Lawrence D. Sherman

Scaling Exponent Predicts Defibrillation Success for Out-of-Hospital Ventricular Fibrillation Cardiac Arrest

BackgroundDefibrillator shocks often fail to terminate ventricular fibrillation (VF) in out-of-hospital cardiac arrest (OOHCA), and repeated failed shocks can worsen the subsequent response to therapy. Because the VF waveform changes with increasing duration of VF, it is possible that ECG analyses could estimate the preshock likelihood of defibrillation success. This study examined whether an amplitude-independent measure of preshock VF waveform morphology predicts outcome after defibrillation. Methods and ResultsClinical data and ECG recordings from an automated external defibrillator were obtained for 75 subjects with OOHCA in a suburban community with police first responders and a paramedic-based emergency medical system. An estimate of the fractal self-similarity dimension, the scaling exponent, was calculated off-line for the VF waveform preceding shocks. Success of the first shock was determined from the recordings. Return of pulses and survival were determined by chart review. The first shock resulted in an organized rhythm in 43% of cases, and 17% of cases survived to hospital discharge. A lower mean value of the scaling exponent was observed for cases in which the first defibrillation resulted in an organized rhythm (P =0.004), for cases with return of pulses (P =0.049), and for cases surviving to hospital discharge (P <0.001). Receiver operator curves revealed the utility of the scaling exponent for predicting the probability of restoring an organized rhythm (area under the curve=0.70) and of survival (area under the curve=0.84). ConclusionsThe VF waveform in OOHCA can be quantified with the scaling exponent, which predicts the probability of first-shock defibrillation and survival to hospital discharge.

Ventricular fibrillation scaling exponent can guide timing of defibrillation and other therapies.

Background—The scaling exponent (ScE) of the ventricular fibrillation (VF) waveform correlates with duration of VF and predicts defibrillation outcome. We compared 4 therapeutic approaches to the treatment of VF of various durations. Methods and Results—Seventy-two swine (19.5 to 25.7 kg) were randomly assigned to 1 of 9 groups (n=8 each). VF was induced and left untreated until the ScE reached 1.10, 1.20, 1.30, or 1.40. Animals were treated with either immediate countershock (IC); 3 minutes of CPR before the first countershock (CPR); CPR for 2 minutes, then drugs given with 3 more minutes of CPR before the first shock (CPR-D); or drugs given at the start of CPR with 3 minutes of CPR before the first shock (Drugs+CPR). Return of spontaneous circulation (ROSC) and 1-hour survival were analyzed with &khgr;2 and Kaplan-Meier survival curves. IC was effective when the ScE was low but had decreasing success as the ScE increased. No animals in the 1.30 or 1.40 groups had ROSC from IC (0 of 16). CPR did not improve first shock outcome in the 1.20 CPR group (3 of 8 ROSC). Kaplan-Meier survival analyses indicated that IC significantly delayed time to ROSC in both the 1.3 (P =0.0006) and the 1.4 (P =0.005) groups. Conclusions—VF of brief to moderate duration is effectively treated by IC. When VF is prolonged, as indicated by an ScE of 1.3 or greater, IC was not effective and delayed time to ROSC. The ScE can help in choosing the first intervention in the treatment of VF.

Ventricular fibrillation exhibits dynamical properties and self-similarity.

Electrocardiographic recordings of ventricular fibrillation (VF) appear chaotic. Previous attempts to characterize the chaotic nature of VF have relied on peak-to-peak intervals [Witkowski et al., Phys. Rev. Lett. 1995;75(6):1230-3; Garfinkel et al., J. Clin. Investig. 1997;99(2):305-314; Hastings et al., Proc. Natl. Acad. Sci. USA 1996;93:10495-9], the frequency spectrum [Goldberger et al., 1986;19:282-289] or other derived measures [Kaplan and Cohen, Circ. Res. 1990;67:886-92], with results that demonstrate some characteristics of chaos. We have sought to determine whether VF is chaotic rather than random and whether the waveform can be described quantitatively using the tools of fractal geometry. We have constructed an attractor, measured the correlation dimensions, estimated the embedding dimension and measured Lyapunov exponents. When the digitized waveform is analyzed directly, VF exhibits nonrandom, chaotic behavior over a decade of sampling frequency. Within the scaling range we have estimated the Hurst exponent, and the self-similarity dimension of the VF waveform, supporting the presence of chaotic dynamics. Furthermore, these characteristics are measurable in a porcine model of VF under different recording conditions, and in VF recordings taken from human subjects immediately prior to defibrillation. Analyses of the Hurst exponents and self-similarity dimensions are correlated with the duration of VF, which may have clinical applications.

