Combination drug therapy with vasopressin,adrenaline (epinephrine) and nitroglycerin improves vital organ blood flow in a porcine model of ventricular fibrillation

There is increasing evidence that the combination of epinephrine (adrenaline) with vasopressin may be superior to either epinephrine or vasopressin alone for treatment of cardiac arrest. However, the optimal combination, and dosage of cardiovascular drugs to minimize side effects, and to improve outcome has yet to be found. We therefore evaluated whether the combination of vasopressin plus epinephrine plus nitroglycerin (EVN), would improve vital organ blood flow during cardiopulmonary resuscitation (CPR) when compared with epinephrine (EPI) alone. After 4 min of ventricular fibrillation (VF) and 4 min of standard CPR, pigs were randomized to the combination of epinephrine (45 microg/kg) plus vasopressin (0.4 U/kg) plus nitroglycerin (7.5 microg/kg; n=12), or epinephrine (40 microg/kg; n=12) alone. Cerebral and myocardial blood flow was measured with radiolabeled microspheres. Defibrillation was attempted after 19 min of VF including 15 min of CPR. Mean+/-SEM coronary perfusion pressures were significantly (P < 0.01) higher 5 min after EVN vs. EPI alone (34+/-3 vs. 24+/-3 mmHg, respectively). At the same time, mean+/-SEM left ventricular, and global cerebral blood flow was also significantly (P < 0.05) higher after EVN vs. EPI alone (0.78+/-0.11 vs. 0.48+/-0.08 ml/min/g; and 0.37+/-0.05 vs. 0.22+/-0.0 3 ml/min/g, respectively). Spontaneous circulation was restored in 11 of 12 animals in the EVN group vs. 6 of 12 swine after EPI alone (P = N.S.). In conclusion, the combination of EVN significantly improved vital organ blood flow during CPR compared with EPI alone. Addition of nitroglycerin to the combination of low dose epinephrine with vasopressin during cardiac arrest may be beneficial.     

Vasopressin with delayed combination of nitroglycerin increases survival rate in asphyxia rat model

Recently, vasopressin has been reported as a more effective drug than epinephrine (adrenaline) for cardiopulmonary resuscitation (CPR). However, vasopressin decreases myocardial blood flow (MBF) because of its strong vasoconstriction, to maintain better coronary perfusion pressure (CPP) compared with epinephrine. Nitroglycerin is well known to be able to maintain MBF and increase survival rate. In a VF model, vasopressin combined with nitroglycerin maintained CPP; however, low survival rates were observed compared with vasopressin alone. We investigated the effectiveness of the delayed use of nitroglycerin combined with vasopressin in a severe asphyxia model. Fourteen Sprague-Dawley male rats were divided into two groups: vasopressin 0.8 U/kg alone (V-Gr.), and nitroglycerin 0.3 microg/kg 45 s after the administration of 0.8 U/kg vasopressin (VN-Gr.). Six min after asphyxia induced by obstructing the tracheal tube, CPR was performed in two ways. Three animals resuscitated in the V-Gr. (42%) and six/seven (84%) in the VN-Gr. (P<0.05). In the 6 min of asphyxia rat model, vasopressin combined with delayed nitroglycerin is more effective than vasopressin alone.     

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.     

Endogenous and exogenous plasma catecholamine levels in cardiac arrest in swine

The use of epinephrine in cardiac arrest remains an area of continuing controversy. This study was undertaken to characterize the effect of endogenous and exogenous epinephrine on plasma epinephrine levels, and the relationship between plasma epinephrine and norepinephrine and mean arterial pressure and diastolic arterial pressure. Nineteen young swine were anesthetized with ketamine and alpha-chloralose and instrumented with arterial and central venous lines. Ventricular fibrillation was induced by pacemaker. At 5 min post arrest cardiopulmonary resuscitation (CPR) was begun with a mechanical resuscitator. Animals were randomized to receive either saline placebo (n = 9), 0.01 mg/kg epinephrine (n = 5) or 0.1 mg/kg epinephrine (n = 5) via the central venous line. Plasma was drawn for high pressure liquid chromatographic analysis of catecholamines every 2 min. The resuscitation was carried on for 30 min after the arrest. Plasma epinephrine levels differed significantly between treated subjects and controls, as did mean arterial pressure and diastolic arterial pressure. There was a correlation between both mean arterial pressure and diastolic arterial pressure with plasma epinephrine and log epinephrine, but no correlation with plasma norepinephrine. The two doses of epinephrine did not differ in the degree to which they elevated the mean arterial pressure and diastolic pressure. We conclude that the endogenous catecholamine response to cardiac arrest while producing norepinephrine and epinephrine levels many times greater than those in the resting animal, is not sufficient to maintain blood pressure. There is a strong correlation between blood pressure and the log of the plasma epinephrine concentration, but epinephrine concentration alone does not solely account for changes in blood pressure during arrest.     

