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 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 x kg(-1) x 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 vasopressin-treated animals, whereas mean arterial blood pressure in all fluid resuscitation and saline placebo pigs was close to aortic hydrostatic pressure (approximately 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.     

Treatment of uncontrolled hemorrhagic shock after liver trauma: fatal effects of fluid resuscitation versus improved outcome after vasopressin

In a porcine model of uncontrolled hemorrhagic shock, we evaluated the effects of vasopressin versus an equal volume of saline placebo versus fluid resuscitation on hemodynamic variables and short-term survival. Twenty-one anesthetized pigs were subjected to severe liver injury. When mean arterial blood pressure was <20 mm Hg and heart rate decreased, pigs randomly received either vasopressin IV (0.4 U/kg; n = 7), an equal volume of saline placebo (n = 7), or fluid resuscitation (1000 mL each of lactated Ringer's solution and hetastarch; n = 7). Thirty minutes after intervention, surviving pigs were fluid resuscitated while bleeding was surgically controlled. Mean (+/- SEM) arterial blood pressure 5 min after the intervention was significantly (P < 0.05) higher after vasopressin than with saline placebo or fluid resuscitation (58 +/- 9 versus 7 +/- 3 versus 32 +/- 6 mm Hg, respectively). Vasopressin improved abdominal organ blood flow but did not cause further blood loss (vasopressin versus saline placebo versus fluid resuscitation 10 min after intervention, 1343 +/- 60 versus 1350 +/- 22 versus 2536 +/- 93 mL, respectively; P < 0.01). Seven of 7 vasopressin pigs survived until bleeding was controlled and 60 min thereafter, whereas 7 of 7 saline placebo and 7 of 7 fluid resuscitation pigs died (P < 0.01). We conclude that vasopressin, but not saline placebo or fluid resuscitation, significantly improves short-term survival during uncontrolled hemorrhagic shock. IMPLICATIONS: Although IV fluid administration is the mainstay of nonsurgical management of trauma patients with uncontrolled hemorrhagic shock, the efficacy of this strategy has been discussed controversially. In this animal model of severe liver trauma with uncontrolled hemorrhagic shock, vasopressin, but not saline placebo or fluid resuscitation, improved short-term survival.     

Endobronchial Vasopressin Improves Survival during Cardiopulmonary Resuscitation in Pigs

Background: Intravenous administration of vasopressin during cardiopulmonary resuscitation (CPR) has been shown to be more effective than optimal doses of epinephrine. This study evaluated the effect of endobronchial vasopressin during CPR.

Methods: After 4 min of untreated ventricular fibrillation and 3 min of CPR, 21 pigs were randomized to be treated with 0.8 U/kg intravenous vasopressin (n = 7), 0.8 U/kg endobronchial vasopressin (n = 9), or an endobronchial placebo of normal saline (n = 5). Defibrillation was performed 5 min after drug administration to attempt return of spontaneous circulation.

Results: All animals in the intravenous and endobronchial vasopressin group were resuscitated successfully, but only two of five animals in the placebo group were. At 2 and 5 min after drug administration, coronary perfusion pressure in the intravenous and endobronchial vasopressin group was significantly higher than in the placebo group (50 +/- 10, 34 +/- 5 vs. 16 +/- 6 mmHg, respectively; and 35 +/- 10, 39 +/- 10 vs. 19 +/- 5 mmHg, respectively; P < 0.05).     

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.     

