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 chi2 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.

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, Fisher's 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.

Dynamic nature of electrocardiographic waveform predicts rescue shock outcome in porcine ventricular fibrillation.

STUDY OBJECTIVE: Survival decreases with duration of ventricular fibrillation, and it is possible that failed rescue shocks increase myocardial damage. Structure in the ECG signal during ventricular fibrillation can be quantified by using the scaling exponent, a dimensionless measure that correlates with ventricular fibrillation duration. This study examined whether the scaling exponent could predict rescue shock success and whether unsuccessful rescue shocks altered the structure of the ventricular fibrillation waveform and the responsiveness to subsequent rescue shocks. METHODS: Ventricular fibrillation was electrically induced in 44 anesthetized swine, which were randomly assigned to receive 70-J biphasic rescue shocks at 2, 4, 6, 8, or 10 minutes. If rescue shocks failed, up to 2 subsequent rescue shocks were performed at 2-minute intervals. The scaling exponent was calculated at 1-second intervals from ECG to quantify the organization of the ventricular fibrillation waveform. RESULTS: A total of 92 rescue shocks were delivered, of which 23 successfully converted ventricular fibrillation to an organized rhythm (immediate success). After these 23 rescue shocks, 14 swine sustained organized rhythms for more than 30 seconds (sustained success). Lower scaling exponent values were associated with increased probability of successful rescue shocks. Receiver operating characteristic curves had an area under the curve of 0.86 for immediate rescue shock success and 0.93 for sustained rescue shock success. Failed rescue shocks increased the rate of scaling exponent increase over time but did not appear to affect subsequent rescue shock success when the scaling exponent was taken into account. CONCLUSION: Highly deterministic ventricular fibrillation, reflected by a low scaling exponent, predicted rescue shock success regardless of antecedent failed rescue shocks. In addition, unsuccessful rescue shocks might decrease post-rescue shock ventricular fibrillation waveform organization.

Hypothermic reperfusion after cardiac arrest augments brain-derived neurotrophic factor activation.

Induction of mild hypothermia improves neurologic outcome after global cerebral ischemia. This study measured levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in hippocampal tissue of rats after resuscitation from 8 minutes of normothermic, asphyxial cardiac arrest. After resuscitation, rats were maintained either at normal temperature (37 degrees C) or cooled to mild hypothermia (33 degrees C, beginning 60 minutes after resuscitation). After 12 or 24 hours, neurotrophin levels in hippocampus were measured by immunoblotting. Ischemia and reperfusion increased hippocampal levels of BDNF. Induction of hypothermia during reperfusion potentiated the increase in BDNF after 24 hours, but not after 12 hours. Levels of NGF were not increased by postresuscitation hypothermia. Hypothermia also increased tissue levels and tyrosine phosphorylation of TrkB, the receptor for BDNF. Increased BDNF levels were correlated with activation of the extracellularly regulated kinase (ERK), a downstream element in the signal transduction cascade induced by BDNF. In contrast to the many deleterious processes during ischemia and reperfusion that are inhibited by induced hypothermia, increasing BDNF levels is a potentially restorative process that is augmented. Increased activation of BDNF signaling is a possible mechanism by which mild hypothermia is able to reduce the neuronal damage typically occurring after cardiac arrest.