Science challenges the dogmas of CPR.
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Cardiopulmonary Resuscitation↗
Biomedical subjects
M H Weil
Publications and source records attributed to M H Weil.
Full-time intensivists for appropriate care of the critically ill and injured.
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Critical Care↗
Funding resuscitation research.
The present trend in managed care has meant downsizing expectations concerning the availability of support for resuscitation research. This trend applies to funding possibilities from industry, governmental agencies, and nongovernmental agencies (Table 1). There will be increasing barriers to making innovations. Truth, science, and good patient care alone will not make potential donors give grants. Investigators must also understand the potential donors' expectations and be persuasive. "Delight your donor". Industries' concerns include intellectual property rights and publications. The National Institutes of Health, recently favoring molecular biology over lifesaving therapies or integrated physiologic research, is an anomaly. The current peer review system propagates itself without having advocates for resuscitation research. This system has become a self-fulfilling prophecy. The American Heart Association is only recently, after 30 yrs of educational activities concerning cardiopulmonary resuscitation, considering putting some basic research money into resuscitation research. In university hospitals, where clinical departments have made significant contributions to innovative, clinically relevant life-support research, funded with incomes from patient care, the sky is beginning to fall. Resuscitation researchers need persuasive advocates with clout and hard data to convince funding agencies to give support to multilevel research and development in areas of pathophysiology and reversibility of terminal states and clinical death--to give these topics a higher priority than is currently available.
American Heart Association↗
Epinephrine increases the severity of postresuscitation myocardial dysfunction.
BACKGROUND: Epinephrine has been the mainstay for cardiac resuscitation for more than 30 years. Its vasopressor effect by which it increases coronary perfusion pressure is likely to favor initial resuscitation. Its beta-adrenergic action, however, may have detrimental effects on postresuscitation myocardial function when administered before resuscitation because it increases myocardial oxygen consumption. In the present study, our focus was on postresuscitation effects of epinephrine when this adrenergic agent was administered during cardiopulmonary resuscitation. Postresuscitation myocardial functions were compared with those of a selective alpha-adrenergic agent, phenylephrine, when epinephrine was combined with a beta 1-adrenergic blocking agent, esmolol, and saline placebo. METHODS AND RESULTS: Ventricular fibrillation was induced in 40 Sprague-Dawley rats. Mechanical ventilation and precordial compression was initiated either 4 or 8 minutes after the start of ventricular fibrillation. The adrenergic drug or saline placebo was administered as a bolus after 4 minutes of precordial compression. Defibrillation was attempted 4 minutes later. Left ventricular pressure, dP/dt40, and negative dP/dt were continuously measured for an interval of 240 minutes after successful cardiac resuscitation. Except for saline placebo, comparable increases in coronary perfusion pressure were observed after each drug intervention. The number of countershocks required for restoration of spontaneous circulation was significantly greater for epinephrine-treated animals (10 +/- 8) when compared with phenylephrine-treated animals (1.8 +/- 0.4, P < .01) and with animals treated with epinephrine combined with esmolol (1.6 +/- 0.9, P < .01). After resuscitation, dP/dt40 and negative dP/dt were significantly decreased and left ventricular end-diastolic pressure was significantly increased in each animal when compared with prearrest levels. However, the greatest impairment followed epinephrine, and this was associated with significantly greater heart rate and the shortest interval of postresuscitation survival of 8 +/- 4 hours, whereas placebo controls survived for 12 +/- 11 hours. Phenylephrine-treated animals survived for 41 +/- 10 hours (P < .01 versus epinephrine), and animals that received a combination of epinephrine and esmolol survived for 35 +/- 11 hours (P < .01 versus epinephrine). When the duration of untreated cardiac arrest was increased from 4 to 8 minutes, the severity of postresuscitation left ventricular dysfunction was magnified, but disproportionate decreases in postresuscitation survival were again observed with placebo and epinephrine when compared with alpha-adrenergic agonists. CONCLUSIONS: In an established rodent model after resuscitation following cardiac arrest, epinephrine significantly increased the severity of postresuscitation myocardial dysfunction and decreased duration of survival. More selective alpha-adrenergic agonist or blockade of beta 1-adrenergic actions of epinephrine reduced postresuscitation myocardial impairment and prolonged survival.
Adrenergic Agonists↗
Benefits of ventilation for CPR.
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Animals↗
Effect of arrest time on the hemodynamic efficacy of precordial compression.
