Non-shockable rhythms: A parametric model for the immediate probability of return of spontaneous circulation.

BACKGROUND: Cardiac arrest can present with asystole, Pulseless Electrical Activity (PEA), or Ventricular Fibrillation/Tachycardia (VF/VT). We investigated the transition intensity of Return of spontaneous circulation (ROSC) from PEA and asystole during in-hospital resuscitation. MATERIALS AND METHODS: We included 770 episodes of cardiac arrest. PEA was defined as ECG with >12 QRS complexes per min, asystole by an isoelectric signal >5 seconds. The observed times of PEA to ROSC transitions were fitted to five different parametric time-to-event models. At values ≤0.1, transition intensities roughly represent next-minute probabilities allowing for direct interpretation. Different entities of PEA and asystole, dependent on whether it was the primary or a secondary rhythm, were included as covariates. RESULTS: The transition intensities to ROSC from primary PEA and PEA after asystole were unimodal with peaks of 0.12 at 3 min and 0.09 at 6 min, respectively. Transition intensities to ROSC from PEA after VF/VT, or following transient ROSC, exhibited high initial values of 0.32 and 0.26 at 3 minutes, respectively, but decreased. The transition intensity to ROSC from initial asystole and asystole after PEA were both about 0.01 and 0.02; while asystole after VF/VT had an intensity to ROSC of 0.15 initially which decreased. The transition intensity from asystole after temporary ROSC was constant at 0.08. CONCLUSION: The immediate probability of ROSC develops differently in PEA and asystole depending on the preceding rhythm and the duration of the resuscitation attempt. This knowledge may aid simple bedside prognostication and electronic resuscitation algorithms for monitors/defibrillators.

Characteristics of circulatory failure after out-of-hospital cardiac arrest: a prospective cohort study.

BACKGROUND: Circulatory failure after out-of-hospital cardiac arrest (OHCA) as part of the postcardiac arrest syndrome (PCAS) is believed to be caused by an initial myocardial depression that later subsides into a superimposed vasodilatation. However, the relative contribution of myocardial dysfunction and systemic inflammation has not been established. Our objective was to describe the macrocirculatory and microcirculatory failure in PCAS in more detail. METHODS: We included 42 comatose patients after OHCA where circulatory variables were invasively monitored from admission until day 5. We measured the development in cardiac power output (CPO), stroke work (SW), aortic elastance, microcirculatory metabolism, inflammatory and cardiac biomarkers and need for vasoactive medications. We used survival analysis and Cox regression to assess time to norepinephrine discontinuation and negative fluid balance, stratified by inflammatory and cardiac biomarkers. RESULTS: CPO, SW and oxygen delivery increased during the first 48 hours. Although the estimated afterload fell, the blood pressure was kept above 65 mmHg with a diminishing need for norepinephrine, indicating a gradually re-established macrocirculatory homoeostasis. Time to norepinephrine discontinuation was longer for patients with higher pro-brain natriuretic peptide concentration (HR 0.45, 95% CI 0.21 to 0.96), while inflammatory biomarkers and other cardiac biomarkers did not predict the duration of vasoactive pressure support. Markers of microcirculatory distress, such as lactate and venous-to-arterial carbon dioxide difference, were normalised within 24 hours. CONCLUSION: The circulatory failure was initially characterised by reduced CPO and SW, however, microcirculatory and macrocirculatory homoeostasis was restored within 48 hours. We found that biomarkers indicating acute heart failure, and not inflammation, predicted longer circulatory support with norepinephrine. Taken together, this indicates an early and resolving, rather than a late and emerging vasodilatation. TRIAL REGISTRATION: NCT02648061.

The inflammatory response is related to circulatory failure after out-of-hospital cardiac arrest: A prospective cohort study.

