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.     

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.     

Fibrillation power, an alternative method of ECG spectral analysis for prediction of countershock success in a porcine model of ventricular fibrillation

BACKGROUND: Noninvasive prediction of defibrillation success after cardiac arrest and cardiopulmonary resuscitation (CPR) may help in determining the optimal time for a countershock, and thus increase the chance for survival. METHODS: In a porcine model (n=25) of prolonged cardiac arrest, advanced cardiac life support was provided by administration of two or three doses of either vasopressin or epinephrine after 3 or 8 min of basic life support. After 4 min of ventricular fibrillation and 18 min of life support, defibrillation was attempted. The denoised power spectral density of 10 s intervals of the ventricular fibrillation electrocardiogram (ECG) was estimated from averaged and smoothed Fourier transforms. We have eliminated the spectral contribution of artifacts from manual chest compressions and provide a definition for the contribution of ventricular fibrillation to the power spectral density. This contribution is quantified and termed "fibrillation power". RESULTS: We tested fibrillation power and two established methods in their discrimination of survivors (n=16) vs. non-survivors (n=9) in the last minute before the countershock. A fibrillation power > or =79 dB predicted successful defibrillation with sensitivity, specificity, positive predictive value and negative predictive value of 98%, 98%, 99% and 97% while a mean fibrillation frequency > or =7.7 Hz was predictive with 85%, 83%, 90% and 77% and a mean amplitude > or =0.49 mV was predictive with 95%, 90%, 94% and 91%. CONCLUSIONS: We suggest that fibrillation power is an alternative source of information on the status of a fibrillating heart and that it may match the established mean frequency and amplitude analysis of ECG in predicting successful countershock during CPR.     

Effects of vasopressin on adrenal gland regional perfusion during experimental cardiopulmonary resuscitation

OBJECTIVE: Despite the important role of the adrenal gland during cardiac arrest, little is known about changes in the adrenal medullary or cortical blood flow in this setting. This study was designed to assess regional adrenal gland perfusion in the medulla and cortex during cardiopulmonary resuscitation (CPR), and after administration of adrenaline (epinephrine) versus vasopressin versus saline placebo. METHODS: After 4 min of untreated ventricular fibrillation, and 3 min of basic life support CPR, 19 animals were randomly assigned to receive either vasopressin (0.4 U/kg; n=7), adrenaline (45 microg/kg; n=6) or saline placebo (n=6), respectively. Haemodynamic variables, adrenal, and renal blood flow were measured after 90 s of CPR, and 90 s and 5 min after drug administration. RESULTS: All values are given as mean+/-S.E.M. Blood flow in the adrenal medulla was significantly higher 90 s after adrenaline when compared with saline placebo in the right adrenal medulla (210+/-14 vs. 102+/-5 ml/min per 100 mg), and in the left adrenal medulla (218+/-14 vs. 96+/-3 ml/min per 100 mg). Blood flow in the adrenal medulla was significantly higher 90 s and 5 min after vasopressin when compared with adrenaline in the right (326+/-22 mg vs. 210+/-14 ml/min per 100 mg, and 297+/-17 vs. 103+/-5 ml/min per 100 mg), and in the left medulla (333+/-25 vs. 218+/-14 ml/min per 100 mg, and 295+/-14 vs. 111+/-7 ml/min per 100 mg). Ninety seconds and five minutes after vasopressin, and 90 s after adrenaline, adrenal cortex blood flow was significantly higher when compared with saline placebo. After 12 min of cardiac arrest, including 8 min of CPR, seven of seven pigs in the vasopressin group, one of six pigs in the adrenaline group, but none of six placebo were successfully defibrillated. CONCLUSION: Both vasopressin and adrenaline produced significantly higher medullary and cortical adrenal gland perfusion during CPR than did a saline placebo; but vasopressin resulted in significantly higher medullary adrenal gland blood flow when compared with adrenaline.     