OBJECTIVES: To evaluate the efficacy of conventional threshold levels of coronary perfusion pressure and end-tidal CO2 as predictors of resuscitability after prolonged cardiac arrest. DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: Twenty-one Sprague-Dawley rats, including three groups of seven animals in each group. INTERVENTIONS: Ventricular fibrillation was untreated for 9, 12, or 15 mins. After an additional 5-min interval of precordial compression, external direct current defibrillation was attempted. MEASUREMENTS AND MAIN RESULTS: All animals were successfully resuscitated after 9 mins of ventricular fibrillation but less than one half of the animals were successfully resuscitated after 15 mins of ventricular fibrillation. Each of seven animals survived for 24 hrs after 9 mins of untreated ventricular fibrillation but none of the animals survived after 15 mins of ventricular fibrillation. In this experimental setting, neither coronary perfusion pressure nor end-tidal CO2 produced by precordial compression was predictive of outcomes when the animals underwent progressively longer intervals of untreated cardiac arrest. CONCLUSIONS: The efficacy of precordial compression--as measured by coronary perfusion pressure and end-tidal CO2 concentration after prolongation of untreated cardiac arrest--was not overtly compromised. However, the previously established critical threshold levels of coronary perfusion pressure and end-tidal CO2 failed as predictors of resuscitability after prolonged intervals of untreated cardiac arrest.
Animals↗
Life measures before and one year after admission to an intensive care unit.
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Critical Care↗
Mechanisms of myocardial hypercarbic acidosis during cardiac arrest.
During the global myocardial ischemia of cardiac arrest and during regional myocardial ischemia due to local impairment of coronary blood flow, intramyocardial carbon dioxide tensions (Pmco2) of ischemic myocardium increase to levels exceeding 400 Torr. The mechanism of such myocardial hypercarbic acidosis is as yet incompletely understood, specifically whether these increases in Pmco2 are due to increased oxidative metabolism, decreased CO2 removal, or buffering of metabolic acids. We therefore measured Pmco2 and the total CO2 content of rat hearts harvested before, during, and after resuscitation from cardiac arrest. Pmco2 significantly increased from an average of 63 to 209 Torr during a 4-min interval of untreated ventricular fibrillation. This was associated with concurrent decreases in intracellular pH from an average of 7.03 to 6.02 units. The total CO2 content of the myocardium simultaneously decreased from 17.0 to 16.5 mmol/kg. Accordingly, increases in Pmco2 and [H+] were observed in the absence of increases in the total CO2 content and therefore the calculated myocardial bicarbonate. These observations in the rat model implicate buffering of metabolic acids by bicarbonate rather than increases in CO2 production or decreases in CO2 removal as the predominant mechanism accounting for myocardial hypercarbia.
Acidosis↗
Mechanical ventilation may not be essential for initial cardiopulmonary resuscitation.
BACKGROUND: In a rodent model of cardiac arrest and resuscitation in which the inspired gas mixture was enriched with oxygen, resuscitability and survival were unaffected by positive pressure ventilation. In the present study, in a larger animal model, tidal volumes generated during precordial compression and with spontaneous gasping were quantitated. METHODS: Domestic pigs with an average weight of 34 kg were anesthetized with pentobarbital. Ventricular fibrillation (VF) was induced electrically. Precordial compression was begun after 4 min of untreated VF. Each of 22 animals received one of two interventions in conjunction with precordial compression: positive pressure ventilation with oxygen or oxygen supplied at the port of a tracheal tube at ambient pressure. After 8 min of precordial compression, defibrillation was attempted. RESULTS: Only very moderate increases in arterial PCO2 were documented during cardiopulmonary resuscitation in the absence of mechanical ventilation but arterial oxygen tension was consistently in excess of 100 mm Hg. Cardiac resuscitability and 48-h survival were approximately the same in animals maintained on inspired oxygen whether or not they were mechanically ventilated (7/11 or 8/11). In the absence of mechanical ventilation, precordial compression and spontaneous gasping yielded minute volumes that exceeded 5 L. CONCLUSION: Positive pressure mechanical ventilation did not improve resuscitability or postresuscitation outcome in this porcine model of cardiac arrest.
Animals↗
Airway protection during experimental CPR.