Synergistic effects of vasopressin plus epinephrine during cardiopulmonary resuscitation

Both epinephrine (Epi) and vasopressin (VP) increase coronary perfusion pressure (CPP) when administered during cardiac arrest. Given their different mechanisms of action we tested the hypothesis that during cardiopulmonary resuscitation (CPR) a combination of VP plus Epi would be superior to either agent alone. Epi(40 microg/kg), VP(0.3 U/kg) and the combination of both agents were assessed in a porcine model of ventricular fibrillation (VF). Maximum CPP (diastolic aortic-right atrial pressures) during CPR was similar among the groups but the time course of action was different in each group: with Epi + VP the increase in CPP was significantly more rapid than with VP alone whereas the CPP remained significantly higher for a longer periods of time with VP or VP + Epi versus Epi alone. Left ventricular blood flow (ml/min per g) determined during CPR two min after drug administration was similar between groups: Epi 1.06 +/- 0.16; VP 0.82 +/- 0.26; Epi + VP 0.83 +/- 0.14 (P = N.S.). Post drug administration. 2 min, cerebral blood flow (ml/min per g) in the VP group (0.76 +/- 0.15) was more than two times higher compared with Epi alone (Epi:0.30 +/- 0.08, P < 0.01 versus VP) and Epi plus VP (Epi + VP:0.23 +/- 0.03, P < 0.01 versus VP). We conclude that combination of VP + Epi during cardiac arrest results in a more rapid rise in CPP when compared with VP alone and a more sustained elevation in CPP than observed with Epi alone. Thus, the synergistic effects of these two potent vasopressor agents may be of benefit during CPR.     

Vasopressin versus continuous adrenaline during experimental cardiopulmonary resuscitation

OBJECTIVE: To evaluate the effects of a bolus dose of vasopressin compared to continuous adrenaline (epinephrine) infusion on vital organ blood flow during cardiopulmonary resuscitation (CPR). METHODS: Ventricular fibrillation was induced in 24 anaesthetised pigs. After a 5-min non-intervention interval, CPR was started. After 2 min of CPR the animals were randomly assigned to receive either vasopressin (0.4 U/kg) or adrenaline (bolus of 20 microg/kg followed by continuous infusion of 10 microg/(kg min)). Defibrillation was attempted after 9 min of CPR. RESULTS: Vasopressin generated higher cortical cerebral blood flow (P < 0.001) and lower cerebral oxygen extraction (P < 0.001) during CPR compared to continuous adrenaline. Coronary perfusion pressure during CPR was higher in vasopressin-treated pigs (P < 0.001) and successful resuscitation was achieved in 12/12 in the vasopressin group versus 5/12 in the adrenaline group (P = 0.005). CONCLUSIONS: In this experimental model, vasopressin caused a greater increase in cortical cerebral blood flow and lower cerebral oxygen extraction during CPR compared to continuous adrenaline. Furthermore, vasopressin generated higher coronary perfusion pressure and increased the likelihood of restoring spontaneous circulation.     

Vasopressin administered with epinephrine is associated with a return of a pulse in out-of-hospital cardiac arrest

OBJECTIVE: Recent data suggest that using vasopressin in combination with epinephrine (adrenaline) may improve treatment of out-of-hospital cardiac arrest. This study examined local experience with the combination of epinephrine and vasopressin administration. METHODS: Data were obtained from an urban, municipal emergency medical service that does not include vasopressin in its formulary. A physician is dispatched to the scene of all cardiac arrest patients treated by this system. Vasopressin could be administered in addition to epinephrine to subjects with out-of-hospital cardiac arrest by the on-scene physician. Demographic information, drug administration and return of pulses were abstracted from patient care records for a 1-year interval. Multivariate logistic regression was used to assess the relationship between vasopressin use and outcomes. RESULTS: During the study period, data were available for 298 subjects receiving epinephrine-only (n=231, 78%), a combination of 40 IU vasopressin and epinephrine (n=37, 12%) or no vasopressor drugs (n=30, 10%). Among patients receiving vasopressor drugs, pulse was restored for 74 subjects (28%), and 56 subjects (21%) had a pulse on arrival at the hospital. Return of pulses was associated with witnessed collapse, bystander CPR, and an initial ECG rhythm of ventricular fibrillation or tachycardia. Subjects receiving vasopressin and epinephrine were more likely to have a return of pulses during the resuscitation (LR: 2.73; 95% CI: 1.24, 6.03) and at hospital arrival (3.85; 1.71, 8.65) than subjects treated with epinephrine alone. CONCLUSIONS: There is an association between using vasopressin in combination with epinephrine and restoration of circulation after out-of-hospital cardiac arrest.     

