Objective criteria for diagnosing high altitude pulmonary edema in acclimatized patients at altitudes between 2700 m and 3500 m
摘要(下面這段是我寫的)
1. 研究對象是在 2700-3500公尺的印度士兵.
2. 發病時間 2-3 天 (2.8 ± 2.2) (0.6~~5天)
1. 研究對象是在 2700-3500公尺的印度士兵.
2. 發病時間 2-3 天 (2.8 ± 2.2) (0.6~~5天)
3. 當血氧濃度高於該海拔正常值. 仍有可能發生高海拔肺水腫
4. 敏感度= 符合設定條件時, 能診斷出高海拔肺水腫的機率
特異性=不符合設定條件時, 真的沒生病的機率
4. 敏感度= 符合設定條件時, 能診斷出高海拔肺水腫的機率
特異性=不符合設定條件時, 真的沒生病的機率
心率超過每分鐘 95 次 (bpm)-- 敏感度0.66 特異性0.83
呼吸頻率超過每分鐘 21 次-- 敏感度0.82 特異性0.94
SPO2 低於 86%-- 敏感度0.95 特異性0.93
舉例. 現在有個遊客. 當他出現類似高海拔反應的症狀時, 心跳是每分鐘85次(低於我們設定的數值 95 bpm). 那麼有 83% 的機率. 他不是高海拔疾病(這裡指高海拔肺水腫).
回到實際面. 每100個病人. 有17 個會被誤診. 這項參數你要不要賭一把.
在臨床醫師的觀點. 當一個非常可能致死的疾病出現. 我會希望能將所有可能的病例都找出來. 這個稱為敏感度. 但敏感度越高的指標. 往往會伴隨沒事卻被判定生病的機率上升. 心率超過 95 bpm 並不是很理想的數值.
臨床醫師最喜歡的參數. 是敏感度和特異性都很高的. 在這篇研究, 血氧濃度是不錯的參數
(但過去有其他研究證實, 血氧濃度沒這麼好的鑑別診斷力. 或許可能是研究樣本差異造成. 例如種族. 性別, 年齡. 當地氣候條件等等 )
(下面是google翻譯的)
背景
用於診斷高原疾病的標準主要基於西方文獻。本研究旨在為海拔 2700 m 至 3500 m 之間的印度士兵制定客觀、簡單且可靠的高原肺水腫 (HAPE) 診斷標準。
方法
對235例2700~3500m海拔高度HAPE患者的臨床資料進行分析。採用受試者工作特徵（ROC）曲線分析來選擇適合週邊醫療機構HAPE診斷的簡單臨床參數。定義了 HAPE 診斷的臨界值及其可靠性。
結果
HAPE 發生在到達海拔 2700 m 至 3500 m 之間後 2.8 ± 2.2 天。呼吸困難、咳嗽、胸部不適和頭痛是最常見的症狀。 89% 的患者發現脈搏血氧飽和度 (SPO2) 值低於該海拔的正常值。臨床參數的 ROC 分析確定，在該海拔高度呼吸環境空氣時，心率超過每分鐘 95 次 (bpm)、呼吸頻率超過每分鐘 21 次、SPO2 低於 86%，作為 HAPE 的診斷。這些臨界值的敏感度和特異性分別為 0.66、0.83 和 0.82 以及 0.94、0.95 和 0.93。
結論
在抵達海拔 2700 公尺之間的頭 5 天內，主訴呼吸困難、咳嗽、胸部不適或頭痛的個體心率超過 95 bpm，呼吸頻率超過每分鐘 21 次，SPO2 低於呼吸室內空氣的 86% 3500 m 高度提示HAPE。
關鍵字：高山症、肺水腫、ROC 曲線
簡介
高海拔 (HA) 醫學和生理學仍然與印度武裝部隊高度相關。大量非 HA 本土部隊在平均海平面以上 9000 英尺的海拔地區服役。 HA環境中氧分壓低、溫度低、大氣濕度低、紫外線輻射強度大，對人體的生理功能提出了挑戰。透過實驗室和現場研究更了解這些生理反應，使得過去十年中高山症 (HAI) 的發生率急劇下降。
眾所周知，有些人比其他人更容易感染 HAI，因此，只要部隊在 HA 環境中生活和工作，HAI 就會繼續發生，儘管發病率較低。1病人和醫療機構之間的第一個接觸點通常是團醫務官 (RMO)，這些病人的管理取決於他的判斷和能力。由於HAI 的診斷通常在偏遠地區進行，無法使用實驗室和影像設施，因此某些基於現場的診斷標準，例如路易斯湖(LL) 共識標準，已被描述用於急性高山症(AMS) 的現場診斷，高原肺水腫（HAPE）和高原腦水腫（HACE）。2
HAI 的現有現場診斷標準主要是根據從發生 HAI 的登山者和遊客收集的西方數據得出的。這個人口可能無法與印度士兵人口相比，因此需要研究這些標準的普遍性。此外，LL 標準（例如心動過速和呼吸急促）是非特異性的，並且不會在給定海拔下為這些參數指定截止值。在給定海拔高度上提供更客觀的 HAPE 診斷標準將是有益的，特別是對於偏遠醫療機構的輔助醫務人員。本研究旨在檢驗 LL 共識標準在印度士兵診斷 HAPE 中的適用性，並提出對於給定海拔可能更具體的診斷標準。
材料與方法
對位於平均海平面以上 3350 公尺的醫管局研究實驗室的 HAI 資料庫進行了分析。選擇資料庫中可用的 HAPE 病例的臨床記錄進行分析。以下 HAPE 病例納入分析：
a.發生海拔高度在2700公尺至3500公尺之間。
b. 由受過訓練的醫生確認的 HAPE 診斷。
c.「完整」的記錄（包含上升情況的詳細資訊、症狀的發作以及在前往醫療機構就診時記錄的臨床檢查體徵）。
以下記錄未包含在分析中：
a.懷疑HAPE診斷但未確診的。
b.記錄不完整。
c. 在接受醫療專業人員檢查之前有接受藥物/吸氧史記錄的患者。
依上述標準，共納入235例HAPE病例進行分析。
醫管局研究實驗室提供的 235 名健康士兵在 3350 公尺海拔的適應醫療數據也經過分析，以確定在海拔約 3000 公尺的頭 6 天內的心率、呼吸頻率和脈搏血氧飽和度值。該中心每天記錄抵達 HA 的前 6 天內的這些參數。該資料庫包含1000多名健康士兵的資料。根據研究組HAPE發生的平均天數，選擇健康士兵相應天的適應醫學數據進行分析。採樣是使用 Microsoft Excel 中的「隨機」函數完成的。這些數據作為健康對照。由於研究組和對照組由混合士兵組成，因此假設這些群體在種族組成上具有可比性。沒有進行詳細的配對。
使用非配對 t 檢定比較 HAPE 病例和對照組的心率、呼吸頻率和 SPO2 值的統計顯著性差異，然後進行受試者工作特徵 (ROC) 曲線分析。3這樣做是為了確定這些易於測量的臨床參數中的哪些可以作為 2700 m 至 3500 m 之間發生的 HAPE 的良好診斷標準。此識別是使用記錄的每個參數的曲線下面積 (AUC) 值來完成的。3 , 4然後確定 ROC 曲線上的最佳操作點，以建議診斷 2700 m 至 3500 m 之間發生的 HAPE 的截止值。 ROC 分析中的最佳操作點是給定資料獲得最高可能靈敏度和特異性的點。與這一點相對應的臨床參數值是作為所研究的臨床病症的診斷標準提出的截止值的邏輯選擇。
