Prediction of countershock success in patients using the autoregressive spectral estimation.

OBJECTIVES: Ventricular fibrillation (VF) is a life-threatening cardiac arrhythmia and within of minutes of its occurrence, optimal timing of countershock therapy is highly warranted to improve the chance of survival. This study was designed to investigate whether the autoregressive (AR) estimation technique was capable to reliably predict countershock success in VF cardiac arrest patients. METHODS: ECG data of 1077 countershocks applied to 197 cardiac arrest patients with out-of-hospital and in-hospital cardiac arrest between March 2002 and July 2004 were retrospectively analyzed. The ECG from the 2.5 s interval of the precountershock VF ECG was used for computing the AR based features Spectral Pole Power (SPP) and Spectral Pole Power with Dominant Frequency weighing (SPPDF) and Centroid Frequency (CF) and Amplitude Spectrum Area (AMSA) based on Fast Fourier Transformation (FFT). RESULTS: With ROC AUC values up to 84.1% and diagnostic odds ratio up to 19.12 AR based features SPP and SPPDF have better prediction power than the FFT based features CF (80.5%; 6.56) and AMSA (82.1%; 8.79). CONCLUSIONS: AR estimation based features are promising alternatives to FFT based features for countershock outcome when analyzing human data.

Prediction of countershock success: a comparison of autoregressive and fast fourier transformed spectral estimators.

OBJECTIVES: Spectral analysis of the ventricular fibrillation (VF) ECG has been used for predicting countershock success, where the Fast Fourier Transformation (FFT) is the standard spectral estimator. Autoregressive (AR) spectral estimation should compute the spectrum with less computation time. This study compares the predictive power and computational performance of features obtained by the FFT and AR methods. METHODS: In an animal model of VF cardiac arrest, 41 shocks were delivered in 25 swine. For feature parameter analysis, 2.5 s signal intervals directly before the shock and directly before the hands-off interval were used, respectively. Invasive recordings of the arterial pressure were used for assessing the outcome of each shock. For a proof of concept, a micro-controller program was implemented. RESULTS: Calculating the area under the receiver operating characteristic (ROC) curve (AUC), the results of the AR-based features called spectral pole power (SPP) and spectral pole power with dominant frequency (DF) weighing (SPPDF) yield better outcome prediction results (85%; 89%) than common parameters based on FFT calculation method (centroid frequency (CF), amplitude spectrum area (AMSA)) (72%; 78%) during hands-off interval. Moreover, the predictive power of the feature parameters during ongoing CPR was not invalidated by closed-chest compressions. The calculation time of the AR-based parameters was nearly 2.5 times faster than the FFT-based features. CONCLUSION: Summing up, AR spectral estimators are an attractive option compared to FFT due to the reduced computational speed and the better outcome prediction. This might be of benefit when implementing AR prediction features on the microprocessor of a semi-automatic defibrillator.

[Responsibility of the anaesthesiologist in the preoperative risk evaluation]. / Die Verantwortung des Anästhesisten in der präoperativen Risikoabklärung.

Correct indications are essential to perform surgical procedures. However, appropriate timing to achieve minimal rates of complications even in high-risk patients or major surgery is at the top of the priority list. Perioperative responsibility is divided between anaesthesiologists and surgeons. While the surgeon is accountable for the surgical procedure, the anaesthesiologist is responsible for preoperative risk evaluation, perioperative management, and maintenance of vital organ functions. Both of these medical specialities must weigh the urgency of the procedure against patient-associated risk factors. Goals are optimal patient safety, efficient preoperative evaluation and subsequent optimisation to reduce the burden for the health care systems. For most patients without underlying diseases, a thorough history and physical examination is sufficient. In teaching hospitals, some laboratory results for screening of organ function are advisable. Patients can be stratified on clinical grounds into low-, medium-, and high-risk categories. Use of these categories, along with consideration of the type and urgency of surgery, allows for a reasonable approach to preoperative testing. Testing directed towards assessment of organ system functional reserve and identification of organs at risk rather than the diagnosis of a specific disease, is the primary goal of preoperative evaluation prior to surgery. These results are essential to prepare an effective anaesthetic plan. Along with increased patient comfort, the number of preoperative hospital days can be reduced by outpatient preoperative evaluation clinics.

