Role Of Sedation Research Articles

Metabolomics and transcriptomics reveal the mechanism of alkaloid synthesis in Corydalis yanhusuo bulbs.

Corydalis yanhusuo W.T. Wang is a traditional herb. Benzylisoquinoline alkaloids (BIAs) are the main pharmacological active ingredients that play an important role in sedation, relieving pain, promoting blood circulation, and inhibiting cancer cells. However, there are few studies on the biosynthetic pathway of benzylisoquinoline alkaloids in Corydalis yanhusuo, especially on some specific components, such as tetrahydropalmatine. We carried out widely targeted metabolome and transcriptomic analyses to construct the biosynthetic pathway of benzylisoquinoline alkaloids and identified candidate genes. In this study, 702 metabolites were detected, including 216 alkaloids. Protoberberine-type and aporphine-type alkaloids are the main chemical components in C. yanhusuo bulbs. Key genes for benzylisoquinoline alkaloids biosynthesis, including 6-OMT, CNMT, NMCH, BBE, SOMT1, CFS, SPS, STOX, MSH, TNMT and P6H, were successfully identified. There was no significant difference in the content of benzylisoquinoline alkaloids and the expression level of genes between the two suborgans (mother-bulb and son-bulb). The expression levels of BIA genes in the expansion stage (MB-A and SB-A) were significantly higher than those in the maturity stage (MB-C and SB-C), and the content of benzylisoquinoline alkaloids was consistent with the pattern of gene regulation. Five complete single genes were likely to encode the functional enzyme of CoOMT, which participated in tetrahydropalmatine biosynthesis in C. yanhusuo bulbs. These studies provide a strong theoretical basis for the subsequent development of metabolic engineering of benzylisoquinoline alkaloids (especially tetrahydropalmatine) of C. yanhusuo.

Nardosinone relieves metabolic-associated fatty liver disease and promotes energy metabolism through targeting CYP2D6

BackgroundNardosinone, a major extract of Rhizoma nardostachyos, plays a vital role in sedation, neural stem cell proliferation, and protection of the heart muscle. However, the huge potential of nardosinone in regulating lipid metabolism and gut microbiota has not been reported, and its potential mechanism has not been studied. PurposeTo explore the regulation of nardosinone on liver lipid metabolism and gut microbiota. MethodsIn this study, the role of nardosinone in lipid metabolism was investigated in vitro and in vivo by adding it to mouse feed and HepG2 cell culture medium. And 16S rRNA gene sequencing was used to explore its regulatory effect on gut microbiota. ResultsResults showed that nardosinone could improve HFD-induced liver injury and abnormal lipid metabolism by promoting mitochondrial energy metabolism in hepatocytes, alleviating oxidative stress damage, and regulating the composition of the gut microbiota. Mechanistically, combined with network pharmacology and reverse docking analysis, it was predicted that CYP2D6 was the target of nardosinone, and the binding was verified by cellular thermal shift assay (CETSA). ConclusionsThis study highlights a novel mechanism function of nardosinone in regulating lipid metabolism and gut microbiota. It also predicts and validates CYP2D6 as a previously unknown regulatory target, which provides new possibilities for the application of nardosinone and the treatment of metabolic-associated fatty liver disease.

The role of sedation in achieving quality standards for colonoscopy: a single-center prospective cohort study

The role of sedation in achieving quality standards for colonoscopy: a single-center prospective cohort study

Dexmedetomidine Versus Remifentanil Monitored Anesthesia Care During Endothelial Keratoplasty: A Retrospective Study

