is a non-depolarizing neuromuscular blocking drug of the benzylisoquinolinium class. It competes with acetylcholine for binding sites. This activity outlines the indications, mechanism of action, safe administration, adverse effects, contraindications, toxicology and monitoring of atracurium.

Pancuronium bromide is a long-acting, bis-quaternary aminosteroid, non-depolarizing, neuromuscular blocking drug (NMBD), which was first synthesized in 1964 and found to possess fewer adverse effects with regards to hemodynamic stability and histamine release as compared to the prototypical NMBD, d-tubocurarine. After the arrival of intermediate-acting NMBDs such as vecuronium, rocuronium, cisatracurium, and atracurium, the use of pancuronium has fallen out of favor with many clinicians due to its long elimination and context-sensitive half time and predominantly renal clearance. This activity outlines the indications, mechanism of action, methods of administration, significant adverse effects, contraindications, monitoring, and toxicity of pancuronium, so providers can direct patient therapy to optimal outcomes in anesthesia and other conditions where pancuronium has therapeutic benefit.

Tetrahydropapaverine (THP) and papaverine are plant natural products with clinically significant roles. THP is a precursor in the production of the drugs atracurium and cisatracurium, and papaverine is used as an antispasmodic during vascular surgery. In recent years, metabolic engineering advances have enabled the production of natural products through heterologous expression of pathway enzymes in yeast. Heterologous biosynthesis of THP and papaverine could play a role in ensuring a stable supply of these clinically significant products. Biosynthesis of THP and papaverine has not been achieved to date, in part because multiple pathway enzymes have not been elucidated. Here, we describe the development of an engineered yeast strain for de novo biosynthesis of THP. The production of THP is achieved through heterologous expression of two enzyme variants with activity on nonnative substrates. Through protein engineering, we developed a variant of N-methylcoclaurine hydroxylase with activity on coclaurine, enabling de novo norreticuline biosynthesis. Similarly, we developed a variant of scoulerine 9-O-methyltransferase capable of O-methylating 1-benzylisoquinoline alkaloids at the 3' position, enabling de novo THP biosynthesis. Flux through the heterologous pathway was improved by knocking out yeast multidrug resistance transporters and optimization of media conditions. Overall, strain engineering increased the concentration of biosynthesized THP 600-fold to 121 µg/L. Finally, we demonstrate a strategy for papaverine semisynthesis using hydrogen peroxide as an oxidizing agent. Through optimizing pH, temperature, reaction time, and oxidizing agent concentration, we demonstrated the ability to produce semisynthesized papaverine through oxidation of biosynthesized THP.

The protease inhibitor, ritonavir, is a strong inhibitor of CYP 3A. The drug is used for management of the human immunovirus and is currently part of an oral antiviral drug combination (nirmatrelvir-ritonavir) for the early treatment of SARS-2 COVID-19-positive patients aged 12 years and over who have recognized comorbidities. The CYP 3A enzyme system is responsible for clearance of numerous drugs used in anesthesia (e.g., alfentanil, fentanyl, methadone, rocuronium, bupivacaine, midazolam, ketamine). Ritonavir will have an impact on drug clearances that are dependent on ritonavir concentration, anesthesia drug intrinsic hepatic clearance, metabolic pathways, concentration-response relationship, and route of administration. Drugs with a steep concentration-response relationship (ketamine, midazolam, rocuronium) are mostly affected because small changes in concentration have major changes in effect response. An increase in midazolam concentration is observed after oral administration because CYP 3A in the gastrointestinal wall is inhibited, causing a large increase in relative bioavailability. Fentanyl infusion may be associated with a modest increase in plasma concentration and effect, but the large between subject variability of pharmacokinetic and pharmacodynamic concentration changes suggests it will have little impact on an individual patient, especially when used with adverse effect monitoring. It has been proposed that drugs that have no or only a small metabolic pathway involving the CYP 3A enzyme be used during anesthesia, for example, propofol, atracurium, remifentanil, and the volatile agents. That anesthesia approach denies children of drugs with considerable value. It is better that the inhibitory changes in clearance of these drugs are understood so that rational drug choices can be made to tailor drug use to the individual patient. Altered drug dose, anticipation of duration of effect, timing of administration, use of reversal agents and perioperative monitoring would better behoove children undergoing anesthesia.

