A multi-center, randomized, double blinded, placebo-controlled trial of amantadine to stimulate awakening in comatose patients resuscitated from cardiac arrest.

Objectives: We hypothesized that the administration of amantadine would increase awakening of comatose patients resuscitated from cardiac arrest. Methods: We performed a prospective, randomized controlled pilot trial, randomizing subjects to amantadine 100mg twice daily or placebo for up to 7 days. The study drug was administered between 72-120 hours after resuscitation and patients with absent N20 cortical responses, early cerebral edema, or ongoing malignant electroencephalography patterns were excluded. Our primary outcome was awakening, defined as following two-step commands, within 28 days of cardiac arrest. Secondary outcomes included length of stay, awakening, time to awakening, and neurologic outcome measured by Cerebral Performance Category (CPC) at hospital discharge. We compared the proportion of subjects awakening and hospital survival using Fisher's exact tests and time to awakening and hospital length of stay using Wilcoxon rank sum tests. Results: After 2 years, we stopped the study due to slow enrollment and lapse of funding. We enrolled 14 subjects (12% of goal enrollment), 7 in the amantadine arm and 7 in the placebo arm. The proportion of patients who awakened within 28 days after cardiac arrest did not differ between amantadine (n=2, 28.57%) and placebo groups (n=3, 42.86%) (p = 1.00). There were no differences in secondary outcomes. Study medication was stopped in three (21%) subjects. Adverse events included a recurrence of seizures (n=2; 14%), both of which occurred in the placebo arm. Conclusion: We could not determine the effect of amantadine on awakening in comatose survivors of cardiac arrest due to small sample size.

Effect of stomach inflation during cardiopulmonary resuscitation on return of spontaneous circulation in out-of-hospital cardiac arrest patients: A retrospective observational study.

BACKGROUND: Gastric inflation caused by excessive ventilation is a common complication of cardiopulmonary resuscitation. Gastric inflation may further compromise ventilation via increases in intrathoracic pressure, leading to decreased venous return and cardiac output, which may impair out-of-hospital cardiac arrest (OHCA) outcomes. The purpose of this study was to measure the gastric volume of OHCA patients using computed tomography (CT) scan images and evaluate the effect of gastric inflation on return of spontaneous circulation (ROSC). METHODS: In this single-center, retrospective, observational study, CT scan was conducted after ROSC or immediately after death. Total gastric volume was measured. Primary outcome was ROSC. Achievement of ROSC was compared in the gastric distention group and the no gastric distention group; gastric distension was defined as total gastric volume in the ≥75th percentile. Additionally, factors associated with gastric distention were examined. RESULTS: A total of 446 cases were enrolled in the study; 120 cases (27%) achieved ROSC. The median gastric volume was 400 ml for all OHCA subjects; 1068 ml in gastric distention group vs. 287 ml in no gastric distention group. There was no difference in ROSC between the groups (27/112 [24.1%] vs. 93/334 [27.8%], p = 0.440). Gastric distention did not have a significant impact, even after adjustments (adjusted odds ratio 0.73, 95% confidence interval [0.42-1.29]). Increased gastric volume was associated with longer emergency medical service activity time. CONCLUSIONS: We observed a median gastric volume of 400 ml in patients after OHCA resuscitation. In our setting, gastric distention did not prevent ROSC.

Association of Initial Illness Severity and Outcomes After Cardiac Arrest With Targeted Temperature Management at 36 °C or 33 °C.

