AIMS: To investigate the effect of ketamine on emergence agitation in children.

METHODS: Databases of MEDLINE, EMBASE, and CENTRAL were systematically searched from their start date until February 2019. Randomized controlled trials comparing intravenous ketamine and placebo in children were sought. The primary outcome was the incidence of emergence agitation. Secondary outcomes included postoperative pain score, duration of discharge time, and the adverse effects associated with the use of ketamine, namely postoperative nausea and vomiting, desaturation, and laryngospasm.

RESULTS: Thirteen studies (1125 patients) were included in the quantitative meta-analysis. The incidence of emergence agitation was 14.7% in the ketamine group and 33.3% in the placebo group. Children receiving ketamine had a lower incidence of emergence agitation, with an odds ratio being 0.23 (95% confidence interval: 0.11 to 0.46), certainty of evidence: low. In comparison with the placebo, ketamine group achieved a lower postoperative pain score (odds ratio: -2.42, 95% confidence interval: -4.23 to -0.62, certainty of evidence: very low) and lower pediatric anesthesia emergence delirium scale at 5 minutes after operation (odds ratio: -3.99, 95% confidence interval: -5.03 to -2.95; certainty of evidence: moderate). However, no evidence was observed in terms of incidence of postoperative nausea and vomiting, desaturation, and laryngospasm.

CONCLUSION: In this meta-analysis of 13 randomized controlled trials, high degree of heterogeneity and low certainty of evidence limit the recommendations of ketamine for the prevention of emergence agitation in children undergoing surgery or imaging procedures. However, the use of ketamine is well-tolerated without any notable adverse effects across all the included trials.

METHODS: This phase 3, open-label, multicenter, long-term (up to 1 year) study was conducted between October 2015 and October 2017. Patients (≥ 18 years) with TRD (DSM-5 diagnosis of major depressive disorder and nonresponse to ≥ 2 OAD treatments) were enrolled directly or transferred from a short-term study (patients aged ≥ 65 years). Esketamine nasal spray (28-mg, 56-mg, or 84-mg) plus new OAD was administered twice a week in a 4-week induction (IND) phase and weekly or every-other-week for patients who were responders and entered a 48-week optimization/maintenance (OP/MAINT) phase.

RESULTS: Of 802 enrolled patients, 86.2% were direct-entry and 13.8% were transferred-entry; 580 (74.5%) of 779 patients who entered the IND phase completed the phase, and 150 (24.9%) of 603 who entered the OP/MAINT phase completed the phase. Common treatment-emergent adverse events (TEAEs) were dizziness (32.9%), dissociation (27.6%), nausea (25.1%), and headache (24.9%). Seventy-six patients (9.5%) discontinued esketamine due to TEAEs. Fifty-five patients (6.9%) experienced serious TEAEs. Most TEAEs occurred on dosing days, were mild or moderate in severity, and resolved on the same day. Two deaths were reported; neither was considered related to esketamine. Cognitive performance generally either improved or remained stable postbaseline. There was no case of interstitial cystitis or respiratory depression. Treatment-emergent dissociative symptoms were transient and generally resolved within 1.5 hours postdose. Montgomery-Åsberg Depression Rating Scale total score decreased during the IND phase, and this reduction persisted during the OP/MAINT phase (mean [SD] change from baseline of respective phase to endpoint: IND, -16.4 [8.76]; OP/MAINT, 0.3 [8.12]).

CONCLUSIONS: Long-term esketamine nasal spray plus new OAD therapy had a manageable safety profile, and improvements in depression appeared to be sustained in patients with TRD.

MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled prospective study, we enrolled 40 children undergoing tonsillectomy. Anesthetic care was standardized. Intraoperative analgesia was provided with remifentanil 0.5 microg x kg(-1) followed by an infusion of 0.25 microg x kg(-1) x min(-1). Group I (ketamine, n = 20) received a bolus dose of ketamine 0.5 mg x kg(-1) followed by a continuous infusion of 2 microg x kg(-1) x min(-1) before start of surgery. The infusion was stopped when surgery ended. Group II (placebo, n=20) received normal saline in the same manner. Pain was assessed postoperatively using the Children's Hospital Eastern Ontario Pain Scale (CHEOPS; range of scores 4 13), and total morphine consumption was recorded in the postanesthesia care unit (PACU). Patients were transferred to the ward and morphine was administered via a patient-controlled analgesia (PCA) device and analgesia was recorded using a visual analogue scale (VAS) (0 - 10).

RESULTS: Intraoperative remifentanil consumption was not different between the ketamine group (0.29+/-0.09 microg x kg x min(-1) ) and the control group (0.24+/-0.07 microg x kg x min(-1)). There were no significant differences between CHEOPS scores and VAS score between the two groups. The total mean morphine consumption in the ward was not significantly different between the two groups: 376.5 +/-91.6 microg x kg(-1) with ketamine and 384.4+/-97.3 microg x kg(-1) with placebo. The time-to-first analgesic requirement was also similar in both groups.

METHOD: The Cochrane Central Register of Controlled Trials (1996 to Feb 2019) and MEDLINE (1966 to Feb 2019) were searched, including the related randomised control trials and reviewed articles to find unpublished trials or trials not obtained via electronic searches. Inclusion criteria for the studies included comparing recovery time, recording clinician satisfaction, and assessing the adverse effects of ketofol.

