Prevention of post-operative delirium using an overnight infusion of dexmedetomidine in patients undergoing cardiac surgery: a pragmatic, randomized, double-blind, placebo-controlled trial.

BACKGROUND: After cardiac surgery, post-operative delirium (PoD) is acknowledged to have a significant negative impact on patient outcome. To date, there is no valuable and specific treatment for PoD. Critically ill patients often suffer from poor sleep condition. There is an association between delirium and sleep quality after cardiac surgery. This study aimed to establish whether promoting sleep using an overnight infusion of dexmedetomidine reduces the incidence of delirium after cardiac surgery. METHODS: Randomized, pragmatic, multicentre, double-blind, placebo controlled trial from January 2019 to July 2021. All adult patients aged 65 years or older requiring elective cardiac surgery were randomly assigned 1:1 either to the dexmedetomidine group or the placebo group on the day of surgery. Dexmedetomidine or matched placebo infusion was started the night after surgery from 8 pm to 8 am and administered every night while the patient remained in ICU, or for a maximum of 7 days. Primary outcome was the occurrence of postoperative delirium (PoD) within the 7 days after surgery. RESULTS: A total of 348 patients provided informed consent, of whom 333 were randomized: 331 patients underwent surgery and were analysed (165 assigned to dexmedetomidine and 166 assigned to placebo). The incidence of PoD was not significantly different between the two groups (12.6% vs. 12.4%, p = 0.97). Patients treated with dexmedetomidine had significantly more hypotensive events (7.3% vs 0.6%; p < 0.01). At 3 months, functional outcomes (Short-form 36, Cognitive failure questionnaire, PCL-5) were comparable between the two groups. CONCLUSION: In patients recovering from an elective cardiac surgery, an overnight infusion of dexmedetomidine did not decrease postoperative delirium. Trial registration This trial was registered on ClinicalTrials.gov (number: NCT03477344; date: 26th March 2018).

Remifentanil is Superior to Propofol for Treating Emergence Agitation in Adults After General Anesthesia.

Background: Emergence agitation (EA) is one of the most common complications in clinical general anesthesia during recovery in adults. Remifentanil and propofol can reduce the incidence of EA, but with no randomized controlled trial to evaluate their effectiveness for treating EA. This study aims to compare the effectiveness of remifentanil and propofol for treating EA following general anesthesia. Patients and methods: Among 152 randomized patients with a mean of 49.5 years, and 99 (65.1%) of them being male, 149 were divided into two groups for subsequent analysis. The remifentanil group (Group R, n = 74) received a 0.5µg kg-1 remifentanil infusion followed by a 0.05µg kg-1 min-1 infusion until 15 minutes, after the onset of agitation. The propofol group (Group P, n = 75) received a 1mg kg-1 propofol infusion once agitation occurred. Emergence agitation was assessed using the Riker Sedation Agitation Score, with a score of ≥5 defining emergence agitation. During the post-anesthesia care unit (PACU), the recurrence of emergence agitation, time to extubation, and discharge from PACU were evaluated. Results: The incidence of reoccurring emergence agitation was lower in Group R (29.7%) compared with Group P (49.3%), with an odds ratio of 0.44 (95% CI 0.22-0.85; P=0.014). The time to extubation was shorter in Group R (mean 12min, range 8-15 min) compared with Group P (mean 17min, range 13-21 min) (P<0.001), as was the time discharge from the PACU (mean 30.5 min, range 25-40 min) vs Group P (mean 37.5 min, range 31-50 min) (P=0.001). Conclusion: Treatment of emergence agitation in adults with remifentanil infusion is more effective than propofol, with a shorter time to extubation and discharge from PACU.

Effect of esketamine on postoperative analgesia and postoperative delirium in elderly patients undergoing gastrointestinal surgery.

