Klaus Rheinberger

Arginine vasopressin, but not epinephrine, improves survival in uncontrolled hemorrhagic shock after liver trauma in pigs

ObjectiveEpinephrine is widely used for treatment of life-threatening hypotension, although new vasopressor drugs may merit evaluation. The purpose of this study was to determine the effects of vasopressin vs. epinephrine vs. saline placebo on hemodynamic variables, regional blood flow, and short-term survival in an animal model of uncontrolled hemorrhagic shock and delayed fluid resuscitation. DesignProspective, randomized, laboratory investigation that used a porcine model for measurement of hemodynamic variables and regional abdominal organ blood flow. SettingUniversity hospital laboratory. SubjectsA total of 21 pigs weighing 32 ± 3 kg. InterventionsThe anesthetized pigs were subjected to a penetrating liver injury, which resulted in a mean ± sem loss of 40% ± 5% of estimated whole blood volume within 30 mins and mean arterial pressures of <20 mm Hg. When heart rate declined progressively, pigs randomly received a bolus dose and continuous infusion of either vasopressin (0.4 units/kg and 0.04 units·kg−1·min−1, n = 7), or epinephrine (45 &mgr;g/kg and 5 &mgr;g·kg−1·min−1, n = 7), or an equal volume of saline placebo (n = 7), respectively. At 30 mins after drug administration, all surviving animals were fluid resuscitated while bleeding was surgically controlled. Measurements and Main ResultsMean ± sem arterial blood pressure at 2.5 and 10 mins was significantly (p < .001) higher after vasopressin vs. epinephrine vs. saline placebo (82 ± 14 vs. 23 ± 4 vs. 11 ± 3 mm Hg, and 42 ± 4 vs. 10 ± 5 vs. 6 ± 3 mm Hg, respectively). Although portal vein blood flow was temporarily impaired by vasopressin, it was subsequently restored and significantly (p < .01) higher when compared with epinephrine or saline placebo (9 ± 5 vs. 121 ± 3 vs. 54 ± 22 mL/min and 150 ± 20 vs. 31 ± 17 vs. 0 ± 0 mL/min, respectively). Hepatic and renal artery blood flow was significantly higher throughout the study in the vasopressin group; however, no further bleeding was observed. Despite a second bolus dose, all epinephrine- and saline placebo–treated animals died within 15 mins after drug administration. By contrast, seven of seven vasopressin-treated animals survived until fluid replacement, and 60 mins thereafter, without further vasopressor therapy (p < .01). Moreover, blood flow to liver, gut, and kidney returned to normal values in the postshock phase. ConclusionsVasopressin, but not epinephrine or saline placebo, improved short-term survival in a porcine model of uncontrolled hemorrhagic shock after liver injury when surgical intervention and fluid replacement was delayed.

Vasopressin, but Not Fluid Resuscitation, Enhances Survival in a Liver Trauma Model with Uncontrolled and Otherwise Lethal Hemorrhagic Shock in Pigs

Background: The authors compared the effects of vasopressin versus fluid resuscitation on survival in a liver trauma model with uncontrolled and otherwise lethal hemorrhagic shock in pigs. Methods: A midline laparotomy was performed on 23 domestic pigs, followed by an incision, and subsequent finger fraction across the right medial liver lobe. During hemorrhagic shock, animals were randomly assigned to receive either 0.4 U/kg vasopressin (n 9), or fluid resuscitation (n 7), or saline placebo (n 7), respectively. A continuous infusion of 0.08 U·k g 1 · min 1 vasopressin in the vasopressin group, or normal saline was subsequently administered in the fluid resuscitation and saline placebo group, respectively. After 30 min of experimental therapy, bleeding was controlled by surgical intervention, and blood transfusion and rapid fluid infusion were subsequently performed. Results: Maximum mean arterial blood pressure during experimental therapy in the vasopressin-treated animals was significantly higher than in the fluid resuscitation and saline placebo groups (mean SD, 72 26 vs. 38 16 vs. 11 7 mmHg, respectively; P < 0.05). Subsequently, mean arterial blood pressure remained at approximately 40 mmHg in all vasopressintreated animals, whereas mean arterial blood pressure in all fluid resuscitation and saline placebo pigs was close to aortic hydrostatic pressure (~15 mmHg) within approximately 20 min of experimental therapy initiation. Total blood loss was significantly higher in the fluid resuscitation pigs compared with vasopressin or saline placebo after 10 min of experimental therapy (65 6 vs. 42 4 vs. 43 6 ml/kg, respectively; P < 0.05). Seven of seven fluid resuscitation, and seven of seven saline placebo pigs died within approximately 20 min of experimental therapy, while 8 of 9 vasopressin animals survived more than 7 days (P < 0.05). Conclusions: Vasopressin, but not fluid resuscitation or saline placebo, ensured survival with full recovery in this liver trauma model with uncontrolled and otherwise lethal hemorrhagic shock in pigs.

