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.

Rationale and Strategies for Development of an Optimal Bundle of Management for Cardiac Arrest.

OBJECTIVES: To construct a highly detailed yet practical, attainable roadmap for enhancing the likelihood of neurologically intact survival following sudden cardiac arrest. DESIGN SETTING AND PATIENTS: Population-based outcomes following out-of-hospital cardiac arrest were collated for 10 U.S. counties in Alaska, California, Florida, Ohio, Minnesota, Utah, and Washington. The 10 identified emergency medical services systems were those that had recently reported significant improvements in neurologically intact survival after introducing a more comprehensive approach involving citizens, hospitals, and evolving strategies for incorporating technology-based, highly choreographed care and training. Detailed inventories of in-common elements were collated from the ten 9-1-1 agencies and assimilated. For reference, combined averaged outcomes for out-of-hospital cardiac arrest occurring January 1, 2017, to February 28, 2018, were compared with concurrent U.S. outcomes reported by the well-established Cardiac Arrest Registry to Enhance Survival. INTERVENTIONS: Most commonly, interventions and components from the ten 9-1-1 systems consistently included extensive public cardiopulmonary resuscitation training, 9-1-1 system-connected smart phone applications, expedited dispatcher procedures, cardiopulmonary resuscitation quality monitoring, mechanical cardiopulmonary resuscitation, devices for enhancing negative intrathoracic pressure regulation, extracorporeal membrane oxygenation protocols, body temperature management procedures, rapid cardiac angiography, and intensive involvement of medical directors, operational and quality assurance officers, and training staff. MEASUREMENTS AND MAIN RESULTS: Compared with Cardiac Arrest Registry to Enhance Survival (n = 78,704), the cohorts from the 10 emergency medical services agencies examined (n = 2,911) demonstrated significantly increased likelihoods of return of spontaneous circulation (mean 37.4% vs 31.5%; p < 0.001) and neurologically favorable hospital discharge, particularly after witnessed collapses involving bystander cardiopulmonary resuscitation and shockable cardiac rhythms (mean 10.7% vs 8.4%; p < 0.001; and 41.6% vs 29.2%; p < 0.001, respectively). CONCLUSIONS: The likelihood of neurologically favorable survival following out-of-hospital cardiac arrest can improve substantially in communities that conscientiously and meticulously introduce a well-sequenced, highly choreographed, system-wide portfolio of both traditional and nonconventional approaches to training, technologies, and physiologic management. The commonalities found in the analyzed systems create a compelling case that other communities can also improve out-of-hospital cardiac arrest outcomes significantly by conscientiously exploring and adopting similar bundles of system organization and care.

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.

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.

Supraglottic airway devices variably develop negative intrathoracic pressures: A prospective cross-over study of cardiopulmonary resuscitation in human cadavers.

AIM OF THE STUDY: Negative intrathoracic pressure (ITP) during the decompression phase of cardiopulmonary resuscitation (CPR) is essential to refill the heart, increase cardiac output, maintain cerebral and coronary perfusion pressures, and improve survival. In order to generate negative ITP, an airway seal is necessary. We tested the hypothesis that some supraglottic airway (SGA) devices do not seal the airway as well the standard endotracheal tube (ETT). METHODS: Airway pressures (AP) were measured as a surrogate for ITP in seven recently deceased human cadavers of varying body habitus. Conventional manual, automated, and active compression-decompression CPR were performed with and without an impedance threshold device (ITD) in supine and Head Up positions. Positive pressure ventilation was delivered by an ETT and 5 SGA devices tested in a randomized order in this prospective cross-over designed study. The primary outcome was comparisons of decompression AP between all groups. RESULTS: An ITD was required to generate significantly lower negative ITP during the decompression phase of all methods of CPR. SGAs varied in their ability to support negative ITP. CONCLUSION: In a human cadaver model, the ability to generate negative intrathoracic pressures varied with different SGAs and an ITD regardless of the body position or CPR method. Differences in SGAs devices should be strongly considered when trying to optimize cardiac arrest outcomes, as some SGAs do not consistently develop a seal or negative intrathoracic pressure with multiple different CPR methods and devices.

Improved Survival With Extracorporeal Cardiopulmonary Resuscitation Despite Progressive Metabolic Derangement Associated With Prolonged Resuscitation.