Vasopressin improves survival after cardiac arrest in hypovolemic shock

Survival after hypovolemic shock and cardiac arrest is dismal with current therapies. We evaluated the potential benefits of vasopressin versus large-dose epinephrine in hemorrhagic shock and cardiac arrest on vital organ perfusion, and the likelihood of resuscitation. In 18 pigs, 35% of the estimated blood volume was withdrawn over 15 min and ventricular fibrillation was induced 5 min later. After 4 min of cardiac arrest and 4 min of standard cardiopulmonary resuscitation, a bolus dose of either 200 microg/kg epinephrine (n = 7), 0.8 unit/kg vasopressin (n = 7), or saline placebo (n = 4) was administered in a blinded, randomized manner. Defibrillation was attempted 2.5 min after drug administration, and all animals were subsequently observed for 1 h without further intervention. Spontaneous circulation was restored in 7 of 7 vasopressin animals, in 6 of 7 epinephrine pigs, and in 0 of 4 placebo swine. At 5 and 30 min after return of spontaneous circulation, median (minimum and maximum) renal blood flow after epinephrine was 2 (0-31), and 2 (0-48) mL. 100 g(-1). min(-1), respectively; and after vasopressin 96 (12-161), and 44 (16-105) mL. 100 g(-1). min(-1), respectively (P: <.01 between groups). Epinephrine animals developed a profound metabolic acidosis by 15 min after return of spontaneous circulation (mean arterial pH, 7.11 +/- 0.01), and by 60 min all epinephrine-treated animals had died. The vasopressin pigs had (P: = 0.015) less acidosis (pH = 7.26+/-0. 04) at corresponding time points, and all survived > or =55 min (P: < 0. 01). In conclusion, treatment of hypovolemic cardiac arrest with vasopressin, but not with large-dose epinephrine or saline placebo, resulted in sustained vital organ perfusion, less metabolic acidosis, and prolonged survival. Based on these findings, clinical evaluation of vasopressin during hypovolemic cardiac arrest may be warranted. IMPLICATIONS: The chances of surviving cardiac arrest in hemorrhagic shock are considered dismal without adequate fluid replacement. However, treatment of hypovolemic cardiac arrest with vasopressin, but not with large-dose epinephrine or saline placebo, resulted in sustained vital organ perfusion and prolonged survival in an animal model of suspended infusion therapy.     

Neither vasopressin nor amiodarone improve CPR outcome in an animal model of hypothermic cardiac arrest

BACKGROUND: Aim of this experimental animal study was to investigate the influence of vasopressin and amiodarone on cardiopulmonary resuscitation (CPR) outcome in a pig model of hypothermic cardiac arrest. METHODS: After surface cooling to a core temperature of 26 degrees C, ventricular fibrillation was induced in 14 12-16-week-old domestic pigs. After 15 min of untreated cardiac arrest, a manual closed chest CPR was started and pigs were randomly assigned to two treatment groups: Group 1 pigs (n = 7) received vasopressin 0.4 U kg-1 as initial drug therapy, followed by a combination vasopressin (0.4 U kg-1) and amiodarone (4 mg kg-1) as subsequent drug therapy. Subsequent drug therapy was administered in animals without permanent restoration of spontaneous circulation after a first series of electrical countershocks 10 min after drug administration. Group 2 pigs (n = 7) received saline placebo as initial drug therapy and saline placebo and amiodarone (4 mg kg-1) as subsequent drug therapy. RESULTS: Vasopressin significantly increased coronary perfusion pressure and defibrillation success (successful defibrillation in five of seven Group 1 vs. none of seven Group 2 pigs, P = 0.02). Due to refibrillation within 30-150 s, the 60-min survival rate was not improved by vasopressin. Subsequent drug therapy with amiodarone had no further effect on defibrillation success or the refibrillation rate. CONCLUSIONS: Data from this experimental animal model suggest that vasopressin and amiodarone may not be beneficial for treatment of ventricular fibrillation associated with severe hypothermia when concomitant measures at core rewarming are not applied.     

Survival with full neurologic recovery after prolonged cardiopulmonary resuscitation with a combination of vasopressin and epinephrine in pigs

