Efficacy and Safety of Ketamine/Esketamine in Bipolar Depression in a Clinical Setting.

Background: Bipolar disorder represents a significant source of morbidity and elevated mortality risk. Ketamine has emerged as a powerful antidepressant; however, there have been few trials of ketamine in bipolar depression and no trials with esketamine in bipolar depression, and few data exist from real-world settings. Here, we report outcomes from a cohort of patients with bipolar depression treated with ketamine/ esketamine in a real-world setting.Methods: Patients with treatment refractory bipolar depression were referred to Yale Psychiatric Hospital Interventional Services for treatment from October 2014 to November 2023. Appropriate patients were treated with intravenous (IV) ketamine (0.5 mg/kg over 40 minutes) or intranasal esketamine (56 or 84 mg). Diagnosis of bipolar depression was done by clinical evaluation by an attending psychiatrist, based on DSM criteria. Clinical outcomes were tabulated from medical records.Results: Overall, 45 patients with bipolar depression were treated with IV ketamine or intranasal (IN) esketamine during the time period specified. Depression severity outcomes were available for 38 patients that completed an acute series, defined as treatment twice weekly for up to 4 weeks. Overall, 15/38 (39%) achieved clinical response (≥50% improvement on the Montgomery-Asberg Depression Rating Scale [MADRS]) and 5/38 (13.2%) achieved remission (≤10 on MADRS) following the acute series. Mean MADRS scores decreased from 31.1 to 19.2 (38.3% mean improvement). Safety data (hypomania/manic symptoms) were available for all 45 patients (518 patient-months of follow-up). No patients experienced any mania/hypomania during the acute series phase (when treatments are given twice weekly). However, 13/45 (28.9%) patients experienced symptoms consistent with a hypomanic or manic episode at some point following the acute phase while continuing to receive ketamine or esketamine during a maintenance phase. There were 16 manic/hypomanic events, indicating 1 event for every 2.7 patient-years. Only 1 event was severe and resulted in hospitalization.Conclusion: In a small sample of patients with bipolar depression treated with ketamine/esketamine, no evidence of mania/hypomania was seen during the acute phase of treatment. Further research is needed to evaluate whether ketamine or esketamine confers heightened risk of affective switch during maintenance treatment.

Association between pre-procedural anxiety and vomiting in children who undergo procedural sedation and analgesia in the emergency department.

INTRODUCTION: Children presenting to the emergency department (ED) often require procedural sedation and analgesia (PSA) prior to procedures. Although ketamine is used widely for PSA safely, there is a risk of adverse effects. Among them, vomiting is significant as it occurs in about 10% of patients and can potentially endanger the airway. Because there is evidence that post-operative complications might be due to anxiety prior to the operation, this study aims to investigate the association between pre-procedural anxiety and vomiting in the ED. METHODS: In this cohort study, a convenient sample of children aged 2 to 14 years who were a candidate for PSA with ketamine in the ED were enrolled. Anxiety was evaluated using the short version of the modified Yale preoperative anxiety scale (mYAS). Vomiting was recorded during the period of hospitalization in the ED and 24 h after discharge by a phone call. Association between anxiety level and vomiting was analyzed using the independent samples t-test and multivariable logistic regression was used to control for covariates. RESULTS: 102 children were enrolled and 93 were included in final analysis. The mean age of participants was 3.95 ± 1.79 years and 55.9% were male. According to the mYAS, the mean score of anxiety was 48.67 ± 21.78 in the waiting room and 59.10 ± 23.86 in the operating room. The mean score of anxiety was 58.3±25.3 and 51.0±20.7 in the vomiting and non-vomiting groups, respectively. At least one episode of vomiting was reported in 23 children of which, 19 took place in the hospital and 4 after discharge. No significant association was observed between pre-procedural anxiety and the occurrence of vomiting. On univariate regression model, the odds ratio of the association between mean anxiety and vomiting was 1.02 (CI 95%: 0.99-1.04) (P-value: 0.16). On the multivariable logistic regression model, after adjusting for all the covariates, the odds ratio was 1.03 (CI 95%: 1.0-1.05) (P-value: 0.05). CONCLUSION: The present study showed that anxiety before procedural sedation and analgesia with ketamine in children was not associated with the incidence of vomiting.