OBJECTIVE: To investigate the analgesic effect of esketamine combined with low-dose sufentanil in elderly patients after gastrointestinal surgery, and whether the anti-inflammatory effect of esketamine is involved in the mechanism of postoperative delirium. METHOD: We enrolled sixty elderly patients (age ≥ 65 years old, American Society of Anesthesiologists (ASA) grade I-III) who underwent gastrointestinal surgery. Patients were randomly assigned to Group C (control group) who received sufentanil 2 ug/kg, and Group E (experimental group) who received sufentanil 1.5 ug/kg + esketamine 1 mg/kg, with 30 patients in each group. All patients underwent total intravenous anesthesia during the surgery and were connected to a patient-controlled intravenous analgesia (PCIA) pump after surgery. The primary outcome was the evaluation of pain at 4, 24, 48 h after surgery which was evaluated by NRS scores. In secondary outcomes, inflammation was assessed by measuring IL-6 levels using ELISA. The postoperative delirium and the occurrence of adverse reactions were observed on the 1st and 3rd day after surgery. RESULTS: The NRS scores at 4, 24, and 48 h after surgery in the experimental group [(4.53 ± 1.22), (3.46 ± 0.73), (1.37 ± 0.99)] were lower than that in the control group [(5.23 ± 1.16), (4.46 ± 0.77), (2.13 ± 0.78)] (P < 0.05). The concentration of serum IL-6 in the experimental group at 24 and 48 h after operation [(15.96 ± 4.65), (11.8 ± 3.24)] were lower than that in the control group [(23.07 ± 4.86), (15.41 ± 4.01)] (P < 0.05); the incidence of postoperative delirium in the experimental group was less than that in the control group (P < 0.05); there was no significant difference in the incidence of postoperative nausea and vomiting between the two groups (P > 0.05), and neither group had nightmares or delirium. CONCLUSION: Esketamine may enhance postoperative pain management compare with sufentanil, and esketamine has anti-inflammatory effects that reduce the incidence of postoperative delirium. TRIAL REGISTRATION: Full name of the registry: Chinese Clinical Trial Registry. TRIAL REGISTRATION NUMBER: ChiCTR2300072374. Date of registration:2023/06/12.

Dexmedetomidine - An Alternative to Midazolam in the Treatment of Ketamine-Induced Emergence Delirium: A Systematic Review.

PURPOSE: Analyze the effectiveness of dexmedetomidine compared to midazolam for the treatment of ketamine-induced emergence delirium in noncardiac surgical patients. DESIGN: Systematic review. METHODS: Guidelines outlined in the Preferred Reporting Items For Systematic Reviews and Meta-analyses (PRISMA)22 were used for this review. PubMed, Cumulative Index To Nursing And Allied Health Literature (CINAHL), MEDLINE, The Cochrane Library, EBSCOhost, National Institute of Health clinical trials, Google Scholar, and gray literature were searched for relevant studies. Only peer-reviewed nonexperimental studies, quasi-experimental studies, and randomized control trials with or without meta-analysis were included. The evidence was assessed using the Johns Hopkins Nursing Evidence-Based Practice guidelines for quality ratings and evidence level. FINDINGS: Five blinded randomized controlled trials, three quasi-experimental studies, and two retrospective nonexperimental studies comprised of 1,024 subjects were evaluated for this review. Dexmedetomidine was more effective at reducing ketamine-induced delirium in adult patients, although midazolam attenuated the psychomimetic effects of ketamine better in pediatric patients. Furthermore, postanesthesia care unit discharge times were similar between patients treated with dexmedetomidine and midazolam. The studies in this review were categorized as Level I, Level II, or Level III and rated Grade A, implying strong confidence in the actual effects of dexmedetomidine in all outcome measures of the review. CONCLUSIONS: The current evidence suggests that dexmedetomidine is an effective alternative for alleviating ketamine-induced delirium in noncardiac adult surgical patients. Multiple studies in this review noted improved hemodynamics and reduced postoperative analgesic requirements after administration of dexmedetomidine in conjunction with ketamine.

Prophylaxis for paediatric emergence delirium in desflurane-based anaesthesia: a network meta-analysis.

PURPOSE: The prevalence of postoperative emergence delirium in paediatric patients (pedED) following desflurane anaesthesia is considerably high at 50-80%. Although several pharmacological prophylactic strategies have been introduced to reduce the risk of pedED, conclusive evidence about the superiority of these individual regimens is lacking. The aim of the current study was to assess the potential prophylactic effect and safety of individual pharmacotherapies in the prevention of pedED following desflurane anaesthesia. METHODS: This frequentist model network meta-analysis (NMA) of randomized controlled trials (RCTs) included peer-reviewed RCTs of either placebo-controlled or active-controlled design in paediatric patients under desflurane anaesthesia. RESULTS: Seven studies comprising 573 participants were included. Overall, the ketamine + propofol administration [odds ratio (OR) = 0.05, 95% confidence intervals (95%CIs) 0.01-0.33], dexmedetomidine alone (OR = 0.13, 95%CIs 0.05-0.31), and propofol administration (OR = 0.30, 95%CIs 0.10-0.91) were associated with a significantly lower incidence of pedED than the placebo/control groups. In addition, only gabapentin and dexmedetomidine were associated with a significantly higher improvement in the severity of emergence delirium than the placebo/control groups. Finally, the ketamine + propofol administration was associated with the lowest incidence of pedED, whereas gabapentin was associated with the lowest severity of pedED among all of the pharmacologic interventions studied. CONCLUSIONS: The current NMA showed that ketamine + propofol administration was associated with the lowest incidence of pedED among all of the pharmacologic interventions studied. Future large-scale trials to more fully elucidate the comparative benefits of different combination regimens are warranted. TRIAL REGISTRATION: PROSPERO CRD42021285200.

