Application Of Ketamine Research Articles

Depression with comorbid borderline personality disorder - could ketamine be a treatment catalyst?

Borderline personality disorder (BPD) is diagnosed in 10-30% of patients with major depressive disorder (MDD), and the frequency of MDD among individuals with BPD reaches over 80%. The comorbidity of MDD and BPD is associated with more severe depressive symptoms and functional impairment, higher risk of treatment resistance and increased suicidality. The effectiveness of ketamine usage in treatment resistant depression (TRD) has been demonstrated in numerous studies. In most of these studies, individuals with BPD were not excluded, thus given the high co-occurrence of these disorders, it is possible that the beneficial effects of ketamine also extend to the subpopulation with comorbid TRD and BPD. However, no protocols were developed that would account for comorbidity. Moreover, psychotherapeutic interventions, which may be crucial for achieving a lasting therapeutic effect in TRD and BPD comorbidity, were not included. In the article, we discuss the results of a small number of existing studies and case reports on the use of ketamine in depressive disorders with comorbid BPD. We elucidate how, at the molecular and brain network levels, ketamine can impact the neurobiology and symptoms of BPD. Furthermore, we explore whether ketamine-induced neuroplasticity, augmented by psychotherapy, could be of use in alleviating core BPD-related symptoms such as emotional dysregulation, self-identity disturbances and self-harming behaviors. We also discuss the potential of ketamine-assisted psychotherapy (KAP) in BPD treatment. As there is no standard approach to the application of ketamine or KAP in individuals with comorbid TRD and BPD, we consider further research in the field as imperative. The priorities should include development of dedicated protocols, distinguishing subpopulations that may benefit most from such treatment and investigating factors that may influence its effectiveness and safety.

A scientometric analysis of research on the role of NMDA receptor in the treatment of depression.

There have been numerous studies on NMDA receptors as therapeutic targets for depression. However, so far, there has been no comprehensive scientometric analysis of this field. Thus, we conducted a scientometric analysis with the aim of better elucidating the research hotspots and future trends in this field. Publications on NMDAR in Depression between 2004 and 2023 were retrieved from the Web of Science Core Collection (WoSCC) database. Then, VOSviewer, CiteSpace, Scimago Graphica, and R-bibliometrix-were used for the scientometric analysis and visualization. 5,092 qualified documents were identified to scientometric analysis. In the past 20 years, there has been an upward trend in the number of annual publications. The United States led the world in terms of international collaborations, publications, and citations. 15 main clusters were identified from the co-cited references analysis with notable modularity (Q-value = 0.7628) and silhouette scores (S-value = 0.9171). According to the keyword and co-cited references analysis, treatment-resistant depression ketamine (an NMDAR antagonist), oxidative stress, synaptic plasticity, neuroplasticity related downstream factors like brain-derived neurotrophic factor were the research hotspots in recent years. As the first scientometric analysis of NMDAR in Depression, this study shed light on the development, trends, and hotspots of research about NMDAR in Depression worldwide. The application and potential mechanisms of ketamine in the treatment of major depressive disorder (MDD) are still a hot research topic at present. However, the side effects of NMDAR antagonist like ketamine have prompted research on new rapid acting antidepressants.

GluN2A mediates ketamine-induced rapid antidepressant-like responses.

Ketamine was thought to induce rapid antidepressant responses by inhibiting GluN2B-containing N-methyl-D-aspartic acid (NMDA) receptors (NMDARs), which presents a promising opportunity to develop better antidepressants. However, adverse side effects limit the broader application of ketamine and GluN2B inhibitors are yet to be approved for clinical use. It is unclear whether ketamine acts solely through GluN2B-dependent mechanisms. The present study reports that the loss of another major NMDAR subunit, GluN2A, in adult mouse brains elicits robust antidepressant-like responses with limited impact on the behaviors that mimic the psychomimetic effects of ketamine. The antidepressant-like behavioral effects of broad NMDAR channel blockers, such as ketamine and MK-801 (dizocilpine), were mediated by the suppression of GluN2A, but not by the inhibition of GluN2B. Moreover, treatment with ketamine or MK-801 rapidly increased the intrinsic excitability of hippocampal principal neurons through GluN2A, but not GluN2B. Together, these findings indicate that GluN2A mediates ketamine-triggered rapid antidepressant-like responses.

