Friedrich W. Ahnefeld

Stress Hormone Response during and after Cardiopulmonary Resuscitation

The purpose of this study was to assess whether plasma adrenocorticotropin, cortisol, vasopressin, and renin concentrations are higher in resuscitated than in nonresuscitated patients during cardiopulmonary resuscitation, and whether there are possible correlations between these hormones and blood pressure or heart rate in the immediate postresuscitation phase. Of 34 consecutive patients (36-85 yr of age) with out-of-hospital cardiac arrest, 20 could be successfully resuscitated and admitted to hospital, whereas in the remaining 14 patients restoration of spontaneous circulation could not be achieved. During cardiopulmonary resuscitation, median adrenocorticotropin, cortisol, vasopressin, and renin concentrations in the external jugular vein were 237 pg/ml, 32.6 micrograms/dl, 122 pg/ml, and 46.5 ng/l, respectively, in resuscitated patients, and 45 pg/ml (P = 0.018), 18.4 micrograms/dl (P = 0.481), 88 pg/ml (P = 0.049), and 11 ng/l (P = 0.017), respectively, in nonresuscitated patients. Median adrenocorticotropin, cortisol, vasopressin, and renin concentrations were 101 pg/ml, 34.6 micrograms/dl, 22 pg/ml, and 25 ng/l, respectively, 60 min after successful resuscitation. No significant correlations were found between hormone levels and blood pressure or heart rate, but there was a significant negative correlation between the interval from collapse to the start of cardiopulmonary resuscitation and plasma cortisol concentrations during cardiopulmonary resuscitation (Spearman rank correlation coefficient = -0.967, P less than 0.001), indicating an impaired cortisol release from the adrenal cortex. The lower hormone concentrations of the nonresuscitated patients measured during cardiopulmonary resuscitation might indicate an impairment in neuroendocrine response.

Effects of active compression-decompression resuscitation on myocardial and cerebral blood flow in pigs.

BACKGROUND This study was designed to assess the effects of a modified cardiopulmonary resuscitation (CPR) technique that consists of both active compression and active decompression of the chest (ACD CPR) versus standard CPR (STD CPR) on myocardial and cerebral blood flow during ventricular fibrillation both before and after epinephrine administration. METHODS AND RESULTS During a 30-second period of ventricular fibrillation cardiac arrest, 14 pigs were randomized to receive either STD CPR (n = 7) or ACD CPR (n = 7). Both STD and ACD CPR were performed using an automated pneumatic piston device applied midsternum, designed to provide either active chest compression (1.5 to 2.0 in.) and decompression or only active compression of the chest at 80 compressions per minute and 50% duty cycle. Using radiolabeled microspheres, median total myocardial blood flow after 5 minutes of ventricular fibrillation was 14 (7 to 30, minimum to maximum) STD CPR versus 30 (9 to 46) mL.min-1 x 100 g-1 with ACD CPR (P < .05). Median cerebral blood flow was 15 (10 to 26) mL.min-1 x 100 g-1 with STD CPR and 30 (21 to 39) with ACD CPR (P < .01). When comparing STD with ACD CPR, aortic systolic (62 mm Hg [48 to 70] vs 80 [59 to 86]) and diastolic (22 [18 to 28] vs 28 [21 to 36]) pressures, calculated coronary systolic (30 [22 to 36] vs 49 [37 to 56]) and diastolic (18 [16 to 23] vs 26 [21 to 31]) perfusion pressures, end-tidal CO2 (1.4% [0.8 to 1.8] vs 2.1 (1.8 to 2.4]), cerebral O2 delivery (3.1 mL.min-1 x 100 g-1 [1.5 to 4.5] vs 5.3 [3.8 to 7.5]), and cerebral perfusion pressure (14 mm Hg [4 to 22] vs 26 [6 to 34]) were all significantly higher with ACD CPR: To compare these parameters before and after vasopressor therapy, a bolus of high-dose epinephrine (0.2 mg/kg) was given to all animals after 5 minutes of ventricular fibrillation. Organ blood flow and calculated perfusion pressures increased significantly in both the STD and ACD groups after epinephrine. The differences observed between STD and ACD CPR before epinephrine were diminished 90 seconds after epinephrine but were again statistically significant when assessed 5 minutes later, once the acute effects of epinephrine had decreased. No difference in short-term resuscitation success was found between the two groups. CONCLUSIONS We conclude that ACD CPR significantly increases myocardial and cerebral blood flow during cardiac arrest in the absence of vasopressor therapy compared with STD CPR:

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)

Comparison of standard and high‐dose adrenaline in the resuscitation of asystole and electromechanical dissociation

Sixty‐eight adults with cardiac arrest (asystole and electromechanical dissociation) were randomly allocated for treatment with standard (1 mg) or high‐dose epinephrine (5 mg). If the first dose of adrenaline 11 or 5 mg) failed, standardized advanced life‐support was applied in all cases. High‐dose adrenaline was associated with higher initial resuscitation success rates (16 of 28) than standard‐dose adrenaline (6 of 40), whereas hospital discharge rates were not significantly different between the groups. Blood pressure was significantly higher in the high‐dose adrenaline group in comparison to the standard dose at 1 and 5 min after resuscitation. Although high‐dose adrenaline appears to improve cardiac resuscitation success, the duration of global cerebral ischaemia seems to determine the ultimate outcome.