[The use of arginine vasopressin during cardiopulmonary resuscitation. An analysis of experimental and clinical experience and a view of the future]. / Der Einsatz von Arginin Vasopressin bei der kardiopulmonalen Reanimation. Eine Analyse der experimentellen und klinischen Erfahrungen sowie ein Ausblick in die Zukunft.

The risks and benefits of epinephrine given during cardiopulmonary resuscitation (CPR) are controversially discussed. Animal experiments revealed beta-receptor-mediated adverse effects of epinephrine such as increased myocardial oxygen consumption, ventricular arrhythmia, ventilation-perfusion defects, and cardiac failure in the postresuscitation phase. In clinical studies, high-dose vs. standard-dose epinephrine was unable to improve resuscitation success. During CPR in patients, endogenous arginine vasopressin (AVP) levels were increased and surviving vs. non-surviving patients had significantly higher AVP levels. This may indicate that the human body discharges AVP during life-threatening situations as an additional vasopressor to catecholamines in order to maintain cardiocirculatory homeostasis. In different experimental CPR models, AVP compared with epinephrine given during CPR significantly improved vital organ blood flow, coronary perfusion pressure, resuscitability, and long-term survival. During prolonged CPR with repeated drug administration, AVP but not epinephrine maintained coronary perfusion pressure on a level that ensured return of spontaneous circulation. Also, AVP can be administered successfully in the intravenous dose into the endobronchial tree, and also intraosseously. When given during CPR, AVP induces a transient splanchnic hypoperfusion, and an increase in systemic vascular resistance, both of which normalized spontaneously; furthermore, an oligo-anuric state was not observed. In two clinical studies, AVP vs. epinephrine improved 24-h survival during out-of-hospital CPR, and comparable CPR outcome during in-hospital CPR. The new CPR guidelines of both the American Heart Association and the European Resuscitation Council assign a given CPR intervention into classes of recommendation [class 1 (definitely recommended), class 2 A (intervention of choice), class 2B (alternative intervention), class X (neutral), or class 3 (not recommended)]. For CPR of adults with shock-refractory ventricular fibrillation, 40 units AVP or 1 mg epinephrine is recommended (class 2B); patients with asystole or pulseless electrical activity should be resuscitated with epinephrine. AVP is not recommended for adult cardiac arrest patients with asystole or pulseless electrical activity; or pediatric cardiac arrest patients due to a lack of clinical data. Until definitive data about AVP vs. epinephrine effects during CPR are available, the present state of knowledge should be interpreted that two vasopressors are available for use instead of one.

The predictive value of ventricular fibrillation electrocardiogram signal frequency and amplitude variables in patients with out-of-hospital cardiac arrest.

UNLABELLED: We evaluated ventricular fibrillation frequency and amplitude variables to predict successful countershock, defined as pulse-generating electrical activity. We also elucidated whether bystander cardiopulmonary resuscitation (CPR) influences these electrocardiogram (ECG) variables. In 89 patients with out-of-hospital cardiac arrest, ECG recordings of 594 countershock attempts were collected and analyzed retrospectively. By using fast Fourier transformation analysis of the ventricular fibrillation ECG signal in the frequency range 0.333-15 Hz (median [range]), median frequency, dominant frequency, spectral edge frequency, and amplitude were as follows: 4.4 (2.4-7.5) Hz, 4.0 (0.7-7.0) Hz, 7.7 (3.7-13.7) Hz, and 0.94 (0.24-1.95) mV, respectively, before successful countershock (n = 59). These values were 3.8 (0.8-7.7) Hz (P = 0.0002), 3.0 (0.3-9.7) Hz (P < 0.0001), 7.3 (2.0-14.0) Hz (P < 0.05), and 0.53 (0.03-3.03) mV (P < 0.0001), respectively, before unsuccessful countershock (n = 535). In patients in whom bystander CPR was performed (n = 51), ventricular fibrillation frequency and amplitude before the first defibrillation attempt were higher than in patients without bystander CPR (n = 38) (median frequency, 4.4 [2.4-7.5] vs 3.7 [1.8-5.3] Hz, P < 0.0001; dominant frequency, 3.8 [0.9-7.7] vs 2.6 [0.8-5.9] Hz, P < 0.0001; spectral edge frequency, 8.4 [4.8-12.9] vs 7.2 [3.9-12.1] Hz, P < 0.05; amplitude, 0.79 [0.06-4.72] vs 0.67 [0.16-2.29] mV, P = 0.0647). Receiver operating characteristic curves demonstrate that successful countershocks will be best discriminated from unsuccessful countershocks by ventricular fibrillation amplitude (3000-ms epoch). At 73% sensitivity, a specificity of 67% was obtained with this variable. IMPLICATIONS: In patients with out-of-hospital cardiac arrest, successful countershocks will be best discriminated from unsuccessful countershocks by ventricular fibrillation amplitude (3000-ms epoch). At 73% sensitivity, a specificity of 67% was obtained with this variable.