Vasopressin in the ICU

PURPOSE OF THE REVIEW: Vasopressin is one of the most important endogenously released stress hormones during shock. In this review, studies published in the past year that add to our understanding of the use of vasopressin in the ICU are discussed. RECENT FINDINGS: Endogenous vasopressin levels are inappropriately low in adults with severe sepsis but not in children with meningococcal septic shock. Vasopressin but not norepinephrine improved renal blood flow and oxygen delivery and prolonged survival in animal models of septic shock. In human vasodilatory shock, the combination of low-dose vasopressin and norepinephrine was found to be safe and effective. In humans, vasopressin can cause gastrointestinal hypoperfusion and ischemic skin lesions. In hypodynamic animal models of sepsis vasopressin compromised oxygen delivery and decreased systemic and gut blood flow.High-dose bolus vasopressin appeared promising in animal studies of hemorrhagic shock and cardiopulmonary arrest and in a large, randomized clinical trial of vasopressin versus epinephrine in human cardiopulmonary arrest with asystole. However, poor neurologic outcomes raised controversy in introducing vasopressin into CPR guidelines. SUMMARY: There is growing evidence that vasopressin infusion in septic shock is safe and effective. Several studies published this year support the hypothesis that vasopressin should be used as a continuous low-dose infusion (between 0.01 and 0.04 U/min in adults) and not titrated as a single vasopressor agent. However, multiple studies highlight the clinical equipoise that exists regarding the use of vasopressin in vasodilatory shock. Guidelines on management of septic shock recommend "cautious use of vasopressin pending further studies."     

Compared to angiotensin II, epinephrine is associated with high myocardial blood flow following return of spontaneous circulation after cardiac arrest

INTRODUCTION: Epinephrine (adrenaline) and vasopressin are used currently to improve myocardial blood flow (MBF) during cardiac arrest. Angiotensin II has also been shown to improve MBF during CPR. We explored the effects of angiotensin II or epinephrine alone, and the combination of angiotensin with epinephrine, on myocardial and cerebral blood flows in a swine model of cardiac arrest. METHODS: Swine were instrumented for regional blood flow measurements. Ventricular fibrillation was induced and CPR begun. Angiotensin II 50 mcg/kg (ANG), epinephrine 0.02 mg/kg (EPI) or the combination (ANG+EPI) was administered. Blood flow was measured during baseline normal sinus rhythm (NSR), before (CPR) and after drug administration (CPR+DRUG), and post reperfusion return of spontaneous circulation (ROSC). RESULTS: All groups had a significant increase in MBF during CPR following drug administration (P<0.05). [table: see text] There was a trend toward higher flows in the EPI groups. The group receiving both EPI and ANG did not have higher blood flows than the EPI or ANG alone groups. Both groups that received EPI had markedly elevated MBF following ROSC compared with angiotensin II (P<0.05). CONCLUSIONS: The combination of ANG and EPI did not improve MBF during cardiac arrest. Epinephrine may increase MBF compared with angiotensin II post-reperfusion.     

Selective Aortic Arch Perfusion Using Serial Infusions of Perflubron Emulsion

Objective : To determine whether selective aortic arch perfusion (SAAP) using serial infusions of oxygenated perflubron emulsion combined with aortic epinephrine (AoE) administration is more effective than conventional therapy in treating cardiac arrest.
Methods : An experimental cardiac arrest model (10 min ventricular fibrillation and 2 min CPR) was used with 12 mixed-breed canines, randomized into 2 groups: control ( n = 6), CPR and IV epinephrine, 0.01 mgkg, at 12 rnin and then every 3 min; or AoE-SAAP ( n = 6), CPR and aortic epinephrine, 0.01 mgkg, at 12 rnin and then every 3 min, and serial SAAP with oxygenated 60% weightholume (w/v) perflubron emulsion as follows: 300 mL over 30 sec at 12 rnin as continuous SAAP without CPR; 150 mL over 20–30 sec at 15 min and 18 rnin as pulsed diastolic SAAP during CPR.
Results : AoE-SAAP resulted in increased coronary perfusion pressure (CPP) and return of spontaneous circulation (ROSC) compared with control. CPR-diastolic (release phase) CPP during pulsed diastolic SAAP was similar to or greater in magnitude than the CPP generated during the initial SAAP infusion without CPR. ROSC for control was 0/6 and for AoE-SAAP was 416 (p < 0.05, Fisher's exact test). Time from initiation of CPR to ROSC with a sustained systolic aortic pressure >60 mm Hg was 8.0 ± 1.2 rnin in the 4 resuscitated AoE-SAAP animals.
Conclusion : The combination of AoE with SAAP infusions of oxygenated perflubron emulsion was more effective than conventional resuscitation therapy. Pulsed diastolic SAAP is a promising method for performing SAAP.     

