alpha-Methylnorepinephrine, a selective alpha2-adrenergic agonist for cardiac resuscitation.

OBJECTIVES: The purpose of this study was to investigate the effects of a selective alpha2-adrenergic agonist, alpha-methylnorepinephrine (alphaMNE) as an alternative vasopressor agent during cardiopulmonary resuscitation (CPR). BACKGROUND: For more than 40 years, epinephrine has been the vasopressor agent of choice for CPR. Its beta- and alpha1-adrenergic effects increase myocardial oxygen consumption, magnify global myocardial ischemia and increase the severity of postresuscitation myocardial dysfunction. METHODS: Ventricular fibrillation (VF) was induced in 20 Sprague-Dawley rats. After 8 min of untreated VF, mechanical ventilation and precordial compression began. AlphaMNE, epinephrine or saline placebo was injected into the right atrium 2 min after the start of precordial compression. As an additional control, one group of animals was pretreated with alpha2-receptor blocker, yohimbine, before injection of alphaMNE. Defibrillation was attempted 4 min later. Left ventricular pressure, dP/dt40, negative dP/dt and cardiac index were measured for an interval of 240 min after resuscitation. RESULTS: Except for saline placebo and yohimbine-treated animals, comparable increases in coronary perfusion pressure were observed after each drug intervention. All animals were successfully resuscitated. Left ventricular diastolic pressure, cardiac index, dP/dt40 and negative dP/dt were more optimal after alphaMNE; this was associated with significantly better postresuscitation survival. Pretreatment with vohimbine abolished the beneficial effects of alphaMNE. CONCLUSIONS: The selective alpha2-adrenergic agonist, alphaMNE, was as effective as epinephrine for initial cardiac resuscitation but provided strikingly better postresuscitation myocardial function and survival.

A comparison of myocardial function after primary cardiac and primary asphyxial cardiac arrest.

Although myocardial dysfunction after resuscitation from ventricular fibrillation (VF) has been extensively investigated, less is known of the function of the myocardium after asphyxial cardiac arrest. The present experimental study was designed to compare postresuscitation left ventricular (LV) function after cardiac arrest caused by asphyxia with that of cardiac arrest induced by dysrhythmia. Four groups of Sprague-Dawley rats, which included eight animals in each group, were investigated. In the first two groups, cardiac arrest followed asphyxia produced by neuromuscular blockade with and without airway obstruction. In a third group, cardiac arrest was induced by electrical fibrillation of the ventricle. The fourth group represented animals in which the duration of asphyxial cardiac arrest was maintained for a time interval corresponding to that of the VF group. The fourth group received approximately the same number of electrical shocks as the third (VF) group. All animals were successfully resuscitated with precordial compression and mechanical ventilation. Postresuscitation measurements, including cardiac output, LV end-diastolic pressure (LVEDP), rate of pressure rise at LV pressure of 40 mm Hg (LV dP/dt40), and negative LV dP/dt, demonstrated decreased myocardial function in each group. No differences in cardiac function were observed between the animals with primary respiratory arrest whether or not the airway was obstructed. However, disproportionate and consistently greater impairment in myocardial function followed primary cardiac arrest due to VF when compared with equal duration of asphyxial cardiac arrest. We conclude that in this healthy animal model, asphyxial cardiac arrest resulted in significantly lesser impairment of postresuscitation myocardial function when compared with cardiac arrest caused by VF.

A comparison of biphasic and monophasic waveform defibrillation after prolonged ventricular fibrillation.

STUDY OBJECTIVE: To compare the effects of biphasic defibrillation waveforms and conventional monophasic defibrillation waveforms on the success of initial defibrillation, postresuscitation myocardial function, and duration of survival after prolonged duration of untreated ventricular fibrillation (VF), including the effects of epinephrine. DESIGN: Prospective, randomized, animal study. SETTING: Animal laboratory and university-affiliated research and educational institute. PARTICIPANTS: Domestic pigs. INTERVENTIONS: VF was induced in 20 anesthetized domestic pigs receiving mechanical ventilation. After 10 min of untreated VF, the animals were randomized. Defibrillation was attempted with up to three 150-J biphasic waveform shocks or a conventional sequence of 200-J, 300-J, and 360-J monophasic waveform shocks. When reversal of VF was unsuccessful, precordial compression was performed for 1 min, with or without administration of epinephrine. The protocol was repeated until spontaneous circulation was restored or for a maximum of 15 min. MEASUREMENTS AND RESULTS: No significant differences in the success of initial resuscitation or in the duration of survival were observed. However, significantly less impairment of myocardial function followed biphasic shocks. Administration of epinephrine reduced the total electrical energy required for successful resuscitation with both biphasic and monophasic waveform shocks. CONCLUSIONS: Lower-energy biphasic waveform shocks were as effective as conventional higher-energy monophasic waveform shocks for restoration of spontaneous circulation after 10 min of untreated VF. Significantly better postresuscitation myocardial function was observed after biphasic waveform defibrillation. Administration of epinephrine after prolonged cardiac arrest decreased the total energy required for successful resuscitation.

Efficacy of early piston-type high-frequency oscillatory ventilation in infants with respiratory distress syndrome.

