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RESEARCH: Paul G Firth, Hui Zheng, Jeremy S Windsor, Andrew I Sutherland, Christopher H Imray, G W K Moore, John L Semple, Robert C Roach, and Richard A Salisbury Mortality on Mount Everest, 1921-2006: descriptive study BMJ 2008; 337: a2654 [Abstract] [Full text]

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Mt Everest, hypoxia and red cell deformability.

Les O. Simpson   (25 December 2008)

Important points to cosider while analyzing the deaths of climbers on Mt Everes !

Matiram Pun   (27 December 2008)

Mt Everest, hypoxia and red cell deformability. 25 December 2008
Les O. Simpson, retired experimental pathologist Dunedin, New Zealand 9077 Send response to journal: Re: Mt Everest, hypoxia and red cell deformability.	It is a great pity that the interesting article by Firth et al concerning deaths on Mt.Everest, failed to refer to those reports which explain the changes in the physical properties of blood which occur during high altitude sickness, and draw attention to the fact that prevention may be possible. To a major degree this related to the choice of the work of Hackett and Roach who considered that cerebral oedema was the most common cause of death. While this may be true, it is clear that the cause of cerebral oedema needs to be elucidated. Hackett et al (1)used MRI to study different stages of high altitude cerebral oedema, which showed an increased water content of white matter manifested as "...intenseT2 signals." They concluded that there was a reversible white matter oedema in which, "...the predominant mechanism is vasogenic movement of fluid and protein out of the vascular compartment, etc." But they did not explain why there was both increased transudation and exudation. In 1934 Landis (2) had pointed out that there was a direct relationship between capillary permeability and intra-capillary pressure. Exudation of proteins occurred at high pressures. Those observations are explicable in terms of the pressure-dependent permeability of basement membranes. (3) This implies that the primary event in high altitude sickness is increased intra-capillary pressure. So it is very relevant that the major determinants of intra-capillary pressure are poorly deformable red cells and increased blood viscosity, and both factors are influenced by hypoxia. If Firth et al had recognised that the work of Hackett et al had not explained the origin of cerebral oedema and had explored the relevant literature, then their conclusions might have been different. In 1976, Cerretelli (4) had recognised that the high haematocrit associated with hypoxia would increase blood viscosity and impair the peripheral circulation. An Italian group in 1984 (5) reported that blood samples from climbers just returned from high altitude showed increased blood viscosity and reduced blood filterability. They noted that pentoxifylline - a drug which lowers blood viscosity and increases red cell deformability - "...appeared to prevent the changes in blood viscosity and erythrocyte deformability." It could be relevant also that the beneficial effects of pentoxifylline on pulmonary blood flow during hypoxia in dogs, has been reported. (6) The effects of fish oil during hypoxia in rats (7) and in humans (8) has been reported. Fish oil-treated rats had a lower mortality,and humans responded with improved red cell deformability. Strangely, no mention was made of a paper by Kamada et al in 1986, which reported that sardine oil improved the fluidity of the red cell membranes in diabetics. What these observations seem to imply is that climbers preparing to venture to high altitudes should take 6 grams daily of fish oil, or 1200mg daily of pentoxifylline, prior to and throughout their climb. The objective would be to maintain near-normal levels of intra-capillary pressure by preventing the hypoxia-induced reduction in red cell deformability. References. 1. Hackett PH, Yarnell PR, Hill R, et al. High-altitude cerebral edema evaluated with magnetic resonance imaging: clinical correlation and pathophysiology. JAMA 1998; 280: 1920-5. 2. Landis EM. Capillary pressure and capillary permeability. Physiol Rev 1934; 14: 404-81. 3. Simpson LO. Biological thixotropy of basement membranes: the key to the understanding of capillary permeability. In: Garlick D (ed) Progress in microcirculation research. The University of New South Wales Committee in Postgraduate Medical Education, Sydney, 1981, pp 55-66. 4. Cerretelli P. Limiting factors to oxygen transport on Mount Everest. J Appl Physiol 1976; 40: 658-67. 5. Palareti G, Coccheri S, Poggi M, et al. Changes in the rheologic properties of blood after a high altitude expedition. Angiology 1984; 35: 451-8. 6. Chick TW, Scotto P, Icenogle MV, et al. Effects of pentoxifylline on pulmonary hemodynamics during acute hypoxia in anaesthetised dogs. Am Rev Respir Dis 1988; 137; 1099-103. 7. Archer SL, Johnson GJ, Gebhard RL, et al. Effect of dietary fish oil on lung lipid profile and and hypoxic pulmonary hypertension. J Appl Physiol 1989; 66: 1662-73. 8. Guezennec CY, Nadaud JF, Satabin P, et al. Influence of polyunsaturated fatty acid diet on the hemorrheological response to physical exercise in hypoxia. Int J Sports Med 1989; 10: 286-91. Competing interests: None declared
Important points to cosider while analyzing the deaths of climbers on Mt Everes ! 27 December 2008
Matiram Pun, Junior Doctor TUTH, IOM, Kathmandu, Nepal Send response to journal: Re: Important points to cosider while analyzing the deaths of climbers on Mt Everes !	Dear Editor, I read the article “Mortality on Mount Everest, 1921-2006: descriptive study” by Paul G Firth(1) et al with great interest. The retrospective analysis of all the deaths in 1921-2006 is definitely a commendable job but the descriptive study has failed to address some of the extremely important points regarding the deaths of climbers, settings and clinical consideration. It is important to mention whether the death was more among those who were making first attempt or subsequent attempts to Everest. How about the medications used by the climbers? Some climbers might be using dexamethasone(2). The summit bid starts at midnight which may be one of the confounding factors for the death while climbing and should be considered. Similarly, crowded climbing and delaying in summit bid should also be considered as delayed summiting has been correlated. The ataxia, how was it considered? It is important to mention that climbers are in crampon, roped and with oxygen cylinder and mask with all gloves and clothing. The ataxia cannot be argued or labeled unless there is Rhomberg’s or sharpened Rhomberg’s test done. The most importantly, the authors have forgotten to consider ‘high altitude deterioration’(3) as an important factor to cause death to such extreme altitudes with the longer time of exposure. The authors go further ahead and prematurely come to speculate that headache, nausea and vomiting not being heralds of high altitude cerebral edema at extreme altitudes. Thank You! Dr Matiram Pun, Secretary of Mountain Medicine Society of Nepal (MMSN) References: 1. Firth PG et al. Mortality on Mount Everest, 1921-2006: descriptive study. BMJ 2008;337:a2654 2. Schoene RB. Dexamethasone: By Safe Means, by Fair Means. High Alt Med Bio 2005; 6 (4). 273-275 3. Ward M. High altitude deterioration. Proc R Soc Lond B Biol Sci. 1954 Dec 15;143(910):40-42. Competing interests: I had been in Everest Region and also to the Everest Base Camp in 2007 Spring and Fall both for the medical research. I worked as a Volunteer physician in Manang and Thorang Phedi Medical Aid Post of Himalayan Rescue Association of Nepal (HRA) in 2008 Spring.