將現有的 HAPE 診斷 LL 標準應用於 HAPE 病例，並計算該群組的 LL 標準的敏感性、特異性、陽性和陰性預測值。由於 LL 標準提到心動過速和呼吸急促是 HAPE 患者的兩種體徵，但沒有指定相同的數值，因此使用心率大於 100 次/分鐘 (bpm) 和呼吸頻率大於 20 次呼吸/分鐘來診斷分別定義心跳過速和呼吸急促，這是臨床上的常態。使用從 ROC 分析獲得的 HR、RR 和 SPO2 的截止值進行類似的計算。對所獲得的兩組數據進行分析，以比較現有和提議的印度士兵 HAPE 診斷臨界值的性能。
結果
HAPE 症狀平均出現時間為到達海拔 2700 m 至 3500 m 後 2.8 ± 2.2 天。 HAPE患者在診斷時報告的各種臨床症狀的頻率如表1所示。呼吸困難、頭痛和咳嗽是最常見的症狀。最不常見的症狀是疲勞。表 2顯示了 HAPE 患者向醫療機構報告時的臨床檢查結果以及在 HA 第三天進行的健康適應對照的結果。與同等海拔的健康適應士兵相比，HAPE 患者的心率和呼吸頻率明顯較高，而 SPO2 值較低。 HAPE患者的心率、呼吸頻率及SPO2值的頻率分佈分別如圖1、圖2、圖3所示。大多數 HAPE 患者的 SPO2 值低於該海拔的預期，其中 48.9% 在診斷時患有心動過速（HR > 100 bpm）（表 3）。
圖 1
235 名 HAPE 患者的心率值頻率分佈顯示，只有 48.9% 的患者心率超過 100 bpm。
圖2
235例HAPE患者呼吸頻率值的頻率分佈。
圖3
235例HAPE患者SPO2值頻率分佈。
表 1HAPE 患者的臨床症狀（依出現頻率排列）。
臨床症狀 ---- 患者人數（患者百分比）
呼吸困難 202 (79.5%)
頭痛 183 (72%)
咳嗽 155 (61%)
胸部不適 99 (39%)
咳痰 31 (12.2%)
失眠 20 (7.9%)
疲勞 11 ( 4.3 ) %)
表 2
HAPE 患者初次診斷時的臨床檢查結果。顯示健康對照中第三天在 HA 中記錄的相同參數的相應值以進行比較。
參數HAPE 患者(n = 235)[平均值 ± 標準差] 健康對照組(n = 235)[平均值 ± 標準差]
心率（次/分鐘） 100.6 ± 17.8 88.5.1 ± 8.3*
呼吸頻率（呼吸/分鐘) 26.1 ± 5.5 16.1 ± 3.0*
收縮壓 (mmHg) 124.8 ± 15.6 126.7 ± 11.5
舒張壓(mmHg) 81.2 ± 10.7 79.2 ± 11.8
SPO2 – 室內呼吸*p < 0.001（未配對t 檢定）。
表 3
235 名 HAPE 患者的心率、呼吸頻率和脈搏血氧飽和度結果分析。臨床參數 患者百分比 心率 > 100 次/分鐘 48.9% SPO2 < 88% 呼吸環境空氣 89%呼吸頻率 > 20次呼吸/分鐘 83% ROC 曲線以及 HR、RR 和 SPO2 的 AUC 如圖 1所示。5。所有三個參數均具有較高的 AUC，範圍從 HR 的 0.86 到 SPO2 的 0.88。每條曲線上的最佳操作點對應於 HR >95 bpm、RR >21 每分鐘和 SPO2 <86%。這些臨界值的敏感度、特異度、陽性及陰性預測值如表4、表5、表6所示。這些建議的臨界值與現有心搏過速(HR > 100 bpm) 和呼吸急促(RR > 20 每分鐘) 標準在海拔2700 m 至3350 m 之間診斷HAPE 的敏感性和特異性的比較如下表所示：
表 7 .
圖 4
心率 (HR) 和呼吸頻率 (RR) 的 ROC 曲線顯示 HR 和 RR 的曲線下面積分別為 0.86 和 0.87。
圖 5
脈搏血氧飽和度值 (SPO2) 的 ROC 曲線顯示曲線下面積為 0.88。
表 4
所選心率臨界值的特異性、敏感性、陽性和陰性預測值計算。
HAPE 患者對照心率 > 95/分鐘 156 13
心率 < 95/分鐘 79 222
靈敏度 = 156/(156 + 79) = 0.66；特異性 = 222/(13 + 222) = 0.94；陽性預測值=156/(156+13)=0.92；陰性預測值 = 222/(79 + 222) = 0.74。
表 5 所選呼吸頻率截止值的特異性、敏感度、陽性和陰性預測值計算。
HAPE 患者對照呼吸頻率 > 21/分鐘 194 12
呼吸頻率 < 21/分鐘 41 223
靈敏度 = 194/(194 + 41) = 0.83；特異性=223/(12+223)=0.95；陽性預測值=194/(194+12)=0.94；陰性預測值 = 223/(41 + 223) = 0.84。
表 6
所選脈搏血氧飽和度值 (SPO2) 截止值的特異性、靈敏度、陽性和陰性預測值計算。
HAPE 患者對照組 SPO2 < 86% 193 16
SPO2 > 86% 42 219
靈敏度 = 193/(193 + 42) = 0.82；特異性 = 219/(16 + 219) = 0.93；陽性預測值=193/(193+16)=0.92；陰性預測值 = 219/(42 + 219) = 0.83。
表 7 現有 LL 標準和建議的臨界值以及診斷 2700-3500 m 發生的 HAPE 的心率、呼吸頻率和 SPO2 的敏感性和特異性的比較。
心率 (bpm) 呼吸頻率 (呼吸/分鐘)SPO2 (%)
建議 >95 現有 >100 建議 >21 現有 >20 建議 <86% 現有 無靈敏度 0.66 0.49 0.83 0.83 0.82
(59.9–72.0) (78. 87.8) (77.0–86.9)
特異性 0.94 1.0 0.95 0.83 0.93
(90.9–97.0) (92.2–97.7) (89.7–96.2)
陽性預測值 a 0.92 1.0 5.95–909. 0)
(88.5 –95.4)
陰性預測值值 a 0.74 0.66 0.84 0.83 0.83
(68.3–79.6) (79.3–88.6) (78.1–87.8)
心率大於100 bpm 且呼吸頻率已大於被呼吸/分鐘來定義「心跳過速」和現有 LL 標準為「呼吸急促」。括號中的數值表示 95% 的置信限。
a 對於給定研究族群中明顯的疾病盛行率有效。
轉至：
討論
據了解，HAPE 的症狀會在高原地區的最初幾天內出現。5研究族群在 2700-3500 m 海拔高度發生 HAPE 的平均時間為 2.8 ± 2.2 天。強調這一事實是因為，在沒有近期海拔升高史或沒有可能的誘發因素（例如嚴重不習慣的運動或呼吸道感染）的情況下，必須謹慎對待提示 HAPE 的症狀。
本研究中患者報告的症狀值得關注。雖然呼吸困難、胸部不適和咳嗽症狀是 HAPE 的眾所周知的特徵，但很大一部分患者 (72%) 也被發現抱怨頭痛。頭痛是一種非特異性症狀，在醫管局出現頭痛可能是由多種因素造成的，包括脫水、睡眠不足、旅途疲勞以及急性高山症並存等。有趣的是，在其他報告中也有報告 HAPE 患者抱怨頭痛。6 , 7儘管根據目前的了解，HAPE 的病理生理學無法解釋頭痛的發生，但這種症狀與 HAPE 的頻繁關聯可能值得在 HAPE 診斷標準中考慮該症狀。
