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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 5  |  Issue : 2  |  Page : 52-55

Delayed-onset high-altitude pulmonary edema: A series of 8 patients


1 Department of TB and Chest, TSM Medical College, Lucknow, Uttar Pradesh, India
2 Department of Physiology, AFMC, Pune, Maharashtra, India

Date of Submission10-Jan-2020
Date of Decision23-Mar-2020
Date of Acceptance13-May-2020
Date of Web Publication06-Jul-2020

Correspondence Address:
Dr. Sanjay Singhal
Department of TB and Chest, TSM Medical College, Lucknow - 226 012, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ed.ed_1_20

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  Abstract 


Clinical studies were performed in eight consecutive patients who developed high-altitude pulmonary edema (HAPE) after 6 days of stay (range: 8–121 days) at the same altitude who were admitted to our hospital. The findings of this series revealed respiratory infection with exertion and cold exposure as the predominant causes of delayed-onset HAPE. HAPE in its delayed-onset form is likely to be more severe based on mortality findings in our series and requires intense monitoring and preparation of contingencies for prompt evacuation in severe or nonresponsive cases.

Keywords: High altitude, hypoxia, pulmonary edema


How to cite this article:
Singhal S, Alasinga BS. Delayed-onset high-altitude pulmonary edema: A series of 8 patients. Environ Dis 2020;5:52-5

How to cite this URL:
Singhal S, Alasinga BS. Delayed-onset high-altitude pulmonary edema: A series of 8 patients. Environ Dis [serial online] 2020 [cited 2020 Oct 25];5:52-5. Available from: http://www.environmentmed.org/text.asp?2020/5/2/52/289027




  Introduction Top


High-altitude pulmonary edema (HAPE) is a life-threatening medical condition of high altitude and usually occurs within 2–4 days of ascent to an altitude above 8000 ft. This period of occurrence enables prevention by taking precautions in the form of gradual ascent and drug prophylaxis.[1] The interest in high-altitude illness is primarily due to increased movement of sojourners to altitudes above 8000 ft for recreational, professional, military, and adventure activities. This series is based on the hospital data in the Ladakh region of Jammu and Kashmir State, India, at an altitude of 11,500 ft. In a population of predominantly lowlanders entering high altitude (~5–6 times a year) for professional reasons, intensive public health initiatives in the form of mandatory acclimatization and gradual ascent have resulted in fall in the incidence of HAPE. This scenario has also resulted in a variation in the presentation of this condition. Till now, only a few cases of HAPE after more than 6 days at the same altitude or HAPE in resident highlander (high-altitude resident pulmonary edema, HARPE) are reported.[2],[3],[4],[5],[6],[7] Here, we report a series of 8 patients admitted for HAPE occurring after more than 6 days at the same altitude.


  Methodology Top


During the 1-year study period, 147 patients (young soldier native of low altitude) were admitted with HAPE to our hospital located at an altitude of 11,500 ft, of them 8 (1.9%) patients developed HAPE after 6 days of stay (range: 8–121 days) at the same altitude. All patients were healthy young male soldiers (age range: 28–40 years), and the diagnosis of HAPE was suspected on the following criteria: cough, dyspnea on history, tachypnea, crepts on chest auscultation, resting room air hypoxemia (oxygen saturation: <90%) determined on pulse oximetry, and the presence of pulmonary infiltrates on chest radiograph. Grade of HAPE severity was assessed as per classification given in [Table 1].[8] Detailed history and medical examination were carried out to find the risk factors contributing to the development of HAPE even after proper acclimatization. Treatment consisted of bed rest, fluid restriction, nifedipine, and oxygen inhalation in all patients and evacuation to a lower altitude in two patients who failed to maintain the oxygen saturation on high-flow oxygen inhalation. The findings of all patients were recorded including response to treatment, details of entry to high altitude, and height of stay prior to onset of symptoms.
Table 1: Severity classification of high-altitude pulmonary edema