Removal of CPR Artifacts From the Ventricular Fibrillation ECG by Adaptive Regression on Lagged Reference Signals

Removing cardiopulmonary resuscitation (CPR)-related artifacts from human ventricular fibrillation (VF) electrocardiogram (ECG) signals provides the possibility to continuously detect rhythm changes and estimate the probability of defibrillation success. This could reduce ldquohands-offrdquo analysis times which diminish the cardiac perfusion and deteriorate the chance for successful defibrillations. Our approach consists in estimating the CPR part of a corrupted signal by adaptive regression on lagged copies of a reference signal which correlate with the CPR artifact signal. The algorithm is based on a state-space model and the corresponding Kalman recursions. It allows for stochastically changing regression coefficients. The residuals of the Kalman estimation can be identified with the CPR-filtered ECG signal. In comparison with ordinary least-squares regression, the proposed algorithm shows, for low signal-to-noise ratio (SNR) corrupted signals, better SNR improvements and yields better estimates of the mean frequency and mean amplitude of the true VF ECG signal. The preliminary results from a small pool of human VF and animal asystole CPR data are slightly better than the results of comparable previous studies which, however, not only used different algorithms but also different data pools. The algorithm carries the possibility of further optimization.

The Prediction of Defibrillation Outcome Using a New Combination of Mean Frequency and Amplitude in Porcine Models of Cardiac Arrest

We estimated the predictive power with respect to defibrillation outcome of ventricular fibrillation (VF) mean frequency (FREQ), mean peak-to-trough amplitude (AMPL), and their combination. We examined VF electrocardiogram signals of 64 pigs from 4 different cardiac arrest models with different durations of untreated VF, different durations of cardiopulmonary resuscitation, and use of different drugs (epinephrine, vasopressin, N-nitro-l-arginine methyl ester, or saline placebo). The frequency domain was restricted to the range from 4.33 to 30 Hz. In the 10-s epoch between 20 and 10 s before the first defibrillation shock, FREQ and AMPL were estimated. We introduced the survival index (SI; 0.68 Hz−1 · FREQ + 12.69 mV−1 · AMPL) by use of multiple logistic regression. Kruskal-Wallis nonparametric one-way analysis was used to analyze the different porcine models for significant difference. The variables FREQ, AMPL, and SI were compared with defibrillation outcome by means of univariate logistic regression and receiver operating characteristic curves. SI increased predictive power compared with AMPL or FREQ alone, resulting in 89% sensitivity and 86% specificity. The probabilities of predicting defibrillation outcome for FREQ, AMPL, and SI were 0.85, 0.89 and 0.90, respectively. FREQ, AMPL, and SI values were not sensitive in regard to the four different cardiac arrest models but were significantly different for vasopressin and epinephrine animals.

A pilot study to evaluate the SMART BAG®: A new pressure-responsive, gas-flow limiting bag-valve-mask device

Reducing inspiratory flow rate and peak airway pressure may be important to minimize the risk of stomach inflation when ventilating an unprotected airway with positive pressure ventilation. In this study, we assessed the effects of a standard self-inflating bag compared with a new pressure-responsive, inspiratory gas flow-limiting device (SMART BAG®) on respiratory mechanics in 60 adult patients undergoing routine induction of anesthesia. Respiratory variables were measured using a pulmonary monitor. The SMART BAG® resulted in significantly decreased inspiratory flow rate and peak airway pressure while providing adequate tidal volume delivery.

