[Advanced vasodilatory shock. One-year survival after arginine vasopressin therapy]. / Fortgeschrittene vasodilatatorische Schockzustände. Einjahresüberleben nach Argininvasopressintherapie.

BACKGROUND: Arginine vasopressin (AVP) is increasingly being used to treat advanced vasodilatory shock states due to sepsis, systemic inflammatory response syndrome (SIRS) or after cardiac surgery. There are currently no data available on long-term survival. PATIENTS AND METHODS: Demographic and clinical data, length of intensive care unit (ICU) stay, 1-year survival and causes of death after ICU discharge of 201 patients who received AVP because of advanced vasodilatory shock were collected retrospectively. RESULTS: The intensive care unit (ICU) survival rate was 39.8% (80 out of 201 patients). After ICU discharge 13 out of the 80 patients died within 1 year resulting in a 1-year survival rate of 33.3% (67 out of 201 patients). In nine patients, the cause of death was attributed to the same disease that led to ICU admission. One-year survival of patients with shock following cardiac surgery (42.1%) was higher than in patients suffering from SIRS (22.6%, p=0.005) or sepsis (28.3%, p=0.06). CONCLUSIONS: If advanced vasodilatory shock can be reversed with AVP and patients can be discharged alive from the ICU, 1-year survival rates appear to be reasonable despite severe multi-organ dysfunction syndrome (MODS).

[Vasopressin as a rescue vasopressor agent. Treatment of selected cardiogenic shock states]. / Vasopressin als Reservevasopressor. Behandlung ausgewählter kardiogener Schockzustände.

Vasodilatory shock is the most common form of shock in the critically ill patient. As a consequence of overwhelming and prolonged mediator production, vasodilatory shock can be the common final pathway of primary non-vasodilatory shock (e.g. cardiogenic or hypovolemic shock). A supplementary infusion of arginine vasopressin (AVP) showed beneficial effects on hemodynamics and potentially on the outcome in patients with vasodilatory shock due to sepsis or after major surgery. In this case series, successful administration of AVP in three surgical patients with primary cardiogenic shock forms is reported. The hemodynamic effects of AVP were comparable to those AVP-induced alterations described in septic shock and seem to be predominantly mediated by potent vasoconstriction and the facilitated reduction of higher, potentially toxic catecholamine doses. Thus, an AVP-induced decrease in heart rate and pulmonary arterial pressures may be particularly beneficial in patients with impaired cardiac function.

Course of vasopressin and copeptin plasma concentrations in a patient with severe septic shock.

In this case report, the course of arginine vasopressin and copeptin, the stable C-terminal part of the arginine vasopressin precursor, is described during the period of critical illness in a septic shock patient. Arginine vasopressin and copeptin concentrations were substantially increased during the initial 36 hours of shock. Subsequently, both hormones continuously decreased, but exhibited another peak in response to stress during extubation. During restoration of cardiovascular stability, endogenous arginine vasopressin levels further decreased and obviously did not contribute to haemodynamic improvement. In contrast, the decrease in arginine vasopressin and copeptin can be at least partly explained by an improvement of cardiovascular function.

Vasopressin as adjunct vasopressor for vasodilatory shock due to non-occlusive mesenteric ischemia.

We present the case of an 83-year-old patient who underwent cardiac surgery and developed postoperative non-occlusive mesenteric ischemia (NOMI), which was treated with a local intra-arterial papaverine and prostaglandin E1 infusion. After successful mesenteric reperfusion, a multiple organ dysfunction syndrome with severe cardiovascular failure developed. High norepinephrine dosages (1.09 microg/kg body weight/min) and catecholamine-related complications (tachycardiac atrial fibrillation) required initiation of supplementary argininevasopressin (AVP) infusion (4 U/h). AVP stabilized vasodilatory shock, ensured adequate gut perfusion pressure and had no adverse clinical or angiographic effects on restitution of gut integrity. In conclusion, after reperfusion of NOMI in this patient, adjunct AVP therapy combined with local vasodilator infusion was beneficial as a potentially life-saving vasopressor.

