Altitude and Travel. Philippe Lagacé-Wiens MD, DTM&H, FRCPC

Transcription

1 Altitude and Travel Philippe Lagacé-Wiens MD, DTM&H, FRCPC

2 Outline Basic physiology of altitude medicine The dangers of altitude and acute altitude illnesses. Diagnosis of altitude related illnesses Treatment of altitude related illnesses Prevention of altitude illnesses. Altitude illness in special populations.

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6 Altitude medicine the basics Oxygen makes up roughly 21% of the gases in our atmosphere. Normal atmospheric pressure is 760 mm Hg, Normal oxygen pressure is 159 mmhg. As elevation increases, atmospheric pressure decreases (oxygen( concentration stays the same).

7 What does it mean? In Winnipeg, oxygen pressure is 155 mmhg ( 97% 97% ) In Cusco, Peru oxygen pressure is : 100 mmhg ( 65% 65% ) In Lhasa, Tibet: 96 mmhg ( 60%( 60% ) In La Paz, Bolivia: 92 mmhg ( 58%( 58% ) Mt. Kilimanjaro: 73 mmhg ( 48%( 48% )

8 Oxygen physiology Haemoglobin carries oxygen from the lungs to the tissues. The amount of oxygen carried depends on the amount of oxygen in the lung and amount of haemoglobin. Haemoglobin is can be fully saturated as long as the atmospheric O 2 pressure is over 115. Occurs at about 2500m

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10 Adaptations to low oxygen pressure Short term: Hyperventilation Increases oxygen in lungs by reducing CO 2 Also increases ph Renal acid-base changes, disordered ventilation Compensates for ph increase Local tissue responses to low oxygen Long term: Not an issue in acute mountain sickness Involves slow increase in oxygen carrying capacity.

11 Dangers of altitude Many forms! Lower oxygen tension Drops by 80 mm (~10 kpa) for each 1000 m Increased UV radiation Up 14% for each 1000m Lower temperatures -6.5ºC C for each 1000m

12 Illnesses associated with altitude Oxygen-related Acute hypoxia AMS HAPE HACE Peripheral Oedema PE/Thromboembolism/stroke Retinopathy Disordered/periodic breathing Physical environment related Exposure Sunburn Snow blindness

13 HAFE Still ignored...

14 Altitude associated illness Diagnosis and Treatment Acute hypoxia AMS and HACE HAPE Disordered breathing

15 Acute hypoxia Rapid reaction to sudden drop in oxygen tension. Occurs minutes to hours after exposure Can be triggered by exertion or other factors that drop blood oxygen level while at altitude. Dizziness, hallucinations, tinnitus, loss of consciousness can occur. Almost guaranteed to occur in unacclimatized persons over ~5500m

16 Acute hypoxia - Treatment Descent and oxygen. Correct causes or triggers of hypoxia. Encouraging hyperventilation can temporize.

17 Acute Mountain Sickness The body s s response to a sudden change in oxygen pressure and subsequent modest hypoxaemia. Clinically differs from acute hypoxia. Occurs 6 12 hours after elevation. Results in a clinical syndrome characterized by: Headache which can progress to debilitating. Fatigue which can progress to lassitude. Insomnia, paroxysmal nocturnal breathing. Poor appetite which can progress to vomiting.

18 AMS - diagnosis Lake Louise score commonly used to diagnose AMS.

19 Altitude headache Cardinal symptom of AMS. Throbbing, frontal/bitemporal Worse in morning and at night. Postural Similar to a hangover headache in quality.

20 Disordered breathing and sleep apnea Common finding at altitudes >3000m Usually in the form of periodic breathing and apnea during sleep. Leads to poor sleep, somnolence, headache. Caused by competing respiratory drives.

21 High Altitude Cerebral Edema HACE is end-stage AMS: Hypoxia causes fluid leak into brain tissue, causing brain swelling and inflammation. Symptoms are similar to AMS but more severe. AMS with any of the following should be considered HACE. Ataxia Confusion Altered consciousness/behaviour Coma Severe vomiting

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23 Treatment of AMS The only 100% effective treatment for AMS is increasing oxygen pressure. This means descent descent, oxygen or a pressure chamber. Anybody with symptoms of HACE or severe AMS must descend! Other modalities only adjunctive

24 Mild AMS Headache, nausea, fatigue, dizziness, insomnia can be treated symptomatically. NSAIDs and acetaminophen have been shown to be equivalent for headache. Anti-emetics (prochlorperazine and promethazine) Acetazolamide can be used to treat (250mg in two doses 8 hours apart) Sedatives or benzodiazepines may contribute to disordered breathing.

