Efficacy Of Intranasal Ketamine Research Articles

Safety and Efficacy of Intranasal Ketamine for Minor Pediatric Procedures: A Systemic Literature Review.

Compared to intravenous anesthetics, intranasalmedication for sedation is a less invasive approach. Intranasal ketamine (IK) is a widely used medication for procedural sedation. Hence, a systematic review was conducted with the aim of evaluating the safety and efficacy of IK among pediatric patients used for procedural sedation. For this purpose, a literature search was conducted on PubMed, Web of Science, and MEDLINE. A total of 247 search results appeared after running the developed query andeight articles passed through the inclusion and exclusion criteria and were included in the study. Most of the studies used 4 to 7 mg/kg dose of IK for pediatric patients. It was found that there was a moderate correlation between the age and dose of IK. Similarly, the dose of IK also had a direct and moderate correlation with the onset of sedation. Regarding the reported side effects, most of the studies reported nausea and vomiting as side effects of IK. Hence, it could be concluded from the study findings that effective sedation can be achieved by using 4 to 7 mg/kg dose of IK. The reported side effects ofIK were minor while parental satisfaction with the drug was very high. Therefore, it can be concluded that the use of IK for procedural sedation among pediatric patients is safe and effective.

The Safety, Clinical, and Neurophysiological Effects of Intranasal Ketamine in Patients Who Do Not Respond to Electroconvulsive Therapy: Protocol for a Pilot, Open-Label Clinical Trial.

BackgroundMajor depressive disorder is among the most disabling illnesses worldwide, with a lifetime prevalence of 16.2%. Research suggests that 20% to 40% of patients with depression do not respond to pharmacotherapy, developing treatment-resistant depression. Electroconvulsive therapy is the gold standard for treating individuals with treatment-resistant depression, with remission rates of approximately 75% to 90%. However, 10% to 25% of patients do not respond to electroconvulsive therapy, and many are unable to tolerate it due to the side effects. Both groups are considered to be patients who do not respond to electroconvulsive therapy, because both groups continue to exhibit symptoms of severe depression, have a limited number of treatment options available, and are in need of rapid treatment. Ketamine, an N-methyl-D-aspartate receptor antagonist, has been shown to exert rapid antidepressant effects in patients with treatment-resistant depression when administered in subanesthetic doses through 40-minute intravenous infusions. Recently, a ketamine compound, esketamine (Spravato), that is administered through the intranasal route received regulatory approval by the US Food and Drug Administration and Health Canada to treat depression. However, esketamine is challenging to access due to high costs and limited availability. Racemic ketamine (rketamine) is cheap and easy to access; however, the effects in patients who have not responded to electroconvulsive therapy have yet to be understood or tested. This study will use transcranial magnetic stimulation to study mechanisms of human brain cortical physiology at the systemic level to identify neurobiomarkers of response.ObjectiveThe objective of this open-label pilot clinical trial is to test the feasibility and safety of intranasal ketamine in patients who have not responded to electroconvulsive therapy. The primary outcome is to determine the feasibility of a larger randomized controlled trial to test the efficacy of intranasal ketamine for patients who have not responded to electroconvulsive therapy for clinical indicators in unipolar depression. The secondary outcome is to determine the preliminary effects of an intervention on clinical outcomes, such as depressive symptoms, suicidal ideation, and quality of living. The third outcome is to explore neurophysiological changes as measured by transcranial magnetic stimulation electromyography and electroencephalography to measure changes in cortical excitability as potential predictors of clinical response.MethodsA sterile solution of racemic ketamine hydrochloride will be administered twice per week for 4 weeks (8 sessions) intranasally to patients with treatment-resistant depression who did not respond to or could not tolerate an acute course of electroconvulsive therapy. We will recruit 25 adults (24-65 years old) over the course of 2 years from an academic psychiatric hospital in Toronto, Canada.ResultsThis study has received ethics approval, and funding has been secured. The study is currently active.ConclusionsThis is the first study to test repeated doses of intranasal rketamine in patients who have not responded to electroconvulsive therapy for depression. Results from this study will (1) inform the development of a larger adequately powered randomized controlled trial to test the efficacy of intranasal ketamine for depression and (2) determine potential neurophysiological markers of clinical response.Trial RegistrationClinical Trials.gov NCT05137938; http://clinicaltrials.gov/ct2/show/NCT05137938International Registered Report Identifier (IRRID)PRR1-10.2196/30163

Efficacy of intranasal ketamine for acute pain management in adults: a systematic review and meta-analysis.