Purpose: Descemet's membrane endothelial keratoplasty (DMEK) is usually performed under topical or locoregional anesthesia; a sedation is often required. Several drugs are administered but undesirable side effects limit the use of each medication. Dexmedetomidine (DEX), a sedative-analgesic, has minimal respiratory depressant effects, and its use in DMEK surgery has not been reported. This study compares the use of DEX versus Remifentanil (REMI) during DMEK. Methods: Retrospective, observational, single-center study. Forty-two patients received sedation with DEX or REMI. Heart rate, blood pressure, oxygen saturation were always recorded during the procedure. The degree of sedation was evaluated using the Ramsay sedation scale; preoperative evaluation of anxiety disorders was carried out with the Hospital Anxiety and Depression Scale, while patients' and surgeon's satisfaction was evaluated using the 7-point Likert-like verbal rating scale. Results: Baseline demographic and clinical characteristics, as well as the baseline anxiety trait were similar for the 2 groups. Patients and surgeons reported higher satisfaction scores with DEX compared to patients receiving REMI (P < 0.01; P < 0.001). The intraoperative Ramsay score was 3 in 62% of patients in Group DEX and 23% in Group REMI; conversely, it was 2 in 38% of DEX Group and 77% in REMI Group (P < 0.02). No statistical difference in the hemodynamic and respiratory parameters between the 2 groups was recorded. Conclusions: With similar stability of hemodynamic and respiratory parameters, Dexmedetomedine provided a deeper sedation than REMI without respiratory depression, resulting in better surgical performance in terms of the patients' and the surgeon's satisfaction, thus suggesting a possible role for sedation during DMEK surgery.

A review of neuroprotective mechanisms of dexmedetomidine

Dexmedetomidine (DEX) is a highly specific and effective α2-adrenergic receptor agonist. Due to its high protein binding rate, intravenous pumping can play a good role in sedation and hypnosis, analgesia, anti-anxiety, reducing inflammation, and so on, so it has been widely used in clinical anesthesia and basic research. In recent years, with the further study of dexmedetomidine, it has been found that it has a certain protective effect on nerve injury caused by various causes.

The Pharmacological Class Alpha 2 Agonists for Stress Control in Patients with Respiratory Failure: The Main Actor in the Different Acts

The role of sedation in patients with acute respiratory failure in the intensive care unit is crucial for improving the adaptation to mechanical ventilation, avoiding lung injury, and reducing stress related to the over-stimulated sympathetic tone. The drug class alpha 2 agonists, alone or in synergic association, can help the clinician achieve these goals. Understanding the principles of pharmacology and applying them to the alpha 2 agonists, clonidine and dexmedetomidine, can lead to different pharmaceutical choices to adapt various sedative approaches to the different stages of acute respiratory failure. A scheme is proposed using these two drugs as a pharmacological continuation for an early weaning and recovery from the intensive care unit.

Role of Sedation and Analgesia during Noninvasive Ventilation: Systematic Review of Recent Evidence and Recommendations.

AimThis systematic review aimed to investigate the drugs used and their potential effect on noninvasive ventilation (NIV).BackgroundNIV is used increasingly in acute respiratory failure (ARF). Sedation and analgesia are potentially beneficial in NIV, but they can have a deleterious impact. Proper guidelines to specifically address this issue and the recommendations for or against it are scarce in the literature. In the most recent guidelines published in 2017 by the European Respiratory Society/American Thoracic Society (ERS/ATS) relating to NIV use in patients having ARF, the well-defined recommendation on the selective use of sedation and analgesia is missing. Nevertheless, some national guidelines suggested using sedation for agitation.MethodsElectronic databases (PubMed/Medline, Google Scholar, and Cochrane library) from January 1999 to December 2019 were searched systematically for research articles related to sedation and analgosedation in NIV. A brief review of the existing literature related to sedation and analgesia was also done.Review resultsSixteen articles (five randomized trials) were analyzed. Other trials, guidelines, and reviews published over the last two decades were also discussed. The present review analysis suggests dexmedetomidine as the emerging sedative agent of choice based on the most recent trials because of better efficacy with an improved and predictable cardiorespiratory profile.ConclusionCurrent evidence suggests that sedation has a potentially beneficial role in patients at risk of NIV failure due to interface intolerance, anxiety, and pain. However, more randomized controlled trials are needed to comment on this issue and formulate strong evidence-based recommendations.How to cite this articleKarim HMR, Šarc I, Calandra C, Spadaro S, Mina B, Ciobanu LD, et al. Role of Sedation and Analgesia during Noninvasive Ventilation: Systematic Review of Recent Evidence and Recommendations. Indian J Crit Care Med 2022;26(8):938–948.

