In Reply

We thank Kla et al. for their interest and comments on our recent publication in Anesthesiology.¹  They raise concerns about the generalizability of the results of our study conducted in young and healthy patients, considering (1) the prevalence of elderly or diabetic patients in surgical patients and (2) the pupillary autonomic dysfunction associated with these two conditions.

Elderly patients make up a significant proportion of the surgical population in the United States and worldwide. According to the Centers for Disease Control and Prevention, 37.4% of inpatient procedures were performed in patients older than 65 yr in 2010.²  However, it also indicates that almost two thirds of these procedures were performed in patients younger than 65 yr. The rates of diagnosed diabetes in the civilian population in 2010 were 1.7% between 0 and 44 yr and 12.2% between 45 and 64 yr.³  These numbers highlight that the pupillary dilatation reflex amplitude evoked by a standardized noxious test to predict movement response to surgical stimulation and individualized administration of general anesthesia could be used in a significant proportion of inpatient procedures.

Studies reporting pupillary autonomic dysfunction in elderly or diabetic patients have examined the changes in pupillary diameter elicited by light/darkness or by mydriatic/myotic eye drops.^4,5  The effects of these two conditions on the changes in pupillary diameter elicited by noxious stimuli such as an electrical current have not yet been examined. The nature and characteristics of the stimuli used affect the amplitude of the pupillary response, and further investigations should examine the consequences of pupillary autonomic dysfunction on the pupillary dilatation reflex to pain in these populations.⁶ 

Contrary to volatile agents and the minimum alveolar concentration, there is currently no available tool in the United States to predict the absence of response to noxious stimuli when using total intravenous anesthesia. Target-controlled infusions of hypnotic and opioid allowing real-time calculation of effect-site concentrations of both agents are available in Europe but not yet in the United States.⁷  This underscores the urgent need for further research in this area to help anesthesiologists in the administration of total intravenous anesthesia.

As indicated by Larson and Gupta⁸  in the accompanying editorial, our study should be viewed as a first step toward “real-time individualized intravenous anesthetics,” and “additional studies examining this pupillary test to predict nonmovement in a more diverse population” are warranted.