Effects of norepinephrine, epinephrine, and dopamine infusions on oxygen consumption in volunteers.

Objective:To determine the relationships between plasma concentrations of norepinephrine, epinephrine, and dopamine and oxygen consumption (Co2) during infusion of these catecholamines.Design:Prospective, randomized variable dose, pharmacologic study in which a noncumu-lative infusion-rate design wa

Endotracheal and endobronchial lidocaine administration : effects on plasma lidocaine concentration and blood gases

ObjectiveTo compare four different methods of endotracheal lidocaine administration with respect to the site of administration. DesignRandomized controlled trial. SettingUniversity hospital. PatientsThirty-two female patients (43.6 ± 11.5 yrs old) undergoing elective gynecologic operations with an anesthesiologic risk classification not higher than ASA II. All patients gave their written informed consent to participate in the study. InterventionsLidocaine at a dose of 2 mg/kg, diluted with normal saline to a total volume of 10 mL, was administered to eight patients by instilling the drug solution from a 10-mL syringe directly into the outer aperture of the endotracheal tube. All other study patients received lidocaine under bronchoscopic control through the work channel of the bronchoscope either a) deep endotracheally, b) into the right main bronchus, or c) into the right lower lobe bronchus. At 10 points in time after drug administration, blood samples were taken for measurement of lidocaine plasma concentration (usinghigh-pressure liquid chromatography) and blood gas analysis. Main Measurements and ResultsTherapeutic blood concentrations (>1.4 μg/mL) could be achieved and toxic blood concentrations (>6 pg/mL) could be avoided with all methods of administration. No significant difference was found between the different methods with regard to peak concentration, time to peak, onset and duration of therapeutic levels, or relative bioavailability. A significant (p < .05) decrease in Pao2 to 75% of the baseline was seen with all methods used. ConclusionsBecause no route of lidocaine administration was superior to the others, the simplest method (instillation into the endotracheal tube) should be used. (Crit Care Med 1991; 19:911)

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.

Plasma lidocaine levels and PaO2 with endobronchial administration: Dilution with normal saline or distilled water?

STUDY OBJECTIVE To determine whether water or 0.9% saline should be used as diluent for endobronchial drug administration. PARTICIPANTS Twelve adult patients. INTERVENTIONS Patients were endobronchially administered 2 mg/kg lidocaine as marker substance in either 10 mL 0.9% saline or 10 mL distilled water during general anesthesia. MEASUREMENTS AND MAIN RESULTS The differences in mean lidocaine plasma levels at five minutes (water vs saline, 2.35 vs 1.59 micrograms/mL) and ten minutes (water vs saline: 2.67 vs 1.88 micrograms/mL) were significant (P less than .05). With the initial mean PaO2 being almost (157 mm Hg; F1O2, 0.3) in the two groups, there was a mean drop of about 60 mm Hg in the saline-diluent group, but only about 40 mm Hg in the water-diluent group one minute after administration (P less than .05). CONCLUSION The use of water resulted in better absorption of lidocaine and less impairment of the PaO2.

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)

Relationship between infusion rates, plasma concentrations, and cardiovascular and metabolic effects during the infusion of norepinephrine in healthy volunteers.

ObjectiveTo determine the relationship between iv infusion rate, plasma concentrations, and hemodynamic and metabolic actions of norepinephrine. DesignNorepinephrine was administered by using five iv infusion rates (0.01 to 0.2 μg/kg/min) for 30 mins each to eight volunteers, for the purpose of constructing cumulative plasma concentration-response curves. SettingLaboratory of the Department of Anesthesiology at a university hospital. Measurements and Main ResultsSystolic and diastolic BP, heart rate, and the plasma concentrations of norepinephrine, glucose, non-esterified fatty acids, and insulin were measured at the end of each infusion rate. During the highest infusion rate, plasma norepinephrine concentrations increased from 199 ± 75 to 7475 ± 1071 pg/mL (1.18 ± 0.44 to 44.18 ± 6.33 nmol/L). Typical hemodynamic responses, such as increases in BP and decreases in heart rate, were seen, while the plasma concentrations of glucose and nonesterified fatty acids increased from 92 ± 10 to 132 ± 17 mg/dL (5.1 ± 0.6 to 7.3 ± 0.9 mmol/L) and 11 ± 4 to 34 ± 6 mg/dL (0.11 ± 0.04 to 0.34 ± 0.06 g/L), respectively, during the 0.2 μg/kg/min infusion rate (p <.05). Despite the increase in glucose concentration, insulin remained at baseline values. Metabolic and hemodynamic effects occurred at similar plasma concentrations throughout the study. ConclusionsAdministration of norepinephrine showed no selective hemodynamic actions. The metabolic responses observed in this investigation were similar to those responses seen during increased endogenous sympathetic nervous system activity, such as stress, exercise, or trauma.