有趣的是，我們的患者沒有疲勞作為主要症狀，因為根據路易斯湖標準，疲勞/虛弱/運動能力下降是 HAPE 的重要診斷症狀。2 , 8只有 4.3% 的患者報告了這種症狀。一個可能的原因可能是，與沉迷於高海拔冒險運動的登山者、徒步旅行者和遊客相比，士兵在高海拔的最初幾天並沒有進行大量的體力活動。因此，一般久坐的士兵可能不會注意到疲勞是 HAPE 的早期和突出症狀。
在我們的研究中，並非所有 HAPE 患者都會出現心搏過速（定義為心率超過 100 bpm）。只有 48.9% 的患者心率超過 100 bpm，這表明超過一半 (51.1%) 在海拔 2700-3500 m 發生 HAPE 的患者可能不會表現出心動過速。眾所周知，心率增加的幅度與上升的高度和疾病的嚴重程度成正比。9 , 10研究族群心率較低可能有多種原因。其中可能包括所討論的海拔高度（2700-3500 m），與其他一些 HAPE 報告相比，該海拔較低，這些患者的病情不太嚴重，可能是早期診斷病情的結果，相對久坐的性質士兵在醫管局進行的活動的適應情況以及士兵由於身體狀況可能較低的靜止心率。與 >100 bpm 的值相比，提出的心率大於 95 bpm 的標準似乎對診斷 HAPE 具有更好的敏感性（0.66 與 0.49），同時保留了高特異性（0.94）。
眾所周知，HAPE 患者的呼吸頻率較高。這些比率應該要多高才能診斷出 HAPE？使用呼吸急速的傳統定義，即呼吸頻率大於每分鐘20次，此參數診斷HAPE的敏感度和特異度為0.83。然而，選擇 21 次呼吸/分鐘的值將特異性提高到 0.95，同時保持靈敏度 0.83。
儘管 HA 的脈搏血氧測定法有其局限性，且其本身可能無法用作診斷參數，但如果謹慎執行，透過脈搏血氧測定法獲得的資訊可以補充整體臨床情況。在目前的一系列患者中，85% 的患者 SPO2 值低於 88%，這是健康個體在 3000 m 處呼吸室內空氣的預期 SPO2 值。脈搏血氧飽和度可能有助於監測 HAPE 患者的病情進展和治療效果。
HR、RR 和 SPO2 的 ROC 分析表明，這三個參數都非常適合作為 HAPE 的診斷參數，因為它們的曲線下面積範圍為 0.86 至 0.88。 0.8 到 0.9 之間的區域表示測試良好，0.9 到 1.0 之間的區域表示優。4在三個參數中，SPO2 似乎是最佳參數，因為它具有最高的 AUC (0.88)。 ROC 分析建議的這三個參數的截止值顯示出非常令人鼓舞的特異性和敏感性水平，可用作診斷 2700 m 至 3500 m 之間發生的 HAPE 的參數。
診斷測試的陽性和陰性預測值受疾病盛行率的影響。隨著人群中疾病盛行率的增加，對該族群應用測試標準會產生更高的陽性預測值和更低的陰性預測值。由於文獻中所報告的HAPE 真實盛行率各不相同，且不同族群之間可能有所不同，因此在解釋本研究中提出的數值時應牢記這一事實，並且如果疾病盛行率與本研究中的盛行率不同，該值也會改變。
儘管盡了最大努力來防止 HAPE 的發生，但 HAPE 的許多人確實發生了這種情況。因此，及時診斷病情至關重要，以防止病情惡化和可能的死亡。診斷 HAPE 的標準必須可靠、客觀，並且易於偏遠地區外圍醫療機構的非醫務人員和輔助醫務人員使用。雖然 LL 標準已被全球接受用於 HAPE 的臨床診斷，但它們相當通用，且不針對海拔高度。因此，建議在最近到達2700-3500 m的環境中，如果個體出現呼吸困難、咳嗽、胸部不適和頭痛症狀，且HR、RR和SPO2值如上所述，則很可能是患有以下疾病的患者： HAPE 並應進行相應的管理（表 8）。與診斷 HAPE 的現有 LL 標準相比，本研究提出的標準顯示出更好的特異性，且不影響敏感性。
表 8
現有路易斯湖 HAPE 診斷標準與本研究提出的標準的比較。
現有標準（路易斯湖）
提議的標準
最近登上高海拔地區的歷史 過去 5 天內到達高海拔地區 (2700–3500 m) 的歷史 出現
以下任何兩種症狀 症狀
• 休息時呼吸困難
• 呼吸困難
• 咳嗽
• 咳嗽
• 虛弱或運動能力下降 • 胸部不適
• 胸悶或充血 • 頭痛
出現以下任兩種徵象 徵象
• 至少一側肺野出現爆裂聲或喘息音 • 心跳 > 95 次/分鐘
• 中樞性發紺 • 呼吸頻率 > 21 次/分鐘
• 心跳過速 • SPO2 < 86%
• 呼吸急促
局限性
本研究基於臨床記錄的回顧性分析，並受到其中所含資訊的限制。假設記錄中的臨床病史和發現結果是準確的。本研究建議的 HAPE 診斷臨床標準需要透過前瞻性地將其應用於 HAPE 診斷和治療的病例並記錄這些標準的適用性來進行驗證。一旦經過驗證，這些標準可以建議用於海拔 2700 m 至 3500 m 之間的 HAPE 現場診斷。
Abstract
Material and methods
The HAI database of a HA Research Laboratory located at 3350 m above mean sea level was analysed. Clinical records of cases of HAPE available in the database were selected for analysis. The following cases of HAPE were included for analysis:
Background
The criteria used for diagnosing high altitude illnesses are largely based on Western literature. This study was undertaken to define objective, simple and reliable diagnostic criteria for high altitude pulmonary edema (HAPE) in Indian soldiers at altitudes between 2700 m and 3500 m.
Methods
Clinical data of 235 cases of HAPE that occurred between 2700 m and 3500 m were analysed. Receiver operator characteristic (ROC) curve analysis was used to select simple clinical parameters suitable for the diagnosis of HAPE at peripheral medical facilities. Cut-off values and their reliability for the diagnosis of HAPE were defined.