Importance: It is uncertain what the optimal target temperature is for targeted temperature management (TTM) in patients who are comatose following cardiac arrest. Objective: To examine whether illness severity is associated with changes in the association between target temperature and patient outcome. Design, Setting, and Participants: This cohort study compared outcomes for 1319 patients who were comatose after cardiac arrest at a single center in Pittsburgh, Pennsylvania, from January 2010 to December 2018. Initial illness severity was based on coma and organ failure scores, presence of severe cerebral edema, and presence of highly malignant electroencephalogram (EEG) after resuscitation. Exposure: TTM at 36 °C or 33 °C. Main Outcomes and Measures: Primary outcome was survival to hospital discharge, and secondary outcomes were modified Rankin Scale and cerebral performance category. Results: Among 1319 patients, 728 (55.2%) had TTM at 33 °C (451 [62.0%] men; median [interquartile range] age, 61 [50-72] years) and 591 (44.8%) had TTM at 36 °C (353 [59.7%] men; median [interquartile range] age, 59 [48-69] years). Overall, 184 of 187 patients (98.4%) with severe cerebral edema died and 234 of 243 patients (96.3%) with highly malignant EEG died regardless of TTM strategy. Comparing TTM at 33 °C with TTM at 36 °C in 911 patients (69.1%) with neither severe cerebral edema nor highly malignant EEG, survival was lower in patients with mild to moderate coma and no shock (risk difference, -13.8%; 95% CI, -24.4% to -3.2%) but higher in patients with mild to moderate coma and cardiopulmonary failure (risk difference, 21.8%; 95% CI, 5.4% to 38.2%) or with severe coma (risk difference, 9.7%; 95% CI, 4.0% to 15.3%). Interactions were similar for functional outcomes. Most deaths (633 of 968 [65.4%]) resulted after withdrawal of life-sustaining therapies. Conclusions and Relevance: In this study, TTM at 33 °C was associated with better survival than TTM at 36 °C among patients with the most severe post-cardiac arrest illness but without severe cerebral edema or malignant EEG. However, TTM at 36 °C was associated with better survival among patients with mild- to moderate-severity illness.

Differential association of subtypes of epileptiform activity with outcome after cardiac arrest.

BACKGROUND: Epileptiform activity is common after cardiac arrest, although intensity of electroencephalographic (EEG) monitoring may affect detection rates. Prior work has grouped these patterns together as "malignant," without considering discrete subtypes. We describe the incidence of distinct patterns in the ictal-interictal spectrum at two centers and their association with outcomes. METHODS: We analyzed a retrospective cohort of comatose post-arrest patients admitted at two academic centers from January 2011 to October 2014. One center uses routine continuous EEG, the other acquires "spot" EEG at the treating physicians' discretion. We reviewed all available EEG data and classified epileptiform patterns. We abstracted antiepileptic drugs (AEDs) administrations from the electronic medical record. We compared apparent incidence of each pattern between centers, and compared outcomes (awakening from coma, survival to discharge, discharge modified Rankin Scale (mRS) 0-2) across EEG patterns and number of AEDs administered. RESULTS: We included 818 patients. Routine continuous EEG was associated with a higher apparent incidence of polyspike burst-suppression (25% vs 13% P < 0.001). Frequency of other epileptiform findings did not differ. Among patients with any epileptiform pattern, only 2/258 (1%, 95%CI 0-3%) were discharged with mRS 0-2, although 24/258 (9%, 95%CI 6-14%) awakened and 36/258 (14%, 95%CI 10-19%) survived. The proportions that awakened and survived decreased in a stepwise manner with progressively worse EEG patterns (range 38% to 2% and 32% to 7%, respectively). Among patients receiving ≥3 AEDs, only 5/80 (6%, 95%CI 2-14%) awakened and 1/80 (1%, 95%CI 0-7%) had a mRS 0-2. CONCLUSION: We found high rates of epileptiform EEG findings, regardless of intensity of EEG monitoring. The association of distinct ictal-interictal EEG findings with outcome was variable.

Neurostimulant use is associated with improved survival in comatose patients after cardiac arrest regardless of electroencephalographic substrate.

