Out-of-Hospital Intranasal Ketamine as an Adjunct to Fentanyl for the Treatment of Acute Traumatic Pain: A Randomized Clinical Trial.

STUDY OBJECTIVE: To evaluate if out-of-hospital administration of fentanyl and intranasal ketamine, compared to fentanyl alone, improves early pain control after injury. METHODS: We conducted an out-of-hospital randomized, placebo-controlled, blinded, parallel group clinical trial from October 2017 to December 2021. Participants were male, aged 18 to 65 years, receiving fentanyl to treat acute traumatic pain prior to hospital arrival, treated by an urban fire-based emergency medical services agency, and transported to the region's only adult Level I trauma center. Participants randomly received 50 mg intranasal ketamine or placebo. The primary outcome was the proportion with a minimum 2-point reduction in self-described pain on the verbal numerical rating scale 30 minutes after study drug administration assessed by 95% confidence interval overlap. Secondary outcomes were side effects, pain ratings, and additional pain medications through the first 3 hours of care. RESULTS: Among the 192 participants enrolled, 89 (46%) were White, (median age, 36 years; interquartile range, 27 to 53 years), with 103 receiving ketamine and 89 receiving placebo. There was no difference in the proportion experiencing improved pain 30 minutes after treatment (46/103 [44.7%] ketamine versus 32/89 [36.0%] placebo; difference in proportions, 8.7%; 95% confidence interval, -5.1% to 22.5%; P=.22) or at any time point through 3 hours. There was no difference in secondary outcomes or side effects. CONCLUSION: In our sample, we did not detect an analgesic benefit of adding 50 mg intranasal ketamine to fentanyl in out-of-hospital trauma patients.

LUCAS Device Use Associated with Prolonged Pauses during Application and Long Chest Compression Intervals.

BACKGROUND: Tenets of high-quality out-of-hospital cardiac arrest (OHCA) resuscitation include early recognition and treatment of shockable rhythms, and minimizing interruptions in compressions. Little is known about how use of a mechanical compression device affects these elements. We hypothesize that use of such a device is associated with prolonged pauses in compressions to apply the device, and long compression intervals overall. METHODS: We systematically abstracted CPR metrics from 4 months of adult non-traumatic OHCA cases, each of which had at least 10 minutes of resuscitation, used a LUCAS device, and had a valid monitor file attached to the patient care report. Our primary outcomes of interest were the duration of each pause in compressions and the duration of compressions between pauses, stratified by whether or not the LUCAS device was used/applied during the segment. Each pause was further evaluated for a possible associated procedure based on pre-defined criteria. Descriptive statistics, chi-square, and Kruskal-Wallis tests were used as appropriate. RESULTS: Fifty-eight cases were included, median age 62.5 years (IQR 49.3-70.8), 47% female, 66% nonwhite. Overall, 633 compression-pause segments were analyzed (517 with and 116 without LUCAS applied). Spacing of pauses was significantly longer with the LUCAS than without [median (IQR) 133 (82-213) seconds vs. 38 (18-62) seconds, p < 0.05]. When using a LUCAS, compressions were continuous for at least 3 min in 166/517 segments, at least 4 min in 89/517 segments, and at least 5 min in 56/517 segments. Without a LUCAS, compressions were longer than 3 min in 7/116 segments. Pauses exceeded 10 s more frequently with LUCAS application (32/38) than airway management or defibrillation (27/80, p < 0.05). Peri-LUCAS pauses exceeded 30 s in 6/38 cases. CONCLUSION: LUCAS use was associated with long compression intervals without identifiable pauses to assess for pulse or cardiac rhythm, and device application was associated with longer pauses than airway management or defibrillation. The clinical significance and effect on patient outcomes remain uncertain and require further study.

Prehospital Stroke Care Part 2: On-Scene Evaluation and Management by Emergency Medical Services Practitioners.

The prehospital phase is a critical component of delivering high-quality acute stroke care. This topical review discusses the current state of prehospital acute stroke screening and transport, as well as new and emerging advances in prehospital diagnosis and treatment of acute stroke. Topics include prehospital stroke screening, stroke severity screening, emerging technologies to aid in the identification and diagnosis of acute stroke in the prehospital setting, prenotification of receiving emergency departments, decision support for destination determination, and the capabilities and opportunities for prehospital stroke treatment in mobile stroke units. Further evidence-based guideline development and implementation of new technologies are critical for ongoing improvements in prehospital stroke care.