BACKGROUND: The likelihood of neurologically favorable survival declines with prolonged resuscitation. However, the ability of extracorporeal cardiopulmonary resuscitation (ECPR) to modulate this decline is unknown. Our aim was to examine the effects of resuscitation duration on survival and metabolic profile in patients who undergo ECPR for refractory ventricular fibrillation/ventricular tachycardia out-of-hospital cardiac arrest. METHODS: We retrospectively evaluated survival in 160 consecutive adults with refractory ventricular fibrillation/ventricular tachycardia out-of-hospital cardiac arrest treated with the University of Minnesota (UMN) ECPR protocol (transport with ongoing cardiopulmonary resuscitation [CPR] to the cardiac catheterization laboratory for ECPR) compared with 654 adults who had received standard CPR in the amiodarone arm of the ALPS trial (Amiodarone, Lidocaine, or Placebo Study). We evaluated the metabolic changes and rate of survival in relation to duration of CPR in UMN-ECPR patients. RESULTS: Neurologically favorable survival was significantly higher in UMN-ECPR patients versus ALPS patients (33% versus 23%; P=0.01) overall. The mean duration of CPR was also significantly longer for UMN-ECPR patients versus ALPS patients (60 minutes versus 35 minutes; P<0.001). Analysis of the effect of CPR duration on neurologically favorable survival demonstrated significantly higher neurologically favorable survival for UMN-ECPR patients compared with ALPS patients at each CPR duration interval <60 minutes; however, longer CPR duration was associated with a progressive decline in neurologically favorable survival in both groups. All UMN-ECPR patients with 20 to 29 minutes of CPR (8 of 8) survived with neurologically favorable status compared with 24% (24 of 102) of ALPS patients with the same duration of CPR. There were no neurologically favorable survivors in the ALPS cohort with CPR ≥40 minutes, whereas neurologically favorable survival was 25% (9 of 36) for UMN-ECPR patients with 50 to 59 minutes of CPR and 19% with ≥60 minutes of CPR. Relative risk of mortality or poor neurological function was significantly reduced in UMN-ECPR patients with CPR duration ≥60 minutes. Significant metabolic changes included decline in pH, increased lactic acid and arterial partial pressure of carbon dioxide, and thickened left ventricular wall with prolonged professional CPR. CONCLUSIONS: ECPR was associated with improved neurologically favorable survival at all CPR durations <60 minutes despite severe progressive metabolic derangement. However, CPR duration remains a critical determinate of survival.

A Case of Neurologically Intact Survival after 2 hours and 50 minutes of Euthermic Cardiac Arrest Treated with Mechanical CPR and Intra-arrest Percutaneous Coronary Intervention.

We report a case of a 56 year old male in ventricular fibrillation (VF) cardiac arrest for a total of 2 hours and 50 minutes who was diagnosed with ST elevation myocardial infarction (STEMI) during a brief 10 min period of return of spontaneous circulation (ROSC). The patient underwent successful percutaneous coronary intervention (PCI) while receiving mechanical chest compressions for ongoing VF. Our case demonstrates the potential for neurologically intact survival in VF cardiac arrest patients despite prolonged periods of VF who are treated with mechanical CPR and intra-arrest PCI.

Consistent head up cardiopulmonary resuscitation haemodynamics are observed across porcine and human cadaver translational models.

AIM: The objectives were: 1) replicate key elements of Head Up (HUP) cardiopulmonary resuscitation (CPR) physiology in a traditional swine model of ventricular fibrillation (VF), 2) compare HUP CPR physiology in pig cadavers (PC) to the VF model 3) develop a new human cadaver (HC) CPR model, and 4) assess HUP CPR in HC. METHODS: Nine female pigs were intubated, and anesthetized. Venous, arterial, and intracranial access were obtained. After 6 min of VF, CPR was performed for 2 min epochs as follows: Standard (S)-CPR supine (SUP), Active compression decompression (ACD) CPR + impedance threshold device (ITD-16) CPR SUP, then ACD + ITD HUP CPR. The same sequence was performed in PC 3 h later. In 9 HC, similar vascular and intracranial access were obtained and CPR performed for 1 min epochs using the same sequence as above. RESULTS: The mean cerebral perfusion pressure (CerPP, mmHg) was 14.5 ±â€¯6 for ACD + ITD SUP and 28.7 ±â€¯10 for ACD + ITD HUP (p = .007) in VF, -3.6 ±â€¯5 for ACD + ITD SUP and 7.8 ±â€¯9 for ACD + ITD HUP (p = .007) in PC, and 1.3 ±â€¯4 for ACD + ITD SUP and 11.3 ±â€¯5 for ACD + ITD HUP (p = .007) in HC. Mean systolic and diastolic intracranial pressures (ICP) (mmHg) were significantly lower in the ACD + ITD HUP group versus the ACD + ITD SUP group in all three CPR models. CONCLUSION: HUP CPR decreased ICP while increasing CerPP in pigs in VF as well as in PC and HC CPR models. This first-time demonstration of HUP CPR physiology in humans provides important implications for future resuscitation research and treatment.

