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Repeated administration of subanesthetic intravenous ketamine may prolong the rapid decrease in suicidal ideation (SI) elicited by single infusions. The purpose of this secondary analysis was to evaluate reduction in SI with a single ketamine infusion compared with an active control, and prolonged suppression of SI with repeated and maintenance infusions. Thirty-seven participants with treatment-resistant depression (TRD) and baseline SI first received a single ketamine infusion during a randomized, double-blind crossover with midazolam. Following relapse of depressive symptoms, participants received six open-label ketamine infusions administered thrice-weekly over 2 weeks. Antidepressant responders (≥50% decrease in Montgomery-Åsberg Depression Rating Scale [MADRS] scores) received four further open-label infusions administered once-weekly. Changes in SI were assessed with the suicide items on the MADRS (item 10, MADRS-SI) and the Quick Inventory of Depressive Symptomatology-Self Report (item 12, QIDS-SI). Linear mixed models revealed that compared with midazolam, a single ketamine infusion elicited larger reduction in SI (P = 0.01), with maximal effects measured at 7 days postinfusion (P < 0.001, Cohen’s d = 0.83). Participants had cumulative reductions in MADRS-SI scores with repeated infusions (P < 0.001), and no further change with maintenance infusions (P = 0.94). QIDS-SI results were consistent with MADRS-SI. Overall, 69% of participants had a complete alleviation of SI following repeated infusions. In TRD, single and repeated ketamine infusions resulted in decreases in SI which were maintained with once-weekly maintenance infusions. This study adds to the growing body of research suggesting ketamine as a possible novel treatment strategy for SI in mood disorders.

Several electrical neural oscillatory abnormalities have been associated with schizophrenia, although the underlying mechanisms of these oscillatory problems are unclear. Animal studies suggest that one of the key mechanisms of neural oscillations is through glutamatergic regulation; therefore, neural oscillations may provide a valuable animal–clinical interface on studying glutamatergic dysfunction in schizophrenia. To identify glutamatergic control of neural oscillation relevant to human subjects, we studied the effects of ketamine, an N -methyl- D -aspartate antagonist that can mimic some clinical aspects of schizophrenia, on auditory-evoked neural oscillations using a paired-click paradigm. This was a double-blind, placebo-controlled, crossover study of ketamine vs saline infusion on 10 healthy subjects. Clinically, infusion of ketamine in subanesthetic dose significantly increased thought disorder, withdrawal–retardation, and dissociative symptoms. Ketamine significantly augmented high-frequency oscillations (gamma band at 40–85 Hz, p =0.006) and reduced low-frequency oscillations (delta band at 1–5 Hz, p <0.001) compared with placebo. Importantly, the combined effect of increased gamma and reduced delta frequency oscillations was significantly associated with more withdrawal–retardation symptoms experienced during ketamine administration ( p =0.02). Ketamine also reduced gating of the theta-alpha (5–12 Hz) range oscillation, an effect that mimics previously described deficits in schizophrenia patients and their first-degree relatives. In conclusion, acute ketamine appeared to mimic some aspects of neural oscillatory deficits in schizophrenia, and showed an opposite effect on scalp-recorded gamma vs low-frequency oscillations. These electrical oscillatory indexes of subanesthetic ketamine can be potentially used to cross-examine glutamatergic pharmacological effects in translational animal and human studies.

Fentanyl is often administered during rapid sequence induction of anesthesia (RSI) in the emergency department (ED) to ameliorate the hypertensive response that may occur. Due to its more rapid onset, the use of alfentanil may be more consistent with both the onset time of the sedative and the commencement of laryngoscopy. As such, we compared the effect of alfentanil and fentanyl on post-induction hemodynamic changes when administered as part of a standardized induction regimen including ketamine and rocuronium in ED RSI. This was a double-blind pilot randomized controlled trial of adult patients requiring RSI in the ED of three urban Australian hospitals. Patients were randomized to receive either alfentanil or fentanyl in addition to ketamine and rocuronium for RSI. Non-invasive blood pressure and heart rate were measured immediately before and at two, four, and six minutes after induction. The primary outcome was the occurrence of at least one post-induction systolic blood pressure outside the pre-specified range of 100-160mmHg (with adjustment for patients with baseline hypertension). Secondary outcomes included hypertension, hypotension, hypoxia, first-pass intubation success, 30-day mortality, and the pattern of hemodynamic changes. A total of 61 patients were included in the final analysis (31 in the alfentanil group and 30 in the fentanyl group). The primary outcome was met in 58% of the alfentanil group and 50% of the fentanyl group (difference 8%, 95% confidence interval: -17% to 33%). The 30-day mortality rate, first-pass success rate, and incidences of hypertension, hypotension, and hypoxia were similar between the groups. There were no significant differences in systolic blood pressure or heart rate between the groups at any of the measured time-points. Alfentanil and fentanyl produced comparable post-induction hemodynamic changes when used as adjuncts to ketamine in ED RSI. Future studies could consider comparing different dosages of these opioids.

