野外與登山醫學-Nifedipine降血壓機轉(文章內討論的並非針對高海拔疾病)

Effects of Nifedipine on Systemic and Pulmonary Vascular Impedance in Subjects Undergoing Cardiac Catheterization
Toshitaka NODA1), Toshio YAGINUMA2),*, Michael F. O’ROURKE3),4), and Saichi HOSODA5)

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硝苯地平對接受心導管插入術的受試者全身和肺血管阻抗的影響 Toshitaka NODA1), Toshio YAGINUMA2),*, Michael F. O'ROURKE3),4), and Saichi HOSODA5) 硝苯地平 10 mg，舌下含服於診斷後的 12 名患者心導管術，導致全身阻力降低，阻抗改變以及升主動脈和左心室壓力波輪廓的改變。儘管每搏量和心輸出量增加，但硝苯地平顯著降低了升主動脈和左心室收縮壓，並且與平均壓力和波反射指數的類似降低有關。在同一患者中，肺血管阻力或阻抗沒有顯著變化，也不在肺動脈或右心室壓力脈搏輪廓中。對於全身循環，與硝酸甘油和硝普鈉一樣，波反射的減少似乎是藥物作用的一個重要因素，並且在治療心絞痛、全身性高血壓和左心室衰竭時它對心臟負荷有有益作用。因此，觀察到的硝苯地平作用歸因於全身動脈和小動脈的血管擴張。（高血壓研究 2006；29：505–513）因此，觀察到的硝苯地平作用歸因於全身動脈和小動脈的血管擴張。（高血壓研究 2006；29：505–513）因此，觀察到的硝苯地平作用歸因於全身動脈和小動脈的血管擴張。（高血壓研究 2006；29：505–513）

簡介 硝苯地平和其他二氫吡啶類鈣通道阻滯劑 (CCB) 廣泛用於治療高血壓、缺血性心髒病和保留左心室收縮功能的心力衰竭 (1–6)。硝苯地平還用於治療主動脈瓣關閉不全 (7) 和肺動脈高壓 (8)。這些藥物可有效降低動脈壓、緩解心肌缺血以及改善收縮和舒張左心室功能 (3, 4, 9)。它們的有益作用歸因於外周小動脈擴張，這會導致平均動脈壓和左心室後負荷降低 (5, 9)。然而，關於硝苯地平對體循環或肺循環中的搏動現象影響的研究很少。雖然硝苯地平已被證明可以降低早期波反射和中心主動脈收縮壓 (10)，但有限的血管阻抗研究並未顯示該藥物對升主動脈阻抗的頻率依賴性成分具有一致的影響 (11, 12)。儘管硝苯地平用於治療肺動脈高壓 (8)，但沒有關於硝苯地平對肺血管阻抗影響的數據。本研究的目的是研究硝苯地平對因已知或疑似缺血性心髒病而接受心導管術的人類受試者的動脈搏動血流動力學以及全身和肺血管阻抗的影響。血管阻抗的有限研究並未顯示藥物對升主動脈阻抗的頻率依賴性成分的一致影響 (11, 12)。儘管硝苯地平用於治療肺動脈高壓 (8)，但沒有關於硝苯地平對肺血管阻抗影響的數據。本研究的目的是研究硝苯地平對因已知或疑似缺血性心髒病而接受心導管術的人類受試者的動脈搏動血流動力學以及全身和肺血管阻抗的影響。血管阻抗的有限研究並未顯示藥物對升主動脈阻抗的頻率依賴性成分的一致影響 (11, 12)。儘管硝苯地平用於治療肺動脈高壓 (8)，但沒有關於硝苯地平對肺血管阻抗影響的數據。本研究的目的是研究硝苯地平對因已知或疑似缺血性心髒病而接受心導管術的人類受試者的動脈搏動血流動力學以及全身和肺血管阻抗的影響。 

結果

12例患者的臨床特徵見表1，對照條件下的基本血流動力學數據見表2。所有患者均為男性，平均年齡55.4±6.3歲（年齡範圍43-63歲）。在左心室和右心室以及主動脈和肺動脈中同時記錄的壓力和流量的代表性描記圖如圖 2 所示，分別為硝苯地平給藥前後的情況。所有患者服用硝苯地平前後血流動力學參數的平均值見表 3。服用硝苯地平可使心率從每分鐘 70 次增加到 84 次，每搏輸出量增加，因此，心輸出量增加更大 (31%)。服用硝苯地平可顯著降低全身而非肺血管阻力（分別從 1,664 到 1,126 dyn s cm-5 [p<0.001] 和 241 到 182 dyn s cm-5 [NS]）。硝苯地平的其他肺血流動力學數據或肺血管阻抗沒有顯著變化，但全身血管阻抗有非常明顯的變化（圖 3）。硝苯地平增加的心輸出量與平均壓力從 102 mmHg 降低到 90 mmHg 相關，表明外周系統阻力降低。與此同時，收縮壓下降了 25 mmHg (p<0.0001)，但舒張壓僅下降了 9 mmHg (p<0.02)。收縮壓的大幅下降與晚期收縮峰振幅的降低有關，並且主要由其引起（圖 1）。2). 測量的主動脈收縮壓波增強被確定為第一個收縮壓肩和壓力峰值之間的壓差 (14, 15)。這從 22 mmHg 下降到 10 mmHg (p<0.0001)。儘管每搏輸出量增加了 8%，但脈壓實際上下降了 30% (p<0.0001)。儘管流量波動增加，但壓力波動的這種減少表明波反射減少或動脈僵硬度降低。壓力波形狀的變化，以及第一次肩部收縮後增強的減少，表明外周波反射減少 (12–14)。阻抗模量從 47 到 29 dyn s cm-5 (p < 0.01) 減少了 43%（從 193 到 110 dyn s cm-5 [p<0.0001]）；這是模量圍繞其特徵值波動的量度。特性阻抗從 103 下降 22% 至 80 dyn s cm−5 ，但這種變化沒有達到統計學意義的水平。特徵阻抗的任何降低都可能是由於動脈壓降低導致近端主動脈的擴張性被動下降。給予硝苯地平後，左心室外部做功的穩定成分沒有顯著增加，心輸出量的增加被平均壓力的下降所抵消。阻抗模量的降低抵消了每搏輸出量和脈動流量的增加，因此外部做功的脈動分量沒有變化，脈動與總外部做功的比率也沒有變化。在肺循環中，服用硝苯地平後平均壓力沒有變化（前後均為 15 mmHg），特徵阻抗也沒有變化（前後分別為 37 和 33 dyn s cm−5）。硝苯地平給藥不影響左心室或右心室的舒張末期壓力，並且不改變波反射的時間，如阻抗相位的零交叉所衡量的那樣（圖 4）。對於升主動脈，硝苯地平給藥前該頻率為 3.3±0.6 Hz，給藥後為 3.4±0.6 Hz (NS)；對於肺動脈，該頻率在硝苯地平之前為 2.5±0.8 Hz，在硝苯地平之後為 2.8±1.2 Hz (NS)。該頻率對應於阻抗模量的最小值，但可以更準確地測量 特性阻抗也沒有（前後分別為 37 和 33 dyn s cm−5）。硝苯地平給藥不影響左心室或右心室的舒張末期壓力，並且不改變波反射的時間，如阻抗相位的零交叉所衡量的那樣（圖 4）。對於升主動脈，硝苯地平給藥前該頻率為 3.3±0.6 Hz，給藥後為 3.4±0.6 Hz (NS)；對於肺動脈，該頻率在硝苯地平之前為 2.5±0.8 Hz，在硝苯地平之後為 2.8±1.2 Hz (NS)。該頻率對應於阻抗模量的最小值，但可以更準確地測量 特性阻抗也沒有（前後分別為 37 和 33 dyn s cm−5）。硝苯地平給藥不影響左心室或右心室的舒張末期壓力，並且不改變波反射的時間，如阻抗相位的零交叉所衡量的那樣（圖 4）。對於升主動脈，硝苯地平給藥前該頻率為 3.3±0.6 Hz，給藥後為 3.4±0.6 Hz (NS)；對於肺動脈，該頻率在硝苯地平之前為 2.5±0.8 Hz，在硝苯地平之後為 2.8±1.2 Hz (NS)。該頻率對應於阻抗模量的最小值，但可以更準確地測量 對於升主動脈，硝苯地平給藥前該頻率為 3.3±0.6 Hz，給藥後為 3.4±0.6 Hz (NS)；對於肺動脈，該頻率在硝苯地平之前為 2.5±0.8 Hz，在硝苯地平之後為 2.8±1.2 Hz (NS)。該頻率對應於阻抗模量的最小值，但可以更準確地測量 對於升主動脈，硝苯地平給藥前該頻率為 3.3±0.6 Hz，給藥後為 3.4±0.6 Hz (NS)；對於肺動脈，該頻率在硝苯地平之前為 2.5±0.8 Hz，在硝苯地平之後為 2.8±1.2 Hz (NS)。該頻率對應於阻抗模量的最小值，但可以更準確地測量

