The effect of norepinephrine versus epinephrine on regional cerebral blood flow during cardiopulmonary resuscitation

alpha-Adrenergic drugs improve cerebral blood flow (CBF) during cardiopulmonary resuscitation (CPR), in part, by reversing carotid artery collapse and by shunting blood from extracerebral to intracerebral vascular structures. Adrenergic drugs with beta 2-agonist properties may cause peripheral vasodilation, and thus may be less beneficial in this setting. The purpose of this study was to compare epinephrine (E), an alpha 1,2, beta 1,2-agonist, with norepinephrine (NE), an alpha 1,2, beta 1-agonist, on CBF during CPR. Twenty swine each weighing greater than 15 kg were instrumented for regional CBF measurements using tracer microspheres. Regional CBF was measured during normal sinus rhythm (NSR). Animals were then placed into ventricular fibrillation (VF). After ten minutes of VF, the animals received closed-chest CPR using a mechanical thumper. Regional CBF was measured during CPR. After three minutes of CPR, the animals were allocated to receive either E, 0.20 mg/kg (N = 5); NE, 0.08 mg/kg (N = 5); NE, 0.12 mg/kg (N = 5); or NE, 0.16 mg/kg (N = 5). Regional blood flows were again measured following drug administration. CBFs following drug administration were compared using an analysis of covariance adjusting for baseline differences during CPR. A Newman-Keuls multiple comparison was used to follow-up significant (P less than or equal to .05) differences. Statistical significance was considered at P less than or equal to .05. There was a clinically significant improvement in cerebral cortical flow with NE, 0.12 mg/kg, and NE, 0.16 mg/kg, compared with NE, 0.08 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Methoxamine versus epinephrine on regional cerebral blood flow during cardiopulmonary resuscitation

The improvement in cerebral blood flow (CBF) during CPR after epinephrine administration has been attributed to epinephrine's alpha-adrenergic properties. Methoxamine, a pure alpha-1 agonist, has only been shown to be comparable to epinephrine in restoring circulation after cardiac arrest in a canine model. This study compares the effectiveness of equipotent doses of epinephrine and methoxamine in improving CBF during CPR after a prolonged cardiac arrest in a swine model. Twenty-five swine, weighing 15.9 to 28.2 kg, underwent instrumentation for regional CBF using tracer microspheres. CBF was determined during normal sinus rhythm. After 10 min of ventricular fibrillation, CPR was begun with a pneumatic compressor. CBF measurements were again made during CPR. After 3 min of CPR, the swine were randomized to receive 0.02 or 0.2 mg/kg epinephrine, 0.1, 1.0, or 10.0 mg/kg methoxamine. Five swine were allocated to each group. CBF measurements were determined after drug administration and compared using a Bonferroni multiple comparison procedure. A p-value less than .05 was considered statistically significant. This study demonstrated that, after a 10-min cardiac arrest, CBF was extremely low, averaging less than 7 ml/min X 100 g during external CPR. There were no clinically significant improvements in regional CBF after 0.02 mg/kg of epinephrine, or the two lowest doses of methoxamine. The addition of 10 mg/kg of methoxamine clinically improved blood flow only to the most caudal CNS structures, including the pons, medulla, and cervical spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of high dose norepinephrine versus epinephrine on cerebral and myocardial blood flow during CPR