We sought to determine the effects of a combination of vasopressin and epinephrine on neurologic recovery in comparison with epinephrine alone and saline placebo alone in an established porcine model of prolonged cardiopulmonary resuscitation (CPR). 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 a combination of vasopressin and epinephrine (vasopressin [IU/kg]/epinephrine [ micro g/kg]: 0.4/45, 0.4/45, and 0.8/45; n = 6), epinephrine alone (45, 45, and 200 micro g/kg; n = 6), or saline placebo alone (n = 5). After 22 min of cardiac arrest, including 18 min of CPR, defibrillation was attempted to achieve the return of spontaneous circulation. Aortic diastolic pressure was significantly (P < 0.01) increased 90 s after each of 3 vasopressin/epinephrine injections versus epinephrine alone versus saline placebo alone (mean +/- SEM: 69 +/- 3 mm Hg versus 45 +/- 3 mm Hg versus 29 +/- 2 mm Hg, 63 +/- 4 mm Hg versus 27 +/- 3 mm Hg versus 23 +/- 1 mm Hg, and 52 +/- 4 mm Hg versus 21 +/- 3 mm Hg versus 16 +/- 3 mm Hg, respectively). Spontaneous circulation was restored in six of six vasopressin/epinephrine pigs, whereas six of six epinephrine and five of five saline placebo pigs died (P < 0.01). Neurologic evaluation 24 h after successful resuscitation revealed only an unsteady gait and was normal 5 days after the experiment in all vasopressin/epinephrine-treated animals. In conclusion, in this porcine model of prolonged CPR, repeated vasopressin/epinephrine administration, but not epinephrine or saline placebo alone, ensured long-term survival with full neurologic recovery. IMPLICATIONS: We present a study to evaluate the effects of a combination of vasopressin and epinephrine during prolonged cardiopulmonary resuscitation on neurological outcome in pigs. We found that all pigs treated with a combination of vasopressin and epinephrine could be resuscitated and had full neurologic recovery observed over an entire period of 5 days.     

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.     

Effects of arginine vasopressin on oxygenation and haemodynamics during one-lung ventilation in an animal model

In a case of arterial hypotension during one-lung ventilation, haemodynamic support may be required to maintain adequate mean arterial pressure. Arginine vasopressin, a potent systemic vasoconstrictor with limited effects on the pulmonary artery pressure, has not been studied in this setting. Twelve female pigs were anaesthetised and ventilated and arterial, central venous and pulmonary artery catheters were inserted. A left-sided double lumen tube was placed via tracheostomy and one-lung ventilation was initiated. The animals were in the left lateral position, with the left lung ventilated and right lung collapsed. Respiratory and haemodynamic values were recorded before and during a continuous infusion of arginine vasopressin sufficient to double the mean arterial pressure. The arginine vasopressin caused a decrease in cardiac output (3.8+/-1.1 vs. 2.7+/-0.7 l/min, P <0.001) and mixed-venous oxygen tension (39.1+/-5.8 vs. 34.4+/-5 mmHg, P=0.003). Pulmonary artery pressure was unchanged (24+/-2 vs. 24+/-3 mmHg, P=0.682). There was no effect of the arginine vasopressin on arterial oxygen tension (226+/-106 vs. 231+/-118 mmHg, P=0.745). However, there was a significant decrease in shunt fraction (28.3+/-6.2 vs. 24.3+/-7.8%, P=0.043) and a significant proportional increase in perfusion of the ventilated lung (78.8+/-9.5 vs. 85.5+/-7.9%, P=0.036). In our animal model of one-lung ventilation, doubling mean arterial pressure by infusion of arginine vasopressin significantly affected global haemodynamics, but had no influence on systemic arterial oxygen tension.     

Cerebral metabolism assessed with microdialysis in uncontrolled hemorrhagic shock after penetrating liver trauma

In a porcine model of uncontrolled hemorrhagic shock, we evaluated the effects of fluid resuscitation versus arginine vasopressin (AVP) combined with hypertonic-hyperoncotic hydroxyethyl starch solution (HHS) on cerebral perfusion pressure (CPP) and on cerebral metabolism using intracerebral microdialysis. Sixteen anesthetized pigs were subjected to uncontrolled liver bleeding until hemodynamic decompensation, followed by resuscitation using either fluid (n = 8) or AVP/HHS (n = 8). Thirty minutes after drug administration, bleeding was controlled by manual compression, and colloid and crystalloid solutions were administered in both groups. All surviving animals were observed for one hour. After hemodynamic decompensation, fluid resuscitation resulted in a smaller increase of CPP than did AVP/HHS (mean +/- sem; 24 +/- 5 vs 45 +/- 7 mm Hg; P < 0.01). Mean (+/- sem) cerebral venous partial pressure of oxygen was significantly decreased (P < 0.01) 5 min after fluid compared with 5 min after AVP/HHS administration (36 +/- 3 vs 64 +/- 4 torr). Cerebral metabolism was comparable in both groups. In conclusion, AVP/HHS proved to be superior to fluid in the initial phase of therapy with respect to CPP and cerebral oxygenation, but was comparable to fluid regarding cerebral metabolism and secondary cell damage in surviving animals.     