Simultaneous application of lidocaine and ketamine during ambulatory infusion therapy: a retrospective analysis.

Background: Infusions with lidocaine or ketamine have been separately established in the treatment of chronic pain. This study aims to retrospectively evaluate the effect of combined infusions of lidocaine and ketamine. Materials & methods: Patient records were screened for receipt of combined ambulatory infusions of lidocaine and ketamine from 2012 through 2021. A scoring system was designed to assess pain response retrospectively. Results: Atotal of 319 patients were included. Median pain reduction in days was 10.00 (interquartile range: 13.25). Side effects were limited to the acute phase of infusions. Atotal of 41.4% of patients who received concomitant pain medication reported a dose reduction. Conclusion: Our data support combined infusions as a safe therapy option, with good short-, medium- and long-term reductions in pain and great heterogeneity in treatment response. Clinical trial registration: ClinicalTrials.gov (NCT05103319).

Application of Ketamine in Pain Management and the Underlying Mechanism.

Since ketamine was approved by the FDA as an intravenous anesthetic, it has been in clinical use for more than 50 years. Apart from its anesthetic effects, ketamine is one of the few intravenous anesthetics with potent analgesic properties. As part of the effort to develop pain management, renewed interest has focused on the use of ketamine for the treatment of acute and chronic pain. Ketamine is commonly used to treat various kinds of chronic pain syndromes and is also applied to control perioperative pain and reduce the consumption of postoperative analgesics. However, its precise mechanisms of action remain mysterious for a large part. Despite extensive research in the field, the mechanism of ketamine is still unclear. Its analgesic effect appears to be largely mediated by blockade of NMDARs, but opioid, GABA, and monoaminergic system seem to partly participate in the pain transmission procedure. Its metabolites also have an analgesic effect, which may prolong pain relief. More recently, the antidepressant effect of ketamine has been considered to reduce pain-related aversion to relieve chronic pain. Overall, the analgesic mechanism of ketamine seems to be a complex combination of multiple factors. Due to its potent analgesic properties, ketamine is an analgesic with great clinical application prospects. Exploring the precise mechanism of action of ketamine will help guide clinical medication and confirm indications for ketamine analgesia. This review aims to list the application of ketamine in pain management and discuss its analgesic mechanism.

Intravenous ketamine for benzodiazepine deprescription and withdrawal management in treatment-resistant depression: a preliminary report

We present the first evidence that sub-anesthetic ketamine infusions for treatment resistant depression (TRD) may facilitate deprescription of long-term benzodiazepine/z-drugs (BZDRs). Long-term BZDR prescriptions are potentially harmful yet common, partly because of challenging withdrawal symptoms. Few pharmacological interventions have evidence for facilitating BZDR discontinuation, and none in patients actively suffering from TRD. In this ambi-directional cohort study, discontinuation of long-term (>6 month) BZDRs was attempted in 22 patients with severe unipolar or bipolar TRD receiving a course of six subanesthetic ketamine infusions over four weeks. We investigated the rates of successful BZDRs deprescription, trajectories of acute psychological withdrawal symptoms, and subsequent BZDRs abstinence during a mean follow-up of 1 year (primary outcome). Clinically significant deteriorations in depression, anxiety, sleep, and/or suicidality during the acute BZDR discontinuation phase were measured by repeated standardized scales and analyzed by latent growth curve models and percent correct classification analysis. Of the 22 eligible patients, all enrolled in this study and 91% (20/22) successfully discontinued all BZDRs by the end of the 4-week intervention, confirmed by urinary analyses. Less than 25% of discontinuers experienced any significant worsening of anxiety, depression, sleep difficulties, or suicidality during treatment. During follow-up (mean [range] duration, 12 [3–24] months), 64% (14/22) of patients remained abstinent from any BZDRs. These preliminary results suggest that ketamine infusions for TRD may facilitate the deprescription of BZDRs, even in patients with active depressive symptoms and significant comorbidity. Further investigation is warranted into this potential novel application of ketamine.

