Medical aspects

The medical aspects of high altitude exposure.

What is High Altitude Pulmonary Edema?

Sojourns to high altitude are common for adventure and recreational purposes. Too rapid an ascent or inability to acclimatize leads…

Sojourns to high altitude are common for adventure and recreational purposes. Too rapid an ascent or inability to acclimatize leads to high altitude illnesses. These include acute mountain sickness (AMS), high altitude cerebral edema (HACE) and high altitude pulmonary edema (HAPE).

The most common cause of death related to high altitude, HAPE is completely and easily reversed if recognized early and treated properly. HAPE is a non-cardiogenic pulmonary edema which occurs in two forms. The first form typically occurs in un-acclimatized lowlanders who ascend rapidly to altitudes greater than 2500-3000 m. The second form, also called re-entry HAPE, occurs in high landers returning after a sojourn at a lower altitude. The two forms very probably share the same pathophysiology. This article discusses the pathophysiological mechanisms responsible for HAPE and elaborates on various modalities for its prevention and treatment.

HAPE was misdiagnosed for centuries, as evidenced by frequent reports of young, vigorous men suddenly dying of “pneumonia” within days of arriving at high altitude. The death of Dr. Jacottet, “a robust, broad-shouldered young man,” on Mont Blanc in 1891 (he refused descent so that he could “observe the acclimatization process” in himself) may have provided the first autopsy report of HAPE. Angelo Mosso wrote, “From Dr. Wizard's post-mortem examination.… the most immediate cause of death was therefore probably a suffocative catarrh accompanied by acute edema of the lungs.… I have gone into particulars of this sorrowful incident because a case of inflammation of the lungs also occurred during our expedition, on the summit of Monte Rossa, from which, however, the sufferer fortunately recovered.”

On an expedition to K2 (Karakoram Range, Pakistan) in 1902, Alistair Crowley described a climber “suffering from edema of both the lungs and his mind was gone.” In the Andes, physicians were familiar with pulmonary edema peculiar to high altitude, but the English speaking world was largely oblivious to the phenomenon. This changed in 1960 when Charles Houston, an Aspen internist, reported on a healthy 21-year old cross country skier who developed pulmonary edema while crossing a 3,650-meter pass. His chest radiograph showed pulmonary edema, while his electrocardiogram displayed nonspecific changes. Although such cases had been termed “high altitude pneumonia”, Houston recognized this to be acute pulmonary edema without heart disease. Houston's series of four patients included a 26-year old physician who undertook a self-examination with a sthethoscope and could detect fine, moist rales. Hultgren performed cardiac catheterization on seven patients with HAPE at the Chulec General Hospital in Peru. The patients had pulmonary hypertension, reduced cardiac outputs, and low pulmonary artery occlusion pressure. The large of number of Indian troops stationed in the Himalayas provided further for description of HAPE in otherwise young healthy men. Since then, many studies and reviews have been published and HAPE is still the subject of intense investigation.

HAPE presents within 2-5 days of arrival at high altitude. It is rarely observed below altitudes of 2500-3000 m and after 1 week of acclimatsation at a particular altitude.

In most cases, it is preceded by symptoms of acute mountain sickness. Early symptoms of HAPE include a subtle nonproductive cough, dyspnoea on exertion and reduced exercise performance. As HAPE progresses, cough worsens and the subject may have a debilitating degree of dyspnoea, even at rest. Orthopnea may occur. Gurgling in the chest and pink frothy sputum indicate advanced cases. The clinical features are cyanosis, tachypnoea, tachycardia and elevated body temperature generally not exceeding 38.5°C. Rales are discrete initially and located over the middle lung fields.

Slow ascent is the most effective method of prevention, and one that is effective even in susceptible individuals. Apart from graded ascent and time for acclimatization, low sleeping altitudes, avoidance of alcohol and sleeping pills, and avoidance of exercise, are the key to preventing HAPE. Since exercise-induced circulatory changes may worsen or cause pulmonary edema, vigorous exercise should be avoided during the first days of altitude exposure by individuals with a history of HAPE.