Management Strategies for Patients with Non-Infectious Cystitis: A Review of the Literature.

PURPOSE OF REVIEW: The management of noninfectious cystitis continues to evolve as new treatments continue to be developed and investigated. This review aims to synthesize the most recent data regarding management strategies for noninfectious cystitis focused on non-ulcerative, ulcerative, eosinophilic, and ketamine-induced cystitis. RECENT FINDINGS: Several novel treatments have shown promise as management options including combination antihistamine therapy, phosphodiesterase 5 inhibitors, alpha lipoic acid supplements, and onabotulinumtoxin A. Recent studies have also found pentosan polysulfate sodium to have adverse ophthalmologic effects. For patients with ulcerative cystitis, recent research has shown that fulguration with or without triamcinolone injections should not be delayed. The treatment of noninfectious cystitis should be patient specific based on factors including etiology and symptom profile. Multimodal regimens are often the most effective. Treatment should be started with conservative options and escalated as necessary to oral treatments, intravesical options, or procedural management.

Effects of adjunctive esketamine on depression in elderly patients undergoing hip fracture surgery: a randomized controlled trial.

BACKGROUND: Depression is a prevalent perioperative psychiatric complication among elderly hip fracture patients. Esketamine has rapid and robust antidepressant effects. However, it is unknown whether it can alleviate depressive symptoms in elderly patients who undergo hip fracture surgery. This study aimed to explore whether the adjunctive esketamine in patient-controlled intravenous analgesia (PCIA) could improve depressive symptoms in elderly patients undergoing hip fracture surgery. METHODS: A single-center, prospective, double-blind and randomized controlled clinical trial was carried out from July 2022 to August 2023 at the Wenzhou People's Hospital among 90 patients, aged ≥ 65 years with hip fracture undergoing elective surgery. Participants were randomly allocated to either the esketamine group (group S) or the control group (group C). In Group S, patients were administered 0.5 mg/kg of esketamine as a PCIA adjuvant for 48 h, while the control group received saline. The primary outcome was the assessment of depressive symptoms using the Geriatric Depression Scale-15 (GDS-15) on postoperative day 2. The secondary outcomes were assessments of depressive symptoms on postoperative day 7 and postoperative day 30, serum levels of brain-derived neurotrophic factor (BDNF) and 5-hydroxytryptamine (5-HT), postoperative pain intensity, the number of effective PCIA presses, sufentanil consumption, and adverse events. RESULTS: The prevalence and GDS-15 scores of depression were significantly lower in group S on postoperative day 2 (28.6% vs. 53.5%; 3.5 ± 1.8 vs. 4.3 ± 1.7, P < 0.05). In group S, the number of effective PCIA presses was significantly lower on postoperative day 2 than that in group C [2(1-4) vs. 1(0-2), P<0.05]. Higher levels of BDNF (23.8 ± 1.7 ng/mL vs. 25.3 ± 2.0 ng/mL, P < 0.05) and 5-HT (219.5 ± 19.5 ng/mL vs. 217.0 ± 22.2 ng/mL, P < 0.05) in the blood were observed on postoperative day 2 in group S. CONCLUSION: In elderly patients aged ≥ 65 years undergoing hip fracture surgery, the administration of adjunctive esketamine in PCIA could improve depressive symptoms and increase levels of BDNF and 5-HT in the blood. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200061956 (Date: 13/07/2022).

Diurnal variation of postoperative delirium in elderly patients undergoing esketamine anesthesia for elective noncardiac surgery: a randomized clinical trial.