Isoflurane attenuates sepsis-associated lung injury

Acute lung injury is one of major complications associated with sepsis, responsible for morbidity and mortality. Patients who suffer from acute lung injury often require respiratory support under sedations, and it would be important to know the role of sedatives in lung injury. We examined volatile anesthetic isoflurane, which is commonly used in surgical setting, but also used as an alternative sedative in intensive care settings in European countries and Canada. We found that isoflurane exposure attenuated neutrophil recruitment to the lungs in mice suffering from experimental polymicrobial abdominal sepsis. We found that isoflurane attenuated one of major neutrophil chemoattractants LTB4 mediated response via its receptor BLT1 in neutrophils. Furthermore, we have shown that isoflurane directly bound to BLT1 by a competition assay using newly developed labeled BLT1 antagonist, suggesting that isoflurane would be a BLT1 antagonist.

Management of psychiatric disorders in patients with cancer.

Management of psychiatric disorders in patients with cancer.

The effect of alpha-2A adrenergic receptor (ADRA2A) genetic polymorphisms on the depth of sedation of dexmedetomidine: a genetic observational pilot study

BackgroundThe genetic polymorphisms of the alpha-2A adrenergic receptor (ADRA2A), which plays a significant role in sedation, anxiety relief, and antinociception, particularly in dexmedetomidine, may differ in the degree of sedation. This study aimed to investigate the effect of the genetic polymorphisms of ADRA2A (rs11195418, rs1800544, rs2484516, rs1800545, rs553668, rs3750625) on the sedative effects of dexmedetomidine. MethodsA total of 131 patients aged 50 years or more from May 2018 to August 2019 were included in this study. The ADRA2A gene variants were evaluated using the TaqMan Assay. Dexmedetomidine diluted in normal saline to a concentration of 4μg.mL-1 was infused at a dose of 2μg.kg-1 to achieve procedural sedation (modified Ramsay sedation scale 4 [mRSS 4]). ResultsA total of 131 patients were evaluated. The genetic polymorphisms (rs11195418) of the ADRA2A receptor gene demonstrated no variation in our participants. The ADRA2A receptor gene polymorphisms (rs1800544, rs2484516, rs1800545, rs553668, and rs3750625) exhibited no differences in total dexmedetomidine doses (p>0.217), bispectral index at mRSS 4 (p>0.620), and time to obtain mRSS 4 (p>0.349). ConclusionThis study suggested that the genetic polymorphisms of ADRA2A did not affect the sedative efficacy of dexmedetomidine.

In Vitro Model of Stretch-Induced Lung Injury to Study Different Lung Ventilation Regimens and the Role of Sedatives

Currently lung injury is managed conservatively through supportive care including mechanical ventilation. However, mechanical ventilation can also cause additional lung injury due to over-stretch along with atelectasis and cytokine release. Here we developed an in vitro mechanical ventilation model using cyclic stretch of lung epithelial cells to mimic high and low tidal volume (TV) ventilation strategy, so that we could use this platform for pathophysiology analysis and screening for therapeutic drugs. We subjected MLE-15 cells to the following treatments. 1) No treatment, 2) lipopolysaccharide (100 ng/mL) stimulation for 24 hours, 3) mechanical stretch initiated at 6-hour time point for 18 hours, 4) LPS stimulation at time point 0 hour, and mechanical stretch was added at 6-hour time point for 18 hours. Biaxial cyclic stretch with a triangular wave was given via the Flexcell FX-6000 tension system to mimic low and high TV. Anesthetics dexmedetomidine and propofol were also tested. Our high TV mimic stretch increased cell death, while low TV mimic stretch did not affect the degree of cell death. Using this system, we examined the effect of sedatives commonly used in intensive care units on cell death and found that dexmedetomidine attenuated necrosis associated with stretch. We described the in vitro cyclic stretch system mimicking high and low TV ventilation. High TV mimetic was associated with increased cell death. Dexmedetomidine attenuated the degree of cell death.