According to preliminary data, glucocorticoids have been found to be effective in preventing HAPE in susceptible adults when taken one day prior to ascent and continued during ascent and stay at 4559 m. Glucocorticoids may be effective by stimulation of cGMP production in hypoxia, increasing in the activity of nitric oxide synthase and by increasing the activity of the epithelial Na+ K+ AT Pase pump. Although prophylaxis with dexamethasone for individuals susceptible to HAPE and AMS appears attractive, before general recommendation can be given further studies are needed to determine the minimal effective dose, its best route of administration (topical vs. systemic) and its safety profile in the setting of mountaineering.

Immediate improvement of oxygenation either by supplemental oxygen, hyperbaric treatment, or by rapid descent is the treatment of choice for HAPE. For the mountaineer in a remote area without medical care, descent has first priority, while the tourist with HAPE visiting a high altitude plateau in the Andes, Himalayas, or Rocky Mountains may stay at altitude if medical facilities are available. If it takes few days in a remote area to reach lower altitude, treatment with nifedipine is strongly recommended. In mountaineers with HAPE at 4559 m, treatment with 20mg slow-release nifedipine taken every six hours led to a persistent relief of symptoms, improvement of gas exchange, and radiographic clearance over an observational period of 34 h. In this study, nifedipine therapy was not associated with hypotension. To date, there are no clinical trials on the use of more selective pulmonary vasodilators such as sildenafil or other phosphodiesterase-5 inhibitors in this setting.

In an area where medical infrastructure and assistance are available, vasodilatory treatment is not strictly necessary because with bed-rest and supplemental oxygen for 24 to 48 hrs, relief of symptoms is achieved within hours and complete clinical recovery within several days while staying at the same altitude.

What is High Altitude Cerebal Edema?

High Altitude Cerebral Edema (HACE) is a severe and potentially fatal manifestation of high altitude illness and is often characterized…

High Altitude Cerebral Edema (HACE) is a severe and potentially fatal manifestation of high altitude illness and is often characterized by ataxia, fatigue, and altered mental status. HACE is often thought of as an extreme form/end-stage of Acute Mountain Sickness (AMS). Although HACE represents the least common form of altitude illness, it may progress rapidly to coma and death as a result of brain herniation within 24 hours, if not promptly diagnosed and treated.

HACE generally occurs after 2 days above 4000m but can occur at lower elevations (2500m) and with faster onset.   Some, but not all, individuals will suffer from symptoms of AMS such as headache, insomnia, anorexia, nausea prior to transitioning to HACE.  Some may also have concomitant High Altitude Pulmonary Edema (HAPE).  HACE in isolation is rare, but the absence of concomitant HAPE or symptoms of AMS prior to deterioration does not rule-out the presence of HACE.

Incidence of HACE is 0.5-1% at altitudes of 4000-5000 m.  HACE affects those of all ages and genders, though younger males may be at higher risk due to continuation of ascent despite symptoms of AMS and faster rate of ascent. Risk factors include prior history of high altitude illness, lack of acclimatization, heavy physical exertion, rapid rate of ascent, and abrupt ascent from lower altitudes. 

Although the exact mechanism of development of HACE is not fully understood, it is thought to be the extreme form/end-stage of AMS. Hypoxia at altitude elicits neuro-hormonal (VEG-F, Nitric Oxide, reactive cytokines, free radicals) and hemodynamic responses resulting in hypoxia-induced cerebral vasodilation leading to over perfusion of microvascular cerebral beds.  This leads to intracranial hypertension with elevated capillary pressure and capillary leakage. The disruption of the blood-brain barrier from these stressors leads to subsequent cerebral edema.  The “tight fit” hypothesis suggests that one’s susceptibility to AMS/HACE is dependent upon the individual’s intracranial space available to compensate for increasing edema. This theory would help to explain the seemingly random nature of AMS that can evolve into HACE.  The “revised theory” to the development of HACE argues against volume overload and intracranial hypertension as the leading cause.  In this model, hypoxia induces free radical formation causing damage/failure of the Na+/K+ ATPase Pump with resultant astrocyte swelling from osmotic-oxidative stress, with subsequent cytotoxic edema. Neither theory is considered the standard by which HACE is fully understood.