The Effect of Intranasal Dexmedetomidine on Emergence Delirium Prevention in Pediatric Ambulatory Dental Rehabilitation Under General Anesthesia: A Randomized Clinical Trial.

Purpose: Sevoflurane is the preferred anesthetic agent for induction and maintenance of ambulatory surgery due to its property of fast onset and recovery. However, it has been recognized as one of the major contributors of emergence delirium. The aim of this study was to evaluate the preventive effect of intranasal dexmedetomidine on the occurrence of emergence delirium in pediatric patients under general anesthesia with sevoflurane. Patients and Methods: Ninety pediatric patients undergoing dental rehabilitation under sevoflurane anesthesia were enrolled in this study. The patients were divided into three groups (n=30 each in the 2 µg/kg dexmedetomidine, 1 µg/kg dexmedetomidine, and control with saline groups). The same volume (0.02mL/kg) of the mixed solution was dropped into the nasal cavity of the children 30 minutes before surgery. We used the Pediatric Anesthesia Emergence Delirium Scale (PAED) to assess the level and incidence of delirium in the post-anesthesia care unit. Results: Compared with the control group, prophylactic use of different dosages of intranasal dexmedetomidine significantly reduces the incidence of ED and severe ED in PACU (P<0.001). Intranasal administration of 2 µg/kg dexmedetomidine was associated with a better acceptance of mask induction and a better tolerance of separation with parents. Conclusion: Both 2 µg/kg and 1 µg/kg intranasal dexmedetomidine can achieve ED preventive effects in PACU in dental rehabilitation under general anesthesia. A dosage of 2 µg/kg is more effective in preventing severe ED and providing better mask acceptance.

Melatonin or its analogs as premedication to prevent emergence agitation in children: a systematic review and meta-analysis.

BACKGROUND: Emergence agitation (EA) is a prevalent complication in children following general anesthesia. Several studies have assessed the relationship between melatonin or its analogs and the incidence of pediatric EA, yielding conflicting results. This meta-analysis aims to assess the effects of premedication with melatonin or its analogs on preventing EA in children after general anesthesia. METHODS: PubMed, EMBASE, the Cochrane Library, ProQuest Dissertations & Theses Global, Web of Science, CNKI, Wanfang Data, clinicaltrials.gov, and WHO International Clinical Trials Registry Platform were searched until 25 November 2022. We included randomized controlled trials that assessed EA in patients less than 18 years old who underwent general anesthesia. We excluded studies that did not use a specific evaluation to assess EA. RESULTS: Nine studies (951 participants) were included in this systematic review. Melatonin significantly reduced the incidence of EA compared with placebos (risk ratio 0.40, 95% CI 0.26 to 0.61, P < 0.01) and midazolam (risk ratio 0.48, 95% CI 0.32 to 0.73, P < 0.01). Dexmedetomidine remarkably decreased the incidence of EA compared with melatonin (risk ratio 2.04, 95% CI 1.11 to 3.73, P = 0.02). CONCLUSIONS: Melatonin premedication significantly decreases the incidence of EA compared with placebos and midazolam. Dexmedetomidine premedication has a stronger effect than melatonin in preventing EA. Nevertheless, further studies are warranted to reinforce and validate the conclusion on the efficacy of melatonin premedication in mitigating EA in pediatric patients.

