Altitude sickness

Introduction

• It is hypoxia rather than hypobaria that results in symptoms
• It is the sleeping altitude that is critical to consider as this is when hypoxaemia is maximal
• Intermediate altitude
  • 1520-2440m (5000 to 8000ft)
  • Decreased exercise performance, increased alveolar ventilation without impairment in arterial oxygen transport
  • If limited ventilatory response or pre-existing hypoxaemia, may have exaggerated symptoms
• High altitude
  • 2440 – 4270m (8000-14000 ft)
  • Decreased arterial oxygen saturation, marked hypoxaemia during exercise/sleep
  • Most cases occur at this altitude due to ease of reaching this as a tourist
• Very high altitude
  • 4270 – 5490m; 14000 – 18000 ft
• Extreme altitude
  • >5490m (>18 000 ft)
  • Severe hypoxaemia and hypocapnoea
  • Progressive physiological deterioration outstrips acclimatisation and continued habitation is impossible

Altitude acclimatisation

• Ventilation
  • Carotid body senses reduced arterial oxygenation and signals medullary respiratory centre to increase ventilation
  • Respiratory depressants or stimulates affect this and chronic hypoxia blunts this response
  • Initial hyperventilation is rapidly attenuated by respiratory alkalosis, which slows this down
  • As renal excretion of bicarb compensates for respiratory alkalosis, pH returns towards normal and ventilation can continue to increase
  • This process of ventilatory acclimatisation takes 4-7 days to culminate
  • With continued ascent, central chemoreceptors reset to progressively lower PaCO2 and completeness of acclimatisation can be gauged by the PaCO2
  • Acetazolamide forces bicarbonate diuresis and greatly facilitates this process

• Blood
  • EPO levels rise within 2 hours with increased RCC over days to weeks
  • Over weeks to months get chronic mountain polycythaemia
  • Oxyhaemoglobin curve shifts are minimal due to balancing physiological effects
  • Hypoxia leads to rise in 2,3-DPG and shifts curve to the right but respiratory alkalosis moves it to the left
• Fluid balance
  • Peripheral venous constriction leads to increased central blood volume, triggering baroreceptors to suppress ADH and aldosterone release leading to diuresis
  • Combined with bicarbonate diuresis, result is decreased plasma volume and hyperosmolality (290-300)
  • Haemoconcentration increases oxygen carrying capacity of the blood
  • Antidiuresis is associated with acute mountain sickness and may contribute to cerebral oedema

• Cardiovascular
  • Stroke volume reduced initially with increased HR to maintain CO
  • Maximum exercising heart rate falls with decreased VO2max
  • Pulmonary circulation constricts in hypoxia
  • Cerebral blood flow transiently rises despite hypocapnoeic alkalosis, which increases O2 delivery to the brain
    • Response limited by increased cerebral blood volume, which may increase ICP and aggravate acute mountain sickness
• Exercise capacity
  • VO2max drops 10% for every 1000m above 1500m
  • Over 10 days, submaximal endurance increases, but VO2max does not

• Limits
  • Considerable weight loss is unavoidable
  • RV strain from excessive pulmonary vasoconstriction, intestinal malabsorption, impaired renal function, polycythaemia leading to microcirculatory sludging and prolonged cerebral hypoxia all limit duration
  • Some individuals show blunted carotid body function leading to inadequate ventilation at high altitude and impairs acclimatisation
• Sleep at high altitude
  • Sleep stage I increased; III and IV decreased
  • More time spent awake with increased arousals
  • Typical Cheyne-Stokes pattern above 2700m consists of 6-12 s apnoeic pauses interspersed with vigorous ventilation
  • Quality of sleep and arterial oxygenation improve with acclimatisation and acetazolamide

Acute hypoxia

• Occurs with sudden and severe hypoxic insult e.g. accidental decompression of aircraft or failure of oxygen systems in mountaineers/pilots, sudden overexertion, acute onset pulmonary oedema, CO poisoning and sleep apnoea
• If unacclimatised, become unconscious at SaO2 <60%, PaO2 <15mmHg
• Reverses with oxygen, rapid descent and correction of underlying cause
• Symptoms include dizziness, light-headedness and dimmed vision through to LOC
• Hyperventilation can prevent LOC

Acute mountain sickness (AMS)

• Syndrome
  • Headache
  • GI disturbance
  • Dizziness
  • Fatigue
  • Sleep disturbance
• Lake Louise self-questionnaire
  • Grades degree of symptoms for each of above
  • Mild 2-4
  • Moderare 5-9
  • Severe 10-15

• Risk factors
  • Occurs in more gradual and less severe hypoxic insult
  • Incidence varies by location, ease of access to high-altitude, rate of ascent and sleeping altitude
  • Sleeping altitude of 2470m seems to be threshold for increased incidence
  • Those with blunted carotid response or low vital capacity are at increased risk
  • Children = adults
  • Those over 50 have less AMS
  • Women have less pulmonary oedema symptoms
  • Obesity has higher risk due to greater nocturnal oxygen desaturation
  • Susceptibility is generally reproducible on repeated exposures
  • No relationship to physical fitness