Results
HAPE occurred 2.8 ± 2.2 days after arrival at altitudes between 2700 m and 3500 m. Breathlessness, cough, chest discomfort and headache were the commonest symptoms. Low pulse oximetry (SPO2) values than normal for this altitude were seen in 89% of patients. ROC analysis of clinical parameters identified a heart rate more than 95 beats per minute (bpm), respiratory rate more than 21 per minute and SPO2 less than 86% while breathing ambient air at this altitude as diagnostic of HAPE. The sensitivity and specificity of these cut-offs was 0.66, 0.83 and 0.82 and 0.94, 0.95 and 0.93 respectively.
Conclusion
A heart rate of more than 95 bpm, respiratory rate more than 21 per minute and SPO2 less than 86% breathing room air in individuals complaining of breathlessness, cough, chest discomfort or headache within the first 5 days of arrival at altitudes between 2700 m and 3500 m is highly suggestive of HAPE.
Keywords: Altitude sickness, Pulmonary edema, ROC curve
Introduction
High altitude (HA) medicine and physiology remains highly relevant to the Indian Armed Forces. A large number of troops, not native to HA, serve at altitudes greater than 9000 ft above mean sea level. The HA environment, with its low partial pressure of oxygen, low temperature, low atmospheric humidity and high levels of ultraviolet radiation challenges human physiological function. A better understanding of these physiological responses through both laboratory-based and field studies has resulted in a dramatic reduction in the incidence of high altitude illnesses (HAIs) over the last decade.
It is an accepted fact that some individuals are susceptible to HAI more than others, and hence, HAI would continue to occur, although with a lower incidence, as long as troops live and work in the HA environment.1 The first point of contact between patients and medical facilities is usually the regimental medical officer (RMO), upon whose judgement and competence, the management of these patients depends. Since the diagnosis of HAI is often at remote locations without access to laboratory and imaging facilities, certain field-based diagnostic criteria, like the Lake Louise (LL) Consensus Criteria, have been described for the field diagnosis of acute mountain sickness (AMS), high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE).2
Existing field-based diagnostic criteria for HAI have largely been arrived at from Western data gathered from mountaineers and tourists who develop HAI. This population may not be comparable with the Indian soldier population and hence the generalisability of these criteria requires study. Additionally, the LL criteria, such as tachycardia and tachypnoea, are non-specific and do not ascribe cut-off values for these parameters at a given altitude. The availability of more objective criteria for diagnosing HAPE at a given altitude would be beneficial, especially for paramedical staff at remote medical facilities. The present study was undertaken to examine the applicability of the LL Consensus Criteria for the diagnosis of HAPE in the Indian soldier and to suggest diagnostic criteria which could be more specific for a given altitude.
The criteria used for diagnosing high altitude illnesses are largely based on Western literature. This study was undertaken to define objective, simple and reliable diagnostic criteria for high altitude pulmonary edema (HAPE) in Indian soldiers at altitudes between 2700 m and 3500 m.
Methods
Clinical data of 235 cases of HAPE that occurred between 2700 m and 3500 m were analysed. Receiver operator characteristic (ROC) curve analysis was used to select simple clinical parameters suitable for the diagnosis of HAPE at peripheral medical facilities. Cut-off values and their reliability for the diagnosis of HAPE were defined.
Results
HAPE occurred 2.8 ± 2.2 days after arrival at altitudes between 2700 m and 3500 m. Breathlessness, cough, chest discomfort and headache were the commonest symptoms. Low pulse oximetry (SPO2) values than normal for this altitude were seen in 89% of patients. ROC analysis of clinical parameters identified a heart rate more than 95 beats per minute (bpm), respiratory rate more than 21 per minute and SPO2 less than 86% while breathing ambient air at this altitude as diagnostic of HAPE. The sensitivity and specificity of these cut-offs was 0.66, 0.83 and 0.82 and 0.94, 0.95 and 0.93 respectively.
Conclusion
A heart rate of more than 95 bpm, respiratory rate more than 21 per minute and SPO2 less than 86% breathing room air in individuals complaining of breathlessness, cough, chest discomfort or headache within the first 5 days of arrival at altitudes between 2700 m and 3500 m is highly suggestive of HAPE.
Keywords: Altitude sickness, Pulmonary edema, ROC curve
Introduction
High altitude (HA) medicine and physiology remains highly relevant to the Indian Armed Forces. A large number of troops, not native to HA, serve at altitudes greater than 9000 ft above mean sea level. The HA environment, with its low partial pressure of oxygen, low temperature, low atmospheric humidity and high levels of ultraviolet radiation challenges human physiological function. A better understanding of these physiological responses through both laboratory-based and field studies has resulted in a dramatic reduction in the incidence of high altitude illnesses (HAIs) over the last decade.
It is an accepted fact that some individuals are susceptible to HAI more than others, and hence, HAI would continue to occur, although with a lower incidence, as long as troops live and work in the HA environment.1 The first point of contact between patients and medical facilities is usually the regimental medical officer (RMO), upon whose judgement and competence, the management of these patients depends. Since the diagnosis of HAI is often at remote locations without access to laboratory and imaging facilities, certain field-based diagnostic criteria, like the Lake Louise (LL) Consensus Criteria, have been described for the field diagnosis of acute mountain sickness (AMS), high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE).2
Existing field-based diagnostic criteria for HAI have largely been arrived at from Western data gathered from mountaineers and tourists who develop HAI. This population may not be comparable with the Indian soldier population and hence the generalisability of these criteria requires study. Additionally, the LL criteria, such as tachycardia and tachypnoea, are non-specific and do not ascribe cut-off values for these parameters at a given altitude. The availability of more objective criteria for diagnosing HAPE at a given altitude would be beneficial, especially for paramedical staff at remote medical facilities. The present study was undertaken to examine the applicability of the LL Consensus Criteria for the diagnosis of HAPE in the Indian soldier and to suggest diagnostic criteria which could be more specific for a given altitude.
Material and methods
The HAI database of a HA Research Laboratory located at 3350 m above mean sea level was analysed. Clinical records of cases of HAPE available in the database were selected for analysis. The following cases of HAPE were included for analysis:
a.Altitude of occurrence between 2700 m and 3500 m.
b.Diagnosis of HAPE confirmed by a trained physician.
c.Records that were ‘complete’ (containing details of ascent profile, onset of symptoms and documented signs on clinical examination at the time of presenting to a medical facility).
The following records were not included in the analysis:
b.Diagnosis of HAPE confirmed by a trained physician.
c.Records that were ‘complete’ (containing details of ascent profile, onset of symptoms and documented signs on clinical examination at the time of presenting to a medical facility).
The following records were not included in the analysis:
a.Where the diagnosis of HAPE was suspected but not confirmed.
b.Incomplete records.
c.Patients with documented history of having being administered drugs/oxygen prior to being examined by a medical professional.
Based on the above criteria, a total of 235 cases of HAPE were included for the analysis.
The acclimatisation medical data of 235 healthy soldiers at 3350 m, available with the HA Research Laboratory, was also analysed to determine values of heart rate, respiratory rate and pulse oximetry values during the first 6 days at an altitude of approximately 3000 m. A daily record of these parameters over the first 6 days of arrival at HA is maintained by the centre. This database contains data of more than 1000 healthy soldiers. Based on the mean day of occurrence of HAPE in the study group, acclimatisation medical data of the healthy soldiers for the corresponding day were chosen for analysis. The sampling was done using the ‘Random’ function in Microsoft Excel. These data served as healthy controls. Since the study and control group comprised a mixed soldier population, it was assumed that the groups were comparable in ethnic composition. A detailed matching for the same was not carried out.
