The Use of Ketamine Sedation for the Treatment of Nail Bed Repairs in the Pediatric Emergency Department.

AIM: This study aimed to determine if sedation with ketamine is safe and effective for the treatment of nail bed injuries in the pediatric emergency department (PED). METHOD: A retrospective cohort study was carried out during a 9-month period in children aged between 18 months and 15 years, presenting to PED requiring nail bed repair. We documented complications of sedation, clinical outcome of the repair both immediate and at follow-up, and parental satisfaction at 4 months. A cost analysis was also undertaken. RESULTS: Ten repairs were performed. There were no serious adverse events. The average satisfaction score was 9.4/10. All patients were discharged from follow-up by 3 months. There was a cost saving of approximately £1500 per case. CONCLUSIONS: We have demonstrated nail bed injury repair facilitated by sedation with ketamine to be safe, effective, and cost efficient in the PED. This management strategy, brought to the fore during the COVID-19 pandemic, should be adopted widely in PEDs.

Antidepressant Effect of Ketamine on Inflammation-Mediated Cytokine Dysregulation in Adults with Treatment-Resistant Depression: Rapid Systematic Review.

Background: Major depressive disorder (MDD) and treatment-resistant depression (TRD) represent a global source of societal and health burden. To advise proper management of inflammation-related depression among TRD patients, it is important to identify therapeutic clinical treatments. A key factor is related to proinflammatory cytokines such as interleukin- (IL-) 1ß, IL-6, and tumor necrosis factor- (TNF-) α which have been implicated in the pathogenesis of depressive symptoms in MDD patients. Ketamine may provide an anti-inflammatory therapeutic strategy by targeting proinflammatory pathways associated with depressive disorders, which may be exacerbated in the ageing population with TRD. Objective: Despite a burgeoning body of literature demonstrating that inflammation is linked to TRD, there is still a lack of comprehensive research on the relationship between proinflammatory biomarkers and ketamine's antidepressant effect on TRD patients. Method: The Cochrane Library and PubMed/MEDLINE databases were systematically searched from inception up to February 1, 2022, adopting broad inclusion criteria to assess clinical topics related to the impact of ketamine on inflammatory cytokines in TRD patients. The present work is in compliance with the World Health Organization Rapid Review Guide. Results: Five out of the seven studies examined in this review show that ketamine infusion may reduce depressive symptoms with a quick start of effect on TRD patients. Based on the Montgomery-Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-D) scores, the overall response rate for ketamine was 56%; that is, 56% of those treated with ketamine had MADRS/HAM-D scores decreased by at least 50%. Conclusions: While the anti-inflammatory effects of ketamine modulate specific proinflammatory cytokines, its rapid antidepressant effect on TRD patients remains inconsistent. However, our study findings can provide a reliable basis for future research on how to improve systemic inflammatory immune disorders and mental health. We suggest that ketamine infusion may be part of a comprehensive treatment approach in TRD patients with elevated levels of depression-specific inflammatory biomarkers.

Association of intranasal esketamine, a novel 'standard of care' treatment and outcomes in the management of patients with treatment-resistant depression: protocol of a prospective cohort observational study of naturalistic clinical practice.

INTRODUCTION: Esketamine is the S-enantiomer of racemic ketamine and has been approved by the Food and Drug Administration for the management of treatment resistant depression, demonstrating effective and long-lasting benefits. The objective of this observational study is to elucidate the association of intranasal (IN) esketamine with beneficial and negative outcomes in the management of treatment resistant major depressive disorder. METHODS AND ANALYSIS: This is a multicentre prospective cohort observational study of naturalistic clinical practice. We expect to recruit 10 patients per research centre (6 centres, total 60 subjects). After approval to receive IN esketamine as part of their standard of care management of moderate to severe treatment resistant depression, patients will be invited to participate in this study. Association of esketamine treatment with outcomes in the management of depression will be assessed by measuring the severity of depression symptoms using the Montgomery-Åsberg Depression Rating Scale (MADRS), and tolerability by systematically tracking common side effects of ketamine treatment, dissociation using the simplified 6-Item Clinician Administered Dissociative Symptom Scale and potential for abuse using the Likeability and Craving Questionnaire (LCQ). Change in depressive symptoms (MADRS total scores) over time will be evaluated by within-subject repeated measures analysis of variance. We will calculate the relative risk associated with the beneficial (reduction in total scores for depression) outcomes, and the side effect and dropout rates (tolerability) of adding IN esketamine to patients' current pharmacological treatments. Covariate analysis will assess the impact of site and demographic variables on treatment outcomes. ETHICS AND DISSEMINATION: Approval to perform this study was obtained through the Health Sciences Research Ethics Board at Queen's University. Findings will be shared among collaborators, through departmental meetings, presented on different academic venues and publishing our manuscript.