BACKGROUND: Experimental studies recently demonstrated that positive pressure ventilation may not be essential for initial cardiopulmonary resuscitation. Nevertheless, oxygen enrichment of inspired gas mixtures and spontaneous gasping were associated with increased resuscitability and survival after cardiac arrest. However, as yet unresolved is the benefit of early airway control under conditions simulating "sudden death" due to ventricular fibrillation. METHODS: Twenty adult, male Sprague-Dawley rats were randomly assigned to one of two groups in which the airway was unprotected or protected by an oropharyngeal airway of our design. Cardiac arrest was induced by an alternating current delivered to the right ventricular endocardium. Oxygen was delivered to a hood that was loosely applied over the head of the each animal at a flow rate of 1 L/min. Precordial compression was initiated after 4 min of untreated ventricular fibrillation and defibrillation was attempted 6 min later. After spontaneous circulation had been restored, a tracheostomy was performed and the animals were mechanically ventilated with 100% oxygen for an additional interval of 1 h. Animals were then returned to their cages and observed for an additional 24 h. RESULTS: Spontaneous circulation was restored in each of the animals who had an oropharyngeal airway and nine of ten animals in the absence of an artificial airway. In each group, seven animals survived for more than 24 h. Animals in which the airway had been protected had significantly greater frequency of spontaneous gasping (28 +/- 13/min vs 13 +/- 9/min; p < 0.05) and significantly higher arterial oxygen saturation (77 +/- 19% vs vs 55 +/- 25%; p < 0.05). CONCLUSION: In the setting of experimental cardiac resuscitation, the insertion of an artificial airway increased the frequency of spontaneous gasping and arterial oxygenation. Nevertheless, no significant differences in resuscitability or postresuscitation survival were associated with insertion of the artificial airway.
Airway Obstruction↗
Hepatic, renal, and cerebral tissue hypercarbia during sepsis and shock in rats.
Earlier observations had indicated profound increases in the carbon dioxide tension of the myocardium, gastric wall, liver parenchyma, and renal cortex in the setting of extreme low-flow states of cardiac arrest and resuscitation, hemorrhagic shock, and anaphylactic shock. In venous blood draining the intestines, kidneys, and pelvic viscera, significant increases in PCO2 have also been observed during septic shock. In the present study, we investigated hepatic, renal, and cerebral cortical tissue carbon dioxide tension during intra-abdominal sepsis and shock in Sprague-Dawley rats. Peritonitis was induced by cecal ligation and fecal spillage. Over an interval of 320 +/- 60 minutes, we measured progressive reduction in mean aortic pressure from 152 +/- 11 mm Hg to 25 +/- 8 mm Hg and a decline in cardiac index from 492 +/- 75 ml/kg/min to 169 +/- 57 ml/kg/min. These hemodynamic deficits were accompanied by increases in liver tissue PCO2, from 58 +/- 4 mm Hg to 110 +/- 27 mm Hg (p = 0.006), in renal tissue PCO2, from 38 +/- 7 mm Hg to 115 +/- 24 mm Hg (p < 0.001), and in cerebral cortical tissue CO2, from 59 +/- 6 mm Hg to 108 +/- 16 mm Hg (p = 0.001). Arterial blood lactate content increased from 0.8 to 5.26 +/- 0.2 mmol/L (p = 0.001). Increases in blood lactate content preceded the changes in tissue PCO2 in each of these organs. These studies demonstrate that tissue hypercarbia is a more general phenomenon of low flow states, including that of circulatory shock associated with septic peritonitis.
Animals↗
Lessons learned from clinical trials on monoclonal anti-endotoxin antibody.
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Antibodies, Monoclonal↗
Increased venous-arterial carbon dioxide tension difference during severe sepsis in rats.
OBJECTIVE: To test the hypothesis that decreases in blood flow during septic shock lead to increases in the venous-arterial PCO2 difference in a rat model of sepsis. DESIGN: Prospective, randomized, controlled experimental study. SETTING: Research laboratory. SUBJECTS: Fifteen Sprague-Dawley rats. INTERVENTIONS: Severe sepsis was induced by cecal ligation and perforation. Ten animals were randomized to no treatment or fluid infusion to maintain the cardiac output at baseline values. An additional five rats served as sham-operated controls. MEASUREMENTS AND MAIN RESULTS: Hemodynamic measurements, arterial and central venous blood gases were obtained at baseline, and then at 3 hrs and 6 hrs after abdominal surgery. In the five septic rats that did not receive volume infusion, cardiac output decreased from 331 +/- 32 to 172 +/- 9 mL/min/kg (p < .001). This decrease in cardiac output was associated with an increase of 13 +/- 2 torr (1.7 +/- 0.2 kPa) in the venous-arterial PCO2 difference (p < .001). Furthermore, the venous-arterial PCO2 gradient correlated linearly with the cardiac output in the same animals (r2 = .52, p < .001). In the septic animals that received volume infusion and in sham animals, cardiac output and the venous-arterial PCO2 remained unchanged from baseline at 6 hrs. CONCLUSION: We conclude that the increase in the venous-arterial PCO2 gradient in severe sepsis appears to be related to reductions in cardiac output.
