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.

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.

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.

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.

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.

Comparison of success rates between two video laryngoscope systems used in a prehospital clinical trial.

OBJECTIVES: The primary aims of this study were to compare paramedic success rates and complications of two different video laryngoscopes in a prehospital clinical study. METHODS: This study was a multi-agency, prospective, non-randomized, cross over clinical trial involving paramedics from four different EMS agencies. Following completion of training sessions, six Storz CMAC™ video laryngoscopes and six King Vision™ (KV) video laryngoscopes were divided between agencies and placed into service for 6 months. Paramedics were instructed to use the video laryngoscope for all patients estimated to be ≥ 18 years old who required advanced airway management per standard operating procedure. After 6 months, the devices were crossed over for the final 6 months of the study period. Data collection was completed using a telephone data collection system with a member of the research team (available 24/7). First attempt success, overall success, and success by attempt, were compared between treatment groups using exact logistic regression adjusted for call type and user experience. RESULTS: Over a 12-month period, 107 patients (66 CMAC, 41 KV) were treated with a study device. The CMAC had a significantly higher likelihood of first attempt success (OR = 1.85; 95% CI 0.74, 4.62; p = 0.188), overall success (OR = 7.37; 95% CI 1.73, 11.1; p = 0.002), and success by attempt (OR = 3.38; 95% CI 1.67, 6.8; p = 0.007) compared to KV. Providers reverted to direct laryngoscopy in 80% (27/34) of the video laryngoscope failure cases, with the remaining patients having their airways successfully managed with a supraglottic airway in 3 cases and bag-valve mask in 4 cases. The provider-reported complications were similar and none were statistically different between treatment groups. Complication rates were not statistically different between devices. CONCLUSION: The CMAC had a higher likelihood of successful intubation compared to the King Vision. Complication rates were not statistically different between groups. Video laryngoscope placement success rates were not higher than our historical direct laryngoscopy success rates.

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.

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 traumatic brain injury (TBI) trial, TXA administered within 2 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 score < 13) and systolic blood pressure ≥ 90 mm Hg within 2 hours of injury to a 2-g out-of-hospital TXA bolus followed by an in-hospital saline infusion, a 1-g out-of-hospital TXA bolus/1-g 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-g TXA bolus group (17%) compared with the other two groups (1-g bolus/1-g infusion 26%, placebo 27%). The estimated adjusted difference between the 2-g bolus and placebo groups was -8·5 percentage points (95% confidence interval [CI], -15.9 to -1.0) and between the 2-g bolus and 1-g bolus/1-g infusion groups was -10.2 percentage points (95% CI, -17.6 to -2.9). Disability Rating Scale at 6 months was lower in the 2-g TXA bolus group than the 1-g bolus/1-g 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. CONCLUSION: A 2-g 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.

Evaluation of the Storz CMAC®, Glidescope® GVL, AirTraq®, King LTS-D™, and direct laryngoscopy in a simulated difficult airway.

OBJECTIVE: The aim of this study was to compare first-attempt and overall success rates and success rates in relation to placement time among 5 different airway management devices: Storz CMAC, Glidescope GVL, AirTraq, King LTS-D, and direct laryngoscopy (DL). METHODS: Emergency medical technician basic (EMT-B), EMT-paramedics (EMT-P), and emergency medicine residents and staff physicians placed each of the 5 devices in a random order into an AirSim (TruCorp, Belfast, UK) part-task training manikin. The difficult airway scenario was created by fixing the manikin head to a stationary object and introducing simulated emesis into the hypopharynx. First-attempt and overall success and success in relation to placement time were compared. Provider feedback about device performance was also evaluated. RESULTS: Ninety-four providers (16 EMT-basics, 54 EMT-paramedics, and 24 emergency department doctors of medicine) consented to participation. First-attempt and overall success rates for DL, King LTS-D, GVL, and CMAC were not statistically different. Compared with DL, the AirTraq was 96% less likely to be placed successfully (odds ratio, 0.04; 95% confidence interval [CI], 0.01-0.14). When time was factored into the model, the odds of successful placement of the King LTS-D were higher compared with DL (hazard ratio [HR], 1.80; 95% CI, 1.34-2.42) and lower for GVL (HR, 0.59; 95% CI, 0.44-0.80) and AirTraq (HR, 0.228; 95% CI, 0.16-0.325). Providers ranked the CMAC first in terms of performance and preference for use in their practice setting. CONCLUSION: Overall success rates for DL, King-LTS-D, and both video laryngoscope systems were not different. When time was factored into the model, the King LTS-D was more likely to be placed successfully.

Supraglottic airway device use as a primary airway during rapid sequence intubation.

