Non-narcotic intravenous medications may be a beneficial adjunct to oral multimodal pain regimens (MMPRs) which reduce but do not eliminate opioid exposure and prescribing after trauma. We ...hypothesized that the addition of a sub-dissociative ketamine infusion (KI) to a standardized oral MMPR reduces inpatient opioid exposure.
Eligible adult trauma patients admitted to the intermediate or intensive care unit were randomized upon admission to our institutional MMPR per usual care (UC) or UC plus sub-dissociative KI for 24 to 72 hours after arrival. The primary outcome was morphine milligram equivalents per day (MME/d) and secondary outcomes included total MME, discharge with an opioid prescription (OP%), and rates of ketamine side effects. Bayesian posterior probabilities (pp) were calculated using neutral priors.
A total of 300 patients were included in the final analysis with 144 randomized to KI and 156 to UC. Baseline characteristics were similar between groups. The injury severity scores for KI were 19 14, 29 versus UC 22 14, 29. The KI group had a lower rate of long-bone fracture (37% versus 49%) and laparotomy (16% versus 24%). Patients receiving KI had an absolute reduction of 7 MME/day, 96 total MME, and 5% in OP%. Additionally, KI had a relative risk (RR) reduction of 19% in MME/day (RR 0.81 0.69 - 0.95, pp = 99%), 20% in total MME (RR 0.80 0.64, 0.99, pp = 98%), and 8% in OP% (RR 0.92 0.76, 1.11, pp = 81%). The KI group had a higher rate of delirium (11% versus 6%); however, rates of other side effects such as arrythmias and unplanned intubations were similar between groups.
Addition of a sub-dissociative ketamine infusion to an oral MMPR resulted in a decrease in opioid exposure in severely injured patients. Sub-dissociative ketamine infusions can be used as a safe adjunct to decrease opioid exposure in monitored settings.
I; Therapeutic/Care Management.
Early detection of large vessel occlusion (LVO) stroke optimizes endovascular therapy and improves outcomes. Clinical stroke severity scales used for LVO identification have variable accuracy. We ...investigated a portable LVO-detection device (PLD), using electroencephalography and somatosensory-evoked potentials, to identify LVO stroke.
We obtained PLD data in suspected patients with stroke enrolled prospectively via a convenience sample in 8 emergency departments within 24 hours of symptom onset. LVO discriminative signals were integrated into a binary classifier. The National Institutes of Health Stroke Scale was documented, and 4 prehospital stroke scales were retrospectively calculated. We compared PLD and scale performance to diagnostic neuroimaging.
Of 109 patients, there were 25 LVO (23%), 38 non-LVO ischemic (35%), 14 hemorrhages (13%), and 32 stroke mimics (29%). The PLD had higher sensitivity (80% 95% CI, 74-85) and similar specificity (80% 95% CI, 77-83) to all prehospital scales at their predetermined high probability LVO thresholds. The PLD had high discrimination for LVO (
-statistic=0.88).
The PLD identifies LVO with superior accuracy compared with prehospital stroke scales in emergency department suspected stroke. Future studies need to validate the PLD's potential as an LVO triage aid in prehospital undifferentiated stroke populations.
Varying rates of complications have been reported for prehospital sedation with ketamine, and the relationship to dosing has not been studied on a large scale. We evaluated the association between ...prehospital ketamine dosing and rates of intubations and other adverse events in patients with behavioral emergencies.
Using the 2018/2019 ESO public-use research datasets, we included all non-traumatic, adult behavioral and drug-related EMS encounters with ketamine administration. Based on consensus guidelines, we stratified patients into "above" and "at/below" the maximum dosing for sedation (2 mg/kg IV/IO or 5 mg/kg IM) using the highest single dose of ketamine given. We created propensity scores for matched subjects using 1:1 propensity score matching. Using logistic regression, we compared rates of intubation and other airway interventions, antipsychotic coadministration, improvement reported by EMS, hypoxia, hypotension, and cardiac arrest between the two groups.
We included 2383 patients: 478 in the above and 1905 in the at/below dose group. Above-dose ketamine was associated with a higher rate of intubation or supraglottic airway placement (6.4% v 3.3%, OR 2.0, 95% CI 1.00-3.90). Other airway interventions were similar (40.0% v 40.0%, OR 1, 95% CI 0.80-1.30). The above-dose group also showed a higher rate of improvement noted by EMS clinicians (92.5% v 88.7%, OR 1.6, 95% CI 1.01-2.40). The rates of antipsychotic coadministration, hypoxia, hypotension, and cardiac arrest were similar between the cohorts.