AIM: Identify EEG patterns that predict or preclude favorable response in comatose post-arrest patients receiving neurostimulants. METHODS: We examined a retrospective cohort of consecutive electroencephalography (EEG)-monitored comatose post-arrest patients. We classified the last day of EEG recording before neurostimulant administration based on continuity (continuous/discontinuous), reactivity (yes/no) and malignant patterns (periodic discharges, suppression burst, myoclonic status epilepticus or seizures; yes/no). In subjects who did not receive neurostimulants, we examined the last 24h of available recording. For our primary analysis, we used logistic regression to identify EEG predictors of favorable response to treatment (awakening). RESULTS: In 585 subjects, mean (SD) age was 57 (17) years and 227 (39%) were female. Forty-seven patients (8%) received a neurostimulant. Neurostimulant administration independently predicted improved survival to hospital discharge in the overall cohort (adjusted odds ratio (aOR) 4.00, 95% CI 1.68-9.52) although functionally favorable survival did not differ. No EEG characteristic predicted favorable response to neurostimulants. In each subgroup of unfavorable EEG characteristics, neurostimulants were associated with increased survival to hospital discharge (discontinuous background: 44% vs 7%, P=0.004; non-reactive background: 56% vs 6%, P<0.001; malignant patterns: 63% vs 5%, P<0.001). CONCLUSION: EEG patterns described as ominous after cardiac arrest did not preclude survival or awakening after neurostimulant administration. These data are limited by their observational nature and potential for selection bias, but suggest that EEG patterns alone should not affect consideration of neurostimulant use.

Combination of initial neurologic examination, quantitative brain imaging and electroencephalography to predict outcome after cardiac arrest.

BACKGROUND: Prognosticating outcome following cardiac arrest is challenging and requires a multimodal approach. We tested the hypothesis that the combination of initial neurologic examination, quantitative analysis of head computed tomography (CT) and continuous EEG (cEEG) improve outcome prediction after cardiac arrest. METHODS: Review of consecutive patients receiving head CT within 24h and cEEG monitoring between April 2010 and May 2013. Initial neurologic examination (Full Outline of UnResponsiveness_Brainstem reflexes (FOUR_B) score and initial Pittsburgh Post-Cardiac Arrest Category (PCAC)), gray matter to white matter attenuation ratio (GWR) on head CT and cEEG patterns were evaluated. The primary outcome was in-hospital mortality. RESULTS: Of 240 subjects, 70 (29%) survived and 22 (9%) had a good neurologic outcome at hospital discharge. Combined determination of GW ratio and malignant cEEG had an incremental predictive value (AUC: 0.776 for mortality and 0.792 for poor neurologic outcome), with 0% false positive rate when compared with either test alone (AUC of GW ratio: 0.683 for mortality and 0.726 for poor outcome, AUC of malignant cEEG: 0.650 for mortality and 0.647 for poor outcome). Addition of FOUR_B or PCAC to this model improved prediction of mortality (p=0.014 for FOUR_B and 0.001 for PCAC) but not of poor outcome (p=0.786 for FOUR_B and 0.099 for PCAC). CONCLUSIONS: Combining GWR with cEEG was superior to any individual test for predicting mortality and neurologic outcome. Addition of clinical variables further improved prognostication for mortality but not neurologic outcome. These preliminary data support a multi-modal prognostic workup in this population.

Long-term survival benefit from treatment at a specialty center after cardiac arrest.

INTRODUCTION: The Institute of Medicine and American Heart Association have called for tiered accreditation standards and regionalization of post-cardiac arrest care, but there is little data to support that regionalization has a durable effect on patient outcomes. We tested the effect of treatment at a high-volume center on long-term outcome after sudden cardiac arrest (SCA). METHODS: We included patients hospitalized at one of 7 medical centers in Southwestern Pennsylvania after SCA from 2005 to 2013. Centers were one regional referral center with an organized systems for post-SCA care, two moderate volume tertiary care centers and 4 low-volume centers. We abstracted clinical characteristics and outcomes at hospital discharge, and for survivors to discharge we queried the National Death Index for long-term survival data. We used Cox regression to determine the unadjusted associations of baseline predictors and survival, and built an adjusted model controlling for baseline predictors. RESULTS: Overall, 987 patients survived to discharge. During 2196 person-years of follow-up, median survival was 5.3 years and there were 396 deaths. In unadjusted analysis, treating center, age, arrest location, Charlson Comorbidity Index, initial rhythm, cardiac catheterization, defibrillator placement, discharge disposition, and neurological status at discharge were associated with long-term outcome. In adjusted analysis, treatment at the high-volume cardiac arrest center was associated with improved survival compared to treatment at other centers (hazards ratio 1.49, 95% confidence interval 1.19-1.86). CONCLUSION: Treatment at a high-volume cardiac arrest center with organized systems for post-arrest care is associated with a substantial long-term survival benefit after hospital discharge.