Non-transport after Prehospital Naloxone Administration Is Associated with Higher Risk of Subsequent Non-fatal Overdose.

Objective: U.S. opioid overdoses increased nearly sixfold from 1999 to 2018, and greater than 1% of all emergency medical services (EMS) encounters now involve naloxone administration. While "treat and release" protocols may have low short-term mortality, the risk of subsequent non-fatal overdoses is not known. This study compares the risk of repeat overdose encounters between patients transported to an emergency department (ED) and those who refused transport after prehospital naloxone administration. Methods: All EMS charts within a large single-tier fire-based urban EMS system between January 1 and August 31, 2018 were reviewed if either naloxone administration or a clinical impression related to opioid overdose was documented. Charts were excluded if there was no documented evidence of an opioid toxidrome (respiratory depression or altered mental status), if there was another clear explanation for the symptoms (e.g., hypoglycemia), or if naloxone was not administered. Ten percent of charts were reviewed by a second author to assess reliability. Cox regression (survival analysis) was used to estimate the risk of a subsequent EMS encounter with naloxone administration following an index encounter with naloxone administration. Results: Of the 2143 charts reviewed, 1311 unique patients with 1600 overdose encounters involving naloxone administration were identified. Inter-rater reliability for chart inclusion was strong [κ = 0.83 (95% CI: 0.72-0.90)]. Police/bystanders administered naloxone in 208/1600 (13.0%) encounters. A substantial proportion of encounters resulted in transport refusal (674/1600, 42.1%). The final Cox model included only refusal vs. acceptance of transport to an ED during the index EMS encounter. Patient age, gender, and naloxone administration prior to EMS arrival were not statistically significant in univariate or multivariable analyses, nor were they significant confounders. Refusal of transport was associated with a hazard ratio of 1.66 (95% CI: 1.23-2.23) for subsequent EMS encounters with naloxone administration. Conclusions: Non-transport after prehospital naloxone administration is associated with an increased risk of subsequent non-fatal overdose requiring EMS intervention. Limitations include the use of a single EMS agency as patients may have had uncaptured overdose encounters in neighboring municipalities.

Ketamine Stability over Six Months of Exposure to Moderate and High Temperature Environments.

Background: All medications should be stored within temperature ranges defined by manufacturers, but logistical and operational challenges of prehospital and military settings complicate adherence to these recommendations. Lorazepam and succinylcholine experience clinically relevant heat-related degradation, whereas midazolam does not. Because ketamine's stability when stored outside manufacturer recommendations is unknown, we evaluated the heat-related degradation of ketamine exposed to several temperature ranges. Methods: One hundred twenty vials of ketamine (50 mg/mL labeled concentration) from the same manufacturer lot were equally distributed and stored for six months in five environments: an active EMS unit in southwest Ohio (May-October 2019); heat chamber at constant 120 °F (C1); heat chamber fluctuating over 24 hours from 86 °F-120 °F (C2); heat chamber fluctuating over 24 hours from 40 °F-120 °F (C3); heat chamber kept at constant 70 °F (manufacturer recommended room temperature, C4). Four ketamine vials were removed every 30 days from each environment and sent to an FDA-accredited commercial lab for high performance liquid chromatography testing. Data loggers and thermistors allowed temperature recording every minute for all environments. Cumulative heat exposure was quantified by mean kinetic temperature (MKT), which accounts for additional heat-stress over time caused by temperature fluctuations and is a superior measure than simple ambient temperature. MKT was calculated for each environment at the time of ketamine removal. Descriptive statistics were used to describe the concentration changes at each time point. Results: The MKT ranged from 73.6 °F-80.7 °F in the active EMS unit and stayed constant for each chamber (C1 MKT: 120 °F, C2 MKT: 107.3 °F, C3 MKT: 96.5 °F, C4 MKT: 70 °F). No significant absolute ketamine degradation, or trends in degradation, occurred in any environment at any time point. The lowest median concentration occurred in the EMS-stored samples removed after 6 months [48.2 mg/mL (47.75, 48.35)], or 96.4% relative strength to labeled concentration. Conclusion: Ketamine samples exhibited limited degradation after 6 months of exposure to real world and simulated extreme high temperature environments exceeding manufacturer recommendations. Future studies are necessary to evaluate ketamine stability beyond 6 months.

Emergency Medical Services Traumatic Brain Injury Protocols Do Not Reflect Brain Trauma Foundation Guidelines.

