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Predictive Value of Preoperative Profiling of Serum Metabolites for Emergence Agitation After General Anesthesia in Adult Patients

ABSTRACT: Background: Emergence agitation (EA) in adult patients under general anesthesia leads to increased postoperative complications and heavy medical burden. Unfortunately, its pathogenesis has not been clarified until now. The purpose of the present study was to explore the relationship between preoperative serum metabolites and EA. Methods: We used an untargeted metabolic analysis method to investigate the different metabolomes in the serum of EA patients and non-EA patients undergoing elective surgical procedures after the induction of general anesthesia. A Richmond Agitation–Sedation Scale score ≥ +2 was diagnosed as EA during postoperative emergence. Non-EA patients were matched with EA patients according to general characteristics. Preoperative serum samples of the two groups were collected to investigate the association between serum metabolites and EA development. Results: The serum samples of 16 EA patients with 34 matched non-EA patients were obtained for metabolic analysis. After screening and alignment with databases, 31 altered metabolites were detected between the two groups. These metabolites were mainly involved in the metabolism of lipids, purines, and amino acids. Analyses of receiver-operating characteristic curves showed that the preoperative alterations of choline, cytidine, glycerophosphocholine, L-phenylalanine, oleamide, and inosine may be associated with adult EA. Conclusion: Multiple metabolic abnormalities (including those for lipids, purines, and amino acids) and other pathological processes (e.g., neurotransmitter imbalance and oxidative stress) may contribute to EA. Several altered metabolites in serum before surgery may have predictive value for EA diagnosis. This study might afford new metabolic clues for the understanding of EA pathogenesis.

SUBMITTER: Wang Q

PROVIDER: S-EPMC8566542 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Emergence agitation (EA) is very common in paediatric patients during recovery from general anaesthesia, but underlying mechanisms remain unknown. This prospective study was designed to profile preoperative urine metabolites and identify potential biomarkers that can predict the occurrence of EA. Methods: A total of 224 patients were screened for recruitment; of those, preoperative morning urine samples from 33 paediatric patients with EA and 33 non-EA gender- and age-matched patients after being given sevoflurane general anaesthesia were analysed by ultra-high-performance liquid chromatography (UHPLC) coupled with a Q Exactive Plus mass spectrometer. Univariate analysis and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) were used to analyse these metabolites. The least absolute shrinkage and selection operator (LASSO) regression was used to identify predictive variables. The predictive model was evaluated through the receiver operating characteristic (ROC) analysis and then further assessed with 10-fold cross-validation. Results: Seventy-seven patients completed the study, of which 33 (42.9%) patients developed EA. EA and non-EA patients had many differences in preoperative urine metabolic profiling. Sixteen metabolites including nine aromatic amino acid metabolites, acylcarnitines, pyridoxamine, porphobilinogen, 7-methylxanthine, and 5'-methylthioadenosine were found associated with an increased risk of EA, and they all exhibited higher levels in the EA group than in the non-EA group. The main metabolic pathways involved in these metabolic changes included phenylalanine, tyrosine and tryptophan metabolisms. Among these potential biomarkers, L-tyrosine had the best predictive value with an odds ratio (OR) (95% CI) of 5.27 (2.20-12.63) and the AUC value of 0.81 (0.70-0.91) and was robust with internal 10-fold cross-validation. Conclusion: Urinary aromatic amino acid metabolites are closely associated with EA in paediatric patients, and further validation with larger cohorts and mechanistic studies is needed. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04807998.

