The effects of prehospital TXA on mortality and neurologic outcomes in patients with traumatic intracranial hemorrhage: a subgroup analysis from the prehospital TXA for TBI trial.

BACKGROUND: In the Prehospital Tranexamic Acid (TXA) for TBI Trial, TXA administered within two hours of injury in the out-of-hospital setting did not reduce mortality in all patients with moderate/severe traumatic brain injury (TBI). We examined the association between TXA dosing arms, neurologic outcome, and mortality in patients with intracranial hemorrhage (ICH) on computed tomography (CT). METHODS: This was a secondary analysis of the Prehospital Tranexamic Acid for TBI Trial (ClinicalTrials.gov [NCT01990768]) that randomized adults with moderate/severe TBI (Glasgow Coma Scale<13) and systolic blood pressure > =90 mmHg within two hours of injury to a 2-gram out-of-hospital TXA bolus followed by an in-hospital saline infusion, a 1-gram out-of-hospital TXA bolus/1-gram in-hospital TXA infusion, or an out-of-hospital saline bolus/in-hospital saline infusion (placebo). This analysis included the subgroup with ICH on initial CT. Primary outcomes included 28-day mortality, 6-month Glasgow Outcome Scale-Extended (GOSE) < = 4, and 6-month Disability Rating Scale (DRS). Outcomes were modeled using linear regression with robust standard errors. RESULTS: The primary trial included 966 patients. Among 541 participants with ICH, 28-day mortality was lower in the 2-gram TXA bolus group (17%) compared to the other two groups (1-gram bolus/1-gram infusion 26%, placebo 27%). The estimated adjusted difference between the 2-gram bolus and placebo groups was -8·5 percentage points (95% CI, -15.9 to -1.0) and between the 2-gram bolus and 1-gram bolus/1-gram infusion groups was -10.2 percentage points (95% CI, -17.6 to -2.9). DRS at 6 months was lower in the 2-gram TXA bolus group than the 1-gram bolus/1-gram infusion (estimated difference -2.1 [95% CI, -4.2 to -0.02]) and placebo groups (-2.2 [95% CI, -4.3, -0.2]). Six-month GOSE did not differ among groups. CONCLUSIONS: A 2-gram out-of-hospital TXA bolus in patients with moderate/severe TBI and ICH resulted in lower 28-day mortality and lower 6-month DRS than placebo and standard TXA dosing. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level II.

Intra-arrest blood-based biomarkers for out-of-hospital cardiac arrest: A scoping review.

Objective: Blood-based biomarkers play a central role in the diagnosis and treatment of critically ill patients, yet none are routinely measured during the intra-arrest phase of out-of-hospital cardiac arrest (OHCA). Our objective was to describe methodological aspects, sources of evidence, and gaps in research surrounding intra-arrest blood-based biomarkers for OHCA. Methods: We used scoping review methodology to summarize existing literature. The protocol was designed a priori following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews. Inclusion criteria were peer-reviewed scientific studies on OHCA patients with at least one blood draw intra-arrest. We excluded in-hospital cardiac arrest and animal studies. There were no language, date, or study design exclusions. We conducted an electronic literature search using PubMed and Embase and hand-searched secondary literature. Data charting/synthesis were performed in duplicate using standardized data extraction templates. Results: The search strategy identified 11,834 records, with 118 studies evaluating 105 blood-based biomarkers included. Only eight studies (7%) had complete reporting. The median number of studies per biomarker was 2 (interquartile range 1-4). Most studies were conducted in Asia (63 studies, 53%).  Only 22 studies (19%) had blood samples collected in the prehospital setting, and only six studies (5%) had samples collected by paramedics. Pediatric patients were included in only three studies (3%). Out of eight predefined biomarker categories of use, only two were routinely assessed: prognostic (97/105, 92%) and diagnostic (61/105, 58%). Conclusions: Despite a large body of literature on intra-arrest blood-based biomarkers for OHCA, gaps in methodology and knowledge are widespread.

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.

Remnant Blood Quantification: Informing the Definition of Minimal Risk in Clinical Research.