BACKGROUND: Whole body ischemia and reperfusion injury after cardiac arrest leads to the massive inflammation clinically manifested in the post-cardiac arrest syndrome. Previous studies on the inflammatory effect on circulatory failure after cardiac arrest have either investigated a selected patient group or a limited part of the inflammatory mechanisms. We examined the association between cardiac arrest characteristics and inflammatory biomarkers, and between inflammatory biomarkers and circulatory failure after cardiac arrest, in an unselected patient cohort. METHODS: This was a prospective study of 50 consecutive patients with out-of-hospital cardiac arrest. Circulation was invasively monitored from admission until day five, whereas inflammatory biomarkers, i.e. complement activation, cytokines and endothelial injury, were measured daily. We identified predictors for an increased inflammatory response, and associations between the inflammatory response and circulatory failure. RESULTS: We found a marked and broad inflammatory response in patients after cardiac arrest, which was associated with clinical outcome. Long time to return of spontaneous circulation and high lactate level at admission were associated with increased complement activation (TCC and C3bc), pro-inflammatory cytokines (IL-6, IL-8) and endothelial injury (syndecan-1) at admission. These biomarkers were in turn significantly associated with lower mean arterial blood pressure, lower cardiac output and lower systemic vascular resistance, and increased need of circulatory support in the initial phase. High levels of TCC and IL-6 at admission were significantly associated with increased 30-days mortality. CONCLUSION: Inflammatory biomarkers, including complement activation, cytokines and endothelial injury, were associated with increased circulatory failure in the initial period after cardiac arrest.

Circulatory trajectories after out-of-hospital cardiac arrest: a prospective cohort study.

BACKGROUND: Circulatory failure frequently occurs after out-of-hospital cardiac arrest (OHCA) and is part of post-cardiac arrest syndrome (PCAS). The aim of this study was to investigate circulatory disturbances in PCAS by assessing the circulatory trajectory during treatment in the intensive care unit (ICU). METHODS: This was a prospective single-center observational cohort study of patients after OHCA. Circulation was continuously and invasively monitored from the time of admission through the following five days. Every hour, patients were classified into one of three predefined circulatory states, yielding a longitudinal sequence of states for each patient. We used sequence analysis to describe the overall circulatory development and to identify clusters of patients with similar circulatory trajectories. We used ordered logistic regression to identify predictors for cluster membership. RESULTS: Among 71 patients admitted to the ICU after OHCA during the study period, 50 were included in the study. The overall circulatory development after OHCA was two-phased. Low cardiac output (CO) and high systemic vascular resistance (SVR) characterized the initial phase, whereas high CO and low SVR characterized the later phase. Most patients were stabilized with respect to circulatory state within 72 h after cardiac arrest. We identified four clusters of circulatory trajectories. Initial shockable cardiac rhythm was associated with a favorable circulatory trajectory, whereas low base excess at admission was associated with an unfavorable circulatory trajectory. CONCLUSION: Circulatory failure after OHCA exhibits time-dependent characteristics. We identified four distinct circulatory trajectories and their characteristics. These findings may guide clinical support for circulatory failure after OHCA. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02648061.

ECG changes during resuscitation of patients with initial pulseless electrical activity are associated with return of spontaneous circulation.

BACKGROUND: Pulseless electrical activity (PEA) is a frequent initial rhythm in cardiac arrest, and ECG characteristics have been linked to prognosis. The aim of this study was to examine the development of ECG characteristics during advanced life support (ALS) and cardiopulmonary resuscitation (CPR) in cardiac arrest with initial PEA, and to assess any association with survival. METHODS: Patients with in-hospital cardiac arrest with initial PEA at St. Olav Hospital (Trondheim, Norway) over a three-year period were included. A total of 2187 combined observations of QRS complex rate (heart rate) and QRS complex width for the duration of ALS were determined from defibrillator recordings from 74 episodes of cardiac arrest. RESULTS: Increasing heart rate and decreasing QRS complex width during ALS was significantly more prevalent in patients who obtained return of spontaneous circulation compared to patients who were declared dead. CONCLUSION: Changes in ECG characteristics during ALS in cardiac arrest presenting as PEA are related to prognosis. An increase in heart rate was observed in the last 3-6 min before ROSC was obtained.

Transitions Between Circulatory States After Out-of-Hospital Cardiac Arrest: Protocol for an Observational, Prospective Cohort Study.