Analgesia and sedation for patients in the intensive care unit: a systematic review

Objective To review the importance of sedation and analgesia in the ICU. Data sources A systematic search of MEDLINE (PubMed, Medscape, ScienceDirect, EMF-Portal) and internet was conducted on all articles published from 1974 to 2016. Study selection English language reports on the importance of sedation and analgesia in the ICU. The initial search presented 157 articles, where 23 had inclusion criteria. Data extraction Articles not reporting on the importance of sedation and analgesia in the ICU in the title or abstract were not included. Five independent investigators extracted data on the methods. Data synthesis Comparisons were made by a structured review with the results tabulated. Seven studies about the importance of the role of sedation and analgesia in the ICU, eight about assessing the adequacy of sedation, and eight about the strategies for administering sedatives in the ICU. Findings Pain perception varies according to the various factors including personality, cultural background, surroundings, and fear. It has been associated with the detrimental effects on sleep, agitation, and stress response. Anxiety is also brought about by continuous noise within the ICU. Patients in the ICU may also suffer from insomnia caused by a loss of normal melatonin secretion. Newer sedation scales are reported to show improvements in validity and reliability. Propofol may be associated with a more rapid wake-up than benzodiazepines. Conclusion Sedation is an important component of the treatment of mechanically ventilated, critically ill patients. Directing treatment to specific and individualized goals will assure that the patient needs are met. The use of a spontaneous waking trial, followed, when possible, by a spontaneous breathing trial, should be implemented widely in the care of critically ill patients requiring mechanical ventilation.

A targeted neurotransmitter quantification and nontargeted metabolic profiling method for pharmacometabolomics analysis of olanzapine by using UPLC-HRMS.

Neurotransmitters (NTs) are specific endogenous metabolites that act as “messengers” in synaptic transmission and are widely distributed in the central nervous system. Olanzapine (OLZ), a first-line antipsychotic drug, plays a key role in sedation and hypnosis, but, it presents clinical problems with a narrow therapeutic window, large individual differences and serious adverse effects, as well as an unclear mechanism in vivo. Herein, a simultaneous targeted NT quantification and nontargeted metabolomics method was developed and validated for pharmacometabolomics analysis of OLZ by using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS). Considering the low physiological concentrations of NTs, a full MS scan and target selective ion monitoring (tSIM) scan were combined for nontargeted metabolomics and targeted NT quantification, respectively. By using this strategy, NTs at a very low physiological concentration can be accurately detected and quantified in biological samples by tSIM scans. Moreover, simultaneously nontargeted profiling was also achieved by the full MS scan. The newly established UPLC-HRMS method was further used for the pharmacometabolomics study of OLZ. Statistical analysis revealed that tryptophan, 5-hydroxytryptophan, 5-hydroxytryptamine, γ-aminobutyric acid etc. were significantly downregulated, while tyrosine was significantly upregulated, which suggested that OLZ could promote the downstream phase II reaction of 5-hydroxytryptamine, inhibit tyrosine hydroxylase activity, and increase the activity of γ-aminobutyric acid transaminase. In conclusion, this method could provide novel insights for revealing the pharmacodynamic effect and mechanism of antipsychotic drugs.

Role of sedation and analgesia in ICU

Alleviation of pain is a basic human right. And patients who experience the greatest pain and suffering are the ones in the intensive care unit (ICU). Sedation allows to prevent the patients’ awareness and reduction of their response to various external stimuli. However, sedation is like a double-edged sword for ICU patients. Over-sedation can cause long-term ventilatory support and increase duration of ICU stay, whereas under-sedation can cause hyper-catabolism, immunosuppression, hypercoagulability and increased sympathetic activity. Pain is widely regarded as the fifth vital sign, and it induces a myriad of deleterious physiological changes in most organ systems. Pain can cause agitation, delirium, and inadequate pain management can have psychological sequelae like post-traumatic stress disorder, depression and anxiety or it can progress to chronic pain. In this review, we will focus on the role of sedation & analgesia in ICU, current practice trends and a holistic approach for better patient care.Citation: Wani MD, Dey C, Mistry T. Role of sedation and analgesia in ICU. Anaesth Pain & Intensive Care 2018;22 Suppl 1:S88-S98

Palmatine plays a role in sedation and hypnosis by increasing 5-hydroxytryptamine