BACKGROUND: Postoperative delirium (POD) is a serious and common complication. The aim of present study is to investigate the diurnal variation of POD and the effects of esketamine in elderly patients. METHODS: A randomized, double-blind, placebo-controlled clinical trial with factorial design was conducted. Patients (aged 65 to 85 years) with normal Mini-Mental State Examination (MMSE) score were stratified by age (≤70 vs. >70) and American Society of Anesthesiologists physical status classification (Ⅱ vs. Ⅲ), then randomly assigned to either morning (08:00-12:00) or afternoon (14:00-18:00) noncardiac operation under general anesthesia with or without esketamine administration (0.2 mg/kg). The primary outcome was the incidence of POD (3-Minute Diagnostic Interview for Confusion Assessment Method-defined Delirium, 3D-CAM) on postoperative days 1, 3, and 7. The secondary outcomes were the scores of MMSE and Hospital Anxiety and Depression Scale. The intention-to-treat analysis of the outcomes were performed by generalized estimating equation. RESULTS: Six patients who did not receive an intervention because of canceled operation were excluded after randomization. The datasets containing 426 cases were analyzed following the intention-to-treat principle after handling missing data via multiple imputation method. The incidence of POD declined from about 55% on postoperative day 1 to 31 and 18% on postoperative days 3 and 7, respectively. Afternoon operation [B=-0.583, OR (95% CI) 0.558 (0.319-0.976); P=0.041], but not esketamine, significantly decreased the incidence of POD. Both esketamine and operation time failed to significantly affect MMSE, HAD, and NRS score. There was no interaction among operation time, esketamine, and follow up time. CONCLUSION: Elderly patients undergoing elective noncardiac surgery in the afternoon displayed lower POD incidence than those operated in the morning. A single low-dose of esketamine before general anesthesia induction failed to significantly decrease the risk of POD but decrease the risk of intraoperative hypotension and emergence agitation.

The efficient method to get better raw brain signal on rat anesthetics experiment.

This paper introduces an efficient methodology for conducting rat anesthesia experiments, aimed at enhancing the quality of raw brain signals obtained. The proposed approach enables the acquisition of animal brain signals during experiments without the confounding influence of muscle noise. Initially, the use of alpha-chloralose (a-c) in conjunction with Isoflurane is introduced to induce anesthesia in rats. Subsequently, Dexdomitor is administered to prevent muscular movements during the collection of brain signals, further refining the signal quality. Experimental outcomes conclusively demonstrate that our anesthesia method produces cleaner raw signals and exhibits improved robustness during data acquisition, outperforming existing methods that rely solely on Isoflurane or the Ketamine-Xylazine combination. Notably, this improved performance is achieved with minimal alterations to vital physiological parameters, including body temperature, respiration, and heart rates. Moreover, the efficacy of a-c in maintaining anesthesia for up to 7 h stands in contrast to the shorter durations achievable with continuous Isoflurane administration or the 30-min window offered by Ketamine-Xylazine, highlighting the practical advantages of our proposed method. Finally, post-experiment observations confirmed that the animals gradually returned to normal behavior without any signs of distress or adverse effects, indicating that our method was both effective and safe.

Extraction of ketamine and dexmedetomidine by extracorporeal life support circuits☠.

BACKGROUND: Patients supported with extracorporeal life support (ECLS) circuits such as ECMO and CRRT often require high doses of sedatives and analgesics, including ketamine and dexmedetomidine. Concentrations of many medications are affected by ECLS circuits through adsorption to the circuit components, dialysis, as well as the large volume of blood used to prime the circuits. However, the impact of ECLS circuits on ketamine and dexmedetomidine pharmacokinetics has not been well described. This study determined ketamine and dexmedetomidine extraction by extracorporeal circuits in an ex-vivo system. METHODS: Medication was administered at therapeutic concentration to blood-primed, closed-loop ex-vivo ECMO and CRRT circuits. Drug concentrations were measured in plasma, hemofiltrate, and control samples at multiple time points throughout the experiments. At each sample time point, the percentage of drug recovery was calculated. RESULTS: Ketamine plasma concentration in the ECMO and CRRT circuits decreased rapidly, with 43.8% recovery (SD = 0.6%) from ECMO circuits after 8 h and 3.3% (SD = 1.8%) recovery from CRRT circuits after 6 h. Dexmedetomidine was also cleared from CRRT circuits, with 20.3% recovery (SD = 1.8%) after 6 h. Concentrations of both medications were very stable in the control experiments, with approximately 100% drug recovery of both ketamine and dexmedetomidine after 6 h. CONCLUSION: Ketamine and dexmedetomidine concentrations are significantly affected by ECLS circuits, indicating that dosing adjustments are needed for patients supported with ECMO and CRRT.