Patients given ketamine doses above consensus recommendations for sedation appeared more likely to receive prehospital intubation but not more likely to experience other adverse events.
Abstract
Background
Evidence for effective pain management and opioid minimization of intravenous ketamine in elective surgery has been extrapolated to acutely injured patients, despite limited ...supporting evidence in this population. This trial seeks to determine the effectiveness of the addition of sub-dissociative ketamine to a pill-based, opioid-minimizing multi-modal pain regimen (MMPR) for post traumatic pain.
Methods
This is a single-center, parallel-group, randomized, controlled comparative effectiveness trial comparing a MMPR to a MMPR plus a sub-dissociative ketamine infusion. All trauma patients 16 years and older admitted following a trauma which require intermediate (IMU) or intensive care unit (ICU) level of care are eligible. Prisoners, patients who are pregnant, patients not expected to survive, and those with contraindications to ketamine are excluded from this study. The primary outcome is opioid use, measured by morphine milligram equivalents (MME) per patient per day (MME/patient/day). The secondary outcomes include total MME, pain scores, morbidity, lengths of stay, opioid prescriptions at discharge, and patient centered outcomes at discharge and 6 months.
Discussion
This trial will determine the effectiveness of sub-dissociative ketamine infusion as part of a MMPR in reducing in-hospital opioid exposure in adult trauma patients. Furthermore, it will inform decisions regarding acute pain strategies on patient centered outcomes.
Trial registration
The Ketamine for Acute Pain Management After Trauma (KAPT) with registration #
NCT04129086
was registered on October 16, 2019.
The restoration of blood-flow following cerebral ischemia incites a series of deleterious cascades that exacerbate neuronal injury. Pharmacologic inhibition of the C3a-receptor ameliorates cerebral ...injury by attenuating post-ischemic inflammation. Recent reports also implicate C3a in the modulation of tissue repair, suggesting that complement may influence both injury and recovery at later post-ischemic time-points.
To evaluate the effect of C3a-receptor antagonism on post-ischemic neurogenesis and neurological outcome in the subacute period of stroke, transient focal cerebral ischemia was induced in adult male C57BL/6 mice treated with multiple regimens of a C3a receptor antagonist (C3aRA).
Low-dose C3aRA administration during the acute phase of stroke promotes neuroblast proliferation in the subventricular zone at 7 days. Additionally, the C3a receptor is expressed on T-lymphocytes within the ischemic territory at 7 days, and this cellular infiltrate is abrogated by C3aRA administration. Finally, C3aRA treatment confers robust histologic and functional neuroprotection at this delayed time-point.
Targeted complement inhibition through low-dose antagonism of the C3a receptor promotes post-ischemic neuroblast proliferation in the SVZ. Furthermore, C3aRA administration suppresses T-lymphocyte infiltration and improves delayed functional and histologic outcome following reperfused stroke. Post-ischemic complement activation may be pharmacologically manipulated to yield an effective therapy for stroke.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
While efforts have been made to document short-term outcomes following poor grade aneurysmal subarachnoid hemorrhage (aSAH), no data exist concerning the degree of delayed improvement in neurological ...function. Here we assess cognitive function, level of independence, and quality of life (QoL) over 12 months following poor grade aSAH.
Data on definitively treated poor grade patients (Hunt and Hess grade IV or V) surviving 12 months post-aSAH were obtained through a prospectively maintained SAH database. Demographic information, medical history, and clinical course were analyzed. Health outcomes assessments completed by surviving patients at discharge (DC), three months (3 M) and 12 months (12 M) follow-up, including the Telephone Interview for Cognitive Status (TICS), Barthel Index (BI), and Sickness Impact Profile (SIP), were used to evaluate cognitive function, level of independence, and QoL.
Fifty-six poor grade patients underwent aneurysm-securing intervention and survived at least 12 months post-aSAH. Thirty-five (63%) surviving patients underwent health outcomes assessments at DC, 3 M and 12 M post-aSAH. A majority of patients had improved scores on the TICS (DC to 3 M: 91%; 3 M to 12 M: 82%), BI (DC to 3 M: 96%; 3 M to 12 M: 92%), and SIP (3 M to 12 M: 80%) following aSAH. Using paired-sample analyses, significant improvement on each test was observed.