Effects of combined administration of vasopressin, epinephrine, and norepinephrine during cardiopulmonary resuscitation in pigs

OBJECTIVE: Synergistic effects of epinephrine and vasopressin may be of benefit during cardiopulmonary resuscitation. However, cerebral perfusion was decreased when epinephrine was combined with vasopressin compared with vasopressin alone. Although a combined infusion of norepinephrine and vasopressin improves hemodynamic variables compared with norepinephrine alone during sepsis, it is unknown whether norepinephrine in addition to vasopressin and epinephrine changes vital organ perfusion during cardiopulmonary resuscitation. DESIGN: Prospective, randomized animal study. SETTING:: University hospital research laboratory. SUBJECTS: Twenty-one domestic pigs. INTERVENTIONS: After 4 mins of ventricular fibrillation and 3 mins of basic life support, the pigs were randomly assigned to receive either 200 microg/kg epinephrine, 0.4 units/kg vasopressin alone, or 45 microg/kg norepinephrine plus 45 microg/kg epinephrine plus 0.4 units/kg vasopressin before defibrillation. MEASUREMENTS AND MAIN RESULTS: Organ perfusion was determined by radiolabeled microspheres. Myocardial blood flow (mean +/- sem) before and 90 secs and 5 mins after drug administration was 8 +/- 2, 25 +/- 6, and 7 +/- 1 mL/min/100 g after high-dose epinephrine, 12 +/- 1, 75 +/- 7, and 60 +/- 10 mL/min/100 g after vasopressin, and 9 +/- 2, 95 +/- 26, and 46 +/- 15 mL/min/100 g after vasopressin/epinephrine/norepinephrine, respectively (p < .05 at 90 secs and 5 mins vasopressin vs. epinephrine and vasopressin/epinephrine/norepinephrine vs. epinephrine). At the same time points, cerebral blood flow was 8 +/- 2, 23 +/- 3, and 17 +/- 3 mL/min/100 g after epinephrine, 11 +/- 3, 55 +/- 7, and 52 +/- 7 mL/min/100 g after vasopressin, and 11 +/- 4, 67 +/- 13, and 53 +/- 12 mL/min/100 g after vasopressin/epinephrine/norepinephrine, respectively (p < .05 at 90 secs and 5 mins vasopressin vs. epinephrine and vasopressin/epinephrine/norepinephrine vs. epinephrine). Two of seven animals in the epinephrine group, four of seven animals in the vasopressin/epinephrine/norepinephrine group, and seven of seven animals in the vasopressin group could be successfully resuscitated (p < .05 vasopressin vs. epinephrine). CONCLUSIONS: Vasopressin with or without epinephrine and norepinephrine resulted in higher myocardial and cerebral perfusion than epinephrine alone, but there was no benefit in adding norepinephrine to vasopressin and epinephrine with regard to cardiac and cerebral blood flow during cardiopulmonary resuscitation.     

Resuscitation from cardiac arrest with adrenaline/epinephrine or vasopressin: effects on intestinal mucosal tonometer pCO(2) during the postresuscitation period in rats

BACKGROUND: The use of vasopressin instead of adrenaline/epinephrine during resuscitation improves vital organ perfusion, but the effects on mesenteric perfusion following successful resuscitation are not fully evaluated. The present study was designed to compare the effects of vasopressin and adrenaline/epinephrine, given to rats during resuscitation from ventricular fibrillation, on to mesenteric ischaemia, as determined by intestinal mucosal tonometer pCO(2) during the postresuscitation period. METHODS AND RESULTS: Male Sprague-Dawley rats (n=28) were allocated randomly to receive vasopressin (0.8 U/kg) or adrenaline/epinephrine (90 microg/kg) after 5 min of ventricular fibrillation. Precordial chest compression was initiated 4 min after the start of ventricular fibrillation, continued for 4 min, and followed by defibrillation. Seven of 14 (vasopressin) and 12 of 14 (adrenaline/epinephrine) rats were successfully defibrillated (P=0.10, Fisher's exact test) and observed for 60 min. Intestinal mucosal tonometer pCO(2) measurements before cardiac arrest and 15, 30, and 60 min following return of spontaneous circulation were 47+/-3, 73+/-8, 63+/-7, and 56+/-6 mmHg in the vasopressin group and 48+/-5, 78+/-7, 67+/-6, and 62+/-6 mmHg in the adrenaline/epinephrine group (P<0.05 at 60 min between vasopressin and adrenaline/epinephrine). Right atrial hemoglobin oxygen saturations at these time points were 73+/-5, 51+/-12, 58+/-11, and 63+/-5% in the vasopressin group and 76+/-7, 44+/-10, 52+/-10 and 54+/-8% in the adrenaline/epinephrine group (P<0.05 at 60 min between vasopressin and adrenaline/epinephrine). CONCLUSIONS: We conclude that in this rat model the administration of vasopressin instead of adrenaline/epinephrine for CPR tends to be associated with lower resuscitation success, but less mesenteric ischaemia during the postresuscitation period in successfully resuscitated rats.     