Reverse CPR: a pilot study of CPR in the prone position

BACKGROUND: Cardiopulmonary resuscitation (CPR), as described in 1960, remains the cornerstone of therapy for cardiopulmonary arrest. Recent case reports have described CPR in the prone position. We hypothesized rhythmic back pressure on a patient in the prone position with sternal counter-pressure (termed reverse CPR here) would increase intra-thoracic pressure and in turn systolic blood pressure (SBP) during cardiac arrest versus standard CPR. METHODS AND RESULTS: Six patients from Columbia Presbyterian Medical Center's Cardiac and Medical Intensive Care Units (CICU and MICU) were enrolled. Eligible patients had suffered circulatory arrest and failed standard CPR for at least 30 min. After enrollment the patients received 15 additional min of standard CPR and then reverse CPR for 15 min. The study's primary endpoint, mean SBP, significantly improved from 48 mmHg during standard CPR to 72 mmHg during reverse CPR (mean improvement=23+/-14 mmHg). Mean calculated mean arterial pressure (MAP) was also improved significantly from 32 mmHg during standard CPR to 46 mmHg during reverse CPR (mean improvement=14+/-11 mmHg). The mean diastolic blood pressure (DBP) improved from 24 mmHg during standard to 34 mmHg during reverse CPR (mean improvement=10+/-12 mmHg). This difference did not meet statistical significance. No patients had return of spontaneous circulation. CONCLUSIONS: Reverse CPR generates higher mean SBP and higher mean MAP during circulatory arrest than standard CPR. These novel findings justify further research into this technique.     

Effects of epinephrine and vasopressin in a piglet model of prolonged ventricular fibrillation and cardiopulmonary resuscitation

OBJECTIVE: We recently demonstrated that vasopressin alone resulted in a poorer outcome in a pediatric porcine model of asphyxial cardiac arrest when compared with epinephrine alone or with epinephrine plus vasopressin in combination. Accordingly, this study was designed to differentiate whether the inferior effects of vasopressin in pediatrics were caused by the type of cardiac arrest. DESIGN: Prospective, randomized laboratory investigation that used an established porcine model for measurement of hemodynamic variables and organ blood flow. SETTING: University hospital laboratory. SUBJECTS: Eighteen piglets weighing 8-11 kg. INTERVENTIONS: After 8 mins of ventricular fibrillation and 8 mins of cardiopulmonary resuscitation, either 0.4 units/kg vasopressin (n = 6), 45 microg/kg epinephrine (n = 6), or a combination of 45 microg/kg epinephrine with 0.8 units/kg vasopressin (n = 6) was administered. Six minutes after drug administration, a second respective bolus dose of 0.8 units/kg vasopressin, 200 microg/kg epinephrine, or a combination of 200 microg/kg epinephrine with 0.8 units/kg vasopressin was given. Defibrillation was attempted 20 mins after initiating cardiopulmonary resuscitation. MEASUREMENTS AND MAIN RESULTS: Mean +/- sem left ventricular myocardial blood flow 2 mins after each respective drug administration was 65 +/- 4 and 70 +/- 13 mL x min(-1) x 100 g(-1) in the vasopressin group; 83 +/- 42 and 85 +/- 41 mL x min(-1) x 100 g(-1) in the epinephrine group; and 176 +/- 32 and 187 +/- 29 mL x min(-1) x 100 g(-1) in the epinephrine-vasopressin group (p <.006 after both doses of epinephrine-vasopressin vs. vasopressin and after the first dose of epinephrine-vasopressin vs. epinephrine, respectively). At the same times, mean +/- sem total cerebral blood flow was 73 +/- 3 and 47 +/- 5 mL x min(-1) x 100 g(-1) after vasopressin; 18 +/- 2 and 12 +/- 2 mL x min(-1) x 100 g(-1) after epinephrine; and 79 +/- 21 and 41 +/- 8 mL x min(-1) x 100 g(-1) after epinephrine-vasopressin (p <.025 after both doses of vasopressin and epinephrine-vasopressin vs. epinephrine). Five of six vasopressin-treated, two of six epinephrine-treated, and six of six epinephrine-vasopressin treated animals had return of spontaneous circulation (nonsignificant). CONCLUSIONS: In this pediatric porcine model of ventricular fibrillation, the combination of epinephrine with vasopressin during cardiopulmonary resuscitation resulted in significantly higher levels of left ventricular myocardial blood flow than either vasopressin alone or epinephrine alone. Both vasopressin alone and the combination of epinephrine with vasopressin, but not epinephrine alone, improved total cerebral blood flow during cardiopulmonary resuscitation. In stark contrast to asphyxial cardiac arrest, vasopressin alone or in combination with epinephrine appears to be of benefit after ventricular fibrillation in the pediatric porcine model.     