Comparison of the effects of ketamine via nebulization versus different pharmacological approaches in pediatric sedation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Nebulized drug delivery is commonly used in pediatric clinical practice. The growing number of literatures have reported the application of nebulized ketamine in pediatric sedation in recent years. This meta-analysis of randomized controlled trials comparing the efficacy and safety of nebulized ketamine versus different pharmacological approaches was conducted to estimate the effects of this technique in pediatric sedation. METHODS: We searched PubMed, Embase, and Cochrane Library from inception to Feb 2023. All randomized controlled trials used nebulized ketamine as presurgical and pre-procedural sedatives in children were included. Sedative effects and various adverse events were considered as the outcomes. RESULTS: Ten studies with 727 pediatric patients were enrolled. Compared to nebulized dexmedetomidine, using of ketamine via nebulization showed similar sedation satisfaction (54.79% vs. 60.69%, RR = 0.88, with 95%CI [0.61, 1.27]), success rate of parental separation (57.27% vs. 73.64%, RR = 0.81, with 95%CI [0.61, 1.08]), and mask acceptability (37.27% vs. 52.73%, RR = 0.71, with 95%CI [0.45, 1.10]). However, the using of combination of two medications (nebulized ketamine plus nebulized dexmedetomidine) was associated with better sedative satisfaction (33.82% vs. 68.11%, RR = 0.50, with 95%CI [0.27, 0.92]) and more satisfactory mask acceptance (45.59% vs. 71.01%, RR = 0.69, with 95%CI [0.56, 0.86]). Compared with nebulized ketamine, using of nebulized dexmedetomidine was associated with less incidence of emergence agitation (18.18% vs. 3.33%, RR = 4.98, with 95%CI [1.88, 13.16]). CONCLUSIONS: Based on current evidences, compared to nebulized dexmedetomidine, nebulized ketamine provides inconspicuous advantages in pediatric sedation, and it has a relatively high incidence of emergence agitation. Combination of nebulized ketamine and dexmedetomidine might be considered as one preferred option in pediatric sedation as it can provide more satisfactory sedative effects. However, there is insufficient evidence regarding nebulized ketamine versus ketamine administered through other routes and nebulized ketamine versus other sedatives. The overall low or moderate quality of evidence evaluated by the GRADE system also calls for more high-quality studies with larger sample sizes in future. RESEARCH REGISTRATION: The protocol of present study was registered with PROSPERO (CRD42023403226).

Effect of preoperative patient education and simulated mouth breathing training on opioid requirements in the post-anesthesia care unit after nasal surgery: a randomized controlled study.

BACKGROUND: A simulated education, prior to surgery about postoperative nasal stuffiness and ease of breathing through the mouth may help patients tolerate discomfort after nasal surgery. This study aimed to investigate the effect of preoperative simulated education on immediate postoperative opioid requirements in patients undergoing elective nasal surgery. METHODS: This randomized controlled trial of 110 patients undergoing nasal surgery randomly allocated patients into either a control (group C) or an education group (group E). One day before surgery, patients in group E were intensively trained to breathe through the mouth by using a nasal clip, with informative explanations about inevitable nasal obstruction and discomfort following surgery. Patients in group C were provided with routine preoperative information. Total intravenous anesthesia (TIVA) with propofol and remifentanil was used for anesthesia. No further opioid was used for analgesia intraoperatively. The primary outcome was index opioid (fentanyl) requirements at the post-anesthesia recovery unit (PACU). Secondary outcomes were emergence agitation, pain scores at the PACU, and postoperative recovery using the Quality of Recovery-15 (QoR15-K). RESULTS: The rate of opioid use in the PACU was 51.0% in the group E and 39.6% in the group C (p = 0.242). Additional request for analgesics other than index opioid was not different between the groups. Emergence agitation, postoperative pain severity, and QoR15-K scores were comparable between the groups. CONCLUSION: Preoperative education with simulated mouth breathing in patients undergoing nasal surgery did not reduce opioid requirements. TRIAL REGISTRATION: KCT0006264; 16/09/2021; Clinical Research Information Services ( https://cris.nih.go.kr ).

The Efficacy of Ramelteon to Prevent Postoperative Delirium After General Anesthesia in the Elderly: A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: Postoperative delirium is common and serious in elderly patients. Several drugs have been proposed as potential prophylactic agents for postoperative delirium. Studies on melatonin receptor agonists showed heterogeneity in age, cognitive function, anesthesia, surgery, interventions, methodologies for assessing outcomes, and results. Our objective was to examine the effect of ramelteon to prevent postoperative delirium in elderly patients, including those with dementia. DESIGN: A stratified, double-blind, randomized, placebo-controlled trial (UMIN000028436, jRCTs031180054). SETTING: Tertiary medical center. PARTICIPANTS: Patients aged older than or equal to 65 years undergoing elective surgery under general anesthesia. INTERVENTION: Ramelteon (8 mg orally) or placebo (lactose) for six nights (the preoperative night and five consecutive nights from postoperative day 1 to 5) at around 9 P.M. MEASUREMENTS: Patients were screened for postoperative delirium using the Confusion Assessment Method for the Intensive Care Unit twice daily until the sixth postoperative day. Patients with positive results were referred to a consultant psychiatrist to establish the diagnosis of delirium. RESULTS: A total of 108 patients were randomly assigned to receive ramelteon (n = 55) or placebo (n = 53). Most of the patients' characteristics were reasonably well-balanced between the two groups. The stratified log-rank test showed no significant difference in preventing postoperative delirium between ramelteon and placebo (χ2 = 0.30, degrees of freedom = 1, p = 0.60). The Cox proportional hazard ratio for ramelteon compared to placebo was 1.40 (95% confidence interval: 0.40-4.85, χ2 for likelihood ratio test = 0.29, degrees of freedom = 1, p = 0.60). CONCLUSION: There was no significant difference in the incidence of postoperative delirium between ramelteon and placebo after general anesthesia in elderly patients.