Effect of nitric oxide synthase modulation on resuscitation success in a swine ventricular fibrillation cardiac arrest model

BACKGROUND: We have demonstrated previously that the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine (L-NNA) decreases free radical generation and nitrosative injury via peroxynitrite formation after epicardial dc shocks. OBJECTIVE: Our purpose was to explore the effects of NOS inhibition and NOS donation on cardiopulmonary resuscitation (CPR) success after cardiac arrest of variable duration. We used the non-selective NOS inhibitor L-NNA and the selective neuronal NOS inhibitor ARR-17477, the NOS donor S-nitroso-N-acetylpenicillamine (SNAP) and the vasodilator Enalaprilat, which lowers arterial pressure via a non-NO mechanism. METHODS: Part I: 17 pigs undergoing 4 min supported (i.e. with closed-chest compression and ventilation) ventricular fibrillation (VF) were divided into two groups: a no-L-NNA group (n=8) receiving IV saline and an L-NNA group (n=9) receiving IV L-NNA (5 mg/kg) for 8 min before VF was induced. Part II: 35 pigs undergoing 6-8 min VF were randomized to three groups: a no-L-NNA group (n=13) receiving IV saline, an L-NNA group (n=11) receiving IV L-NNA (5 mg/kg) and an ARR17477 group (n=11) receiving IV ARR17477 (5 mg/kg) before VF. All animals in Part II underwent unsupported VF (no chest compression or ventilation) for 6 min (n=13) or 8 min (n=22); closed-chest compression, ventilation and epinephrine (adrenaline) were employed after defibrillation. Part III: 12 swine were divided into two groups: control (n=6) receiving saline and an LNNA group (n=6) receiving IV LNNA (5 mg/kg). Swine underwent 6 min unsupported VF and 2 min supported VF before defibrillation. Part IV: 25 animals were studied to determine the effect of the NO donor SNAP and the angiotensin-converting enzyme inhibitor Enalaprilat on coronary perfusion pressure (CPP). RESULTS: In Part I, after defibrillation, with continued ventilation, chest compression and epinephrine, 8/9 L-NNA pigs achieved ROSC versus 4/8 control pigs (p=0.11). After 60 s of CPR, 7/9 pigs in the L-NNA group achieved ROSC versus 2/8 pigs in the no-L-NNA group (p<0.05). Only 2/9 pigs receiving L-NNA required epinephrine (1 mg) after defibrillation, compared to 6/8 pigs requiring at least one dose of epinephrine in the no-L-NNA group (p<0.05). In Part II, there was no significant difference between L-NNA, ARR17477 and control pigs in ROSC. However, control pigs required 6.8+/-1.4S.E. mg epinephrine; L-NNA pigs and ARR17477 pigs required less epinephrine (3.7+/-0.7 and 3.0+/-0.3 mg, both p=0.01). Shorter chest compression was required in the L-NNA group (252+/-38 s, p<0.05) and in ARR17477 group (222+/-15 s, p<0.05) compared to the control group (405+/-77 s). In Part III, L-NNA infusion caused a significant increase in mean blood pressure at baseline, but did not change CPP throughout the experiment. In Part IV, there were no significant differences in the changes of mean blood pressure and CPP between SNAP and Enalaprilat group in all animals throughout the experiment. CONCLUSION: NOS inhibition pre-arrest did not improve survival, but did reduce requirements for epinephrine and closed-chest compression in a swine resuscitation model.     

