Dataset Information

Comparing low-dose intravenous ketamine-midazolam with intravenous morphine with respect to pain control in patients with closed limb fracture.

ABSTRACT:

Background

We assessed the effects of low-dose IV ketamine-midazolam versus morphine on pain control in patients with closed limb fracture(s); and also compared the incidence of adverse events (cardio-pulmonary) between two groups.

Materials and methods

This prospective, single-blind, non-inferiority trial randomized consecutive emergency department (ED) patients aged 18-60 years to two groups: Receiving 300-500 mcg/kg ketamine plus 0.03 mg/kg midazolam, or 0.05-0.1 mg/kg morphine. Visual analogue score (VAS) and adverse events were verified during an interval of 30 minutes.

Results

Two hundred and thirty - six patients were selected, among whom 207 were males (87.3%). The average age was 29 ± 2, (range, 18-60 years). The VAS score at T30 (i.e., 30 minutes after initial analgesic dose) was significantly decreased compared with VAS score at T0, in both groups. No statistically significant difference, however, was observed between the two groups (-6.1 ± 1.1 versus -6.2 ± 1.0; P = 0.16). With regard to systolic blood pressure and respiratory rate, however, a meaningful difference was noted between the two groups (1.5 ± 6.4 versus -2.1 ± 6.6; P = 0.000 for SBP, and -0.2 ± 1.1 versus -1.1 ± 6.1; P = 0.048 for RR).

Conclusion

Low-dose intravenous ketamine plus midazolam has the same analgesic effects as morphine on pain control in trauma patients with closed limb fracture(s), in addition to less respiratory adverse events.

SUBMITTER: Ahmadi O

PROVIDER: S-EPMC4155703 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Publications

Comparing low-dose intravenous ketamine-midazolam with intravenous morphine with respect to pain control in patients with closed limb fracture.

Ahmadi Omid O Isfahani Mehdi Nasr MN Feizi Awat A

Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences 20140601 6

<h4>Background</h4>We assessed the effects of low-dose IV ketamine-midazolam versus morphine on pain control in patients with closed limb fracture(s); and also compared the incidence of adverse events (cardio-pulmonary) between two groups.<h4>Materials and methods</h4>This prospective, single-blind, non-inferiority trial randomized consecutive emergency department (ED) patients aged 18-60 years to two groups: Receiving 300-500 mcg/kg ketamine plus 0.03 mg/kg midazolam, or 0.05-0.1 mg/kg morphine ...[more]

PMID: 25197290

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Project description:IntroductionThis study aims to investigate the effectiveness of intravenous ibuprofen or intravenous ibuprofen plus acetaminophen compared to intravenous morphine in patients with closed extremity fractures.MethodsA triple-blinded randomized clinical trial was conducted at a tertiary trauma center in Iran. Adult patients between 15 and 60 years old with closed, isolated limb fractures and a pain intensity of at least 6/10 on the visual analog scale (VAS) were eligible. Patients with specific conditions or contraindications were not included. Participants were randomly assigned to receive intravenous ibuprofen, intravenous ibuprofen plus acetaminophen, or intravenous morphine. Pain scores were assessed using the visual analog scale at baseline and 5, 15, 30, and 60 min after drug administration. The primary outcome measure was the pain score reduction after one hour.ResultsOut of 388 trauma patients screened, 158 were included in the analysis. There were no significant differences in age or sex distribution among the three groups. The pain scores decreased significantly in all groups after 5 min, with the morphine group showing the lowest pain score at 15 min. The maximum effect of ibuprofen was observed after 30 min, while the ibuprofen-acetaminophen combination maintained its effect after 60 min. One hour after injection, pain score reduction in the ibuprofen-acetaminophen group was significantly more than in the other two groups, and pain score reduction in the ibuprofen group was significantly more than in the morphine group.ConclusionThe study findings suggest that ibuprofen and its combination with acetaminophen have similar or better analgesic effects compared to morphine in patients with closed extremity fractures. Although morphine initially provided the greatest pain relief, its effect diminished over time. In contrast, ibuprofen and the ibuprofen-acetaminophen combination maintained their analgesic effects for a longer duration. The combination therapy demonstrated the most sustained pain reduction. The study highlights the potential of non-opioid analgesics in fracture pain management and emphasizes the importance of initiation of these medications as first line analgesic for patients with fractures. These findings support the growing trend of exploring non-opioid analgesics in pain management.Trial registrationClinicalTrials.gov Identifier: NCT05630222 (Tue, Nov 29, 2022). The manuscript adheres to CONSORT guidelines.

Project description:Hemorrhage is a leading cause of preventable battlefield and civilian trauma deaths. Ketamine, fentanyl, and morphine are recommended analgesics for use in the prehospital (i.e., field) setting to reduce pain. However, it is unknown whether any of these analgesics reduce hemorrhagic tolerance in humans. We tested the hypothesis that fentanyl (75 µg) and morphine (5 mg), but not ketamine (20 mg), would reduce tolerance to simulated hemorrhage in conscious humans. Each of the three analgesics was evaluated independently among different cohorts of healthy adults in a randomized, crossover (within drug/placebo comparison), placebo-controlled fashion using doses derived from the Tactical Combat Casualty Care Guidelines for Medical Personnel. One minute after an intravenous infusion of the analgesic or placebo (saline), we employed a pre-syncopal limited progressive lower-body negative pressure (LBNP) protocol to determine hemorrhagic tolerance. Hemorrhagic tolerance was quantified as a cumulative stress index (CSI), which is the sum of products of the LBNP and the duration (e.g., [40 mmHg x 3 min] + [50 mmHg x 3 min] …). Compared with ketamine (p = 0.002 post hoc result) and fentanyl (p = 0.02 post hoc result), morphine reduced the CSI (ketamine (n = 30): 99 [73-139], fentanyl (n = 28): 95 [68-130], morphine (n = 30): 62 [35-85]; values expressed as a % of the respective placebo trial's CSI; median [IQR]; Kruskal-Wallis test p = 0.002). Morphine-induced reductions in tolerance to central hypovolemia were not well explained by a prediction model including biological sex, body mass, and age (R2=0.05, p = 0.74). These experimental data demonstrate that morphine reduces tolerance to simulated hemorrhage while fentanyl and ketamine do not affect tolerance. Thus, these laboratory-based data, captured via simulated hemorrhage, suggest that morphine should not be used for a hemorrhaging individual in the prehospital setting.

