Volker Wenzel

Thrombolysis during resuscitation for out-of-hospital cardiac arrest.

BACKGROUND Approximately 70% of persons who have an out-of-hospital cardiac arrest have underlying acute myocardial infarction or pulmonary embolism. Therefore, thrombolysis during cardiopulmonary resuscitation may improve survival. METHODS In a double-blind, multicenter trial, we randomly assigned adult patients with witnessed out-of-hospital cardiac arrest to receive tenecteplase or placebo during cardiopulmonary resuscitation. Adjunctive heparin or aspirin was not used. The primary end point was 30-day survival; the secondary end points were hospital admission, return of spontaneous circulation, 24-hour survival, survival to hospital discharge, and neurologic outcome. RESULTS After blinded review of data from the first 443 patients, the data and safety monitoring board recommended discontinuation of enrollment of asystolic patients because of low survival, and the protocol was amended. Subsequently, the trial was terminated prematurely for futility after enrolling a total of 1050 patients. Tenecteplase was administered to 525 patients and placebo to 525 patients; the two treatment groups had similar clinical profiles. We did not detect any significant differences between tenecteplase and placebo in the primary end point of 30-day survival (14.7% vs. 17.0%; P=0.36; relative risk, 0.87; 95% confidence interval, 0.65 to 1.15) or in the secondary end points of hospital admission (53.5% vs. 55.0%, P=0.67), return of spontaneous circulation (55.0% vs. 54.6%, P=0.96), 24-hour survival (30.6% vs. 33.3%, P=0.39), survival to hospital discharge (15.1% vs. 17.5%, P=0.33), or neurologic outcome (P=0.69). There were more intracranial hemorrhages in the tenecteplase group. CONCLUSIONS When tenecteplase was used without adjunctive antithrombotic therapy during advanced life support for out-of-hospital cardiac arrest, we did not detect an improvement in outcome, in comparison with placebo. (ClinicalTrials.gov number, NCT00157261.)

Vasopressin and Epinephrine vs. Epinephrine Alone in Cardiopulmonary Resuscitation

BACKGROUND During the administration of advanced cardiac life support for resuscitation from cardiac arrest, a combination of vasopressin and epinephrine may be more effective than epinephrine or vasopressin alone, but evidence is insufficient to make clinical recommendations. METHODS In a multicenter study, we randomly assigned adults with out-of-hospital cardiac arrest to receive successive injections of either 1 mg of epinephrine and 40 IU of vasopressin or 1 mg of epinephrine and saline placebo, followed by administration of the same combination of study drugs if spontaneous circulation was not restored and subsequently by additional epinephrine if needed. The primary end point was survival to hospital admission; the secondary end points were return of spontaneous circulation, survival to hospital discharge, good neurologic recovery, and 1-year survival. RESULTS A total of 1442 patients were assigned to receive a combination of epinephrine and vasopressin, and 1452 to receive epinephrine alone. The treatment groups had similar baseline characteristics except that there were more men in the group receiving combination therapy than in the group receiving epinephrine alone (P=0.03). There were no significant differences between the combination-therapy and the epinephrine-only groups in survival to hospital admission (20.7% vs. 21.3%; relative risk of death, 1.01; 95% confidence interval [CI], 0.97 to 1.05), return of spontaneous circulation (28.6% vs. 29.5%; relative risk, 1.01; 95% CI, 0.97 to 1.06), survival to hospital discharge (1.7% vs. 2.3%; relative risk, 1.01; 95% CI, 1.00 to 1.02), 1-year survival (1.3% vs. 2.1%; relative risk, 1.01; 95% CI, 1.00 to 1.02), or good neurologic recovery at hospital discharge (37.5% vs. 51.5%; relative risk, 1.29; 95% CI, 0.81 to 2.06). CONCLUSIONS As compared with epinephrine alone, the combination of vasopressin and epinephrine during advanced cardiac life support for out-of-hospital cardiac arrest does not improve outcome. (ClinicalTrials.gov number, NCT00127907.)