Phase II study about efficacy and safety of the continuous intravenous infusion of ketamine as adjuvant to opioids in terminally ill cancer patients with refractory cancer pain.

e24139 Background: The ketamine is used to control refractory cancer pain as adjuvant to opioids. However, usefulness of ketamine has not yet been confirmed due to lack of previous studies. Additionally, most of prior studies were studied in heterogenous patients, and continuous intravenous infusion (CIVI) method was rare. The CIVI method using gradual dose titrations of ketamine is safe. So, it is suitable to terminally ill cancer patients who have available IV access but vulnerable to AEs. This phase II single-arm study investigated efficacy and safety of CIVI of Ketamine in these population. Methods: Cancer patients with expected limited survival time within several months and refractory cancer pain were enrolled. Refractory cancer pain indicates requirements of breakthrough analgesics ≥ 4 times/day or average pain score > personalized pain goal (PPG) in spite of intravenous Morphine Equivalent Daily Dose (MEDD) > 120 mg/day. The CIVI of ketamine was increased from 0.05 mg/kg/hr to 0.5 mg/kg/hr by 0.05 mg/kg/hr every 8hr when average pain score exceeded PPG or breakthrough was needed ≥ 2 times/8hr during 5 days. The primary end-point was overall pain response rate, which indicates complete response (both breakthrough ≤ 3/day and NRS ≤ PPG) plus partial response (breakthrough ≤ 3/day), without unacceptable toxicities. A total of 26 patients are needed to verify assumption of response rate of 40% with width of 0.4 for two-sided 95% CI and assuming 5% drop-out rate. This study was prematurely terminated at enrollment of 21 patients. Results: Among 21 enrolled patients between SEP 2019 and JAN 2023, 20 were analyzed except 1 due to early transfer. Most pain mechanisms were mixed type (n = 15, 75%), while some reported nociceptive pain (n = 3, 15%) or neuropathic pain (n = 2, 10%). The baseline background opioids were MEDD 186 mg/day (range, 124-592), number of breakthrough opioids were 5 (IQR, 5-7). The median PPG were 4 (range, 3-6). After application of ketamine, overall pain response rate was 45% (n = 9), complete pain response was 35% (n = 7) and partial pain response was 10% (n = 2). The other 11 were non-responders (six failed to achieve overall pain response despite of maximal dose or completing 5 days of ketamine, five patients discontinued the treatment due to AEs). AEs included confusion (n = 9, 45%), dizziness (n = 3, 15%), and hypertension (n = 2, 10%). Communication capacities were sustained in 10 patients and decreased in other 10 patients. OS were 21 days (95% CI, 18.1-23.9). Conclusions: Our study showed efficacies and safeties of gradually increasing CIVI of ketamine for terminally ill cancer patients with refractory cancer pain. The CIVI of ketamine can be a useful tool in these patients considering limited treatment options. Further studies comparing usefulness of CIVI of ketamine and usual practice with opioids escalation are needed (NCT03362073). Clinical trial information: NCT03362073 .

Application of Compound Ketamine and Pentobarbital Sodium in Orthopedic Surgery on Mice and Its Anesthesia Effect

Application of Compound Ketamine and Pentobarbital Sodium in Orthopedic Surgery on Mice and Its Anesthesia Effect

The Possible Application of Ketamine in the Treatment of Depression in Alzheimer's Disease.