OBJECTIVES: Implementation of traumatic brain injury (TBI) guideline recommendations for prehospital care is associated with improved outcomes, but prehospital guideline uptake is frequently delayed. Our objective was to estimate how well TBI guidelines are reflected in a national sample of prehospital TBI protocols in 2012 and 2018, 5 and 11 years after guideline publication. Methods: A purposeful sample of publicly accessible prehospital protocols were obtained in 2012, and updates of those protocols were obtained in 2018. Guideline recommendations were codified into a 23-item tool that was used to dual-abstract each prehospital protocol set. Descriptive statistics and chi-square testing were used to compare differences. Fifty-three sets of protocols representing 25 states and multiple administrative structures were identified. Results: None of the protocols contained all twenty-three elements of the guidelines, and more than one-third (19/53, 35%) did not have a TBI-specific protocol. While some individual items appeared more frequently in 2018 than 2012, more than half of the reviewed protocols do not contain guidance on ventilation or definitions of hypoxemia, hypotension, or pupil asymmetry. Conclusions: Evaluation of a diverse sample of EMS protocols demonstrates a significant deficit in the adoption of TBI guidelines more than a decade after publication.

Ventilation in Simulated Out-of-Hospital Cardiac Arrest Resuscitation Rarely Meets Guidelines.

OBJECTIVE: The American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recommend ventilation rates of eight to ten breaths per minute or two ventilations every 30 compressions, and tidal volumes between 500-600 ml. However, compliance with these guidelines is mainly unknown. The objective of this study is to estimate the proportion of simulated adult OHCA cases that meet guideline-based ventilation targets. METHODS: We conducted a blinded prospective observational study of standardized simulated cases of EMS-witnessed adult OHCA. During scheduled training sessions, resuscitations were performed by high-quality CPR trained EMS teams composed of four on-duty, full-time EMT/Paramedics from a large urban fire-based EMS agency. A high-fidelity simulation center allowed complete audio and video monitoring from a control room. Rescuers were unaware of the study, or that ventilation practices were being observed. All interventions, including airway and ventilation strategies, were at the discretion of the clinical team. A calibrated Laerdal SimMan 3 G manikin and associated Laerdal Debrief Viewer software recorded ventilation rate, tidal volume, and minute ventilation. Simulations achieving median ventilation rate 7-10 breaths/min, tidal volume 500-600 ml, and minute ventilation 3.5-6 liters/min were considered meeting guideline-based targets. RESULTS: A total of 106 EMS teams were included in the study. Only 3/106 [2.8% (95% CI: 0.6-8.0)] of the EMS teams demonstrated ventilation characteristics meeting all guideline-based targets. The median ventilation rate was 5.8 breaths/min (IQR 4.4-7.7 breaths/min) with 26/106 [24.5% (95% CI: 17.2-33.7)] between 7-10 breaths/min. The median tidal volume was 413.5 ml (IQR 280.5-555.4 ml), with 18/106 [17.0% (95% CI: 10.9-25.5)] between 500-600 ml. The median minute ventilation was 2.4 L/min (IQR 1.2-3.6 L/min) with 16/106 [15.1% (95% CI: 9.4-23.3)] between 3.5-6.0 L/min. CONCLUSION: During simulated adult OHCA resuscitation attempts, ventilation practices rarely met guideline-based targets, despite being performed by well-trained EMS providers. Methods should be developed to monitor and ensure high-quality ventilation during actual OHCA resuscitation attempts.

Food and Drug Administration and Institutional Review Board Approval of a Novel Prehospital Informed Consent Process for Emergency Research.

