James W. Hoekstra

Median frequency — a new parameter for predicting defibrillation success rate

STUDY HYPOTHESIS Current American Heart Association guidelines recommend immediate defibrillation of ventricular fibrillation. When this is unsuccessful, there are no guidelines to help determine the optimum time at which to defibrillate after the administration of an alpha-adrenergic agonist. Previous studies have shown that the median frequency of the ventricular fibrillation ECG signal correlates with myocardial perfusion during CPR. We hypothesized that median frequency could predict the success of defibrillation and thus accurately determine the most appropriate time at which to defibrillate during ventricular fibrillation. STUDY POPULATION Twenty-two mixed-breed swine weighing more than 15 kg were studied. METHODS Ventricular fibrillation was induced electrically, and the ventricular fibrillation ECG signal was analyzed using fast Fourier analysis. After ten minutes of ventricular fibrillation, mechanical CPR was begun. After three minutes of CPR, the animals received one of three alpha-adrenergic agonists and CPR was continued. Defibrillation was attempted three and one-half minutes after drug administration. The average median frequency 20 seconds before defibrillation was calculated. Sensitivity and specificity of median frequency with respect to defibrillation success were determined. RESULTS A median frequency of 9.14 Hz had a sensitivity of 100% and a specificity of 92.31% in predicting the results of defibrillation in this model. CONCLUSION The median frequency may serve as a valuable parameter to guide defibrillation therapy during ventricular fibrillation.

Effect of First-Responder Automated Defibrillation on Time to Therapeutic Interventions During Out-of-Hospital Cardiac Arrest

STUDY OBJECTIVES The effect of automated defibrillation provided by basic emergency medical technician (EMT) first-responder units on the time intervals to other critical interventions in the management of out-of-hospital cardiac arrests is unknown. The purpose of this study was to define and compare elapsed time intervals to basic CPR, paramedic arrival, initial countershock, endotracheal intubation, IV access, and initial adrenergic drug therapy in first-responder automated defibrillation/paramedic versus basic EMT/paramedic emergency medical services systems. DESIGN Prospectively collected data from a 15-month multicenter study of out-of-hospital, nontraumatic cardiac arrests were analyzed. The mean time intervals to critical therapeutic interventions between first-responder automated defibrillation/paramedic and basic EMT/paramedic groups were compared using the Students t-test with Bonferroni correction. SETTING Three first-responder automated defibrillation/paramedic and three basic EMT/paramedic urban emergency medical services systems. PARTICIPANTS 1,578 patients with out-of-hospital cardiac arrest. INTERVENTIONS The first-responder automated defibrillation/paramedic group received initial ECG analysis and/or automated countershock by first-responder/EMTs; the basic EMT/paramedic group received initial ECG analysis and/or manual countershock by paramedics. RESULTS Elapsed time intervals in minutes +/- SD for first-responder automated defibrillation/paramedic versus basic EMT/paramedic groups, respectively, were as follows: Collapse to CPR, 4.3 +/- 3.9 versus 5.4 +/- 5.2 (P = .017); collapse to countershock, 10.7 +/- 5.9 versus 13.0 +/- 6.0 (P = .017); collapse to paramedic arrival, 13.0 +/- 5.4 versus 10.3 +/- 6.1 (P = .0001); paramedic arrival to IV access, 5.1 +/- 3.9 versus 7.0 +/- 5.0 (P = .0001); paramedic arrival to endotracheal intubation, 4.8 +/- 4.0 versus 6.8 +/- 5.8 (P = .0001); paramedic arrival to initial adrenergic drug therapy, 7.4 +/- 4.5 versus 8.2 +/- 4.7 (P = .015); collapse to IV access, 17.7 +/- 6.1 versus 16.6 +/- 7.4 (P = .10); collapse to endotracheal intubation, 17.3 +/- 6.4 versus 16.6 +/- 7.8 (P = .32); collapse to initial adrenergic drug therapy, 20.4 +/- 6.7 versus 18.1 +/- 7.2 (P = .010). The time intervals from paramedic arrival to IV access, endotracheal intubation, and initial adrenergic drug therapy remained shorter in the first-responder automated defibrillation/paramedic systems despite stratification by presenting cardiac rhythm. CONCLUSION First-responder automated defibrillation/paramedic systems provide not only shorter times to initial countershock, as compared with basic EMT/paramedic systems, but by having delegated initial countershock to first-responders, they also allow for significantly shorter times from paramedic arrival to IV access, endotracheal intubation, and initial adrenergic drug therapy interventions.