Effect of small-dose dopamine on mesenteric blood flow and renal function in a pig model of cardiopulmonary resuscitation with vasopressin

Vasopressin (antidiuretic hormone) seems a promising alternative to epinephrine for cardiopulmonary resuscitation (CPR) in cardiac arrest victims, mediating a pronounced blood flow shift toward vital organs. We evaluated the effects of small-dose dopamine on splanchnic blood flow and renal function after successful resuscitation with this potent vasoconstrictor in an established porcine CPR model. After 4 min of cardiac arrest and 3 min of CPR, animals received 0.4 U/kg vasopressin and were continuously infused with either dopamine 4 microg x kg(-1) x min(-1) (n = 6), or saline placebo (n = 6). Defibrillation was performed 5 min after drug administration; all animals were observed for 6 h after return of spontaneous circulation. During the postresuscitation phase, average mean +/- SD superior mesenteric artery blood flow was significantly (P = 0.002) higher in the dopamine group compared with the placebo group (1185+/-130 vs 740+/-235 mL/min), whereas renal blood flow was comparable between groups (255+/-40 vs 250+/-85 mL/min). The median calculated glomerular filtration rate had higher values in the dopamine group (70-120 mL/min) than in the placebo group (40-70 mL/min; P = 0.1 at 0 min and P = 0.08 at 360 min). We conclude that small-dose dopamine administration may be useful in improving superior mesenteric artery blood flow and renal function after successful resuscitation with vasopressin. IMPLICATIONS: Long-term survival after cardiac arrest may be determined by the ability to ensure adequate organ perfusion during cardiopulmonary resuscitation and in the postresuscitation phase. In this regard, small-dose dopamine improved postresuscitation blood flow to the mesenteric bed when vasopressin was used as an alternative vasopressor in an animal model of cardiac arrest.     

Cardiopulmonary resuscitation during severe hypothermia in pigs: does epinephrine or vasopressin increase coronary perfusion pressure?

The American Heart Association does not recommend epinephrine for management of hypothermic cardiac arrest if body core temperature is below 30 degrees C. Furthermore, the effects of vasopressin administration during hypothermic cardiac arrest are totally unknown. This study was designed to assess the effects of vasopressin and epinephrine on coronary perfusion pressure in a porcine model during hypothermic cardiac arrest cardiopulmonary resuscitation (CPR). Pigs were surface-cooled until their body core temperature was 26 degrees C. After 30 min of untreated cardiac arrest, followed by 3 min of basic life support CPR, 15 animals were randomly assigned to receive, at 5-min intervals, either vasopressin (0.4, 0.4, and 0.8 U/kg; n = 5), epinephrine (45, 45, and 200 microg/kg; n = 5), or saline placebo (n = 5). Compared with epinephrine, mean +/- SEM coronary perfusion pressure was significantly higher (P < 0.05) 90 s and 5 min after the first (35+/-4 vs 22+/-3 mm Hg and 37+/-2 vs 16+/-2 mm Hg) and the second vasopressin administration (40+/-5 vs 26+/-5 mm Hg and 36+/-5 vs 18+/-2 mm Hg, respectively). After the third drug administration, coronary perfusion pressure in the epinephrine group increased dramatically and was comparable to vasopressin. In the saline placebo group, coronary perfusion pressure was significantly lower (P < 0.05) than in the vasopressin and epinephrine groups. Six animals treated with epinephrine or vasopressin had transient return of spontaneous circulation, whereas all placebo animals died (P < 0.05). During CPR in severe hypothermia, administration of both vasopressin and epinephrine resulted in significant increases in coronary perfusion pressure when compared with placebo. IMPLICATIONS: Our study was designed to assess the effects of vasopressin and epinephrine in a porcine model simulating cardiac arrest during severe hypothermia. This study demonstrates that the administration of both emergency drugs results in an increased perfusion pressure in the heart.     