Epinephrine, but not vasopressin, improves survival rates in an adult rabbit model of asphyxia cardiac arrest

Although vasopressin has been reported to be more effective than epinephrine for cardiopulmonary resuscitation in ventricular fibrillation animal models, its efficacy in asphyxia model remains controversy. The purpose of this study was to investigate the effectiveness of vasopressin vs epinephrine on restoration of spontaneous circulation (ROSC) in a rabbit model of asphyxia cardiac arrest. Cardiac arrest was induced by clamping endotracheal tube. After 5 minutes of basic life-support cardiopulmonary resuscitation, animals who had no ROSC were randomly assigned to receive either epinephrine alone (epinephrine group; 200 microg/kg) or vasopressin alone (vasopressin group; 0.8 U/kg). The coronary perfusion pressure (CPP) was calculated as the difference between the minimal diastolic aortic and simultaneously recorded right atrial pressure. Restoration of spontaneous circulation was defined as an unassisted pulse with a systolic arterial pressure of 60 mm Hg or higher for 5 minutes or longer. We induced arrest in 62 rabbits, 15 of whom had ROSC before drug administration and were excluded from analysis. The remaining 47 rabbits were randomized to epinephrine group (n = 24) and vasopressin group (n = 23). Before and after drug administration, CPP in epinephrine group increased significantly (from -4 +/- 4 to 36 +/- 9 mm Hg at peak value, P = .000), whereas CPP in vasopressin group increased only slightly (from 9 +/- 5 to 18 +/- 6 mm Hg at peak value, P = .20). After drug administration, 13 of 24 epinephrine rabbit had ROSC, and only 2 of 23 vasopressin rabbit had ROSC (P < .01). Consequently, we conclude that epinephrine, but not vasopressin, increases survival rates in this adult rabbit asphyxia model.     

Comparison of epinephrine and vasopressin in a pediatric porcine model of asphyxial cardiac arrest

OBJECTIVE: This study was designed to compare the effects of vasopressin vs. epinephrine vs. the combination of epinephrine with vasopressin on vital organ blood flow and return of spontaneous circulation in a pediatric porcine model of asphyxial arrest. DESIGN: Prospective, randomized laboratory investigation using an established porcine model for measurement of hemodynamic variables, organ blood flow, blood gases, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Eighteen piglets weighing 8-11 kg. INTERVENTIONS: Asphyxial cardiac arrest was induced by clamping the endotracheal tube. After 8 mins of cardiac arrest and 8 mins of cardiopulmonary resuscitation, a bolus dose of either 0.8 units/kg vasopressin (n = 6), 200 microg/kg epinephrine (n = 6), or a combination of 45 microg/kg epinephrine with 0.8 units/kg vasopressin (n = 6) was administered in a randomized manner. Defibrillation was attempted 6 mins after drug administration. MEASUREMENTS AND MAIN RESULTS: Mean +/- SEM coronary perfusion pressure, before and 2 mins after drug administration, was 13 +/- 2 and 23 +/- 6 mm Hg in the vasopressin group; 14 +/- 2 and 31 +/- 4 mm Hg in the epinephrine group; and 13 +/- 1 and 33 +/- 6 mm Hg in the epinephrine-vasopressin group, respectively (p = NS). At the same time points, mean +/- SEM left ventricular myocardial blood flow was 44 +/- 31 and 44 +/- 25 mL x min-(1) x 100 g(-1) in the vasopressin group; 30 +/- 18 and 233 +/- 61 mL x min(-1) x 100 g(-1) in the epinephrine group; and 36 +/- 10 and 142 +/- 57 mL x min(-1) x 100 g(-1) in the epinephrine-vasopressin group (p < .01 epinephrine vs. vasopressin; p < .02 epinephrine-vasopressin vs. vasopressin). Total cerebral blood flow trended toward higher values after epinephrine-vasopressin (60 +/- 19 mL x min(-1) x 100 g(-1)) than after vasopressin (36 +/- 17 mL x min(-1) x 100 g(-1)) or epinephrine alone (31 +/- 7 mL x min(-1) x 100 g(-1); p = .07, respectively). One of six vasopressin, six of six epinephrine, and four of six epinephrine-vasopressin-treated animals had return of spontaneous circulation (p < .01, vasopressin vs. epinephrine). CONCLUSIONS: Administration of epinephrine, either alone or in combination with vasopressin, significantly improved left ventricular myocardial blood flow during cardiopulmonary resuscitation. Return of spontaneous circulation was significantly more likely in epinephrine-treated pigs than in animals resuscitated with vasopressin alone.     