Immediate defibrillation versus interventions first in a swine model of prolonged ventricular fibrillation

OBJECTIVES we compared time-dependent rescue shock success when delivered immediately, to defibrillation preceded by 3 min of CPR, with and without high dose epinephrine (HDE) in a swine model of prolonged ventricular fibrillation (VF). Our hypotheses were that pretreatment with CPR and HDE would produce higher rates of successful first-shock defibrillation and would prevent decay of the VF waveform, as measured by the scaling exponent (ScE), when compared to immediate defibrillation. We also sought to determine the predictive value of the ScE in determining post-shock outcomes. METHODS we anesthetized and instrumented 60 domestic swine (19.6-26.4 kg). VF was induced electrically and was untreated for 8, 11 or 14 min. ECG was recorded digitally at a rate of 1000 samples/s with 5-s epochs used to calculate the ScE. We assigned randomly swine to seven groups (number denotes timing of first rescue shock). Three groups had rescue shocks as the first intervention (RSF) after 8 min of VF (RSF-8), 11 min of VF (RSF-11), or 14 min of VF (RSF-14): two groups had CPR for 3 min (then rescue shock) beginning at 8 min (CPR-11) or 11 min of VF (CPR-14); and two groups got CPR for 3 min with 0.1 mg/kg epinephrine (adrenaline) (then rescue shock) beginning at 8 min of VF (HDE-11) or 11 min of VF (HDE-14). Fixed-dose 70 J BDW rescue shocks were used for all shocks. Defibrillation outcome was classified immediately and 30 s post-shock as successful (either restoration of spontaneous circulation [ROSC] or restoration of organized electrical activity [ROEA]), or failed (remained in VF, or asystole). Data were analyzed with RMANOVA, multiple logistic regression, Fishers exact tests, and ROC curves. RESULTS successful first-shock defibrillation occurred in 3/8 (38%) RSF-8; 1/9 (11%) RSF-11; 2/9 (22%) CPR-11; 7/9 (77%) HDE-11; 0/9 (0%) RSF-14; 0/7 (0%) CPR-14; and 1/8 (13%) HDE-14, (p=0.059 IRS-8 vs. HDE-11). First-shock ROSC occurred in 5/9 (56%) HDE-11 animals, 1/8 (13%) HDE-14 and zero in all other groups (p=0.03). Mean ScE values at 11 min VF for the RSF-11 (1.46) was higher than both CPR-11 (1.26), and HDE-11 (1.27); and RSF-14 (1.60) was higher than CPR-14 (1.47) and HDE-14 (1.46); group by time p=0.002. ROC areas under the curves using the ScE as a predictor of shock outcome were 0.84 for immediate success, 0.85 for sustained success, and 0.81 for ROSC. CONCLUSIONS HDE-11 showed a tendency for producing a higher rate of first-shock success and ROSC. Interventions prior to rescue shock prevented deterioration of the VF waveform and improved rescue shock outcomes. The ScE accurately predicted 81-85% of post-rescue shock outcomes.

Scaling Structure of Electrocardiographic Waveform During Prolonged Ventricular Fibrillation in Swine

Ventricular fibrillation (VF) is the most common arrhythmia causing sudden cardiac death. However, the likelihood of successful defibrillation declines with increasing duration of VF. Because the morphology of the electrocardiogram (ECG) waveform during VF also changes with time, this study examined a new measure that describes the VF waveform and distinguishes between early and late VF. Surface ECG recordings were digitized at 200 samples/s from nine swine with induced VF. A new measure called the scaling exponent was calculated by examining the power‐law relationship between the summation of amplitudes of a 1,024‐point (5.12 second) waveform segment and the time scale of measurement. The scaling exponent is a local estimate of the fractal dimension of the ECG waveform. A consistent power‐law relationship was observed for measurement time scales of 0.005–0.040 seconds. Calculation of the scaling exponent produced similar results between subjects, and distinguished early VF (<4‐minute duration) from late VF (≥4‐minute duration). The scaling exponent was dependent on the order of the data, supporting the hypothesis that the surface ECG during VF is a deterministic rather than a random signal. The waveform of VF results from the interaction of multiple fronts of depolarization within the heart, and may be described using the tools of nonlinear dynamics. As a quantitative descriptor of waveform structure, the scaling exponent characterizes the time dependent organization of VF.

