Clinical decision making during resuscitation and guidelines for termination of the resuscitation effort.

Cardiopulmonary resuscitation (CPR) is the appropriate intervention to sustain respiratory and circulatory functions in patients with diseases that are potentially reversible; while CPR is unequivocally inappropriate for patients with terminal diseases when there is a consensus of medical opinion that is no reasonable likelihood of meaningful survival. In practical application patients and their families seek guidance based on understanding. CPR when employed without expectations of benefit, will be likely to further compromise neurological function, produce iatrogenic injury, and add discomfort to the dying patient. The decision not to resuscitate remains a reasoned medical judgement. In some condition, transferring the patient with terminal diseases to an alternate physician or institution is ultimately respectful both for the patient and of physician.

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.

Pupil diameter and light reaction during cardiac arrest and resuscitation.

OBJECTIVE: Traditionally, both pupil diameter and reaction to light have been examined to confirm the diagnosis of death. In the present study, we investigated quantitative changes in pupil diameter and light reaction for assessing the efficacy of cardiopulmonary resuscitation (CPR) and as a predictor of outcome. DESIGN: Controlled experimental study. SETTING: Animal research laboratory at a university-affiliated research institute. SUBJECTS: Fifteen domestic male pigs weighing between 33 and 40 kg. INTERVENTIONS: Ventricular fibrillation was induced with an alternating current delivered to the right ventricular endocardium. After 7 mins of untreated ventricular fibrillation, chest compression and mechanical ventilation were initiated and maintained for 6 mins. Restoration of spontaneous circulation then was attempted by electrical defibrillation. MEASUREMENTS AND MAIN RESULTS: Spontaneous circulation was reestablished in 9 of 15 animals. Pupils were fully dilated, and pupillary reaction to light was absent in 7 of the 9 resuscitated animals during untreated cardiac arrest. Progressive decreases in pupil diameter were observed together with restoration of light reaction during CPR, in each animal that was successfully resuscitated. When the pupils remained dilated and unreactive after 6 mins of CPR, resuscitation efforts were uniformly unsuccessful. A highly significant linear correlation between coronary perfusion pressure generated during precordial compression and pupil diameter was documented. Both were predictive of outcome. CONCLUSIONS: Dynamic changes of pupil diameter and reactions to light during cardiac arrest and resuscitation were correlated with coronary perfusion pressure, and both predicted the likelihood that spontaneous circulation and cerebral function would be restored.

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.

Optimizing timing of ventricular defibrillation.

OBJECTIVE: Our intent was to evolve a prognosticator that would predict the likelihood that an electrical shock would restore a perfusing rhythm. Such a prognosticator was to be based on conventional electrocardiographic signals but without constraints caused by artifacts resulting from precordial compression. The adverse effects of "hands off" intervals for rhythm analyses would therefore be minimized. Such a prognosticator was further intended to reduce the number of electrical shocks and the total energy delivered and thereby minimize postresuscitation myocardial dysfunction. DESIGN: Observational study. SUBJECTS: Medical research laboratory of a university-affiliated research and educational institute. SUBJECTS: Domestic pigs. INTERVENTIONS: Ventricular fibrillation was induced in an established porcine model of cardiac arrest. Recordings of scalar lead 2 over the frequency range of 4-48 Hz were utilized. The area under the curve representing the amplitude and frequency was defined as the amplitude spectrum area (AMSA). MEASUREMENTS AND MAIN RESULTS: A derivation group of 55 animals yielded a threshold value of AMSA that uniformly predicted successful resuscitation. A separate group of 10 animals, a validation group, confirmed that an AMSA value of 21 mV.Hz predicted restoration of perfusing rhythm after 7 of 8 electrical shocks and failure of electrical conversion in 21 of 23 electrical shocks, yielding sensitivity and specificity of about 90%. The negative predictive value of AMSA was 95% and statistically equivalent to that of coronary perfusion pressure, mean amplitude, and median frequency. The positive predictive value that would prompt continuation of cardiopulmonary resuscitation without interruption for an unsuccessful defibrillation attempt was greatly improved with AMSA (78%) as compared with coronary perfusion pressure (42%), mean amplitude (32%), and median frequency (29%). CONCLUSION: AMSA has the potential for guiding more optimal timing of defibrillation without adverse interruption of cardiopulmonary resuscitation or the delivery of unsuccessful high energy electrical shocks that contribute to postresuscitation myocardial injury.

Low-energy biphasic waveform defibrillation reduces the severity of postresuscitation myocardial dysfunction.