Ketamine is a dissociative anesthetic that induces a shift in global consciousness states and related brain dynamics. Portable low-density EEG systems could be used to monitor these effects. However, previous evidence is almost null and lacks adequate methods to address global dynamics with a small number of electrodes. This study delves into brain high-order interactions (HOI) to explore the effects of ketamine using portable EEG. In a double-blinded cross-over design, 30 male adults (mean age = 25.57, SD = 3.74) were administered racemic ketamine and compared against saline infusion as a control. Both task-driven (auditory oddball paradigm) and resting-state EEG were recorded. HOI were computed using advanced multivariate information theory tools, allowing us to quantify nonlinear statistical dependencies between all possible electrode combinations. Ketamine induced an increase in redundancy in brain dynamics (copies of the same information that can be retrieved from 3 or more electrodes), most significantly in the alpha frequency band. Redundancy was more evident during resting state, associated with a shift in conscious states towards more dissociative tendencies. Furthermore, in the task-driven context (auditory oddball), the impact of ketamine on redundancy was more significant for predictable (standard stimuli) compared to deviant ones. Finally, associations were observed between ketamine’s HOI and experiences of derealization. Ketamine appears to increase redundancy and HOI across psychometric measures, suggesting these effects are correlated with alterations in consciousness towards dissociation. In comparisons with event-related potential (ERP) or standard functional connectivity metrics, HOI represent an innovative method to combine all signal spatial interactions obtained from low-density dry EEG in drug interventions, as it is the only approach that exploits all possible combinations between electrodes. This research emphasizes the potential of complexity measures coupled with portable EEG devices in monitoring shifts in consciousness, especially when paired with low-density configurations, paving the way for better understanding and monitoring of pharmacological-induced changes.

Background Children undergoing strabismus surgery under sevoflurane anesthesia often experience emergence agitation (EA) and postoperative vomiting (POV). This study compared the effects of intraoperative dexmedetomidine, ketamine, and placebo on postoperative EA and POV. Methods Eighty-four children (aged two to seven years) undergoing elective strabismus surgery under sevoflurane anesthesia were randomly assigned to one of three groups ( n  = 28 each). Intraoperatively, the placebo, dexmedetomidine, and ketamine groups received normal saline, dexmedetomidine 1 μg·kg −1   iv plus a 1 μg·kg −1 ·hr −1 infusion, and ketamine 1 mg·kg −1 iv plus a 1 mg·kg −1 ·hr −1 infusion, respectively. Agitation scores (Pediatric Anesthesia Emergence Delirium [PAED] scale) and POV were assessed in the postanesthetic care unit (PACU) and for 24 hr on the ward. Pain scores and times to laryngeal mask airway (LMA™) removal, resumption of mental orientation, and discharge from the PACU were also assessed. Results Seventy-eight children completed the study. Peak PAED scores for EA were lower in the dexmedetomidine ( P  < 0.001) and ketamine ( P  = 0.002) groups than in the placebo group. Incidence of POV was lower in the dexmedetomidine group (15%) than in the ketamine (44%; P  = 0.02) or placebo (45.8%; P  = 0.02) groups. Pain scores on the ward were lower in the dexmedetomidine ( P  < 0.001) and ketamine ( P  < 0.001) groups than in the placebo group. Time to LMA removal was similar in all groups. Time for resumption of mental orientation and time to discharge from PACU were longer in the dexmedetomidine and ketamine groups than in the placebo group. Conclusions Dexmedetomidine and ketamine appear to prevent postoperative agitation and pain after sevoflurane anesthesia for pediatric strabismus surgery. Dexmedetomidine also prevents POV.

Emergency physicians often need to control agitated patients who present a danger to themselves and hospital personnel. Commonly used medications have limitations. Our primary objective was to compare the time to a defined reduction in agitation scores for ketamine versus benzodiazepines and haloperidol, alone or in combination. Our secondary objectives were to compare rates of medication redosing, vital sign changes, and adverse events in the different treatment groups. We conducted a single-center, prospective, observational study examining agitation levels in acutely agitated emergency department patients between the ages of 18 and 65 who required sedation medication for acute agitation. Providers measured agitation levels on a previously validated 6-point sedation scale at 0-, 5-, 10-, and 15-min after receiving sedation. We also assessed the incidence of adverse events, repeat or rescue medication dosing, and changes in vital signs. 106 patients were enrolled and 98 met eligibility criteria. There was no significant difference between groups in initial agitation scores. Based on agitation scores, more patients in the ketamine group were no longer agitated than the other medication groups at 5-, 10-, and 15-min after receiving medication. Patients receiving ketamine had similar rates of redosing, changes in vital signs, and adverse events to the other groups. In highly agitated and violent emergency department patients, significantly fewer patients receiving ketamine as a first line sedating agent were agitated at 5-, 10-, and 15-min. Ketamine appears to be faster at controlling agitation than standard emergency department medications.