Effects of vasopressin on left anterior descending coronary artery blood flow during extremely low cardiac output

Because of the possibility of vasopressin-mediated coronary vasospasm, this study was designed to assess effects of vasopressin compared to saline placebo on left anterior descending (LAD) coronary artery blood flow. Twelve anaesthetized domestic swine were prepared for LAD coronary artery blood flow measurement with ultrasonic flow probes, using cardiopulmonary by-pass adjusted to 10% of the prearrest cardiac output. This 10% value approximates that reported for cardiac output during conventional closed-chest CPR. After 4 min of untreated ventricular fibrillation, and 3 min of cardiopulmonary by-pass blood flow, 12 pigs were randomly assigned to receive intravenously, every 5 min, either vasopressin (0.4, 0.4, and 0.8 U/kg; n = 6) or saline placebo (n = 6). The mean +/- S.D. LAD coronary artery blood flow in the vasopressin and placebo pigs was comparable before cardiac arrest, and during cardiopulmonary by-pass low flow; but increased significantly (P < 0.05) 90 s after each of three vasopressin injections compared to placebo (78 +/- 1 versus 42 +/- 2 ml/min; 62 +/- 2 versus 36 +/- 1 ml/min; and 54 +/- 1 versus 27 +/- 1 ml/min), respectively. Coronary vascular resistance decreased significantly (P < 0.05 ) 90 s after each of three vasopressin and placebo injections. In this model, repeated bolus administration of vasopressin, given during simulated extremely low cardiac output improved LAD coronary artery blood flow to prearrest levels without affecting coronary vascular resistance. Conclusions: during extremely low blood flow using cardiopulmonary by-pass, vasopressin improves LAD coronary artery blood flow without affecting coronary vascular resistance.     

Brain tissue oxygen pressure and cerebral metabolism in an animal model of cardiac arrest and cardiopulmonary resuscitation

OBJECTIVE: Direct measurement of brain tissue oxygenation (PbtO2) is established during spontaneous circulation, but values of PbtO2 during and after cardiopulmonary resuscitation (CPR) are unknown. The purpose of this study was to investigate: (1) the time-course of PbtO2 in an established model of CPR, and (2) the changes of cerebral venous lactate and S-100B. METHODS: In 12 pigs (12-16 weeks, 35-45 kg), ventricular fibrillation (VF) was induced electrically during general anaesthesia. After 4 min of untreated VF, all animals were subjected to CPR (chest compression rate 100/min, FiO2 1.0) with vasopressor therapy after 7, 12, and 17 min (vasopressin 0.4, 0.4, and 0.8 U/kg, respectively). Defibrillation was performed after 22 min of cardiac arrest. After return of spontaneous circulation (ROSC), the pigs were observed for 1h. RESULTS: After initiation of VF, PbtO2 decreased compared to baseline (mean +/- SEM; 22 +/- 6 versus 2 +/- 1 mmHg after 4 min of VF; P < 0.05). During CPR, PbtO2 increased, and reached maximum values 8 min after start of CPR (25 +/- 7 mmHg; P < 0.05 versus no-flow). No further changes were seen until ROSC. Lactate, and S-100B increased during CPR compared to baseline (16 +/- 2 versus 85 +/- 8 mg/dl, and 0.46 +/- 0.05 versus 2.12 +/- 0.40 microg/l after 13 min of CPR, respectively; P < 0.001); lactate remained elevated, while S-100B returned to baseline after ROSC. CONCLUSIONS: Though PbtO2 returned to pre-arrest values during CPR, PbtO2 and cerebral lactate were lower than during post-arrest reperfusion with 100% oxygen, which reflected the cerebral low-flow state during CPR. The transient increase of S-100B may indicate a disturbance of the blood-brain-barrier.     