[Treatment of New Daily Persistent Headache With Esketamine: Report of One Case].

New daily persistent headache (NDPH) is a kind of persistent headache that patients can identify the exact date of the sudden onset.It is one of the rare primary headaches difficult to be cured and may lead to disability,seriously affecting the daily life and work.The exact pathogenesis of NDPH remains unclear,which makes the treatment difficult.Here we report a case of refractory NDPH treated by intravenous injection of esketamine at a sub-anesthetic dose.

A study comparing brain wave patterns of fentanyl and ketamine in adult patients undergoing minimally invasive surgery.

This study aimed to investigate and compare the neurophysiological impacts of two widely used anesthetic agents, Fentanyl and Ketamine, on EEG power spectra during different stages of anesthesia in adult patients undergoing minimally invasive surgery. EEG data were collected from patients undergoing anesthesia with either Fentanyl or Ketamine. The data were analyzed for relative power spectrum and fast-to-slow wave power ratios, alongside Spectral Edge Frequency 95% (SEF95), at 3 key stages: pre-anesthesia, during stable anesthesia, and post-anesthesia. EEG Relative Power Spectrum: Initially, both groups exhibited similar EEG spectral profiles, establishing a uniform baseline (P > .05). Upon anesthesia induction, the Fentanyl group showed a substantial increase in delta band power (P < .05), suggesting deeper anesthesia, while the Ketamine group maintained higher alpha and beta band activity (P < .05), indicative of a lighter sedative effect. Fast and Slow Wave Power Ratios: The Fentanyl group exhibited a marked reduction in the fast-to-slow wave power ratio during anesthesia (P < .05), persisting post-anesthesia (P < .05) and indicating a lingering effect on brain activity. Conversely, the Ketamine group demonstrated a more stable ratio (P > .05), conducive to settings requiring rapid cognitive recovery. Spectral Edge Frequency 95% (SEF95): Analysis showed a significant decrease in SEF95 values for the Fentanyl group during anesthesia (P < .05), reflecting a shift towards lower frequency power. The Ketamine group experienced a less pronounced decrease (P > .05), maintaining a higher SEF95 value that suggested a lighter level of sedation. The study highlighted the distinct impacts of Fentanyl and Ketamine on EEG power spectra, with Fentanyl inducing deeper anesthesia as evidenced by shifts towards lower frequency activity and a significant decrease in SEF95 values. In contrast, Ketamine's preservation of higher frequency activity and more stable SEF95 values suggests a lighter, more dissociative anesthetic state. These findings emphasize the importance of EEG monitoring in anesthesia for tailoring anesthetic protocols to individual patient needs and optimizing postoperative outcomes.

Opioid-free anesthesia improves postoperative recovery quality of small and medium-sized surgery: a prospective, randomized controlled study.

BACKGROUND: Opioid anesthesia (OA) is currently the predominant anesthetic method. However, its associated side effects, such as nausea and vomiting, coupled with the principle of enhanced recovery after surgery (ERAS), have spurred the adoption of opioid-free anesthesia (OFA) in select surgical procedures. For small and medium-sized operations, ERAS is particularly important. The aim of this study was to investigate the effect of OFA, utilizing esketamine in combination with dexmedetomidine and sevoflurane, on postoperative recovery quality following small and medium-sized surgical interventions. METHODS: A total of 120 patients who underwent various small and medium-sized operations were randomly allocated to OFA and OA groups. The OA group received sufentanyl and sevoflurane, while the OFA group received esketamine, dexmedetomidine, and sevoflurane. The primary outcome measure was the postoperative quality of recovery-40 scores (QoR-40) 24 hours after surgery. Secondary outcomes included hemodynamic changes at different time intervals, the incidences of adverse events were recorded. RESULTS: Patients in the OFA group exhibited a higher QoR-40 score of 184.0 (182.0, 186.2) compared to 182.0 (180.0, 184.0) in the OA group (P<0.001). The disparities were particularly noble in terms of Physical comfort and Emotional status. Multivariable analysis identified postoperative nausea and vomiting (PONV) as a significant independent factor impacting QoR-40 (ß=-4.49 [-6.1, -2.87], P<0.001). Hemodynamic stability was more pronounced in the OFA than in the OA group. The incidence of PONV was substantially lower in the OFA group (one [1.6%] vs. 14 [25%], P<0.001), with a reduced need for vasoactive drugs (five [7.8%] vs. 15 [26.8%], P=0.005), and a lower incidence of respiratory depression (0 [0%] vs. six [10.7%], P=0.009). CONCLUSIONS: OFA improves the postoperative recovery quality in small and medium-sized surgical procedures, potentially attributed to decreased incidence of PONV. Additionally, OFA facilitates the maintenance of more stable hemodynamics throughout the operation.

