We are pleased to have read and to have the opportunity to respond to the thoughtful comments of Ligouri et al.
We wish to correct the authors in that we did not state that others have attributed the events seen during peripheral nerve block to “‘peripheral vasodilation from the sitting position’ as well as ‘venous pooling in the setting of peripheral
nerve blockade.’” These portions of text were taken from different portions of our review and were presented out of context. In fact, we clearly state that other authors “hypothesized that the etiology of the hypotension and bradycardia was based on a combination
of peripheral vasodilation from the sitting position, increased contractility of the heart secondary to absorbed epinephrine from block mixture, and vigorous contraction of an “empty” ventricle. 1
We do not suggest a causal relationship between the block and venous pooling; rather, that venous pooling, by any cause (sitting, in this example), in the setting of a nerve blockade, has been suggested by others to be causally related to hypotension and bradycardia. D’Allesio et al.2
postulate that this event, along with heightened myocardial contractility (secondary to systemically absorbed block mixture epinephrine), is requisite for the hemodynamic embarrassment in question. We are aware of no
evidence that maintenance of a sitting position is associated with significant venous pooling and decreased ventricular chamber size (as has been reported with tilt table testing) much less activation of the Bezold-Jarisch reflex (BJR). Even in persons undergoing tilt table testing, such a relationship is in fact highly variable, 3–7
and, importantly, tilt testing is not a surrogate for either the afferent or efferent limbs of the BJR.
We agree with Ligouri et al.
in that Liu et al.8
and Davrath et al.
among others, 3,6
inform us that the changes in left ventricular volumes during tilt testing are not significant (are “modest”). Importantly, the postulated requirement for triggering the BJR is “increased contractility in the setting of an empty ventricle” with no definition of “empty” offered. 2
This begs the question of what the definition of “empty” is, and whether the modest reductions cited above are consistent with this definition based on experimental data. To our knowledge, the best quantitative evidence showing a relationship between central and ventricular blood volumes and activation of cardio-inhibitory receptors dates from the 1970s. 10,11
Because ventricular volumes were quantified, the definition for “empty” must be considered, for our purposes, the volume at which those investigators elicited the BJR. Whether the much more “modest” reductions cited above can also elicit the BJR has not
Ligouri et al.
seem to agree with our statement that there is no support in the literature for concentrations of epinephrine resulting from block mixture augmenting cardiac contractility. The Bonica et al.12
article does focus on epidural epinephrine, but given that the translocation of drugs from the epidural space to the systemic circulation is rapid, it is reasonable to use this pharmacokinetic model as a point of maximum reference relative to clearance of drug from peripheral locations. The suggestion by Ligouri et al.
that in the surgical setting, other sources of epinephrine exist is true, but whether they contribute to hemodynamic instability remains speculative.
The concept that Ligouri et al. cite as the key to activation of the reflex, the degree of fractional myocyte shortening relative to central blood volumes, is well founded in the literature. We share their interest in this concept. Although this notion has never been formally evaluated, we agree that it could explain many of the apparent contradictions in the literature.
Finally, we wish to thank the current authors for pointing out that we neglected to address other potential causes of bradycardia and hypotension in the case cited in the review. This represents a key point of our argument against labeling the BJR as the cause of bradycardia and hypotension in the setting of regional anesthetics. As Ligouri so eloquently stated: “There are a variety of potential causes of the hypotension and bradycardia … including local anesthetic toxicity, preexisting cardiac pathology, or other reflexes. Without other information, this case offers no insight into the mechanisms of hypotension and bradycardia in this setting.” Clearly, our patient illustrates that there are other causes of the hemodynamic embarrassment. For reasons that are unclear, other authors in the literature largely have ignored these other potential causes.
We understand and sympathize with the contention of Ligouri et al. that BJR is responsible for the bradycardia and hypotension observed during regional anesthetics, but we disagree with their assertion that the literature supports such a relationship. We remain wedded to our contention that the literature provides minimal support, aside from conjecture, for this causal relationship and, in fact, may support a mechanism other than the BJR. A purpose of our review 1
was to draw attention to the fact that many such concepts lack formal evaluation and that, therefore, using them to support
the argument that the BJR is causally related to hemodynamic responses seen during regional and neuraxial blockade is specious. We do not disagree about the possibility of a causal relationship between certain observations and the BJR, only that assertions
that this relationship exists remain based on speculative notions.
Jason A. Campagna, M.D., Ph.D.*
Christopher Carter, M.D.
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© 2004 American Society of Anesthesiologists, Inc.