This study aimed to compare the efficacy of intranasal (IN) ketamine for pain control with placebo and other analgesics in an emergency setting. Electronic databases of PubMed, Embase, and CENTRAL were searched for randomized controlled trials (RCTs) comparing IN ketamine with placebo or other analgesics up to 1st January 2021. Studies were to be conducted on adults and in an emergency setting. Pain outcomes and adverse events were compared. Seven RCTs were included. Three compared IN ketamine with placebo while others with opioids. Comparing IN ketamine with opioids, the pooled analysis demonstrated no significant difference in pain scores between the two groups at 15 minutes but better pain reduction with opioids at 30 minutes. Comparing IN ketamine with placebo, our analysis demonstrated a non-significant difference but a tendency for better pain relief with IN ketamine at 15 minutes and 60 minutes. Pain scores at 30 minutes were, however, significantly lower with IN ketamine as compared to placebo. The need for rescue analgesics was significantly lower with IN ketamine as compared to placebo. There was no significant difference in the incidence of dizziness and nausea/vomiting between IN ketamine and opioids. As compared to placebo, IN ketamine was associated with an increased incidence of dizziness but not nausea/vomiting. Emergence reactions were significantly increased with IN ketamine as compared to opioids and placebo. There may be a role of IN ketamine for acute pain management in adults in an emergency setting. There is a tendency for better pain control with IN ketamine as compared to control and the possibility of similar efficacy of IN ketamine as compared to opioids. However, the results are not unequivocal and are limited by the low number of studies in literature and limited pain indications studied. Further RCTs are required to strengthen the evidence.

Efficacy of intranasal ketamine and midazolam for pediatric sedation: A double-blind, randomized clinical trial.

Background:Pediatric patients feel significant fear and anxiety when undergoing surgeries. The ideal drug and its administration route have not been found yet. The aim of this study was to compare the efficacy and safety of intranasal (IN) ketamine and midazolam as premedication in children.Methods:We studied 71 eligible pediatric patients undergoing elective urologic surgeries, aged 2 to 6 years. The degree of sedation and separation scores was compared between the two groups. Additionally, hemodynamic parameters, before premedication, after induction of anesthesia, and during surgery were documented and compared between two groups. Postoperatively, any side effect was recorded as well.Results:Finally, the data from 71 children were analyzed. Recovery time was significantly longer in group K (ketamine) compared to group M (midazolam); 27.86±4.42 vs 38.19± 6.67 minutes respectively (P=0.01). No significant difference was observed in terms of sedation score between two groups of K & M; 3.29±0.78 vs 3 ±0.71 respectively (P=0.17), and not regarding separation score; 2.51±0.61 & 2.31±0.52 respectively (P=0.01). Vital signs were kept within the physiological limits in both groups with no marked fluctuations.Conclusion:To produce sedation in young children, both midazolam and ketamine were effective and safe by IN route.

Intranasal Ketamine for Abortive Migraine Therapy in Pediatric Patients: A Single-Center Review

BackgroundKetamine has recently emerged as a promising therapeutic alternative for abortive migraine therapy, likely secondary to N-methyl-d-aspartate antagonism. Most reports examine adults and the intravenous route. Fewer utilize intranasal administration or pediatric populations. Given the limited evidence for intranasal ketamine in pediatric migraine populations, we retrospectively reviewed our experience to further characterize safety and efficacy of intranasal ketamine in this population. MethodsA retrospective review in a free-standing, pediatric medical center was performed examining the utilization of intranasal ketamine at 0.1 to 0.2 mg/kg/dose up to five doses in pediatric migraineurs. Pain scores (scale = 0 to 10) were recorded at baseline and after each dose. Response was characterized as pain score reduction to 0 to −3 and/or reduction of at least 50%. ResultsTwenty-five encounters (25 of 34; 73.5%) were responders (mean pain score reduction of −7.2 from admission to treatment completion). Overall pain reduction from admission to discharge in the entire study population was 66.1%. Side effects were mild and transient. ConclusionsOur experience with intranasal ketamine has promising outcomes in both pain relief and side effect minimization. When other therapeutic options are unavailable, practitioners should consider intranasal ketamine.

A Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder

The N-methyl-D-aspartate glutamate receptor antagonist ketamine, delivered via an intravenous route, has shown rapid antidepressant effects in patients with treatment-resistant depression. The current study was designed to test the safety, tolerability, and efficacy of intranasal ketamine in patients with depression who had failed at least one prior antidepressant trial. In a randomized, double-blind, crossover study, 20 patients with major depression were randomly assigned, and 18 completed 2 treatment days with intranasal ketamine hydrochloride (50 mg) or saline solution. The primary efficacy outcome measure was change in depression severity 24 hours after ketamine or placebo, measured using the Montgomery-Åsberg Depression Rating Scale. Secondary outcomes included persistence of benefit, changes in self-reports of depression, changes in anxiety, and proportion of responders. Potential psychotomimetic, dissociative, hemodynamic, and general adverse effects associated with ketamine were also measured. Patients showed significant improvement in depressive symptoms at 24 hours after ketamine compared to placebo (t = 4.39, p < .001; estimated mean Montgomery-Åsberg Depression Rating Scale score difference of 7.6 ± 3.7; 95% confidence interval, 3.9-11.3). Response criteria were met by 8 of 18 patients (44%) 24 hours after ketamine administration compared with 1 of 18 (6%) after placebo (p = .033). Intranasal ketamine was well tolerated with minimal psychotomimetic or dissociative effects and was not associated with clinically significant changes in hemodynamic parameters. This study provides the first controlled evidence for the rapid antidepressant effects of intranasal ketamine. Treatment was associated with minimal adverse effects. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with major depression.

The PICHFORK (Pain InCHildren Fentanyl OR Ketamine) trial comparing the efficacy of intranasal ketamine and fentanyl in the relief of moderate to severe pain in children with limb injuries: study protocol for a randomized controlled trial

BackgroundThe effectiveness of intranasal (IN) fentanyl as an analgesic for painful pediatric limb injuries in the Emergency Department (ED) has been reported previously. However, efficacy of IN ketamine in sub-dissociative doses is not well studied in the ED setting. A non-blinded pilot study undertaken by this study group suggested that IN ketamine showed similar analgesic effectiveness to that reported with IN fentanyl in similar non-blinded studies. The aim of this randomized, controlled, equivalence trial is to compare the analgesic effect of sub-dissociative dose IN ketamine with IN fentanyl for children with isolated musculoskeletal limb injuries.Methods/DesignThis is a prospective, randomized, controlled, double-blind equivalence trial of children agedthree to thirteen years and less than 50 kg body weight, with isolated musculoskeletal limb injury, presenting to the ED with moderate to severe pain, defined as a verbal response of at least six to a standard 11-point scale (0 = none, 10 = worst pain imaginable). Pain score, sedation, satisfaction with analgesic intervention, and adverse effects will be assessed over a 60 minute interval for each participant. Intranasal ketamine (1 mg/kg) or fentanyl (1.5 microgram/kg) will be administered via blinded syringe and mucosal atomization device in a standardized volume at 0.03 ml/kg, with a maximum volume of 1.5 ml divided equally to both nares. Participants will also receive 10 mg/kg ibuprofen orally. The primary outcome measure will be median change in pain score from pre-administration to 30 minutes post-administration. Non-parametric Mann–Whitney U tests will be computed to compare median change in the primary outcome measure for IN ketamine and fentanyl. A sample size of 36 participants per group is needed to detect the expected 40 mm reduction in pain rating with a 95% confidence interval (CI) no greater than ± 10 mm at 30 minutes. Rescue analgesia will be given as IN fentanyl or intravenous morphine.DiscussionThis is the first randomized-controlled trial comparing the efficacy of these two analgesic agents via the intranasal route. If IN ketamine is found to be equally effective to IN fentanyl for this indication, it will provide another analgesic agent that may be considered for the relief of acute pain in children in the ED.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12612000795897.