The heart rate, respiratory rate and SPO2 values of HAPE cases and controls were compared for statistically significant differences using an unpaired t-test and then subjected to a receiver operator characteristic (ROC) curve analysis.3 This was done to identify which of these easily measurable clinical parameters would serve as good diagnostic criteria for HAPE occurring between 2700 m and 3500 m. This identification was done using the area under the curve (AUC) value for each of the parameter recorded.3, 4 The best operating point on the ROC curve was then identified to suggest cut-off values for diagnosing HAPE occurring between 2700 m and 3500 m. The best operating point in an ROC analysis is that point where the highest possible sensitivity and specificity are obtained for the given data. The value of a clinical parameter corresponding to this point is the logical choice for a cut-off value proposed as criteria for diagnosis of the clinical condition being studied.
The existing LL criteria for diagnosis of HAPE were applied to the HAPE cases and the sensitivity, specificity, positive and negative predicted values of the LL criteria calculated for this cohort. Since the LL criteria mention tachycardia and tachypnoea as two signs in patients with HAPE but do not specify values for the same, a heart rate of greater than 100 beats per minute (bpm) and a respiratory rate greater than 20 breaths/min were used to define tachycardia and tachypnoea respectively, as is the norm in clinical practice. A similar calculation was done using the cut-off values of HR, RR and SPO2 obtained from the ROC analysis. The two sets of data obtained were analysed to compare the performance of the existing and proposed cut-off values for the diagnosis of HAPE in the Indian soldier.
b.Incomplete records.
c.Patients with documented history of having being administered drugs/oxygen prior to being examined by a medical professional.
Based on the above criteria, a total of 235 cases of HAPE were included for the analysis.
The acclimatisation medical data of 235 healthy soldiers at 3350 m, available with the HA Research Laboratory, was also analysed to determine values of heart rate, respiratory rate and pulse oximetry values during the first 6 days at an altitude of approximately 3000 m. A daily record of these parameters over the first 6 days of arrival at HA is maintained by the centre. This database contains data of more than 1000 healthy soldiers. Based on the mean day of occurrence of HAPE in the study group, acclimatisation medical data of the healthy soldiers for the corresponding day were chosen for analysis. The sampling was done using the ‘Random’ function in Microsoft Excel. These data served as healthy controls. Since the study and control group comprised a mixed soldier population, it was assumed that the groups were comparable in ethnic composition. A detailed matching for the same was not carried out.
The heart rate, respiratory rate and SPO2 values of HAPE cases and controls were compared for statistically significant differences using an unpaired t-test and then subjected to a receiver operator characteristic (ROC) curve analysis.3 This was done to identify which of these easily measurable clinical parameters would serve as good diagnostic criteria for HAPE occurring between 2700 m and 3500 m. This identification was done using the area under the curve (AUC) value for each of the parameter recorded.3, 4 The best operating point on the ROC curve was then identified to suggest cut-off values for diagnosing HAPE occurring between 2700 m and 3500 m. The best operating point in an ROC analysis is that point where the highest possible sensitivity and specificity are obtained for the given data. The value of a clinical parameter corresponding to this point is the logical choice for a cut-off value proposed as criteria for diagnosis of the clinical condition being studied.
The existing LL criteria for diagnosis of HAPE were applied to the HAPE cases and the sensitivity, specificity, positive and negative predicted values of the LL criteria calculated for this cohort. Since the LL criteria mention tachycardia and tachypnoea as two signs in patients with HAPE but do not specify values for the same, a heart rate of greater than 100 beats per minute (bpm) and a respiratory rate greater than 20 breaths/min were used to define tachycardia and tachypnoea respectively, as is the norm in clinical practice. A similar calculation was done using the cut-off values of HR, RR and SPO2 obtained from the ROC analysis. The two sets of data obtained were analysed to compare the performance of the existing and proposed cut-off values for the diagnosis of HAPE in the Indian soldier.
Results
The mean time of onset of symptoms of HAPE was 2.8 ± 2.2 days after arrival at altitudes between 2700 m and 3500 m. The frequency of various clinical symptoms reported by HAPE patients at the time of diagnosis is shown in Table 1. Breathlessness, headache and cough were the commonest symptoms. The least common symptom was fatigue. The findings on clinical examination in patients of HAPE at the time of reporting to a medical facility and in the healthy acclimatising controls on day three at HA are shown in Table 2. Patients of HAPE had significantly higher heart rates and respiratory rates and lower SPO2 values compared to healthy acclimatising soldiers at a comparable altitude. A frequency distribution of heart rate, respiratory rate and SPO2 values in patients of HAPE is shown in Fig. 1, Fig. 2, Fig. 3 respectively. Majority of HAPE patients had SPO2 values lower than expected at that altitude and 48.9% of them had tachycardia (HR > 100 bpm) at the time of being diagnosed (Table 3).
Fig. 1
Frequency distribution of heart rate values in 235 patients of HAPE showing that only 48.9% of patients had heart rates more than 100 bpm.
Fig. 2
Frequency distribution of respiratory rate values in 235 patients of HAPE.
Fig. 3
Frequency distribution of SPO2 values in 235 patients of HAPE.
Table 1
Clinical symptoms in patients of HAPE in order of frequency.
Clinical symptomNumber of patients (% of patients)Breathlessness 202 (79.5%)
Headache 183 (72%)
Cough 155 (61%)
Chest discomfort 99 (39%)
Expectoration 31 (12.2%)
Insomnia 20 (7.9%)
Fatigue 11 (4.3%)
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Table 2
Findings on clinical examination in patients of HAPE at the time of initial diagnosis. Corresponding values of the same parameters in healthy controls, recorded on the third day in HA, are shown for comparison.
ParameterHAPE patients
(n = 235)
[Mean ± std dev]Healthy controls
(n = 235)
[Mean ± std dev]Heart rate (beats/min) 100.6 ± 17.8 88.5.1 ± 8.3*
Respiratory rate (breaths/min) 26.1 ± 5.5 16.1 ± 3.0*
Systolic blood pressure (mmHg) 124.8 ± 15.6 126.7 ± 11.5
Diastolic blood pressure (mmHg) 81.2 ± 10.7 79.2 ± 11.8
SPO2 – breathing room air (%) 72.2 ± 12.9 88.5 ± 2.2*
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*p < 0.001 (unpaired t-test).
Table 3
Analysis of heart rate, respiratory rate, and pulse oximetry findings in 235 HAPE patients.