A substantial portion of patients experience cognitive recovery, increased independence, and improved QoL following poor grade aSAH. Delayed follow-up assessments are necessary when evaluating functional recovery in this population. These findings have the potential to impact poor grade aSAH management and prognosis.
Despite a significant body of clinical research and the widespread use of early intervention with aggressive postoperative management, cerebral vasospasm (CV) continues to contribute significantly to ...the morbidity and mortality of aneurysmal subarachnoid hemorrhage (aSAH). Many studies have evaluated predictive factors, although none to date has investigated a possible difference in the incidence of CV between Asian and white patients. We present a review of the modern aSAH literature to examine the incidence of CV in Japan and Europe, two highly researched populations.
A literature search was performed using the Medline and PubMed databases. Studies conducted in Japan or Europe published between 1990 and 2004 that reported an incidence of CV after aSAH were subjected to a thorough review. Data from included studies were categorized by origin (Japan or Europe) and method of CV diagnosis (angiography, delayed ischemic neurological deficit, or new infarct attributable to CV), and then were combined. Recorded incidences then were compared using a chi test, and estimates of the relative risk of vasospasm were computed.
The initial literature search identified 102 studies, and 32 studies met all inclusion criteria. The incidence of vasospasm diagnosed by angiography, delayed ischemic neurological deficit, and computed tomography was significantly greater in Japanese studies (all P < 0.001). The relative risks for Japanese patients as compared with European patients were 2.04, 2.07, and 1.53 for angiographic CV, delayed ischemic neurological deficit, and new infarct, respectively.
Patients in Japanese studies were more likely to experience CV after aSAH across diagnostic methods. This may be a manifestation of genetic differences between Japanese and European populations. Clinicians should consider possible patient differences when interpreting CV research conducted in these populations.
Traumatic brain injury (TBI) is a complex disorder that is traditionally stratified based on clinical signs and symptoms. Recent imaging and molecular biomarker innovations provide unprecedented ...opportunities for improved TBI precision medicine, incorporating patho-anatomical and molecular mechanisms. Complete integration of these diverse data for TBI diagnosis and patient stratification remains an unmet challenge.
The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot multicenter study enrolled 586 acute TBI patients and collected diverse common data elements (TBI-CDEs) across the study population, including imaging, genetics, and clinical outcomes. We then applied topology-based data-driven discovery to identify natural subgroups of patients, based on the TBI-CDEs collected. Our hypothesis was two-fold: 1) A machine learning tool known as topological data analysis (TDA) would reveal data-driven patterns in patient outcomes to identify candidate biomarkers of recovery, and 2) TDA-identified biomarkers would significantly predict patient outcome recovery after TBI using more traditional methods of univariate statistical tests. TDA algorithms organized and mapped the data of TBI patients in multidimensional space, identifying a subset of mild TBI patients with a specific multivariate phenotype associated with unfavorable outcome at 3 and 6 months after injury. Further analyses revealed that this patient subset had high rates of post-traumatic stress disorder (PTSD), and enrichment in several distinct genetic polymorphisms associated with cellular responses to stress and DNA damage (PARP1), and in striatal dopamine processing (ANKK1, COMT, DRD2).
TDA identified a unique diagnostic subgroup of patients with unfavorable outcome after mild TBI that were significantly predicted by the presence of specific genetic polymorphisms. Machine learning methods such as TDA may provide a robust method for patient stratification and treatment planning targeting identified biomarkers in future clinical trials in TBI patients.