• Pathophysiology
  • Hypobaric hypoxia with subsequent cerebral vasodilation and vasogenic oedema, loss of autoregulation and increased vascular permeability
• Clinical features
  • Symptoms usually develop within 1-6 hours but can take 1-2 days
  • Headaches are usually bifrontal, worse with leaning forwards and with Valsalva
  • GI – Anorexia, nausea and sometimes vomiting
  • Lassitude and weakness
  • Sleepiness and deep inner chill are common
  • Often want to be left alone
  • With increasing severity, get worse headache and vomiting with oliguria, lassitude may worsen and ataxia/ALOC indicates high-altitude cerebral oedema
  • Coma may ensure within 12 hours if treatment is delayed

• Clinica examination
  • HR and BP variable but may have postural drop
  • Presenting SpO2 is usually normal or slightly low for a given altitude (see tables) and this corresponds poorly to severity
  • Localised rales in up to 20%
  • Fundoscopy shows venous tortuosity and dilatation, with retinal haemorrhages common at >5000m
  • Facial and peripheral oedema are sometimes seen
• DDx
  • Hypothermia, CO poisoning, pulmonary infection, CNS infection, dehydration, migraine and exhaustion
  • Headaches from AMS dissipate within 10-15 min of O2 delivery (unlike other causes)

• Treatment
  • Initial clinical presentation does not predict eventual severity
  • Three principles:
    • Do not proceed to higher sleeping altitudes in presence of symptoms
    • Descend if symptoms do not abate or become worse despite treatment
    • Descent and treat immediately in presence of ALOC, ataxia or pulmonary oedema
  • Mild – Above + acetazolamide 125-250mg PO BD + analgesics/antiemetics
    • Usually self-resolves within 12-36 hours of further acclimatisation
    • Drop of 300-1000m is usually sufficient
  • Moderate/severe – Low-flow O2 if available, acetazolamide 250mg BD and/or dexamethasone 4mg PO q6h
    • 1-2L NP O2 at night is particularly efficient
  • High-altitude cerebral oedema – Immediate descent, O2 titrated to 90%, dexamethasone 8mg PO/IV/IM then 4mg q6h + hyperbaric if cannot descend
  • High-altitude pulmonary oedema – Immediate descent, O2 titrate to 90%, nifedipine SR 30mg POq12h if no O2/descent, hyperbaric if no descent, minimise pt exertion and keep warm, dexamethasone 4mg PO q6h if cerebral signs arise
  • Period breathing/insomnia – Acetazolamide 62.5-125mg PO at bedtime
  • Acetazolamide
    • Side effects are common with higher dosing regimes with peripheral paresthesia and nausea/drowsiness
    • Sulfa moiety means should avoid in those with anaphylaxis to sulfa antibiotics
    • Also maintains cerebral blood flow despite greater hypocapnoea
  • Analgesia
    • Paracetamol or NSAID’s are effective
    • Aspirin is effective prophylaxis of headache in those not exercising
  • Antiemetic
    • Ondansetron should be first-line antiemetic
  • Zolpidem/zopiclone
    • May be effective for recurrent awakening at night without impairing ventilation
  • Dexamethasone
    • Rapidly improves AMS and can be life-saving in HACE
    • No value in HAPE
    • Can have rebound effect once ceased and recommendation is to perform short taper or follow-up with acetazolamide

• Prevention
  • Graded ascent with adequate time to acclimatise is optimal
  • Spend one night at 150—2000m before rising to >2500m
  • Allow 2 nights for each 1000m gain in camp altitude above 3000m
  • Avoid overexertion, alcohol and respiratory depressants
  • Acetazolamide does not mask serious illness and actually prevents it
    • Reduces symptoms by 75% in those who ascend rapidly to >2500m
    • Dexamethasone is a reasonable alternative 4mg BD starting on day of ascent and continuing for first 2 days at altitude

High-altitude cerebral oedema

• Progressive neurological deterioration in someone with AMS or high-altitude pulmonary oedema
• Clinical features
  • Altered mental status, ataxia, stupor and coma
  • Headache, nausea and vomiting are NOT always present
  • Raised ICP can cause focal herniation signs
  • Usually associated pulmonary oedema
• Treatment
  • O2 supplementation, descent and steroid therapy
  • Acetazolamide can be used as an adjunct
  • If remaining ataxic or confused after descent, need hospitalisation and consider DDx (stroke, SAH, encephalitis, meningitis, venous thrombosis)
  • Evidence is lacking for hypertonic saline, loop diuretics or manitol