INTRODUCTION: This study compared first-attempt placement success rates of the King LTS-D as a primary airway for patients requiring medication-assisted airway management (MAAM) against historical controls. SETTING: Rotor-wing division of a single critical care transportation company METHODS: 53 providers (RNs/EMT-P) consented to participation and were trained in the use of the King LTS-D. All patients in need of MAAM per agency treatment guidelines were screened for inclusion and exclusion criteria. After each placement attempt, providers completed data collection via telephone. The primary endpoint was comparison of first-attempt placement success rate between the King LTS-D and historical control endotracheal intubation (ETI) MAAM patients. Overall placement success, time to placement, pre- and post-placement SaO2, ETCO2 at 2 minutes after placement, and complications were also analyzed. RESULTS: 38 patients received rapid sequence intubation with the King LTS-D by 23 of 58 consented providers. First-attempt success rate was 76% (29/38), with an overall success rate of 84% (32/38). The primary endpoint analysis showed no difference in first-attempt success rate between historical control ETI MAAM data and King LTS-D (71% vs 76%; OR = 0.1.34 [95% CI Intubation time to insertion was 26 seconds (IQR = 12-46). Pre- and post-insertion SaO(1)2 values were 88.9 ± 12.6% and 92.1 ± 12.7%, respectively. Mean ETCO2 at 2 minutes after placement was 34.8 ± 4.0. Vomit in the patient's airway was the most frequently reported complication (46%). CONCLUSION: Success rates with the King LTS-D were not significantly different from historical control ETI data. Time to placement was comparable to previous reports.

Standard cardiopulmonary resuscitation versus active compression-decompression cardiopulmonary resuscitation with augmentation of negative intrathoracic pressure for out-of-hospital cardiac arrest: a randomised trial.

BACKGROUND: Active compression-decompression cardiopulmonary resuscitation (CPR) with decreased intrathoracic pressure in the decompression phase can lead to improved haemodynamics compared with standard CPR. We aimed to assess effectiveness and safety of this intervention on survival with favourable neurological function after out-of-hospital cardiac arrest. METHODS: In our randomised trial of 46 emergency medical service agencies (serving 2·3 million people) in urban, suburban, and rural areas of the USA, we assessed outcomes for patients with out-of-hospital cardiac arrest according to Utstein guidelines. We provisionally enrolled patients to receive standard CPR or active compression-decompression CPR with augmented negative intrathoracic pressure (via an impedance-threshold device) with a computer-generated block randomisation weekly schedule in a one-to-one ratio. Adults (presumed age or age ≥18 years) who had a non-traumatic arrest of presumed cardiac cause and met initial and final selection criteria received designated CPR and were included in the final analyses. The primary endpoint was survival to hospital discharge with favourable neurological function (modified Rankin scale score of ≤3). All investigators apart from initial rescuers were masked to treatment group assignment. This trial is registered with ClinicalTrials.gov, number NCT00189423. FINDINGS: 2470 provisionally enrolled patients were randomly allocated to treatment groups. 813 (68%) of 1201 patients assigned to the standard CPR group (controls) and 840 (66%) of 1269 assigned to intervention CPR received designated CPR and were included in the final analyses. 47 (6%) of 813 controls survived to hospital discharge with favourable neurological function compared with 75 (9%) of 840 patients in the intervention group (odds ratio 1·58, 95% CI 1·07-2·36; p=0·019]. 74 (9%) of 840 patients survived to 1 year in the intervention group compared with 48 (6%) of 813 controls (p=0·03), with equivalent cognitive skills, disability ratings, and emotional-psychological statuses in both groups. The overall major adverse event rate did not differ between groups, but more patients had pulmonary oedema in the intervention group (94 [11%] of 840) than did controls (62 [7%] of 813; p=0·015). INTERPRETATION: On the basis of our findings showing increased effectiveness and generalisability of the study intervention, active compression-decompression CPR with augmentation of negative intrathoracic pressure should be considered as an alternative to standard CPR to increase long-term survival after cardiac arrest. FUNDING: US National Institutes of Health grant R44-HL065851-03, Advanced Circulatory Systems.

Laryngospasm and hypoxia after intramuscular administration of ketamine to a patient in excited delirium.

An advanced life support emergency medical services (EMS) unit was dispatched with law enforcement to a report of a male patient with a possible overdose and psychiatric emergency. Police restrained the patient and cleared EMS into the scene. The patient was identified as having excited delirium, and ketamine was administered intramuscularly. Sedation was achieved and the patient was transported to the closest hospital. While in the emergency department, the patient developed laryngospasm and hypoxia. The airway obstruction was overcome with bag-valve-mask ventilation. Several minutes later, a second episode of laryngospasm occurred, which again responded to positive-pressure ventilation. At this point the airway was secured with an endotracheal tube. The patient was uneventfully extubated several hours later. This is the first report of laryngospam and hypoxia associated with prehospital administration of intramuscular ketamine to a patient with excited delirium.

The emergency department experience with prehospital ketamine: a case series of 13 patients.