BACKGROUND: The post cardiac arrest syndrome (PCAS) is responsible for the majority of in-hospital deaths following cardiac arrest (CA). The major elements of PCAS are anoxic brain injury and circulatory failure. OBJECTIVE: This study aimed to investigate the clinical characteristics of circulatory failure and inflammatory responses after out-of-hospital cardiac arrest (OHCA) and to identify patterns of circulatory and inflammatory responses, which may predict circulatory deterioration in PCAS. METHODS: This study is a single-center cohort study of 50 patients who receive intensive care after OHCA. The patients are followed for 5 days where detailed information from circulatory variables, including measurements by pulmonary artery catheters (PACs), is obtained in high resolution. Blood samples for inflammatory and endothelial biomarkers are taken at inclusion and thereafter daily. Every 10 min, the patients will be assessed and categorized in one of three circulatory categories. These categories are based on mean arterial pressure; heart rate; serum lactate concentrations; superior vena cava oxygen saturation; and need for fluid, vasoactive medications, and other interventions. We will analyze predictors of circulatory failure and their relation to inflammatory biomarkers. RESULTS: Patient inclusion started in January 2016. CONCLUSIONS: This study will obtain advanced hemodynamic data with high resolution during the acute phase of PCAS and will analyze the details in circulatory state transitions related to circulatory failure. We aim to identify early predictors of circulatory deterioration and favorable outcome after CA. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02648061; https://clinicaltrials.gov/ct2/show/NCT02648061 (Archived by WebCite at http://www.webcitation.org/6wVASuOla).

ECG patterns in early pulseless electrical activity-Associations with aetiology and survival of in-hospital cardiac arrest.

INTRODUCTION: Pulseless electrical activity (PEA) is an increasingly common presentation in cardiac arrest. The aim of this study was to investigate possible associations between early ECG patterns in PEA and the underlying causes and survival of in-hospital cardiac arrest (IHCA). METHODS: Prospectively observed episodes of IHCA presenting as PEA between January 2009 and august 2013, with a reliable cause of arrest and corresponding defibrillator ECG recordings, were analysed. QRS width, QT interval, Bazett's corrected QT interval, presence of P waves and heart rate (HR) was determined. QRS width and HR were considered to be normal below 120ms and within 60-100 cardiac cycles per minute, respectively. RESULTS: Fifty-one episodes fulfilled the inclusion criteria. The defibrillator was attached after a median of one minute (75th percentile; 3min) after the onset of arrest. Ninety percent (46/51) had widened QRS complexes, 63% (32/51) were defined as 'wide-slow' due to QRS-widened bradycardia, and only 6% (3/51) episodes were categorized as normal. No unique cause-specific ECG pattern could be identified. Further 7 episodes with a corresponding defibrillator file, but without a reliable cause, were included in analysis of survival. Abnormal ECG patterns were seen in all survivors. None of the patients with 'normal' PEA survived. CONCLUSION: Abnormal ECG patterns were frequent at the early stage of in-hospital PEA. No unique patterns were associated with the underlying causes or survival.

Recognizing the causes of in-hospital cardiac arrest--A survival benefit.

BACKGROUND: The in-hospital emergency team (ET) may or may not recognize the causes of in-hospital cardiac arrest (IHCA) during the provision of cardiopulmonary resuscitation (CPR). In a previous 4.5-year prospective study, this rate of recognition was found to be 66%. The aim of this study was to investigate whether survival improved if the cause of arrest was recognized by the ET. METHODS: The difference in survival if the causes were recognized versus not recognized was estimated after propensity score matching patients from these two groups. RESULTS: Overall survival to hospital discharge was 25%. After propensity score matching, the benefit of recognizing the cause regarding 1-hour survival of the episode was 29% (p<0.01), and 19% regarding hospital discharge, respectively. Variables commonly known to affect the outcome after cardiac arrest were found to be balanced between the two groups. The largest difference was found in patients with non-cardiac causes and non-shockable presenting rhythms. Patient records and pre-arrest clinical symptoms were the information sources most frequently utilized by the ET to establish the causes of arrest. CONCLUSIONS: Patients suffering an IHCA showed a substantial survival benefit if the causes of arrest were recognized by the ET. Patient records and pre-arrest clinical symptoms were the sources of information most frequently utilized in these instances.

Causes of in-hospital cardiac arrest - incidences and rate of recognition.