High-altitude pulmonary oedema

• Most lethal of all 
• Cause of death is usually lack of recognition, misdiagnosis or inability to descend
• Risk factors
  • Excessive exertion
  • Rapid ascent
  • Cold
  • Excessive salt ingestion
  • Respiratory depressants
  • Inherent susceptibility
  • Pulmonary hypertension of any cause
  • Genetic
    • Diminished lung sodium channel activity
    • Excessive hypoxic pulmonary vasoconstriction
    • Immunogenetic factors

• Pathophysiology
  • Non-cardiogenic, hydrostatic oedema
  • CO low; normal LV function
  • PVR and PAP markedly elevated
  • High microvascular pressure leads to fluid accumulation within alveoli
  • Later inflammatory response occurs
• DDx
  • Pneumonia, PE, MI, CCF, mucous plugging and bronchitis
• Clinical features
  • Early dry cough, reduced exercise performance, dyspnoea and increased recovery times
  • Localised rales, usually right mid-lung field are common
  • Resting SpO2 is often 10-20 points lower than usual at given altitude
  • Tachycardia, tachypnoea, dyspnoea at rest, marked weakness, productive cough, cyanosis and generalised rales develop later
  • ALOC and coma eventually

• Early diagnosis is critical and decreased exercise performance and dry cough should be enough to raise suspicion
• Progression of dyspnoea on exertion to dyspnoea at rest is the hallmark
• Typically worse at night
• Prominent P2 and RV heave are common and rales may occur only after exertion
• ECG – RV strain pattern
• Absence of infiltrates on CXR should raise possibility of alternative diagnosis

• Treatment
  • Immediate descent if possible
  • Minimise exertion
  • Oxygen supplementation can entirely reverse findings over 36-72 hours
  • Hyperbaric O2 is a great option if available
  • PEEP mask/CPAP/BiPAP increases SpO2 by 10-20% at high altitude by enhancing alveolar recruitment
  • Nifedipine can reduce PAP but increases SpO2 only slightly
  • Tadalifil 10mg BD 24 hour prior to ascent prevent HAPE in susceptible individuals
  • Inhaled salmeterol BD reduces incident by 50% in those with previous repeat episodes of HAPE
    • Upregulation of lung epithelial sodium channels and increased clearance of alveolar fluid through beta-agonism
  • If develops at <2500m or does not respond to therapy, investigate for PE or shunts

• Discharge criteria
  • Clinically well, PaO2 >60 and SpO2 >90%
  • An episode of HAPE is not a contraindication for repeat ascent but should educate, consider prophylactics and identify symptoms early

Peripheral oedema

• Swelling of face and extremities is common
• Often associated with AMS
• Raises suspicion of HAPE/HACE
• Can be treated with diuretics but resolves with descent

High-altitude retinopathy

• Retinal oedema
• Venous tortuosity and dilatation
• Disc hyperaemia
• Retinal haemorrhages
  • Not considered a reason to descend unless macular and symptomatic
  • Resolve spontaneously in 10-14 days
  • Common above 5000m and lower if concomitant AMS
• Cotton wool exudates

High-altitude bronchitis

• Dry, hacking cough at >2500m due to breathing high volumes of cold, dry air leading to secretions and bronchospasm
• Salbutamol may provide relief as in cough-variant asthma
• Humidifiers overnight are helpful
• Scarfs across mouth to entrap moisture are helpful

Chronic mountain sickness

• Monge’s disease
• Males have much higher incidence and incidence increases with age
• Excessive polycythaemia for given altitude leading to headache, muddled thinking, difficulty sleeping, impaired peripheral circulation, drowsiness and chest congestion
• 50% of patients have underlying COAD or sleep apnoea that worsen acute mountain sickness
• The other 50% have idiopathic hypoventilation with reduced ventilatory drive
• Treatment
  • Phlebotomy, relocation to lower altitude or home O2
  • Respiratory stimulants such as acetazolamide or medroxyprogesterone acetate have been used

Ultraviolet keratitis (Snow blindness)

• Less cloud cover, water vapour and particulate matter in air results in increased UVA and UVB at high altitude
• Radiation increases 5% for every 300m gain and exacerbated by snow reflection
• Symptoms may occur over 6-12 hours
• Severe pain, FB sensation, photophobia, tearing, marked conjunctival erythema, chemosis and eyelid swelling
• Self-limited and heals within 24 hours
• Prevention is key

Chronic disease at altitude

• Chronic lung disease
  • If on home O2, need to increase FiO2
  • Those with chronic hypoxia are already partially acclimatised and do well at moderate elevations
  • Asthmatics do better due to cleaner, lower density air with less allergens
• Atherosclerotic heart disease
  • May have angina with less exertion if >2500m for first few days
  • Fluid accumulation can worsen CCF
• Sickle cell disease
  • Need oxygen supplementation to prevent sickle cell crisis
• Pregnancy
  • Pregnant women who live at high altitudes have higher prevalence of hypertension, LBW infants and neonatal hyperbilirubinaemia but not seen in visitors to high altitude
  • Avoid altitudes where SpO2 <85% (i.e. sleeping at >3000m)

Last Updated on November 23, 2021 by Andrew Crofton