Sympathetic blockade by epidural anesthesia attenuates the cardiovascular response to severe hypoxemia

Blood pressure is usually well maintained during epidural or spinal anesthesia even in the presence of extensive sympathetic blockade. The authors investigated whether hormonal systems support arterial pressure and how the circulation copes with a hypoxic challenge when activation of the sympathetic nervous system is selectively impaired by neural blockade. Accordingly, the effects of high epidural anesthesia alone and combined with hypoxia were evaluated in seven awake trained dogs. On different days, either bupivacaine 0.5% (8-12 ml) or saline (placebo) were randomly injected epidurally and the effects evaluated on cardiovascular (arterial pressure, heart rate) and respiratory (blood gases, oxygen consumption) variables, as well as on hormone plasma concentrations (vasopressin, norepinephrine, epinephrine, renin) during both normoxia and hypoxia. During epidural anesthesia alone, vasopressin increased tenfold (1.7 pg/ml +/- 1.0 SD to 16.8 +/- 13.8, P less than 0.05), norepinephrine decreased (90 pg/ml +/- 31 to 61 +/- 28, P less than 0.05) while epinephrine and renin concentrations remained unchanged. Mean arterial and pulse pressure decreased by 13 mmHg and 23 mmHg (P less than 0.05), respectively. In dogs without sympathetic blockade (saline group), hypoxemia (PaO2: 31 +/- 4 mmHg) evoked an increase in mean blood pressure by 37 mmHg +/- 8 and heart rate by 50 beats per min +/- 17. In contrast, in the presence of sympathetic blockade but with a similar degree of hypoxemia, blood pressure failed to increase (+ 1 mmHg +/- 14) and heart rate rose by only 15 beats per min +/- 11. These differences between groups were statistically significant (P less than 0.001). Hypoxemia induced a similar hypocarbia (PaCO2:25 mmHg) in both groups, indicating that the ventilatory response to hypoxemia was preserved after epidural blockade. During hypoxemia vasopressin concentrations increased 35-fold to 64 pg/ml +/- 38 (P less than 0.0001) compared to base line only during epidural anesthesia, but not after epidural saline (2 pg/ml +/- 2), while other hormones showed no significant differences. The authors conclude that high epidural anesthesia in awake unsedated dogs: 1) almost completely abolishes the normal cardiovascular response to hypoxemia while promoting vasopressin secretion; 2) preserves the ventilatory response to hypoxemia; and 3) is associated with increased vasopressin concentrations, most likely to compensate for decreased cardiac filling and/or arterial blood pressure when sympathoadrenal responses are impaired. Thus, the changes in cardiovascular vital signs in response to severe hypoxemia are markedly blunted when spinal sympathetic outflow is selectively eliminated by epidural anesthesia.     

Dobutamine compensates deleterious hemodynamic and metabolic effects of vasopressin in the splanchnic region in endotoxin shock

BACKGROUND: Vasopressin is a potent vasopressor in septic shock, but it may impair splanchnic perfusion. We compared the effects of vasopressin alone and in combination with dobutamine on systemic and splanchnic circulation and metabolism in porcine endotoxin shock. METHODS: Twelve pigs were randomized to receive either vasopressin (VASO, n = 6) or vasopressin in combination with dobutamine (DOBU, n = 6) during endotoxin shock (E. coli endotoxin infusion). Endotoxin infusion rate was increased to induce hypotension after which vasoactive drugs were started. We aimed to keep systemic mean arterial pressure (MAP) >70 mmHg by vasopressin; the goal of dobutamine infusion was to prevent decrease in cardiac output often associated with vasopressin infusion. Regional blood flows, oxygen delivery and consumption, arterial and regional lactate concentrations were measured. RESULTS: Mean arterial pressure >70 mmHg was achieved in both the VASO and DOBU groups. After the primary decrease of cardiac output by vasopressin, systemic blood flow remained stable in vasopressin-treated animals. However, vasopressin as a monotherapy decreased portal venous blood flow. This was prevented by dobutamine. Vasopressin also induced splanchnic lactate release and arterial hyperlactatemia, which were not observed when dobutamine was combined with vasopressin. CONCLUSION: Dobutamine prevents adverse hemodynamic and metabolic effects of vasopressin in septic shock.     