Vasopressin decreases endogenous catecholamine plasma concentrations during cardiopulmonary resuscitation in pigs

OBJECTIVE: The purpose of this study was to evaluate the effect of vasopressin vs. saline placebo on catecholamine plasma concentrations during cardiopulmonary resuscitation (CPR). DESIGN: Prospective, randomized laboratory investigation by using an established porcine CPR model with instrumentation for measurement of hemodynamic variables, vital organ blood flow, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Sixteen domestic pigs. INTERVENTIONS: After 15 mins of untreated cardiac arrest and 3 mins of CPR, 16 pigs were randomized to be treated with either 0.8 U/kg vasopressin (n = 8) or placebo (normal saline; n = 8). Arterial epinephrine and norepinephrine plasma concentrations were sampled at prearrest, after 1.5 mins of chest compressions, and at 1.5 mins and 5 mins after drug administration during CPR. MEASUREMENTS AND MAIN RESULTS: In comparison with placebo pigs at 1.5 and 5 mins after drug administration, animals resuscitated with vasopressin had significantly (p < .01) higher mean +/- SEM left ventricular myocardial (131+/-27 vs. 10+/-1 mL x mins(-1) x 100 g(-1) and 62+/-13 vs. 9+/-2 mL x mins(-1) x 100 g(-1)); total cerebral (90+/-8 vs. 14+/-3 mL x mins(-1) x 100 g(-1) and 51+/-4 vs. 12+/-2 mL x mins(-1) x 100 g(-1)); and adrenal gland perfusion (299+/-36 vs. 38+/-7 mL x mins(-1) x 100 g(-1) and 194+/-23 vs. 29+/-5 mL x mins(-1) x 100 g(-1)). Significantly lower mean +/- SEM epinephrine concentrations in the vasopressin pigs compared with the placebo group were measured 1.5 mins and 5 mins after drug administration, (24167+/-7919 vs. 80223+/-19391 pg/mL [p < .01] and 8346+/-1454 vs. 71345+/-10758 pg/mL [p < .01]). Mean +/- SEM norepinephrine plasma concentrations in the vasopressin animals in comparison with placebo were at 1.5 and 5 mins after drug administration significantly lower (41729+/-13918 vs. 82756+/-9904 pg/mL [p = .01] and 10642+/-3193 vs. 62170+/-8797 pg/mL [p < .01]). CONCLUSIONS: Administration of vasopressin during CPR resulted in significantly superior vital organ blood flow, but significantly decreased endogenous catecholamine plasma concentrations when compared with placebo.     

Arterial blood gases during cardiac arrest: markers of blood flow in a canine model.

Measures of CO2 have been shown to correlate with coronary perfusion pressure and cardiac output during cardiac arrest. We evaluated arterial pH (pHa) relative to blood flow during cardiac arrest in a canine electromechanical dissociation (EMD) model of cardiac arrest using different resuscitation techniques. Following 15 min of cardiac arrest, 24 mongrel dogs received epinephrine with continued CPR or closed-chest cardiopulmonary bypass. Central arterial blood gases, end-tidal carbon dioxide (PetCO2), coronary perfusion pressure and cardiac output were measured. During CPR, prior to epinephrine or bypass, there was no correlation of pHa, PACO2 and PetCO2, with cardiac output or coronary perfusion pressure. Immediately after instituting the resuscitation techniques, both pHa and PaCO2 showed a significant correlation with cardiac output (pHa; R = -0.78, P less than 0.001 and PaCO2; R = 0.87, P less than 0.001) and with coronary perfusion pressure (pHa; R = -0.75, P less than 0.001 and PaCO2; R = 0.75, P less than 0.001). Eventual survivors (n = 15) had an early significant decrease in pHa, base excess and a significant increase in PaCO2 which was not present in non-survivors (n = 9). Neither pHa nor PaCO2 correlate with blood flow under low flow conditions of CPR. However, with effective circulatory assistance, pHa and PaCO2 reflect systemic blood flow and reperfusion washout.     