Acidosis↗
Spontaneous gasping increases the ability to resuscitate during experimental cardiopulmonary resuscitation.
OBJECTIVE: To evaluate the effect of spontaneous gasping on cardiorespiratory functions and the ability to resuscitate during experimental cardiac arrest. DATA SOURCES: Studies in rat and pig models during cardiac arrest and cardiopulmonary resuscitation (CPR). STUDY SELECTION: We retrospectively examined the role of spontaneous gasping during the course of experimental studies on cardiopulmonary resuscitation. DATA EXTRACTION: The data were extracted to illustrate the mechanisms of spontaneous gasping and its effects on pulmonary gas exchange and blood circulation during CPR. DATA SYNTHESIS: Spontaneous gasping increased PaO2 and decreased PaCO2 values during precordial compression in the absence of mechanical ventilation. The frequency of gasping during precordial compression was greater in successfully resuscitated animals. A significant linear correlation was established between coronary artery perfusion pressure and both the frequency (r2 = .90, p < .01) and the duration (r2 = 0.69, p < .01) of gasping during untreated ventricular fibrillation and before resuscitation was attempted. Like coronary perfusion pressure, the frequency and duration of gasping predicted the success of cardiac resuscitation attempts. CONCLUSIONS: Spontaneous gasping is associated with both pulmonary and hemodynamic effects during cardiac arrest in experimental animals. Spontaneous gasping is biologically useful and is predictive of a more favorable outcome of resuscitative efforts.
Animals↗
Gastric intramural PCO2 as monitor of perfusion failure during hemorrhagic and anaphylactic shock.
Indirect measurement of gastric intramural pH (pHG) utilizing a luminal tonometer in the stomach has been proposed for monitoring the severity and progression of perfusion failure. In the present study, we investigated gastric PCO2 and pHG as indicators and quantitators of the severity of perfusion failure in the experimental rodent model of both hemorrhagic and anaphylactic shock. Gastric intramural PCO2 (PGCO2) and pHG were directly measured with miniaturized sensors inserted into the anterior wall of the stomach. In hemorrhagic shock, animals were bled into a reservoir maintained at a pressure of 35 mmHg. pHG decreased from 7.39 +/- 0.08 to 6.67 +/- 0.11 (P < 0.01), and PGCO2 increased from 53 +/- 4 to 136 +/- 3 Torr (P < 0.01). Anaphylactic shock was induced in animals that had been sensitized 21 days before with crystallized ovalbumin. Antigen challenge produced an immediate reduction in mean aortic pressure from 144 to 60 mmHg. pHG decreased from 7.40 +/- 0.05 to 6.99 +/- 0.07 (P < 0.01), and PGCO2 increased from 48 +/- 5 to 133 +/- 9 Torr (P < 0.01). The increases in PGCO2 were highly correlated with decreases in gastric blood flow in both hemorrhagic (r = 0.96) and anaphylactic shock (r = 0.92). The correlations with pHG were more moderate. These experiments demonstrated prominent increases in PGCO2 and H+ during both hemorrhagic and anaphylactic shock. We further noted that the estimation of pHG based on the assumption that HCO3-concentrations of the stomach wall and arterial blood are the same was not fully sustained.
Anaphylaxis↗
Spontaneous gasping during cardiopulmonary resuscitation without mechanical ventilation.