Most cases develop as a progression of AMS and will include a history of recent ascent to altitude and prior complaints/findings of AMS including a headache, fatigue, nausea, insomnia, and/or lightheadedness.  Some may also have signs/symptoms of HAPE.  Transition to HACE is heralded by signs of encephalopathy including ataxia (usually the earliest clinical finding) and altered mentation which may range from mild to severe.  Other symptoms may include a more severe headache, difficulty speaking, lassitude, a decline in the level of consciousness, and/or focal neurological deficits or seizures.

HACE is a clinical diagnosis with the patient typically presenting with signs of encephalopathy, preceeded by signs and symptoms of Acute Mountain Sickness. The onset of neurological findings such as progressive decline in cognitive/mental function, declining level of consciousness, impaired coordination, slurred speech, and/or lassitude signify the transition from AMS to HACE.  Typical evaluation consists of an abnormal neurological exam, with ataxia often being the earliest finding. Early symptoms may be misinterpreted as exhaustion and it is important to exclude these, as well as other disorders such as dehydration, hypoglycemia, hypothermia, or hyponatremia which all may have signs and symptoms that overlap with that of HACE.  Though rarely available, laboratory testing may show an elevated white blood cell count in the setting of HACE, whereas any number of metabolic abnormalities may be present with the aforementioned others within the differential diagnosis.  Lumbar puncture may have an increased opening pressure with otherwise normal laboratory findings. CT may show cerebral edema, but MRI is a better study to evaluate for more subtle signs of edema and can remain abnormal for days up to weeks.  To date, there has been no direct correlation with the severity of edema with clinical outcome.

The mainstay of treatment is the immediate descent of at least 1000m or until symptoms improve. One should not descend alone and should have assistance to minimize physical exertion, which may worsen the patient’s condition. If descent is not an option, one may use a portable hyperbaric chamber and/or supplemental oxygen to temporize illness, but this should never replace or delay evaluation/descent when possible. If available, dexamethasone 8mg for one dose, followed by 4mg every 6 hours should be given to adults via PO, IM, or IV routes. Pediatric dosing is 0.15 mg/kg every 6 hours. Acetazolamide has proven to be beneficial in only a single clinical study. The suggested dosing regimen for Acetazolamide is 250 mg PO, given twice daily. Though effective in alleviating or temporizing symptoms, none of the adjunct treatment modalities are definitive or a replacement for an immediate descent.

Acclimatization is the best means by which to prevent HACE and all other forms of AMS.  Considerations for prevention of AMS and subsequent HACE is to have a slow rate of ascent with the altitude one sleeps at being more important than the altitude reached.  Final ascent rates of 300-500m per day are recommended for safe and preventative acclimatization.  If signs of AMS develop, stop ascent and if debilitating or severe, descend immediately.   Prophylaxis for HACE/AMS includes both Acetazolamide and Dexamethasone. Ibuprofen is recommended for those with a history of altitude illness. There is less evidence for natural remedies such as ginkgo balboa and coca leaves.  Most advocate training regimens and slow rate of ascent to optimize acclimatization.  This often requires an intense time commitment and is difficult for many to achieve, particularly for those engaged in recreational climbing. Some studies have shown benefit to sleeping in specialized tents at home that provide normobaric hypoxia before departure to higher altitudes, although this has not been validated as a primary preventative measure of AMS or HACE.  

What is Acute Mountain Sickness?

