Nieto Estrada Víctor H, Molano Franco Daniel, Medina Roger David, Gonzalez Garay Alejandro G, Martí-Carvajal Arturo J, Arevalo-Rodriguez Ingrid
Department of Critical Care Medicine, Hospital de San José, Fundación Universitaria de Ciencias de la Salud, Bogotá, Colombia.
Cochrane Database Syst Rev. 2017 Jun 27;6(6):CD009761. doi: 10.1002/14651858.CD009761.pub2.
High altitude illness (HAI) is a term used to describe a group of cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres (8202 feet). Acute hypoxia, acute mountain sickness (AMS), high altitude cerebral oedema (HACE) and high altitude pulmonary oedema (HAPE) are reported as potential medical problems associated with high altitude. In this review, the first in a series of three about preventive strategies for HAI, we assess the effectiveness of six of the most recommended classes of pharmacological interventions.
To assess the clinical effectiveness and adverse events of commonly-used pharmacological interventions for preventing acute HAI.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), Embase (OVID), LILACS and trial registries in January 2017. We adapted the MEDLINE strategy for searching the other databases. We used a combination of thesaurus-based and free-text terms to search.
We included randomized-controlled and cross-over trials conducted in any setting where commonly-used classes of drugs were used to prevent acute HAI.
We used standard methodological procedures as expected by Cochrane.
We included 64 studies (78 references) and 4547 participants in this review, and classified 12 additional studies as ongoing. A further 12 studies await classification, as we were unable to obtain the full texts. Most of the studies were conducted in high altitude mountain areas, while the rest used low pressure (hypobaric) chambers to simulate altitude exposure. Twenty-four trials provided the intervention between three and five days prior to the ascent, and 23 trials, between one and two days beforehand. Most of the included studies reached a final altitude of between 4001 and 5000 metres above sea level. Risks of bias were unclear for several domains, and a considerable number of studies did not report adverse events of the evaluated interventions. We found 26 comparisons, 15 of them comparing commonly-used drugs versus placebo. We report results for the three most important comparisons: Acetazolamide versus placebo (28 parallel studies; 2345 participants)The risk of AMS was reduced with acetazolamide (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.39 to 0.56; I = 0%; 16 studies; 2301 participants; moderate quality of evidence). No events of HAPE were reported and only one event of HACE (RR 0.32, 95% CI 0.01 to 7.48; 6 parallel studies; 1126 participants; moderate quality of evidence). Few studies reported side effects for this comparison, and they showed an increase in the risk of paraesthesia with the intake of acetazolamide (RR 5.53, 95% CI 2.81 to 10.88, I = 60%; 5 studies, 789 participants; low quality of evidence). Budenoside versus placebo (2 parallel studies; 132 participants)Data on budenoside showed a reduction in the incidence of AMS compared with placebo (RR 0.37, 95% CI 0.23 to 0.61; I = 0%; 2 studies, 132 participants; low quality of evidence). Studies included did not report events of HAPE or HACE, and they did not find side effects (low quality of evidence). Dexamethasone versus placebo (7 parallel studies; 205 participants)For dexamethasone, the data did not show benefits at any dosage (RR 0.60, 95% CI 0.36 to 1.00; I2 = 39%; 4 trials, 176 participants; low quality of evidence). Included studies did not report events of HAPE or HACE, and we rated the evidence about adverse events as of very low quality.
AUTHORS' CONCLUSIONS: Our assessment of the most commonly-used pharmacological interventions suggests that acetazolamide is an effective pharmacological agent to prevent acute HAI in dosages of 250 to 750 mg/day. This information is based on evidence of moderate quality. Acetazolamide is associated with an increased risk of paraesthesia, although there are few reports about other adverse events from the available evidence. The clinical benefits and harms of other pharmacological interventions such as ibuprofen, budenoside and dexamethasone are unclear. Large multicentre studies are needed for most of the pharmacological agents evaluated in this review, to evaluate their effectiveness and safety.
高原病（HAI）是一个用于描述一组脑和肺综合征的术语，这些综合征可能在前往海拔2500米（8202英尺）以上地区旅行期间发生。急性缺氧、急性高山病（AMS）、高原脑水肿（HACE）和高原肺水肿（HAPE）被报告为与高原相关的潜在医学问题。在本综述中，这是关于高原病预防策略的三篇系列综述中的第一篇，我们评估了六类最常推荐的药物干预措施的有效性。
评估预防急性高原病常用药物干预措施的临床有效性和不良事件。
我们于2017年1月检索了Cochrane对照试验中心注册库（CENTRAL）、MEDLINE（OVID）、Embase（OVID）、拉丁美洲和加勒比地区卫生科学数据库（LILACS）以及试验注册库。我们调整了MEDLINE检索策略以检索其他数据库。我们使用基于叙词表和自由文本词的组合进行检索。
我们纳入了在任何使用常用药物类别预防急性高原病的环境中进行的随机对照试验和交叉试验。
我们采用了Cochrane预期的标准方法程序。
本综述纳入了64项研究（78篇参考文献）和4547名参与者，并将另外12项研究分类为正在进行中。另有12项研究等待分类评估，因为我们无法获取其全文。大多数研究在高海拔山区进行，其余研究使用低压（低氧）舱模拟高原暴露。24项试验在上升前3至5天提供干预，23项试验在上升前1至2天提供干预。纳入的大多数研究最终海拔达到海平面以上4001至5０00米。几个领域的偏倚风险尚不清楚，相当数量的研究未报告所评估干预措施的不良事件。我们发现了26项比较，其中15项是常用药物与安慰剂的比较。我们报告了三项最重要的比较结果：乙酰唑胺与安慰剂（28项平行研究；2345名参与者）使用乙酰唑胺可降低急性高山病的风险（风险比（RR）0.47，95%置信区间（CI）0.39至0.56；I² = 0%；16项研究；2301名参与者；证据质量中等）。未报告高原肺水肿事件，仅报告了1例高原脑水肿事件（RR 0.32，95%CI 0.01至7.48；6项平行研究；1126名参与者；证据质量中等）。很少有研究报告此比较的副作用，且这些研究表明服用乙酰唑胺会增加感觉异常的风险（RR 5.53，95%CI 2.81至10.88，I² = 60%；5项研究，789名参与者；证据质量低）。布地奈德与安慰剂（2项平行研究；132名参与者）与安慰剂相比，布地奈德的数据显示急性高山病的发病率降低（RR 0.37，95%CI 0.23至0.61；I² =０%；2项研究，132名参与者；证据质量低）。纳入的研究未报告高原肺水肿或高原脑水肿事件，且未发现副作用（证据质量低）。地塞米松与安慰剂（7项平行研究；205名参与者）对于地塞米松，任何剂量的数据均未显示出益处（RR 0.60，95%CI 0.36至1.00；I² = 39%；4项试验，176名参与者；证据质量低）。纳入的研究未报告高原肺水肿或高原脑水肿事件，我们将关于不良事件的证据评级为极低质量。
我们对最常用药物干预措施的评估表明，乙酰唑胺是预防急性高原病的有效药物，剂量为每日250至750毫克。该信息基于中等质量的证据。乙酰唑胺与感觉异常风险增加相关，尽管现有证据中关于其他不良事件的报告很少。布洛芬、布地奈德和地塞米松等其他药物干预措施的临床益处和危害尚不清楚。对于本综述中评估的大多数药物，需要进行大型多中心研究以评估其有效性和安全性。
