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In response to the Letter to the Editor by Dr Stu Lieblich¹ in the latest publication of Anesthesia Progress (61/4), we would like to further expand on the processes that are likely to occur in the scenario described by Cooke and colleagues.²

It was postulated by Lieblich¹ that anaphylaxis could be included in the differential diagnosis of catastrophic cardiovascular collapse. Though this is a distinct possibility, the clinical scenario described by Cooke does not follow traditional manifestations of anaphylactic shock or severe anaphylactoid reaction under general anesthesia. Most scenarios of severe anaphylaxis³ under anesthesia present with hypotension, tachycardia, and shock, not bradycardia as suggested by Lieblich.¹ Though bradycardia can certainly be a part of any scenario when multiple unaccounted factors are at play, in isolated anaphylaxis triggered by an anesthetic agent, the classical initial response is hypotension and tachycardia. Bradycardia would be expected as a late stage decompensation as the mechanisms to maintain cardiac output begin to fail. However, Lieblich¹ does bring up a cardioprotective mechanism, the Bezold-Jarisch reflex, which plays an interesting role in cardiac physiology.

The Bezold-Jarisch reflex⁴ is rightly described as a cardioprotective reflex that can be initiated by either mechanical or chemical stimulation. Mechanical factors, such as increased ventricular contractility due to inadequate left ventricular end-diastolic volume, trigger receptors in the epicardium of the left ventricle that results in decreased sympathetic activity and increased parasympathetic activity. The net result is bradycardia, hypotension, and peripheral vasodilation. Chemical stimulation by prostacyclin and other agents (such as those released during myocardial ischemia) may produce the same cascade of events. When looking at the end results of this reflex and its ability to override other cardiac sympathetic stimulation, it is presumably initiated to help restore cardiac output and protect the myocardium in states where increased myocardial demand will cause damage.

The mechanism behind the BJR is complex, and its role in cardiac physiology is still being investigated. In the case of severe hypovolemia, the BJR is triggered and bradycardia ensues.⁴ Though this may seem counterintuitive, bradycardia will increase ventricular filling time, thus improving stroke volume and ultimately improving cardiac output. Where then does the classical explanation of tachycardia during hypovolemia fit in? Though not fully elucidated, it is likely a complex interplay between the baroreceptor reflex and the BJR, with one being more dominant than the other in different scenarios. Most evidence suggests that when the baroreceptor reflex is intact, it will have the dominant role. In some cases, such as severe hypovolemia, the BJR may become dominant.

There are states in which the Bezold-Jarisch reflex can be activated paradoxically, and by investigating these cases⁵ we may be able to gain a better appreciation of how to respond in clinical scenarios. Take for example the case of hypotension from hypovolemia. Carotid sinus baroreceptors sense hypovolemia (more accurately hypotension), and the baroreceptor reflex arc will be inhibited, thus increasing chronotropy in order to increase cardiac output. This is a favorable outcome, and in most states this baroreceptor reflex helps maintain adequate blood pressure and cardiac output. However, when the increase in cardiac rate and concurrent ionotropy further decreases ventricular filling due to decreased diastolic filling time, such as in hypotension/hypovolemia, the Bezold-Jarisch reflex may be triggered via mechanoreceptors in the left ventricle that will then result in parasympathetic activity that will override the initial baroreceptor mediated reflex. Bradycardia combined with hypovolemia/hypotension is a low cardiac output state which may lead to unconsciousness. This is similar to the mechanism for vasovagal syncope, and the treatment is restoration of normovolemia and/or atropine as a vagolytic to overcome the profound parasympathetic activity. In this scenario, the myocardium is not under undue stress and does not need to be protected, thus the Bezold-Jarisch reflex is acting to destabilize cardiac output in an unnecessary attempt to protect the myocardium.

Returning to the clinical case presented by Cooke et al,² atropine could be an acceptable response to help support cardiac output in the face of hypotension and bradycardia, even if you include the differential of anaphylaxis. The issue at hand is parasympathetic activation and decreased sympathetic tone, and atropine would be an appropriate agent, along with fluid resuscitation, and Trendelenburg positioning. Vassopressin is an excellent alternative to increase blood pressure in this scenario, as Dr Lieblich states,¹ if agents such as atropine, ephedrine, and epinephrine are ineffective.

As a final note, since carotid artery occlusion was confirmed, this may very well have been the initiating signal⁶ as the baroreceptors may have been dysfunctional, thus resulting in the clinical picture described by Cooke¹—hypotension and bradycardia. Additionally, the CVA itself may have been responsible for the altered hemodynamics. Regardless of the cause, a discussion of cardiac physiology and competing reflexes is always a great reason to pause and remember that the differential diagnoses and mechanisms for anesthetic complications are quite broad.