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  Results Top


The clinical details of the patients with delayed-onset HAPE are presented in [Table 2]. All patients were young male soldier (resident of low-altitude posted to high altitude) with a mean age of 34 years (range: 28–40 years), physically active (moderate-to-high-intensity physical activity for 1 h at least 4–5 times a week), and had no previous chronic medical comorbidities. All patients had previously entered high altitude and stayed at moderate high altitude after successful acclimatization [Table 2]. All patients had symptoms of cough, dyspnea, crepts on chest auscultation, and hypoxemia determined by pulse oximetry. All cases reported were admitted in winter and cold exposure (night temperature of −20°C–−30°C and daytime temperature of −2°C–−4°C) was a consistent finding in all patients. All patients had heating arrangement during sleep except no 3 patient who slept without proper heating arrangements. Evaluation of risks factor revealed that respiratory infection with exertion and cold exposure were the predominant causes of delayed-onset HAPE. In one patient, evaluation could not be done due to severe respiratory distress along with clouded consciousness (patient no 4). Mortality was much higher (4 deaths of 8 patients; 50%) in delayed-onset HAPE group as compared to classical HAPE (one death of 139 patients; 0.72%). In patients with delayed-onset HAPE, two deaths occurred despite air evacuation (done after 36 h of hospitalization – patient numbers 2 and 8) to lower altitude as compared to excellent recovery in classical HAPE despite being managed at the same altitude. Of four patients who deceased, two patients had concurrent respiratory infection (patient numbers 2 and 8), one reported late (5 days after development of HAPE – patient no 6), and one had severe HAPE at the time of presentation (patient no 4). One patient developed delayed-onset HAPE after 8 days of stay at extreme high altitude. More than 60% of patients were suffering from upper respiratory infections or influenza-like illness. Two patients gave a history of unaccustomed exertion: one associated with cold exposure and one with acute pharyngitis. Autopsy findings were consistent with the diagnosis of HAPE in all four deceased patients along with high-altitude cerebral edema in one (patient no 4).
Table 2: Summary of patients with delayed-onset high-altitude pulmonary edema

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  Discussion Top


HAPE is one of the most common causes of mortality in regions with heights above 8000 ft. In this case series, we describe the occurrence of HAPE beyond 6 days of stay at high altitude. The severity, risk of complications, and mortality observed in this form of HAPE are much higher compared to HAPE in its classical form despite similar initial clinical and radiological presentation in both the HAPEs. In addition, two patients in the series showed an inadequate response to regular management including descent and expired despite evacuation to near sea level.

The exact mechanism leading to the development of delayed-onset HAPE after prolonged stay at high altitude is not clear. Most of our patients had a history of previous (<1 week) or concomitant respiratory tract infection and unaccustomed exertion. Since all the cases were admitted in winter, cold exposure cannot be ruled out during daily activities. Hence, it is likely that cold exposure was underreported in our study, as central heating facilities were not available to the population under study prior to admission. It is likely that respiratory infections and unaccustomed exertion in the background of cold exposure could have resulted in delayed-onset HAPE similar to cases of HARPE in children who develop pulmonary edema at high altitude without any change in altitude triggered by upper respiratory tract illnesses.[6],[7]

Findings of the series suggest that pathophysiological processes triggered by the above-described risk factors could overcome the protection from HAPE provided by successful acclimatization. Although nonuniform pulmonary vasoconstriction and shear stress have been proposed as pathophysiological mechanisms resulting in HAPE, inflammation may trigger, potentiate, or exacerbate the formation of edema.[9],[10],[11],[12] Hence, the release of vasoactive, inflammatory mediators during infection could have resulted in priming of pulmonary endothelium manifesting as HAPE in response to exertion (as in 2 of 8 cases). Animal experiments have demonstrated a rise in oxygen consumption and ventilation with an increase in nor-epinephrine turnover in hypoxic conditions on cold exposure.[13],[14],[15] Similar processes in humans during cold exposure in hypoxia could be a possible contributing factor leading to delayed-onset HAPE during cold exposure in association with respiratory infections and exertion.

A study on HAPE at extreme altitude has demonstrated that HAPE cannot be prevented at an extreme altitude beyond 18,000 ft by preinduction acclimatization, mountain training, or prolonged stay at such altitude.[4],[16] An isolated case report of a native highlander suffering from HAPE on accustomed exertion raises the possibility of pathophysiological processes overcoming protective effects of acclimatization leading to HAPE.[16] The rare likelihood of delayed-onset HAPE after successful acclimatization could result from a similar phenomenon in susceptible individuals due to interaction of vasoactive inflammatory mediators released due to infection with the endothelium in the background of cold exposure or due to unaccustomed exertion.

The condition of HAPE is managed predominantly by descent to a lower altitude with a recommendation of minimum 1000 m (~3280 ft) descent or till symptoms resolve.[1] In the present series, two patients were evacuated to heights of 1073 ft and 1150 ft from an altitude of 11,500 ft. The decrease in altitude did not result in improvement of symptoms raising the possibility of infection associated pathophysiological mechanisms in addition to the effect of hypobaric hypoxia contributing to the occurrence of delayed-onset HAPE. In the hospital setting, treatment with bed rest and oxygen may be sufficient and evacuation to lower altitude may be unnecessary.[1] Similar management of HAPE at moderate altitude with supplemental oxygen without descent has been successfully carried out in a smaller number in another study.[12] This is in concurrence with our experience in the management of HAPE with oxygen alone at the same altitude. Among other management modalities, continuous positive airway pressure may also improve oxygenation, although the effect on outcomes has only been evaluated in smaller numbers in studies.[14],[15] Nifedipine (potent pulmonary vasodilator) at a dose of 60 mg daily in divided doses can be added in patients who worsen or fails to improve with oxygen and bed rest.[14] There is a lack of systematic studies to suggest effectiveness beta-agonists and phosphodiesterases in patients of HAPE.[11] Diuretics are not recommended in the management of HAPE due to possible worsening of volume depletion in patients of HAPE.[11] HAPE being refractory and not responding to oxygen and descent has been observed in another study where all patients were recent inductees to high altitude and diagnosed to have acute respiratory distress syndrome along with HAPE.[17] This possibility could also have resulted in higher mortality than conventional HAPE in the present series. However, in our cases, autopsy findings were consistent with the diagnosis of HAPE.