RESULTS: Eleven trials consisting of a total of 1274 patients met our criteria and were included in this meta-analysis. Five trials compared ketofol with a single agent, while six trials compared ketofol with combined agents. While comparing between ketofol and a single agent (either ketamine or propofol), ketofol showed significant effect on recovery time (MD: -9.88, 95% CI: - 14.30 to - 5.46; P = 0.0003; I2 = 92%). However, no significant difference was observed while comparing ketofol with combined agents (RR: 0.75, 95% CI: - 6.24 to 7.74; P < 0.001; I2 = 98%). During single-agent comparison, ketofol showed no significant differences in terms of clinician satisfaction (RR: 2.86, 95% CI: 0.64 to 12.69; P = 0.001; I2 = 90%), airway obstruction (RR: 0.72, 95% CI: 0.35 to 11.48; P = 0.81; I2 = 0%), apnoea (RR: 0.9, 95% CI: 0.33 to 2.44; P = 0.88; I2 = 0%), desaturation (RR: 1.11, 95% CI: 0.64 to 1.94; P = 0.28; I2 = 21%), nausea (RR: 0.52, 95% CI: 0.91 to 1.41; P = 0.2; I2 = 38%), and vomiting (RR: 0.63, 95% CI: 0.25 to 1.61; P = 0.18; I2 = 42%). During comparison with combined agents, ketofol was more effective in reducing hypotension (RR: 4.2, 95% CI: 0.2 to 0.85; P = 0.76; I2 = 0%), but no differences were observed in terms of bradycardia (RR: 0.70, 95% CI: 0.14 to 03.63; P = 0.09; I2 = 53%), desaturation (RR: 1.9, 95% CI: 0.15 to 23.6; P = 0.11; I2 = 61%), and respiratory depression (RR: 1.98, 95% CI: 0.18 to 21.94; P = 0.12; I2 = 59%).

CONCLUSION: There is low certainty of evidence that ketofol improves recovery time and moderate certainty of evidence that it reduces the frequency of hypotension. There was no significant difference in terms of other adverse effects when compared to other either single or combined agents.

METHODS: Rats were fed with illicit (a concoction of street ketamine) ketamine in doses of 100 (N=12), or 300 mg/kg (N=12) for four weeks. Half of the rats were sacrificed after the 4-week feeding for necropsy. The remaining rats were taken off ketamine for 8 weeks to allow for any potential recovery of pathological changes before being sacrificed for necropsy. Histopathological examination was performed on the kidney and urinary bladder.

RESULTS: Submucosal bladder inflammation was seen in 67% of the rats fed with 300 mg/kg illicit ketamine. No bladder inflammation was observed in the control and 100 mg/kg illicit ketamine groups. Renal changes, such as interstitial nephritis and papillary necrosis, were observed in rats given illicit ketamine. After ketamine cessation, no inflammation was observed in the bladder of all rats. However, renal inflammation remained in 60% of the rats given illicit ketamine. No dose-effect relationship was established between oral ketamine and changes in the kidneys.

MATERIALS AND METHODS: A retrospective cohort study was conducted between January 2017 and July 2023 in Yogyakarta, Indonesia. A total of 85 children diagnosed with intussusception underwent hydrostatic reduction, which employed water-soluble contrast administered into the rectum. Cases that were unsuccessful in reduction underwent immediate surgical intervention.

RESULTS: Among the 85 children with intussusception underwent reduction, 22 children underwent the SR procedure and 63 underwent NSR procedure. We found a successful outcome in 17 cases (77%) of SR procedure with one recurrent and the other five (23%) got surgical reduction such as anastomosis resection (3 cases) due to Meckel- Diverticula. On the other hand, we found 24 successful cases (38.0%) in NSR procedure with one recurrent after case. 39 others who failed with NSR continued to surgical reduction. Manual reduction was done for 31 patients with one case mortality due to pulmonary bleeding. Anastomosis resection (4 cases) and, stoma (4 cases) were decided for others surgical reduction. The relative risk (RR) on this study was 2.02 (p value < 0.05, CI 95%).

Materials and Methods: The experiment was divided into short-term treatment (45 days) and long-term treatment (90 days), with each group divided into nine sub-groups consisting of six animals each. Sub-groups 1 and 2 served as normal, and N-acetylcysteine (NAC) controls, respectively. Sub-groups 3-9 received sodium arsenite in drinking water (50 mg/L). In addition, sub-group 4 received NAC (210 mg/kg b.wt) orally once daily, sub-groups 5-7 received aqueous seed extract of M. pruriens (350 mg/kg b.wt, 530 mg/kg b.wt, and 700 mg/kg b.wt) orally once daily and sub-groups 8 and 9 received a combination of NAC and aqueous seed extract of M. pruriens (350 mg/kg b.wt and 530 mg/kg b.wt) orally once daily. Following the treatment, the blood was drawn retro-orbitally to assess the liver (serum alanine transaminase [ALT], serum aspartate transaminase, and serum alkaline phosphatase) and kidney (serum urea and serum creatinine) functions. Learning and memory were assessed by passive avoidance test. Animals were sacrificed by an overdose of ketamine, and their Nissl stained hippocampal sections were analyzed for alterations in neural cell numbers in CA1 and CA3 regions.

Results: In the short-term treatment, groups administered with M. pruriens 530 mg/kg b.wt alone and combination of NAC + M. pruriens 350 mg/kg b.wt exhibited a significant improvement in memory retention, less severe neurodegeneration, and decrease in serum ALT levels. In long-term treatment, groups administered with M. pruriens 700 mg/kg b.wt alone and combination of NAC+M. pruriens 350 mg/kg b.wt, respectively, showed better memory retention, decreased neural deficits, and reduced levels of kidney and liver enzymes.