Association of intramyocardial high energy phosphate concentrations with quantitative measures of the ventricular fibrillation electrocardiogram waveform

BACKGROUND Quantitative measures of the ventricular fibrillation (VF) electrocardiogram (ECG) have been correlated with the success of rescue shocks, making them ideal measures for guiding resuscitative interventions. Correlation of intramyocardial energy stores with the change in quantitative VF ECG measures would provide mechanistic insight into their utility. We sought to investigate the relationship between intramyocardial energy stores and four quantitative ECG measures. METHODS Eighteen mixed-breed, domestic swine were sedated, anaesthetized and paralyzed. Swine were block randomized into three groups receiving 5, 10, or 15 min of untreated VF. Thoracotomy was performed and the heart was delivered. VF was induced by a 100 mA transthoracic shock while ECG was recorded. Biopsies of myocardial tissue were taken from the left and right ventricles after the prescribed duration of VF. Adenosine triphosphate (ATP) and adenosine diphosphate (ADP) concentrations in the tissue samples were measured. ECG data immediately prior to each biopsy were analyzed by each of four quantitative ECG methods: Scaling Exponent (ScE), Median Slope (MS), Amplitude Spectrum Area (AMSA), and logarithm of the Absolute Correlation (LAC). ATP and ADP concentrations of VF duration groups were compared. ATP and ADP concentrations were regressed against each quantitative ECG measure. RESULTS ATP concentrations differed between VF duration groups, but ADP concentrations differed only between 5 and 10 min groups. A significant association existed between ATP and three quantitative measures--ScE, MS, and AMSA--but no significant relationship was found for ADP. CONCLUSION Intramyocardial ATP levels correlate with quantitative measures of the ECG during ventricular fibrillation.

Effects of pre-arrest and intra-arrest hypothermia on ventricular fibrillation and resuscitation

BACKGROUND Hypothermia has been shown to improve survival and neurological outcomes for ventricular fibrillation (VF) cardiac arrest. The electrophysiological mechanisms of hypothermia are not well-understood, nor are the effects of beginning cooling during the resuscitation. METHODS AND RESULTS We hypothesized that inducing hypothermia prior to the onset of VF would slow the deleterious changes seen in the ECG during VF and that inducing hypothermia at the start of resuscitation would increase the rates of ROSC and short-term survival in a porcine model of prolonged VF. We randomly assigned 42 domestic swine (27.2+/-2.3 kg) to either pretreatment with hypothermia before induction of VF (PRE), normothermic resuscitation (NORM) or intra-resuscitation hypothermia (IRH). During anesthesia, animals were instrumented via femoral cutdown. Lead II ECG was recorded continuously. PRE animals were cooled before the induction of VF, with a rapid infusion of 4 degrees normal saline (30mL/kg). VF was induced electrically, left untreated for 8min, then mechanical CPR began. During CPR the NORM animals got 30mL/kg body-temperature saline and the IRH animals got 30mL/kg 4 degrees saline. In all groups first rescue shocks were delivered after 13min of VF. We calculated the VF scaling exponent (ScE) for the entire 8min period (compared using GEE). ROSC and survival were compared with Fishers exact test. Mean temperature in degrees C at the onset of VF was PRE=34.7 degrees (+/-0.8), NORM=37.8 (+/-0.9), and IRH=37.9 (+/-0.9). The ScE values over time were significantly lower after 8min in the PRE group (p=0.02). ROSC: PRE=10/14 (71%), NORM=6/14 (43%) and IRH=12/14 (86%); p for IRH vs. NORM=0.02. Survival: PRE=9/14 (64%), NORM=5/14 (36%), IRH 8/14 (57%). CONCLUSION Hypothermia slowed the decay of the ECG waveform during prolonged VF. IRH improved ROSC but not short-term survival compared to NORM. It is possible to rapidly induce mild hypothermia during CPR using an IV infusion of ice-cold saline.

Course of quantitative ventricular fibrillation waveform measure and outcome following out-of-hospital cardiac arrest

BACKGROUND Quantitative measures of the ventricular fibrillation waveform at the outset of resuscitation are associated with survival. However, little is known about the course of these measures during resuscitation and how this course is related to outcome. OBJECTIVE The purpose of this study was to determine how waveform measures change over the course of resuscitation and whether these changes might be used to guide resuscitation. METHODS We evaluated 390 persons treated by emergency providers following out-of-hospital ventricular fibrillation arrest. We assessed the ventricular fibrillation waveform using the amplitude spectrum area (AMSA) from the defibrillators continuous electrocardiogram measured before each of the first three shocks. We used logistic regression to evaluate the relationship of AMSA and the change in AMSA with favorable neurologic survival as determined by the Cerebral Performance Category at hospital discharge 1-2. RESULTS Of the 390 patients who received an initial shock, 273 required a second shock and 210 required a third shock. The mean (standard deviation) for AMSA was 9.64 (0.52) for the 873 total shock cycles. AMSA₁ measured before the first shock was strongly associated with favorable neurologic survival (odds ratio [OR] 3.40, 95% confidence interval [CI] [2.48, 4.66] for 1 SD change). We observed a similar relationship for second-shock AMSA₂ (OR 3.53, 95% CI [2.42, 5.14]) and third-shock AMSA₃ (OR 3.10, 95% CI [2.03, 4.73]). The median change in AMSA was 0.24 for ΔAMSA₁₋₂ and 0.21 for ΔAMSA₂₋₃. A positive median change in AMSA between shocks was associated with favorable neurologic survival (OR 1.44, 95% CI [1.16, 1.80] for ΔAMSA₁₋₂ and OR 1.31, 95% CI [1.01, 1.71] for ΔAMSA₂₋₃). CONCLUSION Given their prognostic and dynamic qualities, quantitative waveform measures may provide an effective real-time strategy to guide individual treatment and improve survival.