Repeated Administration of Vasopressin but Not Epinephrine Maintains Coronary Perfusion Pressure After Early and Late Administration During Prolonged Cardiopulmonary Resuscitation in Pigs

BACKGROUND It is unknown whether repeated dosages of vasopressin or epinephrine given early or late during basic life support cardiopulmonary resuscitation (CPR) may be able to increase coronary perfusion pressure above a threshold between 20 and 30 mm Hg that renders defibrillation successful. METHODS AND RESULTS After 4 minutes of cardiac arrest, followed by 3 minutes of basic life support CPR, 12 animals were randomly assigned to receive, every 5 minutes, either vasopressin (early vasopressin: 0.4, 0.4, and 0.8 U/kg, respectively; n=6) or epinephrine (early epinephrine: 45, 45, and 200 microg/kg, respectively; n=6). Another 12 animals were randomly allocated after 4 minutes of cardiac arrest, followed by 8 minutes of basic life support CPR, to receive, every 5 minutes, either vasopressin (late vasopressin: 0.4 and 0.8 U/kg, respectively; n=6), or epinephrine (late epinephrine: 45 and 200 microg/kg, respectively; n=6). Defibrillation was attempted after 22 minutes of cardiac arrest. Mean+/-SEM coronary perfusion pressure was significantly higher 90 seconds after early vasopressin compared with early epinephrine (50+/-4 versus 34+/-3 mm Hg, P<0.02; 42+/-5 versus 15+/-3 mm Hg, P<0.0008; and 37+/-5 versus 11+/-3 mm Hg, P<0. 002, respectively). Mean+/-SEM coronary perfusion pressure was significantly higher 90 seconds after late vasopressin compared with late epinephrine (40+/-3 versus 22+/-4 mm Hg, P<0.004, and 32+/-4 versus 15+/-4 mm Hg, P<0.01, respectively). All vasopressin animals survived 60 minutes, whereas no epinephrine pig had return of spontaneous circulation (P<0.05). CONCLUSIONS Repeated administration of vasopressin but only the first epinephrine dose given early and late during basic life support CPR maintained coronary perfusion pressure above the threshold that is needed for successful defibrillation.

Cardiac arrest : the science and practice of resuscitation medicine

Part I. Introduction Part II. Basic Science Part IV. The Pathophysiology of Global Ischemia and Reperfusion Part V. Perfusion Pressures Part VI. Therapy of Sudden Death Part VII. External Chest Compression Part VIII. Vasopressor Therapy During Cardiac Arrest Part IX. Postresuscitation Disease and its Care Part X. Special Resuscitation Circumstances Part XI. Special Issues in Resuscitation.

The laryngeal tube: a new simple airway device.

T he face mask, laryngeal mask, and the Combitube (Tyco Healthcare/Sheridan, Argyle, NY) are devices commonly used to ventilate the lungs of nonintubated patients (1,2), but some disadvantages may result in inadvertent ventilation-associated complications. For example, the face mask is associated with large dead space ventilation, leakage, and gastric inflation (3). In contrast, the laryngeal mask is an alternative airway adjunct that is simple to use, resulting in both minimal dead space ventilation and gastric inflation (4,5). Nevertheless, a possible limiting feature of the laryngeal mask may be the risk of aspirating gastric contents (6) because fiberoptic studies have found 6%–9% visualization of the esophagus (7,8). Although the Combitube was developed as an alternative to endotracheal intubation to secure the airway in an emergency setting, its complex structure requires extensive instruction and training to ensure correct placement within an acceptable time (9). The purpose of this study was to assess whether the newly developed Laryngeal Tube (VBM Medizintechnik GmbH, Sulz, Germany), somewhat a single-lumen, shortened Combitube, can provide sufficient ventilation and adequate oxygenation in patients undergoing routine induction of anesthesia.

Influence of tidal volume on the distribution of gas between the lungs and stomach in the nonintubated patient receiving positive-pressure ventilation.

