X-Message-Number: 33223 From: Date: Thu, 13 Jan 2011 06:17:00 EST Subject: Hypertonic saline for brain edema Doug asks about hypertonic saline for cerebral edema in cryopatients. The most succinct answer is that we don't know the answer. However, I think I can do a little better than that. As the papers Doug cites indicate, hypertonic sodium chloride (typically 23% sodium chloride (NaCl): saline) is far superior to anything else for controlling cerebral edema from a variety of causes, including traumatic and post-ischemic brain injury. It is more effective than mannitol, urea, glycerol, or even, very interestingly, other simple salts of sodium. The same is true when the chloride anion is combined with cations other than sodium. There are a couple of credible theories as to why this strange state of affairs should pertain, but there is very little doubt that hypertonic saline is the most effective acute treatment for cerebral edema - in critically ill patients who are noromothermic, or only very slightly hypothermic. And the latter is a very important qualification. In cryonics patients, any sodium chloride given will stay in the patient. This is in sharp contrast to what happens in a living, actively metabolizing patient where the excess NaCl will be fairly rapidly excreted via the kidneys. This will not happen in cryonics patients because the induction of profound/ultraprofound hypothermia will abolish active ion transport in the renal tubules. Even if blood continues to flow under adequate pressure, all that will issue from the kidneys is an non-concentrated plasma ultrafiltrate. Thus, most of sodium (and chloride) will remain 'on-board' in the patient. Unfortunately, two of the principal drivers of cellular edema in both ongoing cerebral ischemia, and in profound or ultraprofound hypothermia, are sodium and chloride. The molecular weight of NaCl is only 58.44, roughly half that of glycerol. Both of the ions that comprise sodium chloride transit across the cell membrane with comparative ease. Under normal conditions, these ions are actively pumped out of cells at a considerable cost in energy expenditure - in fact, about 30% of the cell's resting energy requirement is spent just on regulating ion homeostasis (and thus, in large measure, water balance). In theory (and in the laboratory) adding large amounts of additional sodium chloride IN THE ABSENCE OF ACTIVE ION PUMPING results in much increased cellular edema under conditions of deep hypothermia or continuing hypoxia or ischemia. In the event that cryonics stabilization technology evolves to the point that extracorporeal support can be virtually guaranteed as a RAPID (30-60 min) follow-on to closed chest cardiopulmonary support, hypertonic saline may prove invaluable. Under such conditions, blood washout could be initiated, or hemodilution with concurrent extended moderate hypothermic perfusion might be used. Under such conditions it is possible to 'dial in' any electrolyte concentration deemed desirable by adding a hemofiltration device to the extracorporeal circuit. Having said that, under no circumstances would I suggest hypertonic saline be used in cryopatients until it has been thoroughly validated in a RELEVANT animal model(s). I hope that provides some perspective on this question. And BTW, Aschwin deWolf and I have agonized over just this issue for onto 3 years now - and maybe more. Well over a decade ago, I had the privilege of attending one of the first comprehensive presentations on the clinical use of hypertonic salin e by Rocha e Silva - leader in the field. Since that time, I have been intrigued, if not mesmerized by its potential for improving cerebral perfusion following ischemia. If I ever get into the laboratory again, that would be one of the many things I'd like to investigate. Mike Darwin Content-Type: text/html; charset="US-ASCII" [ AUTOMATICALLY SKIPPING HTML ENCODING! ] Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=33223