Research on the management of acute pain in the prehospital setting is fraught with challenges. The prehospital setting is complex due to constrained time, resources, and training. Research activities must not interfere with the underlying clinical priorities of immediate patient stabilization and rapid transport to an appropriate hospital. The patient's pain, fear, and anxiety immediately after a traumatic event may interfere with undertaking an adequate informed consent process.Pain management trials do not satisfy the criteria for application of the U.S. Food and Drug Administration (FDA) 21 CFR 50.24 exception from informed consent. While nonstandard informed consent processes exist, waiver or alteration of informed consent may be limited if Institutional Review Boards or the FDA consider these studies to involve more than minimal risk related to the setting of the study, even if the interventions themselves might involve no more than minimal risk in other settings. In addition, any study requiring an Investigational New Drug application requires fully documented standard informed consent.Emergency Medical Services agencies and fire departments become research institutions, and paramedics become study staff, but both the institutions and the staff often lack experience conducting human subjects research and are rarely formally affiliated with the academic institution overseeing the research. As such, additional administrative burdens must be overcome in interventional prehospital studies, including additional training in the study protocol, research operations, and human subjects protections. Institutions conducting federally funded studies commit to regulations covering human subjects protections in the form of a Federalwide Assurance (FWA); prehospital organizations participating in research must either obtain an FWA or have coverage extended to them from an academic partner.We describe how these challenges were addressed during Institutional Review Board review and approval of an FDA-regulated randomized placebo-controlled trial of intranasal ketamine (vs. placebo) in acutely injured patients receiving standard of care fentanyl for prehospital pain management (NCT02866071). To our knowledge, this trial is the first instance in the United States of paramedics screening, consenting, enrolling, and administering study medications to patients without direct, real-time support from a dedicated clinical research team.

Intranasal Ketamine as an Adjunct to Fentanyl for the Prehospital Treatment of Acute Traumatic Pain: Design and Rationale of a Randomized Controlled Trial.

Objective: Acute pain management is fundamental in prehospital trauma care. Early pain control may decrease the risk of developing post-traumatic stress disorder (PTSD) and chronic pain. Fentanyl and ketamine are frequently used off-label, but there is a paucity of comparative data to guide decision-making about treatment of prehospital severe, acute pain. This trial will determine whether the addition of single dose of intranasal ketamine to fentanyl is more effective for the treatment of acute traumatic pain than administration of fentanyl alone.Methods: This two-part study consists of prehospital and 90-day follow-up components (NCT02866071). The prehospital trial is a blinded, randomized, controlled trial of adult men (age 18-65 years) rating pain ≥7/10 after an acute traumatic injury of any type. Women will be excluded due to inability to confirm pregnancy status and unknown fetal risk. Paramedics will screen patients receiving standard of care fentanyl and, after obtaining standard informed consent, administer 50 mg intranasal ketamine or matching volume saline as placebo. Upon emergency department (ED) arrival, research associates will serially assess pain, concomitant treatments, and adverse side effects. Enrolled subjects will be approached for consent to participate in the 90-day follow-up study to determine rates of PTSD and chronic pain development. The primary outcome of the prehospital study is reduction in pain on the Verbal Numerical Rating Scale between baseline and 30-minutes after study drug administration. The proportion achieving a reduction of ≥2-points will be compared between study arms using a Chi-square test. Secondary outcomes of the prehospital trial include reduction in reported pain at the time of ED arrival and at 30 minutes intervals for up to three hours of ED care, the incidence of adverse events, and additional opiate requirements prior to ED arrival and within the first three hours of ED care. The outcomes in the follow-up study are satisfaction with life and development of PTSD or chronic pain at 90 days after injury. An intention-to-treat approach will be used.Conclusion: These studies will test the hypotheses that ketamine plus fentanyl, when compared to fentanyl alone, effectively manages pain, decreases opiate requirements, and decreases PTSD at 90 days.

The Cincinnati Prehospital Stroke Scale Compared to Stroke Severity Tools for Large Vessel Occlusion Stroke Prediction.

BACKGROUND: Various screening tools, ranging in complexity, have been developed to predict large vessel occlusion (LVO) stroke in the prehospital setting. Our objective was to determine whether newly-developed LVO stroke scales offer a clinically-meaningful advantage over the Cincinnati Prehospital Stroke Scale (CPSS). METHODS: We retrospectively analyzed prehospital patient care records linked with hospital data from 151 EMS agencies in the United States, between January 1, 2018 and December 31, 2018. We compared the CPSS to the Rapid Arterial Occlusion Evaluation (RACE), Los Angeles Motor Scale (LAMS), and the Vision, Aphasia, Neglect (VAN) assessment for LVO prediction. For each stroke scale, we used the intersection of sensitivity and specificity curves to determine optimal prediction cut-points. We used area under the ROC curve and 95% confidence intervals to assess for differences in discriminative ability between scales. RESULTS: We identified 13,596 prehospital records with one or more documented stroke scales of interest. Among these, 4,228 patients were diagnosed with stroke. Over half (57%, n = 2,415) of patients diagnosed with stroke experienced an acute ischemic stroke. Of patients with ischemic stroke, 26% (n = 628) were diagnosed with LVO. A CPSS score of 2 or higher demonstrated sensitivity = 69% and specificity = 78% for LVO. A RACE score of 4 or higher demonstrated sensitivity = 63%, specificity = 73%. A LAMS score of 3 or higher demonstrated sensitivity = 63%, specificity = 72% and a positive VAN score demonstrated sensitivity = 86%, specificity = 65%. Comparing the area under the ROC curve for each scale revealed no statistically significant differences in discriminative ability for LVO stroke. CONCLUSIONS: In this large sample of real-world prehospital patient encounters, the CPSS demonstrated similar predictive performance characteristics compared to the RACE, LAMS, and VAN for detecting LVO stroke. Prior to implementing a specific screening tool, EMS agencies should evaluate ease of use and associated implementation costs. Scored 0-3, the simple, widely-used CPSS may serve as a favorable prehospital screening instrument for LVO detection with a cut-point of 2 or higher maximizing the tradeoff between sensitivity and specificity.

