Comparison of Nebulized Ketamine to Intravenous Subdissociative Dose Ketamine for Treating Acute Painful Conditions in the Emergency Department: A Prospective, Randomized, Double-Blind, Double-Dummy Controlled Trial.

STUDY OBJECTIVE: We aimed to assess and compare the analgesic efficacy and adverse effects of intravenous subdissociative-dose ketamine to nebulized ketamine in emergency department (ED) patients with acute painful conditions. METHODS: We conducted a prospective, randomized, double-blind, double-dummy clinical trial in adult patients (ages 18 and older) with a numerical rating scale pain score of ≥5. We randomized subjects to receive either a single dose of 0.3 mg/kg of intravenous (IV) ketamine or 0.75 mg/kg of nebulized ketamine through a breath-actuated nebulizer. Primary outcome was the difference in pain scores on the numerical rating scale between groups at 30 minutes postmedication administration. The secondary outcomes included the need for rescue analgesia, occurrences of adverse events in each group, and the difference in pain scores at 15, 30, 60, 90, and 120 minutes. We calculated a 95% confidence interval (CI) for a mean difference at 30 minutes, with a minimum clinically important difference set at 1.3 points. RESULTS: We enrolled 150 subjects (75 per group). Mean pain scores through numerical rating scale were 8.2 for both groups at baseline, which decreased to 3.6 and 3.8 at 30 minutes, yielding a mean difference of 0.23 (95% CI -1.32 to 0.857). We observed no clinically concerning changes in vital signs. No serious adverse events occurred in any of the groups throughout the study period. CONCLUSION: We found no difference between the administration of IV and nebulized ketamine for the short-term treatment of moderate to severe acute pain in the ED, with both treatments providing a clinically meaningful reduction in pain scores at 30 minutes.

The Impact of the Implementation of a Pharmacist-Driven Protocol of Second Dose Cefepime for Adult Patients With Sepsis in the Emergency Department at a Tertiary Care Academic Medical Center.

Purpose: Prior literature evaluating the importance of timely second-dose antibiotics in patients with sepsis has led to better outcomes and a possible reduction in mortality, length of mechanical ventilation, and length of time requiring vasopressors. Objective: To evaluate the impact of a newly developed pharmacist-led two-dose cefepime protocol implemented within an emergency department (ED) service. Methods: This was a retrospective, single-center, pre-post observational cohort study. Institutional review board approval was obtained. The primary endpoint was a reduction in time between the first and the second doses of antibiotics for patients with sepsis who present to the emergency department. Secondary endpoints included length of vasopressor therapy, intensive care unit (ICU) length of stay, hospital length of stay, duration of mechanical ventilation, and mortality. Results: A total of 84 patients were included in the pharmacist-led two-dose hospital protocol and 79 patients were included in the historical control. In the control cohort, the median time between the first and second dose of antibiotics was 12 hours vs 8.5 hours in the tested cohort. The average time requiring vasopressors was 1.20 days for the control cohort vs .46 days for the post-implementation group. Lastly, the median hospital length of stay in days was 8 for the control group vs 7 for the tested cohort. Conclusion: Implementation of a pharmacist-led two-dose cefepime protocol was associated with a numerically lower duration between second-dose antibiotics, days requiring vasopressors, and a slight reduction in hospital length of stay.

Oral Aspirin/ketamine versus oral ketamine for emergency department patients with acute musculoskeletal pain.

OBJECTIVE: The purpose of this study is to investigate if an orally administered combination of aspirin and ketamine will provide better analgesia than a ketamine alone in adult patients presenting to the Emergency Department (ED) with acute musculoskeletal pain. METHODS: We conducted a prospective, randomized, open-label trial of ED patients aged 18 and older presenting with moderate to severe acute musculoskeletal pain as defined by an 11-point numeric rating scale (NRS) with an initial score of ≥5. Patients were randomized to receive either 324 mg of VTS-Aspirin™ and 0.5 mg/kg of oral ketamine (AOK) that is directly swallowed or 0.5 mg/kg of oral ketamine (OK) alone that is swished first and then swallowed. Patients were assessed at baseline, 30, 60, 90, and 120 min. The primary outcome was a difference in pain scores between the two groups at 60 min post-administration. Secondary outcomes included adverse events and the need for rescue analgesia. RESULTS: We enrolled 60 patients in the study (30 per group). The difference in mean pain scores at 60 min between the AOK and OK groups was 2.6 [95% CI: 1.38-3.77] showing a lower mean pain score in the OK group. At 60 min, the AOK group had a change in mean pain score from 8.4 to 6.3 (difference 2.1; 95% CI: 1.35-3.00). The OK group had a change in mean pain score from 7.8 to 3.7 (difference 4.1, 95% CI: 3.25-4.90). No clinically concerning changes in vital signs were observed. No serious adverse events occurred in either group. The most commonly reported adverse effects were dizziness and fatigue. None of the participants required rescue analgesia at 60 min post-medications administration. CONCLUSION: The administration of an oral combination of VTS-Aspirin ™ and ketamine resulted in less analgesia compared to oral ketamine alone, for the short-term treatment of moderate to severe acute musculoskeletal pain in the ED. CLINICALTRIALS: govRegistration: NCT04860804.