BACKGROUND AND METHODS: Do emergency teams (ETs) consider the underlying causes of in-hospital cardiac arrest (IHCA) during advanced life support (ALS)? In a 4.5-year prospective observational study, an aetiology study group examined 302 episodes of IHCA. The purpose was to investigate the causes and cause-related survival and to evaluate whether these causes were recognised by the ETs. RESULTS: In 258 (85%) episodes, the cause of IHCA was reliably determined. The cause was correctly recognised by the ET in 198 of 302 episodes (66%). In the majority of episodes, cardiac causes (156, 60%) or hypoxic causes (51, 20%) were present. The cause-related survival was 30% for cardiac aetiology and 37% for hypoxic aetiology. The initial cardiac rhythm was pulseless electrical activity (PEA) in 144 episodes (48%) followed by asystole in 70 episodes (23%) and combined ventricular fibrillation/ventricular tachycardia (VF/VT) in 83 episodes (27%). Seventy-one patients (25%) survived to hospital discharge. The median delay to cardiopulmonary resuscitation (CPR) was 1min (inter-quartile range 0-1min). CONCLUSIONS: Various cardiac and hypoxic aetiologies dominated. In two-thirds of IHCA episodes, the underlying cause was correctly identified by the ET, i.e. according to the findings of the aetiology study group.

Optimal loop duration during the provision of in-hospital advanced life support (ALS) to patients with an initial non-shockable rhythm.

BACKGROUND: In advanced life support (ALS), time-cycled "loops" of chest compressions form the basis of action. However, the provider must compromise between interrupting compressions and detecting a change in cardiac rhythm. An "optimal" loop duration would best balance these choices. The current international CPR guidelines recommend 2-min loop durations. The aim of this study was to investigate the "optimal" loop duration in patients with initial asystole or pulseless electrical activity (PEA). MATERIALS AND METHODS: Detailed defibrillator recordings from 249 in-hospital cardiac arrests at the University of Chicago Medicine (Chicago, IL) and St. Olav University Hospital (Trondheim, Norway) were analysed. The clinical states of asystole, PEA, ventricular fibrillation/-tachycardia (VF/VT) and return of spontaneous circulation (ROSC) were annotated along the time axis. PEA and asystole were combined as a single state for the analysis of state development. The probability of staying in PEA/asystole over time was estimated non-parametrically. In addition, to distinguish between initial and secondary PEA/asystole, the latter was defined by the transition from VF/VT or ROSC. RESULTS: Among patients with initial PEA (n=179), 25% and 50% of patients had left PEA/asystole after 4 and 9 min of ALS efforts, respectively. The corresponding time points for patients with initial asystole (n=70) were 7.3 and 13.3 min, respectively. The probability of transition from secondary PEA/asystole to ROSC or VF/VT varied between 10% and 20% in each 2-4 min interval. CONCLUSION: The "optimal" first loop duration may be 4 min in initial PEA and 6-8 min in initial asystole. If secondary PEA/asystole is encountered, 2-min loop duration seems appropriate.

Clinical state transitions during advanced life support (ALS) in in-hospital cardiac arrest.

BACKGROUND: When providing advanced life support (ALS) in cardiac arrest, the patient may alternate between four clinical states: ventricular fibrillation/tachycardia (VF/VT), pulseless electrical activity (PEA), asystole, and return of spontaneous circulation (ROSC). At the end of the resuscitation efforts, either death has been declared or sustained ROSC has been obtained. The aim of this study was to describe and analyze the clinical state transitions during ALS among patients experiencing in-hospital cardiac arrest. METHODS AND RESULTS: The defibrillator files from 311 in-hospital cardiac arrests at the University of Chicago Hospital (IL, USA) and St. Olav University Hospital (Trondheim, Norway) were analyzed (clinicaltrials.gov: NCT00920244). The transitions between clinical states were annotated along the time axis and visualized as plots of the state prevalence according to time. The cumulative intensity of the state transitions was estimated by the Nelson-Aalen estimator for each type of state transition, and for the intensities of overall state transitions. Between 70% and 90% of patients who eventually obtained sustained ROSC had progressed to ROSC by approximately 15-20 min of ALS, depending on the initial rhythm. Patients behaving unstably after this time period, i.e., alternating between ROSC, VF/VT and PEA, had a high risk of ultimately being declared dead. CONCLUSIONS: We provide an overall picture of the intensities and patterns of clinical state transitions during in-hospital ALS. The majority of patients who obtained sustained ROSC obtained this state and stabilized within the first 15-20 min of ALS. Those who continued to behave unstably after this time point had a high risk of ultimately being declared dead.