討論 據我們所知，本文是第一個同時確定在人類受試者中使用口服有效血管擴張劑之前和之後呈現給左心室和右心室的脈動水力負荷的文章。輸入阻抗由三部分組成：阻力（平均壓力÷平均流量）、近端動脈硬度（升主動脈或主肺動脈特徵阻抗）和反射率（壓力增加或阻抗波動）(10)。結果很有趣，因為它們對肺阻抗和右心室搏動負荷沒有顯著影響，但對左心室搏動負荷有相當大的影響。觀察到的對全身循環的影響主要歸因於硝苯地平引起的外周阻力降低和波反射減少。升主動脈阻抗被廣泛接受為左心室負荷的表達 (15-26)，而肺血管阻抗被廣泛接受為右心室負荷的表達 (27-29)。已在患有胸痛綜合徵但沒有明確心血管疾病的患者、高血壓患者、心肌病患者以及本文所述的冠狀動脈粥樣硬化患者中進行了研究（表 4）。在過去的血管擴張劑作用研究中，大部分注意力都集中在阻抗模量的零頻率分量——外周阻力上。在 70 年代末和 80 年代初，注意力開始轉移到由潛在疾病或藥物治療引起的特徵阻抗和主動脈硬度的變化 (16-20)。此處描述的全身阻力和肺阻力值與之前報導的相似；主動脈和肺特徵阻抗的值也在之前報告的範圍內（表4）。在這項研究中，我們發現硝苯地平外周系統阻力降低，與心輸出量增加和全身動脈壓下降有關。然而，我們已經表明，這些效應的發生不會改變肺部特徵阻抗，也不會顯著降低全身特徵阻抗。我們已經指出，收縮壓和脈壓的顯著下降，以及主動脈和左心室波輪廓形狀的變化，不能僅用平均壓力和特徵阻抗的變化來解釋。然而，收縮壓和脈壓的降低以及波形的變化可以很容易地解釋為從外周血管末端返回的反射波振幅降低，從而導致外周血管舒張 (10, 16, 24)。這方面的證據是阻抗模量波動的減少，以及在脈衝的一次諧波頻率下升主動脈阻抗模量的顯著下降。硝酸甘油 (23, 24) 和硝普鈉 (18–21) 也出現了類似的變化，這歸因於壓力波反射的減少。這些對波反射的影響在硝普鈉 (21, 22) 的情況下歸因於小動脈擴張，而在硝酸甘油的情況下，阻力小動脈上游的小導管動脈的口徑和順應性發生變化 (10, 23, 24)。在這項研究中，升主動脈阻抗的變化與升主動脈壓力增加的顯著減少有關。這種增加的下降（12 毫米汞柱）與平均全身壓力下降（12 毫米汞柱）的幅度相似，並且在很大程度上解釋了脈壓顯著下降（16 毫米汞柱）。主動脈收縮壓的降低是由壓力增加的減少和平均壓力的下降引起的。兩者都歸因於外周血管擴張，以不同的方式起作用——第一種情況是通過減少波反射，第二種情況是通過減少外周阻力。因此，硝苯地平的有益治療效果主要歸因於外周阻力和波反射的降低。在成熟的成年人中，高主動脈脈搏波速度以及腹主動脈區域的結構變化 (10, 26, 30) 導致波反射不適當地提前返回心臟，並增加收縮晚期心室射血產生的壓力. 這種增壓包括左心室後負荷的重要組成部分 (10, 13, 14, 31)。它的減少，例如通過硝普鈉給藥，導致左心室負荷減少和左心室功能改善，特別是在左心室衰竭患者運動期間（32）。通過這種機制降低收縮壓也部分解釋了這種藥物對高血壓和心絞痛患者的益處 (10, 31)。此處描述的硝苯地平的作用與之前描述的硝普鈉 (18、19、21、22) 和硝酸甘油 (23、24) 的作用相似，儘管與硝酸甘油不同，硝苯地平和硝普鈉均持續降低外周阻力 (18、19、21) ). 然而，有人強調，當測量外周動脈的壓力時，硝酸甘油和硝普鈉的有益作用可能被低估 (8, 10, 33, 34)。不能通過傳統的上肢動脈峰值（收縮壓）和最低（舒張壓）壓力測量來正確解釋或評估早期波反射的不良影響及其減少的有益影響；然而，它們可以通過對肱動脈或橈動脈壓力波輪廓的解釋進行評估 (10, 33, 34)。同樣的原則很可能也適用於硝苯地平。然而，尚未進行任何研究來確定硝苯地平對中央動脈和外周動脈之間壓力波輪廓差異的影響。此處顯示的全身動脈血流動力學結果與 Ting 等人的報告一致。（12），但與 Chang 等人報導的不一致。(11) 在高血壓受試者組中。張等。(11) 發現硝苯地平降低了全身血管阻力，並降低了左心室的穩定成分，但無法證明對升主動脈阻抗的頻率依賴成分有任何影響。他們確實顯示硝苯地平的收縮壓比舒張壓有更大的降低，以及阻抗的一次諧波分量幅度的降低和脈壓的降低，但後兩種效應在統計學上並不顯著。作者只研究了 7 名患者，並且可能在接近造影血管造影時間時獲取了對照數據，當時造影劑的血管舒張作用仍然很明顯。該研究中心輸出量沒有增加的事實引發了一個問題，即藥物是否在採集數據時發揮藥理作用，即舌下給藥後 10-30 分鐘。婷等。(12) 使用了更高劑量的硝苯地平，並且與我們一樣，顯示出波反射測量值和全身血管阻力的降低。婷等。還顯示主動脈特徵阻抗降低。此處提供的數據與 Ting 等人的數據一致。(12) 並支持這樣的概念，即硝苯地平是治療高血壓或其他動脈系統硬化和波反射增加左心室負荷的病症（包括老年人的心力衰竭和冠心病）的合乎邏輯的治療劑（ 24、31、34-36）。然而，對於短效硝苯地平的使用，如本文所用，應注意一件事——即血管阻力降低可能導致冠狀動脈竊血和/或心動過速，從而加重心肌缺血 (10)。單純收縮期高血壓的理想抗高血壓藥物 (37) 和理想的抗心絞痛藥物 (10) 可能是一種與硝酸甘油類似的藥物，降低波反射和主動脈收縮壓，同時保持外周阻力和平均動脈壓 (10, 24, 33–35, 37, 38)。長效硝苯地平在療效和副作用方面與血管緊張素轉化酶抑製劑相當 (39)，並且不會像本研究中使用的短效製劑那樣誘發交感神經刺激和心動過速。