Predictors of Definitive Airway Sans Hypoxia/Hypotension on First Attempt (DASH-1A) Success in Traumatically Injured Patients Undergoing Prehospital Intubation.

Background: Prehospital intubation success is routinely treated as a dichotomous outcome based on an endotracheal tube passing through vocal cords regardless of number of attempts or occurrence of hypoxia, or hypotension, which are associated with worse outcomes. We explore patient, provider, and procedure-related variables associated with successful definitive airway sans hypoxia/hypotension on first attempt (DASH-1A) in traumatically injured subjects undergoing endotracheal intubation at the scene of injury by a helicopter EMS system.Methods: This single-center retrospective chart review included patients with traumatic injuries and at least one attempted intubation by helicopter EMS at the scene of injury. Demographic and clinical variables were tested for association with DASH-1A and overall first-attempt success using univariate comparisons and multivariable logistic regression to produce adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Purposeful backwards stepwise elimination was used to develop logistic regression models for outcomes. Initial inclusion of covariates in multivariable models was based on clinical judgement, known or suspected risk factors and confounders for intubation success, and univariate associations.Results: Of 419 subjects screened, 263 met inclusion criteria. Median age was 34 years and the majority of subjects were Caucasian (95%), male (76%), and suffered blunt trauma (90%). The endotracheal tube was successfully placed on the first attempt in 198 (75.3%) of patients, but only 142 (55.3%) had a successful DASH-1A, and overall, 246 (94%) had an endotracheal tube passed successfully before hospital arrival. Factors significantly associated with successful DASH-1A were no ground EMS intubation attempt prior to arrival [aOR 2.2 (CI 1.0-4.9)], lack of airway secretions/blood [1.9 (1.0-3.4)], Cormack-Lehane Score of I and II [12.3 (4.5-33.2) & 3.2 (1.2-9.1), respectively], and bougie use [5.4 (1.8-15.8)]. For endotracheal tube passing only, the following were significantly associated with first pass success: grade of view I and II [aORs 87.3 (CI 25.8-295.7) & 6.8 (2.3-19.5), respectively], lack of secretions/blood [4.9 (2.1-11.2), bougie use [7.8 (2.3-26.3)], direct laryngoscopy [5.1 (1.5-17.0)] and not using apneic oxygenation through a nasal cannula [2.5 (1.1-5.6)].Conclusion: In our helicopter EMS system, successful endotracheal intubation on the first attempt and without an episode of hypoxia was associated with no ground EMS intubation attempt prior to flight crew arrival, lack of airway secretions/blood, Cormack-Lehane Score, and bougie use.

Potential Impact of C-STAT for Prehospital Stroke Triage up to 24 Hours on a Regional Stroke System.