Dexmedetomidine versus Ketofol for Moderate Sedation in Endoscopic Retrograde Cholangiopancreatography.

OBJECTIVE: To compare the efficacy of dexmedetomidine versus ketofol for moderate sedation in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). STUDY DESIGN: Randomised controlled trial. Place and Duration of the Study: Department of Anaesthesia, SICU and Pain Management, Sindh Institute of Urology and Transplantation, Karachi, Paksitan, from December 2021 to June 2022. METHODOLOGY: Sixty-two patients aged 20-60 years of any gender scheduled for elective ERCP were included. Patients were randomly divided into Dexmedetomidine group (2ml ampule of 100ug/ml diluted in 18ml of normal saline) and Ketofol group (2ml ketamine and 10ml of propofol 1% diluted in 8ml of normal saline) for sedation. The mean difference in time to achieve Ramsay Sedation Scale (RSS) score of 4 and Modified Aldrete's Score (MAS) of 9 were noted as outcomes in each group. In addition, complications during the procedure and recovery were also noted. RESULTS: The mean age was 39.15 ± 9.82 years. There were 33 (53.2%) males and 29 (46.8%) females. The mean time to achieve RSS 4 was significantly lower in patients who were treated with Dexmedetomidine as compared to Ketofol, i.e., 11.84 ± 1.77 minutes vs. 13.10 ± 1.64 minutes respectively (p-value 0.005, 95% CI -2.12 to -0.39). Similarly, the mean time to achieve MAS score 9 was significantly lower in patients who were treated with Dexmedetomidine as compared to Ketofol, i.e., 11.19 ± 1.72 minutes vs. 12.23 ± 1.84 minutes, respectively (p-value 0.026, 95% CI -1.94 to -0.13). CONCLUSION: Dexmedetomidine proved to be more effective than Ketofol for sedation in ERCP, achieving faster sedation and quicker recovery. KEY WORDS: Dexmedetomidine, Ketofol, Sedation, Endoscopic Retrograde Cholangiopancreatography.

The effect of dexmedetomidine-ketamine combination versus dexmedetomidine on behavior of uncooperative pediatric dental patients: a randomized controlled clinical trial.

OBJECTIVE: Uncooperative behavior in pediatric dentistry is one of the most common manifestations of dental anxiety. Managing anxious patients can be attained by moderate sedation. This study aimed to compare the effect of sedation by dexmedetomidine-ketamine combination (DEX-KET) versus dexmedetomidine (DEX) on behavior of uncooperative pediatric dental patients. METHODOLOGY: In total, 56 uncooperative healthy children (3-5 years old) requiring dental treatment were divided randomly into two groups: Group I (study group), which received buccal dexmedetomidine (2 µg/kg) and ketamine (2 mg/kg), and Group II (control group), which received only buccal dexmedetomidine (4 µg/kg). Drugs effects were assessed in terms of hemodynamic parameters, patient's drug acceptance, child behavior, postoperative effect of sedation, amnesic effect, incidence of adverse events, as well as procedural induced stress measured by salivary secretory immunoglobulin A (s-IgA). RESULTS: Hemodynamic results did not reveal a statistically significant difference between the two study groups (P>0.05). There was a significant difference in patient's acceptance to sedative drug between both groups, favoring DEX (p=0.005). Children who received DEX-KET showed significantly better behavior than those who received DEX for local anesthesia (p=0.017) and during operative procedure (p=0.037). Adverse events, post-operative and amnesic effects of drugs were comparable in both groups (p>0.05). Moreover, the mean difference in the salivary s-IgA levels between initial and final value was not statistically significant between both groups (p=0.556). CONCLUSION: Both DEX-KET combination and DEX alone are effective in providing hemodynamic stability. DEX-KET combination significantly improved the behavior of sedated children compared to DEX alone but the drug acceptance was decreased in the DEX-KET group. Both regimens did not have a negative effect on postoperative behavior of children and had comparable amnesic effect with no significant adverse events. Salivary s-IgA is not considered a potential stress biomarker in sedated children.