Effects of vasopressin and epinephrine on splanchnic blood flow and renal function during and after cardiopulmonary resuscitation in pigs

OBJECTIVE: To compare the effects of vasopressin versus epinephrine on splanchnic blood flow during and after cardiopulmonary resuscitation (CPR), and to evaluate the effects of these vasopressors on renal function in the postresuscitation phase. DESIGN: Prospective, randomized laboratory investigation using an established porcine CPR model with instrumentation for continuous measurement of splanchnic and renal blood flow. SETTING: University hospital experimental laboratory. SUBJECTS: A total of 12 anesthetized, 12- to 16-wk-old domestic pigs weighing 30-35 kg. INTERVENTIONS: After 4 mins of cardiac arrest, and 3 mins of CPR, 12 pigs were randomly assigned to receive either 0.4 units/kg vasopressin (n = 6) or 45 microg/kg epinephrine (n = 6). Defibrillation was performed 5 mins after drug administration; all animals were observed for 6 hrs after return of spontaneous circulation (ROSC). MEASUREMENTS AND MAIN RESULTS: Mean +/- SEM superior mesenteric artery blood flow was significantly (p < .05) lower after vasopressin compared with epinephrine at 90 secs after drug administration (13+/-3 vs. 129+/-33 mL/min); at 5 mins after drug administration (31+/-18 vs. 155+/-39 mL/min); at 5 mins after ROSC (332+/-47 vs. 1087+/-166 mL/min); and at 15 mins after ROSC (450+/-106 vs. 1130+/-222 mL/min); respectively. Mean +/- SEM left renal and hepatic artery blood flow after ROSC was comparable in both groups ranging between 120-290 mL/min (renal blood flow), and 150-360 mL/min (hepatic blood flow), respectively. Median urine output after ROSC showed no difference between groups, and highest values (180-220 mL/hr) were observed in the first 60 mins after ROSC. Median calculated glomerular filtration rate showed no difference between groups with values ranging between 30 and 80 mL/min in the postresuscitation phase. Calculated fractional sodium excretion and osmolar relationship between urea and plasma indicated no evidence for renal tubular dysfunction. CONCLUSIONS: In the early postresuscitation phase, superior mesenteric blood flow was temporarily impaired by vasopressin in comparison with epinephrine. With respect to renal blood flow and renal function after ROSC, there was no difference between either vasopressor given during CPR. Vasopressin given during CPR did not result in an antidiuretic state in the postresuscitation phase.     

Effect of phased chest and abdominal compression-decompression cardiopulmonary resuscitation on myocardial and cerebral blood flow in pigs

OBJECTIVE: This study was designed to assess the effects of a phased chest and abdominal compression-decompression cardiopulmonary resuscitation (CPR) device, Lifestick, vs. standard CPR on vital organ blood flow in a porcine CPR model. 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 research laboratory. SUBJECTS: Twelve domestic pigs. INTERVENTIONS: After 4 mins of untreated ventricular fibrillation, either the Lifestick CPR device (n = 6) or standard CPR (n = 6) was started and maintained for an additional interval of 6 mins before attempting defibrillation. MEASUREMENTS AND MAIN RESULTS: During CPR, but before epinephrine, use of the Lifestick CPR device resulted in significantly higher (p < .05) mean (+/- SD) coronary perfusion pressure (23+/-9 vs. 10+/-7 mm Hg), cerebral perfusion pressure (29+/-11 vs. 18+/-10 mm Hg), mean arterial pressure (49+/-10 vs. 36+/-13 mm Hg), end-tidal carbon dioxide (32+/-11 vs. 20+/-7 mm Hg), left ventricular myocardial blood flow (44+/-19 vs. 19+/-12 mL x min(-1) x 100 g(-1)), and total cerebral blood flow (29+/-10 vs. 14+/-12 mL x min(-1) x 100 g(-1)). After 45 microg/kg epinephrine, hemodynamic and vital organ blood flow variables increased to comparable levels in both groups. CONCLUSIONS: Compared with standard CPR, the Lifestick CPR device increased significantly hemodynamic variables and vital organ blood flow during CPR before epinephrine administration.     