Postoperative recovery in preschool-aged children: A secondary analysis of a randomized controlled trial comparing premedication with midazolam, clonidine, and dexmedetomidine.

BACKGROUND: Preoperative anxiety in pediatric patients can worsen postoperative outcomes and delay discharge. Drugs aimed at reducing preoperative anxiety and facilitating postoperative recovery are available; however, their effects on postoperative recovery from propofol-remifentanil anesthesia have not been studied in preschool-aged children. Thus, we aimed to investigate the effects of three sedative premedications on postoperative recovery from total intravenous anesthesia in children aged 2-6 years. METHODS: In this prespecified secondary analysis of a double-blinded randomized trial, 90 children scheduled for ear, nose, and throat surgery were randomized (1:1:1) to receive sedative premedication: oral midazolam 0.5 mg/kg, oral clonidine 4 µg/kg, or intranasal dexmedetomidine 2 µg/kg. Using validated instruments, outcome measures including time for readiness to discharge from the postoperative care unit, postoperative sedation, emergence delirium, anxiety, pain, and nausea/vomiting were measured. RESULTS: After excluding eight children due to drug refusal or deviation from the protocol, 82 children were included in this study. No differences were found between the groups in terms of median time [interquartile range] to readiness for discharge (midazolam, 90 min [48]; clonidine, 80 min [46]; dexmedetomidine 100.5 min [42]). Compared to the midazolam group, logistic regression with a mixed model and repeated measures approach found no differences in sedation, less emergence delirium, and less pain in the dexmedetomidine group, and less anxiety in both clonidine and dexmedetomidine groups. CONCLUSIONS: No statistical difference was observed in the postoperative recovery times between the premedication regimens. Compared with midazolam, dexmedetomidine was favorable in reducing both emergence delirium and pain in the postoperative care unit, and both clonidine and dexmedetomidine reduced anxiety in the postoperative care unit. Our results indicated that premedication with α2 -agonists had a better recovery profile than short-acting benzodiazepines; although the overall recovery time in the postoperative care unit was not affected.

Comparison of the Effects of Dexmedetomidine and Lidocaine on Stress Response and Postoperative Delirium of Older Patients Undergoing Thoracoscopic Surgery: A Randomized Controlled Trial.

Purpose: We investigated the effects of intraoperative intravenous lidocaine or dexmedetomidine infusion on inflammatory factors and cognitive function in patients undergoing thoracoscopic surgery. Patients and Methods: Patients aged >65 years undergoing elective thoracoscopic lobectomy or segmentectomy were randomly grouped as dexmedetomidine group (group D), lidocaine group (group L), and control group (group C). The plasma cortisol, interleukin-6, and tumor necrosis factor-α concentrations were measured before anesthesia (T0) and immediately (T1), 24 h (T2), and 48 h postoperatively (T3). Postoperative delirium (POD) was assessed by 3D-CAM on days 2 and 7. Results: The cortisol concentrations decreased for all groups at T1 from T0 although they were significantly higher at T2. Group L had significantly lower interleukin-6 concentrations at T1 and T2 than the other groups (P<0.05). The interleukin-6 concentrations were significantly higher at T1, T2, and T3 than at T0 for all the groups, significantly lower for groups D and L than for group C at T1 and T2 (P<0.05), and significantly lower for group L than for group D at T2 (P<0.05). The tumor necrosis factor-α concentrations were significantly higher at T1, T2, and T3 than at T0 for all the groups and significantly lower for groups D and L than for group C at T1 and T2 (P<0.05), although they were not statistically significantly different for groups D and L. There were no statistically significant differences in the postoperative incidence of POD between the three groups on days 2 and day 7. Conclusion: Intraoperative continuous intravenous lidocaine or dexmedetomidine infusion reduced surgical stress and inflammatory responses. The inhibitory effect of lidocaine on surgical stress remained significant for up to 24 h postoperatively without affecting patient awakening. However, the administration of either drug failed to prevent postoperative POD.

Automated phenotyping of postoperative delirium-like behaviour in mice reveals the therapeutic efficacy of dexmedetomidine.