Ketamine for post-operative pain treatment in spinal surgery. A protocol for a systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Post-operative pain treatment with ketamine has been demonstrated to have post-operative opioid-sparing and anti-hyperalgesic effects. However, evidence regarding the beneficial and harmful effects and the optimal dose and timing of perioperative treatment with ketamine for patients undergoing spinal surgery is unclear. The objective of this systematic review is to assess the analgesic, serious and non-serious adverse effects of perioperative pain treatment with ketamine for patients undergoing spinal surgery. METHODS: This protocol for a systematic review is written according to The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will search Embase, CENTRAL, PubMed, WHO's ICTRP, EU Clinical Trial Register and ClinicalTrials.gov to identify relevant randomised clinical trials. We will include all randomised clinical trials assessing perioperative ketamine treatment versus placebo or no intervention for patients undergoing spinal surgery. Two authors will independently screen trials for inclusion using Covidence, extract data and assess risk of bias using Cochrane's RoB tool. We will analyse data using Review Manager and Trial Sequential Analysis. Meta-analysis will be performed according to the Cochrane guidelines and results will be validated according to the eight-step procedure suggested by Jakobsen et al. We will present our primary findings in a 'summary of findings' table. We will evaluate the overall certainty of evidence using the GRADE approach. DISCUSSION: This systematic review will assess the beneficial and harmful effects of perioperative pain treatment with ketamine for patients undergoing spinal surgery and have the potential to inform best practice and advance research.

Reviewing the physiology, pharmacology and therapeutic uses of ketamine.

Ketamine is a synthetic drug with unique properties which started to be used therapeutically in humans in the 1970s and is now widely used in all fields of nursing. Ketamine acts on the central nervous system, primarily through inhibiting N-methyl-D-aspartate receptors. However, the precise understanding of its mechanisms of action remains elusive in many respects. Ketamine is frequently used as an anaesthetic in medical and surgical procedures and as an analgesic in children and adults. It is increasingly used in mental health settings to treat depression. It has potential to be used more often in areas such as palliative care and mental health care. This article reviews the physiological and pharmacological properties of ketamine, explores its main therapeutic uses, and considers the associated implications for nursing practice.

Real-world effectiveness of repeated ketamine infusions for treatment resistant depression during the COVID-19 pandemic.

Herein we evaluate the impact of COVID-19 restrictions on antidepressant effectiveness of intravenous (IV) ketamine in adults with treatment-resistant depression (TRD). We conducted a case series analysis of adults with TRD (n = 267) who received four ketamine infusions at an outpatient clinic in Ontario, Canada, during COVID-19 restrictions (from March 2020 - February 2021; n = 107), compared to patients who received treatment in the previous year (March 2019 - February 2020; n = 160). Both groups experienced significant and comparable improvements in depressive symptoms, suicidal ideation, and anxiety with repeated ketamine infusions. Effectiveness of IV ketamine was not attenuated during the COVID-19 period.

Ketamine's rapid antisuicidal effects are not attenuated by Buprenorphine.

Ketamine's rapid antisuicidal action has gathered significant clinical interest in treatment of depression though concerns exist that its actions occur through the Opioid pathway. A recent study additionally reported that Naltrexone blocks antisuicidal effects of Ketamine suggesting that its antisuicidal effects are also due to opioid mechanisms. We present a case of treatment refractory depression with recent suicide attempt and active suicidal ideations who was on an Opioid partial agonist, Buprenorphine, for management of pain. Patient responded to a trial of IV ketamine treatment with rapid improvement in suicidal thoughts. Patient's suicidal ideations decreased after first Ketamine treatment and resolved after second treatment while maintained on Buprenorphine. Our finding shows that Buprenorphine does not block Ketamine's effects on suicidal ideations and therefore Ketamine treatment could be provided safely in controlled environment to those with substance use disorders or with chronic pain while being maintained on Buprenorphine. Additionally, our case suggests that non-Opioid mechanisms may be involved in Ketamine's antidepressant effects and its response to suicidal ideations in those on Opioid partial agonists.

Perspectives of Ketamine Use in COVID-19 Patients.

Hospitalized coronavirus disease 2019 (COVID-19)-infected patients suffer from both physical impairments and mental stress. Respiratory insufficiency and cardiovascular disturbances require most of the intensive care interventions, but they are also accompanied by depressive conditions, sadness and fear of dying. Sedatives are mostly respiratory and cardiovascular depressants and do not provide resistance to the pro-inflammatory burst induced by the virus. Ketamine is a unique and safe drug that enables well-controlled sedation and anesthesia, attenuates depression and mitigates suicidal thoughts, without depressing respiratory or cardiovascular mechanics. This brief communication highlights the benefits potentially provided by ketamine to patients hospitalized for COVID-19 infection.