Raúl J. Gazmuri

Pulmonary ventilation/perfusion defects induced by epinephrine during cardiopulmonary resuscitation.

Background Epinephrine has been shown to impair pulmonary excretion of CO2 during resuscitation. This phenomenon was investigated in a rodent model of cardiac arrest and conventional resuscitation. Methods and Results The effects of racemic epinephrine were compared with the selective a1-agonist methoxamine and with saline placebo during cardiac resuscitation in 15 Sprague-Dawley rats mechanically ventilated with gas containing 70%o oxygen. Epinephrine and methoxamine but not saline placebo significantly increased coronary perfusion pressure from approximately 32 to 55 mm Hg. Following epinephrine, end-tidal Pco2 decreased from approximately 10 to 5 mm Hg. This was associated with a time-coincident decrease in Pao2 from approximately 130 to 74 mm Hg and an increase in Paco2 from approximately 26 to 40 mm Hg. These changes indicated increases in alveolar dead space ventilation concomitant with increases in pulmonary arteriovenous admixture. No such effects were observed after admin-istration of either methoxamine or saline placebo. Each of the 15 rats was successfully resuscitated. However, a significantly larger number of transthoracic countershocks were required after epinephrine compared with methoxamine or placebo before return of spontane-ous circulation. Conclusions Epinephrine induced ventilation/perfusion during cardiopulmonary resuscita-tion as a result of redistribution of pulmonary blood flow.

Simultaneous aortic, jugular bulb, and right atrial pressures during cardiopulmonary resuscitation in humans.

4) Safety of high-dose dipyridamole infusion. We have previously reported preliminary data on the safety of high-dose DET in 952 studies.5 More recently, data on the updated experience derived from a large-scale multicenter trial involving 12 echocardiography laboratories in Italy have become available.0 Until now (and in full accord with the preliminary experience reported from our group5), 2,401 high-dose DET studies have been performed according to the protocol proposed in 1986.4 This protocol requires that 1) two-dimensional echocardiographic monitoring be continuously performed throughout the test and that aminophylline be immediately given whenever obvious dyssynergy is detected and that 2) the high dose (0.28 mg/kg during a 2-minute period) be given only when the test is still negative for echocardiographic criteria at the fourth minute after the low standard dose (0.56 mg/kg during a 4-minute period). It was found that no major side effects occurred (i.e., death, myocardial infarction, or severe arrhythmias) and that more severe forms of myocardial ischemia (aminophylline-resistant ischemia and ST segment elevation in the absence of resting Q wave) were always elicited by the lower standard dose (0.56 mg/kg during 4 minutes). Of note, 305 studies were performed early (< 15 days) after an acute myocardial infarction.10 When continuous echocardiographic monitoring is combined with graded administration of dipyridamole, the higher dose did not imply a greater risk.0 5) Study population. As clearly shown in Table 7 of our study,1 the prognostic value of DET is apparent also in the subset of patients without myocardial infarction, insofar as hard end points are concerned. Using the Cox model, we found that in this subset the most significant predictor of subsequent events (death and myocardial infarction) was a positive DET (A)=7.3, p<0.01). Finally, we thank Dr. Gerson for acknowledging that we have made a series of new and potentially important observations about DET. We cannot share his concerns on the supposed major limitations of the study but certainly agree that we need much larger study populations and multicenter experience on various patient subsets, as well as more follow-up information, to have a clearer idea about the safety, usefulness, and prognostic accuracy of DET. Our view is that, at the moment, high-dose DET is midway on the bridge that links a promising test to an extensively applied diagnostic procedure. Substantial, further information is required for community hospital use, but no real stepup in information will be provided until larger scale application is made. Please do not forget DET is only 5 years old, and answers to all questions are not yet available. Eugenio Picano, MD CNR, Clinical Physiology Institute University of Pisa Pisa, Italy

The clinical rationale of cardiac resuscitation

After failure of external defibrillation, return of cardiac activity with spontaneous circulation is contingent on rapid and effective reversal of myocardial ischemia. Closed-chest cardiopulmonary resuscitation (CPR) evolved about 30 years ago and was almost universally implemented by both professional providers and lay bystanders because of its technical simplicity and noninvasiveness. However, there is growing concern since the limited hemodynamic efficacy of precordial compression accounts for a disappointingly low success rate; especially so if there is a delay of more than 3 minutes before resuscitation is started. There is also increasing concern with the lack of objective hemodynamic measurements currently available for the assessment and quantitation of the effectiveness of resuscitation efforts. Accordingly, the resuscitation procedure proceeds without confirmation that it increases systemic and myocardial blood flows to levels that would be likely to restore spontaneous circulation. Continuous monitoring of end-tidal carbon dioxide (PETCO2) now appears to be a practical measurement which provides a noninvasive quantitative indication of both systemic blood flow and coronary perfusion pressure. Consequently, PETCO2 predicts the likelihood of successful resuscitation and guides the operator who may modify the technique of precordial compression to improve systemic and myocardial perfusion. Among the large polypharmacy for cardiac resuscitation, only alpha-adrenergic agents (which increase coronary perfusion pressure) and especially epinephrine are of proven benefit. Neither buffer agents nor calcium salts appear to improve outcome except under unique conditions. To the contrary, there is increasing awareness of adverse effects of pharmacologic interventions such that they may hinder the return of viable myocardial and cerebral function. This has constrained the routine use of all drugs except for the use of alpha-adrenergic agonists. More invasive interventions by which blood flow is restored such as open-chest cardiac massage or extra-corporeal pump oxygenation (ECPO) are consistently more effective than conventional CPR. Experimentally, both methods promptly restore systemic and myocardial perfusion to viable levels and thereby increase the likelihood that spontaneous circulation is restored even after prolonged cardiac arrest or failure of conventional CPR.

Alkalinizing Agents for the Treatment of Cardiac Arrest

Sodium bicarbonate has been administered during cardiopulmonary resuscitation (CPR) on the assumption that reversal of metabolic (lactic) acidosis would favor cardiac resuscitation. The history of its use is sumarized in Table 9–1. The pioneers of modern-day cardiopulmonary resuscitation, Kouwenhoven et al. (60), proposed that blood pH best be maintained within the normal range. This was intended to improve “cardiac action” and to increase “responsiveness to vasopressor agents” (52). They therefore recommended that sodium bicarbonate be routinely administered to adult patients in amounts of 44 mEq (3.75 g) at intervals of 5–10 min during cardiac resuscitation. The use of sodium bicarbonate was further supported by clinical reports documenting severe metabolic acidosis during CPR in patients whose cardiac function was restored when sodium bicarbonate was administered (28,45,97,98).