Project description:Background: Emergence agitation (EA) is one of the most common and intractable postoperative complications among children undergoing surgery under general anesthesia. Dexmedetomidine, an α(2)-adrenoceptor agonist, offers an ideal sedation, reduces preoperative anxiety, and facilitates smooth induction of anesthesia, and it is widely used in pediatric surgery. We aimed to evaluate the efficacy of dexmedetomidine for preventing emergence agitation in children after general anesthesia. Methods: We comprehensively reviewed PubMed, Cochrane Library, EMBASE, and Web of Science databases to search all randomized controlled trials, published before April 22, 2020, investigating the efficacy of dexmedetomidine in preventing the emergence agitation in children after general anesthesia. The meta-analysis was performed using Review Manager 5.3. The primary outcome was the incidence of emergence agitation. Secondary outcomes included the number of patients requiring rescue analgesic, number of patients with postoperative nausea and vomiting, emergence time, extubation time, and time to discharge from the post-anesthesia care unit. Results: We included a total of 33 studies, comprising 2,549 patients in this meta-analysis. Compared with saline, dexmedetomidine significantly reduced the emergence agitation incidence [risk ratio (RR) 0.29; 95% confidence interval (CI) 0.22-0.37; p < 0.00001], incidence of postoperative nausea and vomiting (RR 0.46; 95% CI 0.3-0.69; p = 0.0002), and the requirement of rescue analgesic (RR 0.29; 95% CI 0.18-0.44; p < 0.00001). Furthermore, children in the dexmedetomidine group experienced a longer emergence time [mean difference (MD) 2.18; 95% CI 0.81-3.56; p = 0.002] and extubation time (MD 0.77; 95% CI 0.22-1.31; p = 0.006) compared with those in the saline group. However, no significant difference was observed in the time to discharge from the post-anesthesia care unit (MD 2.22; 95% CI -2.29-6.74; p = 0.33) between the two groups. No significant differences were observed between the effects of dexmedetomidine and other drugs like midazolam, propofol, fentanyl, tramadol, and clonidine in terms of the emergence agitation incidence and other parameters, except for the requirement of rescue analgesic (RR 0.45; 95% CI 0.33-0.61; p < 0.00001). Conclusions: Dexmedetomidine can prevent emergence agitation, relieves postoperative pain, decreases the requirement of rescue analgesic, and decreases the postoperative nausea and vomiting events.

Project description:ImportanceEmergence agitation is common after nasal surgery under general anesthesia and may lead to serious consequences for the patient, including an increased risk of injury, pain, hemorrhage, and self-extubation. Despite decades of research, studies on the incidence, risk factors, and prevention of emergence agitation in adult patients are ongoing, and opinions differ on the different effects of inhalation and intravenous anesthesia.ObjectiveTo investigate the effect of anesthetic method on the occurrence of emergence agitation after nasal surgery.Design, setting, and participantsThis prospective, randomized, single-blind, clinical trial included 80 patients undergoing open rhinoplasty, septoplasty, turbinoplasty, endoscopic sinus surgery, and functional endoscopic sinus surgery under general anesthesia who were randomized to receive total intravenous anesthesia (TIVA) with remifentanil hydrochloride and propofol (n = 40) or volatile induction and maintenance of anesthesia (VIMA) with sevoflurane and nitrous oxide (n = 40) in Asan Medical Center, a tertiary referral center in Seoul, Republic of Korea. Data were collected from August 24 through October 14, 2016, and analyzed from October 26, 2016, through September 14, 2017.Main outcomes and measuresThe occurrence of emergence agitation defined by the following 2 individual criteria: a Richmond Agitation-Sedation Scale score of at least 1 and a Riker Sedation-Agitation Scale score of at least 5 immediately after extubation.ResultsAmong the 80 patients included in the analysis (68.8% men [n = 55]; mean [SD] age, 41.6 [17.9] years), emergence agitation measured by the Richmond Agitation Sedation Scale occurred in 8 of 40 patients (20.0%) in the VIMA group and 1 of 40 (2.5%) in the TIVA group. The risk difference was 17.5 (95% CI, 3.6-31.4). Emergence agitation measured by the Riker Sedation-Agitation Scale score occurred in 10 of 40 patients (25.0%) in the VIMA group and 1 of 40 (2.5%) in the TIVA group. The risk difference was 22.5 (95% CI, 7.3-37.7).Conclusions and relevanceThe occurrence of emergence agitation after nasal surgery under general anesthesia can be significantly reduced by using TIVA rather than VIMA.Trial registrationCRIS identifier: KCT0002145.