Nifedipine 10 mg, administered sublingually to 12 patients following diagnostic cardiac catheterization, caused reduction in systemic resistance, and change of impedance together with alteration in contour of the ascending aortic and left ventricular pressure waves. The substantial reduction in ascending aortic and left ventricular systolic pressure with nifedipine occurred despite an increase in stroke volume and cardiac output, and was associated with similar reductions in mean pressure and indices of wave reflection. In the same patients, there were no significant changes in pulmonary vascular resistance or impedance, nor in pulmonary artery or right ventricular pressure pulse contour. For the systemic circulation, as with nitroglycerin and nitroprusside, reduction in wave reflection appears to be an important factor in the drug’s action and for its beneficial effects on cardiac load in the treatment of angina pectoris, systemic hypertension and left ventricular failure. Thus the observed effects of nifedipine were attributed to vasodilatation of the systemic arteries and arterioles. (Hypertens Res 2006; 29: 505–513)

Introduction Nifedipine and other dihydropyridine calcium channel blockers (CCBs) are widely used in the treatment of hypertension, ischemic heart disease and cardiac failure with preserved left ventricular systolic function (1–6). Nifedipine is also used in the treatment of aortic valve incompetence (7) and pulmonary hypertension (8). These drugs are effective in lowering arterial pressure, relieving myocardial ischemia, and improving both systolic and diastolic left ventricular function (3, 4, 9). Their beneficial effects have been attributed to peripheral arteriolar dilation, which results in decreases in mean arterial pressure and left ventricular afterload (5, 9). However, therehave been few studies on the effects of nifedipine on pulsatile phenomena, either in the systemic or pulmonary circulations. While nifedipine has been shown to reduce early wave reflection and central aortic systolic pressure (10), the limited studies of vascular impedance have not shown a consistent effect of the drug on the frequency-dependent components of ascending aortic impedance (11, 12). And despite the drug’s use in pulmonary hypertension (8), no data are available on the effects of nifedipine on pulmonary vascular impedance. The purpose of this study was to investigate the effects of nifedipine on pulsatile arterial hemodynamics and systemic and pulmonary vascular impedance in human subjects undergoing cardiac catheterization for known or suspected ischemic heart disease. 

Results

The clinical characteristics of the twelve patients are given in Table 1, and the basic hemodynamic data under control conditions are given in Table 2. All patients were male with an average age of 55.4±6.3 years (age range 43–63 years). Representative tracings of pressure and flow recorded simultaneously in the left and right ventricles, and in the aorta and pulmonary arteries are shown in Fig. 2, before and after administration of nifedipine. The averaged values of hemodynamic parameters in all patients before and after nifedipine administration are given in Table 3. Nifedipine administration led to an increase in heart rate from 70 to 84 beats per min (bpm), as well as an increase in stroke volume and, consequently, an even greater (31%) increase in cardiac output. Nifedipine administration resulted in a significant reduction in systemic but not pulmonary vascular resistance (from 1,664 to 1,126 dyn s cm−5 [p<0.001], and 241 to 182 dyn s cm−5 [NS], respectively). There was no significant change in other pulmonary hemodynamic data or in pulmonary vascular impedance with nifedipine, but there was a very clear change in the systemic vascular impedance (Fig. 3). The increase in cardiac output with nifedipine was associated with a decrease in mean pressure from 102 to 90 mmHg, signifying a decrease in peripheral systemic resistance. Accompanying this, there was a fall of 25 mmHg (p<0.0001) in systolic pressure but only 9 mmHg (p<0.02) in diastolic pressure. The substantial fall in systolic pressure was associated with and largely caused by a reduction in the amplitude of the late systolic peak (Fig. 2). Measured aortic systolic pressure wave augmentation was determined as the pressure difference between the first systolic shoulder and the pressure peak (14, 15). This fell from 22 to 10 mmHg (p<0.0001). Despite the 8% increase in stroke volume, the pulse pressure actually decreased by 30% (p<0.0001). Such a decrease in pressure fluctuation despite an increase in flow fluctuation suggests either a decrease in wave reflection or a decrease in arterial stiffness. The change in shape of the pressure wave, with a reduction in augmentation after the first systolic shoulder, suggests a reduction in the peripheral wave reflection (12–14). This was supported by the 43% reduction (from 193 to 110 dyn s cm−5 [p<0.0001]) of the modulus of impedancefrom 47 to 29 dyn s cm−5 (p<0.01); this is a measure of the fluctuation of modulus around its characteristic value. Characteristic impedance fell by 22% from 103 to 80 dyn s cm−5 , but this change did not reach the level of statistical significance. Any decrease in characteristic impedance could have been due to a passive fall in the distensibility of the proximalaorta with the reduction in arterial pressure. The steady component of external left ventricular work did not increase significantly after nifedipine administration, the increase in cardiac output being offset by a fall in mean pressure. The decrease in impedance modulus more than offset the increase in stroke volume and pulsatile flow, such that the pulsatile component of external work did not change, and neither did the ratio of pulsatile to total external work. In the pulmonary circulation, mean pressure did not change after administration of nifedipine (15 mmHg both before and after), and neither did characteristic impedance (37 and 33 dyn s cm−5 before and after). Nifedipine administration did not affect end-diastolic pressure of the left or right ventricle, and did not alter the timing of wave reflection, as gauged by the zero crossing of the impedance phase (Fig. 4). For the ascending aorta, this frequency was 3.3±0.6 Hz before, and 3.4±0.6 Hz (NS) after nifedipine administration; for the pulmonary artery, this frequency was 2.5±0.8 Hz before, and 2.8±1.2 Hz (NS) after nifedipine. This frequency corresponded to the minimal value of the impedance modulus, but could be measured more accurately