Background and Purpose: Thrombectomy for large vessel occlusion acute ischemic stroke (AIS-LVO) may benefit patients up to 24 hour since last known normal (LKN). Prehospital tools, like the Cincinnati Stroke Triage Assessment Tool (C-STAT), are used to select hospital destination for suspected AIS-LVO patients. The objective of this study was to estimate the potential impact of the expanded thrombectomy time window on suspected AIS-LVO cases transported to the regional comprehensive stroke center (CSC). Methods: From June to November 2015, C-STAT was performed by prehospital providers following a positive prehospital Cincinnati Prehospital Stroke Scale (CPSS) stroke screen in suspected stroke/TIA patients. There was no preferential triage based on C-STAT results. Final diagnoses, including the presence of AIS-LVO was ascertained via medical record review. Impact of positive C-STAT cases on CSC volumes was estimated for up to 24 hours since LKN. Results: Of 158 patients with prehospital suspicion for stroke/TIA, 105 were CPSS positive within 24 hours of onset and had complete C-STAT and clinical data available for analysis. Forty-six percent (17/37) of C-STAT + were non-strokes. C-STAT sensitivity and specificity for LVO were 71% (95% CI 36-92) and 67% (95% CI 58-80), respectively. C-STAT triage would increase transport of prehospital suspected stroke cases to the CSC by 11% (12/105) within six hours and 21% (22/105) within 24 hours. Of 37 C-STAT + patients, only 5 (13.5%) had LVO as final diagnosis. Conclusions: Preferential triage of prehospital suspected stroke patients using C-STAT would increase the number of patients transported to the CSC by 11% within six hours and an additional 10% from six to 24 hours. For every patient with LVO as final diagnosis, approximately an additional 6 non-LVO patients would be triaged to a CSC.

Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury.

Importance: Traumatic brain injury (TBI) is the leading cause of death and disability due to trauma. Early administration of tranexamic acid may benefit patients with TBI. Objective: To determine whether tranexamic acid treatment initiated in the out-of-hospital setting within 2 hours of injury improves neurologic outcome in patients with moderate or severe TBI. Design, Setting, and Participants: Multicenter, double-blinded, randomized clinical trial at 20 trauma centers and 39 emergency medical services agencies in the US and Canada from May 2015 to November 2017. Eligible participants (N = 1280) included out-of-hospital patients with TBI aged 15 years or older with Glasgow Coma Scale score of 12 or less and systolic blood pressure of 90 mm Hg or higher. Interventions: Three interventions were evaluated, with treatment initiated within 2 hours of TBI: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (bolus maintenance group; n = 312), out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (bolus only group; n = 345), and out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (placebo group; n = 309). Main Outcomes and Measures: The primary outcome was favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score >4 [moderate disability or good recovery]) in the combined tranexamic acid group vs the placebo group. Asymmetric significance thresholds were set at 0.1 for benefit and 0.025 for harm. There were 18 secondary end points, of which 5 are reported in this article: 28-day mortality, 6-month Disability Rating Scale score (range, 0 [no disability] to 30 [death]), progression of intracranial hemorrhage, incidence of seizures, and incidence of thromboembolic events. Results: Among 1063 participants, a study drug was not administered to 96 randomized participants and 1 participant was excluded, resulting in 966 participants in the analysis population (mean age, 42 years; 255 [74%] male participants; mean Glasgow Coma Scale score, 8). Of these participants, 819 (84.8%) were available for primary outcome analysis at 6-month follow-up. The primary outcome occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group (difference, 3.5%; [90% 1-sided confidence limit for benefit, -0.9%]; P = .16; [97.5% 1-sided confidence limit for harm, 10.2%]; P = .84). There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%; difference, -2.9% [95% CI, -7.9% to 2.1%]; P = .26), 6-month Disability Rating Scale score (6.8 vs 7.6; difference, -0.9 [95% CI, -2.5 to 0.7]; P = .29), or progression of intracranial hemorrhage (16% vs 20%; difference, -5.4% [95% CI, -12.8% to 2.1%]; P = .16). Conclusions and Relevance: Among patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Outcome Scale-Extended. Trial Registration: ClinicalTrials.gov Identifier: NCT01990768.

Mechanical Ventilation of Severe Traumatic Brain Injury Patients in the Prehospital Setting.

OBJECTIVE: Suboptimal ventilation may impact outcomes in patients with traumatic brain injury (TBI). This study compares the incidence of eucapnia between manually and mechanically ventilated patients with severe TBI during helicopter transport. METHODS: This retrospective chart review included consecutive intubated adults with severe TBI (Glasgow Coma Scale score < 9) transported by helicopter from the scene of injury to a level 1 trauma center between 2009 and 2015. The primary outcome was the first venous partial pressure of carbon dioxide obtained in the emergency department. Hypocapnia, eucapnia, and hypercapnia were defined based on the normal range for the testing instrument. The Fisher exact test was used to compare groups. RESULTS: Of 1,070 trauma patients intubated and transported, 93 met the inclusion criteria with full data. The mean age was 43 years, 81 of 93 were white, and 70 of 93 were men. The mean Injury Severity Score was 29, and 26 of 93 were mechanically ventilated. Hypocapnia occurred in 4 of 93 and hypercapnia in 56 of 93. There was no difference in the rate of eucapnia in manually ventilated compared with mechanically ventilated patients (36% vs. 35%, P = 1.00). CONCLUSION: Eucapnia at emergency department arrival occurred in 36% of patients and was unaffected by whether ventilation was manually or mechanically controlled. Few patients were hypocapnic, indicating a low incidence of hyperventilation during helicopter transport.