Postoperative delirium (POD) is a complicated and harmful clinical syndrome. Traditional behaviour analysis mostly focuses on static parameters. However, animal behaviour is a bottom-up and hierarchical organizational structure composed of time-varying posture dynamics. Spontaneous and task-driven behaviours are used to conduct comprehensive profiling of behavioural data of various aspects of model animals. A machine-learning based method is used to assess the effect of dexmedetomidine. Fourteen statistically different spontaneous behaviours are used to distinguish the non-POD group from the POD group. In the task-driven behaviour, the non-POD group has greater deep versus shallow investigation preference, with no significant preference in the POD group. Hyperactive and hypoactive subtypes can be distinguished through pose evaluation. Dexmedetomidine at a dose of 25 µg kg-1 reduces the severity and incidence of POD. Here we propose a multi-scaled clustering analysis framework that includes pose, behaviour and action sequence evaluation. This may represent the hierarchical dynamics of delirium-like behaviours.

A single preoperative low-dose dexamethasone may reduce the incidence and severity of postoperative delirium in the geriatric intertrochanteric fracture patients with internal fixation surgery: an exploratory analysis of a randomized, placebo-controlled trial.

OBJECTIVE: Postoperative delirium (POD) is a common complication along with poor prognosis in geriatric intertrochanteric fracture (ITF) patients. However, the prevention and treatment of POD remain unclear. Previous studies have confirmed that POD is essentially a consequence of neuro-inflammatory responses. Dexamethasone is a glucocorticoid with comprehensive anti-inflammatory effects, while a high dose of dexamethasone correlates with many side effects or even adverse consequences. Thus, this prospective study aims to discuss whether a single preoperative low-dose dexamethasone can reduce the impact of POD on geriatric ITF patients with internal fixation surgery. METHODS: Between June 2020 and October 2022, there were 219 consecutive ITF patients assessed in our department. Of the 219 ITF patients, 160 cases who met the inclusion and exclusion criteria were finally enrolled and randomly allocated to the dexamethasone group and the placebo group (80 geriatric ITF patients in each group) in this prospective study. The patients in the dexamethasone group received intravenous 10 mg (2 ml) dexamethasone while the patients in the placebo group received intravenous 2 ml saline in 30 min before being sent to the operating room, respectively. The baseline characteristics, surgical information, incidence and severity of POD as the efficacy-related outcomes, and infection events and hyperglycemia as safety-related outcomes (adverse events), were collected and analyzed between the two groups. The severity of POD was evaluated by Memorial Delirium Assessment Scale (MDAS) score. RESULTS: There were no differences in baseline characteristics and surgical information between the dexamethasone group and the placebo group. The dexamethasone group had a lower incidence of POD than the placebo group within the first 5 days after surgery [(9/80, 11.3% vs. 21/80, 26.3%, RR = 0.83, 95% CI 0.71-0.97, P = 0.015]. The dexamethasone group had lower MDAS scores (Mean ± SD) than the placebo group [13.2 ± 1.0 (range 11 to 15) vs. 15.48 ± 2.9 (range 9 to 20), P = 0.011, effect size = 0.514]. There were no differences in infection events and hyperglycemia between the two groups. CONCLUSIONS: A single preoperative low-dose dexamethasone may reduce the incidence and severity of POD in geriatric ITF patients with internal fixation surgery. TRIAL REGISTRATION: ChiCTR2200055281.

Emergence Agitation with Earthquake-Related Traumatic Stress Symptoms After Intravenous Sedation. / Intravenöz Sedasyon Sonrasi Depremle Iliskili Travmatik Stres Belirtileri ile Seyreden Derlenme Ajitasyonu.

Sedation with intravenous anesthetics is a sedation method that is often preferred during minor surgical procedures for anxious patients. Among the anesthetic agents used are drugs such as midazolam and ketamine, which can cause psychiatric symptoms such as loss of control over the behavior of the person (disinhibition) or dissociation. In people with high anxiety levels, a paradoxical rise of anxiety may rarely occur with midazolam, and emergence agitation or delirium may occur after anesthesia with ketamine. Post-traumatic stress disorder is a known risk factor for emergence agitation. Accompanying traumatic stress symptoms are reported to have persisted for a long time in the case reports of emergence agitation with a past history of trauma. It is aimed to discuss the importance of traumatic stress symptoms in sedation management in the post-earthquake period by presenting a case with increased anxiety and emergence agitation with acute stress symptoms such as re-experiencing the earthquake after sedation with intravenous anesthetics for a local surgical procedure immediately after experiencing the Kahramanmaras earthquake on February 6 in Turkey. Keywords: Earthquakes, intravenous anesthetics, emergence, psychomotor agitation, acute stress disorder, post-traumatic stress disorder.