Background We conducted a randomized clinical trial to determine whether adjunctive lidocaine diminishes the incidence of adverse effects in pediatric patients sedated with ketamine. Methods This case‐control study involved 586 consecutive pediatric patients necessitating anesthesia. Then systolic blood pressure, heart rate, respiratory rate, and blood oxygen saturation were observed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN), and creatinine (Cr) levels were tested. General dose of ketamine, the time of onset and duration of anesthesia and postoperative recovery, anesthesia effect, and adverse reaction were subsequently compared. High‐performance liquid chromatography was employed to detect ketamine concentration at different time points after administration, and the postoperative cognition function was further evaluated. Results Intra‐ and post‐operation, the rising degree of ALT, AST, BUN, and Cr in patients treated with ketamine was higher than those in patients treated with the ketamine‐lidocaine complex. General dose of ketamine, the time of onset and duration of anesthesia, postoperative recovery time, and the incidence rate of adverse reaction in patients treated with ketamine‐lidocaine complex were lower, but the concentration of ketamine was higher compared to the patients treated with ketamine. In patients treated with the ketamine‐lidocaine complex, elimination half‐life of ketamine was prolonged, the area under curve was increased, and the plasma clearance rate was decreased relative to those with ketamine alone. Conclusions Ketamine combined with lidocaine may be beneficial in shortening the onset of anesthesia, promoting postoperative awake, prolonging elimination half‐life, increasing area under curve, and decreasing plasma clearance rate and incidence of adverse reactions.

Background Ketamine and fentanyl are commonly used for sedation and induction of anesthesia in critically ill patients. This study aimed to compare the hemodynamic effects of ketamine versus fentanyl bolus in patients with septic shock. Methods This randomized controlled trial included mechanically ventilated adults with septic shock receiving sedation. Patients were randomized to receive either 1 mg/kg ketamine bolus or 1 mcg/kg fentanyl bolus. Cardiac output (CO), stroke volume (SV), heart rate (HR), and mean arterial pressure (MAP) were measured at the baseline, 3, 6, 10, and 15 min after the intervention. Delta CO was calculated as the change in CO at each time point in relation to baseline measurement. The primary outcome was delta CO 6 min after administration of the study drug. Other outcomes included CO, SV, HR, and MAP. Results Eighty-six patients were analyzed. The median (quartiles) delta CO 6 min after drug injection was 71(37, 116)% in the ketamine group versus − 31(− 43, − 12)% in the fentanyl group, P value < 0.001. The CO, SV, HR, and MAP increased in the ketamine group and decreased in the fentanyl group in relation to the baseline reading; and all were higher in the ketamine group than the fentanyl group. Conclusion In patients with septic shock, ketamine bolus was associated with higher CO and SV compared to fentanyl bolus. Clinical trial registration Date of registration: 24/07/2023. ClinicalTrials.gov Identifier: NCT05957302. URL: https://clinicaltrials.gov/study/NCT05957302 .

Various drugs have been used to relieve abdominal pain in patients with renal colic. Ketamine is a popular choice as an analgesic. To compare the effectiveness of intranasal (IN) ketamine versus intravenous (IV) morphine in reducing pain in patients with renal colic. A randomized double-blind controlled trial was performed in 53 patients with renal colic recruited from the emergency department (ED) in 2015. Finally, 40 patients were enrolled in this study. Patients in the ketamine group received IN ketamine 1 mg/kg and IV placebo while patients in the control group received IV morphine 0.1mg/kg and IN placebo. Our goal was to assess visual analogue scale (VAS) changes between the 2 groups. Patients' VAS scores were reported before and 5, 15, 30min after drug injection. Before drug administration, the mean±SD VAS score was 7.40±1.18 in the morphine group (group A) and 8.35±1.30 in the ketamine group (group B) (P-value=0.021). After adjustment by the appropriate analysis, the mean±SD VAS score in group (A) and (B) at 5min were (6.07±0.47 vs 6.87±0.47; mean difference −0.79, 95% confidence interval (CI) −1.48 to −1.04) (P-value=0.025), at 15 and 30min, the mean±SD VAS score in group (A) and (B) were (5.24±0.49 vs 5.60±0.49; mean difference −0.36, 95% CI −1.08 to 0.34) and (4.02±0.59 vs 4.17±0.59; mean difference −0.15, 95% CI −1.02 to 0.71) (P-value=0.304 and 0.719) respectively. IN ketamine may be effective in decreasing pain in renal colic.