Analgesic Efficacy of Oral Aspirin/Ketamine Combination for Management of Acute Musculoskeletal Pain in the Emergency Department - A Proof of Concept Pilot Study.

BACKGROUND: Musculoskeletal pain (MSK) affects one out of three adults and is the most common source of significant long-term pain, physical disability, and under-treatment in the emergency department (ED). OBJECTIVE: We aimed to assess the analgesic efficacy of a combination of oral VTS-Aspirin® (Vitalis Analgesics, New York, NY) and ketamine in managing acute MSK pain in adult ED patients. METHODS: This was a prospective, proof-of-concept, single-arm, pilot study evaluating the analgesic efficacy of a single dose of oral combination of VTS-Aspirin and ketamine in adult ED patients with acute moderate-to-severe MSK pain. The primary outcome included the difference in pain scores on an 11-point numeric pain rating scale at 60 min. Secondary outcomes included the need for rescue analgesia, the occurrence of adverse events at 60 min, and a change in pain scores at 120 min. RESULTS: We enrolled 25 subjects in the study. The mean baseline pain score was 8.6 and the mean pain score at 60 min decreased to 4.8. The oral ketamine dose ranged from 24 mg to 50 mg, with a mean dose of 37.8 mg. No clinically concerning changes in vital signs were noted. No serious adverse events occurred in any of the subjects. Majority of adverse effects were transient and weak in intensity. CONCLUSION: We demonstrated that administration of an oral combination of VTS-Aspirin and ketamine to adult ED patients with acute MSK pain resulted in clinically significant pain relief in 80% of enrolled subjects.

Comparison of Nebulized Ketamine at Three Different Dosing Regimens for Treating Painful Conditions in the Emergency Department: A Prospective, Randomized, Double-Blind Clinical Trial.

STUDY OBJECTIVE: We aimed to assess and compare the analgesic efficacies and adverse effects of ketamine administered through a breath-actuated nebulizer at 3 different dosing regimens for emergency department patients presenting with acute and chronic painful conditions. METHODS: This was a prospective, randomized, double-blinded trial comparing 3 doses of nebulized ketamine (0.75 mg/kg, 1 mg/kg, and 1.5 mg/kg) administered through breath-actuated nebulizer in adult emergency department patients aged 18 years and older with moderate to severe acute and chronic pain. The primary outcome included the difference in pain scores on an 11-point numeric rating scale between all 3 groups at 30 minutes. Secondary outcomes included the need for rescue analgesia (additional doses of nebulized ketamine or intravenous morphine) and adverse events in each group at 30 and 60 minutes. RESULTS: We enrolled 120 subjects (40 per group). The difference in mean pain scores at 30 minutes between the 0.75 mg/kg and 1 mg/kg groups was 0.25 (95% confidence interval [CI] 1.28 to 1.78); between the 1 mg/kg and 1.5 mg/kg groups was -0.225 (95% CI -1.76 to 1.31); and between the 0.75 mg/kg and 1.5 mg/kg groups was 0.025 (95% CI -1.51 to 1.56). No clinically concerning changes in vital signs occurred. No serious adverse events occurred in any of the groups. CONCLUSION: We found no difference between all 3 doses of ketamine administered through breath-actuated nebulizer for short-term treatment of moderate to severe pain in the emergency department.

Analgesic efficacy of morphine sulfate immediate release vs. oxycodone/acetaminophen for acute pain in the emergency department.