A comparison of epinephrine and vasopressin in a porcine model of cardiac arrest after rapid intravenous injection of bupivacaine

In a porcine model, we compared the efficacy of epinephrine, vasopressin, or the combination of epinephrine and vasopressin with that of saline placebo on the survival rate after bupivacaine-induced cardiac arrest. After the administration of 5 mg/kg of a 0.5% bupivacaine solution i.v., ventilation was interrupted for 3 +/- 1 min (mean +/- SD) until asystole occurred. Cardiopulmonary resuscitation (CPR) was initiated after 1 min of cardiac arrest. After 2 min of CPR, 28 animals received, every 5 min, epinephrine; vasopressin; epinephrine combined with vasopressin; or placebo i.v.. Three minutes after each drug administration, up to 3 countershocks (3, 4, and 6 J/kg) were administered; all subsequent shocks were 6 J/kg. Blood was drawn throughout the experiment for the determination of plasma bupivacaine concentration. In the vasopressin/epinephrine combination group, all pigs survived (P < 0.01 versus placebo); in the vasopressin group 5 of 7, in the epinephrine group 4 of 7, and in the placebo group none of 7 swine survived. The plasma concentration of total bupivacaine showed no significant difference among groups. In this model of bupivacaine-induced cardiac arrest, CPR with a combination of vasopressin and epinephrine resulted in significantly better survival rates than in the placebo group. IMPLICATIONS: Although cardiovascular collapse occurs mostly immediately after rapid injection of a local anesthetic in the presence of anesthesiologists, resuscitation may be difficult, and the outcome is usually poor. In this model of bupivacaine-induced cardiac arrest, cardiopulmonary resuscitation with a combination of vasopressin and epinephrine resulted in significantly better survival rates than in the placebo group.     

Milrinone combined with vasopressin improves cardiac index after cardiopulmonary resuscitation in a pig model of myocardial infarction

BACKGROUND: Milrinone used for acute cardiac insufficiency could be of interest during cardiopulmonary resuscitation because of its positive inotropic effects. In this study, the combination of milrinone-vasopressin was compared with epinephrine and vasopressin, as well as with the combination of epinephrine-vasopressin, in reference to hemodynamics. METHODS: Thirty-two pigs underwent ligation of the circumflex coronary artery and induction of ventricular fibrillation lasting for 4 min. Cardiopulmonary resuscitation was performed after randomization to one of four groups: epinephrine (30-microg/kg bolus), vasopressin (0.4-U/kg bolus), epinephrine-vasopressin (15-microg/kg epinephrine bolus, 0.2-U/kg vasopressin bolus), or milrinone-vasopressin (0.4-U/kg vasopressin bolus, 50-microg/kg milrinone bolus over 5 min and a continuous infusion of 0.4 microg.kg.min). The hemodynamic variables were measured before cardiopulmonary resuscitation as well as 4, 8, 15, and 30 min after return of spontaneous circulation. RESULTS: All animals were resuscitated successfully. The animals of the milrinone-vasopressin group displayed significantly (P<0.05) higher cardiac index values (30 min after return of spontaneous circulation: epinephrine, 65.8+/-13.2; vasopressin, 70.7+/-18.3; epinephrine-vasopressin, 69.1+/-36.2; milrinone-vasopressin, 120.7+/-34.8 ml.min.kg) without a decrease in mean arterial pressure or coronary perfusion pressure. CONCLUSIONS: The combination of vasopressin-milrinone as compared with epinephrine during cardiopulmonary resuscitation leads to an improved cardiac index without relevant decrease of mean arterial pressure or coronary perfusion pressure.     

Vasopressin for therapy of persistent traumatic hemorrhagic shock: The VITRIS.at study

While fluid management is established in controlled hemorrhagic shock, its use in uncontrolled hemorrhagic shock is being controversially discussed, because it may worsen bleeding. In the irreversible phase of hemorrhagic shock that was unresponsive to volume replacement, airway management and catecholamines, vasopressin was beneficial due to an increase in arterial blood pressure, shift of blood away from a subdiaphragmatic bleeding site towards the heart and brain and decrease of fluid resuscitation requirements. The purpose of this multicenter, randomized, controlled, international trial is to assess the effects of vasopressin (10 IU IV) vs. saline placebo IV (up to 3 injections at least 5 min apart) in patients with prehospital traumatic hemorrhagic shock that persists despite standard shock treatment. The study will be carried out by helicopter emergency medical service teams in Austria, Germany, Czech Republic, Portugal, the Netherlands and Switzerland. Inclusion criteria are adult trauma patients with presumed traumatic hemorrhagic shock (systolic arterial blood pressure <90 mmHg) that does not respond to the first 10 min of standard shock treatment (endotracheal intubation, fluid resuscitation and use of vasopressors) after arrival of the first emergency physician at the scene. The time window for randomization will close after 30 min of shock treatment. Exclusion criteria are terminal illness, no intravenous access, age <18 years, injury >60 min before randomization, cardiac arrest before randomization, presence of a do-not-resuscitate order, untreated tension pneumothorax, untreated cardiac tamponade, or known pregnancy. Primary study end-point is the hospital admission rate, secondary end-points are hemodynamic variables, fluid resuscitation requirements and hospital discharge rate.     