25 Severe AMS Severe headache, vomiting, anorexia, peripheral oedema without HACE or HAPE. Descent to lower altitude with acclimatization. As little as 500 meters can be very helpful. Acetazolamide 250mg then 250mg 8 hours later. Dexamethasone 4 mg every 6 hours. Combine with descent or acetazolamide! Oxygen or pressure chamber to facilitate descent.

26 HACE Descent to lower altitude. Oxygen or pressure chamber to facilitate descent. Dexamethasone 4 mg every six hours after 8mg loading dose. Furosemide and other diuretics can be considered but quality evidence is lacking.

27 High Altitude Pulmonary Edema Hypoxia and reduced pulmonary gas exchange increases pulmonary artery pressure and results in capillaries leak into lungs. Usually 2 4 days after ascent. AMS not always co-existing. Manifests as persistent dry cough, severe dyspnea and disproportionately limited exercise tolerance. Fever (<38.5ºC), tachypnea and diffuse crackles are common. Haemoptysis/pink sputum is late finding.

28 HAPE - diagnosis Two of: chest tightness, cough, dyspnea at rest, and markedly decreased exercise performance and... Two of: central cyanosis, pulmonary crackles, tachycardia >110 and tachypnea >20 Caution with scoring systems!

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30 HAPE - Treatment Descent to lower altitude. Oxygen or pressure chamber to facilitate descent. Drugs play a small role in management. Nifedipine XR 30mg BID, Nitric oxide Furosemide with or without morphine (standard of care for pulmonary oedema) remains controversial. Role of dexamethasone is not clear.

31 Prediction and Prevention

32 Who gets AMS? There is no way to predict who will get AMS. AMS does not typically occur below 2000m ASL. Faster ascents and group excursions more risky. Younger people at highest risk. More vigorous ascents. Less free intracranial space. Personal history of AMS, HACE or HAPE. Residence below 900m. No apparent association with gender, physical fitness, load.

33 AMS Risk Extreme Frankly insane Very high High Rather challenging Pleasantly invigorating

34 Genetic basis of AMS Genetically determined anatomical variations. Activity of key enzymes NO synthase in HAPE ACE polymorphisms Gender differences? Overall men more likely to get AMS behavioural. No clear gender differences when other factors are adjusted. Hereditary aspect of AMS.

35 Prevention of AMS, HACE and Behaviour HAPE Altering behaviour to reduce likelihood of AMS. Pharmacological Physical Methods to increase oxygen pressure.

36 Behavioural Slow ascent with acclimatization points, especially at high altitude (>3000m). 400m/ day is reasonable. One acclimatization day for each 3 days of increase. Never overnight at higher altitude than where symptoms start. Climb high, sleep low. Avoid sedatives or alcohol. Know the symptoms and ensure groups understand individual variability. Mild activity (no overexertion).

37 Diet? High carbohydrate diet (carbo-loading) with >70% of calories from carbohydrates reduces the risk of AMS. Role of hydration and hyperhydration is in question. Association exists between AMS and dehydration, but not apparently causal. Dehydration can contribute to symptoms. Adequate hydration probably helps acid-base normalization. May prevent thromboembolic phenomena.

38 Chemoprophylaxis of AMS AMS Acetazolamide, dexamethasone HACE Acetazolamide, dexamethasone HAPE Sildenafil, Tadadifil, Nifedipine, Salmeterol

39 Acetazolamide Carbonic anhydrase inhibitor. Increases renal output of bicarbonate causing metabolic acidosis. Accelerates normal physiological changes in response to altitude. Stimulates ventilation (peripheral CA) mg 250mg po BID starting 24 hours pre-ascent and ending 48 hours after maximum altitude is effective for AMS prevention. Reduces severity of symptoms. Paroxysmal nocturnal breathing, insomnia, headache.