Abstract Objectives: When ventilating a nonintubated patient in cardiac arrest, the European Resuscitation Council has recently recommended a decrease in the tidal volume from 0.8 to 1.2 L to 0.5 L, partly in an effort to decrease peak flow rate, and therefore, to minimize stomach inflation. The purpose of the present study was to examine the validity of the European Resuscitation Councils recommendation in terms of gas distribution between lungs and stomach in a bench model that simulates ventilation of a nonintubated patient with a self‐inflatable bag representing tidal volumes of 0.5 and 0.75 L. Design: A bench model of a patient with a nonintubated airway was used consisting of face mask, manikin head, training lung (lung compliance, 50 mL/cm H2 O; airway resistance, 5 cm H2 O/L/sec), adjustable lower esophageal sphincter pressure (LESP) and simulated stomach. Setting: University hospital laboratory. Subjects: Thirty healthcare professionals. Interventions: Healthcare professionals performed 1‐min bag‐mask ventilation at each LESP level of 5, 10, and 15 cm H2 O at a rate of 12 breaths/min, using an adult and pediatric self‐inflating bag, respectively. Volunteers were blinded to the LESP, which was randomly varied. Measurements and Main Results: Both types of self‐inflating bags induced stomach inflation, with higher stomach and lower lung tidal volumes when the LESP was decreased. Lung tidal volume with the pediatric bag was significantly (p < .05) lower at all LESP levels when compared with the adult bag, and ranged between 240 mL at an LESP of 15 cm H2 O and 120 mL at an LESP of 5 cm H2 O. Stomach tidal volume with the adult bag ranged between 250 mL at an LESP of 15 cm H2 O and increased to 550 mL at an LESP of 5 cm H2 O. Stomach tidal volume with the pediatric bag was significantly lower (p < .05) at all LESP levels when compared with the adult bag and ranged between 70 mL at an LESP of 15 cm H2 O and 300 mL at an LESP of 5 cm H2 O. Conclusions: Our data support the recommendation of the European Resuscitation Council to decrease tidal volumes to 0.5 L when ventilating a cardiac arrest victim with an unprotected airway. A small tidal volume may be a better trade‐off in the basic life support phase, as this may provide reasonable ventilation while avoiding massive stomach inflation. (Crit Care Med 1998; 26:364‐368) When ventilating a nonintubated cardiac arrest patient, the European Resuscitation Council has recently recommended a decrease in the tidal volume from 0.8 to 1.2 L [1] to 0.5 L [2], partly in an effort to decrease peak flow rate, and therefore, to minimize stomach inflation. Ventilation volume has an effect on pH, CO2 elimination, and oxygenation when pulmonary blood flow is extremely low, such as during cardiopulmonary resuscitation (CPR) or shock [3]. The Airway and Ventilation Management Working Group of the European Resuscitation Council [2] stated that ventilating a nonintubated cardiac arrest patient with a smaller tidal volume may be a better trade‐off in order to provide reasonable ventilation, while avoiding massive stomach inflation that may result in life‐threatening pulmonary complications. The gas distribution between lungs and stomach during positive‐pressure ventilation in a nonintubated airway depends on patient characteristics (lower esophageal sphincter pressure [LESP], airway resistance, and respiratory system compliance) and performance variables of the rescuer applying positive‐pressure ventilation (tidal volume, peak flow rate, and upper airway pressure). Thus, assessing the above‐mentioned recommendation in a clinical study is difficult to perform due to many confounding variables that are difficult to control and to evaluate when emergently managing therapy during CPR. As an example of the usefulness of laboratory models of ventilation, the American Heart Association [1] recommended increasing inspiratory time when ventilating a nonintubated cardiac arrest patient [1,4]. For example, such a model has the advantage that each variable of respiratory mechanics can be controlled and adjusted to investigate a certain hypothesis. We [4,5] previously studied the effect of tidal volume and peak flow rate on gas distribution between lungs and stomach during mechanical positive‐pressure ventilation, using a modification of the earlier described bench model of an unprotected airway. Although a mechanical ventilator is a valuable tool to study gas distribution in an unprotected airway, a self‐inflatable bag is the device usually used by the emergency medical service and in the hospital during the initial care of a cardiac arrest victim. Thus, the purpose of the present study was to examine the validity of the European Resuscitation Council recommendation [2] in terms of gas distribution between lungs and stomach in a bench model that simulates positive‐pressure ventilation of a nonintubated patient with self‐inflatable bags representing tidal volumes of 0.5 L and 0.75 L. Since observations in an animal model [6] showed that the LESP decreases rapidly after an untreated cardiac arrest, we further evaluated the effect of a decreased LESP on gas distribution between lungs and stomach in this model.