Clinical parameterPercentage of patientsHeart rate > 100/min 48.9%
SPO2 < 88% breathing ambient air 89%
Respiratory rate > 20 breaths/min 83%
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ROC curves and the AUCs for HR, RR and SPO2 are shown in Fig. 4, Fig. 5. All the three parameters were found to have a high AUC ranging from 0.86 for HR to 0.88 for SPO2. The best operating point on each curve corresponded to HR of >95 bpm, RR of >21 per minute and SPO2 of <86%. The sensitivity, specificity, positive and negative predictive values of these cut-off values are as shown in Table 4, Table 5, Table 6. A comparison of the sensitivity and specificity of these proposed cut-off values and the existing criteria of tachycardia (HR > 100 bpm) and tachypnoea (RR > 20 per min) for diagnosing HAPE at altitudes between 2700 m and 3350 m is as shown in Table 7.
Fig. 4
ROC curve for heart rate (HR) and respiratory rate (RR) showing areas under the curve of 0.86 and 0.87 for HR and RR respectively.
Fig. 5
ROC curve for pulse oximetry values (SPO2) showing an area under the curve of 0.88.
Table 4
Specificity, sensitivity, positive, and negative predictive value calculation for selected cut-off value of heart rate.
HAPE patientsControlsHeart rate > 95/min 156 13
Heart rate < 95/min 79 222
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Sensitivity = 156/(156 + 79) = 0.66; specificity = 222/(13 + 222) = 0.94; positive predictive value = 156/(156 + 13) = 0.92; negative predictive value = 222/(79 + 222) = 0.74.
Table 5
Specificity, sensitivity, positive, and negative predictive value calculation for selected cut-off value of respiratory rate.
HAPE patientsControlsRespiratory rate > 21/min 194 12
Respiratory rate < 21/min 41 223
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Sensitivity = 194/(194 + 41) = 0.83; specificity = 223/(12 + 223) = 0.95; positive predictive value = 194/(194 + 12) = 0.94; negative predictive value = 223/(41 + 223) = 0.84.
Table 6
Specificity, sensitivity, positive, and negative predictive value calculation for selected cut-off value of pulse oximetry values (SPO2).
HAPE patientsControlsSPO2 < 86% 193 16
SPO2 > 86% 42 219
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Sensitivity = 193/(193 + 42) = 0.82; specificity = 219/(16 + 219) = 0.93; positive predictive value = 193/(193 + 16) = 0.92; negative predictive value = 219/(42 + 219) = 0.83.
Table 7
A comparison of the sensitivity and specificity of existing LL criteria and proposed cut-off values and of heart rate, respiratory rate, and SPO2 for diagnosing HAPE occurring at 2700–3500 m.
Heart rate (bpm)Respiratory rate (breaths/min)SPO2 (%)
Proposed >95Existing >100Proposed >21Existing >20Proposed <86%Existing nilSensitivity 0.66 0.49 0.83 0.83 0.82
(59.9–72.0) (78.1–87.8) (77.0–86.9)
Specificity 0.94 1.0 0.95 0.83 0.93
(90.9–97.0) (92.2–97.7) (89.7–96.2)
Positive predictive valuea 0.92 1.0 0.94 0.83 0.92
(88.5–95.4) (90.9–97.0) (88.5–95.4)
Negative predictive valuea 0.74 0.66 0.84 0.83 0.83
(68.3–79.6) (79.3–88.6) (78.1–87.8)
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A heart rate of greater than 100 bpm and a respiratory rate of greater than 20 breaths/min have been used to define ‘tachycardia’ and ‘tachypnoea’ for the existing LL criteria. Values in brackets indicate 95% confidence limits.
aValid for a disease prevalence as evident in the given study population.
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Discussion
The symptoms of HAPE are known to develop within the first few days at altitude.5 The mean time of occurrence of HAPE at 2700–3500 m in the study population was 2.8 ± 2.2 days. This fact is emphasised since symptoms suggestive of HAPE, in the absence of a history of recent gain in altitude or a possible precipitating factor such as severe unaccustomed exercise or respiratory infection, must be viewed with caution.
The symptoms reported by patients in the present study merit attention. While symptoms of breathlessness, chest discomfort and cough are well-known features of HAPE, a large percentage of patients (72%) were also found to complain of headache. Headache is a non-specific symptom and its occurrence at HA could be the result of a number of factors ranging from dehydration, lack of sleep and tiredness of travel to co-existence of acute mountain sickness. Interestingly, patients of HAPE have been reported to complain of headache in other reports as well.6, 7 Though the pathophysiology of HAPE, as per current understanding, cannot explain the occurrence of headache, the frequent association of this symptom with HAPE might merit consideration of the symptom in the criteria for diagnosis of HAPE.
The absence of fatigue as a major symptom in our patients is interesting since fatigue/weakness/decreased exercise performance is an important diagnostic symptom of HAPE as per the Lake Louise criteria.2, 8 Only 4.3% of our patients reported this symptom. A possible reason could be that soldiers do not undertake significant physical activity during the initial days at altitude as compared to mountaineers, trekkers and tourists indulging in adventure sport at altitude. The average sedentary soldier may not, therefore, notice fatigue as an early and prominent symptom of HAPE.
Not all patients of HAPE in our study showed tachycardia as defined by a heart rate of more than 100 bpm. Only 48.9% of patients had a heart rate of more than 100 bpm, suggesting that more than half of the patients (51.1%) developing HAPE at altitudes of 2700–3500 m may not manifest tachycardia. The magnitude of increase in heart rate is known to be proportional to the altitude of ascent and the severity of illness.9, 10 The lower heart rates in the study population could be due to a number of reasons. Possible among these are the altitude in question (2700–3500 m), which is lower compared to some of the other reports of HAPE, a less severe illness in these patients, possibly the result of the condition being diagnosed early, the relatively sedentary nature of activities performed at HA by acclimatising soldiers and a possible lower resting heart rates in soldiers due to their physical conditioning. The proposed criterion of a heart rate greater than 95 bpm appears to have better sensitivity for diagnosis of HAPE compared to a value of >100 bpm (0.66 vs 0.49), while retaining a high specificity (0.94).
Patients of HAPE are known to have high respiratory rates. How high should these rates be to suggest a diagnosis of HAPE? Using the conventional definition of tachyapnea, i.e. a respiratory rate greater than 20 per minute, the sensitivity and specificity of this parameter for diagnosing HAPE are found to be 0.83. However, selecting a value of 21 breaths/min improved the specificity to 0.95 while maintaining a sensitivity of 0.83.
Though pulse oximetry at HA has its limitations and may not by itself serve as a diagnostic parameter, the information obtained via pulse oximetry, if carried out with due caution, may supplement the overall clinical picture. In the present series of patients, 85% of the patients had SPO2 values below 88%, which is the expected SPO2 value in healthy individuals breathing room air at 3000 m. Pulse oximetry may have utility in monitoring the progress of the condition and efficacy of treatment in HAPE patients.
The ROC analysis of HR, RR and SPO2 revealed that each of the three parameters is very good as diagnostic parameters for HAPE since their areas under the curve range from 0.86 to 0.88. Areas between 0.8 and 0.9 indicate good tests and between 0.9 and 1.0, excellent.4 Of the three parameters, SPO2 appears the best parameter since it had the highest AUC (0.88). The cut-off values suggested from the ROC analysis for these three parameters show very encouraging levels of specificity and sensitivity for their use as parameters for diagnosing HAPE occurring between 2700 m and 3500 m.