Effects of intra-operative administration of subanesthetic s-ketamine on emergence from sevoflurane anesthesia: a randomized double-blind placebo-controlled study.

BACKGROUND: Ketamine is administered in the perioperative period for its benefits in analgesia, anti-agitation and anti-depression when administered at a small dose. However, it is not clear whether the intra-operative administration of ketamine would affect emergence under sevoflurane anesthesia. To investigate this effect, we designed this trial. METHODS: In this randomized, double-blind, placebo-controlled study, we enrolled 44 female patients aged 18-60 who were scheduled to elective laparoscopic gynecological surgeries. All patients were randomly assigned to saline or s-ketamine group. In s-ketamine group, patients received 0.125 mg/kg s-ketamine 30 min after the start of surgery. In saline group, patients were administered the same volume of saline. Sevoflurane and remifentanil were used to maintain general anesthesia. The primary outcome was emergence time. We also assessed postoperative agitation, cognitive function, and delirium. In addition, we collected and analyzed prefrontal electroencephalogram (EEG) during and after general anesthesia. RESULTS: There were no significant differences in emergence time between s-ketamine group and saline group (10.80 ± 3.77 min vs. 10.00 ± 2.78 min, P = 0.457). Neither postoperative agitation (4 [3, 4] vs. 4 [3, 4], P = 0.835) nor cognitive function (25.84 ± 2.69 vs. 25.55 ± 2.19, P = 0.412) differed between groups. No postoperative delirium was observed in either group. Subanesthetic s-ketamine resulted in active EEG with decreased power of slow (-0.35 ± 1.13 dB vs. -1.63 ± 1.03 dB, P = 0.003), delta (-0.22 ± 1.11 dB vs. -1.32 ± 1.09 dB, P = 0.011) and alpha (-0.31 ± 0.71 dB vs. -1.71 ± 1.34 dB, P = 0.0003) waves and increased power of beta-gamma bands (-0.30 ± 0.89 dB vs. 4.20 ± 2.08 dB, P < 0.0001) during sevoflurane anesthesia, as well as an increased alpha peak frequency (-0.16 ± 0.48 Hz vs. 0.31 ± 0.73 Hz, P = 0.026). EEG patterns did not differ during the recovery period after emergence between groups. CONCLUSION: Ketamine administered during sevoflurane anesthesia had no apparent influence on emergence time in young and middle-aged female patients undergoing laparoscopic surgery. Subanesthetic s-ketamine induced an active prefrontal EEG pattern during sevoflurane anesthesia but did not raise neurological side effects after surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100046479 (date: 16/05/2021).

Single-bolus dexmedetomidine in prevention of emergence delirium in pediatric ophthalmic surgeries: A randomized controlled trial.

Purpose: Emergency delirium (ED), a common postoperative neurologic complication, causes behavioral disturbances leading to self-traumas and also has long-term adverse effects in children. Our aim was to investigate the efficacy of a single-bolus dose of dexmedetomidine in reducing the incidence of ED. Additionally, pain relief, number of patients who needed rescue analgesia, hemodynamic parameters, and adverse events were assessed. Methods: One hundred and one patients were randomly allocated into two groups: 50 patients received 15 mL of dexmedetomidine 0.4 µg/kg (group D) and 51 patients received volume-matched normal saline (group C). Hemodynamic parameters such as heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were monitored regularly throughout the procedure. ED was assessed with Pediatric Anesthesia Emergence Delirium Scale (PAEDS), and pain was measured using the modified Objective Pain Score (MOPS). Results: The incidences of ED and pain were higher in group C than group D (P < 0.0001 and P < 0.0001, respectively). Group D showed significant decrease in MOPS and PAEDS values at 5, 10, 15, and 20 min (P < 0.05), HR at 5 min (P < 0.0243), and SBP at 15 min (P < 0.0127). There was no significant difference in DBP between the two groups at any time point. The mean blood pressure (MBP) at 10 min was significantly less in group D than group C (P < 0.001). Conclusion: Dexmedetomidine 0.4 µg/kg as a single bolus over 10 min immediately after intubation is effective for the prevention of ED and significantly reduces the need of rescue analgesia without compromising the hemodynamic parameters in children undergoing ophthalmic surgery.

The effect of intranasal dexmedetomidine administration on emergence agitation or delirium in pediatric patients after general anesthesia: A meta-analysis of randomized controlled trials.