Depression is a leading cause of disability globally, with a prevalence of 3.8% among the whole population, 5% of the adult population, and 5.7% of the elderly population over 60 years of age. There is evidence that depression is linked to certain neurodegenerative diseases, one being Alzheimer’s disease (AD). The efficacy of conventional antidepressants to treat depression in AD is conflicting, especially regarding selective serotonin reuptake inhibitors (SSRIs). A recent systemic review and meta-analysis of 25 randomized controlled trials including fourteen antidepressant medications showed no high efficacy in treating AD patients’ symptoms. However, ketamine, a nonselective N-methyl-D-aspartate (NMDA) receptor antagonist, can mediate a wide range of pharmacological effects, including neuroprotection, anti-inflammatory and anticancer properties, multimodal analgesia, and treatment of depression, suicidal attempts, and status epilepticus. Esketamine, which is ketamine formulated as a nasal spray, was approved by the Federal Drug Administration (FDA) in March 2019 as an adjuvant drug to treat treatment-resistant depression. NMDA receptor antagonists treat AD through offsetting AD-related pathological stimulation of subtypes of glutamate receptors in the central nervous system. Recent clinical findings suggest that ketamine may provide neuroprotection and reduce neuropsychiatric symptoms associated with AD. In the present investigation, we evaluate the potential role of ketamine and its postulated mechanism in AD management.

Ketamine inhibits TNF-\u03b1-induced cecal damage by enhancing RIP1 ubiquitination to attenuate lethal SIRS

Systemic inflammatory response syndrome (SIRS) is a sepsis-associated inflammatory state and a self-defense mechanism against specific and nonspecific stimuli. Ketamine influences many key processes that are altered during sepsis. However, the underlying mechanisms remain incompletely understood. In this study, TNF-α-treated mice, as well as HT-29 and L929 cell models, were applied to characterize TNF-α-induced systemic and local cecal tissue inflammatory responses. Behavioral, biochemical, histological, and molecular biological approaches were applied to illustrate the related processes. Mice with TNF-α-induced SIRS showed systemic and local cecal tissue inflammatory responses, as indicated by increased levels of high mobility group box 1 protein (HMGB1), chemokines (C-X-C motif) ligand 10 (CXCL10), interleukin-6 (IL-6), and IL-10, as well as high mortality. Ketamine pretreatment alleviated death rates, symptoms, and the production of inflammatory cytokines induced by TNF-α in mice. Moreover, ketamine also protected the mice from TNF-α-induced cecal damage by suppressing the phosphorylation of receptor-interacting serine/threonine-protein kinase 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL). In addition, our results showed that ketamine efficiently inhibited TNF-α-induced necroptosis in HT-29 and L929 cells. Furthermore, we explored the mechanism using different L929 cell lines. The results displayed that ketamine inhibited TNF-α-induced necroptosis by enhancing RIP1 ubiquitination and reducing the RIP1-RIP3 and RIP3-MLKL interactions, as well as the formation of necrosomes. Thus, our study may provide a new theoretical and experimental basis for treating diseases characterized by SIRS-associated inflammatory factor storms. Moreover, our exploration may provide potential molecular mechanisms and targets for therapeutic intervention and clinical application of ketamine.

Comparison of effect of intra socket ketamine and tramadol on postoperative pain after mandibular third molar surgery.

Aim:This study compared the analgesic efficacy of intra socket application of tramadol versus ketamine for preventing pain after mandibular third molar surgery.Materials and Methods:Thirty patients who had undergone third molar surgery were randomly divided into three groups: Group T (tramadol 1 mg/kg), Group K (ketamine 0.5 mg/kg), and Group C (saline 2 mL). The treatment was applied to the extraction sockets using resorbable gel foam. Average time taken for the procedure was recorded. Pain was evaluated postoperatively using a visual analog scale (VAS) at 6 and 24 h postoperatively. Furthermore, the number of analgesics taken in the 1st24 h was recorded. The relevant information was gathered and tabulated. IBM SPSS 2.0 was used to analyze the results and one-way ANOVA test was used to determine the statistical significance.Results:The VAS scores after extraction were statistically higher in Group C than in either treatment group. Group K had the lowest pain intensity. During the 1st6 h, patients reported statistically lower pain intensity scores in Groups K and T versus Group C. At 24 h, Group K had the lowest pain intensity and Group T had less pain than Group C. The number of analgesics taken in the 1st24 h was highest in Group C.Conclusion:This study shows that intra socket use of tramadol and ketamine can be used as effective alternatives for decreasing pain after third molar surgery.