Discussion To our knowledge, this paper is the first to simultaneously determine the pulsatile hydraulic load presented to the left and right ventricle, before and after use of an orally effective vasodilator agent in human subjects. Input impedance is composed of three components: resistance (mean pressure ÷ mean flow), stiffness of proximal arteries (ascending aortic or main pulmonary artery characteristic impedance) and reflectance (augmented pressure or impedance fluctuation) (10). The results are intriguing in that they show no significant effect on pulmonary impedance and right ventricular pulsatile load, but considerable effect on left ventricular pulsatile load. The observed effects on the systemic circulation were largely attributed to the decreased peripheral resistance and decreased wave reflection induced by nifedipine. Ascending aortic impedance is widely accepted as an expression of left ventricular load (15–26), and pulmonary vascular impedance as an expression of right ventricular load (27–29). Studies have been undertaken in patients with chest pain syndromes but without definite cardiovascular disease, in patients with hypertension, in patients with cardiomyopathy, and in patients such as those described here, with coronary atherosclerosis (Table 4). In past studies of vasodilator action, most attention has been directed to the zero frequency component of impedance modulus—the peripheral resistance. In the late 1970s and early 1980s, the attention began to shift to the changes in characteristic impedance and aortic stiffness resulting from the underlying disease or from drug therapy (16–20). The values of the systemic and pulmonary resistance described here are similar to those reported earlier; the values of aortic and pulmonary characteristic impedance are also in the range of those reported before (Table 4). In this study we have shown a decrease in peripheral systemic resistance with nifedipine, in association with an increase in cardiac output and fall in systemic arterial pressure. We have shown, however, that these effects occur without any change in pulmonary characteristic impedance and no significant reduction in systemic characteristic impedance. We have pointed out that the marked falls in systolic pressure and pulse pressure, and the change in shape of the aortic and left ventricular wave contours, cannot be explained solely by the change in mean pressure and characteristic impedance. However, the decrease in systolic and pulse pressure and the change in waveform can readily be explained on the basis of the decrease in the amplitude of the reflected wave returning from peripheral vascular terminations and consequently on peripheral vasodilation (10, 16, 24). The evidence for this is the reduction in fluctuation of the impedance modulus, and the substantial fall in the ascending aortic impedance modulus at the frequency of the first harmonic of the pulse. Similar changes have been noted with nitroglycerin (23, 24) and with nitroprusside (18–21), and have been attributed to a reduction in pressure wave reflection. These effects on wave reflection have been attributed to arteriolar dilation in the case of nitroprusside (21, 22), and in the case of nitroglycerin, to a change in the caliber and compliance of the small conduit arteries immediately upstream from the resistive arterioles (10, 23, 24). In this study, the change in ascending aortic impedance was associated with a marked reduction in pressure augmentation in the ascending aorta. This fall in augmentation (of 12 mmHg) was of similar magnitude to the degree of fall in mean systemic pressure (12 mmHg) and largely explains the marked reduction in pulse pressure (of 16 mmHg). The reduction of aortic systolic pressure was caused both by a reduction in pressure augmentation and a fall in mean pressure. Both are attributable to peripheral vasodilation, acting in different ways—in the first case through a decrease in wave reflection, and in the second through a decrease in peripheral resistance. The beneficial therapeutic effects of nifedipine can thus be largely attributed to reductions in the peripheral resistance and wave reflection. In mature adults, high aortic pulse wave velocity, together with structural changes in the region of the abdominal aorta (10, 26, 30) result in wave reflection returning inappropriately early to the heart, and boosting the pressure generated by ventricular ejection in late systole. This pressure boost comprises a substantial component of the left ventricular afterload (10, 13, 14, 31). Its reduction, such as by nitroprusside administration, leads to a reduction in left ventricular load and an improvement in left ventricular function, especially during exercise in patients with left ventricular failure (32). The decrease in systolic pressure by this mechanism also partially explains the benefit of this drug in patients with hypertension and angina pectoris (10, 31). The effects of nifedipine described here are similar to those previously described for nitroprusside (18, 19, 21, 22) and for nitroglycerin (23, 24), although unlike nitroglycerin, both nifedipine and nitroprusside consistently decrease peripheral resistance (18, 19, 21). It has been stressed, however, that the beneficial effects of nitroglycerin and of nitroprusside may be underestimated when pressure is measured in a peripheral artery (8, 10, 33, 34). The ill effects of early wave reflection, and the beneficial effects of its reduction cannot be properly interpreted or assessed from conventional measurement of the peak (systolic) and lowest (diastolic) pressure in an upper limb artery; they can, however, be assessed from interpretation of the brachial or radial artery pressure wave contour (10, 33, 34). It is quite likely that the same principles also apply to nifedipine. However, no study has yet been conducted to determine the effects of nifedipine on the differences in pressure wave contour between the central and peripheral arteries. The results presented here for systemic arterial hemodynamics are in line with the report by Ting et al. (12), but at variance with those reported by Chang et al. (11) in groups of hypertensive subjects. Chang et al. (11) found a reduction in systemic vascular resistance, and in the steady component of left ventricular work with nifedipine, but were unable to demonstrate any effect on the frequency-dependent components of ascending aortic impedance. They did show a greaterreduction in systolic than in diastolic pressure with nifedipine, as well as a reduction in amplitude of the first harmonic component of impedance, and a reduction of pulse pressure, but the latter two effects were not statistically significant. The authors studied just seven patients and may have taken control data close to the time of contrast angiography, when the vasodilating effect of the contrast agent was still in evidence. The fact that cardiac output did not increase in that study raises a question as to whether the drug was exerting a pharmacological effect at the time data were taken, i.e., 10–30 min after sublingual administration. Ting et al. (12) used a higher dose of nifedipine and showed, as did we, reductions in the measures of wave reflection and in the systemic vascular resistance. Ting et al. also showed a reduction in aortic characteristic impedance. The data presented here are concordant with those of Ting et al. (12) and support the concept that nifedipine is a logical therapeutic agent for management of hypertension or of other conditions (including cardiac failure and coronary disease in older persons) in which the arterial system is stiffened and wave reflection adds to the left ventricular load (24, 31, 34– 36). However, one caveat should be made in regard to the use of short-acting nifedipine, such as used here—namely, the decrease in vascular resistance may cause coronary steal and/ or tachycardia, which could worsen myocardial ischemia (10). The ideal antihypertensive agent in isolated systolic hypertension (37), and the ideal anti-anginal agent (10) may be one which, like nitroglycerin, reduces wave reflection and aortic systolic pressure while maintaining peripheral resistance and mean arterial pressure (10, 24, 33–35, 37, 38). Long-acting nifedipine is comparable to an angiotensin converting enzyme inhibitor in efficacy and side effect profile (39), and does not induce sympathetic stimulation and tachycardia as can the short-acting preparations used in this study.

野外與登山醫學-安眠藥物會不會提高罹患高海拔疾病風險?