Positive and negative predictive values of a diagnostic test are influenced by the prevalence of the disease. As disease prevalence increases in a population, application of the test criteria to that population yields higher positive predictive values and lower negative predictive values. Since the true prevalence of HAPE has been variably reported in literature and may differ among population groups, the values presented in this study should be interpreted keeping this fact in mind and would change, should the disease prevalence be different from that of the present study.
Despite best attempts to prevent its occurrence, HAPE does occur in a number of individuals at HA. A prompt diagnosis of the condition is thus essential, to prevent worsening of the condition and possible fatality. The criteria for diagnosing HAPE need to be reliable, objective, yet simple to use in remote locations by non-medical and para-medical personnel at peripheral medical facilities. While the LL criteria are accepted globally for the clinical diagnosis of HAPE, they are fairly general and not altitude specific. It is therefore suggested that in the setting of recent arrival at 2700–3500 m, an individual with symptoms of breathlessness, cough, chest discomfort and headache, with values of HR, RR and SPO2 as discussed above, is likely to be a patient with HAPE and should be managed accordingly (Table 8). The criteria suggested by this study show better specificity, without compromising the sensitivity, as compared to the existing LL criteria for diagnosing HAPE.
Table 8
A comparison of the existing Lake Louise criteria for diagnosis of HAPE and the proposed criteria of the present study.
Existing criteria (Lake Louise)
The mean time of onset of symptoms of HAPE was 2.8 ± 2.2 days after arrival at altitudes between 2700 m and 3500 m. The frequency of various clinical symptoms reported by HAPE patients at the time of diagnosis is shown in Table 1. Breathlessness, headache and cough were the commonest symptoms. The least common symptom was fatigue. The findings on clinical examination in patients of HAPE at the time of reporting to a medical facility and in the healthy acclimatising controls on day three at HA are shown in Table 2. Patients of HAPE had significantly higher heart rates and respiratory rates and lower SPO2 values compared to healthy acclimatising soldiers at a comparable altitude. A frequency distribution of heart rate, respiratory rate and SPO2 values in patients of HAPE is shown in Fig. 1, Fig. 2, Fig. 3 respectively. Majority of HAPE patients had SPO2 values lower than expected at that altitude and 48.9% of them had tachycardia (HR > 100 bpm) at the time of being diagnosed (Table 3).
Fig. 1
Frequency distribution of heart rate values in 235 patients of HAPE showing that only 48.9% of patients had heart rates more than 100 bpm.
Fig. 2
Frequency distribution of respiratory rate values in 235 patients of HAPE.
Fig. 3
Frequency distribution of SPO2 values in 235 patients of HAPE.
Table 1
Clinical symptoms in patients of HAPE in order of frequency.
Clinical symptomNumber of patients (% of patients)Breathlessness 202 (79.5%)
Headache 183 (72%)
Cough 155 (61%)
Chest discomfort 99 (39%)
Expectoration 31 (12.2%)
Insomnia 20 (7.9%)
Fatigue 11 (4.3%)
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Table 2
Findings on clinical examination in patients of HAPE at the time of initial diagnosis. Corresponding values of the same parameters in healthy controls, recorded on the third day in HA, are shown for comparison.
ParameterHAPE patients
(n = 235)
[Mean ± std dev]Healthy controls
(n = 235)
[Mean ± std dev]Heart rate (beats/min) 100.6 ± 17.8 88.5.1 ± 8.3*
Respiratory rate (breaths/min) 26.1 ± 5.5 16.1 ± 3.0*
Systolic blood pressure (mmHg) 124.8 ± 15.6 126.7 ± 11.5
Diastolic blood pressure (mmHg) 81.2 ± 10.7 79.2 ± 11.8
SPO2 – breathing room air (%) 72.2 ± 12.9 88.5 ± 2.2*
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*p < 0.001 (unpaired t-test).
Table 3
Analysis of heart rate, respiratory rate, and pulse oximetry findings in 235 HAPE patients.
Clinical parameterPercentage of patientsHeart rate > 100/min 48.9%
SPO2 < 88% breathing ambient air 89%
Respiratory rate > 20 breaths/min 83%
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ROC curves and the AUCs for HR, RR and SPO2 are shown in Fig. 4, Fig. 5. All the three parameters were found to have a high AUC ranging from 0.86 for HR to 0.88 for SPO2. The best operating point on each curve corresponded to HR of >95 bpm, RR of >21 per minute and SPO2 of <86%. The sensitivity, specificity, positive and negative predictive values of these cut-off values are as shown in Table 4, Table 5, Table 6. A comparison of the sensitivity and specificity of these proposed cut-off values and the existing criteria of tachycardia (HR > 100 bpm) and tachypnoea (RR > 20 per min) for diagnosing HAPE at altitudes between 2700 m and 3350 m is as shown in Table 7.
Fig. 4
ROC curve for heart rate (HR) and respiratory rate (RR) showing areas under the curve of 0.86 and 0.87 for HR and RR respectively.
Fig. 5
ROC curve for pulse oximetry values (SPO2) showing an area under the curve of 0.88.
Table 4
Specificity, sensitivity, positive, and negative predictive value calculation for selected cut-off value of heart rate.
HAPE patientsControlsHeart rate > 95/min 156 13
Heart rate < 95/min 79 222
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Sensitivity = 156/(156 + 79) = 0.66; specificity = 222/(13 + 222) = 0.94; positive predictive value = 156/(156 + 13) = 0.92; negative predictive value = 222/(79 + 222) = 0.74.
Table 5
Specificity, sensitivity, positive, and negative predictive value calculation for selected cut-off value of respiratory rate.
HAPE patientsControlsRespiratory rate > 21/min 194 12
Respiratory rate < 21/min 41 223
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Sensitivity = 194/(194 + 41) = 0.83; specificity = 223/(12 + 223) = 0.95; positive predictive value = 194/(194 + 12) = 0.94; negative predictive value = 223/(41 + 223) = 0.84.
Table 6
Specificity, sensitivity, positive, and negative predictive value calculation for selected cut-off value of pulse oximetry values (SPO2).
HAPE patientsControlsSPO2 < 86% 193 16
SPO2 > 86% 42 219
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Sensitivity = 193/(193 + 42) = 0.82; specificity = 219/(16 + 219) = 0.93; positive predictive value = 193/(193 + 16) = 0.92; negative predictive value = 219/(42 + 219) = 0.83.
Table 7
A comparison of the sensitivity and specificity of existing LL criteria and proposed cut-off values and of heart rate, respiratory rate, and SPO2 for diagnosing HAPE occurring at 2700–3500 m.
Heart rate (bpm)Respiratory rate (breaths/min)SPO2 (%)
Proposed >95Existing >100Proposed >21Existing >20Proposed <86%Existing nilSensitivity 0.66 0.49 0.83 0.83 0.82
(59.9–72.0) (78.1–87.8) (77.0–86.9)
Specificity 0.94 1.0 0.95 0.83 0.93
(90.9–97.0) (92.2–97.7) (89.7–96.2)
Positive predictive valuea 0.92 1.0 0.94 0.83 0.92
(88.5–95.4) (90.9–97.0) (88.5–95.4)
Negative predictive valuea 0.74 0.66 0.84 0.83 0.83
(68.3–79.6) (79.3–88.6) (78.1–87.8)
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A heart rate of greater than 100 bpm and a respiratory rate of greater than 20 breaths/min have been used to define ‘tachycardia’ and ‘tachypnoea’ for the existing LL criteria. Values in brackets indicate 95% confidence limits.
aValid for a disease prevalence as evident in the given study population.