Estimation of Myocardial Ischemic Injury During Ventricular Fibrillation With Total Circulatory Arrest Using High-Energy Phosphates and Lactate as Metabolic Markers

STUDY OBJECTIVE To define the time course of myocardial ischemic injury using high-energy phosphate (HEP) depletion and the cessation of lactate production as metabolic markers. SETTING Data were collected in a laboratory animal model. TYPE OF PARTICIPANTS Ten immature mixed breed swine weighing 23.2 +/- 3.5 kg. DESIGN After thoracotomy, transmural myocardial biopsies were taken in vivo during normal sinus rhythm and at designated times during ventricular fibrillation with total circulatory arrest (VF-TCA). MEASUREMENTS AND MAIN RESULTS Frozen tissue samples were analyzed for adenine nucleotides, by high-performance liquid chromatography, and lactate by enzymatic assay. At five minutes of VF-TCA, myocardial adenosine triphosphate averaged 50% of control. At 15 minutes of VF-TCA, 89% of animals had myocardial adenosine triphosphate levels above 20% of control and adenylate charge ratio above 0.60. With more than 30 minutes of VF-TCA, all animals had adenosine triphosphate levels below 10% of control and adenylate charge ratio below 0.30. In addition, myocardial lactate levels plateaued after 30 minutes of VF-TCA, indicating the cessation of lactate production. CONCLUSION These results suggest that the myocardium can tolerate VF-TCA for as long as 15 minutes without irreversible injury; however, post-ischemic myocardial dysfunction may occur after as little as five minutes of VF-TCA. With more than 30 minutes of VF-TCA, myocardial injury is likely to be irreversible.

A randomized, placebo-controlled trial of early eptifibatide for non-ST-segment elevation acute coronary syndromes.

BACKGROUND The acute benefits of platelet glycoprotein IIb/IIIa inhibitors for non-ST-segment elevation acute coronary syndromes (NSTE ACS) remain unclear. METHODS In this pilot trial, 311 patients with NSTE ACS were randomly assigned in the emergency department to double-blinded therapy with eptifibatide or placebo for 12 to 24 hours before crossover to open-label eptifibatide. Serial creatine-kinase MB (CK-MB) and quantitative cardiac troponin T levels were collected during the first 24 hours to assess the impact of early platelet glycoprotein IIb/IIIa blockade on infarct size as measured by cardiac markers. RESULTS Median peak CK-MB (10.3 vs 11.8 ng/mL; P =.71) and peak quantitative cardiac troponin T levels (0.2 vs 0.3 ng/mL; P =.95) were similar between treatment groups, respectively. Median calculated peak CK-MB values (41 vs 40 ng/mL; P =.72) and area under the CK-MB curve measurements (980 vs 764 microg/min/L; P =.68) from curve-fitting analyses that could be performed in 106 of 311 patients were also similar. CONCLUSIONS In this pilot trial, early administration of eptifibatide in the emergency department did not modulate serologic measurements of infarct size in patients with NSTE ACS.

Prospective evaluation of Emergency Department patients with potential coronary syndromes using initial absolute CK-MB vs. CK-MB relative index

We compared the predictive properties of an initial absolute creatine kinase-MB (CK-MB) to creatine kinase-MB relative index (CK-MB RI) for detecting acute myocardial infarction (AMI), acute coronary syndromes (ACS), and serious cardiac events (SCE). Consecutive patients > 24 years of age with chest pain who received an electrocardiogram (EKG) as part of their Emergency Department (ED) evaluation had CK and CK-MB drawn at presentation. Patients were followed prospectively during their hospital course. The main outcome was AMI, ACS or SCE (death, AMI, dysrhythmias, CHF, PTCA/stent, CABG) within 30 days. The sensitivity, specificity, PPV and NPV of CK-MB and CK-MB RI to predict AMI, ACS, and SCE were calculated with 95% CIs. We enrolled 2028 patients. There were 105 patients (5.2%) with AMI, 266 (13.1%) with ACS, and 150 with SCE (7.4%). Absolute CK-MB had a higher sensitivity than CK-MB RI for AMI (52.0 vs. 46.9, respectively), ACS (23.5 vs. 20.8, respectively), and SCE (39.6 vs. 36.0, respectively), but a lower specificity than CK-MB RI for AMI (93.2 vs. 96.1, respectively), ACS (93.1 vs. 96.1, respectively) and SCE (93.3 vs. 96.3, respectively); and lower PPV for AMI (35.7 vs. 46.5, respectively), ACS (42.0 vs. 53.4, respectively) and SCE (38.5 vs. 50.5, respectively). The negative predictive values were similar for all outcomes. We conclude that the risk stratification of ED chest pain patients by absolute CK-MB has higher sensitivity, similar NPV, but a lower specificity and PPV than CK-MB relative index for detection of AMI, ACS, and SCE. The optimal test depends upon the relative importance of the sensitivity or specificity for clinical decision-making in an individual patient.