Drug Repositioning Ketamine as a New Treatment for Bipolar Disorder Using Text Mining

Bipolar Disorder (BD), a chronic mental illness, does not have an ideal treatment, and patients with BD have a higher chance of being diagnosed with alcohol abuse, liver disease, and diabetes. The goal of treatment is to prevent a relapse in BD episodes and find a new treatment. The research here looks at the genetics of BD and ignores environmental factors, as they are subjective. Therapy treats known environmental triggers and stressors and explores methods to reduce them. However, therapy alone cannot fully alleviate the symptoms of BD. My research employs text-mining as a primary strategy to obtain relevant genes and drugs pertaining to BD. The main gene involved is the Brain-Derived Neurotrophic Factor (BDNF). Popular drugs currently used for treatment of BD are Lithium and Carbamazepine. Using CMapPy to look at gene expression data, one sees a relationship between the two drug therapies and BDNF. Lithium fails to treat mania and Carbamazepine fails to treat depression, relatively speaking. When comparing gene expression data of Lithium and Carbamazepine with Ketamine, a newer therapy for BD, Ketamine, raises the BDNF level, keeps it elevated, and effectively controls BD episodes. Ketamine does not have the shortcomings that Lithium and Carbamazepine have. Next steps would include conducting a clinical trial with the hopeful application of Ketamine as a new treatment for BD.

A Novel Application of Ketamine for Improving Perioperative Sleep Disturbances.

Perioperative sleep disturbances are commonly observed before, during, and after surgery and can be caused by several factors, such as preoperative negative moods, general anesthetics, surgery trauma, and pain. Over the past decade, the fast-acting antidepressant effects of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine represent one of the most attractive discoveries in the field of psychiatry, such as antidepressant and anxiolytic effects. It is also widely used as a short-acting anesthetic and analgesic. Recent research has revealed new possible applications for ketamine, such as for perioperative sleep disorders and circadian rhythm disorders. Here, we summarize the risk factors for perioperative sleep disturbances, outcomes of perioperative sleep disturbances, and mechanism of action of ketamine in improving perioperative sleep quality.

Parental Attitudes Toward Use of Ketamine in Adolescent Mood Disorders and Suicidality.

Objectives: Investigation into parental decision-making processes involving ketamine is of high priority, given the necessary role of parents in consenting to treatment. In this study, we examined parental attitudes toward the emerging use of ketamine in adolescent mood disorders and suicidality. Methods: Two hundred eighty-three English-speaking parents completed an online survey using Amazon Mechanical Turk on psychiatric use of ketamine, acceptability of treatment, and their perceptions of ketamine treatment. Data quality control measures were used to mitigate invalid reporting. Results: Parents reported high acceptability toward use of ketamine for suicidality, major depressive disorder, and bipolar disorder in adolescents. Primary concerns around ketamine involved its potential side effects and lack of United States Food and Drug Administration (FDA) approval. Responses indicated a preference for short-term applications and less invasive routes of administration for ketamine. Parent history of mental illness, familiarity with psychological treatments, and comfort using other mental health interventions in their children predicted greater acceptability of ketamine. Conclusion: Although ketamine is not currently approved by the FDA for psychiatric use in children nor recommended outside of research protocols, these findings suggest that parents have interest in the application of ketamine as a treatment for pediatric mood disorders and point to future directions for research and clinical orientation.

Neuroprotective effect of ketamine against TNF-α-induced necroptosis in hippocampal neurons.