Cerebrovascular effects of small volume resuscitation from hemorrhagic shock: comparison of hypertonic saline and concentrated hydroxyethyl starch in dogs

To determine if hypertonic and hyperoncotic resuscitation solutions exerted comparable effects on cerebral hemodynamics following hemorrhagic shock, we compared randomly assigned, equal volumes (6.0 ml/kg) of hypertonic (7.2%) saline (HS) and hyperoncotic (20%) hydroxyethyl starch (HES) for resuscitation from acute experimental hemorrhage in 12 anesthetized dogs. Regional cerebral blood flow (radiolabeled microspheres), intracranial pressure (cisternal catheter), and systemic hemodynamics were recorded. Rapid hemorrhage reduced the mean arterial pressure to 45 mm Hg for 30 min. Resuscitation fluids were infused over 5 min. Both fluids restored mean arterial pressure and cardiac output equally. However, at 60 min following resuscitation, cardiac output decreased in the HS group in comparison to the HES group (1.7 +/- 0.1 vs. 3.1 +/- 0.2 L/min, p <0.05). Cardiac output rapidly declined, however, in the HS group in comparison to the HES group (p <0.05 60 min following resuscitation). Intracranial pressure and cerebral perfusion pressure were similar at all intervals. Regional cerebral blood flow was similar following both fluids. Neither fluid restored cerebral oxygen transport to baseline values. Based on these data, the authors conclude that, following severe hemorrhagic shock of brief duration, systemic and cerebral hemodynamic values are restored equally well by highly concentrated colloid or by hypertonic saline, although hypertonic saline only transiently improves cardiac output.     

Endogenous nitric oxide reduces the efficacy of the endothelin system to maintain blood pressure during high epidural anaesthesia in conscious dogs

BACKGROUND AND OBJECTIVE: During high epidural anaesthesia, endothelin only contributes minimally to blood pressure stabilization. This phenomenon could result from the inhibitory action of nitric oxide on the endothelin system. To clarify this, we studied the interaction between nitric oxide and endothelin during high epidural anaesthesia in conscious dogs, in comparison to the interaction of nitric oxide and vasopressin. METHODS: Six animals were used in 45 individual experiments randomly arranged as follows: N-omega-nitro-arginine-methylester 0.3-10 mg kg-1 under physiological conditions or during high epidural anaesthesia (lidocaine 1%) and N-omega-nitro-arginine-methylester (l-NAME) 0.3-10 mg kg-1 after preceding endothelin (Tezosentan(R)) or vasopressin (beta-mercapto-beta,beta-cyclo-penta-methylene-propionyl-O-Me-Tyr-Arg-vasopressin) receptor blockade under physiological conditions or during high epidural anaesthesia. During control experiments normal saline was injected either intravenously (n = 5) or into the epidural space (n = 4). RESULTS: N-omega-nitro-arginine-methylester increased mean arterial pressure dose-dependently in all groups. However, this effect was substantially reduced in the presence of the endothelin receptor antagonist compared to N-omega-nitro-arginine-methylester alone, both under control conditions (7 +/- 3 vs. 21 +/- 3 mmHg; P < 0.05) and during high epidural anaesthesia (17 +/- 3 vs. 30 +/- 1 mmHg; P < 0.05). Blockade of vasopressin showed no similar relationship with N-omega-nitro-arginine-methylester. CONCLUSIONS: The diminished increase in mean arterial pressure after injection of N-omega-nitro-arginine-methylester only during endothelin receptor blockade indicates that endogenous nitric oxide inhibits the action of endothelin during high epidural anaesthesia and might thus explain the reduced efficacy of endothelin in maintaining blood pressure during high epidural anaesthesia.     

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.