Several animal studies have demonstrated an improvement in cerebral blood flow (CBF) and myocardial blood flow (MBF) after the administration of epinephrine (E) 0.20 mg/kg during closed chest CPR. The administration of norepinephrine (NE) in doses of 0.12 and 0.16 mg/kg demonstrated a trend toward improved CBF and MBF during CPR over that seen with E 0.20 mg/kg in the same animal model. The purpose of this study was to compare the effects of a higher dose of NE 0.20 mg/kg to E 0.20 mg/kg to determine if increasing doses of NE would demonstrate further improvement in CBF and MBF during CPR. Fourteen immature swine were anesthetized and instrumented for regional blood flow and hemodynamic measurements. After 10 min of ventricular fibrillation (VF), CPR was begun using a mechanical thumper. After 3 min of CPR, the animals received either E 0.20 mg/kg (n = 7) or NE 0.20 mg/kg (n = 7) through a right atrial catheter. CPR was continued for an additional 3.5 min and defibrillation was then attempted. CBF (ml/min/100 g), MBF (ml/min/100 g), myocardial oxygen delivery (MDo2; ml O2/min/100 g), myocardial oxygen consumption (MVo2; ml O2/min/100 g), and myocardial oxygen extraction ratios (ER, MVo2/MDo2) were measured during normal sinus rhythm (NSR), during CPR, and during CPR following drug administration. Following drug administration, CBF, MBF, MDo2 and MVo2 rose while ER fell in both E and NE groups. There were no significant differences between groups in CBF, ER, or intravascular pressures following drug administration (P greater than or equal to 0.07). The NE group demonstrated significantly higher MBF (118.9 +/- 73.1 vs. 62.2 +/- 45.3, P = 0.04), MVo2 (14.2 +/- 7.7 vs. 7.0 +/- 3.8, P = 0.05), and MDo2 (19.9 +/- 13.4 versus 9.4 +/- 6.3, P = 0.05) compared to the E group following drug administration While NE improved MBF and MDo2 over E during CPR, there was a trend toward lower resuscitation rates with NE (57.1% vs. 85.7% P = 0.56). Any benefit of higher MBF and MDo2 with NE 0.20 mg/kg appears to be offset by proportionately high MVo2 and a trend toward lower resuscitation rates in the NE 0.20 mg/kg animals.     

The effect of epinephrine versus methoxamine on regional myocardial blood flow and defibrillation rates following a prolonged cardiorespiratory arrest in a swine model

Recent studies in swine have shown that larger doses of epinephrine than those currently employed for cardiopulmonary resuscitation (CPR) significantly improve regional myocardial blood flow following prolonged cardiac arrest. The dose-response effect of a pure alpha-adrenergic agonist, methoxamine, on regional myocardial blood flow has not been investigated in this setting. This study compared the effect of high-dose epinephrine with graded doses of methoxamine on regional myocardial blood flow, oxygen delivery/utilization, and defibrillation rates during CPR. Twenty swine were instrumented for regional myocardial blood flow measurements using radiolabeled tracer microspheres. Measurements of regional myocardial blood flow, oxygen delivery, and oxygen consumption were made during normal sinus rhythm. Ventricular fibrillation was then induced. Following 10 minutes of ventricular fibrillation, CPR was initiated with a pneumatic compressor. Regional myocardial blood flow, oxygen delivery, and oxygen consumption were then measured during CPR. Following 3 minutes of CPR, the swine were allocated to one of four treatment groups (five per group): group I, epinephrine 0.2 mg/kg; group II, methoxamine 0.1 mg/kg; group III, methoxamine 1.0 mg/kg; and group IV, methoxamine 10.0 mg/kg. One minute after drug administration, regional myocardial blood flow, oxygen delivery, and oxygen consumption measurements again were made. Three and one half minutes after drug administration, defibrillation was attempted. Regional myocardial blood flow following drug administration was compared using an analysis of covariance. Epinephrine (0.2 mg/kg) significantly improved myocardial blood flow (P less than .002) for all tissues examined compared with all doses of methoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)     

A model for regional blood flow measurements during cardiopulmonary resuscitation in a swine model

Recent reports examining regional blood flow during cardiopulmonary resuscitation (CPR) have been criticized for several reasons: (1) cardiac arrest times of 5 min or less are not reflective of the prehospital setting, (2) anesthetic agents may significantly influence autonomic control of regional blood flow, (3) canine cardiac anatomy and coronary blood supply are not reflective of humans and (4) precise validation data for blood flow measurements have not been reported. This study presents a methodology and model for measuring regional blood flow during CPR after a prolonged cardiac arrest. Fifteen swine weighing 15-25.4 kg were instrumented for regional blood flow measurements using tracer microspheres. Regional cerebral and myocardial blood flow were measured during normal sinus rhythm (NSR) and during CPR following a 10-min cardiopulmonary arrest. Regional blood flow (ml/min/100 g) to the cerebral cortices averaged less than 3% of baseline flow (NSR: right cortex = 41.2 +/- 13.8; left cortex = 41.2 +/- 12.2; CPR: right cortex = 1.3 +/- 1.2; left cortex = 1.3 +/- 1.3). Total myocardial blood flow averaged less than 5% of baseline flow (NSR = 211.5 +/- 104.9; CPR = 9.5 +/- 14.9). The flow data demonstrates minimal cardiac and cerebral perfusion with standard CPR following a 10-min arrest. The variability in the pilot data may be used in determining sample sizes for future studies.     