Guidelines from the Office for Human Research Protections regarding categories of research that institutional review boards (IRBs) may review through expedited procedures limit the volume of blood that can be obtained from research participants for minimal risk research purposes. As defined by the Common Rule, minimal risk research is research in which the probability and magnitude of harm or discomfort anticipated are not greater than the probability and magnitude of harm or discomfort encountered from routine clinical tests. For this study, we considered the volume of remnant blood following routine clinical tests in light of the current definition of minimal risk in research. Conducted at a single institution, this was a prospective cross-sectional study that evaluated blood draws from 122 patients. The median daily remnant blood volume was 11.6 (interquartile range [IQR]: 12.3, 15.2) ml for all patients and 12.9 (IQR: 13.1, 16.9) ml for patients admitted to the intensive care unit. Our findings regarding daily remnant blood volume suggest that the currently allowable blood-volume limits to qualify for expedited review or to qualify as not more than minimal risk research involving blood draws from nonhealthy adults are less than what patients experience in routine medical testing. These findings support permitting an increase in the allowable blood-volume limits to meet the regulatory definition of minimal risk research for obtaining expedited IRB review of studies in which blood samples will be collected.

Ventilation rates measured by capnography during out-of-hospital cardiac arrest resuscitations and their association with return of spontaneous circulation.

BACKGROUND: Clinical guidelines for adult out-of-hospital cardiac arrest (OHCA) recommend a ventilation rate of 8-10 per minute yet acknowledge that few data exist to guide recommendations. The goal of this study was to evaluate the utility of continuous capnography to measure ventilation rates and the association with return of spontaneous circulation (ROSC). METHODS: This was a retrospective observational cohort study. We included all OHCA during a two-year period and excluded traumatic and pediatric patients. Ventilations were recorded using non-invasive continuous capnography. Blinded medically trained team members manually annotated all ventilations. Four techniques were used to analyze ventilation rate. The primary outcome was sustained prehospital ROSC. Secondary outcomes were vital status at the end of prehospital care and survival to hospital admission. Univariable and multivariable logistic regression models were constructed. RESULTS: A total of 790 OHCA were analyzed. Only 386 (49%) had useable capnography data. After applying inclusion and exclusion criteria, the final study cohort was 314 patients. The median ventilation rate per minute was 7 (IQR 5.4-8.5). Only 70 (22%) received a guideline-compliant ventilation rate of 8-10 per minute. Sixty-two (20%) achieved the primary outcome. No statistically significant associations were observed between any of the ventilation parameters and patient outcomes in both univariable and multivariable logistic regression models. CONCLUSIONS: We failed to detect an association between intra-arrest ventilation rates measured by continuous capnography and proximal patient outcomes after OHCA. Capnography has poor reliability as a measure of ventilation rate. Achieving guideline-compliant ventilation rates remains challenging.

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.

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.

Duration of exposure to a prehospital advanced airway and neurological outcome for out-of-hospital cardiac arrest: A retrospective cohort study.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) studies have focused on the benefits and harms of placing an intra-arrest advanced airway, but few studies have evaluated the benefits and harms after successful placement. We hypothesize that increased time in the tumultuous prehospital environment after intra-arrest advanced airway placement results in reduced patient survival. METHODS: This was a secondary analysis of adult, non-traumatic, OHCA patients with an advanced airway placed in the PRIMED trial. The exposure variable was the time interval between successful advanced airway placement and Emergency Department (ED) arrival. The outcome was cerebral performance category (CPC) 1 or 2 at hospital discharge. Multivariable logistic regression, adjusted for Utstein variables and resuscitation-associated time intervals, was used to estimate adjusted odds ratios (aOR). RESULTS: The cohort of complete cases included 4779 patients. The median time exposed to a prehospital advanced airway was 27 min (IQR 20-35). The total prehospital time was 39.4 min (IQR 32.3-48.1). An advanced airway was placed intra-arrest in 3830 cases (80.1%) and post-return of spontaneous circulation (post-ROSC) in 949 cases (19.9%). Overall, 486 (10.2%) of the cohort achieved the CPC outcome, but this was higher in the post-ROSC (21.7%) versus intra-arrest (7.5%) cohort. CPC was not associated with the time interval from advanced airway placement to ED arrival in the intra-arrest airway cohort (aOR 0.98, 95%CI 0.94-1.01). CONCLUSIONS: In OHCA patients who receive an intra-arrest advanced airway, longer time intervals exposed to a prehospital advanced airway are not associated with reduced patient survival.