ClinicalTrials.gov Identifier NCT01565551.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective:Dissociation, a disruption or discontinuity in psychological functioning, is often linked with worse psychiatric symptoms; however, the prognostic value of dissociation after trauma is ...inconsistent. Determining whether trauma-related dissociation is uniquely predictive of later outcomes would enable early identification of at-risk trauma populations. The authors conducted the largest prospective longitudinal biomarker study of persistent dissociation to date to determine its predictive capacity for adverse psychiatric outcomes following acute trauma.Methods:All data were part of the Freeze 2 data release from the Advancing Understanding of Recovery After Trauma (AURORA) study. Study participants provided self-report data about persistent derealization (N=1,464), a severe type of dissociation, and completed a functional MRI emotion reactivity task and resting-state scan 2 weeks posttrauma (N=145). Three-month follow-up reports were collected of posttraumatic stress, depression, pain, anxiety symptoms, and functional impairment.Results:Derealization was associated with increased ventromedial prefrontal cortex (vmPFC) activation in the emotion reactivity task and decreased resting-state vmPFC connectivity with the cerebellum and orbitofrontal cortex. In separate analyses, brain-based and self-report measures of persistent derealization at 2 weeks predicted worse 3-month posttraumatic stress symptoms, distinct from the effects of childhood maltreatment history and current posttraumatic stress symptoms.Conclusions:The findings suggest that persistent derealization is both an early psychological and biological marker of worse later psychiatric outcomes. The neural correlates of trauma-related dissociation may serve as potential targets for treatment engagement to prevent posttraumatic stress disorder. These results underscore dissociation assessment as crucial following trauma exposure to identify at-risk individuals, and they highlight an unmet clinical need for tailored early interventions.
IMPORTANCE: A substantial proportion of the 40 million people in the US who present to emergency departments (EDs) each year after traumatic events develop posttraumatic stress disorder (PTSD) or ...major depressive episode (MDE). Accurately identifying patients at high risk in the ED would facilitate the targeting of preventive interventions. OBJECTIVES: To develop and validate a prediction tool based on ED reports after a motor vehicle collision to predict PTSD or MDE 3 months later. DESIGN, SETTING, AND PARTICIPANTS: The Advancing Understanding of Recovery After Trauma (AURORA) study is a longitudinal study that examined adverse posttraumatic neuropsychiatric sequalae among patients who presented to 28 US urban EDs in the immediate aftermath of a traumatic experience. Enrollment began on September 25, 2017. The 1003 patients considered in this diagnostic/prognostic report completed 3-month assessments by January 31, 2020. Each patient received a baseline ED assessment along with follow-up self-report surveys 2 weeks, 8 weeks, and 3 months later. An ensemble machine learning method was used to predict 3-month PTSD or MDE from baseline information. Data analysis was performed from November 1, 2020, to May 31, 2021. MAIN OUTCOMES AND MEASURES: The PTSD Checklist for DSM-5 was used to assess PTSD and the Patient Reported Outcomes Measurement Information System Depression Short-Form 8b to assess MDE. RESULTS: A total of 1003 patients (median interquartile range age, 34.5 24-43 years; 715 weighted 67.9% female; 100 weighted 10.7% Hispanic, 537 weighted 52.7% non-Hispanic Black, 324 weighted 32.2% non-Hispanic White, and 42 weighted 4.4% of non-Hispanic other race or ethnicity were included in this study. A total of 274 patients (weighted 26.6%) met criteria for 3-month PTSD or MDE. An ensemble machine learning model restricted to 30 predictors estimated in a training sample (patients from the Northeast or Midwest) had good prediction accuracy (mean SE area under the curve AUC, 0.815 0.031) and calibration (mean SE integrated calibration index, 0.040 0.002; mean SE expected calibration error, 0.039 0.002) in an independent test sample (patients from the South). Patients in the top 30% of predicted risk accounted for 65% of all 3-month PTSD or MDE, with a mean (SE) positive predictive value of 58.2% (6.4%) among these patients at high risk. The model had good consistency across regions of the country in terms of both AUC (mean SE, 0.789 0.025 using the Northeast as the test sample and 0.809 0.023 using the Midwest as the test sample) and calibration (mean SE integrated calibration index, 0.048 0.003 using the Northeast as the test sample and 0.024 0.001 using the Midwest as the test sample; mean SE expected calibration error, 0.034 0.003 using the Northeast as the test sample and 0.025 0.001 using the Midwest as the test sample). The most important predictors in terms of Shapley Additive Explanations values were symptoms of anxiety sensitivity and depressive disposition, psychological distress in the 30 days before motor vehicle collision, and peritraumatic psychosomatic symptoms. CONCLUSIONS AND RELEVANCE: The results of this study suggest that a short set of questions feasible to administer in an ED can predict 3-month PTSD or MDE with good AUC, calibration, and geographic consistency. Patients at high risk can be identified in the ED for targeting if cost-effective preventive interventions are developed.
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