Inflammatory markers following resuscitation from out-of-hospital cardiac arrest-A prospective multicenter observational study.

AIM: The post-cardiac arrest syndrome is a complex set of pathophysiological processes including a systemic inflammatory response. The goal of the current investigation was to test the hypothesis that early inflammatory markers are independently associated with in-hospital mortality and poor neurological outcome in patients initially resuscitated from out-of-hospital cardiac arrest. METHODS: This was a preplanned analysis of data collected from a prospective observational multicenter study in adult out-of-hospital cardiac arrest patients. Blood was drawn at baseline, 12 and 24h after return of spontaneous circulation and plasma levels of interleukin (IL)-1ß, IL-1 receptor antagonist (IL-1Ra), IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α were measured. The primary outcome measure was survival to hospital discharge. We utilized a mixed linear model to compare the levels of cytokines in survivors and non-survivors over time. We used multivariable logistic regression to assess the association between IL-6 levels and mortality. RESULTS: A total of 102 patients were analyzed. Non-survivors and patients with poor functional outcome had statistical significant higher IL-1Ra, IL-6, IL-8, and IL-10 levels (all p<0.001) at all time points (0, 12 and 24h) compared to survivors. Baseline IL-6 levels were a good predictor of mortality (AUC=0.83 [95%CI: 0.75-0.92]). Baseline IL-6 levels were strongly associated with mortality in multivariable analysis (OR: 2.58 [95%CI: 1.93-3.45], p<0.001) but were not associated with neurological outcome in multivariable analysis (OR: 1.33 [95%CI: 0.62-2.86], p=0.47). CONCLUSION: Early inflammatory markers, especially IL-6, are higher in patients with a poor outcome after OHCA. IL-6 remained associated with mortality, but not functional outcome, in multivariable analysis adjusting for patient and event characteristics.

Serum Neutrophil Gelatinase-Associated Lipocalin Predicts Survival After Resuscitation From Cardiac Arrest.

OBJECTIVES: In the first days after cardiac arrest, accurate prognostication is challenging. Serum biomarkers are a potentially attractive adjunct for prognostication and risk stratification. Our primary objective in this exploratory study was to identify novel early serum biomarkers that predict survival after cardiac arrest earlier than currently possible. DESIGN: Prospective, observational study. SETTING: A single academic medical center. SUBJECTS: Adult subjects who sustained cardiac arrest with return of spontaneous circulation. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We obtained blood samples from each subject at enrollment, 6, 12, 24, 48, and 72 hours after return of spontaneous circulation. We measured the serum levels of novel biomarkers, including neutrophil gelatinase-associated lipocalin, high-mobility group protein B1, intracellular cell adhesion molecule-1, and leptin, as well as previously characterized biomarkers, including neuron-specific enolase and S100B protein. Our primary outcome of interest was survival-to-hospital discharge. We compared biomarker concentrations at each time point between survivors and nonsurvivors and used logistic regression to test the unadjusted associations of baseline clinical characteristics and enrollment biomarker levels with survival. Finally, we constructed a series of adjusted models to explore the independent association of each enrollment biomarker level with survival. A total of 86 subjects were enrolled. Enrollment levels of high-mobility group protein B1, neutrophil gelatinase-associated lipocalin, and S100B were higher in nonsurvivors than survivors. Enrollment leptin, neuron-specific enolase, and intracellular cell adhesion molecule-1 levels did not differ between nonsurvivors and survivors. The discriminatory power of enrollment neutrophil gelatinase-associated lipocalin level was the greatest (c-statistic, 0.78 [95% CI, 0.66-0.90]) and remained stable across all time points. In our adjusted models, enrollment neutrophil gelatinase-associated lipocalin level was independently associated with survival even after controlling for the development of acute kidney injury, and its addition to clinical models improved overall predictive accuracy. CONCLUSIONS: Serum neutrophil gelatinase-associated lipocalin levels are strongly predictive of survival-to-hospital discharge after cardiac arrest.

