Response to Letter by Albin Regarding Article, “Local Brain Temperature Reduction via Intranasal Cooling With the RhinoChill Device: Preliminary Safety Data in Brain-Injured Patients”
We thank Dr Albin for his interest in our study. Dr Albin took issue with a statement in our article that whole-body (core) cooling must begin before cerebral cooling can begin. He correctly stated that there are ways around this, for example, “differential extracorporeal hypothermia perfusion.” We agree and we would like to clarify that in our article, we made the statement in the context of a discussion on the most widely used techniques/devices for inducing hypothermia, that is, external/surface cooling devices and endovascular devices, all of which cool the core first. Due to its ease of use and portability, the RhinoChill device may be used in the field maximizing hypothermia's potential neuroprotective effects, something that is not possible with extracorporeal perfusion.
Dr Albin also commented on the lack of animal safety and efficacy data. We did mention 1 porcine and 1 sheep study, but due to space limitations, we only presented more clinically relevant human cardiac arrest safety data.1,2 Furthermore, because this was a Phase 1 study, we focused on feasibility and safety. With that said, there have been animal studies of preferential head cooling; some documented safety3,4 and some showed evidence of efficacy.5 One of the latter was an experiment of RhinoChill-induced hypothermia and its effects on resuscitation success after induced ventricular fibrillation in 8 pigs and 8 controls.5 All 8 of the cooled animals survived but only 2 of 8 controls survived and measures of myocardial and neurological function were significantly better in the hypothermia animals.
We agree wholeheartedly with Dr Albin that studies are needed on how low brain temperature can be brought down in humans with the RhinoChill device and what happens to core temperature over a longer period of time.
Lastly Dr Albin correctly noted that we did not present data on intracranial pressure (ICP), which was due to space limitations. ICP data were available for 10 of 15 patients (5 did not have ICP monitors); 5 patients had elevated ICP. We did find that the mean initial ICP was lowered from 16.8±10.4 mm Hg (range, 5–38 mm Hg) to 11.1±5.9 mm Hg (range, 3–20 mm Hg; P=0.14) 60 minutes after initiation of hypothermia. In those with initially elevated ICP, mean 25.8±8 mm Hg (range, 18–38 mm Hg), the mean change was −10.3±11.3 mm Hg and in those with normal initial ICP, mean 8.8±4.4 mm Hg, the change was +0.17±5.6 mm Hg (P=0.086). These differences were not attributable to initial or final brain temperature (38.9°C versus 38.5°C, P=0.67 and 37.6°C versus 37.1°C, P=0.6, respectively). Although mean arterial pressure decreased from 109±27.2 mm Hg to 95±25.2 mm Hg (P=0.04) for all patients combined, the greatest drop was in those with initially high ICP, a drop from 107±25.7 mm Hg to 89.8±19.5 mm Hg (P=0.017). There was no significant change in mean arterial pressure (103±30.2 mm Hg decreased to 99±30.3 mm Hg, P=0.85) in those with normal ICP. One of the likely explanations for the difference in mean arterial pressure response is that there was a physiologically appropriate reduction in mean arterial pressure with the reduction in ICP; however, this and other explanations must be considered as conjecture.
To conclude, we agree with Dr Albin on the need for more data on the safety of prolonged hypothermia with the RhinoChill device and the need for studies of clinical efficacy in human stroke. Hypothermia remains a promising neuroprotectant for a variety of central nervous system injuries, especially those of vascular etiology.
Alex Abou-Chebl, MD
Department of Neurology
University of Louisville School of Medicine
Denise Barbut, MD, MRCP
San Diego, CA
D.B. is founder and Chairman of the Board of Benechill, Inc, the sponsor of the trial.
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