Spontaneous gasping is frequently observed during cardiac arrest, especially when mechanical ventilation is withheld during precordial compression. We related spontaneous gasping to pulmonary gas exchange and cardiac resuscitability in a rodent model of cardiac arrest. Ventricular fibrillation was electrically induced in 15 Sprague-Dawley rats. After 4 min untreated ventricular fibrillation, precordial compression was initiated. Coronary perfusion pressure was maintained between 25 and 30 mm Hg. Oxygen was supplied at the tracheal tube port coincident with start of precordial compression in 10 animals. Five additional control animals were identically treated except they were mechanically ventilated coincident with start of precordial compression. After 6 min precordial compression, defibrillation was attempted and five of 10 nonventilated animals, and all control animals, were resuscitated by direct current countershock. In the successfully resuscitated, nonventilated animals, the frequency of spontaneous gasping during precordial compression progressively increased to an average of 19 gasps/min but it was < 6 gasps/min in nonresuscitated animals. More frequent gasping was associated with correspondingly greater arterial PO2 (110 versus 51 mm Hg, p < 0.01) and lesser PCO2 (55 versus 91 mm Hg, p < 0.01). In control animals, no spontaneous gasping was observed during precordial compression. Arterial PO2 and PCO2 of mechanically ventilated animals was more like that of spontaneously gasping rats. According, the frequency of spontaneous gasping in absence of mechanical ventilation is predictive of cardiac resuscitation success and associated with improved arterial oxygenation and CO2 removal.
Analysis of Variance↗
Cardiopulmonary resuscitation by precordial compression but without mechanical ventilation.
It is widely held that mechanical ventilation is essential for cardiopulmonary resuscitation (CPR). However, cardiac output and therefore pulmonary blood flow is reduced to less than one-third of normal during CPR. We therefore reasoned that ventilatory requirements are correspondingly reduced and postulated that gas exchange may be maintained during precordial compression with oxygen passively delivered to the airway in the absence of mechanical ventilation. After tracheal intubation, Sprague-Dawley rats were randomized. Fifteen animals were maintained on positive-pressure ventilation with room air and an additional 15 animals breathed spontaneously. Cardiac arrest was induced by electrical fibrillation. The inspired gas concentration of oxygen was then increased to 100% in both groups. Precordial compression was begun after 4 min of untreated ventricular fibrillation. After an additional 6 min of precordial compression, resuscitation was attempted by DC countershock. During cardiac resuscitation, there were no significant differences in coronary perfusion pressure between mechanically ventilated and spontaneously breathing animals, but arterial PO2 was significantly lower and arterial PCO2 was significantly higher in the absence of positive-pressure ventilation. However, neither resuscitability nor 24-h survival were affected. Postresuscitation myocardial contractility, reflected in the maximally generated dP/dt40, was also not adversely affected. In the unventilated group, only resuscitated animals developed spontaneous gaspings at an average frequency of 17 +/- 2/min-1. The current emphasis on mechanical ventilation as the highest priority for cardiopulmonary resuscitation is therefore not fully supported under the experimental conditions of this study.
Animals↗
Ventricular fibrillation voltage as a monitor of the effectiveness of cardiopulmonary resuscitation.
Ventricular fibrillation (VF) voltage was previously identified as a predictor of the success of cardiopulmonary resuscitation. In the present study we investigated the mechanism by which VF voltage predicts the success of cardiac resuscitation in a well-established rodent model of cardiac arrest. After 4 minutes of untreated VF, precordial compression was initiated and maintained for 6 minutes. Increases in coronary perfusion pressure during precordial compression were associated with concomitant increases in VF voltage (r = 0.61, p = 0.013). Significantly greater coronary perfusion pressure (24 vs 17 mm Hg) and VF voltage (0.17 vs 0.12 mV) were observed in resuscitated animals. To obviate electrical artifacts produced by precordial compression, boluses of oxygenated blood were injected into the ascending aorta in another 5 animals as an alternative method of cardiac resuscitation. This restored myocardial perfusion before defibrillation. Increases in VF voltage from 0.04 mV to 0.47 mV during aortic infusions were again correlated with coronary perfusion pressure (r = 0.62, p < 0.01) and predicted the success of cardiac resuscitation. Greater VF voltages after initiation of cardiac resuscitation were associated with increases in myocardial creatine phosphate, from 0.23 to 0.70 mmol/kg wet weight, and significant decreases in lactate content, from 22.8 to 13.9 mmol/kg wet weight. Increases in creatine phosphate were highly correlated with increases in VF voltage (r = 0.99, p < 0.01). Accordingly, increases in VF voltage during cardiac resuscitation reflect increases in myocardial perfusion and favorable changes in myocardial energy metabolism. As such, VF voltage, like coronary perfusion pressure, serves as a quantitative predictor of the success of cardiopulmonary resuscitation.
Action Potentials↗