Perioperative Change of High-Sensitive Cardiac Troponin I Concentration in Cats According to Three Different Anaesthesia Protocols.

BACKGROUND: Cardiac troponin I, a particular biomarker, is released into the bloodstream in response to myocardial injury. OBJECTIVES: To evaluate perioperative changes in high-sensitivity cardiac troponin I (hs-cTnI) concentration during ovariohysterectomy in cats undergoing three different anaesthesia protocols. METHODS:  Twenty-one female mixed-breed cats owned by clients aged (2.2 ± 0.7 years) and weight (3.2 ± 0.5 kg) were included in our study. The cats were divided into three groups: propofol-isoflurane (PI) group (n = 7), xylazine-ketamine (XK) group (n = 7) and xylazine-isoflurane (XI) group (n = 7). After pre-anaesthetic propofol (6 mg/kg IV) was administered to cats in Group PI, a mask was placed, and anaesthesia was maintained with 3.0% isoflurane in oxygen. Cats in Group XK underwent general anesthetization with xylazine hydrochloride (2 mg/kg IM) and, 10 min later, ketamine hydrochloride (10 mg/kg IM). Cats in Group XI were administered xylazine hydrochloride (2 mg/kg IM), and then anaesthesia (3.0% isoflurane and oxygen) was continued with a mask. Blood samples were collected from all cats; preoperatively and postoperatively at 0 and 12 h (Pre-, Post-0 h and Post-12 h, respectively). Serum hs-cTnI concentrations were measured with the Advia Centaur TnI-Ultra. RESULTS: In all 21 cats, hs-cTnI concentration increased at Post-0 h and 12 h measurement points compared to Pre-. In the XK group, hs-cTnI concentrations exhibited a significant increase at the Post-0 h (51.30 ng/L) and Post-12 h (157.70 ng/L) time points compared to Pre- (6.70 ng/L) (p < 0.05). CONCLUSIONS: The XK group increased the concentration of hs-cTnI more than other protocols. In the PI group, the increase in hs-cTnI concentrations at Post-0 and 12 h increased less than the other two groups (p < 0.05). The PI group was found to induce less myocardial damage.

Comparison of intranasal ketamine with intranasal midazolam and dexmedetomidine combination in pediatric dental patients for procedural sedation: A crossover study.

BACKGROUND: The main goal of the pediatric dentist is to address and reduce children's fear and anxiety during the dental treatment, especially when conventional behavior-guiding strategies fail. In such cases, the use of pharmacological agents becomes an essential factor to consider. OBJECTIVE: The objective of the study was to compare the efficacy, safety, and acceptability of intranasal ketamine (INK) with the combination of intranasal midazolam and dexmedetomidine (INMzD) in pediatric dental patients for the procedural sedation. PATIENTS AND METHODS: Forty-seven children aged 3-9 years who required dental procedures such as extractions, pulpectomy, and restorations were randomly distributed into two groups using the envelope drawing method. Group INK received 7 mg/kg INK, whereas Group INMzD received a combination of midazolam spray (0.3 mg/kg) and atomized dexmedetomidine (3 µg/kg). RESULTS: INK showed faster onset, faster recovery, and shorter discharge time than INMzD. Both groups had acceptable physiological parameters and no postoperative complications. INK was more accepted by the patients than INMzD. CONCLUSIONS: In terms of efficacy, safety, and acceptability, INK outperformed the combination of INMzD for the procedural sedation.

A real-world pharmacovigilance study of esketamine nasal spray.

