Ketamine For Acute Pain After Trauma (KAPT): A Pragmatic, Randomized Clinical Trial.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. LEVEL OF EVIDENCE: I; Therapeutic/Care Management.

Association of Ketamine Dosing with Intubation and Other Adverse Events in Patients with Behavioral Emergencies.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Ketamine for acute pain after trauma: the KAPT randomized controlled trial.

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.

Portable Neuromonitoring Device Detects Large Vessel Occlusion in Suspected Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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 (C-statistic=0.88). CONCLUSIONS: 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.

Long-term domain-specific improvement following poor grade aneurysmal subarachnoid hemorrhage.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. CONCLUSION: 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.

Racial differences in cerebral vasospasm: a systematic review of the literature.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.