Ingrid M. Bowdler

Comparison of different doses of epinephrine on myocardial perfusion and resuscitation success during cardiopulmonary resuscitation in a pig model

Published results of dose-response effects of adrenergic drugs (epinephrine [E]) vary so much between studies because of differences in animal models and duration of ischemia before drug administration. In this investigation the effects of different doses of E on coronary perfusion pressure (CPP), left ventricular myocardial blood flow (MBF) and resuscitation success were compared during closed-chest cardiopulmonary resuscitation (CPR) after a 4-minute period of ventricular fibrillation in 28 pigs. MBF was measured during normal sinus rhythm using tracer microspheres. After 4 minutes of ventricular fibrillation CPR was performed with the use of a pneumatic piston compressor. After 4 minutes of mechanical measures only, the animals were randomly allocated into four groups of seven, receiving 0.015, 0.030, 0.045, and 0.090 mg/kg E intravenously respectively. MBF measurements were started 45 seconds after E administration; hemodynamic measurements after 90 seconds. Four minutes after the first administration, the same E dose was given before defibrillation. The CPP of animals given 0.015, 0.030, 0.045 and 0.090 mg/kg E were as follows: 16.3 +/- 6.1, 25.6 +/- 5.8, 33.2 +/- 8.4 and 30.4 +/- 6.3 mm Hg. The left ventricular MBF values were: 14 +/- 9, 27 +/- 11, 43 +/- 6, 46 +/- 10 mL/min/100 g. The differences between the groups receiving 0.015 and 0.045 mg/kg and between the groups receiving 0.015 mg/kg and 0.090 mg/kg were statistically significant (P less than .05). Resuscitation success was 14.3%, 42.9%, 100% and 86.7% respectively. A significant difference in resuscitation success was found only between 0.015 mg/kg and 0.045 mg/kg E.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of epinephrine and norepinephrine on cerebral oxygen delivery and consumption during open-chest CPR.

The effect of epinephrine and norepinephrine on cerebral oxygen delivery and consumption after five minutes of cardiopulmonary arrest and three minutes of open-chest cardiac massage was studied in 21 pigs. Norepinephrine, like epinephrine, has a marked alpha- and beta 1-sympathomimetic activity, but compared with epinephrine, the degree of beta 2-stimulation is weak. Epinephrine probably stimulates cerebral oxygen and glucose consumption by its beta 2-adrenergic effect. After three minutes of CPR, three groups of seven animals each blindly received either placebo (control group), 45 micrograms/kg epinephrine, or 45 micrograms/kg norepinephrine. During CPR but before drug administration, cerebral blood flow was 23 +/- 14 mL/min/100 g in the control group, 30 +/- 7 mL/min/100 g in the epinephrine group, and 30 +/- 11 mL/min/100 g in the norepinephrine group. At 90 seconds after epinephrine, cerebral blood flow increased to 54 +/- 14 mL/min/100 g and after norepinephrine, to 58 +/- 22 mL/min/100 g (P less than .05). Cerebral perfusion pressure for both drugs was significantly higher than the control group. Compared with mechanical measures alone, cerebral oxygen delivery rose from 4.3 +/- 1.2 to 7.4 +/- 1.7 mL/min/100 g after epinephrine and from 3.7 +/- 1.4 to 7.3 +/- 2.7 mL/min/100 g after norepinephrine (P less than .05). There was no increase in cerebral oxygen consumption after both catecholamines, and cerebral oxygen extraction ratio decreased. Cerebral glucose delivery increased in relation to glucose consumption, and extraction ratio did not change significantly after both catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of Epinephrine on Systemic, Myocardial, and Cerebral Acid-Base Status during Cardiopulmonary Resuscitation

During cardiopulmonary resuscitation (CPR), arterial pH and carbon dioxide tension (PCO2) do not reflect the marked acidosis and hypercapnia seen in venous blood samples during CPR. Epinephrine causes an increase in myocardial and cerebral blood flow during CPR, but the influence on regional venous PCO2 and pH is as yet unknown. Fourteen pigs were allocated to receive either 0.9% saline (n = 7), or 45 micrograms/kg epinephrine (n = 7) after 5 min of ventricular fibrillation and 3 min of open-chest CPR. Blood samples were obtained during CPR from the aorta, pulmonary artery, great cardiac vein, and sagittal sinus before and 90 s and 5 min after drug administration. Regional blood flow was measured with tracer microspheres. Plasma catecholamines were quantified by high-performance liquid chromatography in arterial blood. PCO2 90 s after drug administration in arterial, mixed venous, myocardial venous, and cerebral venous blood were (means +/- SD) 36 +/- 8, 67 +/- 9, 74 +/- 14, and 79 +/- 19 mmHg in the control group and 35 +/- 11, 62 +/- 12, 73 +/- 10, and 71 +/- 14 mmHg in the epinephrine group. pH values 90 s after drug administration in the same blood samples were 7.29 +/- 0.11, 7.11 +/- 0.09, 7.04 +/- 0.09, and 7.07 +/- 0.10 in the control group and 7.31 +/- 0.13, 7.17 +/- 0.07, 7.08 +/- 0.08, and 7.07 +/- 0.12 in the epinephrine group. Despite a significant increase in myocardial and cerebral blood flow after epinephrine, PCO2 and pH in all blood samples were not different from those of the control group. (ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of epinephrine and dopamine during cardiopulmonary resuscitation