Long-Term Prognostic Value of Gasping During Out-of-Hospital Cardiac Arrest.

BACKGROUND: Gasping is a natural reflex that enhances oxygenation and circulation during cardiopulmonary resuscitation (CPR). OBJECTIVES: This study sought to assess the relationship between gasping during out-of-hospital cardiac arrest and 1-year survival with favorable neurological outcomes. METHODS: The authors prospectively collected incidence of gasping on all evaluable subjects in a multicenter, randomized, controlled, National Institutes of Health-funded out-of-hospital cardiac arrest clinical trial from August 2007 to July 2009. The association between gasping and 1-year survival with favorable neurological function, defined as a Cerebral Performance Category (CPC) score ≤2 was estimated using multivariable logistic regression. RESULTS: The rates of 1-year survival with a CPC score of ≤2 were 5.4% (98 of 1,827) overall, and 20% (36 of 177) and 3.7% (61 of 1,643) for individuals with and without spontaneous gasping or agonal respiration during CPR, respectively. In multivariable analysis, 1-year survival with CPC ≤2 was independently associated with younger age (odds ratio [OR] for 1 SD increment 0.57; 95% confidence interval [CI]: 0.43 to 0.76), gasping during CPR (OR: 3.94; 95% CI: 2.09 to 7.44), shockable initial recorded rhythm (OR: 16.50; 95% CI: 7.40 to 36.81), shorter CPR duration (OR: 0.31; 95% CI: 0.19 to 0.51), lower epinephrine dosage (OR: 0.47; 95% CI: 0.25 to 0.87), and pulmonary edema (OR: 3.41; 95% CI: 1.53 to 7.60). Gasping combined with a shockable initial recorded rhythm had a 57-fold higher OR (95% CI: 23.49 to 136.92) of 1-year survival with CPC ≤2 versus no gasping and no shockable rhythm. CONCLUSIONS: Gasping during CPR was independently associated with increased 1-year survival with CPC ≤2, regardless of the first recorded rhythm. These findings underscore the importance of not terminating resuscitation prematurely in gasping patients and the need to routinely recognize, monitor, and record data on gasping in all future cardiac arrest trials and registries.

Coronary Artery Disease in Patients With Out-of-Hospital Refractory Ventricular Fibrillation Cardiac Arrest.

BACKGROUND: The prevalence of coronary artery disease (CAD) among patients with refractory out-of-hospital (OH) ventricular fibrillation (VF)/ventricular tachycardia (VT) cardiac arrest is unknown. OBJECTIVES: The goal of this study was to describe the prevalence and complexity of CAD and report survival to hospital discharge in patients experiencing refractory VF/VT cardiac arrest treated with a novel protocol of early transport to a cardiac catheterization laboratory (CCL) for extracorporeal life support (ECLS) and revascularization. METHODS: Between December 1, 2015, and December 1, 2016, consecutive adult patients with refractory OH VF/VT cardiac arrest requiring ongoing cardiopulmonary resuscitation were transported by emergency medical services to the CCL. ECLS, coronary angiography, and percutaneous coronary intervention were performed, as appropriate. Functionally favorable survival to hospital discharge (Cerebral Performance Category 1 or 2) was determined. Outcomes in a historical comparison group were also evaluated. RESULTS: Sixty-two (86%) of 72 transported patients met emergency medical services transport criteria. Fifty-five (89%) of the 62 patients met criteria for continuing resuscitation on CCL arrival; 5 had return of spontaneous circulation, 50 received ECLS, and all 55 received coronary angiography. Forty-six (84%) of 55 patients had significant CAD, 35 (64%) of 55 had acute thrombotic lesions, and 46 (84%) of 55 had percutaneous coronary intervention with 2.7 ± 2.0 stents deployed per patient. The mean SYNTAX score was 29.4 ± 13.9. Twenty-six (42%) of 62 patients were discharged alive with Cerebral Performance Category 1 or 2 versus 26 (15.3%) of 170 in the historical comparison group (odds ratio: 4.0; 95% confidence interval: 2.08 to 7.7; p < 0.0001). CONCLUSIONS: Complex but treatable CAD was prevalent in patients with refractory OH VF/VT cardiac arrest who also met criteria for continuing resuscitation in the CCL. A systems approach using ECLS and reperfusion seemed to improve functionally favorable survival.