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 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.     

Effects of hypertonic versus isotonic infusion therapy on regional cerebral blood flow after experimental cardiac arrest cardiopulmonary resuscitation in pigs

OBJECTIVE: To evaluate the effects of hypertonic, isooncotic, and isotonic infusion therapy on cerebral blood flow (CBF) during and after cardiopulmonary resuscitation (CPR) from experimental cardiac arrest (CA). METHODS: In 32 domestic swine (13-23 kg) open chest CPR was initiated after 8 min of ventricular fibrillation. With the onset of CPR animals randomly received 2 ml/kg per 10 min of either hypertonic saline (HS: 7.2% NaCl), hypertonic-isooncotic HES-saline (HHS: 7.2% NaCl in 6% HES 200,000/0.5), isooncotic HES (6% HES 200,000/0.5), or isotonic (normal) saline (NS: 0.9% NaCl). Haemodynamic variables were monitored continuously, and coloured microspheres were used to measure CBF quantitatively before CA, during CPR, and 20, 90 and 240 min after restoration of spontaneous circulation (ROSC). RESULTS: In HES/NaCl treated animals, CBF significantly decreased during CPR compared to the prearrest level (P < 0.01, respectively; MANOVA). In contrast, CBF was sustained during CPR in HS/HHS treated animals and significantly higher compared to animals receiving NS (P < 0.05, respectively). During recirculation severe postischaemic hypoperfusion as indicated by a decrease of CBF below the prearrest level, was present only in animals receiving HES and NS. CONCLUSIONS: Hypertonic solutions (HS/HHS) applied during internal cardiac massage enhanced CBF during CPR and after ROSC.     

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.     

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.     

Increased cortical cerebral blood flow by continuous infusion of adrenaline (epinephrine) during experimental cardiopulmonary resuscitation

OBJECTIVE: To study the effects of continuously administered adrenaline (epinephrine), compared to bolus doses, on the dynamics of cortical cerebral blood flow during experimental cardiopulmonary resuscitation (CPR), and after restoration of spontaneous circulation (ROSC). METHODS: Ventricular fibrillation was induced in 24 anaesthetised pigs. After a 5-min non-intervention interval, closed-chest CPR was started. The animals were randomised into two groups. One group received three boluses of adrenaline (20 microg/kg) at 3-min intervals. The other group received an initial bolus of adrenaline (20 microg/kg) followed by an infusion of adrenaline (10 microg/kg x min). After 9 min of CPR, defibrillation was attempted, and if spontaneous circulation was achieved the adrenaline infusion was stopped. Cortical cerebral blood flow was measured continuously using Laser-Doppler flowmetry. Jugular bulb oxygen saturation was measured to reflect global cerebral oxygenation. Repeated measurements of 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) in jugular bulb plasma were performed to evaluate cerebral oxidative injury. RESULTS: During CPR mean cortical cerebral blood flow was significantly higher (P=0.009) with a continuous adrenaline infusion than with repeated bolus doses. Following ROSC there was no significant difference in cortical cerebral blood flow between the two study groups. No differences in coronary perfusion pressure, rate of ROSC, jugular bulb oxygen saturation or 8-iso-PGF(2alpha) were seen between the study groups. CONCLUSIONS: Continuous infusion of adrenaline (10 microg/kg x min) generated a more sustained increase in cortical cerebral blood flow during CPR as compared to intermittent bolus doses (20 microg/kg every third minute). Thus, continuous infusion might be a more appropriate way to administer adrenaline as compared to bolus doses 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.     