Mining and updating the post-marketing safety signals of esketamine nasal spray for better identification of adverse drug event (ADE) signals and medication monitoring during clinical use to ensure patient medication safety. Downloading data from the US Food and Drug Administration Adverse Event Reporting System from Q1 2019 to Q2 2023, the reporting odds ratio, proportional reporting ratio, Multi-item Gamma Poisson Shrinker, and Bayesian Confidence Propagation Neural Network methods of the disproportionality method were used to mine and analyze ADEs, and finally to screen for signals of ADEs with esketamine nasal spray as the primary suspected drug. The Preferred Terminology of the Medical Dictionary of Regulatory Activities (version 26.0) was used to standardize the description of ADEs and to attribute ADEs to the System Organ Classification. A total of 5132 ADEs reports of esketamine nasal spray as the primary suspected drug were obtained from the Food and Drug Administration Adverse Event Reporting System. The most frequently observed ADEs are dissociation, sedation, and hypertension, while some new rare signals have been detected, such as interstitial cystitis, substance abuse, and drug diversion. The present study identified significant new ADEs signals for esketamine nasal spray, which may provide a source for healthcare professionals to assess patients' symptoms and risk identification.

The impact of ketamine on emergency rapid sequence intubation: a systematic review and meta-analysis.

BACKGROUND: Rapid sequence intubation (RSI) is a crucial step in the resuscitation process for critically ill patients, and the judicious use of sedative drugs during RSI significantly influences the clinical outcomes of patients. Ketamine is a commonly used anesthetic sedative; however, its impact on the mortality of patients undergoing RSI has yielded inconsistent findings. Therefore, we conducted a systematic review and meta-analysis investigating ketamine's role in RSI to provide insights into selecting appropriate sedatives for critically ill patients. METHODS: In this systematic review and meta-analysis, we conducted a systematic search on MEDLINE (PubMed), Embase, and Cochrane Central Register of Controlled Trials, without restricting to randomized controlled trials (RCTs) or cohort studies. The search was performed from inception until Dec 12, 2023, with no language restrictions. All studies comparing the use of sedatives, including ketamine, and documenting in-hospital mortality were included in this study. RESULTS: A total of 991 studies were identified, out of which 15 studies (5 RCTs and 10 cohort studies) involving 16,807 participants fulfilled the inclusion criteria. No significant impact on in-hospital mortality was observed with the use of ketamine compared to other drugs during RSI (OR 0.90, 95%CI 0.72 to 1.12). Low-quality evidence suggested that ketamine might reduce mortality within the first seven days of hospitalization (OR 0.42, 95%CI 0.19 to 0.93), but it may also have a potential effect on prolonging ICU-free days at day 28 (MD -0.71, 95%CI -1.38 to -0.05). There were no significant differences in the results of the other RSI-related outcomes, such as physiological function and adverse events. CONCLUSIONS: Based on existing studies, ketamine showed no significant difference compared to other sedatives in terms of in-hospital mortality, physiological impact, and side effects following RSI. However, it may reduce mortality within 7 days while probably prolong the length of stay in the ICU. TRIAL REGISTRATION: CRD42023478020.

Efficacy and safety of esketamine hydrochloride adjunct to sufentanil in non-surgical patients under mechanical ventilation in the ICU (SENSATION trial): protocol for a multicentre, single-blind, randomised controlled trial.

INTRODUCTION: Pain is common in patients receiving mechanical ventilation in the intensive care unit (ICU). Intravenous opioids are recommended as first-line therapy for pain management; however, opioids have adverse side effects. Based on low-quality evidence, low-dose ketamine is therefore recommended as an opioid adjunct to reduce opioid consumption. Esketamine is an alternative to ketamine with greater efficacy and fewer side effects. However, evidence on the use of esketamine in patients receiving mechanical ventilation is lacking. This study investigates the efficacy and safety of esketamine as an adjunct to sufentanil for analgesic therapy in non-surgical ICU patients under mechanical ventilation. METHODS AND ANALYSIS: This ongoing multicentre, single-blind, randomised controlled trial is being conducted at six ICUs in China. 132 non-surgical patients under mechanical ventilation will be randomly assigned to the standard care and S-ketamine groups at a 1:1 ratio. Patients in the standard care group received a minimal dose of sufentanil as the sole analgesic agent. Patients in the S-ketamine group received a minimal dose of sufentanil in addition to an esketamine infusion at a fixed rate of 0.2 mg/kg/hour for analgesia. The primary outcome is mean hourly sufentanil consumption during the treatment period. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Chongqing University Cancer Hospital (CZLS2022067-A). Participants are required to provide informed consent. The results of this trial will be reported in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200058933.