Tumour necrosis factor‐α (TNF‐α), a crucial cytokine, has various homeostatic and pathogenic bioactivities. The aim of this study was to assess the neuroprotective effect of ketamine against TNF‐α‐induced motor dysfunction and neuronal necroptosis in male C57BL/6J mice in vivo and HT‐22 cell lines in vitro. The behavioural testing results of the present study indicate that ketamine ameliorated TNF‐α‐induced neurological dysfunction. Moreover, immunohistochemical staining results showed that TNF‐α‐induced brain dysfunction was caused by necroptosis and microglial activation, which could be attenuated by ketamine pre‐treatment inhibiting reactive oxygen species production and mixed lineage kinase domain‐like phosphorylation in hippocampal neurons. Therefore, we concluded that ketamine may have neuroprotective effects as a potent inhibitor of necroptosis, which provides a new theoretical and experimental basis for the application of ketamine in TNF‐α‐induced necroptosis‐associated diseases.

Efficacy of topical agents for prevention of postoperative sore throat after single lumen tracheal intubation: a Bayesian network meta-analysis.

The optimal choice of prophylactic drugs to decrease postoperative sore throat is unclear. The objective of this network meta-analysis (NMA) was to compare and rank 11 topical agents used to prevent postoperative sore throat. Various databases were searched independently for randomized-controlled trials (RCTs) comparing topical agents used for the prevention of postoperative sore throat. Inclusion criteria were parallel group studies comparing intervention with active or inactive control and reporting postoperative sore throat. The primary outcome was postoperative sore throat at 24 hr. Secondary outcomes were early sore throat at 4-6 hr, cough, and hoarseness at 24 hr. Evidence was synthesized from 70 RCTs reporting 7,141 patients. Topical application of lidocaine, corticosteroids, ketamine, magnesium, benzydamine, water-based lubricant, and liquorice applied along the tracheal tube, to the tracheal tube cuff, gargled or sprayed were compared with intracuff air and each other. Bayesian NMA showed that magnesium (odds ratio [OR], 0.10; 95% credible interval [CrI], 0.03 to 0.26), liquorice (OR, 0.14; 95% CrI, 0.03 to 0.55), and steroid application (OR, 0.11; 95% CrI, 0.06 to 0.22) most effectively prevented postoperative sore throat at 24 hr. Topical lidocaine was the least effective intervention. Topical application of magnesium followed by liquorice and corticosteroids most effectively prevented postoperative sore throat 24 hr after endotracheal intubation.

Impact of Ketamine on Pain Management in Cesarean Section: A Systematic Review and Meta-Analysis

The pain control effect of ketamine versus control in women during cesarean operation is not well determined. The present meta-analysis aimed to evaluate the clinical efficacy of ketamine versus control in cesarean section anesthesia for reducing the postoperative pain and analgesia. We used meta-analysis to address this concern. Meta-analysis-based study. The databases PubMed, Embase, and the Cochrane Library were systematically searched to identify the relevant randomized controlled trials (RCTs) of ketamine versus control in controlling pain after cesarean section from inception to August 2018. Based on the Cochrane Handbook, the combined analysis was performed using Revman 5.3 software. A total of 20 RCTs with 1,737 patients who underwent cesarean section were included. Meta-analysis showed that the pain score in the ketamine group was less than that of the control group (mean difference [MD], -1.10; 95% confidence interval [CI], -1.61, -0.59; P < 0.0001). Application of ketamine during cesarean section also resulted in decreased consumption of morphine when compared with the control group (MD, -6.11 mg; 95% CI, -9.93, -2.29; P = 0.002). In addition, the first time required for analgesia was significantly longer in the ketamine group than that of the control group (MD, 72.48 minutes; 95% CI, 50.85, 94.11; P < 0.00001). Limited patients were included with moderate strength. Ketamine supplementation during cesarean section reduces pain and morphine consumption and prolongs the postoperative analgesia. Ketamine, cesarean section, randomized controlled trials, meta-analysis.

