We thank Albin for his interest in and for important comments regarding our article.1
His first comment regarding the experimental design was to have another control group of animals that are anesthetized but not arrested. In our study, we used Japanese monkeys to avoid the effects of carotid rete by which many experimental animals can selectively decrease brain temperature with panting. Because we have to reduce the number of animals for compliance with the 3R principles, we examined the effect of pharyngeal cooling in one anesthetized animal. The results were shown in figure 5.
The next comment was related to the unit of cerebral blood flow (CBF) and the residual CBF during cardiac arrest. It has been reported that laser Doppler flowmetry does not measure absolute CBF; rather, it accurately measures relative changes in absolute CBF.2 In our article, therefore, we presented CBF with percent changes of its preischemic value. At the end of cardiac arrest, all animals showed ventricular fibrillation, and CBF was decreased to 7 ± 4% and 5 ± 3% of the preischemia level in the treated and control groups, respectively. It is unlikely that the 2% difference in CBF indicated a significant difference in blood flow reduction during cardiac arrest. It is more likely that decrease in blood flow exceeded the level at which accurate measurement can be performed by Doppler flowmetry.
The comment about the flow rate of perfusate is an important issue. In our study, the flow rate of perfusate was 500 ml/min in both the monkey and patients regardless of body weight (8.2 ± 2.1 kg vs. 47.3 ± 12.4 kg) and cuff volume (size 2, 40 ml vs. size 4, 115 ml). Because core brain temperature in the anesthetized monkey and tympanic temperatures in patients were similarly decreased by 0.9°C and 0.6° ± 0.1°C, respectively, during 30 min of pharyngeal cooling, we assumed that the flow rate of 500 ml/min exceeded the optimum flow rate for monkeys. However, we need to evaluate the optimum flow rate in each cuff size in the future.
We demonstrated that pharyngeal cooling can rapidly and selectively decrease brain temperature. However, because 20% of cardiac output circulates in the brain in normal conditions, it seems that a long duration of brain cooling eventually decreases whole body temperature. Therefore, we would like to use pharyngeal cooling during the acute phase of brain ischemia, especially during cardiac arrest. After recovery of spontaneous circulation, pharyngeal cooling would be replaced by another cooling technique that decreases whole body temperature. For the induction of whole body cooling, intravenous infusion of cold saline is recommended.3 For maintaining a stable temperature at 32°–34°C for 24 h, an endovascular cooling system or a gel-coated pad cooling system has been reported to be reliable.4
Brown et al.5 reported the effects of nasal cooling in an animal study in 1964. To date, several researchers have successfully shown decrease in brain temperature with a nasal or nasopharyngeal cooling technique, with different approaches.6 To the best of my knowledge, various effects of nasal or nasopharyngeal cooling on tympanic temperature in humans were measured in seven studies, including our study.7–12 We cited two of these reports. Our study is the first study in which a pharyngeal cooling cuff was used in humans. Because we should avoid subcutaneous emphysema or edema due to direct contact of cold air or fluid in the nasal and pharyngeal regions, we made a pharyngeal cooling cuff that is similar in shape to the supraglottic airway device. The shape was carefully decided by three-dimensional contrast-enhanced computed tomography images and cadaver dissections to fit the pharynx and carotid arteries. The channel in the cooling cuff was designed by thermal fluid analysis to increase the efficacy of cooling.
Albin suggested increasing the bibliographic review in the article. We agree with his suggestion because we can realize what we need to do by learning from previous works. However, our article focused on clinical application of the pharyngeal cooling technique. Therefore, we cited articles in which results of clinical trials were presented.