Revised resuscitation guidelines: adrenaline versus adrenaline/vasopressin in a pig model of cardiopulmonary resuscitation--a randomised, controlled trial

BACKGROUND: Synergistic effects of adrenaline (epinephrine) and vasopressin may be beneficial during cardiopulmonary resuscitation. However, it is unknown whether either adrenaline alone or an alternating administration of adrenaline and vasopressin is better for restoring vital organ perfusion following basic life support (BLS) according to the revised algorithm with a compression-to-ventilation (c/v) ratio of 30:2. MATERIAL AND METHODS: After 4min of ventricular fibrillation, and 6min of BLS with a c/v ratio of 30:2, 16 pigs were randomised to receive either 45microg/kg adrenaline, or alternating 45microg/kg adrenaline and 0.4U/kg vasopressin, respectively. RESULTS: Coronary perfusion pressure (mean+/-S.D.) 20 and 25min after cardiac arrest was 7+/-4 and 5+/-3mm Hg after adrenaline, and 25+/-2 and 14+/-3mm Hg after adrenaline/vasopressin (p<0.001 and <0.01 versus adrenaline), respectively. Cerebral perfusion pressure was 23+/-7 and 19+/-9mm Hg after adrenaline, and 40+/-10 and 33+/-7mm Hg after adrenaline/vasopressin (p<0.001 and <0.01 versus adrenaline), and cerebral blood flow was 30+/-10 and 27+/-11% of baseline after adrenaline, and 65+/-40 and 50+/-31% of baseline after adrenaline/vasopressin (p<0.05 versus adrenaline), respectively. Return of spontaneous circulation (ROSC) did not differ significantly between the adrenaline group (0/8) and the adrenaline/vasopressin group (3/8). CONCLUSION: Adrenaline/vasopressin resulted in higher coronary and cerebral perfusion pressures, and cerebral blood flow, while ROSC was comparable.     

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.     

Comparison of epinephrine and norepinephrine in the treatment of asphyxial or fibrillatory cardiac arrest in a porcine model

Many animal experiments have shown that alpha-receptor stimulation is a prerequisite for the improvement of myocardial perfusion during CPR. As there are no recent reports on the effectiveness of norepinephrine in the treatment of cardiac arrest, we investigated the effectiveness of epinephrine and norepinephrine after asphyxial or ventricular fibrillation cardiac arrest using a porcine model. After 3 min of asphyxial cardiac arrest, seven animals each received either 45 micrograms/kg epinephrine, 45 micrograms/kg norepinephrine, or placebo (controls). All drugs were given blind. All seven animals given epinephrine could be resuscitated after 174 +/- 53 sec, whereas six of seven given norepinephrine could be resuscitated after 473 +/- 116 sec. None of the seven given the placebo could be resuscitated. After 4 min of ventricular fibrillation cardiac arrest, none of the seven animals that received defibrillating countershocks at 4 min without either mechanical measures or drug therapy, and none of the seven that received CPR and countershocks but no drugs, could be resuscitated. In the group that received CPR plus 45 micrograms/kg epinephrine, defibrillation and restoration of spontaneous circulation were achieved in six of seven animals in 667 +/- 216 sec. In the group that received CPR plus 45 micrograms/kg norepinephrine, defibrillation and restoration of spontaneous circulation were achieved in all seven animals in the significantly shorter time of 86 +/- 18 sec. In this porcine model, norepinephrine appeared superior to the same dose of epinephrine in the treatment of ventricular fibrillation, with respect to resuscitation time.     

The effect of epinephrine on hemodynamics, acid-base status and potassium during spontaneous circulation and cardiopulmonary resuscitation

The effect of a bolus dose of epinephrine on hemodynamics, acid-base status and potassium during spontaneous circulation and cardiopulmonary resuscitation (CPR) was investigated in 24 pigs weighing 20-25 kg over a period of 10 min. In a study of 12 pigs in a stable hemodynamic condition, at the 1- and 2-min point after injection of epinephrine or saline the mean serum potassium concentration was significantly higher in the six animals given epinephrine (6.9 +/- 0.7 and 5.4 +/- 0.6 mmol/l, respectively) than in the six control animals (3.8 +/- 0.6 and 3.9 +/- 0.4 mmol/l, respectively). At the later points of observation (3, 4, 5 and 10 min after injection of either epinephrine or saline) no significant difference was found between the groups. Following 1 min of ventricular fibrillation 12 pigs were resuscitated by closed-chest CPR. Six of these animals received 45 micrograms/kg epinephrine (epinephrine group), the other six animals were given physiological saline (control group). Mean aortic diastolic pressure during the relaxation phase was significantly higher in the epinephrine group than in the control group. There was no difference in cardiac index or acid-base status between the groups. In the epinephrine group mean arterial serum potassium concentrations reached a peak value of 6.7 +/- 1.1 mmol/l at 3 min after injection, when they were significantly (P less than 0.05) higher than in the control group (4.4 +/- 0.5 mmol/l). At 5 and 10 min, the potassium levels sank to 5.9 +/- 0.9 and 5.6 +/- 0.8 mmol/l, respectively, in the epinephrine group, and were no longer significantly different from the control group.     