Algorithms to analyze ventricular fibrillation signals.

Prediction of the success of defibrillation to avoid myocardial injury and performance feedback during CPR requires algorithms to analyze ventricular fibrillation signals. This report reviews investigations on different parameters of ventricular fibrillation electrocardiographic signals, including amplitude, frequency, bispectral analysis, amplitude spectrum area, wavelets, nonlinear dynamics, N(&agr;) histograms, and combinations of several of these parameters. To date, no satisfactory methods have been found that cope with CPR artifacts and show adequate predictive power of successful defibrillation. The usual limitations of the studies are the small number of subjects, which precludes separation into training and test data. Because many investigations are animal studies of untreated short ventricular fibrillation, the results may be different for prolonged ventricular fibrillation in humans. The universality of threshold values has to be examined, and promising new parameters have to be monitored over longer time periods and analyzed for the effects of chest compressions, ventilation, and concomitant vasopressor therapy.

Decreasing peak flow rate with a new bag-valve-mask device: effects on respiratory mechanics, and gas distribution in a bench model of an unprotected airway.

Reducing inspiratory flow rate and peak airway pressure may be important in order to minimise the risk of stomach inflation when ventilating an unprotected airway with positive pressure ventilation. The purpose of this study was to assess the effects of a newly developed bag-valve-mask device (SMART BAG), O-Two Systems International, Ont., Canada) that limits peak inspiratory flow. A bench model simulating a patient with an unintubated airway was used consisting of a face mask, manikin head, training lung (lung compliance, 100 ml/cm H(2)O, airway resistance 4 cm H(2)O/l/s, lower oesophageal sphincter pressure 20 cm H(2)O and simulated stomach). Twenty nurses were randomised to each ventilate the manikin using a standard single person technique for 1 min (respiratory rate, 12/min) with either a standard adult self-inflating bag, or the SMART BAG. The volunteers were blinded to the experimental design of the model until completion of the experimental protocol. The SMART BAG vs. standard self-inflating bag resulted in significantly (P<0.05) lower mean+/-S.D. peak inspiratory flow rates (32+/-2 vs. 61+/-13 l/min), peak inspiratory pressure (12+/-2 vs. 17+/-2 cm H(2)O), lung tidal volumes (525+/-111 vs. 680+/-154 ml) and stomach tidal volumes (0+/-0 vs. 17+/-36 ml), longer inspiratory times (1.9+/-0.3 vs. 1.5+/-0.3 s), but significantly higher mask leakage (26+/-13 vs. 14+/-8%); mask tidal volumes (700+/-104 vs. 785+/-172 ml) were comparable. The mask leakage observed is not an uncommon factor in bag-valve-mask ventilation with leakage fractions of 25-40% having been previously reported. The differences observed between the standard BVM and the SMART BAG are due more to the anatomical design of the mask and the non-anatomical shape of the manikin face than the function of the device. Future studies should remove the mask to manikin interface and should introduce a standardized mask leakage fraction. The use of a two-person technique may have removed the problem of mask leakage. In conclusion, using the SMART BAG during simulated ventilation of an unintubated patient in respiratory arrest significantly decreased inspiratory flow rate, peak inspiratory pressure, stomach tidal volume, and resulted in a significantly longer inspiratory time when compared to a standard self-inflating bag.