Effect of standard-dose versus high-dose epinephrine on myocardial high-energy phosphates during ventricular fibrillation and closed-chest CPR

STUDY OBJECTIVE To evaluate the effects of standard-dose versus high-dose epinephrine on myocardial high-energy phosphate metabolism during resuscitation from cardiac arrest. DESIGN Prospective, nonrandomized, controlled study using a swine model of cardiac arrest and resuscitation. INTERVENTIONS After anesthesia, intravascular pressure instrumentation, and ten minutes of ventricular fibrillation arrest, closed-chest CPR was begun. After three minutes of CPR, animals were allocated to receive either 0.02 mg/kg i.v. standard-dose epinephrine (eight) or 0.2 mg/kg i.v. high-dose epinephrine (nine). The animals underwent thoracotomy and rapid-freezing transmural myocardial core biopsy for high-energy phosphate analysis 3.5 minutes after epinephrine administration. High-energy phosphate values were blindly determined using high-pressure liquid chromatography. RESULTS Intravascular pressure (mm Hg) and high-energy phosphate (nmol/mg protein) results for standard-dose epinephrine versus high-dose epinephrine are, respectively, coronary perfusion pressure, 15.3 +/- 7.8 versus 23.7 +/- 5.5 (P = .0009); phosphocreatine, 0.4 +/- 0.8 versus 6.2 +/- 4.4 (P = .0003); adenosine triphosphate, 9.8 +/- 4.8 versus 12.7 +/- 5.7 (P = .30); adenosine diphosphate, 5.4 +/- 2.1 versus 6.1 +/- 1.3 (P = .41); and adenylate charge, 0.68 +/- 0.12 versus 0.72 +/- 0.12 (P = .87). CONCLUSION High-dose epinephrine does not deplete myocardial high-energy phosphate when given in this model of prolonged ventricular fibrillation. High-dose epinephrine increases coronary perfusion pressure compared with standard-dose epinephrine. High-dose epinephrine administration repletes phosphocreatine during closed-chest CPR, thereby increasing myocardial energy stores.

The effectiveness of bystander CPR in an animal model

Several clinical studies have yielded conflicting results in examining the effectiveness of bystander CPR (BCPR). The purpose of this pilot study was to determine the effectiveness of BCPR in an animal model of cardiac arrest and resuscitation. Ten swine were instrumented for hemodynamic and regional blood flow measurements with tracer microspheres. After two minutes of ventricular fibrillation (VF), the animals received eight minutes of either BCPR (five) or no-bystander CPR (NBCPR; five). Defibrillation was then attempted in both groups. If unsuccessful, CPR was begun and epinephrine 0.02 mg/kg was administered. Defibrillation was attempted again three and one-half minutes after epinephrine administration. Regional myocardial and cerebral blood flows were measured 30 seconds and five and one-half minutes after initiation of BCPR and one minute after epinephrine administration. In the BCPR group, myocardial blood flow was initially 29.0 +/- 33.2 and decreased to 15.0 +/- 21.5 mL/min/100 g during the last two and one-half minutes of BCPR. Cortical cerebral blood flow was initially 2.0 +/- 2.8 and fell to 0.6 +/- 0.8 mL/min/100 g during the last two and one-half minutes of BCPR. There were no statistical differences in myocardial blood flow and cerebral blood flow between the initial or late stages of BCPR (P greater than .14). There were no statistical differences in myocardial blood flow and cerebral blood flow between BCPR and NBCPR groups after epinephrine administration (P greater than .09).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of high dose norepinephrine versus epinephrine on cerebral and myocardial blood flow during CPR