Brain metabolism during cardiopulmonary resuscitation assessed with microdialysis

BACKGROUND AND PURPOSE: Microdialysis is an established tool to analyse tissue biochemistry, but the value of this technique to monitor cardiopulmonary resuscitation (CPR) effects on cerebral metabolism is unknown. The purpose of this study was to assess the effects of active-compression-decompression (ACD) CPR in combination with an inspiratory threshold valve (ITV) (=experimental CPR) vs. standard CPR on cerebral metabolism measured with microdialysis. METHODS: Fourteen domestic pigs were surfaced-cooled to a body core temperature of 26 degrees C and ventricular fibrillation was induced, followed by 10 min of untreated cardiac arrest; and subsequently, standard (n=7) CPR vs. experimental (n=7) CPR. After 8 min of CPR, all animals received 0.4 U/kg vasopressin IV, and CPR was maintained for an additional 10 min in each group; defibrillation was attempted after a total of 28 min of cardiac arrest, including 18 min of CPR. RESULTS: In the standard CPR group, microdialysis measurements showed a 13-fold increase of the lactate-pyruvate ratio from 7.2+/-1.3 to 95.5+/-15.4 until the end of CPR (P<0.01), followed by a further increase up to 138+/-32 during the postresuscitation period. The experimental group developed a sixfold increase of the lactate-pyruvate ratio from 7.1+/-2.0 to 51.1+/-8.7 (P<0.05), and a continuous decrease after vasopressin. In the standard resuscitated group, but not during experimental CPR, a significant increase of cerebral glucose levels from 0.6+/-0.1 to 2.6+/-0.5 mM was measured (P<0.01). CONCLUSION: Using the technique of microdialysis we were able to measure changes of brain biochemistry during and after the very special situation of hypothermic cardiopulmonary arrest. Experimental CPR improved the lactate-pyruvate ratio, and glucose metabolism.     

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.     

Splanchnic and renal blood flow after cardiopulmonary resuscitation with epinephrine and vasopressin in pigs

In laboratory investigations, vasopressin given during CPR resulted in improved vital organ blood flow when compared with epinephrine. Given the profound and long lasting vasopressor effects of vasopressin, we tested the hypothesis that vasopressin given during CPR would result in renal and splanchnic hypoperfusion in the post-resuscitation period when compared with epinephrine. After 4 min of ventricular fibrillation, 16 pigs were randomly assigned to receive either 0.045 mg·kg⁻¹ epinephrine or 0.4 U·kg⁻¹ vasopressin before defibrillation. Splanchnic and renal blood flow were measured 30, 90, and 240 min after restoration of spontaneous circulation (ROSC) in the epinephrine and vasopressin groups and in a control group of eight pigs using radiolabeled microspheres. Hepatic blood flow was measured before arrest and 30, 90, and 240 min after ROSC by means of indocyanine green infusion. Thirty minutes after ROSC, renal and adrenal blood flow were significantly lower in the vasopressin group (300 [273–334] and 256 [170–284] ml·min⁻¹·100 g⁻¹) (median and 25th and 75th percentile) as compared with the epinephrine group (370 [346–429] and 360 [326–420] ml·min⁻¹·100 g⁻¹; P<0.05). Pancreatic, intestinal, and hepatic blood flow were not significantly different in animals after receiving epinephrine or vasopressin. In comparison to epinephrine, vasopressin given during cardiac arrest impairs renal and adrenal perfusion temporarily but does not lead to intestinal or hepatic hypoperfusion in the post-resuscitation phase.     