Timing of Advanced Airway Placement after Witnessed Out-of-Hospital Cardiac Arrest.

Background: Advanced airways (endotracheal tubes, supraglottic airways) are frequently placed by Emergency Medical Services (EMS) in patients with out-of-hospital cardiac arrest (OHCA). However, if an airway is to be placed, it is unknown whether this should occur early or late in the sequence of resuscitation events. This study evaluated the association between the timing of airway placement and the minute-to-minute probability of achieving return of spontaneous circulation (ROSC). Methods: This secondary analysis of Resuscitation Outcomes Consortium Prehospital Resuscitation using an Impedance Valve and Early versus Delayed (ROC PRIMED) study data included adult, non-traumatic, witnessed OHCA patients with airway placement by EMS before ROSC. The primary exposure variable was time from EMS arrival to advanced airway placement. The outcome was prehospital ROSC. Since resuscitations occur over time, a Cox proportional hazards model was fit to estimate the probability of ROSC as a function of the airway timing, adjusting for Utstein variables. Results: A total of 7,547 patients were included. Time to airway placement was 0-5 minutes in 12% of the cohort, >5-10 (36%), >10-15 (29%), >15-20 (14%), >20-25 (5%), >25-30 (2%), and >30 (2%). ROSC occurred in 43%. Time to airway had a statistically significant impact on ROSC. A negative association between the time to airway placement and the hazard of ROSC was observed, such that increasing intervals between EMS arrival and airway placement were associated with decreasing probabilities of ROSC, regardless of initial cardiac rhythm. Conclusions: EMS advanced airway placement has a time-dependent association with ROSC. In witnessed OHCA patients receiving advanced airways, early airway placement is associated with increased probability of ROSC.

Prehospital Prediction of Large Vessel Occlusion in Suspected Stroke Patients.

PURPOSE OF REVIEW: Recent advances in endovascular thrombectomy have made acute ischemic stroke due to a large vessel occlusion more treatable than ever. Rapid access to treatment remains paramount and multiple large vessel occlusion prediction scales have been created to enhance prehospital identification and triage of these patients. This review summarizes the current state of large vessel occlusion prediction scales, proposes a set of ideal scale features, and discusses the future of these scales and prehospital neurological emergency response systems. RECENT FINDINGS: A meta-analysis of the available data concluded that none of the currently published scales are more accurate than the others. However, other studies provide insight into important qualitative features beyond accuracy. At present, only a few large vessel occlusion prediction scales have been studied in the necessary prehospital suspected stroke patient population. Among these small studies, 26-51% of patients identified by scales had large vessel occlusions and 63-84% qualified for triage to a Comprehensive Stroke Center. Valuable scale features include binary scoring, inclusion of gaze deviation and arm weakness, exclusion of neglect, and prehospital validation in a suspected stroke cohort. Patients with neurological emergencies that mimic large vessel occlusion, such as intracranial hemorrhage, may also benefit from triage to Comprehensive Stroke Centers. Prehospital triage is more complex than ever and guidelines, tools, and systems continue to evolve.

Prehospital Triage of Acute Ischemic Stroke Patients to an Intravenous tPA-Ready versus Endovascular-Ready Hospital: A Decision Analysis.

