postresuscitation myocardial dysfunction“>Editorial

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American Journal of Emergency Medicine

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Postresuscitation myocardial dysfunction after asphyxial cardiac arrest: is it time to reconsider the existing paradigm??,??

Postresuscitation myocardial stunning is characterized by tran- sient and reversible global myocardial dysfunction after return of spontaneous circulation (ROSC). Although it was initially described in 1988 by Negovsky [1], its pathophysiology has been recently elucidated [2,3]. The etiology of this syndrome is multifactorial, with the key facts contributing to its emergence being the “no-reflow” phenomenon and Ischemic contracture [2].

Research so far has shown that the severity and duration of postresuscitation myocardial stunning are known to be proportional to the duration of cardiac arrest and cardiopulmonary resuscitation (CPR). However, in this issue of the American Journal of Emergency Medicine, Wu et al [4] present evidence suggesting that the cause of arrest has a significant effect on myocardial function after ROSC. Specifically, the authors randomized 32 pigs into 2 groups according to the mechanism of arrest, ventricular fibrillation cardiac arrest (VFCA), or asphyxiation cardiac arrest (ACA) and left them untreated for 8 minutes, after which CPR was started until ROSC or death. Return of spontaneous circulation was 100% successful in VFCA and 50% successful in ACA. The authors concluded that compared with VFCA, ACA causes more severe cardiac dysfunction associated with less successful resuscitation and shorter survival time. Although the duration of CPR in VFCA group was about half as short as in the ACA group and may have crucially contributed to the aforementioned results, this study highlights the extreme effect of hypoxia on myocardium both during CPR and after ROSC, confirming for one more time that oxygenation is required to reverse physiological derrangments and effectively resuscitate patients with cardiac arrest. In contrast to VFCA, ACA is characterized by a variety of cardiac arrest rhythms, which have the particularity to rarely deteriorate to VF while being especially difficult to treat. Moreover, a common finding in ACA is the frequent alternation of rhythms during CPR. These unique characteristics of ACA together with the findings of Wu et al [4] strengthen the view that ACA and VFCA should be treated as different pathological entities. In VFCA, the resuscitation efforts should aim to increase the possibilities for succesfull defibrillation, whereas after ROSC, treatment must focus on reversing the pathophysiologic manifestations of the postcardiac arrest syndrome. Considering that hypoxemia and hypercarbia both increase the likelihood of a further cardiac arrest and may contribute to secondary brain injury, whereas hyperoxemia causes oxidative stress and harms postischemic neurones [5], the recent guidelines for resuscitation recommend that the fractional inspired concentration should be adjusted to produce an Arterial oxygen saturation (SaO₂) of 94% to 96% in the first hour after

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?? Conflict of interest: None.

ROSC (“controlled reoxygenation”) [6]. Nevertheles, this may be not sufficient in ACA in which anoxia results in more severe and widesrpead myocardial injury, diffuse microcirculation disturbances, and (possibly) irreversible deactivation of enzymes, necessitating an oxygen-con- trolled resucitation based on myocardial tissue oxygen delivery during CPR and myocardial oxygen consumption/contraction efficiency after ROSC. Despite the extreme decrease and/or absence of oxygen before ACA, which may lead to increased Oxygen administration by the medical personnel during CPR, post-ACA SaO₂ at a level of 94% to 96% may be considered as excessive and harmful (relative hyperoxia) because of the harsh myocardial injury after ACA and especially because of the deactivation of myocardial enzymes, which have made the myocardium a tissue incapable to use the offered oxygen. This results in increased oxygen concentration and enhanced toxicity. All these raise significan questions: Is normoxia adequate and safe after ACA? Should we use “permissive hypoxia” during CPR and after ROSC in patients with ACA? If yes, what is the optimal SaO₂, and for how long should we use it? What is the critical level of tissue partial pressure of oxygen, and what constitutes hyperoxic toxicity after ACA? High-quality research on these issues will help to find the answers and improve the resuscitation efforts after ACA.

In the study by Wu et al [4], left ventricular function was more impaired in ACA animals. This raises significant concerns as far as fluid resuscitation and coronary perfusion pressure is concerned both during CPR and during the postresuscitation period. During optimal CPR, the cardiac output is between 25% and 40% of prearrest values, whereas the coronary arteries receive 5% to 15% of this amount. Of note, during the compression phase, the left ventricular intracavitary pressure increases resulting in retrograde Coronary blood flow, whereas on the contrary during the decompression phase, the coronary blood flow is antegrade [2]. During CPR, coronary perfusion and oxygen delivery can be augmented by intravenous fluids and adrenaline. However, right heart intracavitary pressures may be increased after ROSC because of myocardial stunning and and excessive Fluid loading, which increase right ventricular end-diastolic volume. Normally, a fluid bolus would increase right atrial perssure leading to an augmentation of cardiac output through the Frank- Starling mechanism in the intact heart. However, in Postcardiac arrest patients with moderate to severe hemodynamic compromisation and low mean systemic arterial pressure, excessive fluid administration will increase right hear intracavitary pressure and may result in poor coronary perfusion according to the Hagen-Poiseuille law, which states that the fluid flow through a system (such as the coronary arteries) is related to the pressure drop across the system divided by the resistance of the system. In addition, coronary perfusion pressure may be compromised by the institution of positive pressure mechanical ventilation, which decreases venous return and results

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in a rightward shift of the right heart ventricular function curve as a consequence of the decreased effective cardiac compliance and the increased right ventricular afterload (due to increases in Pulmonary vascular resistance caused by the positive intrathoracic pressure).

Although the use of inotropic agents is a Standard therapy of postresuscitation myocardial dysfunction, Wu et al [4] used dopamine in animals with systolic blood pressure less than 50 mm Hg. Dopa- mine is an inotropic agent with robust inotropic and vasoconstrictive actions and generate a more modest inotropic effect than dobutamine or milrinone while maintaining the robust vasopressor effects required in patients with hypotensive shock [7], preserving an effec- tive coronary flow. Of note, myocardial oxygen delivery may be still inadequate despite the systemic hemodynamic and respiratory opti-

References

Athanasios Chalkias PhD MSc “Cardiopulmonary Resuscitation,” Medical School National and Kapodistrian University of Athens

Athens, Greece Hellenic Society of Cardiopulmonary Resuscitation

Athens, Greece

mization after ROSC due to the severe myocaridal injury. Therefore, measurement of intracoronary partial pressure of oxygen and and myocardial oxygen delivery/consumption in future experiments may further help in identifying the optimal titration of inspired oxygen.

Wu et al [4] presents evidence that ACA seems to cause more severe cardiac dysfunction associated with less successful resuscita- tion and shorter survival time compared with other causes of cardiac arrest. Is “permissive hypoxia” the answer to severe myocardial injury after ROSC? The understanding of the pathophysiology of ACA is paramount to the treatment of patients in whom the traditional approach of reversing the pathophysiologic manifestations of the postcardiac arrest syndrome may be inadequate.

Theodoros Xanthos PhD MSc “Cardiopulmonary Resuscitation,” Medical School National and Kapodistrian University of Athens

Athens, Greece Hellenic Society of Cardiopulmonary Resuscitation

Athens, Greece E-mail address: [email protected]

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