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Electronic letters published:
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Dexamethasone, tadalafil and high altitude pulmonary edema
Dose Adjustment of Drugs
High Altitude Limerick
Mental Effects of Dexamethasone
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Marco Maggiorini, MD Intensive Care Unit University Hospital Zurich, Switzerland, Heimo Mairbäurl, Medical Clinic VII, Sports Medicine, University of Heidelberg, Germany
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klinmax{at}usz.unizh.ch Marco Maggiorini, et al.
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Authors replay: I thank Mr Pun and Dr. Ghimire, and Dr Basnyat for their interest and comments on our recent publication. When we designed and performed our study Richalet et al. (1) and Aldashev et al. (2) had not yet published their work on sildenafil to show that it decreases hypoxic pulmonary hypertension. Sildenafil needs to be taken in rather short time-intervals due to its short half life of 4 to 5 hours. Since in our study the effectiveness of two drugs was tested, we needed to match the time of drug intake and chose the phosphodiestrase 5 inhibitor tadalafil with a long half-life (17 hours) . The recommended dosage of tadalafil to treat erectile dysfunction is 10 to 20 mg. Thus, tadalafil 10mg every 12 hours appeared reasonable. Rock and coworkers (3) reported that 4mg dexamethasone every 12 hours significantly reduced symptoms and signs of AMS whereas 1 or 0.25mg were ineffective.. We decided to increase the dose to its maximum used to treat AMS, which was 16mg/day (2 x 8mg) based on previous trials where 4 x 4mg had been used. Based on our subjects clinical background this doseage applied on only 4 consecutive days appeared safe, an assumption that was confirmed in our study. Dr. Basnyat notched that we did not comment on possible dangerous mental side effect of dexamethasone. During our study we daily assessed the mental status of all participants and did not observe any symptoms of inappropriate euphoria or mental disorientation. Moreover, to our knowledge there are no studies indicating that dexamethasone impairs cognitive functions at high altitude. Conversely, two studies on mountaineers above 4000m, who received 8 to 16mg dexamethasone per day, showed an improvement of reaction times and mood status but no effects on personality in cognitive and psychomotor tests (4, 5). Thus, these results suggest that the use of dexamethasone at high altitude might even improve a mountaineer’s awareness while climbing exposed ridges or trekking paths. However, at the present time we cannot generally recommend the routine use of dexamthasone for high altitude pulmonary edema prophylaxis for a time period longer than a few days because of its well-known long term side effects and the lack of safety data in the context of a trekking or climbing expedition in remote areas. 1. Richalet JP, Gratadour P, Robach P, Pham I, Dechaux M, Joncquiert- Latarjet A, et al. Sildenafil Inhibits the Altitude-induced Hypoxemia and Pulmonary Hypertension. Am J Respir Crit Care Med. 2004;29:29. 2. Aldashev AA, Kojonazarov BK, Amatov TA, Sooronbaev TM, Mirrakhimov MM, Morrell NW, et al. Phosphodiesterase type 5 and high altitude pulmonary hypertension. Thorax. 2005 Aug;60(8):683-7. 3. Rock PB, Johnson TS, Larsen RF, Fulco CS, Trad LA, Cymerman A. Dexamethasone as prophylaxis for acute mountain sickness. Effect of dose level. Chest. 1989;95:568-73. 4. Lafleur J, Giron M, Demarco M, Kennedy R, BeLue R, Shields C. Cognitive effects of dexamethasone at high altitude. Wilderness Environ Med. 2003 Spring;14(1):20-3. 5. Jobe JB, Shukitthale B, Banderet LE, Rock PB. Effects of Dexamethasone and High Terrestrial Altitude on Cognitive Performance and Affect. Aviat Space Environ Med. 1991;62(8):727-32. Conflict of Interest:None declared |
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Matiram Pun, Fifth Year Medical Student Member of Mountain Medicine Society of Nepal (MMSN), Maharajgunj Campus, Institute of Medicine, Dr Laxmi V Ghimire
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mati{at}iom.edu.np Matiram Pun, et al.
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The authors (M Maggiorini et al) have come up with the impressive outcome from their trial (Both tadalafil and dexamethasone may reduce the incidence of high-altitude pulmonary edema. A randomized trial.) (1). They have used Tadalafil 10mg or Dexamethasone 8mg twice daily from the morning of the day before ascent till the end of the study. The concern is about dose adjustments of both of these drugs for the trial. Previously another Phosphodiesterase-5 inhibitor Sildenafil has been used 3 x 40mg/day 6-8hrs after arrival to high altitude and maintained for six days to inhibit altitude-induced hypoxemia and pulmonary hypertension (2). Similarly, the other study uses sildenafil 25 or 100mg 8 hourly for 12 weeks to treat high altitude pulmonary arterial hypertension (3). In both of the studies, it has been found effective. In case of dexamethasone, it has been used 8 mg initially and followed by 4 mg every 6 hourly to treat high-altitude cerebral edema (4). Therefore, could authors explain how they chose their drug regimen for their trial of prophylaxis?
REFERENCES: 1. Maggiorini M, Brunner-La Rocca H, Peth S, Fischler M, Böhm T, Bernheim A, et al. Both tadalafil and dexamethasone may reduce the incidence of high-altitude pulmonary edema. A randomized trial. Ann Intern Med. 2006; 145:497-506 2. Richalet J, Gratadour P, Robach P, Pham I, De´chaux M, Joncquiert-Latarjet A, et. al.Sildenafil Inhibits Altitude-induced Hypoxemia and Pulmonary Hypertension. Am J Respir Crit Care Med Vol 171. pp 275–281, 2005 3. Aldashev AA, Kojonazarov BK, Amatov TA, Sooronbaev TM, Mirrakhimov MM, Morrell NW, et al.Phosphodiesterase type 5 and high altitude pulmonary hypertension. Thorax 2005; 60:683–687. 4. West, JB. The Physiologic Basis of High-Altitude Diseases. Ann Intern Med. 2004;141 : 789-800 Conflict of Interest:None declared |
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Peter T. Smyth, MD,FACP GLencoe Regional Health Services
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peter.smyth{at}grhsonline.org Peter T. Smyth
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Reaching the summit was quite-a-thrill, My lungs doing great on todalafil. And to also protect, It's the other effect, When I fell I didn't role down-the-hill. Conflict of Interest:None declared |
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Buddha Basnyat, MD, MSc, FACP Nepal International Clinic
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rishisbas{at}wlink.com.np Buddha Basnyat
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Dear Sir, Neither this article nor the accompanying editorial(1) comments on the important mental side effects of dexamethasone which may include euphoria and mental disorientation. These are potentially dangerous adverse side effects that deserve mention especially if you are climbing a jagged edge or trekking in remote high altitude mountain regions. Sincerely, Buddha Basnyat 1 Swenson ER. Hypoxic lung whiteout: Further clearing but more questions from on high. Annals. 2006; 145: 550-552. Conflict of Interest:None declared |
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