Analysing ventricular fibrillation ECG-signals and predicting defibrillation success during cardiopulmonary resuscitation employing N(alpha)-histograms.

Mean fibrillation frequency may predict defibrillation success during cardiopulmonary resuscitation (CPR). N(alpha)-histogram analysis should be investigated as an alternative. After 4 min of cardiac arrest, and 3 versus 8 min of CPR, 25 pigs received either vasopressin or epinephrine (0.4, 0.4, and 0.8 U/kg vasopressin versus 45, 45, and 200 microg/kg epinephrine) every 5 min with defibrillation at 22 min. Before defibrillation, the N(alpha)-parameter histogramstart/histogramwidth and the mean fibrillation frequency in resuscitated versus non-resuscitated pigs were 2.9+/-0.4 versus 1.7+/-0.5 (P=0.0000005); and 9.5+/-1.7 versus 6.9+/-0.7 (P=0.0003). During the last minute prior to defibrillation, histogramstart/histogramwidth of > or =2.3 versus mean fibrillation frequency > or =8 Hz predicted successful defibrillation with subsequent return of a spontaneous circulation for more than 60 min with sensitivity, specificity, positive predictive value and negative predictive value of 94 versus 82%, 96 versus 89%, 98 versus 93% and 90 versus 74%, respectively. We conclude, that N(alpha)-analysis was superior to mean fibrillation frequency analysis during CPR in predicting defibrillation success, and distinction between vasopressin versus epinephrine effects.

Fibrillation power, an alternative method of ECG spectral analysis for prediction of countershock success in a porcine model of ventricular fibrillation.

BACKGROUND: Noninvasive prediction of defibrillation success after cardiac arrest and cardiopulmonary resuscitation (CPR) may help in determining the optimal time for a countershock, and thus increase the chance for survival. METHODS: In a porcine model (n=25) of prolonged cardiac arrest, advanced cardiac life support was provided by administration of two or three doses of either vasopressin or epinephrine after 3 or 8 min of basic life support. After 4 min of ventricular fibrillation and 18 min of life support, defibrillation was attempted. The denoised power spectral density of 10 s intervals of the ventricular fibrillation electrocardiogram (ECG) was estimated from averaged and smoothed Fourier transforms. We have eliminated the spectral contribution of artifacts from manual chest compressions and provide a definition for the contribution of ventricular fibrillation to the power spectral density. This contribution is quantified and termed "fibrillation power". RESULTS: We tested fibrillation power and two established methods in their discrimination of survivors (n=16) vs. non-survivors (n=9) in the last minute before the countershock. A fibrillation power > or =79 dB predicted successful defibrillation with sensitivity, specificity, positive predictive value and negative predictive value of 98%, 98%, 99% and 97% while a mean fibrillation frequency > or =7.7 Hz was predictive with 85%, 83%, 90% and 77% and a mean amplitude > or =0.49 mV was predictive with 95%, 90%, 94% and 91%. CONCLUSIONS: We suggest that fibrillation power is an alternative source of information on the status of a fibrillating heart and that it may match the established mean frequency and amplitude analysis of ECG in predicting successful countershock during CPR.

The beneficial effect of basic life support on ventricular fibrillation mean frequency and coronary perfusion pressure.