The effectiveness of epinephrine and dopamine for restoring spontaneous circulation after asphyxial or fibrillatory cardiac arrest was compared using a porcine model. Asphyxial arrest: 7 animals received 45 μg/kg epinephrine, 7 animals 2.5 mg/kg dopamine, the remaining 7 animals received no drug treatment. All 7 animals given epinephrine could be resuscitated after 174±53 s, spontaneous circulation could be restored in only 3 of 7 animals given dopamine after 487±63 s and in none of the control animals could spontaneous circulation be established. Ventricular fibrillation: 7 animals were defibrillated without either mechanical measures or drug therapy. The following doses were given before defibrillation and after starting mechanical measures to separate groups of 7 animals each: 45 μg/kg epinephrine, 2.5 mg/kg dopmaine, or no drug therapy. In the absence of either drug or mechanical measures and with mechanical measures only, spontaneous circulation could not be established in any of the cases. After administration of epinephrine, defibrillation and restoration of spontaneous circulation was achieved in 6 of 7 animals in 667±216 s, with dopamine, all the animals could be successfully resuscitated in the shorther time of 174±85 s. Epinephrine was found to be superior to dopamine in the treatment of asphyxial arrest whereas dopamine was found to be better in the management of ventricular fibrillation, probably by improving the balance between myocardial oxygen supply and demand.

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.

The respiratory aspect of the treatment of brain injury associated with acute alcohol intoxication - results of an animal experiment

The effects of spontaneous respiration and mechanical ventilation were examined by investigating the interaction between elevated intracranial pressure and alcohol intoxication. Ethanol (200 ml 48%) was infused in 11 young pigs with elevated cerebral pressure during mechanical ventilation (group 1), 7 young pigs with elevated cerebral pressure during spontaneous respiration (group 2), and 4 young pigs without elevated cerebral pressure during spontaneous respiration (group 3). While the behavior of intracranial pressure during mechanical ventilation in the animals from group 1 was inhomogeneous with a tendency to rise (29-34 mmHg), cerebral pressure (28-55 mmHg) increased drastically in the animals from group 2. This increase was associated with a sharp rise of Pa,CO2 (37.6-73.3 mmHg) and a decrease of Pa,O2 (74 mmHg to 13 mmHg). None of the animals in group 2 survived. Pa,CO2 also rose in alcoholized animals without elevated cerebral pressure (group 3) (41.9-63.9 mmHg); intracranial pressure, however, remained within the normal range. All animals in group 3 survived. Our findings indicate that elevated intracranial pressure and alcohol intoxication have a cumulative or potentiating effect on depression of the respiratory center. Respiratory depression can be prevented by mechanical ventilation and, therefore, a further rise of intracranial pressure generally avoided.

The early use of positive end expiratory pressure (PEEP) ventilation in emergency medicine, and some experiments on pigs

The effects on near drowning of young pigs of positive end expiratory pressure and zero end expiratory pressure were studied. The arterial PO2 and blood gases were examined during recovery from near drowning and after haemorrhagic shock. The cardiovascular parameters were measured after shock. The findings were considered in relation to the use of positive and expiratory pressure in patients. It was recommended that it be only administered by experienced staff in hospitals, and should not exceed 10 mbars, while 5 mbar was adequate and avoided complications in most cases.

An experimental study of respiratory reanimation of piglets following standardized near-drowning in fresh or salt-water.

Abstract A standardized near-drowning procedure was carried out on 34 anaesthetized, mechanically ventilated piglets. Twenty five milliliters of fresh water or 12.5 ml of salt-water/kg body wt were introduced into the trachea followed by an apnoeic interval of 4 or 3 min, respectively, and then by a period of mechanical ventilation for 2 h with 100% oxygen using either zero end-expiratory pressure (ZEEP) or positive end-expiratory pressure (PEEP). Using PEEP ventilation, the initial partial pressure of oxygen ( P O 2 ) and alveolar arterial oxygen gradient (AaDO 2 ) values returned quickly in all groups. However, using ZEEP, values had not returned to normal even at the end of the experiment. In the salt-water group the P O 2 values fell and the AaDO 2 increased during the first half hour after near-drowning — a sign for the initially increasing pulmonary damage. The arterial partial pressure of carbon dioxide ( P CO 2 ) values were the same in all four groups, remaining 20% above the initial values following near-drowning. The initiation of respiration was associated with a tachycardia and an increase in mean blood pressure and cardiac output (CO). These haemodynamic parameters returned ti normal when the animals were no longer hypoxic. PEEP was not found to influence cardio-circulatory function. The continuously increased serum sodium ion concentration and osmolality following near-drowning in salt-water clearly showed the degree of hypertonic dehydration occurring. In comparison, the fresh-water groups showed only a brief increase in haematocrit and potassium ion levels. These changes were not themselves of such magnitude as to require correction. It is recommended that the emergency treatment of all cases of near-drowning should include the use of PEEP ventilation with a pressure of + 5 cmH 2 O as early as possible.