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.

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.

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.

Tranexamic acid administration in the field does not affect admission thromboelastography after traumatic brain injury.

BACKGROUND: No Food and Drug Administration-approved medication improves outcomes following traumatic brain injury (TBI). A forthcoming clinical trial that evaluated the effects of two prehospital tranexamic acid (TXA) dosing strategies compared with placebo demonstrated no differences in thromboelastography (TEG) values. We proposed to explore the impact of TXA on markers of coagulation and fibrinolysis in patients with moderate to severe TBI. METHODS: Data were extracted from a placebo-controlled clinical trial in which patients 15 years or older with TBI (Glasgow Coma Scale, 3-12) and systolic blood pressure of ≥90 mm Hg were randomized prehospital to receive placebo bolus/placebo infusion (placebo), 1 g of TXA bolus/1 g of TXA infusion (bolus maintenance), or 2 g of TXA bolus/placebo infusion (bolus only). Thromboelastography was performed, and coagulation measures including prothrombin time, activated partial thromboplastin time, international ratio, fibrinogen, D-dimer, plasmin-antiplasmin (PAP), thrombin antithrombin, tissue plasminogen activator, and plasminogen activator inhibitor 1 were quantified at admission and 6 hours later. RESULTS: Of 966 patients receiving study drug, 700 had laboratory tests drawn at admission and 6 hours later. There were no statistically significant differences in TEG values, including LY30, between groups (p > 0.05). No differences between prothrombin time, activated partial thromboplastin time, international ratio, fibrinogen, thrombin antithrombin, tissue plasminogen activator, and plasminogen activator inhibitor 1 were demonstrated across treatment groups. Concentrations of D-dimer in TXA treatment groups were less than placebo at 6 hours (p < 0.001). Concentrations of PAP in TXA treatment groups were less than placebo on admission (p < 0.001) and 6 hours (p = 0.02). No differences in D-dimer and PAP were observed between bolus maintenance and bolus only. CONCLUSION: While D-dimer and PAP levels reflect a lower degree of fibrinolysis following prehospital administration of TXA when compared with placebo in a large prehospital trial of patients with TBI, TEG obtained on admission and 6 hours later did not demonstrate any differences in fibrinolysis between the two TXA dosing regimens and placebo. LEVEL OF EVIDENCE: Diagnostic test, level III.

A review of ventilation in adult out-of-hospital cardiac arrest.

Out-of-hospital cardiac arrest continues to be a devastating condition despite advances in resuscitation care. Ensuring effective gas exchange must be weighed against the negative impact hyperventilation can have on cardiac physiology and survival. The goals of this narrative review are to evaluate the available evidence regarding the role of ventilation in out-of-hospital cardiac arrest resuscitation and to provide recommendations for future directions. Ensuring successful airway patency is fundamental for effective ventilation. The airway management approach should be based on professional skill level and the situation faced by rescuers. Evidence has explored the influence of different ventilation rates, tidal volumes, and strategies during out-of-hospital cardiac arrest; however, other modifiable factors affecting out-of-hospital cardiac arrest ventilation have limited supporting data. Researchers have begun to explore the impact of ventilation in adult out-of-hospital cardiac arrest outcomes, further stressing its importance in cardiac arrest resuscitation management. Capnography and thoracic impedance signals are used to measure ventilation rate, although these strategies have limitations. Existing technology fails to reliably measure real-time clinical ventilation data, thereby limiting the ability to investigate optimal ventilation management. An essential step in advancing cardiac arrest care will be to develop techniques to accurately and reliably measure ventilation parameters. These devices should allow for immediate feedback for out-of-hospital practitioners, in a similar way to chest compression feedback. Once developed, new strategies can be established to guide out-of-hospital personnel on optimal ventilation practices.

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.