Combination of initial neurologic examination and continuous EEG to predict survival after cardiac arrest.

BACKGROUND: Prognosticating outcome following cardiac arrest requires a multimodal approach. We tested whether the combination of initial neurologic examination combined with continuous EEG was superior to either test alone for predicting survival after cardiac arrest. METHODS: Review of consecutive patients receiving continuous EEG monitoring between April 2010 and June 2013. Initial neurologic examination was evaluated using the Full Outline of UnResponsiveness (FOUR) score and organ system dysfunction determined using the SOFA score. We defined four categories of initial post-cardiac arrest illness severity (PCAC): (I) awake, (II) coma (not following commands but intact brainstem responses) + mild cardiopulmonary dysfunction (SOFA cardiac + respiratory score < 4), (III) coma + moderate-severe cardiopulmonary dysfunction (SOFA cardiac + respiratory score ≥ 4), and (IV) coma without brainstem reflexes. A second analysis focusing on neurologic injury divided subjects into three groups according to initial FOUR_B score; FOUR_B = 0-1, FOUR_B = 2 and FOUR_B = 4. A blinded rater dichotomized continuous EEG patterns during the first 48h into malignant patterns (non-convulsive status epilepticus, convulsive status epilepticus, myoclonic status epilepticus and generalized periodic epileptiform discharges). The primary outcome was survival to hospital discharge. RESULTS: Of 331 subjects, mean age was 58 (SD 17) years and 206 (62.2%) subjects were male. Ventricular fibrillation or tachycardia (VF/VT) was the initial rhythm for 93 (28.1%) subjects. Among subjects with malignant cEEG, survival to hospital discharge rate was 0% for FOUR_B 0-1, 8.1% for FOUR_B 2 and 12.5% for FOUR_B 4, respectively. In one multivariate analysis, survival was independently associated with VF/VT, FOUR_B of 2, FOUR_B of 4, and non-malignant cEEG. In a separate model, survival was associated with VF/VT, PCAC < 4 and non-malignant cEEG. The AUCs of FOUR_B, cEEG and the combination of FOUR_B and cEEG are 0.740 (95% C.I. 0.684-0.797), 0.674 (95% C.I. 0.615-0.732) and 0.820 (95% C.I. 0.773-0.868) respectively. The AUCs of PCAC, cEEG and the combination of PCAC and cEEG are 0.779 (95% C.I. 0.721-0.838), 0.672 (95% C.I. 0.612-0.7321) and 0.846 (95% C.I. 0.798-0.894) respectively. CONCLUSION: Combining the initial neurologic examination using either FOUR_B or PCAC, with cEEG was superior to any individual test for predicting survival after cardiac arrest. We caution against using these findings to speed prognostication until they are externally validated.

Malignant EEG patterns in cardiac arrest patients treated with targeted temperature management who survive to hospital discharge.