Vasopressin Can Increase Coronary Perfusion Pressure during Human Cardiopulmonary Resuscitation

Objectives : To determine the hemodynamic effect of vasopressin on coronary perfusion pressure (CPP) in prolonged human cardiac arrest.
Methods : A prospective, open-label clinical trial of vasopressin during cardiac resuscitation was performed. Ten patients presenting in cardiac arrest initially received resuscitative measures by emergency physicians according to Advanced Cardiac Life Support (ACLS) gcidelines. A central venous catheter for fluid and drug administration and a femoral artery catheter for measurement of CPP (aortic minus right atrial relaxation phase pressures) were placed. When each patient was deemed nonsalvageable, 1.0 mg epinephrine was given and CPP was measured for 5 minutes, followed by a dose of vasopressin (1.O Ukg). CPP measurements were continued for another 5 minutes.
Results : The mean duration of cardiac arrest (out-of-hospital interval plus duration of ED ACLS) was 39.6 ± 16.5 min. There was no improvement in CPP after 1.0 mg of epinephrine. Vasopressin administration resulted in a significant increase of CPP in 4 of the 10 patients. Patients responding to vasopressin had a mean increase in CPP of 28.2 ± 16.4 mm Hg (range: 10–51.5), with these peak increases occurring at 15 seconds to 4 minutes after administration. The increases in the vasopressin levels after administration did not differ between the responders and nonresponders.
Conclusions : In this human model of prolonged cardiac arrest, 40% of the patients receiving vasopressin had a significant increase in CPP. This pilot study suggests that investigation of earlier use of vasopressin as a therapeutic alternative in the treatment of cardiac arrest is warranted.     

Hemodynamic effects of tracheal administration of vasopressin in dogs.

BACKGROUND: Intravenous administration of vasopressin during cardiopulmonary resuscitation (CPR) has been shown to be more effective than optimal doses of epinephrine. Earlier studies had been performed on a porcine model, but pigs produce lysine vasopressin hormone, while humans and dogs do not. This study was designed to compare the effects of tracheal vasopressin with those of NaCl 0.9% (placebo) on haemodynamic variables in a dog model. METHODS: Five dogs were allocated to receive either vasopressin 1.2 U/kg or placebo (10 ml of NaCl 0.9%) via the tracheal route after being anesthetized and ventilated. Haemodynamic variables were determined and arterial blood gases were measured. RESULTS: All animals of the vasopressin group demonstrated a significant increase of the systolic (from 135+/-7 to 165+/-6 mmHg, P<0.05), diastolic (from 85+/-10 to 110+/-10 mmHg, P<0.05) and mean blood pressure (from 98.5+/-3 to 142.2+/-5, P<0.05). Blood pressure rose rapidly and lasted for more than an hour (plateau effect). Heart rate decreased significantly following vasopressin (from 54+/-9 to 40+/-5 beats per min, P<0.05) but not in the placebo group. These changes were not demonstrated with placebo injection. CONCLUSION: Tracheal administration of vasopressin was followed by significantly higher diastolic, systolic and mean blood pressures in the vasopressin group compared with the placebo group. Blood gases remained unchanged in both groups. Vasopressin administered via the trachea may be an acceptable alternative for vasopressor administration during CPR, when intravenous access is delayed or not available, however, further investigation is necessary.     

Reducing ventilation frequency during cardiopulmonary resuscitation in a porcine model of cardiac arrest