BACKGROUND AND OBJECTIVE: Chest compressions before initial defibrillation attempts have been shown to increase successful defibrillation. This animal study was designed to assess whether ventricular fibrillation mean frequency after 90 s of basic life support cardiopulmonary resuscitation (CPR) may be used as an indicator of coronary perfusion and mean arterial pressure during CPR. METHODS AND RESULTS: After 4 min of ventricular fibrillation cardiac arrest in a porcine model, CPR was performed manually for 3 min. Mean ventricular fibrillation frequency and amplitude, together with coronary perfusion and mean arterial pressure were measured before initiation of chest compressions, and after 90 s and 3 min of basic life support CPR. Increases in fibrillation mean frequency correlated with increases in coronary perfusion and mean arterial pressure after both 90 s (R=0.77, P<0.0001, n=30; R=0.75, P<0.0001, n=30, respectively) and 3 min (R=0.61, P<0.001, n=30; R=0.78, P<0.0001, n=30, respectively) of basic life support CPR. Increases in fibrillation mean amplitude correlated with increases in mean arterial pressure after both 90 s (R=0.46, P<0.01; n=30) and 3 min (R=0.42, P<0.05, n=30) of CPR. Correlation between fibrillation mean amplitude and coronary perfusion pressure was not significant both at 90 s and 3 min of CPR. CONCLUSIONS: In this porcine laboratory model, 90 s and 3 min of CPR improved ventricular fibrillation mean frequency, which correlated positively with coronary perfusion pressure, and mean arterial pressure.

Arginine vasopressin during cardiopulmonary resuscitation and vasodilatory shock: current experience and future perspectives.

Epinephrine use during cardiopulmonary resuscitation (CPR) is controversial because of its receptor-mediated adverse effects such as increased myocardial oxygen consumption, ventricular arrhythmias, ventilation-perfusion defect, postresuscitation myocardial dysfunction, ventricular arrhythmias, and cardiac failure. In the CPR laboratory, vasopressin improved vital organ blood flow, cerebral oxygen delivery, resuscitability, and neurologic recovery more than did epinephrine. In patients with out-of-hospital ventricular fibrillation, a larger proportion of patients treated with vasopressin survived 24 hours than did patients treated with epinephrine. Currently, a large trial of out-of-hospital cardiac arrest patients being treated with vasopressin versus epinephrine is ongoing in Germany, Austria, and Switzerland. The new international CPR guidelines recommend 40 U vasopressin intravenously, and 1 mg epinephrine intravenously, as equally effective for the treatment of adult patients in ventricular fibrillation; however, no recommendation for vasopressin has been made to date for adult patients with asystole and pulseless electrical activity, or in children, because of lack of clinical data. When adrenergic vasopressors were unable to maintain arterial blood pressure in patients with vasodilatory shock, continuous infusions of vasopressin (0.04-0.10 U/min) stabilized cardiocirculatory parameters and even ensured weaning from catecholamines.

[The new international guidelines for cardipulmonary resuscitation: an analysis and comments on the most important changes]. / Die neuen internationalen Richtlinien zur kardiopulmonalen Reanimation. Eine Analyse und Kommentierung der wichtigsten Anderungen.

In August 2000, the American Heart Association and the European Resuscitation Council published the conclusions of the International Guidelines 2000 Conference on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care which contains both the new recommendations and an in-depth review. The discussions and drafting began at a conference in March 1999, followed by a second conference in September 1999, both attended by approx. 250 participants and another conference in February 2000 which was attended by approx. 500 participants. Review of the current state of science, discussion and final consensus continued subsequently via email, conference calls, fax, and personal conversation. During the entire process, scientists and resuscitation councils from all over the world participated, with participants from the United States comprising approx. 60%, and scientists from outside of the United States comprising approx. 40%. In order to ensure that the CPR recomendations are not dominated by any given nation or resuscitation council, most topics were reviewed and interpretated by two scientists from the United States and two scientists from outside of the United States. Accordingly, changes in these new CPR recommendations are the result of an evidence-based review by worldwide experts. The most important changes in the recommendations according to the authors are discontinuation of the pulse-check for lay people, 500 ml instead of 800-1200 ml tidal volume during bag-valve-mask ventilation (FiO2 > 0.4) of a patient with an unprotected airway, verifying correct endotracheal intubation with capnography and an esophageal detector, employing mechanical devices such as interposed abdominal compression CPR, vest CPR, active-compression-decompression CPR, and the inspiratory threshold valve (ITV) CPR as alternatives or adjuncts to standard manual chest compressions, defibrillation with < 200 Joule biphasic instead of with 200-360 Joule monophasic impulses, vasopressin (40 units) and epinephrine (1 mg) as comparable drugs to treat patients with ventricular fibrillation, amiodarone (300 mg) for shock-refractory ventricular fibrillation and intravenous lysis for patients who have suffered a stroke.