 在uptodate上面沒找到明確答案. 不過在這個網站有提到
1. BZD類的鎮定安眠藥物可能會呼吸抑制. 導致血氧降更低. 可能有風險.不建議使用
2. Ambien® or Lunesta 相對上比較安全
在台灣. 與Ambien同成分藥物, 大家比較常聽到的是史蒂諾斯 stilnox, 它們的成分是 zopidem
Lunesta 成分是 Eszopiclone.
Ambien 和 Lunesta 兩類藥物都可能引起夢遊問題, 且這兩種是管制藥物. 需經醫師評估才能處方開立. 
[2019-05-02]3種成分安眠藥可能引發夢遊 衛福部：評估是否強化警示

INSTITUTE FOR ALTITUDE MEDICINE

HOW CAN I PREVENT ALTITUDE ILLNESS?

As with any illness, prevention is always the best approach. These are things you can do to improve your chances of not getting altitude illness.

• Slow ascent to altitude is the key to prevention. Almost anyone can get altitude illness if they go too high, too quickly. Because of the individual differences, a preventive rate of ascent for one person may be too slow or fast for another.
• An overnight stay at an intermediate altitude such as Denver (5280 ft) or preferably a bit higher prior to further ascent into the mountains is very helpful. If traveling to Telluride, overnighting in Ridgway, Ouray, Placerville or Durango would be helpful, especially if the destination is Mountain Village.
• Staying hydrated is important as it aids your body in acclimatizing.
• Avoid use of alcohol or sleeping agents of the benzodiazepine family, since they both suppress breathing and result in lower blood oxygen. Other sleeping pills like Ambien® or Lunesta® do not affect breathing at high altitude and are safe. Avoid over-exertion for 1-2 days after arrival to altitude.
• Acetazolamide (Diamox®) taken 24 hours prior to arrival to altitude and the first 2 days at altitude is 75% effective in preventing AMS. It speeds up the acclimatization process in the body, stimulates breathing, raises blood oxygen and increases urination.
• Gingko biloba, according to some studies was effective in preventing AMS when started 5 days prior to ascending to altitude, at a dose of 100 mg twice a day.

野外與登山醫學-成人嚴重肢體外傷出血---止血法

2024-01-30 15:50
剛在FB看到有網友貼Stop the Bleed 中文翻譯
稍微查詢一下資料. 並更新筆記

另一篇相關筆記在這

到院前止血帶的使用~~ 2014年美國外科醫學會創傷委員會外出血控制指引


底下內容來自 UPTODATE 網站的不同章節
Severe lower extremity injury in the adult patient

Techniques for lower extremity amputation

Complications of total knee arthroplasty



下面是GOOGLE翻譯


Severe lower extremity injury in the adult patient
出血的控制 — 肢體的外部出血，尤其是肢體血管系統交界段（即股總動脈）的出血，會危及生命，應盡快控制[33 ] 。

下肢血管損傷引起的出血通常可以使用直接壓力來控制。然而，由於在院前或戰術環境中轉運過程中長時間施加直接壓力通常不切實際，因此使用了其他方法，包括局部藥物、外部壓力夾和血管內閉塞裝置 [33 ]。這些方法在主流民用臨床實踐中並未被廣泛接受，但已在院前環境中得到美國外科醫師學會的認可 [ 33 ]。

也可以使用止血帶 [ 34,35 ] 或直接夾住可見血管來控制出血。不能夾持不能清楚識別的血管不應 進行 。氣動止血帶通常用於減少肢體手術期間的出血。民間社區對使用止血帶控制肢體出血重新產生了興趣 [ 36 ]。ATLS 贊同明智地使用止血帶治療主要的肢體動脈出血，現在一些民用指南包括止血帶應用作為在直接壓力不成功時控制肢體出血的臨時輔助手段 [ 32,37,38] 或在戰術平民事件期間，這些事件可能會造成彈道或爆炸性傷害（例如，主動射手對峙）[ 39 ]。

已經開發出多種止血帶來治療與戰鬥相關的肢體出血，並且發生缺血和神經系統並發症的風險較低 [ 40,41 ]。戰鬥應用止血帶 (CAT)、緊急和醫療止血帶 (EMT) 和特種作戰部隊戰術止血帶 (SOFTT) 符合美國軍方的有效性標準，並在 >80% 的受試者中阻斷遠端血流 [40,41 ]。這些止血帶的相對有效性已經在人類誌願者中進行了評估，每一種止血帶都顯示出可以減弱四肢的遠端動脈脈搏 [ 42 ]。以下對戰鬥傷亡人群的研究說明了使用止血帶的好處：

●在一項評估了 165 名患者（其中 67 名在院前使用了止血帶）的研究中，與未使用止血帶相比，使用止血帶顯著改善了出血控制（83.3% 對 60.7%），並且二次截肢率沒有差異[40 ]。



●一項針對 232 名戰鬥傷員的前瞻性研究發現，與不使用止血帶相比，使用止血帶（院前或急診）可顯著提高存活率 (77% vs 0%) [41 ]。在這項研究中，沒有因使用止血帶而需要截肢，但報告了四例短暫性神經麻痺。



在院前和院內應用止血帶的平民患者中也證實了類似的結果 [ 43-45 ]。在一項對院前止血帶用於四肢平民創傷的 AAST 多中心前瞻性分析中，院前止血帶的應用被廣泛且安全地採用，並且與休克到達發生率降低相關，而不會增加肢體並發症 [46,47 ]。


Control of hemorrhage — External bleeding from the extremity, and particularly bleeding from the junctional segment of the extremity vasculature (ie, common femoral artery), is life-threatening and should be controlled as soon as possible [33].

Bleeding from lower extremity vascular injury can usually be controlled using direct pressure. However, because prolonged application of direct pressure is often not practical during transport in the prehospital or tactical environment, other approaches have been used including topical agents, external compression clamps, and endovascular occlusion devices [33]. These methods are not widely accepted in mainstream civilian clinical practice but have been endorsed by the American College of Surgeons in the prehospital setting [33].

Bleeding can also be controlled using a tourniquet [34,35] or direct clamping of visible vessels. Clamping vessels that cannot be clearly identified should not be performed. Pneumatic tourniquets are commonly used to lessen bleeding during extremity surgery. There is renewed interest in the civilian community in the use of tourniquets for control of extremity hemorrhage [36]. ATLS endorses the judicious use of a tourniquet for major extremity arterial hemorrhage, and several civilian guidelines now include tourniquet application as a temporary adjunct to control extremity hemorrhage when direct pressure is unsuccessful [32,37,38] or during tactical civilian events, which are situations where ballistic or explosive wounds are possible (eg, an active shooter standoff) [39].

A variety of tourniquets have been developed to manage combat-related extremity hemorrhage with a low risk of ischemia and neurologic complications [40,41]. The Combat Application Tourniquet (CAT), Emergency and Medical Tourniquet (EMT), and Special Operations Forces Tactical Tourniquet (SOFTT) meet the effectiveness standard of the United States military and occlude distal flow in >80 percent of subjects [40,41]. The relative effectiveness of these tourniquets has been evaluated in human volunteers with each shown to attenuate the distal arterial pulse in the extremities [42]. The benefits of tourniquet application are illustrated in the following studies in combat casualty populations:

●In a study that evaluated 165 patients, 67 of whom had a prehospital tourniquet applied, control of bleeding was significantly improved with tourniquet application versus no tourniquet (83.3 versus 60.7 percent), and there were no differences in secondary amputation rates [40].