[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.

Effects of epinephrine in a pig model of hypothermic cardiac arrest and closed-chest cardiopulmonary resuscitation combined with active rewarming.

OBJECTIVE: The aim of the current study was to assess the effects of epinephrine in a pig model of hypothermic cardiac arrest followed by closed-chest cardiopulmonary resuscitation combined with active rewarming, simulating the clinical management of an arrested hypothermic patient in a hospital without cardiopulmonary bypass facilities. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Twelve 12- to 16-week-old domestic pigs. INTERVENTIONS: Pigs were surface cooled to a body core temperature of 28 degrees C. After 4 min of untreated cardiac arrest, manual closed-chest CPR and thoracic lavage with 40 degrees C warmed fluid were started. After 3 min of external chest compression animals were randomly assigned to receive epinephrine (45, 45 and 200 microg/kg) or saline placebo in 5-min intervals. MEASUREMENTS AND MAIN RESULTS: Coronary perfusion pressure was about 15 mmHg in placebo group pigs. Coronary perfusion pressure was significantly higher after epinephrine, but restoration of spontaneous circulation was not more frequent (one of six epinephrine versus three of six saline placebo pigs, P=0.34). After 45 microg/kg epinephrine the arterial PO(2) was significantly lower when compared to the saline placebo. The third 200 microg/kg epinephrine dose resulted in a significantly enhanced mixed venous hypercarbic acidosis. CONCLUSIONS: After a short 4-min period of hypothermic cardiac arrest, epinephrine may not be necessary to maintain coronary perfusion pressure around the threshold usually correlating with successful defibrillation, even during prolonged closed-chest CPR combined with active rewarming. The enhanced mixed venous hypercarbic acidosis in epinephrine-treated animals may support the argument against repeated or high dose epinephrine administration during hypothermic 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.

Developing a vasopressor combination in a pig model of adult asphyxial cardiac arrest.

BACKGROUND: The purpose of this study was to investigate the effects of vasopressin versus epinephrine, and both drugs combined, in a porcine model of simulated adult asphyxial cardiac arrest. METHODS AND RESULTS: At approximately 7 minutes after the endotracheal tube had been clamped, cardiac arrest was present in 24 pigs and remained untreated for another 8 minutes. After 4 minutes of basic life support cardiopulmonary resuscitation, pigs were randomly assigned to receive, every 5 minutes, either epinephrine (45, 200, or 200 microgram/kg; n=6); vasopressin (0.4, 0.8, or 0.8 U/kg; n=6); or epinephrine combined with vasopressin (high-dose epinephrine/vasopressin combination, microgram/kg and U/kg: 45/0.4, 200/0.8, or 200/0.8; n=6; optimal-dose epinephrine/vasopressin combination, 45/0.4, 45/0.8, or 45/0.8; n=6). Mean+/-SEM coronary perfusion pressure was significantly (P<0.05) higher 90 seconds after high- or optimal-dose epinephrine/vasopressin combinations versus vasopressin alone and versus epinephrine alone (37+/-10 versus 25+/-7 versus 19+/-8 versus 6+/-3 mm Hg; 42+/-6 versus 40+/-5 versus 21+/-5 versus 14+/-6 mm Hg; and 39+/-6 versus 37+/-4 versus 9+/-3 versus 12+/-4 mm Hg, respectively). Six of 6 high-dose, 6 of 6 optimal-dose vasopressin/epinephrine combination, 0 of 6 vasopressin, and 1 of 6 epinephrine pigs had return of spontaneous circulation (P<0.05). CONCLUSIONS: Epinephrine combined with vasopressin, but not epinephrine or vasopressin alone, maintained elevated coronary perfusion pressure during cardiopulmonary resuscitation and resulted in significantly higher survival rates in this adult porcine asphyxial model.

The effects of different mouth-to-mouth ventilation tidal volumes on gas exchange during simulated rescue breathing.