Optimizing bag-valve-mask ventilation with a new mouth-to-bag resuscitator

When ventilating an unintubated patient with a self-inflating bag, high peak inspiratory flow rates may result in high peak airway pressure with subsequent stomach inflation; this may occur frequently when rescuers without daily experience in bag-valve-mask ventilation need to perform advanced airway management. The purpose of this study was to assess the effects of a newly developed self-inflating bag (mouth-to-bag resuscitator; Ambu, Glostrup, Denmark) that limits peak inspiratory flow. A bench model simulating a patient with an unintubated airway was used, consisting of a face mask, manikin head, training lung (lung compliance, 100 ml/0.098 kPa (100 ml/cm H(2)O)); airway resistance, 0.39 kPa/l per second (4 cm H(2)O/l/s), oesophagus (LESP, 1.96 kPa (20 cm H(2)O)) and simulated stomach. Twenty nurses were randomised to ventilate the manikin for 1 min (respiratory rate: 12 per minute) with either a standard self-inflating bag or the mouth-to-bag resuscitator, which requires the rescuer to blow up a single-use balloon inside the self-inflating bag, which in turns displaces air towards the patient. When supplemental oxygen is added, ventilation with up to 100% oxygen may be obtained, since expired air is only used as the driving gas. The mouth-to-bag resuscitator therefore allows two instead of one hand sealing the mask on the patients face. The volunteers were blinded to the experimental design of the model until completion of the experimental protocol. The mouth-to-bag resuscitator versus standard self-inflating bag resulted in significantly (P<0.05) higher mean+/-S.D. mask tidal volumes (1048+/-161 vs. 785+/-174 ml) and lung tidal volumes (911+/-148 vs. 678+/-157 ml), longer inspiratory times (1.7+/-0.4 vs. 1.4+/-0.4 s), but significantly lower peak inspiratory flow rates (50+/-9 vs. 62+/-13 l/min) and mask leakage (10+/-4 vs. 15+/-9%); peak inspiratory pressure (17+/-2 vs. 17+/-2 cm H(2)O) and stomach tidal volumes (16+/-30 vs. 18+/-35 ml) were comparable. In conclusion, employing the mouth-to-bag resuscitator during simulated ventilation of an unintubated patient in respiratory arrest significantly decreased inspiratory flow rate and improved lung tidal volumes, while decreasing mask leakage.

The effects of nifedipine on ventricular fibrillation mean frequency in a porcine model of prolonged cardiopulmonary resuscitation.

We assessed the effects of a calcium channel blocker versus saline placebo on ventricular fibrillation mean frequency and hemodynamic variables during prolonged cardiopulmonary resuscitation (CPR). Before cardiac arrest, 10 animals were randomly assigned to receive either nifedipine (0.64 mg/kg; n = 5) or saline placebo (n = 5) over 10 min. Immediately after drug administration, ventricular fibrillation was induced. After 4 min of cardiac arrest and 18 min of basic life support CPR, defibrillation was attempted. Ninety seconds after the induction of cardiac arrest, ventricular fibrillation mean frequency was significantly (P < 0.01) increased in nifedipine versus placebo pigs (mean ± sd: 12.4 ± 2.1 Hz versus 8 ± 0.7 Hz). From 2 to 18.5 min after the induction of cardiac arrest, no differences in ventricular fibrillation mean frequency were detected between groups. Before defibrillation, ventricular fibrillation mean frequency was significantly (P < 0.05) increased in nifedipine versus placebo animals (9.7 ± 1.2 Hz versus 7.1 ± 1.3 Hz). Coronary perfusion pressure was significantly lower in the nifedipine than in the placebo group from the induction of ventricular fibrillation to 11.5 min of cardiac arrest; no animal had a return of spontaneous circulation after defibrillation. In conclusion, nifedipine, but not saline placebo, prevented a rapid decrease of ventricular fibrillation mean frequency after the induction of cardiac arrest and maintained ventricular fibrillation mean frequency at ∼10 Hz during prolonged CPR; this was nevertheless associated with no defibrillation success.

Time of arrival from Bohmian flow

We develop a new conception for the quantum mechanical arrival time distribution from the perspective of Bohmian mechanics. A detection probability for detectors sensitive to quite arbitrary spacetime domains is formulated. Basic positivity and monotonicity properties are established. We show that our detection probability improves and generalizes an earlier proposal by Leavens and McKinnon. The difference between the two notions is illustrated through application to a free wavepacket.