Endothelin-1 elevates regional cerebral perfusion during prolonged ventricular fibrillation cardiac arrest in pigs

Since adrenaline (epinephrine) also has negative effects during and after cardiopulmonary resuscitation (CPR) a non-adrenergic vasoconstrictor like endothelin might be an alternative to increase vital organ blood flow. We studied the effect of different doses of endothelin-1 compared with adrenaline on the ability to resuscitate, cerebral and myocardial blood flow (MBF) in a closed chest cardiac arrest pig model. After 5 min of ventricular fibrillation, CPR with a ventilator and a mechanical compression device was started. At 10 min, 31 pigs were randomized to receive a single dose of endothelin-1 50, 100 or 200 microg or repeated doses of adrenaline 0.04 mg kg(-1) or saline every 3 min. After 25 min, the pigs were defibrillated to achieve restoration of spontaneous circulation. Blood flow was measured with the fluorescent microsphere method. In animals receiving endothelin-1 50, 100 and 200 microg the cerebral blood flow (CBF) increased from median 28 (25th; 75th quartile: 16; 40), 32 (15; 48) and 17 (4; 65) to 36 (31; 54), 47 (39; 57) and 63 (35; 83) ml min(-1) per 100 g, respectively, 6 min after drug administration (P<0.05 endothelin-1 50 microg vs. Control, P<0.01 endothelin-1 100 and 200 microg vs. Control). At the same time CBF decreased in the control and adrenaline group from 36 (21; 41) and 39 (15; 50) to 12 (2; 25) and 24 (15; 26) ml min(-1) per 100 g, respectively, (P<0.05 adrenaline vs. endothelin-1 200 microg). There was no difference in MBF between the treatment groups despite a higher coronary perfusion pressure (CoPP) in the endothelin-1 groups. Restoration of spontaneous circulation could be only achieved in the endothelin-1 50 microg (3 of 7; 43%) and 100 microg (5 of 7; 71%) group. This study suggests that endothelin-1 enhances CBF during CPR better than adrenaline and increases resuscitation success.     

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.     

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.     

Hemodynamic effects of 1-[3,4-dihydroxypheny]-1,2-diaminoethane versus norepinephrine during ventricular fibrillation and cardiopulmonary resuscitation

We hypothesized that substitution of the hydroxyl group (OH) on the beta carbon of norepinephrine (NE) with an amino group would yield a compound, 1-(3,4.dihydroxypheny)- 1,2-diaminoethane (DHPDAE), that would maintain the hemodynamic properties of NE during CPR, but would decrease the rate of post-defibrillation dysrhythmias. Six mixed breed swine weighing greater than 28 kg were studied. The animals were instrumented for cerebral (CBF) and myocardial blood flow (MBF) measurements. Ventricular fibrillation (VF) was induced. After 10 min of VF, CPR was begun. After 3 min of CPR, 2.5 mg/kg of DHPDAE was administered and CPR continued. Defibrillation was attempted 3.5 min after drug administration. CBF, MBF and defibrillation rates were compared to an historical control group receiving 0.16 mg/kg of NE. Outcome variables were compared using a Wilcoxon Rank Sum test and Fisher-exact test. NE significantly improved CBF and MBF compared to DHPDAE. All the animals in the NE group were successfully defibrillated into a perfusing rhythm. Sixty percent of the NE treated animals experienced post-defibrillation ventricular dysrhythmias. None of the animals in the DHPDAE were successfully defibrillated into a perfusing rhythm. Substitution of the hydroxyl group on the beta-carbon of NE with an amino group significantly decreases the hemodynamic properties of the parent molecule.     

Intra-aortic administration of epinephrine above an aortic balloon occlusion during experimental CPR does not further improve cerebral blood flow and oxygenation

Balloon occlusion of the descending aorta during cardiopulmonary resuscitation (CPR) improves coronary and cerebral blood flow. In comparison with an equivalent dose administered through a central venous catheter it has been suggested that epinephrine administration above the aortic occlusion might produce a more rapid increase in coronary perfusion pressure and a shorter time to restoration of spontaneous circulation (ROSC). In a recent study, however, outcome was not improved after intra-aortic epinephrine administration. We hypothesised that epinephrine administered above the aortic occlusion could impose adverse effects on cerebral blood flow and oxygenation, possibly because of an alpha-adrenergic mediated vasoconstriction in the cerebral vascular beds. Twenty-six piglets underwent 5 min of non intervention cardiac arrest followed by 8 min of closed-chest CPR. They were randomised to receive bolus doses of 45 microg/kg epinephrine either above the aortic occlusion or through a central venous catheter. Cerebral cortical blood flow was continuously measured using laser-Doppler technique. Cerebral tissue pH and PCO(2) were also measured using a multi-parameter fiberoptic device and cerebral oxygen extraction was calculated. Balloon inflation resulted in an immediate enhancement of cerebral cortical blood flow. Each of the epinephrine boluses through the central venous catheter resulted in a transient increase in cerebral cortical blood flow. When administered above the aortic balloon occlusion, epinephrine did not result in a further increase in cerebral cortical blood flow, though a significant increase in cerebral perfusion pressure was recorded throughout the CPR period. Cerebral tissue pH monitoring revealed severe acidosis during CPR and long after ROSC, which was refractory to buffering. No differences in the cerebral oxygen extraction ratio were observed between the groups. In conclusion, epinephrine administration above an aortic balloon occlusion was unable to improve cerebral blood flow and oxygenation. In fact, it may even attenuate the beneficial effects of aortic balloon occlusion on cerebral blood flow due to an alpha-adrenergic mediated cerebral vasoconstriction. Further studies, including dose-response and volumes of distribution, are needed to identify the effective beneficial dosage of epinephrine during aortic occlusion with the least possible adverse effects.     