Intraosseous Pressure Monitoring in Healthy Volunteers.

STUDY OBJECTIVE: Invasively monitoring blood pressure through the IO device has not been thoroughly demonstrated. This study attempted to establish baseline values of IO pressure in a healthy human population. METHODS: This was a prospective, healthy volunteer, observational study. Participants had two IO devices placed (humerus and tibia), and participant IO pressures, vital signs, and pain scores were monitored for up to 60 minutes. Participants were contacted at 24-hours and 7 days post-testing to assess for adverse events. Summary statistics were calculated for systolic, diastolic, and mean humeral and tibial IO pressure. The ratio of IO to non-invasive blood pressure was calculated, and Bland Altman plots were created. The slope (linear) of the mean humeral and the tibial IO pressures were also calculated. RESULTS: Fifteen subjects were enrolled between April and July 2015. Fourteen of 15 humeral IOs were placed successfully (93.3%) and all 15 of the tibial IOs were placed successfully. Mean tibial systolic, diastolic, and mean IO pressure were 55.8 ± 27.9, 49.3 ± 27.1, and 48.4 ± 29.4 mm Hg, respectively. Humeral systolic, diastolic, and mean IO pressure were 32.9 ± 16.0, 27.4 ± 15.2, and 24.5 ± 14.3 mm Hg. The mean tibial IO pressure was 52.5% ± 32.0% of external cuff pressure ratio. The mean humeral IO pressure was 26.5% ± 15.2% of the external mean blood pressure. The Bland Altman plots showed an inconsistent relationship between the systolic and diastolic cuff pressure and the IO pressures. We observed a 1% per minute decrease in IO pressure from the initial placement until the final reading. CONCLUSIONS: Intraosseous pressure readings can be obtained in healthy human volunteers. However, absolute IOP values were not consistent between subjects. Future research may determine how IO pressure can be used to guide therapy in ill and injured patients.

Quality of CPR: An important effect modifier in cardiac arrest clinical outcomes and intervention effectiveness trials.

OBJECTIVES: To determine if the quality of CPR had a significant interaction with the primary study intervention in the NIH PRIMED trial. DESIGN: The public access database from the NIH PRIMED trial was accessed to determine if there was an interaction between quality of CPR performance, intervention, and outcome (survival to hospital discharge with modified Rankin Score (mRS) ≤ 3). SETTING: Multi-centered prehospital care systems across North America. PATIENTS: Of 8719 adult patients enrolled, CPR quality was electronically recorded for compression rate, depth, and fraction in 6199 (71.1%), 3750 (43.0%) and 6204 (71.2%) subjects, respectively. "Acceptable" quality CPR was defined prospectively as simultaneous provision of a compression rate of 100/min (± 20%), depth of 5 cm (± 20%) and fraction of > 50%. Significant interaction was considered as p < 0.05. INTERVENTION: Standard CPR with an activated versus sham (inactivated) ITD. MEASUREMENTS AND MAIN RESULTS: Overall, 848 and 827 patients, respectively, in the active and sham-ITD groups had "acceptable" CPR quality performed (n = 1675). There was a significant interaction between the active and sham-ITD and compression rate, depth and fraction as well as their combinations. The strongest interaction was seen with all three parameters combined (unadjusted and adjusted interaction p-value, < 0.001). For all presenting rhythms, when "acceptable" quality of CPR was performed, use of an active-ITD increased survival to hospital discharge with mRS ≤ 3 compared to sham (61/848 [7.2%] versus 34/827 [4.1%], respectively; p = 0.006). The opposite was true for patients that did not receive "acceptable" quality of CPR. In those patients, use of an active - ITD led to significantly worse survival to hospital discharge with mRS ≤ 3 compared to sham (34/1012 [3.4%] versus 62/1061 [5.8%], p = 0.007). CONCLUSIONS: There was a statistically significant interaction between the quality of CPR provided, intervention, and survival to hospital discharge with mRS ≤ 3 in the NIH PRIMED trial. Quality of CPR delivered can be an underestimated effect modifier in CPR clinical trials.