Residual neuromuscular blockade is associated with significant morbidity. It has been widely studied in anaesthesia; however, the incidence of residual neuromuscular blockade in patients managed in the ICU is unknown. We conducted a prospective observational study in a tertiary ICU to determine the incidence of residual neuromuscular blockade using quantitative accelerographic monitoring. We tested for residual neuromuscular blockade (defined as a train-of-four ratio < 0.9) before cessation of sedation in anticipation of tracheal extubation. We also surveyed 16 other ICUs in New Zealand to determine their use of neuromuscular monitoring. A total of 191 patients were included in the final analysis. The incidence (95%CI) of residual neuromuscular blockade was 43% (36-50%), with a similar incidence observed in non-postoperative and postoperative patients. There was a lower risk of residual neuromuscular blockade with atracurium than rocuronium (risk ratio (95%CI) of 0.39 (0.12-0.78)) and a higher risk with pancuronium than rocuronium (1.59 (1.06-2.49)). Our survey shows that, in New Zealand ICUs, monitoring of neuromuscular function is rarely carried out before tracheal extubation. When neuromuscular monitoring is undertaken, it is based on individual clinician suspicion and performed using qualitative measurements. No ICU reported using a quantitative monitor or a clinical guideline. The results demonstrate a high incidence of residual neuromuscular blockade in our ICU patients and identify the type of neuromuscular blocking drug as a possible risk factor. Monitoring neuromuscular function before tracheal extubation is not currently the standard of care in New Zealand ICUs. These data suggest that residual neuromuscular blockade may be an under-recognised problem in ICU practice.

Cisatracurium besylate is an intermediate-acting, non-depolarizing neuromuscular blocking drug (NMBD). Cisatracurium has a benzylisoquinolinium structure and is the 1R cis-1-prime R cis isomer of atracurium. As an NMBD, it has found use as an adjunct to general anesthesia facilitating tracheal intubation and providing skeletal muscle relaxation during surgery. It may also be used to provide skeletal muscle relaxation to facilitate mechanical ventilation in an intensive care unit setting, but must be used with sedation. This activity reviews indications, mechanism of action, administration, contraindications, monitoring, and toxicity associated with cisatracurium, and the role of the interprofessional team in caring for patients who have received cisatracurium.

The objective of this work was to investigate the effect of different doses of cis-atracurium on patients undergoing general anesthesia induction (GAI) during intracranial aneurysm surgery (ICAS). In this work, 90 patients who underwent ICAS under the elective motor-evoked potential (MEP) monitoring in the First Affiliated Hospital of Northwest University (Xi'an No. 1 Hospital) from January 2021 to May 2022 were enrolled as the research objects. Randomly, they were rolled into a S1 group (30 cases, 2 times 95% effective dose (ED95) cis-atracurium), a S2 group (30 cases, 3 times ED95 cis-atracurium), and a S3 group (30 cases, 4 times ED95 cis-atracurium). The endotracheal intubation conditions, the train-of-four (TOF) rate (TOFR), body movement, and spontaneous breathing were compared among the three groups of patients. The results showed that the MEP inhibition time of the patients in the S3 group was much longer than that of the S1 and S2 groups, but it showed no significant difference between the S1 group and S2 group (P > 0.05). The good rates of endotracheal intubation conditions in the S2 group (100%) and S3 group (100%) were obviously higher than the rate in the S1 group (43.33%). The TOFRs of patients in S2 and S3 groups at time t2 and t3 were lower obviously to that at time t0, while the TOFRs of patients in S3 group at time t2 and t3 were still lower in contrast to the S2 group (P < 0.05). The mean arterial pressure (MAP) and heart rate (HR) of patients in all groups were lower at t1, t2, and t3 than at t0 (P < 0.05), while the differences among different groups were not remarkable (P > 0.05). Finally, using 3 times ED95 cis-atracurium for GAI could reduce the risk of intraoperative body movement and spontaneous breathing, as well as the residual degree of muscle relaxation, in patients with ICAS, without affecting MEP monitoring, improving endotracheal intubation conditions, and increasing safety during open neurosurgery operations.