BACKGROUND AND PURPOSE: Cardiac arrest patients treated with targeted temperature management (TTM) have improved neurological outcomes, however mortality remains high. EEG monitoring improves detection of malignant EEG patterns (MEPs), however their prevalence in patients surviving to hospital discharge is unknown. DESIGN/METHODS: We examined consecutive cardiac arrest subjects who received TTM and continuous EEG monitoring at one academic center. Only subjects surviving to hospital discharge were included in the analysis. MEPs were defined as seizures, status epilepticus, myoclonic status epilepticus, or generalized periodic discharges. Subjects with suppression-burst (SB) without concomitant MEPs were categorized as having a "pure" SB pattern. Demographic, survival, hospital discharge disposition, and neurological function data were recorded retrospectively. Outcomes were assessed using the Glasgow-Pittsburgh Cerebral Performance Category (CPC). A CPC score of 1-2 was considered "good" neurological function, and a CPC of 3-4 "poor". RESULTS: Of 364 admissions due to cardiac arrest screened, 120 (29.9%) survived to hospital discharge and met inclusion criteria. MEPs and pure SB were observed in 19 (15.8%) and 22 (18.3%) survivors respectively. Two subjects with MEP and eight subjects with pure SB had good neurological function at discharge, however all SB cases were confounded by the use of anesthetic agents. Presence of MEPs was not an independent predictor of poor neurological function (p=0.1). CONCLUSIONS: MEPs are common among cardiac arrest patients treated with induced hypothermia who survive to hospital discharge. Poor neurological function at discharge was not associated with MEPs. Prospective studies assessing the role of EEG monitoring in cardiac arrest prognostication are warranted.

Reintubation in critically ill patients: procedural complications and implications for care.

INTRODUCTION: In critically ill patients, re-intubation is common and may be a high-risk procedure. Anticipating a difficult airway and identifying high-risk patients can allow time for life-saving preparation. Unfortunately, prospective studies have not compared the difficulty or complication rates associated with reintubation in this population. METHODS: We performed a secondary analysis of a prospective registry of in-hospital emergency airway management, focusing on patients that underwent multiple out-of-operating room intubations during a single hospitalization. Our main outcomes of interest were technical difficulty of intubation (number of attempts, need for adjuncts to direct laryngoscopy, best Cormack-Lehane grade and training level of final intubator) and the frequency of procedural complications (aspiration, arrhythmia, airway trauma, new hypotension, new hypoxia, esophageal intubation and cardiac arrest). We compared the cohort of reintubated patients to a matched cohort of singly intubated patients and compared each repeatedly intubated patient's first and last intubation. RESULTS: Our registry included 1053 patients, of which 151 patients (14%) were repeatedly intubated (median two per patient). Complications were significantly more common during last intubation compared to first (13% versus 5%, P = 0.02). The most common complications were hypotension (41%) and hypoxia (35%). These occurred despite no difference in any measure of technical difficultly across intubations. CONCLUSION: In this cohort of reintubated patients, clinically important procedural complications were significantly more common on last intubation compared to first.

A comparative assessment of adverse event classification in the out-of-hospital setting.

OBJECTIVES: We sought to test reliability of two approaches to classify adverse events (AEs) associated with helicopter EMS (HEMS) transport. METHODS: The first approach for AE classification involved flight nurses and paramedics (RN/Medics) and mid-career emergency physicians (MC-EMPs) independently reviewing 50 randomly selected HEMS medical records. The second approach involved RN/Medics and MC-EMPs meeting as a group to openly discuss 20 additional medical records and reach consensus-based AE decision. We compared all AE decisions to a reference criterion based on the decision of three senior emergency physicians (Sr-EMPs). We designed a study to detect an improvement in agreement (reliability) from fair (kappa = 0.2) to moderate (kappa = 0.5). We calculated sensitivity, specificity, percent agreement, and positive and negative predictive values (PPV/NPV). RESULTS: For the independent reviews, the Sr-EMP group identified 26 AEs while individual clinician reviewers identified between 19 and 50 AEs. Agreement on the presence/absence of an AE between Sr-EMPs and three MC-EMPs ranged from κ = 0.20 to κ = 0.25. Agreement between Sr-EMPs and three RN/Medics ranged from κ = 0.11 to κ = 0.19. For the consensus/open-discussion approach, the Sr-EMPs identified 13 AEs, the MC-EMP group identified 18 AEs, and RN/medic group identified 36 AEs. Agreement between Sr-EMPs and MC-EMP group was (κ = 0.30 95%CI -0.12, 0.72), whereas agreement between Sr-EMPs and RN/medic group was (κ = 0.40 95%CI 0.01, 0.79). Agreement between all three groups was fair (κ = 0.33, 95%CI 0.06, 0.66). Percent agreement (58-68%) and NPV (63-76%) was moderately dissimilar between clinicians, while sensitivity (25-80%), specificity (43-97%), and PPV (48-83%) varied. CONCLUSIONS: We identified a higher level of agreement/reliability in AE decisions utilizing a consensus-based approach for review rather than independent reviews.