The effects of endogenous and exogenous vasopressin during experimental cardiopulmonary resuscitation.

Exogenous vasopressin is a promising vasopressor when blood pressure is critically threatened, but the role of endogenous vasopressin during cardiopulmonary resuscitation (CPR) is unknown. We assessed the role of endogenous versus exogenous vasopressin in a porcine open chest CPR model. Seven minutes before induction of cardiac arrest, seven pigs received 10 microg/kg of a selective vasopressin V(1)-receptor-antagonist (Blocked Vasopressin group); another 12 pigs in two groups received saline administration only. After 4 min of untreated ventricular fibrillation followed by 3 min of basic life support CPR, six animals received 0.8 U/kg vasopressin (Exogenous Vasopressin group), whereas the blocked vasopressin group (n = 7), and the remaining six animals received saline placebo only (Endogenous Vasopressin group). Defibrillation was attempted after 14 min of CPR. During basic life support CPR, left ventricular myocardial blood flow was significantly (P < 0.05) decreased in the Blocked Vasopressin group compared with the Exogenous Vasopressin group and Endogenous Vasopressin group (42 +/- 5 compared with 64 +/- 6 and 66 +/- 6 mL x min(-1) x 100g(-1)). Left ventricular myocardial blood flow was significantly decreased in the Blocked Vasopressin group versus Exogenous Vasopressin group versus Endogenous Vasopressin group 90 s and 5 min after drug administration, respectively (38 +/- 4 and 27 +/- 3 vs 145 +/- 32 and 110 +/- 12 vs 62 +/- 4 and 56 +/- 6 mL x min(-1) x 100g(-1), respectively). None of seven Blocked Vasopressin animals, six of six Exogenous Vasopressin pigs, and six of six Endogenous Vasopressin swine had return of spontaneous circulation after 14 min of cardiac arrest including 10 min of CPR (P < 0.05). In conclusion, pigs with blocked endogenous vasopressin had poor coronary perfusion pressure and left ventricular myocardial blood flow during open chest CPR, and could not be successfully resuscitated. All pigs with effective endogenous vasopressin or pigs with effective endogenous vasopressin and additional exogenous vasopressin had good left ventricular myocardial blood flow during experimental CPR, and survived the 1-h postresuscitation phase. We conclude that endogenous vasopressin is an adjunct vasopressor to epinephrine and may serve as a back-up regulator to maintain cardiocirculatory homeostasis.

[Drug therapy in cardiopulmonary resuscitation]. / Medikamentöse Therapie bei der kardiopulmonalen Reanimation.

In the year 2000, new international guidelines for cardiopulmonary resuscitation (CPR) were published by the American Heart Association, and the European Resuscitation Council. These guidelines are evidence-based, indicating that these recommendations are based primarily on interpretation of data from clinical studies. Levels of recommendation range from class I (proven safe and useful), class IIa (intervention of choice), IIb (alternative intervention), indeterminate (research stage), and class III (unacceptable, no benefit). Administration of drugs during CPR should be performed intravenously or intraosseously (class IIa) or, as a second-line approach, endotracheally (class IIb). Due to lack of evidence, the standard dose of 1 mg epinephrine to treat ventricular fibrillation, pulseless electrical activity, or asystole was categorized as class indeterminate; while a single dose of 40 units vasopressin to treat adults with shock-refractory ventricular fibrillation received a IIb recommendation. Owing to a lack of clinical data, the use of vasopressin was neither recommended to treat adults with pulseless electrical activity or asystole, nor for the use in children. Both endothelin and calcium were not recommended for routine use (class indeterminate). Careful titration of acid-base status with 1 mL/kg 8.4% sodium bicarbonate should only be administered if indicated by blood gas analysis (class indeterminate). If 1 mg epinephrine fails to be effective in adult patients with pulseless electrical activity or asystole, 1 mg atropine can be administered (class indeterminate). Regarding antiarrhythmic drugs, 300 mg amiodarone (class IIb) showed the best results in shock-refractory ventricular fibrillation. The postresuscitation phase has the goal to achieve the best possible neurological performance after return of spontaneous circulation, which requires careful optimization of organ functions.