Effects of intravenous arginine vasopressin on epicardial coronary artery cross sectional area in a swine resuscitation model

Although arginine vasopressin (AVP) has been shown to be a promising drug during cardiopulmonary resuscitation (CPR), concern has been raised about the potential for AVP-mediated vasoconstriction of the coronary arteries. In a prospective, randomized laboratory investigation employing an established porcine model, the effects of AVP on haemodynamic variables, left anterior descending (LAD) coronary artery cross sectional area employing intravascular ultrasound (IVUS), and return of spontaneous circulation were studied. During sinus rhythm, the LAD coronary artery cross sectional area was measured by IVUS at baseline, and 90 s and 5 min after AVP (0.4 U/kg IV). Following a 60 min recovery, ventricular fibrillation was induced. At 4 min, chest compressions were initiated; AVP (0.4 U/kg IV) was injected at 5.5 min, and defibrillation performed at 8 min. LAD coronary artery cross sectional area was measured by IVUS at the pre-arrest baseline, 90 s after drug injection during CPR, and 5 min after return of spontaneous circulation. Compared with baseline, the mid-LAD coronary artery cross sectional area increased significantly (P<.05) 90 s and 5 min after AVP administration (9.2+/-.5mm2 versus 10.7+/-.6mm2 versus 11.7+/-.6mm2, respectively) during normal sinus rhythm. Similarly during ventricular fibrillation and CPR plus AVP, the mid-LAD coronary artery cross sectional area increased at 90 s after AVP compared with baseline (9.5+/-.6mm2 versus 11.0+/-.7mm2; P<.05). Moreover, the cross sectional area increased further 5 min after return of spontaneous circulation (9.5+/-.6mm2 versus 14.0+/-.8mm2, P<.05). In conclusion, in this experimental model with normal coronary arteries, AVP resulted in significantly increased LAD coronary artery cross sectional area during normal sinus rhythm, during ventricular fibrillation with CPR, and after return of spontaneous circulation.     

Intraosseous vasopressin improves coronary perfusion pressure rapidly during cardiopulmonary resuscitation in pigs.

OBJECTIVE: Intravenous administration of vasopressin during cardiopulmonary resuscitation (CPR) may be more effective than optimal doses of epinephrine. The main purpose of this study was to determine whether intraosseous vasopressin achieves serum drug levels comparable with intravenous doses during CPR and, additionally, to evaluate the effects of intraosseous vasopressin during CPR. DESIGN: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, blood gases, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Twelve domestic pigs. INTERVENTIONS: After 4 mins of untreated ventricular fibrillation and 3 mins of CPR, 12 pigs were randomized to be treated with intravenous administration of vasopressin (0.8 unit/kg vasopressin; n = 6) or intraosseous vasopressin (0.8 unit/kg vasopressin; n = 6). Defibrillation was performed 5 mins after drug administration to attempt the return of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS: At both 90 secs and 5 mins after drug administration, intravenous and intraosseous administration of vasopressin resulted in comparable mean (+/-SEM) coronary perfusion pressure (43+/-4 vs. 44+/-3 and 30+/-2 vs. 37+/-2 mm Hg, respectively) and vasopressin plasma concentrations (13,706+/-1,857 vs. 16,166+/-3,114 pg/mL and 10,372+/-883 vs. 8246+/-2211 pg/mL, respectively). All animals in both groups were successfully resuscitated; pigs that received intraosseous vasopressin had a significantly higher (p < .05) mean arterial (92+/-6 vs. 129+/-12 mm Hg) and coronary perfusion pressure (84+/-11 vs. 119+/-11 mm Hg) at 5 mins of return of spontaneous circulation. CONCLUSIONS: Intraosseous vasopressin resulted in comparable vasopressin plasma levels, hemodynamic variables, and return of spontaneous circulation rates as did intravenous vasopressin. Intraosseous vasopressin may be an alternative for vasopressor administration during CPR, when intravenous access is delayed or not available.