Subanesthetic Dose of Esketamine Improves the Sedative and Analgesic Effects of Dexmedetomidine and Remifentanil in Liposuction Anesthesia: A Prospective, Double-Blinded, Randomized Controlled Trial.

Purpose: Esketamine have anesthetic and analgesic properties. This study aimed to observe the enhancing effect of subanesthetic doses of esketamine (0.15-0.3 mg/kg/h) with dexmedetomidine and remifentanil during anesthesia for liposuction surgery. Patients and Methods: A total of 155 subjects were randomized with a 1:1 ratio to Group E (esketamine-dexmedetomidine/remifentanil, n=78) or Group C (saline-dexmedetomidine/remifentanil group, n=77). The primary outcome was satisfaction of patient and surgical team with the procedure. The secondary outcomes were the postoperative Athens Insomnia Scale (AIS) and Hospital Anxiety and Depression Scale (HADS) scores, hemodynamic and respiratory changes, drug consumption, adverse event rates, and predictors associated with patient satisfaction. Results: Patient and surgical team satisfaction with the procedure was significantly higher in Group E than in Group C (4.7 ± 0.6 vs 4.2 ± 0.7, P < 0.001; 4.7 ± 0.5 vs 4.4 ± 0.7, P = 0.005). The postoperative AIS (4 [1, 6] vs 5 [2, 9], P = 0.012) and HADS-A (1 [0, 3] vs 2 [0, 6], P = 0.012) scores were significantly lower in Group E than in Group C. Hemodynamic and respiratory parameters were more stable in Group E than in Group C, with the lower opioids consumption of sufentanil (0 [0, 4] vs 5 [2.5, 7.7], P < 0.001) and remifentanil (700 [480, 900] vs 800 [500, 1200], P = 0.023) in Group E compared to Group C. On ordinal logistics regression, postoperative sleep quality (OR, 0.70; 95% CI, 0.62-0.79), anxiety level (OR, 0.77; 95% CI, 0.62-0.95) and recovery time in post-anesthesia care unit (PACU) (OR, 0.69; 95% CI, 0.56-0.98) were identified as significant predictors associated with patient satisfaction. Conclusion: A subanesthetic dose of esketamine (0.15-0.3 mg/kg/h) as an adjuvant can improves the sedative and analgesic effects of dexmedetomidine and remifentanil during anesthesia for liposuction surgery. Clinical Trial Registration: ChiCTR2400080363.

Safe Ketamine Use and Pregnancy: A Nationwide Survey and Retrospective Review of Informed Consent, Counseling, and Testing Practices.

Objective: Ketamine is contraindicated in pregnancy given the lack of knowledge about potential effects on a developing fetus. This study aimed to characterize current clinical practices specific to pregnancy and reproduction related to the use of ketamine for the treatment of psychiatric illness.Methods: Online surveys were sent to outpatient ketamine clinics across the United States inquiring about practices related to pregnancy. Responses were collected between September and November 2023. Additionally, a retrospective medical record review was conducted to ascertain the frequency of pregnancy testing and contraception use with ketamine treatments administered at a large academic health system. Online, publicly available informed consent documents were also reviewed for language related to pregnancy.Results: Fewer than half of survey respondents (n = 126) discuss specific risks related to pregnancy and fetal ketamine exposure during the informed consent process. Twenty percent of clinics require pregnancy tests prior to treatment, and 10.5% require subsequent testing during treatment; however, 22.9% of clinics do not have a standard process for testing. Only 13.7% of clinics specifically recommend or require use of contraception. Retrospective record review revealed that all patients who received intravenous ketamine for psychiatric indications in an academic medical center were pregnancy tested weekly, but only half were using contraception during treatment.Conclusion: Many women with the potential to become pregnant are treated with ketamine for psychiatric illness. Results of the present study reveal that risks of fetal ketamine exposure are often overlooked, indicating a need for increased awareness about reproductive concerns when prescribing ketamine for the treatment of psychiatric disorders.