A randomized comparison of cardiocerebral and cardiopulmonary resuscitation using a swine model of prolonged ventricular fibrillation

BACKGROUND Cardiocerebral resuscitation (CCR) is reportedly superior to cardiopulmonary resuscitation (CPR) for primary cardiac arrest in the prehospital setting. This study was done using a swine model of prolonged ventricular fibrillation (VF) to quantify the effect of the emergency medical services component of CCR with intraosseous access (CCR-IO) compared with standard CPR with intravenous access (CPR-IV) as it is typically performed during out-of-hospital cardiac arrest (OHCA) resuscitation in a prospective randomized fashion. METHODS Fifty-three animals were instrumented under anesthesia and VF was electrically induced. After 10 min of untreated VF, baseline characteristics were recorded, and animals were block randomized to one of two resuscitation schemes. The controls had mechanical chest compressions at 100/min with ventilations at a ratio of 30:2. Consistent with clinical practice, two 30-s pauses in chest compressions occurred to simulate attempts to accomplish endotracheal intubation at minutes 1 and 3 of CPR and successful IV access was simulated to occur three additional minutes after endotracheal intubation. The CCR group had continuous uninterrupted mechanical chest compressions at 100/min. No active ventilations were provided. A tibial IO needle was placed in real time for vascular access. Both groups received epinephrine (0.1 mg/kg) as soon as access became available followed by 2.5 min of chest compressions before the first 120 J rescue shock attempt. After successful rescue shock, standardized post-resuscitative care was provided to a 20-min endpoint. Failed rescue shock was followed by continued chest compressions with positive pressure ventilation in both groups, repeat doses of epinephrine (0.01 mg/kg) every 3 min, and rescue shock every minute as long as a shockable rhythm persisted. Group comparisons were assessed using descriptive statistics. Proportions with 95% confidence intervals were calculated for VF termination, ROSC, and survival. RESULTS Baseline characteristics and chemistries between the two groups at VF induction and after 10 min of non-treatment were mathematically the same. The proportions of VF termination (0.50 vs. 0.82), ROSC (0.30 vs. 0.59), and 20-min survival (0.19 vs. 0.40) all strongly favored the CCR-IO group. CONCLUSION In this swine model of witnessed VF arrest with no bystander-initiated resuscitation, CCR-IO resulted in substantial improvement in all three outcomes relative to typical emergency medical services provided CPR-IV.

A blinded, randomized controlled evaluation of an impedance threshold device during cardiopulmonary resuscitation in swine ,

BACKGROUND An impedance threshold device (ITD) has been designed to enhance circulation during CPR. A recent study suggests that the ITD does not improve hemodynamics and that it may actually worsen outcomes. We sought to independently assess the effect of the ITD on coronary perfusion pressure (CPP) and passive ventilation (PaCO(2) and PaO(2)) during standard CPR (S-CPR), and its impact on the return of spontaneous circulation (ROSC) and short-term survival in a blinded fashion. METHODS Thirty male swine were instrumented under anesthesia. Ventricular fibrillation (VF) was electrically induced. CPP was continuously recorded. After 8 min of untreated VF, baseline characteristics were documented and S-CPR initiated. After 3 cycles of S-CPR, an ABG was drawn and drugs were given. Following 6 additional cycles of S-CPR, an ABG was drawn and the first rescue shock was delivered. Group comparisons were assessed using descriptive statistics. Proportions with 95% confidence intervals were calculated for outcomes. RESULTS Baseline characteristics between the two groups were the same. The mean CPP in the ITD group was 51.2 mmHg [95% CI: 37.7, 64.7] compared to 50.2 mmHg [95% CI: 37.0, 63.4] in the sham group. The PaCO(2) and PaO(2) were 68 Torr [95% CI: 55.7, 79.5] and 103 Torr [95% CI: 76, 129] in the ITD group and 59 Torr [95% CI: 49.1, 68.5] and 137 Torr [95% CI: 83, 191] in the sham group. The rate of ROSC was 14/15 in both groups and 13 animals in each groups survived. CONCLUSIONS In this independent blinded study, use of the active ITD had no significant impact on CPP, passive ventilation, or outcomes compared to the sham device.