Measuring adverse events in helicopter emergency medical services: establishing content validity.

INTRODUCTION: We sought to create a valid framework for detecting adverse events (AEs) in the high-risk setting of helicopter emergency medical services (HEMS). METHODS: We assembled a panel of 10 expert clinicians (n = 6 emergency medicine physicians and n = 4 prehospital nurses and flight paramedics) affiliated with a large multistate HEMS organization in the Northeast US. We used a modified Delphi technique to develop a framework for detecting AEs associated with the treatment of critically ill or injured patients. We used a widely applied measure, the content validity index (CVI), to quantify the validity of the framework's content. RESULTS: The expert panel of 10 clinicians reached consensus on a common AE definition and four-step protocol/process for AE detection in HEMS. The consensus-based framework is composed of three main components: (1) a trigger tool, (2) a method for rating proximal cause, and (3) a method for rating AE severity. The CVI findings isolate components of the framework considered content valid. CONCLUSIONS: We demonstrate a standardized process for the development of a content-valid framework for AE detection. The framework is a model for the development of a method for AE identification in other settings, including ground-based EMS.

Identification of adverse events in ground transport emergency medical services.

The purpose of this study was to develop a method to define and rate the severity of adverse events (AEs) in emergency medical services (EMS) safety research. They used a modified Delphi technique to develop a consensus definition of an AE. The consensus definition was as follows: "An adverse event in EMS is a harmful or potentially harmful event occurring during the continuum of EMS care that is potentially preventable and thus independent of the progression of the patient's condition." Physicians reviewed 250 charts from 3 EMS agencies for AEs. The authors examined physician agreement using κ, Fleiss's κ, and corresponding 95% confidence intervals (CIs). Overall physician agreement on presence of an AE per chart was fair (κ = 0.24; 95% CI = 0.19, 0.29). These findings should serve as a basis for refining and implementing an AE evaluation instrument.

Hypothermia after cardiac arrest does not alter serum inflammatory markers.

OBJECTIVE: Hypothermia improves survival and neurologic recovery after cardiac arrest. Cardiac arrest also triggers release of cytokines and inflammatory molecules, and it is unknown whether therapeutic hypothermia alters this inflammatory response. This study tested whether therapeutic hypothermia altered levels of inflammatory markers in serum. DESIGN: Prospective, randomized study. SETTING: University research laboratory. SUBJECTS: Adult, male, Sprague-Dawley rats. INTERVENTIONS: Halothane-anesthetized rats were subjected to 8 mins of asphyxial cardiac arrest and resuscitation. Rat temperature was controlled at 37 degrees C throughout the experiment (normothermia) or reduced to 33 degrees C between 1 and 24 hrs after cardiac arrest (hypothermia). Serum cytokines were measured at baseline, 0.5, 1, 3, 6, 12, and 24 hrs after resuscitation using multiplex analyzer or enzyme-linked immunosorbent assay. MEASUREMENTS AND MAIN RESULTS: Hypothermic rats showed improved neurologic recovery at 12 and 24 hrs. Serum levels of tumor necrosis factor-alpha; macrophage inflammatory protein-1alpha; growth-related oncogene/keratinocyte chemokine; interleukin-2, -9, and -10; monocyte chemotactic protein-1; leptin; and intracellular adhesion molecule-1 increased over time, and the levels of interleukin-18 declined over time. No temporal trends in other molecules were detected. Levels of these molecules did not differ between temperature groups during the hypothermia phase (1-24 hrs). CONCLUSIONS: These data suggest that altering the inflammatory response after cardiac arrest is not necessary for the beneficial effects of hypothermia. These data do not support a specific role of circulating cytokines in the neurologic injury after cardiac arrest.