Several animal studies have demonstrated an improvement in cerebral blood flow (CBF) and myocardial blood flow (MBF) after the administration of epinephrine (E) 0.20 mg/kg during closed chest CPR. The administration of norepinephrine (NE) in doses of 0.12 and 0.16 mg/kg demonstrated a trend toward improved CBF and MBF during CPR over that seen with E 0.20 mg/kg in the same animal model. The purpose of this study was to compare the effects of a higher dose of NE 0.20 mg/kg to E 0.20 mg/kg to determine if increasing doses of NE would demonstrate further improvement in CBF and MBF during CPR. Fourteen immature swine were anesthetized and instrumented for regional blood flow and hemodynamic measurements. After 10 min of ventricular fibrillation (VF), CPR was begun using a mechanical thumper. After 3 min of CPR, the animals received either E 0.20 mg/kg (n = 7) or NE 0.20 mg/kg (n = 7) through a right atrial catheter. CPR was continued for an additional 3.5 min and defibrillation was then attempted. CBF (ml/min/100 g), MBF (ml/min/100 g), myocardial oxygen delivery (MDo2; ml O2/min/100 g), myocardial oxygen consumption (MVo2; ml O2/min/100 g), and myocardial oxygen extraction ratios (ER, MVo2/MDo2) were measured during normal sinus rhythm (NSR), during CPR, and during CPR following drug administration. Following drug administration, CBF, MBF, MDo2 and MVo2 rose while ER fell in both E and NE groups. There were no significant differences between groups in CBF, ER, or intravascular pressures following drug administration (P greater than or equal to 0.07). The NE group demonstrated significantly higher MBF (118.9 +/- 73.1 vs. 62.2 +/- 45.3, P = 0.04), MVo2 (14.2 +/- 7.7 vs. 7.0 +/- 3.8, P = 0.05), and MDo2 (19.9 +/- 13.4 versus 9.4 +/- 6.3, P = 0.05) compared to the E group following drug administration While NE improved MBF and MDo2 over E during CPR, there was a trend toward lower resuscitation rates with NE (57.1% vs. 85.7% P = 0.56). Any benefit of higher MBF and MDo2 with NE 0.20 mg/kg appears to be offset by proportionately high MVo2 and a trend toward lower resuscitation rates in the NE 0.20 mg/kg animals.

Regional cerebral blood flow with manual internal cardiac massage versus direct mechanical ventricular assistance

STUDY HYPOTHESIS Previous studies have not discerned the best method for generating regional cerebral blood flow during internal cardiac massage. We hypothesized that regional cerebral blood flow generated by a mechanical method--direct mechanical ventricular assistance (DMVA)--would be superior to manual internal cardiac massage (MAN). STUDY POPULATION Twelve adult Yucatan minipigs weighing more than 44 kg each were studied. METHODS Swine were instrumented for regional cerebral blood flow measurements using tracer microspheres. After 15 minutes of ventricular fibrillation, swine were randomized to receive either MAN or DMVA. Regional cerebral blood flow was measured during normal sinus rhythm and at one minute (VF-1) and six minutes (VF-2) after initiation of circulatory support. Regional cerebral blood flow values were compared using a Wilcoxon rank sum test. RESULTS During VF-1, there was a tendency for DMVA to produce greater regional cerebral blood flow than MAN, although these differences were not statistically significant (DMVA vs MAN as mL/min/100 g): cerebral cortex, 28 versus 11; cerebellum, 49 versus 22; midbrain, 43 versus 16; pons, 55 versus 18; medulla, 55 versus 19; and spinal cord, 33 versus 10. During VF-2, DMVA produced greater regional cerebral blood flows than were produced by MAN: cerebral cortex, 39 versus 12 (P less than .06); cerebellum, 58 versus 20 (P less than 0.5); midbrain, 50 versus 18 (P less than .05); pons, 52 versus 22 (P less than .06); medulla, 53 versus 20 (P less than .05); and spinal cord, 31 versus 12 (P less than .05). CONCLUSION DMVA produces greater regional cerebral blood flow than is produced during MAN after 15 minutes of ventricular fibrillation. DMVA is effective at maintaining regional cerebral blood flow after a prolonged cardiac arrest.

Hemodynamic effects of 1-[3,4-dihydroxypheny]-1,2-diaminoethane versus norepinephrine during ventricular fibrillation and cardiopulmonary resuscitation

We hypothesized that substitution of the hydroxyl group (OH) on the beta carbon of norepinephrine (NE) with an amino group would yield a compound, 1-(3,4-dihydroxyphenyl)-1,2-diaminoethane (DHPDAE), that would maintain the hemodynamic properties of NE during CPR, but would decrease the rate of post-defibrillation dysrhythmias. Six mixed breed swine weighing greater than 28 kg were studied. The animals were instrumented for cerebral (CBF) and myocardial blood flow (MBF) measurements. Ventricular fibrillation (VF) was induced. After 10 min of VF, CPR was begun. After 3 min of CPR, 2.5 mg/kg of DHPDAE was administered and CPR continued. Defibrillation was attempted 3.5 min after drug administration. CBF, MBF and defibrillation rates were compared to an historical control group receiving 0.16 mg/kg of NE. Outcome variables were compared using a Wilcoxon Rank Sum test and Fisher-exact test. NE significantly improved CBF and MBF compared to DHPDAE. All the animals in the NE group were successfully defibrillated into a perfusing rhythm. Sixty percent of the NE treated animals experienced post-defibrillation ventricular dysrhythmias. None of the animals in the DHPDAE were successfully defibrillated into a perfusing rhythm. Substitution of the hydroxyl group on the beta-carbon of NE with an amino group significantly decreases the hemodynamic properties of the parent molecule.