Monitoring of immune activation using biochemical changes in a porcine model of cardiac arrest.

In animal models, immune activation is often difficult to assess because of the limited availability of specific assays to detect cytokine activities. In human monocytes/macrophages, interferon-gamma induces increased production of neopterin and an enhanced activity of indoleamine 2,3-dioxygenase, which degrades tryptophan via the kynurenine pathway. Therefore, monitoring of neopterin concentrations and of tryptophan degradation can serve to detect the extent of T helper cell 1-type immune activation during cellular immune response in humans. In a porcine model of cardiac arrest, we examined the potential use of neopterin measurements and determination of the tryptophan degradation rate as a means of estimating the extent of immune activation. Urinary neopterin concentrations were measured with high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA) (BRAHMS Diagnostica, Berlin, Germany). Serum and plasma tryptophan and kynurenine concentrations were also determined using HPLC. Serum and urine neopterin concentrations were not detectable with HPLC in these specimens, whereas RIA gave weakly (presumably false) positive results. The mean serum tryptophan concentration was 39.0 +/- 6.2 micromol/l, and the mean kynurenine concentration was 0.85 +/- 0.33 micromol/l. The average kynurenine-per-tryptophan quotient in serum was 21.7 +/- 8.4 nmol/micromol, and that in plasma was 20.7 +/- 9.5 nmol/micromol (n = 7), which corresponds well to normal values in humans. This study provides preliminary data to support the monitoring of tryptophan degradation but not neopterin concentrations as a potential means of detecting immune activation in a porcine model. The kynurenine-per-tryptophan quotient may serve as a short-term measurement of immune activation and hence permit an estimate of the extent of immune activation.

Effect of phased chest and abdominal compression-decompression cardiopulmonary resuscitation on myocardial and cerebral blood flow in pigs.

OBJECTIVE: This study was designed to assess the effects of a phased chest and abdominal compression-decompression cardiopulmonary resuscitation (CPR) device, Lifestick, vs. standard CPR on vital organ blood flow in a porcine CPR model. DESIGN: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, vital organ blood flow, blood gases, and return of spontaneous circulation. SETTING: University hospital research laboratory. SUBJECTS: Twelve domestic pigs. INTERVENTIONS: After 4 mins of untreated ventricular fibrillation, either the Lifestick CPR device (n = 6) or standard CPR (n = 6) was started and maintained for an additional interval of 6 mins before attempting defibrillation. MEASUREMENTS AND MAIN RESULTS: During CPR, but before epinephrine, use of the Lifestick CPR device resulted in significantly higher (p < .05) mean (+/- SD) coronary perfusion pressure (23+/-9 vs. 10+/-7 mm Hg), cerebral perfusion pressure (29+/-11 vs. 18+/-10 mm Hg), mean arterial pressure (49+/-10 vs. 36+/-13 mm Hg), end-tidal carbon dioxide (32+/-11 vs. 20+/-7 mm Hg), left ventricular myocardial blood flow (44+/-19 vs. 19+/-12 mL x min(-1) x 100 g(-1)), and total cerebral blood flow (29+/-10 vs. 14+/-12 mL x min(-1) x 100 g(-1)). After 45 microg/kg epinephrine, hemodynamic and vital organ blood flow variables increased to comparable levels in both groups. CONCLUSIONS: Compared with standard CPR, the Lifestick CPR device increased significantly hemodynamic variables and vital organ blood flow during CPR before epinephrine administration.

The effects of repeated doses of vasopressin or epinephrine on ventricular fibrillation in a porcine model of prolonged cardiopulmonary resuscitation.