BACKGROUND: American Stroke Association guidelines for prehospital acute ischemic stroke recommend against bypassing an intravenous tPA-ready hospital (IRH), if additional transportation time to an endovascular-ready hospital (ERH) exceeds 15-20 min. However, it is unknown when the benefit of potential endovascular therapy at an ERH outweighs the harm from delaying intravenous therapy at a closer IRH, especially since large vessel occlusion (LVO) status is initially unknown. We hypothesized that current time recommendations for IRH bypass are too short to achieve optimal outcomes for certain patient populations. METHODS: A decision analysis model was constructed using population-based databases, a detailed literature review, and interventional trial data containing time-dependent modified Rankin Scale distributions. The base case was triaged by Emergency Medical Services (EMS) 110 min after stroke onset and had a 23.6% LVO rate. Base case triage choices were (1) transport to the closest IRH (12 min), (2) transport to the ERH (60 min) bypassing the IRH, or (3) apply the Cincinnati Stroke Triage Assessment Tool and transport to the ERH if positive for LVO. Outcomes were assessed using quality-adjusted life years (QALYs). Sensitivity analyses were performed for all major variables, and alternative prehospital stroke scales were assessed. RESULTS: In the base case, transport to the IRH was the optimal choice with an expected outcome of 8.47 QALYs. Sensitivity analyses demonstrated that transport to the ERH was superior until bypass time exceeded 44 additional minutes, or when the onset to EMS triage interval exceeded 99 min. As the probability of LVO increased, ERH transport was optimal at longer onset to EMS triage intervals. The optimal triage strategy was highly dependent on specific interactions between the IRH transportation time, ERH transportation time, and onset to EMS triage interval. CONCLUSIONS: No single time difference between IRH and ERH transportation optimizes triage for all patients. Allowable IRH bypass time should be increased and acute ischemic stroke guidelines should incorporate the onset to EMS triage interval, IRH transportation time, and ERH transportation time.

Prehospital neurological deterioration in stroke.

BACKGROUND AND PURPOSE: Patients with stroke can experience neurological deterioration in the prehospital setting. We evaluated patients with stroke to determine factors associated with prehospital neurological deterioration (PND). METHODS: Among the Greater Cincinnati/Northern Kentucky region (population ~1.3 million), we screened all 15 local hospitals' admissions from 2010 for acute stroke and included patients aged ≥20. The GCS was compared between emergency medical services (EMS) arrival and hospital arrival, with decrease ≥2 points considered PND. Data obtained retrospectively included demographics, medical history and medication use, stroke subtype (eg, ischaemic stroke (IS), intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH)) and IS subtype (eg, small vessel, large vessel, cardioembolic), seizure at onset, time intervals between symptom onset, EMS arrival and hospital arrival, EMS level of training, and blood pressure and serum glucose on EMS arrival. RESULTS: Of 2708 total patients who had a stroke, 1092 patients (median (IQR) age 74 (61-83) years; 56% women; 21% black) were analysed. PND occurred in 129 cases (12%), including 9% of IS, 24% of ICH and 16% of SAH. In multivariable analysis, black race, atrial fibrillation, haemorrhagic subtype and ALS level of transport were associated with PND. CONCLUSION: Haemorrhage and atrial fibrillation is associated with PND in stroke, and further investigation is needed to establish whether PND can be predicted. Further studies are also needed to assess whether preferential transport of patients with deterioration to hospitals equipped with higher levels of care is beneficial, identify why race is associated with deterioration and to test therapies targeting PND.

Estimated Impact of Emergency Medical Service Triage of Stroke Patients on Comprehensive Stroke Centers: An Urban Population-Based Study.

BACKGROUND AND PURPOSE: The American Stroke Association recommends that Emergency Medical Service bypass acute stroke-ready hospital (ASRH)/primary stroke center (PSC) for comprehensive stroke centers (CSCs) when transporting appropriate stroke patients, if the additional travel time is ≤15 minutes. However, data on additional transport time and the effect on hospital census remain unknown. METHODS: Stroke patients ≥20 years old who were transported from home to an ASRH/PSC or CSC via Emergency Medical Service in 2010 were identified in the Greater Cincinnati area population of 1.3 million. Addresses of all patients' residences and hospitals were geocoded, and estimated travel times were calculated. We estimated the mean differences between the travel time for patients taken to an ASRH/PSC and the theoretical time had they been transported directly to the region's CSC. RESULTS: Of 929 patients with geocoded addresses, 806 were transported via Emergency Medical Service directly to an ASRH/PSC. Mean additional travel time of direct transport to the CSC, compared with transport to an ASRH/PSC, was 7.9±6.8 minutes; 85% would have ≤15 minutes added transport time. Triage of all stroke patients to the CSC would have added 727 patients to the CSC's census in 2010. Limiting triage to the CSC to patients with National Institutes of Health Stroke Scale score of ≥10 within 6 hours of onset would have added 116 patients (2.2 per week) to the CSC's annual census. CONCLUSIONS: Emergency Medical Service triage to CSCs based on stroke severity and symptom duration may be feasible. The impact on stroke systems of care and patient outcomes remains to be determined and requires prospective evaluation.