Objective of this study was to investigate the sedative and hypnotic effects of palmatine and to observe whether its mechanism is related to 5-hydroxytryptamine (5-HT) and GABA. The sedative and hypnotic effects of palmatine on mice were observed with mouse autonomic activity test, direct sleep test, pentobarbital sodium in suprathreshold and subthreshold dose sleep test. The content of GABA and 5-HT in brain homogenate was determined by ELISA method. Mouse brain specimens were observed by immunohistochemistry for 5-HT expression in the nucleus of mouse brain. Palmatine could reduce spontaneous activities of mice, prolong the sleep time of mice induced by pentobarbital sodium in suprathreshold dose and shorten the sleep latency. And it could increase the number of mice falling asleep induced by pentobarbital sodium in subthreshold dose and the incidence of falling asleep, but with no direct sleep effect. In addition, it enhanced the 5-HT content in brain, but had no effect on GABA content, and had no toxicity to PC12 cells. Palmatine plays a significant role in sedation and hypnosis, which may be associated with the increase of intra-cerebral 5-HT.

Botulinum Toxin: Techniques Within Pediatric Physiatry.

Intramuscular botulinum toxin injections are used for treatment of focal spasticity in children, particularly in those with a diagnosis of cerebral palsy. There are a variety of techniques used when performing botulinum toxin injections without clear standards for pediatric providers. To describe current practice techniques for botulinum toxin injections among pediatric physiatrists. Cross-sectional survey using RedCap Software. Pediatric physiatrists who perform botulinum toxin injections. Survey of 307 pediatric physiatrists. Analysis of data from the 2017 practice survey of pediatric physiatrists in the United States. Physicians were asked the primary botulinum toxin used, common dosing information, the role of localization, and the role of sedation and distraction in their practice. Nearly all pediatric physiatrists use OnabotulinumtoxinA as the primary formulation of botulinum toxin. The maximum dose per body weight used per injection series had a median of 15 units/kilogram and a median maximum total dose of 500 units. Sixty-five percent of pediatric physiatrists report using sedation, of any type, for botulinum toxin injections. When using sedation, the most common primary method was general anesthesia (38.9%), followed by enteral or nasal anxiolytic with the patient awake (26.2%). The most common reported intended injection site for botulinum toxin was "in multiple sites spread throughout the muscle" (67.9%), and then "one site of the muscle at the motor point" (17.1%). Large muscles were injected using primarily anatomic guidance (75.6%) and electromyography (50.8%), and small muscles were primarily completed with electromyography (73.6%) and anatomic guidance (49.2%). There is considerable variability present in one common procedure performed by pediatric physiatrists. NA.

Ten important articles on noninvasive ventilation in critically ill patients and insights for the future: A report of expert opinions

BackgroundNoninvasive ventilation is used worldwide in many settings. Its effectiveness has been proven for common clinical conditions in critical care such as cardiogenic pulmonary edema and chronic obstructive pulmonary disease exacerbations.Since the first pioneering studies of noninvasive ventilation in critical care in the late 1980s, thousands of studies and articles have been published on this topic. Interestingly, some aspects remain controversial (e.g. its use in de-novo hypoxemic respiratory failure, role of sedation, self-induced lung injury). Moreover, the role of NIV has recently been questioned and reconsidered in light of the recent reports of new techniques such as high-flow oxygen nasal therapy.MethodsWe conducted a survey among leading experts on NIV aiming to 1) identify a selection of 10 important articles on NIV in the critical care setting 2) summarize the reasons for the selection of each study 3) offer insights on the future for both clinical application and research on NIV.ResultsThe experts selected articles over a span of 26 years, more clustered in the last 15 years. The most voted article studied the role of NIV in acute exacerbation chronic pulmonary disease. Concerning the future of clinical applications for and research on NIV, most of the experts forecast the development of innovative new interfaces more adaptable to patients characteristics, the need for good well-designed large randomized controlled trials of NIV in acute “de novo” hypoxemic respiratory failure (including its comparison with high-flow oxygen nasal therapy) and the development of software-based NIV settings to enhance patient-ventilator synchrony.ConclusionsThe selection made by the experts suggests that some applications of NIV in critical care are supported by solid data (e.g. COPD exacerbation) while others are still waiting for confirmation. Moreover, the identified insights for the future would lead to improved clinical effectiveness, new comparisons and evaluation of its role in still “lack of full evidence” clinical settings.