40 Acetazolamide Indications: Rapid ascent to >3000m or rapid increase in sleep altitude (e.g to 5000m in one day). Past history of AMS or HACE. Side effects can be disturbing... Annoying to painful paresthesias of fingers/toes. Taste alteration of carbonated beverages. Diuresis, cloudy urine, nausea. RARE: Myelosuppression, SJS, crytaluria. Start with lowest effective dose (125 mg BID) People with sulfa allergy CAN take.

41 Dexamethasone Considered second line due to side effects. May prevent HACE and HAPE by reducing capillary leak and inflammation. Reduces incidence of headache, vomiting. Is more effective when combined with acetazolamide. Dose for prevention is 4mg BID.

42 Nifedipine Should not be used to prevent HAPE. Only shown to be effective in preventing HAPE in individuals with repeated history of HAPE going to high altitude. Recommended only in limited situations. Individuals with recurrent HAPE and needing to go at high altitude without access to oxygen or ability for slow ascent.

43 cgmp phosphodiesterase type 5 inhibitors Sildenafil (Viagra ) ) and Tadalafil (Cialis ) have been shown to be effective in preventing HAPE and improving gas exchange and should be considered in people with a history of HAPE who must ascend rapidly.

44 β-adrenergic agonists Salmeterol, taken prophylactically at 125μg every 12 hours reduced incidence of HAPE by 50% in subjects with a previous episode of HAPE.

45 Other drugs for prevention Temazepam has been shown to reduce periodic breathing. Theophylline (caffeine-like 250 mg BID effective to reduce AMS. Sumatriptan reduced symptoms of AMS when taken prophylactically in one study.

46 Summary of pharmacological management of AMS syndromes PREVENTION TREATMENT Drug AMS HACE HAPE AMS HACE HAPE Analgesics (e.g. Ibuprophen) Yes Yes No Yes Yes No Acetazolamide Yes Yes? Yes No No Dexamethasone Yes Yes? Yes Yes No Nifedipine No No? No No Yes Furosemide No No No No No? Salbutamol No No Yes No No No Sildenafil/Tadalafil No No Yes No No No Theophylline Yes? No No No No Nitric oxide No No No No No Yes Descent, oxygen and barotherapy are effective for all forms on altitude illness and should be considered first line for all severe forms of the disease.

47 Physical (oxygen) Use of oxygen as prevention for AMS is not routine. Used to prevent severe AMS at extreme altitudes Used intermittently, nocturnally or continuously. Used prophylactically on train to Lhasa

48 Special populations Certain populations require special considerations at high altitude: Children Pregnant women Diabetics Underlying diseases of cardiovascular and respiratory system.

49 Children May be more susceptible to AMS. Quality studies are lacking Difficult to assess symptoms of AMS in young children. Symptoms same in children over 8 years. Use Lake Louise Score Modified Lake Louise score recommended in children less than 8 years old.

50 Modified Lake Louise Score Unexplained fussiness intensity and amount. How well child is eating. How playful child is. How well child is sleeping.

51 Pregnancy Theoretical risks: Altitude = remoteness Access to care in case of complications, early labour... Reduced oxygen delivery to foetus Dehydration and thrombosis

52 Pregnancy Simulated altitude up to 2600 m doesn t t appear to harm the foetus. Oxygen levels remain normal. Caution reasonable if there are complications. Women living at altitude have a higher than expected rate of miscarriage and LBW. Reasons unclear, not significant in acute exposure. Dehydration can exacerbate hypercoagulable state. Hypercoagulability after long-term exposure.

53 Diabetes Risk of AMS, HACE and HAPE appear no different. Glycemic control is profoundly affected by exercise and altitude. Need very careful monitoring and expect poor control. Ketoacidosis can occur Anorexia is common with altitude. Temperature and environmental considerations. Medications, shivering etc...

54 Diabetes and AMS prophylaxis Acetazolamide can predispose individuals to ketoacidosis. Dexamethosone causes hyperglycemia and can lead to ketoacidosis.

55 COPD Individuals with COPD and asthma cannot compensate as well for hypoxia with hyperventilation. With COPD, FEV 1 > 1.5L and expected PaO 2 > 55mmHg PaO 2Alt = (0.52PaO 2 ) + (11.9FEV 1 ) 1.76 PaO 2Alt

56 Asthma Patients with mild intermittent or mild persistent disease (controlled) may ascend to altitudes as high as 5000 m. Caution patients with more severe disease against high-altitude travel, particularly into remote areas. Should have excellent control Continue baseline medications and carry peak flow meter and supply of rescue inhalers and prednisone for potential exacerbations Consider using balaclava or bandana over mouth to warm and humidify air in cold environments.