●A prospective study of 232 combat casualties found a significantly improved survival rate (77 versus 0 percent) when using a tourniquet (prehospital or emergency department) versus no tourniquet [41]. In this study, no amputations were required due to tourniquet use, but four transient nerve palsies were reported.



Similar results have been demonstrated in civilian patients with both pre-hospital and in-hospital tourniquet application [43-45]. In an AAST multicenter prospective analysis of prehospital tourniquet use for extremity civilian trauma, prehospital tourniquet application was being widely and safely adopted and was associated with decreased incidence of arrival in shock without increasing limb complications [46,47].

另一個章節 Techniques for lower extremity amputation


下面是GOOGLE翻譯.
下肢截肢技術

止血帶 — 止血帶已被證明可以減少術中失血，並減少膝上和膝下截肢術後輸血的需要 [ 14 ]。然而，止血帶對因肢體缺血而接受截肢術的患者可能作用不大。

要使用止血帶，首先使用彈性壓縮（例如，Esmarch）對肢體放血，然後通常在大腿近端（膝上和膝下截肢）或小腿（足部截肢）放置無菌止血帶並吹氣至收縮壓的1.5～2.0倍。如果有相關的軟組織感染，則省略放血。

標準技術 —— 在對下肢缺血患者進行下肢截肢時，特定的手術技術可最大限度地減少組織缺血，這些做法同樣適用於下肢灌注正常的患者的下肢截肢，例如肢體損傷的年輕患者或患者患有 Charcot 足畸形。

●輕輕地處理軟組織。



●通過保持手術刀垂直於皮膚表面避免皮膚和組織的斜面。



●不要將皮膚與下面的筋膜分開，以防止皮瓣缺血。



●使用皮膚鉤或細齒鉗縮回皮膚，不要壓碎器械（例如 Debakey 鑷子）。一些外科醫生僅依靠輕柔的手指回縮。



●解剖命名的動脈和靜脈，彼此分開，分別結紮和分開，以防止動靜脈瘺的形成。監督主要動脈並在更近端結紮它們。簡單結紮足以用於閉塞或部分閉塞的血管（最小流量）。對於大多數靜脈，簡單的結紮就足夠了。



●將神經結紮在其橫斷點的近端，以盡量減少神經束膜的出血，並在負重表面近端急劇橫斷神經，以避免神經瘤的發展，神經瘤可導致慢性殘肢痛。目標肌肉神經再支配和再生性周圍神經界面是減少術後神經瘤形成的備選方案 [ 15-17 ]。



●通過使用縫合結紮止血來盡量減少電烙術的使用。



●避免在承重表面上產生手術疤痕（新的或舊的）。



●通過在皮膚和骨骼切面之間插入肌肉和筋膜來防止疤痕收縮。



●近似無張力的皮瓣。用單絲縫合線或釘書釘閉合皮膚是可以接受的。



●避免過度修剪小狗耳朵或其他輕微的外觀違規行為。雖然大量多餘的軟組織會干擾假體的正確貼合，但輕微的不規則會重塑。



●解剖完成後徹底沖洗傷口，以清除任何碎屑或骨碎片。



●使用肌成形術（將拮抗肌群縫合固定到骨上）或肌固結術（將肌肉縫合到骨膜上）穩定拮抗肌群，以防止肌肉萎縮和骨骼錯位 [18 ]。



●斜角骨突和銼刀鋒利的邊緣光滑。



●避免過多的骨膜剝離，以防止環死骨或骨質過度生長。



●用間斷的可吸收縫合線逐層關閉截肢殘端。使用皮膚釘與感染風險增加有關 [ 19 ]。


Tourniquets — Tourniquets have been shown to reduce intraoperative blood loss and decrease the need for postoperative blood transfusion in above-knee and below-knee amputations [14]. However, tourniquets are probably of little benefit in patients undergoing amputation for extremity ischemia.

To use a tourniquet, the extremity is first exsanguinated using elastic compression (eg, Esmarch), followed by placement of a sterile tourniquet usually in the proximal thigh (above-knee and below-knee amputation) or calf (foot amputations) and insufflated to 1.5 to 2.0 times the systolic pressure. Exsanguination is omitted if there is associated soft tissue infection.

Standard techniques — Specific surgical techniques minimize tissue ischemia when performing lower extremity amputation in patients with lower extremity ischemia, and these practices are equally applicable to lower extremity amputation in patients with normal lower extremity perfusion, such as the younger patient with extremity injury or a patient with a Charcot foot deformity.

●Handle the soft tissues gently.



●Avoid beveling of the skin and tissues by maintaining the scalpel perpendicular to the skin surface.



●Do not separate the skin from the underlying fascia to prevent ischemia of the skin flaps.



●Use skin hooks or fine-toothed forceps to retract the skin, and not crushing instruments (eg, Debakey forceps). Some surgeons rely only on gentle finger retraction.



●Dissect named arteries and veins free from one another and ligate and divide each separately to prevent arteriovenous fistula formation. Oversew major arteries and ligate them more proximally. Simple ligation is adequate for occluded or partially occluded vessels (minimal flow). Simple ligation suffices for most veins.



●Ligate nerves just proximal to their point of transection to minimize bleeding from the perineurium and transect the nerve sharply proximal to the weight-bearing surface to avoid the development of neuroma, which can lead to chronic stump pain. Target muscle reinnervation and a regenerative peripheral nerve interface are alternative options to consider to decrease postoperative neuroma formation [15-17].



●Minimize the use of electrocautery by using suture ligatures for hemostasis.



●Avoid creating surgical scars (new or old) on the weight-bearing surface.



●Prevent scar retraction by interposing muscle and fascia between the skin and cut surface of bone.



●Approximate skin flaps without tension. Skin closure with either monofilament sutures or staples is acceptable.



●Avoid excessive trimming of small dog-ears or other minor cosmetic irregularities. Although a large amount of redundant soft tissue will interfere with proper prosthetic fit, minor irregularities will remodel.



●Irrigate the wound thoroughly once the dissection is complete to remove any debris or bony fragments.



●Stabilize antagonistic muscle groups using myoplasty (suture fixation of antagonistic muscle groups to bone) or myodesis (suturing the muscle to the periosteum) to prevent muscle atrophy and skeletal misalignment [18].



●Bevel bony prominences and file sharp edges smooth.



●Avoid excessive periosteal stripping to prevent ring sequestra or bony overgrowth.



●Close the amputation stump in layers with interrupted absorbable sutures. The use of skin staples has been associated with an increased risk for infection [19].

下面是第三個章節



下面是第三個章節
Complications of total knee arthroplasty
Peroneal nerve palsy — The most common severe neurologic complication after TKA is peroneal nerve palsy [14].