The association of health status and providing consent to continued participation in an out-of-hospital cardiac arrest trial performed under exception from informed consent.

OBJECTIVES: Emergency medical research performed under federal regulation 21 § CFR 50.24 provides a means to protect human subjects and investigate novel time-sensitive treatments. Although prospective individual consent is not required for studies conducted under this regulation, consent from a legally authorized representative (LAR) or the patient at the earliest feasible opportunity is required to obtain short- and long-term outcome data. The objective of this study was to determine which demographic, cardiac arrest, and patient outcome characteristics predicted the likelihood of obtaining informed consent following enrollment under exception from informed consent in a multicenter cardiac arrest study. METHODS: This investigation was an analysis of data collected during a multisite, randomized, controlled, out-of-hospital cardiac arrest clinical trial performed under 21 § CFR 50.24. Research personnel attempted to obtain informed consent from LARs and subjects for medical records review of primary outcome data, as well as consent for neurologic outcome assessments up to 1 year post-cardiac arrest. Hospital discharge and neurologic status were obtained from public records and/or medical records up until the time consent was formally denied, in accordance with federal regulations and guidance. Local institutional review boards also allowed medical records review for cases where consent was neither obtained nor declined despite multiple consent attempts. Patient demographic, cardiac arrest, and clinical outcome characteristics were analyzed in univariate multinomial regression models, with consent status (obtained, denied, neither obtained nor denied) as the dependent variable. A multivariate multinomial logistic regression was then performed. An exploratory secondary analysis following the same process was performed after assigning patients who neither consented nor declined to the declined consent group. RESULTS: Among a total study population of 1,655 cardiac arrest subjects, 457 were transported and had consent attempted (27.6%). The survival status and neurologic function at the time of hospital discharge were known in 440 of 457 (96%) subjects. In the multivariate analysis, initial rhythm of ventricular fibrillation/ventricular tachycardia (VF/VT) and survival with good neurologic outcome were strong predictors of obtaining consent (odds ratio [OR] = 3.15, 95% confidence interval [CI] = 1.73 to 5.75; OR = 7.64, 95% CI = 2.28 to 25.63, respectively). The exploratory secondary analysis also showed initial rhythm of VF/VT and survival with good neurologic outcome as strong predictors of obtaining consent (OR = 1.86, 95% CI = 1.17 to 2.95; OR = 4.52, 95% CI = 2.21 to 9.26, respectively). CONCLUSIONS: Initial arrest rhythm and survival with good neurologic outcome were highly predictive of obtaining consent in this cardiac arrest trial. This phenomenon could result in underrepresentation of outcome data in the study arm with the worse outcome and represents a significant potential confounder in studies performed under 21 § CFR 50.24. Future revisions to the exception from informed consent regulations should allow access to critical survival data recorded as part of standard documentation, regardless of patient consent status.

Evaluation of intraosseous pressure in a hypovolemic animal model.

BACKGROUND: In emergent situations, access to the vascular bed is frequently required for fluid and medication administration. Central venous catheter placement is associated with risk and may slow resuscitation in the unstable patient. The purpose of this study was to determine whether intraosseous pressure (IOP) could be consistently recorded and how similar this pressure was to central venous and arterial pressure in a porcine hemorrhagic shock model. MATERIALS AND METHODS: After sedation, eight female swine had catheters placed in the femoral vein, aorta via femoral artery, and superior vena cava. IOP lines were placed in the proximal humerus, distal femur, and proximal tibia. Pressure readings were recorded continuously through the five stages of progressive hypovolemia. Pressure data were descriptively summarized, with the percent of change of IOP at each stage compared with arterial pressure using a multilevel mixed effects linear model with log transformation. RESULTS: The IOP baseline values were between 16 and 18 mm Hg, approximately 22% of baseline arterial pressure. The intraosseous (IO) waveform mostly closely resembled the arterial pressure waveform, including the presence of a dichroitic notch. Pressure variations caused by ventilation (respiratory variability) were also identified in all the tracings. The rate of pressure change in the humeral IO most closely matched the change in arterial pressure rate. IO blood gas analysis showed gas composition to most closely match venous blood. CONCLUSIONS: IOP was reliably obtained in this porcine model and suggests potential for clinical application in humans.