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Discussion
The symptoms of HAPE are known to develop within the first few days at altitude.5 The mean time of occurrence of HAPE at 2700–3500 m in the study population was 2.8 ± 2.2 days. This fact is emphasised since symptoms suggestive of HAPE, in the absence of a history of recent gain in altitude or a possible precipitating factor such as severe unaccustomed exercise or respiratory infection, must be viewed with caution.
The symptoms reported by patients in the present study merit attention. While symptoms of breathlessness, chest discomfort and cough are well-known features of HAPE, a large percentage of patients (72%) were also found to complain of headache. Headache is a non-specific symptom and its occurrence at HA could be the result of a number of factors ranging from dehydration, lack of sleep and tiredness of travel to co-existence of acute mountain sickness. Interestingly, patients of HAPE have been reported to complain of headache in other reports as well.6, 7 Though the pathophysiology of HAPE, as per current understanding, cannot explain the occurrence of headache, the frequent association of this symptom with HAPE might merit consideration of the symptom in the criteria for diagnosis of HAPE.
The absence of fatigue as a major symptom in our patients is interesting since fatigue/weakness/decreased exercise performance is an important diagnostic symptom of HAPE as per the Lake Louise criteria.2, 8 Only 4.3% of our patients reported this symptom. A possible reason could be that soldiers do not undertake significant physical activity during the initial days at altitude as compared to mountaineers, trekkers and tourists indulging in adventure sport at altitude. The average sedentary soldier may not, therefore, notice fatigue as an early and prominent symptom of HAPE.
Not all patients of HAPE in our study showed tachycardia as defined by a heart rate of more than 100 bpm. Only 48.9% of patients had a heart rate of more than 100 bpm, suggesting that more than half of the patients (51.1%) developing HAPE at altitudes of 2700–3500 m may not manifest tachycardia. The magnitude of increase in heart rate is known to be proportional to the altitude of ascent and the severity of illness.9, 10 The lower heart rates in the study population could be due to a number of reasons. Possible among these are the altitude in question (2700–3500 m), which is lower compared to some of the other reports of HAPE, a less severe illness in these patients, possibly the result of the condition being diagnosed early, the relatively sedentary nature of activities performed at HA by acclimatising soldiers and a possible lower resting heart rates in soldiers due to their physical conditioning. The proposed criterion of a heart rate greater than 95 bpm appears to have better sensitivity for diagnosis of HAPE compared to a value of >100 bpm (0.66 vs 0.49), while retaining a high specificity (0.94).
Patients of HAPE are known to have high respiratory rates. How high should these rates be to suggest a diagnosis of HAPE? Using the conventional definition of tachyapnea, i.e. a respiratory rate greater than 20 per minute, the sensitivity and specificity of this parameter for diagnosing HAPE are found to be 0.83. However, selecting a value of 21 breaths/min improved the specificity to 0.95 while maintaining a sensitivity of 0.83.
Though pulse oximetry at HA has its limitations and may not by itself serve as a diagnostic parameter, the information obtained via pulse oximetry, if carried out with due caution, may supplement the overall clinical picture. In the present series of patients, 85% of the patients had SPO2 values below 88%, which is the expected SPO2 value in healthy individuals breathing room air at 3000 m. Pulse oximetry may have utility in monitoring the progress of the condition and efficacy of treatment in HAPE patients.
The ROC analysis of HR, RR and SPO2 revealed that each of the three parameters is very good as diagnostic parameters for HAPE since their areas under the curve range from 0.86 to 0.88. Areas between 0.8 and 0.9 indicate good tests and between 0.9 and 1.0, excellent.4 Of the three parameters, SPO2 appears the best parameter since it had the highest AUC (0.88). The cut-off values suggested from the ROC analysis for these three parameters show very encouraging levels of specificity and sensitivity for their use as parameters for diagnosing HAPE occurring between 2700 m and 3500 m.
Positive and negative predictive values of a diagnostic test are influenced by the prevalence of the disease. As disease prevalence increases in a population, application of the test criteria to that population yields higher positive predictive values and lower negative predictive values. Since the true prevalence of HAPE has been variably reported in literature and may differ among population groups, the values presented in this study should be interpreted keeping this fact in mind and would change, should the disease prevalence be different from that of the present study.
Despite best attempts to prevent its occurrence, HAPE does occur in a number of individuals at HA. A prompt diagnosis of the condition is thus essential, to prevent worsening of the condition and possible fatality. The criteria for diagnosing HAPE need to be reliable, objective, yet simple to use in remote locations by non-medical and para-medical personnel at peripheral medical facilities. While the LL criteria are accepted globally for the clinical diagnosis of HAPE, they are fairly general and not altitude specific. It is therefore suggested that in the setting of recent arrival at 2700–3500 m, an individual with symptoms of breathlessness, cough, chest discomfort and headache, with values of HR, RR and SPO2 as discussed above, is likely to be a patient with HAPE and should be managed accordingly (Table 8). The criteria suggested by this study show better specificity, without compromising the sensitivity, as compared to the existing LL criteria for diagnosing HAPE.
Table 8
A comparison of the existing Lake Louise criteria for diagnosis of HAPE and the proposed criteria of the present study.
Existing criteria (Lake Louise)
Proposed criteria
History of recent ascent to high altitude History of arrival at high altitude (2700–3500 m) within last 5 days
Any two of the following symptoms Symptoms
• Dyspnoea at rest
Any two of the following symptoms Symptoms
• Dyspnoea at rest
• Breathlessness
• Cough
• Cough
• Cough
• Weakness or decreased exercise performance • Chest discomfort
• Chest tightness or congestion • Headache
• Chest tightness or congestion • Headache
Any two of the following signs Signs
• Crackles or wheeze in at least one lung field • Heart rate > 95 beats/min
• Central cyanosis • Respiratory rate > 21/min
• Tachycardia • SPO2 < 86%
• Tachypnoea
• Crackles or wheeze in at least one lung field • Heart rate > 95 beats/min
• Central cyanosis • Respiratory rate > 21/min
• Tachycardia • SPO2 < 86%
• Tachypnoea
Limitations
This study is based on the retrospective analysis of clinical records and limited by the information contained therein. It is assumed that the documentation of the clinical history and findings in the records are accurate. The clinical criteria suggested for the diagnosis of HAPE by this study need to be validated by applying them prospectively to cases of HAPE being diagnosed and managed at HA and documenting the applicability of these criteria. Once validated, these criteria can be suggested for the field diagnosis of HAPE at altitude between 2700 m and 3500 m.
This study is based on the retrospective analysis of clinical records and limited by the information contained therein. It is assumed that the documentation of the clinical history and findings in the records are accurate. The clinical criteria suggested for the diagnosis of HAPE by this study need to be validated by applying them prospectively to cases of HAPE being diagnosed and managed at HA and documenting the applicability of these criteria. Once validated, these criteria can be suggested for the field diagnosis of HAPE at altitude between 2700 m and 3500 m.
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