Ketamine Continuous Infusions in Critically Ill Infants and Children

To review the role of ketamine continuous infusions (CINs) in critically ill children for sedation and analgesia, withdrawal, and bronchospasm. Relevant articles were identified using MEDLINE (1946 to December 2015), EMBASE (1988 to December 2015), International Pharmaceutical Abstracts (1970 to December 2015), and the Cochrane Library (1996 to December 2015) using the terms ketamine, children, and CIN. All English-language articles in humans identified from data sources were evaluated. Three studies and 8 case reports/series representing 74 patients were included. Ketamine is an N-methyl-d-aspartate (NMDA) receptor antagonist that blocks glutamate in the limbic system, resulting in sedation and analgesia. Additionally, it provides bronchodilation by increasing catecholamine transmission and stimulation of β2 receptors. The majority of reports evaluated ketamine for bronchospasm in children with status asthmaticus or bronchospasm refractory to conventional treatments. A total of 72 patients (97.3%) received a loading dose ranging from 0.2 to 2 mg/kg prior to CIN initiation. The CIN dosing range was 0.2 to 3.6 mg/kg/h. Children who received ketamine for sedation or opioid withdrawal received a lower dose than children initiated on it for bronchospasm: 0.24 to 0.9 versus 0.2 to 3.6 mg/kg/h, respectively. Duration of use ranged from 1 to 96 hours. Six of the reports mentioned that the ketamine CIN was tapered prior to discontinuation. Approximately 10.8% of patients included in the analysis experienced adverse events, with only 3 children (4.1%) experiencing emergence phenomenon. Limited evidence was noted, so ketamine CINs could be considered an adjunct therapy at this time. Further prospective studies should be conducted to determine ketamine's role in sedation and analgesia, withdrawal treatment, and bronchospasm treatment.

Impact of sedation and analgesia during noninvasive positive pressure ventilation on outcome: a marginal structural model causal analysis.

There are limited data available about the role of sedation and analgesia during noninvasive positive pressure ventilation (NPPV). The objective of study was to estimate the effect of analgesic or sedative drugs on the failure of NPPV. We studied patients who received at least 2 h of NPPV as first-line therapy in a prospective observational study carried out in 322 intensive care units from 30 countries. A marginal structural model (MSM) was used to analyze the association between the use of analgesic or sedative drugs and NPPV failure (defined as need for invasive mechanical ventilation). 842 patients were included in the analysis. Of these, 165 patients (19.6%) received analgesic or sedative drugs at some time during NPPV; 33 of them received both. In the adjusted analysis, the use of analgesics (odds ratio 1.8, 95% confidence interval 0.6-5.4) or sedatives (odds ratio 2.8, 95% CI 0.85-9.4) alone was not associated with NPPV failure, but their combined use was associated with failure (odds ratio 5.7, 95% CI 1.8-18.4). Slightly less than 20% of patients received analgesic or sedative drugs during NPPV, with no apparent effect on outcome when used alone. However, the simultaneous use of analgesics and sedatives may be associated with failure of NPPV.

End-of-Life Delirium: Issues Regarding Recognition, Optimal Management, and the Role of Sedation in the Dying Phase

ContextIn end-of-life care, delirium is often not recognized and poses unique management challenges, especially in the case of refractory delirium in the terminal phase. ObjectivesTo review delirium in the terminal phase context, specifically in relation to recognition issues; the decision-making processes and management strategies regarding its reversibility; the potential refractoriness of delirium to symptomatic treatment; and the role of sedation in refractory delirium. MethodsWe combined multidisciplinary input from delirium researchers and knowledge users at an international delirium study planning meeting and relevant electronic database literature searches (Ovid Medline, Embase, PsycINFO, and CINAHL) to inform this narrative review. ResultsThe overall management strategy for delirium at the end of life is directed by the patient's prognosis in association with the patient's goals of care. As symptoms of delirium are often refractory in the terminal phase, especially in the case of agitated delirium, the judicious use of palliative sedation is frequently required. However, there remains a lack of high-level evidence for the management of delirium in the terminal phase, including the role of antipsychotics and optimal sedation strategies. For the family and health-care staff, clear communication, education, and emotional support are vital components to assist with decision making and direct the treatment care plan. ConclusionFurther research on the effectiveness of delirium management strategies in the terminal phase for patients and their families is required. Further validation of assessment tools for diagnostic screening and severity measurement is needed in this patient population.