The association between ketamine given for prehospital chemical restraint with intubation and hospital admission.

INTRODUCTION: Intramuscular ketamine has become increasingly popular for prehospital chemical restraint of severely agitated or violent patients because of its favorable adverse effect profile, rapid onset, and wide therapeutic window. However, there is currently no literature quantifying the need for intubation or hospital admission for these patients once they reach the emergency department. METHODS: Medical records for patients receiving prehospital ketamine who were transported to a single level 1 trauma center were abstracted. Ketamine dose, patient weight, final disposition, and presence of intubation were recorded. Exclusion criteria were missing dose or weight and ketamine given for an indication other than chemical restraint. Statistical analysis was preformed with unadjusted Student t test. Statistical significance was defined as P < .05. RESULTS: A convenience sample of 51 consecutive patients was identified with 2 excluded because of missing data, leaving 49 for analysis. Ketamine dosing ranged from 2.25 to 9.42 mg/kg (mean, 5.26 ± 1.65 mg/kg). Significant differences were noted between those who required intubation (n = 14) and those who did not (n = 35) (6.16 ± 1.62 mg/kg vs 4.90 ± 1.54 mg/kg, P = .02). No patients were intubated prehospital. There was an increased dose in patients admitted to a medical ward (57%, 28/49) that approached statistical significance (5.62 ± 1.80 vs 4.78 ± 1.31, P = .06). CONCLUSION: Intubation was observed in our emergency department in 29% of patients administered intramuscular ketamine for prehospital chemical restraint. There was a positive association between higher ketamine doses and both endotracheal intubation and hospital admission. Future research should aim to define the minimum effective ketamine dose for successful chemical restraint.

One-year outcomes of out-of-hospital administration of intravenous glucose, insulin, and potassium (GIK) in patients with suspected acute coronary syndromes (from the IMMEDIATE [Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care] Trial).

The Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care Trial of very early intravenous glucose-insulin-potassium (GIK) for acute coronary syndromes (ACS) in out-of-hospital emergency medical service (EMS) settings showed 80% reduction in infarct size at 30 days, suggesting potential longer-term benefits. Here we report 1-year outcomes. Prespecified 1-year end points of this randomized, placebo-controlled, double-blind, effectiveness trial included all-cause mortality and composites including cardiac arrest, mortality, or hospitalization for heart failure (HF). Of 871 participants randomized to GIK versus placebo, death occurred within 1 year in 11.6% versus 13.5%, respectively (unadjusted hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.57 to 1.23, p = 0.36). The composite of cardiac arrest or 1-year mortality was 12.8% versus 17.0% (HR 0.71, 95% CI 0.50 to 1.02, p = 0.06). The composite of hospitalization for HF or mortality within 1 year was 17.2% versus 17.2% (HR 0.98, 95% CI 0.70 to 1.37, p = 0.92). The composite of mortality, cardiac arrest, or HF hospitalization within 1 year was 18.1% versus 20.4% (HR 0.85, 95% CI 0.62 to 1.16, p = 0.30). In patients presenting with suspected ST elevation myocardial infarction, HRs for 1-year mortality and the 3 composites were, respectively, 0.65 (95% CI 0.33 to 1.27, p = 0.21), 0.52 (95% CI 0.30 to 0.92, p = 0.03), 0.63 (95% CI 0.35 to 1.16, p = 0.14), and 0.51 (95% CI 0.30 to 0.87, p = 0.01). In patients with suspected acute coronary syndromes, serious end points generally were lower with GIK than placebo, but the differences were not statistically significant. However, in those with ST elevation myocardial infarction, the composites of cardiac arrest or 1-year mortality, and of cardiac arrest, mortality, or HF hospitalization within 1 year, were significantly reduced.

Use of an intraosseous device for invasive pressure monitoring in the ED.

Venous access is essential to providing emergency care for critically ill or injured patients. Obtaining peripheral or central access can be problematic and time consuming. Intraosseous (IO) fluid administration provides similar flow rates and central circulation times compared to central lines, but use of these devices to monitor blood pressure has not been explored. We report a case of successful IO pressure (IOP) monitoring through an IO during the resuscitation of a 31-year-old male. This is the first report of monitoring IOP in a clinical setting and comparing it to traditional measures of central pressure.