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.

Survival with full neurologic recovery and no cerebral pathology after prolonged cardiopulmonary resuscitation with vasopressin in pigs

OBJECTIVES We sought to determine the effects of vasopressin and saline placebo in comparison with epinephrine on neurologic recovery and possible cerebral pathology in an established porcine model of prolonged cardiopulmonary resuscitation (CPR). BACKGROUND It is unknown whether increased cerebral blood flow during CPR with vasopressin is beneficial with regard to neurologic recovery or detrimental owing to complications such as cerebral edema after return of spontaneous circulation. METHODS After 4 min of cardiac arrest, followed by 3 min of basic life support CPR, 17 animals were randomly assigned to receive every 5 min either vasopressin (0.4, 0.4 and 0.8 U/kg; n = 6), epinephrine (45, 45 and 200 microg/kg; n = 6) or saline placebo (n = 5). The mean value +/- SEM of aortic diastolic pressure was significantly (p < 0.05) higher 90 s after each of three vasopressin versus epinephrine versus saline placebo injections (60 +/- 3 vs. 45 +/- 3 vs. 29 +/- 2 mm Hg; 49 +/- 5 vs. 27 +/- 3 vs. 23 +/- 1 mm Hg; and 50 +/- 6 vs. 21 +/- 3 vs. 16 +/- 3 mm Hg, respectively). After 22 min of cardiac arrest, including 18 min of CPR, defibrillation was attempted to achieve return of spontaneous circulation. RESULTS All the pigs that received epinephrine and saline placebo died, whereas all pigs on vasopressin survived (p < 0.05). Neurologic evaluation 24 h after successful resuscitation revealed only an unsteady gait in all vasopressin-treated animals; after 96 h, magnetic resonance imaging revealed no cerebral pathology. CONCLUSIONS During prolonged CPR, repeated vasopressin administration, but not epinephrine or saline placebo, ensured long-term survival with full neurologic recovery and no cerebral pathology in this porcine CPR model.

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.

Improving Standard Cardiopulmonary Resuscitation with an Inspiratory Impedance Threshold Valve in a Porcine Model of Cardiac Arrest

To improve the efficiency of standard cardiopulmonary resuscitation (CPR), we evaluated the potential value of impeding respiratory gas exchange selectively during the decompression phase of standard CPR in a porcine model of ventricular fibrillation. After 6 min of untreated cardiac arrest, anesthetized farm pigs weighing 30 kg were randomized to be treated with either standard CPR with a sham valve (n = 11) or standard CPR plus a functional inspiratory impedance threshold valve (ITV™) (n = 11). Coronary perfusion pressure (CPP) (diastolic aortic minus right atrial pressure) was the primary endpoint. Vital organ blood flow was assessed with radiolabeled microspheres after 6 min of CPR, and defibrillation was attempted 11 min after starting CPR. After 2 min of CPR, mean ± sem CPP was 14 ± 2 mm Hg with the sham valve versus 20 ± 2 mm Hg in the ITV group (P < 0.006). Significantly higher CPPs were maintained throughout the study when the ITV was used. After 6 min of CPR, mean ± sem left ventricular and global cerebral blood flows were 0.10 ± 0.03 and 0.19 ± 0.03 mL · min−1 · g−1 in the Control group versus 0.19 ± 0.03 and 0.26 ± 0.03 mL · min−1 · g−1 in the ITV group, respectively (P < 0.05). Fifteen minutes after successful defibrillation, 2 of 11 animals were alive in the Control group versus 6 of 11 in the ITV group (not significant). In conclusion, use of an inspiratory impedance valve during standard CPR resulted in a marked increase in CPP and vital organ blood flow after 6 min of cardiac arrest.