A prospective study of ketamine as primary therapy for prehospital profound agitation.

OBJECTIVE: We investigated the effectiveness of ketamine as a primary therapy for prehospital profound agitation. METHODS: This was a prospective observational study of patients receiving 5mg/kg of intramuscular ketamine for profound agitation, defined as a score of +4 on the Altered Mental Status Scale (AMSS), a validated ordinal scale of agitation from -4 (unresponsive) to +4 (most agitated). The primary outcome was time to adequate sedation (AMSS<+1). Secondary outcomes included need for additional sedatives, intubation frequency, complications associated with ketamine, and mortality. RESULTS: Forty-nine patients were enrolled. Median age was 29years (range 18-66); 76% (37/49) were male. Median time to adequate sedation was 4.2min (95% CI: 2.5-5.9, range 1-25min) and 90% (44/49) had adequate sedation prehospital. Seven patients (14%) received a second sedative prehospital. Intubation occurred in 57% (28/49) of patients. Mechanical ventilation lasted <24h in 82% (23/28) of patients, and <48h in 96% (27/28) of patients. A single physician intubated 36% (10/28) of the patients. Complications related to ketamine included hypersalivation (n=9, 18%), vomiting (n=3, 6%), and emergence reaction (n=2, 4%). One patient died from complications of septic shock on hospital day 29, likely unrelated to ketamine. CONCLUSIONS: In patients with prehospital profound agitation, ketamine provides rapid effective sedation when used as a primary therapy. Intubation was common but accompanied by a short duration of mechanical ventilation and appears to have been subject to individual physician practice variation.

A Prospective Observational Study of Patients Receiving Intravenous and Intramuscular Olanzapine in the Emergency Department.

STUDY OBJECTIVE: Parenteral olanzapine is an emerging therapy for a variety of conditions in the emergency department (ED). Intramuscular administration is standard; however, intravenous administration has been proposed as a safe alternative route. We investigate the safety and efficacy of both intramuscular and intravenous olanzapine in the ED when used for a variety of indications. METHODS: This was a prospective observational study of patients presenting to an urban Level I trauma center ED. Trained research associates screened the ED for patients receiving parenteral olanzapine. The primary outcome of the study was incidence of respiratory depression measured with standard markers. Secondary outcomes included use of additional doses or sedatives, corrected QT interval (QTc) data, time to nadir sedation, adverse events, and physician assessment of efficacy. RESULTS: There were 784 patients included in the final analysis. Intravenous olanzapine was administered to 295 patients; 489 received intramuscular olanzapine. Respiratory depression occurred in 11 of 295 patients (3.7%; 95% confidence interval [CI] 1.6% to 5.9%) receiving intravenous olanzapine and 10 of 489 (2.0%; 95% CI 0.8% to 3.3%) receiving intramuscular olanzapine. Seven patients required intubation, 2 in the intravenous group and 5 in the intramuscular group. Nonrespiratory complications occurred in 8 patients, 6 of 295 (2.0%; 95% CI 0.4% to 3.6%) in the intravenous group and 2 of 489 (0.4%; 95% CI 0% to 0.96%) in the intramuscular group. Dysrhythmias were isolated to 2 episodes of bradycardia requiring only supportive care. CONCLUSION: These data suggest that, with proper monitoring, administration of olanzapine, both intramuscular and intravenous, is safe for several indications in the ED.

A prospective study of ketamine versus haloperidol for severe prehospital agitation.

CONTEXT: Ketamine is an emerging drug for the treatment of acute undifferentiated agitation in the prehospital environment, however no prospective comparative studies have evaluated its effectiveness or safety in this clinical setting. OBJECTIVE: We hypothesized 5 mg/kg of intramuscular ketamine would be superior to 10 mg of intramuscular haloperidol for severe prehospital agitation, with time to adequate sedation as the primary outcome measure. METHODS: This was a prospective open label study of all patients in an urban EMS system requiring chemical sedation for severe acute undifferentiated agitation that were subsequently transported to the EMS system's primary Emergency Department. All paramedics were trained in the Altered Mental Status Scale and prospectively recorded agitation scores on all patients. Two 6-month periods where either ketamine or haloperidol was the first-line therapy for severe agitation were prospectively compared primarily for time to adequate sedation. Secondary outcomes included laboratory data and adverse medication events. RESULTS: 146 subjects were enrolled; 64 received ketamine, 82 received haloperidol. Median time to adequate sedation for the ketamine group was 5 minutes (range 0.4-23) vs. 17 minutes (range 2-84) in the haloperidol group (difference 12 minutes, 95% CI 9-15). Complications occurred in 49% (27/55) of patients receiving ketamine vs. 5% (4/82) in the haloperidol group. Complications specific to the ketamine group included hypersalivation (21/56, 38%), emergence reaction (5/52, 10%), vomiting (5/57, 9%), and laryngospasm (3/55, 5%). Intubation was also significantly higher in the ketamine group; 39% of patients receiving ketamine were intubated vs. 4% of patients receiving haloperidol. CONCLUSIONS: Ketamine is superior to haloperidol in terms of time to adequate sedation for severe prehospital acute undifferentiated agitation, but is associated with more complications and a higher intubation rate.

Executive Attention Impairment in Adolescents With Major Depressive Disorder.

Neural network models that guide neuropsychological assessment practices are increasingly used to explicate depression, though a paucity of work has focused on regulatory systems that are under development in adolescence. The purpose of this study was to evaluate subsystems of attention related to executive functioning including alerting, orienting, and executive attention networks, as well as sustained attention with varying working memory load, in a sample of depressed and well adolescents. Neuropsychological functioning in 99 adolescents diagnosed with major depressive disorder (MDD) and 63 adolescent healthy controls (M = 16.6 years old) was assessed on the Attention Network Test (ANT) and the Continuous Performance Test, Identical Pairs. Adolescents with MDD, particularly those who were not medicated, were slower to process conflict (slower reaction time on the Executive Attention scale of the ANT) compared to controls, particularly for those who were not undergoing psychopharmacological treatment. Tentative evidence also suggests that within the MDD group, orienting performance was more impaired in those with a history of comorbid substance use disorder, and alerting was more impaired in those with a history of a suicide attempt. Adolescents with depression showed impaired executive attention, although cognitive performance varied across subgroups of patients. These findings highlight the importance of examining neurocognitive correlates associated with features of depression and suggest an avenue for future research to help guide the development of interventions.