BACKGROUND: Emergence agitation or delirium can occur in pediatric patients after anesthesia. Dexmedetomidine is known to reduce the impairment of postoperative cognitive function. AIMS: This study aimed to identify the role of intranasal administration of dexmedetomidine in lowering the development of emergence agitation or emergence delirium in pediatric patients after general anesthesia. METHODS: Electronic databases, including PubMed, EMBASE, CENTRAL, Scopus, and Web of Science, were searched to identify studies. The primary outcome was the proportion of patients who underwent emergence agitation or emergence delirium after the surgery. Secondary outcomes included emergence time and incidence of postoperative nausea and/or vomiting. We estimated the odds ratio and mean difference with 95% confidence intervals for the determination of effect size using a random-effects model. RESULTS: In total, 2103 pediatric patients from 20 randomized controlled trials were included in the final analysis. The incidence of emergence agitation or emergence delirium was 13.6% in the dexmedetomidine group and 33.2% in the control group. The pooled effect size revealed that intranasal dexmedetomidine administration significantly reduced the incidence of postoperative emergence agitation or emergence delirium in pediatric patients undergoing surgery under general anesthesia (odds ratio 0.25, 95% confidence interval 0.18-0.34; p = .0000; I2 = 37.74%). Additionally, significant difference was observed in emergence time between the two groups (mean difference 2.42, 95% confidence interval 0.37-4.46; p = .021; I2 = 98.40%). Children in the dexmedetomidine group had a significantly lower incidence of postoperative nausea and/or vomiting than those in the control group (odds ratio 0.39, 95% confidence interval 0.24-0.64; p = .0002; I2 = 0.00%). CONCLUSIONS: Intranasal dexmedetomidine reduced the incidence of emergence agitation or emergence delirium in pediatric patients after general anesthesia.

In a secondary analysis from a randomised, double-blind placebo-controlled trial Dexmedetomidine blocks cholinergic dysregulation in delirium pathogenesis in patients with major surgery.

Dexmedetomidine is an alpha-2 adrenoreceptor agonist with anti-inflammatory and anti-delirogenic properties. Pathogenesis of postoperative delirium (POD) includes cholinergic dysfunction and deregulated inflammatory response to surgical trauma. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are discussed as biomarkers for both POD and severity in acute inflammation. To show whether there is a link between blood cholinesterase activities and dexmedetomidine, we performed a secondary analysis of a randomised, double-blind, placebo-controlled trial that recently showed a lower incidence of POD in the dexmedetomidine group. Abdominal or cardiac surgical patients aged ≥ 60 years were randomised to receive dexmedetomidine or placebo intra- and postoperatively in addition to standard general anaesthesia. We analysed the course of perioperative cholinesterase activities of 56 patients, measured preoperatively and twice postoperatively. Dexmedetomidine resulted in no change in AChE activity and caused a rapid recovery of BChE activity after an initial decrease, while placebo showed a significant decrease in both cholinesterase activities. There were no significant between-group differences at any point in time. From these data it can be assumed that dexmedetomidine could alleviate POD via altering the cholinergic anti-inflammatory pathway (CAIP). We advocate for further investigations to show the direct connection between dexmedetomidine and cholinesterase activity.

Effects of dexmedetomidine on postoperative sleep quality: a systematic review and meta-analysis of randomized controlled trials.

STUDY OBJECTIVES: To assess the effect of dexmedetomidine (DEX) on postoperative sleep quality using polysomnography (PSG) to identify possible interventions for postoperative sleep disturbances. METHODS: An electronic search of PubMed/MEDLINE, EMBASE, Cochrane Library and Web of Science was conducted from database inception to November 20, 2022. Randomized controlled trials (RCTs) on the effect of DEX administration on postoperative sleep quality using PSG or its derivatives were included. No language restrictions were applied. The sleep efficiency index (SEI), arousal index (AI), percentages of stage N1, N2 and N3 of non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep were measured in our meta-analysis. RESULTS: Five studies, involving 381 participants were included. Administration of DEX significantly improved SEI, lowered AI, decreased the duration of stage N1 sleep and increased the duration of stage N2 sleep compared to placebo groups. There were no significant differences in the duration of stage N3 sleep and REM sleep. DEX administration lowered the postoperative Visual Analogue Scale (VAS) score and improved the Ramsay sedation score with no adverse effect on postoperative delirium (POD). However, high heterogeneity was observed in most of the primary and secondary outcomes. CONCLUSIONS: Our study provides support for the perioperative administration of DEX to improve postoperative sleep quality. The optimal dosage and overall effect of DEX on postoperative sleep quality require further investigation using large-scale randomized controlled trials.