Project description:BackgroundSubanesthetic ketamine may reduce perioperative consumption of opioids. We studied whether intravenous S-ketamine alters the pharmacokinetics of oral morphine in healthy volunteers.MethodsIn this paired, randomized, double-blind, crossover trial, 12 participants under a 2-hour intravenous S-ketamine (0.57 mg/kg/h) or placebo infusion received oral morphine (0.2 mg/kg) at 30 minutes. Plasma concentrations of ketamine, morphine, and their major metabolites were quantified for 24 hours. The primary end point was area under the curve (AUC)0-24 of morphine. Other pharmacokinetic variables for morphine and its metabolites were studied as secondary end points. The data were analyzed as between-phase comparisons for each participant using Wilcoxon matched-pairs signed-rank tests (tmax) or paired t-tests on log-transformed variables (other variables).ResultsWhile the AUC0-24 was similar between the 2 phases, S-ketamine reduced the AUC0-1.5 of oral morphine by 69% (ratio to control, 0.31; 90% confidence interval [CI], 0.15-0.65; P = .0171) and increased its tmax from 0.5 (range, 0.50-1.5) to 1.0 hour (range, 0.50-4.0; P = .010). The AUC0-1.5 of morphine-6-glucuronide (M6G) was reduced by 84% (0.16; 90% CI, 0.07-0.37; P = .0025) and maximum plasma concentration (Cmax) by 43% (0.57; 90% CI, 0.40-0.81; P = .0155), while its tmax was increased from 1.5 (range, 1.0-2.0) to 4.0 (range, 1.0-8.0; P = .0094) hours by S-ketamine. Similarly, the AUC0-1.5 of morphine-3-glucuronide (M3G) was reduced by 85% (0.15; 90% CI, 0.05-0.43; P = .0083), and tmax increased from 1.0 (range, 0.5-1.5) to 4.0 hours (range, 1.0-8.0; P = .0063). In addition, the M6G-to-morphine and M3G-to-morphine metabolic AUC ratios were decreased by 47% (0.53; 90% CI, 0.39-0.71; P = .0033) and 52% (0.48; 90% CI, 0.27-0.85; P = .0043) during 0 to 1.5 hours and by 15% (0.85; 90% CI, 0.78-0.92; P = .0057) and 10% (0.90; 90% CI, 0.83-0.98; P = .0468) during 0 to 24 hours, respectively. One participant was excluded from the analyses due to vomiting in the S-ketamine phase.ConclusionsIntravenous S-ketamine inhibited the metabolism of oral morphine and delayed its absorption, resulting in a net reduction in the exposure to morphine during the first 1.5 hours. Intravenous S-ketamine may delay the absorption and impair the efficacy of orally administered analgesics and other drugs.

Project description:Promising initial data indicate that the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine may be beneficial in post-traumatic stress disorder (PTSD). Here, we explore the neural correlates of ketamine-related changes in PTSD symptoms, using a rich battery of functional imaging data (two emotion-processing tasks and one task-free scan), collected from a subset of participants of a randomized clinical trial of repeated-dose intravenous ketamine vs midazolam (total N = 21). In a pre-registered analysis, we tested whether changes in an a priori set of imaging measures from a target neural circuit were predictive of improvement in PTSD symptoms, using leave-one-out cross-validated elastic-net regression models (regions of interest in the target circuit consisted of the dorsal and rostral anterior cingulate cortex, ventromedial prefrontal cortex, anterior hippocampus, anterior insula, and amygdala). Improvements in PTSD severity were associated with increased functional connectivity between the ventromedial prefrontal cortex (vmPFC) and amygdala during emotional face-viewing (change score retained in model with minimum predictive error in left-out subjects, standardized regression coefficient [β] = 2.90). This effect was stronger in participants who received ketamine compared to midazolam (interaction β = 0.86), and persisted following inclusion of concomitant change in depressive symptoms in the analysis model (β = 0.69). Improvement following ketamine was also predicted by decreased dorsal anterior cingulate activity during emotional conflict regulation, and increased task-free connectivity between the vmPFC and anterior insula (βs = -2.82, 0.60). Exploratory follow-up analysis via dynamic causal modelling revealed that whilst improvement in PTSD symptoms following either drug was associated with decreased excitatory modulation of amygdala→vmPFC connectivity during emotional face-viewing, increased top-down inhibition of the amygdala by the vmPFC was only observed in participants who improved under ketamine. Individuals with low prefrontal inhibition of amygdala responses to faces at baseline also showed greater improvements following ketamine treatment. These preliminary findings suggest that, specifically under ketamine, improvements in PTSD symptoms are accompanied by normalization of hypofrontal control over amygdala responses to social signals of threat.

Dataset Information

Comparing low-dose intravenous ketamine-midazolam with intravenous morphine with respect to pain control in patients with closed limb fracture.

Background

Materials and methods

Results

Conclusion

Publications

Comparing low-dose intravenous ketamine-midazolam with intravenous morphine with respect to pain control in patients with closed limb fracture.

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