The effect of adenosine A1 receptor antagonism on return of spontaneous circulation and short-term survival in prolonged ventricular fibrillation.

BACKGROUND: Endogenous adenosine (ADO) is cardioprotective during ischemia and its myocardial concentration increases during untreated ventricular fibrillation (VF). We have previously shown that ADO A1 receptor (ADOA1R) antagonism hastens the time-dependent decay in VF waveform morphology during the circulatory phase of cardiac arrest. OBJECTIVE: To determine the effect of ADOA1R antagonism on ROSC and short-term survival in prolonged VF. METHODS: Thirty-six swine were assigned by block randomization to one of three groups: a group that received only vehicle (CONTROL), an ADOA1R antagonist pretreatment group (PRE), and a group that was given ADOA1R antagonist during resuscitation (DURING). The animals were instrumented under anesthesia, and ADOA1R antagonist or vehicle, per group assignment, was infused 5 minutes prior to VF induction. At minute 8 of untreated VF, chest compression with ventilation was initiated and a standard drug cocktail, with ADOA1R antagonist or vehicle, was given. The first rescue shock (150 J biphasic) was delivered after 11 minutes of VF. Proportions with 95% confidence intervals (CIs) were calculated for the two outcome measures. RESULTS: The baseline characteristics and chemistry values for the three groups were mathematically the same. The DURING group had a greater proportion of female animals (seven of 12) in comparison with the CONTROL group (two of 12) (p=0.03). ADOA1R antagonism hastened the decay of VF as previously demonstrated, but the rate of ROSC was the same for all groups: CONTROL=seven of 12, PRE=six of 12, and DURING=seven of 12. There were also no differences in short-term survival: CONTROL=four of 12, PRE=five of 12, and DURING=seven of 12. CONCLUSIONS: In this study, ADOA1R antagonism had no effect on outcome whether given before induction of VF or upon resuscitation after 8 minutes of untreated VF. The role of endogenous ADO in prolonged VF remains unclear.

Errors of omission in the treatment of prehospital chest pain patients.

OBJECTIVE: Despite the widespread use of standard treatment protocols, there are few published data regarding paramedic protocol adherence. In this descriptive study, the authors sought to assess the frequency and nature of deviations from a standardized treatment protocol for the chief complaint of chest pain. They also sought to quantify any time delays in treatment of potential ischemic cardiac chest pain. METHODS: A retrospective review of written documentation obtained from four ambulance services in a mid-Atlantic state was completed. A convenience sample of consecutive emergency medical services (EMS) records was obtained from January 2001 to May 2002, and 75 calls were selected from each service (N = 300). RESULTS: Neither the median scene times nor the response times varied among the four services in the study. However, the suburban ambulance service (service 1) did have a significantly longer transport time (19 minutes) than the rural (14 minutes) and the urban (11 and 10 minutes) services (p < 0.05). Documentation of history and physical characteristics varied widely for each service. The patient took aspirin 10% of the time prior to EMS arrival, yet paramedics gave it additionally 50% of the time, while nitroglycerin was given in 73% of cases of suspected cardiac ischemia. Posttreatment vital signs for nitroglycerin were documented 30% of the time for three of the four services, while the other service documented these 75% of the time. Medical command contact varied by agency (80-100%), as did the receipt and completion of medical orders. CONCLUSIONS: Paramedics may delay transport of patients with potential cardiac ischemia. Deviations from protocol occur frequently and the care documented for prehospital patients with chest pain is variable. The expected care described by written protocols does not correlate with the treatment documented.