57 Pulmonary hypertension Should be counselled against going to high altitude. No trials to assess risk, but theoretical risk of HAPE. If travel not avoidable, use HAPE prophylaxis, oxygen.

58 Angina, CAD and Heart Failure No increased risk of AMS, HACE or HAPE. Higher risk of effort angina and dysrythmia. Minimal exertion at moderate altitude in well compensated patients is low risk. Recommendations Gradual ascent. Ensure BP, heart rate/rhythm control. Limitation of activity to less than the symptom-limiting degree at sea level, especially during the first 1 to 3 days.

59 Angina, CAD and Heart Failure Counsel against high altitude if: New-onset or unstable angina. Frequent or high-grade grade ventricular ectopy. Severe or poorly controlled hypertension. Co-existing pulmonary disease Myocardial infarction within several weeks or months is a relative contraindication.

60 Take home points Altitude sickness is preventable. Behavioural and pharmacological approaches exist. People travelling to areas above 2500 m should be aware of altitude sickness. People going to very high altitude, who are anxious about altitude sickness or who are pregnant or have underlying pulmonary, cardiac or chronic disease should be referred to an expert.

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62 14. Leaf DE, Goldfarb DS. Mechanisms of action of acetazolamide in the t prophylaxis and treatment of acute mountain sickness. J Appl Physiol 2007;102: Luks AM, Swenson ER. Travel to high altitude with pre-existing existing lung disease. Eur Respir J 2007;29: Maggiorini M, Brunner-La Rocca HP, Peth S, et al. Both tadalafil and dexamethasone may reduce the incidence of high-altitude pulmonary edema: a randomized trial. Ann Intern Med 2006;145:497 6;145: Moraga FA, Flores A, Serra J, Esnaola C, Barriento C. Ginkgo biloba decreases acute mountain sickness in people ascending to high altitude at Ollague (3696 m) in northern Chile.. Wilderness Environ Med 2007;18: Nerin MA, Palop J, Montano JA, Morandeira JR, Vazquez M. Acute mountain m sickness: influence of fluid intake. Wilderness Environ Med 2006;17: Oelz O, Maggiorini M, Ritter M, et al. Nifedipine for high altitude pulmonary oedema. Lancet 1989;2: Rock PB, Johnson TS, Larsen RF, Fulco CS, Trad LA, Cymerman A. Dexamethasone D as prophylaxis for acute mountain sickness. Effect of dose level. Chest 1989;95: Rodway GW, Hoffman LA, Sanders MH. High-altitude altitude-related disorders-- --Part II: prevention, special populations, and chronic medical conditions. Heart Lung 2004;33: Rodway GW, Hoffman LA, Sanders MH. High-altitude altitude-related disorders-- --Part I: Pathophysiology, differential diagnosis, and treatment. Heart Lung 2003;32: Sartori C, Allemann Y, Duplain H, et al. Salmeterol for the prevention ention of high-altitude pulmonary edema. N Engl J Med 2002;346: Schoene RB. Illnesses at high altitude. Chest 2008;134: Stream JO, Grissom CK. Update on high-altitude pulmonary edema: pathogenesis, prevention, and treatment. t. Wilderness Environ Med 2008;19: Swenson ER. Carbonic anhydrase inhibitors and hypoxic pulmonary vasoconstriction. Respir Physiol Neurobiol 2006;151: Swenson ER, Teppema LJ. Prevention of acute mountain sickness by acetazolamide: as yet an unfinished story. J Appl Physiol 2007;102: Wright A, Brearey S, Imray C. High hopes at high altitudes: pharmacotherapy for acute mountain sickness and high- altitude cerebral and pulmonary oedema. Expert Opin Pharmacother 2008;9: Ziaee V, Yunesian M, Ahmadinejad Z, et al. Acute mountain sickness ss in Iranian trekkers around Mount Damavand (5671 m) in Iran. Wilderness Environ Med 2003;14:214-9.

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