Objective: To compare the anesthetic effects of mivacurium and cisatracurium besylate in laser laryngeal microsurgery, and to provide clinical evidence and reference for further optimization of muscle relaxation application. Methods: From October 2021 to January 2022, fifty-six patients of Beijing Tongren Hospital, Capital Medical University, scheduled for laser laryngeal microsurgery with general anesthesia, were enrolled. These patients, aged 18-65 years old, 25 males and 31 females, were divided into two groups (n=28) by random number table method. Cisatracurium besylate group (group C): cisatracurium besylate was injected at 0.1 mg/kg. Normal saline was continuously infused during operation. Mivacurium group (group M):Mivacurium was injected at 0.25 mg/kg and continuously infused at 0.3 mg·kg-1·h-1 during operation.The intubation time, the extubation time, recovery index, Cooper's score, Cormack-Lehane grade, surgical condition grade, postoperative residual neuromuscular block and allergic related adverse events were compared between the two groups. Results: The intubation time and the extubation time of group M were (3.7±1.1) and (16.2±5.0) min, which were statistically significant shorter than those of group C (4.9±0.7) and (26.4±8.6) min (all P<0.05). The recovery indexes of the patients in group M and group C were (4.5±3.4) and (6.2±5.0) min. The Cooper's scores of the two groups were both 9(9, 9). The Cormack-Lehane grades of the two groups were all grade Ⅰ. The number of cases with good/excellent surgical condition grades in group M and group C were 5/23 and 0/28. There were no significant differences in recovery index, Cooper's score, Cormack-Lehane grades and surgical condition grades between the two groups (all P>0.05). The TOF ratio of group M in the post anesthesia care unit (PACU) was (95.7±2.6) %, which was significantly higher than (92.9±3.9) % of group C(P=0.015). There were no significant differences in MAP and HR between the two groups at different time points (all P>0.05). The incidence of skin flushing in group M and group C was 10.7% (3/28) and 0, and the difference was not statistically significant (P=0.074). There were no cases of severe hypotension, significantly elevated airway pressure or airway spasm in both groups. Conclusion: In laser laryngeal microsurgery, compared with cisatracurium besylate, mivacurium has shorter intubation time and extubation time, stable hemodynamics, no significant increase in allergic related adverse events. mivacurium is safe and effective.

In order to evaluate the application of EEG intelligent detection in gynecological anesthesia depth, the application of ANGEL-6000 EEG depth monitor in laparoscopic gynecological anesthesia was proposed. This method was applied to 60 patients who underwent elective laparoscopic gynecological surgery in our hospital from February to August 2016. Inclusion criteria were ASA i ∼ ii; the average age was (37.8 ± 6.6) years from 20 to 50 years old; the average body weight was (51.53 ± 3.87) kg; conscious and no communication barriers; and patients without instrument ventilation. The patients were divided into observation group and control group according to the random number table method, with 30 patients in each group. The two groups were anesthetized with the same anesthetic drugs, and their consciousness index was monitored. IoC values were recorded before induction of anesthesia (T0), 5 min after intubation (T1), 5 min after operation (T2), intraoperative exploration (T3), at the end of operation (T4), 1 min before extubation (T5), and 5 min after extubation (T6). The dosage of anesthetic drugs, operation time, extubation time, and operation time of the two groups were statistically analyzed. Compared with the operation time of patients in the two groups, the extubation time, awake time, and time out of the operating room of patients in the control group were longer than the observation group. The IoC values of patients in the control group at T0 and T6 time points were lower than those in the observation group at each time point from T1 to T5. Comparison of perioperative dose of remifentanil and atracurium between the two groups was performed. The control group used more propofol dose in perioperative period. The application of neuroelectric signal in laparoscopic gynecological surgery to detect changes in perioperative IoC value can well reflect the level of consciousness of patients and reflect the effect of perioperative stimulation at different time points on the EEG of patients in real time.