Anaphylactic Shock Decreases Cerebral Blood Flow More Than What Would Be Expected From Severe Arterial Hypotension

Abstract

To the Editor In a recent issue of Shock (1), a very important paper was published with the title: “Anaphylactic Shock Decreases Cerebral Blood Flow More Than What Would Be Expected From Severe Arterial Hypotension.” The authors of this article concluded that, in anaphylactic shock, severe impairment of the cerebral blood flow takes place, which could not be explained by the level of arterial hypotension. In their experiments with rat model of anaphylaxis, the tissue oxygen partial pressure decreased very rapidly, as early as 1 min following the onset of anaphylaxis, and this was attributed to the early and direct action of anaphylactic mediators on cerebral vessels. Indeed, mast cell mediators such as histamine, chymase, and leukotrienes can induce cerebral artery spasm (2), and platelet-activating factor can reduce cerebral blood flow (3), leading to postischemic hypoperfusion. Therefore, cerebral ischemia and brain injury following anaphylactic shock could be due to direct action of anaphylactic mediators on the cerebral arterial system and not due to arterial hypotension. The above came to support our view on pathophysiology of anaphylactic shock that systemic vasodilatation and plasma and volume loss due to vascular permeability, reduced venous return, reduced cardiac output, and coronary hypoperfusion are not the sole primary cause of tissue damage. Experimental and clinical evidence has shown that, in anaphylactic shock, the coronary arteries could be the primary target of anaphylaxis (4), resulting in the development of Kounis anaphylaxis–associated coronary syndrome (5). In an experiment with ovalbumin-sensitized guinea pigs, which took place more than 20 years ago (6), it was concluded that the registered anaphylactic damage was not due to peripheral vasodilatation, and this can be definitely excluded. This was based on the finding that within 3 min after antigen administration, the left ventricular end-diastolic pressure and arterial blood pressure increased, indicating pump failure. Contemporarily, electrocardiographic recordings uniformly showed signs of acute myocardial ischemia. The blood pressure started declining steadily after 4 min. Today, Dr Stephan Felix (6), the author who performed the above experiments, still believes that, in anaphylactic shock, tissue ischemia is due to disturbances of vasomotion of the coronaries (either coronary vasospasm or disturbances of the microcirculation). However, he cannot exclude fluid extravasation (personal communication, email, November 26, 2012). Other experiments (7), with isolated guinea pig hearts undergoing anaphylaxis following intra-aortic injection of antigen, have shown a prompt and prolonged decrease in coronary blood flow, an abrupt heart rate increase reaching the peak within 2 min, and a transient increase in ventricular contractile force. It has been shown also (8) that anaphylactic cardiac damage is dissociated temporarily into two sets of events: an initial primary coronary reaction caused by intracardiac release of histamine and a subsequent cardiovascular reaction secondary to systemic release of mediators. There are, currently, patients with anaphylactic cardiac shock who did not respond to intravenous fluid administration and antiallergic therapy but required coronary event treatment protocol. In a patient (9) who was stung by multiple wasps and developed type I variant of Kounis syndrome with anaphylactic shock and myocardial ischemia, treatment with 2 L of normal saline, adrenaline, hydrocortisone, and antihistamines did not have any immediate effect, and the patient recovered in a later stage with vasopressors and myocardial infarction protocol treatment. In an atopic female nurse (10) with previous atopic eczema, asthma, and allergy to milk protein, who suffered an anaphylactic reaction, hemodynamic status was unresponsive to intravenous administration of fluids such as Ringer’s acetate and antiallergic treatment with adrenaline and corticosteroids, but the patient recovered with myocardial infarction protocol treatment. It was commented that hemodynamic disturbance was most probably due to myocardial stunning leading to reduced cardiac output rather than due to fluid extravasation. In another patient with hymenoptera sting–induced anaphylactic shock (11), urgent coronary angiography revealed acute coronary thrombosis, and the patient recovered with intra-aortic balloon pump assistance and myocardial infarction treatment. Differentiating global hypoperfusion from primary tissue suppression due to mast cell mediator action on systemic arterial vasculature seems to be challenging. Combined tissue suppression from arterial involvement and peripheral vasodilatation, perhaps, occur simultaneously. Although the mechanisms of anaphylactic shock still remain to be elucidated, the above effects resemble those during endotoxin administration and postischemic hypoperfusion (3). In this aspect, the experiments of Davidson et al (1) help to understand the pathophysiology of anaphylactic shock, but further studies are needed to determine the importance of mediators of anaphylaxis in cerebral and myocardial pathobiology. Nicholas Kounis George N. Kounis George D. Soufras Andreas Mazarakis Department of Medical Sciences Patras Highest Institute of Education and Technology Patras, Grecce