  Conclusion Top


The findings of this series suggest a high index of suspicion for HAPE even after successful acclimatization at high altitude. The likelihood of HAPE rises in association with unaccustomed exercise, concomitant respiratory infections, and cold exposure. HAPE in its delayed-onset form is likely to be more severe based on mortality findings in our series. This requires intense monitoring and preparation of contingencies for prompt evacuation in severe or nonresponsive cases. Furthermore, the interaction of respiratory infections with HAPE should be studied further to enable better prognosis prediction of this life-threatening condition.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Blake CI, Banchero N. Effects of cold and hypoxia on ventilation and oxygen consumption in awake guinea pigs. Respir Physiol 1985;61:357-68.  Back to cited text no. 1
    
2.
Durmowicz AG, Noordeweir E, Nicholas R, Reeves JT. Inflammatory processes may predispose children to high-altitude pulmonary edema. J Pediatr 1997;130:838-40.  Back to cited text no. 2
    
3.
Singhal S, Bhattachar SA, Paliwal V, Pathak K. Delayed-onset high-altitude pulmonary edema. Int J Adv Med Health Res 2014;1:96-8.  Back to cited text no. 3
    
4.
Yanamandra U, Patyal S, Mukherji R, Nair V. High-altitude pulmonary oedema in native highlanders. BMJ Case Rep 2014;2014. pii: bcr2013202513.  Back to cited text no. 4
    
5.
Bhattarai A, Acharya S, Yadav JK, Wilkes M. Delayed-onset high altitude pulmonary edema: A case report. Wilderness Environ Med 2019;30:90-2.  Back to cited text no. 5
    
6.
Ebert-Santos C. High-Altitude pulmonary edema in mountain community residents. High Alt Med Biol 2017;18:278-84.  Back to cited text no. 6
    
7.
Liptzin DR, Abman SH, Giesenhagen A, Ivy DD. An approach to children with pulmonary edema at high altitude. High Alt Med Biol 2018;19:91-8.  Back to cited text no. 7
    
8.
Kaminsky DA, Jones K, Schoene RB, Voelkel NF. Urinary leukotriene E4 levels in high-altitude pulmonary edema. A possible role for inflammation. Chest 1996;110:939-45.  Back to cited text no. 8
    
9.
Khan ID. Extreme altitude pulmonary oedema (EAPO) in acclimatized soldiers. Med J Armed Forces India 2012;68:339-45.  Back to cited text no. 9
    
10.
Johnson TS, Young JB, Landsberg L. Norepinephrine turnover in lung: Effect of cold exposure and chronic hypoxia. J Appl Physiol Respir Environ Exerc Physiol 1981;51:614-20.  Back to cited text no. 10
    
11.
Luks AM, McIntosh SE, Grissom CK, Auerbach PS, Rodway GW, Schoene RB, et al. Wilderness Medical Society consensus guidelines for the prevention and treatment of acute altitude illness. Wilderness Environ Med 2010;21:146-55.  Back to cited text no. 11
    
12.
Luks AM, Schoene RB, Swenson ER. High altitude. In: Masson RJ, et al., editors. Murray and Nadel's Textbook of Respiratory Medicine. 5th ed. Philadelphia, PA: Saunders, Elsevier; 2010. pp. 1651-73.  Back to cited text no. 12
    
13.
Larson EB. Positive airway pressure for high-altitude pulmonary oedema. Lancet 1985;1:371-3.  Back to cited text no. 13
    
14.
Schoene RB, Swenson ER, Hultgren HN. High-altitude pulmonary edema. In: Hornbein TF, Schoene RB, editors. High Altitude an Exploration of Human Adaptation. New York: Marcel Dekker; 2001. p. 782.  Back to cited text no. 14
    
15.
Schoene RB, Roach RC, Hackett PH, Harrison G, Mills WJ Jr. High altitude pulmonary edema and exercise at 4,400 meters on Mount McKinley. Effect of expiratory positive airway pressure. Chest 1985;87:330-3.  Back to cited text no. 15
    
16.
Zafren K, Reeves JT, Schoene R. Treatment of high-altitude pulmonary edema by bed rest and supplemental oxygen. Wilderness Environ Med 1996;7:127-32.  Back to cited text no. 16
    
17.
Ma SQ, Wu TY, Cheng Q, Li P, Bian HP. Acute respiratory distress syndrome secondary to High-altitude pulmonary edema: A diagnostic study. J Med Lab Diag 2013;4:1-7.  Back to cited text no. 17
    



 
 
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