OBJECTIVE: Previous research demonstrated that administration of Morphine Sulfate Immediate Release (MSIR) results in similar analgesic efficacy to Oxycodone but with significantly lesser degrees of euphoria and reward. The purpose of this study sit to investigate if MSIR combined with Acetaminophen can serve as an opioid analgesic alternative to Oxycodone combined with acetaminophen (Percocet) for acute pain in the Emergency Department (ED). METHODS: A prospective, randomized, double-blind trial of ED patients aged 18 to 64 years presenting with moderate to severe acute pain as defined by an 11-point numeric rating scale (NRS) with an initial score of ≥5 (0 = no pain and 10 = very severe pain). Patients were randomized to receive either 15 mg MSIR combined with 650 mg of Acetaminophen or 10 mg Oxycodone combined with 650 mg Acetaminophen. Patients were assessed at baseline, 30, 45 and 60 min. The primary outcome was reduction in pain at 60 min. Secondary outcomes include drug likeability and adverse events. RESULTS: 80 patients were enrolled in the study (40 per group). Demographic characteristics were similar between the groups (P > 0.05). Mean NRS pain scores at baseline were 8.44 for the MSIR group and 8.53 for the Percocet group (P = 0.788). Mean pain scores decreased over time but remained similar between the groups: 30 min (6.03 vs. 6.43; P = 0.453), 45 min (5.31 vs. 5.48; P = 0.779), and 60 min (4.22 vs. 4.87; P = 0.346). Reduction in mean NRS pain scores were statistically significant from baseline to 30, 45 and 60 min within each group (P < 0.0001 at each time point for both groups). The largest NRS mean difference was from baseline to 60 min: 4.2 (95% CI: 3.43 to 5.01) for MSIR group and 3.61 (95% CI: 2.79 to 4.43) for Percocet group. No clinically significant changes or any serious adverse events were observed in either group. CONCLUSION: MSIR provides similar analgesic efficacy as Percocet for short-term pain relief in the ED, similar rates of nausea/vomiting, and lower rates of likeability of the drug.

Dynamics of atmospheric carbon dioxide over different land cover types in India.

This study presents an analysis of high-resolution space borne retrievals of the column-averaged dry-air mole fraction of carbon dioxide [Formula: see text] and the role of vegetation in controlling atmospheric CO2 dynamics over the Indian region. Nadir and glint mode [Formula: see text] retrievals from the Orbiting Carbon Observatory-2 (OCO-2) spectrometer for the period September 2014-July 2017 are studied with satellite-derived normalized difference vegetation index (NDVI) and rainfall over different land cover types. The atmospheric [Formula: see text] variability shows a strong negative correlation with satellite-derived NDVI. Higher rainfall favours the vegetative growth and photosynthetic activity, thus lowers atmospheric [Formula: see text] concentration. The mean monthly [Formula: see text] over terrestrial region of India is observed as 400.18 ± 3.85 ppm with seasonal variations over different land cover types. The correlation of [Formula: see text] with NDVI over mixed forest and deciduous broadleaf forest types was estimated as - 0.86, - 0.76 (p < 0.01), respectively. The study could also highlight strong seasonal [Formula: see text] variability at higher latitudinal zones of India. It is significant to note that space-based observations indicate that atmospheric carbon dioxide levels have surpassed a significant milestone of 400 ppm in recent times. The study provides significant inputs towards improving our understanding of terrestrial biogeochemical carbon cycle over India.

Intravenous subdissociative-dose ketamine versus morphine for acute geriatric pain in the Emergency Department: A randomized controlled trial.

STUDY OBJECTIVE: We compare the analgesic efficacy and safety of subdissociative intravenous-dose ketamine (SDK) versus morphine in geriatric Emergency Department (ED) patients. METHODS: This was a prospective, randomized, double-blind trial evaluating ED patients aged 65 and older experiencing moderate to severe acute abdominal, flank, musculoskeletal, or malignant pain. Patients were randomized to receive SDK at 0.3 mg/kg or morphine at 0.1 mg/kg by short intravenous infusion over 15 min. Evaluations occurred at 15, 30, 60, 90, and 120 min. Primary outcome was reduction in pain at 30 min. Secondary outcomes included overall rates of adverse effects and incidence of rescue analgesia. RESULTS: Thirty patients per group were enrolled in the study. The primary change in mean pain scores was not significantly different in the ketamine and morphine groups: 9.0 versus 8.4 at baseline (mean difference 0.6; 95% CI -0.30 to 1.43) and 4.2 versus 4.4 at 30 min (mean difference -0.2; 95% CI -1.93 to1.46). Patients in the SDK group reported higher rates of psychoperceptual adverse effects at 15, 30, and 60 min post drug administration. Two patients in the ketamine group and one in the morphine group experienced brief desaturation episodes. There were no statistically significant differences with respect to changes in vital signs and need for rescue medication. CONCLUSION: SDK administered at 0.3 mg/kg over 15 min provides analgesic efficacy comparable to morphine for short-term treatment of acute pain in the geriatric ED patients but results in higher rates of psychoperceptual adverse effects. ClinicalTrials.gov Registration #: NCT02673372.