UNLABELLED: The American Heart Association recommends tidal volumes of 700 to 1000 mL during mouth-to-mouth ventilation, but smaller tidal volumes of 500 mL may be of advantage to decrease the likelihood of stomach inflation. Because mouth-to-mouth ventilation gas contains only 17% oxygen, but 4% carbon dioxide, it is unknown whether 500-mL tidal volumes given during rescue breathing may result in insufficient oxygenation and inadequate carbon dioxide elimination. In a university hospital research laboratory, 20 fully conscious volunteer health care professionals were randomly assigned to breathe tidal volumes of 500 or 1000 mL of mouth-to-mouth ventilation gas (17% oxygen, 4% carbon dioxide, 79% nitrogen), or room air control (21% oxygen, 79% nitrogen) for 5 min. Arterial blood gases were taken immediately before, and after breathing 5 min of the experimental gas composition. When comparing 500 versus 1000 mL of mouth-to-mouth ventilation tidal volumes with 500 mL of room air, 500 mL of mouth-to-mouth ventilation tidal volume resulted in significantly (P < 0.05) lower mean +/- SEM arterial oxygen partial pressure (70 +/- 1 versus 85 +/- 2 versus 92 +/- 3 mm Hg, respectively), and lower oxygen saturation (94 +/- 0.4 versus 97 +/- 0.2 versus 98 +/- 0.2%), but increased arterial carbon dioxide partial pressure (46 +/- 1 versus 40 +/- 1 versus 39 +/- 1 mm Hg, respectively). Sixteen of 20 volunteers had to be excluded from the experiment with 500 mL of mouth-to-mouth ventilation gas after about 3 min instead of after 5 minutes as planned because of severe nervousness, sweating, and air hunger. We conclude that during simulated mouth-to-mouth ventilation, only large (approximately 1000 mL), but not small (approximately 500 mL) tidal volumes were able to maintain both sufficient oxygenation and adequate carbon dioxide elimination. IMPLICATIONS: To provide efficient mouth-to-mouth ventilation, it is important to administer tidal volumes of 1000 mL; tidal volumes of 500 mL were not adequate.

The efficacy of epinephrine or vasopressin for resuscitation during epidural anesthesia.

Cardiopulmonary resuscitation (CPR) during epidural anesthesia is considered difficult because of diminished coronary perfusion pressure. The efficacy of epinephrine and vasopressin in this setting is unknown. Therefore, we designed this study to assess the effects of epinephrine versus vasopressin on coronary perfusion pressure in a porcine model with and without epidural anesthesia and subsequent cardiac arrest. Thirty minutes before induction of cardiac arrest, 16 pigs received epidural anesthesia with bupivacaine while another 12 pigs received only saline administration epidurally. After 1 min of untreated ventricular fibrillation, followed by 3 min of basic life-support CPR, Epidural Animals and Control Animals randomly received every 5 min either epinephrine (45, 45, and 200 microg/kg) or vasopressin (0.4, 0.4, and 0.8 U/kg). During basic life-support CPR, mean +/- SEM coronary perfusion pressure was significantly lower after epidural bupivacaine than after epidural saline (13 +/- 1 vs 24 +/- 2 mm Hg, P < 0.05). Ninety seconds after the first drug administration, epinephrine increased coronary perfusion pressure significantly less than vasopressin in control animals without epidural block (42 +/- 2 vs 57 +/- 5 mm Hg, P < 0.05), but comparably to vasopressin after epidural block (45 +/- 4 vs 48 +/- 6 mm Hg). Defibrillation was attempted after 18 min of CPR. After return of spontaneous circulation, bradycardia required treatment in animals receiving vasopressin, especially with epidural anesthesia. Systemic acidosis was increased in animals receiving epinephrine than vasopressin, regardless of presence or absence of epidural anesthesia. We conclude that vasopressin may be a more desirable vasopressor for resuscitation during epidural block because the response to a single dose is longer lasting, and acidosis after multiple doses is less severe compared with epinephrine.

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.