Clinical manifestations of peroneal nerve injury include paresthesia, numbness, and extensor weakness (ie, foot drop) (table 1). Patients at highest risk are those with severe valgus deformity or flexion contracture. Intraoperatively, the nerve can be damaged by stretching due to correction of a valgus deformity or flexion contracture, inappropriate placement of a lateral retractor, or prolonged tourniquet time >120 minutes. However, studies indicate that nerve injury from tourniquet use is quite rare, especially when used at lower tourniquet pressures and for shorter time periods [15,16]. Postoperatively, the patient can develop a peroneal nerve palsy from swelling, hematoma, or direct compression of the nerve (eg, leg externally rotated lying in bed). Additionally, patients with previous spinal pathology may be more likely to develop peroneal nerve palsy due to the "double-crush phenomenon." Initial management includes loosening tight dressings and flexing the knee to 30 degrees to relieve pressure on the nerve. Radiographs should also be ordered to ensure no prosthetic-related issues. Fortunately, the majority of patients have complete improvement in 12 to 18 months [14,17]. (See "Foot drop: Etiology, diagnosis, and treatment".)

Tourniquet-related ischemic injury — Tourniquet use, commonly used in TKA to reduce intraoperative blood loss, has been associated with ischemic injury [18]. Nevertheless, tourniquets are widely used and generally considered safe for TKA [19]. Higher cuff pressures and longer duration of cuff use are associated with increasing complications. Thus, the tourniquet should be used at the lowest pressure and for the least ischemic time possible. Some surgeons use 100 mmHg above systolic blood pressure (BP), while others may use twice the systolic BP as their cuff pressure setting. (See "Total knee arthroplasty", section on 'Tourniquet use' and "Clinical features and diagnosis of acute lower extremity ischemia".)

下面是第四個章節-成年患者的嚴重上肢損傷


肢體出血的控制 — 對於無法通過直接壓力充分控制的上肢出血，回顧性研究表明，肢體止血帶可減少出血且並發症發生率較低[ 6-8 ]。

氣動止血帶 (PT) 通常用於減少擇期上肢手術期間的出血。它們也可用於急診室以控制肢體出血，從而提高患者的生存率 [ 9,10 ]。標準 PT 可用於控制上肢腋窩遠端的出血。PT 的充氣壓力應小於 250 mmHg，如果可能，PT 袖帶應放置在距開放性傷口至少 5 cm 的位置。PT 不應連續充氣超過兩個小時，以避免缺血並發症 [ 6-8 ]。患者應前往手術室快速控制出血。

在院前或軍事環境中，最常用的止血帶是無風式戰鬥應用止血帶 (CAT) 或特種部隊戰術止血帶（SOFT-T wide）。如有必要，可以用一隻手快速塗抹這些。在一項回顧性研究中，對上肢應用 CAT 的軍人中有 94% 實現了出血的絕對控制，並且沒有死亡報告 [11 ]。美國軍方的戰術戰鬥傷員護理委員會定期審查商用止血帶的性能 [ 12 ]。對於腋窩處的交界性傷口，建議使用傷口包紮，最好使用止血敷料，並持續加壓 [ 13]]. 市場上有一些交界性止血帶，但目前沒有足夠的證據推薦使用它們。此外，據報導，在戰場上，對腋窩應用專門的止血帶可以控制腋窩（交界處）出血 [ 14 ]。


Control of extremity hemorrhage — For upper extremity hemorrhage that is not adequately controlled with direct pressure, retrospective studies have shown that extremity tourniquets reduce bleeding with a low rate of complications [6-8].

Pneumatic tourniquets (PTs) are commonly used to reduce bleeding during elective upper extremity surgery. They can also be used in the emergency department setting to control extremity hemorrhage to improve patient survival [9,10]. Standard PTs can be used to control hemorrhage in the upper extremity distal to the axilla. The inflation pressure of the PT should be less than 250 mmHg, and the PT cuff should be placed at least 5 cm proximal to the open wound, if possible. The PT should not be inflated continuously for more than two hours to avoid ischemic complications [6-8]. The patient should proceed to the operating room for rapid hemorrhage control.



In the prehospital or military setting, the most commonly used tourniquets are the windless style Combat Application Tourniquet (CAT) or Special Forces Tactical Tourniquet (SOFT-T wide). These can be applied rapidly with one hand, if necessary. In a retrospective study, 94 percent of the service personnel who had applied a CAT to the upper extremity achieved absolute control of hemorrhage, and no deaths were reported [11]. The Tactical Combat Casualty Care Committee of the United States military routinely reviews the performance of commercial tourniquets [12]. For junctional wounds at the axilla, wound packing, ideally with a hemostatic dressing, along with continuous pressure is recommended [13]. There are some junctional tourniquets on the market, but there is insufficient evidence to recommend their use at this time. Also, in the battlefield, application of a specialized tourniquet to the axilla has been reported to control axillary (junctional) hemorrhage [14].

野外與登山醫學-高海拔肺水腫臨床表現 from uptodate

高海拔肺水腫(HAPE)臨床表現. 底下資料來自 uptodate 網站
1. 初始症狀沒有特異性, 就像感冒症狀, 容易被忽略
2. 罹患HAPE的人, 大約一半會同時罹患AMS急性高山病
3. 經過給氧治療可快速改善(通常10-15分鐘內)
    其他疾病,例如心衰竭,腎衰竭
4. 同一海拔待七天後, 如果沒有發生HAPE腫, 之後不太可能發生HAPE

下面是google翻譯的

成人的表現
症狀和體徵 —  HAPE 通常開始於輕微的干咳和用力時氣短，通常是在上坡行走時 [ 9,13 ]。這種非特異性症狀很容易被誤認為是良性上呼吸道感染或歸因於高海拔或疲憊時的正常呼吸困難。最初的症狀通常在到達新高度後兩到四天出現。偶爾，HAPE 會急劇發展。這種情況更常發生在夜間或劇烈運動後。在同一海拔高度一周後，HAPE 幾乎不再出現。

隨著 HAPE 的進展，呼吸困難在休息時變得明顯，並且在任何嘗試用力時都變得嚴重。即使在水平面上行走也變得費力。HAPE 的主要臨床特徵是早期從勞力性呼吸困難進展為靜息時呼吸困難。在大約 50% 的病例中，HAPE 伴有急性高山病 [ 10 ]。(參見 “急性高山病與高原腦水腫” )

隨著症狀的進展，咳嗽可能會咳出粉紅色、泡沫狀的痰，並可能產生鮮血。嚴重受限的運動耐力會變得虛弱，嚴重的低氧血症可能危及生命，而沒有迅速下降或補充氧氣。嚴重的低氧血症可能會導致嗜睡或伴隨高原腦水腫 (HACE)。

體格檢查常見心動過速、呼吸急促和低燒（最高 38°C）。最初，吸氣濕羅音可能在右中葉更為突出，但隨著 HAPE 的進展而變得雙側和彌散。右中葉的聽診最好在中外側胸壁進行。頸動脈體功能遲鈍的人，無論是遺傳性的還是獲得性的（例如，頸動脈內膜切除術、頸部放療），可能都沒有呼吸道症狀，而是出現嗜睡、意識模糊和其他中樞神經系統症狀和發現，這些症狀和發現可能更常與 HACE 相關。