Acute mountain sickness (AMS) and high altitude pulmonary oedema (HAPO) are common causes of morbidity and mortality seen in unacclimatized…

Acute mountain sickness (AMS) and high altitude pulmonary oedema (HAPO) are common causes of morbidity and mortality seen in unacclimatized persons shortly after ascent to high altitude. High altitude is defined as altitudes more than 3000 meters while extreme high altitude is altitudes more than 5800 m. Altitude related illnesses that develop shortly after ascent to high altitudes can present with either cerebral or pulmonary syndromes. AMS and high-altitude cerebral oedema (HACO) refer to the cerebral abnormalities and HAPO to pulmonary abnormalities. In 2001 hospital admission rate for AMS in Indian army was reported to be 0.13/1000 personnel while admission rate for HAPO was 0.15/1000. HAPO and HACO are significant because they are potentially fatal if not treated in time.

Acute mountain sickness is a syndrome of nonspecific symptoms and is therefore subjective. The Lake Louise consensus group defined acute mountain sickness as the presence of headache in an unacclimatized person who has recently arrived at an altitude above 3000m plus and the presence of one or more of the following: a) gastrointestinal symptoms like anorexia, nausea or vomiting, b) insomnia, c) dizziness and d) lassitude or fatigue. The pathophysiological processes that cause acute mountain sickness are unknown. However, symptoms of acute mountain sickness may be the result of cerebral swelling, either through vasodilatation induced by hypoxia or through cerebral oedema. Impaired cerebral auto regulation, the release of vasogenic mediators and alteration of the blood-brain barrier by hypoxia may also be important. Similar mechanisms are thought to cause cerebral oedema at high altitude, which may represent a more severe form of acute mountain sickness. The symptoms typically develop within 6 to 10 hours after ascent, but sometimes as early as 1 hour. Importance of AMS lies in its early recognition as it may progress to HACO, clinically identified with onset of ataxia, altered consciousness or both in a person suffering from acute mountain sickness. Many conditions mimic acute mountain sickness and high altitude cerebral oedema which may delay the diagnosis and early treatment. The main differential diagnoses are acute psychosis, carbon monoxide poisoning, subdural haematoma, hypoglycemia, ingestion of alcohol, seizures and stroke.

Management of AMS follows three axioms: a) further ascent should be avoided until the symptoms have resolved, b)patients with no response to medical treatment should descend to a lower altitude and c) if and when HACO is suspected, patients should urgently descend to a lower altitude. Descent and supplementary oxygen are the treatments of choice and for severe illness, the combination provides optimal therapy. Remarkably, a descent of only 500 to 1000 m usually leads to resolution of acute mountain sickness while high-altitude cerebral oedema may require further descent. Simulated descent with portable hyperbaric chambers, now commonly available in remote locations, are also effective. Medical therapy becomes crucial when descent is not immediately possible.  Various drugs have been tried for high altitude illnesses with variable effect. A small, placebo-controlled study showed that the administration of acetazolamide reduced the severity of symptoms. Dexamethasone is as effective as acetazolamide and starts acting within 12 hours while acetazolamide takes around 24 hours. Other drugs which have been used are ibuprofen and sumatriptan. For high altitude related insomnia acetazolamide is effective. Newer non-benzodiazepine sedatives like zolpidem, which do not depress ventilation are also effective.

For the prevention of high-altitude illness, the best strategy is a gradual ascent to promote acclimatization. Depending on the altitudes, acclimatization in Armed forces is carried out in three stages.

  • a)First stage (3000m to 3600m) acclimatization for total 06 days
  • b)Second stage (3600m to 4500m) acclimatization for total 04 days
  • c)Third stage (>4500m) acclimatization for total 04 days

 

In each stage a person is made to rest for the first 02 days and then gradually made to walk and subsequently climb the slopes in a graded fashion.

Drug treatment for prophylaxis is recommended if rapid ascent is unavoidable. Acetazolamide is the preferred drug. Prophylactic aspirin can be used for prevention of headache.