This study evaluated ventricular fibrillation mean frequency and amplitude to predict defibrillation success in a porcine cardiopulmonary resuscitation (CPR) model using repeated administration of vasopressin or epinephrine. After 4 min of cardiac arrest and 3 min of CPR, 10 pigs were randomly assigned to receive either vasopressin (early vasopressin: 0.4, 0.4, and 0.8 units/kg, respectively, n = 5) or epinephrine (early epinephrine: 45, 45, and 200 microg/kg, respectively, n = 5). Another 11 animals were randomly allocated after 4 min of cardiac arrest and 8 min of CPR to receive every 5 min either vasopressin (late vasopressin: 0.4 and 0. 8 units/kg, respectively, n = 5) or epinephrine (late epinephrine: 45 and 200 microg/kg, n = 6). Ventricular fibrillation mean frequency and amplitude on defibrillation were significantly higher in the vasopressin groups than in the epinephrine groups, respectively. In vasopressin versus epinephrine animals, mean frequency immediately before defibrillation was 9.6 +/- 1.5 Hz vs 7. 0 +/- 0.7 Hz (P < 0.001), mean amplitude was 0.65 +/- 0.26 mV vs 0. 21 +/- 0.14 mV (P < 0.001, and coronary perfusion pressure was 27 +/- 9 mm Hg vs 8 +/- 4 mm Hg (P < 0.00001), respectively. In contrast to no epinephrine animals, all vasopressin animals were successfully defibrillated and survived 1 h (P < 0.05). Mean fibrillation frequency and amplitude predicted successful defibrillation and may serve as noninvasive markers to monitor continuing CPR efforts. Furthermore, vasopressin was superior to epinephrine in maintaining these variables above a threshold necessary for successful defibrillation.

Intraosseous vasopressin improves coronary perfusion pressure rapidly during cardiopulmonary resuscitation in pigs.

OBJECTIVE: Intravenous administration of vasopressin during cardiopulmonary resuscitation (CPR) may be more effective than optimal doses of epinephrine. The main purpose of this study was to determine whether intraosseous vasopressin achieves serum drug levels comparable with intravenous doses during CPR and, additionally, to evaluate the effects of intraosseous vasopressin during CPR. DESIGN: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, blood gases, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Twelve domestic pigs. INTERVENTIONS: After 4 mins of untreated ventricular fibrillation and 3 mins of CPR, 12 pigs were randomized to be treated with intravenous administration of vasopressin (0.8 unit/kg vasopressin; n = 6) or intraosseous vasopressin (0.8 unit/kg vasopressin; n = 6). Defibrillation was performed 5 mins after drug administration to attempt the return of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS: At both 90 secs and 5 mins after drug administration, intravenous and intraosseous administration of vasopressin resulted in comparable mean (+/-SEM) coronary perfusion pressure (43+/-4 vs. 44+/-3 and 30+/-2 vs. 37+/-2 mm Hg, respectively) and vasopressin plasma concentrations (13,706+/-1,857 vs. 16,166+/-3,114 pg/mL and 10,372+/-883 vs. 8246+/-2211 pg/mL, respectively). All animals in both groups were successfully resuscitated; pigs that received intraosseous vasopressin had a significantly higher (p < .05) mean arterial (92+/-6 vs. 129+/-12 mm Hg) and coronary perfusion pressure (84+/-11 vs. 119+/-11 mm Hg) at 5 mins of return of spontaneous circulation. CONCLUSIONS: Intraosseous vasopressin resulted in comparable vasopressin plasma levels, hemodynamic variables, and return of spontaneous circulation rates as did intravenous vasopressin. Intraosseous vasopressin may be an alternative for vasopressor administration during CPR, when intravenous access is delayed or not available.

Vasopressin improves vital organ blood flow after prolonged cardiac arrest with postcountershock pulseless electrical activity in pigs.

OBJECTIVE: Although a benefit of vasopressin when compared with epinephrine was shown during cardiopulmonary resuscitation (CPR) after a short duration of ventricular fibrillation cardiac arrest, the effect of vasopressin during prolonged cardiac arrest with pulseless electrical activity is currently unknown. DESIGN: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, vital organ blood flow, blood gases, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Eighteen domestic pigs. INTERVENTIONS: After 15 mins of cardiac arrest and 3 mins of chest compressions, 18 animals were randomly treated with either 0.8 units/kg vasopressin (n = 9) or 200 microg/kg epinephrine (n = 9). MEASUREMENTS AND MAIN RESULTS: Compared with epinephrine, vasopressin resulted, at both 90 secs and 5 mins after drug administration, in significantly higher (p < .05) median (25th-75th percentiles) left ventricular myocardial blood flow (120 [range, 96-193] vs. 54 [range, 11-92] and 56 [range, 41-80] vs. 21 [range, 11-40] mL/min/100 g, respectively) and total cerebral blood flow (85 [78-102] vs. 24 [18-41] and 50 [44-52] vs. 8 [5-23] mL/min/100 g, respectively). Spontaneous circulation was restored in eight of nine animals in the vasopressin group and in one of nine animals in the epinephrine group (p = .003). CONCLUSIONS: Compared with a maximum dose of epinephrine, vasopressin significantly increased left ventricular myocardial and total cerebral blood flow during CPR and return of spontaneous circulation in a porcine model of prolonged cardiac arrest with postcountershock pulseless electrical activity.