氧飽和度 — 脈搏血氧飽和度顯示飽和度值 (SpO 2) 至少比預期高度低 10 點，絕對值可能低至 40% 到 50%。通常情況下，考慮到低氧血症的嚴重程度，患者的表現比預期的要好，並且氧飽和度會隨著吸氧而迅速改善（通常在 10 到 15 分鐘內）。 在 X 光片上看到的嚴重浸潤性肺過程中，SpO 2 的這種快速校正和補充氧氣的​​臨床狀態實際上是 HAPE 的特徵性特徵，因為其他肺部過程（例如，肺炎，急性失代償性心力衰竭）不會發生這種情況能夠引起如此嚴重的低氧血症並伴有瀰漫性爆裂音或乾囉音。

因此，脈搏血氧儀通常是區分 HAPE 與其他疾病的有用工具。然而，預期的 SpO 2 值隨許多因素而變化，包括海拔高度、適應程度和速度、患者的缺氧通氣驅動和測量方法（例如，脈搏血氧儀之間的差異）；因此應該仔細解釋。SpO 2 在高海拔地區的第一天最低，並在四天內上升到接近最大值，通常比第一天高 3 到 5 個點。儘管正常個體在任何給定海拔高度的預期值都可能有很大差異，但比較 SpO 2 與同一旅行團中一起到達高海拔地區的其他人進行測量有助於建立相對“正常”範圍。下圖提供了 SpO 2 和其他參數在一定海拔範圍內的近似平均值（圖 1 和 表 3）。

在兒童中的表現 — 在兒童中，HAPE 通常表現為在一到兩天內呼吸窘迫加重，但也可能發展得更突然。年幼的兒童可能僅表現出蒼白或紫紺和意識低落，但大多數會出現呼吸急促、低氧血症和濕囉音 [ 14 ]。在嬰兒中，肺動脈壓升高和胎兒分流，沒有 HAPE，可導致嚴重的低氧血症。(參見 上文‘病理生理學’ 和 “高原病：獨特的兒科注意事項” )

單獨的 HAPE 不會 導致 體溫升高超過 38.3°C（101°F），並且應該評估體溫較高的幼兒是否有其他發熱原因。呼吸道感染和HAPE可並存。(參見 “3-36 月齡兒童不明原因發熱的評估和處理” )

兒童的鑑別診斷包括肺炎、未檢測到的心內分流和（嬰兒）因高原肺動脈高壓而開放胎兒分流。一些作者建議對發生 HAPE 的兒童進行結構性心臟問題評估 [ 14,15 ]。（參見 “左向右分流的病理生理學” 和 “嬰兒和兒童孤立性室間隔缺損 (VSDs)：解剖學、臨床特徵和診斷” 和 “兒童孤立性房間隔缺損 (ASDs)：分類、臨床特徵”和診斷” 和 “兒童社區獲得性肺炎：臨床特徵和診斷”，關於‘臨床表現’一節。）

CLINICAL PRESENTATION

Presentation in adults
Symptoms and signs — HAPE generally begins with a subtle, nonproductive cough, and shortness of breath with exertion, often when walking uphill [9,13]. Such nonspecific symptoms are easily mistaken for a benign upper respiratory tract infection or attributed to normal breathlessness at high altitude or exhaustion. Initial symptoms typically appear two to four days after arrival at a new altitude. Occasionally, HAPE develops precipitously. This occurs more often at night or after severe exertion. HAPE almost never develops after a week at the same altitude.

As HAPE progresses, dyspnea becomes noticeable at rest and severe with any attempt at exertion. Even walking on a level surface becomes an effort. A cardinal clinical feature of HAPE is the early progression from dyspnea with exertion to dyspnea at rest. In about 50 percent of cases, HAPE is accompanied by acute mountain sickness [10]. (See "Acute mountain sickness and high-altitude cerebral edema".)

As symptoms progress, the cough can become productive of pink, frothy sputum and may produce frank blood. Severely restricted exercise tolerance becomes debilitating, and severe hypoxemia may become life threatening without prompt descent or supplemental oxygen. Severe hypoxemia may cause drowsiness or concomitant high-altitude cerebral edema (HACE).

On physical examination, tachycardia, tachypnea, and low-grade fever (up to 38°C) are common. Inspiratory crackles may be more prominent in the right middle lobe initially but become bilateral and diffuse as HAPE progresses. Auscultation of the right middle lobe is best performed at the mid-lateral chest wall. Persons with blunted carotid body function, genetic or acquired (eg, carotid endarterectomy, neck radiation), may present without respiratory symptoms and instead with drowsiness, confusion, and other central nervous system symptoms and findings that might more commonly be associated with HACE.

Oxygen saturation — Pulse oximetry reveals saturation values (SpO2) at least 10 points lower than expected for the altitude, and absolute values may be as low as 40 to 50 percent. Typically, the patient appears better than expected given the severity of hypoxemia, and the oxygen saturation improves promptly (usually within 10 to 15 minutes) in response to supplemental oxygen. This rapid correction of the SpO2 and clinical status with supplemental oxygen in the setting of a severe infiltrative lung process seen on radiograph are virtually pathognomonic for HAPE, as this does not occur with other pulmonary processes (eg, pneumonia, acute decompensated heart failure) capable of causing such severe hypoxemia and associated with diffuse crackles or rhonchi.

Thus, pulse oximetry is often a useful tool for distinguishing HAPE from other conditions. However, expected SpO2 values vary with a number of factors, including the altitude, degree and rate of acclimatization, patient's hypoxic ventilatory drive, and method of measurement (eg, variation among pulse oximeters); and therefore should be interpreted carefully. SpO2 is lowest on the first day at high altitude and rises over four days to a near-maximum value, usually 3 to 5 points higher than day one. Although expected values can vary widely in normal individuals at any given altitude, comparing SpO2 measurements with others in the same travel group who arrived at high altitude together can help to establish a relative "normal" range. The following figures provide approximate average values for SpO2 and other parameters at a range of altitudes (figure 1 and table 3).

Presentation in children — In children, HAPE typically presents as increasing respiratory distress over one to two days but may develop more precipitously. Young children may manifest only pallor or cyanosis and depressed consciousness, though most will have tachypnea, hypoxemia, and crackles [14]. In infants, increased pulmonary artery pressure and fetal shunting, without HAPE, can cause severe hypoxemia. (See 'Pathophysiology' above and "High-altitude disease: Unique pediatric considerations".)

HAPE alone does not cause an elevation in body temperature over 38.3°C (101°F), and young children with a higher temperature should be assessed for other causes of fever. Respiratory infection and HAPE can coexist. (See "Fever without a source in children 3 to 36 months of age: Evaluation and management".)

The differential diagnosis in children includes pneumonia, undetected intracardiac shunts, and (in infants) opening of fetal shunts in response to high-altitude pulmonary hypertension. Some authors suggest that children who develop HAPE should be evaluated for structural heart problems [14,15]. (See "Pathophysiology of left-to-right shunts" and "Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis" and "Isolated atrial septal defects (ASDs) in children: Classification, clinical features, and diagnosis" and "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Clinical presentation'.)