Berger Marc Moritz, Sareban Mahdi, Schiefer Lisa Maria, Swenson Kai E, Treff Franziska, Schäfer Larissa, Schmidt Peter, Schimke Magdalena M, Paar Michael, Niebauer Josef, Cogo Annalisa, Kriemler Susi, Schwery Stefan, Pickerodt Philipp A, Mayer Benjamin, Bärtsch Peter, Swenson Erik R
Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
University Institute of Sports Medicine, Prevention and Rehabilitation, Paracelsus Medical University, Salzburg, Austria.
J Appl Physiol (1985). 2022 Jun 1;132(6):1361-1369. doi: 10.1152/japplphysiol.00806.2021. Epub 2022 May 5.
Acetazolamide prevents acute mountain sickness (AMS) by inhibition of carbonic anhydrase. Since it also reduces acute hypoxic pulmonary vasoconstriction (HPV), it may also prevent high-altitude pulmonary edema (HAPE) by lowering pulmonary artery pressure. We tested this hypothesis in a randomized, placebo-controlled, double-blind study. Thirteen healthy, nonacclimatized lowlanders with a history of HAPE ascended (<22 h) from 1,130 to 4,559 m with one overnight stay at 3,611 m. Medications were started 48 h before ascent (acetazolamide: = 7, 250 mg 3 times/day; placebo: = 6, 3 times/day). HAPE was diagnosed by chest radiography and pulmonary artery pressure by measurement of right ventricular to atrial pressure gradient (RVPG) by transthoracic echocardiography. AMS was evaluated with the Lake Louise Score (LLS) and AMS-C score. The incidence of HAPE was 43% versus 67% (acetazolamide vs. placebo, = 0.39). Ascent to altitude increased RVPG from 20 ± 5 to 43 ± 10 mmHg ( < 0.001) without a group difference ( = 0.68). Arterial Po fell to 36 ± 9 mmHg ( < 0.001) and was 8.5 mmHg higher with acetazolamide at high altitude ( = 0.025). At high altitude, the LLS and AMS-C score remained lower in those taking acetazolamide (both < 0.05). Although acetazolamide reduced HAPE incidence by 35%, this effect was not statistically significant, and was considerably less than reductions of about 70%-100% with prophylactic dexamethasone, tadalafil, and nifedipine performed with the same ascent profile at the same location. We could not demonstrate a reduction in RVPG compared with placebo treatment despite reductions in AMS severity and better arterial oxygenation. Limited by small sample size, our data do not support recommending acetazolamide for the prevention of HAPE in mountaineers ascending rapidly to over 4,500 m. This randomized, placebo-controlled, double-blind study is the first to investigate whether acetazolamide, which reduces acute mountain sickness (AMS), inhibits short-term hypoxic pulmonary vasoconstriction, and also prevents high-altitude pulmonary edema (HAPE) in a fast-climbing ascent to 4,559 m. We found no statistically significant reduction in HAPE incidence or differences in hypoxic pulmonary artery pressures compared with placebo despite reductions in AMS and greater ventilation-induced arterial oxygenation. Our data do not support recommending acetazolamide for HAPE prevention.
乙酰唑胺通过抑制碳酸酐酶预防急性高原病（AMS）。由于它还能减轻急性低氧性肺血管收缩（HPV），因此可能通过降低肺动脉压力来预防高原肺水肿（HAPE）。我们在一项随机、安慰剂对照、双盲研究中对这一假设进行了检验。13名有HAPE病史的健康、未适应环境的低地居民在<22小时内从1130米上升至4559米，在3611米处过夜停留一次。在上升前48小时开始用药（乙酰唑胺：n = 7，250毫克，每日3次；安慰剂：n = 6，每日3次）。通过胸部X线摄影诊断HAPE，通过经胸超声心动图测量右心室与心房压力梯度（RVPG）来评估肺动脉压力。用路易斯湖评分（LLS）和AMS - C评分评估AMS。HAPE的发生率为43%，而安慰剂组为67%（乙酰唑胺与安慰剂相比，P = 0.39）。上升到高原使RVPG从20±5 mmHg增加到43±10 mmHg（P < 0.001），两组之间无差异（P = 0.68）。动脉血氧分压降至36±9 mmHg（P < 0.001），在高原时服用乙酰唑胺时高8.5 mmHg（P = 0.025）。在高原时，服用乙酰唑胺者的LLS和AMS - C评分仍然较低（两者均P < 0.05）。尽管乙酰唑胺使HAPE发生率降低了35%，但这一效果无统计学意义，且远低于在同一地点以相同上升模式使用预防性地塞米松、他达拉非和硝苯地平约70% - 100%的降低率。尽管AMS严重程度降低且动脉氧合改善，但与安慰剂治疗相比，我们未能证明RVPG降低。受样本量小的限制，我们的数据不支持推荐乙酰唑胺用于快速上升至4500米以上的登山者预防HAPE。这项随机、安慰剂对照、双盲研究首次调查了可减轻急性高原病（AMS）、抑制短期低氧性肺血管收缩且能预防快速攀升至4559米时高原肺水肿（HAPE）的乙酰唑胺。尽管AMS降低且通气诱导的动脉氧合增加，但与安慰剂相比，我们发现HAPE发生率无统计学意义的降低，且低氧性肺动脉压力无差异。我们的数据不支持推荐乙酰唑胺用于预防HAPE。