Effects of the specific bradycardic agent zatebradine on hemodynamic variables and myocardial blood flow during the early postresuscitation phase in pigs.

Cardiopulmonary resuscitation (CPR) leads to an excessive stimulation of the sympathetic nervous system that may result in tachycardia and malignant arrhythmias in the postresuscitation phase. The attenuation of this reaction by a specific bradycardic agent has not been compared to beta-blockade and placebo. After 4 min of ventricular fibrillation, and 3 min of CPR, 21 pigs were randomized to receive 45 microg/kg epinephrine in combination with either a specific bradycardic agent (0.5 mg/kg zatebradine; n = 7), or a beta-blocker (1 mg/kg esmolol; n = 7), or placebo (normal saline; n = 7). Two minutes after drug administration, defibrillation was performed to restore spontaneous circulation (ROSC). Hemodynamic variables, left ventricular contractility, right ventricular function, and myocardial blood flow were studied at prearrest, and for 3 h after ROSC. In comparison with esmolol and placebo, zatebradine resulted in a significant reduction in heart rate during the postresuscitation period, and reduced the number of premature ventricular contractions in the first 5 min after ROSC. This reduction in heart rate was associated with a significantly higher right ventricular ejection fraction, stroke volume, and endocardial/epicardial perfusion ratio at 5 min after ROSC. In comparison with placebo, esmolol administration decreased heart rate only moderately, but significantly reduced right ventricular stroke volume and cardiac output at 5 min after ROSC. Although only one dose and only one administration pattern of zatebradine has been investigated, we conclude that zatebradine administration during CPR effectively reduced heart rate without compromising myocardial contractility during the postresuscitation phase in pigs.

Vasopressin combined with epinephrine decreases cerebral perfusion compared with vasopressin alone during cardiopulmonary resuscitation in pigs.

BACKGROUND AND PURPOSE: It is unknown whether a combination of vasopressin and epinephrine may be superior to vasopressin alone by targeting both nonadrenergic and adrenergic receptors. METHODS: After 15 minutes of cardiac arrest (13 minutes of ventricular fibrillation and 2 minutes of pulseless electrical activity) and 3 minutes of chest compressions, 16 animals were randomly treated with either 0.8 U/kg vasopressin (n = 8) or 0.8 U/kg vasopressin combined with 200 microg/kg epinephrine (n = 8). RESULTS: Comparison of vasopressin with vasopressin and epinephrine at 90 seconds and 5 minutes after drug administration resulted in comparable mean (+/-SEM) coronary perfusion pressure (54+/-3 versus 57+/-5 and 36+/-4 versus 35+/-4 mm Hg, respectively), cerebral perfusion pressure (59+/-6 versus 65+/-8 and 40+/-6 versus 39+/-6 mm Hg, respectively), and median (25th to 75th percentiles) left ventricular myocardial blood flow [116 (81 to 143) versus 108 (97 to 125) and 44 (35 to 81) versus 62 (42 to 74) mL x min(-1) x 100 g(-1), respectively], but significantly increased (P<0.05) total cerebral blood flow [81 (77 to 95) versus 39 (34 to 58) and 50 (43 to 52) versus 28 (16 to 35) mL x min(-1) x 100 g(-1), respectively]. Return of spontaneous circulation rates in both groups were comparable (vasopressin, 7 of 8; vasopressin and epinephrine, 6 of 8). CONCLUSIONS: Comparison of vasopressin with vasopressin and epinephrine resulted in comparable left ventricular myocardial blood flow but significantly increased cerebral perfusion.