We investigated whether the combination of surfactant replacement therapy and early application of high-frequency oscillatory ventilation (HFOV) was more effective in patients with respiratory distress syndrome (RDS) than late application of HFOV and conventional mechanical ventilation (CMV). To determine this, we retrospectively reviewed the cases of 126 neonates with RDS who received surfactant replacement therapy within 4 hr after birth. Patients were grouped into those who received HFOV immediately after birth (HFOV group), those who initially were ventilated by CMV and subsequently received HFOV (CMV/HFOV group), and those who did not receive HFOV (CMV group). Changes in respiratory system compliance (Crs), arterial-alveolar oxygen gradient (a/ApO(2)), and mean airway pressure (MAP) were compared. Infants who received HFOV were less mature than those who received CMV. The a/ApO(2) measured immediately after birth before surfactant replacement therapy was significantly lower in the HFOV and CMV/HFOV group than in the CMV group. After 72 hr, the Crs in the HFOV group was higher than in any other group and was significantly higher than the CMV/HFOV group at 48 and 120 hr. These results suggest that initiating HFOV in combination with surfactant replacement therapy immediately after birth provides effective ventilatory support for infants with RDS.

Decreases in mesenteric blood flow associated with increases in sublingual PCO2 during hemorrhagic shock.

We investigated relationships between visceral blood flow, intestinal wall carbon dioxide tension (PCO2), and sublingual PCO2 during hemorrhagic shock. In five pigs, cardiac output declined 81% and superior mesenteric blood flow 77% during hemorrhage. Duodenal PCO2 increased from an average of 50 to 121 mmHg and sublingual PCO2 concurrently increased from an average of 46 to 101 mmHg. Within 60 min after reinfusion of shed blood, duodenal and sublingual PCO2 returned to baseline values. Decreases in mesenteric blood flow were correlated with increases in sublingual (r = 0.91; P < 0.001) and duodenal (r = 0.89; P < 0.001) tissue PCO2. In five randomized "sham hemorrhage" control animals, neither decreases in cardiac output or mesenteric blood flow nor increases in duodenal or sublingual PCO2 were observed. Decreases in mesenteric blood flow during hemorrhage were therefore associated with early and comparable increases in tissue PCO2 in both visceral and sublingual sites.

Echo-Doppler observations during cardiac arrest and cardiopulmonary resuscitation.

We describe a series of investigations that used transesophageal echo-Doppler observations during cardiac arrest and cardiopulmonary resuscitation. Regular contractions of the left atrium persisted during the initial 7 mins of untreated ventricular fibrillation. Ventricular chamber deformation and mitral valve closing and opening followed precordial compression and relaxation. Stroke volumes computed from differences between diastolic and systolic areas of the left ventricle were predictive of the success of the resuscitation. Progressive decreases in left ventricular compliance were associated with decreases in left ventricular diastolic and stroke volumes and progressed to a stone heart.

Comparisons between sublingual and gastric tonometry during hemorrhagic shock.

STUDY OBJECTIVES: To compare sublingual tissue PCO(2), a disarmingly simple and noninvasive measurement of the severity of perfusion failure, with gastric tonometric PCO(2) during hemorrhagic shock in five male domestic pigs weighing between 35 and 40 kg. DESIGN: Prospective animal study. SETTING: Animal laboratory in a research institution. PARTICIPANTS: Domestic pigs. INTERVENTIONS: Hemorrhagic shock was induced by a modification of the Wigger's method. BP was maintained at 50 mm Hg for 120 min followed by reinfusion of shed blood at a rate of 100 mL/min with the aid of an infusion pump. MEASUREMENTS AND RESULTS: During bleeding, the mean arterial pressure decreased from an average of 127 to 42 mm Hg, and cardiac output decreased from 7.7 to 2.4 L/min. Arterial blood lactate concentration concurrently increased from 1.2 to 13.9 mmol/L. Sublingual PCO(2) (PslCO(2)) increased from 59 to 105 mm Hg, and gastric PCO(2) increased from 61 to 111 mm Hg. The correlation between time-coincident sublingual and gastric measurements of PCO(2) was r = 0.91 (p<0.0001). Bland-Altman analyses demonstrated a close correspondence between the two measurements. The reinfusion of shed blood promptly reversed the hemodynamic abnormalities and reestablished gastric and PslCO(2) to near baseline values. This contrasted with a delayed reversal of lactic acidosis. CONCLUSIONS: Under experimental conditions of hemorrhagic shock, sublingual capnometry yielded measurements that were interchangeable with those of gastric tonometry.

Neonatal Legionnaires' disease. Histopathological findings in an autopsied neonate.

A neonatal case of legionnaires' disease (LD) is reported. A male neonate was admitted to our hospital with high fever and dyspnea, which had started 5 days after birth, and died due to severe pneumonia at 10 days old. An autopsy revealed small areas of granular consolidation scattered diffusely in the bilateral lungs. Microscopic examination of the lungs showed mainly lobularly distributed pneumonia. Extensive exudation of macrophages and neutrophils was observed in the terminal respiratory tract and alveolar spaces. Warthin-Starry and Gimenez staining and electron microscopy detected many coccobacilli in the cytoplasm of exudated macrophages and neutrophils. Immunofluorescence staining using antiserum against Legionella pneumophila, serogroup 1, showed a positive reaction. Bacteriological examinations of aspirate from the respiratory tract and autopsied lung tissue confirmed the presence of Legionella pneumophila, serogroup 1. Extrapulmonary LD was not detected. LD usually affects aged or immunocompromised hosts, but there was no evidence of immune deficiency in this case. Pediatric cases of LD have rarely been reported, and a survey of the literature revealed few neonatal cases. The present case may alert neonatologists and other medical personnel to the possibility of neonatal LD infection.