Both clinical and experimental studies have demonstrated substantial impairment of ventricular function after resuscitation from cardiac arrest. Indeed, postresuscitation myocardial dysfunction has been implicated as a potentially important mechanism, accounting for fatal outcomes after successful resuscitation in 70% of victims within the first 72 hrs. Recent experimental studies implicated the total electrical energy delivered during defibrillation as an important correlate with the severity of postresuscitation myocardial dysfunction and postresuscitation survival. This prompted us to investigate the option of using lower electrical energy biphasic waveform defibrillation. We compared the effects of low-energy biphasic waveform defibrillation with conventional monophasic waveform defibrillation after a short (4 mins), intermediate (7 mins), or prolonged (10 mins) interval of untreated ventricular fibrillation. Biphasic waveform defibrillation with a fixed energy of 150 joules proved to be as effective as conventional monophasic damped sine waveform defibrillation for restoration of spontaneous circulation, with significantly lower delivered energy. This was associated with significantly less severity of postresuscitation myocardial dysfunction. The low-energy biphasic waveform defibrillation is, therefore, likely to be the future direction of transthoracic defibrillation in settings of cardiopulmonary resuscitation.

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.

K(ATP) channel activation reduces the severity of postresuscitation myocardial dysfunction.

Postresuscitation myocardial dysfunction has been recognized as a leading cause of the high postresuscitation mortality rate. We investigated the effects of ischemic preconditioning and activation of ATP-sensitive K(+) (K(ATP)) channels on postresuscitation myocardial function. Ventricular fibrillation (VF) was induced in 25 Sprague-Dawley rats. Cardiopulmonary resuscitation (CPR), including mechanical ventilation and precordial compression, was initiated after 4 min of untreated VF. Defibrillation was attempted after 6 min of CPR. The animals were randomized to five groups treated with 1) ischemic preconditioning, 2) K(ATP) channel opener, 3) ischemic preconditioning with K(ATP) channel blocker administered 1 min after VF, 4) K(ATP) channel blocker administered 45 min before induction of ischemic preconditioning, and 5) placebo. Postresuscitation myocardial function, as measured by the rate of left ventricular pressure increase at 40 mmHg, the rate of left ventricular decline, cardiac index, and duration of survival, was significantly improved in both preconditioned and K(ATP) channel opener-treated animals. K(ATP) channel blocker administered 45 min before induction of ischemic preconditioning completely abolished the myocardial protective effects of preconditioning. We conclude that ischemic preconditioning significantly improved post-CPR myocardial function and survival. These results also provide evidence that the myocardial protective effects of ischemic preconditioning are mediated by K(ATP) channel activation.

Tissue PCO2 as universal marker of tissue hypoxia.

The author reviews the relationship between tissue PCO2 and tissue perfusion; the use of gastric tonometry and sublingual tonometry are described.

End-tidal carbon dioxide as a noninvasive indicator of cardiac index during circulatory shock.

OBJECTIVE: To document the relationships between cardiac index and end-tidal carbon dioxide tension (PetCO2 during diverse low-flow states of circulatory shock. DESIGN: Randomized, prospective, controlled studies on animal models of hemorrhagic, septic, and cardiogenic shock. SETTING: University-affiliated research laboratory. SUBJECTS: Sixteen anesthetized domestic pigs weighing 35-45 kg. INTERVENTIONS: Hemorrhagic shock was induced in five pigs by bleeding followed by reinfusion of shed blood. Septic shock was induced in five pigs by infusion of live Escherichia coli. Cardiogenic shock followed an interval of global myocardial ischemia after inducing and reversing ventricular fibrillation in six pigs. MEASUREMENTS AND MAIN RESULTS: PetCO2 was continuously measured. Cardiac index was measured intermittently by using conventional thermodilution techniques. Cardiac index was correlated with PetCO2 by polynomial regression and Bland-Altman analyses. PetCO2 was highly correlated with cardiac index during hemorrhagic shock (r2 = .69, p < .01), septic shock (r2 = .65, p < .01), and cardiogenic shock (r2 = .81, p < .01). PetCO2 predicted thermodilution cardiac index with bias of -11+/-27 (+/-2 SD) mL/min/kg during hemorrhagic shock, 1.3+/-20.4 (+/- 2 SD) mL/min/kg during septic shock, and -1+/-12 (+/-2 SD) mL/min/kg during cardiogenic shock. CONCLUSIONS: Cardiac output and PetCO2 were highly related in diverse experimental models of circulatory shock in which cardiac output was reduced by >40% of baseline values. Therefore, measurement of PetCO2 is a noninvasive alternative for continuous assessment of cardiac output during low-flow circulatory shock states of diverse causes.