Efficacy Of Intravenous Ketamine Research Articles

Efficacy of intravenous ketamine and intranasal esketamine with dose escalation for Major depression: A systematic review and meta-analysis

ObjectiveIntravenous (IV) racemic ketamine and intranasal (IN) esketamine have demonstrated rapid antidepressant effects in treatment-resistant depression (TRD). This systematic review aims to evaluate the efficacy and safety of ketamine and esketamine at various dosages for depression. MethodsWe included randomized controlled trials (RCTs) with parallel group dose comparison of ketamine and esketamine for depression/TRD. Ovid Medline, Embase, PsycINFO, Scopus and Cochrane databases were searched. Standardized mean differences were calculated using Hedges'-g to complete random effects meta-analysis. The efficacy outcomes were changes in depression outcomes for IV ketamine and IN esketamine respectively. Safety was assessed by reported adverse effects. ResultsA random effects meta-analysis of studies (n = 12) showed efficacy in reducing depression symptoms with IV ketamine (Hedges'g = 1.52 [0.98–2.22], Z = 4.23, p < 0.001) and IN esketamine (Hedges' g = 0.31 [0.18–0.44], Z = 4.53, P < 0.001) compared to control/placebo. Treatment response was observed at IV ketamine doses ≤0.2 mg/kg, >0.2–0.5 mg/kg and > 0.5 mg/kg. Higher IV ketamine doses (>0.5 mg/kg) did not lead to greater treatment response. Esketamine doses of 56–84 mg were superior to 28 mg dose. LimitationsOverall quality of evidence was low and limited by small number of studies. Publication bias was high. ConclusionsThis meta-analysis suggests that IV ketamine may be efficacious at doses as low as 0.2 mg/kg, with increasing dose response at 0.5 mg/kg, without demonstrable increased benefit at 1 mg/kg, based on a small number of studies. Efficacy for IN esketamine increases with doses above 28 mg with best response being found between 56 and 84 mg for reducing depressive symptoms.

Efficacy of intravenous ketamine as premedicant for prevention of intraoperative hypotension after spinal anesthesia in parturients posted for elective cesarean section

Background: Hypotension following spinal anesthesia (SA) in lower segment cesarean section can be deleterious to the parturient and to fetus. Ketamine acts by stimulating the cardiovascular system leading to high blood pressure and increase in heart rate (HR) and cardiac output. Aims and Objectives: This study aimed to assess the efficacy of 15 mg of prophylactic intravenous ketamine in elective cesarean section for prevention of hypotension after SA. Materials and Methods: This double-blinded randomized controlled study was conducted on 98 participating parturients who were American Society of Anesthesiologists term pregnant women. The parturients were randomly divided into two groups (n=49 in each). All the parturients received SA. Ketamine group - Group K received 15 mg of ketamine IV bolus in 3 mL saline and control group - Group C received the same volume of normal saline IV bolus. HR and systolic blood pressure (SBP) were recorded at baseline at 5, 10, 15, and 20 min after the injection and then every 15 min till the end of the operation. Incidences of hypotension were recorded. The total number dose of ephedrine used, APGAR score, and Visual Analog Scale scores were recorded. The Ramsay Sedation Score was also recorded at baseline, then 5, 10, 15, 30, and 45 min after injection, and then at the end of the operation. Results: This study showed a statistically significant increase in the incidence of hypotension and higher use of intravenous ephedrine 6 mg boluses in the control group when compared to the ketamine group. Forty-two parturients in the control group developed hypotension compared to 23 parturients in the ketamine group with P&lt;0.001. The total ephedrine dose was significantly lower among the ketamine group. Sedation was observed for the first 15 min intraoperatively in the ketamine group with P=0.001. There was no statistically significant difference in APGAR score between the two groups. Conclusion: There was significantly higher hemodynamic stability in the ketamine group with regard to SBP, diastolic blood pressure, and HR. Hence, low-dose ketamine, when used as a premedicant, is an effective agent that can be used in preventing post-spinal intraoperative hypotension in parturients undergoing cesarean section delivery.

Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial.