Project description:BackgroundThe differences in the incidence and severity of emergence agitation (EA) and emergence times between desflurane and sevoflurane anesthesia have not been as clearly elucidated in children as in adults.MethodsThe design of the study is a systematic review with meta-analysis of randomized controlled trials. The study methodology is based on the Cochrane Review Methods. A comprehensive literature search was conducted to identify clinical trials comparing the incidence or severity of EA and emergence times in children anesthetized with desflurane or sevoflurane. Two reviewers independently assessed each study according to predefined inclusion criteria and extracted data from each study using a prespecified data extraction form. The data from each study were combined using a fixed effect or random effect model to calculate the pooled risk ratio (RR) or standardized mean difference (SMD) and 95% confidence interval (CI). Funnel plots were used to assess publication bias. Subgroup and sensitivity analyses were performed.ResultsFourteen studies met the inclusion criteria. Among the 1196 patients in these 14 studies, 588 received desflurane anesthesia and 608 received sevoflurane anesthesia. The incidence of EA was comparable between the 2 groups (pooled RR = 1.21; 95% CI: 0.96-1.53; I = 26%), and so was the severity of EA (EA score) between the 2 groups (SMD = 0.12; 95% CI: -0.02 to 0.27; I = 0%). Extubation and awakening times were shorter in the desflurane group than in the sevoflurane group; the weighted mean differences were -2.21 (95% CI: -3.62 to -0.81; I = 93%) and -2.74 (95% CI: -3.80 to -1.69; I = 85%), respectively. No publication bias was found in the funnel plot. The subgroup analysis based on the type of EA scale showed a higher incidence of EA in the desflurane group than in the sevoflurane group in studies using 3-, 4-, or 5-point EA scales; the pooled RR was 1.38 (95% CI: 1.10-1.73; I = 37%).ConclusionThe incidence and severity of EA were comparable between desflurane and sevoflurane anesthesia in children; however, emergence times, including extubation and awakening times, were shorter in desflurane anesthesia.

Project description:Objective Emergence from anesthesia starts from the limbic structures and then spreads outwards to brainstem, reticular activating systems, and then to the cortex. Epilepsy surgery often involves resection of limbic structures and hence may disrupt the pattern of emergence. The aim of this study was to explore the pattern of emergence from anesthesia following epilepsy surgery and to determine associated variables affecting the emergence pattern. Setting and Design Tertiary care center, prospective observational study. Materials and Methods We conducted a prospective observation pilot study on adult patients undergoing anterior temporal lobectomy and amygdalohippocampectomy for epilepsy. Anesthesia management was standardized in all patients, and they were allowed to wake up with "no touch" technique. Primary outcome of the study was the pattern of emergence (normal emergence, agitated emergence, or slow emergence) from anesthesia. Secondary outcomes were to explore the differences in preoperative neuropsychological profile and limbic structure volumes between the different patterns of emergence. Quantitative variables were analyzed using Student's t -test. Qualitative variables were analyzed using chi-square test. Results Twenty-nine patients completed the study: 9 patients (31%) had agitated emergence, and 20 patients had normal emergence. Among the agitated emergence, 2 patients had Riker scale of 7 indicating violent emergence. Patient demographics, anesthetic used, neuropsychological profile, and limbic structure volumes were similar between normal emergence and agitated emergence groups. However, two patients who had severe agitation (Riker scale of 7) had the lowest intelligence quotient. Conclusion Our pilot study showed that emergence agitation is not uncommon in patients undergoing epilepsy surgery. However, due to smaller sample size, the role of preoperative neuropsychologic profile and hippocampal volumes in predicting the pattern of emergence is inconclusive.

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Predictive Value of Preoperative Profiling of Serum Metabolites for Emergence Agitation After General Anesthesia in Adult Patients

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