Registered clinical trials investigating ketamine for psychiatric disorders

As interest has grown in the potential psychiatric applications of ketamine, the number of registered clinical trials has grown substantially. Herein, we summarize and analyze clinical trials registered with ClinicalTrials.gov that assess the treatment of any psychiatric disorder with ketamine or ketamine enantiomers (e.g., S-ketamine, R-ketamine), with a focus on ongoing clinical trials. A ClinicalTrials.gov search on February 21, 2020 returned 140 registered trials. Frequency data was analyzed to determine the distribution of study designs. The majority of trials (70%) investigated the therapeutic effect of ketamine in mood disorders (unipolar: 60%, bipolar: 0.7%, both: 5.7%). Suicidal ideation (13.1%), post-traumatic stress disorder (5.4%), and obsessive-compulsive disorder (3.6%) were also investigated. Intravenous (IV) administration was the most common route with 87% of the studies using IV ketamine. Single-dose studies represented 50% of IV ketamine studies. Few studies were assessing maintenance treatment. Most studies were phase I or II with few definitive phase III trials registered. Given the large number of ongoing studies assessing psychiatric application of ketamine, researchers and relevant stakeholders should consider not only completed, published studies, but also ongoing registered studies in adjudicating the most relevant research questions. More definitive phase III trials and maintenance studies of IV ketamine for mood disorders are required, as numerous completed and ongoing studies have already assessed and demonstrated the proof-of-concept of acute antidepressant effects in phase I and II trials.

The efficacy of ketamine for postoperative pain control in adolescent patients undergoing spinal fusion surgery for idiopathic scoliosis.

The use of ketamine in conjunction with morphine to reduce postoperative pain has been explored in several different surgery subtypes with conflicting results. Ketamine has shown promise to have both opioid sparing and analgesic effects in the postoperative setting. This study aimed to elucidate ketamine's ability to reduce morphine equivalent consumption and improve patient satisfaction after spinal fusion surgery for the correction of idiopathic scoliosis. This surgery is known to be associated with significant postoperative pain which impedes the ability to improve patient satisfaction, and may complicate the recovery timeline. Currently, the standard therapeutic regimen consists of patient-controlled analgesia morphine and the use of other opioids such as hydromorphone. A prospective, randomized double-blinded, placebo-controlled trial was performed to compare the standard morphine equivalent therapy alone against a standard therapy in conjunction with ketamine. Fifty adolescent patients were enrolled and randomized. Results yielded a significant reduction in postoperative morphine equivalent consumption (p = 0.042), adjusted postoperative pain scores (p < 0.001), and incidence of nausea and vomiting (p = 0.045). The application of ketamine as an analgesic in conjunction with the current standard of morphine equivalent therapy may serve as a superior pain control regimen for spinal surgeries in young population. This regimen enhancement may be generalizable to other surgery subtypes within similar populations. LEVEL OF EVIDENCE: Level I.

Topical application of ketamine to prevent postoperative sore throat in adults: A systematic review and meta-analysis.

Postoperative sore throat is a leading undesirable postoperative outcome. Ketamine is an N-methyl-d-aspartate receptor antagonist and its topical application is used for chronic pain and oral/throat indications. We conducted a systematic review to assess the efficacy of preoperative, topical ketamine application for preventing postoperative sore throat. We searched MEDLINE, EMBASE, and CENTRAL through September 23, 2019 for randomized controlled trials in which at least one intervention was topical ketamine to prevent postoperative sore throat in adults undergoing endotracheal intubation. The primary outcome was the incidence of sore throat at 24hours postoperatively. The comparators were non-analgesic controls (placebo, no treatment, or usual care) or active agents. We pooled the data using a random-effects model. We included 41 randomized controlled trials involving 3784 participants. Topical ketamine was associated with reduced incidence of sore throat at 24hours postoperatively compared to non-analgesic methods (risk ratio, 0.45; 95% CI, 0.37-0.54; P<.001). We found significant publication bias, but the results remained unchanged with a trim-and-fill analysis. Trial sequential analysis (TSA) suggested that the efficacy of topical ketamine was adequate (TSA-adjusted 95% CI, 0.33-0.56). The GRADE quality for this evidence was moderate. Topical ketamine was inferior to a combination of nebulized ketamine and clonidine in preventing postoperative sore throat. Preoperative, topical ketamine application may be more effective than non-analgesic methods in preventing postoperative sore throat. The number of studies did not suffice to determine the place of topical ketamine among agents to prevent postoperative sore throat.