BACKGROUND: There are no published reports examining the effects that ketamine administered prior to hospital arrival has on patients after their transfer to the emergency department (ED). OBJECTIVE: In order to better understand the risk-benefit ratio for the prehospital use of ketamine, we examined the ED courses of 13 patients to whom emergency medical services (EMS) had administered ketamine for chemical restraint. METHODS: This project was undertaken as part of our EMS system's continuous quality improvement (CQI) process. Data were collected retrospectively. All patients who were given ketamine by EMS providers under our medical direction were identified by prehospital care report queries. The treating paramedic and emergency physician were provided a CQI form after disposition of the patient from their care. The data were tabulated and descriptive statistics were calculated. RESULTS: Thirteen patients were given ketamine by EMS providers, with 13 of 13 having EMS records and 12 of 13 having ED records available for review. Time from ketamine administration to peak sedation was <5 minutes in 11 patients and 20 minutes for two patients. On emergency physician examination, five of 12 patients had Richmond Agitation Sedation Scale (RASS) scores of -5 (unarousable), one of 12 had a RASS score of -4 (deep sedation), four of 12 had RASS scores of -3 (moderate sedation), and two of 12 had RASS scores of -2 (light sedation). Three patients developed hypoxia, two in the ED and one prior to hospital arrival. Two of these patients required intubation and one was treated with jaw thrust. Indications for intubation were recurrent laryngospasm and intracranial bleeding. One additional patient experienced a single episode of hypersalivation, which was successfully treated with suctioning of the oropharynx. Of the nonintubated patients, three of 10 were diagnosed with an emergence reaction and five of 10 required additional sedation. The primary diagnosis on ED disposition was drug/ethanol intoxication (3), psychosis (4), intracranial bleeding (1), seizure (1), suicidal ideation (1), agitation (1), and altered mental status (1). Five patients were discharged from the ED, seven were admitted (two to the intensive care unit, four to medicine, and one to psychiatry), and one patient's disposition was unknown. CONCLUSIONS: In this series of 13 patients, ketamine administered by EMS produced moderate or deeper sedation. Respiratory complications included hypoxia, laryngospasm, and hypersalivation. Emergence reactions occurred in 30% of nonintubated patients, but they were successfully treated with small doses of benzodiazepines.

Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: the IMMEDIATE randomized controlled trial.

CONTEXT: Laboratory studies suggest that in the setting of cardiac ischemia, immediate intravenous glucose-insulin-potassium (GIK) reduces ischemia-related arrhythmias and myocardial injury. Clinical trials have not consistently shown these benefits, possibly due to delayed administration. OBJECTIVE: To test out-of hospital emergency medical service (EMS) administration of GIK in the first hours of suspected acute coronary syndromes (ACS). DESIGN, SETTING, AND PARTICIPANTS: Randomized, placebo-controlled, double-blind effectiveness trial in 13 US cities (36 EMS agencies), from December 2006 through July 31, 2011, in which paramedics, aided by electrocardiograph (ECG)-based decision support, randomized 911 (871 enrolled) patients (mean age, 63.6 years; 71.0% men) with high probability of ACS. INTERVENTION: Intravenous GIK solution (n = 411) or identical-appearing 5% glucose placebo (n = 460) administered by paramedics in the out-of-hospital setting and continued for 12 hours. MAIN OUTCOME MEASURES: The prespecified primary end point was progression of ACS to myocardial infarction (MI) within 24 hours, as assessed by biomarkers and ECG evidence. Prespecified secondary end points included survival at 30 days and a composite of prehospital or in-hospital cardiac arrest or in-hospital mortality, analyzed by intent-to-treat and by presentation with ST-segment elevation. RESULTS: There was no significant difference in the rate of progression to MI among patients who received GIK (n = 200; 48.7%) vs those who received placebo (n = 242; 52.6%) (odds ratio [OR], 0.88; 95% CI, 0.66-1.13; P = .28). Thirty-day mortality was 4.4% with GIK vs 6.1% with placebo (hazard ratio [HR], 0.72; 95% CI, 0.40-1.29; P = .27). The composite of cardiac arrest or in-hospital mortality occurred in 4.4% with GIK vs 8.7% with placebo (OR, 0.48; 95% CI, 0.27-0.85; P = .01). Among patients with ST-segment elevation (163 with GIK and 194 with placebo), progression to MI was 85.3% with GIK vs 88.7% with placebo (OR, 0.74; 95% CI, 0.40-1.38; P = .34); 30-day mortality was 4.9% with GIK vs 7.7% with placebo (HR, 0.63; 95% CI, 0.27-1.49; P = .29). The composite outcome of cardiac arrest or in-hospital mortality was 6.1% with GIK vs 14.4% with placebo (OR, 0.39; 95% CI, 0.18-0.82; P = .01). Serious adverse events occurred in 6.8% (n = 28) with GIK vs 8.9% (n = 41) with placebo (P = .26). CONCLUSIONS: Among patients with suspected ACS, out-of-hospital administration of intravenous GIK, compared with glucose placebo, did not reduce progression to MI. Compared with placebo, GIK administration was not associated with improvement in 30-day survival but was associated with lower rates of the composite outcome of cardiac arrest or in-hospital mortality. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00091507.

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.

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.

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.