Adolescent depression is prevalent and is associated with significant morbidity and mortality. Although intravenous ketamine has shown efficacy in adult treatment-resistant depression, its efficacy in pediatric populations is unknown. The authors conducted an active-placebo-controlled study of ketamine's safety and efficacy in adolescents. In this proof-of-concept randomized, double-blind, single-dose crossover clinical trial, 17 adolescents (ages 13-17) with a diagnosis of major depressive disorder received a single intravenous infusion of either ketamine (0.5 mg/kg over 40 minutes) or midazolam (0.045 mg/kg over 40 minutes), and the alternate compound 2 weeks later. All participants had previously tried at least one antidepressant medication and met the severity criterion of a score >40 on the Children's Depression Rating Scale-Revised. The primary outcome measure was score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 24 hours after treatment. A single ketamine infusion significantly reduced depressive symptoms 24 hours after infusion compared with midazolam (MADRS score: midazolam, mean=24.13, SD=12.08, 95% CI=18.21, 30.04; ketamine, mean=15.44, SD=10.07, 95% CI=10.51, 20.37; mean difference=-8.69, SD=15.08, 95% CI=-16.72, -0.65, df=15; effect size=0.78). In secondary analyses, the treatment gains associated with ketamine appeared to remain 14 days after treatment, the latest time point assessed, as measured by the MADRS (but not as measured by the Children's Depression Rating Scale-Revised). A significantly greater proportion of participants experienced a response to ketamine during the first 3 days following infusion as compared with midazolam (76% and 35%, respectively). Ketamine was associated with transient, self-limited dissociative symptoms that affected participant blinding, but there were no serious adverse events. In this first randomized placebo-controlled clinical trial of intravenous ketamine in adolescents with depression, the findings suggest that it is well tolerated acutely and has significant short-term (2-week) efficacy in reducing depressive symptoms compared with an active placebo.Reprinted from Am J Psychiatry 2021; 178:352-362 with permission from American Psychiatric Association Publishing.

Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial.

Adolescent depression is prevalent and is associated with significant morbidity and mortality. Although intravenous ketamine has shown efficacy in adult treatment-resistant depression, its efficacy in pediatric populations is unknown. The authors conducted an active-placebo-controlled study of ketamine's safety and efficacy in adolescents. In this proof-of-concept randomized, double-blind, single-dose crossover clinical trial, 17 adolescents (ages 13-17) with a diagnosis of major depressive disorder received a single intravenous infusion of either ketamine (0.5 mg/kg over 40 minutes) or midazolam (0.045 mg/kg over 40 minutes), and the alternate compound 2 weeks later. All participants had previously tried at least one antidepressant medication and met the severity criterion of a score >40 on the Children's Depression Rating Scale-Revised. The primary outcome measure was score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 24 hours after treatment. A single ketamine infusion significantly reduced depressive symptoms 24 hours after infusion compared with midazolam (MADRS score: midazolam, mean=24.13, SD=12.08, 95% CI=18.21, 30.04; ketamine, mean=15.44, SD=10.07, 95% CI=10.51, 20.37; mean difference=-8.69, SD=15.08, 95% CI=-16.72, -0.65, df=15; effect size=0.78). In secondary analyses, the treatment gains associated with ketamine appeared to remain 14 days after treatment, the latest time point assessed, as measured by the MADRS (but not as measured by the Children's Depression Rating Scale-Revised). A significantly greater proportion of participants experienced a response to ketamine during the first 3 days following infusion as compared with midazolam (76% and 35%, respectively). Ketamine was associated with transient, self-limited dissociative symptoms that affected participant blinding, but there were no serious adverse events. In this first randomized placebo-controlled clinical trial of intravenous ketamine in adolescents with depression, the findings suggest that it is well tolerated acutely and has significant short-term (2-week) efficacy in reducing depressive symptoms compared with an active placebo.

Emergence agitation in children after sevoflurane anaesthesia: a comparative evaluation of ketamine and varying doses of fentanyl

Introduction: Sevoflurane, inhalational anaesthetic of choice in children, is associated with high incidence of emergence agitation (EA). But that “one drug” which can significantly reduce or prevent EA still eludes us. Thus we aimed at studying the efficacy of intravenous ketamine and varying doses of intravenous fentanyl on postoperative emergence agitation in children receiving sevoflurane anaesthesia. Materials and methods : This prospective, double blind, randomized comparative study was conducted on 114 children, 2-10 years, with ASA physical status I-II. They were undergoing herniotomy under sevoflurane anaesthesia and were randomly divided into Group A receiving ketamine 0.5 mg/kg, Group B fentanyl 2mcg/kg and Group C fentanyl 3mcg/kg at the time of induction. Postoperatively emergence agitation was assessed every 5 min during first 60 min of PACU stay using Aono's four point scale . We also observed recovery characteristics including time to extubation, time to emergence, discharge from PACU and postoperative complications. Results: The incidence of EA was significantly low in Group A (31.6%) and Group C (28.9%) compared to group B (65.8%), with no significant difference between Group A and Group C. Incidence of EA was higher in preschool children. A prolonged PACU stay was observed in all children who developed EA, with lesser duration of PACU stay noted in fentanyl 3 mcg/kg group. Conclusion: Intravenous administration of either ketamine 0.5 mg/kg or fentanyl 3mcg/kg i.v. at the time of induction reduces the incidence of EA effectively when compared with fentanyl 2mcg/kg, without delaying recovery. DOI: http://dx.doi.org/10.4038/slja.v23i1.7514