INTRODUCTION: American Heart Association/American College of Cardiology guidelines recommend a compression-to-ventilation ratio (C/V ratio) of 15:2 during cardiopulmonary resuscitation (CPR) for out-of-the-hospital cardiac arrest. Recent data have shown that frequent ventilations are unnecessary and may be harmful during CPR, since each positive-pressure ventilation increases intrathoracic pressure and may increase intracranial pressure and decrease venous blood return to the right heart and thereby decrease both the cerebral and coronary perfusion pressures. HYPOTHESIS: We hypothesized that reducing the ventilation rate by increasing the C/V ratio from 15:2 to 15:1 will increase vital-organ perfusion pressures without compromising oxygenation and acid-base balance. METHODS: Direct-current ventricular fibrillation was induced in 8 pigs. After 4 min of untreated ventricular fibrillation without ventilation, all animals received 4 min of standard CPR with a C/V ratio of 15:2. Animals were then randomized to either (A) a C/V ratio of 15:1 and then 15:2, or (B) a C/V ratio of 15:2 and then 15:1, for 3 min each. During CPR, ventilations were delivered with an automatic transport ventilator, with 100% oxygen. Right atrial pressure, intratracheal pressure (a surrogate for intrathoracic pressure), aortic pressure, and intracranial pressure were measured. Coronary perfusion pressure was calculated as diastolic aortic pressure minus right atrial pressure. Cerebral perfusion pressure was calculated as mean aortic pressure minus mean intracranial pressure. Arterial blood gas values were obtained at the end of each intervention. A paired t test was used for statistical analysis, and a p value < 0.05 was considered significant. RESULTS: The mean +/- SEM values over 1 min with either 15:2 or 15:1 C/V ratios were as follows: intratracheal pressure 0.93 +/- 0.3 mm Hg versus 0.3 +/- 0.28 mm Hg, p = 0.006; coronary perfusion pressure 10.1 +/- 4.5 mm Hg versus 19.3 +/- 3.2 mm Hg, p = 0.007; intracranial pressure 25.4 +/- 2.7 mm Hg versus 25.7 +/- 2.7 mm Hg, p = NS; mean arterial pressure 33.1 +/- 3.7 mm Hg versus 40.2 +/- 3.6 mm Hg, p = 0.007; cerebral perfusion pressure 7.7 +/- 6.2 mm Hg versus 14.5 +/- 5.5 mm Hg, p = 0.008. Minute area intratracheal pressure was 55 +/- 17 mm Hg . s versus 22.3 +/- 10 mm Hg . s, p < 0.001. End-tidal CO(2) with 15:2 versus 15:1 was 24 +/- 3.6 mm Hg versus 29 +/- 2.5 mm Hg, respectively, p = 0.001. Arterial blood gas values were not significantly changed with 15:2 versus 15:1 C/V ratios: pH 7.28 +/- 0.03 versus 7.3 +/- 0.03; P(aCO(2)) 37.7 +/- 2.9 mm Hg versus 37.6 +/- 3.5 mm Hg; and P(aO(2)) 274 +/- 36 mm Hg versus 303 +/- 51 mm Hg. CONCLUSIONS: In a porcine model of ventricular fibrillation cardiac arrest, reducing the ventilation frequency during CPR by increasing the C/V ratio from 15:2 to 15:1 resulted in improved vital-organ perfusion pressures, higher end-tidal CO(2) levels, and no change in arterial oxygen content or acid-base balance.     

Vasopressin versus epinephrine during cardiopulmonary resuscitation: a randomized swine outcome study.

In animal models, vasopressin improves short-term outcome after cardiopulmonary resuscitation (CPR) for ventricular fibrillation compared to placebo, and improves myocardial and cerebral hemodynamics during CPR compared to epinephrine. This study was designed to test the hypothesis that vasopressin would improve 24-h neurologically intact survival compared to epinephrine. After a 2-min untreated ventricular fibrillation interval followed by 6 min of simulated bystander CPR, 35 domestic swine (weight, 25+/-1 kg) were randomly provided with a single dose of vasopressin (20 U or approximately 0.8 U kg(-1) intravenously) or with epinephrine (0.02 mg kg(-1) intravenously every 5 min). Ten minutes after initial medication administration (18 min after induction of ventricular fibrillation), standard advanced life support was provided, starting with defibrillation. Animals that were successfully resuscitated received 1 h of intensive care support and were observed for 24 h. Coronary perfusion pressures were higher in the vasopressin group 2 and 4 min after vasopressin administration (28+/-2 versus 18+/-1 mm Hg, P<0.01, and 26+/-3 versus 18+/-2 mm Hg, P<0.05, respectively). The vasopressin group tended to be successfully defibrillated on the first attempt more frequently (8/18 versus 3/17, P = 0.15). Return of spontaneous circulation (ROSC) was attained in 12/18 (67%) vasopressin-treated pigs versus 8/17 (47%) epinephrine-treated pigs, P = 0.24. Twenty-four hour neurologically normal survival occurred in 11/18 (61%) versus 7/17 (41%), respectively, P = 0.24. In conclusion, vasopressin administration during CPR improved coronary perfusion pressure, but did not result in statistically significant outcome improvement.