Correlation of transconjunctival PO2 with cerebral oxygen delivery during cardiopulmonary resuscitation in dogs

The relationship between transconjunctival PO2 (PcjO2) and cerebral oxygen delivery (DO2) was examined in dogs during sinus rhythm and CPR with an inflatable vest. Microsphere-determined cerebral blood flow (CBF), DO2, and PcjO2 readings were normal during sinus rhythm. During CPR, with carotid pressure of 82 +/- 11/25 +/- 5 (SEM) mm Hg, cerebral perfusion and DO2 fell by 53% and 57%, respectively, while PcjO2 fell by 87%. After epinephrine administration, carotid pressure increased to 128 +/- 13/48 +/- 9 mm Hg, and CBF and DO2 rose to 130% and 115% of pre-arrest levels, respectively, but PcjO2 readings remained at 11% of control values. Thus, PcjO2 failed to reflect accurately either CBF or DO2 during CPR. In the presence of epinephrine, PcjO2 does not seem to provide an accurate index of the effectiveness of CPR.     

A PET study of regional cerebral blood flow after experimental cardiopulmonary resuscitation

Cerebral blood flow (CBF) during cardiopulmonary resuscitation and after restoration of spontaneous circulation (ROSC) from cardiac arrest has previously been measured with the microspheres and laser Doppler techniques. We used positron emission tomography (PET) with [15O]--water to map the haemodynamic changes after ROSC in nine young pigs. After the baseline PET recording, ventricular fibrillation of 5 min duration was induced, followed by closed-chest cardiopulmonary resuscitation (CPR) in conjunction with IV administration of three bolus doses of adrenaline (epinephrine). After CPR, external defibrillatory shocks were applied to achieve ROSC. CBF was measured at intervals during 4h after ROSC. Relative to the mean global CBF at baseline (32+/-5 ml hg(-1)min(-1)), there was a substantial global increase in CBF at 10 min, especially in the diencephalon. This was followed by an interval of cortical hypoperfusion and a subsequent gradual return to baseline values.     

Buffer administration during CPR promotes cerebral reperfusion after return of spontaneous circulation and mitigates post-resuscitation cerebral acidosis

To explore the effects of alkaline buffers on cerebral perfusion and cerebral acidosis during and after cardiopulmonary resuscitation (CPR), 45 anaesthetized piglets were studied. The animals were subjected to 5 min non-interventional circulatory arrest followed by 7 min closed chest CPR and received either 1 mmol/kg of sodium bicarbonate, 1 mmol/kg of tris buffer mixture, or the same volume of saline (n=15 in all groups), adrenaline (epinephrine) boluses and finally external defibrillatory shocks. Systemic haemodynamic variables, cerebral cortical blood flow, arterial, mixed venous, and internal jugular bulb blood acid-base status and blood gases as well as cerebral tissue pH and PCO(2) were monitored. Cerebral tissue acidosis was recorded much earlier than arterial acidaemia. After restoration of spontaneous circulation, during and after temporary arterial hypotension, pH in internal jugular bulb blood and in cerebral tissue as well as cerebral cortical blood flow was lower after saline than in animals receiving alkaline buffer. Buffer administration during CPR promoted cerebral cortical reperfusion and mitigated subsequent post-resuscitation cerebral acidosis during lower blood pressure and flow in the reperfusion phase. The arterial alkalosis often noticed during CPR after the administration of alkaline buffers was caused by low systemic blood flow, which also results in poor outcome.